Block 4

UNIT 1 CEREBRO VASCULAR DISEASES
Structure
1.0 Objectives
1.1 Introduction
1.2 Epidemiology
1.3 Normal Anatomy and Physiology
1.4 Classification
1.5 Ischaemic Cerebro Vascular Diseases
1.6 Aetiopathogenesis and Pathophysiology
1.7 Clinical Features
1.8 Laboratory Evaluation and Other Investigations
1.9 Differential Diagnosis
1.10 Prevention of Stroke
1.11 Treatment of Acute Stroke
1.12 Course and Prognosis
1.13 Let Us Sum Up
1.14 Key Words
1.15 Answers to Check Your Progress
1.16 Further Readings
1.0 OBJECTIVES
After reading this unit, you will be able to:
l define, classify and identify clinical manifestations of stroke;
l evaluate investigations, and risk factors;
l plan prevention and strategies to manage etiology and risk factors; and
l discuss prognosis.
1.1 INTRODUCTION
After reading the previous block, we will now discuss cerebro vascular lesions. Understanding
of basic pathophysiology of cerebro vascular lesions have enabled neurologist to approach
the problem and treat it more effectively at the molecular level. Imaging modalities like CT,
MRI, angiography and 3D CT angiography have been found to be useful in making an early
accurate diagnosis. Medical interventions like thrombolysis and cytoprotective measures
and surgical interventions such as carotid end arterectomy and other revascularization
procedures have helped in prevention of neurological deficit and future recurrences. An
attempt has been made to provide information for you to be able to manage stroke and
reduce its mortality and morbidity.
1.2 EPIDEMIOLOGY
Stroke is a major cause of morbidity and mortality through out the world with some hard facts
about it. It is perhaps the second leading cause of death and third in the United States of America.
In the US, an estimated 750,000 stroke cases occur annually. According to the American Heart
Association, there are an estimated 4 million stroke survivors and that there is an incidence of
one stroke every 53 seconds and one stroke death every 3.3 minutes in the US.
There is lack of reliable information on stroke epidemiology for the Indian subcontinent and
its national morbidity or mortality patterns. After an acute attack as many as 30% die in first 5
few days and amongst the survivors, 25% are rendered disabled.
CNS and Neuro-psychiatric Definitions
Disorders
The World Health Organization (WHO) defines stroke as “rapidly developing clinical signs
of focal or global disturbance of cerebral function, with symptoms lasting 24 hours or longer
or leading to death with no apparent cause other than of vascular origin”.
The definition includes subarachnoid haemorrhage (SAH) but excludes transient ischaemic
attacks (TIA), subdural haematomas, or haemorrhage or infarction caused by infection or
tumor.
Usually, ‘stroke’ is defined as a rapid onset of focal neurological deficit over

minutes to hours (stroke-in evolution), resulting from diseases of cerebral vasculature
and its contents. TIA implies complete recovery of such a deficit within 24 hours.
The cerebral vessels (extra/intracranial arteries, capillaries, veins and venous sinuses)
may show abnormality of their lumen (e.g. narrowing by atheroma etc.) or may be
occluded by thrombo-embolism. Among other factors, alterations in viscosity and
morphology of blood constituents (red cells, leucocytes, platelets) also contribute to
impaired blood flow. Cerebral or subarachnoid haemorrhage is consequent to rupture
through some inherent weakness of the vessel wall (e.g. aneurysms, angiomatous
malformations) (Table 1.1).
Table 1.1: Various Manifestations of Stroke

1) Stroke with recovery
l TIA
2) Stroke with permanent deficit
l Ischaemic
l Haemorrhagic
l Intracranial
l Subarachnoid
l Embolic
1.3 NORMAL ANATOMY AND PHYSIOLOGY

The cerebral circulation is divided into an anterior and posterior circulation (Table 1.2).
Table 1.2: Anterior and Posterior Circulation
l Anterior circulation
– Internal carotid artery and its branches
l MCA : Middle cerebral artery
l ACA : Anterior cerebral artery
l Anterior choroidal artery
l Posterior circulation
– Vertebral artery
– Basilar and Posterior cerebral artery.
The main cerebral circulation is sustained by circle of Willis formed by

l Anterior cerebral arteries and anterior communicating arteries.
l Posterior cerebral arteries and posterior communicating arteries.
The anterior circulation basically supplies majority of cerebral parenchyma except small part
of occipital lobe while posterior circulation supplies cerebellum and brain stem.
Collateral arteries play an important role in cerebral circulation. The main ones are as follows:
(1) the anastomoses around the orbit, of the branches of the external carotid artery with those
6 of ophthalmic artery; (2) Circle of Willis formed by anterior communicating arteries which
connect the two anterior cerebral arteries and posterior communicating arteries which connect Cerebro Vascular Diseases
two posterior cerebral arteries; (3) corticopial network.
Physiology of Cerebral Circulation and Cerebral Metabolism
The brain depends on minute to minute supply of oxygenated blood. The normal functions
are solely dependent upon a relatively constant supply of oxygen and glucose, as well as other
nutrients derived from the blood perfusing it (55 to 70 ml of blood per 100 gm of brain per
min). The principal source of energy is almost exclusively derived from oxidation of glucose
and it has been estimated that 1500 gm of brain would require uninterrupted supply of 150 gm
of glucose and 72 litres of oxygen per 24 hours. Constancy of cerebral circulation is maintained
by a series of baroreceptors and vasomotor reflexes under the control of lower brain stem.
Cerebral blood flow (CBF) is directly proportional to the arteriovenous pressure gradient,
which reflects general hemodynamic parameters (heart rate, blood volume etc.); and is inversely
proportional to the resistance to blood flow. If for any reason, the CBF is critically reduced
below the threshold of 23 ml/100 gm/min (e.g. systemic hypotension, occlusion of major artery,
etc.), and if after a short period of time, is restored to level above 23 ml, the impairment of
functions are restored. A fall of CBF below 8.0 to 9.0 ml/min results in ischaemia or infarction
regardless of duration. The state of hypo perfusion of the brain (CBF between 8 to 23 ml/100
gm/min) is called the ‘ischaemic penumbra’.
The mean arterial blood pressure, cerebrovascular and tissue resistance, local metabolic products
(pH, PaO2, PaCO2 tension etc.) together with several known and unknown factors, help to
maintain the critical threshold of blood flow for energy and metabolism. Furthermore, cortical
blood flow varies in different areas of the brain and a self regulatory mechanism (‘auto
regulation’) determines the regional flow to meet local metabolic needs. For example, with an
increase in partial pressure of CO2, the arterioles dilate to increase blood flow and vice versa.
The precise role of vasoconstrictor (sympathetic) and vasodilator nerve impulse in the regulation
of vascular tone and local blood flow is much debated, but circulating neurochemical transmitters
(serotonin, catecholamines, etc.) do modify the local needs.
Conversely, in the region of cerebral ischaemia, there is ‘paralysis of auto regulation’ and
the microvasculature is non-reactive to pressure change, to vasoactive agents and to other
forms of stimuli. The cerebral vasculature in this ischaemic zone becomes permeable to protein
and fluid leaks in the vicinity (extra-cellular cerebral edema). Such events also lead to local
hemoconcentration and vascular stasis. Thus, cerebral infarction is not the mere result of
ischaemia from occluded blood vessels (e.g. cerebral thrombosis or embolism), but an end
result of a series of highly complex ischaemia modifying events.
To protect the brain from such haemodynamic ischaemic insult, nature has provided additional
collateral pathways. Collateral circulation, described earlier, provides blood supply of good
caliber with low resistance. In addition, extra cranial anastomoses between the cervical
branches of the ipsilateral external carotid, subclavian and vertebral arteries have also been
identified. Such pre-Willisian arterial anastomoses help to maintain cerebral blood supply
in individuals even with occlusion of a major artery in the neck. Likewise, large precapillary
anastomoses exist between the anterior, middle and posterior cerebral arteries and various
cerebellar arteries. Such post-Willisian anastomoses further protect cerebral tissue from
the effects of occlusion of single cortical branches. Thus, in an individual with symmetrical
circle of Willis, despite major extra cranial arterial occlusions, sufficient blood may
still reach the territory through the collateral to prevent on-coming cerebral ischaemic
insult. On the other hand, in presence of generalized arterial disease (atherosclerosis),
congenital variations and multiple skipped stenotic lesions, these collateral pathways prove
inadequate in maintaining normal blood flow and predispose to cerebral ischaemia or
infarction.
Some infarcts are devoid of blood and, therefore, pallid (pale infarct) whereas other show mild
congestion, especially at their margins; and still others show an extensive extravasation of
blood from many small vessels in the infarcted tissue (red or haemorrhagic infarct). In
haemorrhage, blood leaks from the vessel directly into the brain, ventricles or subarachnoid
space. Once this is arrested, blood slowly disintegrates and is absorbed over weeks and months.
Mass of blood clot can cause physical disruption of tissue and pressure on the surrounding
structures.
7
CNS and Neuro-psychiatric Risk Factors
Disorders
Table 1.3: Risk Factors
l Modifiable
1) Hypertension
2) Diabetes mellitus
3) Smoking
4) Obesity
l Non-modifiable
1) Age
2) Sex
Most important risk factors (RF) (Table 1.3) are hypertension and diabetes mellitus, which
are held responsible for hastening the atherosclerotic process in both the large and small
arteries. Furthermore, hypertension is the most important risk factor in the genesis of primary
intracerebral haemorrhage; and numerous studies indicate that long-term control of hypertension
decreases the incidence of atherothrombotic cerebral infarction and intracerebral haemorrhage.
Heart diseases especially heart failure, myocardial infarction/coronary artery disease play a
major role. Tobacco smoking, obesity, hyperlipidaemia, altered blood viscosity etc. are also
considered to be important risk factors for strokes. Cerebral embolism is usually secondary to
structural cardiac disease and arrhythmias.
1.4 CLASSIFICATION
After going through the physiology of cerebral circulation, the strokes are classified as follows
(Table 1.4) :
Table 1.4: Classification of Strokes
I) Ischaemic Strokes
With Cerebral Infarction
1) Cerebral thrombosis with or without atherosclerosis

2) Cerebral embolism (congenital and acquired valvular disease, cardiomyopathy, myocardial
infarction, endocarditis, prolapsed mitral valve etc.
3) Lacunar strokes (deep, small cerebral infarcts)
4) Cerebral venous thrombosis and cortical thrombophlebitis
5) Artheritis (syphilitic, tubercular, rheumatic, Takayasu’s disease, collagen diseases etc.)
6) Blood disease (polycythemia, sickle cell anaemia, thrombotic states, hyperproteinemia etc).
7) Arterial hypotension and anoxic encephalopathy
8) Dissecting aneurysms of brachio-cephalic vessels
9) Angiographic complications
10) Infarction of undermined cause
With Cerebral Ischaemia
1) Transient ischaemic attacks (platelet-fibrin micro emboli associated with atheroma etc.)
2) Arterial hypotension or haemodynamic crisis (e.g. massive gastro-intestinal bleeding).
3) Cardiac arrhythmias (atrial fibrillation, complete heart block or sick-sinus syndrome etc.)
4) Migraine
5) Local embolism from atherosclerotic plaque and paradoxical embolism
6) Miscellaneous (e.g. drugs and oral contraceptives, disseminated intravascular coagulopathy,
cerebral malaria, Behcet’s syndrome, congophilic angiopathy, homocystinuria, hyperviscosity
syndrome, paraproteinemia, etc.)
II) Haemorrhagic Strokes
1) Hypertensive cerebral haemorrhage

2) Ruptured aneurysm (saccular, mycotic etc.)
8
3) Ruptured angioma (arterial, venous or mixed) Cerebro Vascular Diseases
4) Trauma
5) Blood dyscrasias (leukaemia, purpura, hyperviscosity syndrome and other bleeding
diasthesis)
6) Complication of anticoagulant therapy
7) Bleeding in brain tumours
8) Miscellaneous causes (arteritis, bleeding in haemorrhagic infarct, etc.)
9) Undetermined source (normal blood pressure without aneurysm or arteriovenous
malformation)
10) Rare types (after vasopressor therapy, on exertion, arteriography)
III) Strokes of Undetermined Origin
1) Moyamoya disease
2) Fibromuscular dysplasia
3) Binswanger’s subcortical arteriosclerotic encephalopathy
4) Leukoariosis
5) Buerger’s disease (Thrombo-angitis obliterans—cerebral form)
6) Aortic arch syndrome (non-inflammatory)
Check Your Progress 1

1) Define Transient Ischaemic Attack (TIA).
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2) Enumerate type of stroke with permanent deficit.

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3) What are the important risk factors responsible for atherosclerosis and stroke?
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1.5 ISCHAEMIC CEREBROVASCULAR DISEASES

If for any reason, such as cardiac arrest or prolonged hypotension (below 70 mm Hg), the
brain tissue is significantly deprived of its nutrition for more than three minutes, death of brain
parenchyma (cerebral infarction) ensues. The sylvian region is commonly involved in middle
cerebral artery occlusion (mid-field infarct), whereas with the internal carotid artery lesion,
the cerebral infarction is mostly located in distal or watershed territory (end field infarction).
A ‘mid-field’ infarct produced by occlusion of a small penetrating vessel with poor collateral
circulation in the neighbourhood pathways, may prove catastrophic, whereas an ‘end-field’
infarct resulting from occlusion of a major vessel in the neck (e.g. carotid artery block), with
good collateral circulation, may be asymptomatic. Obstruction to venous return can also result
in infarction (e.g. cerebral venous thrombosis). Acutely infarcted brain tissue is soft and swollen,
frequently herniates downwards and may compress the vital centres within the brain stem,
ending in a fatal outcome. Like infarction elsewhere in the body, cerebral infarcts heal by
gliosis (fibrosis). It is frequently replaced by a firm scar or a cystic cavity. It must, however, be
appreciated that transient cerebral ischaemia may not leave any trace of identifiable cerebral
damage by conventional tests.
1.6 AETIOPATHOGENESIS AND PATHOPHYSIOLOGY

Cerebral infarction is usually attributed to partial/total occlusion of its regional microvasculature
by thromboembolism. Cerebral atheroma is by far the most common underlying intimal vascular
pathology. 9
CNS and Neuro-psychiatric Recent studies on molecular and metabolic events leading to infarction have shown that
Disorders there is a dense central core surrounded by a less dense zone of ischaemia (‘penumbra’),
and neuronal death occurs in this central focus unless perfusion is quickly restored. On the
other hand, cells in the zone of penumbra remain viable for at least three hours (‘therapeutic
window’) and can be salvaged by reperfusion, neuroprotective agents, etc. to prevent further
damage. Major factors, which enhance nerve cell injury are intracellular failure of ionic
pump functions or ‘leaks’, changes in Na/K gradients, acidosis, the release of free radicals
and other unknown factors, which in turn disrupt blood brain barrier (BBB) and the
microvascular function. Here, energy depletion from brain hypoxia is one of the key events
that fails to maintain normal concentrations of cellular adenosine triphosphate (ATP), leading
to delay in re-synthesis of macromolecular proteins essential for cell structure. Such energy
failures also induce proteolysis and lipolysis, in addition to production of arachidonic acid
and platelet activating factors, free radicals etc. resulting in further neuronal damage
(ischaemic cascade hypothesis). Thus, the severity of cerebral infarct is not the mere result
of ischaemia from occluded vessels but the end result of several highly complex ‘ischaemia-
modifying factors’. The precise role of leukocyte-endothelial interactions, receptor
activation, post-ischaemic hypo/hyper perfusion injuries, nitric oxide, nerve growth factors
and gene expression are under study.
1.7 CLINICAL FEATURES

Obesity, feeble to absent or unequal peripheral arterial pulsations, vascular bruits, raised blood
pressure, postural hypotension and retinopathy may be detected on a general physical
examination.
Before a thrombotic lesion becomes manifest, in about 60 per cent of the subjects, prodromal
warning symptoms may precede an oncoming insult. These episodes of TIA are usually
brief (lasting for a few minutes to less than an hour) and may come on singly or in successive
spells over a number of hours, days or months but usually leave no significant residual
signs. These TIAs, which may come at any time to the day or night and which do not appear
to be related to posture or the level of blood pressure, may resolve altogether. In some
cases, an evolving or a full blown stroke follows the last ischaemic spell. Haemodynamic
crisis, disturbances in haemostasis, failure of collateral circulation and other ‘ischaemia
modifying factors’ have been considered as alternative possibilities for stroke where no
source of embolisation (heart, atheromatous plaques in aorta or its branches) has been found
after complete investigations.
When the stroke evolves in a stepwise manner (thrombus in evolution) the symptoms may
appear in each limb in succession or simultaneously. This stuttering, intermittent progression,
rather than a slow gradual onset, is very typical of cerebral thrombosis. Not infrequently, the
stroke may announce itself abruptly as a single major catastrophic event (accomplished
infarction or completed stroke). The other clinical manifestations depend on the site of the
arterial occlusion. The specific neurovascular syndromes which may result, are described
below:
Internal Carotid Syndrome
The cervical portion of the internal carotid artery, near the carotid sinus is a common site for
both severe atheroma and thrombotic occlusion. About 30 per cent of all occlusive lesions are
located in this segment. Many of these lesions may be silent or asymptomatic and sufficient
blood reaches the occluded territory through the external ‘carotid-ophthalmic’ anastomosis or
from superficial and deep cervical anastomoses or from the opposite carotid artery through the
anterior segment of the circle of Willis.
In symptomatic carotid thrombosis, ‘warning symptoms’ precede a major insult in 50 per cent
of the subjects. These symptoms include brief episodes of confusion, difficulty with speech
(aphasia, dysarthria, dyslexia) and paraesthesia, with or without motor weakness of the opposite
side. Ipsilateral ‘amaurosis fugax’ (transient monocular blindness) fleeting or semi-permanent
hemiplegia or hemisensory deficit is pathognomonic of a carotid artery syndrome. However, it
is noted in only 15 to 20 per cent of the subjects.
The carotid occlusions are almost indistinguishable from those of a middle cerebral syndrome.
Feeble internal carotid or superficial temporal artery pulsations, dilated pupil, poorly pulsating
retinal vessels (with or without optic atrophy) on the side of suspected carotid lesion and
ocular or cervical bruits on the ipsilateral side may suggest the correct diagnosis. Carotid
Doppler sonography or angiography are of great help for an accurate diagnosis; and also to
10 ascertain the degree of stenosis and the collateral flow.
In subjects with an old or silent occlusive carotid axis lesion on one side, a ‘new’ lesion on the Cerebro Vascular Diseases
other side may prove catastrophic. Here, the physical findings of a bilateral hemiplegia
(quadriplegia) with coma can be easily mistaken for a basilar artery syndrome.
Anterior Cerebral Syndrome
The cortical branches mainly supply the medial and superior surface of the frontal lobe and
the parietal lobe up to the paracentral lobule. The penetrating branches supply the anterior
limb of the internal capsule and part of the head of the caudate nucleus.
An anterior cerebral occlusion proximal to the anterior communicating artery, in subjects
with a symmetrical circle of Willis, is frequently asymptomatic. An occlusion, distal to the
anterior communicating artery, manifests itself by a sensory-motor paralysis of the opposite
lower extremity, with mild weakness of the opposite shoulder. Mental changes, rectal and
urinary incontinence, gait disturbances, apraxia, grasp and sucking reflexes may accompany
the above findings.
Occlusion of an unpaired anterior cerebral artery (supplying both the hemispheres) results in
a cortical type of paraplegia, with sphincter incontinence and a mental state in which the
patient is alert but mute (akinetic mutism). Aphasia and hemianopia are never seen.
Occlusion of the penetrating branches of the so called Heubner’s artery is frequently blamed
for ataxic tremor of the contralateral limbs. Frontal ataxia, apraxia (ideomotor dyspraxia) of
the limbs and gait may also be present.
Middle Cerebral Syndrome
The cortical branches supply most of the lateral surface of the cerebral hemisphere, except for
the regions supplied by the anterior and posterior cerebral arteries. The areas include sensory-
motor cortex, motor and sensory speech centres, auditory area and visual radiation. The
penetrating branches (lenticulostriate arteries) supply the putamen, globus pallidus, genu and
posterior limb of the internal capsule.
The clinical picture of middle cerebral artery occlusion is variable. Contralateral hemiplegia,
hemianaesthesia with or without homonymous hemianopia and aphasia (dominant and non-
dominant) is the common outcome. However, occlusion of upper division results in contralateral
hemiparesis with sensory deficit and expressive aphasia (Broca’s aphasia) whereas Wernicke’s
aphasia is commonly seen with occlusion of the lower division on dominant side. Even
monoplegic symptoms can occur with occlusive lesions of single cortical branches.
Occlusion of penetrating branches (lenticulostriate arteries) have been repeatedly blamed
for a dense sensorimotor hemiplegic syndrome (“capsular hemiplegia”) but with such an
occlusion, significant sensory loss seldom occurs, whereas ‘pure motor hemiplegia’ is not
uncommon.
Posterior Cerebral Syndrome
This artery supplies the medial and inferior portions of the occipital and temporal lobes. Its
branches also supply the mid-brain, cerebral peduncle and most of the thalamic and sub thalamic
regions.
Thrombotic occlusions of the posterior cerebral arteries are relatively rare. A contralateral
homonymous hemianopia is the most significant finding and this results from infarction of the
primary visual area (calcarine cortex); the central vision is frequently spared, even in cases
with bilateral disease (gun-barrel vision). Other manifestations of visual dysfunction include
illusory or distorted vision, visual-object agnosia and various forms of dyslexia with dysgraphia.
The pupillary reflexes are preserved. A contralateral hemiplegia from lesion of the cerebral
peduncle (peduncular hemiplegia) and thalamic syndrome (Dejerine and Roussy syndrome)
may also be present. In the thalamic syndrome, there is varying degree of sensory loss to all
modalities and spontaneous burning or agonizing pains are frequent (analgia dolorosa). Memory
loss (amnesia) denotes a lesion of the medial temporal cortex. Contralateral involuntary
choreoathetosis or ataxic tremors are rarely observed.
Vertebro-basilar Syndrome
Both vertebral arteries, after traversing through the bony vertebral canal, unite intracranially
to form the basilar trunk. Their short para median and long circumferential branches supply
the entire brain stem, cerebellum and the vestibular apparatus. Ischaemic disorders, therefore,
manifest by episodes of vertigo, dizziness, diplopia, dysarthria, dysphasia, incoordination of
the gait and limbs and bilateral signs of sensori-motor deficits. Occipital headaches may be
present. 11
CNS and Neuro-psychiatric Ipsilateral 3rd nerve palsy (dilated pupil, ptosis and external strabismus) with contralateral
Disorders hemiplegia (Weber’s syndrome) or with crossed cerebellar ataxia (Claude’s syndrome) is
diagnostic of mid-brain localisation. Homolateral paralysis of the 6th (abducens) and 7th (facial)
nerves (internal squint and facial palsy) with contralateral hemiplegia and hemianaesthesia
(Millard-Gubler syndrome) is suggestive of a pontine lesion. Palatal paralysis and ataxia of
limbs, with impairment of posterior column sensations on one side of the body, together with
diminution of pain and thermal sense on the opposite limbs (Wallenburg’s syndrome) indicates
a lateral medullary infarction.
Not infrequently, quadriplegia with a bilateral conjugate, lateral gaze and de-efferented and
mute state have been described (locked-in syndrome), suggestive of infarction of basal points
(sparing tegmentum) from mid basilar occlusion.
Occlusion of isolated cerebellar branches may produce dizziness, nausea, vomiting, nystagmus,
appendicular or truncal ataxia without sensory-motor deficit in any limb. Such a syndrome
should be differentiated from cerebellar haemorrhage where emergency surgical decompression
proves life saving.
1.8 LABORATORY EVALUATION AND OTHER

INVESTIGATIONS
After detailed history and meticulous neuromedical examination including palpation and
auscultation of brachiocephalic and peripheral pulses, the relevance and priority of any
laboratory test in acute stroke should be the clinicians’ judgement. The value of careful
ophthalmoscopic examination of retina and its vasculature for disease and embolic fragments
needs greater emphasis. Often, stroke subjects are rushed for treatment with CT scan in absence
of valuable clinical data.
According to American Heart Association (AHA) guidelines, all patients with stroke should
have following investigations:
Routine haematological tests
Complete Blood cell count
Platelets count
Prothrombin time
Partial Thromboplastin time
Serum Electrolytes and Glucose
Renal panel
Hepatic panel
Routine diagnostic tests
Electrocardiogram
Chest radiograph
In addition EEG may be required if seizure is suspected to be the cause of altered consciousness.
Special tests for detection of sickle cells, LE cells, RA test or protein electrophoretic pattern
are performed when indicated. 2-D Echo or holter monitoring should be done only when
required. Examination of cerebrospinal fluid (CSF), within 7 days of ictus, is very helpful in
diagnosis of 80 per cent of haemorrhagic strokes and nearly 90 per cent of subarachnoid
haemorrhage (SAH) cases.
Computerized tomography (CT) is a single most important non-invasive investigation to
distinguish an infarction from cerebral hematoma. This modality is almost 100% sensitive for
diagnosis of intracranial haemorrhage.
The precise role of newer neuroimaging tests like magnetic resonance imaging (MRI) and
positron emission tomography (PET) are also helpful in visualizing hypoxic lesions producing
TIA/RIND which are often missed by CT scan. Peri-infarct parenchyma which appears normal
on CT scan often shows abnormality on MRI; and ischaemic/demyelinating lesions or
ischaemic penumbra surrounding the lesions can be differentiated. MRI has structural
advantage over CT, the most important being clear identification of structures in the posterior
fossa, brain stem infarction, especially lacunes. Angiography remains the gold standard for
assessment of CBF. Digital subtraction angiography (DSA), by intravenous route, not only
outlines the entire brachio-cephalic circulation but is considered relatively safe and non-
12 invasive procedure. Unfortunately, it has failed to give clear-cut definitions of abnormalities
as visualized (e.g. atheromatous plaques), and many centers have now reverted to intra- Cerebro Vascular Diseases
arterial DSA, by selective catheterization, to study the areas of interest, mainly for
symptomatic carotid artery stenosis. Duplex carotid scanning and MR angiography are other
valuable scanning procedures.
1.9 DIFFERENTIAL DIAGNOSIS

Prodromal warning symptoms, abrupt onset of a focal neurological deficit, stuttering or
intermittent progression, a constellation of symptoms and signs diagnostic of a well defined
neurovascular syndrome, clear CSF, some degree of recovery and evidence of vascular disease
elsewhere in the body (absent carotid pulsations or bruits over the major vessels, history of
angina pectoris, myocardial ischaemia or a previous stroke, arrhythmia, intermittent claudication
in the legs with feeble pulses is highly suggestive of stroke.
Bogousslavsky et al reported 1000 consecutive patients with cerebral infarction or haemorrhage.
Headache was a presenting complaint in 51% of non-comatose patients with haemorrhage but
also occurred in 16% of those with infarction. Pure motor hemiparesis was present in 49% of
patients with infarction compared with 17% of the patients with haemorrhage. Pure sensory
symptoms were rare. Language disturbances occurred in both group of patients but isolated
Wernicke’s aphasia or Wernicke’s aphasia with hemianopia was rare in those with haemorrhage.
Progressive neurological deficit and decreased consciousness were most common in patients
with haemorrhage (52% and 50%, respectively) but also occurred in patients with cerebral
infarction (26% and 11%, respectively). This suggests that although the history and physical
examination often suggests the correct diagnosis, enough overlap exists so that diagnostic
imaging should be performed in all cases of suspected stroke.
In distinguishing cerebral haemorrhage from cerebral infarction the following collective
criteria, though not always diagnostic, may prove helpful in suspecting an intracerebral
bleed. These are: (i) moderately severe to intense headache (throbbing, pulsating or pounding)
in a known hypertensive subject, accompanied by nausea and vomiting; (ii) altered state of
consciousness (drowsiness progressing to deepening coma) with irregular respiration;
(iii) neck stiffness accompanied by dissociated eye movements, or forced gaze deviation;
(iv) blurred disc margins or pre-retinal haemorrhage, with changes suggestive of hypertensive
retinopathy; (v) hemiparesis on one side with shivering movements or even frank convulsions
on the non-paralysed side, or quadriparesis with an extensor plantar response on both sides,
etc. The blood in CSF will help to settle the diagnosis.
However, haemorrhagic cerebral infarction in a hypertensive subject and occult intracerebral
bleed (hematoma or slit haemorrhage) may even show a clear CSF at onset, and here the value
of urgent CT scanning to arrive at a diagnosis cannot be ignored. It should be noted that
immediate mortality from massive cerebral infarction is in the range of 30 per cent, and nearly
30 per cent survive from small intracerebral bleed. Therefore, another CSF examination on the
third or fourth day may reveal slight xanthochromia. On the other hand, embolic haemorrhagic
cerebral infarction and a leaking intracerebral bleed may show blood-stained CSF and an
angiographic examination as well as a CT scan may prove very useful in arriving at a diagnosis.
Other investigations are of little diagnostic help.
Subdural hematoma and other mass lesions (e.g. intracerebral hematoma, brain tumor,
brain abscess, etc.) may mimic a stroke. Here, a clinical history of headaches or seizures,
papilloedema, raised spinal fluid pressure and xanthochromia with elevated protein, midline
shift or a calcified pineal gland (when present) on skull X-rays, high voltage slow waves
on EEG and abnormally high local concentration of radio-isotope in brain scan, all point
to the true nature of the lesion. Cerebral angiography helps to settle the diagnosis, whereas
isodense subdural hematomas may be misdiagnosed as infarct on CT scan. A history of
head injury, careful cranial examination for marks of injury, a blood stained CSF and
characteristic X-ray findings (e.g. fracture) easily differentiate post traumatic conditions
from strokes. When depressed consciousness occurs without an adequate history, the
differential diagnosis may also include metabolic abnormalities (hypoglycemia, electrolyte
imbalance, thiamine deficiency), toxic ingestion, endocrinopathy, seizure or psychiatric
disorder.
Post-epileptic hemiplegia (Todd’s paralysis) with complete recovery may simulate transient
cerebral ischaemia. Clinical history suggestive of seizure disorders with EEG abnormalities in
a young subject proves helpful in arriving at a correct diagnosis. Posterior fossa tumors, the
administration of sedatives or tranquillizers, multiple sclerosis, vestibular disorders and hysteria
may simulate vertebro-basilar artery disease, but seldom present diagnostic problems. Here,
13
CNS and Neuro-psychiatric meticulous history with serial clinical observations proves more helpful rather than fancy
Disorders tests including a CT scan.
1) Describe clinical features of middle cerebral syndrome.
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2) Which is gold standard assessment for cerebral blood flow (CBF)?

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1.10 PREVENTION OF STROKE

During the past five years, important results in an unprecedented number of clinical trials
have refined the approach to stroke prevention. Stroke prevention is cost-effective and often
cost-saving. Most strokes can now be prevented using proven interventions, but the challenge
remains to apply these treatments effectively in clinical practice.
The primary aim of prevention is to identify and modify treatable risk factors like diabetes,
hypertension, heart disease and smoking. Patient should be advised to take a low animal fat
diet, reduction in dietary salt, avoid alcohol consumption and moderate exercise.
Etiology and Risk Factor Management
Stroke is a heterogeneous syndrome in which multiple disorders can lead to occlusion or rupture
of blood vessels supplying the brain. Optimal prevention depends on identifying the specific
cause of threatened stroke. Severe cervical carotid artery stenosis is present in about 15 per
cent of patients with brain ischaemia.
Isolated Systolic Hypertension: Treatment of isolated systolic hypertension in the elderly reduces
the risk of stroke and is generally well tolerated if carefully administered. A recent large,
randomized trial showed that the benefits of treatment can be achieved with dihydropyridine
calcium channel blockers and angiotensin-converting enzyme inhibitors. Treatment also reduces
the incidence of congestive heart failure and other cardiovascular events.
Cholesterol Reduction with Statin Drugs: At present, the value of cholesterol reduction with
statins to prevent stroke has not been established specifically by clinical trials for patients with
threatened stroke. Nonetheless, the use of statins in patients with cerebral ischemia to prevent
myocardial infarction and vascular death is often clinically indicated. There is growing consensus
for the use of statins in the primary prevention of stroke but final recommendations are yet to
come.
Homocysteine: Elevations of serum total homocysteine levels have been correlated with risk
for myocardial infarction and ischemic stroke, especially in middle-aged persons. Because
small doses of folate correct the abnormality, there is considerable interest in this easily treatable
potential risk factor for stroke.
Antiplatelet Therapies
In the medical therapy for secondary prevention, antiplatelet agents have important role. Aspirin
and ticlopidine are widely recognized as being effective for prevention of recurrent stroke in
patients with TIA or ischemic stroke. Two additional antiplatelet therapies for stroke prevention
have recently emerged: clopidogrel and high-dose dipyridamole. Other new antiplatelet
agents, such as the oral glycoprotein-IIb/IIIa inhibitors triflusal and indobufen, have not yet
been adequately tested in patients with threatened stroke because of cerebrovascular disease.
Aspirin: Most clinicians prescribe 325 mg per day. The U.S. Food and Drug Administration
recently recommended that aspirin dosages between 50 and 325 mg per day be used for stroke
prevention.
Ticlopidine: Ticlopidine is given in a dose of 250 mg twice a day.
Monitoring of the white blood cell count is required every two weeks during the first three
months of therapy with ticlopidine to detect leukopenia, which occurs in 1 to 2 per cent of
recipients; skin rash and diarrhoea preclude continued use of ticlopidine in about 15 per cent
14 of patients. Because of these potential side effects, most clinicians reserve ticlopidine for use
in patients who experience cerebral ischemia while they are taking aspirin or for aspirin- Cerebro Vascular Diseases
intolerant patients.
Clopidogrel: Clopidogrel, a congener of ticlopidine is given in dosage of 75 mg per day The
toxicity of clopidogrel in a dosage of 75 mg per day was comparable to that of aspirin in a
dosage of 325 mg per day, with no increase in leukopenia. Clopidogrel is considered to be
second line treatment in patients intolerant for aspirin and first line treatment for patients with
stroke and peripheral arterial disease. The main hinderance to its use is its cost.
Dipyridamole: Dipyridamole combined with aspirin was widely used in the early 1980s for
stroke prevention, until critical analysis cast doubt on its efficacy. A recent large European
randomized trial found high-dose dipyridamole (200 mg twice daily, in a sustained-release
preparation) plus aspirin (25 mg twice daily) to be superior to aspirin alone, with a 21 per cent
risk reduction relative to aspirin (P=0.006). Efficacy of four antiplatelet agents are given in
Table 1.5. Aspirin is recommended as first-line antiplatelet therapy, reserving clopidogrel for
“aspirin failures” or aspirin-intolerant patients.
Table 1.5: Antiplatelet Therapies for Stroke Prevention: Estimates of Comparative Efficacy
Agents Dosage Stroke

Relative risk NNT versus aspirin*
reduction versus
placebo (%)
Aspirin 75-1300 mg/day 25

Ticlopidine 250 mg twice daily 25-40 ~80
Clopidogrel 75 mg/day 30 ~250
Dipyridamole: With 200 mg twice daily 35-40 ~80
Aspirin
* NNT versus aspirin — the number needed to treat with the agent instead of aspirin for one year to
prevent one stroke. A stroke rate of 8 per cent per year was used for these calculations
Role of Anticoagulation
Warfarin: Available antiplatelet agents offer only partial protection against strokes (i.e., 25 to
40 per cent risk reduction), and more efficacious antithrombotic agents would be useful.
However, anticoagulation with warfarin has not been established as beneficial for patients
with TIA or ischemic stroke caused by common cerebrovascular diseases. In contrast, warfarin
is highly efficacious for prevention of stroke in patients with cardioembolic causes of brain
ischaemia. Some clinicians advocate the use of warfarin for patients with inoperable symptomatic
carotid stenosis, intracranial atherosclerotic stenosis or “antiplatelet failures”.
Clinical trials continue to demonstrate important benefits of warfarin (target INR: 2 to 3)
for primary and secondary stroke prevention in high-risk patients with nonvalvular AF.
Adjusted dose warfarin therapy reduces the risk of stroke in patients with AF by about two
thirds. Aspirin therapy for preventing stroke in AF patients reduces strokes by about 20
per cent.
There are various surgical measures besides medical therapy, these include carotid end-
arterectomy and intracranial-extracranial anastomosis to prevent stroke.
1.11 TREATMENT OF ACUTE STROKE

The treatment of stroke has been revolutionised in the last two decades, comprising various
newer investigative and therapeutic modalities have made it possible to treat actively and
reduce the mortality and sequaelae associated with stroke. Medical treatment includes the
treatment for hypertension, the treatment of acute neurological complication and specific medical
therapy.
Supportive care
The initial evaluation of the patient with ischaemic stroke should identify any critical areas that
need to be immediately addressed. The ABC – airway, breathing and circulation – are functions that
may require immediate attention and support. There is a general agreement in the AHA guidelines
to recommend airway support and ventilatory assistance in patients with a depressed level of
consciousness; and supplemental oxygen to hypoxic patients.
Elevated Blood Pressure: Unless systolic blood pressure exceeds 220 mm Hg or diastolic 15
CNS and Neuro-psychiatric pressure exceeds 120 mm Hg (sustained on repeated measurement), elevated blood pressure
Disorders should not be treated within the first days after ischemic stroke. The ischemic penumbra loses
autoregulation, and perfusion is directly linked to mean arterial pressure. Acute elevations in
blood pressure are often transient, and spontaneous declines are common. Overzealous treatment
of hypertension following acute ischemic stroke can convert the ischemic penumbra into an
infarct. The two exceptions to this general recommendation are as follows: (1) after use of
tissue plasminogen activator (t-PA), blood pressure should be maintained below 185/110 mm
Hg, and (2) in the presence of myocardial infarction, heart failure or aortic dissection, elevated
blood pressure should be treated aggressively. If antihypertensive therapy is necessary, agents
that have a rapid onset and predictable response should be used.
Fever: In patients with acute stroke, fever is not uncommon. Whatever the cause, fever should
be suppressed in these patients. In experimental models of brain ischaemia as well as in clinical
studies, even mild elevations in body temperature consistently worsen the neurologic outcome
from ischaemic insults.
Hyperglycemia: In the setting of acute stroke, hyperglycemia may be deleterious to the ischemic
penumbra by permitting anaerobic metabolism with the creation of local lactic acidosis. It has
not been shown that control of glucose improves stroke outcome in humans; however, based
on observational and experimental studies, the general consensus is that glucose levels should
be kept below 150 mg per dL (8.3 mmol per L).
In the treatment of acute neurological complications measures are taken to control the brain
oedema, maintain adequate cerebral perfusion and to prevent brain herniation. The initial
treatment for brain oedema includes fluid restriction, treatment of hypoxia and head end
elevation by 20×30° later on if there is deterioration in the condition then patient may be
treated by osmotic diruretics (Mannitol, Glycerol) and by ventilatory support. Corticosteroids
do not have role in the management of cerebral oedema. Convulsions are usually treated with
parenteral anticonvulsant drugs like Epsolin and calmpose.
Patients are usually observed for haemorrhagic transformation of infarcts and CT head can
give reliable information.
Pharmacologic Interventions
Improved outcome with the use of intravenous thrombolysis is perhaps the most important
advance that has been made in the care of patients with ischemic stroke. More than two dozen
agents and interventions are currently undergoing clinical testing for use in the treatment of
acute ischemic stroke. The only specific intervention validated by adequate clinical trials and
labeled for this use by the U.S. Food and Drug Administration (FDA) is t-PA (given within
three hours of stroke onset). However, the results of ongoing clinical trials may soon expand
available therapeutic options.
Thrombolytics
Thrombolytic therapy had been a subject of controvery because of high incidence of intracerebral
haemorrhage. The current American recommendations are to treat selected patients with t-PA
(tissue plaminogen activator). It has been shown that its use within three hours of ischaemic
stroke onset, there was substantial improved long-term functional outcome in these cases if
given within three hours of ischaemic stroke onset. Intra-arterial delivery of thrombolytic agents
has been tried in the carotid and the vertebrobasillar circulation but no good results. Over all
benefits by streptokinase, Aspirin and Heparin in treatment of acute ischaemic strokes did not
show promising result.
Cytoprotective Agents: These agents increase the tolerance of neurons to ischemia and have
shown promising results in experimental models. None, however, has been shown to be
beneficial in adequate clinical trials to date. Various potentially neuroprotectants are:
Sodium /Calcium Channel modulators: Fos-phenytoin, Nimodipine, 8W6 19C 89, Lifarzine.
NMDA antagonists : Competetive–Selfotel, Eliprodil and Noncompetitve–Cerestat,
Remacemide desglycine.
Energy restorers: Piracetam
GABA Agonists: Clomethiazole
Miscellaneous actions: Lubeluzole
Large trials testing citicoline and clomethiazole should be completed soon. These agents appear
16 to be safer than fibrinolytic therapies and may have a longer time window for efficacy.
Among all the neuroprotective agents, calcium channel antagonists have shown promising Cerebro Vascular Diseases
beneficial agents. Nimodipine is the widest compound used, produces less symptoms of
hypotension, fewer cardiac inotropic and chronotropic effects and has better penetration into
the brain and brain vessels. The dosage ranged from 60-240 mg/day. The greatest benefit was
seen in patients within 12 hours of onset of stroke in patients within 12 hrs of the onset of
stroke.
There are certain complications related to stroke. These include pneumonia because of
aspiration, urinary tract infection due to catheter, venous thrombo embolisium and pressure
sores, these should be adequately treated.
1) Enumerate Antiplatelet drugs.
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2) What are the surgical measures used in stroke?

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3) Enumerate agents used as cytoprotective agents.

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4) Name one thrombolytic agent used in acute stroke.

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1.12 PROGNOSIS
In subjects who survive, some degree of recovery is the rule. Chances of significant recovery
are remote when no improvement is noted within the first 6 to 8 weeks. About 20 to 25 per cent
of the subjects with massive cerebral infarction and brain swelling die during acute phase.
Here, old age, presence of severe neurological deficit with coma and pyrexia, intercurrent
infections, and basilar artery thrombosis are of grave prognostic significance. Recurrent episodes
are frequent, but there is no way to predict the same in a given subject. However, control of
‘risk factors’ is beneficial.
Management of Haemorrhagic Stroke

No specific strategies have been found useful in improving the prognosis except treatment of
bleeding disorder. 70% die of hypertensive intracerebral haemorrhage. The size and location
of the haematoma determine the prognosis. General management is basically the same as in
ischaemic stroke.
1.13 LET US SUM UP

Stroke is one of the leading cause of death and disability and community surveys from different
regions of India reveals incidence from 44-842,000 per 100,000 persons. After an acute attack
as many as 30% die in first few days and 25% are rendered disabled amongst the survivors.
Various risk factors like Hypertension, Diabetes mellitus, smoking and obesity have been
implicated in causation of stroke. Diagnosis is based on good clinical history, precise
neurological examination with laboratory evaluation including CT Scan, MRI and angiography
(both Magnetic resonance and catheter angiography). Management of acute strokes has
improved because of early reporting of cases, more availability of acute care, trial of
thrombolytic therapies during and after lapse of therapeutic windows, better management of
cerebral oedema and therapies by newer neuroprotective agents. Neuroimaging has helped to 17
CNS and Neuro-psychiatric predict the future outcome, and cerebral oedema and preventive therapy in need based cases.
Disorders The role of surgery for ischaemic lesions as well as for vasoocclusive disease is now well
established which includes end-arterectomies, various by-pass surgeries, thromoboctomies
and revascularisation procedures.
1.14 KEY WORDS

Internal carotid syndrome : Atheroma and thrombotic occlusion of cervical portion
of the internal carotid artery leading to symptoms of
difficulty with speech and paraesthesia, with or without
motor weakness of the opposite side.
Middle cerebral syndrome : Contralateral hemiplegia, hemianaesthesia with or

without homonymous hemianopia and aphasia
contribute part of syndrome.
Mid-field infarct : Occulation of middle cerebral artery in sylvian region.
Transient Ischaemic Attack (TIA) : Sudden onset of focal neurological deficit over minutes
to hours and complete recovery within 24 hrs.
Vertebrobasilar syndrome : Manifestation by episodes of vertigo, dizziness,

diplopia, dysarthria, dysphagia, in co-ordination of the
gait and limbs and bilateral signs of sensori-motor
deficits.
1.15 ANSWERS TO CHECK YOUR PROGRESS

1) TIA is usually defined as rapid onset of focal neurological deficit over minutes to hours.
Recovery is complete within 24 hours.
2) This includes ischaemic, haemorrhagic and embolic type.
3) Most common risk factors are hypertension, diabetes, smoking and obesity.

1) Middle cerebral syndrome is characterised by contralateral hemiplegia, hemianaesthesia
with or without homonymous hemianopia and aphasia.
2) Angiography (both DSA and MRI) remains the gold standard for assessment of CBF.
1) Antiplatelet drugs are a) Aspirin b) Ticopidine and c) Clopidrogel

2) Various surgical measures used are Endarterectomis, thrombectmies and revascularisation
procedure.
3) Cytoprotective agents available are calcium channel modulators, piracetam,

Glomethiazole. Amongst all, the nimodipine is the widest compound used.
4) Tissue Plaminogen activator (t-PA) is commonly used within 3 hours of ischaemic stroke
onset.
1.16 FURTHER READINGS

Easton, J.D., Hauser, S.L., Martin, J.B. (1998), "Cerebrovascular Diseases" in Fauci, A.S. e t
al., Harrison’s Principles of Internal Medicine, 14th edn., McGraw Hill, Inc. NY pp 2323-
2348.
Taylor, C.L., Selman, W.R. (2000), "Emergensy Management of Ischemic Stroke",
Neurosurgery Clinics of North America, 11(2) 365-375.
Wolf, P.A., D’Agostino, R.B. (1998), "Epidemiology of Stroke", in Barnet, H.J.M., Mohr,
J.P., Stein, B.M., Yatsu, F.M. (eds), Stroke Pathophysiology, Diagnosis and Management,
3rd edn., Churchill Livingstone Philadelphia PA, 3-28.
18
UNIT 2 DEPRESSIVE AND PSYCHIATRIC
DISORDERS
Structure
1.0 Objectives
2.1 Introduction
2.2 Epidemiology and Classification
2.3 Assessment of Depressed Patient
2.3.1 Screening History
2.3.2 Physical Examination
2.3.3 Investigation
2.3.4 Treatment
2.3.5 Prognosis
2.4 Identifying Other Psychiatric Disorders
2.5 Let Us Sum Up
2.6 Key Words
Annexure
2.0 OBJECTIVES
After reading this unit, you should be able to:
l elicit information about clinical history and symptoms;
l diagnose and manage common problems; and
l refer to tertiary care in case it is difficult to treat a case.
2.1 INTRODUCTION
You will realize after reading this unit that depression is a major public health problem. It constitutes
10-30% of the OPD attendance in general hospital. It is an under diagnosed and under treated
disorder. There is a large heterogenecity in both, aetiology, symptomaology and response to treatment
compared to younger people. You thus will realize after reading the unit that diagnosis in time lead
to avoidance of unnecessary laboratory investigations and unrelated drug administration and more
side effects. Elderly not responding to adequate antidepressed therapy, a history of several episodes
of depression and excitement, psychomotor retardation, high suicidal risk needs a psychiatrist opinion.
You must learn to identify elderly who would require this referral.
2.2 EPIDEMIOLOGY AND CLASSIFICATION

Community based studies find symptoms of depression is as high as 15% in people over 65
years of age. Symptoms are more common in women. There is presumptive evidence that
ecological, cultural and social factors have considerable influence on the incidence and clinical
manifestations. Depression is characterized by a sad mood, slow thinking and activity, with
loss of interest and pleasure. It has been classified as mild, moderate or severe. Depression is
also seen in bipolar effective disorders, persistent mood status and recurrent depressive state.
Causes of depression are enumerated in Table 2.1. Increased physical ill health, psychological
factors and an aging brain, all contribute to the high prevalence.
Table 2.1: Causes of Depression
Biological Psychological Social factors
l Genetic factors l Poor self esteem l Reduced social network
l Neurotransmitter loss l Lack of capacity for l Loneliness
Intimacy
l Physical ill health l Physical ill health l Bereavement
(e.g. Neuroendocrine function) (e.g. Cancer)
l Poverty
l Physical ill health like
disability and increased
dependence on others. 19
CNS and Neuro-psychiatric There are certain physical diseases like, anaemia, diabetes mellitus, some nutritional disorders,
Disorders hypothyroidism, patients on antihypertensive drugs, steroids and malignancy which may present
with depressive symptoms.
According to I.C.D. 10, the criteria to diagnose depression include the following:
l Common symptoms of depression

l Depressed mood
l Loss of interest
l Loss of energy or feeling of fatigue
While other symptoms include the following:
1) Reduced concentration
2) Reduced self esteem
3) Guilt feelings
4) Pessimism regarding the future
5) Self harm or suicidal ideas
6) Altered sleep
7) Decreased appetite.
2.3 ASSESSMENT OF DEPRESSED PATIENT

Detection of depression in the elderly has improved in the recent past. A reliable clinical
diagnosis is the first step towards successful management of depression. Besides a good clinical
examination and history the use of some screening instruments seem promising.
2.3.1 Screening History
Some screening for depressed patient procedures are also seem promising. The four item scale
(Table 2.2) is a good starting point for assessing depression and usefully supported by a check-
list of vulnerability factors (Table 2.3).
Table 2.2: Four Item Scale

Items Score Points
1. Are you basically satisfied with your life? No Yes
2. Do you feel your life is empty? Yes No
3. Are you afraid that something bad is going to happen to you? Yes No
4. Do you feel happy most of the time? No Yes
Table 2.3: Vulnerability Factor

Factors
l Does the patient have a history of depression? Yes No
l Is the patient socially isolated? Yes No
l Does the patient suffer from chronic illhealth problem? Yes No
l Has there been a recent bereavement? Yes No
Elderly people scoring more than GDS-4 or more than one on the vulnerability checklist should
be subjected to more detailed assessment. You must refer such cases to psychiatrist for further
evaluation and management.
2.3.2 Physical Examination

The physical examination will exclude medical illness like Parkinson’s disease or occult
carcinoma of the lung, large bowel or pancreas, which is a common comorbidity. Patient with
disability and discomfort as seen in pagets disease react secondary in the form of depression.
Nutrition and hydration, that should also be evaluated in elderly.
20
You should not confused with the normal blues. Everyone has brief down periods and Depressive and Psychiatric Disorders
sometimes depression strikes for perfectly understandable reason, the death of the house, the
retirement from service. However, majority of the people gradually adjust to their loses. The
symptoms and signs of depression usually divided into core groups seen in all types of
depression and others may be seen to a variable degree in the subtypes.
Core Group of signs and symptoms are:
1) Specific alteration in mood (characterized by the feeling of sadness, hopelessness

and pessimism).
2) Marked changes in sleep pattern ( Insomnia)
3) Decreased energy ( Fatigue)
4) Negative self-concept associated with feeling of guilt
5) Loss of interest in social environment due to sad, anxious or empty mood
6) Self neglect
7) Loss of appetite and weight loss, sometimes weight gain and overeating
8) Thoughts of death or suicidal threats.
However, try to elicit other warning signs of depression which are not obvious such as Diurnal
variation, agitation or psychomotor retardation, symptoms like constipation or dryness of mouth,
somatic symptoms and loss of libido.
As you examine your patients clinically, you may realize that recognizing depression in elderly
require special clinical skills and experience. In cases of suspicion of depression, you must
refer the case to a psychiatrist.

1) Define depression in elderly people
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2) Classify the types of depression.
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3) Describe common symptoms of depression.
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2.3.3 Investigations
Investigations are usually none, but may be needed to exclude differential diagnosis. Besides,
the elderly patients are extremely vulnerable to metabolic disturbances secondary to the effects
of a severe depressive illness, such as failure to maintain an adequate fluid intake. Urea and
electrolyte may be altered by dehydration in the elderly depressed. Metabolic upset causes
restlessness, agitation and confusion. Full Blood count and ESR are carried out to rule out
chronic infections. Presence of anemia causes lassitude, B12 and Folate deficiency resulting
from a poor diet can lead to altered cognitive function and confusion. Thyroid function test is
required to rule out hypothyroidism. X-ray chest will rule out of carcinoma, heart failure and
chronic chest illness. Additional investigations include ECG, EEG and computed tomography
of brain (CT Scan).
1) What is the importance of four-item scale?
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CNS and Neuro-psychiatric 2) What are the tests done to rule out medical illness?
Disorders
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2.3.4 Treatment
The elderly respond well to drug therapy, which include monoamine oxidase inhibitor like
phenelzine, Tranylcypromine and Tricyclic antidepressants like imipramine. These drugs are
relatively safe, cheap and highly effective. Dosage and side effects of these drugs is given in
Table 2.4. Antidepressant drugs do not effect the normal person (in a base line state) but
corrects an abnormal condition.
Table 2.4: Tricyclic Antidepressants
Drugs Average Dose Common Side Effects
1) Imipramine 75-250 mg. Constipation, urinary hesitancy
2) Doxipine 75-250 mg. Tachycardia, sedation, weight gain
3) Clomipramine 75-250 mg.
4) Nortriptyline 75-250 mg.
5) Amitriptyline 75-250 mg.
6) Trimipramine 75-250 mg.
The development of SSRI (Selective serotinin reuptase inhibitors) are safe, effective and
well tolerated by the elderly. Drugs in this category are Fluoxetine and Sertraline (Table
2.5). The average duration of depressive episode is 6-12 mouth and medications are to be
continued for this period. When patient fails to respond therapy, then you should refer the
case to specialist.
Table 2.5: Selective Serotinin Reuptase Inhibitors
Drugs Average Dose Common Side Effects
Fluoxetine 20 - 40 mg. Nausea, diarrhea insomnia anorexia
Sertraline 50 - 150 mg. Nausea, tremors, dry mouth diarrea
Fluvoxamine 100 to 200 mg. Nausea, drowsiness, sweating, anorexia
Other Drugs
Venlaxaxine 112.5 to 225 mg. Nausea, drowsiness, dizziness, dry mouth
Bupripion 150 to 300 mg. Agitation, insomnia, anorexia
Lithium
Lithium acts as a mood stabilizer in the prophylaxis of bipolar depression but has also
antidepressant effect. It can be used alone as an antidepressant or as an adjunct to treatment
with other antidepressants. Most patients tolerate lithium well and as long as serum levels are
monitored and kept within the range.
Dose 900-1200 mg. of lithium carbonate (LiCO3 )/day. Therapeutic lithium level ( 0.6-1.2 m/
l) level of more than 2.0 meq/l results in toxicity.
Common toxic effect are neurological and nephrological and endocrinological especially
Hypothyroidism.
Electro Convulsive Therapy
ECT is a useful form of treatment in elderly depressive patients, if patient is highly suicidal
and there are no serious physical illness. The only real absolute contradiction to ECT is the
clinical evidence of raised intracranial pressure.
About 10-30% of depressive patients fail to respond to adequate drug therapy. In these cases
ECT is worth consideration. ECT is specially beneficial when the patient comes with acute
suicidal preoccupation and severe guilt feelings with modern techniques ensuring safe
anesthesia, muscle relevant and adequate oxygenation and by using unilateral electrodes,
22 most of drawbacks of ECT can be eliminated.
Psychotherapy Depressive and Psychiatric Disorders
Psychotherapy has been found to be useful in mild to moderate depression. Cognitive therapy
seems to be particularly appropriate method for older depressed patients. It requires special
skills and training to give cognitive psychotherapy.
Family Therapy
Family problems may contribute to the developments of a depressive illness and the
support of a patient family is most important in ensuring a successful outcome of
treatment.
Psychosocial Intervention
A full understanding of the patients social is as important as the understanding of his

psychological make up. In many situations, a tactful intervention by the therapist may be
therapeutically as effective as psychotherapy. Both psychodynamic and cognitive
behavioural approaches are equally successful with elderly. However in the recent past
cognitive therapy has been found to be particularly appropriate method for treating
depressive patients.
2.3.5 Prognosis
The early and increasing recognition of depression in the elderly by adequate treatment using
a combination of pharmacotherapy and psychosocial intervention leads to good prognosis
while complete recovery without relapse is the goal of the treatment, a brief but treatable
relapse should not herald therapeutic nihilism in the elderly anymore than it does in the young
or middle aged population, with depression physical illhealth is possibly the single biggest
factor, with those suffering from chronic disability or progressive illness being most vulnerable
to relapse.
1) Name three important Tricyclic antidepressants, which are cheap and safe.
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2) Fluoxetine and sertaline belong to which group of drugs.
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3) What is absolute contraindication for ECT in depressed elderly.
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2.4 IDENTIFYING OTHER PSYCHIATRIC

DISORDERS
You have already read about depression and how to assess a depressed patient. Now let us read
about other psychiatric disorders. These include:
l Anxiety Disorder
l Post Traumatic Stress Disorder
l Obsessive Compulsive Disorder
l Hypochondriasis
l Somatisation Disorder
l Paranoid Disorder 23
CNS and Neuro-psychiatric Supportive psychotherapy is the main line of treatment. If significant anxiety and depression
Disorders are present, antianxiety or antidepressant drugs may be used.
Anxiety Disorders
Anxiety is a universal phenomenon observed in everyday life in all age groups and is one of
the commonest clinical manifestation in a general functions clinic.
Definition
Basically anxiety is an emotion of usually unpleasant nature which can be both distressing
and unbearable. Secondly anxiety is a prospective emotion directed towards the future in
contrast to emotions such as regret and guilt which refer to past events. Thirdly it is related to
a feeling of threat which has little or no objective external basis. Fourthly, anxiety leads to
multiple and mixed somatic, endocinological, physiological, biochemical, autonomic and other
associated behaviour changes.
In medicine, anxiety is a technical term with a precise meaning and is different from fear but
has in common with that emotion, it’s unpleasant anticipation of future and its basis is in past
memory and experience. In everyday geriatric practice anxiety disorder is seen commonly
either as generalized anxiety disorder mixed anxiety, phobic anxiety, disorder, obsessive
conpulsive disorders, adjustment disorders and other neurotic disorders.
In generalized anxiety disorder there are symptoms which include restlessness,

shakeness and excessive sweating, palpitation and gastro intestinal symptoms, and
palpitation.
Post Traumatic Stress Disorders
In this condition, there is always a history of recent traumatic experiences like accidents or
intressing traumatic death. The disorder is characterized by experiencing of the trauma through
dreams and working thoughts with marked emotional disturbances.
Obsessive Compulsive Disorder
It is a very distressing condition where obsession are recurrent intrusive thoughts, impulses,
images or feelings which the person tries to resist while compulsion are conscious repetitive
behaviors like hand washing or mental acts e.g., counting numbers that the person feels and
are driven to perform in response to an obsession.
Treatment
Treatment includes use of benzodiazepines like lorazepam, buspirone, psychotherapy

relaxation excersises, in anxiety disorders and behaviour therapy like thought stopping
and response prevention are used with use of antidepressant drug like clomipramine(75-
250 mg/day) or fluoxetine(20-80 mg/dl) in obsessive compulsive disorders. In case of
panic attacks, Alprazolam is effective. For social phobias, propanol has been found to be
useful.
Hypochondriasis
In hypochondriasis, there is persistent preoccupation with possibility of having one or more

serious and progressive physical disorders. Normal sensations or symptoms are often interpreted
by the patient as abnormal or distressing. Hypochondriasis is usually occurs as a symptom in
the course of other psychiatric disorders, such as depression or anxiety disorder. A diagnosis
of hypochondrical disorder is made only if hypochondrical symptoms are occurring in the
absence of other psychiatric disorders.
The most common symptoms are pain and symptoms gastrointestinal and cardiovascular
systems. Symptoms usually run a waxing and wanning course.
Hypochondriasis can be differentiated from somatisation disorder by the emphasis, which the
patient lay on presence of serious physical illness rather on symptoms as happens in somatisation
disorder.
Somatisation Disorder
It is characterized by multiple, recurrent and frequently changing physical symptoms of several

24 years’ duration. There is a long and complicated medical history of contact with both primary
and specialist medical services during which many negative investigations or fruitless Depressive and Psychiatric Disorders
operations may have been carried out.
The history is usually vague, imprecise, inconsistent and disorganized. The patients often
describe their complaints in a dramatic, emotional and exaggerated fashion using vivid and
colorful language. Marked anxiety and depressive symptoms may be present.
Paranoid Disorders
Nearly 10 per cent of the elderly patient seeking psychiatric treatment suffer from paranoid
disorders. Stressful life circumstances, deafness, impaired vision and loneliness are
important contributing factors. There occur persistent persecutory delusions. Response to
treatment is not so good. Antipsychotic drugs like Risperidone are Olanzapine are drugs
of choice.
1) Which of the following symptoms has been reported less commonly in Indian
elderly patients with depression as compared to those in the West?
a) Marked changes in sleep pattern

b) Somatic symptoms
c) Guilt feelings
d) Reduced family interest
e) Retardation
2) Which of the following is not related with etiology of depression?
a) Genetic factors
b) Physical ill health
c) Poverty
d) Neurotransmitter excess
e) Aging brain
3) Which of the following psychotherapies has been found specifically effective in
depression?
a) Psychodynamic therapy
b) Cognitive therapy
c) Behaviour therapy
d) Family therapy
e) Supportive therapy
4) Percentage of patients of depression who fail to respond to adequate drug therapy is :

a) 5-10%
b) 10-30%
c) 20-40%
d) 30-40%
e) 40-50%
5) Doses of Antidepressant required for elderly depressed as compared to those for

adults are:
a) Same
b) Higher
c) Slightly lower
d) Lower to the level of about half 25
CNS and Neuro-psychiatric
Disorders 2.5 LET US SUM UP
Depressive and psychiatric illness are fairly common in 15 % over 65 years of age. Ecological,
cultural and social factors influence the incidence and clinical manifestations. Diagnosis of
depression is based on I.C.D.10 criteria laid down by WHO. Screening test help in
differentiating the normal depression with Psychiatric illness. Investigations are usually none
but help in ruling out underlying medical illnesses. Treatment includes monoamine oxidase
and Tricyclic antidepressant, which are safe and effective. Lithium and ECT are used in 10-
30% cases where drug therapy failed. Early recognition and adequate treatment leads to good
prognosis but relapse may occur, physical ill health is the major risk factor in causing relapses.
Other psychiatric disorders include Anxiety disorders, post traumatic stress disorders, obscession,
compulsive disorders, and paranoid (occurs in 10% seeking Psychiatric treatment). Anti anxiety
or anti depressant drugs along with supportive Psychotherapy is the main line of treatment.
2.6 KEYWORDS
Depression : is characterised by sad mood, slow thinking, with a loss
of interest and pleasure.
Hypochondriosis : is a condition relates to persistent preoccupation with one
or more serious and physical disorders.
Obsessive Compulsive disorder : is a recurrent intrusive thoughts, impulse or feeling
inspite of trying to resist and compulsive disorder relates
to repetitive behaviour such as hard working etc.
Somatisation disorder : relates to multiple, recurrent and frequently changing
physical symptoms of several year duration.

1) There is no standard definition of depression .It is characterized by a sad mood, slow
thinking and activity, loss of interest and pleasure.
2) There are three types of depression. They are classified as mild, moderate and severe
depression.
3) Common symptoms include reduced concentration, reduced self-esteem, guilt feeling,
pessimism regarding the future, self harm or suicidal ideas, decreased appetite and al-
tered sleep.
1) Four items scale is a good screening test for assessing depression. If the score is more
than one on GDS-4 or more than one in the vulnerability check list the patient should be
to Psychiatrist.
2) Tests done to rule out medical illness are complete blood count, X- Ray Chest, thyroid
function test. Additional test includes ECG, EEG and CT Scan.
Check your Progress 3
1) Imipramine, Amitriptyline and Trimepramine are cheap and safe and well tolerated by
elderly.
2) They belong to SSRI group. ( Selective Serotinine reuptase Inhibitors).
3) Increased Intracranial pressure is an absolute contraindication for FCT in depressed elderly.
Check your Progress 4
1) c
2) d
3) b
4) b
26 5) d
Depressive and Psychiatric Disorders
Annexure
Depression
Diagnostic Flow Chart
Patient may present with single or multiple complaints
Physical symptoms
Sleeplessness - Fatiguability
Headache- Multiple somatic complaints.
Psychological Social symptoms

symptoms Loss of interest
sadness
Check for
Poor sleep l Loss of weight

Poor Appetite l Gradual loss of interest
Poor activity l Feels worthless
Feels sad and cries without reason l Loss of energy
l constipation
Schizophrenic Features Present at least 5 Evidence of taking drugs

l Talking to self l Reser-pine
l Laugh to self l Mdopa, oral contraceptives
l Feels controlled by
Suspect depression l Parkinsonism
l Gross memory disturbance
External forces
l Thought interference
l Can read other thoughts
l Hears varies Treat accordingly
refer if necessary
Absent Depression Absent

Confirmed
Check for Absent Treat with Reassess after Good Continue

Suicidal attempts Antidepressant 3-4 weeks Treatment
or
Suicidal ideas
Present Refer Not satisfied
27
UNIT 3 COGNITIVE IMPAIRMENT AND
DEMENTIA
Structure
3.0 Objectives
3.1 Introduction
3.2 Pathophysiology of the Brain in Normal Aging and Dementia
3.3 Types of Dementia
3.4 Dementia of Alzheimer’s Type
3.4.1 Epidemiology
3.4.2 Early Detection and Screening
3.4.3 Clinical Picture
3.4.4 Differential Diagnosis
3.4.5 Treatment Guidelines
3.5 Organic Mental Disorders Involving Functions other than Cognitive Functions
3.6 Delirium
3.7 Organic Amnesic Disorder
3.8 Let Us Sum Up
3.9 Key Words
3.0 OBJECTIVES
After reading this unit, you should be able to:
l evaluate a case of cognitive impairment and dementia including Alzheimer's
disease;
l diagnose and differentiate it from related disorders;
l provide relevant treatment plan; and
l establish linkage with other disciplines, as commorbidity in old age is quite

common.
3.1 INTRODUCTION
Dementia is the most common mental disorder due to neurologic disease and affects 1-2% of
60 year olds and becomes increasingly common among over age of 80. The dementing
disorders are a group of brain diseases that leads most often gradually to the loss of mental
functions including memory and other intellectual and functional abilities. More than 70
different conditions can cause dementia, where victims suffer impairment of memory and
other intellectual abilities that leave them confused, disoriented and incapable of
communicating normally. They show personality changes, various emotional reactions to
their illness and behavioural symptoms such as tendency to wander overtime. They experience
increasingly difficult in carrying out simple activities of daily life, may loose bladder and
bowel control and ultimately become totally dependent on others to provide for their personal
need and safety.
The cognitive dysfunction may be primary as in diseases, injuries or insults that affect the
brain directly. It may be secondary as in systemic diseases and disorders that affect the brain
28 one of the multiple organs or system of the body involved.
Cognitive Impairment and Dementia
3.2 PATHOPHYSIOLOGY OF THE BRAIN IN including Alzheimer’s Disease
NORMAL AGING AND DEMENTIA
In normal aging, there occurs reduction in the speed of mental processes and difficulty in
learning new tasks. Recall is also affected. But such changes do not interfere with the person’s
personal, social or occupational life, as happens in dementia.
Recent studies suggest that cognitive decline is not a normal consequence of aging. It has been
observed on longitudinal study that subjects who eventually develop dementia of Alzheimer’s
type show quite normal cognitive performance on the test battery over a period of years but
then show a sharp downturn in performance. Secondly in cognitive functions, memory is the
key to the self, providing us with our sense of who we are, when that has gone, where is the self
and the person’s personality is totally lost.
The pathophysiology of dementia’s is complex and as there are multiple causes, which include
the social, biological and psychological factors besides neurochemical and viral factors have
been attributed. Basically any brain pathology (which is insidious in nature) can cause dementia.
Alzheimer’s disease is the commonest cause of dementia. Here two important risks factors
have been attributed, first the increasing age and second risk factor is genetic predisposition
specially defect in chromosome 14, 19 and 25. Besides other factors have been implicated
like aluminium poisoning and viral causes.
3.3 TYPES OF DEMENTIA

Dementia has been classified into 3 groups as per DSM IV classification. These groups are as
a) Dementia, associated with primary dementing illness, trauma, infections, intoxication etc.,
b) amnestic disorder and c) unspecified (Table 3.1).
Table 3.1: Types of Dementia
I. Primary Dementia
Dementia of the Alzheimer’s Type, With Early Onset
Dementia of the Alzheimer’s Type, With Late Onset
Vascular Dementia
Dementia Due to HIV Disease
Dementia Due to Head Trauma
Dementia Due to Parkinson’s Disease
Dementia Due to Huntington’s Disease
Dementia Due to Pick’s Disease
Dementia Due to Creutzfeldt-Jakob Disease
Dementia Due to the General Medical Conditions
II. Amnestic Disorders

Amnestic Disorder Due to the General Medical Conditions
Substance-Induced Persisting Amnestic Disorder
III. Unspecified Dementia’s
Although the spectrum of psychopathological manifestations of dementia described above are broad.
However they can be granted into two main categories.
a. Dementia’s of Alzheimer’s Type

b. Dementia’s due to other causes
1) Define Dementia.
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29
CNS and Neuro-psychiatric 2) What are types of Dementia?
Disorders
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3.4 DEMENTIA OF ALZHEIMER’S TYPE

Definition: Alzeimers disease is primary degenerative cerebral disease of unknown etiology,
with characteristic neuropathological and neurochemical features. The disease is usually
insidious in onset to develop, slowly but steadily over a period of years. This period can be
short or considerably long. The onset can be in any age group but the incidence is higher in
later life. In cases with early onset of disease there is likelihood of a family history of similar
dementia, a more rapid course and prominence of features of parietal or temporal lobe damage,
including aphasia or dysprexia. In cases with a late onset, the course tends to be slower and
cognitive impairment is more marked.
3.4.1 Epidemiology
It is more common with increasing age. It is very rare in the age group of 40-45, although it can
occur, increases in the age group 60-65, and in the age group over 80 it is very common. Some
researchers believe that almost 50% of people over 80 will get Alzheimer’s disease. Only two
risk factors have been discovered, first is increasing age and the second is genetic predisposition.
Genetic transmission has been reported 10-30% of cases. Three genetic defects have been
identified, one on chromosome 14, 19 and on 21. Many other factors have been implicated
such as viral infection, aluminium poisoning, elderly mother at birth of the patient, family
history of other genetic defects. None have been found to increase the risk of Alzheimer’s
disease.
3.4.2 Early Detection and Screening
As the onset of the disease is insidious and slow and progressive, the early detection of the
disease is important. Screening has been defined as the presumptive identification of
unrecognized disease or defect by the application of tests, examinations or other procedures,
which can be applied rapidly.
A screening test sorts out apparently well persons, who probably have a disease from those
who probably do not. A screening test is not intended to be diagnostic.
Hence the first step is to administer a simple test, which can measure cognitive impairment by
a Mental Status Questionnaire and the short portable Mental Status Questionnaire. The second
stage case identification includes, diagnostic procedures, which include a number of
standardized psychogeriatric interviews which are based on clinical diagnostic concepts but
also make use of scores derived from rating scales.
The lack of detailed diagnostic criteria is specially significant in early case identification,
since without a clear definition there can be no reliable case identification.
The third stage of screening include assessment of associated impairments and disabilities. A
comprehensive screening and diagnosis cannot be confined to psychiatric diagnosis and
treatment alone. For this reason, a multidimensional concept is indicated in assessment as
well as in care programme. The techniques of multi level assessment developed in recent
years appear to provide the most suitable working tools for screening and diagnosis.
3.4.3 Clinical Picture
Onset is insidious, usually after 65, though sporadic cases can occur earlier. The disease runs
a progressive course. The initial symptoms are impairment of memory and subtle personality
changes, usually reported by the family members, the patient often being unaware of this
symptoms. Mild anxiety and depressive symptoms are frequently present in the early stages.
In Alzheimers disease there is progressively increasing impairment of memory and other

intellectual abilities. Although the problems may initially be manifested in such ways as
forgetfulness, poor judgement or difficulty making calculations and handling money, the
cognitive losses ultimately leave the person confused, disoriented and incapable of
30
communicating Normally Commonly personality changes are there, which may range from Cognitive Impairment and Dementia
apathy and social withdrawal to quarrelsomeness and agitation and frequently display various including Alzheimer’s Disease
emotional reactions to their illness, such as anxiety, depression or suspiciousness, other
symptoms, such as disturbed sleep, hallucinations and delusional ideas or tendency to wander
aimlessly are also common.
Overtime even customary daily activities are lost. Eventually they may lose elementary physical
abilities such as bladder and bowel control and become totally dependent on others to provide
for their personal needs and safety.
Urinary and faecal incontinence may occur at later stages. Seizures, coma and death are the
final outcome.
Suspiciousness, obsessiveness, irritability and outbursts of anger may also appear in the early
stages of illness. These are followed by disturbances in orientation and judgement, and may
lead to purposeless wandering. The patient may be found far away from home in a dazed
condition. Neurological defects, such as gait disturbances, aphasia, apraxia and agnosia may
occur.
The peculiar tragedy of Alzheimer’s disease and other related dementia’s is that they dissolve
the mind and steal the humanity of the victim, leaving a body from which the person has
largely been removed. Simultaneously dementia’s devastate lives of spouses and other family
members, who must endure their deterioration of their loved ones and the loss of the person
and relationship that is implied. Caregivers face the agony of seeing their loved ones minds
and personalities disappear from bodies that may frequently remain otherwise healthy and
shoulder heaving physical, social and emotional burdens over a prolonged period of time. The
effects on the afflicted families are personally profound and financially devastating.
1) Define Alzheimer’s disease.

..........................................................................................................................................
..........................................................................................................................................
..........................................................................................................................................
2) What are the steps in arriving diagnosis of Alzheimer’s disease?

..........................................................................................................................................
..........................................................................................................................................
..........................................................................................................................................
3) What are risk factors in development of Alzheimer’s disease?

..........................................................................................................................................
..........................................................................................................................................
..........................................................................................................................................
4) Enumerate clinical features of Alzheimer’s disease.

..........................................................................................................................................
..........................................................................................................................................
..........................................................................................................................................
3.4.4 Differential Diagnosis
Diagnosis in an established case of dementia is not difficult, but it requires considerable skill
to diagnose it in early stages. It can be easily confused with pseudodementia (depression
mimicking dementia) in the initial stages, and also needs to be differentiated from normal
ageing. Third important differential diagnosis is delirium. Let us see three different diagnosis
one by one.
a) Depressive Pseudodementia
In it, depression presents like dementia. As already mentioned, depressive features may
be present in the initial stages of dementia. Important differentiating features are given
in Table 3.2.
31
CNS and Neuro-psychiatric Table 3.2: Differentiation between Dementia and pseudodementia
Disorders
Dementia Pseudodementia
I. Onset and Course
l Onset can be dated with some precision l Onset can be dated only within broad limits
l Intellectual deficits antedate depression l Depressive symptoms antedate cognitive
dysfunction
l Slow progression of symptoms l Rapid progression of symptoms after onset.
II. Presentation of Symptoms
l Patient tries to conceal his deficits. l Patient complains much cognitive loss,
emphasizes his disability and highlights
failures.
III. Past History
l No past history of depression may be present l Past history of depression may be present.
IV. Appearance and Behaviour
l Sloppy, neglected and apathetic; l Sad, worried look
emotional liability present.
V. Response to Questions
l Evasive, angry and may be sarcastic l Slow, “I don’t know” response Present
VI. Intellectual Performance
l Global impairment l Confined to memory impairment
b) Delirium
Delirium is another common ailment in elderly and needs to be differentiated. Delirium is an acute
organic mental disorder which can usually be distinguished from dementia by presence of
rapid onset, brief duration, fluctuation of cognitive impairment during the course of the day,
marked disturbance in sleep-wake cycle, impaired orientation, clouding of consciousness and
visual hallucinations. Important differentiating features from dementia are shown in Table
3.3.
Table 3.3: Differentiation between Dementia and Delirium
Dementia Delirium
I. Onset
Insidious Acute
II. Duration
<1 month Usually > 1month
III. Orientation
May be intact Impaired
IV. Thinking
Impoverished Disorganised
V. Attention
Intact Poor
VI. Awareness and alertness
(Consciousness)
Intact Fluctuating
VII. Perception
Hallucination not present Hallucinations present
VIII. Sleep-wakefulness Cycle
Always disrupted Usually normal
32
3.4.5 Treatment Guidelines Cognitive Impairment and Dementia
including Alzheimer’s Disease
There is no specific drug treatment. However treatment guidelines include the following
principles:
First step in management is to find out the cause, if any. A complete medical history and
thorough physical examination should be carried out. CT scan is helpful in confirming the
diagnosis and also in finding the cause in some cases such as space occupying lesions. Other
relevant investigations should be done, for example, thyroid function tests, if hypothyroidism
is suspected.
If a treatable cause is found, specific treatment is started, e.g., thyroid replacement therapy for
hypothyroidism, and neurosurgical treatment for subdural haematoma and normal pressure
hydrocephalus.
General treatment consists of good nutritious diet, nursing care, family support and attention
to visual and auditory deficits, if any. If any other physical ailments, such as urinary tract
problems, cardiac or pulmonary disorders are present, specific treatment should be given. It is
essential to counsel the family regarding nature of illness for its effective management. Family
has a very important role to play in management of dementia. Considering the breaking of
joint families in India and increase in the elderly living alone due to their children moving
away, institutions for the elderly such as old age homes, day care centers, etc., are needed
especially for the elderly ill, where they can be taken care of.
Family members need the opportunity to receive a clear diagnosis and explanation of the
problem and assistance in assessing their changing care need as the disease progresses and the
care demand on the family increase. Care begins in the home and in the community. The
challenge is in determining when homecare becomes the option of choice or when nursing
home care is necessary. Both forms of care are essential and mutually supportive components
of long-term care, neither can substitute for the other.
Medical care involves symptomatic management of treating both psychological and physical
symptoms and treatment of medical comorbidity when present. Antianxiety and antidepressant
drugs if anxiety and depressive symptoms are present. Risperidone or thioridazine are effective
in controlling agitation, if present. The use of vitamins like B and E have been found useful in
some cases as these vitamins help in neutralizing toxic elements in the body. Tacrine a
cholinesterase inhibitor has been found to produce significant improvement in 20 to 25 % of
patients with Alzheimers disease. Similarly RIVASTIGMINE can delay the progression of
Alzheimer disease.
Balanced diet and proper fluid management is important part of treatment. Treatment of
behavioural manifestations of Alzheimer’s is helpful. As a part of care, personal hygiene and
toilet habits form an integral part of management.
1) Which of the following is the specific drug for Alzheimer’s disease?
a) Piracetam
b) Thioridazine
c) Risperidone
d) Rivastigmine
e) Venlafaxine
2) Which of the following is not a feature of dementia?
a) Impoverished thinking
b) Insidious onset
c) Cognitive impairment
d) Impaired orientation
e) Anxiety and depressive symptoms
33
Disorders 3.5 ORGANIC MENTAL DISORDERS INVOLVING
MENTAL FUNCTIONS OTHER THAN COGNITIVE
FUNCTIONS
In these disorders, there is disturbance in thinking, perception, emotions or personality, but
consciousness and cognitive functions are not affected. In clinical picture, these resemble the
corresponding functional psychiatric disorders but there is:
1) Evidence of cerebral disease, damage or dysfunction, or of physical disease, known to
be associated with the respective syndrome.
2) A temporal relationship (weeks or few months) between the development of the underlying
disease and the onset of mental syndrome.
3) Recovery from the mental disorder occurs following removal or improvement of the
underlying presumed cause.
4) Absence of evidence to suggest an alternative cause of the mental syndrome (such as a
strong family history or precipitating stress). Various disorders included in this group
are:
Organic Hallucinosis
It is characterized by presence of persistent or recurrent hallucinations, usually visual or auditory,

occurring in clear consciousness.
Common causes are psychoactive drug abuse (e.g., alcohol, LSD, cannabis products, etc.) and
tumors of occipital or temporal region of brain.
Organic Delusional Disorder
It presents as persistent or recurrent delusions, which may be accompanied by hallucinations.

Important causes are drugs like amphetamines, cannabis products, alcohol, etc., and lesions of
temporal lobe.
Organic Mood Disorder
The clinical picture resembles that of mania or depression. Post infective depression occurring
after bacterial or viral infections comes under this category. Drugs, endocrine disorders, brain
tumors, encephalitis and meningitis are important causes of organic mood disorder.
Antihypertensives and hormonal contraceptives are common causes of organic depression.
Organic Personality Change or Disorder
It is characterized by a marked change in personality style and traits from previous level of
functioning, which may occur following head injury, cerebral tumors or brain insult due to any
other cause.
Organic Anxiety Disorder
Organic anxiety disorder is characterized by prominent, recurrent panic attacks or by generalized

anxiety attributable to some clearly defined organic factor.
Central nervous stimulants, such as amphetamines, caffeine, cocaine, adrenaline and drugs
like atropine can cause this disorder. Hyperthyroidism, hypothyroidism, vitamin B 12 deficiency
and phaeochromocytoma are other important causes.
3.6 DELIRIUM
Delirium is an organic mental disorder of acute onset characterized by concurrent disturbances
of consciousness, attention, perception, thinking, memory, psychomotor behavior, emotion
and sleep-wake cycle. It is usually a transient condition and has a fluctuating course. Most
cases recover within four weeks. Delirium is common condition in medical and surgical
inpatients. About 10 percent of all hospital inpatients manifest some degree of delirium. The
figure rises to 30 per cent in-patients in surgical and coronary intensive care units, specially in
elderly patients.
34
Aetiology Cognitive Impairment and Dementia
Delirium is due to generalized disturbance of brain metabolism. There are a large number of
causes. Important causes include encephalitis, meningitis, systemic infections (e.g., typhoid,
pneumonia, malaria, etc.), head injury, drugs (e.g., sedatives, anticholinergics, steroids, opiates,
etc.), withdrawal from alcohol or other psychoactive substances, endocrinal disturbances,
metabolic disturbances (e.g., hypoxia, hypercapnia, renal or hepatic dysfunction, fluid and
electrolyte disturbances), and epilepsy.
Clinical Picture
Delirium can occur at any age but is more common in old age. Risk to develop delirium is high
in the elderly (age above 60), and in persons with history of head injury and alcohol or drug
abuse.
Onset is very rapid. Patient may have been in perfect good health just before the onset of the
illness. The presenting symptoms include poor attention and concentration. The patient is
very easily distracted, so much so that he is unable to hold a sustained and meaningful
conversation. The sensorium may wax and wane; one moment he is conscious and alert, the
next moment he is drowsy. Disorientation, especially for time and place, and confusion are
present. There is impairment of immediate recall and recent memory but remote memory is
intact. Visual hallucinations are often present. Mood is fluctuating and ranges from acute fear
and panic to depression or even euphoria. Sleep is disturbed. In severe cases there may be
complete insomnia or reversal of sleep-wake cycle. Patient may talk irrelevantly. At times, he
is hyperactive, even excited to the point of exhaustion, or may remain dull and lethargic,
hardly taking any interest in his surroundings.
Course
Delirium is reversible, if underlying cause is diagnosed and treated. Many untreated cases
also recover spontaneously. In some cases, delerium may progress to dementia and is sometimes
followed by depression or post traumatic stress disorder. Ten to thirty per cent of patients may
progress on to coma or death.
Management
Management is to identify the cause and treat it. General nursing care, good nutrition and
maintenance of fluid and electrolyte balance are essential components of treatment.
The patient should be kept in a dimly lit room during night time. Frequent visiting by the staff
and family, and explanations and reassurances from the staff help in improving orientation.
Haloperidol 2-10 mg I/M stat and SOS is effective in controlling agitation. Oral haloperidol in
dosage of 5-20 mg/day in divided doses should be given. For insomnia, benzodiazepin such as
diazepam 5-10 mg HS given orally can be prescribed. Once the symptoms are over, treatment
may be given for another week, and then gradually stopped.
1) What are clinical features of Delirium?.

..........................................................................................................................................
..........................................................................................................................................
..........................................................................................................................................
2) How will you differentiate Delirium from Dementia?

..........................................................................................................................................
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3.7 ORGANIC AMNESIC DISORDER

In organic amnesic disorder, there occurs impairment in recent memory (impaired learning of
new material), and anterograde and retrograde amnesia in the presence of clear consciousness
and no impairment of other cognitive functions. Immediate recall is not affected.
35
CNS and Neuro-psychiatric There is history of objective evidence of brain insult involving hippocampal region. Common
Disorders causes include thiamine deficiency associated with alcohol dependence, brain trauma, cerebral
hypoxia and cerebral tumors involving hippocampal region.
Treatment
Treatment is aimed at the cause. If thiamine deficiency is the cause, thiamine supplementation
in doses of 100 mg/day is indicated.
3.8 LET US SUM UP

The dementia’s are a group of brain diseases that lead most often gradually to the loss of
mental functions including memory and other intellectual and functional abilities. More than
70 different conditions can cause dementia’s. The term does not imply a specific cause or
pathologic process. Common symptoms are disturbance in memory attention and orientation
changes in personality and in daily living.
Alzheimer’s type is the commonest form of dementia. We do not know the cause. It is insidious
and slow growing disease. It has no specific treatment nor any specific drug so far. It not only
afflicts the victims but devastates the whole family.
3.9 KEY WORDS

Alzheimer’s Disease : Primary degenerative cerebral disease of unknown aeitiology with
characteristics neuopathological neurochemical features.
Dementia : Group of brain disease results in loss of mental function and functional
abilties.
Pseudodementia : Depression mimicking dementia.

1) Dementia is defined as group of brain diseases, characterized by loss of mental function
including memory, intellectual and functional abilities.
2) Three types of Dementia include Dementia associated with primary disease of brain,
infections, degenerative condition and endocrine diseases, Amnestic Disorder, and
unspecified dementia.
1) Alzheimer’s disease is defined as primary degenerative cerebral disease of unknown

aetiology with characteristic neeuropathological and neuro chemical features.
2) There are three steps in arriving at diagnosis.
Ist Step : Documentation of loss of cognition.
IInd Step : Documentation that the loss of cognition is disabling the patient in
Activity of daily living.
IIIrd Step : Exclude other causes of loss of cognition.
3) There are two established risk factors
1) Increasing age
2) Genetic Defects
4) Clinical features includes 1) Impairment of memory, 2) Subtle personality changes,
3) Mild anxiety and depressive symptomns present in early stages.
1) Rivastigmine
2) Impaired orientation
36
Check Your Progress 4 Cognitive Impairment and Dementia
1) Clinical freatures include 1) concurrent disturbances of consciousness, attention,
perception, thinking, memory, psychomotor behaviour, emotion and sleep cycle, 2) usually
transient condition and has fluctuating course.
2) In delirium the onset is acute, duration usually >1 month, orientation is impaired, thinking
is disorganised and attention is poor. Awareness and alertness is fluctuating.
37
UNIT 4 NEURODEGENERATIVE
DISORDERS
Structure
4.0 Objectives
4.1 Introduction
4.2 Movement Disorders in Elderly
4.2.1 Parkinson’s Disease
4.2.2 Huntington’s Disease
4.2.3 Essential Tremor
4.2.4 Dystonias
4.3 Neuropathies in Elderly

4.3.1 Causes of Peripheral Neuropathy in Elderly
4.3.2 Investigations of Peripheral Neuropathy
4.3.3 Treatment
4.4 Disorders of Muscles in Elderly

4.4.1 Causes of Myopathies
4.4.3 Treatment
4.5 Disorders of Neuromuscular Junction in Elderly

4.5.1 Myasthenia Gravis
4.5.2 Lambert-Eaton Myasthenic Syndrome (LEMS)
4.6 Let Us Sum Up

4.7 Key Words
4.8 Answer to Check Your Progress
4.0 OBJECTIVES
After completing this unit, you will be able to:
l identify the cardinal features of Parkinson’s disease and differentiate Parkinson’s disease
from other parkinsonism;
l evaluate an elderly person with Parkinson’s disease and plan its treatment schedule;
l identify other movement disorders in elderly and refer to specialist;
l diagnose and assess and evaluate neuropathies in elderly; and
l diagnose and evaluate neuro-muscular problems in elderly.
4.1 INTRODUCTION
Common neuropsychiatric disorders in the elderly are stroke, dementia, depression, Parkinson’s
disease and neuropathies etc. Vascular disorders, depression and dementia have already been
covered in the preceding chapters. We shall now proceed to discuss disorders of movements,
neuropathies and neuromuscular junctions in the elderly.
Neurological disorders in elderly are difficult to identify especially if they have insidious
onset and are slowly progressive, because elderly being weak and frail attribute incapacity of
disease to aging. Hence , special care must be taken to examine the elderly in detail to identify
these disorders.
In this unit we will learn about Parkinson’s disease, the commonest movement disorder in the
38
elderly, some other disorders which resemble Parkinson’s disease superficially which are Neurodegenerative Disorders
also known as parkinsonism. In addition, we will also learn about some not so common
movement disorders, neuropathies and neuromuscular disorders in the elderly.
4.2 MOVEMENT DISORDERS IN ELDERLY

As you know movement disorders are a group of neurological diseases in which there is
either occurrence of excessive abnormal movements or paucity and/ or slowness of normal
movements in the absence of paralysis or weakness. These are therefore known as hyperkinetic
and hypo-kinetic movement disorders respectively. The prototype of hypokinetic disorders
is Parkinson’s disease. Hyperkinetic movement disorders consist of tremor, chorea, dystonia,
ballism, tics and myoclonus. Of the hyperkinetic disorders, common ones seen in elderly are
essential tremor (ET) Huntington’s disease (Huntingtons’ chorea) and focal dystonias. The
disease is caused by degeneration of pigmented neurons in substantia nigra resulting in
diminished levels of dopamina in the brain.
4.2.1 Parkinson’s Disease
Parkinson’s disease was first described by James Parkinson in 1817. This is a disease of
elderly and its prevalence increases from 1% in people over the age of 65 years to 5% in
people over the age of 80 years. It occurs in all parts of the world and affects men and women
equally. The disease has insidious onset and is slowly progressive leading to severe morbidity
in advanced stage. The disease is caused by degeneration of pigmented neurons in substantia
nigra resulting in diminished levels of dopamine in the brain.
Etiology
Though the etiology of the disease is not well known, there are some hypothesis as given
below:
1) Accelerated aging
2) Environmental toxins
3) Genetic factors
Clinical Features
The cardinal clinical features are:

l Rest tremor at 4-6 Hz
l Bradykinesia or slowness of movements
l Rigidity, typically cogwheel type
l Postural instability which comes later on in the course of disease
Characteristically the disease starts asymmetrically with tremor in one hand which resembles
“pill rolling” movements. This then spreads to involve leg on the same side followed by
involvement of the opposite side.
Bradykinesia is characterized by slowness and paucity of all movements. It is manifested

clinically as following :
1) “Masked facies” due to in-frequent blinking and infrequent change of facial expressions
2) Monotonous, soft voice
3) Drooping of saliva due to infrequent swallowing movements
4) Lack of postural adjustments
5) Absence of arm swing while walking
6) Dragging of feet while walking
7) Shuffling gait and festination
Rigidity is characterized by increased tone of all muscles. It may have cogwheel characteristics
due to presence of tremors. This can be appreciated when the patients limbs are moved passively.
Rigidity results in the following :
1) Stooped posture 39
CNS and Neuro-psychiatric 2) Aches and pains in body
Disorders
3) Stiffness of the body
Postural instability comes on later in the disease and results in frequent falls.
Other features like difficulty in walking, retropulsion in which there is tendency to run from
walking to pace, retropulsion with tendency fall backwards and lateropulsion with tendency
to fall side ways is also seen. Dementia, hallucinations and autonomic symptoms like postural
hypotension, urinary incontinence and constipation may occur in advances disease. Eventually,
the patient becomes rigid, helpless, incapacitated needing help for all self care activities.
Diagnosis
The diagnosis of Parkinson’s disease is made on clinical grounds. There are no confirmatory
tests. Insidious onset, slowly progressive disorder asymmetrical symptoms of tremor , rigidity
and bradykinesia help in arriving at the diagnosis.Other conditions which cause parkinsonism
should be excluded by thorough history and examination.
Differential Diagnosis
Parkinson’s disease should be differentiated from a number of disorders which resemble
Parkinson’s disease and are collectively called parkinsonism. These disorders also occur in
the elderly people. They are as follows:
1) Drug induced parkinsonism is caused by drugs such as reserpine and phenothiazines
due to their action of blockade of dopaminergic transmission. This is characterized by
symmetrical symptoms.
2) Post encephalitic parkinsonism was seen after Von economos’ encephalitis. This disorder
is also symmetrical and presence of tics and oculogyric crisis are common in this disorder.
3) Certain known causes like repeated head injury (in boxers), cerebral hypoxia, repeated
cerebro vascular accidents and poisoning by manganese and carbon mono-oxide can
also result in symmetrical parkinsonism.
4) Syndrome of Parkinsonism
l Progressive supranuclear palsy (Steele-Richardson-Olszewski Syndrome) is
characterized by parkinsonian features along with rigidity of neck, walking difficulty
and frequent falls early in the course of disease with disturbance of ocular motility.
l Multiple system atrophy (MSA) is characterized by symmetrical parkinsonian
features along with pyramidal, cerebellar, autonomic and mental disturbance in
various combinations.
Management
Prudent management of a patient of Parkinson’s disease requires: (a) patient education, (b)
assessment of deficit, (c) assessment of patients requirement, (d) physiotherapy, (e) positive
attitude, (f) drugs and (g) surgery
a) Patient education : Patient is told about the nature of illness, need for regular treatment
and what to expect in future.
b) Assessment of deficit is done to prescribe the correct treatment
c) Assessment of patients requirement : The treatment is different if the patient is the sole
bread earner, if his job requires high degree of physical activity, if the patient is in show
business or if the patient is retired.
d) Physiotherapy is helpful in reducing rigidity and aches and pains and keeps the patient
agile.
e) Positive attitude help the patient cope up with his disabilities.

f) Drugs : Following drugs are used in the treatment of Parkinson’s disease.
1) Levodopa: Levodopa is the gold standard in the treatment of Parkinson’s disease.
It restores the dopamine level in the brain. It is usually combined with peripheral
dopa-decarboxylase inhibitor to prevent conversion of levodopa to dopamine
outside the brain, thus reducing the dose of levodopa and the side effects of levodopa.
The combination is available in the ratio of 4:1 of levodopa and carbidopa
40 (100+25mg) or 10:1 ratio(100+10mg, 250+25mg). The dose and timing of
medication is adjusted according to the needs of the individual patient. Neurodegenerative Disorders
2) Anticholinergic drugs are helpful in controlling tremors. Care should be taken

while prescribing anticholinergic drugs because they can cause confusion,
hallucinations, narrow angle glaucoma and urinary retention. Usual dose is 2-4
mg/day.
3) Amantadine has mild antiparkinsonian action and acts by releasing dopamine from
presynaptic terminals. Usual dose is 100-300 mg/day.It can cause ankle edema in
small number of patients.
4) Dopamine agonists: A large number of drugs act directly on dopamine receptors.

There are two major types of dopamine agonists: ergot derivatives e.g. bromocriptine,
cabergoline, lisuride and non-ergot derivatives such as pramipexole and ropinirole.
Dopamine agonists can be started alone in early Parkinson’s disease or used in
combination with levodopa. Dopamine agonists should be started in low dose and
the dose should slowly built up. It is important to start dopamine agonists in young
PD patients because the side effects of long term use of levodopa can thus be avoided.
5) Monoamine oxidase- B inhibitors are a group of drugs which prevent catabolism

and reuptake of dopamine. Therefore, they are useful in the treatment of Parkinson’s
disease (eg. selegiline).
6) Catechol O-methyl transferase inhibitors: These also act by preventing catabolism

of dopamine (e.g. tolcapone, entacapone).
g) Surgery : Though modern treatment is very successful, patients with advanced Parkinson’s
disease may have complications of advanced disease and long term levodopa therapy
such as motor fluctuations, hallucinations and psychosis. Neurosurgical treatment can be
undertaken under these circumstances. Essentially, three types of surgeries are done:
ablative type in which a discrete lesion is made in any of specified areas of brain. The
other types of surgery are deep brain stimulation in which thalamus or globus pallidus or
sub thalamic nucleus is stimulated. The third type of surgery is the transplantation
surgery in which adrenal medullary tissue or fetal mesenchymal tissue is transplanted in
the brain of PD patient.
Indications of surgery in Parkinson’s disease are:
1) Advanced Parkinson’s disease

2) Severe dyskinesias, hallucinations and motor fluctuations.
3) Absence of dementia, life threatening concurrent illness, and postural disturbance.
1) Define Hypokinetic disorder and name one prototype.

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2) Describe cardinal features of Parkinson’s disease.

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3) Name drugs used in treatment of Parkinson’s disease.

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4) Which are drugs used in controlling tremors?

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CNS and Neuro-psychiatric 5) What are indications of surgery?
Disorders
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4.2.2 Huntington’s Disease (Huntington’s Chorea)
After learning of Hypokinetic disorder, now we will discuss Hyperkinetic movement disorder.
Huntington’s disease was described by George Huntington in 1872 in New York, USA. The
disease is caused by a genetic disorder which results in expansion of trinucloetide CAG on
chromosome 9. This results in production of an abnormal protein called Huntingtin. The disease
has an autosomal dominant mode of inheritance and therefore 50% of children of an affected
parent are at risk of developing this disease.
Clinical Features
Both sexes are equally affected. The usual age of onset is 5th decade, but can affect older and
younger people. A phenomenon of anticipation is seen in families of Huntington’s disease.
This means that if a child inherits the disease from father, the age of onset in the child is much
younger. This is due to larger expansion of CAG repeats in the offspring. Such a phenomenon
is not seen when the disease is inherited from mother. Main clinical features consist of chorea
which may manifest as frequent grimacing, irregular, arrythmic bizarre movements of limbs,
irregular respiration and abnormal gait. Associated with chorea there is some rigidity and
slowness of activity. Dementia is one of the main features of clinical picture and is slowly
progressive. Most patients also have depression. The disease runs a slowly progressive course
and death usually occurs due to inter-current infection and rarely by suicide.
Differential Diagnosis
A large number of disorders resemble Huntington’s disease superficially. They are:
1) Sydenhams’ chorea: this occurs in children and young adults and is associated with
rheumatic fever and rheumatic heart disease.
2) Overdose of levodopa in Parkinson’s disesae can resemble Huntington’s disease, but

careful history will help in establishing time sequence of symptoms and arrive at correct
diagnosis.
3) Drug induced chorea: Drugs such as phenothiazines, lithium, rarely carbamazepine

and phenytoin can result in choreiform movements and may persist for some months
even after the incriminating drugs are discontinued.
4) Rarely, elderly people can have chorea due to infarction of discrete areas in brain like
caudate nucleus. Chorea due to infarction affects one half of the body and is not
generalized.
Investigations
1) Clinical history and examination are most important in the diagnosis
2) CT scan: which will show atrophy of caudate nucleus and dilatation of frontal horn of
lateral ventricles.
3) Genetic tests: This is now available and can show CAG expansion on chromosome 9.
Treatment
l No treatment is available which can halt the progress of the disease
l Drugs like butyrophenones (haloperidol) and phenothiazines can suppress chorea.

l For depression tricyclic antidepressants can be used.

1) Huntingtons disease belong to which group of disorder?
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42 ..........................................................................................................................................
2) What are cardinal features of this disease? Neurodegenerative Disorders
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3) Which are the investigations needed to confirm the diagnosis?

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4) Which are the drugs used in suppressing the chorea?
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4.2.3 Essential Tremor
Essential tremor is a common hereditary disorder. It may occur at any age but is also seen in
elderly and is then called senile tremors.
Clinical Features
The disorder runs in families. The tremor is typically more marked in holding posture like
holding a cup of tea etc. Hence it is called postural tremor. It has very fast frequency (8-12 Hz).
It is suppressed by alcohol consumption. Neurological examination does not show any other
abnormalities and all investigations are also normal.
It may be necessary to differentiate it from thyrotoxic tremor or tremors due to drugs such as
lithium, sodium valproate and adrenergic agents like salbutamol etc.
Treatment
l Tremors respond very well to adrenergic – blocking agents (propranalol) 20-40 mg
three times a day.
l Primidone in small doses (i.e. 50mg) at times is also effective in suppressing tremors.
4.2.4 Dystonias
Dystonias are abnormal involuntary contractions of muscles resulting in twisting and torsion
of the affected body part. They may be associated with tremors and sometimes with myoclonus.
Though generalized dystonias affecting the whole body is common in children, focal dystonias
involving a localized part of the body is common in older people.
Focal dystonias can involve face (cranial dystonia or Meige’s syndrome), neck (spasmodic
torticollis), arm (writers’ cramp) or larynx (spasmodic dysphonia). Meige’s syndrome is
characterized by abnormal dystonic movements of face. It could be localized to eyes
(blepharospasm) and jaw muscles (oro-mandibular dystonia). This is the commonest type of
dystonia in the elderly. Spasmodic torticollis results in twisting and turning of the neck to one
side with pain. Writer’s cramp are characterized by abnormal posture, cramping and pain in
hand, forearm and arm during writing and other specific acts with hands like typing, using
hand tools or musical instruments or while eating or counting currency notes.
Treatment
1) Treatment is difficult
2) Use of anticholinergic agents like trihexyphenidyl is helpful.
3) Benzodiazepines like lorazepam is helpful in some patients.
4) Dopamine antagonists (haloperidol) or dopamine receptor blocking agents (tetrabenazine)
can be used cautiously in the treatment of focal dystonia.
5) Recently, injection with botulinum toxin has been used for treatment of focal dystonias
with good results. The effect lasts 10-12 weeks and needs to be repeated.
43
CNS and Neuro-psychiatric Check Your Progress 3
Disorders
1) Classify dystonia.
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2) What is the commonest cause of focal dystonia?

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4.3 NEUROPATHIES IN ELDERLY

After description of movement disorder, we will now aprised you of disorder of peripheral
nerve. Peripheral neuropathy is a general term meaning disorder of peripheral nerves due to
any cause. Some of the causes of peripheral neuropathy in the elderly are same as those in
younger people and some are special for the elderly. The clinical diagnosis of peripheral
neuropathy is made on the basis of a history of tingling and numbness in distal parts of feet and
hands, weakness and wasting of distal part of limbs manifest by foot drop, slipping of foot-
wear from feet while walking and difficulty in using fingers for activities like buttoning shirt,
holding small things, screwing ear –rings etc. On examination, the patients may have graded
sensory impairment, which means the most distal parts will have maximum deficit and as one
moves proximally the impairment will become less, in a “stocking and glove” distribution.
The weakness and wasting is in distal distribution and deep tendon jerks will be absent or
diminished. The patient may have difficulty walking on heel and may slap the floor with feet
while walking as foot drop becomes more apparent. When loss of proprioceptive sensation is
prominent ataxia may be out of proportion to weakness and the patient may also complain of
a feeling of “walking on cotton wool” even when he walks on hard surface. Sometimes there is
disturbance of autonomic functions in the form of diminished distal sweating and swelling of
feet. The skin may also show evidence of trophic changes in long-standing cases.
Though this is the typical description of peripheral neuropathy, you should also be aware of
variations like mono-neuritis multiplex, in which individual nerves are affected and
predominantly proximal type of disorder as occurs in acute demyelinating polyneuropathy
(AIDP or Gullian Barre syndrome) may sometimes occur. The diagnosis of peripheral
neuropathy also requires ascertainment of the cause of neuropathy in addition to confirming
the diagnosis of neuropathy.
4.3.1 Causes of Peripheral Neuropathy in Elderly
There are many causes of peripheral neuropathies in the elderly. These have been listed in
Table 4.1. However, there are some which are more frequently encounter in the elderly. These
are described below.
Gullian Barre Syndrome
Though AIDP (Gullian Barre Syndrome) occurs generally in young people, when it affects
elderly, the prognosis is poorer. It is characterized by acute to subacute (upto 6 weeks) onset
of weakness especially of the proximal group of muscles resulting in difficulty in getting up
from squatting position and difficulty in raising arm above the shoulder level. Sensory
involvement is minimum or rare. The disease progresses rapidly and can cause weakness of
facial muscles, bulbar muscles resulting in difficulty in speech and swallowing and weakness
of respiratory muscles.
Diabetic Neuropathy
It is common among patients of diabetes mellitus of long duration with poor diabetic control.
Though diabetic patients can have many types of polyneuropathies, the commonest is distal
symmetrical chronic sensory type of neuropathy associated with pain, tingling and numbness
of feet and absent ankle jerks. Other types of neuropathies in diabetes mellitus are chronic
distal symmetrical sensory-motor neuropathy, diabetic mononeuritis multiplex, acute or
subacute proximal motor neuropathy, chronic proximal motor neuropathy and trunkal
neuropathy etc.
44
Neurodegenerative Disorders
Table 4.1: Causes of Peripheral Neuropathies in Elderly
l Acute demyelinating polyneuropathy (AIDP or Gullian Barre Syndrome)
l Metabolic causes
l Diabetic neuropathy
l Ureamic neuropathy
l Vitamin B12 deficiency
l Toxic causes
l Alcoholic neuropathy
l Drugs (antitubercular, anti-neoplastic, gold)
l Heavy metals (arsenic, lead)
l Cancers
l Predominantly axonal type
l Predominantly demyelinating type
l Infection
l Leprosy
l AIDS neuropathy
l Gammopathies
l Monoclonal
l Macroglobulineamia
l Cryoglobulineamia
Polyneuropathy
Polyneuropathy associated with cancers is common in elderly. It may occur as a manifestation
of para-neoplastic syndrome or may be due to the drugs used in the treatment of the cancer.
Common cancers associated with peripheral neuro-pathies are oat cell carcinoma of lung,
breast carcinoma, lymphomas including Hodgkin’s, multiple myeloma, solitary plasma cytoma
and ploycythemia vera. The peripheral neuropathy with cancers is usually mild, sensory and
is of both axonal and demyelinating type.
Drug induced Neuropathies
They are generally axonal and less often demyelinating, more often sensory or sensory-motor
and of chronic type.
Leprous Neuropathy
Leprous neuropathy in elderly has the same pattern as in the younger people. It can manifest as
mono-neuritis multiplex involving ulnar nerves or small cutaneous nerves with hypopigmented,
atrophic and hypesthetic skin patches and thickened nerves especially dosal cervical nerve,
ulnar nerve, median nerve or lateral popleteal nerve. Rarely, leprous neuropathy can present as
distal symmetrical predominantly sensory neuropathy with thickened nerves and painless, non-
healing ulcers on feet.
Association of neuropathies and dysproteineamia is common and can occur with monoclonal
gammapathies (IgA, IgM and IgG), multiple myeloma, solitary (osteosclerotic or osteolytic)
myeloma or cryoglobulineamia. They are severe, chronic, usually sensory and do not reverse
with treatment except in the case of solitary osteosclerotic type which responds very well to
surgical or radiotherapy of primary lesion.
4.3.2 Investigation of Peripheral Neuropathy
Before proceeding to investigate a patient of peripheral neuropathy complete history of any

systemic illness (e.g. diabetes mellitus), systemic malignancy (weight loss, blood in sputum,
post menopausal bleeding etc), bone pain, exposure to drugs for medical or non-medical reasons,
exposure to toxins (e.g. organophosphorus insecticides, pesticides), exposure to intoxicants
(arsenic, lead etc.) and antecedent illness (such as upper respiratory infection, dog bite, other
infections etc.) should be obtained. Systemic examination should be thorough and should
include examination for aneamia, jaundice, breast lump, prostate enlargement, chest
examination, Mees’ lines on nail (arsenic neuropathy), blue line on gums (lead poisoning),
state of nourishment, skin changes, bony tenderness, nerve thickening etc. Besides, this 45
CNS and Neuro-psychiatric investigations include are:-
Disorders
1) Complete blood count, heamoglobin, ESR, smear examination for type of anaemia.
2) Blood sugar examination

3) X-ray chest
4) Serum protein electrophoresis
5) Electrodiagnostic test (nerve conduction studies and electro-myogram). This will confirm
the diagnosis of peripheral neuropathy and distinguish between demyelination or
axonopathy as the dominant type of neuropathy.
4.3.3 Treatment
Treatment of peripheral neuropathy is aimed at treating the underlying cause, providing physical
aids and physiotherapy. In case tingling and painful dysesthesia causes discomfort some
treatment can be given to alleviate them.
Treatment of Cause
1) Diabetes mellitus if present should be controlled.
2) If peripheral neurpathy is due to drugs and toxins they should be identified and
withdrawn
3) In case of malignancy they should be treated surgically or by radiotherapy.
4) Neuropathies due to dysprotienemia respond very well to plasmapheresis.
5) Neuropathy due to vitamin B12 deficiency responds very well to intramuscular infection
of vitamin B12 in doses of 1000µgm every day for a week, then every week for 4 weeks
and thereafter once in three months.
6) Demyelinating neuropathies respond to oral steroids.
Treatment of Painful Dysesthesia
l Anti-epileptic drugs e.g. carbamazepine (200mg 2or 3 times in a day) or diphenyl

hydantoin (5-7mg/kg/day)
l Amitryptalline (10-25mg/day) at night
l Gabapentine (300 – 900mg/day) in divided doses
l Capsain ointment locally. The problem with Capsain is that for initial 2 weeks there
is increase in burning paraesthesiae.
Physical Aids and Physiotherapy
l In case of severe foot drop special shoes with toe-lifting springs should be advised
l Physiotherapy helps in building up paralysed and weak muscles.
l Ataxia due to disturbance of joint and position sensation can be treated by gait
training.
1) What are the cardinal features of peripheral neuropathy?

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2) What are the common causes of peripheral neuropathy inthe elderly?

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3) How to investigate a case of Peripheral neuropathy in the elderly? Neurodegenerative Disorders
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4.4 DISORDERS OF MUSCLES IN ELDERLY

After nerve involvement, we will concentrate on muscle disorder, that are Disorders of muscles
are called myopathies (myo=muscle, pathy = disease). The myopathies are characterized by
slowly progressive muscle weakness involving specific muscle groups. In majority of
myopathies, the proximal groups of muscles are predominantly affected resulting in difficulty
in getting up from squatting position, difficulty in walking causing waddling gait and difficulty
in combing hair. Myotonic disorders, in addition, display presence of myotonia in which the
muscles relax very slowly after forceful contraction. This can be elicited clinically by asking
the patient to clench the first tightly and then asking the patient to open the fist quickly or by
tapping the muscle with knee hammer which will leave a dimple on the muscle. There are no
sensory symptoms or paraesthesiae, no fasciculations and the deep tendon jerks are preserved
(except when the muscle is very severely wasted).
4.4.1 Causes of Myopathies

There are several causes of myopathies: genetically determined (muscular dystrophies),
endocrine/metabolic, toxic, inflammatory, disorders of muscle energy metabolism, disorders
of lipid metabolism and paraneoplastic myopathies. Among those listed above only a few
types of myopathies are seen in the elderly which are presented in Table 4.2.
Table 4.2: Common Types of Myopathies in Elderly
l Muscular dystrophies
— Fascioscapulohumeral dystrophy
— Myotonic dystrophy
— Scapuloperoneal dystrophy
— Oculopharyngeal dystrophy
— Distal dystrophy
l Inflammatory/Infective myopathy
— Polymyositis
— Dermatomyositis
— AIDS
l Metabolic/endocrine myopathies
— Thyroid
— Parathyroid
— Other endocrine disorders
l Toxic myopathy
— Clofibrate Cholesterol lowering drug
— Perhexilene (Angina)
— Corticoid
— D-Penicillamine
— Chloroquine
— Labetalol/propranolol etc.
We shall now discuss briefly the more common types of myopathies seen in elderly.
Facioscapulohumeral type of muscular dystrophy is inherited as autosomal dominant disorder
with onset in 3rd or 4th decade. Both sexes are equally affected. Since this disease causes
minimal disability and does not affect longevity, elderly patients with this disease may be
seen. As the name implies there is weakness and wasting of facial muscles (food sticking in
the vestibule of month, liquids drooping from the angle of month, inability to whistle), shoulder 47
CNS and Neuro-psychiatric and arm muscles (winging of scapula, difficulty in raising arm above shoulder level). Foot
Disorders drop also occurs due to weakness of peroneal muscles.
Myotonic dystrophy is also an autosomal dominant disorder. The disease starts in 2nd or 3rd
decade, but due to its mild nature older individuals are also seen with this disease. Weakness
initially involves eyelids, neck muscles and distal muscles of limbs. Myotonia can be
demonstrated in affected muscles. Other characteristic features in these patients are:
characteristic droopy face, cataract, wasting of sternocleido-mastoid, gonadal atrophy and
intellectual impairment. Cardiac abnormality in the form of rhythm disturbance occurs in
some patients. The disease is transmitted by mutation on chromosome 19q.
Scapuloperoneal dystrophy is characterized by foot drop and winging of scapulae. It presents

in 3rd-5th decade.
Oculopharyngeal dystrophy is characterized by slowly progressive ptosis and limitation of eye
movements. The pupils are spared. Patients do not complain of diplopia because the disease is
symmetrical. It usually presents in 5th or 6th decade. Involvement of pharyngeal muscles
occurs later with dysphagia.
Distal muscular dystrophy is very rare. It causes weakness and wasting of hands and feet quite
like neuropathy but there is no sensory impairment and deep tendon jerks are normal.
Poly myositis/dermatomyositis: This is a form of inflammatory myopathy of unknown etiology.
In polymyositis (PM) skin is spared whereas in dermatomyositis (DM) skin is also involved. It
is caused by autoimmune mechanism. Five groups of PM/DM are identified. They are primary
idiopathic PM, primary idiopathic DM, PM/DM associated with neoplasia, childhood PM/
DM and PM/DM associated with other connective tissue disorder.
This disorder is more common in women (2:1). The disease usually runs a subacute or chronic
course, but rarely may start acutely. Pain in muscles is seen in about 10-15% patients and is
more common if the disease occurs acutely. Muscles affected are proximal group of muscles
of pelvic and shoulder girdle resulting in difficulty in getting up from floor and combing hair.
Weakness of pharyngeal muscles, neck muscles and respiratory muscles is common. Ocular
muscles are never affected. In DM skin changes in the form of diffuse or localized erythema,
scaling and maculo-papular eruption are common. Classical rash is lilac coloured (heliotrope)
rash around eye-lid, bridge of nose and cheek (butterfly distribution). Vasculitis and calcification
of skin is more common in children. Evidence of other collagen vascular diseases like systemic
lupus erythematosus (SLE), rheumatoid arthritis and polyarteritis nodosa occurs in about 20%
of cases. Though the deep tendon jerks are preserved normally in majority of patients, its
absence suggests involvement of peripheral nerves. This is commonly seen in patients with
malignancy. Patients with malignancy usually have DM and are elderly men. Common
malignancies associated with PM/DM are lung, breast, ovary, gastrointestinal and
myeloproliferative and may be detected up to 2 years after the onset of PM/DM. Involvement
of heart is common (30%) and is in the form of ECG changes or even myo-cardial ischeamia.
Myositis in AIDS is common and occurs in all stages of disease.
Several metabolic and endocrine disorders can lead to muscle weakness esp. of the proximal
group. These are hypothyroidism, thyrotoxicosis hyper-and hypo-parathyroidism, adrenal
disorders, pituitary disorders and diabetes mellitus. Hypothyroidism is associated with painful,
aching enlarged muscles esp. calves (Hoffmann’s syndrome) and thyrotoxicosis commonly
involves proximal muscles and extra-ocular muscles with exophthalmos.
A large number of drugs and toxins cause myopathies. These are generally reversible after
stopping the incriminating agent.
The primary investigations are done to confirm a myopathy and secondary tests are done to
identify the cause and assess involvement of other organs.
Primary tests include:
1) Serum creatinine kinase (CK) It is elevated in almost all disorders of muscles. They are
increased to very high levels in disorders with active muscle degeneration like Duchenne
muscular dystrophy (up to 200 times normal) and PM(Poliomyositis) (up to 20 times
normal), whereas in endocrine myopathy it may be elevated only mildly. Other enzymes
like aldolase, lactic dehydrogenase, SGOT and SGPT are also elevated.
48
2) Electromyography (EMG) is useful in deciding if muscle weakness and wasting is due Neurodegenerative Disorders
to primary muscle disease (myopathic) or due to disease of nerve or anterior horn cells
(neurogenic). The myopathic pattern shows small potentials with normal phases and
complete recruitment of motor units on forced contraction. On the other hand neurogenic
pattern consists of high amplitude potentials with increased number of phases and
incomplete recruitment of motor units on forceful contraction. In addition, the nerve
conduction studies are normal in disorders of muscles and are impaired in disorders of
nerves.
3) Muscle biopsy is useful in confirming the diagnosis and can also show presence of
muscle necrosis with presence of inflammatory cells in PM/DM.
Secondary tests include:

l History of exposure to drugs and intoxicants
l Heamogram with ESR
l Renal and liver function tests
l Thyroid, adrenal and other endocrine function tests if indicated
l Serum electrolytes
l ECG, X ray chest
l Tests for collagen vascular disease
l In case malignancy is suspected, screening for malignancy may be done
4.4.3 Treatment
1) No specific treatment is available for muscular dystrophies

2) In the distal and scapuloperoneal muscular dystrophy with foot drop, toe lifting shoes
can be prescribed.
3) Myopathies due to endocrine disturbance respond to treatment of the incriminating
disorder.
4) Myopathies due to drugs and toxins also respond to withdrawl of the incriminating agent.
5) Myotonia in patients with myotonic dystrophy can cause problem. This can be treated
with diphenyl hydantoin, quinine or procainamide.
6) Treatment of PM/DM consists of treating the cause (collagen vascular disease,
malignancy). In idiopathic cases steroids (1-2mg/kg/day) can be given. If response is
inadequate azathioprine (2.5-3.5mg/kg/day) can be given. Other drugs used are
cyclophosphamide and methotraxate. In case the disease is rapidly progressive intravenous
immunoglobulins and plasmapheresis can be given.
7) Physiotherapy is important in the long-term management of all types of patients.

1) What are the main features of myopathies?
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2) What are the common causes of myopathies in elderly?

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3) How to investigate a case of myopathy in elderly?

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49
Disorders 4.5 DISORDERS OF NEUROMUSCULAR JUNCTION IN
ELDERLY
Lastly, you will be aprised of disorder of neuromuscular junction, you know that Neuromuscular
junctions (NMJ) are areas in the muscle where a peripheral nerve makes contact with the
muscle at the synapse. The terminal part of the nerve at the NMJ is termed as pre-synaptic and
the part of the muscle as post synaptic. The neurotransmitter liberated when a nerve impulse
reaches the NMJ is acetyl-choline (Ach). There are two main disorders affecting the NMJ,
namely myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). In MG
the defect is post-synaptic and there are antibodies against the Ach receptor on the post-synaptic
membrane with eventual destruction of the synapse. In LEMS on the other hand the defect is
pre-synaptic and essentially consists of reduction of Ach at the pre-synaptic membrane.
4.5.1 Myasthenia Gravis
As mentioned earlier Myasthenie gravis (MG) is a pre-synaptic disorder of NMJ and results in
easy fatiguability of muscles along with weakness, which particularly affects the proximal
group of muscles, ocular muscles and bulbar muscles. It is an auto-immune disorder with
antibodies against ACH receptors are present.
Clinical Features
Though MG affects younger people, a small number of people older than 50 years are also
affected. Usually it affects men in later life i.e. in 50’s and 60’s. A large number of these
patients have thymoma. The clinical picture is characterized by easy fatigability and weakness.
The disease runs a fluctuating course with diurnal variations and remissions and relapses. The
muscles affected are ocular and eye lid muscles causing ptosis and diplopia which is seen in
about 85% of patients. Facial muscles and bulbar muscles may be affected giving rise to
abnormal facial expression, difficulty in chewing, nasal quality of speech, nasal regurgitation
of fluids and dysphagia. Involvement of limb muscles starts from proximal group but becomes
generalized when severe. Weakness of respiratory muscles causes dyspnoea and requires use
of assisted ventilation.
Investigations
1) Neostigmine or Ediophonium test. After assessing the patient, neostigmine (15mg) IM

or edrophonium (1mg) IV is given and patient is evaluated for reversal of weakness at
frequent intervals.
2) Electrodiagnostic test is done by stimulating a peripheral nerve (median or ulnar nerve)

repeatedly at 3-5Hz and recording the action potentials. In myasthenic patient there is
reduction in amplitude of the potential by more than 10-15%. This test is called repetitive
nerve stimulation test and the response is called decremental response.
3) Ach receptor antibody can be estimated in serum. It is present in about 80% MG patients.
It may be present in only 50% patients when MG is confined to ocular muscles.
4) Xray chest or CT scan of chest should be done to look for thymoma, thymic enlargement
or lung carcinoma.
5) Attempt should be made to look for other auto-immune disorders.
Treatment
Treatment of MG can be divided in two main groups:
a) Symptomatic therapy
b) Therapy to induce remission
Symptomatic therapy is achieved by use of neostigmine (15mg) one to four or five times a day
orally or pyridostigmine (60mg) one to four times a day orally. The dose can be increased or
decreased according to the need of the patient.
For induction of remission several measures are used. They are: thymectomy, steroids
(prednisolone 1-2mg/kg body weight /day), azathioprine (2-3mg/kg body weight/day),
cyclosporine, plasmapheresis and intravenous immunoglobulin.
50
4.5.2 Lambert-Eaton Myasthenic Syndrome (LEMS) Neurodegenerative Disorders
This is a pre-synaptic disorder of the NMJ. It is a rare disorder and is generally associated
with malignancy, commonly small cell carcinoma of lungs. This is also an autoimmune
disorder in which the antibodies are directed against the calcium channels of motor nerves.
The disorder resembles myasthenia gravis as patients with LEMS have diplopia, ptosis and
proximal muscle weakness. But patients with LEMS have absent deep tendon reflexes,
autonomic changes such as dry month and increment response on repetitive nerve stimulation
test.
Response to treatment is poor and consists of immunosuppression by drugs and plasma
pheresis.
Essentially, there are two types of movement disorders; the hypo-kinetic rigid syndromes and
hyper-kinetic syndromes. Parkinson’s disease (PD) is the commonest type of hypo-kinetic
rigid syndrome in the elderly. PD is characterized by rest tremor, rigidity, bradykinesia and
postural instability. PD should be differentiated from Steele Richardson-Oszwalski syndrome,
drug induce parkinsonism, multiple system atrophy and parkinsonism due to repeated head
injury. Apart from Parkinsonism other movement disorders in elderly are essential tremors and
focal dystonias. Among focal dystonias, cranial dystonia (Meige’s syndrome) is the commonest
disorder.
Peripheral neuropathy is a disorder of peripheral nerves and is characterized by sensory
impairment, weakness and wasting and loss of deep tendon jerks in the distal parts of the body.
Rarely, it can affect a single nerve or several discrete nerves, in that case it is called mono-
neuritis multiplex. It is caused by a large number of factors, some of which are also seen in
younger people. Evaluation of an elderly patient with peripheral neuropathy requires
confirmation of diagnosis and investigating for the extent of involvement and the cause of
neuropathy especially metabolic causes and malignancy. Specific treatment is available for
some causes of neuropathy.
1) Name the disorders of neuromuscular junction.
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2) What is the cause of Myasthemia gravis (MG)?

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3) What is the cause of Lambert-Eaton myasthenic syndrome (LEMS)?

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4) How to investigate a case of Myasthemia gravis (MG) in the elderly?

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4.6 LET US SUM UP

The disorders of muscles are collectively called myopathies. Generally, myopathies involve
the proximal group of muscles. Though a large majority of myopathies occur in children and
young adults, a small number have their onset in 4-5th decade. Due to the benign nature of
these disorders they are slowly progressive and are compatible with longer life and therefore
can be observed even in the elderly. Apart from a limited number of muscular dystrophies,
muscle disorders commonly seen in elderly are polymyositis/dermatomyositis, metabolic/
endocirne myopathies and rarely toxic myopathies.
51
CNS and Neuro-psychiatric Disorders of neuromuscular junction can affect either at the pre-synaptic level as in LEMS or
Disorders at the post synaptic level as in MG. Of the two disorders, MG is commoner. MG is characterized
by fluctuating weakness with remissions and relapses. In both the disorders ocular, bulbar,
neck, proximal limb muscles and respiratory muscles are affected in varied combination. LEMS
is characterized by involvement of autonomic nervous system and therefore these patients
may also complain of dryness of mouth and absent deep tendon jerks.
4.7 KEY WORDS

Acetylcholine : This is a substance liberated at the synapse to transmit impulse.
Neuromuscular junction : Area where peripheral nerve makes contact with the muscle at
the synapse.
Polymyositis : Inflammation of muscle involve a specific group of muscle.

1) Slowness of normal movements in the absence of paralysis or weakness is known as

Hypokinesia and Prototype is Parkinson’s disease.
2) The cardinal symptoms of Parkinson’s disease are: rest tremor, rigidity, bradykinesia
and postural instability
3) Drugs used in treatment of Parkinson’s disease are levodopa, combination of levodopa
and calidopa.
4) Anticholinegic drugs are used in controlling the tremors and sometimes cause confusion,
hallucination, urinary retention and glaucoma.
5) Indications for surgery in parkinson’s disease are:-
a) Advanced Parkinson’s disease.
b) Severe dyskinesis as hallucination and Motor fluctuation.
c) Absence of dementia, life threating concurrent illness and postural disturances.

1) Huntingtons disease belongs to hyperkinetic movement disorder group.
2) Chorea, rigidity, slowness of activity and dementia are the cardinal features of the disease.
3) Besides clinical history and physical examination, CT Scan head and Genetic test to
show CAG expansion on chromosome 9, are the investigations required to confirm the
diagnosis.
4) Drugs used to suppress chorea are haloperidol and phenothiazines.
1) Dystonias can be classified as:

a) Generalised dystonia
b) Focal dystonia
— Cranial dystonia
— Cervical dystonia (spasmodic torticollis)
— Spasmodic dysphonia
— Writer’s cramp
2) The commonest cause of dystonia in the elderly is Meige’s syndrome or cranial
dystonia.

1) Cardinal features of peripheral neuropathy are:
i) “Glove and stocking” type of sensory impairment

52
ii) Distal numbness and paraesthesiae Neurodegenerative Disorders
iii) Distal wasting and weakness with foot drop

iv) Diminished or absent deep tendon jerks
v) Trophic changes of skin (in chronic cases)
2) Common causes of peripheral neuropathy in elderly are:

i) Metabolic
ii) Toxic/drug induced
iii) Associated with cancers
iv) Associated with gammopathies
v) AIDP
vi) Leprosy
3) Investigations of a case of peripheral neuropathy in elderly are as given below:
i) Complete blood count, ESR
ii) Smear for RBC morphology
iii) Blood sugar
iv) X-ray chest
v) Serum protein electrophoresis
vi) Serum B12 level
vii) Examination of breast, prostate, pelvis
viii) Ultrasound abdomen, pelvis
ix) Stool for occult blood
x) Nerve conduction studies and EMG
1) The main features of myopathies are
i) Pure motor disorder
ii) Weakness and wasting of muscles
iii) Most often proximal group of muscles are affected. Specific groups of muscles
are affected, some are spared.
iv) Presence of muscle hypertrophy in some disorders (eg. Duchenne muscular
dystrophy, hypothyroid myopathy).
v) Presence of myotonia in myotonic dystrophies
vi) Deep tendon jerks are preserved
vii) Features of causative factors may be available on history or examination.
2) Common causes of myopathies in elderly are:
i) Muscular dystrophies
— Fascioscapulonumeral
— Myotonic Dystrophy
— Scapuloperoneal
— Oculopharyngeal
— Distal muscular dystrophy
ii) Metabolic myopathy
iii) Polymyositis/dermatomyositis
iv) Toxic myopathies
53
CNS and Neuro-psychiatric 3) Investigation of a case of peripheral neuropathy in elderly involves the following:
Disorders
i) Pedigree chart and examination of family members if affected
ii) Serum CK, aldolase
iii) EMG
iv) Muscle Biopsy
v) Complete heamogram, ESR
vi) Thyroid function tests
vii) X ray chest
viii) E C G
ix) Examination of breast, pelvis, prostate examination especially in patients with
dermatomyositis
x) Ultrasound abdomen and pelvis in patients with DM
1) The disorders of NMJ are myasthenia gravis and Lambert Eaton myasthenic syndrome.
2) Myasthenia gravis is an autoimmune disorder in which antibodies are formed against the
acetyl choline receptors on the post synaptic membrane resulting in destruction of the
post synaptic membrane.
3) LEMS is caused by antibodies against calcium channels in the presynaptic membrane
which help in release of acetyl choline. Due to this there is reduction in the release of
acetylcholine at the nerve terminal when an impulse arises.
4) Following investigations should be done in a case of MG in the elderly
i) Prostigmine/Edrophonium test to prove improvement in weakness with
prostigmine/edrophonium injection.
ii) Repetitive nerve stimulation test to prove presence of abnormal
fatiguability.
iii) X-ray chest or CT scan chest to look for thymic hyperplasia, thymoma, lung
malignancy.
Thyroid function tests, because of common association between both hypo-and hyper-thyroid
state with MG and control of myasthenic symptoms with control of thyroid status.
54
UNIT 5 INFECTIONS OF THE CENTRAL
NERVOUS SYSTEM, SLEEP
DISORDERS AND COMA
Structure
5.0 Objectives
5.1 Introduction
5.2 Meningitis
5.2.1 Pathogenesis
5.2.2 Aetiological Agents
5.3 Clinical Features

5.4 Investigations
5.5 Treatment
5.6 Prevention
5.7 Tubercular Meningitis
5.8 Fungal and Viral Infections
5.9 Brain Abscess
5.10 Sleep Disorders
5.11 Coma
5.12 Let Us Sum Up
5.13 Key Word
5.0 OBJECTIVES
After reading this unit, you will be able to:
l diagnose common infections of central nervous system in the elderly;
l appreciate types of infections and their mode of presentations;
l investigate and manage different types of infections;
l diagnose and treat sleep disorders; and
l list common cause of coma and manage comatose patients.
5.1 INTRODUCTION
In the previous unit, you have learnt about neuro degenerative order. As you know in this
unit, we shall touching CNS with sleep disorders and coma. Infections of the Central nervous
system that occur by invasion of Bacteria poses major challenge to geriatrician. Most of the
bacterial infection have great impact on the elderly and have higher mortality and morbidity
than in the younger adults. These infections are mostly preventable and curable and need
good understanding of the diagnosis, treatment and prevention in the aged.
The mortality rate due to the bacterial meningitis is three times in elderly than compared to
young. The risk and severity of infection are directly related to the virulence and inoculum of
the bacteria and depend on the integrity of the host defense. In the present publications as well
as all previous studies reported 56% of community-acquired meningitis occurred in over 50
years of age and have higher mortality rate. (10%). Noso-comial meningitis related to
neurosurgical procedures has also a cause of increase incidence of meningitis in the aged.
The diagnosis and clinical features are more subtle than in the young adults and poses
challenges to make interpretation of clinical signs and symptoms more difficult. They
55
CNS and Neuro-psychiatric have more mental status abnormalities, and are more likely to have convulsions,
Disorders neurologic deficits and hydrocephalus. Elderly with meningitis may not high fever and
at times remain afebrile. It has been seen that CSF findings in elderly patients are the
same as seen in young adults with meningitis. The treatment of bacteial meningitis
requires immediate initiation of antibiotic therapy to prevent high morbidity and mortality
of the infections. Other infections which may affect the central nervous systems are
Tuberculosis, viral and fungal and can present with varied clinical manifestations and
will be discussed briefly. Sometimes brain abscess often presents with focal neurological
deficit. Headache, change of mental status may be misdiagnosed as cerebral tumours or
CVA. Besides we will also discuss about sleep disorders and strategies to treat them.
There are many causes of coma and brief account will emphasise on general management
will be touched upon.
5.2 MENINGITIS
Infections of the meninges by pathogenic organisms results in inflammation of the brain
and is called meningitis. The term aseptic meningitis refers to the form of meningitis
where the cerebrospinal fluid is bacteriologically sterile and accompanied by a
lymphocytic pleocytosis. Viral meningitis is the most common cause of Aseptic
Meningitis. The term Meningitis refers to stiffness of the neck and irritability of the
meninges. It occurs in situations such as sub-arachnoid haemorrhage, enteric fever,
pneumonia and tonsillitis etc. Meningitis present with characteristic combination of
pyrexia, headache and neck stiffness, the severity of these features varies according to
the causative organisms. The abnormalities in CSF are very helpful in distinguishing the
cause of meningitis.
5.2.1 Pathogenesis
Bacteria may reach subarachnoid space of the elderly patient by several different
mechanisms. 1. Via the blood stream following bacteraemic illness. 2. By way of direct
inoculation from adjacent foci of infection as in patients with otitis media, sinusitis, or
mastoiditis. Most cases of head trauma or after a neurosurgical procedure develop
meningitis. 3. Infections may also occur iatrogenically following lumbar puncture, ENT
Surgery.
5.2.2 Aetiological Agents
Streptococcus pneumonia is the most common organism responsible for more than one
half of all cases of meningitis reported in several studies (Table 5.1). Gram negative bacilli
cause meningitis both by bacteremic spread of infection and as a nosocomial infection
after neurosurgery. E.coli is the most common organism cause meninigitis secondary to
pneumonia or U.T.I. E.coli and Klebsiella pneumonia are the common organisms found
after surgical procedure. More unusual organisms such as Acinetobacter have also been
reported.
Table 5.1: Aetiology of Bacterial Meningitis

Aetiologic Organism Percentage(%) Possible Source of Infection
1) Streptococcus pneumoniae 54 Pneumonia, otitis media, skull
fracture, mastoiditis.
2) Neisseria meningitis 16 Pharyngitis
3) Gram- negative bacilli 8 Head trauma, neurosurgery,
urinary tract manipulation,
osteomyelitis, decubitus ulcer
pneumonia.
4) Staphylococcus aureus 6 Acute bacterial endocarditis
pneumonia, neurosurgery.
5) Streptococci 4 Subacute endocarditis,
nerurosurgery.
6) Hemophilus influenza 2 Ottitis media, pneumonia.
7) Unknown 3 Not kmown.
8) Listeria monocytogenes 7 Not seen in India.
56
Neisseria meningitidis is a common cause of bacterial meningitis in adult but does occur in Infections of the Central Nervous
System, Sleep Disorders and Coma
the elderly (16%). The spread is by air borne route and epidemics occur particularly in cramped
living conditions. The organisms invades through the naso-pharynx producing septicaemia
leading to involvement of meninges.
Meningococcal meningitis is the most common form of meningitis seen in adults, but less
common in the elderly. Outbreaks have occurred in nursing homes and hospitals conditions
like acute or chronic otitis media, diabetes, alcoholism and splenectomy predispose to this
form of meningitis. Presence of meningeal signs and petechial or macular rash point towards
the diagnosis of Meningococcal meningitis. Haemophilus influenzae does occur in older but
usually associated with non capsulated organism where as in children, the type β encapsulated
causes infections.
5.3 CLINICAL FEATURES

Headache, fever and neck stiffness are the classical presenting features of the meningitis
but these features in elderly are more subtle. Sometimes older patients often have cervical
spine disease and poor mobility of neck. This makes the interpretation of these signs more
difficult.
Alteration in mental status such as drowsiness lethargy or coma associated with seizures,
neurologic deficits and hydrocephalus have been reported. Nausea, vomitting, photophobias
are also common complaints observed in the elderly. Fever is sometimes not recorded and at
times patient is afebrile. Patients with contagious spread of infection usually complaint of ear
or facial pain. A diffuse encephalopathy may occur and sign of papilloedema as a result of
increased intracranial pressure may occur.
Physical examination is being carried out to evaluate the presence of neck rigidity which is
seen in 56-92% cases. Cranial nerve examination and funduscopy are also carried out to
find out the presence of increased Intracranial pressure or brain abscess. Mental status should
be carefully assessed and followed. Examination of head should include search for any
fracture, haematoma, otitis media and examination of respiratory system to rule out
pneumonia, and examination of CVS to detect underlying valvular heart diseases and
endocarditis. Further, the examination of costovertebrae tenderness, petechial lesions and
pressure sores will provide important clue about source of infections in arriving at diagnosis
of meningitis.
5.4 INVESTIGATIONS
Performance of lumber puncture (LP) without delay is advised in both old and the
young. About 35% patients present with focal neurologic findings and fundus
examination is mandatory before the lumbar puncture is done as it is contraindicated
in patients with brain abscess and increased intracranial pressure. Hence, computrised
tomography (CT) or MRI is advised before this procedure is carried out. The CSF
findings in bacterial meningitis is summarised in Table 5.2. Lumbar puncture will
show prulent fluid with WBC count between 500-10,000/cumm. Polymorphonuclear
leukocytes accounts for 90% of the total count. Mono-nuclear cell has been found
high in Listeria monocytogenes meningitis. However, lack of cellular response in
CSF has been reported in majority of the cases. Blood glucose level are usually low
and serum glucose and CSF glucose ratio is usually less than 50% Protein level is
elevated above 50mg/dl. If protein levels are very high than point towards poor
prognosis.
Gram staining is usually positive in 60-90% cases, if Gram stain is negative than latex
fixation, coaggulatination and counter immuno electrophoresis are done to demonstrate
bacterial antigen. Other tests such as lactic acid levels and C-reactive proteins measurement
have been found useful in differentiating bacterial from viral meningitis. Blood and CSF
cultures are to be done in all suspected cases of bacterial meningitis. In addition, sputum,
urine and wound cultures may be helpful in determining the causative agents and also the
source of infections.
57
CNS and Neuro-psychiatric Table 5.2: CSF Findings in Bacterial Meningitis
Disorders
Opening Pressure >180mm H2 O
W.B.C. 500-10,000 cu/mm Neutrophils
predominate more than 90% of total
count
Glucose <40 mg/dl.
CSF/ serum glucose ratio < 0.40
Proteins > 50 mg/dl.
Gram’s stain +ve in 60-90%
Culture +ve in 80% cases
Latex agglutination Specific for antigens of S. Pneumoniae,
N. Meningitidis, E.coli, H. Influenzae
Limbus amebocyte lysate assay +ve in gram negative meningitis.
PCR for bacterial DNA Specificity and sensitivity unknown.
5.5 TREATMENT
Appropriate antibiotic therapy to be started immediately. The combination of ampicillin and
3rd generation cephalosporin are normally recommended to cover all pathogens likely to cause
meningitis. After CSF findings and gram stain and culture report available, then appropriate
antibiotics should be chosen, to be a, bactericidal for causative agents and able to diffuse
across the Blood brain barrier. (Table 5.3). Role of corticosteroids in elderly is yet to be
established. Dehydrated or volume depeleted patients are treated with colloid or crystalloid to
improve blood pressure and urine output. Septic shock may sometime develop and is treated
by parenteral fluid and dopamine administration.
Specialised care should be given to a comatose patients and frequent suctioning and frequent
change in posture to prevent bed sores are carried out. A condom catheter is preferred to a
Foleys unless urinary retention develops. A repeat lumbar puncture is necessary in patients
who do not respond to the therapy.
Table 5.3: Antibiotic of Choice for Bacterial Meningitis
1) Neisseria meningitis Penicillin sensitive Pencicillin G or

Ampicillin
Penicillin resistant Ceftriaxone or
Cefotaxime
2) Streptococcus Pneumoniae Penicillin sensitive Penicillin G
Penicillin resistant Vancomycin+
Ceftriaxone/Cefotaxime.
3) Gram-negative bacilli 3rd Generation Ceftriaxone or
Cephalosporin Cephalosporin Cefotaxime.
4) Staphylococcus aureus Methicillin sensitive Nafcillin or oxacillin
5) Staphylococcus aureus Methicillin resistant Vancomycin
6) Pseudomonas aerogenosa Ceftazidine
7) β heamolytic streptococci Penicillin
8) Listeria monocytogenes Ampicillin
9) Hemophilus Influenzae Ceftriaxone or Cefotaxime.
5.6 PREVENTION
Although there are no data available to support the prevention of pneumoccal meningitis
but it is found that pneumococcal vaccine does decrease the severity of pneumoccocal
respiratory infections. Hence, currently available pneumococcal vaccine has been routinely
recommended in all patients above 65 years of age which may be of some benefit to older
patients.
58
Check Your Progress 1 Infections of the Central Nervous
1) What is Meningitis?
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2) Enumerate two common causes of meningitis in old age?

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3) Describe CSF findings in acute Bacterial Pyogenic meningitis.

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4) Name antibiotics effective against Streptococcal pneumonae meningitis.
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5.7 TUBERCULAR MENINGITIS

In elderly, tuberculosis of meninges, is a serious disorder and is nearly always due to the
human type of tubercle bacilli. A few isolated cases of meningitis due to a typical mycobacteria
can occur. It is often an insiduous disease and presents with non-specific symptoms of fatigue,
anorexia, nausea and an altered mental status presenting as dementia in an elderly. A miliary
mottling in the X-ray Chest may be the only feature which differentiates tubercular meningitis
from cryptococcal meningitis. Duration of symptoms range from two days to six months.
Meningeal signs are present in less than half of the cases. Evidence of raised intracraneal
pressure such as papillooedema, brady cardia, hypotension may be present. Occular palsies,
particularly sixth nerve involvement has been seen in 30-70% of cases. Sensorial disturbances
include confusion, disorientation, drowsiness and varying grades of unconsciousness has been
seen along with focal neurological deficit. Convulsions are observed in 50% of the patients.
Untreated patients progress to comatose state, metabolic disturbances, irregular respiration,
and generalized seizures.
Investigations
CSF findings usually reveal elevated protein levels above 50 mg/dl and low glucose below 40
mg/ dl. Mononuclear cells predominate except in early infection, there may be
polymorphonuclear cells. Acid-fast positivity varies and range from 10-80% cases. Adenosine
deaminase activity has been reported in the CSF and value of 9 units/L or greater suggests
tubercular meningitis. Radioimmunoassay has been used for detecting tubercular antigen which
becomes negative after therapy. Tuberculostearic acid, a structural component of mycobacterium
tuberculosis can be detected by gas-liquid chromatography. PCR testing and immunomagnetic
enrichment may also give evidence of tubercular meningitis.
Prognosis depends on age, duration of symptoms and neurologic deficits. Mortality is greatest
in patients older than 50( 60%). Clinical staging has been utilized to treat meningitis based on
neurological status:
Stage I : Cational, no Focal neurologic signs or hydrocephalus.
Stage II : Confusion, depression or focal neurologic deficits.
Stage III : Stuporous or dense paraplegia or hemiplegia.
With the early diagnosis and treatment, cure is seen in 80-90% cases. However, patients
usually present late and with complication and hence treatment of the diseases is
unsatisfactory. About 20-30% cases are left with residual physical or mental defects such
as mental retardation, visual and hearing defects, motor deficits, metabolic and endocrinal
abnormalities. 59
CNS and Neuro-psychiatric Treatment
Disorders
Antitubercular drugs like rifampicin, isoniazid (INH) and Pyrazinamide (PZA) penetrate the
blood brain barrier to achieve adequate CSF concentrations. Streptomycin is not recommended
as it causes otoxicity and Nephrotoxicity. Several studies suggest the adjunctive use of cortico-
steroids for Stage II and Stage III patients, starting with dose of prednisone at 80mg/ day,
which may be gradually reduce over 4 to 6 weeks, as guided by the patients symptoms. If
hydrocephalus is present, ventricular shunting procedures has been found beneficial. Multidrug
resistant tuberculosis needs several drugs include quinolone, amikacin, kanamycin, capreomycin
and PAS.
1) Describe symptoms of TB Meningitis.
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2) Which is most common nerve involvement in TB Meningitis.

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3) Describe CSF findings in Tubercular meningitis.

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4) Describe clinical staging based on neurological status.

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5.8 FUNGAL AND VIRAL INFECTIONS

1) Fungal Meningitis
Usually occurs in patients who are immuno comprised and is a recognised complication of
human immuno-deficiency virus (HIV) in 20-50% cases. It is caused by cryptococcus and
candida and cause inflammation of meninges in a manner very similar to Tuberculosis.
Diagnosis is based on CSF findings which are similar to that of tuberculosis. There is lymphocyte
predominance and India ink is positive in 50% or more of cases. A cryptococcal antigen is
positive in 90% of cases. MRI and CT Scan helpful to rule out basal meningitis which occurs
in tuberculosis and presence of hydrocephalus which at times seen in some of cases of
cryptococcal meningitis.
High CSF opening pressure, along with low CSF glucose, fewer than 20 white cells in the CSF,
high titre of cryptococcal antigen and presence of HIV disease point towards the poor prognosis.
Treatment
Amphotericin B is the drug of choice but Flucytosine and Fluconazole have also been found
useful in the treatement of cryptococcal meningitis. Recently, a new liposomal Amphotericin
B have been added to treat meningitis. A combination with flucytocine and fluconazole has
been explored in patients with acquired immuno deficiency disease (HIV).
2) Viral Meningitis
Viral Meningitis refers to inflammation of the meninges and has sudden onset and a short
course over days to week. The majority of the viruses enters the CNS via haemato-genous
route. It is a beningn self limiting illness.
Aetiology
60 A large number of viruses have been implicated include: 1. Enteroviruses 2. Mumps
3. Arena 4. Herpes viruses 5. Retroviruses (HIV) 6. Others include influenza, adenovirus Infections of the Central Nervous
and arboviruses. System, Sleep Disorders and Coma
Clinical Features
Mostly seen in adult but do occur in elderly. It is often preceded by a prodormal phase consisting
of non specific symptoms such as fever, headache, weakness and malaise. The sensorium is
clear and focal neurological signs are rare. Symptoms usually reach a maximum within one
week and subsides within two weeks.
Investigations
CSF findings show normal glucose and protein levels and an excess of lymphocytes. The
virus can be identified by increase in specific antibody titres.
Treatment
There is no specific treatement as the disease is usually benign and self limiting. The patient
is treated symptomatically. Majority of the patients recover without any sequaele.
3) Herpes Simplex Encephalitis
It is a serious infection of the CNS and is caused by herpes simplex virus type I. It occurs in
both sexes and has no seasonal association. High Mortality- (60-80%) has been reported in
patients over 50 years of age. However, 5-10 % cases recover without any neurologic
sequelae.
Clinical Features
There is an abrupt onset of personality change, altered sensorium, fever and Headache. There
occur some localizing signs such as speech deficits, temporal lobe seizueres, hemiparesis,
olfactory hallucinations and nasal field defects.
Diagnosis
The spinal fluid findings are non- specific with an slightly elevated number of lymphocytes.
However, increase in leukocytes may be found in the early course of the disease. The EEG
(Electroencephalogram) may show slow wave complexes at regular to 2-3 second intervals,
usually localized to the temporal lobe. CT Scan demonstrate abnormality in 70% cases but
MRI is more sensitive and positive in the early course of the disease. Newly PCR technology
done in CSF fluid is helpful in making the diagnosis. Definitive diagnosis is usually made by
brain biopsy by appropriate culture and histology.
Treatment
Effective therapy consists of acyclovir at a dose of 10mg/kg every 3 hours for 10-12 days. If
patients show renal insufficiency then dose has to be adjusted according to creatinine clearance.
Dehydration is to be avoided.
Prognosis depends on the level of consciousness at the start of the therapy. If treatment is
delayed or patient is comatosed then these patients develop neurologic sequelae.
5.9 BRAIN ABSCESS

It is collection of pus in the brain and presents a mass lesion with focal neurologic deficits.
Infections spread through ear and sinus infection appear to be more common in younger adults
than the older than 60 years of age. Mean duration of symptoms is usually 10-15 days. Mortality
usually ranges between 30-50% and with the advent of CT scan, early diagnosis is possible.
This has decreased mortality to 4-20%.
Clinical Features
Fever is usually absent in 40-50% patients and common symptoms such as headache, change
of mental status, focal neurologic deficits, are some times misdiagnosed as cerebral tumour or
cerebrovascular accidents which are very common in elderly. The single abscess is generally
localized in frontal lobe or parietal lobe rather than occipital or temporal region. Generalized
seizures can prompt hospitalization and about 50% of patients may present focal neurologic
signs (such as hemiparesis or focal seizure. These patients may go into diffuse neurologic
dysfunction and became comatosed. They may also have neuropsychiatric manifestations.
Fundus examination reveals papilledema.
61
CNS and Neuro-psychiatric Pus culture from brain abscess will show same organisms as seen in the adult patients. Often
Disorders Viridans Streptococcus and Streptococcus milleri are the common pathogens. Fusobacterium
and other anaerobes were also isolated from pus culture.
A lumbar puncture, which reveal slightly elevated WBC count may be dangerous particularly
with focal neurolgic signs and raised Intracranial pressure. Hence, it should be avoided, 70%
patients show show more than 500 WBC count suggesting a bacterial meningitis and spinal
fluid culture is usually sterile.
Majority of cases with abscess demonstrate radiologic appearance of “dough nut ring”. This
may be seen in lesions with necrotic tumours and cerebral infarct. MRI and CT Scan are
helpful in making the diagnosis.
Treatment
Medical therapy is recommended in cases where abscess is less than 2 cm in diamet er along
with high density which is suggestive of cerebritis. A combination of a β –lactam agent with
chloramphenicol or metronidazole or Tinidazole has been advised. Microbiologic culture
obtained through Stereotaxic biopsy will guide the appropriate antibiotic therapy. Parenteral
ceftriaxone or cefotaxime has also been found useful in the treatment of brain abscess. The
duration of treatment has been variable and majority of authors recommend approximately
4-6 weeks of antibiotics which includes the combination of parenteral and oral agents.
Surgery is the only option if abscess is big and culture of the aspirated material help
administration of appropriate antibiotics in curing the disease. 46% cases still have neurologic
sequelae inspite of appropriate antibiotics given.
5.10 SLEEP DISORDERS

Sleep is the process that allows functioning throughout the day without feeling drowsy and
impairment in concentration, memory and the performance. A person normally sleep
approximately 1/3rd of the day (8 hr). Changes in structure and quality have long been
associated as a feature of the aging process. Development in research methodology, especially
polysomnography have demonstrated changes in sleep pattern with advancing age and there
is increase incidence of insomnia in general population. Insomnia has been defined as
inadequate or poor quality sleep characterised by one or more of the following:
1) Difficulty in falling asleep

2) Difficulty in maintaining sleep
3) Waking up too early in the morning and
4) Non- Refreshing sleep.
The understanding in sleep and its disorders is important in knowing the risks involved in
deterioration in quality of life, the development of emotional problems such as depression, the
worsening of the cognitive impairment and the risk for motor vehicle accident and for mortality
which may be adversely affected by too much sleep (more than nine hours) as mediated by
sleep apnea or too little sleep (less than 5 hours out of 24) and hence quality of sleep affect the
quality of life and death.
Before discussing the sleep disorders, we would like to aprise you about the changes that
occur in the elderly. Sleep becomes ‘shallow’ i.e. the auditory threshold for awakening diminishes
which is manifested by reduction in slow wave sleep the deepest level of non rapid eye movement
sleep (non-REM). There is increase in intermittent wakefulnes during the night as the age
advances. Both long and short arousal, are observed mostly in second half of the night and
results in fragmented nocternal sleep. There is evidence of frequent napping in day-time and
older persons spend more time in bed often not asleep. The 24-hour sleep-wake patterns become
polyphasic. Gradually as age increases, the prevalence of both sleep disorded breathing and
periodic limb movements are seen in about 25% cases. This accounts for decreasing
physiological ability to deep sleep and involved in day-time sleepiness. The sleep disorder is
1.5 times more common in persons aged > 65 years compared to younger counterparts and
incidence in women is 1.3 times greater than in men.
Clinical Manifestation
Elderly presents with sleep onset problems (i.e. trouble getting to sleep), sleep maintainence
62 problems (i.e. trouble staying asleep) and early morning awakening (EMA). These symptoms
may be present singly or in combination and may be transient or chronic (long-term). According Infections of the Central Nervous
to 1. CD-10 sleep disorders is divided into organic and non-organic. The non-organic include System, Sleep Disorders and Coma
dysomnias (the disturbances of the amount, quality, or the timing of sleep) and the parasomnias
(abnormal episodic events occuring during sleep).
Non-organic insomnia is a dysomnia characterised by persistent difficulty in getting to sleep

or staying asleep. It should be atleast 3 times a week for atleast one month. It markedly interferes
with social or occupational functioning.
The prevalence of insomnia increases steadily with age and reported by upto one in 3 people aged
65 years and above. It is more common in women than men (Table 5.4). Changes in both nature
and the duration of sleep is affected by increasing age and complaints of early morning awakening
(EMA) is also affected as age increases. The common causes of insomnia are listed in Table 5.5.
Table 5.4: Prevalence of Insomnia in Elderly

Location Age Prevalance Women Men EMA
overall (%)
Florida(US) 60-69 20.9 22.6 18.3 4.0
70+ 25.9 29.4 20.0 3.3
Nottingham 65+ 22.5 27.7 14.6 33.6
(UK)
Paris (France) 55+ 31.0 42.5 22.5 NR
Mannhein (Germany) 66-92 23.0 29.1 7.9 NR
East Boston ( US) 65+ 33.7 36.4 29.4 26.0
Iowa (US) 65+ 23.2 25.4 19.5 15.0
Table 5.5: Causes of insomnia
l Transient/acute/Intermittent
1) Stress
2) Unfamiliar sleep environment
3) Sleep/wake schedule problem (Jet leg, shift work).
4) Non conducive sleep environment (excessive noise, extreme temperature).
5) Drugs (Benzodiazepine withdrawl induced rebound insomnia).
l Chronic Insomnia
1) Menopause
2) Medical disorders (COPD, GERD, CHF, Muscoskeletal pains (Arthritis),
diabetes, hyperthyroidism, prostatic problems, cancer etc.)
3) Psychiatric disorders (depression, anxiety, menicets).
4) Medication side-effects
5) Behavioural conditioning (learned insomnia)
6) Sleep related breathing disorder. (Obstructive sleep apnoea syndrome).
7) Sleep related movement disorders (restless legs syndrome, periodical disorder).
8) Delay: sleep phase disorder (circadian rhythm disorder).
History taking and diagnosis

Insomnia is often unrecognised and untreated because of non-reporting by the elderly to the
doctor. The doctor should follow the diagnostic algorithm for insomnia (Table 5.6). The first
step is to ascertain whether insomnia is related to patient’s medical condition and or its treatment.
It is often associated with pain, limitation of mobility, frequent urination and breathing difficulty.
The second step is to see whether insomnia is associated with self medication or by a substance
abuse disorder like consumption of alcohol, nicotine or caffeine. The third step is to differentiate
it from psychiatric disorder like mood disorder (depression or anxiety) or related with
neurodegenerative conditions like parkinsonism and delerium. The fourth step is to rule out
the possibility of circadian rhythm sleep disorder. The fifth step is to find out whether elderly
have primary sleep disorder such as restless legs or sleep-disordered breathing. Finally, if
these more specific sleep disorders have been ruled out, then patients represent a primary or
idiopathic form of insomnia. In this form of insomnia, the patient worries obsessively about 63
CNS and Neuro-psychiatric not sleeping and gets into a vicious cycle that is called “Conditional insomnia”.
Disorders
Table 5.6: Diagnostic Algorithm for Insomnia
1) Its duration of insomnia is less than one month. If so search for acute and recent precipitant like
adverse life event. If more than one month, consider the following additional diagnostic possibility.
2) Can the complaint be adequately explained by concurrent medical disorders and/or their treatment
i.e. nocturnal cardiac ischemia, chronic obstructive airway disease, gastrooesophageal reflux disease.
3) Self medication and or/ substance abuse like alcohol abuse.
4) Mental or neuropsychiatric disorder (depression and anxiety), breavement, dementia, delerium.
5) Circadian rhythm sleep disorder.
6) Breathing related sleep disorder.
7) Primary or conditioned insomnia.
Lab Studies
Polysomnography is used to study the formal sleep, consist of overnight monitoring of sleep
done in laboratory by EEG (Electroencephalogram) EOG (Electro-oculogram) and chin
electromyogram (EMG) and of respiration, ECG and anterior tibialil EMG. Two consecutive
nights may be required in the evaluation of patients not responding to routine intervention. It is
not used routinely and usually preferred when clinician suspects sleep disordered breathing
(sleep apnoea syndrome) or other abnormal events observed during sleep like marked
behavioural disturbances, periodic limb movement disorder, seizure or cardiac arrythmia. The
formal sleep studies is also undertaking in patients with excessive day-time sleepiness and narcolepsy.
The differential diagnosis of excessive day-time sleepiness is summarised in Table 5.7.
Table 5.7: Differential Diagnosis of Excessive Sleepiness
1) Inadequate sleep at night (secondary to medical disorders or inadequate sleep hygiene).

2) Iatrogenic cases (long acting sedative hympnoties)
3) Circulation rhythm sleep disorder.
4) Breathing related sleep disorder (i.e. suggested by loud snoring and obesity).
5) Narcolepsy-Cataplepsy.
6) Sleep disorder related to mental disorder.
7) Periodic limb movement disorder or restless leg syndrome.
Management of Insomnia
Primary idiopathic insomnia is best treated by behavioural intervention and it has been shown that
sleep hygiene education is not effective when used alone but stimulus control and sleep restriction
approaches have been found most effective and does require skill, time and energy. (Table 5.8). If
non- pharmacological techniques are not sufficient then short-term therapy with an adjunctive
benzodiazapine sedative hyniotics or with zolpidem is quite reasonable (Table 5.9).
There is now widespread agreement that hypnotic medication should not be the mainstay of
the treatment for majority of causes of disturbed sleep. Benzodiazapine is preferred, in acute
insomnia following a major life event such as bereavement or admissin to I..C.U. and lorazepam
with short elimination half lives in the doses of 0.5-1.0 mg, oxazepam 15 mg or temazeapam
7.5-15 mg at bed time. They are less likely to cause day time sedation than drugs with longer
elimination half-lives (flurazepam). Zolpidem 5 mg at bed-time is also good hypnotic sedative
and offer additional advantage of no loss of efficacy over 35 days and absence of rebound
insomnia or drug related impairment of memory.
The management of chronic insomnia is based on elimination of any psychiatric casuse.

Low-dose trazodone or trimipramine have been found a useful intervention in the
management of chronic insomnia associated with mood disorder and when given along
with a program of good sleep hygiene, appropriate restriction of time in bed and stimulus
control. Diphen hydramine is a mild drug for insomnia and has been widely prescribed
but have side effects in elderly who are cholinergically brittle. Therefore, more safe
and efficacious agents among the benzodiazepines or with Zolpidem are usually
preferred.
Treatment options include non-pharmacological methods (Table 5.8) and pharmacological

therapies (Table 5.9).
64
Table 5.8: Non-Pharmacololical Methods Infections of the Central Nervous
1) Sleep hygiene instructions:
l Maintain a regular sleep/wake schedule.
l Participate in a relaxing activity until tired and go to bed when sleepy.
l Use the bed and bedroom only for sleep.
l Avoid day-time and mid-after-noon naps.
l Avoid stimulants such as caffeine or nicotine and alcohol before bed-times.
2) Stimulus control;
l Prepare a set of instructions designed to establish the bed-room as cues for steep instead of
wakefulness.
3) Sleep Restriction:
l Limit the length of time spent in bed, creating partial sleep deprivation, which results in
deeper and more continous sleep.
l Improves sleep efficiency (total sleep time/time spent in bed) and helps consolidate sleep.
4) Relaxing training
l Biofeed back: teaches relaxation by conditioning specific muscular and EEG activity.
l Autogenic training : teaches relaxation by associating pleasant visual images with relaxing
sensations.
l Progressive muscular relaxation: teaches relaxation by tensing and relaxing muscle groups.
l Hypnosis.
5) Cognitive therapy
l Psychotherapy aimed at changing the patient’s assumptions and perceptions about the
insomnia.
Table 5.9: Drug Therapy of Insomnia
Type of drug Example Mechanism/Comment
1) Non-barbiturate, non- Chloralhydrate l Prolonged use can lead to

benzodiazepines. Glutethimide dependency.
2) Barbiturates Amylobarbitone, l Depress action of CNS
Butobarbitone l Lethal in overdose.
3) Benzodiazepines Nitrazepam, l Binds to GABA receptors.
Flurazepam, oxazepam, l Act selectively in areas of brain
lorazepam, temazepam. involved and psychomotor
functioning.
4) Non-benzodiazepines Zolpidem, Zopicline, l Bind selectively to GABAreceptors
in CNS with calming effects.
5) Antidepressants Amitryptyline, l Are hypnotics
Tradozone, l Somehave serotinin like mode of
Nefazodone, Paroxetine action.
l Useful for patients with depression.
6) Antihistamine Diphenhydramine, l Antagonise central histamine-I
Doxylamine. receptors.
7) Others Melatonin, Trytophan l It regulates sleep onset via its
receptors in CNS.
l Regulates circadian clock via
receptors in suprachiasmatic
nucleus.

1) Define Insomnia.
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2) Name drug which causes insomnia.

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CNS and Neuro-psychiatric ..........................................................................................................................................
Disorders
3) Enumerate lab investigations for insomnia.
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4) Name non-benzodiszepines used in the treatment of insomnia.
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5.11 COMA
As you know, coma is the severest form of medical alertness and responsiveness, a deep sleep
like state from which the patient cannot be aroused by painful stimuli. It is different from
Stupor, which is a lesser degree of unarousability state, where the patient can be briefly aroused
by painful stimuli. You should also be familiar with the situation of drowiness, which simulates
light sleep and is characterized by easy arousal and persistent alertness for short periods.
The principle factors responsible for coma are :
1) Damage of substantial protion of RAS
2) Destruction of major portions of cerebal hemispheres
3) Suppression of the thalmocerebral function
The main causes of coma are enlisted in Table 5.10.
Table 5.10: Causes of Coma

A) Metabolic
1) Drug overdose (Alcohol, sedative drugs, opiates etc.)
2) Hypoglycemia or Hyperglycemia
3) Renal Failure
4) Hepatic Failure
5) Hypothyroidism (Myxedema coma)
6) Cardiorespiratory Failure
7) Hypoxic Encephalopathy
8) Shock from any cause
9) Electrolye Imbalance (Hyponatremia, Hypernatremia, Hypercalcemia)
10) Profound Nutritional deficiency
B) Structural
i) Diffuse
a) Meningitis
b) Encephalitis
c) Cerebral Malaria
d) Sub-archanoid Haemorrhage
e) Epilepsy
f) Head Injury
g) Hypertensive Encephalopathy
ii) Focal
a) Supra-tentorial
1) Cerebral Haemorrhage
2) Cerebral Infarction
3) Subdural haematoma
66
4) Extra dural haematoma Infections of the Central Nervous
5) Tumour
6) Cerebral abscess
7) Pituitary Apoplexy
b) Sub-tentorial
1) Cerebellar haemorrhage
2) Ponitive haemorrhage
3) Brainstem infarction
4) Tumour
5) Cerebellar abscess
6) Transtentorial herniation
Establishing Coma
The first thing you should make sure is that the unresponsiveness is due to coma as it can be
confused with the following :
1) Pseudo-coma which may occur in psychiatric states i.e. hysteria. It can be differentiated
from coma as it is characterized by the presence of all motor reflexes. The patient avoids
response to lifting and dropping of the arm and has active resistance to eye-lid elevation.
2) Locked-in-state, where the patient has no means of producing speech or voluntary limb,
face and pharyngeal movements though vertical eye movements and lid elevation remain
unaffected, allowing the patient to signal. Infarction or haemorrhage of the ventral pons
is the usual cause.
3) Akinetic mutism is another clinical state, which may be interpreted as stupor or coma.
Here a patient who is partially or fully awake, tries to make impressions and think, but
remains immobile and mute, particularly when unstimulated. This state results from damage
in the region of the medical thalamic nuclei, the frontal lobe or from hydrocephalous.
History and Physical Examination

The history is of great importance in arriving at a provisional diagnosis in the case of coma. A
sudden onset of coma suggests a cerebro-vascular disorders, such as sub-arachnoid haemorrhage
or stroke, trauma or seizures. A gradual deterioration, usually points towards a metabolic cause,
tumour or infection. One should also inquire about a previous history of diabetes, hypertension,
renal disease, hepatic dysfunction and cardiac disease.. History of drugs or toxic exposure is
an important component to be asked for.
The examinations of vitals include temperature, pulse, respiratory rate and pattern and blood
pressure. All these should be measured quickly. Fever suggests a sytemic infection, bacterial
meningitis or encephalitis and is only rarely attributable to brain lesions. High body temperature
(42-44 oC) associated with dry skin, should arouse the suspicion of heat stroke or anticholinergic
drug intoxication. Tachypnea may indicate acidosis or pneumonia. Marked hypertension is a
sign of hypertensive encephalopathy or rapid rise in intracranial pressure and it may also be
acute after trauma or head injury. Hypotension is a characteristic feature of coma, associated
with alcohol or barbiturate intoxication and internal haemorrhage. The fundoscopy examination
is valuable to check raised intra-cranial pressure. Generalized cutaneous petechiae indicate
thrombotic or bleeding diathesis.
Neurological Assessment
You should carry out the following examination.
i) Level of consciousness is assessed by Glasgow Coma Scale.

1) Eye Opening
Spontaneous - 4
To speech - 3
To pain - 2
None - 1
2) Best Verbal Response
Oriented - 5 67
CNS and Neuro-psychiatric Confused - 4
Disorders
Inappropriate - 3
Incomprehensible - 2
None - 1
3) Best Motor Response
Obeying - 6
Localisting - 5
Withdrawal - 4
Flexing - 3
Extending - 2
None - 1
(Interpretation : The Scale is based on an aggregate (sum total) of three types of responses.
This range is from 15 (normal) to 3.
ii) Respiration :
Cheyne-stokes Respiration is characterised by periods of hyperventilation alternating with
periods of aponea. This may be seen in bilateral deep hemispheric and basal ganglionic
dysfunction. The upper brain stem may also be involved.
iii) Pupils :
Pupillary reactions are examined with a bright, diffused light. Normally reactive and round
pupils essentially exclude mid-brain damaga. An unreactive or large pupil or one that is poorly
reactive, signifies a compression or stretching of the 3rd nerve from the effect of mass.
Unilaterally dilated and a fixed pupil, is usually sue to 3rd nerve palsy as a result of transtorial
herniation.
iv) Occular movements :
Eye movements, are the second signs of importance in determining whether the brain
stem has been affected. Spontaneous eye movements in coma, often take the form of
conjugate horizontal roving and exclude the mid-brain and pons lesions. One should
also see the occulocephatic reflexs and occulo-vestibular reflex, to rule out brain stem
lesions.
v) Motor response :
Lack of restless movements on one side, or an outturned leg at rest indicates hemiplegia.
Intermittent twitching movements of a face, foot or finger indicates a sign of convulsion and/
or seizures. Multifocal myoclonus almost, always indicates a metabolic disorder. Decorticate
regidity and decerebrate rigidity, suggest severse bilateral damage to the mid-brain.
Laboratory Studies and Imaging
The following studies are useful in the diagnosis of confusional states and coma. These are :
examination of blood and urine, CT or MRI, EEG and CSF examination. Arterial gas analysis
is helpful in acid-base disorder and lung disease. The metabolic disorders commonly seen in
clinical practices, require estimations of electrolytes, glucose, calcium, osmolarity and renal
and hepatic function. Toxicological analysis is necessary in patients with coma, where diagnosis
is not clear. CT and MRI have been found to be useful to rule out various causes of coma, that
are radiologically detectable. The EEG is useful in metabolic or drug induced confusional
states, but is rarely diagnostic, with the important exceptions of coma due to herpes virus
encephalitis and Creuzfeldt-Jako disease. However, a majority of medical causes of coma,
can be established without a neuroimaging study.
Management
Once coma has been confirmed, a complete medical examination is usually deferred, until the
patient has been stabilized. Immediate therapeutic measures have to be initiated to prevent
further neurological damage. Hypotension, hypoglycemia, hypercalcemia, hypoxia,
hypercapnia and hyperthermia should be corrected rapidly.
A) Initial Management
1) Establishment of an efficient airway
68
l If the patient is breathing normally, an oropharynegeal airway of adequate size is Infections of the Central Nervous
inserted and taped to prevent the tongue from obstructing the airway. System, Sleep Disorders and Coma
l If breathing is disturbed, then cuffed endotracheal tube is inserted and assisted

ventilation is started.
l If intubation is required for more than 48-72 hours, a tracheostomy is preferable.
l Cervical injury should be ruled out in the case of trauma and if suspected, the neck
should be immobilized with a hard collar.
2) A peripheral venous access is secured to administer fluid and drugs.
3) Blood is withdrawn for biochemical investigations and toxic screening.
4) Maintenance of blood pressure is ensured and hypotension is corrected with normal
saline to ensure adequate cerebral, renal and cardiac perfusion.
5) Specific measures to be taken are as follows :
a) IV thiamine 100mg to prevent Wernicke’s encephalopathy
b) 50 ml of 50% dextrose if hypoglycemia is suspected.
c) IV naloxone (2mg IV) if opiod intoxication suspected
d) IV atropine for organosphosphorous intoxication
e) IV physostigmine for anticholinergic poisoning.
f) IV chloroquine or quinine if cerebral malaria is suspected.
g) IV flumazenil if Benzodiazepines toxicity is suspected.
6) Management of seizures:
l IV Diazepam
l IV phenytoin
l IV Phenobarbitone
l IV Thiopentone
B) Management of Specific Purpose
Trauma, sepsis, CNS infections, cerebrovasular accidents, tumours, metabolic derangements
are treated accordingly, as you have learnt earlier in different units.
C) General Care of the Patient
1) Prevention of aspiration of secretions by regular nasopharyngeal and oral cavity suction.
2) Prevention of bed sores : This has been discussed in detail earlier. However, the essential
steps include :
l Patient has to be turned every two hours.
l The sheets should be dry and tightly drawn.
l Bony prominences should be padded.
l A water/air mattress should be used.
l The back should be regularly clearned with spirit.
3) Nutrition is provided by IV solutions initally and later by naso-gastric feeding after the
condition becomes stable.
4) Bladder and bowel care:
l Condom catheter may be used in the males
l If an indwelling catheter becomes necessary, a three way catheter should be used
with continuous irrigation with mild acetic acid solution, which acidifies the urine
and prevents stone formation.
l Catheters should be clamped intermittently for bladder training
l Urine must be set regularly for routine and culture examination
5) Eyes : Corneal injury is prevented by taping the eyelids and using lubricant eye-drops.
6) Physiotherapy : Passive physiotherapy to prevent stiffness of joints.
D) Management of Raised ICP
1) IV Mannitol 69
CNS and Neuro-psychiatric 2) Dexamethasone
Disorders
3) Glycerol
Prognosis
Outcome of the coma, depends on the underlying cause, long-term care and medical resources.
Metabolic and drug induced comas have good prognosis as compared to traumatic coma.
Glasgow coma scale, is devised to predict the values in each case of brain trauma. For anoxic
and metabolic coma, clinical signs such as pupillary and motor responses after 1st day, 3 rd
day and 77th day have shown to have prognostic value. The absence of the cortical waves of
the somatosensory evoked potential, suggests poor outcome of comatosed patient from any
underlying aetiology.
1) Define coma.
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2) Name four important types of metabolic coma.

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3) What is pseudo coma?

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4) What is the cause of decorticate rigidity and decerebrate rigidity?

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5) Name the specific diseases which are diagnosed by EEG.

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5.12 LET US SUM UP

Bacterial infections in elderly have a great impact on mortality and morbidity including quality
of life. It has become a more common problem in elderly over the past two decades which is
preventable and curable and needs early diagnosis and prompt initiation of therapy. Clinical
features are more subtle as compared to young adult. At times, triad of feature, fever, headache
and neck stiffness are not present and only lumbar puncture gave the final diagnosis. The
combination of ampicillin and 3rd generation cephalosporins has been recommended to cover
all pathogens likey to cause meningitis. Streptococcus pneumoniae is the most common
organism to cause meningitis in the elderly, outcome is excellent if appropriate antibiotic
started immediately. Pneumococcal vaccines is now available and should be recommended in
all patients over the age of 65 years, although no definite specific data is reported to support
this.
Tubercular meningitis is a serious disorder in elderly and is often insidous and accompanied
by confusion, disorientation, varying grades of unconsciousnes, focal neurological deficit,
convulsions and nerve palsy. Diagnosis is made by lumbar puncture. Treatment usually cure
the disease in 80-90%. About 20-30% are left with some some residual physical or mental
defects. Hydrocephalus if present is treated surgically by ventricular shunt.
Inflammation of meninges by viruses and cryptococcus has also been seen in older people. It
consists of non specific symptoms with normal sensorium and no focal neurological signs.
70
Diagnosis in cases of viral infection is based on normal glucose and protein levels with presence Infections of the Central Nervous
of predominant lymphocytes in CSF. Specific antibody titre to viruses may be increased. System, Sleep Disorders and Coma
Fungal meningitis is difficult to differentiate from Tubercular meningitis. However, India ink
is positive in 50% or more cases and cryptococcal antigen is seen in 90% cases. There is no
specific treatment in cases of virus infection however, the fungal infection is treated by
Amphotericin B, Flucytosive and new liposomal Amphotericin B. Herpes Simplex encephalitis
carries high mortality in older people and accompanied by altered sensorium, localizing signs
and nasal field defects. EEG changes and MRI including CT Scan help in arriving at diagnosis.
Therapy with Acyclovir can improve the symptomatology in some of the cases.
Brain abscess presents with a mass lesion with focal neurologic deficit. Mortality is very high
(30-50%) with advent of CT Scan & MRI, the early diagnosis has made significant contribution
in reducing the mortality to 4-20%.
Advancing age as well as senescent changes directly influence the structure and quality of
sleep. Problems related to disturbed sleep are multifactorial and require broad and flexible
clinical approach. Therapeutic approaches have been well systamitized and special emphasis
given to sleep assessments, health education and sleep hygiene and appropriate pharmacologic
and psychologic strategies in treating complex sleep problems in the elderly.
Coma is a state unconsciousness from which a patient cannot be aroused by painful stimuli
and all reflexes are lost. It can occur due to damage of substantial portion of RAS, cerebral
hemispheres and suppression of thalamocerebral function. Diagnosis is established by meticulus
history and neurological examination. Level of consciousness is assessed by Glasgow Coma
Scale. Biochemical examination of blood and urine, CT or MRI, EEG and CSF examination
and ABG analysis help in arriving at diagnosis of major causes of coma. The treatment is
based on the establishment of an efficient airway, maintenance of vital functions and specific
measures to treat underlying causes. Symptomatic treatment includes management of seizures,
intracranial pressures, nutritional care, bladder and bowel care. The outcome of coma depends
on the long term care as well as medical resources. Metabolic and drug induced coma have
better prognosis as compared to traumatic coma. However the absence of the cortical waves
of the somatosensory evoked potential indicate a poor outcome.
5.13 KEY WORD

Cheyne-Stokes Respiration : Periods of Hyper ventilation alternating with periods of
Apnoea.

1) Inflammation of meninges of the brain caused by pathogenic organism is called
Meningitis.
2) Two common causes of meningitis are
a) Streptococcal pneumoniae.
b) Gram negative bacilli.
3) CSF findings are:
a) Turbidity
b) Polymorphs 500-10,000/ cumm.
c) Glucose< 40 mg/dl.
d) Proteins 0.5-2.g/dl.
e) Gram stain +ve.
4) The antibiotics effective against streptococcal pneumonae meningites depends upon

whether the organisms are pencillin sensitive or resistance.
For pencillin sensitive–Pencillin G.
For Pencillin resistant–Vancomycin + Ceftriaxone/Cefotaxime.
71
CNS and Neuro-psychiatric Check Your Progress 2
Disorders
1) Tubercular meningites presents with non-specific symptoms of fatigue, anorexia, nausea,
altered mental status, evidence of papilloelema, sixth cranial nerve palses and focal
neurological deficits.
2) Most common nerve involvement is 6th nerve palsy.
3) CSF finding reveal 1. Elevated protein level above 50mg/dl. 2. Low glucose level below
40mg/dl. 3. Predominant mononuclear cells. 4. Raised Adenosine deaminase activity
more than 9 units/L.5. Postive PCR in CSF fluid.
4) Clinical stages are:
Stage I - Rational, no focal neurologic signs or hydrocephalus.
Stage II - Confusion, depression, or focal neurologic deficits.
Stage III - Stuporos or dense paraplegia or hemiplegia.
1) Insomnia has been defined as inadequate or poor quality sleep characterised by one or
more of the situations like 1. difficulty in falling asleep. 2. Difficulty in maintaining
sleep. 3. Waking up too early in the morning and 4. non refreshing sleep.
2) Benzodiazepine
3) Lab investigations include Polysomnography, EEG. EOG and chin EMG, ECG and
anterior tibial EMG.
4) Non-benzodiazepines used in treatment of insomia include Zolpidem, Zopicline and Zolepon.
1) Coma is a state of reduced alertness and responsiveness from which a patient cannot be
aroused by painful stimuli.
2) The four important causes are :
a) Hypo or Hyper glycaemic coma
b) Drug intoxication
c) Hepatic Coma
d) Uraemic Coma (Renal failure)
3) Pseudocoma is characterized by the presence of all motor reflexes. The patient avoids
response to lifting and dropping of the arm and shows active resistance to eyelid elevation.
4) The cause of decorticate rigidity is a severe bilateral damage to the mid-brain.
5) There are two diseases namely Creutzfeldt-Jakob disease and Herpes virus encephalitis
that are diagnosed by EEG.
72

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UNIT 1 CEREBRO VASCULAR DISEASES

Usually, ‘stroke’ is defined as a rapid onset of focal neurological deficit over

Table 1.1: Various Manifestations of Stroke

2) Stroke with permanent deficit

1.3 NORMAL ANATOMY AND PHYSIOLOGY

Table 1.2: Anterior and Posterior Circulation

The main cerebral circulation is sustained by circle of Willis formed by

Physiology of Cerebral Circulation and Cerebral Metabolism

1) Cerebral thrombosis with or without atherosclerosis

With Cerebral Ischaemia

II) Haemorrhagic Strokes

1) Hypertensive cerebral haemorrhage

Check Your Progress 1

2) Enumerate type of stroke with permanent deficit.

1.5 ISCHAEMIC CEREBROVASCULAR DISEASES

1.6 AETIOPATHOGENESIS AND PATHOPHYSIOLOGY

1.7 CLINICAL FEATURES

1.8 LABORATORY EVALUATION AND OTHER

1.9 DIFFERENTIAL DIAGNOSIS

2) Which is gold standard assessment for cerebral blood flow (CBF)?

1.10 PREVENTION OF STROKE

Agents Dosage Stroke

Aspirin 75-1300 mg/day 25

1.11 TREATMENT OF ACUTE STROKE

2) What are the surgical measures used in stroke?

3) Enumerate agents used as cytoprotective agents.

4) Name one thrombolytic agent used in acute stroke.

Management of Haemorrhagic Stroke

1.13 LET US SUM UP

1.14 KEY WORDS

Middle cerebral syndrome : Contralateral hemiplegia, hemianaesthesia with or

Mid-field infarct : Occulation of middle cerebral artery in sylvian region.

Vertebrobasilar syndrome : Manifestation by episodes of vertigo, dizziness,

1.15 ANSWERS TO CHECK YOUR PROGRESS

Check Your Progress 2

1) Antiplatelet drugs are a) Aspirin b) Ticopidine and c) Clopidrogel

3) Cytoprotective agents available are calcium channel modulators, piracetam,

1.16 FURTHER READINGS

2.2 EPIDEMIOLOGY AND CLASSIFICATION

l Common symptoms of depression

2.3 ASSESSMENT OF DEPRESSED PATIENT

2.3.1 Screening History

Table 2.2: Four Item Scale

Table 2.3: Vulnerability Factor

2.3.2 Physical Examination

Core Group of signs and symptoms are:

1) Specific alteration in mood (characterized by the feeling of sadness, hopelessness

Check Your Progress 1

Electro Convulsive Therapy

A full understanding of the patients social is as important as the understanding of his

Check Your Progress 3

2.4 IDENTIFYING OTHER PSYCHIATRIC

l Post Traumatic Stress Disorder

l Obsessive Compulsive Disorder

In generalized anxiety disorder there are symptoms which include restlessness,

Post Traumatic Stress Disorders

Obsessive Compulsive Disorder

Treatment includes use of benzodiazepines like lorazepam, buspirone, psychotherapy

In hypochondriasis, there is persistent preoccupation with possibility of having one or more

It is characterized by multiple, recurrent and frequently changing physical symptoms of several

Check Your Progress 4

a) Marked changes in sleep pattern

4) Percentage of patients of depression who fail to respond to adequate drug therapy is :