MEDICAL DISORDERS OF THE CNS

-Course outline
-CVA
 Course outline

1. Diseases of the Central nervous system: Brain

and the spinal cord
2. Peripheral nerves disorders
3. Diseases of muscle and the neuromuscular
junction
 Course outline
Brain:
1. Vascular: CVA ( stroke)
2. Infections: bacterial, viral and tuberculous meningitis
3. Epilepsy and convulsive disorders
4. Headaches
5. Parkinsonism and other movement disorders
6. Inflammatory disorders: multiple sclerosis
7. Degenerative disorders: Motor neuron disease (MND) and
Amyotropic lateral sclerosis( ALS)
8. Tumours of the CNS
9. Raised ICP
 Course outline
Spinal cord:
1. Medical disorders of the spinal cord and spinal cord
syndromes
Peripheral Nerves:
2. Peripheral neuropathies: Gullain Barre syndrome
Diseases of the neuro muscular junction:
3. Myesthenia gravis
4. LES
Muscle:
1. Myopathies
 objectives
1. Understand the Basic anatomy and physiology
of the CNS
2. Understand the Approach to the patient
presenting with neurological symptoms
3. To understand the Etiology, pathophysiology,
clinical presentation, diagnosis and treatment of
common medical disorders of central and
peripheral nervous system
 Introduction
Approach to the patient presenting with neurological symptoms
1. Focused/ detailed hx and P/E
2. Clinical impression: hemiplegia, paraplegia, monoplegia,
altered mental status
3. Anatomic diagnosis: localize the lesion:
- Brain
- Spinal cord
- Peripheral nerve
- Neuromuscular junction
- Muscle
 Introduction
4. Define the pathophysiology
- what pathologies /etiologies can affect that particular
location of the nervous system?
- vascular
- infection
- inflammatory
- degenerative disease
- Tumour
- Metabolic
5. Diagnosis and differential diagnosis
Vascular disorders of the CNS: CVA (stroke)

• Definition, classification, pathophysiology

• Epidemiology, risk factors
• Clinical presentation, stroke syndromes
• Investigations
• Treatment: acute, long term, rehabilitation,
complications
• Stroke prevention: primary, secondary
 CVA
• A stroke, or cerebrovascular accident, is
defined as the abrupt onset of a neurologic
deficit that is attributable to a focal vascular
cause (ABRUPT onset: ‘as if the patient was "struck
by the hand of God’’
 Stroke: classification
• Stroke is classified into two major types:
1. Brain ischemia (80%): due to CNS vascular occlusion:
- Thrombosis
- Embolism
- Systemic hypoperfusion causing brain ischemia

2. Brain hemorrhage (20%): due to intracerebral

(intraparenchymal) hemorrhage or subarachnoid hemorrhage
• Stroke has occurred if the neurologic signs and symptoms last
for >24 h
 Stroke classification
Transient ischemic attack (TIA):
• Older definition:
A diagnosis of TIA requires that all neurologic signs and
symptoms resolve within 24 h
• Most TIA resolve within 1hr
• NB: The risk of stroke after a TIA is ~10–15% in the first 3
months, with most events occurring in the first 2 days.
Therefore, Since etiologies for stroke and TIA are identical,
evaluation for TIA is similar to that of ischemic stroke
TIA: Current definition:
• TIA is now defined as a transient episode of neurologic
dysfunction caused by focal brain, spinal cord, or retinal
ischemia, without acute infarction.
• This tissue-based definition of TIA relies on the absence
of end-organ injury as assessed by imaging or other
techniques.
• The proposed advantages of the tissue-based definition
are that the defined end point is biological (tissue injury)
rather than the previous arbitrary (24 hours) definition.
 Ischaemic stroke
pathophysiology
• Results from Acute occlusion of an intracranial
vessel causing reduction in blood flow to the
brain region it supplies
• A fall in cerebral blood flow to zero causes
death of brain tissue within 4–10 min
• If blood flow is restored prior to a significant
amount of cell death, the patient may
experience only transient symptoms, i.e., a TIA
 Ischaemic stroke
• Ischemic penumbra: Tissue surrounding the
core region of infarction. This tissue is ischemic
but reversible if blood flow is restored fast
• But will eventually infarct if no change in flow
occurs,
• Saving the ischemic penumbra is the goal of
acute treatment of stroke (establish blood flow
within < 3hrs)
 Ischaemic stroke: pathophys…..
The cascade of cerebral ischemia:
• Reduction in blood supply starving neurons of
glucose, which in turn results in failure of
mitochondria to produce energy(ATP)
• mitochondrial dysfunction leads to production of
Free radicals
• Free radicals cause catalytic destruction of
membranes and damage other vital functions of cells
CELL DEATH
Ischaemic stroke: pathophysiology
• Focal cerebral infarction occurs via two
distinct pathways
1. Necrotic pathway (main pathway)
There is rapid, cellular cytoskeletal
breakdown due principally to energy failure
of the cell;
2. Apoptotic pathway :
cells become programmed to die
 Ischaemic stroke: pthophys……
• Fever and hyperglycemia dramatically
worsens ischemia: suppress fever and prevent
hyperglycemia as much as possible.
 Ischaemic stroke: etiology
1. Thrombosis:
Refers to local in situ obstruction of an artery.
The obstruction occurs due to disease of the
arterial wall such as
- Arteriosclerosis
- Dissection
- Fibromuscular dysplasia
- Carotid artherosclerosis
 Ischemic stroke: etiology
2. Embolism :
Vascular occlusion from embolism occurs when particles of
debris originating elsewhere block arterial access to a
particular brain region examples:
Main source is Cardio-embolism:
- In Atrial fibrillation
- Mural atrial or ventricular thrombus: in myocardial infarction
or stasis in markedly reduced chamber contractility
- Bacterial endocarditis
- Prosthetic valves
 Ischemic stroke: etiology
3. Systemic hypo-perfusion
Often manifests as syncope but can present as a stroke syndrome
4. Other less common causes of ischemic stroke( esp in the young)
- Hypercoagulable disorders
- CNS Vasculitis
- Subarachnoid hemorrhage vasospasm
- Drugs: cocaine, amphetamine (vasospasms)
- Arterio-venous abnormalities such as Moya moya disease
- Cerebral vein and Venous sinus thrombosis
 Risk factors for ischemic stroke
Non modifiable modifiable
• Age • Hypertension
• Gender(male>females) • Heart disease(atrial fib, ccf)
• Race( higher in Asian) • Diabetes
• Hyperlipidemia
• Smoking
• Excess alcohol consumption
• Polycythemia
• Oral contraceptives
 Clinical presentation
• Common neurological Deficits: hemiplegia,
higher cerebral function deficit, brainstem
symptoms, hemianopia
• Clinically, stroke can either be:
1. Complete: focal deficit is persistent, not
worsening
2. Evolving: focal deficit continues to worsen after
6 hrs of onset
3. TIA
 Clinical presentation
• The pattern of Neurological deficits vary according to the
vessel affected and the vascular territory, described as
Stroke syndromes:
1. Anterior circulation syndrome
(carotid artery middle cerebral artery  anterior cerebral
artery)
2. Posterior circulation syndrome( posterior cerebral artery,
Vertebral artery, Posterior Inferior Cerebellar Arteries and
basilar artery)
3. Lacunar vessels: very localized neurological deficits, Pure
motor stroke
 Lateral aspect:
middle cerebral artery territory
 Investigations
1. What type of stroke: imaging of the brain: CT
scan/ MRI
2. What is the etiology: Heart and carotid artery
Ecg, Echocardiogram,
carotid doppler U/S, Carotid angiography
MRA( MR Angiography if arterial venous
malformations suspected)
3. What are the risk factors/rare causes of stroke:
- CBC, (polycythemia, thrombocytopenia, thrombocytosis
- lipid profile
- blood glucose(DM)
- Coagulation system: clotting screen, thrombophilia
screen( fibrinogen, protein S/C, antothrombin iii, Factor V
leiden)
- Screen for CNS or systemic vasculitidis ( ANA, Ds DNA,
ANCA, PANCA)
- Sickle cell testing
 Treatment of sichemic stroke
• Emergency care: airway maintenance, cardiovascular support, and
rapid transport to the nearest acute stroke care facility ( a facility
with neurology, neurosurgery, neuroradiology, and critical care)
• Acutely ( within 3 hrs) : goal is revascularization to limit stroke
extension to the penumbra:
- Thrombolysis if no C/I
- Interventional : Carotid angiography and endarterectomy in
significant carotid stenosis

• NB; anticoagulation is only indicated if the etiology of the stroke is

cardiac ( AF/ mural thrombus)
 ischemic stroke: Treatment:
• In Patients presenting later than 3hrs after ischemic
stroke, the goal is:
1. Preventing and managing complications
2. Reducing the patients disability- nursing and
rehabilitation
3. Preventing a recurrence: secondary prevention:
Antiplatelet therapy: aspirin75-325mg/day ( or other
antiplatelets clopidogrel, dypiridamole)
- Statins - role of statins in secondary prevention of
stroke : High dose statins e.g Artovastain 40-80mg/day
 Ischemic Stroke: RX
• Managing the risk factors: dyslipidemia,
cardiac disease( IHD, MI, Low EF) etc
• Blood pressure management after ischemic
stroke
• Blood glucose - maintain normoglycemia
• Hydration and oxygenation
• Treat fever because it worsens the stroke.
 Stroke:RX
Blood pressure management after ischemic stroke
• Blood vessels distal to the obstruction are dilated.
Blood flow in these dilated vessels is thought to be
dependent upon the systemic blood pressure.
Rapidly Lowering the systemic bps in patients with
acute ischemic stroke has been associated with
clinical deterioration.
 Stroke RX: BP lowering
• Most consensus guidelines recommend that
BP NOT be treated acutely in the patient with
ischemic stroke unless the hypertension is
extreme (systolic BP>220 mmHg or diastolic
BP>120 mmHg)
• When treatment is indicated, cautious
lowering of BP by abt 15% during the first 24
hours after stroke onset is suggested
 Complications of stroke
• Pneumonia
• Seizures
• Pressure sores
• Urinary tract infections( catheterized)
• Pressure sores
• Constipation/ urinary retention
• Deep venous thrombosis
• Dehydration and electrolyte abnormalities
 Hemorrhagic stroke

• Intracranial hemorrhage can be:

- Intracebral
- Subarachnoid
- Subdural
 Intracerebral hemorrhage(ICH)
• ICH Results from rupture of a vessel within the brain
parenchyma resulting in an acute focal stroke
• Entry of blood into the brain parenchyma during
intracerebral hemorrhage causes immediate cessation of
function in that area
• Cerebral edema forms around the clot: both edema and
hematoma acts as mass lesion causing cerebral ischemia
The mass may be large enough to cause raised ICP; midline
shifts and even coning and rapid death
• Neurologic symptoms usually increase gradually over
minutes or a few hours
 ICH: Etiology
• The most common causes of ICH are:
- Hypertension
- Trauma
- Bleeding disorders
- Anticoagulation therapy
- Thrombolytic therapy
- Illicit drug use (mostly amphetamines and cocaine)
- Vascular malformations
- Amyloid angiopathy
 ICH: Etiology
• Less frequent causes include:
- Bleeding into tumors
- Aneurysmal rupture
- Vasculitis
- Hemorrhagic infarctions (Hemorrhage may occur in
area of infarction)
- Carvenous hemangiomas
- Berry anneurysms ( esp around circle of willis)
- Alcohol Abuse
 ICH: Treatment
• Initial goals of treatment include preventing
hemorrhage extension, prevention and
management of secondary brain injury 
• Emergency care: airway maintenance,
cardiovascular support, and rapid transport to
the nearest acute stroke care facility
 ICH: Treatment
• In the acute phase of ICH, patients may require:
- Intubation and mechanical ventilation
- Anticoagulation reversal
- Blood pressure control
- Interventions for elevated intracranial
pressure and/or mass effect ( mannitol,
hyperventilation)
- Treatment for seizures
 ICH: Treatment
• Smaller hematomas do not require
intervention, they are gradually absorbed
• Large intracerebral haematomas and patients
with marked neurological impairment require
urgent neurosurgical consultation

Neurosurgical intervention: Ventriculostomy or

surgical hematoma evacuation
 Subarachnoid hemorrhage(SAH)
• Rupture of arterial aneurysms is the major cause of subarachnoid
hemorrhage (SAH)
• Aneurysm rupture releases blood directly into the cerebrospinal fluid
(CSF) under arterial pressure
• The blood spreads quickly within the CSF, rapidly increasing intracranial
pressure
• Death or deep coma ensues if the bleeding continues
• The bleeding usually lasts only a few seconds but rebleeding is common
• With causes of SAH other than aneurysm rupture (eg, vascular
malformations, bleeding diatheses, trauma, amyloid angiopathy, and
illicit drug use), the bleeding is less abrupt and may continue over a
longer period of time
 SAH
• Symptoms of SAH begin abruptly, occurring at night in 30% of
cases
• The primary symptom is a sudden, severe headache (97% of cases)
classically described as the "worst headache of my life"
• The headache is lateralized in 30% of patients, predominantly to
the side of the aneurysm
• The onset of the headache may or may not be associated with a
brief loss of consciousness, seizure, nausea, vomiting, focal
neurologic deficit, or stiff neck
• There are usually no important focal neurologic signs at
presentation unless bleeding occurs into the brain and CSF at the
same time (meningo-cerebral hemorrhage)
 Hemorrhagic CVA: investigation

As for ischemic stroke above, but once an

intracerebral or sub-arachnoid hemorrhage is
identified in the initial imaging:

MRI/MRA (contrast angiography) is

recommended to identify the source of the
bleeding and guide intervention
 BP in hemorrhagic stroke
• Lowering BP must take into account :
- The potential benefits (reducing further bleeding)
- And risks ( reducing cerebral perfusion further worsen
ischemia)
• Systolic BP of >150 mm Hg, acute lowering of SBP to abt 140
mm Hg is thought to be safe
• Choice of BP lowering drug:
First line - Intravenous labetalol: with Continous BP monitoring,
stop labetalol when achieve desired BP 
Other first- line agents include: nitroglycerin, and intravenous
nicardipine 
Hemorrhagic stroke: Neurosurgeon consult

Treatment of intracranial hemorrhage often

require a neurosurgical intervention
• Urgent Neurosurgical consult for:
- Large Intracerebral hemorrhages with mass
effect and marked neurological impairment
- Subdural hemorrhage
- Subarachnoid hemorrhage