2010

NEUROLOGY

SANKET
SHAH
(KESAR SAL)
Available on www.mysarthee.co.cc
 NORMAL CSF

Constituent Conventional Units

Glucose 40–70 mg/dL
Lactate 10–20 mg/dL
Total protein
Lumbar 15–50 mg/dL
Cisternal 15–25 mg/dL
Ventricular 6–15 mg/dL
Albumin 6.6–44.2 mg/dL
IgG 0.9–5.7 mg/dL
IgG indexb 0.29–0.59

Oligoclonal bands <2 bands not present in

(OGB) matched serum sample
Ammonia 25–80 g/dL

CSF pressure 50–180 mmH2O

CSF volume (adult) ~150 mL

Red blood cells 0
Leukocytes
Total 0–5 mononuclear cells per
mm3

Differential
Lymphocytes 60–70%
Monocytes 30–50%
Neutrophils None
a
Since cerebrospinal fluid concentrations are equilibrium values,
measurements of the same parameters in blood plasma
obtained at the same time are recommended. However, there is
a time lag in attainment of equilibrium, and cerebrospinal levels
of plasma constituents that can fluctuate rapidly (such as
plasma glucose) may not achieve stable values until after a
significant lag phase.
b
IgG index = CSF IgG(mg/dL) x serum albumin(g/dL)/Serum
IgG(g/dL) x CSF albumin(mg/dL).

CSF IN BACTERIAL
MENINGITIS
The diagnosis of bacterial meningitis is made by


examination of the CSF

 In an immunocompetent patient with

1.no known history of recent head trauma,

2. a normal level of consciousness, and
3.no evidence of papilledema or focal neurologic
deficits,
it is considered safe to perform LP without prior
neuroimaging studies.
 If LP is delayed in order to obtain neuroimaging

studies, empirical antibiotic therapy should be initiated after

blood cultures are obtained.

1 Opening >180 mmH2O

pressure (90%)

2 White blood 10/uL to 10,000/uL; neutrophils predominate

cells (90%)
3 Red blood Absent in nontraumatic tap
 cells
4 Glucose <40 mg/Dl
5 CSF/serum <0.4
glucose (60%)
6 Protein >45 mg/dL
(90%)
7 Gram's stain Positive in
(>60%)
8 Culture Positive in
(>80%)
9 Latex May be positive in patients with meningitis due
agglutinatio to S. pneumoniae, N. meningitidis, H.
n influenzae type b, E. coli, group B streptococci
10 Limulus Positive in cases of gram-negative meningitis
lysate
11 PCR Detects bacterial DNA
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  Use of the CSF/serum glucose ratio corrects for
hyperglycaemia that may mask a relative decrease in the
CSF glucose concentration.
 The CSF glucose concentration is low when the
CSF/serum glucose ratio is <0.6.
 A CSF/serum glucose ratio <0.4 is highly suggestive of
bacterial meningitis but may also be seen in other
conditions, including fungal, tuberculous, and carcinomatous
meningitis.

 The Limulus amebocyte lysate assay is a rapid diagnostic

test for the detection of gram-negative endotoxin in CSF and
thus for making a diagnosis of gram-negative bacterial
meningitis.
 The test has a specificity of 85–100% and a sensitivity
approaching 100%. Thus, a positive Limulus amebocyte
lysate assay occurs in virtually all patients with gram-
negative bacterial meningitis, but false positives may occur.

1. INTRO
Acute infections of the nervous system are among the most
important problems in medicine because early recognition, efficient
decision-making, and rapid institution of therapy can be lifesaving.

2. DEFINITION
• Bacterial meningitis is an Acute purulent infection within the
subarachnoid space.
 • It is associated with a CNS inflammatory reaction that may
result in decreased consciousness, seizures, raised intracranial
pressure (ICP), and stroke.
3. EPIDEMIOLOGY
Currently, the organisms most commonly responsible for community-
acquired bacterial meningitis are
• Streptococcus pneumoniae (~50%),
• N. meningitidis (~25%),
• Group B streptococci (~15%),
• Listeria monocytogenes (~10%).
• H. influenzae now accounts for <10% of cases of bacterial
meningitis in most series.
4. ETIOLOGY
• S. pneumoniae
the most common cause of meningitis in adults >20 years of
age
Predisposing factors
1) pneumococcal pneumonia.
2) coexisting acute or chronic pneumococcal sinusitis or
otitis media,
3) alcoholism,
4) diabetes,
5) splenectomy,
6) hypogammaglobulinemia,
7) complement deficiency,
8) head trauma with basilar skull fracture and CSF
rhinorrhea.

• N. Meningitides
children and young adults between the ages of 2 and 20.
The risk of invasive disease following nasopharyngeal colonization
depends on both bacterial virulence factors and host immune
defense mechanisms
Individuals with deficiencies of any of the complement
components, including properdin, are highly susceptible to
meningococcal infections.
• Enteric gram-negative bacilli
common cause of meningitis in individuals with chronic and
debilitating diseases such as diabetes, cirrhosis, or alcoholism and
in those with chronic urinary tract infections
Gram-negative meningitis can also complicate neurosurgical
procedures, particularly craniotomy.

• Group B streptococcus,
previously responsible for meningitis predominantly in neonates,
but it has been reported with increasing frequency in individuals
>50 years of age, particularly those with underlying disease
• L. Monocytogenes
important cause of meningitis in neonates (<1 month of age),
pregnant women, individuals >60 years, and
immunocompromised individuals of all ages.
Foodborne human listerial infection

• H. influenzae type b
meningitis in children has declined dramatically since the
introduction of the Hib conjugate vaccine
 More frequently, H. influenzae causes meningitis in unvaccinated

children and adults.

• Staphylococcus aureus and coagulase-negative staphylococci

important causes of meningitis that occurs following invasive
neurosurgical procedures, particularly shunting procedures for
hydrocephalus

5. PATHOPHYSIOLOGY

REFFER HARRISON FIGURE 376-2

6. CLINICAL PRESENTATIONS
• PRESENTATION
an acute fulminant illness that progresses rapidly in a few hours
1)

OR
2) subacute infection that progressively worsens over several
days
• CLASSICAL TRIAD
1) fever,
2) headache,
3) nuchal rigidity
• OTHER IMPORTANT
1) decreased level of consciousness
2) Nausea,
3) projectile vomiting,
4) photophobia
• Seizures
1) Focal
2) Generalised
• RAISED ICP
1) major cause of obtundation and coma
2) 90% of patients will have a CSF opening pressure >180 mmH2O,

and 20% have opening pressures >400 mmH2O.

3) deteriorating or reduced level of consciousness,
4) papilledema,
5) dilated poorly reactive pupils,
6) sixth nerve palsies,
7) decerebrate posturing,
8) Cushing reflex (bradycardia, hypertension, and irregular
respirations).
9) CEREBRAL HERNIATION as a complication
• Specific clinical features
1) rash of meningococcemia, which begins as a diffuse
erythematous maculopapular rash resembling a viral exanthem;
however, the skin lesions of meningococcemia rapidly become
petechial. Petechiae are found on the trunk and lower extremities,
in the mucous membranes and conjunctiva, and occasionally on
the palms and soles
.
 2) RICKETTISIAL RASH-characteristic rash within 96 h of the onset
of symptoms. The rash is initially a diffuse erythematous
maculopapular rash that may be difficult to distinguish from that
of meningococcemia. It progresses to a petechial rash, then to a
purpuric rash and, if untreated, to skin necrosis or gangrene. The
color of the lesions changes from bright red to very dark red, then
yellowish-green to black. The rash typically begins in the wrist and
ankles and then spreads distally and proximally within a matter of
a few hours, involving the palms and soles

7. DIAGNOSIS
• CSF
 The diagnosis of bacterial meningitis is made by

examination of the CSF

 In an immunocompetent patient with

4.no known history of recent head trauma,

5. a normal level of consciousness, and
6.no evidence of papilledema or focal neurologic
deficits,
it is considered safe to perform LP without prior
neuroimaging studies.
 If LP is delayed in order to obtain neuroimaging

studies, empirical antibiotic therapy should be initiated after

blood cultures are obtained.

1 Opening >180 mmH2O

pressure (90%)

2 White blood 10/uL to 10,000/uL; neutrophils predominate

cells (90%)
3 Red blood Absent in nontraumatic tap
cells
4 Glucose <40 mg/Dl
5 CSF/serum <0.4
glucose (60%)
6 Protein >45 mg/dL
(90%)
7 Gram's stain Positive in
 (>60%)
8 Culture Positive in
(>80%)
9 Latex May be positive in patients with meningitis due
agglutinatio to S. pneumoniae, N. meningitidis, H.
n influenzae type b, E. coli, group B streptococci
10 Limulus Positive in cases of gram-negative meningitis
lysate
11 PCR Detects bacterial DNA
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 Use of the CSF/serum glucose ratio corrects for
hyperglycaemia that may mask a relative decrease in the
CSF glucose concentration.
 The CSF glucose concentration is low when the
CSF/serum glucose ratio is <0.6.
 A CSF/serum glucose ratio <0.4 is highly suggestive of
bacterial meningitis but may also be seen in other
conditions, including fungal, tuberculous, and carcinomatous
meningitis.

 The Limulus amebocyte lysate assay is a rapid diagnostic

test for the detection of gram-negative endotoxin in CSF and
thus for making a diagnosis of gram-negative bacterial
meningitis.
 The test has a specificity of 85–100% and a sensitivity
approaching 100%. Thus, a positive Limulus amebocyte
lysate assay occurs in virtually all patients with gram-
negative bacterial meningitis, but false positives may occur.
• NEURO IMAGINNING STUDY
MRI is preferred over CT because of its superiority in
demonstrating areas of cerebral edema and ischemia.
diffuse meningeal enhancement is often seen after the
administration of gadolinium
• BIOPSY
Petechial skin lesions, if present, should be biopsied. The rash of
meningococcemia results from the dermal seeding of organisms
with vascular endothelial damage, and biopsy may reveal the
organism on Gram's stain.

8. DIFFERENTIAL DIAGNOSIS
1. Viral meningoencephalitis, and particularly herpes simplex
virus (HSV) encephalitis
2. Rickettsial disease can resemble bacterial meningitis
3. Ehrlichioses
4. Focal suppurative CNS infections , including subdural and
epidural empyema and brain abscess
5. Subarachnoid hemorrhage
6. chemical meningitis due to rupture of tumor contents into the
CSF
7. sarcoid, systemic lupus erythematosus (SLE), and Behçet's
syndrome

9. TREATMENT
• GOAL
Bacterial meningitis is a medical emergency.
The goal is to begin antibiotic therapy within 60 min of a patient's
arrival in the emergency room
• Empirical antimicrobial therapy
initiated in patients with suspected bacterial meningitis before the
results of CSF Gram's stain and culture are known
 Antibiotics Used in Empirical Therapy of Bacterial Meningitis
and Focal CNS Infectionsa

Indication Antibiotic
1. Preterm infants Ampicillin + Cefotaxime
to infants <1
month
2. Infants 1–3 Ampicillin + Cefotaxime or
mos ceftriaxone
3. Immunocompe vancomycin + Cefotaxime or
tent children >3 ceftriaxone
mos and adults
<55
4. Adults >55 and Ampicillin + cefotaxime or ceftriaxone
adults of any age + vancomycin
with alcoholism or
other debilitating
illnesses
5. Hospital- Ampicillin + ceftazidime +
acquired vancomycin
meningitis,
posttraumatic or
postneurosurgery
meningitis,
neutropenic
patients, or
patients with
impaired cell-
mediated
immunity

Total Daily Dose and Dosing Interval

Antimicr Child (>1 month) Adult
obial
Agent
Ampicillin 200 (mg/kg)/d, q4h 12 g/d, q4h
Cefotaxim 200 (mg/kg)/d, q6h 12 g/d, q6h
e
Ceftriaxon 100 (mg/kg)/d, q12h 4 g/d, q12h
e
Ceftazidi 150 (mg/kg)/d, q8h 6 g/d, q8h
 Antibiotics Used in Empirical Therapy of Bacterial Meningitis
and Focal CNS Infectionsa

Indication Antibiotic
1. Preterm infants Ampicillin + Cefotaxime
to infants <1
month
2. Infants 1–3 Ampicillin + Cefotaxime or
mos ceftriaxone
3. Immunocompe vancomycin + Cefotaxime or
tent children >3 ceftriaxone
mos and adults
<55
4. Adults >55 and Ampicillin + cefotaxime or ceftriaxone
adults of any age + vancomycin
with alcoholism or
other debilitating
illnesses
5. Hospital- Ampicillin + ceftazidime +
acquired vancomycin
meningitis,
posttraumatic or
postneurosurgery
meningitis,
neutropenic
patients, or
patients with
impaired cell-
mediated
immunity
me
Vancomyc 60 (mg/kg)/d, q6h 2 g/d, q12h
in

• Specific Antimicrobial Therapy

Meningococcal Meningitis
o Although ceftriaxone and cefotaxime provide adequate
empirical coverage for N. meningitidis, penicillin G remains the
 antibiotic of choice for meningococcal meningitis caused by
susceptible strains

Pneumococcal Meningitis
o Antimicrobial therapy of pneumococcal meningitis is initiated
with a cephalosporin (ceftriaxone, cefotaxime, or cefepime)
and vancomycin
o A 2-week course of intravenous antimicrobial therapy is
recommended for pneumococcal meningitis.
o Patients with S. pneumoniae meningitis should have a repeat

LP performed 24–36 h after the initiation of antimicrobial

therapy to document sterilization of the CSF
Listeria Meningitis
o Meningitis due to L. monocytogenes is treated with ampicillin
for at least 3 weeks
o The combination of trimethoprim [10–20 (mg/kg)/d] and
sulfamethoxazole [50–100 (mg/kg)/d] given every 6 h may
provide an alternative in penicillin-allergic patients.
Staphylococcal Meningitis
o Meningitis due to susceptible strains of S. aureus or coagulase-
negative staphylococci is treated with nafcillin
o Vancomycin is the drug of choice for methicillin-resistant
staphylococci and for patients allergic to penicillin.
o CSF should be monitored during therapy. If the CSF is not
sterilized after 48 h of intravenous vancomycin therapy, then
either intraventricular or intrathecal vancomycin, 20 mg once
daily, can be added.
Gram-Negative Bacillary Meningitis
o The third-generation cephalosporins—cefotaxime, ceftriaxone,
and ceftazidime—are equally efficacious for the treatment of
gram-negative bacillary meningitis, with the exception of
meningitis due to P. aeruginosa, which should be treated with
ceftazidime, cefepime, or meropenem
o A 3-week course of intravenous antibiotic therapy is
recommended for meningitis due to gram-negative bacilli.

• ADJUNCT THERAPY
 Dexamethasone exerts its beneficial effect by inhibiting the
synthesis of IL-1 and TNF at the level of mRNA, decreasing CSF
outflow resistance, and stabilizing the blood-brain barrier.
The rationale for giving dexamethasone 20 min before antibiotic
therapy is that dexamethasone inhibits the production of TNF by
macrophages and microglia only if it is administered before these
cells are activated by endotoxin.

• INCREASED INTRACRANIAL PRESSURE

Emergency treatment of increased ICP includes
1) elevation of the patient's head to 30–45°,
2) intubation and hyperventilation (PaCO2 25–30 mmHg),

3) mannitol.

10. PROGNOSIS
• MORTALITY
 Mortality is 3–7% for meningitis caused by H. influenzae, N.
meningitidis, or group B streptococci;
 15% for that due to L. monocytogenes;
 20% for S. pneumoniae.
• SEQUELE
Moderate or severe sequelae occur in ~25% of survivors, although
the exact incidence varies with the infecting organism.
Common sequelae include
i. decreased intellectual function,
ii. memory impairment,
iii. seizures,
iv. hearing loss and dizziness,
v. gait disturbances.

Neurocysticercosis
INTRO
 • Neurocysticercosis is the most common parasitic disease of the CNS
worldwide.
• Humans acquire cysticercosis by the ingestion of food contaminated with
the eggs of the parasite T. solium.

Clinical Presentation
1. The most common manifestation of neurocysticercosis is new-onset
partial seizures with or without secondary generalization.
2. When present in the subarachnoid or ventricular spaces, cysticerci can
produce increased ICP
3. Spinal cysticerci can mimic the presentation of intraspinal tumors.

Diagnosis
• The lesions of neurocysticercosis are readily visualized by MRI or CT
scans.
• A very early sign of cyst death is hypointensity of the vesicular fluid on
T2-weighted images when compared with CSF.
• Parenchymal brain calcifications are the most common finding and
evidence that the parasite is no longer viable.

Treatment
• Anticonvulsant therapy is initiated when the patient with
neurocysticercosis presents with a seizure.
• Antiepileptic therapy can be stopped once the follow-up CT scan shows
resolution of the lesion.
• Long-term antiepileptic therapy is recommended when
1)seizures occur after resolution of edema and resorption
2) calcification of the degenerating cyst.

• Cysticidal drugs accelerate the destruction of the parasites, resulting in a

faster resolution of the infection.
• albendazole 15 mg/kg per day in two doses for 8 days.
• praziquantel 50 mg/kg per day for 15 days,

ACUTE STROKE
MANAGEMENT
1. PRIMARY STEPS
• After the clinical diagnosis of stroke is made, an
orderly process of evaluation and treatment should follow
• The first goal is to prevent or reverse brain injury.
• Attend to the patient's (ABC)airway, breathing,
circulation, and treat hypoglycemia or hyperglycemia if
identified.
• Perform an emergency noncontrast head CT scan in
order to differentiate between ischemic stroke and
hemorrhagic stroke; there are no reliable clinical findings
that conclusively separate ischemia from hemorrhage,
although
1. a more depressed level of consciousness,
2. higher initial blood pressure, or
3. worsening of symptoms after onset

favor hemorrhage, and a deficit that remits suggests

ischemia.

2. Medical Support
• When ischemic stroke occurs, the immediate goal is to
optimize cerebral perfusion in the surrounding ischemic
penumbra.

• Attention is also directed toward preventing the

common complications of bedridden patients—
infections (pneumonia, urinary tract, and skin) and deep
venous thrombosis (DVT) with pulmonary embolism.
1. pneumatic compression stockings to prevent DVT;
2. subcutaneous heparin appears to be safe as well and
can be used concomitantly.

• Because collateral blood flow within the ischemic brain

is blood pressure dependent, there is controversy about
whether blood pressure should be lowered acutely.
• Blood pressure should be lowered if
 1. there is malignant hypertension
2. concomitant myocardial ischemia
3. if blood pressure is >185/110 mmHg and thrombolytic
therapy is anticipated.
• When faced with the competing demands of
myocardium and brain, lowering the heart rate with a β1-
adrenergic blocker (such as esmolol) can be a first step to
decrease cardiac work and maintain blood pressure.

• Fever is detrimental and should be treated with antipyretics

and surface cooling.

• Serum glucose should be monitored and kept at <110

mg/dL using an insulin infusion.

• Between 5 TO 10% of patients develop enough cerebral

edema to cause obtundation or brain herniation.
• Edema peaks on the second or third day but can cause mass
effect for ~10 days. The larger the infarct, the greater the
likelihood that clinically significant edema will develop.
• Water restriction and IV mannitol may be used to
raise the serum osmolarity, but hypovolemia should be
avoided as this may contribute to hypotension and
worsening infarction.
• hemicraniectomy (craniotomy and temporary removal
of part of the skull) markedly reduces mortality, and the
clinical outcomes of survivors are acceptable.
• Prophylactic suboccipital decompression of large
cerebellar infarcts before brainstem compression, is
practiced at most stroke centers

• Special vigilance is warranted for patients with

cerebellar infarction.
• Such strokes may mimic labyrinthitis because of prominent
vertigo and vomiting;
 • the presence of head or neck pain should alert the physician
to consider cerebellar stroke from vertebral artery
dissection.

3. Intravenous Thrombolysis
• recombinant tPA (rtPA)
• The time of stroke onset is defined as the

1. time the patient's symptoms began or

2. the time the patient was last seen as normal.
3. Patients who awaken with stroke have the onset
defined as when they went to bed
Administration of Intravenous Recombinant Tissue Plasminogen
Activator (rtPA) for Acute Ischemic Strokea

Indication Contraindication
Clinical diagnosis of
1. 1. Sustained BP >185/110
stroke despite treatment
2. Onset of symptoms 2. Platelets <100,000;
to time of drug 3. HCT <25%;
administration <=3 h 4. glucose <50 or >400
3. CT scan showing no mg/dL
hemorrhage or edema 5. Use of heparin within 48
of >⅓ of the MCA h and prolonged PTT, or
territory elevated INR
4. Age >=18 years 6. Recent myocardial
5. Consent by patient infarction
or surrogate 7. Prior stroke or head
injury within 3 months;
8. prior intracranial
hemorrhage
9. Major surgery in
preceding 14 days
10. Gastrointestinal
bleeding in preceding 21
days
11. Minor stroke symptoms
12. Rapidly improving
 symptoms
13. Coma or stupor
Administration of rtPA
1. Intravenous access with two peripheral IV lines (avoid
arterial or central line placement)
2. Review eligibility for rtPA
3. Administer 0.9 mg/kg intravenously (maximum 90 mg) as

10% of total dose by bolus, followed by remainder of total

dose over 1 h
4. Frequent cuff blood pressure monitoring
5. For decline in neurologic status or uncontrolled blood
pressure, stop infusion, give cryoprecipitate, and reimage
brain emergently
6. No other antithrombotic treatment for 24 h
7. Avoid urethral catheterization for >=2 h

4. Endovascular Techniques
• Ischemic stroke from large-vessel intracranial occlusion
results in high rates of mortality and morbidity.
• Occlusions in such large vessels [middle cerebral artery
(MCA), internal carotid artery(ICA), and the basilar
artery(BA)] generally involve a large clot volume and
often fail to open with IV rtPA alone.
• Endovascular mechanical thrombectomy has recently
shown promise as an alternative treatment of acute stroke
in
1. patients who are ineligible for, or have
contraindications to, thrombolytics or
2. in those who have failed to have vascular
recanalization with IV thrombolytics.
• endovascular thrombectomy device to restore patency of
occluded intracranial vessels within 8 h of ischemic
stroke symptoms.

5.Antithrombotic Treatment
Platelet Inhibition
 • Aspirin is the only antiplatelet agent that has been proven
effective for the acute treatment of ischemic stroke;

6.Neuroprotection
• Neuroprotection is the concept of providing a treatment that
prolongs the brain's tolerance to ischemia.
• Hypothermia is a powerful neuroprotective treatment in
patients with cardiac arrest and is neuroprotective in animal
models of stroke, but it has not been adequately studied in
patients with ischemic stroke.

7.Stroke Centers and Rehabilitation

• Patient care in comprehensive stroke units followed by
rehabilitation services improves neurologic outcomes
and reduces mortality.
.
•Proper rehabilitation of the stroke patient includes
early physical, occupational, and speech therapy.
• It is directed toward
1. educating the patient and family about the patient's
neurologic deficit,
2. preventing the complications of immobility
3. providing encouragement and instruction in
overcoming the deficit.

• The goal of rehabilitation is

1. to return the patient to home and
2. to maximize recovery by providing a safe, progressive
regimen suited to the individual patient.
•

8.Restraint therapy (immobilizing the

unaffected side) has been shown to improve
hemiparesis following stroke, even years following the stroke,
suggesting that physical therapy can recruit unused neural
pathways.
• This finding suggests that the human nervous system is
more adaptable than originally thought and has stimulated
active research into physical and pharmacologic strategies
that can enhance long-term neural recovery

CEREBRAL VENOUS
THROMBOSIS - MX
Medical Care
• Medical management of the patient with cerebral venous thrombosis
(CVT) is similar to that of patients with arterial stroke as far as stabilizing
the patient is concerned.
• Patients with altered mental status or hemiplegia should be given
nothing by mouth to prevent aspiration.
• Intravenous fluids should not be hypotonic solutions. Normal saline is
recommended at a rate of approximately 1000 mL in 24 hours.
• To decrease intracranial pressure, the head should be elevated 30-40° at
all times.
• supplemental oxygen only when level of consciousness is decreased.

• Seizures should be treated with appropriate anticonvulsants.

• Fosphenytoin is recommended for treatment of seizures in those

patients who require a parenteral formulation.

• Alternatively, phenobarbital or sodium valproate injection may be

utilized if the patient has allergy to phenytoin.

• Diazepam or lorazepam may be used to treat status epilepticus, but the

patient also should be given an anticonvulsant with a longer duration of

action to prevent recurrent seizures.

Specific therapy for CVT

Anti coagulation
• should be considered seriously in the management of cerebral venous
thrombosis (CVT).
• Conversion to warfarin as maintenance therapy is then suggested.
 • prevent propagation of the clot to more extensive areas of the cerebral
venous system.

Heparin
Adult
Initial infusion: 18 U/kg/h IV; aPTT checked in 6 h and q6h after any dosage
change, as well as every am;
adjust dose according to following parameters
aPTT = <1.2 times control: 80 U/kg bolus with increase of 4 U/kg/h
aPTT = 1.2-1.5 times control: 40 U/kg bolus with increase of 2 U/kg/h
aPTT = 1.5-2.3 times control: No change in infusion rate needed
aPTT = 2.3-3 times control: Decrease infusion rate by 2 U/kg/h
aPTT > 3 times control: Hold infusion for 1 h and decrease rate by 3
U/kg/h

Warfarin
• warfarin treatment should be maintained for 3-6 mo
Adult
Initial: 5 mg PO qd; adjust dose by monitoring INR (target, 2.5)

Thrombolytics
• These agents cause lysis of the clot.
• This treatment at present is limited to specialized centers but should be
considered for patients with significant deficit.

Urokinase
• Given in CVT by catheterization of venous sinus or by direct instillation at
surgery during thrombectomy.
Adult
2,50,000 U/h instilled directly or via venous sinus catheter; additional doses
of 50,000 U; total dose 1,000,000 U over 2 h

Streptokinase
Adult
Instilled directly or via venous sinus catheter

Surgical Care
• In cases of severe neurologic deterioration, open thrombectomy and
local thrombolytic therapy have been described as beneficial.
 • Recently, decompressive craniectomy has been reported as a treatment
strategy, with varied results.

Lateral medullary syndrome

DEFINITON
• Lateral medullary syndrome (also called Wallenberg
syndrome and posterior inferior cerebellar artery
syndrome{PICA}) is a disease in which the patient has a
constellation of neurologic symptoms due to injury to the
lateral part of the medulla , resulting in tissue ischemia and
necrosis.

CAUSES
occlusion of any of five vessels may be responsible—
1) vertebral,
2) posterior inferior cerebellar,
3) superior lateral medullary arteries,
4) middle lateral medullary arteries,
5) inferior lateral medullary arteries

CLINICAL FEATURES
• This syndrome is characterized by
 1. sensory deficits affecting the trunk and extremities on the
opposite side of the infarction
2. sensory deficits affecting the face and cranial nerves on
the same side with the infarct.

This crossed finding is diagnostic for the syndrome.

• On side of lesion

1) Pain, numbness, impaired sensation over half the face:

Descending tract and nucleus fifth nerve
2) Ataxia of limbs, falling to side of lesion: Uncertain—restiform
body, cerebellar hemisphere, cerebellar fibers,
spinocerebellar tract (?)
3) Nystagmus, diplopia, oscillopsia, vertigo, nausea, vomiting:
Vestibular nucleus
4) Horner's syndrome (miosis, ptosis, decreased sweating):
Descending sympathetic tract
5) Dysphagia, hoarseness, paralysis of palate, paralysis of vocal
cord, diminished gag reflex: Issuing fibers ninth and tenth
nerves
6) Loss of taste: Nucleus and tractus solitaries
7) Numbness of ipsilateral arm, trunk, or leg: Cuneate and gracile
nuclei
8) Weakness of lower face: Genuflected upper motor
neuron(UMN) fibers to ipsilateral facial nucleus

• On side opposite lesion

1) Impaired pain and thermal sense over half the body, sometimes
face: Spinothalamic tract

TREATMENT
Treatment for lateral medullary syndrome involves focusing
on
 1. relief of symptoms and
2. active rehabilitation

IMMEDIATE
1. A feeding tube inserted through the mouth or gastrostomy
may be necessary if swallowing is impaired.
2. Speech therapy may be beneficial
3. In some cases, medication may be used to reduce or
eliminate pain.
4. One of the most unique and difficult to treat symptoms that
occur due to Wallenberg syndrome are interminable,
violent hiccups. The hiccups can be so severe that patients
often struggle to eat, sleep and carry on conversations.
5. Depending on the severity of the blockage caused by the
stroke, the hiccups can last for weeks. Unfortunately there
are very few successful medications available to mediate the
inconvenience of constant hiccups.
LONG TERM
1. Long term treatment generally involves the use of blood
thinners like warfarin.
2. Patients will often remain on these medications or an aspirin
regimen for the rest of their lives in order to minimize the
risk of another stroke.
3. Other medications may be necessary in order to suppress
high blood pressure and risk factors associated with strokes.

Transient Ischemic
Attacks
DEFINITION
 • TIAs are episodes of stroke symptoms that last only briefly; the
standard definition of duration is <24 h, but most TIAs last <1 h.
• Amaurosis fugax, or transient monocular blindness, occurs from

emboli to the central retinal artery of one eye. This may indicate
carotid stenosis as the cause or local ophthalmic artery disease.
RISK
• The risk of stroke after a TIA is ~10–15% in the first 3 months,
with most events occurring in the first 2 days.
Risk Factors for Ischemic Stroke and TIA
• Identification and control of modifiable risk factors is the best
strategy to reduce the burden of stroke, and the total number of
strokes could be reduced substantially by these means

1. Hypertension
2. Atrial fibrillation
3. Diabetes
4. Smoking
5. Hyperlipidemia
6. Asymptomatic carotid
stenosis
7. Symptomatic carotid stenosis
(70–99%)
8. Symptomatic carotid stenosis
(50–69%)

CAUSES
Common Causes
Uncommon Causes
Thrombosis Hypercoagulable disorders
Lacunar stroke (small
vessel) Venous sinus thrombosis
Large vessel thrombosis
Dehydration Fibromuscular dysplasia
Embolic occlusion
Artery-to-artery Vasculitis
Carotid bifurcation
Aortic arch Cardiogenic
Uncommon Causes
Arterial dissection Mitral valve calcification
Cardioembolic Atrial myxoma
Atrial fibrillation Intracardiac tumor
Mural thrombus
Myocardial infarction Subarachnoid hemorrhage
Dilated cardiomyopathy vasospasm
Valvular lesions
Mitral stenosis Drugs: cocaine, amphetamine
Mechanical valve
Bacterial endocarditis Eclampsia
Paradoxical embolus
Atrial septal defect
Patent foramen ovale

MANAGEMENT PLAN
• FIG 364-1 HARRISON

Primary and Secondary Prevention of Stroke and TIA

General Principles
• A number of medical and surgical interventions, as well as
lifestyle modifications, are available for preventing stroke.
Atherosclerosis Risk Factors
• statin drugs reduce the risk of stroke
• patients with recent stroke or TIA - prescribe atorvastatin, 80

mg/d.
• Tobacco smoking should be discouraged in all patients
Antiplatelet Agents
• Platelet antiaggregation agents can prevent atherothrombotic
events, including TIA and stroke
• Aspirin, clopidogrel, and the combination of aspirin plus extended-
release dipyridamole are the antiplatelet agents most commonly
used for this purpose.
• Ticlopidine has been largely abandoned because of its adverse
effects.
 • The choice of antiplatelet agent and dose must balance the risk of
stroke, the expected benefit, and the risk and cost of treatment.
Anticoagulation Therapy and Embolic Stroke
• Several trials have shown that anticoagulation (INR range, 2–3) in
patients with chronic nonvalvular (nonrheumatic) atrial fibrillation
prevents cerebral embolism and is safe.
• For primary prevention and for patients who have experienced
stroke or TIA, anticoagulation with warfarin reduces the risk by
about 67%, which clearly outweighs the 1% risk per year of a
major bleeding complication.
• If the embolic source cannot be eliminated, anticoagulation should
in most cases be continued indefinitely.
• Many neurologists recommend combining antiplatelet agents with
anticoagulants for patients who "fail" anticoagulation (i.e., have
another stroke or TIA).

Weber's syndrome
INTRO
• Weber's syndrome is a form of stroke characterized by the presence of
an oculomotor nerve palsy and contralateral hemiparesis or hemiplegia.

Cause
o It is caused by midbrain infarction as a result of occlusion of the
paramedian branches of the posterior cerebral artery(PCA) or of
basilar bifurcation perforating arteries.
o Weber's Syndrome has presented as a manifestation of
decompression illness in a recreational scuba diver.[2]

Presentation
This lesion is usually unilateral and affects several structures in the midbrain
including:
Structure
Effect
damaged
1. substantia
contralateral parkinsonism
nigra
2. corticospinal contralateral hemiparesis and typical upper motor
fibers neuron findings
3. corticobulbar difficulty with contralateral lower facial muscles and
tract hypoglossal nerve functions
4. oculomotor ipsilateral oculomotor nerve palsy with a drooping
 eyelid and fixed wide pupil pointed down and out. This
nerve fibers
leads to diplopia

Benedikt syndrome
INTRO
• Benedikt syndrome,or paramedian midbrain syndrome, is a rare
type of posterior circulation stroke of the brain, with a range of
neurological symptoms affecting the midbrain, cerebellum and other
related structures

Causes
• Benedikt syndrome is caused by a lesion ( infarction, hemorrhage,
tumor, or tuberculosis) in the tegmentum of the midbrain and
cerebellum.
• Specifically, the median zone is impaired.
• It can result from occlusion of the posterior cerebral artery.

Characterization
Neuroanatomical structures affected
include CNIII nucleus,
Red nucleus,
corticospinal tracts,
brachium conjunctivum, and
cerebellum.
• It is characterized by the presence of
1)an CN III oculomotor nerve palsy and
2)contralateral hemiparesis (weakness) and
3)cerebellar ataxia including tremor.

Treatment
• Deep brain stimulation may provide relief from some symptoms of
Benedikt syndrome, particularly the tremors associated with the disorder

Foville's syndrome
INTRO
 • Foville's syndrome is caused by the blockage of the perforating
branches of the basilar artery in the pons.

Structures affected
1. the PPRF, (paramedian pontine reticular formation)
2. nuclei of cranial nerves VI and VII,
3. corticospinal tract,
4. medial lemniscus,
5. the medial longitudinal fasciculus.

Presentation
1. ipsilateral horizontal gaze palsy
2. facial nerve palsy
3. contralateral hemiparesis,
4. hemisensory loss,
5. internuclear ophthalmoplegia.

MULTIPLE
SCLEROSIS
DEFINITION
• Demyelinating disorders characterized by inflammation and
selective destruction of central nervous system (CNS) myelin. The
peripheral nervous system (PNS) is spared, and most patients
have no evidence of an associated systemic illness.
CHARACTERISTIC FEATURES
• Multiple sclerosis (MS) is characterized by a triad of inflammation,
demyelination, and gliosis (scarring);
• the course can be relapsing-remitting or progressive.
• Lesions of MS typically occur at different times and in different
CNS locations (i.e., disseminated in time and space).
EPIDEMIOLOGY
• MS is approximately threefold more common in women than men.
 • The age of onset is typically between 20 and 40 years, but the
disease can present across the lifespan.
• Geographical gradients have been repeatedly observed in MS,
with prevalence rates increasing at higher latitudes. high rates are
found throughout northern Europe, the northern United States,
and Canada. By contrast, the prevalence is low in Japan , in other
parts of Asia, in equatorial Africa, and in the Middle East.
• viral infections (e.g., poliomyelitis and measles viruses), human

herpes virus type 6 (HHV-6) or Chlamydia pneumonia, remote

Epstein-Barr virus (EBV) infection
• Evidence also supports an important genetic influence on MS

Clinical Manifestations
• The onset of MS may be abrupt or insidious.
• Clinical course of multiple sclerosis (MS).
A. Relapsing/remitting MS. (RR)
B. Secondary progressive MS. (SP)
C. Primary progressive MS. (PP)
D. Progressive/relapsing MS.(PR)

• Symptoms may be severe or seem so trivial that a patient may

not seek medical attention for months or years.
Initial Symptoms of MS

Symptom
1. Sensory loss
2. Optic neuritis
3. Weakness
4. Paresthesias
5. Diplopia
6. Ataxia
7. Vertigo
8. Paroxysmal attacks
9. Lhermitte
10. Pain
11. Dementia
12. Visual loss
Symptom
13. Facial palsy
14. Impotence
15. Myokymia
16. Epilepsy
17. Falling

• Exercise-induced weakness is a characteristic symptom of MS

• Heat sensitivity refers to neurologic symptoms produced by an
elevation of the body's core temperature. For example, unilateral
visual blurring may occur during a hot shower or with physical
exercise (Uhthoff's symptom)
• Lhermitte's symptom is an electric shock like sensation (typically
induced by flexion or other movements of the neck) that radiates
down the back into the legs. Rarely, it radiates into the arms. It is
generally self-limited but may persist for years. Lhermitte's
symptom can also occur with other disorders of the cervical spinal
cord (e.g., cervical spondylosis).

Diagnostic Criteria
Diagnostic Criteria for MS

1. Examination must reveal objective abnormalities of the CNS.

2. Involvement must reflect predominantly disease of white

matter long tracts, usually including
(a) pyramidal pathways,
(b) cerebellar pathways,
(c) medial longitudinal fasciculus,
(d) optic nerve,
(e) posterior columns.

3. Examination or history must implicate involvement of two or

more areas of the CNS.

(a). MRI may be used to document a second lesion when only one
site of abnormality has been demonstrable on examination.
• A confirmatory MRI must have either four lesions involving the
white matter or three lesions if one is periventricular in
location.
• Acceptable lesions must be >3 mm in diameter.
 (b). Evoked response testing may be used to document a second
lesion not evident on clinical examination.

4. The clinical pattern must consist of

(a) two or more separate episodes of worsening involving

different sites of the CNS, each lasting at least 24 h and occurring
at least 1 month apart, or
(b) gradual or stepwise progression over at least 6 months if
accompanied by increased IgG synthesis or two or more
oligoclonal bands.

5. The patient's neurologic condition could not better be

attributed to another disease.
Diagnostic Categories
1. Definite MS: All five criteria fulfilled.

2. Probable MS: All five criteria fulfilled except

(a) only one objective abnormality despite two symptomatic
episodes or
(b) only one symptomatic episode despite two or more objective
abnormalities.

3. At risk for MS: Criteria 1, 2, 3, and 5 fulfilled; patient has only

one symptomatic episode and one objective abnormality.

DIFFERENTIAL DIAGNOSIS
Disorders that Can Mimic MS

1. Acute disseminated encephalo myelitis (ADEM)

2. Antiphospholipid antibody syndrome
3. Behçet's disease
4. Human immunodeficiency virus (HIV) infection
5. Lyme disease
6. Neoplasms (e.g., lymphoma, glioma, meningioma)
7. Sarcoid
8. Sjögren's syndrome
9. Stroke and ischemic cerebrovascular disease
10. Syphilis
11. Systemic lupus erythematosus and related collagen vascular
disorders
12. Vitamin B12 deficiency
INVESTIGATIONS REFER DAVIDSON
MANAGEMENT REFER DAVIDSON

Migraine Headache
INTRO & TRIGGERS
• Migraine, the second most common cause of primary
headache,
• affects approximately 15% of women and 6% of men.

Symptoms Accompanying Severe Migraine Attacks

Symptom
1) Nausea
2) Vomiting
3) Diarrhea
4) Light headedness
5) Scalp tenderness
6) Visual disturbances
7) Photophobia
8) Photopsia
9) Vertigo
10) Seizure
11) Syncope
12) Alteration of consciousness
13) Confusional state
14) Paresthesias

• Headache can be initiated or amplified by various triggers,

including
 1) glare, bright lights,
2) sounds,
3) hunger;
4) excess stress;
5) physical exertion;
6) stormy weather or
7) barometric pressure changes;
8) hormonal fluctuations during menses;
9) lack of or excess sleep; and
10) alcohol or other chemical stimulation.
• Knowledge of a patient's susceptibility to specific
triggers can be useful in management strategies involving
lifestyle adjustments.

Diagnosis and Clinical Features

• A high index of suspicion is required to diagnose
migraine:
• migraine aura, consisting of visual disturbances with
flashing lights or zigzag lines moving across the visual field
or of other neurologic symptoms, is reported in only 20–25%
of patients
• Patients with episodes of migraine that occur daily or
near-daily are considered to have chronic migraine .
• Migraine must be differentiated from tension-type
headache , the most common primary headache syndrome
seen in clinical practice.
• Migraine at its most basic level is headache with
associated features, and tension-type headache is
headache that is featureless. Most patients with disabling
headache probably have migraine.
Simplified Diagnostic Criteria for Migraine

• Repeated attacks of headache lasting 4–72 h in patients

with a normal physical examination,
• no other reasonable cause for the headache,
• and:
At least 2 of the following Plus at least 1 of the
features: following features:
1. Unilateral pain 1. Nausea/vomiting
2. Throbbing pain 2. Photophobia and
phonophobia
3. Aggravation by
movement
4. Moderate or severe
intensity

• Patients with acephalgic migraine experience recurrent

neurologic symptoms, often with nausea or vomiting, but
with little or no headache.
• Vertigo can be prominent; it has been estimated that one-
third of patients referred for vertigo or dizziness have a
primary diagnosis of migraine.

MANAGEMENT-
• refer KDT

CLUSTER HEADACHE

Cluster Headache
1. Gender M>F
2. Pain

Type Stabbing, boring

Severity Excruciating
Site Orbit, temple
3. Attack 1/alternate day– 8/d
frequency
4. Duration of 15–180 min
attack
5. Autonomic Yes
features
6. Migrainous Yes
features
7. Alcohol Yes
trigger
 Cluster Headache
8. Cutaneous No
triggers
9. Abortive • Sumatriptan injection or
treatment nasal spray
• Oxygen
10. Prophylactic • Verapamil
treatment • Methysergide
• Lithium

Toxic
headache
• Toxic headache Is usually caused by fever from acute bacterial illnesses
or from exposure to various chemicals including from fumes, pollution
and allergens.
• Causes
1) Nitrite.

2) carbon tetrachloride

3) organophosphate pesticides,

4) acetaldehyde from alcohol (a hangover)

5) Toxic shock syndrome

6) carbon monoxide poisoning.

7) amphetamines

• Treatment
Caffeine can be used to alleviate a vascular headache by constricting
dilated arteries.

CT vs MRI
CT Scans
INDICATIONS
• If initial evaluations indicate a skull fracture or intracranial
bleeding, a CT (or CAT) scan is usually ordered.
• The CT scans can reveal
1) hematomas,
2) hemorrhages, and
3) skull fractures
•giving the neurologist exactly the information necessary for
deciding if emergency treatment is needed and precisely
where.

TECHNIQUE
• a way to obtain detailed X-ray pictures of cross-sections
through the body.
ADVANTAGE
• Testing is fast and results are quick; making it exceptionally
valuable when prompt diagnosis and treatment are critical.
• Unlike some other scanning methods, the CT scan can be
taken while the patient is hooked up to IV’s or other medical
equipment.
DRAAWBACKS
• Irradiation

MRI
INDICATIONS
• Magnetic Resonance Imaging (”MRI”) is not often used in
acute head injury cases.
• After the acute phase has passed, the doctor may want an
MRI to evaluate the location and extent of brain injury to
determine further treatment and rehabilitation options.
TECHNIQUE
 • MRI uses powerful magnetic fields and the magnetic
reaction of the body’s cells to construct cross-sectional
images Similar to CT scans.
ADVANTAGE
1) Because it doesn’t use X-rays, it can be safer than CT if
multiple imaging sessions are expected.
2) Variations of MRI technology can also examine brain
functioning and identify injuries not visible in CT scans. But
even the detail available using MRI cannot detect mild
concussions.
3) It gives finer details than CT.

DRAWBACKS INCLUDE:
1) Longer to perform
2) Not as readily available as a CT scanner in most hospitals
3) Is not practical for patients hooked up to medical
equipment
4) Cannot be used if patient has metal embedded anywhere
in the body
5) Is not tolerated well by some patients because of the
confined space inside the MRI machine
6) Expensive

Alzheimer's
Disease
INTRO
• AD can occur in any decade of adulthood, but it is the most common
cause of dementia in the elderly.
Clinical Manifestations
• The cognitive changes with AD tend to follow a characteristic pattern,
beginning with memory impairment and spreading to language and
visuospatial deficits.
• In the early stages of the disease,
1) the memory loss may go unrecognized or be ascribed to
benign forgetfulness.
2) Once the memory loss begins to affect day-to-day activities the
disease is defined as MCI. Approximately 50% of MCI individuals
will progress to AD within 5 years.
3) Slowly the cognitive problems begin to interfere with daily
activities, such as keeping track of finances, following instructions
on the job, driving, shopping, and housekeeping.
• In the middle stages of AD,
1) the patient is unable to work, is easily lost and confused, and
requires daily supervision.
2) Social graces, routine behavior, and superficial conversation may
be surprisingly intact.
3) Language becomes impaired—first naming, then comprehension, and
finally fluency. In some patients, aphasia is an early and prominent
feature.
4) Apraxia emerges, and patients have trouble performing sequential
motor tasks.
5) Visuospatial deficits begin to interfere with dressing, eating,
solving simple puzzles, and copying geometric figures. Patients may
be unable to do simple calculations or tell time.
• In the late stages of the disease,
1) some persons remain ambulatory but wander aimlessly.
2) Loss of judgment, reason, and cognitive abilities is inevitable.
3) Delusions are common and usually simple in quality, such as
delusions of theft, infidelity, or misidentification.
4) Approximately 10% of AD patients develop Capgras' syndrome,
believing that a caregiver has been replaced by an impostor.
5) Some patients develop a shuffling gait with generalized muscle
rigidity associated with slowness and awkwardness of movement.
• In end-stage AD,
1) patients become rigid, mute, incontinent, and bedridden.
2) Help may be needed with the simplest tasks, such as eating,
dressing, and toilet function.
3) They may show hyperactive tendon reflexes.
4) Myoclonic jerks may occur spontaneously or in response to physical
or auditory stimulation.
5) Generalized seizures may also occur.

• death results from

1) malnutrition,
 2) secondary infections,
3) pulmonary emboli,
4) heart disease.
• The typical duration of AD is 8–10 years, but the course can range from 1
to 25 years.

DIAGNOSIS
• Early in the disease course, other etiologies of dementia should be
excluded.
• Neuroimaging studies (CT and MRI) do not show a single specific pattern
with AD and may be normal early in the course of the disease.
• As AD progresses, diffuse cortical atrophy becomes apparent, and MRI
scans show atrophy of the hippocampus .
• Imaging helps to exclude other disorders, such as primary and secondary
neoplasms, multi infarct dementia, diffuse white matter disease, and
NPH;
• it also helps to distinguish AD from other degenerative disorders with
distinctive imaging patterns such as FTD or CJD.
• Functional imaging studies in AD reveal hypoperfusion or
hypometabolism in the posterior temporal-parietal cortex
• The EEG in AD is normal or shows nonspecific slowing.
• Routine spinal fluid examination is also normal.

Treatment
• The management of AD is challenging and gratifying,
• The primary focus is on long-term amelioration of associated behavioral
and neurologic problems.
• Building rapport with the patient, family members, and other caregivers
is essential to successful management.
• In the early stages of AD, memory aids such as notebooks and posted
daily reminders can be helpful.

• Donepezil, rivastigmine, galantamine, memantine, and tacrine are the

drugs presently approved by the Food and Drug Administration (FDA) for
treatment of AD. Due to hepatotoxicity, tacrine is no longer used.

• In patients with moderately advanced AD, a prospective trial of the

antioxidants selegiline , tocopherol (vitamin E), or both, slowed
institutionalization and progression to death.
• Because vitamin E has less potential for toxicity than selegiline and is
cheaper, the doses used in this study of 1000 IU twice daily are offered
to many patients with AD.
 • Mild to moderate depression is common in the early stages of AD and
responds to antidepressants or cholinesterase inhibitors.
• Selective serotonin reuptake inhibitors (SSRIs) are commonly used due
to their low anticholinergic side effects.

• Generalized seizures should be treated with an appropriate

anticonvulsant, such as phenytoin or carbamazepine.

• The newer generation of atypical antipsychotics, such as risperidone and

olanzapine, are being used in low doses to treat these neuropsychiatric
symptoms.

EXTRA PYRAMIDAL
SYSTEM
INTRO

• The extrapyramidal system is composed of motor fibers which do not

pass through the medullary pyramids but which nevertheless exert a
measure of control over bodily movements.

BASIC PARTS

• the extrapyramidal system can be divided into three controlling systems:

1) cortically originating indirect pathways,

2) feedback loops,
3) auditory-visual-vestibular descending pathways.

Cortically Originating Indirect Descending Pathways

o At the same time signals are being transmitted over the pyramidal
system to produce a specific movement, additional signals relative to the
movement are also relayed to the basal nuclei, red nucleus, and
brainstem reticular formation.
 o The basal nuclei evaluate the command signal sent down the
pyramidal pathways and may contribute to the establishment of needed
background muscle tone for the movement. The nuclei are able to do
this in part by projecting to the red nuclei, which influence spinal cord
alpha and gamma motor neurons via rubrospinal tracts.
o Similar indirect routing to the spinal cord is achieved through
corticoreticulospinal and corticorubrospinal pathways .
o The function of these indirect pathways to the spinal cord motor
neurons may include more than providing background muscle tone for
movements directed by the motor cortex.
o Even so, because the red nucleus receives input from the basal and
cerebellar nuclei as well as direct input from the cerebral cortex, its
function may include modifying or "fine tuning" the motor neurons which
innervate the muscles involved in a given movement.

Feedback Loops

o The feedback loops described here include neural circuits in which a

signal sample is fed back to a "comparator," which is in a position to
compare the signal with some desired condition and subsequently take
steps to "adjust" or "modify" it.
o The extrapyramidal system includes two such feedback systems:
1) cortically originating extrapyramidal system feedback loops (COEPS
feedback loops)
2) proprioceptor originating extrapyramidal system feedback loops
(POEPS feedback loops).

o The CO EPS feedback loops are

1) composed of fibers originating in the motor cortex which synapse
in subcortical centers.
2) After integrating and evaluating the signals, the centers project
fibers back to the cortical source for modification.
3) In loop A the signal is "tapped off" to the corpus striatum (caudate
and putamen), which in turn project to the globus pallidus.
Pallidothalamic fibers then project to the thalamus, which completes
the loop by projecting back to the cortical source. Somewhere in this
loop the original signal sent down the pyramidal tracts is compared
and evaluated with other input relative to the movement. After
appropriate integration, modifying feedback signals are returned to
the cortex via the thalamocortical fibers.
4) In loop B the sample signal is sent to pontine nuclei for subsequent
referral to the cerebellum, where it is probably compared to
 proprioceptive input coming from muscles, tendons, and joints
involved in the movement. This input probably includes such things
as the current state of muscle tone and the relative position and
movement of the limb involved. Following integration of this input,
the cerebellum then projects its output to the thalamus (via denta-
tothalamic tracts) which then completes the loop by sending fibers
back to the cortical source through thalamocortical projections.
5) In loop C. the sample signal is sent to the substantia nigra. which
projects in turn to the corpus striatum. From here the feedback
circuit is identical to that illustrated in loop A.

o POEPS feedback loops.

1) In this system the modification is not directed back toward the
cortical source (as are the COEPS loops), but to the spinal cord motor
neurons instead.
2) The principal loop involves the relay of muscle, tendon. and joint
proprioceptive information to the cerebellum via the spinocerebellar
tracts.
3) The signals are integrated in the cerebellum and probably compared
with the intended signals sampled by corticopontocerebellar pathways.
4) It could then direct modification through its projections to the
vestibular. reticular, and rubral nuclei and their respective descending
tracts to the appropriate motor neurons of the spinal cord.

Auditory Visual Vestibular Descending Pathways

 Postural adjustments in response to auditory, visual. and vestibular

signals is an additional way to regulate the activity of spinal motor
neurons.
 Auditory and visual input to the tectal nuclei of the midbrain may be
responsible for producing reflex movements of the body in response to a
sudden sound or bright light.
 Similarly. input from the vestibular apparatus to the vestibular nuclei
and cerebellum no doubt plays a role in reflex postural adjustments
through the vestibulospinal and other tracts.

Mononeuropathy Multiplex
DEFINITION
 • Mononeuropathy multiplex refers to the multifocal involvement of
individual peripheral nerves.
• Mononeuritis multiplex more often an inflammatory cause is
responsible, and in such cases the disorder is referred to as
mononeuritis multiplex.

CAUSES
• systemic (67%) and nonsystemic (33%) vasculitis & less commonly,
vasculitic neuropathy may present as mononeuritis multiplex;

• Among the systemic vasculitis,

1)polyarteritis nodosa(PAN),
2)rheumatoid arthritis(RA),
3) systemic lupus erythematosus (SLE),
4) Churg-Strauss syndrome,
5) Wegener's granulomatosis,
6) hypersensitivity vasculitis
these are often associated with constitutional symptoms such as fever and
weight loss .
• vasculitic neuropathy
1) The common fibular nerve is affected in ~75% of patients with;
symptoms consist of a painful foot drop.
2) The ulnar, median, and radial nerves may also be involved.

Treatment
Therapy of the systemic vasculitis
• can stabilize and in some cases improve the neuropathy.
• Glucocorticoids [prednisone (1.5 mg/kg per day)] plus a cytotoxic agent
(usually oral cyclophosphamide at 2 mg/kg per day) is the treatment of
choice .
• Prednisone can be changed to an alternate-day regimen after 1 month to
minimize side effects.
• Once a clinical response is documented, prednisone may be tapered by
5 mg every 2–4 weeks.
• The cytotoxic agent is usually continued for 1 year.

Therapy of hypersensitivity vasculitis

• focused primarily upon removal of the offending antigen trigger.

Treatment of localized vasculitis

 • restricted to the peripheral nervous system can be less aggressive than
for systemic vasculitis because the risk of death from untreated disease
is very low.
• Monotherapy with either oral glucocorticoids or a brief course of
cyclophosphamide (3–6 months) may be sufficient.
.

Guillain-Barré Syndrome
DEFINITION

• Guillain-Barré syndrome (GBS) is an acute, frequently severe, and

fulminant polyradiculoneuropathy that is autoimmune in nature

Diagnostic Criteria for Guillain-Barré Syndrome

Required
1. Progressive weakness of 2 or more limbs due to
neuropathy
2. Areflexia
3. Disease course <4 weeks
1. Exclusion of other causes
• vasculitis (PAN,SLE, Churg-Strauss syndrome),
• toxins (organophosphates, lead),
• botulism,
• diphtheria,
• porphyria,
• localized spinal cord or cauda equina syndrome
Supportive
1. Relatively symmetric weakness
2. Mild sensory involvement
3. Facial nerve or other cranial nerve involvement
4. Absence of fever
5. Typical CSF profile (acellular, increase in protein level)
6. Electrophysiologic evidence of demyelination

Treatment
• In the vast majority of patients with GBS, treatment should be initiated
as soon after diagnosis as possible.
• ~2 weeks after the first motor symptoms, immunotherapy is no longer
effective.

• Either high-dose intravenous immune globulin (IVIg) or plasmapheresis

can be initiated, as they are equally effective.
• IVIg is often the initial therapy chosen because of its ease of

administration and good safety record. IVIg is administered as five daily

infusions for a total dose of 2 g/kg body weight, perhaps accounting for
the therapeutic effect.
• A course of plasmapheresis usually consists of ~40–50 mL/kg plasma

exchange (PE) four times over a week.

• treatment reduces the need for mechanical ventilation by nearly half ,
and increases the likelihood of full recovery at 1 year.

• In patients who are treated early in the course of GBS and improve,
relapse may occur in the second or third week. Brief retreatment with
the original therapy is usually effective.

• Glucocorticoids have not been found to be effective in GBS.

• Occasional patients with very mild forms of GBS, especially those who
appear to have already reached a plateau when initially seen, may be
managed conservatively without IVIg or PE.

• In the worsening phase of GBS, most patients require monitoring in a

critical care setting, with particular attention to
1. vital capacity,
2. heart rhythm,
3. blood pressure,
4. nutrition,
5. deep vein thrombosis prophylaxis,
6. cardiovascular status,
7. early consideration (after 2 weeks of intubation) of tracheotomy,

8. chest physiotherapy.
• As noted, ~30% of patients with GBS require ventilatory assistance,
sometimes for prolonged periods of time (several weeks or longer).
• Frequent turning and assiduous skin care are important, as are daily

range-of-motion exercises to avoid joint contractures

• daily reassurance as to the generally good outlook for recovery.
MYESTHENIA
GRAVIS
INTRODUCTION
• Myasthenia gravis (MG) is a neuromuscular disorder
characterized by weakness and fatigability of skeletal muscles.
• The underlying defect is a decrease in the number of available
acetylcholine receptors (AChRs) at neuromuscular junctions due
to an antibody-mediated autoimmune attack.

CLINICAL FEATURES
• MG is not rare, having a prevalence of 1–7 in 10,000.
• It affects individuals in all age groups, but peaks of incidence
occur in women in their twenties & thirties and in men in their
fifties & sixties. (20-30/50-60)
• Overall, women are affected more frequently than men, in a
ratio of ~3:2.

• The course of MG is often variable. Exacerbations and

remissions may occur, particularly during the first few years
after the onset of the disease.
• Remissions are rarely complete or permanent.

• The cardinal features are weakness and fatigability of muscles.

• The weakness increases during repeated use (fatigue) and may
improve following rest or sleep.
• The distribution of muscle weakness often has a
characteristic pattern.

1. The cranial muscles, particularly the lids and

extraocular muscles, are often involved early in the course of
MG, and diplopia and ptosis are common initial complaints.
2. Facial weakness produces a "snarling" expression when the
patient attempts to smile.
3. Weakness in chewing is most noticeable after prolonged
 effort, as in chewing meat.
4. Speech may have a nasal timbre caused by weakness of the
palate or a dysarthric "mushy" quality due to tongue weakness.
5. Difficulty in swallowing may occur as a result of weakness
of the palate, tongue, or pharynx, giving rise to nasal
regurgitation or aspiration of liquids or food.

• In ~85% of patients, the weakness becomes generalized,

affecting the limb muscles as well.
• The limb weakness in MG is often proximal and may be
asymmetric.
• Despite the muscle weakness, deep tendon reflexes are
preserved.

• If weakness remains restricted to the extraocular muscles

for 3 years, it is likely that it will not become generalized, and
these patients are said to have ocular MG.

• Motor power survey: quantitative testing of muscle strength

• Forward arm abduction time (5 min)
• Absence of other neurologic signs

INVESTIGATIONS

1 Antibodies to AChR or MuSK

• As noted above, anti-AChR antibodies are detectable in the

serum of ~85% of all myasthenic patients
• The presence of anti-AChR antibodies is virtually
diagnostic of MG, but a negative test does not exclude the
disease.

• Antibodies to MuSK have been found to be present in ~40% of

AChR antibody-negative patients with generalized MG, and their
presence is a useful diagnostic test in these patients.

2 Electrodiagnostic Testing

• Repetitive nerve stimulation often provides helpful diagnostic

evidence of MG.
 1. Anti-AChE medication is stopped 6–24 h before testing.
2. It is best to test weak muscles or proximal muscle groups.
3. Electric shocks are delivered at a rate of two or three per
second to the appropriate nerves, and action potentials are
recorded from the muscles.
4. In normal individuals, the amplitude of the(EMAP) evoked
muscle action potentials does not change at these rates of
stimulation.
5. However, in myasthenic patients there is a rapid reduction
of >10–15% in the amplitude of the evoked responses.
6. As a further test, a single dose of edrophonium may be
given to prevent or diminish this decremental response.

3 Anticholinesterase Test

• The edrophonium test is now reserved for patients with

clinical findings that are suggestive of MG but who have negative
antibody and electrodiagnostic test results.
• Edrophonium is used most commonly for diagnostic
testing
• In some cases it is helpful to use a longer-acting drug such
as neostigmine (15 mg PO), since this permits more time for
detailed evaluation of strength.

4 Single-fiber electromyography:

• blocking and jitter, with normal fiber density;

• confirmatory, but not specific

5 For ocular or cranial MG:

• exclude intracranial lesions by CT or MRI

6 Recommended laboratory tests or procedures to

guide tratment

1. CT or MRI of mediastinum ( thymoma, hyperplasia)

2. Tests for lupus erythematosus, antinuclear antibody,
rheumatoid factor, antithyroid antibodies
3. Thyroid-function tests (TFT)
4. PPD skin test (occult infection)
5. Chest radiography (tb)
6. Fasting blood glucose measurement, hemoglobin A1c (DM)
7. Pulmonary-function tests (asthama)
 8. Bone densitometry in older patients(Osteoporesis)

TREATMENT

• Virtually all myasthenic patients can be returned to full

productive lives with proper therapy.

1. Anticholinesterase Medications

• Pyridostigmine is the most widely used anticholinesterase drug.

• Treatment is begun with a moderate dose, e.g., 30–60 mg
three to four times daily.
• The frequency and amount of the dose should be tailored
to the patient's individual requirements throughout the day. For
example, patients with weakness in chewing and
swallowing may benefit by taking the medication before meals
so that peak strength coincides with mealtimes.

2. Thymectomy

• In the absence of a tumor, the available evidence suggests

that up to 85% of patients experience improvement after
thymectomy;
• It is the consensus that thymectomy should be carried out
in all patients with generalized MG who are between the ages of
puberty and at least 55 years.

3. Immunosuppression

• For the intermediate term, glucocorticoids and cyclosporine or

tacrolimus generally produce clinical improvement within a period
of 1–3 months.
• for the long-term treatment of patients with MG. The
beneficial effects of azathioprine and mycophenolate mofetil

Glucocorticoid Therapy

• The initial dose should be relatively low (15–25 mg/d)

• The dose is increased stepwise, as tolerated by the patient
 (usually by 5 mg/d at 2- to 3-day intervals), until there is marked
clinical improvement or a dose of 50–60 mg/d is reached.
• This dose is maintained for 1–3 months and then is
gradually modified to an alternate-day regimen over the
course of an additional 1–3 months;

Other Immunosuppressive Drugs

Mycophenolate mofetil
• A dose of 1–1.5 g bid is recommended.
• This drug has become the choice for long-term treatment
of myasthenic patients.
• Unfortunately, the cost of mycophenolate is still very high

AZATHIOPRENE
• An initial dose of 50 mg/d should be used to test for adverse
side effects.
• If this dose is tolerated, it is increased gradually until the white
blood count falls to ~3000–4000/uL.
• The typical dosage range is 2–3 mg/kg total body weight.

Cyclosporine and tacrolimus

• The usual dose of cyclosporine is 4–5 mg/kg per day,
• The average dose of tacrolimus is 0.1 mg/kg per day, given in
two equally divided doses
• Side effects of these drugs include hypertension and
nephrotoxicity, which must be closely monitored.

Cyclophosphamide
• a course of high-dose cyclophosphamide may induce long-
lasting (possibly permanent) benefit by "rebooting" the immune
system.

4. Plasmapheresis

• A course of five exchanges (3–4 L per exchange) is generally

administered over a 10- to 14-day period.
• Plasmapheresis produces a short-term reduction in anti-
AChR antibodies, with clinical improvement in many patients.
• It is useful as a temporary expedient in seriously affected
patients or to improve the patient's condition prior to surgery
(e.g., thymectomy).
 5. Intravenous Immunoglobulin

• The indications for the use of IVIg are the same as those
for plasma exchange
• This treatment has the advantages of not requiring special
equipment or large-bore venous access.
• The usual dose is 2 g/kg, which is typically administered over 5
days (400 mg/kg per day).
Management of Myasthenic Crisis
• Myasthenic crisis is defined as an exacerbation of weakness
sufficient to endanger life; it usually consists of respiratory
failure caused by diaphragmatic and intercostal muscle weakness.

• Crisis rarely occurs in properly managed patients.

• Treatment should be carried out in intensive care units

• The possibility that deterioration could be due to excessive
anticholinesterase medication ("cholinergic crisis") is best
excluded by temporarily stopping anticholinesterase drugs.
• The most common cause of crisis is intercurrent infection.This
should be treated immediately
• The myasthenic patient with fever and early infection
should be treated like other immunocompromised patients.
• Early and effective antibiotic therapy, respiratory
assistance, and pulmonary physiotherapy are essentials of
the treatment program.
• As discussed above, plasmapheresis or IVIg is frequently
helpful in hastening recovery.

Drugs to Avoid in Myasthenic

Patients
• As a rule, the listed drugs should be avoided
whenever possible, and myasthenic patients should
be followed closely when any new drug is introduced.

Drugs That May Exacerbate MG ( AB LMN PQ)

Antibiotics
• Aminoglycosides: e.g., streptomycin, tobramycin, kanamycin
• Quinolones: e.g., ciprofloxacin, levofloxacin, ofloxacin, gatifloxacin
• Macrolides: e.g., erythromycin, azithromycin,

Beta-blocking agents
• Propranalol, atenolol, metoprolol

Botulinum toxin
• Botox exacerbates weakness

Local anesthetics and related agents

• Procaine,
• xylocaine in large amounts
• Procainamide (for arrhythmias)

Magnesium

Nondepolarizing muscle relaxants for surgery

• D-Tubocurarine (curare),
• pancuronium, vecuronium, atracurium

Penicillamine

Quinine derivatives
• Quinine, quinidine, chloroquine, mefloquine

Drugs with Important Interactions in MG

• Cyclosporine
• Azathioprine Avoid allopurinol—combination may
result in myelosuppression.

Generalized, Tonic-Clonic Seizures

(Grand Mal)
INTRO
• Primary generalized, tonic-clonic seizures are the main seizure type in
~10% of all persons with epilepsy.
 • They are also the most common seizure type resulting from metabolic
derangements and are therefore frequently encountered in many
different clinical settings.

CLINICAL FEATURE
• The seizure usually begins abruptly without warning, although some
patients describe vague premonitory symptoms in the hours leading up
to the seizure.

• The initial phase of the seizure is usually tonic contraction of muscles

throughout the body, accounting for a number of the classic features of
the event.
1) Tonic contraction of the muscles of expiration and the larynx at
the onset will produce a loud moan or "ictal cry."
2) Respirations are impaired, secretions pool in the oropharynx, and
cyanosis develops.
3) Contraction of the jaw muscles may cause biting of the tongue.
4) A marked enhancement of sympathetic tone leads to increases in
heart rate, blood pressure, and pupillary size.
• After 10–20 s, the tonic phase of the seizure typically evolves into the
clonic phase, produced by the superimposition of periods of muscle
relaxation on the tonic muscle contraction.
• The periods of relaxation progressively increase until the end of the ictal
phase, which usually lasts no more than 1 min.

• The postictal phase is characterized by

1) unresponsiveness,
2) muscular flaccidity,
3) excessive salivation that can cause stridorous breathing and
partial airway obstruction.
4) Bladder or bowel incontinence may occur at this point.
• Patients gradually regain consciousness over minutes to hours, and
during this transition there is typically a period of postictal confusion.
• Patients subsequently complain of headache, fatigue, and muscle ache
that can last for many hours.
• The duration of impaired consciousness in the postictal phase can be
extremely long, i.e., many hours, in patients with prolonged seizures or
underlying CNS diseases such as alcoholic cerebral atrophy.

• There are many variants of the generalized tonic-clonic seizure, including

pure tonic and pure clonic seizures.
 • Brief tonic seizures lasting only a few seconds are especially noteworthy
since they are usually associated with specific epileptic syndromes
having mixed seizure phenotypes, such as the Lennox-Gastaut syndrome

INVESTIGATIONS
• Laboratory Studies
1. Routine blood studies are indicated to identify the more common
metabolic causes of seizures, such as abnormalities in electrolytes,
glucose, calcium, or magnesium, and hepatic or renal disease.
2. A screen for toxins in blood and urine should also be obtained from all
patients in appropriate risk groups, especially when no clear
precipitating factor has been identified.
3. A lumbar puncture is indicated if there is any suspicion of meningitis or
encephalitis, and it is mandatory in all patients infected with HIV, even in
the absence of symptoms or signs suggesting infection.
• Electrophysiologic Studies
1. All patients who have a possible seizure disorder should be evaluated
with an EEG as soon as possible.
2. The EEG during the tonic phase of the seizure shows a progressive
increase in generalized low-voltage fast activity, followed by generalized
high-amplitude, polyspike discharges.
3. In the clonic phase, the high-amplitude activity is typically interrupted by
slow waves to create a spike-and-wave pattern.
4. The postictal EEG shows diffuse slowing that gradually recovers as the
patient awakens.

• Brain Imaging
1. Almost all patients with new-onset seizures should have a brain
imaging study to determine whether there is an underlying structural
abnormality that is responsible.
2. MRI has been shown to be superior to CT for the detection of cerebral
lesions associated with epilepsy.
3. Functional imaging procedures such as positron emission tomography
(PET) and single photon emission computed tomography (SPECT) are
also used to evaluate certain patients with medically refractory seizures

MANAGEMENT

• Therapy for a patient with a seizure disorder is almost always multimodal

and includes
 1) treatment of underlying conditions,
2) avoidance of precipitating factors,
3) suppression of recurrent seizures by prophylactic therapy with
antiepileptic medications or surgery,
4) addressing a variety of psychological and social issues.

• Treatment of Underlying Conditions

1) If the sole cause of a seizure is a metabolic disturbance such as
an abnormality of serum electrolytes or glucose, then treatment is
aimed at reversing the metabolic problem and preventing its
recurrence.
2) If the apparent cause of a seizure was a medication (e.g.,
theophylline) or illicit drug use (e.g., cocaine), then appropriate
therapy is avoidance of the drug
3) Seizures caused by a structural CNS lesion such as a brain tumor,
vascular malformation, or brain abscess may not recur after
appropriate treatment of the underlying lesion.
• Avoidance of Precipitating Factors
1) a patient who has seizures in the setting of sleep deprivation
should obviously be advised to maintain a normal sleep schedule.
2) Many patients note an association between alcohol intake and
seizures, and they should be encouraged to modify their drinking
habits accordingly.
3) There are also relatively rare cases of patients with seizures that
are induced by highly specific stimuli such as a video game monitor,
music, or an individual's voice ("reflex epilepsy").
4) If there is an association between stress and seizures, stress
reduction techniques such as physical exercise, meditation, or
counseling may be helpful.
• When to Initiate Antiepileptic Drug Therapy
1) patient with recurrent seizures of unknown etiology
2) a known cause that cannot be reversed.

• Antiepileptic Drug Selection for Generalized Seizures

1) Valproic acid and lamotrigine are currently considered the best
initial choice for the treatment of primary generalized, tonic-clonic
seizures.
2) Phenytoin, followed by topiramate, carbamazepine, and
zonisamide are suitable alternatives.
Valproic acid 20–60 mg/kg; bid-qid
Lamotrigine 150–500 mg/d; bid
 Phenytoin 3–6 mg/kg, adult; 4–8 mg/kg, child; qd-bid
• When to Discontinue Therapy
o Overall, about 70% of children and 60% of adults who have their
seizures completely controlled with antiepileptic drugs can eventually
discontinue therapy.
• Treatment of Refractory Epilepsy
o Approximately one-third of patients with epilepsy do not respond to
treatment with a single antiepileptic drug, and it becomes necessary
to try a combination of drugs to control seizures

STATUS
EPILEPTICUS
DEFINITION
• Status epilepticus refers to continuous seizures or
repetitive, discrete seizures with impaired
consciousness in the interictal period.
• The duration of seizure activity sufficient to meet the
definition of status epilepticus has traditionally been
specified as 15–30 min.
• However, a more practical definition is to consider
status epilepticus as a situation in which the duration of
seizures prompts the acute use of anticonvulsant
therapy. For GCSE, this is typically when seizures last
beyond 5 min.

SUB-TYPES
• Status epilepticus has numerous subtypes, including
• generalized convulsive status epilepticus (GCSE)
1. persistent generalized electrographic seizures,

2. persistent coma,

3. persistent tonic-clonic movements,

• nonconvulsive status epilepticus
1. persistent absence seizures
2. persistent partial seizures,
3. persistent confusion
4. persistent partially impaired consciousness, and

5. persistent minimal motor abnormalities.

GCSE

• The most common causes of GCSE are

1. refractory epilepsy,
2. drug toxicity
3. anticonvulsant withdrawal or noncompliance,
4. metabolic disturbances,
5. CNS infection,
6. CNS tumors,
7. head trauma.

CLINICAL
• GCSE is obvious when the patient is having overt
convulsions.
• However, after 30–45 min of uninterrupted seizures, the
signs may become increasingly subtle. Patients may
have mild clonic movements of only the fingers or fine,
rapid movements of the eyes.
• There may be paroxysmal episodes of tachycardia,
hypertension, and pupillary dilation. In such cases, the
EEG may be the only method of establishing the
diagnosis.
• Thus, if the patient stops having overt seizures, yet
remains comatose, an EEG should be performed to rule
out ongoing status epilepticus.

MANAGEMENT
• GCSE is an emergency and must be treated
immediately
• The first step in the management of a patient in GCSE is
 1. to attend to any acute cardiorespiratory problems
or hyperthermia,
2. perform a brief medical and neurologic
examination,
3. establish venous access,
4. send samples for laboratory studies to identify
metabolic abnormalities.
• Anticonvulsant therapy should then begin without
delay; a treatment approach is shown in harrison fig
363-3.

• The treatment of nonconvulsive status epilepticus is

somewhat less urgent than GCSE, since the ongoing
seizures are not accompanied by the severe metabolic
disturbances seen with GCSE.
• However, evidence suggests that nonconvulsive status
epilepticus, especially that caused by ongoing, focal
seizure activity, is associated with cellular injury in the
region of the seizure focus, so that the condition should
be treated as promptly as possible using the general
approach described for GCSE.

Brown-Séquard syndrome
INTRO

• Brown-Séquard syndrome is a loss of sensation and motor function that

is caused by the lateral hemisection of the spinal cord.
Classification
• Any presentation of spinal injury that is an incomplete lesion can be
called a partial Brown-Séquard or incomplete Brown-Séquard syndrome,
so long as it is characterized by a motor deficit and numbness to touch
and vibration on the same side of the spinal injury and loss of pain and
temperature sensation on the opposite side
Causes
• Brown-Séquard syndrome may be caused by
 1. a spinal cord tumour,
2. trauma (such as a gunshot wound or puncture wound to the neck
or back),
3. ischemia (obstruction of a blood vessel), or
4. infectious or inflammatory diseases such as tuberculosis, or
multiple sclerosis.
• The most common cause is penetrating trauma such as a gunshot wound
or stab wound to the spinal cord. This may be seen most often in the
cervical (neck) or thoracic spine.
Pathophysiology & CLINICAL PRESENTATION

Brown-Séquard syndrome's symptoms:

* = Side of the lesion
1 = hypertonic paralysis
2 = spastic paralysis and loss of vibration and proprioception (position
sense) and fine touch
3 = loss of pain and temperature sensation
• As a result of the injury to three main brain pathways the patient will
present with three lesions:
1. The corticospinal lesion produces spastic paralysis on the same side
of the body (the loss of moderation by the UMN).
2. The lesion to fasciculus gracilis or fasciculus cuneatus results in
ipsilateral loss of vibration and proprioception (position sense) as well as
loss of all sensation of fine touch.
3. The loss of the spinothalamic tract leads to pain and temperature
sensation being lost from the contralateral side beginning one or two
segments below the lesion.
Diagnosis
• Magnetic resonance imaging (MRI) is the imaging of choice in spinal cord
lesions.
Treatment
• Treatment is directed at the pathology causing the paralysis.
• If it is because of trauma such as a gunshot or knife wound, there may
be other life threatening conditions such as bleeding or major organ
damage which should be dealt with on an emergent basis.
 • If the syndrome is caused by a spinal fracture, this should be identified
and treated appropriately.
• Although steroids may be used to decrease cord swelling and
inflammation, the usual therapy for spinal cord injury is expectant

Subacute Sclerosing
Panencephalitis (SSPE)
DEFINITION
• SSPE is a rare chronic, progressive demyelinating disease of the CNS
associated with a chronic nonpermissive infection of brain tissue with
measles virus.

INCIDENCE
• The incidence has declined dramatically since the introduction of a
measles vaccine.

CLINICAL FEATURES
• Most patients give a history of primary measles infection at an early age
(2 years), which is followed after a latent interval of 6–8 years by the
development of progressive neurologic disorder.
• patients are between 5 and 15 years old at diagnosis.
• Initial manifestations include
1) poor school performance
2) mood and personality changes.
• Typical signs of a CNS viral infection, including fever and headache, do
not occur.
• As the disease progresses, patients develop
1) progressive intellectual deterioration,
2) focal and/or generalized seizures,
3) myoclonus,
4) ataxia,
5) visual disturbances.
• In the late stage of the illness, patients are
1) unresponsive,
2) spastic quadriparetic,
3) hyperactive tendon reflexes
4) extensor plantar responses.

Diagnostic Studies
 • MRI is often normal early, although areas of increased T2 signal
develop in the white matter of the brain and brainstem as
disease progresses.
• The EEG may initially show only nonspecific slowing, but with disease
progression, patients develop a characteristic periodic pattern with
bursts of high-voltage, sharp, slow waves every 3–8 s, followed
by periods of attenuated ("flat") background.
• The CSF is
1) acellular
2) normal or mildly elevated protein concentration
3) a markedly elevated gamma globulin level (>20% of total CSF
protein).
4)CSF anti-measles antibody levels are invariably elevated,
5)oligoclonal anti-measles antibodies are often present.
• Measles virus can be cultured from brain tissue using special
cocultivation techniques.
• Viral antigen can be identified immunocytochemically,
• viral genome can be detected by in situ hybridization or PCR
amplification.

Treatment
• No definitive therapy for SSPE is available.
• Treatment with isoprinosine (100 mg/kg per day), alone or in
combination with intrathecal or intraventricular alpha interferon, has
been reported to prolong survival and produce clinical improvement in
some patients

Wernicke encephalopathy
INTRO
• Wernicke encephalopathy is a syndrome characterised by
1) ophthalmoplegia,
2) ataxia,
3) confusion,
4) impairment of short-term memory
•

Cause
1. thiamine (vitamin B1) deficiency
2. prolonged alcohol, amphetamine consumption resulting in thiamine
deficiency.
3. gastric disorders as carcinoma, chronic gastritis,
4. Crohn's disease,
5. repetitive vomiting, particularly after bariatric surgery.
Presentation
• Wernicke's encephalopathy begins abruptly, usually with
1) eye movement disorders (nystagmus, gaze palsies, and
ophthalmoplegia, especially of the lateral rectus muscles),
2) gait ataxia,
3) confusion,
4) confabulation,
5) short-term memory loss.
• The classic triad of the syndrome is
1) encephalopathy (brain damage),
2) ophthalmoplegia (eye paralysis),
3) ataxia (loss of coordination).
• Untreated, it may progress to Korsakoff's psychosis, coma and death.

Treatment
• Treatment begins with intravenous or intramuscular injection of
thiamine, followed by assessment of central nervous system and
metabolic conditions.
• In the presence of sub-clinical thiamine deficiency, a large dose of sugar
(especially glucose) can precipitate the onset of overt encephalopathy;
therefore, correcting hypoglycemia should not be attempted before
thiamine replenishment.
• Rehydration to restore blood volume should follow, as needed.

• When treated early, recovery may be rapid and complete; though there
are almost always some minor neurological signs that persist

The Alcohol Withdrawal Syndrome

INTRO
• Once the brain has been repeatedly exposed to high doses of alcohol,
any sudden decrease in intake can produce withdrawal symptoms, many
of which are the opposite of those produced by intoxication.

CLINICAL FEATURES
• Because alcohol has a short half-life, these withdrawal symptoms
generally begin within 5–10 h of decreasing ethanol intake, peak in
intensity on day 2 or 3, and improve by day 4 or 5.
• Features include
1) tremor of the hands (shakes or jitters);
2) agitation and anxiety;
3) autonomic nervous system overactivity including an increase in
pulse, respiratory rate, and body temperature;
4) insomnia, sometimes accompanied by frightening dreams.
5) 2 TO 5% of alcoholics experience withdrawal seizures, often within
48 h of stopping drinking
• Anxiety, insomnia, and mild levels of autonomic dysfunction may
persist to some degree for 4–6 months as a protracted abstinence
syndrome, which may contribute to the tendency to return to drinking.

• The term delirium tremens (DTs) refers to an uncommon state of

intense acute withdrawal that includes
1. delirium (mental confusion, agitation, and fluctuating levels of
consciousness)
2. tremor
3. Autonomic overactivity (e.g., marked increases in pulse, blood
pressure, and respirations).

TREATMENT
• The first step is to perform a thorough physical examination in all
alcoholics who are considering stopping drinking, including a search for
1. evidence of liver failure,
2. gastrointestinal bleeding,
3. cardiac arrhythmia,
4. infection,
5. glucose or electrolyte imbalance.
• The second step is to offer reassurance that the acute withdrawal is
short lived and to offer adequate nutrition and rest.
1. All patients should be given oral multiple B vitamins, including
50–100 mg of thiamine daily for a week or more.
2. Because most alcoholics who enter withdrawal are either
normally hydrated or mildly overhydrated, IV fluids should be
avoided unless there is evidence of significant recent bleeding,
vomiting, or diarrhea.
3. Medications can usually be administered orally.
• The third step in treatment is to recognize that most withdrawal
symptoms are caused by the rapid removal of a CNS depressant, in this
case, alcohol.
 1. While most CNS depressants are effective, benzodiazepines have
the highest margin of safety and lowest cost and are, therefore, the
preferred class of drugs.
2. Benzodiazepines with short half-lives are especially useful for
patients with serious liver impairment or evidence of preexisting
encephalopathy or brain damage.
• Treatment of the patient with DTs can be challenging, and the
condition is likely to run a course of 3–5 days regardless of the therapy
employed.
1. The focus of care is to identify and correct medical problems and
to control behavior and prevent injuries.
2. Many clinicians recommend the use of high doses of a
benzodiazepine (as much as 800 mg/d of chlordiazepoxide),
3. Other clinicians recommend the use of antipsychotic medications,
such as haloperidol, Or olanzapine
• Generalized withdrawal seizures rarely require aggressive
pharmacologic intervention beyond that given to the usual patient
undergoing withdrawal, i.e., adequate doses of benzodiazepines.
• The rare patient with status epilepticus must be treated
aggressively .

HAZARD OF ALCHOHOL
(ALCHOHOLISM)
INTRO
 Alcohol dependence is defined as repeated alcohol-related difficulties in
at least three of seven areas of functioning that cluster together over a
12-month period.
 Alcohol abuse is defined as repetitive problems with alcohol in any one
of four life areas—social, interpersonal, legal, and occupational
 Not everyone develops each of the problems described below.

NERVOUS SYSTEM
CNS & PNS
1. a blackout, an episode of temporary anterograde amnesia, in which the
person forgets all or part of what occurred during a drinking evening.
2. disturbed sleep. sometimes disturbing dreams.
3. snoring and exacerbate sleep apnea
4. impaired judgment and coordination, increasing the risk of accidents and
injury
5. Heavy drinking can also be associated with headache, thirst, nausea,
vomiting, and fatigue the following day, a hangover syndrome that is
responsible for significant financial losses in most work environments.
 6. peripheral neuropathy
7. cerebellar degeneration or atrophy.
8. Wernicke's (ophthalmoparesis, ataxia, and encephalopathy)
9. Korsakoff's (retrograde and anterograde amnesia) syndromes.

PSYCHIATRY
1. alcohol and/or drug dependence.
2. schizophrenia
3. manic depressive disease
TEMPORARY PSCHIATRIC
1. anxiety disorders such as panic disorder.
2. intense sadness lasting for days to weeks
3. temporary severe anxiety
4. auditory hallucinations

The Gastrointestinal System

Esophagus and Stomach
1. epigastric distress and gastrointestinal bleeding.
2. hemorrhagic gastritis.
3. Violent vomiting can produce severe bleeding through a Mallory-
Weiss lesion
Pancreas and Liver
1. acute pancreatitis
2. alcohol-induced hepatitis,
3. cirrhosis

Cancer
1. breast cancer
2. oral and esophageal cancers
3. rectal cancers

Hematopoietic System
1. If heavy drinking is accompanied by folic acid deficiency, there can
also be hypersegmented neutrophils, reticulocytopenia, and a
hyperplastic bone marrow;
2. if malnutrition is present, sideroblastic changes can be observed.
3. a possible false-negative tuberculin skin test
4. mild thrombocytopenia

Cardiovascular System
1. a dose-dependent increase in blood pressure
2. increased risk for coronary artery disease
3. an increased risk for cardiomyopathy.
4. Mural thrombi can form in the left atrium or ventricle
 5. mitral regurgitation.
6. Atrial or ventricular arrhythmias, especially paroxysmal tachycardia,
can also occur after a drinking binge in individuals showing no other
evidence of heart disease—a syndrome known as the "holiday heart."
This condition is observed transiently in the majority of alcoholics
entering treatment.

Genitourinary System Changes, Sexual Functioning, and

Fetal Development

MALE
1. decrease erectile capacity in men.
2. irreversible testicular atrophy with shrinkage of the seminiferous tubules,
3. decreases in ejaculate volume,
4. a lower sperm count .

FEMALE
1. amenorrhea,
2. infertility,
3. an increased risk of spontaneous abortion.
PREGNANCY
1. serious consequences for fetal development.
2. The fetal alcohol syndrome can include any of the following:

 facial changes with epicanthal eye folds;

 poorly formed ear concha;
 small teeth with faulty enamel;
 cardiac atrial or ventricular septal defects;
 an aberrant palmar crease
 limitation in joint movement;

 microcephaly with mental retardation..

Musculoskeletal
1.skeletal muscle weakness caused by acute alcoholic myopathy
2. increased risk for fractures and osteonecrosis of the femoral head.

VERTIGO
DEFINITION
• an illusory or hallucinatory sense of movement of the body or
environment, most often a feeling of spinning

PHYSIOLOGY
• Three sensory systems subserving spatial orientation and posture;
1. The vestibular system is
2. the visual system (retina to occipital cortex)
3. the somatosensory system that conveys peripheral information
from skin, joint, and muscle receptors.

Physiologic Vertigo
• This occurs in normal individuals when
(1) the brain is confronted with an intersensory mismatch among the
three stabilizing sensory systems;
(2) the vestibular system is subjected to unfamiliar head movements to
which it is unadapted, such as in seasickness;
(3) unusual head/neck positions, such as the extreme extension when
painting a ceiling; or following a spin.

Pathologic Vertigo
• This results from lesions of the visual, somatosensory, or vestibular
systems.
• Visual vertigo
1. caused by new or incorrect eyeglasses or by the sudden onset of an
extraocular muscle paresis with diplopia;
• Somatosensory vertigo,
1. rare in isolation,
2. usually due to a peripheral neuropathy or myelopathy
• vestibular vertigo
1. The most common cause of pathologic vertigo
2. involving either its end organ (labyrinth), nerve, or central
connections.
3. The vertigo is associated with jerk nystagmus and is frequently
accompanied by nausea, postural unsteadiness, and gait ataxia.
4. Since vertigo increases with rapid head movements, patients
tend to hold their heads still.
Labyrinthine Dysfunction
 • This causes severe rotational or linear vertigo.
• The fast phases of nystagmus beat away from the lesion side,
• the tendency to fall is toward the side of the lesion, particularly in
darkness or with the eyes closed.

• Acute unilateral labyrinthine dysfunction

1. Infection- herpes simplex virus type 1,
2. trauma,

3. ischemia.
o presumably due to occlusion of the labyrinthine branch of the
internal auditory artery, may be the sole manifestation of
vertebrobasilar insufficiency ;
• Acute bilateral labyrinthine dysfunction
o usually the result of toxins such as drugs or alcohol.
o The most common offending drugs are the aminoglycoside
antibiotics
• Recurrent unilateral labyrinthine dysfunction,
o in association with signs and symptoms of cochlear disease
(progressive hearing loss and tinnitus), is usually due to Ménière's
disease
• Positional vertigo
o precipitated by a recumbent head position, either to the right or to
the left.
o Benign paroxysmal positional (or positioning) vertigo (BPPV) of the
posterior semicircular canal is particularly common.
o Although the condition may be due to head trauma, usually no
precipitating factors are identified.
Benign Paroxysmal Positional Vertigo and Central Positional Vertigo

Features BPPV Central

1. Latency 3–40 s None: immediate vertigo and
nystagmus
2. Fatigability Yes No

3. Habituation Yes No

4. Intensity of Severe Mild

vertigo
5. Reproducibilit Variable Good
y
 • A perilymphatic fistula
o should be suspected when episodic vertigo is precipitated by
Valsalva or exertion
o The condition is usually caused by head trauma or barotrauma or
occurs after middle ear surgery.
Vertigo of Vestibular Nerve Origin
• The most common cause of eighth cranial nerve dysfunction is a tumor,
usually a schwannoma (acoustic neuroma) or a meningioma.
• auditory symptoms are the most common manifestations.
Central Vertigo
• Lesions of the brainstem or cerebellum can cause acute vertigo, but
associated signs and symptoms usually permit distinction from a
labyrinthine etiology
Features of Peripheral and Central Vertigo

Sign or Symptom Peripheral (Labyrinth) Central (Brainstem or

Cerebellum)
1. Direction of Unidirectional; fast phase Bidirectional or
associated opposite lesion unidirectional
nystagmus
2. Purely Uncommon Common
horizontal
nystagmus
3. Vertical Never present May be present
nystagmus
4. Severity of Marked Often mild
vertigo
5. Direction of Toward slow phase Variable
fall
6. Duration of Finite (minutes, days, May be chronic
symptoms weeks) but recurrent
7. Tinnitus Often present Usually absent
and/or deafness
8. Associated None Extremely common (e.g.,
CNS diplopia, hiccups, cranial
abnormalities neuropathies, dysarthria)
9. Common BPPV, infection Vascular, demyelinating,
causes (labyrinthitis), Ménière's, neoplasm
neuronitis, ischemia,
trauma, toxin
 • migraine aura

• Vestibular epilepsy, vertigo secondary to temporal lobe epileptic activity,

is rare.

• Psychogenic Vertigo
o It should be suspected in patients so "incapacitated" by their symptoms
that they adopt a prolonged housebound status.
o a psychogenic etiology is almost certain when nystagmus is absent
during a vertiginous episode.

DIAGNOSTIC EVALUATION
• The simplest provocative test for vestibular dysfunction is rapid rotation
and abrupt cessation of movement in a swivel chair.
• Patients with symptoms of positional vertigo should be appropriately
tested .
• A final provocative and diagnostic vestibular test, requiring the use of
Frenzel eyeglasses, is vigorous head shaking in the horizontal plane for
about 10 s. If nystagmus develops after the shaking stops, even in the
absence of vertigo, vestibular dysfunction is demonstrated. The
maneuver can then be repeated in the vertical plane.
• If the provocative tests establish the dizziness as a vestibular symptom,
an evaluation of vestibular vertigo is undertaken

MANAGEMENT
Treatment of acute vertigo consists of bed rest (1–2 days maximum) and
vestibular suppressant drugs
Treatment of Vertigo

Agenta

1. Antihistamines
Meclizine
Promethazinec For acute vertigo only
c

2. Benzodiazepines
Diazepam
Clonazepam
3. Phenothiazines
Prochlorperazinec For acute vertigo only
c
Agenta

4. Anticholinergicd d
For motion sickness only.

Scopolamine transdermal
5. Sympathomimeticsd d
For motion sickness only.

Ephedrine
6. Combination d
For motion sickness only.
preparationsd

Ephedrine and
promethazine
7. Exercise therapy
Repositioning For benign paroxysmal positional vertigo.
maneuverse

Vestibular rehabilitationf

8. Other
Diuretics or low-salt (1 g/d) For Ménière's disease.
dietg

Antimigrainous drugsh h
For migraine-associated vertigo

Inner ear surgeryi For perilymphatic fistula and refractory cases of

i

Ménière's disease.

Glucocorticoidsc For acute vertigo only

c

SYNCOPE
DEFINITION & INTRO
• Syncope, a transient loss of consciousness and postural tone due
to reduced cerebral blood flow, is associated with spontaneous
recovery.

• It may occur suddenly, without warning, or may be preceded by

symptoms of faintness ("presyncope").
• These symptoms include
1. lightheadedness,
2. dizziness,
3. a feeling of warmth,
4. diaphoresis,
5. nausea, and
6. visual blurring
7. occasionally proceeding to transient blindness.

• Syncope may be benign when it occurs as a result of normal

cardiovascular reflex effects on heart rate and vascular tone, or serious
when due to a life-threatening cardiac arrhythmia.
• Syncope may occur as a single event or may be recurrent.
• Recurrent, unexplained syncope, particularly in an individual
with structural heart disease, is associated with a high risk of death
(40% mortality within 2 years)

CAUSES

I. Disorders of Vascular Tone or Blood Volume

A. Reflex syncopes
1. Neurocardiogenic
2. Situational
o Cough
o Micturition
o Defecation
o Valsalva
o Deglutition
3. Carotid sinus hypersensitivity
B. Orthostatic hypotension
 1. Drug-induced (antihypertensive or vasodilator drugs)
2. Pure autonomic failure (idiopathic orthostatic hypotension)
3. Multisystem atrophies
4. Peripheral neuropathy (diabetic, alcoholic, nutritional, amyloid)
5. Physical deconditioning
6. Sympathectomy
7. Decreased blood volume
II. Cardiovascular Disorders
A. Structural and obstructive causes
1. Pulmonary embolism
2. Pulmonary hypertension
3. Atrial myxoma
4. Mitral valvular stenosis
5. Myocardial disease (massive acute myocardial infarction)
6. Left ventricular myocardial restriction or constriction
7. Pericardial constriction or tamponade
8. Aortic outflow tract obstruction
9. Aortic valvular stenosis
10. Hypertrophic obstructive cardiomyopathy
B. Cardiac arrhythmias
1. Bradyarrhythmias
a. Sinus bradycardia, sinoatrial block, sinus arrest, sick-sinus
syndrome
b. Atrioventricular block
2. Tachyarrhythmias
a. Supraventricular tachycardia with structural cardiovascular
disease
b. Atrial fibrillation with the Wolff-Parkinson-White syndrome
c. Atrial flutter with 1:1 atrioventricular conduction
d. Ventricular tachycardia
III. Cerebrovascular Disease
A. Vertebrobasilar insufficiency
B. Basilar artery migraine
IV. Other Disorders that May Resemble Syncope
A. Metabolic
1. Hypoxia
2. Anemia
3. Diminished carbon dioxide due to hyperventilation
4. Hypoglycemia
B. Psychogenic
1. Anxiety attacks
 2. Hysterical fainting
C. Seizures

DIFFERENTIAL DIAGNOSIS
1 Anxiety Attacks and Hyperventilation Syndrome

• the symptoms are not accompanied by facial pallor and are not
relieved by recumbency.

2 Seizures
Features that Distinguish Generalized Tonic-Clonic Seizure from Syncope

Features Seizure Syncope

1. Immediate Usually none Emotional stress, Valsalva,
precipitating factors orthostatic hypotension,
cardiac etiologies
2. Premonitory None or aura Tiredness, nausea,
symptoms (e.g., odd odor) diaphoresis, tunneling of vision
3. Posture at onset Variable Usually erect
4. Transition to Often Gradual over seconds
unconsciousness immediate
5. Duration of Minutes Seconds
unconsciousness
6. Duration of tonic 30–60 s Never more than 15 s
or clonic movements
7. Facial appearance Cyanosis, Pallor
during event frothing at
mouth
8. Disorientation and Many minutes to <5 min
sleepiness after event hours
9. Aching of muscles Often Sometimes
after event
10. Biting of tongue Sometimes Rarely
11. Incontinence Sometimes Sometimes
12. Headache Sometimes Rarely

3 Hypoglycemia

4 Hysterical Fainting

• Lack of change in pulse and blood pressure or color of the skin

 and mucous membranes distinguish it from the vasodepressor faint.

TREATMENT

SITE OF CARE
• Patients with syncope should be hospitalized when there is a
possibility that the episode may have resulted from a life-threatening
abnormality or if recurrence with significant injury seems likely.
• These individuals should be admitted to a bed with continuous
electrocardiographic monitoring.

• Patients who are known to have a normal heart and for whom
the history strongly suggests vasovagal or situational syncope
may be treated as outpatients if the episodes are neither frequent nor
severe.

GENERAL

• Certain precautions should be taken regardless of the cause of

syncope.

WHAT WILL PATIENT DO ?

• Patients with frequent episodes, or those who have experienced

syncope without warning symptoms, should avoid situations in
which sudden loss of consciousness might result in injury (e.g., climbing
ladders, swimming alone, operating heavy machinery, driving).

• At the first sign of symptoms, patients should make every effort to

avoid injury .
• Patients should lower their head to the extent possible and preferably
should lie down.
• Lowering the head by bending at the waist should be avoided
because it may further compromise venous return to the heart.

ROLE OF RELATIVE & FRIENDS

• When appropriate, family members or other close contacts should

be educated as to the problem.
• This will ensure appropriate therapy and may prevent delivery
of inappropriate therapy (chest compressions associated with
cardiopulmonary resuscitation) that may inflict trauma.

PT WITH LOST COCIOUSNESS

1. Patients who have lost consciousness should be placed in a position

that maximizes cerebral blood flow, offers protection from trauma, and
 secures the airway.
2. Whenever possible, the patient should be placed supine with the head
turned to the side to prevent aspiration and the tongue from blocking
the airway.
3. Assessment of the pulse and direct cardiac auscultation may assist
in determining if the episode is associated with a bradyarrhythmia or a
tachyarrhythmia.
4. Clothing that fits tightly around the neck or waist should be
loosened.
5. Peripheral stimulation, such as sprinkling cold water on the face, may
be helpful.
6. Patients should not be given anything by mouth or be permitted to
rise until the sense of physical weakness has passed.

SPECIFIC
• The treatment of syncope is directed at the underlying cause.

Patients with vasovagal syncope

• Patients with vasovagal syncope should be instructed to avoid

situations or stimuli that have caused them to lose consciousness and to
assume a recumbent position when premonitory symptoms occur.
• These behavioral modifications alone may be sufficient for
patients with infrequent and relatively benign episodes of vasovagal
syncope, particularly when loss of consciousness occurs in response to a
specific stimulus.
• Episodes associated with intravascular volume depletion may be
prevented by salt and fluid loading prior to provocative events.
• Drug therapy may be necessary when vasovagal syncope is resistant
to the above measures, when episodes occur frequently, or when
syncope is associated with a significant risk for injury.
• BETA-Adrenergic receptor antagonists (metoprolol, 25–50 mg bid;
atenolol, 25–50 mg qd; or nadolol, 10–20 mg bid; all starting doses),
the most widely used agents
• Serotonin reuptake inhibitors (paroxetine, 20–40 mg qd; or
sertraline, 25–50 mg qd), appear to be effective for some patients.
• Bupropion SR (150 mg qd), another antidepressant, has also been used
with success.
• BETA-Adrenergic receptor antagonists and serotonin reuptake inhibitors
are well tolerated and are often used as first-line agents for
younger patients.
• Hydrofludrocortisone (0.1–0.2 mg qd), a mineralocorticoid,
promotes sodium retention, volume expansion, and peripheral
vasoconstriction by increasing BETA-receptor sensitivity to endogenous
catecholamines.
• Hydrofludrocortisone is useful for patients with intravascular volume
depletion and for those who also have postural hypotension.
• Proamatine (2.5–10 mg bid or tid), an ALPHA-agonist, has been used
 as a first-line agent for some patients.
• However, in some patients, proamatine and
hydrofludrocortisone may increase resting supine systemic
blood pressure, which may be problematic for those with hypertension.
• Disopyramide (150 mg bid), a vagolytic antiarrhythmic drug with
negative inotropic properties, and transdermal scopolamine, another
vagolytic, have been used to treat vasovagal syncope, as have
theophylline and ephedrine.
• Side effects associated with these drugs have limited their use for this
indication.

• Dual-chamber cardiac pacing may be effective for patients with

frequent episodes of vasovagal syncope, particularly for those with
prolonged asystole associated with vasovagal episodes.
• Pacemakers that can be programmed to transiently pace at a
high rate (90–100 beats/min) after a profound drop in the patient's
intrinsic heart rate are most effective.

Patients with orthostatic hypotension

• Patients with orthostatic hypotension should be instructed to rise

slowly and systematically (supine to seated, seated to standing) from the
bed or a chair.
• Movement of the legs prior to rising facilitates venous return from the
lower extremities.
• Whenever possible, medications that aggravate the problem
(vasodilators, diuretics, etc.) should be discontinued.
• Elevation of the head of the bed [20–30 cm (8–12 in.)] and use of
compression stockings may help.
• Additional therapeutic modalities include salt loading and a variety
of pharmacologic agents including
1. sympathomimetic amines,
2. monamine oxidase inhibitors,
3. beta blockers,
4. levodopa.

Glossopharyngeal neuralgia

• Glossopharyngeal neuralgia is treated with carbamazepine, which

is effective for syncope as well as for pain.

carotid sinus hypersensitivity

• Patients with carotid sinus hypersensitivity should be instructed to

avoid clothing and situations that stimulate carotid sinus baroreceptors.
• They should turn their entire body, rather than just their head, when
looking to the side.

Those with intractable syncope due to the cardioinhibitory response

to carotid sinus stimulation
 should undergo permanent pacemaker implantation.

Noncompressive
Myelopathies
CAUSES
 The most frequent causes of noncompressive acute transverse
myelopathy (ATM) are
1. spinal cord infarction;
2. systemic inflammatory disorders, including SLE and
sarcoidosis;
3. demyelinating diseases, including multiple sclerosis (MS);
4. postinfectious or idiopathic transverse myelitis,
5. infectious (primarily viral) .

INVESTIGATIONS
 After spinal cord compression is excluded, the evaluation
generally requires a lumbar puncture and a search for underlying
systemic disease
Evaluation

1. MRI of spinal cord with and without contrast

• exclude compressive causes.
2. CSF studies:
• Cell count, protein, glucose, IgG index/synthesis rate,
• oligoclonal bands,
• VDRL;
• Gram's stain, acid-fast bacilli, and India ink stains;
• PCR for VZV, HSV-2, HSV-1, EBV, CMV, HIV;
• antibody for HTLV-I, M. pneumoniae, and Chlamydia
pneumoniae;
 • viral, bacterial, mycobacterial, and fungal cultures.
3. Blood studies for infection:
• HIV;
• IgG and IgM enterovirus antibody;
• IgM mumps, measles, rubella,
4. Immune-mediated disorders:
• ESR;
• ANA; dsDNA;
• rheumatoid factor;
• antiphospholipid and anticardiolipin antibodies;
5. Sarcoidosis:
• Serum angiotensin-converting enzyme;
• serum Ca;
• 24 hour urine Ca;
• chest x-ray;
• chest CT;
6. Demyelinating disease:
• Brain MRI scan,
• evoked potentials,
• CSF oligoclonal bands,
7. Vascular causes:
• CT myelogram;
• spinal angiogram.

CLINICAL FEATURE & BRIEF MANAGEMENT

Spinal Cord Infarction
• Acute infarction in the territory of the anterior spinal artery
produces
1) paraplegia or quadriplegia,
2) dissociated sensory loss affecting pain and temperature sense

but sparing vibration and position sense, and loss of sphincter

control ("anterior cord syndrome").
 3) Onset may be sudden and dramatic but more typically is
progressive over minutes or a few hours.
4) Sharp midline or radiating back pain localized to the area of
ischemia is frequent.
5) Areflexia due to spinal shock is often present initially; with
time, hyperreflexia and spasticity appear.
6) Less common is infarction in the territory of the posterior spinal

arteries, resulting in loss of posterior column function.

• The antiphospholipid antibody syndrome is treated with
anticoagulation.
• Drainage of spinal fluid has reportedly been successful in some
cases of cord infarction
Inflammatory and Immune Myelopathies (Myelitis)

• Systemic Inflammatory Disorders

1) SLE . Responses to glucocorticoids and/or cyclophosphamide
2) Sjögren's syndrome,
3) Behçet's syndrome,
4) Vasculitis
5) sarcoid myelopathy -Initial treatment is with oral

glucocorticoids; immunosuppressant drugs are used for

resistant cases.
• Demyelinating Myelopathies
1) Multiple sclerosis
2) Neuromyelitis optica (NMO)
o Intravenous methylprednisolone (500 mg qd for 3 days)
followed by oral prednisone (1 mg/kg per day for several
weeks, then gradual taper) has been used as initial
treatment.
o A course of plasma exchange is indicated for severe cases
if glucocorticoids are ineffective.
• Postinfectious Myelitis
Many cases of myelitis, termed postinfectious or postvaccinal,
1)

follow an infection or vaccination.

2) Epstein-Barr virus (EBV),
3) cytomegalovirus (CMV),
4) mycoplasma,
5) influenza,
6) measles,
 7) varicella,
8) rubeola,
9) mumps.
• Acute Infectious Myelitis
1) Herpes zoster
2) HSV types 1 and 2,
3) EBV,
4) CMV,
5) rabies virus

6) mycobacterial myelitis (most are essentially abscesses)

7) Listeria monocytogenes,

8) Lyme disease
9) Syphilis
10) Schistosomiasis
11) Toxoplasmosis
o Herpes zoster, HSV, and EBV myelitis are treated with
intravenous acyclovir (10 mg/kg q8h) or oral valacyclovir (2
gm tid) for 10–14 days;
o CMV with ganciclovir (5 mg/kg IV bid) plus foscarnet (60
mg/kg IV tid), or cidofovir (5 mg/kg per week for 2 weeks).