Neurology Notes

2010

SANKET SHAH

(KESAR SAL)Available on www.mysarthee.co.cc

NEUROLOGY

NORMAL CSF

Constituent Conventional UnitsGlucose 40–70 mg/dLLactate 10–20 mg/dLTotal 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 (OGB)

<2 bands not present in matched serum sample

Ammonia 25–80 g/dL

CSF pressure 50–180 mmH2O

CSF volume (adult) ~150 mLRed blood cells 0Leukocytes Total 0–5 mononuclear cells per mm3

Differential Lymphocytes 60–70%

Constituent Conventional Units Monocytes 30–50% Neutrophils None

aSince 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.bIgG 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.

>1A<<>PPMPDC

erebrospinal Fluid (CSF) Abnormalit

ies in Bacterial Meningitis

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

1)an acute fulminant illness that progresses rapidly in a few hours 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.

>1A<<>PPMPDCerebrospinal

Fluid (CSF) Abnormalities in Bacte

rial Meningitis

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 Antibiotic1.Preterm infants to

infants <1 monthAmpicillin + Cefotaxime

2.Infants 1–3 mos Ampicillin + Cefotaxime or ceftriaxone 3.Immunocompetent

children >3 mos and adults <55

vancomycin + Cefotaxime or ceftriaxone

4.Adults >55 and adults of any age with alcoholism or other debilitating illnesses

Ampicillin + cefotaxime or ceftriaxone + vancomycin

5.Hospital-acquired meningitis, posttraumatic or postneurosurgery meningitis, neutropenic patients, or patients with impaired cell-mediated immunity

Ampicillin + ceftazidime + vancomycin

Total Daily Dose and Dosing Interval

Antimicrobial Agent

Child (>1 month) Adult

Ampicillin 200 (mg/kg)/d, q4h 12 g/d, q4h

Cefotaxime 200 (mg/kg)/d, q6h 12 g/d, q6h

Ceftriaxone 100 (mg/kg)/d, q12h 4 g/d, q12h

Ceftazidime 150 (mg/kg)/d, q8h 6 g/d, q8h

Vancomycin 60 (mg/kg)/d, q6h 2 g/d, q12h

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, or3. 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 1. Clinical diagnosis of

stroke 2. Onset of symptoms to

time of drug administration <=3 h

3. CT scan showing no hemorrhage or edema of >⅓ of the MCA territory

4. Age >=18 years 5. Consent by patient or

surrogate

Contraindication 1. Sustained BP >185/110

despite treatment 2. Platelets <100,000; 3. HCT <25%;4. glucose <50 or >400 mg/dL 5. Use of heparin within 48 h

and prolonged PTT, or elevated INR

6. Recent myocardial infarction7. 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 symptoms12. 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 TreatmentPlatelet 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 parametersaPTT = <1.2 times control: 80 U/kg bolus with increase of 4 U/kg/haPTT = 1.2-1.5 times control: 40 U/kg bolus with increase of 2 U/kg/haPTT = 1.5-2.3 times control: No change in infusion rate neededaPTT = 2.3-3 times control: Decrease infusion rate by 2 U/kg/haPTT > 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

AdultInitial: 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.

Adult2,50,000 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 AdultInstilled 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 syndromeDEFINITON

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.

CAUSESocclusion 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 nucleus4)Horner's syndrome (miosis, ptosis, decreased sweating): Descending sympathetic

tract5)Dysphagia, hoarseness, paralysis of palate, paralysis of vocal cord, diminished gag

reflex: Issuing fibers ninth and tenth nerves6)Loss of taste: Nucleus and tractus solitaries7)Numbness of ipsilateral arm, trunk, or leg: Cuneate and gracile nuclei8)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

TREATMENTTreatment 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.Diabetes4.Smoking5.Hyperlipidemia6.Asymptomatic carotid stenosis7.Symptomatic carotid stenosis (70–99%)8.Symptomatic carotid stenosis (50–69%)

CAUSES

Common Causes

Uncommon Causes

Thrombosis Lacunar stroke (small vessel) Large vessel thrombosis DehydrationEmbolic occlusion Artery-to-artery Carotid bifurcation Aortic arch Arterial dissectionCardioembolic Atrial fibrillation Mural thrombus

Hypercoagulable disorders

Venous sinus thrombosis

Fibromuscular dysplasia Vasculitis

Cardiogenic Mitral valve calcification Atrial myxoma Intracardiac tumor

Uncommon Causes

Myocardial infarction Dilated cardiomyopathy Valvular lesions Mitral stenosis Mechanical valve Bacterial endocarditisParadoxical embolus Atrial septal defect Patent foramen ovale

Subarachnoid hemorrhage vasospasm Drugs: cocaine, amphetamine

Eclampsia

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 syndromeINTRO

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 damaged Effect1. substantia nigra contralateral parkinsonism 2. corticospinal fibers contralateral hemiparesis and typical upper motor neuron findings

3. corticobulbar tract difficulty with contralateral lower facial muscles and hypoglossal nerve functions

4. oculomotor nerve fibers

ipsilateral oculomotor nerve palsy with a drooping eyelid and fixed wide pupil pointed down and out. This leads to diplopia

Benedikt syndromeINTRO

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

1) include CNIII nucleus,

2)Red nucleus,

3)corticospinal tracts,

4)brachium conjunctivum, and

5)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 syndromeINTRO

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 SCLEROSISDEFINITION

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

Symptom1.Sensory loss2.Optic neuritis3.Weakness4.Paresthesias5.Diplopia6.Ataxia7.Vertigo8.Paroxysmal attacks9.Lhermitte10. Pain11. Dementia12. Visual loss13. Facial palsy14. Impotence15. Myokymia16. Epilepsy17. 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 syndrome3.Behçet's disease4.Human immunodeficiency virus (HIV) infection5.Lyme disease6.Neoplasms (e.g., lymphoma, glioma, meningioma)7.Sarcoid8.Sjögren's syndrome9.Stroke and ischemic cerebrovascular disease10. Syphilis11. Systemic lupus erythematosus and related collagen vascular disorders12. Vitamin B12 deficiency

INVESTIGATIONS REFER DAVIDSON

MANAGEMENT REFER DAVIDSON

Migraine HeadacheINTRO & TRIGGERS

Migraine, the second most common cause of primary headache, affects approximately 15% of women and 6% of men.

Symptoms Accompanying Severe Migraine Attacks

Symptom1) Nausea2) Vomiting3) Diarrhea4) Light headedness5) Scalp tenderness6) Visual disturbances 7) Photophobia8) Photopsia9) Vertigo10) Seizure11) Syncope12) Alteration of consciousness13) Confusional state14) 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 features:

Plus at least 1 of the following features:

1. Unilateral pain 1. Nausea/vomiting2. Throbbing pain 2. Photophobia and phonophobia3. 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 Headache1. Gender M>F2. Pain

Type Stabbing, boringSeverity ExcruciatingSite Orbit, temple

3. Attack frequency 1/alternate day– 8/d4. Duration of attack 15–180 min5. Autonomic features Yes6.Migrainous features Yes7. Alcohol trigger Yes8. Cutaneous triggers No9. Abortive treatment Sumatriptan injection or nasal

spray Oxygen

10. Prophylactic treatment

Verapamil 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 MRICT ScansINDICATIONS

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

MRIINDICATIONS

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 DiseaseINTRO

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 integra-

tion, 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 dentatothalamic 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 MultiplexDEFINITION

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 SyndromeDEFINITION

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 weakness2. Mild sensory involvement3. Facial nerve or other cranial nerve involvement4. Absence of fever5. 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 GRAVISINTRODUCTION

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 EPILEPTICUSDEFINITION 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 toxicity3. 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 syndromeINTRO

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 lesion1 = hypertonic paralysis2 = spastic paralysis and loss of vibration and proprioception (position sense) and fine touch3 = 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 encephalopathyINTRO

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 SyndromeINTRO

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 cancer2. 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.

VERTIGODEFINITION

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 Central1. Latency

3–40 s None: immediate vertigo and nystagmus

2. Fatigability

Yes No

3. Habituation

Yes No

4. Intensity of vertigo Severe Mild5. Reproducibility

Variable Good

A perilymphatic fistula o should be suspected when episodic vertigo is precipitated by Valsalva or exertiono 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

associated nystagmus

Unidirectional; fast phase opposite lesion

Bidirectional or unidirectional

2. Purely horizontal nystagmus

Uncommon Common

3. Vertical nystagmus Never present May be present4. Severity of vertigo Marked Often mild5. Direction of fall Toward slow phase Variable6. Duration of

symptomsFinite (minutes, days, weeks) but recurrent

May be chronic

7. Tinnitus and/or deafness

Often present Usually absent

8. Associated CNS abnormalities

None Extremely common (e.g., diplopia, hiccups, cranial neuropathies, dysarthria)

9. Common causes BPPV, infection (labyrinthitis), Ménière's, neuronitis, ischemia, trauma, toxin

Vascular, demyelinating, neoplasm

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

MeclizinePromethazinec cFor acute vertigo only

2. Benzodiazepines DiazepamClonazepam

3. Phenothiazines Prochlorperazinec

cFor acute vertigo only

4. Anticholinergicd dFor motion sickness only.

Scopolamine transdermal5. Sympathomimeticsd dFor motion sickness only.

Ephedrine6. Combination preparationsd dFor motion sickness only.

Ephedrine and promethazine7. Exercise therapy

Repositioning maneuverse

For benign paroxysmal positional vertigo.

Vestibular rehabilitationf

8. Other Diuretics or low-salt (1 g/d) dietg

For Ménière's disease.

Antimigrainous drugsh

hFor migraine-associated vertigo

Inner ear surgeryi

iFor perilymphatic fistula and refractory cases of Ménière's disease.

Agenta

Glucocorticoidsc cFor acute vertigo only

.

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. Situationalo Cougho Micturitiono Defecationo Valsalvao 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 volumeII. 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 tachycardiaIII. Cerebrovascular Disease A. Vertebrobasilar insufficiency B. Basilar artery migraineIV. 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 Syncope1. Immediate precipitating

factors Usually none Emotional stress, Valsalva, orthostatic

hypotension, cardiac etiologies2. Premonitory symptoms None or aura (e.g.,

odd odor)Tiredness, nausea, diaphoresis, tunneling of vision

3. Posture at onset Variable Usually erect4. Transition to

unconsciousnessOften immediate Gradual over seconds

5. Duration of unconsciousness Minutes Seconds6. Duration of tonic or clonic

movements30–60 s Never more than 15 s

7. Facial appearance during Cyanosis, frothing Pallor

Features Seizure Syncopeevent at mouth

8. Disorientation and sleepiness after event

Many minutes to hours

<5 min

9. Aching of muscles after event Often Sometimes10. Biting of tongue Sometimes Rarely11. Incontinence Sometimes Sometimes12. 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 MyelopathiesCAUSES

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 MANAGEMENTSpinal 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 Disorders1)SLE . Responses to glucocorticoids and/or cyclophosphamide 2)Sjögren's syndrome,3)Behçet's syndrome,4)Vasculitis5)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 Myelitis1)Many cases of myelitis, termed postinfectious or postvaccinal, 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 Myelitis1)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 disease9)Syphilis10) 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).