Top Banner
Part A/Module A2/Session 4 Conditions of the Neurological System Part A: Module A2 Session 4
56
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Page 1: Session 4

Part A/Module A2/Session 4

Conditions of the

Neurological System

Part A: Module A2Session 4

Page 2: Session 4

Part A/Module A2/Session 4

Objectives

1. Describe the various etiological agents that cause neurological disorders

2. Give key points when taking a history3. Describe the clinical presentation of each disorder4. List the recommended diagnostics and common

findings for each disorder5. Understand the treatment and management of

neurological disorders6. Discuss preventive measures7. Make a differential diagnosis using a case study

approach

Page 3: Session 4

Part A/Module A2/Session 4

Overview

Reported incidence of neurological abnormalities on

clinical examination varies greatly, from 16% to 72%

among hospitalized patients

A wide range of neurological manifestations is

reported: cognitive defects, focal deficits such as

hemiplegia and acute peripheral facial palsy, painful

feet syndrome, encephalopathy

Some of these manifestations are directly caused by

HIV itself, others are the result of OIs caused by

different pathogens or drugs

Page 4: Session 4

Part A/Module A2/Session 4

Major Pathogens

Protozoal infection Toxoplasma Gondii (toxoplasmosis)Mycobacterial infection M. tuberculosis (TB meningitis)Bacterial Strep pneumoniae,

Neisseria meningitis (bacterial meningitis) Fungal infection Cryptococcus neoformans (cryptococcal meningitis)Viral infection Cytomegalovirus (CMV)Other: Progressive multifocal leukoencephalopathy

(PML)Primary CNS lymphoma

HIV-associated dementia (HAD)

Painful sensory and motor peripheral neuropathies

Neurosyphilis

Page 5: Session 4

Part A/Module A2/Session 4

Chart 2. Conditions of the Neurological SystemPathogen Signs and

symptomsDiagnostics

(lab & x-ray)

Management and Treatment

Unique features/caveats

Protozoal Infection Toxoplasma Gondi (toxoplasmosis)

Mycobacterial infection - M. tuberculosis (TB meningitis)

Bacterial InfectionStrep pneumoniae, Neisseria meningitis(Bacterial meningitis

Fungal InfectionCryptococcus neoformans (cryptococcal meningitis)

Viral Infection- Cytomegalovirus (CMV)- Progressive multifocal - leukoencephalopathy (PML)

Other- Primary CNS lymphoma- HIV-associated dementia (HAD)- painful sensory and motor peripheral neuropathies- neurosyphilis

Page 6: Session 4

Part A/Module A2/Session 4

Protozoal infection: Protozoal infection: Toxoplasma Gondii Toxoplasma Gondii (toxoplasmosis)(toxoplasmosis)Presenting Signs and SymptomsPresenting Signs and Symptoms

Clinical symptoms may evolve• Focal neurological deficits, e.g., seizures,

hemiparesis, hemiplegia, cerebellar tremor, cranial nerve palsies, hemisensory loss, visual problems or blindness, personality changes, cognitive disorders

• Headache (severe, localized)• Fever• Confusion• Myalgia• Arthralgia

Page 7: Session 4

Part A/Module A2/Session 4

CSF values• Normal: 20-30%• Protein: 10-150/ml• WBC: 0-40 (monos)• Blood: FBC

***** An HIV-infected individual presenting with typical

signs and symptoms and normal cerebrospinal fluid findings should be put on treatment for toxoplasmosis

Diagnostics

Page 8: Session 4

Part A/Module A2/Session 4

Cerebral toxoplasmosis

Page 9: Session 4

Part A/Module A2/Session 4

Management and Treatment

Provide physiotherapy as necessary

Start anti-convulsant treatment

• Epanutin 50 – 100 mg bid or tid or tegretol 100 –

200 mg bid or tid (to be started only if the patient

has convulsion)

Page 10: Session 4

Part A/Module A2/Session 4

Management and Treatment, continued

Start Treatment for acute phase:• Pyrimethamine 100 – 200 mg loading dose, then

50 – 100 mg/day po + folinic ( or folic) acid 10 mg/day po + sulfadiazine 1-2g qid for at least 6 weeks

or• Trimethoprim/Sulfamethoxazole (10/50mg/kg

daily) for 4 weeksor

• Clindamycin (600mg tid) + pyrimethamine 100mg daily loading dose followed by 50 mg daily + folinic acid 10 mg daily

Page 11: Session 4

Part A/Module A2/Session 4

Unique features, CaveatsUnique features, Caveats

One of the most common HIV-related neurological complications

If patient does not receive maintenance therapy, disease will recur. Usually occurs when CD4<100

Check blood picture regularly as relatively high doses of drugs can lead to toxicities

Leukopenia thrombocytopenia and rash are common. Folinic acid reduces the risk of myelosuppression

During treatment, patients should maintain a high fluid intake and urine output

Preventive measures and prophylaxis: See Part One, Module 2/Session 10

Page 12: Session 4

Part A/Module A2/Session 4

Treatment after a case of Toxo

Preferred regimen for suppressive therapy required

after a patient has had Toxo:

• Pyrimethamine 25-75 mg po qd + folinic acid 10 mg qd + sulfadiazide 0.5-1.0 gm po qid

If allergic to sulfa

• Give Dapsone po 100 mg po once daily or Clindamycin IV (or oral) 600 mg qid or Atovaquine 750 mg po qid

Page 13: Session 4

Part A/Module A2/Session 4

Mycobacterial Infection: M. tuberculosis (TB Meningitis)

Presenting Signs and Symptoms

Gradual onset of headache and decreased consciousness

• Low grade evening fevers• Night sweats• Weight loss• Neck stiffness and positive Kernig’s sign• Cranial nerve palsies result from exudate

around base of the brain

Page 14: Session 4

Part A/Module A2/Session 4

CSF Values

• Normal: 5-10%• Protein: High (40mg/dl-100 mg/dl)• WBC: 5-2000 (average is 60-70%

monos)• Glucose: low (<20 mg/dl)• AFB smear pos: 20%

Diagnostics

Page 15: Session 4

Part A/Module A2/Session 4

Unique features, CaveatsUnique features, Caveats

CD4<350

Up to 10% of HIV/AIDS patients who present with TB will show involvement of the meninges. This results either from the rupture of a cerebral tuberculoma or it is blood-borne

Always exclude cryptococcal meningitis by CSF microscopy (India ink stain)

Page 16: Session 4

Part A/Module A2/Session 4

Bacterial Infection: Strep pneumoniae, Neisseria Meningitis (Bacterial Meningitis)

Presenting Signs and Symptoms

Symptoms tend to present within one week of infection. May be preceded by a prodromal respiratory illness or sore throat.

- Fever - Vomiting

- Headache - Malaise

- Stiff neck - Irritability

- Photophobia - Drowsiness

- Coma

Page 17: Session 4

Part A/Module A2/Session 4

CSF Values

• leukocytosis

• cerebrospinal fluid shows increased pressure

• cell count (100 –10,000/mm3)

• protein (>100 mg/dl)

• decreased glucose (<40 mg/dl or <50% of the simultaneous glucose blood level)

• gram-stained smear of the spun sediment of the CSF can reveal the etiologic agent

Diagnostics

Page 18: Session 4

Part A/Module A2/Session 4

Management and Treatment

Penicillin (24 million units daily in divided doses every 2-3 hours)or

Ampicillin (12 gr daily in divided doses every 2-3 hours) or

Chloramphenicol (4 to 6 grams IV/day). Treatment should be continued for 10 to 14 days.

Crystalline penicillin 2-3 mega units and chloramphenicol 500-750 mg every 6 hours for 10-14 days

Page 19: Session 4

Part A/Module A2/Session 4

Unique features, CaveatsUnique features, Caveats

Often encountered during late stages of HIV disease. Prompt diagnosis and aggressive management and treatment ensure a quick recovery

Page 20: Session 4

Part A/Module A2/Session 4

Fungal Infection: Cryptococcus neoformans (cryptococcal meningitis)

Presenting Signs and Symptoms

Presentation usually nonspecific at onset. This may be true for > 1 month. • Protracted headache and fever may be the only

signs• Nausea, vomiting, and stiff neck may be absent

and focal neurological signs uncommon.• Extraneural symptoms:

- skin lesions, pneumonitis, pleural effusions and retinitis

• Fever, malaise, nuchal pain signify a worse prognosis, and nausea and vomiting and altered mental status in terminal stages

Page 21: Session 4

Part A/Module A2/Session 4

CSF Values• Normal 20%• Protein 30-150/dl• WBC: 0-100 (monos)• Glucose decreased: 50-70mg/dl• Culture positive: 95-100%• India ink positive: 60-80%• Crypt Ag nearly 100% sensitive and specific

Diagnostics

Page 22: Session 4

Part A/Module A2/Session 4

Cryptoccocal meningitis: CSF

Indian ink examination

Page 23: Session 4

Part A/Module A2/Session 4

Management and Treatment

Preferred regimen: • Amphotericin P 0.7 mg/kg/day IV, +

flucytosine 100 mg/kg/day po x 14 days, followed by Fluconazole 400 mg/day x 8-10 weeks. Finally, maintenance therapy with Fluconazole 200mg/day for life

Page 24: Session 4

Part A/Module A2/Session 4

Management and Treatment, continued

Alternate regimen:• Amphotericin B 0.7 mg/kg/day IV + flucytosine

100mg/kg/day po x 14 days followed by itraconazole 200mg bid for 8 weeks

• Fluconazole 400 mg/day po x 8 weeks followed by 200 mg once daily

• Itraconazole 200 mg po tid x 3days, then 200 mg po bid x 8 weeks after initial treatment with amphotericin

• Fluconazole 400 mg/day po + flucytosine 100 mg/kg/day po

Page 25: Session 4

Part A/Module A2/Session 4

Unique features, CaveatsUnique features, Caveats

If untreated, it is slowly progressive and ultimately fatal

Most common life-threatening fungal infection in HIV/AIDS patients. Also the most common cause of meningitis in patients with HIV/AIDS in Africa and Asia. Occurs most often in patients with CD4<50

It is better prevented than treated

Page 26: Session 4

Part A/Module A2/Session 4

Unique features, Caveats, continuedUnique features, Caveats, continued

Headache is secondary to fungal accumulation. Headache increases gradually over time and then follows a recurring pattern. It becomes harder to get rid of, and then becomes continuous. This is what the patient reports.

Requires lifelong suppressive treatment unless immune reconstitution occurs

Page 27: Session 4

Part A/Module A2/Session 4

Viral Infection: Cytomegalovirus (CMV)

Presenting Signs and Symptoms

Fever delirium, lethargy, disorientation, malaise, headache most common

Stiff neck, photophobia, cranial nerve deficits less common

No focal neurological deficits

Gastrointestinal symptoms: diarrhea, colitis,

esophageal ulceration appear in 12-15% of patients Respiratory symptoms, i.e, pneumonitis, present ~1%

Page 28: Session 4

Part A/Module A2/Session 4

Retinal exam to check for changes. Consult an ophthalmologist

CMV retinitis, characterized by creamy yellow white, hemorrhagic, full thickness retinal opacification, which can cause visual loss and lead to blindness if untreated; patient may be asymptomatic or complain of floaters, diminished acuity or visual field defects. Retinal detachment if disease is extensive

UGI endoscopy when indicated

Diagnostics

Page 29: Session 4

Part A/Module A2/Session 4

Page 30: Session 4

Part A/Module A2/Session 4

Management and Treatment

Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h

x 14-21 days; ganciclovir 5mg/kg IV bid x 14-21

days. Patients without immune recovery will

need to be on maintenance therapy lifelong for

retinitis

Extra-ocular; ganciclovir and/or foscarnet

Page 31: Session 4

Part A/Module A2/Session 4

Unique features, caveatsUnique features, caveats

Evolution occurs in less than 2 weeks Usually when CD4<100  Although any part of the retina may be involved,

there is a predilection for the posterior pole; involvement of the optic nerve head and macula region is common

Characteristically involves the retinal vessels which

are always abnormal in areas involved by retinitis. There is minimal or no accompanying uveitis

  Rare but devastating illness in resource poor

settings. Treatment is very expensive and usually not available. CMV management needs special care. Therefore, early referral is essential

Page 32: Session 4

Part A/Module A2/Session 4

Viral Infection: Progressive mulltifocal leukoencephalopathy (PML)

Presenting Signs and Symptoms

Afebrile, alert, no headache Progressively impaired speech, vision, motor

function Cranial nerve deficit and cortical blindness Cognition affected relatively late

Page 33: Session 4

Part A/Module A2/Session 4

CT brain scan may be normal or remarkable for areas of diminished density or demyelination (deterioration of the covering of the nerve)

PCR of CSF for detection of JC virus JC virus PCR is positive in about 60% of the cases Differential diagnosis:

Toxoplasmosis

Primary CNS lymphoma

 

Definitive diagnosis is by brain biopsy (if available)

Diagnostics

Page 34: Session 4

Part A/Module A2/Session 4

Management and Treatment

There is no treatment for this illness

ART can improve symptoms and prolong life

Page 35: Session 4

Part A/Module A2/Session 4

Unique features, CaveatsUnique features, Caveats

An end-stage complication of HIV, caused by the JC virus

  PML is rare in the general community, but relatively

common in HIV infection (affecting 4% of all AIDS patients). Routine testing for HIV should be considered for any patient with PML

  Evolution occurs over weeks to months

CD4<100

Page 36: Session 4

Part A/Module A2/Session 4

Primary CNS lymphoma

Presenting Signs and Symptoms

Disease progresses slowly over a few weeks Afebrile Headache Focal and multifocal neuro deficits (confusion,

hemiplegia, seizures) Mental status change (60%), personality or

behavioral Seizures (15%)

Page 37: Session 4

Part A/Module A2/Session 4

Cerebral lymphoma

Page 38: Session 4

Part A/Module A2/Session 4

CT Scan/MRI Location: pre-ventricular in one or more site Prominent edema, irregular and solid on

enhancement.   CSF:

• Normal;—30-50%• Protein—10-150/ml• WBC—0-100 (monos)• Cytology positive in <5%• Suspect with negative toxo IgG or failure to

respond to empiric toxo treatment

Diagnostics

Page 39: Session 4

Part A/Module A2/Session 4

Management and Treatment

There is no cytotoxic chemotherapy for this disease. Irradiation can help some patients, but is considered palliative 

Corticosteroids can also help some patients

Page 40: Session 4

Part A/Module A2/Session 4

Unique features, CaveatsUnique features, Caveats

Primary CNS Lymphoma is RARE in the general

community, but affects about 2% of AIDS patients

Survival after diagnosis is usually limited (a few

months only)

Typical end-stage complication of HIV disease

Evolution: 2-8 weeks

Usually occurs when CD4<100

Page 41: Session 4

Part A/Module A2/Session 4

HIV-associated dementia (HAD)

Presenting Signs and Symptoms

In up to 10% of patients it is the first manifestation of HIV disease

Afebrile; general lethargy

Triad of cognitive, motor and behavioral

dysfunction

Early - concentration and memory deficits,

inattention, motor-uncoordination, ataxia,

depression, emotional lability

Late - global dementia, paraplegia, mutism

Page 42: Session 4

Part A/Module A2/Session 4

Neuropsychological tests show subcortical dementia Mini-mental exams not very sensitive

Diagnostics

Page 43: Session 4

Part A/Module A2/Session 4

AIDS dementia complex

Page 44: Session 4

Part A/Module A2/Session 4

Management and Treatment

Possible benefit from ARV agents that penetrate the

CNS (AZT, d4T, ABC, nevirapine)

Benefit of AZT at higher dose for mild or moderately

severe cases is established; monitor therapy with

neurocognitive tests

Anecdotal experience indicates response to ART if

started early

Page 45: Session 4

Part A/Module A2/Session 4

Management and Treatment, continued

Sedation for those who are agitated and aggressive

—use smaller doses initially to avoid over-sedation

Close monitoring: to prevent self-harm, ensure

adequate nutrition, diagnose and treat OIs early

Psychological support for caregivers—exhausting

work; caregivers need regular breaks and may

need counseling

Page 46: Session 4

Part A/Module A2/Session 4

Painful Sensory and Motor Peripheral Neuropathies

Presenting signs and symptoms Burning pain and numbness in toes and feet, ankles,

calves, fingers in more advanced cases Paraplegia Autonomic dysfunction Poor bowel/bladder control Dizziness secondary to postural hypotension Contact hypersensitivity in some cases Mild/moderate muscle tenderness Muscle weakness Later: Reduced pinprick/vibratory sensation; reduced or

absent ankle/knee jerks Sweating

Page 47: Session 4

Part A/Module A2/Session 4

Electromyography/nerve conduction velocities show predominantly axonal neuropathy

CPK usually elevated

CSF - look for cytomegalovirus or herpes simplex virus infections—lymphomatous infiltration

Spinal fluid to determine etiology

Serum B12 and TSH Quantitative sensory testing or thermal thresholds

may be helpful

Diagnostics

Page 48: Session 4

Part A/Module A2/Session 4

Management and Treatment

Exclude neurotoxic drugs, alcoholism, diabetes, B12

deficiency, thyroid problems and treat underlying

causes if known.

Discontinue presumed neurotoxic medication

Provide proper nutrition and vitamin supplements

Page 49: Session 4

Part A/Module A2/Session 4

Management and Treatment, continnued

Pain control:• Ibuprofen 600-800 mg po tid or codeine for

modest symptoms• Amitryptiline 25-50 mg at night• Phenytoin 50-100 mg bid or carbamazapine 100-

200 mg tid– especially for episodic shooting pain. May have to combine antidepressants with anti-convulsants

• Methadone or morphine for severe symptoms• Lidocaine 10-30% ointment for topical use

Physical therapy may be helpful, but may be hampered by pain

Nutrition counseling and psychological support

Page 50: Session 4

Part A/Module A2/Session 4

Unique features, CaveatsUnique features, Caveats

Differential: toxoplasmosis, primary CNS lymphoma  Management and treatment is difficult. Consider physical therapy combined with pain

management.

Page 51: Session 4

Part A/Module A2/Session 4

Neurosyphilis

Presenting Signs and Symptoms

Can be asymptomatic

Headache, fever, photophobia, meningismus seizures, focal findings, cranial nerve palsies

Tabes dorsalis—sharp pains, parasthesias, decreased DTRs, loss of pupil response

General paresis— memory loss, dementia, personality changes, loss of pupil response

Meningovascular strokes, myelitis

Ocular syphilis—iritis, uveitis, optic neuritis

Page 52: Session 4

Part A/Module A2/Session 4

CT Scan/MRI: Aseptic meningitis—may show meningeal enhancement. General paresis—cortical atrophy, sometimes with infarcts. Meningovascular syphilis—deep strokes. May present like dementia.

CSF: Protein—45-200/ml WBCs—5-100 (monos) VDRL positive—sensitivity 65%; specificity 100%

positive Serum VDRL and FTA-ABS are clue in >90%; false

neg serum VDRL in 5-10% with tabes dorsalis or general paresis

Definitive diagnosis: positive CSF, VDRL (found in 60-70%)

Diagnostics

Page 53: Session 4

Part A/Module A2/Session 4

Management and Treatment

Give Aq penicillin G, 18-24 mil units/day x 10-14 days

Follow-up VDRL every 6 months until negative

 Indications to re-treat:• CSF WBC fails to decrease at 6 months or CSF

still abnormal at 2 years• Persisting signs and symptoms of inflammatory

response at 3 months• Four-fold increase in CSF VDRL at 6 months

Failure of CSF VDRL of 1:16 to decrease by two-fold by 2 months or four-fold by 12 months

Page 54: Session 4

Part A/Module A2/Session 4

Unique features, CaveatsUnique features, Caveats

RARE: affects only 0.5% of all HIV/AIDS patients

Most common forms in HIV-infected persons are ocular, meningeal, and meningovascular

Some evidence that syphilis progresses more rapidly in the context of HIV infection, so that complications such as meningovascular syphilis may occur at an unusually early phase.

 

Page 55: Session 4

Part A/Module A2/Session 4

Unique features, Caveats, continuedUnique features, Caveats, continued

Recommended that syphilis testing be offered to all clients presenting for VCT in high prevalence areas because it is treatable in early stages, and has an accelerated course in HIV.

CD4<350

Page 56: Session 4

Part A/Module A2/Session 4

Thank You