session 4
DESCRIPTION
TRANSCRIPT
Part A/Module A2/Session 4
Conditions of the
Neurological System
Part A: Module A2Session 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
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
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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
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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
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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
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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
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Cerebral toxoplasmosis
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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)
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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
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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
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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
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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
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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
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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)
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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
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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
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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
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Unique features, CaveatsUnique features, Caveats
Often encountered during late stages of HIV disease. Prompt diagnosis and aggressive management and treatment ensure a quick recovery
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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
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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
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Cryptoccocal meningitis: CSF
Indian ink examination
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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
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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
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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
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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
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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%
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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
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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
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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
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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
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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
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Management and Treatment
There is no treatment for this illness
ART can improve symptoms and prolong life
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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
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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%)
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Cerebral lymphoma
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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
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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
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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
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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
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Neuropsychological tests show subcortical dementia Mini-mental exams not very sensitive
Diagnostics
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AIDS dementia complex
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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
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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
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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
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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
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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
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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
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Unique features, CaveatsUnique features, Caveats
Differential: toxoplasmosis, primary CNS lymphoma Management and treatment is difficult. Consider physical therapy combined with pain
management.
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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
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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
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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
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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.
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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
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Thank You