Transcript Session 3: Neurologic Diseases and HIV

Neurologic Diseases and
HIV
HAIVN
Harvard Medical School AIDS
Initiative in Vietnam
1
Learning Objectives
By the end of this session, participants
should be able to:
 Outline the 2 most common causes
of headache and fever in PLHIV
 Describe how to diagnose, including
potential differential diagnoses, a
focal neurological deficit
 Describe causes and treatment for
peripheral neuropathy in PLHIV
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I. Headache
3
Differential Diagnoses of
Headache and Fever
Meningitis:
 Cryptococcal
Meningitis
 Tuberculosis
Meningitis
 Bacterial Meningitis
• Strep pneumoniae,
Neisseria meningitidis

Syphilitic Meningitis
Other Infectious
Causes:
 Toxoplasma
Encephalitis
 Brain Abscess
(Staph aureus
especially with IDU)
 Sinusitis (bacterial
or viral)
 Herpes
Meningoencephalitis
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Cryptococcal Meningitis


Occurs in advanced AIDS: CD4<100
Clinical manifestations:
• Headache
• Fever
• Nuchal rigidity (only 25%)
• Vomiting
• Confusion
• Blurred vision, photophobia
Often associated with elevated intracranial pressure
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Cryptococcus Neoformans

Disseminated disease may occur
• Fungal pneumonias
• Skin lesions

10-40% of patients with
disseminated cryptococcal disease
have no neurological symptoms
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Cryptococcus Meningitis:
Diagnosis (1)
Lumbar Puncture:
 High CSF pressure
 WBC often not elevated (usually < 50
cells/μl)
 Glucose normal to low
 Protein normal to high
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Cryptococcus Meningitis:
Diagnosis (2)


Positive CSF India Ink in 75%
Cryptococcal Antigen (CRAG)
• CSF > 90% positive
• Serum > 99% positive
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Cryptococcus Meningitis:
Management
Vietnam MOH, HIV/AIDS Treatment Guidelines, 2009
Treatment
Standard Treatment
If symptoms are mild or if
amphotericin is not
available or not tolerated
Maintenance therapy
Dosage
• Amphotericin B: 0.7-1mg/kg/day
x 14 days, then
• Fluconazole 800-900 mg/day for
8 weeks
• Fluconazole 800-900 mg/day for
8-10 weeks
• Fluconazole 150-200 mg/day
until on ARV with CD4 > 200 for
9
6 months
Cryptococcus Meningitis:
Management of High Intracranial Pressure (1)



Normal pressure < 20
cm/H2O (200 mm/H2O)
Elevated pressure
causes severe headache
and results in increased
mortality and morbidity
Visual loss as
consequence of high
pressure
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Cryptococcus Meningitis:
Management of High Intracranial Pressure (2)



Daily lumbar punctures (LP)
Each time remove 15-20 CC CSF or until
the patient’s headache improves
Mannitol and corticosteroids not effective
for lowering pressure
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Tuberculosis Meningitis




Common in HIV, slow chronic onset is usual
Typical symptoms: fever, headache,
confusion
May be focal signs or cranial nerve palsies
due to space occupying lesions and/or
cerebral mass effect
Often other features of TB
• examine chest and lymph nodes

Main differential is cryptococcal meningitis
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TB Meningitis: Diagnosis
CSF:



Pressure may be
raised
Lymphocytosis or
mixed cells in CSF
Typically:
• Protein very high (2-6
g/dL)
• Low glucose (<45
mg/dL)

AFB are difficult to
find in CSF


Perform India Ink
staining to help
exclude or confirm
cryptococcal
meningitis
Look for TB
elsewhere in body
by CXR, sputum,
and aspiration of
lymph nodes where
appropriate
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TB: National Treatment Protocol
9-12 month regimens recommended
for TB meningitis
MOH Protocol
Alternate regimens
for HIV patients*
Alternate regimens
for HIV patients
with severe TB
disease*
Induction Phase
2 months
Maintenance
Phase
SRHZ
HE x 6 months
(S)ERHZ
RH x 4 months
SRHZE
HRZE x 1 month,
then
H3R3E3 x 5
months 14
TB Meningitis Treatment:
Steroids


Concurrent steroid treatment
reduces mortality by 31%
Doses:
Thwaites, NEJM, 2004; CDC, MMWR 58:RR-4, 2009
Medication
Dosing
Dexamethasone
• 0.3-0.4 mg/kg/day x 1 week
• then taper over 5-7 weeks
or...
Prednisone
• 1 mg/kg/day x 3 wks
• then taper over 3-5 wks
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II. Focal Neurological Deficit
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Focal Neurologic Deficit
Common causes in HIV:
 Toxoplasma encephalitis
 Tuberculoma
 Progressive Multifocal
Leukoencephalopathy (PML)
 Primary CNS lymphoma
 Abscess
• Bacterial brain abscess in active IDUs
• Cryptococcoma

Stroke
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Tuberculoma



Less common than
meningitis, but
should be
considered in any
patient with a
history of TB
Lesions may present
as single or multiple
mass lesions
Look for TB
elsewhere in body
by CXR, sputum, etc
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Tuberculomas
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Cerebral Toxoplasmosis


Seen in patients with CD4<100
Manifestations:
• Focal neurological signs (unilateral
paralysis)
• Generalized neurological signs
(confusion, epilepsy, coma, etc.)
• Meningeal signs are rare
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Cerebral Toxoplasmosis –
Diagnosis (1)

MRI of cerebral
toxoplasmosis
showing 2 ring
enhancing
lesions –
“lighting up”
with
intravenous
contrast
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Cerebral Toxoplasmosis –
Diagnosis (2)

CT scan of brain
done without
intravenous
contrast showing
edema around
multiple lesions
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Cerebral Toxoplasmosis:
Treatment
Treatment Type
Medication Regimen
Cotrimoxazole:
TMP 10 mg/kg/day IV or orally divided into
twice daily doses
Acute Treatment
for 6 weeks
Maintenance
Therapy:
Discontinue when
patient is on ART
with CD4 count >
100 cells/mm3 ≥ 6
months
OR:
Pyrimethamine
200 mg loading dose,
then 50-75 mg once
daily
+
Sulfadiazine
2-4 g initial dose,
then 1- 1.5 g every
6 hours
Cotrimoxazole:
960 mg (SMX 800mg / TMP 160mg) orally once per
day
OR:
Pyrimethamine
25-50 mg/day
+
Sulfadiazine
1g x every 6 hours
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Progressive Multifocal
Leukoencephalopathy (PML) (1)

Etiology: JC Virus (JCV)
• Polyomavirus
• Most adults colonized

Clinical:
• Focal deficit
• Gate disturbance,
• Visual loss, sensory loss

Diagnosis: CT or MRI
• Hypodense white-matter lesions
• No mass effect, no contrast
enhancement
• CSF examination normal

Treatment: ARV
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Progressive Multifocal
Leukoencephalopathy (PML) (2)

27 year old male patient in HCMC with
right arm weakness and dysarthria
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Bacterial Brain Abscess and
Emboli

Etiology:
• Endocarditis secondary to IDU
• Staphylococcus aureus infection

Clinical:
• Signs of recent injecting
• Embolic events: subungal hematoma,
Osler’s nodes (palms and feet), hematuria

Diagnosis:
• Cardiac ultrasound
• Positive blood culture
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Primary Cerebral Lymphoma (1)
Etiology
 Associated with
Epstein-Barr Virus
(EBV)
 CD4 < 100
cells/mm3
Clinical
 Headache, usually
no fever
 Onset usually
slower than
toxoplasmosis
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Primary Cerebral Lymphoma (2)
Diagnosis and Treatment:
 Difficult to distinguish from
toxoplasmosis on CT/MRI
 Incurable
• so rule out and try empiric treatment for
treatable causes before making diagnosis

Treatment: radiation, chemotherapy
• May show brief initial response to steroids
• ARV may improve survival
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Diagnostic Approach to Focal CNS Deficit
Perform head CT scan
if available
If head CT not available:
- begin empiric treatment for toxoplasma and
- follow clinical course over 1-2 weeks
If patient improves,
complete treatment
course and commence
maintenance therapy
If status worsens or
diagnosis remains in
question, proceed
with head CT and
further evaluation29
III. Peripheral Neuropathy
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Causes of Peripheral
Neuropathy

Vitamin deficiency
•
•
•
•

B12
Folate
Pyridoxine
Thiamine
Infectious Diseases
• Syphilis
• CMV
• HIV

Metabolic Diseases
• Diabetes

Drug induced
• Alcohol
• ARV: d4T, ddI
• TB: INH
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Clinical Manifestations of
Neuropathy



Usually starts
distally (toes or
finger tips) and
progresses towards
center
Numbness, burning,
cold
Reduced sensation
of:
• Pain
• Temperature
• vibration




Reflexes reduced
Strength and joint
position usually
normal unless
severe
With treatment can
improve, but very
slowly
Can be irreversible if
not treated
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Peripheral Neuropathy:
Prevention
Type of
Patient
Prevention Management
Patients on
ARV
• Switch d4T to AZT after 12
months
Patients on
• Ensure that patients are given
TB treatment
pyridoxine (B6) 25-50 mg/day
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Peripheral Neuropathy:
Treatment
1. Treat the Cause
2. Treat the pain
Cause
Recommendation
Drug
Type/Dosing
d4T
•switch to AZT or
TDF
Analgesics
Alcohol
• stop drinking
•Paracetamol
•NSAIDs
INH
•vitamin B6 50
mg/day
•consider stopping
INH early
Vitamin supplements: B6,
folate, B12
Amitriptyline 25 – 75
mg/day
Carbamazepine
Morphine if very severe
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Quick Quiz
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CSF Profile of HIV-related OIs
CSF
Opening
pressure
Protein
content
Cell count
Cryptococcal
meningitis
Very
high
Slightly
elevated or
normal
Slightly
elevated or
normal
TB
meningitis
High or
normal
Slightly
elevated to
very high
Elevated
Toxoplasmal
encephalitis
Microscopy Culture
+
India ink
stain
+
(lymphocytes
predominate)
+/- - -
+/-
Normal
Normal or
slightly
elevated
Normal
-
-
Bacterial
meningitis
High
Very high
Granulocytes
predominate
+/-
+
Lymphoma
Normal
Normal
Normal
-
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-
Key Points



Fever and headache in PLHIV are
indications for a lumbar puncture to
evaluate for meningitis
The most common causes of focal
neurologic deficits are Toxoplasma,
TB, and CNS Lymphoma
Medications (d4T, INH) are common
causes of peripheral neuropathy
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Thank you!
Questions?
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