1. Disorders of the CNS

2. The purpose of the session
• The purpose of the session:
to discuss common causes, diagnosis and
differential diagnosis, treatment and prophylaxis of
neurologic complications in patients with HIV/AIDS
• Objectives:
after completing this session, the participants will
be able to:
– Identify common causes of neurologic complications in
patients with HIV/AIDS
– Recognize common neurologic complications in patients
with HIV/AIDS and provide a differential diagnosis
– Provide prophylaxis and treatment of the most common
neurologic complications in patients with HIV/AIDS

3. CNS illnesses with HIV infection
• Toxoplasmosis
• HSV Encephalitis
• Cytomegalovirus Encephalitis
• Cryptococcal meningitis
• Dementia
• Primary CNS Lymphoma
• Progressive Multifocal
Leukoencephalopathy

4. Toxoplasmosis
• CAUSE: Latent T. gondii infection
• In HIV-infected persons toxoplasmosis
mainly appears as encephalitis or as
disseminated disease
• FREQUENCY: 30% of AIDS patients with
latent T. gondii infection (positive serology)
and no prophylaxis
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.

5. PRESENTATION of TOXOPLASMOSIS
• Toxoplasmosis may be suspected by the
clinical findings:
– altered mental status
– fever
– seizures
– headaches
– focal neurologic findings, including motor
deficits, cranial nerve palsies, movement
disorders, dysmetria, visual-field loss, and
aphasia
– over 80% have CD4 <100 cells/mm3
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.

6. Toxoplasmosis diagnosis
• CT or MRI scans: multiple ring enhancing lesions
• IgG for toxoplasma may help in establishing the
diagnosis in the absence of neuroimaging
techinques (T. gondii serology is positive in >95%)
• PCR for T. gondii in CSF is 50% sensitive and
96% to 100% specific.
• Can be confirmed by histologic examination of
tissue obtained by brain biopsy
• Response to therapy is characteristically prompt
and impressive
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.

7. Toxoplasmosis treatment
Pyrimethamine 200mg Single PO Single dose
THEN
Pyrimethamine 25-50mg TID PO 6-8 weeks
PLUS
Folinic acid 15mg OD PO 6-8 weeks
PLUS
Sulphadiazine 1g Every 6 h PO 6-8 weeks
• Instead of sulphadiazine in this regimen, the following may be
used:
- Clindamycin 600mg every 6 h IV/PO for 6 weeks then 300-450mg QID
PO for life, OR
- Azithromycin 1200mg OD PO for 6 weeks then 600mg OD PO for life,
OR
- Clarithromycin 1g BID PO for 6 weeks then 500mg BID PO for life, OR
- Atovaquone 750mg QID PO for 6 weeks then 750mg BID PO for life
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.

8. Herpes simplex virus
• HSV may also cause meningoencephalitis and
meningitis
• HSV encephalitis leads to the development of
multiple lesions in different parts of the brain and
typical changes may be seen on CT scan studies
of the brain
• First line treatment: Aciclovir 10mg/kg every 8
hours IV 14-21 days OR
• Second line treatment: Foscarnet (suspected
resistance to aciclovir) 40 mg/kg every 8 to 12 h
IV 14 d
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.

9. Cytomegalovirus Encephalitis
• CAUSE: CMV + CD4 count <50 cells/mm3
• FREQUENCY: <0.5% of AIDS patients
• PRESENTATION: Rapid progressive delirium, cranial
nerve deficits, nystagmus, ataxia, headache with fever
± CMV retinitis
• DIAGNOSIS:
- MRI shows periventricular confluent lesions with
enhancement
- CMV PCR in CSF shows sensitivity of >80% and specificity of
90%
- Cultures of CSF for CMV are usually negative
• TREATMENT: Ganciclovir, foscarnet, or both IV
John G. Bartlett. Medical management of HIV infection, 2003

10. Cryptococcal meningitis
• INCIDENCE: 8% to 10%
• PRESENTATION: Fever, headache, alert (75%),
less common are visual changes, stiff neck,
cranial nerve deficits, seizures (10%); no focal
neurologic deficits
• CD4 count <100 cells/mm3
• CT, MRI: Usually normal
• DIAGNOSIS: Culture positive (95-100%), Crypt
Ag (>95% sensitive and specific)
- Definitive diagnosis: CSF antigen and/or positive
culture
• TREATMENT: see handout D4-2
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.
John G. Bartlett. Medical management of HIV infection, 2003

11. Dementia
• CAUSE: Chronic encephalitis with progressive or
static encephalopathy due to CNS HIV infection
with prominent immune activation
• INCIDENCE: 7% after AIDS in pre-HAART era;
2% to 3% more recently. Prevalence is increasing
with longer survival
• PRESENTATION:
- Early symptoms: Apathy, memory loss, cognitive
slowing, depression, and withdrawal. Motor defects
include gait instability and reduced hand coordination
- Late stages: global loss of cognition, severe
psychomotor retardation, and mutism
John G. Bartlett. Medical management of HIV infection, 2003

12. Dementia (continued)
• PHYSICAL EXAMINASTIONS
- in early stages:
defective rapid eye movement, rapid limb movement,
and generalized hyperreflexia
- In late stages:
tremor, clonus, and frontal release signs
• DIAGNOSIS: History, physical examination, and
screening with HIV Dementia Scale as noted
above (see handout D4-2)
• TREATMENT: HAART has reduced the
frequency of dementia
John G. Bartlett. Medical management of HIV infection, 2003

13. Primary CNS Lymphoma
• CAUSE: Virtually all are EBV-associated
• FREQUENCY: 2% to 6% in pre-HAART era –
1000x higher than in the general population
• PRESENTATION: Focal or non-focal signs
• CD4 count is usually <50 cells/mm3
• DIAGNOSIS:
- MRI (single lesion or multiple lesions that are isodense
or hypodense and usually homogeneous, but sometimes
ring forms)
- CSF EBV DNA is >94% specific and 80% sensitive
- brain biopsy
John G. Bartlett. Medical management of HIV infection, 2003

14. Factors favoring CNS lymphoma
• Typical neuro imaging results (above)
• Negative T. gondii serology
• Failure to respond to empiric treatment
of toxoplasmosis within 1 to 2 weeks
• Lack of fever
• Thallium SPECT scan with early thallium
uptake
John G. Bartlett. Medical management of HIV infection, 2003

15. Therapy of primary CNS
Lymphoma
- Standard: Radiation + corticosteroids
- Chemotherapy: May be +Standard. Usually
for patients with elevated CD4 counts.
Preliminary results with methotrexate without
radiation were promising
• RESPONSE: Response rates to radiation
treatment plus corticosteroids is 20% to 50%,
but these results are temporary
John G. Bartlett. Medical management of HIV infection, 2003

16. Progressive Multifocal
Leukoencephalopathy
• CAUSE: Activation of JC virus (which is
ubiquitous) in patients who are immunodeficient
• FREQUENCY: 1% to 2%
• PRESENTATION: Cognitive impairment, visual
field deficits, hemiparesis speech defects,
incoordination with no fever.
• CD4 count is usually 35-100 cells/mm3, but a
subset of 7% to 25% have CD4 counts >200
cells/mm3
John G. Bartlett. Medical management of HIV infection, 2003

17. Progressive Multifocal
Leukoencephalopathy (continued)
• DIAGNOSIS
- MRI shows hypodense lesions of white matter without
edema or enhancement
- PCR for JCV in CSF with sensitivity of 80% and
specificity of 95%
• TREATMENT: None with established merit
• PROGNOSIS: Median duration of survival is 1 to
6 months
John G. Bartlett. Medical management of HIV infection, 2003