cns illnesses eng_d4-2

Disorders of the CNS

• 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

The purpose of the session

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

Leukoencephalopathy

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.

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


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


Toxoplasmosis treatment

• 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

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


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


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

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



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


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


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


Factors favoring CNS lymphoma

1. Typical neuro imaging results (above)2. Negative T. gondii serology3. Failure to respond to empiric treatment of

toxoplasmosis within 1 to 2 weeks4. Lack of fever5. Thallium SPECT scan with early thallium

uptake


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


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


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


cns illnesses eng_d4-2

Health & Medicine

medical management

care protocols

independent states

line treatment

hiv infection

gondii infection

treatment

brain