CNS OIs In AHD

Question 1

list the CNS OI in advanced HIV disease

Answer 1

 CNS toxoplasmosis
 Cryptococcal meningitis
 Tuberculous meningitis/Tuberculoma
 Progressive multifocal leucoencephalipathy
 CMV polyradiculopathy/Encepalitis

Question 2

Etiology of CRYPTOCOCCAL MENINGITIS

Answer 2

This is caused by Cryptococcus neoformans which is a yeast-like fungus.
 Pigeon dropping common contain serotypes A or D.
 Infection is acquired through inhalation.
 It is the leading cause of meningitis in patients with AIDS.
 It occurs late in the course of HIV/AIDS when the CD4 count drops below 100

Question 3

CRYPTOCOCCAL MENINGITIS pathogenesis

Answer 3

Inhaled from the environment (soil contaminated with bird droppings).
Disseminates hematogenously to the CNS causing meningoencephalitis.

Question 4

CRYPTOCOCCAL MENINGITIS C/F

Answer 4

 Low grade fever, nausea, vomiting, headache
 Both fever and nuchal rigidity are often mild or lacking
 Papilledema is seen in 1/3 of patients
 Neck stiffness, photophoba- meningeal signs (30%)
 Late manifestations: confusion, altered state of consciousness coma.
 Extracranial manifestations:
o Pulmonary or disseminated disease that includes the skin (10%)
o Cutaneous Cryptococcosis: centrally umbilicated multiple lesions on the
face (look very much like Molluscum contagiosum)
o Pulmonary disease
o Fungemia
o Lymphadenopathy
o The prostate gland may be a reservoir for smoldering infection

Question 5

CRYPTOCOCCAL MENINGITIS diagnosis

Answer 5

 LP-CSF analysis
o Opening pressure is high
o WBC with differential, protein, glucose is normal in 1/3 of patients
o India Ink- positive in 60-80%
o CSF cryotptoccal antigen- Positive in 95-99%
o Cryptococcal culture- Gold standard

Question 6

CRYPTOCOCCAL MENINGITIS TREATMENT

Answer 6

A. Induction phase
Amphotericin B + Flucytosine for 2 weeks
B. Consolidation phase
Fluconazole ( 400-800 mg for 2 weeks)
C. Maintenance phase
Secondary prophylactic
Fluconazole (200 mg for at least 12 months)
D. Initiation of ART

Question 7

CNS TOXOPLASMOSIS

Answer 7

This is caused by the protozoa Toxoplasma gondii.
 It is a zoonotic infection and cats are the definite host and excrete the oocysts in
their feces and can be transmitted from animal to humans.
 T. gondii cysts are also found in under-cooked meat.
 This is the second most common cause of secondary CNS infection in patients
with AIDS.
 It is generally a late complication of HIV infection and usually occurs when the
CD4 cell count is less than 100/mm3
.

Question 8

CNS TOXOPLASMOSIS C/F

Answer 8

 Onset- subacute
 Fever, headache, hemiparesis, seizures and altered mental status
 Focal neurological signs (90%)
 Encephalitis picture (10%)- confusion or common and become more toxic
 Commonly affected areas- basal ganglia, brain stem and cerebellum
 Extracranial manifestations:
o Chorioretinitis
o Myocarditis
o Pneumonitis (lung)

Question 9

CNS TOXOPLASMOSIS DIAGNOSIS

Answer 9

 Clincial: history and physical examination
 Neuroimaging (CT/MRI):
o Multiple ring enchancing lesions are
seen in 90% of patients with mass
effect and edema. (A solitary lesion on
MRI makes the diagnosis unlikely)
o Preferential location: basal ganglia,
grey-white junction, white matter
 Therapeutic trial +/- histology (biopsy)
o Histology: brain biopsy- in patients
with treatment failure (not possible in
Zambia)
 Serologic assays are of limited value, a
negative toxoplasma antibody test makes the
diagnosis less likely. increased IgG and IgM usually negative in reactivation

Question 10

CNS TOXOPLASMOSIS TX

Answer 10

Septrine 1st line
Pyrimethamine + sulfadiazine 2nd line

Question 11

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) ETIOLOGY

Answer 11

 This is due to reactivation of JC virus (John Cunningham virus).
 It is seen in 2-4% of AIDS patients

Question 12

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) CHARACTERIZED BY…

Answer 12

 PML is characterized by progressive damage (-pathy) or inflammation of the
white matter (leuko-) of the brain (encephalo-) at multiple locations (multiple)

Question 13

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) C/F

Answer 13

 Occurs late in the course of HIV when CD count <100
 Subacute onset
 The patient is afebrile, alert without headache
 Multifocal neurologic deficit
 Classic triad:
o Dementia
o Hemiparesis
o Hemianopsia

Question 14

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) DIAGNOSIS

Answer 14

 CSF is often non-diagnostic.
o CT shows multifocal, non-contrast enhancing hypodense lesions without
mass effect but MRI is more sensitive.
o Common areas of involvement: cortical white matter of frontal and
parietaloccipital lobes. Lesions can occur anywhere
 Serology: 90% adults are seropositive for JC virus so this is not useful in
diagnosis
 JCV PCR or brain biopsy may help to make diagnosis

Question 15

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) TX

Answer 15

 There is no effective treatment but initiation of HAART increases survival.

Question 16

TB MENINGITIS

Answer 16

It is commonly seen in children and
immune-compromised people
particularly patients with HIV
Most common cause of mortality in advanced HIV
Other forms of TB are not HIV opportunistic infections.
Etiology
Mycobacterium tuberculosis infection of the meninges
Seen at any stage of immunosuppression especially CD4 < 200cells/mm3
Hematogenous spread to the meninges forming basal exudates and granulomas

Question 17

TB MENINGITIS C/F

Answer 17

Patients with TB meningitis present with, behavioral changes and neck rigidity for about two weeks or more.

Headache ( subacute or chronic)
Fever
Vomiting
Altered mental state
Cranial nerve palsies ( commonly III & VI)
Hydrocephalus
Seizures
Stroke like features

Question 18

TB MENINGITIS DIAGNOSIS

Answer 18

CSF Examination
High protein
Low glucose
Lymphocytic predominance
Appearance is turbid
Opening pressure is raised or normal
2. Gene Xpert
3. MRI/ CT
Shows basal meningeal enhancement, tuberculomas and infarct

Question 19

TB MENINGITIS TX

Answer 19

Initiation phase
4 fixed dose (HRZE) for 2 months
2. Continuation phase
for 10months
3. Adjuvant phase
Steroids for 1 month then tapered down

Question 20

PRIMARY CNS LYMPHOMA

Answer 20

Activated by EBV
Occurs especially in patients with CD4 count < 50cells/mm3
It is a high grade, non- Hodgkin B-cell lymphoma
Occurs almost exclusively in immunocompromised patients

Question 21

PRIMARY CNS LYMPHOMA PATHOGENESIS

Answer 21

Arises from B cells infected with EBV
The immunodeficient environment allows for unchecked EBV driven proliferation ( EBV acts like a driver that causes B cells to multiply uncontrollably leading to lymphoma because of immunosuppression)

Question 22

PRIMARY CNS LYMPHOMA C/F

Answer 22

 Confusion, lethargy, memory loss (57%)
 Hemiparesis or aphasia (40%)
 Seizures (14%)
 Cranial nerve palsy (9%)
 Headaches only (3%)
 No fever unless concomitant infection

Question 22

PRIMARY CNS LYMPHOMA DIAGNOSIS

Answer 22

 CT/MRI: Multiple lesions as frequent or as single lesions (irregular and solid
enhancement, subependymal enhacement more specific, variable mass
effect. Localization mainly periventricular)
 CSF: EBV DNA PCR- CSF (85-100% sensitive, 98-100% specific)
 Histology: diffuse infiltrating, multicentric tumor of B cell lineage with the
presence of EBV genome in approximately 100%.

Question 23

PRIMARY CNS LYMPHOMA TX

Answer 23

 Cytotoxic chemotherapy is not effective
 Radiotherapy can help some patients
 Response to steroid variable

Question 24

Other CNS Condition in Advanced HIV

Answer 24

Neurosyphilis CMV encephalitis Trypanosomiasis Metabolic encephalopathy