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Introduction:
Recognized in 1982 – dreaded disease of the20th century
40
million (WHO) in 2000 - India 5 million
HIV is a
retrovirus that grows in T Helper Lymphocytes leading to their
progressive depletion & susceptibility to opportunistic infection
With
earlier, more accurate and specific diagnosis of HIV infection ,
longevity resulting in more affliction of other systems
Reduction/prevention of opportunistic infection most significant
development in management of HIV. Full blown AIDS can be postponed even
to 10 years.
With no
vaccine yet available, behavioral changes appear to be the only way to
reduce the prevalence of HIV infection
Today it
is possible to preserve health and prolong life
Treatment still imperfect, costly and demanding
Post
exposure prophylaxis (Zidovudine ) ???
Transmission in health workers only thro’ cuts from contaminated needles
and splashes on mucous membrane from blood, semen, breast milk,
cervicovaginal secretions and CSF. Saliva alone has not been proved to
be a transmitting agent.
Refusal
to treat HIV patient US Supreme Court ruling
CDC
universal precautions triple latex gloving, thimble protection
Specific effects on the
CNS:
40 TO
70% of HIV infected patients develop symptomatic neurological disorders
often debilitating and life threatening. Autopsy studies reveal 90% CNS
involvement
Diagnosis difficult as those with HIV infection may also have coexisting
alcoholism, diabetes, migraine, cervical spondylosis, HNP etc. all of
which are common in the general population
Localization complex as multiple levels may be involved simultaneously
or sequentially
Clinically, often mild neurological changes are overlooked in the face
of other life threatening problems
Drug
induced, metabolic and nutritional factors could account for many
neurological manifestations rather than HIV infection of the CNS per se
30%-40%
present with neurological signs and symptoms at time of AIDS diagnosis,
12% have some complaint of neurological dysfunction and 10% have no
neurological complaints.
Nitric
Oxide implicated as a potential mediator of BBBB in AIDS
Neurological complications length of stay and total hospital charges
for HIV infected patients (16.3 vs 9.3 days,)
Decision
making for treating AVM etc.
Diagnosis:
CSF
studies for identifying HIV virus, and various other opportunistic
infective pathogens with appropriate PCR.
Serum
immunoglobulin studies – indirect evidence
Quantitative measurement of HIV antigen
Detailed CD4 Cell count
CT/MRI
Stereotactic biopsy - safe and effective.
Algorithm for evaluation of AIDS patient with neurological diseases.
Impact
of ‘neurological AIDS’
1995:
# Equal to those with epilepsy, > Parkinson’s disease, 11000
stereotactic biopsy’s in AIDS patients in the USA >> incidence of
malignant astocytoma, meningiomas
Poll of
neurosurgeons in the US in ’89 indicated that 90% would perform a
surgical procedure if it would have a +ve impact on patient care
The
future : Astroglial cells represent a target for HIV infection in
the central nervous system.. However, activation of the nuclear factor
NF-kappaB and its binding to HIV long terminal repeat (LTR) can induce
HIV replication. Moreover, nitric oxide (NO) can affect NF-kappaB
activation in glial cells. NO may reduce HIV replication in human
astroglial cells by inhibiting HIV-1 LTR transcriptional activity. t NO
donors reduce viral replication in HIV-1-infected human astrocytoma T67
cells, taken as an astroglial model. Furthermore, using transfected T67
cells, NO donors inhibit HIV-1 LTR transcriptional activity. These
results suggest that the use of NO-releasing drugs may represent a
potential in HIV replication in astrocytes.
Specific nervous system
involvement:
Type of
involvement depends on HIV viral load, sub type of the virus, resultant
specific depletion of specific type of Helper Lymphocytes and prior
exposure to preventive drugs e.g. Lymphoma more common when CD4 count is
less than 50 to 100 cells
HIV
Dementia – mild cognition impairment to frank dementia
Encephalitis
Toxoplasmosis (? Empirical Chemotherapy before biopsy, ? ¯ incidence
with prior antimicrobial prohylaxis) focal / diffuse meningo
encephalitis, blood vessel thrombosis à infarction à necrosis à mass
effect. Incidence 12%-13% Respond clinically and radiologically
Pyrimethamine and Sulfadiazine 1 yr survival
Cytomegalo virus detection of CMV DNA in CSF. Treatment – GANCICLOVIR,
FOSCARNET, CIDOFOVIR HAART (Highly Active Antiretroviral Therapy) has
¯ incidence of CMV disease in AIDS.
CMV
retinitis à Blindness
Atypical
herpes simplex virus
Subacute
measles encephalitis (SME)
Epstein-Barr virus and Kaposi's sarcoma
Meningitis
Cryptococcal – 10% of AIDS Patients develop this, More common among
African-Americans, Typical meningitis not seen in 70%. CT mostly
normal. Diagnosis CSF analysis. Inspite of amphotericin B /
5-flucytosine mortality 20%.
Tuberculous – 4 million world wide with TB + HIV. Resistant strains of
TB more common. 2/3 mass lesion, 1/3 meningitis. Mycobacterium avium
more common in AIDS patients. Facial palsy, peripheral neuropathy
associated – very poor survival
Fungal
– Candida albcans – abscess excision with amphotericin B: coccidioides
immitis also rapidly progressive.
Bacterial – Listeria monocytgenes most common. Nocardia asteroids also
common.
Meningoencephalitis
Myelitis
Primary
CNS Lymphoma – more common in AIDS population. Median survival 3-4
months. Radiation Chemotherapy.
Non
Hodgkin’s Lymphoma
Progressive Multifocal Leucoencephalopathy (Papova virus infection) –
dementia, blindness aphasia hemiperasis, ataxia – hypodense areas
without mass effect occurs in 4%-5% of AIDS Patient. Survival 2 months.
Intrathecal cytosine arabinoside.
Neurosyphilis
Vacuolar
Myelopathy – diffused degeneration of thoracic spinal cord? B12
deficiency. – spastic paraparesis, ataxia bowel bladder involvement
Myopathy
Distal
Symmetric Polyneuropathy – more common with DIDANOSINE, ZALCITABINE and
STAVUDINE.
Inflammatory Demyelinating Polyneuropathy
Mononeuropathy multiplex
Progressive polyradiculopathy
Spinal
extradural Leiomyoma
Recurrent brain abscess
Brain
Tuberculoma
CAT
scratch fever à painful radiculopathy
Cerebravascular complications – infarction, hemorrhage.
Drug
induced neurological complications – extra pyramidal, acute myelopathy,
startle myoclonus, dysphasia and delirium – as new drugs are constantly
being developed neurological drug induced complication will become more.
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