This document provides a literature review on neurological manifestations in HIV positive patients and the correlation with cerebrospinal fluid (CSF) parameters. It summarizes several studies that examined the prevalence and nature of neurological disorders in HIV patients and their relationship to CD4 count and other CSF markers. Many studies found neurological problems to be common and correlated with immunosuppression. Cryptococcal meningitis was a frequent opportunistic infection. Accurately diagnosing neurological conditions is important for treatment, and CSF analysis continues to be useful for this despite modern imaging technologies.

1. STS-2010
CO-REALTION OF CSF AND
NEUROLOGICAL FINDINGS IN HIV
POSITIVE PATIENTS
Student Ref. ID - 2010-01973

2. INTRODUCTION
HIV (Human Immuno-deficiency Virus) is a retro-virus that causes AIDS (Acquired Immuno
Deficiency Syndrome). It is one of the deadliest diseases in today’s world. It causes profound
immune-suppression, opportunistic infections and various neurological manifestations.
The neurological impairment that occurs in HIV infected individuals may be either primary
to pathogenic process of HIV infection or secondary to opportunistic infections or
neoplasm’s1
which are very disabling with regards to social, economical, physical, mental
state of that particular patient.
Neurological problem occur throughout the course of disease and may be inflammatory,
demyelinating or degenerative in nature1
. Among the more frequent opportunistic diseases
that involve CNS are toxoplasmosis, cryptococcosis, progressive multi-focal leuco-
encephalopathy and primary CNS lymphoma. Other less common are mycobacterial
infections, syphilis and infection with CMV, HTLV-1 and acanthamoeba1
.
The diseases, which are produced primarily due to pathogenic process of HIV infection
include aseptic meningitis, HIV encephalopathy (AIDS dementia complex), various
myelopathies, neuropathies and myopathy1
.
Among the neoplasm’s are primary CNS lymphoma and Kaposi’s sarcoma1
.
The type of neurological disease produced in HIV infected patient depends on age, sex, race,
geographic distribution, type of virus, host response, stage of the disease, viral load, degree
of impairment of cell mediated immunity and genetic predisposition1
.
Accurate clinical and investigational diagnosis of these conditions is very important in their
treatment. Nowadays, the diagnostic modalities available are CSF analysis with respect to
CSF biochemistry including sugar and proteins, cytology, staining, cultures, antibody titres in
serum to various infecting organisms, Neuro-imaging studies like CT/MRI Brain & Spinal
cord, PET scan, EMG and NCV. However, the CSF analysis still maintains its place in the era
of modern neuro-imaging modalities such as CT/MRI Brain and PET scan.
The CSF analysis gives both the qualitative and microbiological/cytological information
about the CSF samples of the patients under study.
In this study we present a series of 100 HIV positive patients who presented with
neurological manifestations. For this purpose CSF parameters are essential. This is an
attempt to study the frequency, distribution and co-relating the neurological manifestations
with the CSF parameters and compare this data with various other similar studies conducted
in other parts of India and world.
By this study we come to know that CSF parameters play a very essential role in the
diagnosis of various neurological manifestations in HIV positive patients.

3. REVIEW OF LITERATURE
The history of HIV is filled with triumphs and failures; living and death. The HIV time line
began early in 1981. In July of that year, the New York Times reported an outbreak of a rare
form of cancer among gay men in New York and California. This "gay cancer" as it was called
at the time was later identified as Kaposi's Sarcoma, a disease that later became the face of
HIV/AIDS. About the same time, emergency rooms in New York City began to see a rash of
seemingly healthy young men presenting with fevers, flu-like symptoms, and a rare
pneumonia called Pneumocystis. This was the beginning of what has become the biggest
health care cancer in modern history. Twenty-five years later the disease still plagues
society.
Here we discuss a few landmarks in the development of HIV/AIDS from the day it first
emerged and now has become one of the dreadful diseases all over the world.
1981
As stated above, 1981 saw the emergence of Kaposi's Sarcoma and Pneumocystis among
gay men in New York and California. When the centres for Disease Control reported the new
outbreak they called it "GRID" (gay-related immune deficiency), stigmatizing the gay
community as carriers of this deadly disease. However, cases started to be seen in
heterosexuals, drug addicts, and people who received blood transfusions, proving that the
syndrome knew no boundaries.
1983
Researchers at the Pasteur Institute in France isolate a retrovirus that they believe is related
to the outbreak of HIV/AIDS. Thirty-three countries around the world had confirmed cases
of the disease that was once limited to New York and California. Controversy arises a year
later when the US government announces their scientist, Dr. Robert Gallo isolates a
retrovirus HTLV-III, that he too claims is responsible for AIDS. Two years later it's confirmed
that HTLV-III and the Pasteur retrovirus are indeed the same virus, yet Gallo is still credited
with its discovery. An international committee of scientists rename the virus HIV.
1985 – ELISA developed
The controversy surrounding HIV/AIDS continues when Robert Gallo’s lab patents an HIV
test that was later approved by FDA. This was the sensitive enzyme-linked immunosorbent
assay (ELISA) was developed, which led to an appreciation of scope and evolution of HIV
epidemic at first in the United States and other developed nations and ultimately among
developing nations throughout the world1
.

4. 1987 - A Treatment Arrives
A new treatment emerges that is hailed as the first huge step in beating HIV/AIDS. The drug
Retrovir (AZT, Zidovudine) is FDA approved and begins to be used in high doses to treat
people infected with HIV. Politically, HIV/AIDS is a topic that most avoid. But in response to
public pressure, President Ronald Reagan finally acknowledges the HIV/AIDS problem and
for the first time uses the term "AIDS" in a public speech.
1992 - Combination Therapy Arrives
The FDA approves the first drug to be used in combination with AZT. The addition of the
drug Hivid (Zalcitabine) marks the beginning of HIV/AIDS combination therapies. But a more
disturbing development centres around HIV tainted blood. Three French senior health
officials knowingly sell HIV tainted blood, resulting in the infection of hundreds of
transfusion recipients, most of whom have haemophilia1
.
1993
People who are infected and scientists alike are confused and concerned when a British
study, the Concorde Trials, offers proof that AZT monotherapy does nothing to delay
progression to AIDS in asymptomatic patients. As a result, the AZT debate emerges, with
one side proclaiming AZT saves lives and the other denouncing AZT as useless; the
"rethinker" movement is born.
1996 - Protease Inhibitors Arrive
Treatment options take another step forward with the introduction of power HIV-fighting
drugs called Protease Inhibitors. The use of these drugs in combination with existing
HIV/AIDS drugs proves effective in controlling HIV. These new "triple-therapies" give
patients and scientists new hope in eliminating HIV/AIDS. But that hope is dashed when a
year later, scientists find HIV/AIDS "hides" in reservoirs in the body, making total elimination
of the virus virtually impossible.
1997
In late 1996 data from AIDS Clinical Trials Group study 076 (ACTG 076) made it clear that
Retrovir (AZT) used during pregnancy and at the time of delivery drastically reduces
transmission of HIV from mother to child. Those findings led to protocols that now
drastically reduce transmission from mother to child from 1 in 4 to less than 3%.
1998
More than 15 years after the prediction there would be of an AIDS vaccine within 2 years,
the first human trials in the United States of an HIV/AIDS vaccine begins. In a desperate
attempt to get affordable HIV/AIDS drugs to the hardest hit areas of Africa, European drug

5. companies ignore US patent laws and begin making generic versions of HIV/AIDS
medications. In response, US drug companies file lawsuits to stop such practices.
2000
The AIDS "rethinker" movement gets international attention and support when South
African president Thabo Mbeki questions the use and effectiveness of HIV medications as
well as offering doubt that HIV causes AIDS. In response, the international scientific
community issues the Durban Declaration, offering proof that HIV and AIDS are indeed connected.
2004
As the emphasis on simpler therapies continues, regimen pill burdens are greatly improved
with the release of two new combination drugs, Truvada ([Viread [tenofovir] + Emtriva
[FTC]) and Epzicom (Ziagen [abacavir] + Epivir [3TC]) as well as two new protease inhibitors,
Reyataz and Lexiva. In December, the first generic formulation of an HIV medication is
approved by the FDA, instilling hope that HIV medication prices may soon fall down.
2005
HIV statistics have become sobering to say the least.
4.9 million people were newly infected in 2005
40.3 million people worldwide living with HIV/AIDS.
And as the numbers continue to climb, work on an HIV vaccine has for the most part failed.
Once thought to be "just around the corner" it had become obvious in 2005 that an HIV
vaccine is still years away. Medication advances continue but long term side effects of HIV
medication use are becoming more evident. So much so that experts now agree that for
many patients, waiting to start HIV medications is the best course of action. Finally, 2005
saw a rise in HIV rates on college campuses and risky behaviour among those people already
infected is still a problem.
2006
Experts conclude that HIV has its origin in the jungles of Africa among wild chimps. Experts
go on to report that evidence suggests that the simian form of HIV (SIV) entered the human
species and became HIV by way of monkey bites or ingesting monkey meat and brains.
While the origins of HIV are clearer, the means to pay for HIV care and medications has
become more complicated. India surpasses South Africa as the world's largest HIV
population and in the US infection rates of HIV are steady while STDs are on the rise.

6. 2009
Scientists at the University of North Carolina at Chapel Hill announce they have decoded the
structure of an entire HIV genome. How this will affect the future of HIV treatment,
prevention, and education is not entirely known. What we do know is that the more we
know about HIV, the better we can fight its affects on public health in the US and around the
world.

7. Neurologic manifestations affecting the nervous system at all levels and stages of HIV
infection are common and increasing with the extended survival of HIV-positive persons.
According to a study done at Nizam’s Institute of Medical Sciences in Hyderabad by Teja VD,
Talasila SR, Vemu L. (Mar,2005)2
revealed not only high prevalence of neurological events
but also their nature, clinical presentations and symptoms. This was necessary for precise
diagnosis and parallel assessment of CD4 count for practical management of a specific
therapy for the HIV infected patient.
A similar study done at Tbilisi, Georgia by Bolokadze N. Et al (Dec,2008)3
provides convincing
evidence that neurological disorders with HIV infection might serve as an indicator for
advanced HIV infection, immunosuppression and decreased CD4+ T cell counts. This data
shows correlation between type of neurological manifestations of HIV infection and CD4+ T
lymphocyte count.
Pandya R, Krentz HB, Gill MJ, and Power C (May, 2005)4
investigated Health Related Quality
of Life (HRQoL) parameters among HIV infected individuals with and without neurological
manifestations. This study indicated that while HIV-related neurological diseases are
associated with reduced HRQoL scores, they suggested enhanced neurological care has a
positive impact on HIV patients overall well-being.
Odiase FE, Ogunrin OA, Ogunniyi AA (May, 2007)5
in their study for Memory Performance in
HIV positive cases found out that, there was no significant memory disturbance among HIV
positive asymptomatic subjects despite the presence of impaired attention and
psychomotor slowing and the severity of immune suppression (as indicated by CD4+ T
lymphocyte count) is a strong determinant of cognitive decline in HIV/AIDS.
Robinson-Papp J. Et al (Aug,2008)6
in their study for motor function and HIV associated
cognitive decline proposed that motor, affective and behavioural abnormalities predict
cognitive impairment in HIV positive patients in this HAART-era cohort. The HIV Dementia
Motor Scale (HDMS) may be useful in the assignment of HIV associated neuro-cognitive
impairment in HIV populations in which normative data or neuro-psychological test design is
not optimal.
HIV infection is associated with autonomic neuropathy which in turn hampers the quality of
life and can have fatal consequences. According to a study done by Compostella C,
Compostella L and D’Elia R (Feb, 2008)7
in Africa the most common autonomic dysfunction
symptoms were: orthostatic intolerance, secretomotor and gastro-intestinal dysfunction.
CD4+ T lymphocyte counts were not related to autonomic symptom scores. Thus they
proposed that African HIV positive patients report symptoms of autonomic dysfunction,
despite normal or borderline autonomic reflex responses.

8. In a study done at Harare, Zimbabwe by Innocent T. Et al (July, 2000)8
proposed that all the
cases suspected to have meningitis had high HIV sero-positivity irrespective of later whether
they were confirmed to have meningitis or not. Cryptococcal Meningitis was found to be the
most common type with 45% of all cases of meningitis and 100% of HIV sero-positivity.
According to a study done by Jarvis JN et al (Mar, 2010)9
at Cape Town, SA, it was found that
cryptococcal and tuberculous meningitis were the commonest cause of adult meningitis in
the setting of high HIV and TB prevalence. TB Meningitis is probably under-diagnosed by the
laboratory investigations, as evidenced by large numbers presenting with sterile
lymphocytic markedly abnormal CSFs.
Similar results of under-diagnosis of TB Meningitis in HIV patients due to lack of meningism
in elderly and atypical CSF findings were observed in a study conducted by Karstaedt AS et al
in South Africa (Nov. 1998)10
.
A study conducted in South Africa by Patel VB, et al (Aug,2010)11
proposed that RD-1
ELISPOT (Enzyme Linked Immunospot) assay, using cerebrospinal fluid mononuclear cells
and in conjunction with other rapid confirmatory tests (Gram stain and cryptococcal latex-
agglutinaqtion test), is an accurate rapid rule-in test for diagnosis of TBM in a TB and HIV
endemic setting.
In a study conducted by Ngo AT et al (June, 2007)12
, it was proposed that short-term
mortality of co-infected patients with HIV and Tuberculosis remains high in developing
countries.
According to a study in Argentina by Metta HA et al (Jul-Sept. 2002)13
, it was proposed that
manifestations and severity of cryptococcosis maintained its features throughout, in those
cases which were not treated with HAART. All the cases in this study showed neurological
involvement and treatment was not able to modify the mortality in this setting.
In a study conducted at New Delhi, India by Wadhwa A. Et al (July, 2008)14
provides
information about increasing incidence of Cryptococcal meningitis after AIDS pandemic. It
also indicates progression of HIV infection towards AIDS and is useful as a reference in
starting ART in a setting where facilities for determination of CD4 count are not available.
According to a study by Bicanic T. Et al (Mar, 2009)15
it was proposed that aggressive
management of raised opening pressure through repeated CSF drainage appeared to
prevent any adverse impact of raised opening pressure on outcome of patients with
cryptococcal meningitis.
In a study conducted at Bangalore, India by Neelam Khanna, et al (Mar, 1996)16
it was
proposed that comparison of clinical and laboratory parameters between HIV positive and
HIV negative cases showed that CSF cell responses were poor, culture of cryptococci from
non-neural sites was more frequent and mortality was higher in HIV positive group.

9. According to a study by Martinez Fernandez EM, et al (May, 1999)17
, proposed that the
possibility of Cryptococcal infection cannot be ruled out regardless of CSF biochemical
results and immune-suppression levels (CD4+ T cell count).
In a study done by Monaco LS and Tamayo Antabak N. (Oct-Dec, 2008)18
found that of all
the HIV positive cases Cryptococcosis appeared as a first marking disease in 34% cases.
HIV associated polyneuropathy has become the most common neurological complication of
HIV infection and is one of the main risk factors for the development of neuropathy
worldwide.
In a study done by Hahn K. Et al (Apr, 2010)19
, proposed that HIV should always be
considered as an underlying cause in patients with neuropathy.
According to a study done by Modi M, Mochan A. and Modi G. (May, 2009)20
In South Africa
it was found that seizures in HIV are a nonspecific manifestation of seizure mechanism.
In patients with HIV infection and AIDS, the most common cause of focal intra-cranial lesion
is Toxoplasma gondii infection. In a study done by Kurne A, et al (Jan-Apr, 2006)21
it was
proposed that until proven otherwise, HIV/AIDS patients presenting with focal neurological
complaints should be accepted as having central nervous system toxoplasmosis.
In a study conducted by von Giesen HJ, et al (Spring 2005)22
, proposed that motor
performance correlated significantly with time dependent HDS (HIV Dementia Scores)
subscores for psychomotor speed and construction and HDS subscores. HDS scores also
showed significant correlations to age, premorbid and actual intelligence and duration of
HIV seropositivity. Thus HDS can be used for screening of neuro-AIDS.
According to a study done by Abdulle S, et al (Aug, 2007)23
, proposed that the CSF
neurofilament can be used as a useful sensitive marker in evaluating the presence and
activity of ongoing CNS damage in HIV infection.
Le C and DeFreitas D (Dec, 2008)24
reported a case of HIV-infected man who developed
idiopathic intra-cranial hypertension (which is a cause of vision loss in HIV positive patients)
and despite repeated lumbar puncture, acetazolamide and neurosurgical intervention, he
could not regain his vision.

10. ETIOLOGY/PATHOPHYSIOLOGY/CLINICAL FEATURES/LAB
DIAGNOSIS AND MANAGEMENT
Etiopathogenesis:
HIV infected individuals can experience a variety of neurological abnormalities due to,
 Opportunistic infections
 Neoplasm’s
 Direct effect of HIV or its products
In addition to the lymphoid system, nervous system is also a major target of HIV
infection25
.
The main cell types that are infected in the brain in vivo are those of
monocyte/macrophage lineage, including monocytes migrated from the peripheral
blood to brain and resident microglial cells. HIV entry into the brain is facilitated by
ability of the virus infected and immune activated macrophages to induce adhesion
molecules such as E-selectin and Vascular cell adhesion molecules (VCAM-1) on brain
endothelium. HIV gp120 enhances the expression of intra-cellular adhesion
molecule-1 (ICAM-1) in glial cells that facilitate the entry of HIV infected cells into
CNS and promote syncytia formation.1, 25
Galactosyl ceramide is an essential component of the gp120 receptor on neural
cells and antibodies to it inhibit entry of HIV into neural cell lines in vitro.
HIV isolates from the brain are almost exclusively M-tropic i.e R5 strains. HIV
infected individuals who are heterozygous for CCR5D32 appear to be relatively
protected against the development of HIV encephalopathy compared to wild type
individuals.1, 25
Because neurons are not affected by HIV and the extent of neuropathologic
changes is often less than might be expected from the severity of neurological
symptoms25
, HIV mediated effects on the brain tissue are thought to be due to a
combination of,
 Direct effects, either toxicity or function inhibitory of gp120 on neuronal
cells. The HIV gp120 shed by virus infected monocytes could cause
neurotoxicity by antagonizing the function of vasoactive intestinal
polypeptide (VIP), by elevating intracellular calcium levels and by decreasing
nerve growth factor levels in cerebral cortex.1,25
 Indirect effects, either by viral products or by various soluble factors, such as
IL-1, TNF-alpha, IL-6, TGF-beta, IFN-gamma, platelet-activating factor and
endothelin that are produced by infected microglia. In addition nitric oxide,
eicosanoids and quinolinic acid can contribute to neurotoxicity.1,25

11. The likelihood that HIV or its products are involved in
neuropathogenesis is supported by the observation that neuropsychiatric
abnormalities may undergo remarkable and rapid improvement upon the
initiation of antiretroviral therapy (ART).
The neurological problems that occur in HIV infected individuals are
categorized as follows,
a. Opportunistic infections
- Toxoplasmosis
- Cryptococcosis
- Progressive multifocal leucoencephalopathy
- CMV infection
- Syphilis
- Mycobacterium Tuberculosis
b. Neoplasms
- Primary CNS lymphoma
- Kaposi’s sarcoma
c. Result of HIV-1 infection
- Aseptic meningitis
- HIV Encephalopathy (AIDS dementia complex)
d. Myelopathy
- Vacuolar myelopathy
- Pure sensory ataxia
- Paresthesia / dysesthesia
e. Peripheral Neuropathy
- Acute inflammatory demyelinating polyneuropathy (Gullian-Barre
Syndrome)
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Distal symmetric polyneuropathy
f. Myopathy

12. TOXOPLASMOSIS
CNS toxoplasmosis has been the most common cause of intracerebral mass lesion in HIV-
infected patients. Toxoplasmosis is generally a late complication of HIV and usually occurs in
patients with CD4+ counts < 200/cmm.1
Clinical Features:
The most common clinical features are fever, headache and focal neurological deficits. They
include seizure, hemiparesis, aphasia as a manifestation of these focal deficits or seen as a
picture influenced by accompanying cerebral oedema as confusion, dementia, lethargy
which can later progress to coma1
.
Investigations:
CT scan of the brain usually shows multiple-ring enhancing lesions with predilection for
cortex and deep gray-matter structures such as basal ganglia. The cerebellum and brain
stem are less commonly involved. Radiological findings may vary markedly as single lesions
and lesions with diffuse enhancement as well as non-enhancing lesions can appear.
The diagnosis however is suspected on the basis of MRI findings of multiple lesions in
multiple locations in addition to surrounding oedema1
.
CSF analysis in these cases is non-diagnostic, it can be normal or may show mononuclear
pleocytosis and elevated protein.
Treatment:
Standard treatment is sulfadiazine (4 to 6 gm/day in r divided doses) and pyrimethamine (a
200 mg loading dose followed by 50-70 mg/day) with leucoverin as needed for minimum of
4-6 weeks.1
Alternative therapeutic regimens include clindamycin in combination with pyrimethamine,
atovaquone plus pyrimethamine, azithromycin plus pyrimethamine plus rifabutin.
Patients with CD4+ T cell counts < 100/cmm and IgG antibody to Toxoplasma should receive
primary prophylaxis with single double strength tablet of sulfadiazine and pyrimethamine.

13. CRYPTOCOCCOSIS
Cryptococcus neoformans is another CNS opportunistic infection. It is the initial AIDS
defining illness in many cases and occurs in patients with CD4+ T cell count of < 100/cmm1
.
It usually presents as acute meningitis but also can have rare presentations like
cryptococcoma and cryptococcal cerebritis.
Clinical Features:
Clinical manifestations can be remarkably benign with vague malaise or nausea alone. More
commonly, headache and fever are presenting features. An acute confusion as cranial nerve
palsies. Stiff neck (meningeal sign) is absent in up to 70% of cases. Cryptococcoma in
addition can have focal neurological deficits where as those with cryptococcal cerebritis
present with seizures or altered mental state. Hence clinicians must maintain a high index of
suspicion for cryptococcal disease, particularly in the setting of new onset of headache.
Investigations:
CSF can be normal or may show mononuclear pleocytosis, elevated proteins, low glucose
and high opening pressure.1,16
The diagnosis can be made by identification of organisms in
CSF with India ink preparation or by the determination of cryptococcal antigen.1
CT/MRI is usually normal or may reveal only atrophy. Uncommonly, cryptococcomas occur,
particularly in the basak ganglia due to spread of organism from basal cisterns by way of the
lenticulostriate arteries. In case of cryptococcal cerebritis and docal meningeal and
parenchymal enhancement is seen in seen on MRI.
Treatment:1
Induction therapy:
- Inj. Amphotericin B in the dose of 0.5-0.7 mg/kg/day preceded by test
dose for a minimum period of 2weeks.
- Flucytosine can be added in the dose of 25mg/kg 6hrly for 2 weeks.
Maintenance therapy:
- Chronic suppressive treatment for life is required with oral
Fluconazole 400 mg once daily for 10 weeks followed by 200 mg/day
until CD4+ T cell count has increased to >200 cells/ul for 6 months in
response to HAART (Highly Active Anti-Retroviral Therapy).

14. MYCOBACTERIUM TUBERCULOSIS
It is also an opportunistic infection of CNS in HIV patients. The commonest presentations are
tuberculous meningitis and tuberculoma.
Clinical Features:
Tubercular meningitis presents as chronic meningitis with symptoms of fever, vomiting,
headache, visual disturbances, focal neurodeficits, altered sensorium and seizures. On
clinical examination, signs of meningism are present with pappiloedema. Clinical course may
be complicated by involvement of cranial nerve palsies in few cases.
Tuberculomas present as mass lesion, it can be single or multiple.
Investigation:
CSF analysis shows reduced sugar level, markedly elevated proteins and lymphocytic
pleocytosis in the range of 100-150 cells/cmm. CSF PCR for Tuberculosis is highly sensitive
and specific investigation for diagnosis of tubercular meningitis .
CT/MRI of brain chows meningeal enhancement with predominantly basal cisterns and
ependyma. Tuberculomas are seen as ring enhancing lesions mainly in cortical distribution.
Treatment:1
Anti-Tubercular drugs are given for the duration 18 months, with three months of intensive
phase and 15 months of maintenance phase.
Intensive Phase -
Combination chemotherapy including isoniazid (5mg/kg), rifampicin (10 mg/kg),
pyrazinamide (15-30 mg/kg), Inj. Streptomycin (15 mg/kg) are commonly used . Ofloxacin
400 mg/day can be added to the regimen because of its better CNS penetration.
Maintenance Phase –
Isoniazid and rifampicin are continued for the rest of 15 months during this phase.
ASEPTIC MENINGITIS
Many patients with this syndrome have primary HIV meningoencephalitis. The meningitis
can manifest at the time of seroconversion and can recur spontaneously or become chronic.

15. Clinical Features:
Patients with aseptic meningitis present initially with headache, photophobia, meningismus,
occasionally in association with altered mental status or cranial neuropathies. In
investigating the above symptoms aseptic meningitis must be a diagnosis of exclusion.
Investigation:
Because of high incidence of CSF abnormalities in HIV infected patients, regardless of
symptoms interpretation of CSF in this population can be difficult. CSF analysis shows
lymphocytic pleocytosis, elevated protein levels and normal sugar levels.1
HIV ENCEPHALOPATHY
The role of HIV-1 proliferation itself in the development of AIDS dementia complex (ADC) is
controversial. Although viral strains that are particularly efficient at replicating in brain
macrophages may play a role in the pathogenesis of brain injury, a heavy “viral load” in
brain has not been linked consistently with clinical AIDS dementia. This is generally a late
complication of HIV infection that progresses slowly over months and is seen in patients
with CD4+ T counts > 350 cells/cmm1
.
Activated macrophages, whether infected with HIV or not are capable of secreting potent
neurotoxins, including pro-inflammatory cytokines and generating oxygen free radicals that
can damage cells or lead to neuronal dysfunction or death. Soluble factors from these
macrophages were found to be highly neurotoxic.1, 25
Clinical Features:
A major feature is development of dementia, a decline in cognitive ability from a previous
level. It may present as impaired ability to concentrate, increased forgetfulness, difficulty
reading or increased difficulty performing difficult tasks.1
Patients may also present with
motor and behavioural abnormalities.1
Investigations:
There is no specific criteria for diagnosis of HIV encephalopathy and thus it depends upon
demonstrating the decline in cognitive function which can be achieved objectively by
performing a MMSE (Mini Mental Status Examination).1
On CSF analysis of these patients, non-specific finding of an increase in CSF cells and protein
levels is noted. While HIV RNA can be detected in CSF and also HIV can be cultured, this
finding is not specific for HIV encephalopathy. There appears to be no co-relation between
the presence of HIV in CSF and HIV encephalopathy.1

16. The various molecular and clinical observations regarding ADC are well supported by newer
imaging modalities such as Positron Emission Tomography (PET scan) which show the
metabolic rather than the structural changes in the brains of individuals with early stage of
HIV-associated cognitive impairment.
Treatment:1
Combination ARV (Anti-Retroviral Therapy) is of benefit in patients with HIV
encephalopathy. These patients have an increased sensitivity to the side effects of these
drugs. The use of these drugs for symptomatic treatment is associated with an increased
risk of extrapyramidal side effects and therefore, they must be monitored very carefully.

17. AIMS AND OBJECTIVES
1. To study the neurological manifestations in HIV positive patients.
2. To study CSF parameters in HIV positive patients.
3. To co-relate CSF study and neurological findings in HIV positive patients.
4. To see the outcome of neurological problem after the treatment.

18. MATERIALS AND METHODS
In the present study, the clinical profile of 100 HIV positive patients who presented with
neurological manifestations was studied. This is an observational study conducted over a
period from 20th
June 2010 to 21st
August 2010 in the Department of Medicine, of our
Medical College and Hospital.
Selection criteria
All HIV positive patients presenting with neurological manifestations like
fever, vomiting, headache, altered mental status, decline in cognitive ability, behavioural
problems, focal neurodeficits, gait ataxia, loss of / impaired sensations, bowel / bladder
dysfunction, skin lesions, swellings and signs of meingism like neck stiffness were selected.
The demographical data like name, age, sex, address, occupation, marital
status, socio-economic status were all collected in all patients.
History of high risk behaviours, major surgery and blood transfusions were
asked in all patients.
The diagnosis of HIV was confirmed by 2 HIV ELISA positive reports in the
symptomatic patients.
All patients were subjected to detailed general examination and systemic
examination with special attention to CNS. The CNS examination of the patients included
- Higher function examination
- Cranial nerve examination
- Motor system examination
- Sensory system examination
- Tests for cerebellar dysfunction
- Signs of meningism like neck stiffness etc.
All patients were subjected to routine investigations like haemogram and
blood biochemistry.
Other investigations like CSF analysis, serology and neuro-imaging studies were
undertaken as appropriate to individual patient only when mandatory for the research
project.

19. The lumbar puncture was done for collection of CSF with all aseptic measures
with written consent from the patient.
The CSF sample was analysed in the Dept. Of Biochemistry, Pathology and
Microbiology of our Hospital, for
1. Biochemistry including sugars and proteins
2. Cytology
3. Staining including Grams staining, Acid fast bacilli and India Ink preparation
The following reference values were considered abnormal
 CSF sugar < 40 mg/dl [N/R - 50-80 mg/dl]
 CSF protein > 45 mg/dl [N/R - 20-45 mg/dl]
 WBC > 10/cmm [N/R - No PMNs and under 6 lymphocytes]
Thus based upon the CSF analysis and neurological examination the patients the
patients were categorised into three groups as follows:
 Group I – HIV positive patients with neurological manifestations and abnormal CSF
findings.
 Group II – HIV positive patients with neurological manifestations but normal CSF
analysis.
 Group III – HIV positive patients without neurological manifestations with abnormal
CSF analysis.
Neuro-imaging techniques like CT scan of the brain and MRI of brain and spinal cord
in patients presenting with focal neuro-deficits, seizures, features of raised ICT,
altered sensorium, paraplegia to aid in diagnosis of conditions like
1. Toxoplasmosis
2. Tuberculoma
3. Progressive multifocal leucoencephalopathy
4. Brain abscess
5. Primary CNS Lymphoma

20. Guidelines for Diagnosis of Different Neurological manifestations:
1. Meningitis
All HIV positive patients presenting with fever, headache,
vomiting, altered sensorium, visual disturbances and signs of meningism
were subjected to CSF analysis with respect to sugar, proteins, cytology and
staining for organisms in CSF. Depending upon the abnormalities present,
patients were classified into four groups mentioned above
CT/MRI Brain was done to look for evidence of meningitis or
complications associated with it.
2. Neuropathy
All patients presenting with symptoms of tingling, numbness,
paresthesia, dysesthesia, hypoesthesia and anesthesia and weakness
involving distal group of muscles were considered to have peripheral
neuropathy.
3. Intra-cranial space occupying lesions(ICSOL)
This is the radiological diagnosis and differential diagnosis in the
setting of HIV positive cases include Toxoplasmosis, Tuberculoma, Primary
CNS lymphoma, Progressive multifocal leucoencephalopathy and Brain
abscess
The lesions can be single or multiple, with or without
enhancement on injection of contrast material. The characteristic finding is
the presence of mass effect.
The radiological procedures were also helpful in the diagnosis of
various other cases like Cerebrovascular accidents (CVA), Lumbar canal
stenosis, Cerebral Venous Sinus Thrombosis (CVST).
4. HIV Encephalopathy
There are no specific criteria for the diagnosis of HIV
Encephalopathy. The diagnosis depends upon demonstrating the decline in
cognitive function. Mini Mental Status Examination (MMSE) was used to
accomplish this. CSF analysis was done to rule out infective pathology.
CT/MRI Brain in some of the patients show marked cerebral atrophy.
5. Seizure disorders
New onset seizures in HIV infected patients were classified as
isolated seizures when no cause could be arrived at after detailed clinical
evaluation supported by CSF analysis and neuro-imaging studies.

21. OBSERVATIONS AND RESULTS
A total of 100 cases of HIV positive patients presenting with neurological manifestations
were observed during the study period.
Table I – Sex distribution:
Sex Total %
Male 82 82%
Female 18 18%
Total 100 100%
Fig. 1 – Sex distribution
In the present study the total number of male patients were 82 (82%) and total number of
female patients were 18 (18%).
The Male : Female ratio is found to be 4.55 : 1.
0
10
20
30
40
50
60
70
80
90
Males Females
No.ofpatients
Sex distribution

22. Table II – Age distribution:
Age
group No. of patients Total %
Male Female
11-20 2 2 4 4%
21-30 16 6 22 22%
31-40 42 10 52 52%
41-50 22 0 22 22%
Total 82 18 100 100%
Fig. 2 – Age distribution
Out of the 100 patients,
i. 4% (50% males & 50% females) were in the age-group of 11-20 years,
ii. 22% (72.7% males and 27.3% females) were in the age-group of 21-30 years,
iii. 52% (80.8% males and 19.2% females) cases were found to be in the age-group
of 31-40 years,
iv. 22% (100% males) were in the age-group of 41-50 years of age.
The age-group between 31-40 years contributed the largest percentage of cases. The mean
age at the presentation was found to be 35.8 ~ 36 years.
0
5
10
15
20
25
30
35
40
45
11-20 21-30 31-40 41-50
No.ofpatients
Age distribution
Males
Females

23. Table III – Neurological manifestation of HIV disease:
Diagnosis Frequency %
Cerebellar ataxia 2 1.92
Cerebrovascular Infarct 5 4.80
Cranial Neuropathy 2 1.92
CVST (Cerebral Venous Sinus
Thrombosis) 2 1.92
HIV Encephalopathy 18 17.30
ICSOL (Intra-cranial space
occupying lesions) 6 5.76
Lumbar Canal Stenosis 1 0.96
Meningitis 52 50.00
Neuropathy 3 2.88
Seizure Disorder 3 2.88
Unknown 10 9.61
Total 104 100%
Fig. 3 – Distribution of Neurological Manifestations of HIV Disease
In the present study out of 104 neurological events, cerebellar ataxia was present in 2
(1.92%), Cerebrovascular Infarct was seen in 5 (4.8%), Cranial Neuropathy was seen in 2
(1.92%), CVST was seen in 2 (1.92%), HIV Encephalopathy was present in 18 (17.3%), Mass
lesions were present in 6 (5.76%), Meningitis was present in 52 (50%), Neuropathy was
present in 3 (2.88%), Seizures were seen in 3 (2.88%) and Idiopathic were noted amongst 10
(9.61%) of all cases.
0 10 20 30 40 50 60
Cerebellar ataxia
Cerebrovascular infarct
Cranial Neuropathy
CVST
HIV Encphalopathy
ICSOL
Lumbar Canal Stenosis
Meningitis
Neuropathy
Seizure disorder
Unknown
No. of patients
Neurological manifestations in HIV

24. Of these, the commonest neurological manifestation was found to be Meningitis in 50% of
cases followed by HIV Encephalopathy in 17.3% cases, Idiopathic in 10%, Mass lesions were
present in 5.76% and Neuropathy was seen in 2.88% of all cases.
Table IV – Types of Meningitis in HIV disease
Type of Meningitis
no. of
cases %
Tuberculous 36 69.23
Croytococcal 8 15.38
Aseptic 6 11.53
Pyogenic 2 3.84
Total 52 100
Fig. 4 – Types of Meningitis in HIV disease
As shown in Fig. 3 Meningitis was seen amongst 50% cases of the study. Fig. 8, shows
different types of Meningitis in the study. In the present study, the most commonest form
of meningitis was found to be Tuberculous meningitis in 69.23% of all cases, followed by
Cryptococcal meningitis in 15.38% cases, Aseptic meningitis in 11.53% cases and Pyogenic
meningitis in 3.84% of all cases.
Types of Meningitis
Tuberculous
Cryptococcal
Aseptic
Pyogenic

25. Table V – Presenting Complaint’s
Clinical Presentation no.of patients %
Abnormal movements 4 4
Altered Sensorium 32 32
Backache 4 4
Breathlessness 4 4
Chest Pain 2 2
Convulsions 10 10
Diarrhoea 6 6
Diplopia 2 2
Fever 82 82
Gen.Weakness 56 56
Giddiness 2 2
Headache 84 84
Loss of balance 6 6
Pain in abdomen 2 2
Vomiting 48 48
Fig. 5 – Presenting Complaint’s
In the present study, the commonest of the neurological clinical presentations was found to
be Headache in 84% cases, followed by other presenting complaints such as, fever in 82%
cases, Generalised weakness in 56% cases, Vomiting in 48% cases, Altered sensorium in 32%
cases, 10% cases presented with convulsions, 6% with loss of balance and 4% with abnormal
movements.
0
10
20
30
40
50
60
70
80
90
No.ofpatients
Presenting complaints of patients

26. Table VI – Distribution of CT/MRI findings
Presentation/ Findings no. of cases %
Basal exudates 8 10.25
CVST 2 2.56
Gen. Atrophy 12 15.38
Gen. Oedema 14 17.94
ICSOL 6 7.69
Infarct/Bleed 5 6.14
Mass effect 6 7.69
Meningeal enhancement 6 7.69
Mid line shift 4 5.12
Multiple lesions 8 10.25
Single lesion 6 7.69
Vertebral canal stenosis 1 1.28
Total 78 100%
Fig. 6 – Distribution of CT/MRI findings
In the present study, appropriate cases were subjected to CT/MRI evaluation and the most
frequent cases of Generalised oedema were noted in 17.94% of cases, this was followed by
Generalised atrophy of neuro-parenchyma in 15.38% of cases, Basal exudates and multiple
lesions were found in 10.25% of cases, Mass effect, ICSOL (Toxoplasma?, Tuberculoma?),
Single lesions and meningeal enhancement were noted in 7.69% of cases, Infarcts were
noted in 6.14% of cases, also midline shift was seen in 5.12%, also CVST and Vertebral canal
stenosis was seen in 2.56% and 1.28% respectively of all the cases.
0
2
4
6
8
10
12
14
No.ofpatients
CT/MRI findings

27. Table VII – Distribution of normal and abnormal CSF findings
Total %
Normal CSF 30 30%
Abnormal CSF 70 70%
Total 100 100%
Fig. 7 – Distribution of normal and abnormal CSF analysis
In the present study, 30% cases of HIV presenting with neurological manifestations showed
normal CSF, while 70% cases showed abnormality in their CSF analysis reports.
0
10
20
30
40
50
60
70
Normal CSF Abnormal CSF
No.ofpatients
CSF nature

28. Table VIII – Distribution of different CSF findings
Findings Total %
Lymphocytosis 31 22.30
India Ink 8 5.75
Increased protiens 36 25.89
Decreased sugar 28 20.14
Acid Fast Bacilli 36 25.89
Total 139 100%
Fig. 8 – Distribution of different CSF findings
Present study shows marked variations on CSF analysis of the patients. As shown in Fig. 6,
70% cases showed abnormality on CSF analysis. The various CSF abnormalities were,
elevated proteins and Acid fast bacilli in 25.89% cases, lymphocytosis in 22.33% cases, India
Ink preparations were positive in 5.75% cases and reduced sugars in CSF were seen in
20.14% of all the cases.
0
5
10
15
20
25
30
35
40
Lymphocytosis India Ink Increased
proteins
Decreased sugars Acid fast bacilli
No.ofpatients
Different CSF findings

29. Table IX – Distribution of cases according to CSF sugars
Sugar in CSF(mg/dl) Cryptococcal Tuberculous
Frequency % Frequency %
Normal 5 62.5 11 30.55
Reduced (<40mg/dl) 3 37.5 25 69.44
Fig. 9 – Comparative analysis of CSF sugars in Cryptococcal and Tuberculous
meningitis
In the present study, out of 8 cases of cryptococcal meningitis, 5 (62.5%) had normal CSF
sugar while it was reduced in 3 (37.5%) of cases.
Out of 36 cases of tuberculous meningitis, 11 (30.55%) had normal CSF sugar and it was
reduced in 25 (69.44%) of all cases.
Thus, patients with Tuberculous meningitis have much lower CSF sugar level to those
compared with cryptococcal meningitis.
0
5
10
15
20
25
30
Normal CSF sugar (50-
80mg/dl)
Reduced CSF sugar
(<40mg/dl )
No.ofpatients
CSF Sugar levels
Cryptococcal
TB

30. Table X – Distribution of cases according to CSF proteins
Proteins in
CSF(mg/dl)
Cryptococcal Tuberculous
Frequency % Frequency %
Normal (20-45 mg/dl) 1 12.5 4 11.11
Elevated (>45mg/dl) 7 87.5 32 88.89
Fig. 10 – Comparative analysis of CSF proteins in Cryptococcal and
Tuberculous meningitis
In the present study, out of 8 cases of cryptococcal meningitis, only 1 (12.5%) has normal
CSF protein levels while it was elevated in the rest of 7 (87.5%) of the cases.
Out of 36 cases of tuberculous meningitis, 4 (11.11%) cases reported with normal CSF
protein reports and the rest 32 (88.89%) cases reported markedly elevated CSF protein
levels.
Thus, cryptococcal meningitis tend to have much lower rise in CSF proteins than those
compared with tuberculous meningitis in which it is markedly elevated.
0
5
10
15
20
25
30
35
Normal CSF protein (20-45
mg/dl)
Elevated CSF protein (>45
mg/dl)
No.ofpatients
CSF Protein levels
Cryptococcal
Tuberculous

31. Table XI – Distribution of cases according to WBC count in CSF.
Range of WBCs
(cells/cmm.)
Cryptococcal Tuberculous
Frequency % Frequency %
0-50 6 75 5 13.88
50-100 1 12.5 10 27.77
100-150 1 12.5 19 52.77
>150 0 0 2 5.55
Fig. 11 – Distribution of CSF cells in Cryptococcal and Tuberculous meningitis
In the present study, out of 8 patients of cryptococcal meningitis, 6 (75%) had CSF WBC
count between 0-50 and only one case each (12.5%) was found to have counts between 50-
100 and 100-150 groups while none had the cell count of >150 cells/cmm.
Out of 36 patients of tuberculous meningitis, 5 (13.88%) had CSF WBC count between 0-50,
10 (27.77%) had cell counts between 50-100, 19 (52.77%) had cell count between 100-150
and 2 cases (5.55%) had cell count of >150 cells/cmm.
Thus, patients with cryptococcal meningitis had a lesser degree of pleocytosis in their CSF
than those with tuberculous meningitis.
0
2
4
6
8
10
12
14
16
18
20
0-50 50-100 100-150 >150
No.ofpatients
WBC Range in CSF (in cells/cmm.)
Cryptococcal
Tuberculous

32. Table XII – Outcome of patients
Outcome
Gender
Total %Male Female
Death 22 2 24 24%
Discharged 60 16 76 76%
Total 82 18 100 100%
Fig. 12 – Outcome of the patients
In the present study, 24 out of 100 cases died even after intensive treatment on ambulatory
ventilation, of which 22 were males and 2 were females. However 76 cases were discharged
after their specific treatment, of which 60 were males and 16 were females.
0
10
20
30
40
50
60
Death Discharged
No.ofpatients
Outcome of patients
Male
Female

33. DISCUSSION
1. Sex Distribution
In this study out of 100 patients, 82 are males and 18 are females. The Male : Female
ratio is estimated to be 4.55 : 1.
Studies show that males are at a higher risk of developing HIV/AIDS due to practice
of high risk behaviour, multiple sexual partners, intravenous drug abuse, homo-
sexuality.
Gongora Rivera F et al, (2000)26
in their study on neurological manifestations of HIV
disease, the male: female ratio was found to be 8.31: 1. In a similar study on 194
patients, by Jacqueline Ferreira de Oliveira et al, (2006)27
the male: female ratio was
found to be 2.28: 1.
2. Age Distribution
The present study shows prevalence of HIV patients with neurological manifestations
more commonly in the age-group of 31-40 years contributing 52% and the mean age
was found to be 35.8 years.
Recent studies suggest that the occurrence of neurological manifestations of HIV is
more common among the younger age group.
Gongora Rivera F et al (2000)26
in their study observed patients ranging from 9 to 75
years of age, with the mean age of 33.8 years. Jacqueline Ferreira de Oliveira et al,
(2006)27
in their study found the mean age to be 35.8 years.
3. Distribution of Neurological manifestations
All the HIV positive patients presenting only with neurological manifestations were
selected for the study. Gongora Rivera F et al (2000)27
in their study found that the
prevalence of HIV with neurological manifestation was 39%
In this study, out of the total of 104 neurological events observed in patients,
meningitis was seen in 50% of the cases with HIV Encephalopathy in 17.3%, few
cases remained un-diagnosed contributing 9.61% of all, Intra-cranial space occupying
lesions (ICSOL)(Toxoplasma?, Tuberculoma?) in 5.76% cases, Cerebrovascular infarct
in 4.8% cases, cranial neuropathies and seizure disorder were seen in 2.88% of the
cases, cerebellar ataxia, cranial neuropathy and CVST (cerebral venous sinus
thrombosis) were seen in 1.92% cases and a single case of lumbar canal stenosis.
The neurological complications that occur in HIV patients may be primary to the
pathogenic process of HIV infection or secondary to opportunistic infections or
neoplasms.
Gongora Rivera F et al (2000)26
in their study on 149 HIV positive patients, 50.3%
cases presented with neurological manifestations, most commonly presented was
brain toxoplasmosis in 32.2% cases, meningitis in 30.2% cases, AIDS dementia
complex in 8.7% cases, 5.4% cases of ischaemic cerebrovascular disease.

34. 4. Distribution of Meningitis
As we can see in Table III meningitis is the most common presentation of HIV
disease, seen in 50% of all cases. Among them, tuberculous meningitis was found to
be the most common variety in 69.23% of the cases of meningitis followed by
cryptococcal in 15.38% cases, aseptic in 11.53% cases and pyogenic in 3.84% cases.
TB meningitis is the most common infectious disease of CNS in India, which is in
contrast to cryptococcal meningitis and toxoplasmosis observed in western
countries. It is because of the fact that here, tuberculosis is the most common
opportunistic infection in HIV disease which has a tremendous affinity to affect CNS.
Gongora Rivera F et al (2000)26
, in their study, the most common form of meningitis
was cryptococcal in 21.5% cases followed by tuberculous in 8.7% cases, aseptic in
1.34% cases.
Jacqueline Ferreira de Oliveira et al (2006)27
in their study found toxoplasmosis as
the most common form of CNS infections in HIV patients i.e 42.3%, followed by
cryptococcal meningitis in 12.9% and TB meningitis in 10.8% of the cases.
R. B. Lipton et al (1991)28
in their study on 49 HIV-1 infected patients found
cryptococcal meningitis in 39% and toxoplasmosis in 16% of the cases.
5. Distribution of Clinical presentation
In this study, the clinical presentation of the patients was also taken into
consideration. Headache alone accounted for 84% of all presentation’s, the other
significant clinical presentations were fever in 82% cases, generalised weakness in
56% cases, vomiting in 48% cases and convulsions in 10% of the cases.
R. B. Lipton et al (1991)28
in their study of 49 HIV-1 infected patients found headache
as an identifiable presentation in 82% of the cases.
F. Bissuel et al (1994)29
in their retrospective study of 270 HIV infected patients
found that 21.11% of the patients had developed fever.
David M. Holtzman et al (1989)30
in their study on 100 HIV patients found seizures to
be the presenting symptom in 18 cases.
Fever is a frequent clinical presentation in HIV patients and can occur due to primary
HIV or any other opportunistic infections in HIV. Generalised weakness occurs as a
result of breakdown of the immune system of the patient which causes recurrent
infections. Seizures in HIV may be due to direct effect of HIV on the brain31
or due
to other causes such as cerebral mass lesions, HIV Encephalopathy, cryptococcal
meningitis. Phenytoin is the drug of choice in such cases. However, the prognosis of
such cases depends on the underlying cause.31

35. 6. Distribution of CT/MRI findings
In the present study, the appropriate patients were subjected for CT/MRI evaluation
and generalised oedema was found more frequently in 17.94% cases. Other findings
were generalised atrophy in 15.38% cases, basal exudates and multiple lesions in
10.25% cases, Intra-cranial space occupying lesions, mass effect and meningeal
enhancement in 7.69% of cases, infarct/bleed in 6.14% and mid-line shift in5.12% of
the cases was seen.
M. Whiteman et al (1995)32
in their study on 25 HIV positive patients noted 36%
showed meningeal enhancement, 44% showed enhancing parenchymatous lesions.
MJ Popovich et al (1990)33
verified CT scans of 35 patients with intra-cranial
cryptococcosis and found 43% normal, diffuse atrophy in 34% cases, mass lesions in
11% and diffuse cerebral oedema in 3% cases.
Jose Enrique Cohen et al (1996)34
in their case report mentioned that AIDS related
cerebral atrophy may not only have predisposed the patient to the development of
an extracerebral collection, but may have also favourably influenced the resolution
of haematoma.
7. CSF Analysis
CSF analysis of the HIV patients showed marked variations. CSF was normal in 30%
cases and showed abnormality in 70% cases (Table VII). CSF abnormality was seen in
the form of elevated proteins, reduced sugars, lymphocytosis, positive India ink
preparations and acid fast smears.
In the present study, we make comparative study between cases of cryptococcal
meningitis and tuberculous meningitis as the CSF abnormalities are markedly noticed
among these two groups of patients.
Here, out of 8 cases of cryptococcal meningitis, 62.5% cases had normal CSF sugars
while the rest 37.5% cases reported reduced CSF sugar levels, also CSF protein levels
in these cases were normal in 12.5% cases and showed elevated proteins in 87.5% of
the cases. On CSF cytology reports of these cases, we found 75% cases had CSF WBC
counts between 0-50, 12.5% cases each in the range of 50-100 and 100-150
(WBC ranges in cells/cmm.)
Out of 36 cases of tuberculous meningitis, 30.55% showed normal CSF and reduced
CSF sugars noted in 69.44% of the cases. CSF protein levels in these cases were
normal in 11.11% cases and reported elevated levels in the rest 88.89% of cases. On
CSF cytology of these cases, we found that 13.88% cases had CSF WBC counts
between 0-50, 27.77% between 50-100, 52.77% between 100-150 and 5.5% cases
had counts > 150. (WBC ranges in cells/cmm.)

36. Thus we can see that,
i. Patients with TB meningitis have lower CSF sugar level as compared to
cryptococcal meningitis.
ii. Patients with TB meningitis have a marked rise in CSF protein levels as
compared to cryptococcal meningitis and
iii. Patients with TB meningitis show a higher degree of pleocytosis in CSF than
those compared with CSF cryptococcal meningitis.
Irina Elovaara et al (2003)35
in their study on HIV infected patients reported that CSF
leucocytes were increased in the early stage of the disease, but later the cellular
reaction subsided.
Lars-Magnus Andersson et al (1999)36
in their study, analysed 52 HIV positive
patients for the CSF tau protein levels and reported significantly higher mean CSF tau
protein concentration in patients with AIDS Dementia Complex (ADC). They also
suggested that CSF tau might be used as a biochemical marker for axonal
degeneration and for the diagnosis of HIV-1 infected patients.

37. CONCLUSION
1. The neurological manifestations in HIV disease are found to be more commonly in
the younger age-group.
2. Males are affected more frequently than females.
3. Meningitis, HIV Encephalopathy, intra-cerebral mass lesions, cerebrovascular
accidents, neuropathy, seizure disorders are the most common of the neurological
manifestations in HIV infected patients in decreasing frequency. Cases of cerebellar
ataxia, cranial neuropathy, lumbar canal stenosis were also noted.
4. Headache, fever, generalised weakness, vomiting, convulsions, altered sensorium,
meningism are found to be the most frequent clinical findings. Few patients also
presented with breathlessness, backache, loss of balance, giddiness and chest pain.
5. On CT/MRI evaluation of the patients a broad spectrum of intra-cranial
abnormalities were noted. There was generalised oedema, generalised atrophy of
the neuroparenchyma, basal exudates, multiple lesions, intra-cranial mass lesions,
mass effect, mid-line shift, meningeal enhancement were noted in most of the cases.
6. Tuberculous meningitis is found to be the most common meningitis followed by
cryptococcal, aseptic and pyogenic meningitis.
7. 70% of all the cases presented with abnormal CSF findings. The CSF analysis showed
reports of markedly elevated protein levels, reduced sugar levels, lymphocytic
pleocytosis, positive India ink preparations and acid fast smears.
8. It was also found that, the patients with TB meningitis have much lower CSF sugar
levels than those with cryptococcal meningitis and the protein levels in CSF of TB
meningitis patients is markedly elevated as compared to cryptococcal meningitis.
9. On CSF cytology it was observed that, cryptococcal meningitis had a lesser degree of
lymphocytic pleocytosis than TB meningitis.
Thus we conclude with promise that all the HIV infected patients must and should be
suspected to have a neurological manifestations until and unless proved otherwise by
thorough clinical evaluation and relevant investigations as many a times patient present
with subtle symptoms and signs.
HIV patients presenting with neurological manifestations need to be accurately diagnosed
and treated promptly. In today’s world, availability of advanced technologies in the field of
medical sciences such as neuro-imaging studies like CT/MRI, PET scan, EMG, NCV has
become very easy for the physicians and clinicians all over the world. CSF analysis of the
patients under study, has provided the both the qualitative and microbiological/cytological
information. Thus, CSF analysis still maintains its place in the era of modern neuro-imaging
modalities such as CT/MRI Brain and PET scan.

38. SUMMARY
The present study titled ‘Co-relation of CSF and Neurological Findings in HIV positive
patients’ is a cross-sectional study conducted from 20th
June to 21st
August 2010. This study
was done with an aim to find out the various neurological manifestations in HIV infected
patients and co-relate them with the CSF analysis of the respective patients.
1. Males were affected more frequently than females. 82% of the study patients were
males and the rest 18% were females. Male: Female ratio was 4.55: 1.
2. The most common age group affected was 31-40 years of age accounting for 52% of
all patients. Mean age was 35.8 ~ 36 years.
3. An overall of 104 neurological manifestations in HIV infected patients were
observed. Meningitis was the most common manifestation in 50% cases, followed by
HIV encephalopathy in 17.3% cases, Idiopathic were 9.61% cases, Intra-cranial mass
lesions were 5.76%, cerebrovascular infarcts in 4.8%, neuropathy and seizures were
in 2.88%, CVST, cranial neuropathy and cerebellar ataxia in 1.92%, lumbar canal
stenosis was also seen in a case (0.96%).
4. Meningitis was seen as the most common neurological manifestation. It was seen as
Tuberculous meningitis in 69.23% of all meningitis cases, cryptococcal in 15.38%,
aseptic in 11.53% and pyogenic in 3.84% of all cases of meningitis.
5. The most common clinical presentation was headache in 84% cases followed by,
Fever in 82%, generalised weakness in 56%, vomiting in 48%, altered sensorium in
32%, convulsions in 10%, diarrhoea and loss of balance in 6%, abnormal movements,
backache and breathlessness in 4%, chest pain, diplopia, giddiness and pain in
abdomen was seen in 6% cases.
6. On CT/MRI evaluation of the patients generalised oedema was seen in 17.94% cases,
atrophy in 15.38% cases, basal exudates and multiple lesions in 10.25% cases, Intra
cranial mass lesions, mass effect, meningeal enhancement in 7.69% cases, Infarct in
6.14%, mid-line shift was seen in 5.12% cases, CVST in 2.56% cases and a single case
of lumbar canal stenosis was also noted.
7. On CSF analysis of the patients, 70% came up with abnormal CSF findings. Among
them, elevated proteins were noted in 25.89% cases, lymphocytosis in 22.3% cases,
reduced sugars in 20.14% cases and acid fast smears wee positive in 25.89% of cases.
8. The CSF analysis of patients with tuberculous meningitis showed that 69.44% cases
had reduced sugars, 88.89% patients had markedly elevated proteins and 52.77%
cases had lymphocytic pleocytosis with cell counts between 100-150 cells/cmm. The
patients with cryptococcal meningitis showed 37.5% cases had reduced sugars,
proteins were elevated in 87.5% cases and lymphocytic pleocytosis with cell counts
between was 50-100 cells/cmm. Was seen in 75% of the cases.
9. Death was seen in 24% of all the cases even after intensive treatment on ambulatory
ventilation of which 22 were males and 2 were females.

39. SUGGESTIONS
i. All the patients with neurological manifestations must and should be monitored
and treated carefully.
ii. CSF analysis of the HIV patients should be done unless contra-indicated as it
provides both the qualitative and cytological/microbiological profile of the CSF
and is of tremendous importance in the diagnosis of such patients.
iii. CSF analysis with respect to CSF proteins, sugars, CSF cytology, CSF staining
(Gram stain, Acid Fast or Ziehl-Neelsen and India ink preparations), culture and
sensitivity provide a very significant information to aid in the accurate diagnosis
and thereby the treatment of the HIV patients with neurological manifestations.
iv. CSF analysis along with other diagnostic tools such as CT/MRI, PET scan, EMG,
NCV all must be evaluated in the appropriate patients for the correct diagnosis.
The immunological profile of the patient must also be determined as it is helpful
in the treatment and prognosis of the patients.
v. CD4+ T lymphocyte counts of the patients must be determined, they aid in
knowing the appropriate disease and the extent of spread of the HIV into the
body as well as providing treatment course in the patients.
vi. HIV-RNA viral load testing should also be done in patients suspected to have an
acute HIV infection.
vii. The HIV-RNA test and the CD4+ T lymphocyte count are prognostic indicators of
HIV infection and can be used to monitor progression and treatment efficacy.
viii. Even in today’s world of highly advanced medical technologies and
methodologies, the CSF analysis has still maintained its place in providing correct
diagnosis and thereby treatment of the patients.

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2. Teja VD, Talasila SR, Vemu L, Neurological Manifestations of HIV infection: an Indian
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3. Bolokadze N, Gabunia P et al, Neurological complications in patients with HIV/AIDS.
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