Human Immunodeficiency Virus (HIV) infection is a global pandemic. According to the
data released by UNAIDS in 2007, India had 2.5 million people living with HIV infection.[1]
Next to sub-Saharan Africa, it has the second largest burden of HIV-related illness.
Though the main targets of HIV infection are the cells of the immune system, the nervous
system is often damaged during the course of infection, not only by disease processes
that are secondary to immune dysfunction but also by more fundamental effects of the
retrovirus.
Neurological disease is the first manifestation of symptomatic HIV infection in roughly
10–20% of patients, while about 60% of patients with advanced HIV disease will have
clinically evident neurological dysfunction.[2–4] Autopsy studies of patients with
advanced HIV disease have demonstrated pathologic abnormalities of the nervous system
in 75–90% of cases,[2
5
6] thus proving that the incidence of subclinical neurological disease is even higher.
This may be explained by the fact that the central nervous system (CNS) is a sanctuary
site for HIV infection and there is poor CNS penetration of antiviral drugs due to
the presence of intact blood brain barrier.[2] We undertook this study to see the
prevalence of the various neurological manifestations in HIV-positive admitted patients
who presented to a tertiary hospital in our setup.
The study was carried out for a period of 1 year from November 2010 to October 2011
in the Gandhi ward of Department of Medicine, King George's Medical University, Lucknow,
India. A total of 105 HIV-positive patients of more than 14 years of age who were
admitted were enrolled in the study, of which 80 patients were suffering from Acquired
Immunodeficiency Syndrome (AIDS). Out of the total 105 HIV-positive patients, 43 patients
had neurological manifestations. Patients with HIV-unrelated developmental, neurological,
medical, and neurobehavioral conditions that potentially impaired cognition were excluded
from the study. Selected patients having neurological manifestations were subjected
to detailed history, examination, and other routine and special investigations as
required for that particular case's diagnosis and management. HIV was serologically
confirmed by enzyme-linked immunosorbent assay (ELISA), and CD4 estimation was carried
out by flow cytometer using Syflow counter. Informed consent was taken from each patient
enrolled for the study, and the university ethical committee reviewed and approved
the study.
A total of 105 HIV-infected patients were enrolled in the study. The mean age of all
patients was 34.3±7.8 years, and the same was observed in the HIV-positive patients
with neurological manifestations. The mean age of males in the study was 35.0±7.7
years and that of females was 31.11±7.6 years. Majority of patients (49.5%) were in
the age group of 31–40 years, followed by 30.5% in the age group of 21–30 years. Male
to female ratio was 4.5:1. Contact with commercial sex workers was the most common
mode (75.24%) of transmission among males. 94.7% (18/19) females in the study got
the infection from their HIV-positive husbands. Contaminated blood transfusion was
the next most common mode of transmission (5.7%). One patient was an intravenous drug
abuser, and in one patient no source of infection could be found.
Out of the 105 patients enrolled in the study, 43 (40.9%) were suffering from neurological
manifestations. Among the HIV-positive patients with neurological manifestations;
fever was the most common presenting symptom (83.7%), followed by headache (67.4%),
coma, or confusion (58.1%) and seizure (14.0%). Two patients presented with blurring
of vision, both of which subsequently were found to be suffering from cytomegalovirus
(CMV) retinitis. Meningitis was the leading cause of headache, coma, and seizures
[Table 1].
Table 1
Distribution of symptoms in patients with and without neurological manifestations
Meningitis was the most common neurological manifestation present in 29 (67.44%) patients,
followed by AIDS dementia complex (ADC) in 4 patients (9.30%). Cranial nerve involvement
was present in patient with chronic inflammatory demyelinating polyneuropathy (CIDP),
and epidural hematoma was an additional finding in patient with pyogenic meningitis
[Table 2]. Among the meningitis types, tubercular meningitis was the most common type
present in 21 (70.0%) patients, followed by cryptococcal and pyogenic meningitis in
7 (23.3%) and 2 patients (6.7%), respectively. One case each of cryptococcal meningitis
and pyogenic meningitis was a follow-through case of tuberculosis meningitis and was
already on anti-tubercular therapy (ATT). In the intracranial space occupying lesion
(ICSOL), one patient had tubercular abscess on computed tomography (CT) scan head,
the second patient's CT scan showed ring-enhancing space occupying lesion leading
to possibility of neurocysticercosis (NCC)/tuberculomas, and the third patient had
multiple ring-enhancing lesions leading to possibility of toxoplasma. One patient
(2.33%) presented with paraplegia due to L2–L3 vertebral compression collapse and
was tubercular in nature. Tuberculosis was very common etiology (55.8%).
Table 2
Neurological manifestations in HIV.positive patients
CD4 count could be done only in 84 patients in our study. In 38 HIV-infected patients
with neurological manifestations, the mean CD4 count was 177.9±105.0, of which 24
(63.2%) patients had CD4 count less than 200. The remaining 46 HIV cases without neurological
manifestation had mean CD4 count as 211.0±114.4, of which 21 (45.7%) had CD4 count
less than 200 [Table 3]. The incidence of neurological manifestations increased with
decrease in CD4 count. Eleven out of 20 (55%) patients with tubercular meningitis
had CD4 count less than 200, but in cryptococcal meningitis 5 out of 6 (83.3%) patients
had CD4 less than 100.
Table 3
Distribution of patients according to CD4 count (n = 84)
All the cases in this study had infection with HIV-1. Infection with HIV-2 or dual
infection was not seen. Other studies[7
8] have reported infection with HIV-2 in 3–9% of all HIV-infected persons. This difference
in our study may be due to the possible geographic confinement of HIV-2 and also due
to the fact that HIV-2 infection has more indolent course.
Mean age for all the cases was 34.3±7.8 years. The age distribution is comparable
to the study done by Teja et al.[9] in which the median age was 36 years and most
of the patients were in the age group of 30–40 years. The mean age in a study was
34.9±12 years.[10] Similarly in our study, maximum patients were in the age group
of 31–40 years, followed by the age group of 21–30 years. Early clinical manifestation
can be due to lack of effective anti-retroviral (ARV) compared to developed countries,
and they succumb to this disease at an early age. Most of our patients are contracting
the infection during adolescence, which is due to lack of sexual education and awareness
of the spread of this disease.
Male to female ratio in our study was 4.5:1. Other studies have reported this ratio
varying from 3:1 to 6:1. In a study done by Teja et al.,[9] the ratio was 3.9:1, whereas
another study has reported a ratio of 3:1.[10] However, the ratio is nearly 1:1 in
North America and Africa.[11] In India, males are the bread earners and most of them
harbor the disease from commercial sex workers, when they go far away from their family
to earn their livelihood. Most of them are laborers and belong to low socioeconomic
status. Females mostly contract this disease from their husbands; their health is
neglected and they are unable to seek medical care due to gender bias and male dominance
in our society. The major route of transmission of this infection among males is contact
with commercial sex workers. However, in the United States, homosexual contact is
the common route, but it is not so in India as this relationship is taboo.[11]
Neurological manifestations are common in HIV-infected persons. There has been considerable
morbidity and increased mortality due to neurological complications, which can affect
the nervous system at all levels and at all stages of HIV disease. In our study, out
of a total of 105 patients, 40.9% had neurological involvement. Close to our findings,
a study has reported 44.6% neurological manifestations present in HIV-infected patients
of their studied cases.[12] In our study on HIV patients with neurological manifestation,
fever was the most common symptom in 83.7% patients, followed by headache (67.4%),
coma, or confusion (58%), and 14.0% patients presented with convulsions. These were
comparable to the study done by Pal et al.[13] in which fever was the commonest symptom
(92%), followed by confused or comatose state (71%), and 33% patients had convulsions.
A study from the USA has also reported the presence of headache as a common symptom
in their studied group; however, they were not different between HIV-seropositive
and -seronegative subjects.[14] Seizures were a relatively frequent complication of
HIV infection and may be a consequence of opportunistic infections, neoplasms, or
HIV encephalopathy. However, in our study, only 14% presented with seizures. This
is contrary to a finding reported in a study in which cerebral mass lesions were the
most common cause responsible for 32% cases of new-onset seizures in patients with
HIV infection.[15] This difference can be due to the small number of patients of ICSOL
present in our study.
Among the neurological manifestations, meningitis was found in a majority of cases
(67.4%) in our study, whereas other neurological manifestations were even less than
10% individually. Similar to our study, meningitis was found in 71.9% of HIV patients
with neurological manifestation in another study.[16] Contrary findings have also
been reported (17.8% of cases).[12] This is because patients visiting out-patient
clinics formed the study group in that study, whereas our study group comprised only
indoor patients who were admitted in critical condition. Our study shows that in neurologically
manifested HIV patients, tubercular meningitis manifested more than cryptococcal meningitis
(48.9% vs. 16.3%). Studies have reported tubercular meningitis to be present in 43.8%
versus 28.1% and 25.1% versus 11.0% of cryptococcal meningitis.[9
16] Contrary to the above two studies, it has been reported in another study that
cryptococcal meningitis was more common than tubercular meningitis (58% vs. 16%) in
their group of patients.[12] The difference in the prevalence of tubercular and cryptococcal
meningitis in various Indian studies can be due to the difference in prevalence of
tuberculosis in various parts of the country. In our study, tuberculosis also manifested
as tuberculoma, suspected tubercular abscess as ICSOL, and compression collapse due
to Pott's spine, seen in one case each.
Tuberculosis was the leading cause of neurological disorders (55.8%) in our study,
presenting as opportunistic as well as co-infection indicating the dual epidemic.
Tuberculosis and HIV infection have profound impact on each other. HIV infection increases
the risk of developing active tuberculosis by 15–30 times. According to NACO, tuberculosis
is the commonest opportunistic infection, both pulmonary and extrapulmonary (62.2%)
in India, which can explain its high incidence in HIV-infected individuals in India
as compared to western countries. In another study, tuberculosis was present in 54.8%
of all patients, which is close to our findings.[10] In our study, 13.3% had pulmonary
tuberculosis and 41.9% had extrapulmonary tuberculosis including 7.6% of miliary tuberculosis.
Extrapulmonary tuberculosis is common among HIV-positive patients as shown in various
series; extrapulmonary tuberculosis, alone or in association with pulmonary disease,
has been documented in 40–60% of all cases in HIV co-infected patients. In extrapulmonary
tuberculosis, tubercular meningitis formed 47.7% in our study, and it has been also
seen that in advanced diseases, Mycobacteria and meningitis are frequent.[17]
The mean CD4 count in patients with neurological manifestations was 191.71±117.7,
and 64.7% of neurologically manifested HIV patients had CD4 count less than 200. With
lowering of CD4 count accounts for more neurological disorders in HIV patients. Studies
have also reported the presence of neurological complication as well as other clinical
manifestations associated with decreased CD4 count and increased viral load. 55% of
our patients with tubercular meningitis had CD4 count less than 200, but in cryptococcal
meningitis 83% patients had CD4 less than 100.[18
19] This shows that irrespective of CD4, tubercular meningitis is the most opportunistic
infection; however, prognosis is poor with low CD4. Similar to our findings, a study
from the USA[20] has also stated that tuberculosis meningitis can occur at any CD4
count level, while cryptococcal meningitis usually occurs when CD4 count is less than
200.
HIV dementia or HIV encephalopathy or ADC is the nonfocal disorder characterized by
preserved alertness. In our study, 9.3% patients presented with ADC. Two other studies
have reported ADC to be present in 4.3%and 5% of HIV patients with neurological manifestations,
respectively.[12
21] Studies from western countries have shown that 20–30% of patients with advanced
HIV infection go on to develop ADC.[22] The prevalence in our study is low, probably
because of it being a late manifestation of HIV disease and many patients succumbing
to other complications before progressing to this stage in the underdeveloped countries.
Progressive multifocal leukoencephalopathy (PML) is one of the rare CNS-related disorders
observed commonly in HIV patients, caused by JC virus. PML was present in only one
patient (2.33%) in our study, who presented with seizures as first manifestation with
CD4 count of 51. Another study has also reported that PML was present in only 5.2%
patients.[16]
In conclusion, our study has shown that secondary neurological disorders were more
common due to opportunistic infection, which can also be attributed to the fact that
patients are not availing highly active anti-retroviral therapy (HAART) due to high
cost of the drugs and lack of widespread availability of facility for HIV/AIDS center.
Tuberculosis was the prominent etiology of all neurological disorders in HIV patients
irrespective of immune status. Moreover, HIV itself presented as various neurological
problems throughout the course of infection. The dual epidemic of tuberculosis and
HIV has to be controlled immediately with emphasis on awareness of the disease progression
and prevention. Our observations differed from those of developed countries, which
may be attributed to the different socioeconomic status, culture, and unawareness
of sexual education.