Biomedical subjects

M Gourie-Devi

Publications and source records attributed to M Gourie-Devi.

At least 19 recordsLinked to original sources

PubMed2001

Cyclophosphamide attenuates the degenerative changes induced by CSF from patients with amyotrophic lateral sclerosis in the neonatal rat spinal cord.

Our earlier studies have shown that cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), when intrathecally injected into the neonatal rats, produces an aberrant phosphorylation of neurofilaments (NF) in the ventral horn neurons and reactive astrogliosis in the spinal cord. We wanted to investigate the effect of cyclophosphamide in the spinal cords of neonatal rats exposed to ALS-CSF. A single dose (5 microg in 5 microl saline) of cyclophosphamide was injected, 24 h after the administration of CSF samples from ALS and non-ALS neurological patients into the spinal subarachnoid space of 3-day-old rat pups. Rats were sacrificed after a period of 24 h, and stained with antibodies against the phosphorylated NF (SMI-31 antibody) and glial fibrillary acidic protein (GFAP). Cyclophosphamide treatment resulted in a 50% decrease in the number of SMI-31 stained neuronal soma in ventral horns of spinal cords of ALS-CSF exposed rats. This was accompanied by a decrease in the number of GFAP immunoreactive astrocytes. Furthermore, lactate dehydrogenase (LDH) activity was also decreased significantly, following cyclophosphamide treatment. These results suggest that cyclophosphamide could exert a neuroprotective effect against the neurotoxic action of factor(s) present in the ALS-CSF.

Amyotrophic Lateral Sclerosis↗

PubMed2001

Sympathetic skin response in monomelic amyotrophy.

OBJECTIVES: Monomelic amyotrophy (MMA) a variant of motor neuron disease, has the characteristic features of wasting and weakness usually confined to a single upper or lower limb occurring predominantly in young males and a benign outcome. Symptoms of increased sweating, coldness and cyanosis have been observed in a few patients. The objective was to evaluate the involvement of the sympathetic nervous system in MMA by measuring sympathetic skin response. METHODS: Electromyography, motor and sensory nerve conduction studies were done in all the four limbs of 9 patients with atrophy of one upper limb. Stimulation at Erb's point, and above and below elbow was done to look for evidence of conduction block. The sympathetic skin response (SSR) was recorded in all the limbs of these patients. Wasting and weakness of right upper limb in 7 patients and left upper limb in 2 patients was seen. The mean age was 28.3+/-10.1 years. Twenty-five age matched (24.8+/-4.8 years) healthy subjects served as controls. RESULTS: The mean SSR latency in the affected upper limbs of 9 patients was prolonged compared to the 25 control subjects (1.51+/-0.07 s vs 1.42+/-0.19 s, P=0.03). The mean value of SSR latency in 18 upper limbs of the 9 patients which included atrophied and unatrophied limbs was also prolonged compared to the controls (1.50+/-0.08 s vs 1.42+/-0.19 s, P=0.05). There was no significant difference of the mean latency of SSR between the atrophied upper limbs and the clinically normal upper limbs (1.51+/-0.07 s vs 1.49+/-0.09 s, P=0.51). The mean SSR latency in the lower limbs of the patients (2.09+/-0.09 s) did not significantly differ from the control subjects (1.97+/-0.28 s, P=0.09). Motor and sensory nerve conduction was normal and there was no evidence of conduction block. CONCLUSION: In MMA the sympathetic nervous system is involved in the atrophic upper limb and also in the clinically unaffected upper limb but not in the lower limbs.

Adult↗

PubMed2001

Disabilities in children with Duchenne muscular dystrophy: a profile.

Proper assessment of disabilities is essential for rehabilitation of patients with Duchenne muscular dystrophy. The aim of this study was to identify and quantify the disabilities in children with Duchenne muscular dystrophy and correlate them with impairment. Thirty-one patients with Duchenne muscular dystrophy of age four years and above were studied. The motor functions were evaluated using total motor score, upper and lower extremity function grades and timed function tests. Disability was quantified with Barthel index. The mean scores of motor scales were: total motor score -52 +/- 7.8, total functional grade -4.4 +/- 1.9 and timed function score -12.5 +/- 5.8. Barthel index scores ranged from 45-95 with a mean of 70.8 +/- 12.7. Motor scales correlated with each other and with Barthel index. Thirty children had disabilities in multiple spheres of life, which were significantly influenced by the motor power. Barthel index was useful in identifying and quantifying specific areas of disabilities in these children. Evaluation of disabilities using specific measures may be crucial for planning comprehensive management.

Activities of Daily Living↗

PubMed2000

Pathology of Madras type of motor neuron disease (MMND)--a histological and immunohistochemical study.

A neuropathological report of Madras type of motor neuron disease (MMND) is presented and the differences from other forms of MND are discussed. An 18-year-old girl presented with nerve deafness and slowly progressive bulbo-spinal muscular atrophy, characteristic of MMND. Post-mortem examination of the spinal cord showed a severe loss of anterior horn cells, prominent dilatation of vessels, diffuse, but sparse sprinkling of microglial cells and lymphocytes, and demyelination and sclerosis of the ventrolateral columns. Neuronal depletion and marked gliosis was noted in the cochlear nucleus on both sides, while other bulbar motor nuclei were also involved. The cochlear nerve showed demyelination and axonal loss. Trigeminal and vestibular ganglia revealed features of ganglionitis. The possibility of an inflammatory aetiology for MMND needs to be considered.

Adolescent↗

PubMed2000

HIV antibody profiles in serum and CSF of patients with neurological disease can serve as predictors of outcome.

The serum and CSF antibody profiles were investigated in 100 patients with HIV in relation to the type and severity of neurological disease. Among them, 87 were positive for anti-HIV antibodies in the CSF. In 30 of 87 patients detailed analysis by western blot could be performed. In 20 of 30 the profiles were dissimilar, with more of bands being found in the serum than in the CSF. The correlation of western blot profiles to the clinical outcome indicated that the number of anti-HIV antibody bands as well as the index in the CSF of fatal cases were significantly less compared with non-fatal cases (p=0.019 and p=0.039 respectively).

Adolescent↗

PubMed2000

Profile of neurologic disorders associated with HIV/AIDS from Bangalore, south India (1989-96).

One hundred patients (95 males, 5 females, mean age at presentation 31.6 +/- 9.4 yr) with various neurological disorders associated with HIV infection during 1989-1996 were evaluated at NIMHANS, Bangalore. Eighty patients belonged to group I associated with opportunistic neuroinfections and 20 to group II--non infectious neurological disorders. Cryptococcal meningitis either alone (n = 31) or associated with tuberculous meningitis (n = 6) was the most common (46.3%) followed by neurotuberculosis either alone (n = 24) or with cerebral toxoplasmosis (n = 4) accounting for 35 per cent. Other opportunistic neuroinfections included cerebral toxoplasmosis, herpes zoster, fulminant pyogenic meningitis and neurosyphilis. Clinical characteristics, diagnostic clues, their laboratory and radiological profiles and problems encountered in diagnosis and management of these opportunistic infections are highlighted. In group II (19 males and one female; mean age of 32.6 +/- 9.4 yr), two patients had cortical dementia, three acute brain stem involvement, two epilepsy and one had features suggestive of progressive multifocal leukoencephalopathy. Two patients of group I during follow up developed cortical dementia. Six had peripheral nervous system involvement similar to Guillain-Barre syndrome. Sixty six patients (63 of group I and 3 of group II) progressed to AIDS, 33 patients from group I and one patient from group II succumbed to the disease. With the rapid increase in the incidence of HIV/AIDS and an increase in the neurological manifestations of HIV/AIDS it is important to recognise the magnitude of the problem for health planning in India.

AIDS-Related Opportunistic Infections↗

PubMed1998

Reactive astrogliosis in neonatal rat spinal cord after exposure to cerebrospinal fluid from patients with amyotrophic lateral sclerosis.

Previous studies have proposed the presence of circulating toxic factor(s) in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). In the present study we show that there is an increased number of astrocytes intensely immunoreactive for glial fibrillary acidic protein (GFAP) in the gray matter of the spinal cords of neonatal rats exposed to ALS CSF. There is also increased expression of GFAP in the astrocytes of the white matter of neonatal rat spinal cords exposed to ALS CSF. Western blot analysis also confirmed the increased expression of GFAP. Accordingly, our study provides for the first time a clear evidence for the pathological response of glia to the circulating toxic factor(s) in the CSF of ALS patients.

Amyotrophic Lateral Sclerosis↗

PubMed1998

Correlation of clinical profile of myotonic dystrophy with CTG repeats in the myotonin protein kinase gene.

The molecular genetic analyses (PCR and Southern hybridization) of Indian patients with myotonic dystrophy (DM) were carried out to determine the degree of repeat expansion and an attempt was made to correlate the repeat number with disease severity. A scoring system based on the salient clinical features was devised to objectively assess the disease severity. The repeat expansion was seen in 11 of 12 patients examined and showed an inverse correlation with the age of onset confirming the phenomenon of anticipation. This was further established in the two pedigrees studied, clearly demonstrating both clinical and genetic anticipation. The clinical severity score, however, did not correlate well with the repeat number. Nonetheless, such molecular genetic analyses may have immense value as a screening procedure to identify premutations as well as in prenatal diagnoses.

Adolescent↗

PubMed1997

Temporary amelioration of symptoms with intravenous cyclophosphamide in amyotrophic lateral sclerosis.

Based on the evidence that autoimmunity may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), a variety of immunomodulating agents have been used in the treatment. In an uncontrolled trial we treated 44 patients of ALS with intravenous cyclophosphamide (IVCP) at a total dose of 1.5 g/m2 given over a period of 8 to 10 days. The patients were evaluated using neurological score which included bulbar, motor and daily activity scores before and following treatment. Twenty three patients showed a significant improvement (P=<0.001) in the composite and the individual scores. The improvement persisted only for 2 to 3 months. Amongst them the severely (7) and moderately (16) affected (score less than or more than 150) showed almost a similar response to treatment. A comparison of the improved group of 23 patients with the unimproved group of 21 patients did not reveal any significant factors which influenced the response to IVCP. However, there was a suggestion that patients below the age of 60 years and a duration of illness less than 12 months may respond to the drug. In conclusion, treatment with intravenous cyclophosphamide resulted in mild and temporary improvement in clinical status of the patients with amyotrophic lateral sclerosis. This may be considered as an alternative method of treatment in developing countries where newer drugs are not available and affordable.

Adult↗

PubMed1997

Variable histomorphology of muscle in congenital muscular dystrophy.

Congenital muscular dystrophy (CMD) is a relatively uncommon disease with a controversial nosological status. That collagen synthesis could be the primary abnormality has been suggested earlier (Fidzianska et al., 1982). Amongst eighteen cases of CMD diagnosed during the past twelve years, muscle biopsy in three cases revealed prominence of myofibre necrosis and phagocytosis, and serum CPK was markedly elevated suggesting a rapidly progressive form. In twelve cases, marked increase in endomysial collagen, pronounced fallout of myofibres and significant fibre diameter variation was seen. This was associated with myonecrosis and regenerative activity of mild degree resembling the classical form of CMD. In the remaining three cases, polyfocal, polyphasic necrosis was noticed. Fibre splitting was more frequently observed, better delineated in the enzyme histochemical preparations, affecting both fibre types, while endomysial fibrofatty tissue was only moderately increased. The histomorphology in the latter group resembled that of limb girdle dystrophy. Ultrastructural findings in all the eighteen cases correlated well with light microscopic observations. lmmunohistochemical studies done on three of the eighteen cases showed normal localization of dystrophin protein. Such variable histomorphology, revealing a spectrum of myopathic features, suggests that the primary change in CMD is likely to be in the myofibre rather than in collagen synthesis.

Biopsy↗

PubMed1997

Co-existence of cerebral cysticercosis with Japanese encephalitis: a prognostic modulator.

In this study, we investigated the frequency of co-existence of cerebral cysticercosis (CC) in Japanese encephalitis (JE) cases with special emphasis on its role in predicting the final clinical outcome. Amongst the 163 confirmed cases of JE, 37.42% (61/163) had co-existent CC. This was confirmed by antibody detection in the CSF of 45 cases, CT scan of the brain in 6 cases and at autopsy in 3 cases. In 2 cases confirmation was possible by CT scan as well as at autopsy, in 4, CSF antibody levels and CT scan were suggestive of CC while in 1, CSF antibodies and autopsy were suggestive of CC The co-occurrence of Cysticercus cellulosae in the brain emerged as a prognosticator of poor outcome in JE cases (P < 0.03).

Adolescent↗

PubMed1997

Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients.

To investigate the prognostic role of tumour necrosis factor (TNF) in Japanese encephalitis virus (JEV) infection, we measured the immunoreactive forms of TNF concentrations in the serum and cerebrospinal fluid (CSF) of 47 laboratory-confirmed cases of JE. It was observed that TNF levels were elevated (> 15 pgm/ml) in all the 47 serum samples (range 19.4-923.8 pg/ml), while in 46/47 CSF samples TNF was elevated (range 10.8-376 pg/ml). The mean (SD) TNF levels in the serum of fatal cases was 234.34 pg/ml (304.40) as compared to the mean of 85.31 pg/ml (SD 153.92) in nonfatal cases. Similar observations were also made with respect to the TNF levels in the CSF; the mean of fatal cases was 69.39 pg/ ml (SD 39.00) in contrast to the mean of 62.41 pg/ml (SD 75.25) of nonfatal cases. The increase in TNF levels did not show any correlation to the duration of illness. It was further observed that the mortality rate increased with increasing concentrations of TNF in the serum and CSF. Correlation of laboratory parameters to final outcome revealed that TNF concentrations above 50 pg/ ml in serum correlated significantly (P = .05) with a fatal outcome, whilst high levels of JEV-IgM antibodies (> 500 units) in the CSF correlated with a nonfatal outcome (P = .03). These results suggest that TNF can be used as a possible prognosticator of a fatal outcome in JEV infection.

Adolescent↗

PubMed1996

Identification of antibody responses to Mycobacterium tuberculosis antigens in the CSF of tuberculous meningitis patients by Western blotting.

One of the adjunctive modes of diagnosing tuberculous meningitis (TBM) is to detect immune responses in the cerebrospinal fluid (CSF) to the Mycobacterium tuberculosis antigen. Up to 70% of clinical TBM reveal the presence of antimycobacterial antibody by the enzyme-linked immunosorbant assay. Defining the specificity of this immune response by Western blotting on separated M. tuberculosis antigen has been attempted in this study. Only antimycobacterial antibody-positive TBM cases were included in the study. An analysis of 30 such TBM cases showed a major immune reactivity to the 30- to 40-kDa region (93%) while a lower degree of immune reactivity was seen to the 14-kDa region (87%) and to the 18- to 25-kDa region (60%). Grossly the antibody reactivity on Western blot correlated with the ELISA results. Assessment of antimycobacterial antibody in the neurologic control CSF samples of pyogenic meningitis [n = 10], cryptococcal meningitis [6], neurocysticercosis [28], neurosyphilis [8], viral meningoencephalitis [8], carcinomatous meningitis [8], iatrogenic meningitis [6], and nonneurological control CSF samples from patients undergoing spinal anesthesia [20] revealed the presence of antibody in the CSF of 2 of the 10 pyogenic meningitis and 5 of the 28 neurocysticercosis cases. A Western blot analysis of these 7 cases revealed immune reactivity to 30- to 40-kDa regions only in 2 cases (1 of pyogenic and 1 of neurocysticercosis). The remaining 5 CSF samples did not reveal any immune reactivity on Western blotting, although ELISA demonstrated antimycobacterial antibodies. The antibody response to M. tuberculosis lipoarabinomannan and 38-kDa antigen by ELISA revealed 70.58 and 41.17% positivity, respectively. Thus this study has demonstrated that, by Western blotting, the major immune response is to the 30- to 40-kDa region, namely, lipoarabinomannan. Further, this finding will be useful for specific immunodiagnosis of the TBM.

Antibodies, Bacterial↗

PubMed1996

Significance of mycobacterial immune complexes (IgG) in the diagnosis of tuberculous meningitis.

SETTING: Tuberculous meningitis (TBM) has high mortality, especially in children. Early accurate diagnosis and adequate treatment would reduce this mortality. Diagnosis of TBM remains an enigma because of low cerebrospinal fluid (CSF) culture positivity for Mycobacterium tuberculosis and weak clinical correlation with conventional immunoassays. OBJECTIVE: To evaluate significance of mycobacterial immune complexes (IgG) and anti-mycobacterial antibodies in the diagnosis of TBM. METHOD: CSF from TBM patients and various types of other neurological (both infectious and non-infectious) and non-neurological cases was studied for the presence of IgG and anti-mycobacterial antibodies using antigen capture (by anti-BCG) and multilayered ELISA (using M. tuberculosis soluble extract), respectively. RESULTS: IgG in CSF could be detected in 33 of 55 (60%) and anti-mycobacterial antibodies in 30 of 55 (55%) TBM cases. Presence of IgG, anti-mycobacterial antibodies or both could be detected in 45 of 55 (82%) of the TBM cases. Excepting three of the pyogenic meningitis CSF, none of the infectious (49), non-infectious neurological cases (30) and non-neurological controls (32) showed the presence of IgG or anti-mycobacterial antibodies. CONCLUSION: Detection of IgG along with anti-mycobacterial antibodies aids in diagnosis of a large proportion of TBM cases.

Antibodies, Bacterial↗

PubMed1996

Neuro-epidemiological pilot survey of an urban population in a developing country. A study in Bangalore, south India.

A feasibility study was conducted in an urban population of 3,040 in Bangalore, South India, to understand the baseline characteristics, evaluate screening questionnaires, identify potential problems and determine the magnitude of the problems. The target population was selected by a random method, from four census enumeration blocks of a specific urban area. A two-phase study design was adopted consisting of screening by trained field investigators in the initial stage and clinical examination by a neurologist in the second stage. The information was collected by an interview method on a house-to-house basis. Evaluation of the screening instruments yielded high sensitivity and specificity rates, and it became clear that there is a need to reduce false-positive results in the screening questionnaire for individuals above 7 years of age. The prevalence of neurological disorders was 32.8 per 1,000 population (with a rate of 7.8/1,000 for epilepsy). It appears feasible to detect a wide range of neurological disorders using the methods described.

Adolescent↗

PubMed1995

Japanese encephalitis virus antigen in the human brain and its topographic distribution.

This study reports the pathological findings and the distribution of viral antigen in the brains of 13 confirmed and autopsied cases of Japanese encephalitis (JE) in correlation with other virus-specific immunological parameters measured in the cerebrospinal fluid (CSF) antemortem. Japanese encephalitis virus (JEV)-specific antibodies were detected in the CSF of 10 of 13 patients, JEV antigen was detected in the CSF of 7 of 13 and JEV-specific immune complexes were detected in the CSF of 3 of 11 patients. Viral antigen was localised immunocytochemically in the brain tissue of 11 of 13 cases, indicating, that viral antigen could not be cleared from the tissues by the antibody. The topographic distribution of the tissue-associated antigen in the thalamus, hippocampus, substantia nigra and medulla oblongata explain the evolution of post JE sequelae.

Antigens↗

PubMed1995

Proliferative response of human peripheral blood mononuclear cells to Japanese encephalitis virus.

Cell-mediated immune response to Japanese encephalitis virus (JEV) and its purified envelope (E) protein was measured in 45 laboratory confirmed JE patients using a proliferation assay of peripheral blood mononuclear cells (PBMC). In parallel, JEV-specific IgM antibodies were measured by ELISA. No correlation was observed between the antibody response and results of the lymphocyte proliferation assay. Only 11 of the 42 patients positive in the antibody test were positive in the proliferation assay, and PBMC from 14/45 (31%) patients did not respond to either phytohemagglutinin and to JEV and/or its purified E protein antigen. No correlation was observed between the cell-mediated immune response and the final clinical outcome (fatality vs. recovery).

Adolescent↗

PubMed1994

Neurofilament phosphorylation is enhanced in cultured chick spinal cord neurons exposed to cerebrospinal fluid from amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease, is characterized by degeneration of lower and upper motor neurons. Serum and cerebrospinal fluid (CSF) of ALS patients have been found to exert toxic effects on neurons in culture. We report here increased phosphorylation of neurofilaments (NF) in the soma of chick spinal cord neurons in culture when exposed to CSF of ALS patients. Spinal cord neurons were cultured from 10-day embryonic chick and exposed to culture medium supplemented with CSF or serum (10%) from ALS and non-ALS patients for 48 h. There was a significant increase in the number of neuronal soma staining with antibodies against phosphorylated NF, following exposure to CSF from ALS patients. Such an increase, however, was not observed in cultures exposed to serum from ALS patients and also serum and CSF from non-ALS patients. These results suggest that the CSF of ALS patients may contain factor(s) which induces aberrant phosphorylation of NF in the soma, a probable forerunner to the formation of neurofibrillary tangles and eventual degeneration of neurons.

Amyotrophic Lateral Sclerosis↗