PubMed HealthSearch

Biomedical subjects

N H Wadia

Publications and source records attributed to N H Wadia.

At least 19 recordsLinked to original sources

Multiple sclerosis is prevalent in the Zoroastrians (Parsis) of India.

Using Schumacher's classification, we determined the prevalence rate of clinically definite multiple sclerosis (MS) in the distinct but tiny Zoroastrian (largely Parsi) community in the adjacent cities of Bombay (latitude, 18.55 degrees) and Poona (Pune). On prevalence day, 16 clinically definite cases of MS were counted, 14 in Bombay and 2 in Poona, from a total Zoroastrian population of 50,053 and 3,399, respectively. The crude prevalence ratio was 26 per 100,000 for Bombay and 58 per 100,000 for Poona. The age-adjusted prevalence ratio for Bombay was 24 per 100,000, with 95% confidence limits of 13.1 to 40.3. These are much higher than the low rates believed to be prevalent in India, and are comparable with those found in parts of Europe and the United States.

Cross-Sectional Studies

IgM deposits at nodes of Ranvier in a patient with amyotrophic lateral sclerosis, anti-GM1 antibodies, and multifocal motor conduction block.

We studied a patient with amyotrophic lateral sclerosis, multifocal motor conduction block, and IgM anti-GM1 antibodies. A sural nerve biopsy demonstrated deposits of IgM at nodes of Ranvier by direct immunofluorescence. The deposits were granular and located in the nodal gap between adjacent myelin internodes, and in some instances, they extended along the surface of the paranodal myelin sheath. When injected into rat sciatic nerve, the serum IgM bound to the nodes of Ranvier, and the binding activity was removed by preincubation with GM1. These observations suggest that anti-GM1 antibodies may have caused motor dysfunction by binding to the nodal and paranodal regions of peripheral nerve.

Adult

Prevalence of multiple sclerosis in the Parsis of Bombay.

We carried out a door-to-door-survey to screen a community of 14,010 people (Parsis living in colonies in Bombay, India) for possible neurologic diseases, and used defined diagnostic criteria to evaluate people who tested positive on the screening survey. There were three clinically definite cases of multiple sclerosis (21/100,000). This is the first prevalence survey for multiple sclerosis in a large developing country.

Humans

Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan.

An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.

Adolescent

The syndrome of continuous muscle fiber activity. Evidence to suggest proximal neurogenic causation.

Four patients with the syndrome of continuous muscle fiber activity were seen in a period of 6 years. Young females predominated. Remarkable improvement followed phenytoin sodium and carbamazepine administration in three patients, one of whom was "cured" within 4 years. In the remaining patient the response was inconstant. Electromyography showed abnormal spontaneous activity with diphasic and triphasic potentials appearing as doublets and multiplets. Waxing and waning was observed. D-tubocurarine and succinylcholine abolished the spontaneous activity excluding the muscle and the myoneural junction as its source. Spinal anesthesia, thiopental sodium, sleep and baclofen had no effect on it, ruling out a central source. In three patients, nerve blocks at the knee and elbow or wrist abolished this activity pointing to a proximal site of origin in the nerve somewhere between the spinal cord and the nerve block. In the remaining patient such a block significantly reduced but did not abolished the activity suggesting a dual source above and below the block. Finally successive examinations in one of our patients led us to believe that this activity may arise from different sites at varying times. It appears that regardless of the site of origin of the activity in the motor axon the counter part clinical syndrome remains the same.

Adolescent

Some observations on SMON from Bombay.

Nine patients in whom subacute myelo-opticoneuropathy (SMON) was diagnosed with varying degrees of confidence are discussed. The cases were discovered after a retrospective examination of our records for the period 1967-71, and a prospective search from March 1972 to date. Subacute myelopathy with predominant dysaesthesiae and greater involvement of the pyramidal tracts was seen more often than fully developed SMON. Subacute myelopathy was seen in six instances, opticomyelopathy in two and myeloneuropathy only once. Clioquinol could not be excluded as an aetiological agent. The difference in the reported prevalence of SMON between Japan and India is noted, and factors which may account for this difference are discussed. Problems related to the diagnosis of SMON outside Japan, and particularly in India, are stressed.

Adult

The B-vitamins in malnutrition with alcoholism. A model of intervitamin relationships.

1. The B-vitamin status of fifty-nine patients, mainly from the lower socio-economic classes in Bombay, with a history of chronic malnutrition, and of alcoholism of 1-5-20 years' duration, was studied before and during treatment, and in relation to their clinical, especially neurological, condition. These patients were divided into two neurological categories: (I) those with peripheral neuropathy (mainly sensory and distal) alone, (2) those with mental changes (mainly confusion and disorientation) also. Both categories frequently showed pellagrous pigmentation and mucocutaneous signs of B-vitamin deficiency. 2. Thiamin and erythrocyte transketolase (EC 2.2.1.1) activity, riboflavin, nicotinic acid, pantothenic acid, total and pyridoxal fraction of vitamin B6, folate and total vitamin B12 were estimated in the blood and the cerebrospinal fluid (CSF) of these patients, and also in the blood of sixty-nine control subjects and in the CSF of some of them. The concentrations of all the vitamins, except vitamin B12, were highly significantly lower in the blood of patients of category I compared to the controls, and erythrocyte transketolase activity and pyridoxal concentration in patients of category 2 were significantly lower than those of category I patients. Blood pantothenic acid and folate concentrations were reduced less consistently. 3. Serum vitamin B12 concentration was significantly increased (though within normal range) in the patients compared to the control group, probably because of the moderate hepatic insufficiency (as assessed by liver function tests) in the former. 4. The concentrations of thiamin, riboflavin, nicotinic acid and total vitamin B6 were also highly significantly lower in the CSF in patients of category I compared with controls. Furthermore, thiamin, nicotinic acid and total vitamin B6 concentrations were significantly lower in patients of category 2 than those of category I patients, indicating that CSF levels reflect better the neurological status of these patients. 5. There was a moderate increase in the blood concentration of all the vitamins tested, after a relatively poor hospital diet alone. There was a concurrent increase in the blood levels of thiamin, riboflavin, nicotinic acid and pantothenic acid after parenteral treatment with either thiamin or nicotinic acid. The administration of pyridoxine resulted in a significant increase in the blood levels of riboflavin and the pyridoxal fraction of vitamin B6.

Adult

Nature of muscular change in osteomalacia: light- and electron-microscope observations.

Thirteen muscle biopsy specimens (mainly the gluteus maximus) from 12 patients with laboratory confirmation of osteomalacia and proximal muscle weakness in 10 were examined by light and electron microscopy. Light microscopy revealed mild diffuse non-specific atrophy of the muscle fibres in 10 cases, severe generalised atrophy in one and patchy group atrophy in one. There was no myopathic change in specimens from cases with either a nutritional aetiology, or a mixed aetiology. The former, mostly women gave a history of severe chronic malnutrition often accompanied by repeated pregnancies and prolonged lactation; those with a mixed aetiology gave, in addition, evidence of a metabolic or endocrine disorder such as hyperparathyroidism, hyperthyroidism, uraemia, or treatment with anti-epileptic drugs or were of uncertain origin. Electron-microscope examination of muscle from the nutritional group showed atrophic changes in the fibres, such as loss of myofibrils, prominence of mitochondria and glycogen, loosening and folding of the basement-membrane but good preservation of the remaining myofibrils. In contrast muscle from cases of mixed aetiology showed, in addition to the atrophic features, clear degenerative changes in the myofibrils and the mitochondria, accumulation of amorphous material at the site of myofibrillar loss and of lipofuscin in muscle fibres, vascular endothelium and satellite cells. The earliest degenerative change was in the "I" band, involving actin filaments and "Z" line. The triads were generally preserved but the sarcoplasmic reticulum appeared affected in a patient with tetany and severe mitochondrial degeneration. In a patient with thyrotoxicosis, proliferation of central nuclei, "Z" line streaming and formation of "T" tubular aggregates were seen. In one patient with hyperparathyroidism and hypercalcaemia, severe myofibrillar degeneration and mitochondria showing osmiophilic deposits, possibly of calcium phosphate, were encountered. It is concluded: (1) that all osteomalacic muscle weakness is not myopathic but a non-specific atrophy occurring probably on the basis of disuse and malnutrition, and (2) patients with an added metabolic or endocrinological disorder show in addition to the atrophy, degenerative changes in the muscle fibre and its sub-cellular components consistent with myopathy, and these patients should be clearly distinguished from those with a background of malnutrition only.

Adolescent

Model of an oculomotor subsystem.

One of the complex control systems present in the human body is the oculomotor control system. There are two major modes of ocular movements, viz. saccadic and smooth pursuit. More knowledge about the neuromuscular mechanisms controlling these eye movements is obtained if experiments are carried out on subjects whose two types of eye movements are differentially affected due to disorders at their higher centres of control. Eye movements of patients with a novel form of Heredo-familial Spinocerebellar Degeneration have been measured and quantified. These have been compared with those of normal subjects. Subsequent analysis indicates a continuous fourth order transfer function for the smooth pursuit eye-in-skull movements in the horizontal plane with head stationary.

Cerebellar Ataxia

Profile of multiple sclerosis in the bombay region. On the basis of critical clinical appraisal.

Using internationally accepted strict clinical criteria, 30 patients with probable multiple sclerosis (MS) fron the Bombay region have been described. They were personally studied and followed up over a period of 15 years. In addition, 9 patients with neuromyelitis optica and 6 with a mixed neurological picture of MS and neuromyelitis optica have been described. As in Japan, the neuromyelitis optica type of presentation was relatively more frequent in our material than in the West. In this small series MS was more frequent in patients with a better socio-economic status, in the Parsee community and in patients with a fair complexion, whereas neuromyelitis optica was more frequent in patients with poor socio-economic status. A relatively high proportion of patients (nearly half of the MS patients with optic nerve involvement and two-thirds of the MS--neuromyelitis optica group) had bilateral optic nerve involvement. Except in 2 patients, the tempo and course of the disease in our patients with MS was comparable to that seen in the West. In 3 patients with MS the initiation of symptoms or appearance of fresh symptoms was related to vaccination. In addition to the above 45 patients, 29 other cases of possible demyelination have been reviewed. Nine of these had one or more remission and relapse but in the same site as the first episode. Seventeen had a solitary episode of spinal cord or brainstem disturbance with some remission and 3 had multiple lesions but without remission or clear dissemination in time. In the absence of a specific diagnostic test or autopsy, such atypical cases will remain unclassified. To conclude, MS does occur in the Bombya region and elsewhere in India but the incidence is much less than in the West. Further studies and especially careful follow-up of atypical cases may show that the prevalence is higher than it seems today.

Adolescent

Interrelationships between the B-vitamins in B12-deficiency neuromyelopathy. A possible malabsorption-malnutrition syndrome.

Five patients presenting clinically with a form B12-deficiency neuromyelopathy, with cord involvement in all and proximal muscle weakness in two of them, were investigated for their neurologic, hematologic and vitamin status. Megaloblastosis and achlorhydria were present in all, and impaired absorption of 57Co vitamin B12 and of D-xylose was detected in four. Total cyanide extracted vitamin B12 (A) was lowered in all cases and noncyanide extractable (B) in four of the five, being zero in three. All five responded to injections of hydroxocobalamin. In two patients sequential estimations showed that both A and B, especially the latter, rose steeply initially, normalizing at 50% of A after some weeks. Moiety B is suggested to be physiologically the more active and dissociable form of vitamin B12. Markedly elevated initial serum folate levels, and their subsequent fall under treatment with B12, indicated the operation of the "methyltetrahydrofolate trap". Blood levels of thiamin, nicotinic acid and pantothenic acid were within normal limits. However, serum riboflavin (B2) total vitamin B6 and pyridoxal were reduced in all where tested. Vitamin B6 deficiency could have resulted from its own malabsorption and have contributed to be B12 deficiency. Vitamin B2 and B6 levels also corrected themselves on B12 therapy. The B-vitamin deficiencies in our patients probably resulted from intestinal malabsorption, with a possible factor of malnutrition consequent to their strictly vegetarian diet.

Achlorhydria