Deletional mutations of dystrophin gene and carrier detection in eastern India.

Objective. To determine the pattern of deletions of the dystrophin gene, the major class of mutations among the Duchenne and Becker muscular dystrophy patients of eastern India and to analyze the carrier frequency of the female members of the proband’s family. Methods. Deletional mutations occurring in patients have been characterized by multiplex polymerase chain reaction. Carrier state of mothers and sisters of probands were analyzed by either of two methods: 1) typing polymorphic short tandem repeat markers in or around the regions of deletion, by radioactive polymerase chain reaction and 2) quantitative real time amplification of the region of deletion. Results. Deletions were detected in 67 (62.04%) out of 108 male patients, about 76.12% of these being localized in the central hot spot region of the gene, i.e., between exon 42 to exon 53 and 17.91% at the proximal hot spot i.e., between exon 1 to exon 20. In the present study were found 43 types of deletions, out of which 25 (58%) were new deletions, which were not described earlier among the Indian patients. Distribution pattern of deletions in different hot spot regions has been compared with that of other countries and statistical analysis reveals significant difference between countries (p<0.001). Correlation of the pattern of deletion with clinical phenotype of patients has been discussed. Interesting case of germline mosaicism and its implications in counseling has also been discussed. Conclusion. About half the mothers of affected probands were not carriers of the deletion, underscoring the need to use real time techniques for carrier detection.

A 5 years prospective study of incidence, morbidity and mortality profile of stroke in a rural community of eastern India.

Community-based longitudinal study on stroke is rare in India. It has been predicted that the stroke incidence will be higher in developing countries than developed countries. Hence a five years prospective study was planned to carry out in the rural Bengal, India based on WHO protocol to determine the incidence rate, risk factors, morbidity and mortality profile of stroke. In a two-stage procedure, 20717 subjects out of 20842 people from a cluster of 12 villages was surveyed by house-to-house method and the screened cases were examined by a team of neurologists including post stroke surveillance for one year. Altogether 128 first ever stroke cases were detected over 5 years showing an average annual incidence rate of 123.57 per 100,000 persons [age adjusted incidence rate (AAIR)--262/100,000; based on USA population, 1990] and sex-specific AAIR (274/100,000) among women is slightly higher than men (253/100,000). Age-specific stroke incidence rate showed increasing rate from fourth decade up to seventh decade in both sexes when the rate was maximum. First 30 days mortality recorded was 18% with men suffering twice than women. Follow-up after one year revealed speech improvement in 47%, residual spasticity in 46% and independency in activities daily living in 62% of cases. Age and sex matched case control study has shown that hypertension (OR - 2.79), heart disease (OR - 6.20) and smoking (OR - 3.92) are significant risk factors.This study had indicated a higher age adjusted incidence rate of stroke in India as compared to that of developed country and hypertension, heart disease and smoking are important risk factors.

Central nervous system fungal infection--a report of three cases.

Fungal infections of the central nervous system in three apparently immunocompetent patients are being reported. Two cases of cerebral aspergillosis presenting as intracranial granulomas such as rhinocerebral and intracranial forms, and one of cryptococcal meningitis could be successfully diagnosed by newer diagnostic modality such as antigen detection techniques. The case with cryptococcal infection had typical neuroimaging feature which helped to suspect the underlying diagnosis. Aspergillus galactomannan detection in the cerebrospinal fluid helped in the early diagnosis and appropriate therapy of one patient.

Epidemiological study of neurological disorders in a rural population of Eastern India.

The study was conducted to determine the prevalence of neurological diseases in a rural community in Eastern India through a community based survey with the help of trained doctors following on WHO protocol (1981) translated in local vernacular, among 20842 rural residents (male-11037, female-9805, census India-1991, the State of West Bengal in Eastern India) over a period of one yearfrom May 1992 to April 1993 in two phases. Professionals screened the patients by house to house survey in the first phase and later on they were examined in details in temporary clinics in second phase. A total of 606 patients were identified and classified according to well-defined diagnostic criteria. The commonest diseases per 100,000 were headache: 870, vertebral diseases with neurological involvement: 540, seizure disorders: 360, vertigo: 230, stroke: 147, movement disorders: 140, peripheral neuropathy: 80. The age and sex specific prevalence showed increasing frequency of neurological disorders with advancing age in both genders excepting slight dip in the fourth and fifth decades among females. In the present study prevalence of headache, epilepsy, stroke and Parkinson's disease was lower than that of in the Western countries. Different inclusion criteria, multiethnicity, different environmental factors, poor medical facility and insufficient number of aged population may be responsible for lower prevalence of chronic neurological disorders as compared to Western countries. Increase in the life expectancy in future will lead to increasing burden of chronic neurological diseases in absolute term in Indian society considering the one billion population at present.

Botulinum toxin: a dreaded toxin for use in human being.

Botulinum toxin is a dreaded biological toxin elaborated by Clostridium botulinum. The action of this toxin is to cause paralysis of both voluntary and involuntary muscles. The unique property of paralysing capability of muscles has been used for the benefit of human beings. Dr Allan Scot, an ophthalmologist, first used the toxin in a patient with squint in 1981 and since then the botulinum toxin is being used in various disorders characterised by muscle overactivity such as spasticity in both children and adult, dystonic conditions such as blepharospasm, cervical dystonia, spasmodic dysphonia, writer's cramp, etc, hemifacial spasm and headache. Its main action is at the terminal nerve endings of myoneural junction and it prevents release of acetylcholine from vesicles thus causing chemical denervation. Its action persists for 3 to 4 months on an average. Its side effects such as drooping, diplopia, dysphagia, depending on the sites of injection, are few and usually transient. Generalised anaphylaxis is almost unknown. Now botulinum toxin is being used in non-neurological conditions where muscles are under spasmodic state such as achalasia cardia, anal fissure, spasm of urethral sphincter, etc. Because of wider safety range and fewer complications, botulinum toxin has been an important therapeutic armamentarium in different branches of medicine and surgery.

Epidemiology of epilepsy--Indian perspective.

There are about 20 epidemiological studies on epilepsy from different parts of India. They include both rural and urban studies. The prevalence rate stands at around 5/1000 population (at this rate present estimate of total epileptics in this country is about 5 million) and incidence rate varies from 38 to 49.3 per 100,000 population per year from two community-based studies in India. Case-control studies indicate that febrile seizures, family history of epilepsy and head trauma are significant risk factors. Type of seizure pattern showed maximum number of cases belonged to generalised seizures which is different from Western countries where partial seizure is the commonest variety. Treatment gap, which is a measure of per cent of patient populations not receiving the treatment, estimated to be up to 73.7% to 78% in India. Aetiology is unknown in about two-thirds of cases. Hot water epilepsy is unique in South India and single solitary ring enhancing lesion in brain imaging is a common feature in Indian subcontinent. Evaluation of prevalence study indicates that more case-control studies to find out the aetiology, pharmaco-economic study to find out the affordable drug for general public and mass health education should be undertaken to dispel the social stigma and to bring about change in the attitude about the disease.