Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene.

BACKGROUND AND PURPOSE: Diagnostic evaluation of limb-girdle muscular dystrophy type 2A (LGMD2A) involves specialized studies on muscle biopsy and mutation analysis. Mutation screening is the gold standard for diagnosis but is difficult as the gene is large and multiple mutations are known. This study evaluates the utility of two known founder mutations as a first-line diagnostic test for LGMD2A in the Agarwals. MATERIALS AND METHODS: The Agarwals with limb-girdle muscular dystrophy (LGMD) phenotype were analyzed for two founder alleles (intron 18/exon 19 c.2051-1G>T and exon 22 c.2338G>C). Asymptomatic first-degree relatives of patients with genetically confirmed mutations and desirous of counseling were screened for founder mutations. RESULTS: Founder alleles were detected in 26 out of 29 subjects with LGMD phenotype (89%). The most common genotype observed was homozygous for exon 22 c.2338 G>C mutation followed by compound heterozygosity. Single founder allele was identified in two. Single allele was detected in two of the five asymptomatic relatives. CONCLUSION: Eighty-nine percent of the Agarwals having LGMD phenotype have LGMD2A resulting from founder mutations. Founder allele analysis can be utilized as the initial noninvasive diagnostic step for index cases, carrier detection, and counseling.

Is pushing the wall, the best known method for scapular winging, really the best? A Comparative analysis of various methods in neuromuscular disorders.

INTRODUCTION: 'Pushing the wall' has found acceptance in medical teachings. Other methods of scapular winging are less known. Comparative evaluation of the five available methods has not been undertaken. This study focuses on evaluation of the available methods in groups of neuromuscular disorders to select the most sensitive method and to characterize patterns of scapular winging. A survey of methods practiced by clinicians also forms a part of the study. MATERIALS AND METHODS: Prospective study. Part A: questionnaire based survey of clinicians to explore the preferred method of examination for scapular winging. Part B: comparative analysis of five methods of scapular winging in four categories of neuromuscular disorders [facioscapulohumeral muscular dystrophy (FSHD), limb girdle muscular dystrophy, dystrophinopathies and neurogenic disorders]. RESULTS AND CONCLUSIONS: Forward lowering of arms was the most sensitive method [100%]. The use of this method in clinical teachings and routine bedside examination should be promoted. Pushing the wall was the most popular method, but was fourth in the sensitivity [60.41%]. Arm maneuvers can bring out winging, when it is not apparent at rest. FSHD patients had a unique combination of winging at rest, persistence of winging throughout the range of motion and elevation of scapulae.

Once myasthenic, always myasthenic? observations on the behavior and prognosis of myasthenia gravis in a cohort of 100 patients.

BACKGROUND: The natural history of myasthenia gravis [MG] is unpredictable: In the first few years the disease course is worst with subsequent gradual disease stabilization. However, some patients tend to have continued disease activity or resurgence of the disease many years into the illness. The factors correlating with disease course need further evaluation. AIMS: To study the patterns of remissions, worsening and exacerbations in patients with MG and correlate various factors affecting them. SETTINGS AND DESIGN: Retrospective, Institute Review Board (IRB) approved study in tertiary referral neurology center. MATERIALS AND METHODS: Hundred patients with acquired MG confirming the inclusion criteria were studied. Pharmacological remissions, complete stable remissions, exacerbations, worsening episodes were analyzed with respect to age of onset, disease extent, disease severity at onset and worst of illness, acetyl choline receptor antibody positivity, thymectomy status, period of disease, pharmacotherapy and crisis episodes. RESULTS AND CONCLUSIONS: In this cohort the percentage of new remission rates per year steadily declined after the first year. Ocular myasthenia had lesser clinical worsening episodes and high chance of complete stable remission. Generalized disease had less chance drug free remission. The risk of episodes of worsening persisted at a steady rate over a period of time, being maximum in the first year. The risk of exacerbations was unpredictable and could occur after prolonged clinical quiescence, often was related to reduction of immunosuppression. The disease course did not differ significantly in the juvenile and adult age-groups. There was a strong case for permanent immunomodulation in MG.

Neurology as career option among postgraduate medical students.

BACKGROUND: In the context of inadequacy of neurology workforce in India, it is important to understand factors that post-graduate medical students consider for and against choosing neurology as their career option. Understanding these factors will help in planning strategies to encourage students to pursue a career in neurology. At present, there is a paucity of studies addressing this issue in India. AIMS AND OBJECTIVES: (1) To analyze factors, which post-graduate students consider for and against choosing neurology as a career specialty. (2) To access the level and quality of neurology exposure in the current MBBS and MD curricula. MATERIALS AND METHODS: Statewide questionnaire based study was conducted in the state of Maharashtra for students eligible to take DM neurology entrance examination (MD Medicine and MD Pediatrics). RESULTS: In this survey, 243 students were enrolled. Factors bringing students to neurology were - intellectual challenge and logical reasoning (72%), inspired by role model teachers (63%), better quality-of-life (51%) and scope for independent practice without expensive infrastructure (48%). Factors preventing students from taking neurology were - perception that most neurological diseases are degenerative (78%), neurology is mainly an academic specialty (40%), neurophobia (43%) and lack of procedures (57%). Inadequate exposure and resultant lack of self-confidence were common (31%, 70-80%). 84% of the students felt the need for a short term certification course in neurology after MD. CONCLUSIONS: To attract more students to neurology, "role model" teachers of neurology could interact and teach students extensively. Neurologists' efforts to shed their diagnostician's image and to shift their focus to therapeutics will help change the image of neurology. Out-patient neurology clinics should be incorporated early in the student's career. Procedures attract students; hence, they should be made conversant with procedures and interventions. Increasing the level of neurological exposure in our current MBBS and MD curriculum is necessary. A case could be made for consideration of short certification course in neurology for physicians.