Proprioceptive loss in leprous neuropathy: a study of 19 patients.

BACKGROUND: Leprosy presents commonly with mononeuritis multiplex, affecting mainly the exteroceptive sensations. Neuropathy with a significant afferent large fiber element is considered to be an uncommon manifestation of leprous neuropathy. AIMS: To evaluate the clinical and neurophysiologic aspects of a subset of patients with leprous neuropathy having clinical proprioceptive loss. SETTINGS AND DESIGN: Prospective study of patients with a diagnosis of peripheral neuropathy secondary to leprosy having proprioceptive loss. MATERIALS AND METHODS: Consecutive patients seen during a two-year period (2004 and 2005) diagnosed to have leprous neuropathy with proprioceptive abnormalities on clinical examination were included. The diagnosis of leprosy was achieved by clinical features along with positive skin biopsy, split skin smears or nerve biopsy. Their clinical and electrophysiological characteristics were studied. STATISTICAL METHODS : The results were analyzed using Chi-Square test. Values less than 0.05 were considered to be statistically significant . RESULTS AND CONCLUSIONS: We observed predominance (68.42%) of multibacillary of leprosy. Symmetrical neuropathies outnumbered mononeuritis multiplex (12:7). The pan sensory neuropathy had a mean duration of 24.32 months, but sometimes appeared early in the course of the disease. Areflexia and electrophysiological evidence of proximal affection was common, reflecting proximal spread of neuropathic process. Such patients have a higher incidence of developing deformities and ulcerations and they represent a vulnerable subset of patients with leprosy.

Limb girdle muscular dystrophies in India.

The recent years have seen remarkable progress in the field of limb girdle muscular dystrophies (LGMDs) with the advances in immunocytochemistry and genetics. Based on this, many subgroups have emerged. Protein products and genes are getting defined and newer mechanisms of disease are being recognized. Limb girdle muscular dystrophies are common in India. The clinical material is plentiful, and from various centers in the country, phenotypes have been studied. With the help of immunocytochemistry, sarcoglycanopathies and dysferlinopathies have been studied. Genetic information on these subgroups is now beginning to emerge. The laboratory facilities are limited and available in select centers in large institutes. Establishment of genetic laboratories and sophisticated muscle pathology techniques will further elucidate the LGMDs in India.

Study of idiopathic inflammatory myopathies with special reference to borderland between idiopathic inflammatory myopathies and muscular dystrophies.

Background: Idiopathic inflammatory myopathies (IIMs) form important treatable myopathies, hence it is important to recognize and categorize them. In some cases, the differential diagnosis between IIM and muscular dystrophies can be difficult. Aim: To study the clinical and laboratory features of patients with IIMs and compare and contrast this group with limb girdle muscular dystrophies (LGMDs). Setting and Design: A prospective study for the period of five years [1999-2004] was undertaken at a tertiary neuromuscular center. Materials and Methods: Bohan and Peter criteria were used for the diagnosis of IIM and Bushby criteria were used for the diagnosis of LGMD. Patients underwent history, clinical examination, hematological tests, electrophysiological studies and muscle biopsy. The biopsies were studied for histology and immunocytochemistry. A clinical scoring system was evolved to differentiate IIM from LGMD and was validated in a blinded manner. Receiver operator curves were used as the statistical method to analyze the sensitivity and specificity. Results and Conclusions: In the IIM group, dermatomyositis was most common, followed by polymyositis, occurring in young females. Overlap group was less common. In patients with polymyositis, onset in upper girdle was associated with adverse outcome. The scoring system helped to differentiate IIM from LGMD, mainly using clinical pointers. This was particularly valuable in chronic cases.

Duchenne and Becker muscular dystrophies: An Indian update on genetics and rehabilitation.

The application of molecular diagnostic techniques has greatly improved the diagnosis, carrier detection, prenatal testing and genetic counseling for families with Duchenne and Becker muscular dystrophy (D/BMD) in India. The prediction of Duchenne muscular dystrophy (DMD) patients to have out-framed deletions and Becker's muscular dystrophy (BMD) patients to have in-frame deletions of dystrophin gene holds well in the vast majority of cases. Mutation detection is obviously critical for diagnosis but it may also be important for future therapeutic purposes. These factors underscore the need for earlier referral, genetic counseling and provision of support and rehabilitation services which are the main priorities for psychosocial assessment and intervention at medical and social levels.

Twenty-two year follow-up of an Indian family with dysferlinopathy-clinical, immunocytochemical, western blotting and genetic features.

Long-term observations over a period of 22 years in an Indian family with primary dysferlinopathy are recorded, defining phenotypic variability. In the propositus, the dystrophy began distally in the tibialis anterior muscles, before involving the gastrocnemius. Transient painful calf hypertrophy, followed by calf wasting was observed. The proximal lower and upper limbs weakened after three to four years. The younger sibling presented with the proximo-distal phenotype. Both patients showed very high creatine kinase values early into the illness. Disease progression was slow. The younger sibling lost ambulation 14 years after onset, while the elder one remains ambulatory 22 years into the illness. Muscle biopsy showed dystrophic features and absence of dysferlin. Monocyte western blotting confirmed absence of dysferlin. Genetic analysis detected a heterozygous mutation in Exon 54 [c.6124C>T] in the DYSF gene. This is the first family with a diagnosis of dysferlinopathy supported by genetic data, reported from India.

Becker muscular dystrophy in Indian patients: Analysis of dystrophin gene deletion patterns.

Background: Becker muscular dystrophy (BMD) is caused by mutations in the dystrophin gene with variable phenotypes. Becker muscular dystrophy patients have low levels of nearly full-length dystrophin and carry in-frame mutations, which allow partial functioning of the protein. Aim: To study the deletion patterns of BMD and to correlate the same with reading frame rule and different phenotypes. Setting: A tertiary care teaching hospital. Design: This is a prospective hospital-based study. Materials and Methods: Thirty-two exons spanning different "hot spot" regions using Multiplex PCR techniques were studied in 347 patients. Two hundred and twenty-two showed deletions in one or more of the 32 exons. Out of these, 46 diagnosed as BMD patients were analyzed. Results: Forty-six BMD patients showed deletions in both regions of the dystrophin gene. Out of these 89.1% (41/46) were in-frame deletions. Deletions starting with Exon 45 were found in 76.1% (35/46) of the cases. Mutations in the majority of cases i.e. 39/46 (84.8%) were seen in 3' downstream region (Exon 45-55, distal rod domain). Few, i.e. 5/46 (10.8%) showed deletions in 5' upstream region (Exons 3-20, N-terminus and proximal rod domain) of the gene, while in 2/46 (4.4%) large mutations (>40 bp) spanning both regions (Exons 3-55) were detected. Conclusion: This significant gene deletion analysis has been carried out for BMD patients particularly from Western India using 32 exons.

Severe childhood autosomal recessive muscular dystrophy, mental subnormality and chorea.

Severe childhood autosomal recessive muscular dystrophy (SCARMD) is characterized by a severe Duchene muscular dystrophy like phenotype. Most such cases represent alpha or gamma sarcoglycanopathies. Mental subnormality is very uncommon and other central nervous system deficits have not been documented in patients with SCARMD. We report a brother and sister with the SCARMD phenotype, who additionally had static mental subnormality and choreiform movements. Work-up for sarcolgycan genes, dystrophin gene and known causes of mental retardation and chorea was normal.

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Indian patients.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder involving degeneration of anterior horn cells of spinal cord resulting in progressive muscle weakness and atrophy. AIMS: The molecular analysis of two marker genes for spinal muscular atrophy (SMA) i.e, the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP) was conducted in 39 Indian patients with clinical symptoms of SMA. Out of these, 28 showed homozygous deletions and the phenotypic features of these SMA patients were compared with the corresponding genotypes. SETTINGS: A tertiary care teaching Hospital. DESIGN: This is a prospective hospital based study. MATERIALS AND METHODS: Polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was used to detect the deletion of exon 7 and exon 8 of SMN1 gene, as well as multiplex PCR for exon 5 and 13 of NAIP gene. RESULTS: Exons 7 and 8 of SMN and NAIP (exon 5) were homozygously deleted in 73% of SMA I and 27% of SMA II patients. SMN exon 7 and 8 deletions without NAIP deletions were seen in 27% of type I SMA and 46% of SMA type II patients. Two patients of type III SMA showed single deletion of SMN exon 7 along with 27% of SMA type II patients. CONCLUSION: With the advent of molecular biology techniques, SMN gene deletion studies have become the first line of investigation for confirmation of a clinical diagnosis of SMA. The findings of homozygous deletions of exons 7 and/or 8 of SMN1 gene confirms the diagnosis of SMA, even in patients with atypical clinical features. Deletions of NAIP gene were mainly seen in severely affected patients, hence is useful for predicting the prognosis.

Childhood ataxia with cerebral hypomyelination (CACH) syndrome: a study of three siblings.

We report a family of three siblings with Childhood Ataxia with Cerebral Hypomyelination. All the siblings presented with early onset cerebellar ataxia beginning around five years of age with mild mental retardation. MRI showed diffuse white matter signal changes in all three patients with cerebellar atrophy while the spectroscopy was abnormal only in the eldest who was the most severely affected. The cases are reported for their rarity as well as for an opportunity of observing this uncommon disease in its stages of evolution in three siblings.