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Background and PurposeStudies of cases of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) confirmed by multiplex ligation-dependent probe amplification (MLPA) have determined the clinical characteristics, genotype, and relations between the reading frame and phenotype for different countries. This is the first such study from India.MethodsA retrospective genotype-phenotype analysis of 317 MLPA-confirmed patients with DMD or BMD who visited the neuromuscular clinic of a quaternary referral center in southern India.ResultsThe 317 patients comprised 279 cases of DMD (88%), 32 of BMD (10.1%), and 6 of intermediate phenotype (1.9%). Deletions accounted for 91.8% of cases, with duplications causing the remaining 8.2%. There were 254 cases of DMD (91%) with deletions and 25 (9%) due to duplications, and 31 cases (96.8%) of BMD with deletions and 1 (3.2%) due to duplication. All six cases of intermediate type were due to deletions. The most-common mutation was a single-exon deletion. Deletions of six or fewer exons constituted 68.8% of cases. The deletion of exon 50 was the most common. The reading-frame rule held in 90% of DMD and 94% of BMD cases. A tendency toward a lower IQ and earlier wheelchair dependence was observed with distal exon deletions, though a significant correlation was not found.ConclusionsThe reading-frame rule held in 90% to 94% of children, which is consistent with reports from other parts of the world. However, testing by MLPA is a limitation, and advanced sequencing methods including analysis of the structure of mutant dystrophin is needed for more-accurate assessments of the genotype-phenotype correlation.

Background: COVID-19 related strokes (CORS) are increasingly being diagnosed across the world. The knowledge about the clinical profile, imaging findings and outcomes are still evolving. Here we describe the characteristics of a cohort of 62 CORS patients from 13 hospitals, from Bangalore city, south India. Objective: To describe the clinical profile, neuroimaging findings, interventions and outcomes in CORS patients Methods: Multicenter retrospective study of all CORS patients from 13 hospitals from south India from 1st June 2020 to 31st August 2020.Demographic, clinical, laboratory and neuroimaging data were collected along with treatment administered and outcomes. SARS-CoV-2 infection was confirmed in all cases by RT- PCR testing. The data obtained from the case records were entered in SPSS 25 for statistical analysis. Results: During the 3-month period we had 62 CORS patients, across 13 centers. 60 (97%) had ischemic strokes while 2 (3%) had hemorrhagic strokes. The mean age of patients was 55.66 ±13.20 years, with 34 (77.4%) males. 26 % (16/62) of patients did not have any conventional risk factors for stroke. Diabetes Mellitus was seen in 54.8%, hypertension was present in 61.3%, coronary artery disease in 8% and atrial fibrillation in 4.8%. Base line NIHSS score was 12.7 ±6.44. Stroke severity was moderate (NIHSS 5-15) in 27 (61.3%) patients, moderate to severe (NIHSS 16-20) in 13 (20.9%) patients and severe (NIHSS 21-42) in 11(17.7%) patients. According to TOAST classification for ischemic strokes, 48.3% was stroke of undetermined etiology, 36.6% had large artery atherosclerosis, 10% had small vessel occlusion and 5% had cardioembolic strokes. 3 (5%) received intravenous thrombolysis with tenecteplase 0.2 mg/Kg and 3 (5%) underwent mechanical thrombectomy two endovascular and one surgical. Duration of hospital stay was 16.16± 6.39 days. 16% (13/62) died in hospital, while 37 (59.7%) had a mRS of 3-5 at discharge. Hypertension, atrial fibrillation and higher baseline NIHSS scores were associated with increased mortality. A comparison to 111 historical controls during the non COVID period showed a higher proportion of strokes of undetermined etiology, higher mortality and higher morbidity in CORS patients. Conclusion:CORS are increasing being recognized in developing countries like India. Stroke of undetermined etiology appears to be the most common TOAST subtype of CORS. CORS were more severe in nature and resulted in higher mortality and morbidity. Hypertension, atrial fibrillation and higher baseline NIHSS scores were associated with increased mortality.

This is the first study from India and possibly in English literature, comparing the sensitivity and pattern of mutations by both mPCR and MLPA in the same cohort of DMD. It further validates that 36.4% of MLPA-negative cases were confirmed to have DMD by IHC. The clinical accuracy has been very high in our cohort. MLPA-negative samples should be subjected for next-generation sequencing before contemplating a biopsy.

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