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Background: Ultrasonography (USG) of the diaphragm is a promising alternative to pulmonary function tests (PFT) for assessing respiratory function in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Methods: We studied 33 patients fulfilling Awaji criteria (definite = 14; probable = 12; possible = 7) and 33 age and gender‐matched controls. Diaphragm thickness was measured using USG at the end of expiration (DTex) and end of inspiration (DTin). The thickness ratio (TR) was calculated as DTin/DTex. The mean age at onset and duration were 49.73 ± 12.7 years and 13.57 ± 9.7 months, respectively. Men = 25 (75.8%); Limb onset ALS/MND = 24 patients (72.7%); bulbar onset = 9 (27.3%). Results: Compared to controls, ALS/MND patients had reduced mean DTex (2.22 ± 0.29 mm vs. 2.02 ± 0.32 mm, p =.012) and DTin (4.0 ± 0.71 mm vs. 3.41 ± 0.38 mm, p <.001). PFTs done in 31 patients showed restrictive abnormality in 80.6%. Significant positive correlation was seen between percentage of predicted forced vital capacity (FVC%) and DTin (p =.009) and TR (p =.037) but not with DTex (p =.852). No significant correlation was seen between diaphragmatic thickness and other PFT parameters or ALSFRS scores. Conclusion: The diaphragmatic thickness showed a significant decrease in ALS/MND as compared to controls. End‐inspiratory diaphragmatic thickness and TR correlated well with %FVC. Thus, diaphragmatic USG could be a potential alternative to PFTs in assessing respiratory function in ALS/MND patients having the advantage of less patient participation and ease of performing in late stages of ALS/MND. [ABSTRACT FROM AUTHOR]

We present a case of a 10-year-old boy with 1-month history of proximal more than the distal weakness of all four limbs with myalgias, contractures, and bulbar symptoms on a background history of exertional myalgias for 2 years. His power was grade two-three. Investigations showed elevated creatine phosphokinase (CPK). His auto-antibody profile showed anti- nuclear matrix protein 2 (NXP2) antibody positivity. Muscle magnetic resonance imaging (MRI) showed extensive T2 fat-saturated hyperintense signal changes in the glutei, thigh, and leg muscles suggestive of active myositis. He improved significantly with immunomodulation with steroids, intravenous immunoglobulins (Iv Ig), and mycophenolate mofetil (MMF). He was continued on monthly pulse steroids and MMF. He is on regular follow-up. This is a rare case of anti-NXP2 antibody-mediated inflammatory myositis and the first report from India. [ABSTRACT FROM AUTHOR]

Background and purpose: Congenital muscular dystrophies (CMDs) and congenital myopathies (CMs) are a group of genetically and clinically heterogeneous degenerative primary muscle disorders with onset at birth or during infancy. Due to vast heterogeneity, clinical examination and protein‐based analyses often fail to identify the genetic causes of these diseases. The aim of this study was to genetically diagnose a cohort of 36 difficult‐to‐diagnose CMD and CM cases of Indian origin using next‐generation sequencing methods. Methods: Whole‐exome sequencing (WES) was performed to identify pathogenic mutations in previously reported CMD and CM‐related genes using variant calling and stringent variant filtration process. Subsequently, in silico homology modelling and molecular dynamics simulations (MDS) studies were undertaken for a number of novel and missense variants. Results: A total of 33 and 21 rare and deleterious mutations were identified in 28 genes previously reported in CMD and CM based on OMIM, ClinVar and Orphanet, respectively. We could accurately diagnose 54% patients (n = 12/22) in the CMD group and 35% patients (n = 5/14) in the CM group. Furthermore, MDS studies for mutations located in LMNA, LAMA2 and RYR1 suggest that the wild‐type proteins are more stable than their mutant counterparts, implying a potential mechanism of pathogenesis. Conclusion: The WES findings led us to identify reported as well as novel variants for the first time in Indian patients with CMD and CM. This allowed us to achieve an accurate genetic diagnosis, which was difficult using conventional diagnostic tools. Transferring these WES findings to clinical practice will help guide clinical care of the affected patients and inform genetic counselling. [ABSTRACT FROM AUTHOR]

We present a case of a 40-year-old man with rapid decline in cognition followed by Parkinsonism, apraxia and stimulus sensitive myoclonus within 9 months of onset. Magnetic Resonance imaging (MRI) showed periventricular confluent white matter changes with persistent diffusion restriction even after 9 months. Clinical exome sequencing showed colony stimulating factor 1 receptor (CSF1R) gene mutation. The phenotype, MRI and genotype are suggestive of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). This is the first case being reported from India. Differential diagnosis of young onset dementia is broad. Therefore, finding the exact etiology is challenging. Neuroimaging and genetic analysis greatly aid in the final diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Duchenne muscular dystrophy (DMD) is induced by a wide spectrum of mutations such as exon deletions, duplications and small mutations in the dystrophin gene. This is the first study on the mutational spectrum in a cohort of DMD children from India, with an emphasis to compare the mutations in familial and sporadic forms. Results: Multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS) identified 525 and 70 cases of DMD, respectively, while 11 cases showed absent dystrophin staining with no mutations detected. Families with two or more affected males contributed to 12% of the entire cohort. The mutations comprised of exonic deletions in 492/606 (81.2%), duplications in 33/606 (5.4%) and small mutations (point mutations and INDELs) in 70/606 (11.5%) cases. MLPA identified significantly more larger mutations in sporadic (88.2%) than in familial cases (75.3%). The mutations in NGS were: [nonsense = 40 (57.1%); frameshift = 17 (24.3%); splice variant = 12 (17.1%)]. Nonsense mutations were more common in familial than in sporadic cases: 17.8% vs 10.7%. The familial group reported an earlier onset of disease (2.8 ± 1.7 years) as compared to sporadic cases (3.8 ± 1.6 years). Conclusion: MLPA could identify mutations in a high percentage of our DMD children. The preponderance of small mutations was noted to be distinctly higher in the familial group. Intriguingly, the familial form of DMD formed a small percentage of the entire cohort. The reasons could be increasing awareness among parents and physicians with early identification of DMD cases, genetic counseling and prenatal testing. [ABSTRACT FROM AUTHOR]

Hirayama disease is generally considered to be a sporadic disorder, except for a few reports of familial occurrence. In this study, we describe eight patients from four families with cervical flexion induced myelopathy (CFIM)/Hirayama disease (HD) and intra-familial phenotypic variations. All underwent clinical and electrophysiological evaluation, while seven of them had contrast MR imaging of cervical spine in flexion. There was significant intra-familial variability: distal bimelic form in four patients, classical monomelic form in three and proximo-distal form in one. Irrespective of the clinical phenotype, MRI showed characteristic dynamic changes of posterior dural detachment with prominent epidural enhancement extending variably from C3 vertebral level to dorsal spine in six patients. One patient with 28 years of illness, had only lower cervical cord atrophy without dynamic changes while another patient demonstrated forward dural displacement with epidural enhancement even after 38 years of disease duration. [ABSTRACT FROM PUBLISHER]

The article describes the case of a 61-year-old male with progressive dysphagia, dysarthria, fatigable chewing difficulty and worsening limb weakness and was diagnosed of generalized Myasthenia gravis (MG). Topics discussed include clinical characteristics of MG, his treatment received, and findings of a review of MG-Morvan's syndrome (MoS) cases.

Background and Objectives: Cardiovascular magnetic resonance imaging (CMRI) is the noninvasive technique of choice for early detection of cardiac involvement in Duchenne and Becker muscular dystrophy (DMD and BMD, respectively), but is seldom used in routine clinical practice in the Indian context. We sought to determine the prevalence of CMRI abnormalities in patients with DMD and BMD and to compare the CMRI parameters with the phenotypic and genotypic characteristics. Methods: A prospective, observational study was conducted on patients genetically diagnosed with DMD and BMD who could complete CMRI between March 2020 and March 2022. Abnormal CMRI was the presence of any late gadolinium enhancement (LGE) that signifies myocardial fibrosis (LGE positivity), regional wall motion abnormality, or reduced left ventricular ejection fraction (LVEF <55%). Results: A total of 46 patients were included: 38 patients with DMD and eight with BMD. Cardiac abnormality was seen in 23 (50%) patients. LGE was more common than impaired LVEF in DMD (16, 42.1%), while impaired LVEF was more common in BMD (5, 62.5%). LGE was most frequently found in lateral wall (18/19) followed by inferior (6/19), septal (5/19), anterior (2/19), and apex (1/19). Among the various clinicodemographic parameters, only age (r = 0.495, P = 0.002) and disease duration (r = 0.407, P = 0.011) were found to significantly correlate with LGE in patients with DMD. No association was found between the various CMRI parameters and the genotype. Conclusions: The current study highlights the differences in myocardial fibrosis and LV dysfunction between DMD and BMD, along with other CMRI parameters. Notably, a genotype--CMRI correlation was not found in the current cohort, which needs to be further explored. [ABSTRACT FROM AUTHOR]

The article focuses on a rare case of cerebral sparganosis in a young child, a parasitic disease caused by the Spirometra tapeworm. Topics include the child's presentation with focal seizures and intracranial lesions, diagnostic challenges given the resemblance to tuberculoma, and the diagnostic process involving MRI and eosinophilia.

• We report a recurrent intronic homozygous c.1023+5G> A desmin mutation in indian patients. • Second report of recessive desminopathy associated with mixed limb girdle CMS – myofibrillar myopathy. • Partial loss of desmin leading to NMJ dysfunction and CMS phenotype. • Leaky splice site with intron retention leads to partial desmin loss. Recessive desminopathies are rare and often present as severe early-onset myopathy. Here we report a milder phenotype in three unrelated patients from southern India (2 M, 1F) aged 16, 21, and 22 years, who presented with childhood-onset, gradually progressive, fatigable limb-girdle weakness, ptosis, speech and swallowing difficulties, without cardiac involvement. Serum creatine kinase was elevated, and repetitive nerve stimulation showed decrement in all. Clinical improvement was noted with pyridostigmine and salbutamol in two patients. All three patients had a homozygous substitution in intron 5: DES(NM_001927.4):c.1023+5G> A , predicted to cause a donor splice site defect. Muscle biopsy with ultrastructural analysis suggested myopathy with myofibrillar disarray, and immunohistochemistry showed partial loss of desmin with some residual staining, while western blot analysis showed reduced desmin. RT-PCR of patient muscle RNA revealed two transcripts: a reduced normal desmin transcript and a larger abnormal transcript suggesting leaky splicing at the intron 5 donor site. Sequencing of the PCR products confirmed the inclusion of intron 5 in the longer transcript, predicted to cause a premature stop codon. Thus, we provide evidence for a leaky splice site causing partial loss of desmin associated with a unique phenotypic presentation of a milder form of desmin-related recessive myopathy overlapping with congenital myasthenic syndrome. [ABSTRACT FROM AUTHOR]

Guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B (GMPPB) is a cytoplasmic enzyme that catalyzes the synthesis of GDP-mannose, a crucial substrate for several glycosylation pathways. Reports of pathogenic variants in the GMPPB gene are infrequent. As of April 2023, 109 cases with pathogenic variants in the GMPPB gene have been reported worldwide. Here, we present two siblings born of consanguineous parentage from Southern India. This is a retrospective study on genetically confirmed siblings with GMPPB pathogenic variants. The siblings, a 15-year-old girl, and a 13-year-old boy, presented with progressive limb-girdle weakness and cataracts from early childhood. The girl had exertion-induced breathlessness and mental subnormality. Creatine kinase levels were 5750 and 4320 IU/L. An echocardiogram of the heart revealed global hypokinesia, moderate left ventricular dysfunction, and mild mitral regurgitation with dilation of the left atrium and left ventricle in the girl child. Exome sequencing showed a homozygous pathogenic variant (NM_021971.4 (GMPPB): c.358A>G (p.Met120Val) in Exon 4 of GMPPB gene in both the siblings. Thus, we report an unusual early onset LGMD phenotype of GMPPB-related disorder with cardiac involvement and cataracts from a single family. [ABSTRACT FROM AUTHOR]

Objective: To determine the sleep architecture and sleep respiratory abnormalities and to correlate with sleep symptoms in patients with Myotonic dystrophy type 1 (DM1).Methods: We recruited a cohort of genetically confirmed patients with DM1, who attended the Neuromuscular clinic between July 2016 and December 2019. Clinical, sleep and whole night polysomnography data were collected. The analysis of sleep architecture, sleep respiratory parameters and comparison with healthy controls (HC) was performed in our sleep laboratory.Results: A total of 59 patients with DM1 underwent sleep evaluation. Hypersomnolence in 42 (77.8%), ESS>10 in 23 (39%), and PSQI>5 in 18 (30.5%) were found in patients with DM1. Thirty-one (68.89%) patients with DM1 and 22 (95.65%) HC had more than 4-h of total sleep time (TST). More than 4 h of TST was taken to compare respiratory and sleep architecture parameters. Patients with DM1 had reduced sleep efficiency, reduced N2 sleep, and increase in N1 sleep, wake index, stage shift index, nocturnal sleep-onset REM periods compared to HC. AHI>15 was found in 16 (51.61%) DM1 and in 3 HC (13.64%). AHI had positive correlation with BMI, but not with age, ESS or disease progression (MIRS). All DM1 with AHI>15; 8(80%) and 1(33.33%) in AHI5to15, and AHI<5 groups, respectively had hypersomnolence.Conclusion: In this first study on Indian cohort, daytime hypersomnolence, poor nocturnal sleep quality, sleep architecture irregularities are identified to be common in patients with DM1. These abnormalities may be explained by sleep-related breathing disorders that are highly prevalent in these patients. [ABSTRACT FROM AUTHOR]

Hirayama disease (HD) is a cervical compressive myelopathy. Anterior cervical discectomy and fusion (ACDF) is identified as the best surgical approach. We evaluated surgical outcomes and factors influencing ACDF in HD. Between 2015 and 2019, 126 patients with HD underwent ACDF. Contrast magnetic resonance imaging of the cervical spine in full flexion was performed. Clinical examination and preoperative/postoperative assessment of hand function using Fugl-Meyer assessment, Jebsen-Taylor hand function test, and handheld dynamometry were performed at 3-monthly intervals for 1 year. Surgical outcomes were assessed as per the Odom criteria and Hirayama outcome questionnaire. Age at onset and duration of illness were 12–31 years (mean, 18 ± 2.7) and 1–96 months (32.7 ± 24.4), respectively. All patients had progressive weakness and wasting of the affected limb. Cord atrophy was seen in 97.1%, with epidural detachment and engorgement of the posterior epidural venous plexus in all. All patients underwent ACDF. Of these patients, 54% had an excellent/good outcome and 39% had a satisfactory outcome as per the Odom scale at last follow-up (mean, 44.9 ± 16.5 months) after surgery. Handheld dynamometry showed improvement from preoperative values to 1 year follow-up. Duration of illness and age at onset had a negative correlation and the preoperative Fugl-Meyer score had a positive correlation with improvement. ACDF resulted in remarkable improvement or stabilization in neurologic deficits in many patients with HD. Because motor disability ensues over time, early surgical intervention during the progressive phase is advocated. [ABSTRACT FROM AUTHOR]

Background: Kennedy disease (KD) is a slowly progressive lower motor neuron degenerative disease. The prevalence of KD is unknown in India. Aim: To describe the phenotypic and laboratory features of an Indian cohort of KD patients. Methods: A retrospective study was done on seven genetically confirmed KD patients based on demographic, clinical and laboratory details. Results: Mean age at onset and presentation was 37 ± 11.9 and 44.6 ± 13.5 years respectively. Progressive asymmetric proximal and distal limb weakness was the commonest symptom (57.1%). All patients had motor symptoms along with non‐specific symptoms such as cramps from the onset. Easy fatigability, decremental response along with ptosis were noted in two patients, which was a novel finding. Gynaecomastia and tongue wasting with fasciculations were universal findings. All five patients with nerve conduction studies showed sensorimotor neuropathy. Magnetic resonance imaging muscle done in two patients showed a prominent moth‐eaten appearance in the thigh and posterior leg compartment in one patient. The mean cytosine‐adenine‐guanine repeats were 44 ± 3.7, and there was no association between age of onset or severity with repeat length. Only one patient required an assistive device for ambulation after 15 years of symptom onset. Conclusions: This study showed phenotypic heterogeneity in the Indian cohort. The age of onset was earlier with a slowly progressive indolent course as compared with other ethnic cohorts. This highlights the importance of considering the KD diagnosis in patients with the indolent course and suspected ALS diagnosis even with ptosis and fatigability in an appropriate clinical context. [ABSTRACT FROM AUTHOR]

Background: DM1 is a multisystem disorder caused by expansion of a CTG triplet repeat in the 3' non-coding region of DMPK. Neuropsychological consequences and sleep abnormalities are important associations in DM1. Objective: To describe the clinical phenotype, disease progression and characterize the sleep alterations and cognitive abnormalities in a sub-set of patients. Materials and Methods: A retrospective study on 120 genetically confirmed DM1 cases. Findings in neuropsychological assessment and multiple sleep questionnaires were compared with 14 age and sex matched healthy individuals. All 120 patients were contacted through letters/telephonic consultation/hospital visits to record their latest physical and functional disabilities. Results: The mean age at symptom onset was 23.1 ± 11.4 years, M: F = 3.8:1, mean duration of illness = 14.3 ± 9.5 years. Clinically 54.2% had adult onset form, juvenile = 27.5%, infantile = 10.8%, late adult onset = 7.5%. Paternal transmission occurred more frequently. The predominant initial symptoms were myotonia (37.5%), hand weakness (21.7%), lower limb weakness (23.3%) and bulbar (10%). Twenty patients completed sleep questionnaires (SQ). Abnormal scores were noted in Epworth sleepiness scale (55%); Pittsburgh sleep quality index (45%); Berlin SQ (30%); Rapid eye movement sleep Behaviour Disorder SQ (15%); Restless leg syndrome rating scale (10%). Neuropsychological assessment of 20 patients revealed frontal executive dysfunction, attention impairment and visuospatial dysfunction. Frontal lobe was most affected (72%) followed by parietal (16%) and temporal lobe (12%). Conclusions: The current study provides a comprehensive account of the clinical characteristics in Indian patients with DM1. Hypersomnolence was most commonly seen. Excessive daytime sleepiness and Sleep disordered breathing were the most common sleep related abnormality. Cognitive impairment comprised predominantly of frontal lobe dysfunction. [ABSTRACT FROM AUTHOR]

Sarcoglycanopathy is the most frequent form of autosomal recessive limb-girdle muscular dystrophies caused by mutations in SGCB gene encoding beta-sarcoglycan proteins. In this study, we describe a shared, common haplotype co-segregating in 14 sarcoglycanopathy cases from 13 unrelated families from south Indian region with the likely pathogenic homozygous mutation c.544 T > G (p.Thr182Pro) in SGCB. Haplotype was reconstructed based on 10 polymorphic markers surrounding the c.544 T > G mutation in the cases and related family members as well as 150 unrelated controls from Indian populations using PLINK1.9. We identified haplotype H1 = G, A, G, T, G, G, A, C, T, G, T at a significantly higher frequency in cases compared to related controls and unrelated control Indian population. Upon segregation analysis within the family pedigrees, H1 is observed to co-segregate with c.544 T > G in a homozygous state in all the pedigrees of cases except one indicating a probable event of founder effect. Furthermore, Identical-by-descent and inbreeding coefficient analysis revealed relatedness among 33 new pairs of seemingly unrelated individuals from sarcoglycanopathy cohort and a higher proportion of homozygous markers, thereby indicating common ancestry. Since all these patients are from the south Indian region, we suggest this region to be a primary target of mutation screening in patients diagnosed with sarcoglycanopathy. [ABSTRACT FROM AUTHOR]

The article describes the case of a 63-year-old man, previously treated for COVID-19, who developed foul-smelling blackish discharge from the nasal cavities. Cited are the medical history of the patient, the findings of physical and laboratory investigations which led to the diagnosis of progressive multifocal leukoencephalopathy, and patient outcome following treatment with amphotericin B and posaconazole.

Collagen XII, a member of a protein family called fibril associated collagen with interrupted triple helices (FACIT), is an important component of extracellular matrix and is essential for bridging the neighbouring fibrils. Mutations in collagen XII have been recently described to cause a rare extracellular matrix-related myopathy in those whose phenotype resembles collagen VI-related dystrophies and were negative for pathogenic variants in COL6A genes. The authors report a 4-year old girl presented with a phenotype mimicking Ullrich congenital muscular dystrophy and genetically confirmed to have pathogenic variants in COL12A1 gene thus, expanding the phenotypic spectrum of COL12A1-related myopathy. [ABSTRACT FROM AUTHOR]