Collagen XII-Related Myopathy: An Emerging Spectrum of Extracellular Matrix-Related Myopathy.

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.

Insights from Magnetic Evoked Field Analysis in Patients with Wilson's Disease.

Aims: To study the latency, amplitude, and source localization of magnetic evoked field (MEF) responses to visual, auditory, and somatosensory stimuli in Wilson's disease (WD) using magnetoencephalography (MEG) and compare it with "healthy" controls, and correlate the observations with disease severity and brain MRI. Methods: MEF of 28 patients with neurological WD (age: 22.82 ± 5.8 years; M:F = 12:16) and 21 matched controls (age: 25.0 ± 4.6 years; M:F = 10:11) were recorded using MEG. Source localization was performed using standard models on the components of M100, M20, and M100 for visual, somatosensory, and auditory evoked fields, respectively and its latency/amplitude was correlated with disease severity. Results: There were significant differences in source location between control and WD during visual evoked field (VEF) and auditory evoked field (AEF) studies. Latencies of M20 (right-p = 0.02; left-p = 0.04) and M32 (right-p = 0.01) components of SSEF were significantly prolonged. The amplitude of M20 was significantly reduced in patients bilaterally (P = 0.001). There was a trend for the prolonged latency of M100 of VEF in patients (P = 0.09). Five patients had reduced right M145 compared to 8 controls. The left somatosensory evoked fields (SSEF) latency correlated with disease severity (P = 0.04). There was no significant correlation between major components of other MEF with disease severity or MRI score. Conclusions: This study, first of its kind to use MEF analysis in a large cohort of patients with WD, detected subclinical but a variable degree of abnormalities, most consistently of SSEF. It provides valuable insights of functioning and localization of various pathways in a disease known to have protean clinical manifestations and widespread MRI changes.

Disorders of Tetrahydrobiopterin Metabolism: Experience from South India.

BACKGROUND: Disorders of tetrahydrobiopterin metabolism represent a rare group of inherited neurotransmitter disorders that manifests mainly in infancy or childhood with developmental delay, neuroregression, epilepsy, movement disorders, and autonomic symptoms. METHODOLOGY: A retrospective review of genetically confirmed cases of disorders of tetrahydrobiopterin metabolism over a period of three years (Jan 2018 to Jan 2021) was performed across two paediatric neurology centres from South India. RESULTS: A total of nine patients(M:F=4:5) fulfilled the eligibility criteria. The genetic variants detected include homozygous mutations in the QDPR(n=6), GCH1(n=2), and PTS(n=1) genes. The median age at onset of symptoms was 6-months(range 3-78 months), while that at diagnosis was 15-months (8-120 months), resulting in a median delay in diagnosis of 9-months. The main clinical manifestations included neuroregression (89%), developmental delay(78%), dystonia(78%) and seizures(55%). Management strategies included a phenylalanine restricted diet, levodopa/carbidopa, 5-Hydroxytryphtophan, and folinic acid. Only, Patient-2 afforded and received BH4 supplementation at a sub-optimal dose later in the disease course. We had a median duration of follow up of 15 months (range 2-48 months). Though the biochemical response has been marked; except for patients with GTPCH deficiency, only mild clinical improvement was noted with regards to developmental milestones, seizures, or dystonia in others. CONCLUSION: Tetrahydrobiopterin deficiencies represent a rare yet potentially treatable cause for non-phenylketonuria hyperphenylalaninemia with better outcomes when treated early in life. Screening for disorders of biopterin metabolism in patients with hyperphenylalaninemia prevents delayed diagnosis. This study expands the genotype-phenotype spectrum of patients with disorders of tetrahydrobiopterin metabolism from South India.

Pediatric neurobrucellosis: a systematic review with case report.

Pediatric neurobrucellosis represents a common anthropozoonosis in endemic areas but only anecdotal reports are available till date. Using appropriate search terms in the database platforms of MEDLINE, SCOPUS and Web of Sciences, we performed a systematic review of all the cases of pediatric neurobrucellosis published in the medical literature till date, in the light of a case report. The protocol was registered under PROSPERO (CRD42022333907). Our search strategy yielded 187 citations of which 51 citations were included. A total of 119 cases were reviewed. Of these cases, eight of them had insufficient data. The most common presentation was meningitis with or without encephalitis (n = 79, 71.2%). A high prevalence of cranial neuropathies (n = 22, 20.7%) was observed in the pediatric population in which abducens palsy was the most common (n = 9, 8.1%). Diagnosis was based on multimodal investigations including standard agglutination test (n = 44, 39.6%), Rose Bengal test (n = 37, 33.3%), blood culture (n = 23, 20.7%), serology (n = 20, 18.0%) and cerebrospinal fluid (CSF) culture (n = 11, 9.9%). Rifampicin-based triple drug regimen was the most commonly employed (83/102, 81.4%). Pediatric neurobrucellosis was associated with greater frequency of sequalae (5.4%), deafness (2.7%) and mortality (2.7%), when compared to that of general population. Neurobrucellosis mimics neuro-tuberculosis in various aspects. The review highlights several unique aspects of this entity in children. A high index of suspicion can ensure prompt diagnosis, timely initiation of management and favorable outcomes.

Pediatric neurobrucellosis represents a common zoonosis in endemic areas but only anecdotal reports are available till date. Using appropriate search terms in the database platforms of MEDLINE, SCOPUS and Web of Sciences, we performed a systematic review of all the cases of pediatric neurobrucellosis published in the medical literature till date, in the light of a case report. Our search strategy yielded 187 citations of which 51 citations were included. A total of 119 cases were reviewed. When compared to the largest series in neurobrucellosis, a higher frequency of meningitis was observed in the pediatric age group (71.2% vs. 37%). A high prevalence of cranial neuropathies (n = 22, 20.7%) was observed in the pediatric population in which abducens palsy was the most common (n = 9, 8.1%). Diagnosis was based on multimodal investigations including standard agglutination test (n = 44, 39.6%), Rose Bengal test (n = 37, 33.3%), blood culture (n = 23, 20.7%), serology (n = 20, 18.0%) and CSF culture (n = 11, 9.9%). Rifampicin-based triple drug regimen was the most commonly employed (83/102, 81.4%). Our systematic review highlighted the wide and heterogeneous spectrum of manifestations of neurobrucellosis in the pediatric population. A high index of suspicion can ensure prompt diagnosis, timely initiation of management and favorable outcomes.

Standardising Dementia Diagnosis Across Linguistic and Educational Diversity: Study Design of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB).

OBJECTIVES: While the burden of dementia is increasing in low- and middle-income countries, there is a low rate of diagnosis and paucity of research in these regions. A major challenge to study dementia is the limited availability of standardised diagnostic tools for use in populations with linguistic and educational diversity. The objectives of the study were to develop a standardised and comprehensive neurocognitive test battery to diagnose dementia and mild cognitive impairment (MCI) due to varied etiologies, across different languages and educational levels in India, to facilitate research efforts in diverse settings. METHODS: A multidisciplinary expert group formed by Indian Council of Medical Research (ICMR) collaborated towards adapting and validating a neurocognitive test battery, that is, the ICMR Neurocognitive Tool Box (ICMR-NCTB) in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam), for illiterates and literates, to standardise diagnosis of dementia and MCI in India. RESULTS: Following a review of existing international and national efforts at standardising dementia diagnosis, the ICMR-NCTB was developed and adapted to the Indian setting of sociolinguistic diversity. The battery consisted of tests of cognition, behaviour, and functional activities. A uniform protocol for diagnosis of normal cognition, MCI, and dementia due to neurodegenerative diseases and stroke was followed in six centres. A systematic plan for validating the ICMR-NCTB and establishing cut-off values in a diverse multicentric cohort was developed. CONCLUSIONS: A key outcome was the development of a comprehensive diagnostic tool for diagnosis of dementia and MCI due to varied etiologies, in the diverse socio-demographic setting of India.

Expert Group Meeting on Aphasia: A Report.

A multidisciplinary team of experts took stock of the current state of affairs about many aspects of aphasia in India, including community burden, diagnostic assessment, therapy, rehabilitation, research, education, and advocacy. The broad spectrum of aphasiology was matched by the types of participants ranging from neurologists, speech-language pathologists, clinical psychologists, linguists, to experts in neuroimaging and computer sciences. Threadbare discussion in 16 sessions over 3 days leads to the identification of pressing problems and possible solutions. Many action plans have been envisaged and recommendations made. A few examples with high priority are community-based and hospital-based study incidence and prevalence of aphasia, development of test batteries for the assessment of many components of speech and communication in Indian languages which are validated on rigorous psychometric, and linguistic criteria, national registry for aphasia, educational modules about aphasia for different target groups, resources for advocacy and its training, a bank of research questions and outlines of research protocols for young professionals to pursue. The expert group will continue to oversee execution of some of the actionable plans in short and long term.