ObjectiveLimb‐girdle muscular dystrophies (LGMDs), one of the most heterogeneous neuromuscular disorders (NMDs), involves predominantly proximal‐muscle weakness with >30 genes associated with different subtypes. The clinical‐genetic overlap among subtypes and with other NMDs complicate disease‐subtype identification lengthening diagnostic process, increases overall costs hindering treatment/clinical‐trial recruitment. Currently seven LGMD clinical trials are active but still no gene‐therapy‐related treatment is available. Till‐date no nation‐wide large‐scale LGMD sequencing program was performed. Our objectives were to understand LGMD genetic basis, different subtypes’ relative prevalence across US and investigate underlying disease mechanisms.MethodsA total of 4656 patients with clinically suspected‐LGMD across US were recruited to conduct next‐generation sequencing (NGS)‐based gene‐panel testing during June‐2015 to June‐2017 in CLIA‐CAP‐certified Emory‐Genetics‐Laboratory. Thirty‐five LGMD‐subtypes‐associated or LGMD‐like other NMD‐associated genes were investigated. Main outcomes were diagnostic yield, gene‐variant spectrum, and LGMD subtypes’ prevalence in a large US LGMD‐suspected population.ResultsMolecular diagnosis was established in 27% (1259 cases; 95% CI, 26–29%) of the patients with major contributing genes to LGMD phenotypes being: CAPN3(17%), DYSF(16%), FKRP(9%) and ANO5(7%). We observed an increased prevalence of genetically confirmed late‐onset Pompe disease, DNAJB6‐associated LGMD subtype1E and CAPN3‐associated autosomal‐dominant LGMDs. Interestingly, we identified a high prevalence of patients with pathogenic variants in more than one LGMD gene suggesting possible synergistic heterozygosity/digenic/multigenic contribution to disease presentation/progression that needs consideration as a part of diagnostic modality.InterpretationOverall, this study has improved our understanding of the relative prevalence of different LGMD subtypes, their respective genetic etiology, and the changing paradigm of their inheritance modes and novel mechanisms that will allow for improved timely treatment, management, and enrolment of molecularly diagnosed individuals in clinical trials.

Against common belief, syncope can occur in sitting as well as in supine position. Emotional triggers were commoner in patients with syncope in supine and sitting positions while prodromal symptoms and circumstances were similar for all positions. Syncope should be considered in body positions other than standing.

Neuropathies form an integral part of the symptomatology of leprosy. Neuropathies of leprosy take various forms and shapes. At one end is the cutaneous nerve involvement adjacent to the anaesthetic skin patch and the other is of symmetrical pansensory neuropathy and the devastating sensory ataxia of leprous ganglionits. Lepra reactions add to the spectrum. Hosts immunological status largely decides the clinical manifestations seen in nerves and skin. A wide array of diagnostic techniques like ultrasonography, magnetic resonance neurography, serological markers, molecular tests, skin biopsy and in selected cases, the nerve biopsy with special stains and electron microscopy are obtainable to help the clinical diagnosis. The unsuspecting clinician, lack of community awareness and limited availability of diagnostic tests are important adverse factors in the total outcome. Multi drug therapy is efficacious and corticosteroids reduce the impact of nerve damage in leprosy. The efficacy, dose and duration of corticosteroid therapy are presently inexact and other immune suppressants like azathioprine are being evaluated. Chronic disabilities and residual deficits require attention of multiple specialties. In the coming time, focus on prevention could lead to favourable results. This review will discuss the classification systems, common and uncommon clinical features, diagnostic armamentarium and therapeutic and preventive aspects of neuropathies of leprosy.

The aim of this study is to describe the clinical presentation of central skull base osteomyelitis and to discuss the classical imaging findings and various diagnostic and therapeutic challenges faced in the management of this condition. This is a retrospective analysis of inpatient case records, carried out in a multidisciplinary tertiary care hospital. The study subjects included five elderly diabetic patients presenting to the ENT surgeon or neurologist with headache followed by multiple cranial nerve paralysis with no temporal bone involvement in four patients and a past history of otitis externa in one patient. These patients were diagnosed to have an infective pathology of the central skull base detected by imaging and confirmed by biopsy in three. All were treated successfully with antibiotics administered for an average period of 6 weeks. Three patients followed up over 4 years and showed no relapses. One succumbed to other medical co morbidities after 8 months and one diagnosed a month prior is still under follow up. A symptom complex of headache and cranial neuropathies usually raises the suspicion of malignancy. Central skull base osteomyelitis, a relatively uncommon pathology, must also be considered as a possible differential diagnosis despite absence of a definite septic focus. Imaging studies showing bony destruction and adjacent soft tissue involvement should raise the suspicion of this clinical entity. Malignancy needs to be ruled out by biopsy. Early diagnosis and prompt initiation of antibiotics administered for an adequate duration is of paramount importance in successfully treating these patients. A multidisciplinary approach is needed for a successful outcome.

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.

Founder mutations have immediate clinical application, at least in selected population groups. Clinically available gene panels may provide a definitive molecular diagnosis for heterogeneous disorders such as LGMD.

Detecting enlargement of accessible nerves is very helpful in assessing patients with peripheral nerve disorders, as only a few types of neuropathy lead to nerve thickening. The three leading causes are leprosy, hereditary motor and sensory neuropathies (types 1 and 3) and chronic inflammatory demyelinating neuropathies. MRI, neurography and ultrasonography allow assessment of clinically inaccessible portions of deep-seated nerves, plexuses and roots. As a result, isolated proximal segment thickenings, as found in chronic inflammatory sensory polyradiculopathy, can now be better evaluated and managed. Similarly, focal nerve enlargements due to infection, inflammation, infiltration and neoplasm are being identified and treated effectively. We present a practical approach to the diagnosis and management of patients with enlarged peripheral nerves, plexuses and roots, including cranial nerves.

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