Acquired hyperexcitable peripheral nerve disorders: Clinical and laboratory features, therapeutic responses, and long-term follow-up.

INTRODUCTION/AIMS: Hyperexcitable peripheral nerve disorders (HPNDs) are rare. Although their clinical and laboratory features have been well studied, information on treatment and follow-up is limited. The aim of this study is to explore the long-term clinical, investigative, and therapeutic profile of patients with acquired HPNDs. METHODS: This study retrospectively analyzed patients from a single tertiary care center with HPND (January 2012 to January 2022). Patients were recruited according to published inclusion and exclusion criteria. Details of clinical features, diagnostic tests, therapeutic interventions, and follow-up were recorded. This study included patients with follow-up of 2 or more years. RESULTS: A total of 32 patients (M = 26, F = 6) were studied. The common clinical features included myokymia, neuropathic or shock-like pain, cramps, sleep disturbances, encephalopathy, cerebellar ataxia, and seizures. A total of 81.25% of patients responded favorably to corticosteroids and membrane stabilizers. Among the nonresponders, five received intravenous immunoglobulin (IVIG), and one received plasma exchange (PLEX). Two patients required rituximab due to poor responses to the above treatments. The mean duration of response was 6 weeks (4-24 weeks) from the initiation of treatment. All patients had favorable outcomes, reaching clinical remission within 1-5 years from the initiation of treatment. Only two patients had relapses. Immunotherapy could be stopped in 78% of patients within 3 years and 100% by 5 years. DISCUSSION: Chronic immunosuppression starting with corticosteroids is required for satisfactory outcomes of HPNDs. These disorders usually run a monophasic course, and relapses are uncommon.

A case of non-Hodgkin lymphoma diagnosed after 35-month of initial presentation as recurrent vitritis with multiple negative biopsies.

To report a case of non-Hodgkin lymphoma (NHL) that was diagnosed 35-month of initial ocular manifestation. Retrospective chart review. A 53-year-old male presented with painless diminution of vision in both eyes. He subsequently underwent extensive laboratory investigations including multiple vitreous biopsies with a suspicion of intraocular lymphoma. Cytology from the vitreous aspirate failed to diagnose any relevant pathology. After 35-month from the onset of his ocular symptom, a brain biopsy revealed a round cell tumor suggestive of NHL. Even with high index of suspicion, consultation with ocular oncologist, imaging, and diagnostic vitrectomy, the diagnosis of lymphoma remains challenging.

Nodo-paranodopathies: Concepts, Clinical Implications, and Management.

Peripheral neuropathies are traditionally categorized into demyelinating or axonal. It has been proposed that dysfunction at nodal/paranodal region may be a key for better understanding of pathophysiology in patients with immune mediated neuropathies. In last few years, antibodies targeting node and paranode of myelinated nerves have been increasingly detected in patients with immune mediated neuropathies. These patients have clinical phenotype similar common inflammatory neuropathies like Guillain Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy with some additional atypical neurological and systemic features, and they respond poorly to conventional first line immunotherapies like IVIG. This review summarizes the structure of the node, concept and pathophysiology of nodopathies. We provide an overview of clinical phenotypes in patients with specific nodal/paranodal antibodies, along with electrophysiological and other diagnostic features and suggest therapeutic line of management based on current evidence.

Medical Management of Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is a painful condition, often leading to poor quality of life. OBJECTIVE: The aim of this review was to discuss the various treatment modalities for the medical management of TN. MATERIALS AND METHODS: We reviewed the available literature on TN in clinical databases including PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews, with a specific focus on the pharmacological treatment and newer drugs under development for the treatment of TN. RESULTS: Carbamazepine (CBZ) is the gold standard of treatment for TN. The first-line drugs for the treatment of TN are CBZ and oxcarbazepine (OXC). A proportion of cases (30%) are initially resistant to the first-line drugs. Alternative drugs need to be considered if the first-line drugs are not well tolerated or become ineffective with prolonged therapy. The second-line drugs comprise lamotrigine, baclofen, gabapentin, and pregabalin used as monotherapy or in combination with CBZ/OXC. Botulinum toxin A may be a promising presurgical option. Newer drug like vixotrigine has shown good results in phase two randomized control trials. About 50% of cases develop treatment resistance to oral drugs over the subsequent years of therapy and require surgical options. CONCLUSION: The first-line drugs for the treatment of TN (irrespective of the age group or type) are CBZ and OXC. Combination therapy with second-line or other drugs may become necessary with poor response to CBZ/OXC, or if adverse events occur. Patients should be offered surgical options if there is poor response or tolerance to the medical therapy.

Neuropathies of leprosy.

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.

Chronic immune polyradiculopathies: Three clinical variants of one disease?

INTRODUCTION: Chronic immune polyradiculopathies (sensory, motor, and mixed) are uncommon. METHODS: In this single-center, retrospective study, the inclusion criteria for participants were progressive sensory ataxia and/or areflexic limb weakness; tibial somatosensory evoked potential (SSEP) abnormalities of the N22 and P40 potentials with normal sensory and motor nerve conduction studies or root involvement, according to magnetic resonance imaging (MRI); and albuminocytological dissociation. RESULTS: Eight patients were included in our study. Two had weakness, two had sensory ataxia, and four had both weakness and ataxia. Patients with weakness had abnormal SSEPs and patients with sensory ataxia also had absent F waves. Electromyography showed chronic denervation. MRI scans confirmed thickening and enhancement of roots. The patients responded to corticosteroid treatment. DISCUSSION: The overlapping clinicoelectrophysiological findings and similarities in radiological and therapeutic responses suggest that these entities are clinical variants of the same disease. The terms CIS(m)P, CI(s)MP, and CISMP (for chronic immune sensory motor polyradiculopathy) could be used to denote the predominant clinical involvement.

Early and consistent pattern of proximal weakness in GNE myopathy.

BACKGROUND: GNE myopathy is widely regarded as a distal myopathy. Involvement of proximal musculature in this condition has not been systematically studied. METHODS: The phenotype of genetically confirmed patients with GNE myopathy was analyzed. Fourteen groups of muscles were evaluated with Medical Research Council (MRC) grading and the average muscle scores (AMS:1-10) were calculated. RESULTS: Fully documented AMS data was available in 31 of 65 patients. It showed a consistent pattern of severe weakness of hip adductors, hip flexors, knee flexors, and foot dorsiflexors, with milder weakness of the hip extensors and abductors. The knee extensors were largely unaffected. The proximal weakness appeared early in the course of the disease. Proximal muscle weakness was also present in the remaining 34 patients in whom the data were limited. A variant in exon 13 (c.2179G > A) was very common (81.5%). CONCLUSIONS: The GNE phenotype in this Indian cohort exhibited mixed proximal and distal involvement. Weakness of adductors and flexors of the hip formed an integral part of the phenotype.

What is New in Idiopathic Inflammatory Myopathies: Mechanisms and Therapies.

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of disorders that cause muscle weakness and also have extramuscular manifestations involving various organ systems; namely the lung, skin, heart, and joints. Previously classified broadly as dermatomyositis (DM) and polymyositis now the spectrum of the disease has evolved into more clinical subtypes. There are now five clinicoserological subtypes recognized worldwide DM, antisynthetase syndrome (AS), overlap myositis (OM), immune mediated necrotizing myopathy (IMNM), and inclusion body myositis. Each of these subtypes has a unique phenotype and specific antibodies associated. With the evolving treatment options from the use of immunosuppressive medications to the use of targeted therapy with biologic agents, and further understanding of the pathogenesis of inflammatory myositis, we may have more effective treatment options. We discuss in this review, various myositis-associated antibodies associated with each clinicoserological subtype of IIM and their role. We also describe the evolving therapies and the evidence for the newer biologic therapies in the treatment of IIMs.

COVID 19: Neuromuscular Manifestations.

COVID-19 pandemic is ongoing and information on the neurological aspects of this viral infection is being gathered. Neuromuscular manifestations have been reported uncommonly in these early stages of the analysis. This manuscript studies the available information on the neuromuscular manifestations of COVID-19.

Bias in Clinical Practice.

Role of bias in errors of decision making is receiving increasing attention. It is turning out to be one of the main sources of mistakes. Hence, it is important to be aware of biases and to design strategies toward an unbiased approach. Biases are of various types, and the potential sources of bias can be related to the consultant, patients and factors related to working conditions. Availability bias, base rate neglect, confirmation bias, conjunction rule, diagnostic momentum bias, framing effect and confirmation bias are the common types, and these have been discussed in this manuscript using a scenario-based format. Two types of human thinking, the rapid intuitive mode and the slow reflective mode, their pros and cons and their role in biases are discussed. Strategies to enhance awareness of biases, tips to improve reasoning, promote freethinking, enhance decision-making skills and resorting to checklists have been deliberated to achieve an unbiased approach.

Clinical practice with steroid therapy for Duchenne muscular dystrophy: An expert survey in Asia and Oceania.

BACKGROUND: Several studies on clinical practice for Duchenne muscular dystrophy (DMD) have been conducted in Western countries. However, there have been only a few similar studies in Asia and Oceania. Here, we investigate the steroid therapy-related clinical practice for DMD among the local experts. In 2015, we conducted a DMD expert survey in Asia and Oceania to acquire information regarding patients with DMD and to assess current clinical practice with the cooperation of Asian and Oceanian Myology Centre, a neuromuscular disease research network. RESULTS: We obtained survey responses from 87 out of 148 clinicians (62%) from 13 countries and regions. In China, 1385 DMD patients were followed-up by 5 respondent neurologists, and 84% were between 0 and 9 years of age (15% were 10-19 years, 1% > 19 years). While in Japan, 1032 patients were followed-up by 20 clinicians, and the age distribution was similar between the 3 groups (27% were 0-9 years, 35% were 10-19 years, 38% were >19 years). Most respondent clinicians (91%) were aware of DMD standard of care recommendations. Daily prednisolone/prednisone administration was used most frequently at initiation (N = 45, 64%). Inconsistent opinion on steroid therapy after loss of ambulation and medication for bone protection was observed. CONCLUSIONS: Rare disease research infrastructures have been underdeveloped in many of Asian and Oceanian countries. In this situation, our results show the snapshots of current medical situation and clinical practice in DMD. For further epidemiological studies, expansion of DMD registries is necessary.

Sex Hormones and Cognition: Where Do We Stand?

Hypothalamic-pituitary-gonadal axis regulates the reproductive system. The overall health and wellbeing of a woman is subject to fluctuations in the sex hormones throughout her lifespan. Menopause, either natural or surgically induced, is often associated with cognitive complaints, especially memory disturbances. Sex hormones, besides affecting the reproductive function, affect the central nervous system in many ways. Here, we aim to review the role of sex hormones in cognition and the current evidence on use of or against menopausal hormonal therapy as a cognition enhancer in women with cognitive disturbances, including those with Alzheimer's disease.

Guidelines versus ground lines: Tuberculosis of the central nervous system.

AIM: This questionnaire-based national survey is aimed at understanding the patterns of practice of various aspects of central nervous system (CNS) tuberculosis (TB) among neurologists. SETTINGS AND DESIGN: Neurology department of a tertiary medical college. MATERIALS AND METHODS: A questionnaire was sent through email to all practicing neurologists in India. The responses were analyzed. STATISTICAL ANALYSIS: Inferential statistics. RESULTS: In all, 144 responses were received (out of the 853 questionnaires sent). The major discrepancies were in the primary antitubercular drug regimen (HRZE + HR), duration for tubercular meningitis (TBM) [12 months] and tuberculoma (12-18 months) to develop, follow-up (varied), linezolid use (varied), proportion of drug-resistant cases (<25%), and not taking histological aids (91%). The cerebrospinal fluid (CSF) TB polymerase chain reaction (PCR) utility (75%), not using CSF adenosine deaminase [ADA] (58%), the strategy to stop antitubercular drugs, and the use of steroids (77%) were according to guidelines. CONCLUSION: The present survey, for the first time, provides ground-level evidence of various aspects of CNS TB as practiced by neurologists in India. The major diversity was observed in therapeutics such as the choice of antitubercular drugs, its duration, linezolid use beyond the recommended duration, and knowledge of drug resistance. The monitoring aspects of CNS TB also showed variations. The investigational aspects of CNS TB such as using TB PCR, not using CSF ADA, and regular neuroimaging revealed a good clinical practice. Other CSF parameters require uniformity. This survey thus helps to identify areas of future work in CNS TB in India.

Rare Complication of Carotid Stenting: New-Onset Refractory Status Epilepticus: A Study of Five Patients.

INTRODUCTION: New-onset refractory status epilepticus (NORSE) is uncommon and almost 50% of cases are cryptogenic. We report the rare development of NORSE following carotid artery stenting (CAS), a procedure which is increasingly being used to treat the carotid stenosis. MATERIALS AND METHODS: Patients who developed NORSE following CAS for the prevention of stroke over a period of 5 years were analyzed retrospectively. The degree of internal carotid artery stenosis (ICA) was estimated as per the NASCET criteria. RESULTS: We analyzed five patients (age: 56-83 years). NORSE was reported within 30 min to 14 days post-CAS. Status epilepticus was focal in two patients, generalized in two, and one had nonconvulsive status epilepticus. All patients were treated with multiple antiepileptic drugs. Four patients recovered and survived and one succumbed. Two patients had comorbid hypertension and two had diabetes and hypertension. Four patients had hemiparesis due to the contralateral middle cerebral artery territory infarction and one patient had syncope. Two patients had postinfarction gliosis. CONCLUSIONS: We report a new cause of NORSE, following CAS. Stroke resulting in gliosis and cerebral hyperperfusion syndrome are the proposed mechanisms.