Clinical Reasoning: A 22-Year-Old Woman With Episodic Weakness and Jaundice.

We report a case of a 22-year-old woman who presented with recurrent episodes of quadriparesis, often accompanied by jaundice. Neurologic examination showed symmetrical proximal predominant quadriparesis with generalized hyporeflexia. The differential diagnoses included were of metabolic, inflammatory, genetic (including channelopathies), and autoimmune causes. Serum creatine phosphokinase levels and electrophysiologic studies helped narrow the differential. The final diagnosis was one that was responsive to vitamin supplementation. This report provides a systematic clinical approach to a case of episodic weakness with jaundice and respiratory failure.

Spectrum of Auto-antibodies in NMO and MOG Associated CNS Demyelination- The SANMAD Study.

This observational study explored coexisting organ-specific and non-organ-specific autoantibodies in Neuromyelitis optica spectrum disorder(NMOSD) and Myelin oligodendrocyte glycoprotein-IgG-1(MOG-IgG1) associated central nervous system demyelination(MOGAD) in a South Asian cohort from March 2017-2023. Of the 250 cases, 148 were MOGAD(82pediatric) and 102 were NMOSD(15 pediatric). 17.6 % tested positive for ≥1 antibody, with NMOSD showing a higher positivity rate (25.5 %) than MOGAD(12.2 %,p = 0.011). Double antibody positivity occurred more in NMOSD (5.9 %vs.MOGAD,1.4 %,p = 0.045). Three NMOSD cases had Sjogren syndrome with higher Anti-Ro-52 prevalence(12.7 %vs.4.1 %,p = 0.014). NMOSD patients with ≥1 antibody positivity had more constitutional symptoms (45.5 %vs.23.1 %,p = 0.045). Significant associations were found between NMOSD and female gender, having ≥1 antibody-positive status, and testing positive for Anti-Ro-52 and SS-A antibodies (p < 0.05).

Electroencephalographic outcomes and predictors of epilepsy in autoimmune encephalitis.

BACKGROUND: An abnormal EEG is pivotal in diagnosis, exclusion of mimickers and prognosticating epilepsy in Autoimmune Encephalitis (AE). However, little is known about the short and long term electroencephalographic outcomes and predictors of epilepsy in AE. This study aims to describe the seizure characteristics and electrophysiological markers of various AE subtypes and assess the clinical and electrophysiological predictors of autoimmune epilepsy. METHODS: Clinical features and EEGs in 74 patients (acute phase=39 and post-acute phase defined after a minimum eight weeks after acute phase=35) of AE fulfilling the proposed criteria were reviewed in their respective acute phases and at six months follow-up. RESULTS: The mean age of presentation (N = 74, 45 females) was 21.8 (21.8 ± 17.0) years. 38 (51 %) patients were <18 years. Seizures were present in 55 (74 %) patients with poor response to ASMs (p = 0.039). 39 (52.7 %) EEGs were abnormal in acute phase. Anti-NMDAR AE had most frequently abnormal EEG (63.4 %). Poor background reactivity and theta range slowing were most common abnormalities. FIRDA, EDB and delta range slowing were seen in seropositive AE (P = 0.003). Mutism, psychiatric features and incontinence correlated with abnormal EEG (p = 0.013, p = 0.028 and p = 0.025). Background slowing and epileptiform discharges predicted worse cognitive scores at follow-up (p = 0.012). Eight (11.9 %) patients developed epilepsy. Status epilepticus at presentation (p = 0.009), seronegative status (p = 0.0020), delayed initiation of immunotherapy (p = 0.012), abnormal MRI (p = 0.003) and abnormal EEG (p = 0.004) at onset indicate development of autoimmune epilepsy CONCLUSIONS: FIRDA, EDB and delta range slowing with refractory seizures suggest AE. Epileptiform abnormalities, status epilepticus and seronegativity predict autoimmune epilepsy.

Decoding Multiple Antibody Positivity: Lessons from Paraneoplastic Sensory Ataxia.

Paraneoplastic neurologic syndromes are cancer-associated, immune-mediated neurologic manifestations that may involve any part of the nervous system. They usually present with characteristic neurologic features and should be considered in high-risk phenotypes such as limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus, sensory neuronopathy, enteric neuropathy, and Lambert-Eaton myasthenic syndrome. The diagnosis is made by antibody positivity in the serum or cerebrospinal fluid, in the presence of an appropriate clinical phenotype. Findings on antibody testing by immunoblot should always be verified by immunofluorescence. We report a rare case of sensory neuronopathy with triple paraneoplastic antibody positivity (anti-Hu, anti-collapsing response-mediator protein 5, and anti-amphiphysin) on immunoblot but only anti-Hu positivity on immunofluorescence. The presence of lower facial dyskinesias should raise the possibility of an immune-mediated neurologic syndrome in the appropriate clinical context.

Exploring the evidence for mitochondrial dysfunction and genetic abnormalities in the etiopathogenesis of tropical ataxic neuropathy.

Tropical ataxic neuropathy (TAN) is characterised by ataxic polyneuropathy, degeneration of the posterior columns and pyramidal tracts, optic atrophy, and sensorineural hearing loss. It has been attributed to nutritional/toxic etiologies, but evidence for the same has been equivocal. TAN shares common clinical features with inherited neuropathies and mitochondrial disorders, it may be hypothesised that genetic abnormalities may underlie the pathophysiology of TAN. This study aimed to establish evidence for mitochondrial dysfunction by adopting an integrated biochemical and multipronged genetic analysis. Patients (n = 65) with chronic progressive ataxic neuropathy with involvement of visual and/or auditory pathways underwent deep phenotyping, genetic studies including mitochondrial DNA (mtDNA) deletion analysis, mtDNA and clinical exome sequencing (CES), and respiratory chain complex (RCC) assay. The phenotypic characteristics included dysfunction of visual (n = 14), auditory (n = 12) and visual + auditory pathways (n = 29). Reduced RCC activity was present in 13 patients. Mitochondrial DNA deletions were noted in five patients. Sequencing of mtDNA (n = 45) identified a homoplasmic variant (MT-ND6) and a heteroplasmic variant (MT-COI) in one patient each. CES (n = 45) revealed 55 variants in nuclear genes that are associated with neuropathy (n = 27), deafness (n = 7), ataxia (n = 4), and mitochondrial phenotypes (n = 5) in 36 patients. This study provides preliminary evidence that TAN is associated with a spectrum of genetic abnormalities, including those associated with mitochondrial dysfunction, which is in contradistinction from the prevailing hypothesis that TAN is related to dietary toxins. Analysing the functional relevance of these genetic variants may improve the understanding of the pathogenesis of TAN.

Clinicopathological Features of Amyloid Neuropathy: A Four Decade Experience.

BACKGROUND: Peripheral neuropathy is one of the manifestations of primary or familial amyloidosis. Published studies from India are limited. MATERIALS AND METHODS: We reviewed the clinical and pathological features of amyloid neuropathy diagnosed at our Institute over the last 39 years. RESULTS: Fifty-five cases of amyloid neuropathies were diagnosed between 1981 and 2019, constituting 0.28% of peripheral nerve biopsies (55/19,081). Age at presentation ranged from 24 to 81 years (mean-48 years) with male preponderance [M:F = 3.58:1]. Duration of symptoms at presentation varied from 3 months to 10 years (mean-2.31 years). Majority presented with small fiber neuropathy (85%). Pure sensory symptoms predominated in 23%, while 72% had sensorimotor neuropathy and 35.8% had autonomic involvement, with isolated autonomic failure in one patient. Amyloid neuropathy was clinically suspected in 22.6% of nonfamilial cases. Familial amyloid neuropathy was suspected in eight patients. Genetic testing detected ATTR and gelsolin mutation in one each of tested patients. Nerve biopsies revealed characteristic birefringent amyloid deposits stained mahogany brown by Congo red predominantly surrounding endoneurial microvessels (34.5%), also in perineurium and epineurium in 25.45% cases. Preferential loss of small diameter myelinated fibers was noted. Axonal degeneration or regeneration was conspicuously absent. CONCLUSION: Amyloid neuropathy is uncommon (0.28% of nerve biopsies in our series). Nerve biopsy is essential for the diagnosis. We report our experience of amyloid neuropathy and underscore the importance of making an assiduous search for amyloid deposits in the appropriate setting. Awareness of this entity is important for early diagnosis in the light of emerging therapeutic advances.

Clinicopathological Features in Morvan's Syndrome: An Autopsy Case Study.

Morvan's syndrome is a rare, complex autoimmune syndrome comprising peripheral nerve hyperexcitability, dysautonomia, insomnia, and encephalopathy. In this case report, we highlight the clinical and pathological findings of an elderly gentleman who presented to us with clinical features of Morvan's syndrome associated with anti-contactin-associated protein 2 (CASPR-2) antibodies. Histopathology [Figure 3] revealed cortical atrophy with gliosis and mild microglial proliferation. Microglial activation and gliosis were observed in the hippocampus, hypothalamus, and thalamus. Brainstem showed multifocal inflammation. Mild inflammation was observed in the leptomeninges. Morvan's syndrome is an autoimmune disease with antibodies targeted against CASPR within the voltage-gated potassium channel (VGKC) complex. Early diagnosis and treatment play a key role in the management of patients. Most patients show a good response when treated with plasmapheresis and steroids. This patient presented to us late into the illness and succumbed.

Therapeutic role of plasma exchange in the management of stiff person syndrome: experience from a tertiary care centre.

INTRODUCTION: The stiff person syndrome (SPS) is a rare and disabling neurological disorder characterized by muscle stiffness, painful spasms and rigidity involving the proximal and axial limb muscles, with an estimated incidence of 1 case per million per year. The first line of treatment for symptomatic management includes gamma-aminobutyric acid (GABA)ergic agonists, benzodiazepines and baclofen. The therapeutic plasma exchange (TPE), alone or as an adjuvant to other forms of immunomodulation, has been used as a therapeutic option, particularly in refractory cases. METHODS: An observational study was performed to review SPS patient symptoms, comorbidities, electromyography (EMG) studies and treatment, identifying autoantibodies, therapeutic plasma exchange (TPE) procedural details and clinical response. MAIN RESULTS: Five patients (4 male and one female) were treated with TPE during the study period as adjuvant therapy. The average age was 47 years (range 34 - 61 years), and anti-glutamic acid decarboxylase 65-kilodalton isoform (anti-GAD65) antibodies were positive in 80 % (4/5) of the patient population. All patients received immunosuppressive drugs along with TPE. Four patients received TPE during the first admission and one received it during the third hospital admission. All patients showed good improvement immediately after TPE, but it was not a sustainable effect. CONCLUSION: TPE may be helpful as adjuvant therapy for SPS patients to provide relief from clinical symptoms.

Use of Two Novel Dyes to Enhance Visualization of Cut Ends of the Vessel in Microvascular Anastomosis-An Experimental Study of 45 Rats.

BACKGROUND: Good visualization is a prerequisite for performing microvascular anastomosis. The most commonly used dye, methylene blue, has several limitations: it is washed off quickly and stains all the vessel layers. The objective of our study is to use 2 new novel dyes for improving visualization. METHODS: After ethical committee approval, 2 Dyes (2% cresyl violet, 1% eosin) were studied in 3 groups, 20 rats in each group and 5 rats in the combined group. End-to-side anastomosis was performed in the classic fashion in 45 rats. After venotomy, the dye was applied to the raw surface of the vessels and subsequently, anastomosis was performed. The improvement in visualization was judged by 3 blinded experts and nonexperts in 4 groups on a scale of 1-10. Scores were statistically analyzed. After 2 weeks, animals were re-explored to check the delayed patency, and segments were harvested for histopathologic analysis. RESULTS: The immediate and delayed patency rates were 100% (45/45) and 97% (33/34), respectively. In statistical analysis, the combined group (P = 0.005)was judged statistically significant because of the contrast in color. All the layers were stained by both dyes, staining lasted until the end of the surgery. Visibility of the cut ends was better in cresyl violet. All histopathologic findings suggested normal changes at the anastomotic site. CONCLUSIONS: This study showed that the use of these 2 dyes was not only feasible but highly efficacious. Even though all the layers were stained by both the dyes, the visibility of the cut ends was better. In both dyes, staining lasted until the end of surgery. To the best of our knowledge, this is the first study that has used these 2 novel dyes to improve visualization in microvascular anastomosis in an experimental setting.

Epilepsia Partialis Continua as a Sequelae of Measles Infection in Children With Hematolymphoid Malignancies.

PURPOSE: To share our clinical experience with the diagnosis and management of children with hematolymphoid malignancies presenting with epilepsia partialis continua (EPC) as a sequelae of measles infection. MATERIALS AND METHODS: In December 2022, a series of children in our hemato-oncology unit presented with focal status epilepticus with no conclusive evidence pointing toward any underlying etiology. One such child had a typical measles rash a few weeks before the onset of this focal status epilepticus. After a series of cases with a similar presentation, a clinical pattern suspicious for measles became evident. cerebrospinal fluid polymerase chain reaction was positive for measles virus with measles immunoglobin M detected in the serum. This led to the diagnosis of measles inclusion-body encephalitis in a series of children who presented with EPC over a period of 3 months. EPC is a rare manifestation of measles that is seen only in immunocompromised patients. RESULTS: Among the 18 children reported in this series, only 10 had a history of rashes. The rash was mostly transient and elicited only on retrospective history taking. Five of the 18 children who did not lose consciousness during the prolonged seizure episode survived the disease but had residual neurologic sequelae. Among the 18 children, two were unimmunized and immunization status could not be confirmed in three other children. CONCLUSION: This case series highlights the threats posed by measles infection in children with cancer who are immunosuppressed because of the underlying disease and ongoing chemotherapy. Loss of herd immunity because of declining measles immunization rates secondary to vaccine hesitancy and COVID-19 lockdown pose a greater risk of measles infection and its complications for patients with deficient immune systems.

Hermite-scan imaging for differentiating glioblastoma from normal brain: Simulations and ex vivo studies for applications in intra-operative tumor identificationa).

Hermite-scan (H-scan) imaging is a tissue characterization technique based on the analysis of raw ultrasound radio frequency (RF) echoes. It matches the RF echoes to Gaussian-weighted Hermite polynomials of various orders to extract information related to scatterer diameter. It provides a color map of large and small scatterers in the red and blue H-scan image channels, respectively. H-scan has been previously reported for characterizing breast, pancreatic, and thyroid tumors. The present work evaluated H-scan imaging to differentiate glioblastoma tumors from normal brain tissue ex vivo. First, we conducted 2-D numerical simulations using the k-wave toolbox to assess the performance of parameters derived from H-scan images of acoustic scatterers (15-150 µm diameters) and concentrations (0.2%-1% w/v). We found that the parameter intensity-weighted percentage of red (IWPR) was sensitive to changes in scatterer diameters independent of concentration. Next, we assessed the feasibility of using the IWPR parameter for differentiating glioblastoma and normal brain tissues (n = 11 samples per group). The IWPR parameter estimates for normal tissue (44.1% ± 1.4%) were significantly different (p < 0.0001) from those for glioblastoma (36.2% ± 0.65%). These findings advance the development of H-scan imaging for potential use in differentiating glioblastoma tumors from normal brain tissue during resection surgery.

Role of magnetoencephalography in predicting the epileptogenic zone and post-operative seizure outcome - A retrospective study.

PURPOSE: Study assessed the role of MSI in predicting the post-operative seizure outcome. METHODS: This retrospective study included patients who underwent MEG and epilepsy surgery and had a minimum 6 months of postoperative follow-up. Concordance of MEG cluster with post-surgical resection cavity was classified as follows Class I) Concordant and region-specific, Class II) Concordant and region non-specific, Class III) Concordant lateralization only and Class IV) Discordant lateralization. The relationship between MSI concordance and post-operative seizure outcome was assessed. RESULTS: A total of 183 patients (M: F = 109:74) were included. The mean age at onset of seizures: 8.0 ± 6.4 years. The dipoles were frequent in 123(67.2 %). The primary cluster orientation was regular in 59 (32.2 %) and mixed in 124 (67.8 %) patients. Concordance between MEG and resection cavity: Class I - 124 (67.8 %), class II- 30 (16.4 %), class III- 23 (12.6 %), and class IV- 6 (3.3 %). The post-surgically mean duration of follow-up was 19.52 ± 11.27 months. At 6-month follow-up period, 144 (78.7 %) patients had complete seizure freedom out of which 106 (73.6 %) had class I concordance. Concordance of MEG with resection cavity was associated with a good outcome at 6 months (p = 0.001), 1 year (p = 0.001), 2 years (p = 0.0005) and 5 years (p = 0.04). MEG cluster characteristics had no association with seizure outcome except the strength of the cluster and outcome at 3 years (p = 0.02) follow-up. CONCLUSION: The study supports that the complete resection of the MEG cluster had high chance of seizure-freedom and can be used as a complementary noninvasive presurgical evaluation tool.

Localisation of eloquent cortex using magnetoencephalography and its clinical implications.

OBJECTIVES: This study aimed to localise the eloquent cortex and measure evoked field (EF) parameters using magnetoencephalography in patients with epilepsy and tumours near the eloquent cortex. METHODS: A total of 41 patients (26 with drug-refractory epilepsy and 15 with tumours), with a mean age of 33 years, were recruited. Visual evoked field (VEF), auditory evoked field (AEF), sensory evoked field (SSEF), and motor-evoked field (MEF) latencies, amplitudes, and localisation were compared with those of a control population. Subgroup analyses were performed based on lobar involvement. Evoked Field parameters on the affected side were compared with those on the opposite side. The effect of distance from the lesion on nearby and distant evoked fields was evaluated. RESULTS: AEF and VEF amplitudes and latencies were reduced bilaterally (p < 0.05). Amplitude in the ipsilateral SSEF was reduced by 29.27% and 2.16% in the AEF group compared to the contralateral side (p = 0.02). In patients with temporal lobe lesions, the SSEF amplitude was reduced bilaterally (p < 0.02), and latency was prolonged compared with controls. The MEF amplitude was reduced and latency was prolonged in patients with frontal lobe lesions (p = 0.01). EF displacement was 32%, 57%, 21%, and 16% for AEF, MEF, VEF, and SSEF respectively. Patients in the epilepsy group had distant EF abnormalities. CONCLUSIONS: EF amplitude was reduced and latency was prolonged in the involved hemisphere. Distant EF amplitudes were more affected than latencies in epilepsy. Amplitude and distance from the lesion had negative correlation for all EF. EF changes indicated eloquent cortical displacement which may not be apparent on MRI.

Evaluation of a rapid, chip-based, micro-PCR assay for detection of rabies virus in human and canine specimens.

Rabies, a lethal zoonotic encephalitis, remains a significant global health concern, causing an estimated 60 000 annual fatalities worldwide. Dogs serve as the primary reservoirs and vectors for transmitting this infection to humans. Definitive diagnosis of rabies in both human and animal cases necessitates laboratory testing involving various clinical specimens. However, the complexity of laboratory infrastructure and the need for skilled personnel, along with the challenge of maintaining cold-chain integrity during sample referral, hinder the decentralization of diagnostic facilities. This study aimed to assess the efficacy of the Truenat rabies assay, a rapid, portable, semiautomated, and closed PCR-based system, for the diagnosis of rabies in both humans and animals. The Truenat assay demonstrated a sensitivity of 100% and a specificity of 86.96% when compared with the fluorescent antibody test (FAT), as the reference standard, on 147 canine brain samples tested. Notably, the Truenat assay exhibited a sensitivity and specificity of 100% when tested on 48 human brain specimens. Furthermore, an examination of 148 human antemortem samples (cerebrospinal fluid, saliva, and skin biopsy) using both the Truenat assay and a validated real-time reverse transcriptase PCR assay revealed a κ value of 0.505, indicative of a moderate level of agreement between the two tests. Thus, the Truenat assay offers a robust, reliable, and affordable point-of-care solution to enhance rabies diagnostic capacity in endemic areas.

Neuroanatomical zones of human traumatic brain injury reveal significant differences in protein profile and protein oxidation: Implications for secondary injury events.

Traumatic brain injury (TBI) causes significant neurological deficits and long-term degenerative changes. Primary injury in TBI entails distinct neuroanatomical zones, i.e., contusion (Ct) and pericontusion (PC). Their dynamic expansion could contribute to unpredictable neurological deterioration in patients. Molecular characterization of these zones compared with away from contusion (AC) zone is invaluable for TBI management. Using proteomics-based approach, we were able to distinguish Ct, PC and AC zones in human TBI brains. Ct was associated with structural changes (blood-brain barrier (BBB) disruption, neuroinflammation, axonal injury, demyelination and ferroptosis), while PC was associated with initial events of secondary injury (glutamate excitotoxicity, glial activation, accumulation of cytoskeleton proteins, oxidative stress, endocytosis) and AC displayed mitochondrial dysfunction that could contribute to secondary injury events and trigger long-term degenerative changes. Phosphoproteome analysis in these zones revealed that certain differentially phosphorylated proteins synergistically contribute to the injury events along with the differentially expressed proteins. Non-synaptic mitochondria (ns-mito) was associated with relatively more differentially expressed proteins (DEPs) compared to synaptosomes (Syn), while the latter displayed increased protein oxidation including tryptophan (Trp) oxidation. Proteomic analysis of immunocaptured complex I (CI) from Syn revealed increased Trp oxidation in Ct > PC > AC (vs. control). Oxidized W272 in the ND1 subunit of CI, revealed local conformational changes in ND1 and the neighboring subunits, as indicated by molecular dynamics simulation (MDS). Taken together, neuroanatomical zones in TBI show distinct protein profile and protein oxidation representing different primary and secondary injury events with potential implications for TBI pathology and neurological status of the patients.

NIMHANS Neuropsychological Battery for Elderly in Parkinson's Disease Patients: Validation and Diagnosis using MDS PD-MCI Task Force Criteria in Indian Population.

Introduction: Cognitive impairment is a common non-motor feature of Parkinson's Disease (PD). Diagnosis of mild cognitive impairment is challenging and routinely missed in clinical practice. Our study aimed to study the efficacy of NIMHANS Neuropsychological Battery for Elderly (NNB-E) in diagnosing subtle cognitive deficits in PD patients. Objective: The aim of this study is to validate NNB-E and evaluate cognitive impairment in PD patients in comparison with healthy controls. Methods: We recruited 31 PD patients and 31 healthy controls in the current study. We validated NNB-E using receiver operating characteristic (ROC) curve analysis, Crohnbach's alpha, principal component analysis, and Pearson product-moment correlation, and studied the cognitive impairments using NNB-E in the non-demented PD patients and controls who scored ≥24 on HMSE. Results: Cognitive performance of PD patients was poor compared to controls. NNB-E showed good internal consistency and construct validity with Crohnbach's alpha of 0.861 and area under the curve (AUC) of 0.878. The battery was able to detect mild cognitive impairment in 74.1% of patients and 6.4% of controls. The ROC curve showed that the overall sensitivity of the battery was 73.2% and specificity was 92.6% at an optimal cutoff score. Different cutoff values set for defining PD-MCI as per MDS task force criteria resulted in varying frequencies of MCI ranging from 25.8% to 71%. Conclusion: Our study established the validity of NNB-E in PD patients, and this tool was suitable for diagnosing PD-MCI and discriminating PD patients from normal controls in the Indian population. This study also showed PD-MCI at various cutoff scores with greater impairment in executive and attention domains.