"De Novo" Hypercapnic Respiratory Failure Unmasking Neuromuscular Disorders: Experiences From a Tertiary Care Center and Review of Literature.

OBJECTIVES: Neuromuscular disorders could have respiratory involvement early or late into illness. Rarely, patients may present with a hypercapnic respiratory failure (with minimal motor signs) unmasking an underlying disease. There are hardly any studies which have addressed the spectrum and challenges involved in management of this subset, especially in the real-world scenario. METHODS: A retrospective study comprising consecutive patients hospitalized with hypercapnic respiratory failure as the sole/dominant manifestation. The clinical-electrophysiological spectrum, phrenic conductions, diaphragm thickness, and outcomes were analyzed. RESULTS: Twenty-seven patients were included, the mean age was 47.29 (SD 15.22) years, and the median duration of respiratory symptoms was 2 months (interquartile range [IQR] 1-4). Orthopnea was present in 23 patients (85.2%) and encephalopathy in 8 patients (29.6%). Phrenic nerve latencies and amplitudes were abnormal in 83.3% and 95.6%, respectively. Abnormal diaphragm thickness was noted in 78.5%. Based on a comprehensive electrophysiological strategy and paraclinical tests, an etiology was established in all. Reversible etiologies were identified in 17 patients (62.9%). These included myasthenia gravis (anti-AChR and MuSK), inflammatory myopathy, riboflavin transporter deficiency neuronopathy, Pompe disease, bilateral phrenic neuritis, and thyrotoxicosis. Respiratory onset motor neuron disease was diagnosed in 8 patients (29.6%). Despite diaphragmatic involvement, a functional respiratory recovery was noted at discharge (45%) and last follow-up (60%). Predictors for good outcomes included female sex, normal nerve conductions, and recent-onset respiratory symptoms. DISCUSSION: A good functional recovery was noted in most of the patients including respiratory onset motor neuron disease. A systematic algorithmic approach helps in proper triaging, early diagnosis, and treatment. Clinical and electrodiagnostic challenges and observations from a tertiary care referral center are discussed.

Peripheral nervous system and neuromuscular disorders in the emergency department: A review.

INTRODUCTION: Acute presentations and emergencies in neuromuscular disorders (NMDs) often challenge clinical acumen. The objective of this review is to refine the reader's approach to history taking, clinical localization and early diagnosis, as well as emergency management of neuromuscular emergencies. METHODS: An extensive literature search was performed to identify relevant studies. We prioritized meta-analysis, systematic reviews, and position statements where possible to inform any recommendations. SUMMARY: The spectrum of clinical presentations and etiologies ranges from neurotoxic envenomation or infection to autoimmune disease such as Guillain-Barré Syndrome (GBS) and myasthenia gravis (MG). Delayed diagnosis is not uncommon when presentations occur "de novo," respiratory failure is dominant or isolated, or in the case of atypical scenarios such as GBS variants, severe autonomic dysfunction, or rhabdomyolysis. Diseases of the central nervous system, systemic and musculoskeletal disorders can mimic presentations in neuromuscular disorders. CONCLUSIONS: Fortunately, early diagnosis and management can improve prognosis. This article provides a comprehensive review of acute presentations in neuromuscular disorders relevant for the emergency physician.

Do Bone Mineral Density, Trabecular Bone Score, and Hip Structural Analysis Differ in Indian Men with Parkinson's Disease? A Case-Control Pilot Study from a Tertiary Center in Southern India.

Objective: Parkinson's disease (PD) is a neurodegenerative condition that is characterized by bradykinesia, rigidity, and gait instability. Inherent to this condition is an increased predisposition to falls and fractures. Bone health in Parkinson's disease in India has not been studied thus far. This study aimed to assess the bone mineral density (BMD), trabecular bone score (TBS), and hip structural analysis (HSA) in Indian men with PD and compare them with matched controls. Methodology: A case-control study done at a tertiary care center from southern India. Bone biochemistry, BMD, TBS, and HSA were assessed. Results: Among 40 cases and 40 age, gender, and body mass index (BMI)-matched controls, there was no significant difference in BMD between both groups. The mean (SD) TBS at the lumbar spine [1.349 (0.090)] was significantly (P = 0.019) lower in men with PD as compared to matched controls [1.401 (0.089)]. Among the parameters of HSA, the buckling ratios were significantly higher at the femoral neck [11.8 (2.2) vs 9.4 (2.2); P = 0.001] and inter-trochanteric region [9.4 (2.1) vs 7.8 (1.4); P = 0.002] among cases as compared to matched controls. Vitamin D deficiency was significantly higher in this cohort of patients as was bone turnover marker indicating bone loss and a high bone turnover state. Conclusion: A comprehensive bone health assessment comprising BMD, TBS, and HSA may be required to capture all aspects of bone strength in Indian men with PD as BMD assessment as a stand-alone tool may not suffice to obtain all information pertaining to fracture risk in these individuals.

Interventions in cerebrovascular emergencies among patients with Paroxysmal nocturnal haemoglobinuria - A word of caution.

INTRODUCTION: Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal hematopoietic disorder, where there is deficiency of glycosylphosphatidylinositol (GPI) anchored proteins in the cell membrane, leading to increased complement sensitivity of red blood cells, intravascular hemolysis and vascular inflammation. Arterial and venous strokes in patients with PNH are a rarity posing significant diagnostic and therapeutic challenges. We report our experience with management of PNH patients with cerebrovascular emergencies. METHODS: We report 2 patients with PNH, one who was previously diagnosed with PNH and had arterial stroke, the other had an index presentation of cerebral venous sinus thrombosis (CVT) and was subsequently diagnosed with PNH. We also present the systematic review of literature reporting similar cases, highlighting the challenges in management. RESULTS: Both patients presented to our centre with cerebrovascular emergency. The first patient was a diagnosed with PNH, and presented with left hemispheric infarction caused by thrombosis of middle cerebral artery. He was thrombolysed and underwent mechanical thrombectomy, which was unsuccessful in view of repeated re - thrombosis of the vessel. The patient survived with significant disability. The second patient had severe cerebral venous sinus thrombosis with large right hemispheric hemorrhagic venous infarction. She underwent emergency decompressive hemicraniectomy complicated by massive blood loss and disseminated intravascular coagulation. She subsequently had recurrent life threatening intracranial bleed secondary to platelet transfusions, thrombocytopenia, and use of contrast agents. She progressed to develop Budd Chiari syndrome and was initiated on Eculuzimab. She became transfusion independent, however remained in minimally conscious state and succumbed to sepsis. CONCLUSIONS: Management of arterial and venous strokes is complex in patients with PNH. Invasive procedures and platelet transfusions are to be avoided in acute thrombosis, till robust evidence is available establishing the safety of the same in patients with PNH. Eculuzimab is a promising option, but far from reach for patients in developing countries.

Cerebral venous sinus thrombosis: changing trends in the incidence, age and gender (findings from the CMC Vellore CVT registry).

BACKGROUND: Multiple cerebral venous sinus thrombosis (CVT) registries from various geographical regions indicate that female gender, the use of contraceptive pills, pregnancy and puerperium are important risk factors. In this study, we report the changes in the epidemiology of patients with CVT managed over the past 26 years. METHODS: The CMC Vellore CVT registry is a prospectively maintained database at the Christian Medical College, Vellore since January 1995. Stata software was used to analyse the data and assess the changes in the incidence, age and gender distribution over the previous 26 years. RESULTS: Among 1701 patients treated during the study period, 908 (53%) were women and 793 (47%) were men. The mean incidence of CVT was 49 per 100 000 admissions before 2010, which increased to 96 per 100 000 after 2010. Male gender had a higher odds of developing CVT (OR - 2.07 (CI 1.68 to 2.55, p<0.001). This could be attributed to the declining incidence of postpartum CVT after 2010 compared with the decade before 2010 (50% vs 20%). The mean age at presentation had increased from 24.5 to 33.2 years in the last decade. CONCLUSIONS: There was a clear change in the gender pattern from being a condition with female preponderance, to one where equal or more men are being affected. Lower incidence of postpartum CVT cases could be the driving factor. An increase in the overall incidence of CVT cases was noted, probably due to a higher index of clinical suspicion and better diagnostic imaging modalities.

Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions.

Adult-onset leukodystrophies though individually rare are not uncommon. This group includes several disorders with isolated adult presentations, as well as several childhood leukodystrophies with attenuated phenotypes that present at a later age. Misdiagnoses often occur due to the clinical and radiological overlap with common acquired disorders such as infectious, immune, inflammatory, vascular, metabolic, and toxic etiologies. Increased prevalence of non-specific white matter changes in adult population poses challenges during diagnostic considerations. Clinico-radiological spectrum and molecular landscape of adult-onset leukodystrophies have not been completely elucidated at this time. Diagnostic approach is less well-standardized when compared to the childhood counterpart. Absence of family history and reduced penetrance in certain disorders frequently create a dilemma. Comprehensive evaluation and molecular confirmation when available helps in prognostication, early initiation of treatment in certain disorders, enrollment in clinical trials, and provides valuable information for the family for reproductive counseling. In this review article, we aimed to formulate an approach to adult-onset leukodystrophies that will be useful in routine practice, discuss common adult-onset leukodystrophies with usual and unusual presentations, neuroimaging findings, recent advances in treatment, acquired mimics, and provide an algorithm for comprehensive clinical, radiological, and genetic evaluation that will facilitate early diagnosis and consider active treatment options when available. A high index of suspicion, awareness of the clinico-radiological presentations, and comprehensive genetic evaluation are paramount because treatment options are available for several disorders when diagnosed early in the disease course.

Opsoclonus myoclonus ataxia syndrome, ovarian teratoma and anti-NMDAR antibody: an 'unresolved' mystery.

Background: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is characterised by the combination of opsoclonus and arrhythmic action myoclonus with axial ataxia and dysarthria. In adults, a majority are paraneoplastic secondary to solid organ tumours and could harbour antibodies against intracellular epitopes; however, certain proportions have detectable antibodies to various neuronal cell surface antigens. Anti-N-methyl-D-aspartate (NMDAR) antibodies and ovarian teratomas have been implicated in OMAS. Methods: Report of two cases and review of literature. Results: Two middle-aged women presented with subacute-onset, rapidly progressive OMAS and behavioural changes consistent with psychosis. The first patient had detectable antibodies to NMDAR in the cerebrospinal fluid (CSF) alone. Evaluation for ovarian teratoma was negative. The second patient had no detectable antibodies in serum or CSF; however, she had an underlying ovarian teratoma. Patient A was treated with pulse steroids, therapeutic plasma exchange (TPE) followed by bortezomib (BOR) and dexamethasone, while patient B was treated with steroids, TPE followed by surgical resection of ovarian teratoma. Both patients had favourable outcomes and were asymptomatic at the 6 monthly follow-up. Conclusions: With coexistent neuropsychiatric manifestations, OMAS can be considered a distinct entity of autoimmune encephalitis, pathogenesis being immune activation against known/unknown neuronal cell surface antigens. The observation of absence of anti-NMDAR antibody in patients with teratoma-associated OMAS and vice versa is intriguing. Further research on the potential role of ovarian teratoma in evoking neuronal autoimmunity and its targets is required. The management challenge in both cases including the potential use of BOR has been highlighted.

Effectiveness of Adjunctive High-Dose Infliximab Therapy to Improve Disability-Free Survival Among Patients With Severe Central Nervous System Tuberculosis: A Matched Retrospective Cohort Study.

BACKGROUND: Few treatment options exist for patients with severe central nervous system (CNS) tuberculosis (TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients are sparse. METHODS: We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing 2 groups of adults with CNS TB. Cohort A received at least 1 dose of infliximab after optimal ATT and steroids between March 2019 and July 2022. Cohort B received only ATT and steroids. Disability-free survival (mRS score ≤2) at 6 months was the primary outcome. RESULTS: Baseline MRC grades and mRS scores were similar between the cohorts. Median duration before initiation of infliximab therapy from start of ATT and steroids was 6 (IQR: 3.7-13) months and for neurological deficits was 4 (IQR: 2-6.2) months. Indications for infliximab were symptomatic tuberculomas (20/30; 66.7%), spinal cord involvement with paraparesis (8/30; 26.7%), and optochiasmatic arachnoiditis (3/30; 10%), worsening despite adequate ATT and steroids. Severe disability (5/30 [16.7%] and 21/60 [35%]) and all-cause mortality (2/30 [6.7%] and 13/60 [21.7%]) at 6 months were lower in cohort A versus cohort B, respectively. In the combined study population, only exposure to infliximab was positively associated (aRR: 6.2; 95% CI: 2.18-17.83; P = .001) with disability-free survival at 6 months. There were no clear infliximab-related side effects noted. CONCLUSIONS: Infliximab may be an effective and safe adjunctive strategy among severely disabled patients with CNS TB not improving despite optimal ATT and steroids. Adequately powered phase 3 clinical trials are required to confirm these early findings.

Sensitivity and specificity of phrenic nerve electrophysiology to predict mechanical ventilation in the Guillain-Barré syndrome.

INTRODUCTION/AIMS: In Guillain-Barré syndrome (GBS), the sensitivity and specificity of phrenic compound muscle action potential (CMAP) measurements to predict endotracheal mechanical ventilation are unknown. Hence, we sought to estimate sensitivity and specificity. METHODS: We performed a 10-year retrospective analysis of adult GBS patients from our single-center laboratory database (2009 to 2019). The phrenic nerve amplitudes and latencies before ventilation were recorded along with other clinical and demographic features. Receiver operating curve (ROC) analysis with area under the curve (AUC) was used to determine the sensitivity and specificity with 95% confidence interval (CI) for phrenic amplitudes and latencies in predicting the need for mechanical ventilation. RESULTS: Two hundred five phrenic nerves were analyzed in 105 patients. The mean age was 46.1 ± 16.2 years, with 60% of them being male. Fourteen patients (13.3%) required mechanical ventilation. The average phrenic amplitudes were lower in the ventilated group (P = .003), but average latencies did not differ (P = .133). ROC analysis confirmed that phrenic amplitudes could predict respiratory failure (AUC = 0.76; 95% CI, 0.61 to 0.91; P < .002), but phrenic latencies could not (AUC = 0.60; 95% CI, 0.46 to 0.73; P = .256). The best threshold for amplitude was ≥0.6 mV, with sensitivity, specificity, and positive and negative predictive values of 85.7%, 58.2%, 24.0%, and 96.4%, respectively. DISCUSSION: Our study suggests that phrenic CMAP amplitudes can predict the need for mechanical ventilation in GBS. In contrast, phrenic CMAP latencies are not reliable. The high negative predictive value of phrenic CMAP amplitudes ≥0.6 mV can preclude mechanical ventilation, making these a useful adjunct to clinical decision-making.

Clinical efficacy and safety of efgartigimod for treatment of myasthenia gravis.

Treatment of acute exacerbations and refractory myasthenia gravis (MG) remains challenging despite advances in immunotherapy. Frequent use of plasmapheresis and immunoglobulins are associated with adverse events and strain on resources. The neonatal Fc receptor (FcRn) facilitates IgG recycling and FcRn antagonism enhances the degradation of IgG pathogenic autoantibodies without compromising adaptive and innate immunity. Efgartigimod, an FcRN antagonist, has been shown in well-designed clinical trials to improve clinical status and reduce autoantibody levels without significant safety concerns. Efgartigimod has received approvals for use in the United States, Japan and Europe. It is plausible that efgartigimod is effective across different subgroups and varied spectrums of MG severity. Novel strategies involving FcRn modulation and long-term follow-up studies will help provide further insights and expand the therapeutic repertoire.

Therapies for myasthenia gravis (MG) have been directed at removing or suppressing autoantibodies that cause disease. Despite advances in immunotherapy, the treatment of MG is challenging, especially in the case of worsening symptoms and refractory disease (disease that does not respond to treatment). The neonatal Fc receptor (FcRn), which is a protein in the blood, facilitates the recycling of a type of antibody called IgG. IgG autoantibodies are versions of IgG that mistakenly target and react with a person's own tissues or organs and are thought to play a role in MG. Blocking the FcRn receptor with a drug causes IgG autoantibodies to break down, stopping them from causing disease. Clinical trials have shown improvements in disease severity associated with a reduction in the autoantibodies that cause MG. Efgartigimod is a well-tolerated drug that inhibits IgG autoantibodies with minor side effects such as headache and upper respiratory (lung) and urinary tract infections. Efgartigimod may be a potential treatment strategy in patients with MG. Studies are now being carried out to determine how efgartigimod works in a real-world setting.

Leukotriene A4 hydrolase (LTA4H rs17525495) gene polymorphisms and paradoxical reactions in extrapulmonary tuberculosis.

Paradoxical reactions (PRs) are poorly studied complex immunological phenomena, among patients with tuberculosis (TB). When PRs involves critical structures like the central nervous system (CNS), immunomodulatory therapy is often required. Predictors for PRs in TB to pre-empt appropriate treatment strategies in high-risk groups are lacking. TT genotype of Leukotriene A4 hydrolase (LTA4H) promoter region rs17525495 polymorphisms are associated with exaggerated immune responses in Tuberculous meningitis (TBM), the most severe form of extrapulmonary tuberculosis (EPTB). The association of these polymorphisms with PRs is not known. We evaluated this plausibility among 113 patients with EPTB, at high risk of PRs. Majority [81 (71.7%)] had disseminated tuberculosis with prominent CNS [54 (47.8%)] and lymph node involvement [47 (41.6%)]. Human immunodeficiency Virus (HIV) co-infection was seen among 23 (20.3%) patients. PRs were noted in 38.9% patients, at a median duration of 3 months (IQR 2-4). LTA4H rs17525495 single nucleotide polymorphism (SNP) analysis showed 52 (46%) patients had CC, 43 (38.1%) had CT and 18 (15.9%) had TT genotypes. There was no statistically significant difference in occurrence [CC 38.5% vs CT 39.5% vs TT 38.7%] and time of onset [median (IQR)] of PRs across the genotypes [CC 3 (1-4.7), CT 3 (2-5), TT 2 (2-3)]. PRs was shown to be significantly linked with HIV co-infection (RR 0.6, 95% CI 0.29-1.28), culture positivity (RR 0.5, 95% CI 0.28-1.14), TB Lymphadenitis (RR 0.7, 95% CI 0.44-1.19) and CNS involvement RR 2.1, 95% CI 1.27-3.49) in the univariate analysis (p < 0.2). On multivariate analysis, CNS involvement alone was associated with PRs (aRR 3.8 (1.38-10.92); p < 0.01). PRs were associated with CNS involvement but not with LTA4H rs17525495 polymorphisms.

Chronic flaccid quadriparesis from tract specific myelopathy in neurosyphilis.

INTRODUCTION: Tract-specific myelopathies with distinctive imaging features are uncommon and typically occur with metabolic or paraneoplastic syndromes. We report a unique case of tract-specific myelopathy with neurosyphilis. CASE PRESENTATION: A 53-year-old male presented with a four-month history of flaccid quadriparesis, sensory loss, and bladder dysfunction. His MRIs revealed striking symmetric T2-weighted hyperintensities in the lateral corticospinal tracts and dorsal columns of the cervical spinal cord that extended rostrally into the pyramidal decussation and medial lemnisci of the medulla oblongata. Nerve conduction and needle electromyography studies excluded axonal or demyelinating lower motor neuron disorders. The patient reported previous untreated primary syphilis and was seropositive on the T.pallidum hemagglutination assay. Penicillin therapy resulted in substantial clinical improvement. DISCUSSION: Although syphilitic meningomyelitis is well-reported, our patient was unique because of the persistent flaccidity (possibly suggesting prolonged spinal shock) and striking tract-specific MRI patterns. These features are novel in syphilitic myelitis and suggest unknown mechanisms of tract-specific tropism and neuronal injury. CONCLUSIONS: "Tract-specific" complete transverse myelopathy with persistent flaccid weakness and areflexia is a novel presentation of neurosyphilis. Early recognition and crystalline penicillin therapy can alleviate morbidity. Our report describes this patient's findings and discusses the differential diagnoses of tract-specific myelopathies.

The Utility of COMPASS-31 Questionnaire to Predict Autonomic Dysfunction in Patients With Cervical/Upper Thoracic Compressive Myelopathy.

BACKGROUND: Patients with cervical/upper thoracic compressive myelopathy may have autonomic dysfunction. The composite autonomic severity score (CASS) is the gold standard test to detect autonomic dysfunction, and the self-rated composite autonomic system scale (COMPASS-31) questionnaire is a screening tool to diagnose autonomic dysfunction. This study compared the COMPASS-31 and modified CASS scores for the detection of autonomic dysfunction in patients with compressive myelopathy. METHODS: Patients with cervical/upper thoracic compressive myelopathy scheduled for decompressive surgery completed a COMPASS-31 questionnaire and underwent autonomic function tests to calculate the modified CASS score before surgery. RESULTS: Forty-two patients were included in the study; 19 (45.2%) had mild autonomic dysfunction, 5 (11.9%) had moderate autonomic dysfunction, and 18 (42.9%) had severe autonomic dysfunction. Median (interquartile range) of modified CASS and COMPASS-31 scores were 19 (6.33) and 3 (2.5), respectively. There was a positive correlation between modified CASS and COMPASS-31 scores ( r =0.43; P =0.004). Receiver operating characteristic curve analysis confirmed that COMPASS-31 had fair accuracy for prediction of moderate to severe autonomic dysfunction (area under the curve, 0.74; 95% confidence interval, 0.64-0.82; P =0.009). A cut-off of 30 for total COMPASS-31 score had a sensitivity of 52.2% and specificity of 89.5% to detect moderate to severe autonomic dysfunction, with positive and negative predictive values of 85.7% and 60.7%, respectively. CONCLUSION: Patients with cervical/upper thoracic compressive myelopathy had varying degrees of autonomic dysfunction based on the modified CASS. There was a positive correlation between the modified CASS and COMPASS-31 questionnaire. A COMPASS-31 score of >30 30 could be utilized to predict moderate to severe autonomic dysfunction in patients with compressive myelopathy.

Therapies in Autoimmune Peripheral Neuropathies beyond Intravenous Immunoglobulin, Plasma Exchange and Corticosteroids: An Analytical Review.

Autoimmune neuropathies are often treatable. First-line immunotherapies include intravenous immunoglobulin (IVIG), plasma exchange and corticosteroids. However, nearly 15-30% of patients are either refractory, partially responsive or chronically dependent on these first-line agents. Lack of full response leads to increased disability in addition to adverse financial implications. Consequently, there is an unmet need for more effective treatments to manage this subset of patients. There has been a remarkable increase in the knowledge about immunopathogenesis, antigenic targets, clinical phenotype correlation, and novel therapeutic agents in the last two decades. These novel agents target specific components of the immune system (humoral, cellular immunity, and complement) and have the potential to improve the management of these disorders. Unfortunately, high-quality evidence from large, controlled studies is scarce considering the relative rarity of these refractory cases, heterogeneity of clinical presentations and ethical concerns limiting the use of a placebo arm. An adaptive clinical trial design in a homogenous cohort with standardized outcomes in multiple centers and the use of historical controls will likely provide valuable scientific evidence about the efficacy and safety of these therapies. In this review, we examine the status of the newer immunotherapies in the treatment of autoimmune neuropathies based on existing data.

Rituximab therapy for neuro - inflammatory disorders - Real world experience from South India.

BACKGROUND AND OBJECTIVES: To determine the real-world data regarding the use of Rituximab (RTX) in neuroinflammatory disorders (NIDS) and assess the outcomes following RTX treatment. METHODS: A cohort of consecutive patients with NIDS started on RTX (2018-2020) was included. The outcomes assessed were the proportion with favourable clinical response (FCR) as defined by clinical remission/ improvement using disease specific disability scores, comparative efficacy based on timing of initiation and B cell kinetics. RESULTS: A total of 97 patients with NIDS were included. The mean age was 36.43 (±14.4) years and median duration of follow - up being 15 months (IQR 12-16). Forty patients (41.2%) were initiated on RTX "early" in disease course. Favourable clinical response at last follow-up was seen in 94.9% (n = 92). The mean change in disability score (mRS) was 1.89 (SD 1.30) (p < 0.001). RTX appeared more effective when initiated "early" with higher remission rates (75% vs. 42%, p 0.015). B cell kinetics varied across NIDS, with 73% having adequate depletion at 6 months. Minor adverse events including infusion related reactions were reported in 9%. CONCLUSIONS: RTX has a favourable efficacy and safety profile. Future prospective studies are needed to establish the optimal timing of initiation and need for disease-based dosage regimens.

Management and Outcomes of COVID - 19 Associated Cerebral Venous Sinus Thrombosis.

BACKGROUND: Systemic hyper-coagulabilty leading to micro and macro thrombosis is a known complication of Coronavirus disease - 2019(COVID -19). The postulated mechanism appears to be the viral activation of endothelium, triggering the coagulation pathways. Thrombosis of the cerebral veins and sinuses (CVT), a potentially serious condition, has been increasingly reported with COVID - 19 infection. In this clinical study we attempt to describe the clinical profile, investigations and outcomes of patients with COVID- 19 associated CVT. METHODS: This is a single center prospective observational study from South India. The study included patients (aged >18 years) with concomitant COVID infection and CVT. The clinical, laboratory, imaging characteristics, management and outcomes were described and compared with COVID negative CVT patients. RESULTS: Out of 97 cases of CVT treated at our center during the first and second waves of the COVID pandemic 11/97 (11%) were COVID related CVT. Among these 11 patients, 9 (81%) had presented with only CVT related symptoms and signs and were tested positive for COVID - 19 infection during the pre-hospitalization screening. Respiratory symptoms were absent in 90% of the patients. Headache (100%) and seizures (90%) were the common presenting symptoms. The median time to diagnosis was 6 hours, from presentation to the emergency department. Transverse sinus was involved 10/11 (90%) and majority of them (9/11) had Haemorrhagic Venous Infarction (HVI). Acute inflammatory markers were elevated in comparison with non COVID CVT patients, with the mean serum D-dimer being 2462.75 ng/ml and the C-reactive protein was 64.5 mg/dl. Three patients (30%) underwent decompressive hemicraniectomy (DHC) because of large hemispheric HVI. All patients survived in the COVID CVT group while the mortality in the non COVID group was 4%. At 6 months follow up excellent outcome (modified Rankin Scale (mRS) score of 0-2) was noted equally in both groups. CONCLUSIONS: Symptoms and signs of CVT may be the only presentation of COVID-19 infection. Prompt recognition and aggressive medical management including DHC offers excellent outcomes.

Role of Pain-Related Evoked Potential in the Diagnosis of Meralgia Paresthetica.

INTRODUCTION: Entrapment of the lateral femoral cutaneous nerve (LFCN) of thigh results in meralgia paresthetica (MP). Standard electrophysiological tests for MP are technically demanding and unreliable. We aimed to study the role of pain-related evoked potentials (PREP) in the diagnosis of MP. METHODS: Patients with MP and normal volunteers were included. PREP was recorded by stimulating the skin over the lateral thigh 20 cm below the anterior-superior iliac spine and recording from the cortex at Cz. RESULTS: A total of 28 subjects and 56 LFCNs were studied. 36 nerves had MP and 20 were normal. The mean PREP latency was 118 (8) ms among normal controls and 164 (10.8) ms in MP. The optimal cut-off point for the diagnosis of MP was 134 ms. Area under receiver operator characteristic curve was 0.97; sensitivity was 91.7% and specificity was 100%. CONCLUSION: PREP is reliable and easy to use electrophysiological test in establishing the diagnosis of MP.