Therapeutic response to rituximab in seropositive neuromyelitis optica: Experience from a tertiary care center in South India.

Objectives: Neuromyelitis optica (NMO) is a severe central nervous system demyelinating disease caused by autoantibodies to anti-aquaporin-4 immunoglobulin-G (AQP4-IgG). Rituximab, a monoclonal antibody targeting CD20 cells, is effective in neuromyelitis optica spectrum disorder (NMOSD) in several observational studies and small randomized controlled trials. However, this includes both AQP4-IgG antibody positive and negative cases. Whether rituximab is more effective in seropositive NMO is unknown. The aim of the study was to determine the efficacy of rituximab in seropositive NMO. Materials and Methods: This single-center ambispective study with retrospective data collection and prospective follow-up included patients with NMOSD who were positive for AQP4-Ig-G and treated with rituximab. Efficacy outcomes assessed were annualized relapse rate (ARR), disability progression by expanded disability status scale (EDSS), very good outcome (defined as no relapse and an EDSS ≤3.5), and persistent antibody positivity. Safety was also monitored. Results: Between June 2017 and December 2019, 15 AQP4-IgG-positive cases were identified. The mean (± SD) age was 36 ± 17.9 years and 73.3% were females. Transverse myelitis followed by optic neuritis was the most common presentations. Rituximab was initiated after a median period of 19-weeks from the disease onset. The mean number of rituximab doses received was 6.4 ± 2.3. After a mean follow-up duration of 107 ± 74.7 weeks from the first dose of rituximab, ARR significantly reduced from 0.5 ± 0.9 to 0.02 ± 0.08, difference 0.48 ± 0.86 (95% confidence intervals [CI], 0.0009-0.96; P = 0.05). The number of relapses also reduced significantly from 0.6 ± 0.8-0.07 ± 0.26 , a difference of 0.53 ± 0.91 (95% CI, 0.026-1.05; P = 0.041). EDSS also significantly reduced from 5.6 ± 2.5-3.3 ± 2.9 , a difference of 2.23 ± 2.36 (95% CI, 0.93-3.54; P = 0.003). Very good outcome was obtained in 73.3% (11 of 15); P = 0.002. AQP4-IgG remained positive in 66.7% (4 of 6) when repeated after a mean period of 149.5 ± 51.1 weeks after the first dose of rituximab. Neither pre-treatment ARR, EDSS, time to initiate rituximab, the total number of rituximab doses, or time to repeat AQP4-IgG were significantly associated with persistent antibody positivity. No serious adverse events were observed. Conclusion: Rituximab exhibited high efficacy and good safety in seropositive NMO. Larger trials in this subgroup are warranted to confirm these findings.

Prevalence and Risk Factors of Peripheral Neuropathy in Parkinson's Disease.

Introduction: A lesser studied aspect of Parkinson's disease (PD) is its associated peripheral sensory-motor neuropathy. Peripheral neuropathy is an intriguing aspect of PD, a problem not given sufficient attention and which if tackled properly could make a difference to the multifaceted sufferings of the PD patient. Studies regarding the prevalence of peripheral neuropathy and its risk factors in patients with PD are scarce from the Indian subcontinent. Methods: This prospective observational study was conducted in a tertiary care teaching hospital in South India. Patients diagnosed with idiopathic Parkinson's disease (IPD) were screened and enrolled. All the patients underwent detailed evaluation of symptoms, signs, and electrophysiology (Nerve conduction study, Sympathetic skin response), stimulated skin wrinkling with Eutectic Mixture of Local Anesthetics. Patients found to have large/small fiber neuropathy underwent additional tests to exclude other causes of neuropathy. Results: A total of 154 patients with IPD were enrolled in the study (mean age: 61.96 ± 9.15 years, mean duration of disease was 4.08 ± 3.16 years). The mean Hoehn and Yahr (H and Y) score was 2.3 ± 0.825 and the mean Unified Parkinsons Disease Rating Scale (UPDRS)-3 score in the ON state was 23.07 ± 11.14. The mean cumulative levodopa dose was 482.68 ± 651.76 (median: 292; range: 4728.57) grams. Peripheral neuropathy was found in 49 patients (31.8%), large fiber in 28 (18.2%) and small fiber in 47 (30.5%); an overlap of large and small fiber neuropathy was seen in 26 patients (16.9%). Around 34% of patients had serum homocysteine levels >20 mg/dl. In univariate analysis, duration of disease, levodopa cumulative dose, serum homocysteine level, H and Y score, UPDRS-3 ON score, Toronto Clinical Neuropathy Score (P < 0.001 for all), age at presentation, and rigidity predominant presentation (P = 0.02 for both) were associated with large fiber neuropathy. All of these variables were also associated with the presence of small fiber neuropathy (P = 0.004 for age at presentation and P < 0.001 for rest), except the type of PD presentation. However, in multivariate logistic regression analysis, only duration of disease, levodopa cumulative dose, and H and Y score were associated with the presence of large and small fiber neuropathy. Conclusions: In our cohort, majority of the patients were in early-stage PD and around one-fifth and one-third of patients suffer from large and small fiber polyneuropathy, respectively. Large and small fiber neuropathy in PD is mainly associated with duration of disease, levodopa cumulative dose, and H and Y score.

Guillain-Barré syndrome following ChAdOx1 nCoV-19 COVID-19 vaccination: A case series.

ChAdOx1 nCoV-19 is an effective and well-tolerated coronavirus disease 2019 (COVID-19) vaccine. Rare cases of serious adverse events have been reported with this vaccine. We report three patients who developed Guillain-Barré syndrome following ChAdOx1 nCoV-19 vaccination, who did not have active or prior COVID-19 infection. The neurological illness in all patients had an onset of 11-13 days after the first dose of vaccine. All were characterized by sensorimotor weakness of the upper and lower limbs, with facial diplegia in one and dysautonomia in the other. Nerve conduction studies were consistent with demyelination in two and axonopathy in one. Cerebrospinal fluid analysis showed albuminocytological dissociation in two patients. All patients had moderate-to-severe disability. They were treated with intravenous immunoglobulin, with stabilization of the disease. Proper monitoring and prompt reporting of such cases is required to ensure safety of the vaccine.

Clinical Course, Imaging Characteristics, and Therapeutic Response in Myelin Oligodendrocyte Glycoprotein Antibody Disease: A Case Series.

Myelin oligodendrocyte glycoprotein (MOG) antibody disease is a novel central nervous system autoimmune disorder which forms part of aquaporin 4 (AQP-4) negative, neuromyelitis optica (NMO) spectrum disorder. It has a distinct clinical profile, neuroimaging features and courses from AQP-4 positive NMO and multiple sclerosis. This article is a case series of six patients with MOG antibody disease with longitudinal follow-up for up to 8 months.

Long-term Response of Cerebrospinal Fluid Pressure in Patients with Idiopathic Intracranial Hypertension - A Prospective Observational Study.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is increased intracranial pressure (ICP) with normal cerebrospinal fluid (CSF) contents, in the absence of an intracranial mass, hydrocephalus, or other identifiable causes. The current knowledge of the treatment outcome of IIH is limited, and the data on the natural history of this entity are scant. OBJECTIVE: The objective of the study is to study the treatment response of IIH by serially measuring the CSF opening pressure and to delineate the factors influencing the same. MATERIALS AND METHODS: A prospective observational study in a cohort of fifty patients with IIH in whom CSF opening pressure was serially measured at pre-specified intervals. RESULTS: The mean CSF opening pressure at baseline was 302.4 ± 51.69 mm of H2O (range: 220-410). Even though a higher body mass index (BMI) showed a trend toward a higher CSF opening pressure, the association was not significant (P = 0.168). However, the age of the patient had a significant negative correlation with the CSF pressure (P = 0.006). The maximum reduction in CSF pressure occurred in the first 3 months of treatment, and thereafter it plateaued. Remission was attained in 12 (24%) patients. BMI had the strongest association with remission (P = 0.001). CONCLUSIONS: In patients with IIH, treatment response is strongly related to BMI. However, patients with normal BMI are also shown to relapse and hence should have continuous, long-term follow-up. The reduction in CSF pressure attained in the first 3 months could reflect the long-term response to treatment.

Accuracy of the ice test in the diagnosis of myasthenic ptosis.

BACKGROUND: Diagnosis of myasthenia gravis is difficult, especially when the disease is restricted to ocular muscles. It is a well-known observation that myasthenic ptosis improves with cold and based on this, the ice pack test has been used as a tool in its differential diagnosis. The aim of the study is to investigate the diagnostic value of ice pack test as a preliminary test in the differential diagnosis of myasthenia and to find out the percentage of positivity and negativity of the ice pack test. MATERIALS AND METHODS: The study included patients seeking treatment for ptosis in a tertiary care center in Kerala. All patients were subjected to the ice pack test. Evaluation of patients was made by recording the marginal reflex distance (MRD). MRD was recorded before and after the application of ice pack, and an improvement of more than 2 mm was considered positive. Patients were divided into two groups: (1) those who had ptosis and features suggestive of myasthenia; and, (2) those who had ptosis but no features of myasthenia. Patients of both groups were subjected to relevant investigations and the diagnosis of myasthenia was established. RESULTS: Ice cold test was positive in 48 (96%) patients and negative in two patients of the myasthenia group. In the control group, 6 (12%) patients had a false positive ice cold test and in the remaining 44 patients (88%), ice cold test was negative. CONCLUSION: Ice pack test has a high specificity and sensitivity in the differential diagnosis of myasthenic ptosis.

Plasmapheresis in neurological disorders: Experience from a tertiary care hospital in South India.

BACKGROUND: Therapeutic plasma exchange (PE) or plasmapheresis is the treatment of choice in many neurological disorders. Even though it is safe in experienced hands, there is a major concern about its safety among physicians. OBJECTIVES: To analyze our experience with 230 patients who underwent PE for various neurological disorders. MATERIALS AND METHODS: Retrospective review of PE procedures done during a period of 48 months, from July 2007 to June 2011 in a tertiary care teaching hospital in South India. Indications, clinical results and technical factors are discussed. RESULTS: The main indication for PE was GBS (203 patients; 88.3%). Age of patients ranged from 14-65 (mean = 42.3 years). The most common complications were paraesthesias and/or cramps (36.1%) and hypotension (32.2%). Four pregnant patients who underwent PE had good recovery with one intrauterine death. There was no mortality. CONCLUSION: The analysis of 240 cases of PE done in our department shows that the procedure is safe, with only minimal procedure related complications and no mortality.

Recurrence rate of seizure following discontinuation of anti-epileptic drugs in patients with normal long term electroencephalography.

BACKGROUND: The usefulness of electroencephalography (EEG) in predicting seizure recurrence after antiepileptic drugs (AED) tapering is a controversial subject. There have been no studies which tested the additional yield of long-term over routine EEG recordings in predicting seizure recurrence after AED withdrawal. OBJECTIVE: The primary objective of our study is to determine the recurrence rate of seizure following AED withdrawal in patients with focal epilepsy, unknown cause who had normal long-term electroencephalography (LTEEG) and secondary objective is to analyze the variables that would predict seizure recurrence. MATERIALS AND METHODS: This was a prospective observational study. A total of 91 patients were included. 62 patients who had normal routine and LTEEG entered the final phase of the study were followed-up regularly for 1 year or until seizure recurrence whichever was earlier. RESULTS: A total number of 91 patients were enrolled for the first phase of the study. Of these, 13 (14.29%) patients had an abnormal routine EEG. Of the remaining patients, another 16 (17.58%) had abnormal LTEEG. The remaining 62 patients with normal routine and long-term EEG entered the final phase of the study. Of these, 17 patients (27.41%) had seizure recurrence during the follow-up while 45 (72.58%) remained seizure free until the end of the 1 year follow-up. The significant variables associated with a higher risk of seizure relapse were a positive past history of seizure recurrence on prior drug withdrawal (relative risk: 2.19, confidence interval: 1.01-4.74, P < 0.05) and the duration of epilepsy until seizure control was achieved (P < 0.009). CONCLUSIONS: The recurrence rate of seizure in patients with a normal LTEEG is 27.41%. A positive past history of seizure recurrence and a longer time to achieve seizure freedom with AED increased the risk of seizure recurrence.

Acute stroke-like presentation of acquired hepatocerebral degeneration.

Neurological manifestations in liver diseases have been well-described. Parkinsonism developing in cirrhotic patients is a unique clinical, neuroradiological, and biological entity. The symptoms are often insidious in onset and occur after liver disease has made its presentation. Acute dysarthria as the presenting manifestation of cirrhosis is rare. Here we report three cases where liver disease made an unusual presentation as acute dysarthria. In all cases the abruptness of the onset prompted the treating physicians to make a diagnosis of stroke. The computed tomography (CT) scans of all these patients did not show any evidence of stroke. This was followed by magnetic resonance imaging (MRI) which showed the characteristic symmetric high-signal intensities in globus pallidus and substantia nigra in T1-weighted images, a reflection of increased tissue concentrations of manganese that helped in making a retrospective diagnosis of liver disease, confirmed later by altered serum albumin to globulin ratios and altered liver echo texture in ultra sonogram.

First case of scrub typhus with meningoencephalitis from Kerala: An emerging infectious threat.

Scrub typhus is a rickettsial disease caused by Orientia tsutsugamushi, one of the most common infectious diseases in the Asia-Pacific region. It has been reported from northern, eastern, and southern India, and its presence has been documented in at least 11 Indian states. However, scrub typhus meningoencephalitis has not been well documented in Kerala. We report two cases of scrub typhus meningoencephalitis from northern Kerala. The diagnosis was made based on the clinical pictures, presence of eschar, and a positive Weil-Felix test with a titer of > 1:320. The first patient succumbed to illness due to respiratory failure and the second patient improved well.

Cerebral venous thrombosis presenting as multiple lower cranial nerve palsies.

Cerebral venous thrombosis (CVT) is a well-recognized entity, but its clinical presentation is varied and often mimics many neurological disorders, making it a diagnostic challenge. Cerebral venous thrombosis has a wide spectrum of signs and symptoms, which may evolve suddenly or over weeks. It mimics many neurological conditions such as meningitis, encephalopathy, idiopathic intracranial hypertension, and stroke. Cerebral venous thrombosis presenting as multiple lower cranial nerve palsies, are rarely reported. We describe a pregnant lady who presented with sensorineural deafness of the right ear and paralysis of the 9(th), 10(th), and 12(th) cranial nerves on the right side. She was diagnosed to have thrombosis of the right transverse sinus and sigmoid sinus with extension to the jugular vein and confluence of sinuses. She improved with anticoagulant treatment.

Guillain-Barre syndrome and SIADH.

BACKGROUND: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in Guillain-Barré syndrome (GBS) is a very often overlooked entity even though it is well-described. However, most of the previous observations are case reports. There are no systematic studies of SIADH in GBS. OBJECTIVE: To assess the incidence and characteristics of SIADH in patients with GBS and to assess whether it is a predictor of poor outcome. METHODS: We prospectively studied 50 patients with GBS admitted to the Department of Neurology in a tertiary care hospital in South India from January 2009 to April 2010. After obtaining clinical history, electrophysiologic studies were performed to determine the GBS subtype. SIADH was diagnosed based on modified Bartter and Schwartz criteria. RESULTS: SIADH was detected in 24 of the 50 patients (48%) at some stage of the illness (median 8.8 days after GBS onset). Six of them had mild SIADH, 12 patients had moderate SIADH, and 6 patients had severe SIADH. MRC sumscore at the time of admission and discharge was higher in patients with SIADH (p < 0.001) when compared to the normal group. Bulbar weakness and need for ventilatory support were higher in GBS with SIADH (13 vs 1, p < 0.001). Mean duration of hospitalization was longer in SIADH (29.15 vs 10.57, p < 0.001). Most of the patients with GBS with SIADH required plasmapheresis (23 vs 8, p < 0.001). There are 4 variables significantly associated with mortality, which include age >50, ventilatory support, hyponatremia, and bulbar weakness. CONCLUSIONS: SIADH is a common and important electrolyte disorder encountered in GBS. It has significant association with severity of GBS and is an indicator of poor prognosis. It can be symptomatic even though the majority of patients are asymptomatic.