Analysis of spatio-temporal propagation of occipito-frontal spikes in childhood epilepsies by 3D sequential voltage mapping and dipole localization.

OBJECTIVE: We sought to study the spatio-temporal propagation of occipito-frontal spikes in childhood epilepsies by voltage mapping and dipole localization and identify types of occipito-frontal spikes based on onset, propagation, and stability of their dipoles. METHODS: Sleep EEG data of children, aged 1-14 years, with a minimum 1 h of recording from June 2018 to June 2021, were analyzed to identify occipito-frontal spikes. In total, 150 successive occipito-frontal spikes were manually selected from each EEG and using a source localization software were averaged using automated pattern matching with a threshold of 80%, and sequential 3D voltage maps of averaged spike were analyzed. Stability quotient (SQ) was calculated as the total number of averages/150. Stable dipole was defined as SQ ≥ .8. Dipole analysis was performed with principal component analysis using an age-appropriate template head model. RESULTS: Ten children with occipito-frontal spikes were identified; five with self-limited epilepsy with autonomic seizures (SeLEAS) and five with non-SeLEAS epilepsies. Three types of occipito-frontal spikes were identified: (1) narrow occipito-frontal spikes with stable dipoles seen in all five children with SeLEAS which were "apparently" synchronous and bilateral clone-like with an occipito-frontal interval of 10-30 ms and a homogeneous propagation pattern from a unilateral medial parieto-occipital region to an ipsilateral mesial frontal region; (2) wide occipito-frontal spikes with stable dipoles seen in one child with non-SeLEAS and developmental and/or epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS) with an occipito-frontal interval of 45 ms, caused by focal spike propagation from a deeper temporal focus to ipsilateral peri-rolandic cortex; and (3) wide occipito-frontal spikes with unstable dipoles seen in four children with non-SeLEAS lesional epilepsies with an occipito-frontal latency of >50 ms and heterogeneous propagation patterns with poor intra-individual dipole stability. SIGNIFICANCE: We successfully identified different types of occipito-frontal spikes in childhood epilepsies. Although the term "occipito-frontal" is used to describe these spikes on the 10-20 EEG system, true propagation from occipital to frontal regions is not necessary. It is possible to differentiate idiopathic from symptomatic cases by analyzing the stability quotient and the occipito-frontal interval of occipito-frontal spikes.

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.

Classification of electrical status epilepticus in sleep based on EEG patterns and spatiotemporal mapping of spikes

Objective: We firstly aimed to describe and classify EEG patterns in electrical status epilepticus in sleep (ESES), and secondly subclassify EEG patterns based on analysis of spikes using spatio-temporal mapping and electrical source analysis. Methods: Overnight EEGs (minimum: eight hours) of 30 children, aged 2-12 years, with ESES (spike-wave index: at least 50%) were selected. Average reference montage was used for dipole analysis and mapping. The location and orientation of the dipoles were determined by mapping positive and negative poles and applying the rules of mapping. The onset and propagation of the spikes and the latency between the two hemispheres (for bisynchronous spikes) were determined (based on source analysis using BESA research 7.1). Results: (1) ESES was classified as "generalised" (80%) and focal (20%) patterns; (2) the bisynchronous subtype in the "generalised" pattern was due to apparently synchronous bilateral activation of spikes (with lead-in of 20-60 ms from one hemisphere) with a tangential/oblique dipole (source analysis localised these spikes to around the peri-rolandic cortex); (3) the classic description of ESES spikes as "diffuse" spikes with bifrontal maxima is a misinterpretation using the 10-20 EEG system .Using voltage mapping and source analysis, cortical activation in the rolandic cortex was identified which imparts diffuse frontal negativity and parieto-occipital positivity; (4) ESES spikes showed intraspike and interspike dipole instability and the orientation of dipoles changed due to local spike propagation around the source and into the depth of the sulcus (which we refer to herein as "dancing dipoles"); and (5) focal ESES were classified as parietal, occipital and temporo-occipital patterns;a frontal ESES pattern was not seen. Significance: Based on detailed mapping and source analysis of ESES, we have successfully reinterpreted various misconceptions in the literature. We have simplified the interpretation of complicated EEG patterns by extracting the primary and propagated sources which aid the classification of ESES. As the dipole is always stable in self-limited childhood epilepsy with centrotemporal spikes, we believe that the phenomenon of an intrinsically unstable dipole is a reliable qualitative EEG marker of ESES.

Impact of the COVID-19 Pandemic on the Frequency, Clinical Spectrum and Outcomes of Pediatric Guillain-Barré Syndrome in India: A Multicentric Ambispective Cohort Study.

Objective: To study impact of COVID-19 pandemic on frequency, clinical/electrophysiological profile and treatment outcomes in pediatric Guillain-Barré syndrome (GBS). Background: GBS is the most frequent cause of pediatric acute flaccid paralysis. The effect of the COVID-19 pandemic on pediatric GBS is unclear in the literature. Methods: We conducted an ambispective, multicentric, cohort study involving 12 of 27 centres in GBS Consortium, during two periods: pre-COVID-19 (March-August 2019) and during COVID-19 (March-August 2020). Children ≤12 years who satisfied National Institute of Neurological Diseases and Stroke criteria for GBS/variants were enrolled. Details pertaining to clinical/laboratory parameters, treatment and outcomes (modified Rankin Scale (mRS) at discharge, GBS Disability score at discharge and 3 months) were analysed. Results: We enrolled 33 children in 2019 and 10 in 2020. Children in 2020 were older (median 10.4 [interquartile range 6.75-11.25] years versus 5 (2.5-8.4) years; P = 0.022) and had more sensory symptoms (50% versus 18.2%; P = 0.043). The 2020 group had relatively favourable mRS at discharge (median 1 (1-3.5) versus 3 (2-4); P = 0.042) and GBS disability score at 3 months (median 0 (0-0.75) versus 2 (0-3); P = 0.009) compared to 2019. Multivariate analysis revealed bowel involvement (P = 0.000) and ventilatory support (P = 0.001) as independent predictors of disability. No child in 2020 had preceding/concurrent SARS-CoV2 infection. Conclusions: The COVID-19 pandemic led to a marked decline in pediatric GBS presenting to hospitals. Antecedent illnesses, clinical and electrophysiological profile of GBS remained largely unchanged from the pre-pandemic era.

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.

Impact of COVID-19 on Guillain-Barre Syndrome in India: A Multicenter Ambispective Cohort Study.

Introduction/Aims: Studies conducted during the coronavirus disease 2019 (COVID-19) pandemic have reported varied data regarding the incidence of Guillain-Barre syndrome (GBS). The present study investigated demographic and clinical features, management, and outcomes of patients with GBS during a specified period of the COVID-19 pandemic, and compared these features to those of GBS in the previous year. Methods: A multicenter, ambispective cohort study including 26 centers across India was conducted. Data from a pre-COVID-19 period (March 1 to August 31, 2019) were collected retrospectively and collected ambispectively for a specified COVID-19 period (March 1 to August 31, 2020). The study was registered with the Clinical Trial Registry India (CTRI/2020/11/029143). Results: Data from 555 patients were included for analysis: pre-COVID-19 (n = 334) and COVID-19 (n = 221). Males were more commonly affected during both periods (male:female, 2:1). Gastroenteritis was the most frequent antecedent event in 2019 (17.4%), whereas fever was the most common event in 2020 (10.7%). Paraparesis (21.3% versus [vs.] 9.3%, P = 0.001) and sensory involvement (51.1% vs. 41.3%; P = 0.023) were more common during COVID-19 in 2020, whereas back pain (26.3% vs. 18.4%; P = 0.032) and bowel symptoms (20.7% vs. 13.7%; P = 0.024) were more frequent in the pre-COVID period. There was no difference in clinical outcomes between the two groups in terms of GBS disability score at discharge and 3 months after discharge. Independent predictors of disability in the pre-COVID period included areflexia/hyporeflexia, the requirementfor intubation, and time to bulbar weakness; in the COVID-19 period, independent predictors included time from onset to admission, intubation, and intubation requirement. The mortality rate was 2.3% during the entire study period (13/555 cases). Discussion: Results of this study revealed an overall reduction in the frequency of GBS during the pandemic. The lockdown likely reduced the risk for antecedent infections due to social distancing and improved hygiene, which may have resulted in the reduction of the frequency of GBS.

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.