Cardiac Rhythm Aberrations in Subacute Sclerosing Panencephalitis: Insights From Heart Rate Variability Analysis.

PURPOSE: Subacute sclerosing panencephalitis (SSPE) is a fatal neurological disorder resulting from persistent measles virus infection within the brain. Although neurological manifestations have been well-documented, the impact of SSPE on cardiac autonomic function, assessed through heart rate variability (HRV), remains understudied. METHODS: In this prospective single-center study conducted from January 2022 to March 2023 in Southern India, 30 consecutive SSPE patients and age- and sex-matched controls underwent electrocardiogram recordings for HRV analysis. Various HRV parameters were assessed, including time-domain metrics (SD of normal-to-normal intervals, root mean square of successive differences between normal heartbeats, percentage of successive normal interbeat intervals greater than 50 msec), SD1 and SD2 for Poincaré plot analysis, and frequency-domain metrics (low frequency %, high frequency %, low frequency:high frequency ratio). RESULTS: In the study, SSPE patients exhibited markedly reduced HRV. Specifically, SD of normal-to-normal intervals (P = 0.003), percentage of successive normal interbeat intervals greater than 50 msec (P = 0.03), and SD2 (P = 0.0016) were significantly lower compared with controls. Frequency-domain analysis did not reveal significant distinctions. Correlation analysis demonstrated a negative relationship between percentage of successive normal interbeat intervals greater than 50 msec and SSPE severity (r = -0.37, P = 0.042). Heart rate variability did not significantly differ between SSPE stages or with clinical variables. The interbeat interval range showed a narrower distribution in SSPE subjects. CONCLUSIONS: Our study highlights the clinical relevance of HRV analysis in SSPE and autonomic dysfunction throughout the disease course underscoring its importance in SSPE. This investigation provides valuable insights into cardiac autonomic dysfunction probably because of affliction of the central autonomic networks caused by the disease process and may be a contributing factor to mortality in SSPE.

Variational mode decomposition-based EEG analysis for the classification of disorders of consciousness.

Aberrant alterations in any of the two dimensions of consciousness, namely awareness and arousal, can lead to the emergence of disorders of consciousness (DOC). The development of DOC may arise from more severe or targeted lesions in the brain, resulting in widespread functional abnormalities. However, when it comes to classifying patients with disorders of consciousness, particularly utilizing resting-state electroencephalogram (EEG) signals through machine learning methods, several challenges surface. The non-stationarity and intricacy of EEG data present obstacles in understanding neuronal activities and achieving precise classification. To address these challenges, this study proposes variational mode decomposition (VMD) of EEG before feature extraction along with machine learning models. By decomposing preprocessed EEG signals into specified modes using VMD, features such as sample entropy, spectral entropy, kurtosis, and skewness are extracted across these modes. The study compares the performance of the features extracted from VMD-based approach with the frequency band-based approach and also the approach with features extracted from raw-EEG. The classification process involves binary classification between unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS), as well as multi-class classification (coma vs. UWS vs. MCS). Kruskal-Wallis test was applied to determine the statistical significance of the features and features with a significance of p < 0.05 were chosen for a second round of classification experiments. Results indicate that the VMD-based features outperform the features of other two approaches, with the ensemble bagged tree (EBT) achieving the highest accuracy of 80.5% for multi-class classification (the best in the literature) and 86.7% for binary classification. This approach underscores the potential of integrating advanced signal processing techniques and machine learning in improving the classification of patients with disorders of consciousness, thereby enhancing patient care and facilitating informed treatment decision-making.

Phenotypic features of epilepsy due to sodium channelopathies - A single center experience from India.

Objectives: Nearly 40% of pediatric epilepsies have a genetic basis. There is significant phenotypic and genotypic heterogeneity, especially in epilepsy syndromes caused by sodium channelopathies. Sodium channel subunit 1A (SCN1A)-related epilepsy represents the archetypical channel-associated gene that has been linked to a wide spectrum of epilepsies of varying severity. Subsequently, other sodium channels have also been implicated in epilepsy and other neurodevelopmental disorders. This study aims to describe the phenotypes in children with sodium channelopathies from a center in Southern India. Materials and Methods: This is a retrospective, descriptive, and single-center study. Out of 112 children presenting with epilepsy who underwent genetic testing between 2017 and 2021, 23 probands (M: F = 12:11) were identified to have clinically significant sodium channel mutations. Clinical presentation, electroencephalography, and imaging features of these patients were recorded. The utility of genetic test results (e.g., in planning another child, withdrawal of medications, or change in treatment) was also recorded. Results: Age at onset of seizures ranged from day 4 of life to 3.5 years. Clinical epilepsy syndromes included generalized epilepsy with febrile seizures plus (n = 3), Dravet syndrome (n = 5), early infantile epileptic encephalopathy (n = 7), drug-resistant epilepsy (n = 5), and epilepsy with associated movement disorders (n = 3). The most common type of seizure was focal with impaired awareness (n = 18, 78.2%), followed by myoclonic jerks (n = 8, 34.78%), epileptic spasms (n = 7, 30.4%), bilateral tonic-clonic seizures/generalized tonic-clonic seizures (n = 3, 13%), and atonic seizures (n = 5, 23.8%). In addition to epilepsy, other phenotypic features that were discerned were microcephaly (n = 1), cerebellar ataxia (n = 2), and chorea and dystonia (n = 1). Conclusion: Sodium channelopathies may present with seizure phenotypes that vary in severity. In addition to epilepsy, patients may also have other clinical features such as movement disorders. Early clinical diagnosis may aid in tailoring treatment for the given patient.

Mastoid fluid signal in acute cerebral venous thrombosis is is associated with increased clot burden.

PURPOSE: Mastoid air cell abnormalities in the form of hyperintense T2 fluid signal have been reported in cases of acute Cerebral Venous Thrombosis (CVT) without otologic infection and have been hypothesized to be a result of venous congestion rather than infectious mastoiditis. The aim of this study was to investigate a link between the spectrum of mastoid abnormalities and clot burden in patients with acute CVT. METHODS: A retrospective study of adult patients admitted to the National Institute of Mental Health and Neurosciences between 2016 and 2023 who were diagnosed with acute CVT and had no clinical evidence of active or recent ear infections was conducted. Pre- and post-contrast MR Images were analyzed to identify the dural sinuses and/or cerebral veins involved and the presence of fluid signal in the mastoid. Fluid signal in the mastoid was graded from 0 to 3 as described by Shah et al- no fluid signal (grade 0), thin curvilinear hyperintensities (grade 1), thick crescenteric hyperintensities (grade 2), and complete hyperintensity (grade 3). Clot Burden Score (CBS) was calculated by assigning one point for each sinus involved, one point for extension of thrombus into the intracranial Internal Jugular Vein (IJV), one point for thrombosis of cortical veins and one point for thrombosis of deep cerebral veins. RESULTS: A total of 89 patients with acute CVT were included in the final analysis. Median time from presentation to MRI was 2 days (range 0-13). 51 patients (57.3%) had fluid signal in the mastoid air cells on T2-weighted images, of whom 33 showed mucosal contrast enhancement. Higher grade of fluid signal in the mastoid was present ipsilateral to the side of venous thrombosis in 59 out of 60 patients with posterior fossa CVT. CBS was significantly different between patients with different grades of fluid signal (p = 0.002). Grade 2-3 fluid signal was associated with higher clot burden (CBS > 3) in both the entire study population (n = 89) - OR = 8.281, 95 %CI: 2.758-24.866 (p < 0.001) and among patients with posterior fossa CVT - OR = 4.375, 95 %CI: 1.320-14.504 (p = 0.016). Among patients with posterior fossa CVT, grade 2-3 fluid signal was associated with left sided transverse and/or sigmoid sinus thrombosis - OR = 5.600, 95 %CI: 1.413-22.188 (p = 0.014), and extension of thrombosis into the IJV - OR = 4.606, 95 %CI: 1.162-18.262 (p = 0.030). CONCLUSION: T2 fluid signal in the mastoid is associated with venous congestion in adults with acute CVT without evidence of otologic infection. Moderate-to-severe T2 fluid signal in the mastoid air cells is associated with increased clot burden.

Resting-State Functional MRI/PET Profile as a Potential Alternative to Tri-Modality EEG-MR/PET Imaging: An Exploratory Study in Drug-Refractory Epilepsy.

Objective The study explores whether the epileptic networks associate with predetermined seizure onset zone (SOZ) identified from other modalities such as electroencephalogram/video electroencephalogram/structural MRI (EEG/VEEG/sMRI) and with the degree of resting-state functional MRI/positron emission tomography (RS-fMRI/PET) coupling. Here, we have analyzed the subgroup of patients who reported having a seizure on the day of scan as postictal cases and compared the findings with interictal cases (seizure-free interval). Methods We performed independent component analysis (ICA) on RS-fMRI and 20 ICA were hand-labeled as large scale, noise, downstream, and epilepsy networks (Epinets) based on their profile in spatial, time series, and power spectrum domains. We had a total of 43 cases, with 4 cases in the postictal group (100%). Of 39 cases, 14 cases did not yield any Epinet and 25 cases (61%) were analyzed for the final study. The analysis was done patient-wise and correlated with predetermined SOZ. Results The yield of finding Epinets on RS-fMRI is more during the postictal period than in the interictal period, although PET and RS-fMRI spatial, time series, and power spectral patterns were similar in both these subgroups. Overlaps between large-scale and downstream networks were noted, indicating that epilepsy propagation can involve large-scale cognition networks. Lateralization to SOZ was noted as blood oxygen level-dependent activation and correlated with sMRI/PET findings. Postoperative surgical failure cases showed residual Epinet profile. Conclusion RS-fMRI may be a viable option for trimodality imaging to obtain simultaneous physiological information at the functional network and metabolic level.

Response to Steroids in IQSEC2-Related Encephalopathy Presenting with Rett-Like Phenotype and Infantile Spasms.

Introduction IQSEC2-related encephalopathy is an X-linked childhood neurodevelopmental disorder with intellectual disability, epilepsy, and autism. This disorder is caused by a mutation in the IQSEC2 gene, the product of which plays an important role in the development of the central nervous system. Case Report We describe the symptomatology, clinical course, and management of a 17-month-old male child with a novel IQSEC2 mutation. He presented with an atypical Rett syndrome phenotype with developmental delay, autistic features, midline stereotypies, microcephaly, hypotonia and epilepsy with multiple seizure types including late-onset infantile spasms. Spasms were followed by worsening of behavior and cognition, and regression of acquired milestones. Treatment with steroids led to control of spasms and improved attention, behavior and recovery of lost motor milestone. In the past 10 months following steroid therapy, child lags in development, remains autistic with no further seizure recurrence. Conclusion IQSEC2-related encephalopathy may present with Rett atypical phenotypes and childhood spasms. In resource-limited settings, steroids may be considered for spasm remission in IQSEC2-related epileptic encephalopathy.

Efficacy of pulse intravenous methylprednisolone in epileptic encephalopathy: a randomised controlled trial.

BACKGROUND: High-level evidence for using steroids in epileptic encephalopathy (EE), other than West syndrome (WS), is lacking. This study investigated the efficacy and safety of pulse intravenous methylprednisolone (IVMP) in EE other than WS. METHODS: This is an open-label evaluator-blinded randomised controlled study. Children aged 6 months or more with EE other than WS were included. Eighty children were randomised into intervention and non-intervention groups with 40 in each group. At the first visit (T1) seizure frequency, electroencephalographic (EEG) and Vineland Social Maturity Scale (VSMS) were obtained, and antiseizure medication (ASM) were optimised. After 1 month (T2), subjects were randomised to intervention (ASM+3 months IVMP pulse) or non-intervention group (only ASM) with 40 subjects in each group. They were followed up for 4 months (T3) and assessed. RESULTS: After 4 months of follow-up, 75% of patients receiving IVMP had >50% seizure reduction versus 15.4% in control group (χ2=28.29, p<0.001) (RR 4.88, 95% CI 2.29 to 10.40), median percentage change in seizure frequency (91.41% vs 10%, p<0.001), improvement in EEG (45.5% vs 9.4%, χ2=10.866, p=0.001) and social age domain of VSMS scores (Z=-3.62, p<0.001) compared with baseline. None of the patients in the intervention group had any serious side-effects. DISCUSSION: Three-month pulse IVMP therapy showed significant improvement in seizure frequency, EEG parameters and VSMS scores, with no steroid-related serious adverse effects. It can be considered as a safe and effective add on treatment in children with EE other than WS. TRIAL REGISTRATION NUMBER: CTRI/2019/02/017807.

Network alterations in eating epilepsy during resting state and during eating using Magnetoencephalography.

OBJECTIVE: Eating epilepsy presents various imaging and electrophysiological features along with various seizure triggers. As such, network changes in eating epilepsy have not been comprehensively explored. This study was conducted to illustrate resting state network changes in eating epilepsy and to study the changes in network configurations during eating. METHODS: Magnetoencephalography recordings of nineteen patients with drug-resistant eating epilepsy were compared with healthy controls during resting state. A subgroup of nine patients and 12 controls had MEG recordings during eating. Network changes were analyzed using phase lag index across 5 frequency bands [delta, theta, alpha, beta, and gamma] using clustering coefficient (CC), betweenness centrality (BC), path length (PL), modularity (Q), and small worldness (SW). RESULTS: During the resting state, PL was decreased in patients with epilepsy in the delta, theta, and gamma band. Q was lower in patients with epilepsy in the beta and gamma bands. During eating, in patients with epilepsy, PL and SW were increased in all frequency bands, and Q was decreased in the beta band and increased in the rest of the frequency bands. Patients with mixed types of seizures showed higher PL in all bands except alpha, higher Q in all bands, and higher SW in the alpha and beta bands. Node-wise changes in CC and BC implicated changes in DMN and 'eating' networks. CONCLUSION: Reflex Eating epilepsy presents with a hyperconnected network that exacerbates during eating. The cause of seizure onset and loss of consciousness in eating epilepsy might be due to aberrant network interaction between the regions of the brain involved with eating, such as the sensorimotor cortex, lateral parietal cortex, and insula with the limbic cortex and default mode network across multiple frequency bands.

The Spectrum of Neuro-COVID: A Study of a Comprehensively Investigated Large Cohort from India.

Background: Though reports of neurological manifestations of COVID-19 have emerged from various parts of the world, the cohorts reported are from the West and mostly derived from electronic databases. Much remains unknown regarding neuro-COVID in developing countries. India is the second-worst affected country, and this study reports the neurological manifestations of COVID-19 in a comprehensively evaluated cohort. Objective: The aim of this study was to describe the range of neurological manifestations of COVID-19 in India with an emphasis on the risk factors, laboratory and imaging findings and short-term outcome. Methods: Retrospective review of hospital records of all confirmed COVID-19 patients with neurological manifestations, receiving inpatient care in two neurology referral hospitals were done. All demographic, clinical details, investigations, and treatment were analysed. Results: A total of 120 confirmed COVID-19 cases presenting with neurological symptoms were included. The mean age of illness and duration of illness was 48.03 ± 17.3 years and 10.9 ± 17.3 days respectively. New onset of neurological symptoms occurred in 100 cases while 20 patients had worsening of pre-existing neurological illness. Stroke was the commonest neurological disorder (43%), followed by encephalopathy (23%) and Guillain-Barre syndrome (10%). Other unusual neurological manifestations included new-onset headache (7%), seizures including denovo status epilepticus (5%) and meningo-encephalitis (5%). Nearly half of the patients had preceding COVID-19 symptoms. Poor outcome at discharge was seen in 40% and mortality occurred in 15%. Conclusion: Stroke and encephalopathy constitute the most common neurological manifestations. The absence of preceding COVID-19 symptoms in nearly half the cases is striking. Poor outcome was seen in nearly 50% despite early recognition and management.

FDG-PET in Autoimmune Encephalitis: Utility, Pattern of Abnormalities, and Correlation with Autoantibodies.

Background: Fluorodeoxyglucose-positron emission tomography (FDG-PET) in autoimmune encephalitis (AE) as an adjunctive investigation helps in characterizing the type of AE based on characteristic metabolic patterns. Objectives: We aimed to study the following: (i) the sensitivity of FDG-PET in the diagnosis of AE, (ii) describe abnormal patterns of metabolism of various subtypes of AE, and (iii) correlate serum serology with FDG-PET abnormalities. Materials and Methods: This study was conducted at a tertiary university hospital in South India. The demographic profile, clinical features, and investigations (FDG-PET, magnetic resonance imaging (MRI) brain, electroencephalography (EEG), cerebrospinal fluid (CSF)) were reviewed. The nuclear medicine physician performed blinded qualitative visual and semi-quantitative analysis of the 18-FDG-PET (fluorine 18-FDG-PET) findings of these patients. Results: Twenty-nine (M:F: 11:18) patients were recruited; among them, 22 (75.8%) patients had autoimmune antibodies; the rest seven (24.1%) patients were seronegative. Among the 22 seropositive patients, 9 (31%) patients were positive for anti-N-methyl-D-aspartate receptor (NMDAR), 8 (28%) for anti-leucine-rich glioma inactivated 1 (LGI-1), 4 (14%) for anti-contactin-associated protein 2 (CASPR2), 1 (3%) for anti-glutamic acid decarboxylase (GAD)-65, and rest 7 (24%) patients were seronegative. The patterns most commonly observed were isolated hypermetabolism (41%), isolated hypometabolism (41%), and combined hypermetabolism with hypometabolism (18%). The fraction of abnormalities was lower for MRI (17/22; 73.9%) than for FDG-PET (27/29; 93.1%). FDG-PET correlated with serology in 10 (34%) cases [NMDAR: 6 (60%) and LGI-1: 4 (40%)]. The sensitivity of FDG-PET was 94.1% when compared with MRI. Discussion and Conclusion: FDG-PET correlated with serology in only one-third of patients. The most consistent pattern in both seropositive and seronegative AE is characterized by parieto-occipital hypometabolism and fronto-temporal with basal ganglia hypermetabolism.

Clinical spectrum of pediatric drug refractory epilepsy secondary to parieto-occipital gliosis.

BACKGROUND: Parieto-occipital (PO) gliosis secondary to perinatal insult, is often associated with neurologic sequelae such as epilepsy, which can be drug resistant. OBJECTIVE: To evaluate the spectrum of epilepsy among patients presenting with seizures in association with PO gliosis and to determine factors that influence the development of epileptic encephalopathy (EE) in these patients. METHODS: We retrospectively evaluated patients aged < 16 years with drug refractory epilepsy and PO gliosis who underwent video electroencephalography (Video EEG). We evaluated the clinical, electrophysiological and radiological profile including treatment responsiveness of subjects with EE. RESULTS: One hundred one patients (M: F=3:1) with mean age of onset of epilepsy at 28.9 ± 33.1 months were recruited into the study. Based on video EEG findings, Based on video EEG findings, the commonest type of focal onset ictus was tonic seizures with impaired awareness (n = 26, 29.9%). Myoclonic jerks (n = 20, 23%) were the commonest type of generalised onset seizures. Ictal onset from parieto occipital region were observed in 28 patients. Ictal onset from frontal, temporal and fronto temporal region were observed in 6 (6.8%), 7(7.9%) and 9 (8.9%) patients, respectively. Comparison of the seizure types and ictal onset among subgroups of patients with occipital gliosis, parieto-occipital gliosis and parieto-occipital with frontal gliosis revealed that the extent of gliosis did not significantly affect seizure semiology or ictal onset. EE was significantly associated with presence of neonatal seizures (p = 0.04), hypoglycaemia (p = 0.005), longer duration of ICU stay (Z score = -3.55, p < 0.001) and younger age of onset of seizures (Z score = - 2.97, p = 0.03). Eleven out of eighteen (64.7%) subjects with EE showed greater than 50% improvement in seizure frequency following three months of pulse intravenous methylprednisolone therapy. CONCLUSIONS: Among subjects with PO gliosis on MRI, the seizure semiology is unaffected by laterality, radiologic extension beyond the occipital cortex or presence of ulegyria. Patients with PO gliosis can have florid interictal epileptiform discharges anteriorly and can have seizures with ictal onset from frontal and temporal region. Development of EE is strongly related to the age of onset of seizures, neonatal seizures, prolonged NICU admission, rather than the radiological findings. Subjects with EE and PO gliosis show good response to intravenous pulse methylprednisolone.

EEG-based P300 in mesial temporal lobe epilepsy and its correlation with cognitive functions: A case-control study.

OBJECTIVE: P300 is an event-related potential, being explored as an objective tool to assess cognition. This study aimed to investigate the characteristics of auditory and visual P300 in patients with TLE having unilateral HS using electroencephalography (EEG) and to study its correlation with cognition. METHODS: This is a cross-sectional case-control study, where P300 characteristics in thirty patients with unilateral hippocampal sclerosis with refractory epilepsy were compared with fifteen age-, gender-, and years of education-matched healthy controls (M: F-10:5, mean age-28 ±â€¯4.76 years). Among patients, 15 belonged to the right HS group (M: F-9:6, age at onset-12.92 ±â€¯10.22 years, duration of epilepsy-16.67 ±â€¯9.38 years) and 15 to the left HS group (M: F-8:7, age at onset-10.62 ±â€¯7.18 years, duration of epilepsy-15.53 ±â€¯10.14 years). All subjects underwent EEG-based auditory and visual oddball tasks and cognitive assessment. The P300 latencies (in milliseconds) as well as amplitudes (in microvolts) were predicted in EEG and were correlated with cognitive scores. Source localization of P300 was performed with the CLARA algorithm. RESULTS: The auditory P300 latencies in controls, right HS, and left HS were 323.93 ±â€¯40.28, 351.06 ±â€¯47.23, and 328.80 ±â€¯36.03, respectively (p = 0.18) and its amplitudes were 2.3040 ±â€¯1.46, 2.77 ±â€¯1.19, and 2.68 ±â€¯1.78, respectively (p = 0.48). Visual P300 latencies in controls, right HS, and left HS were 365.87 ±â€¯47.37, 359.67 ±â€¯64.45, and 376.00 ±â€¯60.06, respectively (p = 0.51) and its amplitudes were 3.93 ±â€¯2.28, 2.09 ±â€¯1.45, and 3.56 ±â€¯1.74, respectively (p = 0.014). Further, when compared to the control group the cognitive scores were lower in the patient group (p < 0.05). SIGNIFICANCE: In comparison to the controls, patients with right HS recorded lesser amplitude on visual P300 and lower scores on cognitive tests. P300 and cognitive parameters exhibited varied relationship. P300 could be a complementary objective tool to assess cognition in patients with TLE.

Altered vascular permeability but not angiogenesis may play a role in the epileptogenesis of human hippocampal sclerosis.

OBJECTIVE: We investigated the role of angiogenesis and vascular permeability in the pathogenesis of human drug-resistant epilepsy due to hippocampal sclerosis. METHODS: Resected hippocampi from 30 histologically confirmed cases of hippocampal sclerosis and 30 age-matched post-mortem controls were examined by immunohistochemical quantitation of vascular endothelial markers, CD31 and CD105 (markers of newly formed vessels), and data were analysed relative to MR volumetry. The blood-brain barrier was evaluated based on immunohistochemistry for IgG, albumin, VEGF and AQP4. RESULTS: Mean vascular density in the hippocampus was 8.71/mm2 in hippocampal sclerosis samples compared to 7.94/mm2 in age-matched controls. No statistically significant increase in vascular density was found in hippocampal sclerosis samples. Although no neoangiogenesis was found in hippocampal sclerosis samples based on CD105, breakdown of the blood-brain barrier, enhanced neuronal expression of VEGF, and perivascular seepage of IgG and albumin with uptake within neurons and astrocytes were found. Redistribution of the water channel protein, AQP4, reflected by change from normal punctate labelling to intense diffuse staining in hippocampal sclerosis samples, indicated an altered glia-vascular interface, disrupting blood-brain barrier permeability. SIGNIFICANCE: Our data show no objective histological evidence of angiogenesis in hippocampal sclerosis samples. When controlled for the confounding variable of hippocampal area, there was no difference in vascular density between cases and controls. A leaky blood-brain barrier and redistribution of AQP4 were identified which may contribute to epileptogenesis. This constitutes the largest study in the published literature evaluating a role of vascular permeability and angiogenesis in human hippocampal sclerosis.