Insights from Magnetic Evoked Field Analysis in Patients with Wilson's Disease.

Aims: To study the latency, amplitude, and source localization of magnetic evoked field (MEF) responses to visual, auditory, and somatosensory stimuli in Wilson's disease (WD) using magnetoencephalography (MEG) and compare it with "healthy" controls, and correlate the observations with disease severity and brain MRI. Methods: MEF of 28 patients with neurological WD (age: 22.82 ± 5.8 years; M:F = 12:16) and 21 matched controls (age: 25.0 ± 4.6 years; M:F = 10:11) were recorded using MEG. Source localization was performed using standard models on the components of M100, M20, and M100 for visual, somatosensory, and auditory evoked fields, respectively and its latency/amplitude was correlated with disease severity. Results: There were significant differences in source location between control and WD during visual evoked field (VEF) and auditory evoked field (AEF) studies. Latencies of M20 (right-p = 0.02; left-p = 0.04) and M32 (right-p = 0.01) components of SSEF were significantly prolonged. The amplitude of M20 was significantly reduced in patients bilaterally (P = 0.001). There was a trend for the prolonged latency of M100 of VEF in patients (P = 0.09). Five patients had reduced right M145 compared to 8 controls. The left somatosensory evoked fields (SSEF) latency correlated with disease severity (P = 0.04). There was no significant correlation between major components of other MEF with disease severity or MRI score. Conclusions: This study, first of its kind to use MEF analysis in a large cohort of patients with WD, detected subclinical but a variable degree of abnormalities, most consistently of SSEF. It provides valuable insights of functioning and localization of various pathways in a disease known to have protean clinical manifestations and widespread MRI changes.

A real world multi center study on efficacy and safety of natalizumab in Indian patients with multiple sclerosis.

BACKGROUND: Natalizumab (NTZ) is increasingly being used in Indian multiple sclerosis (MS) patients. There are no reports on its safety and efficacy, especially with respect to the occurrence of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: To describe the patient characteristics, treatment outcomes, and adverse events, especially the occurrence of PML in NTZ-treated patients. METHODS: A multicentre ambispective study was conducted across 18 centres, from Jan 2012 to Dec 2021. Patients at and above the age of 18 years treated with NTZ were included. Descriptive and comparative statistics were applied to analyze data. RESULTS: During the study period of 9 years, 116 patients were treated with NTZ. Mean age of the cohort was 35.6 ± 9.7 years; 83/116 (71.6%) were females. Relapse rate for the entire cohort in the year before NTZ was 3.1 ± 1.51 while one year after was 0.20±0.57 (p = 0.001; CI 2.45 -3.35). EDSS of the entire cohort in the year before NTZ was 4.5 ± 1.94 and one year after was 3.8 ± 2.7 (p = 0.013; CI 0.16-1.36). At last follow up (38.3 ± 22.78 months) there were no cases of PML identified. CONCLUSIONS: Natalizumab is highly effective and safe in Indian MS patients, with no cases of PML identified at last follow up.

Posterior Quadrant Disconnection for Childhood Onset Sub-Hemispheric Posterior Head Region Epilepsy: Indications in an Indian Cohort and Outcome.

BACKGROUND: Posterior quadrant disconnection (PQD) is an under-utilized surgical technique in the management of refractory epilepsy. There is a dearth of data pertinent to post-PQD seizure outcomes. METHODS: This retrospective study analyzed patients with drug-resistant childhood-onset epilepsy who underwent PQD at our center from 2009 to 2018. The clinical, imaging, and electrophysiological data were reviewed. The seizure outcome was noted from the latest follow-up in all patients. RESULTS: Fifteen patients underwent PQD, with a mean age at onset of epilepsy of 3.3 ± 4.6 years. All patients had seizure onset in childhood with focal onset of seizures, and in addition, 5 had multiple seizure types. All cases underwent presurgical workup with MRI, video-EEG, psychometry, while PET/MEG was done if required. Engel Ia and ILAE I outcomes were considered to be favorable. The histology of the specimen showed 9 patients (60%) had gliosis, 4 (26.7%) had focal cortical dysplasia (FCD), while 1 patient had nodular heterotopia and another had polymicrogyria-pachygyria complex. Postoperative follow-up was available in 14 cases. One patient was lost to follow-up. Mean follow-up duration for the cohort was 45 + 24 months. At last, follow-up (n = 14), 66.7% (10 cases) had favorable outcome (Engel Ia). At the end of 1-year follow-up, up to 73% (n = 11) of the patients were seizure-free. Four patients developed transient hemiparesis after surgery which improved completely by 3-6 months. CONCLUSIONS: Gliosis was more common etiology requiring PQD in our series than Western series, where FCD was more common. PQD is a safe and effective surgical modality in childhood-onset epilepsy with posterior head region epileptogenic focus.

Cortical-Subcortical morphometric signature of hot water epilepsy patients.

BACKGROUND: Cortical and subcortical grey matter (GM) morphometric changes have been demonstrated Temporal Lobe Epilepsy (TLE) or Idiopathic Generalized Epilepsies (IGE). Hot Water Epilepsy (HWE) has not hitherto been studied in these perspectives. PURPOSE: To investigate the cortical and subcortical grey matter in subjects with HWE in terms of thickness, volume, and surface area using Surface-Based Morphometry (SBM). To assess relationships of SBM-derived metrics with clinical variables. MATERIALS AND METHODS: Ninety-nine people with HWE and 50 age-matched healthy controls underwent high resolution volumetric MRI brain. These were processed with FreeSurfer to obtain SBM parameters i:e cortical thickness, cortical volume, and Cortical surface area. Volumes of seven subcortical GM structures (hippocampus, globus pallidus, nucleus ambiguous(NA), caudate nucleus, putamen, thalamus, and amygdala) were computed. Intergroup morphometric differences and their correlation with epilepsy-specific clinical variables were calculated. RESULTS: SBM revealed a global reduction in bihemispheric cortical thickness and left hemispheric cortical volume. Besides, a regional difference in the morphometric measures was noted in temporo-limbic, parietal, pre-cuneus, and the cingulate region. Reduced volume of thalami and left caudate alongside an increased volume of the bilateral amygdala, bilateral nucleus ambiguous (NA), right caudate, and putamen was the other cardinal observation. CONCLUSION: HWE subjects show alterations in the morphometry of the cortical ribbon and the subcortical grey matter. The temporal semiology, 'reflex nature' pathophysiology correlates involvement of temporo-limbic structures/somatosensory cortex, while the involvement of structures like pre-cuneus, posterior cingulate, and frontal regions are in agreement with functional networks related loss of awareness. That bilateral amygdala swelling occurs in HWE is a novel observation and may signal that it could be a distinct variant of Mesial TLE.

Alteration of T Cell Phenotypes in HIV-Neurotuberculosis Coinfection.

BACKGROUND: Neurotuberculosis is one of the commonest HIV associated opportunistic infections of the central nervous system in India. HIV-TB coinfection may lead to altered frequencies of T cells, thereby influencing the course and progression of the disease. METHODS: We examined the frequencies of T cell subsets in HIV infected individuals with neurotuberculosis (HIV+nTB+) as compared to individuals with HIV associated systemic TB (HIV+sTB+), asymptomatic HIV (HIV+TB-), non-HIV neuro TB (HIV-nTB+), non-HIV systemic TB (HIV-sTB+), and healthy controls (HIV-TB-). Activation and senescence profiles of CD4 and CD8 T cells and memory subsets in peripheral blood mononuclear cells were studied by flow cytometry. RESULTS: The significant observations among the T cell subsets in HIV+nTB+ were: (1) Naïve T cells: decreased CD4 T cells compared to HIV-sTB+ (P = 0.005); decreased CD8 T cells compared to HIV-nTB+ and HIV-TB- (P ≤ 0.007), (2) Memory T cells: expanded CD4 TEMRA cells compared to HIV-nTB+, HIV-sTB+, and HIV-TB- (P ≤ 0.003); expanded CD8 TEMRA cells compared to HIV-nTB+ and HIV-TB- (P ≤ 0.005), (3) Activated T cells: higher CD4 T cells compared to HIV-nTB+, HIV-sTB+, and HIV-TB- (P ≤ 0.004); higher CD8 T cells compared to HIV + TB-, HIV-nTB+, HIV-sTB+, and HIV-TB- (P ≤ 0.001), and (4) Senescent T cells: increased CD8 T cells compared to HIV-nTB+ and HIV-TB- groups (P = 0.000). CONCLUSIONS: Increased activation compared to HIV+TB-, HIV-nTB+, HIV-sTB+, and HIV-TB- groups and increased senescence compared to HIV-nTB+ and HIV-TB- groups were observed in CD8 T cells in HIV+nTB+, suggesting that the frequencies of these T cell subsets are altered to a greater extent in these individuals. © 2018 International Clinical Cytometry Society.

Epilepsy surgery for focal cortical dysplasia: Seizure and quality of life (QOLIE-89) outcomes.

AIM: Surgery for drug resistant epilepsy (DRE) with focal cortical dysplasia (FCD) often requires multiple non-invasive as well as invasive pre-surgical evaluations and innovative surgical strategies. There is limited data regarding surgical management of people with FCD as the underlying substrate for DRE among the low and middle-income countries (LAMIC) including India. METHODOLOGY: The presurgical evaluation, surgical strategy and outcome of 52 people who underwent resective surgery for DRE with FCD between January 2008 and December 2016 were analyzed. The 2011 classification proposed by Blumcke et al., was used for histo-pathological categorization. The Engel classification was used for defining the seizure outcome. The surgical outcome was correlated with the preoperative clinical presentation, video encephalogram (VEEG) recording, magnetic resonance imaging (MRI), invasive monitoring, surgical findings as well as histopathology and the quality of life in epilepsy (QOLIE)- 89 scores. RESULTS: Fifty-two patients underwent resective surgery for FCD (mean age at onset of seizure: 7.94 ± 6.23 years; duration of seizures prior to surgery: 12.95 ± 9.56 years; and, age at surgery: 20.88 ± 12.51 years). The following regional distribution was found; temporal-24 (language-13), frontal-15 (motor cortex- 5), parietal-5 (sensory cortex-4), occipital-1 and multilobar-7. Forty-seven percent of the cases had FCD in the right hemisphere and 53% had FCD in the left hemisphere. Invasive monitoring was performed for identification of the epileptogenic zone (EZ) as well as eloquent cortex in 7 cases and an intra-operative electro-corticography (ECoG) was used in 32 cases. Histopathology revealed the following distribution; FCD IA-4, IB- 1, IC-5, IIA-8, IIB-18, IIIA-13, IIIB -1, IIIC-1 and IIID-1. After a median follow up of 3.7 years after surgery, 84% of patients had Engel's Ia outcome. QOLIE-89 scores improved from 38.33 ± 4.7 (31.14-49.03) before surgery to 75.21 ± 8.44 (56.49-90.49) after surgery (P < 0.001). The younger age of the patient (<20 years) at surgery (P = 0.013), a lower pre-operative score (<9) on seizure severity scale (P = 0.012), focal discharges without propagation on ictal VEEG (P < 0.001), absence of acute post-operative seizures (P < 0.001) and Type II FCD (P = 0.045) were the significant predictors for a favorable seizure outcome. CONCLUSION: Surgical management of people with DRE and FCD is possible in countries with limited resources. Meticulous pre-surgical evaluation to localize the epileptogenic zone and complete resection of the focus and lesion can lead to the cure or control of epilepsy; and, improvement in the quality of life was observed along with seizure-free outcome.

A Comparative Study of Midazolam and Target-Controlled Propofol Infusion in the Treatment of Refractory Status Epilepticus.

BACKGROUND: The recommended treatment for refractory status epilepticus (RSE) is the use of anesthetic agents, but evidence regarding the agent of choice is lacking. This study was designed to compare target-controlled infusion of propofol versus midazolam for the treatment of RSE regarding seizure control and complications. METHODS: This prospective, randomized study recruited 23 adult patients with RSE due to any etiology and treated with either propofol or midazolam titrated to clinical seizure cessation and gradual tapering thereafter. The primary outcome measure was seizure control and the secondary outcomes were duration of the Intensive Care Unit stay and duration of mechanical ventilation, occurrence of super RSE (SRSE), and complications. RESULTS: We recruited 23 patients (male:female = 18:5) into this study (propofol Group-11; midazolam Group-12). Overall, seizure control was noted in 34.8%, with successful seizure control in 45% of patients in the propofol group and 25% in midazolam group (P = 0.4). Mortality was similar in both the groups (propofol group [8/11; 72.7%] compared to the midazolam group [7/12; 58.3%] [P = 0.667]). The duration of hospital stay was significantly shorter in the propofol group compared to midazolam (P = 0.02). The overall incidence of SRSE was 69.5% in this study. The complication rate was not significantly different between the groups. CONCLUSIONS: The choice of anesthetic agent does not seem to affect the overall outcome in RSE and SRSE. Target-controlled propofol infusion was found to be equal in its efficacy to midazolam for the treatment of RSE. High mortality might be due to SRSE secondary to the underlying brain pathology.

Six decades of Neurology at NIMHANS: A historical perspective.

The Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka has a long tradition of excellence in education, teaching, research, and patient care. Its exceptional alumni, as well as current and past faculty members, have made considerable contributions to the development of neurological services throughout the world. The six decades of its existence have seen a momentous growth in clinical, investigative, and community Neurology. As a result of the immense scientific individual as well as collaborative contributions of the faculty members in various departments, the Institute has had the honour of attaining the status of an autonomous 'Institute of National Importance' under the Ministry of Health, Government of India, through a novel concept of collaboration and partnership of central and state governments. This article traces the dedicated pursuit of members of the Department of Neurology, NIMHANS, in managing neurologic diseases through compassionate patient-centred care, transformative research and education.

Pattern recognition receptor mRNA expression and cytokine and granzyme levels in HIV infected individuals with neurotuberculosis.

Neurotuberculosis is one of the commonest HIV-associated opportunistic infections (OI) of the CNS. Cross-talk between HIV, Mycobacterium tuberculosis and host immune responses may alter expression of pattern recognition receptors (PRRs), thereby affecting cytokine profiles and functional responses. We examined PRR mRNA expression and cytokine and granzyme levels in HIV infected individuals with neurotuberculosis and found significant downregulation of TLR9 and increased MDA5 expression compared to healthy subjects. Significantly higher Granzyme A and IFN-γ levels were also observed in the CSF of this group compared to CSF from non-infectious controls. These alterations may lead to inappropriate recruitment of immune cells to the CNS, leading to disease severity.

Rare SLC1A1 variants in hot water epilepsy.

Hot water epilepsy is sensory epilepsy, wherein seizures are triggered by an unusual stimulus: contact with hot water. Although genetic factors contribute to the etiology of hot water epilepsy, molecular underpinnings of the disorder remain largely unknown. We aimed to identify the molecular genetic basis of the disorder by studying families with two or more of their members affected with hot water epilepsy. Using a combination of genome-wide linkage mapping and whole exome sequencing, a missense variant was identified in SLC1A1 in a three-generation family. Further, we examined SLC1A1in probands of 98 apparently unrelated HWE families with positive histories of seizures provoked by contact with hot water. In doing so, we found three rare variants, p.Asp174Asn, p.Val251Ile and p.Ile304Met in the gene. SLC1A1 is a neuronal glutamate transporter which limits excitotoxicity and its loss-of-function leads to age-dependent neurodegeneration. We examined functional attributes of the variants in cultured mammalian cells. All three non-synonymous variants affected glutamate uptake, exhibited altered glutamate kinetics and anion conductance properties of SLC1A1. These observations provide insights into the molecular basis of hot water epilepsy and show the role of SLC1A1 variants in this intriguing neurobehavioral disorder.

Role of magnetoencephalography and stereo-electroencephalography in the presurgical evaluation in patients with drug-resistant epilepsy.

In selected patients with drug-resistant focal epilepsies (DRFE), who otherwise are likely to be excluded from epilepsy surgery (ES) because of the absence of a magnetic resonance imaging (MRI)-demonstrable lesion or discordant anatomo-electro-clinical (AEC) data, magnetoencephalography (MEG) may help to generate an AEC hypothesis and stereo-electroencephalography (SEEG) may help to verify the hypothesis and proceed with ES. The sensitivity of MEG is much better in localizing the spiking zone in relation to lateral temporal and extratemporal cortical regions compared to the mesial temporal structures. MEG has a dominant role in the presurgical evaluation of patients with MRI-negative DRFEs, insular epilepsies, and recurrent seizures after failed epilepsy surgeries, and in guiding placement of invasive electrodes. Moreover, postoperative seizure freedom is better if MEG spike source localized cortical region is included in the resection. When compared to subdural grid electrode recording, SEEG is less invasive and safer. Those who are otherwise destined to suffer from uncontrolled seizures and their consequences, SEEG guided ES is a worthwhile and a cost-effective option. Depending on the substrate pathology, there is > 80-90% chance of undergoing ES and 60-80% chance of becoming seizure-free following SEEG. Recent noninvasive techniques aimed at better structural imaging, delineating brain connectivity and recording specific intracerebral EEG patterns such as high frequency oscillations might decrease the need for SEEG; but more importantly, make SEEG exploration more goal-directed and hypothesis-driven.

Reduced small world brain connectivity in probands with a family history of epilepsy.

BACKGROUND AND PURPOSE: The role of inheritance in ascertaining susceptibility to epilepsy is well established, although the pathogenetic mechanisms are still not very clear. Interviewing for a positive family history is a popular epidemiological tool in the understanding of this susceptibility. Our aim was to visualize and localize network abnormalities that could be associated with a positive family history in a group of patients with hot water epilepsy (HWE) using resting-state functional magnetic resonance imaging (rsfMRI). METHODS: Graph theory analysis of rsfMRI (clustering coefficient γ; path length λ; small worldness σ) in probands with a positive family history of epilepsy (FHE+, 25) were compared with probands without FHE (FHE-, 33). Whether a closer biological relationship was associated with a higher likelihood of network abnormalities was also ascertained. RESULTS: A positive family history of epilepsy had decreased γ, increased λ and decreased σ in bilateral temporofrontal regions compared to FHE- (false discovery rate corrected P ≤ 0.0062). These changes were more pronounced in probands having first degree relatives and siblings with epilepsy. Probands with multiple types of epilepsy in the family showed decreased σ in comparison to only HWE in the family. CONCLUSION: Graph theory analysis of the rsfMRI can be used to understand the neurobiology of diseases like genetic susceptibility in HWE. Reduced small worldness, proportional to the degree of relationship, is consistent with the current understanding that disease severity is higher in closer biological relations.

Monitoring peri-ictal changes in heart rate variability, oxygen saturation and blood pressure in epilepsy monitoring unit.

PURPOSE: The peri-ictal autonomic disturbances have been studied as predictors of seizure outcome and as markers of seizure onset. We studied the changes in heart rate (HR), HRV, oxygen saturation and blood pressure (BP) in the peri-ictal period in patients with drug-resistant localization-related epilepsy. METHODOLOGY: Ninety one subjects undergoing video-EEG monitoring, underwent continuous HR, SpO2, BP and Lead II ECG monitoring. The changes during the preictal, ictal and postictal periods were analyzed for 57 seizures in 42 patients with artifact-free recordings and correlated with VEEG ictal onset and MRI characteristics. RESULTS: Ictal tachycardia was noted in 15 (26.3%) seizures, of which, 60% had temporal lobe onset. HR increased by an average of 20.1% from pre-ictal to ictal phases (p=0.04). Ictal bradycardia was noted in one event with right temporal seizure onset. Heart rate variability (HRV) analysis of the preictal, ictal and postictal phases showed an increase in the sympathetic and decrease in parasympathetic activity during the ictus with relatively preserved total power. Ictal oxygen desaturation (84.1%±3.5%) was noticed in 10 (17.5%) seizures. Ictal hypertension was observed in 15 (26.3%); ictal hypotension was noted in 5 (8.7%) seizures. Both the systolic BP and diastolic BPs increased from the pre-ictal to ictal phase (p=0.01). CONCLUSIONS: Peri-ictal dysautonomia can present in variable patterns and can be measured and compared over different modalities such as BP, HR and HRV. Though degree of tachycardia and increase in BP were higher during extratemporal onset of seizures, a fall in variability was noted in seizures of temporal lobe origin. Oxygen desaturation is not an uncommon event during the peri-ictal period in localization related epilepsy.

Combined MEG-EEG source localisation in patients with sub-acute sclerosing pan-encephalitis.

To study the genesis and propagation patterns of periodic complexes (PCs) associated with myoclonic jerks in sub-acute sclerosing pan-encephalitis (SSPE) using magnetoencephalography (MEG) and electroencephalography (EEG). Simultaneous recording of MEG (306 channels) and EEG (64 channels) in five patients of SSPE (M:F = 3:2; age 10.8 ± 3.2 years; symptom-duration 6.2 ± 10 months) was carried out using Elekta Neuromag(®) TRIUX™ system. Qualitative analysis of 80-160 PCs per patient was performed. Ten isomorphic classical PCs with significant field topography per patient were analysed at the 'onset' and at 'earliest significant peak' of the burst using discrete and distributed source imaging methods. MEG background was asymmetrical in 2 and slow in 3 patients. Complexes were periodic (3) or quasi-periodic (2), occurring every 4-16 s and varied in morphology among patients. Mean source localization at onset of bursts using discrete and distributed source imaging in magnetic source imaging (MSI) was in thalami and or insula (50 and 50 %, respectively) and in electric source imaging (ESI) was also in thalami and or insula (38 and 46 %, respectively). Mean source localization at the earliest rising phase of peak in MSI was in peri-central gyrus (49 and 42 %) and in ESI it was in frontal cortex (52 and 56 %). Further analysis revealed that PCs were generated in thalami and or insula and thereafter propagated to anterolateral surface of the cortices (viz. sensori-motor cortex and frontal cortex) to same side as that of the onset. This novel MEG-EEG based case series of PCs provides newer insights for understanding the plausible generators of myoclonus in SSPE and patterns of their propagation.

Autonomic function in reflex and non-reflex epilepsy--an exploratory study.

PURPOSE: Seizures are known to affect diverse areas of the Central Autonomic Network (CAN) resulting in varied autonomic symptoms. The objectives of the study were to characterize neuro-cardiac autonomic regulation in hot water epilepsy (HWE) with or without spontaneous seizure, and to analyze the effect of Carbamazepine (CBZ). METHODS: Seventy patients of HWE [42 drug-naïve 'HWE only' and 28 'HWE with spontaneous complex partial seizure (CPS),' on CBZ] and 40 spontaneous CPS on CBZ were recruited after informed consent. Fifty healthy volunteers served as control. Conventional cardiac autonomic function tests, Heart Rate Variability (HRV), Blood Pressure Variability (BPV), and baroreflex sensitivity (BRS) were performed. RESULTS: Significant dysfunction was evidenced in most of the autonomic function parameters in all the epilepsy subgroups when compared with controls. Significant reduction in the parasympathetic activity in HWE patients was observed. Significant impairment of short-term fluctuation of blood pressure in 'HWE with spontaneous CPS' compared to 'healthy volunteers' was detected. Compared to 'HWE only', 'HWE with spontaneous CPS' showed impaired sympathovagal balance. The BRS were also altered in 'HWE with spontaneous CPS' compared to 'HWE only'. The comparison of 'spontaneous CPS' with 'HWE with spontaneous CPS' and 'HWE only' showed reduced parasympathetic and sympathetic activities. CONCLUSION: Both cardiovascular reflexes and autonomic cardiovascular regulation were altered in HWE, more so in 'HWE with spontaneous seizures'. Compared to those on CBZ, drug naïve had severe effect on vagal tone and CBZ did not alter cardiac autonomic functions in reflex as well as in non-reflex epilepsies.

Clinical, electrophysiological, imaging, pathological and therapeutic observations among 18 patients with Rasmussen's encephalitis.

We studied the clinical, electrophysiological, imaging and pathological features of 18 patients with Rasmussen's encephalitis (RE). This descriptive study included 18 patients (six males, 12 females) with RE who were evaluated for demographic and phenotypic details, electroencephalogram (EEG) results, MRI results, pathological features, virological markers and outcome. Radiological staging as per Bien et al. and pathological staging in accordance with Robitaille et al. were performed. Simple partial seizures were the most common initial manifestation. During the disease course, epilepsia partialis continua (EPC) developed in 15/18 (83.3%) and hemiparesis in 17/18 (94.4%) patients. EEG revealed hemispheric slowing (100%), interictal epileptiform discharges (100%) and ictal pattern (44.4%). Brain MRI revealed unihemispheric focal cortical atrophy (100%), white matter changes (88.2%), basal ganglia-ipsilateral caudate and putamen involvement (50.0%) and progression of atrophy on serial MRI (100%). Unusual presentations in this series included late onset (n=1), and isolated lingual EPC (n=1). Diagnostic biopsies in two patients revealed Robitaille stage 3 disease. The six hemispherotomy specimens showed stage 2 disease in one, stage 3 in three and stage 4 in two cases. Heterogeneity in disease stage in the different neuroanatomical regions and within the same cortical segment reflected progression of immune-mediated damage. Immunomodulation provided only temporary benefit. Patients who underwent functional hemispherotomy had reduction in seizure frequency and improved quality of life. The clinical, EEG and MRI findings are in accordance with the established literature. MRI staging was concordant with Robitaille pathological staging. Immunomodulation did result in transient reduction in seizure frequency while surgery in six produced reasonable benefit.

Clinical and imaging characteristics of 16 patients with autoimmune neuronal synaptic encephalitis.

OBJECTIVES: Autoimmune neuronal synaptic encephalitis (AIE) encompasses a heterogeneous group of disorders characterized by immune-mediated neuronal cell destruction. In this study, we aim to study the clinical features, imaging profile and treatment outcome of patients with AIE. METHODS: This is a chart review of 16 (M: F-3:13) patients with AIE from 2011 to 2015. RESULTS: Among the patients, 10 had anti-NMDA, 4 had anti-TPO, and 2 had anti-VGKC antibody positivity. Cognitive impairment and seizures were the predominant symptoms present in nearly all patients, followed by psychiatric disturbances (87.5%), mutism (62.5%), movement disorders (62.5%), myoclonic jerks (37.5%) and visual hallucinations (18.75%). Magnetic resonance imaging (MRI) of the brain was available in 15 patients; it was abnormal in 53.3% patients. Abnormalities were seen in all patients with anti-VGKC positivity; and, 60% of patients with anti-NMDA positivity. Imaging was normal in 26.7% of the patients (3: anti-NMDA; and, 1: anti-TPO positivity); and, diffuse cerebral atrophy was noted in rest of the 20% (3: anti-TPO positivity) patients. All patients improved gradually with immunomodulation. CONCLUSIONS: All patients with anti-VGKC, anti-NMDA and anti-TPO antibody positivity presented with a triad of behavioral changes, impaired cognition and seizures. Mutism was a predominant symptom in patients with an anti-NMDA antibody positivity, which may help in the early identification of this disorder. MRI brain showed changes restricted to limbic structures in anti-NMDA and anti-VGKC antibody positivity. An early diagnosis and treatment of autoimmune encephalitis is essential for a better outcome and for prevention of long-term sequel.

Seizure Frequency Can Alter Brain Connectivity: Evidence from Resting-State fMRI.

BACKGROUND AND PURPOSE: The frequency of seizures is an important factor that can alter functional brain connectivity. Analysis of this factor in patients with epilepsy is complex because of disease- and medication-induced confounders. Because patients with hot-water epilepsy generally are not on long-term drug therapy, we used seed-based connectivity analysis in these patients to assess connectivity changes associated with seizure frequency without confounding from antiepileptic drugs. MATERIALS AND METHODS: Resting-state fMRI data from 36 patients with hot-water epilepsy (18 with frequent seizures [>2 per month] and 18 with infrequent seizures [≤2 per month]) and 18 healthy age- and sex-matched controls were analyzed for seed-to-voxel connectivity by using 106 seeds. Voxel wise paired t-test analysis (P < .005, corrected for false-discovery rate) was used to identify significant intergroup differences between these groups. RESULTS: Connectivity analysis revealed significant differences between the 2 groups (P < .001). Patients in the frequent-seizure group had increased connectivity within the medial temporal structures and widespread areas of poor connectivity, even involving the default mode network, in comparison with those in the infrequent-seizure group. Patients in the infrequent-seizure group had focal abnormalities with increased default mode network connectivity and decreased left entorhinal cortex connectivity. CONCLUSIONS: The results of this study suggest that seizure frequency can alter functional brain connectivity, which can be visualized by using resting-state fMRI. Imaging features such as diffuse network abnormalities, involvement of the default mode network, and recruitment of medial temporal lobe structures were seen only in patients with frequent seizures. Future studies in more common epilepsy groups, however, will be required to further establish this finding.