Corpus Callosotomy for Non-Localizing Drug Resistant Epilepsy with Drop Attacks.

BACKGROUND: Corpus callosotomy (CC) is a surgical palliative procedure done for a selected group of patients with drug resistant epilepsy (DRE) to stop drop attacks and prevent falls. METHODS: We performed a retrospective chart review of consecutive patients who underwent CC for DRE with drop attacks at our center between 2015 and 2019. Clinical, imaging details and surgical findings were noted. Clinical outcomes and functional status were evaluated. RESULTS: During the study period, 17 patients underwent corpus callosotomy (Male: Female 14:3). The mean age at surgery was 10.3 years (standard deviation - 5.85, interquartile range [IQR] = 6.5). The mean age at onset of seizure was 2.23 years (standard deviation - 3.42, IQR = 1.5). Preoperative seizure frequency ranged from 2 to 60 attacks per day (median: 20, IQR= 36). All patients had atonic seizures/drop attacks. One patient underwent anterior CC and 16 underwent complete CC. Three patients had complications in the postoperative period. The median follow-up was 26 months. All patients had cessation of drop attacks immediately following surgery. One patient with anterior CC had a recurrence of drop attacks for which she underwent completion CC. Another patient had recurrent drop attacks 3 years later and was found to have a residual callosal connection. Three patients had complete seizure freedom and 4 patients had a <50% reduction in seizure frequency. CONCLUSIONS: Our study lends additional support to the efficacy of CC in patients with DRE, with the cessation of drop attacks. It also provided a reasonable reduction in seizure frequency. Complete CC led to better control of drop attacks.

Spectrum of Neurological Complications Following COVID-19 Vaccination in India.

BACKGROUND AND PURPOSE: According to WHO statistics, approximately 6.9 billion people worldwide had been vaccinated against SARS-CoV-2 as at October 27, 2021, including around 1.0 billion people in India. Most Indian recipients received the Covishield (ChAdOx1-S/nCoV-19) vaccine, followed by the Covaxin (an inactivated SARS-CoV-2 antigen) vaccine. This study was conducted to characterize the neurological phenotypic spectrum of patients with adverse events following immunization with any of the available COVID-19 vaccines in India (Covishield or Covaxin) during the study period and their temporal relationship with vaccination. METHODS: This ambispective multicenter hospital-based cohort study covered the period from March to October 2021. The study included all cases suspected of having neurological complications following COVID-19 vaccination. RESULTS: We report a spectrum of serious postvaccination neurological complications comprising primary central nervous system demyelination (4 cases), cerebral venous thrombosis (3 cases), Guillain-Barre syndrome (2 cases), vaccine-induced prothrombotic immune thrombocytopenia syndrome (2 cases), cranial nerve palsies (2 cases), primary cerebral hemorrhage (1 case), vestibular neuronitis (1 case), chronic inflammatory demyelinating polyneuropathy (1 case), generalized myasthenia (1 case), and seizures (1 case). CONCLUSIONS: Although the benefits of vaccination far outweigh its risks, clinicians must be aware of possible serious adverse events associated with COVID-19 vaccinations.

Disseminated Cysticercosis in Indian Scenario - Experience from a Teaching University Hospital.

Background and Objectives: Neurocysticercosis (NCC) due to Taenia Solium is a major public health problem. Our objective was to study patients with disseminated cysticercosis (DCC) who had NCC in the brain along with an additional site in the body and assess their clinical, radiological profile, and response to therapy. Materials and Methods: A chart review of DCC with a high lesion load of NCC ≥20 (DNCC) in the brain was performed. Results: Sixteen (M:F = 13:3) patients were diagnosed with DNCC with a mean age of presentation of 35.1 ± 14.2 years. Headache was the predominant symptom, followed by seizures (93.75%), vomiting (43.75%), behavioral disturbances (31.25%), fever (12.5%), encephalopathy (12.5%), visual disturbances (6.25%), and muscle pain and limb weakness (6.25%). CT brain showed multiple active parenchymal cysts in all, and calcifications in 68.75%. MRI brain revealed involvement of cortex and subcortical structures in all, followed by cerebellum (81.25%) and brainstem (75%). Intramedullary spinal lesion was observed in 12.5% cases. Albendazole with steroids was used in 15 patients. In 93.3% patients, there was complete improvement in seizures; 12.5% subjects had persistent memory and behavioral abnormalities. One subject required decompressive craniectomy; mortality was observed in two subjects. Conclusions: We hereby report one of the largest case series on disseminated cysticercosis with a high lesion load of NCC in the brain. A comprehensive clinical, imaging, therapeutic response with repeat imaging and long-term follow-up has given us a better understanding of this difficult-to-treat neurological disorder. We suggest cautious use of anti-parasitic therapy under the cover of corticosteroids to prevent irreversible neurological sequelae.

Neurology Exit Examination System in India: A Survey of Examiners' Perceptions and Recommendations.

Background: The traditional Neurology exit examination in India has remained unchanged over the last few decades. In developed countries, objective evaluation methods have replaced the traditional ones. A need for such methods has not been explored in India. Objective: We aimed to study the perceptions and key recommendations of Neurology examiners on the existing examination pattern. Material and Methods: We conducted an online survey of examiners perceptions and recommendations using a set of 10 multiple-choice questions and an open-ended question. Results: 46 examiners provided completed responses suitable for analysis. Nearly equal proportions (30%) of the examiners had 10 years, 10-25 years and >25 years' experience. 92% were not satisfied with current system, 95% did not find adequate time for correction of theory scripts, 90% felt that theory questions were random, and 95% had legibility issues. 84% felt that the practical exams do not test true learning, 98% felt the examination stress impairs the performance and 85% felt that there are no objective criteria to pass the candidate. 83% felt the current system-needed changes. The key suggestions provided by the examiners to improve the system included objective assessments like MCQ, OSCE, OSLER and DOPS, inclusion of larger number of short answer type questions and periodic internal assessments of the candidates. Conclusions: A vast majority of examiners favoured changes to the current examination system and provided key recommendations. A larger study is needed to extrapolate these findings to the rest of India.

Evaluation of one-year effectiveness of clobazam as an add-on therapy to anticonvulsant monotherapy in participants with epilepsy having uncontrolled seizure episodes: An Indian experience.

OBJECTIVES: To prospectively study the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy. METHODS: We conducted a prospective, observational study at 28 neurology outpatient clinics in India from June 2017 to October 2019. Consecutive patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy were initiated on clobazam. Patients were followed up at 1, 3, 6, 9, and 12 months. Seizure control and adverse events were assessed through personal interviews and seizure diaries. RESULTS: Out of 475 eligible patients, data of 429 patients (men: 65.5%) were evaluated (46 excluded due to protocol deviations). The median age was 25 (range, 3-80 years) years and the median duration of epilepsy was 3 (0.1-30) years. The majority of patients had focal epilepsy (55.0%) and genetic generalized epilepsy (40.1%). The one-year follow-up was completed by 380 (88.5%) patients. At one-year follow-up, 317 (83.4%; N = 380) patients in the study remained seizure free. These 317 patients who were seizure free at 12 months comprised 73.9% of the evaluable population (N = 429). In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment. During one-year follow-up, a total of 113 (22.6%) patients experienced at least one adverse event which included 103 (20.6%) patients who experienced 386 episodes of seizures. CONCLUSION: The study provides preliminary evidence that clobazam is effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy. TRIAL REGISTRATION NUMBER: CTRI/2017/12/010906.

Medium-chain Triglyceride Ketogenic Diet as a Treatment Strategy for Adult Super-refractory Status Epilepticus.

How to cite this article: Dutta K, Satishchandra P, Borkotokey M. Medium-chain Triglyceride Ketogenic Diet as a Treatment Strategy for Adult Super-refractory Status Epilepticus. Indian J Crit Care Med 2022;26(1):139-140.

Neuropathological spectrum of drug resistant epilepsy: 15-years-experience from a tertiary care centre.

Neuropathology of drug resistant epilepsy (DRE) has direct bearing on the clinical outcome. Classification of the most common pathologies, hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) have undergone several revisions and studies on the surgical pathology of DRE employing the updated ILAE classification are scarce. Here, we report the neuropathological spectrum of 482 surgically treated cases of DRE from a single institute using the latest ILAE classifications along with clinicoradiologic correlation. Majority of the cases (324, 67.2%) had temporal lobe epilepsy (TLE), with 158 (32.8%) having extratemporal seizure focus. Among TLE, HS was most common (n = 208, 64.2%), followed by neoplasms (42, 13%), FCD (26, 8%) and dual pathology (23, 7%). Less frequent were vascular malformations (cavernoma-3, arteriovenous malformation-1), mild malformation of cortical development (mMCD, 3), gliotic lesions (5), cysticercosis (2), double pathology (2) and polymicrogyria (1). Among extratemporal epilepsies, FCD was most common (46, 29.1%), followed by neoplasms (29, 18.3%), gliotic lesions (27, 17.1%), Rasmussen encephalitis (18, 11.4%), hypothalamic hamartoma (12, 7.6%), malformations of cortical development (10, 6.3%) and vascular malformations (6, 3.8%). Less frequent were double pathology (2, cysticercosis + FCD type IIb, DNET + FCD type IIb), mMCD (2), cysticercosis (1) and dual pathology (1). No underlying pathology was detected in 12 cases (2.5%). Radiopathological concordance was noted in 83%. In 36 cases (7.5%), histopathology detected an unsuspected second pathology that included FCD type III (n = 16) dual pathology (n = 18) and double pathology (n = 2). Further, in four MRI negative cases, histopathology was required for a conclusive diagnosis.

Auditory Temporal Ordering in Patients with Medial Temporal Lobe Epilepsy with and without Hippocampal Sclerosis.

CONTEXT: Temporal lobe epilepsy can affect central auditory processing (CAP) skills. Auditory temporal ordering (ATO) is a CAP skill that can be evaluated using duration pattern test (DPT). AIM: The aim is to evaluate ATO in patients with medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (MTLE + HS) and without hippocampal sclerosis (MTLE-HS) and in their subgroups. SETTINGS AND DESIGN: It was a prospective cross-sectional behavioral observational study conducted in a tertiary neuropsychiatric hospital. SUBJECTS AND METHODS: The subjects were patients with refractory MTLE (N = 100), comprising 50 "MTLE + HS" patients and 50 "MTLE-HS". Age-range matched normal healthy subjects (n = 50) formed the control group. Both groups were administered duration pattern test (DPT). STATISTICAL ANALYSIS USED: Analysis of variance (ANOVA) with post hoc analysis, Dunnett's two-sided and Bonferroni, paired sample t-test, Pearson's correlation, and independent t-test. RESULTS: The clinical groups performed significantly poorer than the control group, and however, did not differ significantly between them. The age at onset and the duration of the seizures did not have significant relation with the test measures. CONCLUSIONS: Patients with "MTLE + HS" as well as those with "MTLE-HS" and their respective subgroups revealed abnormal ATO indicating CAP dysfunction.

Dual/double pathology in neurocysticercosis causing drug resistant epilepsy - Chance association or causal?

INTRODUCTION: Neurocysticercosis (NCC) as cause of drug resistant epilepsy (DRE) is commonly reported from India. We reviewed the neuropathological findings in patients undergoing resective surgery for DRE due to NCC, to determine the pathomechanism of epileptogenesis. METHODS: Clinical, demographic and neuropathological findings of histologically confirmed cases of NCC causing DRE between 2005-2019 were reviewed. NeuN, GFAP, phosphorylated neurofilament, vimentin, CD34 for glial/ neuronal alterations, and Masson trichrome, Luxol Fast blue for evidence of fibrosis/ demyelination was used to determine cause of epileptogenesis. RESULTS: There were 12 cases of NCC associated with dual/ double pathology, which constituted 3.02 % (12/398) of all the operated DRE. [Age range: 17-37y, Male:Female = 1.4:1]. Seizure duration ranged from 3-32y, with seizure onset between 4-27y. On MRI, lesions were of variable signal intensity on T1 and isointense on T2 with blooming on GRE/ SWI, and CT revealed calcification. Majority (11/12) had associated hippocampal sclerosis (HS) type 1 (dual pathology), localised to the same side as cysticercal cyst, suggesting it may be involved in the pathogenesis of HS. Ten had single cysticercal lesion involving ipsilateral hippocampus in 6, parahippocampal gyrus in 2, amygdala and temporal lobe in 1 case each. One had multiple NCC located in bilateral frontal, parietal and ipsilateral hippocampus. Adjacent cortex around the NCC evaluated in 6 cases, revealed inflammation, gliosis, axonal disruption/ beading, and variable synaptic/ neuronal dystrophic changes. There was a single case of NCC with Focal cortical dysplasia (FCD) type IIb (double pathology). In 11/12 cases Engel's post-surgery outcome was available with all having class I outcome. CONCLUSION: HS was most common pathology associated with cysticercosis (Dual pathology), localised ipsilateral to the cysticercal cyst, suggesting that HS is a secondary/ epiphenomenon. Perilesional changes such as inflammation, gliosis, dystrophic synaptic and axonal pathology play a role in inducing or perpetuating the epileptiform activity. The association of FCD IIb with NCC in one case is likely to be a chance occurrence.

Dissecting Aneurysm of the Basilar Artery-A Rare Complication of Bacterial Meningitis in a Postoperative Case of CSF Rhinorrhea.

Basilar artery dissections are rare events which present with subarachnoid hemorrhage (SAH), brain ischemia, and usually have a fatal outcome. Few case reports of mycotic dissections are published in literature. We report a case of a young male who underwent surgical treatment for post-traumatic CSF rhinorrhea. He presented 3 years later with signs of bacterial meningitis. During medical management with antibiotic therapy, he developed basilar artery aneurysm in a span of 2 days, had subarachnoid hemorrhage and deteriorated. CSF culture grew alpha hemolytic streptococci. Despite medical management, he developed brain stem infarcts and succumbed. This report highlights a rare fatal complication of mycotic dissecting aneurysm of the basilar artery following meningitis, which developed acutely in hospital, while on treatment. Antibiotic therapy had not altered the course of disease. It is advisable to investigate for presence of ruptured mycotic aneurysms or dissection in cases of bacterial meningitis leading to SAH.

Magnetoencephalography imaging of high frequency oscillations strengthens presurgical localization and outcome prediction.

In patients with medically refractory epilepsy, resective surgery is the mainstay of therapy to achieve seizure freedom. However, ∼20-50% of cases have intractable seizures post-surgery due to the imprecise determination of epileptogenic zone. Recent intracranial studies suggest that high frequency oscillations between 80 and 200 Hz could serve as one of the consistent epileptogenicity biomarkers for localization of the epileptogenic zone. However, these high frequency oscillations are not adopted in the clinical setting because of difficult non-invasive detection. Here, we investigated non-invasive detection and localization of high frequency oscillations and its clinical utility in accurate pre-surgical assessment and post-surgical outcome prediction. We prospectively recruited 52 patients with medically refractory epilepsy who underwent standard pre-surgical workup including magnetoencephalography (MEG) followed by resective surgery after determination of the epileptogenic zone. The post-surgical outcome was assessed after 22.14 ± 10.05 months. Interictal epileptic spikes were expertly identified, and interictal epileptic oscillations across the neural activity frequency spectrum from 8 to 200 Hz were localized using adaptive spatial filtering methods. Localization results were compared with epileptogenic zone and resected cortex for congruence assessment and validated against the clinical outcome. The concordance rate of high frequency oscillations sources (80-200 Hz) with the presumed epileptogenic zone and the resected cortex were 75.0% and 78.8%, respectively, which is superior to that of other frequency bands and standard dipole fitting methods. High frequency oscillation sources corresponding with the resected cortex, had the best sensitivity of 78.0%, positive predictive value of 100% and an accuracy of 78.84% to predict the patient's surgical outcome, among all other frequency bands. If high frequency oscillation sources were spatially congruent with resected cortex, patients had an odds ratio of 5.67 and 82.4% probability of achieving a favourable surgical outcome. If high frequency oscillations sources were discordant with the epileptogenic zone or resection area, patient has an odds ratio of 0.18 and only 14.3% probability of achieving good outcome, and mostly tended to have an unfavourable outcome (χ2 = 5.22; P = 0.02; φ = -0.317). In receiver operating characteristic curve analyses, only sources of high-frequency oscillations demonstrated the best sensitivity and specificity profile in determining the patient's surgical outcome with area under the curve of 0.76, whereas other frequency bands indicate a poor predictive performance. Our study is the first non-invasive study to detect high frequency oscillations, address the efficacy of high frequency oscillations over the different neural oscillatory frequencies, localize them and clinically validate them with the post-surgical outcome in patients with medically refractory epilepsy. The evidence presented in the current study supports the fact that HFOs might significantly improve the presurgical assessment, and post-surgical outcome prediction, where it could widely be used in a clinical setting as a non-invasive biomarker.

Comparing the efficacy of sodium valproate and levetiracetam following initial lorazepam in elderly patients with generalized convulsive status epilepticus (GCSE): A prospective randomized controlled pilot study.

PURPOSE: This randomized control study was conducted to compare the efficacy of sodium valproate (SVP) and levetiracetam (LEV) following initial intravenous lorazepam in elderly patients (age: >60years) with generalized convulsive status epilepticus (GCSE) and to identify predictors of poor seizure control. METHODS: A total of 118 patients (mean age: 67.5 ± 7.5 years, M:F = 1.6:1), who had presented with GCSE were randomized into the SVP or LEV treatment arms. All patients received initial intravenous lorazepam (0.1 mg/kg) followed by one of the two antiepileptic drugs (AEDs), parenteral SVP (20-25 mg/kg) or LEV (20-25 mg/kg). Those who failed to achieve control with the initial AED, were crossed over to receive the other AED. One-hundred patients (SVP = 50; LEV = 50) completed the study. RESULTS: SE could be controlled with lorazepam and one of the AEDs (SVP or LEV) in 71.18% (84/118). Intention-to-treat analysis showed that the two groups did not differ significantly in terms of seizure control [SVP: 41/60 (68.3%); LEV: 43/58 (74.1%), p = 0.486]. Of 100 patients who completed the study, seizure control was achieved in 38/50(76%) in the SVP and 43/50(86%) in the LEV group (p = 0.202). After crossing over to the second AED, SE could be controlled in an additional in 50% (6/12) in SVP (+LEV) group and in 14.3% (1/7) in LEV (+SVP) group. Overall, after the second AED, seizure control was achieved in 77.1% (91/118). Higher STESS was associated with poor therapeutic response (p = 0.049). CONCLUSIONS: The efficacy of SVP and LEV following initial lorazepam in controlling GCSE in elderly population was comparable, hence the choice of AED could be individualized.

Proteomic Analysis of the Human Anterior Pituitary Gland.

The pituitary function is regulated by a complex system involving the hypothalamus and biological networks within the pituitary. Although the hormones secreted from the pituitary have been well studied, comprehensive analyses of the pituitary proteome are limited. Pituitary proteomics is a field of postgenomic research that is crucial to understand human health and pituitary diseases. In this context, we report here a systematic proteomic profiling of human anterior pituitary gland (adenohypophysis) using high-resolution Fourier transform mass spectrometry. A total of 2164 proteins were identified in this study, of which 105 proteins were identified for the first time compared with high-throughput proteomic-based studies from human pituitary glands. In addition, we identified 480 proteins with secretory potential and 187 N-terminally acetylated proteins. These are the first region-specific data that could serve as a vital resource for further investigations on the physiological role of the human anterior pituitary glands and the proteins secreted by them. We anticipate that the identification of previously unknown proteins in the present study will accelerate biomedical research to decipher their role in functioning of the human anterior pituitary gland and associated human diseases.

Improvement in Obsessive-Compulsive Disorder Following Right Anterior Temporal Lobectomy and Amygdalohippocampectomy in a Patient with Refractory Temporal Lobe Epilepsy with Right Mesial Temporal Sclerosis.

There are reports of co-occurrence of obsessive-compulsive disorder (OCD) in patients with temporal lobe epilepsy (TLE). We present a report of a patient with refractory TLE due to hippocampal sclerosis with concomitant OCD on pharmacotherapy for both. She underwent surgery for standard anterior temporal lobectomy with amygdalohippocampectomy and reported improvement in obsessive-compulsive symptoms subsequently. We seek to further evidence of interaction between the two conditions and argue to undertake future research exploration on the same.

Effects of Chronic Carbamazepine Treatment on the ECG in Patients with Focal Seizures.

BACKGROUND AND OBJECTIVES: Several mechanisms have been proposed for the sudden unexpected death in epilepsy patients, such as cardiac arrhythmias, a decrease in heart rate variability and the use of anti-epileptic drugs (AEDs). Although carbamazepine is commonly used as an AED, the exact working mechanism of this drug as well as its effect on the heart are not completely understood. The aim of this study was to determine whether chronic carbamazepine therapy in patients with focal seizures and impaired awareness has an effect on the electrocardiogram (ECG). SUBJECTS AND METHODS: This cross-sectional study included 36 patients with focal seizures and impaired awareness treated for 12-32 months with carbamazepine monotherapy and 38 healthy volunteers. A 5-min modified three-electrode chest lead ECG with lead II configuration was recorded using LabChart 7 ECG software module at 1000-Hz sampling frequency. All data analysis was performed using custom-made Matlab 2015b scripts. ECGs of patients and controls were compared with respect to heart rate, time intervals and measures of short- and long-term variation. RESULTS: There were no significant differences in heart rate and ECG time intervals between the patient and control groups. Measures on short- and long-term variability also did not show any significant group differences. CONCLUSION: Our study shows that chronic use of carbamazepine as monotherapy does not have any significant effects on ECG time intervals or measures of short- and long-term variability.

Alterations in natural killer and dendritic cell subsets in individuals with HIV-associated neurotuberculosis.

One of the commonest HIV-associated opportunistic infections of the central nervous system is neurotuberculosis. Interaction between HIV, Mycobacterium tuberculosis and host immune system in co-infected individuals may result in altered frequencies of immune cells, thereby modulating dissemination and disease progression. We examined the frequencies of natural killer (NK) cell and dendritic cell (DC) subsets in HIV infected individuals with neurotuberculosis (HIVNTB) as compared to individuals with HIV associated systemic TB (HIVSTB), asymptomatic HIV, non-HIV NTB, non-HIV STB, and healthy controls. Peripheral blood mononuclear cells (PBMC) were stained with fluorochrome-conjugated monoclonal antibodies- Lineage cocktail (containing CD3, CD14, CD19, and CD20), HLA-DR, CD16, CD56, CD11c, and CD123, fixed with 2% paraformaldehyde and analyzed on the flow cytometer. The pDCs were significantly reduced in all HIV infected groups, with a marked reduction in HIVNTB cases as compared to healthy controls. While the CD56- CD16bt NK cell subset displayed a significant increase in frequency in all three HIV infected groups compared the three HIV negative groups, the CD56dim CD16bt subset was significantly lower in frequency in the HIVNTB compared to healthy controls. The decreased frequencies of plasmacytoid DCs and cytotoxic NK cells, which are crucial for innate immune defence against HIV, may result in ineffective virus control and lead to an exacerbated course of disease in HIVNTB individuals.

Magnetoencephalographic imaging of ictal high-frequency oscillations (80-200 Hz) in pharmacologically resistant focal epilepsy.

OBJECTIVE: Specificity of ictal high-frequency oscillations (HFOs) in identifying epileptogenic abnormality is significant, compared to the spikes and interictal HFOs. The objectives of the study were to detect and to localize ictal HFOs by magnetoencephalography (MEG) for identifying the seizure onset zone (SOZ), evaluate the cortical excitability from preictal to ictal transition, and establish HFO concordance rates with other modalities and postsurgical resection. METHODS: Sixty-seven patients with drug-resistant epilepsy had at least 1 spontaneous seizure each during MEG acquisition, and analysis was carried out on 20 seizures from 20 patients. Ictal MEG data were bandpass filtered (80-200 Hz) to visualize, review, and analyze the HFOs co-occurring with ictal spikes. Source montages were generated on both hemispheres, mean fast Fourier transform was computed on virtual time series for determining the preictal to ictal spectral power transition, and source reconstruction was performed with sLORETA and beamformers. The concordance rates of ictal MEG HFOs (SOZ) was estimated with 4 reference epileptogenic regions. RESULTS: In each subject, transient bursts of high-frequency oscillatory cycles, distinct from the background activity, were observed in the periictal continuum. Time-frequency analysis showed significant spectral power surge (85-160 Hz) during ictal state (P < .05) compared to preictal state, but there was no variation in the peak HFO frequencies (P > .05) for each subgroup and at each source montage. HFO source localization was consistent between algorithms (k = 0.857 ± 0.138), with presumed epileptogenic zone (EZ) comparable to other modalities. In patients who underwent surgery (n = 6), MEG HFO SOZ was concordant with the presumed EZ and the surgical resection site (100%), and all were seizure-free during follow-up. SIGNIFICANCE: HFOs could be detected in the MEG periictal state, and its sources were accurately localized. During preictal to ictal transition, HFOs exhibited dynamic augmentation in intrinsic epileptogenicity. Spatial overlap of ictal HFO sources was consistent with EZ determinants and the surgical resection area.

Source analysis of epileptiform discharges in absence epilepsy using Magnetoencephalography (MEG).

PURPOSE: Magnetoencephalography (MEG) was used to record and localize the sources of the epileptiform discharges, in absence epilepsy, at three different time intervals to infer the sources of involvement during generation and propagation. METHODS: Twenty patients with absence epilepsy (M:F=1:1; age: 10.2±3.4years), which included 12 patients with childhood absence epilepsy (CAE) and 8 patients with juvenile absence epilepsy (JAE), were recruited in this prospective MEG based study. MEG epileptiform discharges were divided into three sub-groups based on the duration viz., 1s (very short),>1-9.9s (short) and ≥10s (long) and the discharges of each group were averaged independently in each patient. MEG source analysis was performed on these averaged discharges, of each of the subgroups, at the onset, during middle and offset. RESULTS: The source locations obtained, in lobar and gyri levels, were compared across these three groups of varying duration of discharges and in the CAE and JAE subjects. It was observed that the most frequent location of sources from the sublobar, limbic and frontal lobes in all the discharge groups at different time intervals. Also, it was noted that there were only subtle and variable degree of the differences of source localization of epileptic discharges among CAE and JAE subgroups. CONCLUSION: The study provided novel findings regarding origin and propagation of sources of epileptiform discharges in patients with childhood and juvenile absence epilepsies. Such analysis further improves the understanding of network involvement of subcortical and cortical regions in these patients.

Microtubule-associated defects caused by EFHC1 mutations in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common form of epilepsy with a substantial genetic basis to its etiology. While earlier studies have identified EFHC1 as a causative gene for JME, subsequent studies have suggested that ethnicity may play a role in determining expression of the JME phenotype among individuals carrying EFHC1 mutations. Here, we report on our studies on EFHC1 in JME patients from India. We examined the complete structure of the EFHC1 transcript from 480 JME patients and 700 control chromosomes by direct sequencing. Functional correlates of mutations were studied by immunolocalization experiments in cultured mammalian cells and protein homology modeling by in silico methods. Thirteen mutations, of which 11 were previously not known, were identified in 28 JME patients. These mutations accounted for about 6% of the patients examined. Functional studies suggest that these EFHC1 mutations result in microtubule-related abnormalities during cell division. In silico analysis for a subset of mutations suggests that they may affect EFHC1 protein domains, compromising its ability to interact with other proteins. Our observations strengthen the evidence supporting a role for EFHC1 in JME in a population ethnically and geographically distinct from the one in which the gene was initially identified, and broaden the extent of allelic heterogeneity in the gene.