Avoidance of Pitfalls and Complications During Surgery for Temporal Lobe Epilepsy.

Anterior temporal lobectomy with amygdalohippocampectomy is the most common epilepsy surgery, which, in cases of mesial temporal lobe epilepsy caused by mesial temporal sclerosis, usually leads to improvements in seizure control, cognitive function, and quality of life. Nevertheless, while the primary goal of intervention is achieved in a large majority of patients, a small number of them, unfortunately, encounter complications. Some morbidity is nonspecific and may be noted after any craniotomy (e.g., surgical site infections, meningitis, bone flap osteomyelitis, and operative site or craniotomy-related hematomas). On the other hand, certain complications are specifically associated with surgery for temporal lobe epilepsy and can be discussed from the etiological standpoint: mechanical injuries of the brain; injury of eloquent neuronal structures; arterial and venous injuries; cerebral venous thrombosis; remote cerebellar hemorrhage; and postoperative hydrocephalus, seizures, and psychiatric disorders. In many cases, these complications are manifested in the early postoperative period by alterations of consciousness and a focal neurological deficit, and it may require immediate decisions on their appropriate management.

Localisation of eloquent cortex using magnetoencephalography and its clinical implications.

OBJECTIVES: This study aimed to localise the eloquent cortex and measure evoked field (EF) parameters using magnetoencephalography in patients with epilepsy and tumours near the eloquent cortex. METHODS: A total of 41 patients (26 with drug-refractory epilepsy and 15 with tumours), with a mean age of 33 years, were recruited. Visual evoked field (VEF), auditory evoked field (AEF), sensory evoked field (SSEF), and motor-evoked field (MEF) latencies, amplitudes, and localisation were compared with those of a control population. Subgroup analyses were performed based on lobar involvement. Evoked Field parameters on the affected side were compared with those on the opposite side. The effect of distance from the lesion on nearby and distant evoked fields was evaluated. RESULTS: AEF and VEF amplitudes and latencies were reduced bilaterally (p < 0.05). Amplitude in the ipsilateral SSEF was reduced by 29.27% and 2.16% in the AEF group compared to the contralateral side (p = 0.02). In patients with temporal lobe lesions, the SSEF amplitude was reduced bilaterally (p < 0.02), and latency was prolonged compared with controls. The MEF amplitude was reduced and latency was prolonged in patients with frontal lobe lesions (p = 0.01). EF displacement was 32%, 57%, 21%, and 16% for AEF, MEF, VEF, and SSEF respectively. Patients in the epilepsy group had distant EF abnormalities. CONCLUSIONS: EF amplitude was reduced and latency was prolonged in the involved hemisphere. Distant EF amplitudes were more affected than latencies in epilepsy. Amplitude and distance from the lesion had negative correlation for all EF. EF changes indicated eloquent cortical displacement which may not be apparent on MRI.

Novel insights into the genetic profile of hereditary spastic paraplegia in India.

The Hereditary Spastic Paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by length dependent degeneration of the corticospinal tracts. Genetic data related to HSPs are limited from India. We aimed to comprehensively analyse the phenotypic characteristics and genetic basis of a large cohort of HSP from India. Patients with HSP phenotype were evaluated for their clinical features, electrophysiological and radiological abnormalities. Genetic analyses were carried out by clinical exome sequencing (n = 52) and targeted sequencing (n = 5). The cohort comprised of 57 probands (M:F 40:17, age: 3.5-49 years). Based on the phenotype, the cohort could be categorized as 'pure' (n = 15, 26.3%) and 'complicated' (n = 42, 73.7%) HSP. Brain MRI showed thin corpus callosum (n = 10), periventricular hyperintensities (n = 20), cerebral atrophy (n = 3), cerebellar atrophy (n = 3) and diffuse atrophy (n = 4). Sixty-seven variants representing 40 genes were identified including 47 novel variants. Forty-eight patients (84.2%) had variants in genes previously implicated in HSP and other spastic paraplegia syndromes (SPG genes = 24, non-SPG genes = 24); among these 13 had variations in more than one gene and 12 patients (21.0%) had variations in genes implicated in potentially treatable/modifiable metabolic disorders (MTHFR = 8, MTRR = 1, ARG1 = 2 and ABCD1 = 1). In nine patients, no genetic variants implicated in spastic paraplegia phenotype were identified. Thus, the present study from India highlights the phenotypic complexities and spectrum of genetic variations in patients with HSP including those implicated in metabolically modifiable disorders. It sets a platform for carrying out functional studies to validate the causal role of the novel variants and variants of uncertain significance.

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.

Role of altered IL-33/ST2 immune axis in the immunobiology of Guillain-Barré syndrome.

BACKGROUND: The IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL-33/ST2 axis can induce autoimmune reaction and inflammatory responses. Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy, mostly caused by post-infection autoimmunity. The role of IL-33/ST2 axis is not known in GBS. This study aimed to explore the role of IL-33/ST2 axis in GBS. METHODS: Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159, rs7044343, rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753) coding for suppressor of tumorigenicity 2 (ST2) were genotyped in 179 GBS patients and 186 healthy controls by TaqMan Allelic Discrimination Assay. Plasma levels of IL-33 and sST2 were measured in a subset of GBS patients (n = 80) and healthy controls (n = 80) by ELISA. RESULTS: The frequencies of CC genotype of rs10192157 (p = 0.043) and TT genotype of rs10206753 (p = 0.036) SNPs of Il1rl1 gene differed significantly between GBS patients and healthy controls. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk for GBS. In addition, the plasma sST2 levels were significantly elevated in GBS patients compared to healthy subjects (24,934.31 ± 1.81 pg/ml vs. 12,518.97 ± 1.51 pg/ml, p < 0.001). Plasma sST2 levels showed a significant correlation with the disability scores at the peak of neurological deficit in GBS patients. CONCLUSIONS: The IL-33/ST2 axis is suggested to influence the immunopathogenesis of GBS. Genetic variants of Il1rl1 gene might serve as a risk determinant of GBS and plasma sST2 levels might emerge as a biomarker of severity of GBS, if replicated further by other studies.

Variations within Toll-like receptor (TLR) and TLR signaling pathway-related genes and their synergistic effects on the risk of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is the commonest post-infectious polyradiculopathy. Although genetic background of the host seems to play an important role in the susceptibility to GBS, genes conferring major risk are not yet known. Dysregulation of Toll-like receptor (TLR) molecules exacerbates immune-inflammatory responses and the genetic variations within TLR pathway-related genes contribute to differential risk to infection. The aim of this study was to delineate the impact of genetic variations within TLR2, TLR3, and TLR4 genes as well as TLR signaling pathway-related genes such as MyD88, TRIF, TRAF3, TRAF6, IRF3, NFκß1, and IκBα on risk of developing GBS. Fourteen polymorphisms located within TLR2 (rs3804099, rs111200466), TLR3 (rs3775290, rs3775291), TLR4 (rs1927911, rs11536891), MyD88 (rs7744, rs4988453), TRIF (rs8120), TRAF3 (rs12147254), TRAF6 (rs4755453), IRF3 (rs2304204), NFκß1 (rs28362491), and IκBα (rs696) genes were genotyped in 150 GBS patients and 150 healthy subjects either by PCR-RFLP or TaqMan Allelic Discrimination Assay. Genotypes of two polymorphic variants, Del/Del of rs111200466 insertion and deletion (INDEL) polymorphism of TLR2 gene and TT of rs3775290 single nucleotide polymorphism (SNP) of TLR3 gene had significantly higher frequencies among GBS patients, while the frequencies of TT genotype of rs3804099 SNP of TLR2 gene and TT genotype of rs11536891 SNP of TLR4 gene were significantly higher in controls. Gene-gene interaction study by Multifactor Dimensionality Reduction analysis also suggested a significant combined effect of TLR2, and NFκß1 genes on the risk of GBS. The SNPs in the IκBα and IRF3 genes correlated with severity of GBS. The genes encoding TLRs and TLR signaling pathway-related molecules could serve as crucial genetic markers of susceptibility and severity of GBS.

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.

Leukodystrophy Due to eIF2B Mutations in Adults.

Vanishing white matter disease (VWMD) due to eIF2B mutations is a common leukodystrophy characterised by childhood onset, autosomal recessive inheritance, and progressive clinical course with episodic worsening. There are no reports of genetically confirmed adult patients from India. We describe the phenotype of two adults with genetically confirmed VWMD and typical radiological findings. Both had spastic ataxia and cognitive and behavioural disturbances. Other neurological features included myoclonic jerks and parkinsonism. At the last follow-up (duration: 2-9 years), one patient was wheelchair-bound. VWMD is rare in adults but should be suspected based on radiological findings and confirmed by eIF2B mutation.

Exploring immunoreactivity of TTF-1 and AVP in hypothalamic hamartoma.

INTRODUCTION: Hypothalamic hamartoma (HH) is a rare developmental disorder presenting with gelastic seizures or precocious puberty attributed to gonadotrophin-releasing hormone expression by the hamartoma. The histogenesis of HH is uncertain, and diagnosis of HH is difficult in small biopsies due to its close resemblance to normal hypothalamic nuclei. TTF-1 and arginine vasopressin (AVP) are associated with gonadotropin-releasing hormone release. MATERIALS AND METHODS: In this study, we explored the expression pattern of TTF-1 and AVP in HH and its utility, if any, in diagnosis. We reviewed the clinical, radiologic, and histopathological features of 23 HH diagnosed over the past decade at our Institute. RESULTS: The age at presentation ranged from 11 months to 34 years with gelastic seizures (82.6%), precocious puberty (17.4%), and developmental delay (8.7%) as presenting symptoms. On imaging, all the lesions (n = 9) involved the posterior and tuberal group of hypothalamic nuclei, while 5 cases involved the anterior hypothalamus. Anatomically, the lesions involved mammillary body, arcuate and periventricular nuclei. On histopathology, 52% cases revealed nodular arrangement of small neurocytic cells separated by glial stroma. TTF-1 and AVP immunoreactivity was absent in all the cases, whereas in normal hypothalamus, AVP was expressed in periventricular nuclei. CONCLUSION: Our results suggest that immunoexpression of TTF-1 is absent in HH, particularly in those arising from the posterior hypothalamus, and this can be used in small biopsies to distinguish from a normal hypothalamus as well as from posterior pituitary tumors.

Seizure detection and epileptogenic zone localisation on heavily skewed MEG data using RUSBoost machine learning technique.

Background: Epilepsy is a neurological disorder which is characterised by recurrent and involuntary seizures. Magnetoencephalography (MEG) is clinically used as a presurgical tool in locating the epileptogenic zone by localising either interictal epileptic discharges (IEDs) or ictal activities. The localisation of ictal onset provides reliable and more accurate seizure onset zones rather than localising the IEDs. Ictals or seizures are presently detected during MEG analysis by manually inspecting the recorded data. This is laborious when the duration of recordings is longer. Methods: We propose a novel method which uses statistical features such as short-time permutation entropy (STPE), gradient of STPE (GSTPE), short-time energy (STE) and short-time mean (STM) extracted from the ictal and interictal MEG data of drug resistant epilepsy patients group. Since the data is heavily skewed, the RUSBoost algorithm with k-fold cross-validation is used to classify the data into ictal and interictal by using the four feature vectors. This method is further used for localising the epileptogenic region using region-specific classifications by means of the RUSBoost algorithm. Results: The accuracy obtained for seizure detection is 93.4%. The specificity and sensitivity for the same are 93%. The localisation accuracies for each lobe are in the range of 88.1-99.1%. Discussion: Through this ictus detection method, the current scenario of laborious inspection of the ictal MEG can be reduced. The proposed system, thus, can be implemented in real-time as a better and more efficient method for seizure detection and further it can prove to be highly beneficial for patients and health-care professionals during real-time MEG recording. Furthermore, the identification of the epileptogenic lobe can provide clinicians with useful insights, and a pre-cursor for source localisation.

Antecedent infections in Guillain-Barré syndrome patients from south India.

Guillain-Barré syndrome (GBS) is the commonest post-infectious inflammatory peripheral neuropathy with undiscerned aetiology. The commonly reported antecedent infections implicated in India include Campylobacter jejuni, chikungunya, dengue, and Japanese encephalitis (JE). In this study from south India, we investigated the role of these four agents in triggering GBS. This case-control study was performed on 150 treatment-naive patients with GBS and 150 age and sex-matched controls from the same community. IgM immunoreactivity for C. jejuni, chikungunya, and dengue was detected by enzyme-linked immunosorbent assay (ELISA) in serum of patients with GBS and control subjects. Immunoreactivity against JE was detected in serum as well as cerebrospinal fluid (CSF) from patients (n = 150) and orthopaedic control (n = 45) subjects. The immunoreactivity against infections was compared between demyelinating and axonal subtypes of GBS. Overall, 119/150 patients with GBS had serological evidence of antecedent infection. Amongst those with evidence of antecedent infection, 24 (16%), 8 (5%), and 9 (6%) patients were exclusively immunoreactive to chikungunya, JE, and C. jejuni, respectively. In the remaining patients (78/119), immunoreactivity to multiple pathogens was noted. Immunoreactivity to C. jejuni infection was found in 32% of GBS patients compared to 2.7% controls (P < .001), whereas to chikungunya virus was reported in 66.7% of patients with GBS compared to 44.7% controls (P = .006). Anti-dengue immunoreactivity was significantly associated with the demyelinating subtype of GBS. Patients positive for JE IgM (CSF) manifested demyelinating electrophysiology. In this large case-control study, immunoreactivity against multiple infectious agents was observed in a subset of patients. Chikungunya was the commonest antecedent infection, followed by C. jejuni.

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.

P300 in mesial temporal lobe epilepsy and its correlation with cognition - A MEG based prospective case-control study.

PURPOSE: To assess the role of P300 in patients with temporal lobe epilepsy (TLE) with unilateral hippocampal sclerosis (HS) using magnetoencephalography (MEG) based auditory and visual oddball tasks, and to assess its correlation with neuropsychological tests. METHODS: Thirty-patients (M:F-17:13, onset-11.77 ±â€¯8.75 years, duration-16.10 ±â€¯9.61 years) with TLE-HS (Left:15, Right:15) and fifteen-healthy age, gender and years of education matched controls (M:F-10:5, age-28.13 ±â€¯4.76 years) underwent auditory and visual oddball tasks in MEG and cognition assessment using Indian Council of Medical Research (ICMR)-cognitive test battery. Independent component analysis (ICA) was applied to the magnetic evoked field responses for the detection of the P300 component. Source localization of P300 was performed with Classical LORETA Analysis Recursively Applied (CLARA). The latency and amplitude of P300 were estimated and subsequently correlated with cognitive scores. RESULTS: The visual P300 amplitude in the TLE group was lower when compared to the control group. In subgroup comparison (controls vs. right HS vs. left HS), visual P300 amplitudes were lower in the right HS group compared to both left HS and control groups (p-value = 0.014). On the other hand, no significant difference for auditory P300 latency or amplitude was noted between patients and controls as well as between subgroups. A negative correlation found between the MEG visual P300 amplitude and Indian Trial Making Test (TMT)-B duration in the patient group. CONCLUSION: Patients with TLE-HS have decreased visual-P300 amplitude. A significant correlation found between visual P300 amplitude and cognitive tests of visuospatial attention and working memory. Overall, MEG based visual P300 amplitude can be further explored with large sample size studies to establish as a complementary objective test for cognitive assessment in TLE.

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.

Content-Based Estimation of Brain MRI Tilt in Three Orthogonal Directions.

In a general scenario, the brain images acquired from magnetic resonance imaging (MRI) may experience tilt, distorting brain MR images. The tilt experienced by the brain MR images may result in misalignment during image registration for medical applications. Manually correcting (or estimating) the tilt on a large scale is time-consuming, expensive, and needs brain anatomy expertise. Thus, there is a need for an automatic way of performing tilt correction in three orthogonal directions (X, Y, Z). The proposed work aims to correct the tilt automatically by measuring the pitch angle, yaw angle, and roll angle in X-axis, Z-axis, and Y-axis, respectively. For correction of the tilt around the Z-axis (pointing to the superior direction), image processing techniques, principal component analysis, and similarity measures are used. Also, for correction of the tilt around the X-axis (pointing to the right direction), morphological operations, and tilt correction around the Y-axis (pointing to the anterior direction), orthogonal regression is used. The proposed approach was applied to adjust the tilt observed in the T1- and T2-weighted MR images. The simulation study with the proposed algorithm yielded an error of 0.40 ± 0.09°, and it outperformed the other existing studies. The tilt angle (in degrees) obtained is ranged from 6.2 ± 3.94, 2.35 ± 2.61, and 5 ± 4.36 in X-, Z-, and Y-directions, respectively, by using the proposed algorithm. The proposed work corrects the tilt more accurately and robustly when compared with existing studies.

Ganglioside complex antibodies in an Indian cohort of Guillain-Barré syndrome.

BACKGROUND: Antibodies against ganglioside complexes (GSCs) are associated with various clinical features and subtypes of Guillain-Barré syndrome (GBS). METHODS: One-hundred patients were evaluated for antibodies to GSCs formed by combination of GM1, GM2, GD1a, GD1b, GT1b, and GQ1b using manual enzyme linked immuno-sorbent assay (ELISA). RESULTS: Twenty-six patients were GSC antibody-positive, most frequent being against GM1-containing GSC (76.9%). Gender distribution, mean age, symptom-duration, antecedent events, electrophysiological subtypes, requirement for mechanical ventilation, and median duration of hospital stay were comparable between the GSC antibody-positive and negative groups. There was no association between specific GSC antibody and electrophysiological subtypes or clinical variants. After controlling for false discovery rate (FDR) using the Benjamini-Hochberg method, the number of subjects who improved in overall disability sum score, modified Erasmus GBS outcome score, and neuropathy symptom score at discharge was significantly higher in the GSC antibody-positive group. Improvements in Medical Research Council sum scores and Hughes Disability Scale during the hospital stay between the GSC antibody-positive and negative groups were not significantly different after controlling for FDR. CONCLUSIONS: The GSC antibody-positive group had better outcome at hospital discharge in some of the disability scores. Pathophysiological pathways among patients without GSC antibodies may be different and this requires further evaluation.

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.

Machine learning identifies "rsfMRI epilepsy networks" in temporal lobe epilepsy.

OBJECTIVES: Experimental models have provided compelling evidence for the existence of neural networks in temporal lobe epilepsy (TLE). To identify and validate the possible existence of resting-state "epilepsy networks," we used machine learning methods on resting-state functional magnetic resonance imaging (rsfMRI) data from 42 individuals with TLE. METHODS: Probabilistic independent component analysis (PICA) was applied to rsfMRI data from 132 subjects (42 TLE patients + 90 healthy controls) and 88 independent components (ICs) were obtained following standard procedures. Elastic net-selected features were used as inputs to support vector machine (SVM). The strengths of the top 10 networks were correlated with clinical features to obtain "rsfMRI epilepsy networks." RESULTS: SVM could classify individuals with epilepsy with 97.5% accuracy (sensitivity = 100%, specificity = 94.4%). Ten networks with the highest ranking were found in the frontal, perisylvian, cingulo-insular, posterior-quadrant, thalamic, cerebello-thalamic, and temporo-thalamic regions. The posterior-quadrant, cerebello-thalamic, thalamic, medial-visual, and perisylvian networks revealed significant correlation (r > 0.40) with age at onset of seizures, the frequency of seizures, duration of illness, and a number of anti-epileptic drugs. CONCLUSIONS: IC-derived rsfMRI networks contain epilepsy-related networks and machine learning methods are useful in identifying these networks in vivo. Increased network strength with disease progression in these "rsfMRI epilepsy networks" could reflect epileptogenesis in TLE. KEY POINTS: • ICA of resting-state fMRI carries disease-specific information about epilepsy. • Machine learning can classify these components with 97.5% accuracy. • "Subject-specific epilepsy networks" could quantify "epileptogenesis" in vivo.

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation.

BACKGROUND: Data on antibody profile in myasthenia gravis (MG) from India are limited. OBJECTIVES: To investigate antibody profile in patients with MG and their clinical correlates. PATIENTS AND METHODS: Patients of MG (n = 85, M:F::1.1:1, mean age: 39.29 ± 17.3 years, mean symptom duration: 72.94 ± 91.8 months) were evaluated for clinical features, MG foundation of America (MGFA) score, response to treatment, and outcome at last follow-up. Antibodies to acetylcholine receptor (AChR), muscle-specific kinase (MUSK), titin and ryanodine receptor (RYR) were analysed using ELISA. RESULTS: Based on the regional distribution of weakness, the cohort could be categorized as: generalized: 60, ocular: 16 and oculo-bulbar: 9. Sixty patients were followed up for a mean duration of 26.74 ± 13.8 months. Outcome at last follow-up was as follows: remission-22, no remission-33 and dead-5. AChR and MUSK antibodies were detected in 58 and 8 patients, respectively. Frequency of generalized MG, worse MGFA score during the disease course and thymomatous histology significantly correlated with presence of AChR-antibodies, though outcome at last follow-up was comparable between AChR-antibody positive and negative groups. Patients with MUSK antibodies had oculo-bulbar or generalized MG and frequent respiratory crisis, but majority improved or remitted with treatment. Titin antibodies were detected in 31.8% and RYR antibodies in 32.9%. Their presence did not correlate with age at onset of MG, severity or presence of thymoma. CONCLUSION: This report highlights the spectrum of antibodies in MG in an Indian cohort. AChR-antibody positivity correlated with clinical severity. Outcome was good in majority of MUSK antibody-positive MG. The role of other antibodies, complementary vs epiphenomenon, remains open.

Comprehensive cytokine profiling provides evidence for a multi-lineage Th responses in Guillain Barré Syndrome.

Guillain Barré Syndrome (GBS) is one of the commonest acquired immune-mediated neuropathies, often preceded by infections. Although cellular immune responses are shown to substantially account for the pathophysiology of GBS, the precise mechanistic basis of risk and disease course remains enigmatic till date. Cytokines are best known for their abilities to drive cellular immunity and inflammation through their co-ordinated actions. Data obtained from clinical and animal model studies suggest important implications of some of the cytokines in the progression and recovery of GBS. However, these studies were performed on few cytokines and small set of GBS patients, thereby lacking a complete understanding of the patterns of association of cytokines representing Th1, Th2, and Th17 responses with GBS. We studied 65 well-characterized GBS patients and 73 age- and sex-matched healthy controls. A panel of 15 cytokines representing Th1, Th2 and Th17 pathways was assayed using Multiplex Suspension Array platform. Plasma levels of five cytokines were found to be altered in GBS patients compared to healthy control subjects: (i) IL-1ß exhibited reduced levels, and (ii) IFN-γ, IL-4, IL-21 and IL-33 were elevated in GBS patients. The most important finding of this study was up-regulated expression of IL-21 and IL-33 in patients with GBS. Given the role of IL-33 as an alarmin, the elevated level of this cytokine provides important indication about a much broader role of cytokines in GBS. This study also provides evidence towards a multi-lineage Th cells (Th1, Th2 and Th17) associated cytokine responses in the pathophysiology of GBS.