Publications by authors named "Ramshekhar N Menon"

41 Publications

Unmasking the entity of 'drug-resistant' perioral myoclonia with absences: the twitches, darts and domes!

Epileptic Disord 2021 Apr 12. Epub 2021 Apr 12.

Sree Chitra Tirunal Institute for Medical Sciences and Technology, Dept of Neurology, Thiruvananthapuram, Kerala, India.

Perioral myoclonia with absences (POMA) is not recognized as a unique electro-clinical syndrome and studies suggest its inclusion under the genetic generalized epilepsy (GGE) spectrum. The aim of this study was to explore the prevalence and electro-clinical homogeneity of this disorder in an epilepsy monitoring unit. Between 2013 and 2019, among drug-resistant epilepsy patients who were referred for video-telemetry, those diagnosed with POMA based on the presence of documented absences with prominently observed peri-oral muscular contractions accompanied by generalized EEG features were included. Among 62 patients who were diagnosed with absence epilepsy, five finally met the criteria for POMA (8.1%) with late childhood or adolescent onset of epilepsy. Four (80%) had a referral diagnosis of focal epilepsy based on historical focal features with exacerbation of seizures on oxcarbazepine. All five patients demonstrated brief absences with orbicularis oris muscle contractions accompanied by subtle focal phenomenology. One patient had concurrent axial-appendicular myoclonic jerks precipitated by hyperventilation. While four patients had strikingly identical interictal and ictal characteristics of typical absence epilepsy, one patient demonstrated additional atypical generalized polyspike discharges without a "dart-dome" morphology. Therapeutic response to introduction of sodium valproate was noted in all five patients. Features that were not consistent with the diagnosis were apparent in one patient who was re-classified with combined focal and generalized epilepsy. Differentiating aspects in this patient included multifocal discharges, background slowing, fast-recruiting ictal rhythms and valproate resistance. This is one of the largest case series of POMA. This entity, which falls under the spectrum of GGE, remains under-diagnosed and its distinctive electro-clinical features need to be recorded in order to prevent misclassification as focal epilepsy of probable opercular origin. Background-slowing, atypical ictal rhythms and valproate unresponsiveness are not consistent with the diagnosis of this unique absence epilepsy. [Published with video sequences].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2021.1265DOI Listing
April 2021

Adult-onset subacute sclerosing panencephalitis.

Pract Neurol 2021 Apr 13. Epub 2021 Apr 13.

Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India

Subacute sclerosing panencephalitis (SSPE) is a lethal slow viral disease of the central nervous system caused by a defective measles virus. The onset is mostly in childhood, manifesting clinically as decline in academic performance, behavioural changes, motor dysfunction and myoclonus. Adult-onset SSPE is rare and can present as rapidly progressive dementia. We present a young man of Indian origin with adult-onset SSPE with rapidly progressive dementia but no localising neurological signs. The diagnostic clues were parieto-occipital white matter changes on MR brain scan and history of childhood fever with rash. High titres of antimeasles antibody in cerebrospinal fluid confirmed the diagnosis. The long latency from primary measles virus infection to symptom onset can be misleading in adults. SSPE should be considered in adults with dementia, especially in tropical countries where vaccination coverage is suboptimal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/practneurol-2020-002880DOI Listing
April 2021

Impaired intrinsic functional connectivity among medial temporal lobe and sub-regions related to memory deficits in intracranial dural arteriovenous fistula.

Neuroradiology 2021 Apr 10. Epub 2021 Apr 10.

Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, 695011, India.

Purpose: The functional changes concerning memory deficits in dural arteriovenous fistula (dAVF) brain are inadequately understood. This study aimed to understand the functional connectivity alterations of brain regions widely affirmed for explicit and implicit memory functions in dAVF patients (DP) and look into the frequency effects of the altered functional networks.

Methods: Resting-state functional magnetic resonance imaging (rsfMRI) analysis was done in the memory-associated regions of 30 DP and 30 healthy controls (HC). Frequency decomposition was used to determine potential frequency-dependent functional connectivity changes. They underwent neuropsychological tests and were correlated with changes in memory networks compared with HC.

Results: The results showed weaker functional connectivity among the medial temporal lobe and sub-regions in DP suggestive of dysfunction of explicit and implicit memory functions, which corroborated with the positive correlation between memory scores and hippocampal-parahippocampal connectivity of DP, along with a significant group difference of lower memory and cognitive performance in DP assessed by neuropsychological tests. A frequency-dependent study of the altered rsFC revealed lower functional connectivity strength and impaired neural coupling manifested at some sub-band frequencies indicative of disturbed cortical rhythm in DP.

Conclusion: This pilot study gives insights into significant intrinsic functional connectivity changes in the memory regions of the dAVF brain. The results may have clinical implications in the choice of interventional management of dAVF and can impact clinical decision making for realizable prevention of progressive memory impairment and irreversible brain damage in such patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00234-021-02707-wDOI Listing
April 2021

Validation of Indian Council of Medical Research Neurocognitive Tool Box in Diagnosis of Mild Cognitive Impairment in India: Lessons from a Harmonization Process in a Linguistically Diverse Society.

Dement Geriatr Cogn Disord 2020 7;49(4):355-364. Epub 2021 Jan 7.

Departments of Neurology and Neuropsychology, All India Institute of Medical Sciences, Delhi, India.

Background/aims: In a linguistically diverse country such as India, challenges remain with regard to diagnosis of early cognitive decline among the elderly, with no prior attempts made to simultaneously validate a comprehensive battery of tests across domains in multiple languages. This study aimed to determine the utility of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB) in the diagnosis of mild cognitive impairment (MCI) and its vascular subtype (VaMCI) in 5 Indian languages.

Methods: Literate subjects from 5 centers across the country were recruited using a uniform process, and all subjects were classified based on clinical evaluations and a gold standard test protocol into normal cognition, MCI, and VaMCI. Following adaptation and harmonization of the ICMR-NCTB across 5 different Indian languages into a composite Z score, its test performance against standards, including sensitivity and specificity of the instrument as well as of its subcomponents in diagnosis of MCI, was evaluated in age and education unmatched and matched groups.

Results: Variability in sensitivity-specificity estimates was noted between languages when a total of 991 controls and 205 patients with MCI (157 MCI and 48 VaMCI) were compared due to a significant impact of age, education, and language. Data from a total of 506 controls, 144 patients with MCI, and 46 patients with VaMCI who were age- and education-matched were compared. Post hoc analysis after correction for multiple comparisons revealed better performance in controls relative to all-cause MCI. An optimum composite Z-score of -0.541 achieved a sensitivity of 81.1% and a specificity of 88.8% for diagnosis of all-cause MCI, with a high specificity for diagnosis of VaMCI. Using combinations of multiple-domain 2 test subcomponents retained a sensitivity and specificity of >80% for diagnosis of MCI.

Conclusions: The ICMR-NCTB is a "first of its kind" approach at harmonizing neuropsychological tests across 5 Indian languages for the diagnosis of MCI due to vascular and other etiologies. Utilizing multiple-domain subcomponents also retains the validity of this instrument, making it a valuable tool in MCI research in multilingual settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000512393DOI Listing
January 2021

Do Spike Domain Analysis Interictally Correlate With the Ictal Patterns in Temporal Lobe Epilepsy?

J Clin Neurophysiol 2020 Oct 14. Epub 2020 Oct 14.

R. Madhavan Nayar Center for Comprehensive Epilepsy Care, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.

Purpose: To study if one can conceptualize the scalp ictal onset pattern through analysis of interictal spike domain analysis in temporal lobe epilepsy (TLE).

Methods: Seventy-four patients with unilateral mesial temporal sclerosis (MTS) were categorized into "type A" interictal epileptiform discharges (IEDs) with negativity over infero-lateral scalp electrodes over temporal region and contralateral central region showing positivity; all IEDs other than type A were categorized as type B. The ictal electrographic patterns was termed "focal" when confined to side of MTS, was "regional" when lateralized to the ipsilateral hemisphere; "diffuse" if nonlateralized/localized; and ictal onset contralateral to MTS termed as "discordant."

Results: A total of 377 seizures and 5,476 spikes were studied. These were divided into four types: (1) type A IEDs ipsilateral to MTS (44 patients), (2) type A IEDs bitemporally (16 patients), (3) type A IEDs contralaterally (7 patients) and type B IEDs ipsilaterally, and (4) bilateral type B IEDs (7 patients). The ictal pattern was either focal or regional in 51 of 60 patients (85%) with type A IEDs; it was "diffuse" in 9 patients (15%). Diffuse ictal onset was seen in 12 of 14 (86%) with either ipsilateral/bitemporal type B IEDs. Ictal onset on the opposite hemisphere was noted in 2 (14%).

Conclusions: Type A IEDs signify a focal ictal onset and type B IEDs suggest a diffuse ictal onset in patients with MTS on one side.

Significance: Interictal spike domain analysis helps predicting ictal patterns in temporal lobe epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNP.0000000000000785DOI Listing
October 2020

Predictors of one-year language and seizure outcomes in children with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS).

Seizure 2020 Oct 28;81:315-324. Epub 2020 Aug 28.

R Madhavan Nayar Centre for Comprehensive Epilepsy Care, Dept of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, Kerala, 695011, India.

Purpose: Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS), with its associated impact on language, is an important cause of morbidity with epilepsy in children. The effects of various treatment-approaches and the aetiological/electrophysiological factors affecting therapeutic response are not fully understood.

Method: A retrospective study of patients admitted to the institute and diagnosed to have CSWS pattern on EEG was conducted. Spike and Wave Frequency/100 s(SWF) was calculated from sleep-EEG records. Language development and seizure outcomes were assessed at baseline and 1 year.

Results: Fifty-two children were included (idiopathic CSWS, N = 19; symptomatic CSWS N = 33).The 2 groups differed in terms of younger age at seizure onset in symptomatic CSWS (p = 0.006), early age at language regression (p = 0.046), history of neonatal seizures (p = 0.038) and slowing of background activity on EEG (p = 0.024). Language regression was noted in 63.5 % of the cohort. Twenty-five (48%) patients received steroids with improvement in seizures (p < 0.001). Twenty-one (40.3 %) received steroids and intravenous immunoglobulin (IVIG) with improvement in seizure score (p = 0.002) at 1 year. Both immune-modulation arms irrespective of etiological subgroups had comparable proportions of children with expressive and receptive language gains. On 1 year follow-up, seizure remission was noted in 13(25 %) patients, with improved seizure score in 32/39 (61.5 %) patients and language improvement in 32 children (60.8 %). Patients with normal background on baseline EEG, generalised spikes, absent frontal-negative spikes and SWF < 170 were found to have improved language estimates on follow-up.

Conclusions: Despite clinical and therapeutic outcome differences between idiopathic and symptomatic CSWS, immune-modulation appears effective irrespective of aetiology. Analysis of EEG variables enables prediction of language outcomes at 1 year follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2020.08.025DOI Listing
October 2020

Methylenetetrahydrofolate Reductase Deficiency as a Cause of Treatable Adult-onset Leukoencephalopathy and Myelopathy.

Clin Neuroradiol 2021 Mar 3;31(1):277-281. Epub 2020 Sep 3.

Neuroradiology Division, Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00062-020-00947-6DOI Listing
March 2021

Electroclinical Phenotype-Genotype Homogeneity in Drug-Resistant "Generalized" Tonic-Clonic Seizures of Early Childhood.

Clin EEG Neurosci 2020 Sep 3:1550059420953735. Epub 2020 Sep 3.

Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, Kerala, India.

Purpose: Children with refractory focal to bilateral tonic-clonic seizures, despite normal high-resolution imaging, are often not subjected to genetic tests due to the costs involved and instead undergo multimodality presurgical evaluation targeted at delineating a focal onset. The objective of this study was to ascertain genotype-phenotype correlations in this group of patients.

Method: An online hospital database search was conducted for children who presented in 2019 with drug-resistant epilepsy dominated by nonlateralizing focal-onset/rapid generalized (bilateral) tonic-clonic seizures (GTCS), subjected to presurgical evaluation and subsequent genetic testing due to absence of a clear focus hypothesis.

Results: Phenotypic homogeneity was apparent in 3 children who had onset in infancy with drug-resistant GTCS (predominantly unprovoked and occasionally fever provoked) and subsequent delayed development. 3-Tesla magnetic resonance imaging (MRI) scans were negative and video EEG documented a homogeneous pattern of multifocal and/or generalized epileptiform discharges with phenomenology favoring probable focal-onset/generalized-onset bilateral tonic-clonic seizures. All 3 tested positive for gene variants (heterozygous missense substitution variants in 2 children, one of which was novel and a novel duplication in one that led to frameshift and premature truncation of the protein), suggestive of -mediated epilepsy. This electroclinical profile constituted 3 out of 25 patients with -epilepsy phenotypes at our center.

Conclusions: These cases suggest that children with early-onset drug-resistant "generalized" epilepsy are likely to have a genetic basis although the presentation may not be typical of Dravet syndrome. Hence, genetic testing for variants is recommended in children with drug-resistant MRI negative focal-onset/generalized-onset bilateral tonic-clonic seizures before subjecting them to exhaustive presurgical workup and to guide appropriate treatment and prognostication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1550059420953735DOI Listing
September 2020

Does resting state functional connectivity differ between mild cognitive impairment and early Alzheimer's dementia?

J Neurol Sci 2020 Nov 13;418:117093. Epub 2020 Aug 13.

Cognition and Behavioural Neurology Section, Department of Neurology, SreeChitraTirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India. Electronic address:

Purpose: This study aimed to investigate differences in functional connectivity (FC) among different resting state networks (RSN) in clinically non-progressive mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Methods: Using 3T MRI acquired resting-state functional MRI (rs-fMRI), we attempted identification of different RSN using independent component analysis (ICA) in amnestic-MCI, convertors to early AD and age-matched cognitively normal healthy controls. Regions of interest (ROI) that showed significant differences in connectivity on group ICA were selected as seeds for seed-voxel analysis. Group differences in FC for each network-connectivity map were entered into a general linear model with age, gender and total intra-cranial volume (TIV) as covariates.

Results: In this cross-sectional design 31 HC, 30 MCI and 30 MCI-convertors to early AD were evaluated. Seed-based analysis between AD and controls revealed reduced posterior connectivity within the default mode (DMN), dorsal attention (DAN) and antero-posterior connectivity with sensori-motor (SMN) networks. Reduced cerebellar connectivity of DMN and posterior connectivity within the frontal parietal network (FPN) separated AD from MCI. MCI-control comparisons revealed differences only on ICA. Positive correlation was observed between FC in DMN network clusters with verbal list-learning (r = 0.50) and recall scores (r = 0.51) in AD, the latter additionally demonstrating correlation with SMN clusters (r = 0.50).

Conclusions: Widespread network hypo-connectivity is apparent in AD as opposed to MCI non-convertors in comparison to controls, along with positive correlation with memory scores. Reduced connectivity involving DMN and FPN helps to differentiate between AD and MCI-nonconvertors to dementia. Longitudinal studies are required into utility of these measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2020.117093DOI Listing
November 2020

Genotype-phenotype correlates of infantile-onset developmental & epileptic encephalopathy syndromes in South India: A single centre experience.

Epilepsy Res 2020 10 18;166:106398. Epub 2020 Jun 18.

R. Madhavan Nayar Center for Comprehensive Epilepsy Care, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.

Introduction: A paucity of literature exists on genotype- phenotype correlates of 'unknown-etiology' infantile-onset developmental-epileptic encephalopathies (DEE) from India. The primary objective was to explore the yield of genetic testing in identifying potential disease causing variants in electro-clinical phenotypes of DEE METHODS: An observational hospital-based study was undertaken on children with unexplained refractory seizure-onset ≤12 months age and developmental delay, whose families consented and underwent genetic testing during a three year time period (2016-2018) by next-generation sequencing (NGS) or multiplex ligand protein amplification. Yield was considered based on demonstration of pathogenic/likely pathogenic variants only and variants of unknown significance (VUS) were documented.

Results: Pathogenic/likely pathogenic variants were identified in 26 (31.7 %) out of 82 children with DEE. These included those variants responsible for primarily DEE- 21(76.7 %); neuro-metabolic disorders- 3(18.6 %) and chromosomal deletions- 2(4.7 %). Of these patients, early-infantile epilepsy onset ≤ 6 months age was noted in 22(84.6 %). The DEE studied included Ohtahara syndrome associated with STXBP1 and SCN8A variants with yield of 50 % (2/4 tested); early myoclonic encephalopathy (no yield in 2); West syndrome with CDKL5, yield of 13.3 % (2/15 tested); epilepsy of infancy with migrating partial seizures due to CACNA1A and KCNT1 variants, yield of 67 % (2/3 tested); DEE-unclassified with KCNQ2, AP3B2, ZEB2, metabolic variants (SUOX, ALDH7A1, GLDC) and chromosome deletions (chr 1p36, chr2q24.3); yield of 32 % (8/25 tested). Patients with Dravet syndrome/Dravet-like phenotypes (N = 33) had variants in SCN1A (N = 10), SCN1B, CHD2; yield of 36.4 % (12/33 tested; 57.1 % from NGS). Eighteen patients with potential variants (SCN1A, SCN2A, SCN8A, KCNQ2, ALDH7A1 which also included VUS) could be offered targeted therapy.

Conclusions: Our study confirms a good yield of genetic testing in neonatal and infantile-onset DEE provided robust phenotyping of infants is attempted with prognostic and therapeutic implications, particularly relevant to centres with resource constraints.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eplepsyres.2020.106398DOI Listing
October 2020

Personality disorders in temporal lobe epilepsy: What do they signify?

Acta Neurol Scand 2020 Sep 25;142(3):210-215. Epub 2020 May 25.

R.Madhavan Nayar Center for Comprehensive Epilepsy Care, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India.

Objectives: To estimate the prevalence of personality disorders in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and compare it with general population and analyze their implications on treatment outcome.

Materials And Methods: TLE was diagnosed based on clinical history, MRI, and Video EEG data. IPDE-ICD10 screening questionnaire was applied to investigate personality disorder in 120 subjects, 60 cases, and 60 normal controls. Bear-Fedio inventory (BFI) was used to study different behavior traits in patients with TLE and controls.

Results: Prevalence of personality disorders was higher (71.7% in cases versus 38.3% in controls) in patients with TLE compared to controls (P < .001). Some personality traits like schizoid (P = .002), dissocial (P = .001), impulsive (P = .003), anankastic (P < .001), anxious (P < .001), and dependent (P < .001) personalities were found to have high prevalence in TLE. Personality disorder was higher among those cases who had been tried on more than two antiepileptic drugs (AEDs) (P = .033) and in those with duration of illness more than 10 years (P = .026). Cases also showed significantly higher score in BFI for all behavioral traits except for aggression. No significant difference of BFI score was seen based on laterality of epileptic focus, gender, duration of illness, or number of AEDs tried.

Conclusion: There is a significantly higher prevalence of personality disorders in patients with TLE. Specific interventions for these disorders should be considered at the earliest pari passu with AEDs and surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13259DOI Listing
September 2020

Clinical and Genetic Profile of Autism Spectrum Disorder-Epilepsy (ASD-E) Phenotype: Two Sides of the Same Coin!

Clin EEG Neurosci 2020 Nov 2;51(6):390-398. Epub 2020 Mar 2.

Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.

The clinical phenotype of autism spectrum disorder and epilepsy (ASD-E) is a common neurological presentation in various genetic disorders, irrespective of the underlying pathophysiological mechanisms. Here we describe the demographic and clinical profiles, coexistent neurological conditions, type of seizures, epilepsy syndrome, and EEG findings in 11 patients with ASD-E phenotype with proven genetic etiology. The commonest genetic abnormality noted was mutation (3), mutation (2), and 1p36 deletion (2). The median age of onset of clinical seizures was 6 months (range, 10 days to 11 years). The most common seizure type was focal onset seizures with impaired awareness, observed in 7 (63.6%) patients followed by epileptic spasms in 4 (30.8%), generalized tonic-clonic and atonic seizures in 3 (27.3%) patients each and tonic seizures in 2 (18.2%) patients and myoclonic seizures in 1 (9.1%) patient. Focal and multifocal interictal epileptiform abnormalities were seen in 6 (54.6%) and 5 (45.5%) patients, respectively. Epileptic encephalopathy and focal epilepsy were seen in 7 (63.6%) and 4 (36.4%) patients, respectively. The diagnostic yield of genetic testing was 44% (11 of 25 patients) and when variants of unknown significance and metabolic defects were included, the yield increased to 60% (15 of 25 patients). We conclude that in patients with ASD-E phenotype with an underlying genetic basis, the clinical seizure type, epilepsy syndrome, and EEG patterns are variable. Next-generation exome sequencing and chromosomal microarray need to be considered in clinical practice as part of evaluation of children with ASD-E phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1550059420909673DOI Listing
November 2020

Novel Face-Name Paired Associate Learning and Famous Face Recognition in Mild Cognitive Impairment: A Neuropsychological and Brain Volumetric Study.

Dement Geriatr Cogn Dis Extra 2019 Jan-Apr;9(1):114-128. Epub 2019 Mar 12.

Cognition and Behavioral Neurology Subsection, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.

Purpose: To assess visual associative learning and famous face recognition ability among subjects with stable amnestic mild cognitive impairment (MCI) relative to early stage dementia due to Alzheimer's disease (AD) and cognitively normal healthy controls (NC) and to correlate these differences with volumetric changes on MRI.

Methods: A hospital-based cross-sectional observational study was conducted on 61 participants. The subjects underwent neuropsychological evaluation, including validated newly designed tests for novel face-name paired association learning recall and famous face recognition. MRI volumetry was done on a subset of patients to ascertain the topographical patterns of volume loss.

Results: There were significant differences in performance on free recall for face-name paired associate learning in MCI ( = 22) compared to NC ( = 20) ( < 0.001) and MCI compared to AD ( = 19; < 0.001). Significant differences were also noted in scores on the famous personalities test between MCI and NC ( = 0.007), and MCI and AD ( = 0.032). The free recall component of face-name pair associative learning significantly correlated with left cuneus ( = 0.005; = 0.833) and right cuneus ( = 0.003; = 0.861) volume in AD with no significant correlation among MCI and NC cohorts.

Conclusions: Novel and semantically familiar face-name associative recalls are significantly impaired in MCI, and these potentially predate the MRI volumetric changes in MCI. Our findings expand the spectrum of recall deficits in MCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000496476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589478PMC
March 2019

Do quantified sleep architecture abnormalities underlie cognitive disturbances in amnestic mild cognitive impairment?

J Clin Neurosci 2019 Sep 17;67:85-92. Epub 2019 Jun 17.

Comprehensive Care Centre for Sleep Disorders, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India.

The study was designed to gauge association between occult sleep-related breathing disturbances and sleep architecture changes on cognitive trajectories in subjects with amnestic mild cognitive impairment (aMCI) relative to cognitively normal healthy controls, phenotyped by neuroimaging. Subjects with aMCI and normal cognition were prospectively recruited. Following standardized neuropsychological and sleep questionnaire assessment they underwent a single overnight polysomnography (PSG); multimodality MRI was used to ascertain age-corrected radiological differences between the 2 groups. The aMCI cohort was followed up longitudinally with serial cognitive assessments for the next 3 years. Thirty seven subjects with aMCI and 24 control subjects consented for evaluation. Although occult moderate to severe obstructive sleep apnea (OSA) was more prevalent in aMCI (43.6%) as opposed to controls (22.7%); higher median apnea-hypopnea index (AHI = 11.5) and total apnea-hypopnea time (26.6 min) were also noted in aMCI relative to controls (6.6 and 11.4 min respectively), the differences were not statistically significant. In the aMCI group, better sleep efficiency, longer duration of REM sleep correlated with higher associative learning, free-recall/recognition memory performance. Higher AHI had negative correlation with visual memory scores. However longitudinal cognitive trends in the aMCI group over 3 years reflected relative stability (only 5% progressed to AD) notwithstanding imaging differences from controls and appeared to be independent of sleep parameters. The study concluded that despite associations between sleep efficiency, REM sleep and sleep-related breathing variables with neuropsychological test-scores in aMCI, these appear to be comorbidities rather than causative factors for the degree of cognitive impairment or its longitudinal trajectory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2019.06.014DOI Listing
September 2019

Seizure outcome and its predictors after frontal lobe epilepsy surgery.

Acta Neurol Scand 2019 Oct 8;140(4):259-267. Epub 2019 Jul 8.

Department of Neurology, R.Madhavan Nayar Center for Comprehensive Epilepsy Care, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.

Objectives: Frontal lobe epilepsy (FLE) surgery is the second most common focal resective surgery for drug-resistant epilepsy. Not many studies are available regarding the long-term surgical outcome of FLE. We studied the longitudinal outcome and predictors of seizure outcome following FLE surgery in a sizeable cohort of patients.

Materials & Methods: A total of 73 consecutive patients who underwent FLE surgery between January 1997 and May 2015 with a minimum follow-up of 1 year (range 1-16 years) were studied. Primary outcome was seizure freedom at last follow-up (Engel Class IA). "Seizure freedom" separately was defined as absence of seizures till last follow-up. Outcome predictors were subjected to multivariate analysis. Using Kaplan-Meier curve, we assessed the post-operative seizure freedom over time.

Results: Twenty-five patients (34%) were seizure-free till last follow-up. The seizure freedom was 45%, 34%, 26%, 20% and 14% at the end of 1st, 2nd, 3rd, 4th and 5th post-operative year, respectively. Engel class I outcomes were 48%, 41%, 56%, 57% and 53% at end of 1st, 2nd, 3rd, 4th and 5th post-operative year, respectively. Predictors of seizure recurrence on multivariate analysis were older age at surgery (P = 0.032), longer duration of epilepsy (P = 0.031), presence of interictal epileptiform discharges in post-operative EEG on 7th day (P = 0.005), 3 months (P = 0.005) and 1 year (P = 0.0179). In subgroup analysis, duration of epilepsy of less than 2 years before surgery was a significant predictor for achieving seizure freedom (P = 0.029).

Conclusions: These results emphasize early surgery for better outcome in frontal lobe epilepsy. Post-operative EEG remained a good predictor for long-term outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13139DOI Listing
October 2019

Glutamatergic response to a low load working memory paradigm in the left dorsolateral prefrontal cortex in patients with mild cognitive impairment: a functional magnetic resonance spectroscopy study.

Brain Imaging Behav 2020 Apr;14(2):451-459

Medical Image Processing Laboratory, Department of Imaging Sciences and Interventional Radiology (IS & IR), Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, 695 011, India.

Working memory deficits have been widely reported in mild cognitive impairment (MCI). However, the neural mechanisms of working memory dysfunction in MCI have not been clearly understood. In this study, we used proton functional magnetic resonance spectroscopy (H-fMRS) and functional magnetic resonance imaging (fMRI) to understand the underlying neurobiology of working memory deficits in patients with MCI. We aimed at detecting the changes in the concentration of glutamate and blood oxygen level dependent (BOLD) activity using H-fMRS and fMRI respectively during a low load verbal (0 back and 1 back) working memory in the left dorsolateral prefrontal cortex (DLPFC) between patients with MCI and healthy controls. Fifteen patients with amnestic MCI and twenty two age, gender and education matched healthy controls underwent a low load verbal working memory H-fMRS and fMRI. We observed significant increase in glutamate during working memory task (both 0 back and 1 back) in healthy controls and such changes were absent in patients with MCI. However, percent signal changes representing BOLD activity during both 0 back and 1 back was not significantly different between two groups. Our findings suggest that H-fMRS complements fMRI in understanding the working memory mechanism in the left DLPFC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11682-019-00122-7DOI Listing
April 2020

Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients.

J Neurol 2019 Aug 8;266(8):1919-1926. Epub 2019 May 8.

Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India.

Background: Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge.

Methods: We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform.

Results: We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function.

Conclusion: In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-019-09358-1DOI Listing
August 2019

Novel genotype-electroclinical phenotype correlations in sporadic early-onset childhood myoclonic-atonic epilepsy.

Neurol India 2019 Jan-Feb;67(1):264-267

R Madhavan Nayar Centre for Comprehensive Epilepsy Care, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0028-3886.253628DOI Listing
January 2020

Mitochondrial acetoacetyl-CoA thiolase enzyme deficiency in a 9-month old boy: Atypical urinary metabolic profile with a novel homozygous mutation in ACAT1 gene.

Neurol India 2018 Nov-Dec;66(6):1802-1804

Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0028-3886.246264DOI Listing
September 2019

Status epilepticus related to pregnancy: Devising a protocol for use in the intensive care unit.

Neurol India 2018 Nov-Dec;66(6):1629-1633

Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.

Background: Status epilepticus (SE) related to pregnancy is rare and carries a significant risk to both the mother and the fetus.

Objectives: We conducted this study to devise a protocol for the management of SE related to pregnancy in a cohort of female patients admitted with SE during pregnancy.

Materials And Methods: All women who developed SE related to pregnancy (gestation, labor, and puerperium) between January 2000 and December 2016 were included. Data was collected using a structured proforma.

Results: There were 17 women who had SE related to pregnancy, of whom 10 had refractory SE. The various causes of refractory SE were eclampsia (N = 2), posterior reversible encephalopathy syndrome (PRES) due to various causes other than eclampsia (N = 3), cortical venous thrombosis (CVT) [N = 3], subarachnoid hemorrhage (SAH) [N = 1], and N-methyl-D-aspartate (NMDA) receptor antibody-mediated encephalitis (N = 1). Six out of 10 women with refractory SE (60%) and five out of 10 fetuses (50%) had a good outcome.

Conclusion: There is a dearth of literature with regards to SE related to pregnancy and little or no guidelines exist for its management. Awareness about the diverse etiologies other than eclampsia is important. A protocol-based approach to the diagnosis and management of SE is necessary to ensure best outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0028-3886.246279DOI Listing
September 2019

Do auras predict seizure outcome after temporal lobe epilepsy surgery?

Epilepsy Res 2018 11 27;147:109-114. Epub 2018 Aug 27.

R. Madhavan Nayar Center for Comprehensive Epilepsy Care, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.

Purpose: The success of epilepsy surgery lies in identifying the ictal onset zone accurately. The significance of auras has little been explored on surgical outcome in drug-resistant epilepsy. This study focuses on the clinicopathological correlation of aura(s) and its role in predicting surgical outcome in drug-resistant temporal lobe epilepsy (TLE). We compared surgical outcome in TLE between patients with and without aura and identified the clinico-pathological, radiological and surgical differences between the two groups.

Methods: Consecutive patients who underwent presurgical evaluation from January 2009 to December 2014 for drug-resistant TLE who underwent anterior temporal lobectomy (ATL) were included. Patients were followed up at 3months, 12 months and then annually.

Results: Among 456 patients, 344(75%) had aura. Multivariate logistic regression showed that prototype EEG pattern at ictal onset (OR 2.12, 95% CI 1.18-3.06, p = 0.012) and right sided epileptogenic zone (OR 1.82 95% CI 1.18-3.78, p = 0.007) were significantly associated with presence of aura. There was no difference in surgical outcome between those with and without aura. But patients with auditory aura (OR 7.28, CI 2.80-18.95, p = 0.0002) and vertiginous aura (OR 3.01, CI 1.55-7.85, p = 0.028) had a poor surgical outcome. Bivariate analysis showed that normal MRI (p = 0.028) and normal/indeterminate pathology (p = 0.001) were significantly more common with auditory/vertiginous auras.

Conclusions: Mere presence of aura does not affect outcome after TLE surgery. However, auditory and vertiginous auras are predictors of poor surgical outcome. These patients require more extensive screening for an ictal onset zone beyond standard limits of ATL before surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eplepsyres.2018.08.006DOI Listing
November 2018

Multimodality Neuroimaging in Mild Cognitive Impairment: A Cross-sectional Comparison Study.

Ann Indian Acad Neurol 2018 Apr-Jun;21(2):133-139

Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.

Background And Purpose: Mild cognitive impairment (MCI) is a focus of considerable research. The present study aimed to test the utility of a logistic regression-derived classifier, combining specific quantitative multimodal magnetic resonance imaging (MRI) data for the early objective phenotyping of MCI in the clinic, over structural MRI data.

Methods: Thirty-three participants with cognitively stable amnestic MCI; 15 MCI converters to early Alzheimer's disease (AD; diseased controls) and 20 healthy controls underwent high-resolution T1-weighted volumetric MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (H MR spectroscopy). The regional volumes were obtained from T1-weighted MRI. The fractional anisotropy and mean diffusivity maps were derived from DTI over multiple white matter regions. The H MRS voxels were placed over posterior cingulate gyri, and N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myoinositol (mI/Cr), and NAA/mI ratios were obtained. A multimodal classifier comprising MR volumetry, DTI, and MRS was prepared. A cutoff point was arrived based on receiver operator characteristics analysis. Results were considered significant, if < 0.05.

Results: The most sensitive individual marker to discriminate MCI from controls was DTI (90.9%), with a specificity of 50%. For classifying MCI from AD, the best individual modality was DTI (72.7%), with a high specificity of 87.9%. The multimodal classifier approach for MCI control classification achieved an area under curve (AUC) (AUC = 0.89; < 0.001), with 93.9% sensitivity and 70% specificity. The combined classifier for MCI-AD achieved a highest AUC (AUC = 0.93; < 0.001), with 93% sensitivity and 85.6% specificity.

Conclusions: The combined method of gray matter atrophy, white matter tract changes, and metabolite variation achieved a better performance at classifying MCI compared to the application of individual MRI biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/aian.AIAN_379_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073958PMC
August 2018

Electroclinical characteristics and syndromic associations of "eye-condition" related visual sensitive epilepsies-A cross-sectional study.

Seizure 2018 May 30;58:62-71. Epub 2018 Mar 30.

R Madhavan Nayar Centre for Comprehensive Epilepsy Care, Dept of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.

Purpose: The systematic study of visual phenomena such as eye closure (ECLS), eye-closed/fixation-off sensitivity (FOS) [terminology proposed as eye-condition sensitive (ECS) epilepsy] distinct from photosensitivity is rarely explored in literature.

Methods: Clinical, electroencephalographic (EEG) and imaging records of patients attending an epilepsy clinic were screened. Inclusion criterion was demonstrable electrographic visual sensitivitiy in the form of ECS parameters with/without photosensitivity. Subsequently, detailed analysis of their data was undertaken.

Results: Fifty two patients had one or more ECS parameters. Mean age of onset of epilepsy of the cohort was 10.26 ± 7.79 yrs. A family history of seizures was noted in 17% of the cohort. ECLS, FOS, combination of both, co-existent scotosensitivity and photosensitivity were noted in 32.6%, 48.1%, 19.2%, 23.1% and 30.8% respectively. Epilepsy syndromes included late-onset childhood occipital epilepsy-Gastaut variant (23.1%), reflex occipital lobe epilepsy with ECS without photosensitivity (21.2%), idiopathic photosensitive occipital epilepsy (13.5%), genetic generalized epilepsy (13.5%) and symptomatic epilepsy (28.7%) predominated by patients with posterior cortex gliosis or who were imaging negative. The idiopathic group also had lower seizure score and marked sleep activation of epileptiform abnormalities. Co-existent phostosensitivity was associated with a significantly higher predisposition for female gender, ECLS, generalized seizures and spikes with lower prevalence of FOS and extra-occipital spikes. Parieto-occipital spikes were noted in 88.4% patients.

Conclusion: Syndromic heterogeneity is evident in ECS epilepsies. These form a unique subset of visual-sensitive epilepsy syndromes with focal or generalized seizure subtypes of idiopathic or symptomatic etiologies, with and without associated photosensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2018.03.027DOI Listing
May 2018

Association between glutamate/glutamine and blood oxygen level dependent signal in the left dorsolateral prefrontal region during verbal working memory.

Neuroreport 2018 04;29(6):478-482

Medical Image Processing Laboratory, Department of Imaging Sciences and Interventional Radiology.

Functional MRI (fMRI) has provided much insight into the changes in the neuronal activity on the basis of blood oxygen level dependent (BOLD) phenomenon. The dynamic changes in the metabolites can be detected using functional proton magnetic resonance spectroscopy (H-fMRS). The strategy of combining fMRI and H-fMRS would facilitate the understanding of the neurochemical interpretation of the BOLD signal. The dorsolateral prefrontal region is critically involved in the processing of working memory (WM), as demonstrated by the studies involving the neuroimaging, neuropsychological, and electrophysiological experiments. In this study, we tested the association between BOLD signal and changes in brain metabolites in the left dorsolateral prefrontal region using N-back verbal WM task. We used single-voxel task-based H-MRS acquired in the left dorsolateral prefrontal region and fMRI during the performance of N-back verbal WM task to investigate the association between changes in metabolites and BOLD response in 10 healthy participants. The correlation between changes in metabolites and percent signal change was examined by the Pearson correlation. The Pearson correlation analysis revealed a significant positive correlation between the BOLD signal and glutamate/glutamine in the left dorsolateral prefrontal region during the verbal WM. Our finding suggests that glutamate/glutamine cycle plays a critical role in the neuronal activation as reflected by the changes in the BOLD response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNR.0000000000001000DOI Listing
April 2018

Clinical-radiological-pathological correlation in an unusual case of refractory epilepsy: a two-year journey of whodunit!

Epileptic Disord 2018 Feb;20(1):51-59

Department of Neurology, SCTIMST, Thiruvananthapuram, Kerala.

New-onset refractory focal epilepsy poses significant challenges to the clinician in the absence of specific diagnostic biomarkers. Differential diagnoses based on imaging may be expanded by a veritable spectrum of peri-ictal imaging findings that may mask the underlying substrate. We report a 13-year-old girl who presented with refractory focal seizures of left parieto-occipital origin with cytotoxic gyral oedema noted over the same region on imaging. Despite an initial negative autoantibody profile, the patient was treated with immunosuppression, followed by serial relapses requiring immune-modulation. Over the next year, her syndrome persisted as focal left posterior cortex epilepsy that necessitated occipital lobectomy, following a relapsing-remitting radiological profile, consistent with peri-ictal MRI changes. Histopathology was inconclusive for any definitive substrate. After a period of quiescence, she developed focal motor seizures of right hemispheric origin with progressive encephalopathy, at which point a repeat cerebrospinal fluid anti-N-methyl-D-aspartate receptor antibody profile returned positive. The patient was managed with steroids and rituximab with a good clinical outcome. We hypothesise that persistent or relapsing-remitting focal gyral oedema in unexplained refractory focal epilepsy mandates consideration of focal encephalitis secondary to autoimmunity, and late appearance of intrathecal auto-antibody synthesis correlates with evolution into a more diffuse disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2018.0955DOI Listing
February 2018

Task-based metabolic changes in the left dorsolateral prefrontal region during the letter N-back working memory task using proton magnetic resonance spectroscopy.

Neuroreport 2018 Jan;29(2):147-152

Medical Image Processing Laboratory, Department of Imaging Sciences and Interventional Radiology.

Neuroimaging and electrophysiological studies have consistently provided evidence on the role of dorsolateral prefrontal cortex in working memory. Recent studies have shown that the changes in metabolites in the brain could be detected upon functional activation using proton magnetic resonance spectroscopy. Therefore, we carried out a study in healthy control participants to understand the changes in metabolites during a letter N-back working memory task in the left dorsolateral prefrontal region. Single-voxel spectra were acquired from the left dorsolateral prefrontal region in 10 healthy control participants. The concentrations of metabolites were measured using a point-resolved spectroscopy sequence at three different time points, namely, before, during, and after the performance of the task. Repeated-measures analysis of variance indicated a main effect of time for glutamate concentrations and not for other metabolites. The healthy control participants showed a significant increase in glutamate concentrations during the performance of the letter N-back task. It was then followed by a significant decrease in the glutamate concentrations returning to the baseline after the task. The proposed method would be useful in understanding the dynamic changes in glutamate during the letter N-back task to examine the cognitive impairment in various neurodegenerative and psychiatric disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNR.0000000000000943DOI Listing
January 2018

Arterial spin labeling hyperperfusion in Rasmussen's encephalitis: Is it due to focal brain inflammation or a postictal phenomenon?

J Neuroradiol 2018 Feb 18;45(1):6-14. Epub 2017 Sep 18.

Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, Kerala, India. Electronic address:

Background And Purpose: The study evaluated the utility of arterial spin labeling (ASL) perfusion imaging in Rasmussen's encephalitis (RE).

Material And Methods: The hospital electronic database was searched using the search words "encephalitis," "autoimmune encephalitis" and "Rasmussen's encephalitis" for the period of 1 Jan 2015 to 31 Jan 2017. Clinically diagnosed cases of RE for which epilepsy protocol magnetic resonance imaging (MRI) with perfusion imaging (ASL) performed on a 3T scanner were retrieved. The diagnosis of RE was based on Bien's criteria (Bien et al., 2005). We obtained patient's demographic details, clinical features, electrophysiological studies, and follow-up data from electronic hospital records.

Results: We included nine patients with RE of whom seven patients showed increased perfusion, and two patients decreased perfusion. Among these patients, MRI changes of gyral hyperintensity without volume loss corresponded to regional ASL hyperperfusion in six patients and ASL hypoperfusion in one patient. Two patients who showed ASL hypoperfusion had corresponding atrophy on MRI. Eight patients of RE had epilepsia partialis continua (EPC) or daily seizures, and one patient was seizure-free post-surgery. Five patients showed a concordance of ASL hyperperfusion with clinical ictal onset zone. Among the seven patients with ASL hyperperfusion, the finding was concordant (complete or partial) with the electroencephalogram (EEG) ictal onset zone in six patients and with interictal epileptiform discharges (IED) in seven patients.

Conclusion: Increased perfusion in ASL of the involved brain parenchyma in RE is a common MRI finding and may be due to either active inflammation of the brain involved or a seizure-related finding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurad.2017.08.002DOI Listing
February 2018

Is 'burned-out hippocampus' syndrome a distinct electro-clinical variant of MTLE-HS syndrome?

Epilepsy Behav 2017 04 23;69:53-58. Epub 2017 Feb 23.

R Madhavan Nayar Centre for Comprehensive Epilepsy Care, Department of Neurology, SreeChitraTirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India.

Aim: To study the clinical, electrophysiological and imaging characteristics of patients with unilateral mesial temporal lobe epilepsy (MTLE) with contralateral ictal onset on scalp EEG, viz. 'burned-out hippocampus' syndrome (MTLE-BHS).

Methods: MTLE-BHS was defined as TLE with unilateral hippocampal sclerosis (HS) without any dual pathology on MRI and contralateral ictal onset on scalp EEG, unlike in classical hippocampal sclerosis (HS). Consecutive "MTLE-BHS" patients evaluated at our Centre for Comprehensive Epilepsy Care from January 2005 to July 2014 were studied. Twenty-five cases of classic MTLE-HS operated during the same period were also analyzed for comparison.

Results: Seventeen patients were diagnosed to have MTLE-BHS. Mean age of seizure onset was 9.5±7.7years and the mean duration of epilepsy was18.2±7.3years. Epigastric aura was more common in MTLE-HS and fear, secondary generalized seizures and temporal polar changes on MRI were more prevalent in the MTLE-BHS subgroup. In the latter group, five (29%) exhibited seizure semiology and 2 (12%) had interictal discharges discordant to the side of MTS. Eight (47%) patients in the MTLE-BHS sub-group had normal medial temporal volume on Scheltens scale. Eight patients among MTLE-BHS underwent surgery (4 following intracranial monitoring that localized to the side of HS) with Engel class I outcome at 1year follow-up in 6 and Engel class II outcome in 2.

Conclusion: Attenuation of ipsilateral fast ictal rhythms on scalp EEG as well as neocortical changes are likely to be deterministic factors for MTLE-BHS as opposed to the severity of hippocampal atrophy. Considering good post-operative outcomes, intracranial monitoring for surgical selection is not mandatory in MTLE-BHS despite discordant semiology and ictal onset, in the presence of inter-ictal, functional imaging and neuropsychology data concordant to the side of HS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2017.01.003DOI Listing
April 2017

Post-stroke cognitive impairment - A cross-sectional comparison study between mild cognitive impairment of vascular and non-vascular etiology.

J Neurol Sci 2017 Jan 24;372:356-362. Epub 2016 Oct 24.

Cognition and Behavioural Neurology Section, Department of Neurology, SreeChitraTirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India.

Purpose: To elucidate the cognitive profiles of post-stroke vascular mild cognitive impairment (VaMCI) in comparison to MCI of non-vascular etiology and cognitively normal healthy controls at a tertiary-care hospital in southern India.

Results: Logistic regression analysis adjusted for age and sex comparing VaMCI [N=50] with controls [N=27] revealed significant impairment in visual, verbal learning-recall and executive function scores. As compared to the MCI group [N=36], VaMCI had significantly higher scores on Weschler's Memory Scale (WMS) verbal subset delayed recall scores (p=0.045, odds ratio [OR]=2.62, 95% CI=1.02-6.76) with lower scores on WMS-visual immediate learning scores (p=0.042, OR=0.35, 95% CI=0.13-0.96), Rey Auditory Verbal Learning Test (RAVLT) total learning scores (p=0.001, OR=0.17, 95% CI=0.06-0.48) and 20 minute recall (p=0.026, OR=0.33, 95% CI=0.12-0.88), Delayed Matching to Sample test (DMS-48) abstract immediate (p=0.002, OR=0.20, 95% CI=0.07-0.56), abstract delayed recognition sub-sets (p=0.014, OR=0.28, 95% CI=0.10-0.78) and made more total errors on Wisconsin Card Sorting Test (WCST; p=0.040, OR=2.70, 95% CI=1.05-7.14) while the MCI group significantly had more commission errors on RAVLT (p≤0.001, OR=0.13, 95% CI=0.05-0.38) and WCST - perseverative errors (p=0.036, OR=0.30, 95% CI=0.10-0.93). Significant differences were noted in word-list learning-recall (p=0.012) and WMS verbal delayed recall (p=0.014) between VaMCI with mild versus moderate to severe deep white matter hyperintensities on neuroimaging.

Conclusions: Cognitive impairment following minor stroke involves episodic verbal and visual memory over and above executive function in comparison to MCI of non-vascular etiology. Close cognitive followup is warranted with adequate risk stratification and management especially in the presence of sub-cortical leukoaraiosis which is contributory to cognitive decline in this group of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2016.10.031DOI Listing
January 2017

Epilepsy with myoclonic absences: Electroclinical characteristics in a distinctive pediatric epilepsy phenotype.

Epilepsy Behav 2016 11 19;64(Pt A):242-247. Epub 2016 Oct 19.

R Madhavan Nayar Centre for Comprehensive Epilepsy Care, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India.

Purpose: The purpose of this article was to study the electroclinical characteristics and seizure outcome of children with epilepsy with myoclonic absences (EMA).

Method: In this descriptive cohort study, we reviewed clinical records of patients who met the criteria for EMA. Each patient's demographic data, birth/developmental history, seizure semiology/pattern, antiepileptic drugs (AED), clinical examination, video-electroencephalography (VEEG), and neuroimaging data were reviewed. Response to AED and change in seizure frequency/pattern on follow-up were noted. Responders were defined by seizure freedom/>50% reduction in seizure frequency on follow-up.

Result: Twelve children were diagnosed with EMA between 2008 and 2013 [50% male; mean age of onset: 3.5years]. Main seizure types were the characteristic myoclonic absences (100%) and generalized tonic-clonic seizures (42%). Ictal correlate on VEEG was 3- to 3.5-Hz spike-and-wave discharges (82%) and fast recruiting bifrontal rhythm (25%). One patient had specific MRI abnormalities. Mean duration of follow-up was 23.9months. Seizure frequency had significantly improved on follow-up (p=0.005), and at last follow-up, nine patients were in the responder group: four seizure-free for at least 1year, two with >90%, and three with >50% reduction in seizure frequency. The number of AED reduced significantly between initial visit and last follow-up among responders. Two patients on follow-up developed different seizure patterns, with generalized tonic and complex partial seizures. One responder expired because of unprovoked generalized convulsive status epilepticus.

Conclusion: This cohort, the largest from the Indian subcontinent on the rare syndrome of EMA, suggests mild heterogeneity in a seemingly homogenous electroclinical phenotype. Clinical semiology while unique may demonstrate focality and variable ictal patterns. Most patients respond to either valproate monotherapy or valproate-lamotrigine combination; however, the prognosis remains guarded. The seizures of a minority of patients remain drug-refractory and may evolve into tonic or complex partial seizures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2016.08.023DOI Listing
November 2016