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1.
Epilepsy Behav ; 151: 109608, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38183927

RESUMO

BACKGROUND: Patients with epilepsy suffer from depression and anxiety that reduces quality of life. Cognitive behavioral therapy (CBT) among various non pharmacological treatment recommended for depression and anxiety. Since there are several articles reporting CBT treatment for depression in patients with epilepsy, we conduct a meta-analysis to evaluate the effectiveness of CBT for adult patients with epilepsy. METHODS: Four electronic databases PubMed, Scopus, Embase, and the Cochrane library searched for relevant studies. A detailed "RISK of bias" assessment has been done for included studies. Funnel plot was used for assessing publication Bias. R Software- RStudio 2022 was used to calculate standard mean difference (SMD). The study has been registered in PROSPERO (CRD42023447655). RESULTS: Eventually, a Total 13 studies involving 1222 patients met the eligibility criteria. There was decline in the Patient Health Questionnaire (PHQ) [SMD = -0.42, 95 % CI = -0.63 to -0.22], Neurologic Disorder Depression Inventory-Epilepsy (NDDI-E) [SMD = -0.53, 95 % CI = -0.75 to -0.31], Beck depression Inventory (BDI) [SMD = -0.69, 95 % CI = -1.08 to -0.30], Hospital Anxiety and Depression Scale-Depression (HADS-D) [SMD = -0.73 , 95 % CI = -0.94 to -0.52] and Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A) [SMD = -0.66, 95 % CI = -0.87 to -0.45] score of the CBT group than that of the control group at post-intervention. The results showed that the improvement in QOLIE-31 score of the CBT group than that of the control group [SMD = 0.67, 95 % CI = 1.33] at post-intervention. CONCLUSION: The result of our study showed that Cognitive behavioral therapy is a superior therapy for treating anxiety and depression in epilepsy patients. CBT was effective in improving Quality of life in patients with epilepsy. However, the sample size varied across the trials, additional high-quality studies are needed in the future.


Assuntos
Terapia Cognitivo-Comportamental , Epilepsia , Adulto , Humanos , Depressão/etiologia , Depressão/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia Cognitivo-Comportamental/métodos , Ansiedade/etiologia , Ansiedade/terapia , Epilepsia/complicações , Epilepsia/terapia
2.
Int J Neurosci ; : 1-15, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38060511

RESUMO

INTRODUCTION: Granule cell dispersion (GCD) is pathognomonic of hippocampal sclerosis seen in the mesial temporal lobe epilepsy (MTLE). Current animal studies indicate deficiency of Reelin is associated with abnormal granule cell migration leading to GCD. The present study aimed to evaluate complete Reelin signalling pathway to assess whether Reelin deficiency is related to MTLE. MATERIALS AND METHODS: Hippocampal sclerosis was confirmed by H and E stain. To explore the amount and cellular location of the Reelin cascade molecules, the hippocampal tissues from MTLE surgery and controls (n = 15 each) were studied using Immuno-histochemistry (IHC). Additionally, confocal imaging was used to validate the IHC findings by co-localization of different proteins. Quantification of IHC images was performed using histo-score and confocal images by Image J software. RESULTS: Immune expression of active Reelin was significantly reduced in patients. Reelin receptors were deranged, apolipoprotein E receptor 2 was increased while very low-density lipoprotein receptor was reduced. Disabled-1, a downstream molecule was significantly reduced in MTLE. Its ultimate target, cofilin was thus disinhibited and expressed more in MTLE. Reelin cleaving protease, matrix metalloprotease-9 (MMP-9) and MMP-9 inhibitor, tissue inhibitor of matrix protease-1, showed reduced expression in extracellular matrix. Semi-quantification of immunohistochemistry was done using Histo (H) score. H score of Reelin in diseased patients was 15 against 125 for control patients. These results were validated by confocal fluorescence microscopy. CONCLUSIONS: Reelin signalling cascade was deranged in chronic MTLE. Pharmacological manipulation of Reelin cascade can be done at various levels and it may provide novel treatment options for MTLE.

3.
Epilepsy Behav ; 128: 108569, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35104733

RESUMO

BACKGROUND: Effectiveness of different tele-medicine strategies varies in different medical conditions. Use of basic tele-medicine strategy like mobile health (m-health) can be an effective option in different medical conditions in a resource-poor setting. AIMS: To study effectiveness and satisfaction of tele-medicine among persons with epilepsy (PWE) in a developing nation during COVID-19 pandemic. METHODS: Persons with epilepsy aged 18 years or more who have attended epilepsy clinic at least once physically and were asked for regular follow-up were included. A cross-sectional telephonic survey was conducted to assess effectiveness of tele-medicine over past 1 year. Satisfaction was assessed by tele-medicine satisfaction questionnaire. RESULT: 31.9% of PWE have used tele-medicine facility in last 1 year and 58.2% were unaware of the availability of such a facility. Among those who utilized tele-medicine, 95.3% were able to explain their concerns satisfactorily during tele-consultation and change in prescription was done in 42.8%. None experienced any new adverse event. Overall, more than 95% were satisfied with tele-consultation and more than 80% wanted to use it again. CONCLUSION: Even basic tele-medicine strategies can be a very effective and satisfactory mode of follow-up for PWE in resource-poor settings. Steps should be undertaken to make people aware of the availability of such a facility.


Assuntos
COVID-19 , Epilepsia , Telemedicina , Adolescente , Estudos Transversais , Epilepsia/epidemiologia , Epilepsia/terapia , Seguimentos , Humanos , Pandemias , Satisfação Pessoal , SARS-CoV-2
4.
Acta Neurol Scand ; 144(3): 236-250, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33987835

RESUMO

Temporal lobe epilepsy (TLE) with enlargement of the amygdala (AE) is a distinct clinical entity with contrasting clinical features from TLE with hippocampal sclerosis (HS). The objectives of this systematic analysis were to study the clinical characteristics and treatment outcome of people with TLE with AE. Pubmed, Embase, Cochrane, Web of Science, Scopus, and Medline were searched using the keywords amygdala enlargement, temporal lobe epilepsy, epilepsy, and seizure in November 2020. We found 18 studies that satisfied the inclusion criteria. A total of 361 patients were included in this analysis. The mean age of onset was 36.2 years, and febrile seizure was uncommon compared to TLE with HS subjects. The type of aura and automatism was similar to TLE with HS, though less prevalent. Electroencephalography (EEG) was usually concordant with the side of AE. Anti-seizure medications (ASM), surgical, and immunotherapy were used in different studies. 86 patients underwent surgery with Engel I outcome in 69.7%. Histopathology of the resected samples was predominantly dysplasia and gliosis. A group of patients that responded well to immunotherapy with subsequent reduction of amygdala volume (AMV) purported an autoimmune etiology of AE. Heterogeneity was the main drawback that prevented comparability among the studies. The methods of measurement of AMV also differed widely in the included studies, and standardization of its method is still lacking. This analysis suggests TLE with AE as a distinctive group of patients either due to a developmental anomaly or autoimmune etiology.


Assuntos
Epilepsia do Lobo Temporal , Tonsila do Cerebelo , Eletroencefalografia , Epilepsia do Lobo Temporal/terapia , Hipocampo , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Convulsões
5.
Acta Neurol Scand ; 143(3): 242-247, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33006755

RESUMO

BACKGROUND: The choice of antiepileptic drug (AED) in newly diagnosed neurocysticercosis (NCC) patients with epilepsy continues to be arbitrary. We compared efficacy and side effect profile of levetiracetam (LEV) and carbamazepine (CBZ) for the treatment of seizures in newly diagnosed patients with NCC. PATIENTS AND METHODS: This was an open-labeled randomized comparative monotherapy study including newly diagnosed drug naïve patients of NCC (n = 99) presenting with seizures who were randomized in 1:1 ratio using computed generated numbers. All patients were followed up for at least six months after start of treatment. The primary outcome measure was seizure control over six months following start of AEDs. RESULTS: Fifteen (15.2%) patients [CBZ- 4(8.2%); LEV- 11(22%)] developed recurrence of seizures. A trend (p = 0.09) was found toward better control of seizures in CBZ compared to LEV. Two (4%) patients in LEV group and 17 (34.6%) patients in CBZ group developed drug-related minor side effects (p < 0.0001). Three patients in CBZ group needed discontinuation of therapy due to skin rash. Eleven patients who relapsed while on LEV did not have any recurrence of seizures after switching over to CBZ. Out of 3 patients who relapsed while receiving CBZ and were changed to LEV, two developed seizures during follow-up. CONCLUSION: CBZ and LEV could be used as alternatives in newly diagnosed patients of NCC at the behest of minor side effects in the CBZ group.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Levetiracetam/uso terapêutico , Neurocisticercose/complicações , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Epilepsy Behav ; 123: 108280, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34500435

RESUMO

BACKGROUND: Knowledge and attitude of doctors toward epilepsy surgery are essential for management and timely referral of people with Drug refractory epilepsy (DRE). This study aimed at analyzing knowledge, attitude, and barriers for epilepsy surgery among medical residents. METHODS: A survey consisting of 16 statements in a Likert-like scale and one open-ended question was conducted among residents joining different postgraduate courses after MBBS (GR) and super-specialty courses after MD (PG) within 2 months of joining the institute. PGs with a postgraduate degree in internal medicine, pediatrics, or psychiatry were included. Demographic data were analyzed using descriptive statistics. Difference in response to the survey statements was analyzed using independent t test. RESULTS: 115 participated in the survey of which 97 were GRs. Participants belonged to 22 different states and 3 were foreign nationals. 45% of participants did not know the definition of DRE. There was a difference of opinion among GRs and PGs regarding surgery as a treatment option for epilepsy and feasibility of epilepsy surgery in children (p < .05). PGs were more confident in treating PWE and preferred to refer people with DRE to a higher center early (p < .05). Lack of knowledge was the commonest barrier for epilepsy surgery. CONCLUSION: A substantial number of participants lacked the basic knowledge of DRE and epilepsy surgery. Lack of knowledge was perceived to be the commonest barrier for epilepsy surgery. Dissemination of basic knowledge and development of protocols for identification and referral of people with DRE are the need of the hour.


Assuntos
Epilepsia , Conhecimentos, Atitudes e Prática em Saúde , Criança , Epilepsia/cirurgia , Humanos , Índia , Inquéritos e Questionários , Centros de Atenção Terciária
7.
Epilepsy Behav ; 61: 242-247, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27394671

RESUMO

INTRODUCTION: Matrimony remains a challenging psychosocial problem confronting people with epilepsy (PWE). People with epilepsy are less likely to marry; however, their marital prospects are most seriously compromised in arranged marriages. AIMS: The aim of this study was to document marital prospects and outcomes in PWE going through arranged marriage and to propose optimal practices for counseling PWE contemplating arranged marriage. METHODS: A MEDLINE search and literature review were conducted, followed by a cross-disciplinary meeting of experts to generate consensus. RESULTS: People with epilepsy experience high levels of felt and enacted stigma in arranged marriages, but the repercussions are heavily biased against women. Hiding epilepsy is common during marital negotiations but may be associated with poor medication adherence, reduced physician visits, and poor marital outcome. Although divorce rates are generally insubstantial in PWE, divorce rates appear to be higher in PWE undergoing arranged marriages. In these marriages, hiding epilepsy during marital negotiations is a risk factor for divorce. CONCLUSIONS: In communities in which arranged marriages are common, physicians caring for PWE are best-equipped to counsel them about their marital prospects. Marital plans and aspirations should be discussed with the family of the person with epilepsy in a timely and proactive manner. The benefits of disclosing epilepsy during marital negotiations should be underscored.


Assuntos
Divórcio/psicologia , Emoções , Epilepsia/psicologia , Casamento/psicologia , Revelação da Verdade , Consenso , Feminino , Humanos , Masculino
8.
Indian J Med Res ; 143(5): 581-90, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27488001

RESUMO

BACKGROUND & OBJECTIVES: Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. METHODS: Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. RESULTS: The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. INTERPRETATION & CONCLUSIONS: Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.


Assuntos
Arilamina N-Acetiltransferase/genética , Convulsões/induzido quimicamente , Tuberculoma/tratamento farmacológico , Tuberculose Meníngea/tratamento farmacológico , Acetilação/efeitos dos fármacos , Adulto , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Inativação Metabólica/genética , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Masculino , Fenitoína/administração & dosagem , Fenitoína/efeitos adversos , Projetos Piloto , Polimorfismo de Nucleotídeo Único/genética , Convulsões/tratamento farmacológico , Convulsões/genética , Convulsões/patologia , Tuberculoma/genética , Tuberculoma/patologia , Tuberculose Meníngea/genética , Tuberculose Meníngea/patologia
9.
Epilepsia ; 56(11): 1747-52, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26513213

RESUMO

OBJECTIVE: Being a common cause of epilepsy in endemic areas, neurocysticercosis (NCC) is expected to account for a sizable proportion of patients with drug-refractory epilepsy (DRE) as well. However, data regarding prevalence of DRE in NCC are sparse. This study aimed to determine the prevalence of DRE as well as identification of clinical and radiologic factors that lead to DRE in patients with NCC. METHODS: This study was conducted in a tertiary-care postgraduate teaching institute in Northern India from July 2011 to July 2013. Two hundred patients with epilepsy due to NCC (definite [n = 59, 29.5%] or probable [n = 141, 70.5%]) based on diagnostic criteria by Del Brutto et al. were enrolled in the study in both a prospective (n = 51 [25.5%]) and a retrospective manner (n = 149 [74.5%]), and were followed for a minimum period of 1 year. RESULTS: Thirteen patients with NCC were found to be refractory to drug therapy. Prevalence of DRE was found to be 65 of 1,000 NCC patients with epilepsy in the present study. The risk factors associated with high risk of DRE were male sex (p = 0.035), older age (p = 0.016), pig-raising practices (p = 0.003), pork eating (p = 0.04), and presence of multiple (>2) (p = 0.0001) or mixed stage lesions (p = 0.007) on neuroimaging. On multivariate analysis, it was found that residing in an area where pig raising is prevalent (p = 0.01) and presence of multiple (>2) (p = 0.004) lesions on neuroimaging are associated with increased risk of DRE. SIGNIFICANCE: NCC is only rarely associated with the development of DRE. The common risk factors associated with increased chance of DRE include pig-rearing practices and presence of multiple (>2) lesions on neuroimaging.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/etiologia , Neurocisticercose/complicações , Neurocisticercose/diagnóstico , Vigilância da População , Adolescente , Adulto , Epilepsia Resistente a Medicamentos/epidemiologia , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Neurocisticercose/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
10.
Neuropharmacology ; 251: 109931, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38570067

RESUMO

The prospective involvement of the Wnt/ß-catenin signaling pathway in epilepsy, with the proposed therapeutic uses of its modulators, has been suggested; however, comprehensive knowledge in this regard is currently limited. Despite postulations about the pathway's significance and treatment potential, a systematic investigation is required to better understand its implications in chronic epilepsy. We investigated the role of key proteins like ß-catenin, GSK-3ß, and their modulators sulindac and 6-BIO, in Wnt/ß-catenin pathway during chronic phase of temporal lobe epilepsy. We also evaluated the role of modulators in seizure score, seizure frequency and neurobehavioral parameters in temporal lobe epilepsy. We developed status epilepticus model using lithium-pilocarpine. The assessment of neurobehavioral parameters was done followed by histopathological examination and immunohistochemistry staining of hippocampus as well as RT-qPCR and western blotting to analyse gene and protein expression. In SE rats, seizure score and frequency were significantly high compared to control rats, with notable changes in neurobehavioral parameters and neuronal damage observed in hippocampus. Our study also revealed a substantial upregulation of the Wnt/ß-catenin pathway in chronic epilepsy, as evidenced by gene and protein expression studies. Sulindac emerged as a potent modulator, reducing seizure score, frequency, neuronal damage, apoptosis, and downregulating the Wnt/ß-catenin pathway when compared to 6-BIO. Our findings emphasize the potential of GSK-3ß and ß-catenin as promising drug targets for chronic temporal lobe epilepsy, offering valuable treatment options for chronic epilepsy. The promising outcomes with sulindac encourages further exploration in clinical trials to assess its therapeutic potential.


Assuntos
Epilepsia do Lobo Temporal , Estado Epiléptico , Ratos , Animais , Via de Sinalização Wnt , Sulindaco/farmacologia , Sulindaco/uso terapêutico , beta Catenina/metabolismo , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Estudos Prospectivos
11.
Eur J Pharmacol ; 966: 176375, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38307381

RESUMO

The role of the Wnt/ß-catenin signaling pathway in epilepsy and the effects of its modulators as efficacious treatment options, though postulated, has not been sufficiently investigated. We evaluated the involvement of ß-catenin and GSK-3ß, the significant proteins in this pathway, in the lithium chloride-pilocarpine-induced status epilepticus model in rodents to study acute phase of temporal lobe epilepsy (TLE). The modulators studied were 6-BIO, a GSK-3ß inhibitor and Sulindac, a Dvl protein inhibitor. The disease group exhibited increased seizure score and seizure frequency, and the assessment of neurobehavioral parameters indicated notable alterations. Furthermore, histopathological examination of hippocampal brain tissues revealed significant neurodegeneration. Immunohistochemical study of hippocampus revealed neurogenesis in 6-BIO and sulindac groups. The gene and protein expression by RT-qPCR and western blotting studies indicated Wnt/ß-catenin pathway downregulation and increased apoptosis in the acute phase of TLE. 6-BIO was very efficient in upregulating the Wnt pathway, decreasing neuronal damage, increasing neurogenesis in hippocampus and decreasing seizure score and frequency in comparison to sulindac. This suggests that both GSK-3ß and ß-catenin are potential and novel drug targets for acute phase of TLE, and treatment options targeting these proteins could be beneficial in successfully managing acute epilepsy. Further evaluation of 6-BIO to explore its therapeutic potential in other models of epilepsy should be conducted.


Assuntos
Epilepsia do Lobo Temporal , Estado Epiléptico , Ratos , Animais , Pilocarpina , Via de Sinalização Wnt/fisiologia , Lítio/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , beta Catenina/metabolismo , Sulindaco/efeitos adversos , Sulindaco/metabolismo , Hipocampo/metabolismo , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/metabolismo , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/tratamento farmacológico
12.
Ann Indian Acad Neurol ; 26(4): 549-552, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970282

RESUMO

Scrub typhus infection is reemerging leading cause of acute febrile illnesses in post-rainy or monsoon season in Southeast Asia. It is caused by Orientia tsutsugamushi and spread by the bite of chiggers, larval forms of trombiculid mites. The clinical picture can range from simple acute febrile illness to multiorgan dysfunction. Neurological manifestations also vary from aseptic meningitis, meningoencephalitis, cerebral infarction, acute disseminated encephalomyelitis, transverse myelitis, and psychiatric manifestations. Here, we present a case series of eight cases of scrub meningoencephalitis diagnosed based on clinical, laboratory, and radiological criteria.

13.
Lancet Reg Health Southeast Asia ; 8: 100094, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37384142

RESUMO

Background: Diphtheria, Tetanus, and whole-cell Pertussis (DTwP) vaccination-associated seizures form the commonest type of serious adverse event following immunization in India and are an important reason for vaccine hesitancy. Our study explored the genetic explanation of DTwP vaccination-associated seizures or subsequent epilepsies. Methods: Between March 2017 and March 2019, we screened 67 children with DTwP vaccination-associated seizures or subsequent epilepsies, and of those, we studied 54 without prior seizures or neurodevelopmental deficits. Our study design was cross-sectional with a 1-year follow-up having both retrospective and prospective cases. We performed clinical exome sequencing focused on 157 epilepsy-associated genes and multiplex ligation-dependent probe amplification of the SCN1A gene at enrolment. We applied the Vineland Social Maturity Scale for neurodevelopmental assessment at follow-up. Findings: Of 54 children enrolled and underwent genetic testing (median age 37.5 months, interquartile range 7.7-67.2; diagnosis at enrolment: epilepsy 29, febrile seizure 21, and febrile seizure-plus 4), we found 33 pathogenic variants of 12 genes. Of 33 variants, 13 (39%) were novel. Most pathogenic variants were found in SCN1A gene (n = 21/33; 64%), SCN8A in 2 children, and 10 children had one variant in CDKL5, DEPDC5, GNAO1, KCNA2, KCNT1, KCNQ2, NPRL3, PCDH19, RHOBTB2, and SLC2A1. Five or more seizures (odds ratio [OR] = 5.3, confidence interval [CI]: 1.6-18.4, p = 0.006), drug-resistant epilepsy (OR = 9.8, 95% CI: 2.6-30.7, p = 0.001) and neurodevelopmental impairment (social quotient < 70) (OR = 5.6, 95% CI: 1.65-17.6, p = 0.006) were significant predictors of genetic diagnosis. Interpretation: Our study provides proof-of-concept for genetic aetiology in children with DTwP vaccination-associated seizures or subsequent epilepsies and has important implications for vaccination policies in developing countries. Funding: International Pediatric Association Foundation, Inc. (IPAF): Ihsan Dogramaci research award 2016/2017; Indian Council of Medical Research (ICMR), New Delhi, India: No.3/1/3/JRF-2016/HRD/LS/71/10940.

14.
Basic Clin Neurosci ; 14(1): 57-72, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37346868

RESUMO

Introduction: Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis. Methods: The aim of this study was to investigate the Reelin signalling pathway in the MTLE patients. Therefore, we studied each step in the Reelin signalling pathway for the gene and protein expressions, in the hippocampal tissue obtained from patients undergoing surgery for MTLE and compared it with age matched normal autopsy cases. Results: We found statistically significant decrease (P<0.001) in the Reelin mRNA expression in MTLE patients. Among the two reelin receptors, apolipoprotein E receptor 2 (ApoER2) was significantly increased whereas very low density lipoprotein receptor (VLDLR) was decreased among the patients. Disabled 1 (Dab1), the downstream target of reelin, was found to be decreased. Dab1 in turn inhibits Cofilin, which is responsible for cytoskeletal reorganization, thus limiting aberrant neuronal migration. Statistically significant over expression of Cofilin protein was found in the patient group. Matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteases-1 (TIMP-1), both of which are involved in processing of Reelin, were down regulated in 70-85% of cases. Conclusion: The whole pathway was found to be deranged in MTLE. These results indicate that Reelin signalling pathway is disturbed at various points in the MTLE patients and might be involved in the pathogenesis & progression of MTLE. Our results extend the existing information regarding the components of the Reelin pathway and further, establish a link between pathway disturbance and MTLE.

15.
J Glob Infect Dis ; 15(3): 101-107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37800084

RESUMO

Introduction: Acute encephalitis syndrome (AES) or acute febrile encephalopathy is a clinical condition characterized by altered mental status occurring after or along with a short febrile illness. In developing countries, infections are the predominant cause of AES. Prominent infections known to cause AES include viruses (such as herpes simplex virus [HSV], Japanese Encephalitis [JE] virus, dengue, enteroviruses [EVs]), bacteria, fungus, and parasites. In the present study, we aim to analyze the etiology, clinical features, and predictors of mortality in patients presenting with acute febrile encephalopathy or acute encephalitic syndrome. The present study was a prospective observational study conducted at Post Graduate Institute of Medical Education and Research a tertiary care center in Chandigarh, India. Methods: A total of 105 patients with ≥18 years of age with fever (body temperature >101° F for duration ≤14 days) and altered sensorium (Glasgow coma scale [GCS] score ≤10) lasting for more than 24 h, either accompanying the fever or following it were enrolled. Demographic and clinical details were recorded on pro forma. Cerebrospinal fluid (CSF) analysis was performed for all the enrolled patients at admission for cytology, CSF glucose to blood glucose ratio, protein levels, gram stain and culture sensitivity, adenosine deaminase levels, polymerase chain reaction for HSV/EV/mycobacterium tuberculosis (TB) and immunoglobulin M Enzyme-linked immune assay for JE. Computed tomography of the brain was done in all patients while magnetic resonance imaging (MRI) of the brain was carried out in 75 patients. Results: Among the 105 patients, tubercular meningitis was seen in 27 (25.7%) patients followed by acute pyogenic meningitis in 18 (17.1%) patients. Probable viral encephalitis was present in 12 (11.4%) cases. Septic encephalopathy (n = 10) and scrub typhus encephalitis (n = 8), HSV encephalitis (n = 6), dengue encephalitis (n = 4), leptospirosis (n = 3) were the other infections causing acute febrile encephalitis in our study. In addition to fever and altered sensorium common symptoms observed were headache (52.4%), vomiting (35.2%), and seizures (29.5%). The factors predicting increased mortality were female gender, fever of more than 38°C at admission, GCS <7, MRI showing disease-related findings like altered signal intensity bilateral medial temporal and insular area in herpes simplex encephalitis, etc., changes, and the group of patients where a definite diagnosis could not be established during the hospital stay. Conclusions: Tubercular meningitis/central nervous system TB is the predominant cause of acute febrile encephalopathy in developing countries. Scrub and dengue encephalitis are emerging as an important cause of acute febrile encephalopathy and occur predominantly in postmonsoon seasons. Acute febrile encephalopathy remains an important cause of mortality in patients presenting to Emergency Department (ER). The strongest predictors of mortality are low GCS and undiagnosed cases of AES.

16.
Basic Clin Neurosci ; 14(5): 615-630, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38628830

RESUMO

Introduction: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue. Methods: We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15). Results: Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy. Conclusion: Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.

17.
Neurol India ; 63(3): 304-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26053798
18.
Indian J Pharmacol ; 52(5): 378-382, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33283769

RESUMO

OBJECTIVES: The objectives of this study were to determine the relationship between genetic polymorphisms in gene encodings for CYP3A4 and carbamazepine (CBZ)-induced dose-related side effects in North Indian people with epilepsy. PATIENTS AND METHODS: The current prospective study included 37 patients with CBZ-induced dose-related side effects and 102 patients who did not experience side effects while on CBZ. The genotyping for CYP3A4 allele (CYP3A4*16) was done using real-time polymerase chain reaction (RT-PCR) in Applied Biosystems 7500 RT-PCR System (USA). CBZ was administered in all patients at a dose varying from 15 to 20 mg/kg daily. RESULTS: Various demographic variables were comparable between the groups except that control of seizures was far better in controls. After testing, it was found that none of our patients had the presence of CYP3A4*16 allele. CONCLUSION: CYP3A4*16 allele is not represented significantly in North Indian people with CBZ-induced dose-related side effects.


Assuntos
Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Citocromo P-450 CYP3A/genética , Epilepsia/tratamento farmacológico , Adolescente , Adulto , Alelos , Anticonvulsivantes/administração & dosagem , Carbamazepina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Índia , Masculino , Polimorfismo Genético , Estudos Prospectivos , Adulto Jovem
19.
Liver Int ; 29(5): 629-35, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19302444

RESUMO

Low-grade or minimal hepatic encephalopathy (MHE) is characterised by relatively mild neurocognitive impairments, and occurs in a substantial percentage of patients with liver disease. The presence of MHE is associated with a significant compromise of quality of life, is predictive of the onset of overt hepatic encephalopathy and is associated with a poorer prognosis for outcome. Early identification and treatment of MHE can improve quality of life and may prevent the onset of overt encephalopathy, but to date, there has been little agreement regarding the optimum method for detecting MHE. The International Society on Hepatic Encephalopathy and Nitrogen Metabolism convened a group of experts for the purpose of reviewing available data and making recommendations for a standardised approach for neuropsychological assessment of patients with liver disease who are at risk of MHE. Specific recommendations are presented, along with a proposed methodology for further refining these assessment procedures through prospective research.


Assuntos
Transtornos Cognitivos/diagnóstico , Encefalopatia Hepática/complicações , Testes Neuropsicológicos , Transtornos Cognitivos/etiologia , Humanos , Índice de Gravidade de Doença
20.
Phytother Res ; 23(9): 1281-6, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19283724

RESUMO

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability-enhancer. The present study aimed at evaluating the effect of piperine on the steady-state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t-test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC(0-12hr) (p < 0.001), average C(ss) (p < 0.001), t(1\2el) (p < 0.05) and a decrease in K(el) (p < 0.05), in both the dose groups, whereas changes in K(a) and t(1\2a) were not significant. Cmax (p < 0.01) and t(max) (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption.


Assuntos
Alcaloides/farmacocinética , Benzodioxóis/farmacocinética , Carbamazepina/farmacocinética , Epilepsia/tratamento farmacológico , Piperidinas/farmacocinética , Alcamidas Poli-Insaturadas/farmacocinética , Adulto , Área Sob a Curva , Disponibilidade Biológica , Carbamazepina/sangue , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piper/química , Adulto Jovem
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