Effect of reduction of antiepileptic drugs in patients with drug-refractory epilepsy

AbstractPurposeThe present study was conducted with the aim of evaluating the effects of reducing the number of antiepileptic drugs (AEDs) administered to patients with drug-refractory epilepsy (DRE) during their admission and document any change in seizure frequency in subsequent follow up.MethodsA total of 962 patients with DRE who were admitted to the neurology wards waiting for connection to video EEG were recruited for this prospective study. After their admission to the neurology ward, modifications in the number and dosage of AEDs were done with a target of a maximum of three AEDs in every patient. Drug tapering was done using a standardized protocol. The primary outcome was the change in seizure frequency in the follow-up period of 6 months. Secondary outcome measures were the adverse event profile (AEP) and the quality of life (QOL).ResultsOf the 1134 patients screened, 962 patients gave consent to participate in the study. The mean number of AEDs received by each patient was 4.24. After the tapering following a standardized protocol each patient received a mean of 2.65 AEDs per patient. In 82.70% patients with DRE, there was either a reduction or no change in seizure frequency in the subsequent 6 months follow up. There was a significant reduction in the AEP score after the reduction in the number of AEDs (P=0. 001).ConclusionOur study proves that optimization of reduction of the number of AED's in patients with DRE leads to reduction or no change in seizure frequency with a significant decrease in adverse effects

Regional Differences in Post-discharge Stroke Care in India: A Qualitative Study

Background: Stroke is the fourth leading cause of death and fifth leading cause of disability in India. Stroke rehabilitation can reduce mortality and improve outcomes, but India has limited resources to provide comprehensive stroke care after hospitalisation. Consequently, stroke survivors and family carers experience a range of challenges with long-term care and support. Secondary prevention and stroke rehabilitation services are important in post-discharge stroke care; however, there is insufficient information on post-discharge stroke services in India. Aim: This study aims to explore the clinical staff perspectives of post-discharge stroke services across different regions of India. Methods: Semi-structured interviews were undertaken with a purposive sample of health professionals from multidisciplinary stroke teams at the All India Institute of Medical Sciences, New Delhi (North), Baptist Christian Hospital (North-East), Sree Chitra Tirunal Institute for Medical Sciences and Technology (South) between July and August 2021. The interviews were conducted, translated, and transcribed by the research team. Data were analysed thematically using NVivo software. Results: Twenty-six health professionals participated: 9 Nurses, 7 Doctors, 5 Physiotherapists, 2 Speech and Language Therapists, and 1 Social Worker, Dietician, and Palliative Care team member. Four themes were identified: Integrated Inpatient Discharge Care Planning; Patient and Caregiver Engagement; Post-Discharge Care and Support; Resources and Workforce. Conclusion: Patient and caregiver engagement is an integral part of post-discharge processes; however, regional variation exists in the discharge planning, staff, resources, and services available for post-discharge support. Moreover, patient and caregiver challenges vary across geographical locations, educational backgrounds, financial status, family, and support networks

Impact of dengue virus (serotype DENV-2) infection on liver of BALB/c mice: a histopathological analysis

In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces. There were marked increases in the infiltration of mononuclear cells. The areas of hemorrhage and micro- and macrovesicular steatosis were noted. Necrosis and apoptosis were abundantly present. The hallmark of viral infection, i.e., cytopathic effects, included intracellular edema and vacuole formation, cumulatively led to sinusoidal and lobular collapse in the liver. The histopathological studies on autopsy specimens of fatal human DENV cases are important to shed light on tissue damage for preventive and treatment modalities, in order to manage future DENV infections. In this framework, the method present here on BALB/c mouse model may be used to study not only the effects of infections by other DENV serotypes, but also to investigate the effects of novel drugs, such as recently developed nano-formulations, and the relative recovery ability with intact immune functions of host

Thrombolytic therapy for acute ischemic stroke: 3 h and beyond

The current status of thrombolytic therapy approved by the US Food and Drug Administration is intravenous recombinant plasminogen activator given within 3 h of the onset of ischemic stroke. Intra-arterial therapy is possible for up to 6 h but is not Food and Drug Administration-approved for this purpose. Based on current radiologic methods (i.e., magnetic resonance imaging and perfusion computed tomography scans), it is being increasingly realized that the time window for effective thrombolytic therapy is variable, and salvageable tissue in the form of the ischemic penumbra may exist for longer periods of time and could therefore offer a greater time window based on these imaging studies. Development of an effective neuroprotective drug would greatly enhance the stability of the penumbra and offer further opportunities for extending the time window for reperfusion

Role of heparin and low-molecular-weight heparins in the management of acute ischemic stroke

The numerous large-scale randomized clinical trials performed during the last decade on either unfractionated heparin, or low molecular weight heparin have not been able to demonstrate undisputed benefits in patients with acute ischemic stroke, compared with no treatment or aspirin. However, a large number of these trials, including the International Stroke Trial and Chinese Acute Stroke Trial, exhibit severe methodological limitations and need to be interpreted with caution. Knowledge of thromboembolism pathophysiology and clinical experience leads to the theory that heparins will prevent red thrombus formation, propagation and embolism. Heparins effectively prevent venous thrombosis and pulmonary embolism. More trials are needed to test heparins in patients whose cardiocerebrovascular lesions are better defined by newer neuroimaging techniques. The efficacy of heparins has not been adequately tested in patients with defined stroke subtypes and occlusive vascular lesions. Heparins should not be indiscriminately given to all patients with acute ischemic stroke. High-quality, randomized trials that adequately study heparin use in patients using modern technology for vascular lesions and stroke subtypes are lacking, and need to be performed

Role of vascular endothelial growth factor and other growth factors in post-stroke recovery

Stroke is a major health problem world-wide and its burden has been rising in last few decades. Until now tissue plasminogen activator is only approved treatment for stroke. Angiogenesis plays a vital role for striatal neurogenesis after stroke. Administration of various growth factors in an early post ischemic phase, stimulate both angiogenesis and neurogenesis and lead to improved functional recovery after stroke. However vascular endothelial growth factors (VEGF) is the most potent angiogenic factor for neurovascularization and neurogenesis in ischemic injury can be modulated in different ways and thus can be used as therapy in stroke. In response to the ischemic injury VEGF is released by endothelial cells through natural mechanism and leads to angiogenesis and vascularization. This release can also be up regulated by exogenous administration of Mesenchymal stem cells, by various physical therapy regimes and electroacupuncture, which further potentiate the efficacy of VEGF as therapy in post stroke recovery. Recent published literature was searched using PubMed and Google for the article reporting on methods of up regulation of VEGF and therapeutic potential of growth factors in stroke

Antihypertensive medications for risk reduction of first and recurrent ischemic stroke

It is increasingly clear that even a small reduction in blood pressure results in a substantial risk reduction of vascular events including ischemic stroke. Recently, several comparative prospective trials of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers have demonstrated that, for equivalent reductions in blood pressure, these drugs may confer a greater effect on the prevention of primary and recurrent ischemic stroke compared with other antihypertensive medications. Given this information from prospective randomized trials, it appears that this class of drugs should be the first-line treatment for hypertension in patients at risk of a first or recurrent ischemic stroke. This review will critically assess the scientific basis and rationale of the use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in primary and secondary stroke prevention

pi.-Facial selectivities in cycloadditions to norbornyl- and norbornenyl-fused p-benzoquinones

The stereochemistry of the Diels-Alder cycloaddition of several dienes to the facially perturbed dienophiles 2,3-norbornenobenzoquinone (3) and 2,3-norbornanobenzoquinone (4) has been examined. Unambiguous structural proof for the adducts formed has been obtained from complementary 'H and I3C NMR spectral data and in two cases through X-ray crystal structure determination. While 1,3-~yclopentadiene1, ,3-~yclohexadienea, nd cyclooctatetraene exhibit preference for addition to 3 from the bottom side, the stereochemical outcome is reversed in their response to 4.1,3-DiphenyIisobenzofuran and 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadieenneg aged 3 from the top side with marked selectivity, which is further enhanced in their reaction with 4. The observed stereoselectivities seem to be essentially controlled by steric interactons at the transition state. Model calculations provide support for this interpretation

Hemispherotomy for intractable epilepsy

Context: Hemispherotomy is a surgical procedure for hemispheric disconnection. It is a technically demanding surgery. Our experience is presented here. Aims: To validate and compare the two techniques for hemispherotomy performed in patients with intractable epilepsies. Settings and Design: A retrospective study 2001-March 2007: Nineteen cases of hemispherotomies from a total of 462 cases operated for intractable epilepsy. Materials and Methods: All the cases operated for intractable epilepsy underwent a complete epilepsy surgery workup. Age range 4-23 years (mean 5.2 years), 14 males. The seizure frequency ranged from 2-200 episodes per day; four were in status; three in epilepsia partialis continua. The pathologies included Rasmussen's, hemimegelencephaly (unilateral hemispheric enlargement with severe cortical and subcortical changes), hemispheric cortical dysplasia, post-stroke, post-traumatic encephalomalacia and encephalopathy of unknown etiology. The techniques of surgery included vertical parasaggital approach and peri-insular hemispherotomy. Neuronavigation was used in seven cases. Results: Class I outcome [Engel's] was seen in 18 cases and Class II in one assessed at 32-198 weeks of follow-up. The four patients in status epilepticus had Class I outcome. Four patients had an initial worsening of weakness which improved to preoperative level in five to eight weeks. Power actually improved in three other patients at 32-36 weeks of follow-up, but hand grip weakness persisted. In all the other patients, power continued to be as in preoperative state. Cognitive profile improved in all patients and 11 cases returned back to school. Conclusions: Both techniques were equally effective, the procedure itself is very effective when indicated. Four of our cases were quite sick and were undertaken for this procedure on a semi-emergency basis

Autoimmune encephalitis: A potentially reversible cause of status epilepticus, epilepsy, and cognitive decline

Objectives: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE), epilepsy, and cognitive decline. Design: Observational, prospective case series. Setting: All India Institute of Medical Sciences, New Delhi, India. Materials and Methods: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI), cerebrospinal-fluid analysis (CSF), and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctor′s information) were noted. Results: There were 15 (males = 10) patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years). The most common onset was subacute (64%) and four (29%) patients presented as SE. Predominant clinical presentations were seizures (100%) almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40%) it was normal, six (40%) showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%), voltage-gated potassium channel antibody in five (36%), two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA) antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67%) cases. One death occurred, due to delayed presentation. Conclusions: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis