Posts Tagged Epilepsy

[VIDEO] What’s, Why’s and How’s of the Vagus Nerve Stimulator

Dr Nemechek Discusses the Vagus Nerve Stimulator, how it’s used and what it can do for a patient.

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[EDITORIAL] Reducing birth defects in women with epilepsy – Neurology

Merely 20 years ago, a report of the Quality Standards Subcommittee of the American Academy of Neurology recommended that antiepileptic drug (AED) selection for pregnant women with epilepsy should be based on the AED “deemed most appropriate for her seizure type.”1 Scientifically, lumping all AEDs together when chemical structures and mechanisms of action differ greatly was questionable, but the evidence for differential effects on fetal outcomes was sparse. Multiple research studies have now made it clear that the level of risk for major congenital malformation (MCMs) differs substantially among AEDs. The prevalence of MCMs is highest with valproate monotherapy2,3 compared to other monotherapies, and includes neural tube defects, heart malformations, cleft palate, hypospadias, and polydactyly. Likewise, the prevalence of MCMs is higher in polytherapy combinations that include valproate, compared to polytherapies that exclude valproate. MCM rates with some AED monotherapies even approximate the rates in the general population (e.g., levetiracetam, lamotrigine).2,3

via Reducing birth defects in women with epilepsy | Neurology

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[Abstract + References] Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy

Abstract

Cannabidiol (CBD) is a major active component of the Cannabis plant, which, unlike tetrahydrocannabinol (THC), is devoid of euphoria-inducing properties. During the last 10 years, there has been increasing interest in the use of CBD-enriched products for the treatment of epilepsy. In 2018, an oil-based highly purified liquid formulation of CBD (Epidiolex) derived from Cannabis sativa was approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). The mechanisms underlying the antiseizure effects of CBD are unclear but may involve, among others, antagonism of G protein-coupled receptor 55 (GPR55), desensitization of transient receptor potential of vanilloid type 1 (TRPV1) channels, and inhibition of adenosine reuptake. CBD has complex and variable pharmacokinetics, with a prominent first-pass effect and a low oral bioavailability that increases fourfold when CBD is taken with a high-fat/high-calorie meal. In four randomized, double-blind, parallel-group, adjunctive-therapy trials, CBD given at doses of 10 and 20 mg/kg/day administered in two divided administrations was found to be superior to placebo in reducing the frequency of drop seizures in patients with LGS and convulsive seizures in patients with DS. Preliminary results from a recently completed controlled trial indicate that efficacy also extends to the treatment of seizures associated with the tuberous sclerosis complex. The most common adverse events that differentiated CBD from placebo in controlled trials included somnolence/sedation, decreased appetite, increases in transaminases, and diarrhea, behavioral changes, skin rashes, fatigue, and sleep disturbances. About one-half of the patients included in the DS and LGS trials were receiving concomitant therapy with clobazam, and in these patients a CBD-induced increase in serum levels of the active metabolite norclobazam may have contributed to improved seizure outcomes and to precipitation of some adverse effects, particularly somnolence.

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[WEB SITE] Can Stem Cells be Used to Treat Epilepsy?

The primary pathogenesis of genetic forms of epilepsy is an abnormal expression of certain receptors in the brain that lead to an enhanced excitation and reduced inhibition. Some cases occur following oxygenation deprivation during birth.

Other later-life forms of epilepsy may be attributed to damage to the brain e.g. stroke, brain tumours, traumatic brain injury, drug misuse or a brain infection.

To date, there are several key treatment strategies to help people have fewer seizures. Predominantly, anti-epileptic drugs are used to treat the frequency and severity of epilepsy. However, these have to be taken routinely, and are not a long-term solution. They also have many undesired side-effects. However, anti-epileptic drugs may not work for everyone, therefore other treatments are used, including surgery and dietary modifications (e.g. keto-diet). Therefore, the need to find effective long-term solutions is needed to treat epilepsy.

Epileptic seizure. Image Credit: Rainer Fuhrmann / Shutterstock

Epileptic seizure. Image Credit: Rainer Fuhrmann / Shutterstock

What are Stem Cells?

Stem cells are cells that have the ability to develop into different specialised cell types of the body. Most cells in the body are post-mitotic, meaning they are unable to divide and grow into new types of tissues. However, stem cells are able to divide after periods of no apparent activity and are able to transform into different body cell types, including muscle cells, nerve cells and blood cells.

Embryonic stem cells. Illustration Credit: Nobeastsofierce / Shutterstock

Embryonic stem cells. Illustration Credit: Nobeastsofierce / Shutterstock

Traditionally, stem cells were only able to be isolated from embryos (animal and human) and some adult somatic stem cells, such as those found in e.g. bone marrow. However, due to advances in science and technology, adult cells taken from tissues such as e.g. skin, are now able to be reprogrammed into stem-cell like cells called induced pluripotent stem cells (iPSCs). These iPSCs may be able to function in very similar ways to those previously only obtainable through embryo donation.

iPSCs can be genetically manipulated to form a variety of different body cells e.g. neurons and muscle cells. However, much more work is needed before iPSCs can be used to replace dysfunctional cells within the body, though many advances have been made, especially in animal studies, including successful replacement of damaged heart cells with lab grown heart cells from the animals.

Can Stem Cells be Used to Treat Epilepsy?

As most cases of epilepsy can be attributed to receptor expression differences within the brain (due to mutations), correcting these may in theory reduce the likelihood of electrical seizures developing in the brain.

In addition, during status epilepticus, the excitation overload sometimes kills neurons, especially within the hippocampus. This can actually worsen the condition over time and lead to the development of temporal lobe epilepsy (TLE). Whilst anti-epileptic medication may treat the seizures, the damage caused to the temporal lobe is often irreversible and permanent, and current therapies do not address this.

As previously discussed, the reduction in inhibition in the brain, primarily due to loss of GABA-ergic interneurons, coupled with increased excitation of neurons, is key in the development of epilepsy including TLE.

Scientists therefore have speculated that enhancing inhibition by GABA-neurons may alleviate status epilepticus due to renewed inhibitory balance.

A study by Upadhya and colleagues (published in 2019 in PNAS); aimed to investigate whether iPSCs grafted into the brain of rats could reduce seizures and reverse damage in the hippocampus. They found that medial ganglionic eminence (MGE) cells derived from human-derived iPSCs, grafted into the hippocampus successfully reduced the frequency of seizures and reduced GABA-ergic neuronal loss.

Furthermore, there was an improvement to cognition and mood. Although this study was performed in rats, the implications of this research has far reaching potential to be used clinically.

Another study, a Phase I clinical trial in 22 patients, using autologous mesenchymal stem cells in epilepsy patients was shown to reduce overall seizure frequency (published in Advances in Medical Sciences by Hlebokazov and colleagues in 2017). Stem cells were obtained from patients’ own bone marrow, and administered intravenously and through a single injection into the spinal cord. After 1 year, 3 out of 10 patients achieved complete remission (no seizures) and another 5 patients that previously did not respond to drugs began to respond favourably. No side effects were observed in any of the patients.

This study is promising and showed a good safety profile for the patients. It appears that stem cells were associated with  alleviation of pathological hallmarks as well as the symptoms of epilepsy. Though this was only a Phase I trial with a very small cohort, additional controlled trials with placebos are needed in a larger cohort to make any definitive conclusions on the efficacy and safety.

In summary, stem cell based therapies, show promising results in the treatment of diseases including epilepsy. Animal and clinical studies have shown the remarkable efficacy of stem cells’ regenerative properties. However, larger clinical trials are needed before stem cell therapy can become routine. It is also expensive with therapies starting at around $5,000-$8,000 per treatment, though they can be as expensive as $25,000. In the UK, the NHS does not offer stem cell therapy routinely, only for a very small number of people in designated centres for diseases such as MS.

In the United States, the only type of stem cell therapy that has been extensively studied and approved for human treatment involves use of hematopoietic stem cells for patients with certain types of cancer.

Sources:

  1. NHS.uk, 2019. Epilepsy. https://www.nhs.uk/conditions/epilepsy/
  2. NIH.gov, 2019. Stem Cell Information. https://stemcells.nih.gov/info/basics/1.htm
  3. Upadhya et al, 2019. Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration. PNAS. 116(1):287-96. https://www.pnas.org/content/116/1/287.short?rss=1
  4. Hlebokazov et al, 2017. Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study. Adv Med Sci. 62(2):273-279. https://www.ncbi.nlm.nih.gov/pubmed/28500900

Further Reading

 

Last Updated: Jul 5, 2019

Osman Shabir

 

Written by

Osman Shabir

Osman is a Neuroscience PhD Research Student at the University of Sheffield studying the impact of cardiovascular disease and Alzheimer’s disease on neurovascular coupling using pre-clinical models and neuroimaging techniques.

 

via Can Stem Cells be Used to Treat Epilepsy?

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[Abstract] Epilepsy under the scope of ultra-high field MRI

Highlights

Ultra-high field magnetic resonance imaging can resolve sub-millimeter anatomy and quantify constitutive brain molecules.

Structural and susceptibility imaging can probe the brain for changes in the course of epilepsy.

Ex vivo high-resolution imaging can identify specific histological patterns related to demyelination and cell death.

Multimodal histological-MRI studies can help to confront preoperative diagnosis and postoperative outcome.

UHF-MRI offer potential biomarkers in epilepsy diagnosis and monitoring

Abstract

Ultra-high field magnetic resonance imaging (UHF-MRI) is capable of unraveling anatomical structures in a submillimeter range. In addition, its high resonance regime allows the quantification of constitutive molecules in a spatially sensitive manner, a crucial capability for determining the extent and localization of a probable epileptogenic region or the severity of the epilepsy. The main technical challenges for data acquisition under UHF are to produce a strong, homogeneous transverse field, while keeping the tissue power deposition within the safe regulatory guidelines. The nonuniformities caused by destructive and constructive interferences at UHFs required new technologies to accelerate and increase yield regarding time spent and quality achieved. Image quality is the paramount contribution of UHF high-resolution imaging, which is capable to disclose fine details of the hippocampal formation and its surroundings and their changes in the course of epilepsy. Other sequences like diffusion tensor imaging (DTI) and multiecho susceptibility imaging at 7 T in vivo can assist the creation of normative atlases of the hippocampal subfields or the reconstruction of the highly arborized cerebral blood vessels. In our review, we specify the impact of these advanced relevant techniques onto the study of epilepsy. In this context, we focused onto high field high-resolution scanners and clinically-enriched decision-making. Studies on focal dysplasias correlating ex vivo high-resolution imaging with specific histological and ultrastructural patterns showed that white matter hyperintensities were related to a demyelination process and other alterations. Preliminary results correlating thick serial sections through bioptic epileptogenic tissue could extend the strategy to localize degenerated tissue sectors, correlate nature and extent of tissue loss with preoperative diagnosis and postoperative outcome. Finally, this protocol will provide the neurosurgeon with a detailed depiction of the removed pathologic tissue and possible adverse effects by the pathologic tissue left in situ.

This article is part of the special issue “NEWroscience 2018”

via Epilepsy under the scope of ultra-high field MRI – ScienceDirect

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[Abstract] The Role of EEG in the Erroneous Diagnosis of Epilepsy

Summary

Errors in diagnosis are relatively common in medicine and occur in all specialties. The consequences can be serious for both patients and physicians. Errors in neurology are often because of the overemphasis on “tests” over the clinical picture. The diagnosis of epilepsy in general is a clinical one and is typically based on history. Epilepsy is more commonly overdiagnosed than underdiagnosed. An erroneous diagnosis of epilepsy is often the result of weak history and an “abnormal” EEG. Twenty-five to 30% of patients previously diagnosed with epilepsy who did not respond to initial antiepileptic drug treatment do not have epilepsy. Most patients misdiagnosed with epilepsy turn out to have either psychogenic nonepileptic attacks or syncope. Reasons for reading a normal EEG as an abnormal one include over-reading normal variants or simple fluctuations of background rhythms. Reversing the diagnosis of epilepsy is challenging and requires reviewing the “abnormal” EEG, which can be difficult. The lack of mandatory training in neurology residency programs is one of the main reasons for normal EEGs being over-read as abnormal. Tests (including EEG) should not be overemphasized over clinical judgment. The diagnosis of epilepsy can be challenging, and some seizure types may be underdiagnosed. Frontal lobe hypermotor seizures may be misdiagnosed as psychogenic events. Focal unaware cognitive seizures in elderly maybe be blamed on dementia, and ictal or interictal psychosis in frontal and temporal lobe epilepsies may be mistaken for a primary psychiatric disorder.

via The Role of EEG in the Erroneous Diagnosis of Epilepsy : Journal of Clinical Neurophysiology

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[Abstract + References] Epilepsy and Anticonvulsant Therapy in Brain Tumor Patients – Book Chapter

Book Chapter

Authors: Sylvia C. Kurz, David Schiff, Patrick Y. Wen

Abstract

Seizures are common in patients with brain tumors and may have a significant impact on quality of life. The actual seizure risk varies based on tumor histology and tumor location. Seizures are most common in patients with glioneuronal tumors and temporal, insular, or frontal lobe tumor location. Antiepileptic drug therapy is indicated in patients with a history of seizure, and the choice of symptomatic treatment should follow the principles of treatment for focal symptomatic epilepsy. In general, antiepileptic drugs that interact with the hepatic CYP450 co-enzymes should be avoided in brain tumor patients if possible due to potential drug-chemotherapy interactions. Levetiracetam represents the antiepileptic drug of choice in patients with brain tumors and has been demonstrated to be efficacious and is well tolerated in brain tumor patients. Lacosamide is an alternative anticonvulsant agent with increasing experience supporting its efficacy and favorable side effect profile.

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via Epilepsy and Anticonvulsant Therapy in Brain Tumor Patients | SpringerLink

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[NEWS] Predicting seizures before they happen

Date: June 10, 2019

Source: RCSI

Summary: A new study has found a pattern of molecules that appear in the blood before a seizure happens. This discovery may lead to the development of an early warning system, which would enable people with epilepsy to know when they are at risk of having a seizure.

FULL STORY

A new study has found a pattern of molecules that appear in the blood before a seizure happens. This discovery may lead to the development of an early warning system, which would enable people with epilepsy to know when they are at risk of having a seizure.

Researchers at FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, hosted at RCSI (Royal College of Surgeons in Ireland) led the study, which is published in the current edition of the Journal of Clinical Investigation (JCI).

FutureNeuro and RCSI researchers have discovered molecules in the blood that are higher in people with epilepsy before a seizure happens. These molecules are fragments of transfer RNAs (tRNAs), a chemical closely related to DNA that performs an important role in building proteins within the cell. When cells are stressed, tRNAs are cut into fragments. Higher levels of the fragments in the blood could reflect that brain cells are under stress in the build up to a seizure event.

Using blood samples from people with epilepsy at the Epilepsy Monitoring Unit in Beaumont Hospital, Dublin and in a similar specialist centre in Marburg, Germany, the group found that fragment levels of three tRNAs “spike” in the blood many hours before a seizure.

“People with epilepsy often report that one of the most difficult aspects of living with the disease is never knowing when a seizure will occur,” said Dr Marion Hogg, FutureNeuro investigator, Honorary Lecturer at RCSI, and the study’s lead author.

“The results of this study are very promising. We hope that our tRNA research will be a key first step toward developing an early warning system.”

Approximately 40,000 people in Ireland have epilepsy and one third of those do not respond to current treatments, meaning they continue to experience seizures. The World Health Organisation estimates that more than 50 million people worldwide have epilepsy.

“New technologies to remove the unpredictability of uncontrolled seizures for people with epilepsy are a very real possibility,” said Professor David Henshall, Director of FutureNeuro and Professor of Molecular Physiology and Neuroscience at RCSI who was a co-author on the paper.

“Building on this research we in FutureNeuro hope to develop a test prototype, similar to a blood sugar monitor that can potentially predict when a seizure might occur.”

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Materials provided by RCSINote: Content may be edited for style and length.


Journal Reference:

  1. Marion C. Hogg, Rana Raoof, Hany El Naggar, Naser Monsefi, Norman Delanty, Donncha F. O’Brien, Sebastian Bauer, Felix Rosenow, David C. Henshall, Jochen H.M. Prehn. Elevation of plasma tRNA fragments precedes seizures in human epilepsyJournal of Clinical Investigation, 2019; DOI: 10.1172/JCI126346

via Predicting seizures before they happen — ScienceDaily

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[Book Chapter] Pregnancy and Epilepsy

VD Kapadia – Medical Disorders in Pregnancy

Epilepsy is the most common neurological disorder, with 50 million people affected by it worldwide. Nearly 50% of these affected individuals are women. The burden of  epilepsy in women in India is to the tune of 2.73 million, with 52% of them being in …

Continue —> Pregnancy and Epilepsy [PDF]

 

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[ARTICLE] EFFICACY OF SHORT TERM VIDEO EEG IN DETECTING PSYCHOGENIC NON-EPILEPTIC SEIZURES – Full Text PDF

Abstract

Background: Short term video Electroencephalography (SVEEG) is a non-invasive diagnostic procedure typically last for about 1-5 hours. SVEEG can be utilize to differentiate epileptic from Psychogenic Non-epileptic Seizures (PNES).

Objective: To assess the yield of short term video EEG in detecting PNES.

Methods:Retrospective analysis of short term video EEG in a tertiary level hospital. Patient history, provisional diagnosis, previous EEG and imaging reports were tabulated. Various short term video EEG findings like epileptiform abnormalities, PNES and other non-epileptic events were analyzed in detail. According to the provisional diagnosis formed two groups; Suspecting NEE and suspecting seizure disorders. Change in the provisional diagnosis after SVEEGs were also studied.

Results: A total of 417 SVEEGs analyzed: 34(8.2%) patients developed events to suggest PNES, 16(3.8%) patients had other non-epileptic events; 96(23%) showed interictal epileptiform discharges, 15 (3.6%) showed seizures and 90(21.6%) patients showed non-specific EEG abnormalities. Around 60% SVEEGs were conclusive.

Conclusion: A diagnostic event was recorded during SVEEG in majority of patients in the PNES group. SVEEG is a cost effective and useful diagnostic procedure; especially to identify non-epileptic events.

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