Posts Tagged Epilepsy

[WEB SITE] The Relationship Between Epilepsy and Sleep

The Thomas Haydn Trust in an aid to understanding Epilepsy and Sleep has published this mobile article. This article is not extensive and should not be used as medical advice; it’s intended for information purposes only. This dictionary is also available for download from http://www.thomashaydntrust.com/publications.htm in .pdf format. [Please note that this is version 1 and further updates may be availalbe]

Written by

M C Walker, S M Sisodiya

Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London, and National Society for Epilepsy, Chalfont St Peter, Bucks. London, and National Society for Epilepsy, Chalfont St Peter, Bucks. September 2005. This article can be reproduced for educational purposes.

Introduction

Epilepsy has a complex association with sleep. Certain seizures are more common during sleep, and may show prominent diurnal variation. Rarely, nocturnal seizures are the only manifestation of an epileptic disorder and these can be confused with a parasomnia. Conversely, certain sleep disorders are not uncommonly misdiagnosed as epilepsy. Lastly, sleep disorders can exacerbate epilepsy and epilepsy can exacerbate certain sleep disorders. This chapter is thus divided into four sections: normal sleep physiology and the relationship to seizures; the interaction of sleep disorders and epilepsy; and the importance of sleep disorders in diagnosis.

Normal sleep physiology and the relationship to seizures

Adults require on average 7 – 8 hours sleep a night. This sleep is divided into two distinct states – rapid eye movement (REM) sleep and non-REM sleep. These two sleep states cycle over approximately 90 minutes throughout the night with the REM periods becoming progressively longer as sleep continues. Thus there is a greater proportion of REM sleep late on in the sleep cycles. REM sleep accounts for about a quarter of sleep time. During REM sleep, dreams occur; hypotonia or atonia of major muscles prevents dream enactment. REM sleep is also associated with irregular breathing and increased variability in blood pressure and heart rate. Non-REM sleep is divided into four stages (stages I – IV) defined by specific EEG criteria. Stages I/II represent light sleep, while stages III/IV represent deep, slow-wave sleep.

Gowers noted that in some patients, epileptic seizures occurred mainly in sleep. Sleep influences cortical excitability and neuronal synchrony. Surveys have suggested that 10 – 45% of patients have seizures that occur predominantly or exclusively during sleep or occur with sleep deprivation. EEG activation in epilepsy commonly occurs during sleep, so that sleep recordings are much more likely to demonstrate epileptiform abnormalities. These are usually most frequent during non-REM sleep and often have a propensity to spread so that the epileptiform discharges are frequently observed over a wider field than is seen during the wake state. Sleep deprivation (especially in generalised epilepsies) can also ‘activate’ the EEG, but can induce seizures in some patients. Thus many units perform sleep EEGs with only moderate sleep deprivation (late night, early morning), avoidance of stimulants (e.g. caffeine-containing drinks) and EEG recording in the afternoon. Sleep-induced EEGs in which the patient is given a mild sedative (e.g. chloral hydrate) are also useful.

Sleep and generalised seizures

Thalamocortical rhythms are activated during non-REM sleep giving rise to sleep spindles. Since similar circuits are involved in the generation of spike-wave discharges in primary generalised epilepsy, it is perhaps not surprising that non-REM sleep often promotes spike-wave discharges. Epileptiform discharges and seizures in primary generalised epilepsies are both commonly promoted by sleep deprivation. Furthermore, primary generalised seizures often occur within a couple of hours of waking, whether from overnight sleep or daytime naps. This is most notable with juvenile myoclonic epilepsy in which both myoclonus and tonic-clonic seizures occur shortly after waking, and the

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syndrome of tonic-clonic seizures on awakening described by Janz. Seizure onset in this syndrome is from 6 – 35 years and the prognosis for eventual remission is good.

Certain epileptic encephalopathies show marked diurnal variation in seizure manifestation and electrographic activity. An example is the generalised repetitive fast discharge during slow-wave sleep occurring in Lennox-Gastaut syndrome. Another example is electrical status epilepticus during sleep (ESES). This is characterised by spike and wave discharges in 85 – 100% of non-REM sleep. This phenomenon is associated with certain epilepsy syndromes, including Landau-Kleffner, Lennox-Gastaut syndrome, continuous spikes and waves during sleep and benign epilepsy of childhood with rolandic spikes. ESES can thus be a component of a number of different epilepsy syndromes with agedependent onset, many seizure types, and varying degrees of neuropsychological deterioration. Indeed, ESES has been described in the setting of an autistic syndrome alone with no other

manifestation of epilepsy.

Sleep and partial epilepsies

Inter-ictal epileptiform abnormalities on the EEG occur more frequently during sleep, especially stage III/IV sleep (slow-wave sleep). The discharges have a greater propensity to spread during sleep, and thus are often seen over a wider field than discharges occurring during wakefulness. Temporal lobe seizures are relatively uncommon during sleep, while frontal lobe seizures occur often predominantly (sometimes exclusively) during sleep. Nocturnal frontal lobe seizures can be manifest as: brief stereotypical, abrupt arousals; complex stereotypical, nocturnal movements; or episodic nocturnal wanderings with confusion. Inherited frontal lobe epilepsies can manifest with only nocturnal events that can be confused with parasomnias (see below). Autosomal dominant nocturnal frontal lobe epilepsy is such an epilepsy. This has been associated with mutations in alpha-4 and beta-2 subunits of the neuronal nicotinic acetylcholine receptor. Onset is usually in adolescence with seizures occurring frequently, sometimes every night. The seizures are provoked by stress, sleep deprivation and menstruation, and often respond well to carbamazepine.

The interaction of sleep disorders and epilepsy

Seizures can disrupt sleep architecture. Complex partial seizures at night disrupt normal sleep patterns, decrease REM sleep and increase daytime drowsiness. Daytime complex partial seizures can also decrease subsequent REM sleep, which may contribute to impaired function. Antiepileptic drugs (AEDs) can also disrupt normal sleep patterns, although there are conflicting data (this is partially due to drugs having different short-term and long-term effects). Carbamazepine, for example, given acutely reduces and fragments REM sleep, but these effects are reversed after a month of treatment. The GABAergic drugs can have a profound effect on sleep; phenobarbitone and benzodiazepines prolong non-REM sleep and shorten REM sleep, while tiagabine increases slow-wave sleep and sleep efficiency. Gabapentin and lamotrigine may both increase REM sleep.

Certain sleep disorders are more common in patients with epilepsy. This is particularly so with obstructive sleep apnoea which is more common in patients with epilepsy and can also exacerbate seizures. Indeed, sleep apnoea is approximately twice as common in those with refractory epilepsy than in the general population. The reasons why this is so are unknown, but may relate to increased body weight, use of AEDs, underlying seizure aetiology or the epilepsy syndrome itself.

Patients with obstructive sleep apnoea often find that seizure control improves with treatment of the sleep apnoea. Topiramate may also be a particularly useful drug in these cases.

The importance of sleep disorders in differential diagnosis

On occasions nocturnal seizures can be misdiagnosed as a primary sleep disorder (see above). Conversely, certain sleep disorders can be misdiagnosed as epilepsy and the more common of these will be discussed below. Sleep disorders tend to occur during specific sleep phases and thus usually occur at specific times during the night, while seizures usually occur at any time during the night. There may also be other clues in the history, including age of onset, association with other symptoms (see below) and the stereotypy of the episodes (seizures are usually stereotypical).

In cases where there is some uncertainty, video-EEG polysomnography is the investigation of choice. There are, however, instances in which the diagnosis can be difficult even after overnight video-EEG telemetry as frontal lobe seizures can be brief with any EEG change obscured by movement artefact, and it is often the stereotypy of the episodes that confirms the diagnosis.

Abnormalities of sleep are divided into three main categories: 1) dysomnias or disorders of the sleepwake cycle; 2) parasomnias or disordered behaviour that intrudes into sleep, and 3) sleep disorders associated with medical or psychiatric conditions. Although there is an extensive list of conditions within each of these categories, we will confine ourselves to the clinical features of the more common conditions that can be confused with epilepsy.

Narcolepsy

Narcolepsy is a specific, well-defined disorder with a prevalence of approximately one in 2000. It is a life-long condition usually presenting in late teens or early 20s. Narcolepsy is a disorder of REM sleep and has as its main symptom excessive daytime sleepiness. This is manifest as uncontrollable urges to sleep, not only at times of relaxation (e.g. reading a book, watching television), but also at inappropriate times (e.g. eating a meal or while talking). The sleep is itself usually refreshing. The other typical symptoms are cataplexy, sleep paralysis and hypnagogic/hypnopompic hallucinations. These represent REM sleep phenomena such as hypotonia/atonia, and dreams occurring at inappropriate times. Cataplexy is a sudden decrease in voluntary muscle tone (especially jaw, neck and limbs) that occurs with sudden emotion like laughter, elation, surprise or anger. This can manifest as jaw dropping, head nods or a feeling of weakness or, in more extreme cases, as falls with ‘paralysis’ lasting sometimes minutes. Consciousness is preserved. Cataplexy is a specific symptom of narcolepsy, although narcolepsy can occur without cataplexy. Sleep paralysis and hypnagogic hallucinations are not particularly specific and can occur in other sleep disorders and with sleep deprivation (especially in the young). Both these phenomena occur shortly after going to sleep or on waking.

Sleep paralysis is a feeling of being awake, but unable to move. This can last minutes and is often very frightening, so can be associated with a feeling of panic. Hypnagogic/hypnopompic hallucinations are visual or auditory hallucinations occurring while dozing/falling asleep or on waking; often the hallucinations are frightening, especially if associated with sleep paralysis.

Narcolepsy is associated with HLA type. Approximately 90% of all narcoleptic patients with definite cataplexy have the HLA allele HLA DQB1*0602 (often in combination with HLA DR2), compared with approximately 25% of the general population. The sensitivity of this test is decreased to 70% if cataplexy is not present. The strong association with HLA type has raised the possibility that narcolepsy is an autoimmune disorder. Recently loss of hypocretin-containing neurons in the hypothalamus has been associated with narcolepsy, and it is likely that narcolepsy is due to deficiency in hypocretin (orexin).

Since narcolepsy is a life-long condition with possibly addictive treatment, the diagnosis should always be confirmed with multiple sleep latency tests (MSLT). During this test five episodes of sleep are permitted during a day; rapid onset of sleep and REM sleep within 15 minutes in the absence of sleep deprivation are indicative of narcolepsy.

The excessive sleepiness of narcolepsy can be treated with modafinil, methylphenidate or dexamphetamine and regulated daytime naps. The cataplexy, sleep paralysis and hypnagogic/hypnopompic hallucinations respond to antidepressants (fluoxetine or clomipramine are the most frequently prescribed). People with narcolepsy often have fragmented, poor sleep at night, and good sleep hygiene can be helpful.

Sleep apnoea

Sleep apnoea can be divided into the relatively common obstructive sleep apnoea and the rarer central sleep apnoea. Obstructive sleep apnoea is more common in men than women and is associated with obesity, micrognathia and large neck size. The prevalence may be as high as 4% in men, and 2% in women. The symptoms suggestive of obstructive sleep apnoea are loud snoring, observed nocturnal apnoeic spells, waking at night fighting for breath or with a feeling of choking, morning headache, daytime somnolence, personality change and decreased libido. Although the daytime somnolence can be as severe as narcolepsy, the naps are not usually refreshing and are longer. Obstructive sleep apnoea and central sleep apnoea can be associated with neurological disease, but central sleep apnoea can also occur as an idiopathic syndrome. The correct diagnosis requires polysomnography with measures of oxygen saturations and nasal airflow or chest movements. To be pathological a sleep apnoea or hypopnoea (a 50% reduction in airflow) has to last ten seconds and there need to be more than five apnoeas/hypopnoeas per hour (the precise number to make a diagnosis varies from sleep laboratory to sleep laboratory).

Uncontrolled sleep apnoea can lead to hypertension, cardiac failure, pulmonary hypertension and stroke. In addition, sleep apnoea has been reported to worsen other sleep conditions, such as narcolepsy, and to worsen seizure control.

Treatment of sleep apnoea should include avoidance of alcohol and sedatives and weight reduction. Pharmacological treatment is not particularly effective, although REM suppressants such as protriptyline can be helpful. The mainstays of treatment are surgical and include tonsillectomies, adenoidectomy and procedures to widen the airway, and the use of mechanical devices. Dental appliances to pull the bottom jaw forward can be effective in mild cases, but continuous positive airway pressure administered by a nasal mask has become largely the treatment of choice for moderate/severe obstructive sleep apnoea. In cases associated with neuromuscular weakness intermittent positive pressure ventilation is often necessary.

Restless legs syndrome/periodic limb movements in sleep

Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) can occur in association or separately. Most people with RLS also have PLMS, but the converse is not true and most people with PLMS do not have RLS. RLS is characterised by an unpleasant sensation in the legs, often described as tingling, cramping or crawling, and an associated overwhelming urge to move the legs. These sensations are usually worse in the evening, and movement only provides temporary relief. RLS affects about 5% of the population. Periodic limb movements in sleep are brief, repetitive jerking of usually the legs that occur every 20 – 40 seconds. These occur in non-REM sleep and can cause frequent arousals. PLMS occurs in about 50% of people over 65 years. These conditions can also be associated with daytime jerks. Both RLS and PLMS can be familial, but can be secondary to peripheral neuropathy (especially diabetic, uraemic and alcoholic neuropathies), iron deficiency, pregnancy and rarely spinal cord lesions.

Symptomatic relief can be achieved with benzodiazepines, gabapentin and opioids, but L-DOPA and dopamine agonists are the mainstay of treatment.

Sleep-wake transition disorders

The most common of these are hypnic jerks or myoclonic jerks that occur on going to sleep or on waking. They are entirely benign in nature, and require no treatment. They can occur in association with other sleep disorders. Rhythmic movement disorder is a collection of conditions occurring in infancy and childhood characterised by repetitive movements occurring immediately prior to sleep onset that can continue into light sleep. One of the most dramatic is headbanging or jactatio capitis nocturna. Persistence of these rhythmic movements beyond the age of ten years is often associated with learning difficulties, autism or emotional disturbance. Sleep-talking can occur during non-REM and REM sleep, but is often seen with wake-sleep transition and is a common and entirely benign phenomenon.

Nocturnal enuresis

Nocturnal enuresis is a common disorder that can occur throughout the night. Although diagnosis is straightforward, it can recur in childhood, and also occurs in the elderly, with approximately 3% of women and 1% of men over the age of 65 years having the disorder. Thus, on occasions, it can be misdiagnosed as nocturnal epilepsy.

Non-REM parasomnias

Non-REM parasomnias usually occur in slow-wave (stage III/IV) sleep. These conditions are often termed arousal disorders and indeed can be induced by forced arousal from slow-wave sleep. There are three main non-REM parasomnias – sleepwalking, night terrors and confusional arousal. These disorders often have a familial basis, but can be brought on by sleep deprivation, alcohol and some drugs. They can also be triggered by other sleep disorders such as sleep apnoea, medical and psychiatric illness. Patients are invariably confused during the event, and are also amnesic for the event. These conditions are most common in children, but do occur in adults.

Sleepwalking may occur in up to 25% of children, with the peak incidence occurring from age 11 – 12 years. The condition is characterised by wanderings often with associated complex behaviours such as carrying objects, and eating. Although speech does occur, communication is usually impossible. The episode usually lasts a matter of minutes. Aggressive and injurious behaviour is uncommon, and should it occur then polysomnography may be indicated to exclude an REM sleep parasomnia (see below), and to confirm the diagnosis. Night terrors are less common and are characterised by screaming, and prominent sympathetic nervous system activity – tachycardia, mydriasis and excessive sweating. Both these conditions are usually benign and rarely need treatment. If dangerous behaviour occurs, then treatment may be indicated. Benzodiazepines, especially clonazepam, are usually very effective.

REM parasomnias

Nightmares are REM phenomena that can occur following sleep deprivation, with certain drugs (e.g. L-DOPA) and in association with psychological and neurological disease. Sleep paralysis (see narcolepsy) is also an REM parasomnia, and may be familial.

Of more concern are REM sleep behaviour disorders. These consist of dream enactment. They are often violent, and tend to occur later in sleep when there is more REM sleep. These are rare and tend to occur in the elderly. In over one-third of cases, REM sleep behaviour disorders are symptomatic of an underlying neurological disease such as dementia, multisystem atrophy, Parkinson’s disease, brainstem tumours, multiple sclerosis, subarachnoid haemorrhage and cerebrovascular disease. In view of this, a history of possible REM sleep behaviour disorder needs to be investigated by polysomnography, and if confirmed, then possible aetiologies need to be investigated. REM sleep behaviour disorders respond very well to clonazepam.

Further reading

• BAZIL CW (2002) Sleep and epilepsy. Semin Neurol 22(3) , 321-327.

• FOLDVARY-SCHAEFER NJ (2002) Sleep complaints and epilepsy: the role of seizures,

antiepileptic drugs and sleep disorders. Clin Neurophysiol 19(6) , 514-521.

• MALOW BA (2002) Paroxysmal events in sleep. J Clin Neurophysiol 19(6) , 522-534.

• SCHNEERSON J. Handbook of Sleep Medicine . Blackwell Science, Oxford.

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Source: The Relationship Between Epilepsy and Sleep – Wattpad

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[BLOG POST] You Probably Didn’t Aware Of These Surprising Epileptic Seizure Causes

Epileptic Seizure Causes

Epileptic Seizure has no known cause in about half of those with the condition. In the other, the condition may be traced to various factors.

Genetic influence. Some types of epilepsy, which are categorized by the type of seizure you experience or the part of the brain that is affected, run in families. In these cases, it’s likely that there’s a genetic effect.

Researchers have associated some types of this disorder to specific genes that Epileptic Seizure Causes, also include genes though it’s estimated that up to 500 genes could be tied to the condition. For most people, genes are only part of the cause of this disorder. Certain genes may make a person more sensitive to environmental conditions that provoke seizures.

Head trauma. Epileptic Seizure Causes by Head trauma as a result of a car accident or other traumatic injury.

Brain conditions. Brain conditions that cause damage to the brain, such as brain tumors or strokes, can cause Epileptic Seizure. Stroke is a leading cause of epilepsy in adults older than age 35.

Infectious diseases. Infectious diseases, such as meningitis, AIDS and viral encephalitis, can cause epilepsy.

Prenatal injury. Before birth, babies are sensitive to brain damage that could be caused by several factors, such as an infection in the mother, poor nutrition or oxygen deficiencies. This brain damage can result in epilepsy or cerebral palsy.

  • Different epilepsies are due to many different underlying Epileptic Seizure Causes.Epileptic Seizure Causes can be complex, and sometimes hard to identify. A person might start having seizures because they have one or more of the following.
  • A genetic tendency that is not inherited, but is a new change in the person’s genes.
  • A structural (sometimes called ‘symptomatic’) change in the brain, such as the brain not developing properly, or damage caused by a brain injury, infections like meningitis, a stroke or a tumour. A brain scan, such as Magnetic Resonance Imaging (MRI), may show this.
  • Structural changes due to genetic conditions such as tuberous sclerosis, or neurofibromatosis, which can cause growths affecting the brain.Developmental disorders. Epilepsy can sometimes be associated with developmental disorders, such as autism and neurofibromatosis
  • A genetic tendency, passed down from one or both parents (inherited). source

Source:  You Probably Didn’t Aware Of These Surprising Epileptic Seizure Causes

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[WEB SITE] New method uses advanced noninvasive neuroimaging to localize and identify epileptic lesions

Epilepsy affects more than 65 million people worldwide. One-third of these patients have seizures that are not controlled by medications. In addition, one-third have brain lesions, the hallmark of the disease, which cannot be located by conventional imaging methods. Researchers at the Perelman School of Medicine at the University of Pennsylvania have piloted a new method using advanced noninvasive neuroimaging to recognize the neurotransmitter glutamate, thought to be the culprit in the most common form of medication-resistant epilepsy. Their work is published today in Science Translational Medicine.

Glutamate is an amino acid which transmits signals from neuron to neuron, telling them when to fire. Glutamate normally docks with the neuron, gives it the signal to fire and is swiftly cleared. In patients with epilepsy, stroke and possibly ALS, the glutamate is not cleared, leaving the neuron overwhelmed with messages and in a toxic state of prolonged excitation.

In localization-related epilepsy, the most common form of medication-resistant epilepsy, seizures are generated in a focused section of the brain; in 65 percent of patients, this occurs in the temporal lobe. Removal of the seizure-generating region of the temporal lobe, guided by preoperative MRI, can offer a cure. However, a third of these patients have no identified abnormality on conventional imaging studies and, therefore, more limited surgical options.

“Identification of the brain region generating seizures in location-related epilepsy is associated with significantly increased chance of seizure freedom after surgery,” said the new study’s lead author, Kathryn Davis, MD, MSTR, an assistant professor of Neurology at Penn. “The aim of the study was to investigate whether a novel imaging method, developed at Penn, could use glutamate to localize and identify the epileptic lesions and map epileptic networks in these most challenging patients.”

“We theorized that if we could develop a technique which allows us to track the path of and make noninvasive measurements of glutamate in the brain, we would be able to better identify the brain lesions and epileptic foci that current methods miss,” said senior author Ravinder Reddy, PhD, a professor of Radiology and director of Penn’s Center for Magnetic Resonance and Optical Imaging.

Reddy’s lab developed the glutamate chemical exchange saturation transfer (GluCEST) imaging method, a very high resolution magnetic resonance imaging contrast method not available before now, to measure how much glutamate was in different regions of the brain including the hippocampi, two structures within the left and right temporal lobes responsible for short- and long-term memory and spatial navigation and the most frequent seizure onset region in adult epilepsy patients.

The study tested four patients with medication-resistant epilepsy and 11 controls. In all four patients, concentrations of glutamate were found to be higher in one of the hippocampi, and confirmatory methods (electroencephalography and magnetic resonance spectra) verified independently that the hippocampus with the elevated glutamate was located in the same hemisphere as the epileptic focus/lesion. Consistent lateralization to one side was not seen in the control group.

While preliminary, this work indicates the ability of GluCEST to detect asymmetrical hippocampal glutamate levels in patients thought to have nonlesional temporal lobe epilepsy. The authors say this approach could reduce the need for invasive intracranial monitoring, which is often associated with complications, morbidity risk, and added expense.

“This demonstration that GluCEST can localize small brain hot spots of high glutamate levels is a promising first step in our research,” Davis said. “By finding the epileptic foci in more patients, this approach could guide clinicians toward the best therapy for these patients, which could translate to a higher rate of successful surgeries and improved outcomes from surgery or other therapies in this difficult disease.”

Source: Penn Medicine

Source: New method uses advanced noninvasive neuroimaging to localize and identify epileptic lesions

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[WEB SITE] How Ketogenic Diets Curb Inflammation 

Summary: The neurological benefits experienced by those with epilepsy who follow ketogenic diets may be a result of the low carb diet lowering brain inflammation, researchers report.

Source: UCSF.

Ketogenic diets — extreme low-carbohydrate, high-fat regimens that have long been known to benefit epilepsy and other neurological illnesses — may work by lowering inflammation in the brain, according to new research by UC San Francisco scientists. The UCSF team has discovered a molecular key to the diet’s apparent effects, opening the door for new therapies that could reduce harmful brain inflammation following stroke and brain trauma by mimicking the beneficial effects of an extreme low-carb diet

“It’s a key issue in the field — how to suppress inflammation in brain after injury,” said Raymond Swanson, MD, a professor of neurology at UC San Francisco, chief of the neurology service at the San Francisco Veterans Affairs Medical Center, and senior author of the new study.

In the paper, published online September 22, 2017 in the journal Nature Communications, Swanson and his colleagues found the previously undiscovered mechanism by which a low carbohydrate diet reduces inflammation in the brain. Importantly, the team identified a pivotal protein that links the diet to inflammatory genes, which, if blocked, could mirror the anti-inflammatory effects of ketogenic diets.

“The ketogenic diet is very difficult to follow in everyday life, and particularly when the patient is very sick,” Swanson said. “The idea that we can achieve some of the benefits of a ketogenic diet by this approach is the really exciting thing here.”

Low-Carb Benefits

The high-fat, low-carbohydrate regimen of ketogenic diets changes the way the body uses energy. In response to the shortage of carb-derived sugars such as glucose, the body begins breaking down fat into ketones and ketoacids, which it can use as alternative fuels.

In rodents, ketogenic diets — and caloric restriction, in general — are known to reduce inflammation, improve outcomes after brain injury, and even extend lifespan. These benefits are less well-established in humans, however, in part because of the difficulty in maintaining a ketogenic state.

In addition, despite evidence that ketogenic diets can modulate the inflammatory response in rodents, it has been difficult to tease out the precise molecular nuts and bolts by which these diets influence the immune system.

Intricate Molecular Waltz

In the new study, the researchers used a small molecule called 2-deoxyglucose, or 2DG, to block glucose metabolism and produce a ketogenic state in rats and controlled laboratory cell lines. The team found that 2DG could bring inflammation levels down to almost control levels.

This image shows hippocampal slices.

Immunostaining for Iba1 and iNOS identify activated microglia in mouse hippocampal slice cultures after 24 h incubation with LPS (10 μg/ml) or LPS + 2DG (1 mM) NeuroscienceNews.com image is credited to Swanson et al./Nature Communications.

“I was most surprised by the magnitude of this effect, because I thought ketogenic diets might help just a little bit,” Swanson said. “But when we got these big effects with 2DG, I thought wow, there’s really something here.”

The team further found that reduced glucose metabolism lowered a key barometer of energy metabolism — the NADH/NAD+ ratio — which in turn activated a protein called CtBP that acts to suppress activity of inflammatory genes.

In a clever experiment, the researchers designed a drug-like peptide molecule that blocks the ability of CtBP to enter its inactive state —essentially forcing the protein to constantly block inflammatory gene activity and mimicking the effect of a ketogenic state.

Peptides, which are small proteins, don’t work well themselves as drugs because they are unstable, expensive, and people make antibodies against them. But other molecules that act the same way as the peptide could provide ketogenic benefits without requiring extreme dietary changes, Swanson said.

The study has applications beyond brain-related inflammation. The presence of excess glucose in people with diabetes, for example, is associated with a pro-inflammatory state that often leads to atherosclerosis, the buildup of fatty plaques that can block key arteries. The new study could provide a way of interfering with the relationship between the extra glucose in patients with diabetes and this inflammatory response.

Source: How Ketogenic Diets Curb Inflammation – Neuroscience News

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[European Commission] Predicting and treating epilepsy – CORDIS

Predicting and treating epilepsy

Epilepsy is a devastating condition affecting over 50 million people worldwide. An EU consortium is using a combinatorial approach to identify biomarkers and develop antiepileptogenic therapeutics.
Predicting and treating epilepsy

A five-year EU-funded project, EPITARGET (Targets and biomarkers for antiepileptogenesis), is studying the processes leading to epilepsy in adults. The consortium, consisting of 18 partners from 9 countries, aims to identify novel biomarkers and their combinations in clinically relevant animal models. These biomarkers, defining the different stages of epilepsy, will be used to predict/diagnose early and late stages of the evolution of the disease.

After the first year the project advanced significantly towards its objectives. Sample collection from various animal models of epileptogenesis is ongoing. The project developed a biocompatible electrode for fast and sensitive glucose measurement in the brain.

EPITARGET characterised expression patterns of a number of molecules at various time points after epileptogenic insults. They include lipid mediators and their receptors, microRNAs, immunoproteasomes, free radicals and antioxidants, amyloidogenic factors, inflammatory molecules, extracellular matrix proteins and synaptic proteins.

The consortium members are investigating complex mechanisms of epileptogenesis with the goal to design disease-modifying combinatorial treatment strategies, targeted to the different stages. EPITARGET optimised the two-stage approach for drug screening and explored pharmacokinetics and tolerability of combinations of clinically available drugs in naive and epileptic rodents. For targeting compounds to the brain, EPITARGET developed a lipid encapsulation approach. The first formulation of amiloride is undergoing in vitro and in vivo testing. The first generation of long-term transgene expression viral vectors was already verified in vivo.

EPITARGET findings using animal models will be translated into clinical use by validating biomarkers in human blood and brain tissue samples. Ongoing sample collection includes human brain tissue and biofluids from status epilepticus, traumatic brain injury and pharmacoresistant epilepsy patients. The creation of animal and human databases is under way. The first year of the project resulted in 20 peer-reviewed publications.

Upon completion, EPITARGET is expected to improve diagnosis of epilepsy, and to develop new antiepileptogenic treatments and means to predict their efficacy. It will improve the quality of life for millions of people and reduce treatment costs.

Source: European Commission : CORDIS : Projects and Results : Predicting and treating epilepsy

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[WEB SITE] Keppra – The Law Offices of Gregory Krasovsky

 

Keppra

The dangerous drug attorneys at the Law Offices of Gregory Krasovsky can provide legal advice and representation to individuals and families considering pursuing a Keppra lawsuit. In order for a plaintiff to secure a maximum settlement in litigation of a Keppra claim, regardless of whether in an individual lawsuit or in a class action lawsuit, it is crucial that the law firm representing you have a competent and experienced team of Keppra lawyers to guide you through all of the legal hurdles as well as direct you to sufficient funding (litigation funding or legal finance) to cover pharmaceutical litigation costs. Contact  a Keppra attorney today to schedule a free consultation and take your first step to obtaining compensation for losses caused by Keppra side effects.

Keppra, which is generically known as Levetiracetam, is an anticonvulsant drug used to treat epilepsy. Keppra was originally manufactured and marketed by UCB Pharmaceuticals Inc., but now it is available as a generic and is manufactured by a number of firms. Unfortunately, Keppra has a number of serious side effects that can, at times, outweigh its benefits for people who are suffering from epilepsy. Some of the most serious Keppra adverse effects include suicidal tendencies and birth defects.

There are many Levetiracetam side effects. These include, but are not limited to, the following:

  • Suicidal Ideation
  • Suicidal Tendencies
  • Suicide
  • Headache
  • Unsteady Walk
  • Depression
  • Hallucinations
  • Fever
  • Sore Throat
  • Mood Changes
  • Changes in Skin Color
  • Anxiety
  • Birth Defects

A 2005 Food and Drug Administration (FDA) study of suicidal ideation in relation to epilepsy drugs has indicated that people taking those drugs, such as Keppra, are twice as likely to suffer from suicidal thoughts as are those who have not been taking these drugs.

Unlike many other drugs, such as Wellbutrin, people taking Keppra are likely to experience suicidal ideation regardless of what age group they might happen to fall into. The aforementioned study tracked almost 30,000 people, and the rick of suicide was spread fairly evenly across the population. Of the 28,000 people who had taken Keppra in this study, four of them had actually committed suicide. These unfortunate incidents serve to confirm the danger of this unsafe drug.

Although Keppra’s ability to cause birth defects is still under investigation, there is some amount of evidence that seems to confirm that Keppra is more harmful to unborn babies than was previously thought. Currently, the FDA has placed Keppra in the Category C for pregnancy, which indicates that there is little human risk. However, AdverseEvents, Inc. believes that Keppra should perhapd be in Category D, which indicates that a significant enough risk to pregnancy exists.

Keppra is similar to another prototypical nootropic drug called piracetam. Keppra is also thought to be a possible treatment for Tourette syndrome, autism, bipolar disorder, and anxiety disorder.

The attorneys at this Keppra law firm believe that drugs should not cause the same ailments that they are meant to cure. If you or your loved one has been injured as a result of taking Keppra, you might be entitled to compensation. Contact our attorneys today to schedule a free consultation.

Source: Keppra – The Law Offices of Gregory Krasovsky

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[WEB SITE] Seizures Follow Similar Path Regardless of Speed

Summary: By capturing a cell by cell view of seizures propagating through a mouse brain, researchers discovered neurons fire in a sequential pattern, regardless of how quickly the seizure occurs. The findings confirm seizures are not a result of neurons going haywire.

Source: Columbia University.

Of the 50 million people who suffer from epilepsy worldwide, a third fail to respond to medication. As the search for better drugs continues, researchers are still trying to make sense of how seizures start and spread.

In a new study in Cell Reports, researchers at Columbia University come a step closer by showing that the neurons of mice undergoing seizures fire off in a sequential pattern no matter how quickly the seizure propagates — a finding that confirms seizures are not the result of neurons randomly going haywire.

“This is good news,” said the study’s senior author, Dr. Rafael Yuste, a neuroscientist at Columbia. “It means that local neuronal circuits matter, and that targeting the right cells may stop or even prevent some types of brain seizure.”

To induce the seizures, researchers injected a tiny area of cortex in awake mice with two types of drugs–one that increases neuronal firing and another that blocks the inhibitory interneurons that control information flow between cells. Recording the seizures as they rippled outward, researchers found that cells in the mouse’s brain systematically fired one after the other. Under both models, the seizure spread across the top layer of cortex in a wave-like pattern before descending into its lower layers.

Unexpectedly, they found that whether the seizure lasted 10 seconds or 30 seconds, it followed the same route, like a commuter stuck in traffic. The concept of neurons firing in a reliable pattern no matter how fast the seizure is traveling is illustrated on the cover of Cell Reports, drawn by the study’s lead author, Dr. Michael Wenzel.

“The basic pattern of a string stretched between two hands stays the same whether the hands move closer together or farther away,” he says. “Just as neurons maintain their relative firing patterns regardless of how slowly or quickly the seizure unfolds.”

Researchers were able to get a cell-by-cell view of a seizure propagating through a mouse’s brain using high-speed calcium imaging that allowed them to zoom in 100 times closer than electrode techniques used on the human brain.

Image shows brain.

Researchers were able to get a cell-by-cell view of a seizure propagating through a mouse’s brain using high-speed calcium imaging that allowed them to zoom in 100 times closer than electrode techniques used on the human brain. NeuroscienceNews.com image is in the public domain.

It may be the first time that researchers have watched a seizure unfold at this level of detail, and their findings suggest that inhibitory neurons may be a promising area of future research, said Dr. Catherine Schevon, a neurology professor at Columbia University Medical Center who was not involved in the research.

“The role of inhibitory restraint in seizure development is an area that few have studied at micrometer scale,” she said. “This could be a useful treatment target for future drug development or stem cell interneuron implants.”

Source: Seizures Follow Similar Path Regardless of Speed – Neuroscience News

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[WEB SITE] Types of Seizures – Epilepsy Ontario

Types of Seizures

There are several different types of seizures. Most seizures can be categorized as either focal or generalized.

1. Focal (or partial) seizures

 Focal (or partial) seizures Section

Focal (or partial) seizures occur when seizure activity is limited to a part of one brain hemisphere. There is a site, or a focus, in the brain where the seizure begins. There are two types of focal seizures:

If you have epilepsy, ask your healthcare provider to explain what type of seizures you have. Learning the names and terms for your seizure type(s) can help you describe it accurately to others.

2. Generalized Seizures

Generalized Seizures Section

Generalized seizures occur when there is widespread seizure activity in the left and right hemispheres of the brain. The different types of generalized seizures are:

Additional Seizure Types

Additional Seizure Types Section

Infantile Spasms
Infantile spasms are a type of epilepsy seizure but they do not fit into the category of focal or generalized seizures.

Psychogenic Non-epileptic Seizures (PNES)
Psychogenic non-epileptic seizures are not due to epilepsy but may look very similar to an epilepsy seizure.

Source: Types of Seizures – Epilepsy Ontario

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[WEB SITE] What should you do if a friend has a seizure?

Seizures are a fairly common occurrence, but would you know what to do – and what not to do – if you witnessed one?

Ten percent of people are expected to experience a seizure at some point during their lifetime, but would you know what to do if someone was having a seizure right next to you? Would you recognize it for what it was? Here, we give you an overview of different types of seizures and offer some helpful first aid tips.

Seizures normally take place when there is an abnormal “spike” of electrical activity in the brain. More often than not, seizures are associated with brain conditions (usually epilepsy) but can sometimes also be experienced by people without an epilepsy diagnosis.

In the United States, 3 million adults and 470,000 children have epilepsy, according to estimatesfrom the Centers for Disease Control and Prevention (CDC). This means that 1 in 10 people may experience a seizure in their lifetime.

Epileptic seizures fall under two categories: generalized seizures (in which the whole brain is affected), and focal, or partial, seizures (which are localized and only affect one part of the brain).

All types of seizures usually happen suddenly, and most people who experience them cannot tell that they are coming, so they will be unable to give any warning. Also, typically, an individual experiencing a seizure will not remember what happened during that episode.

One person prone to seizures due to her epilepsy describes her experiences.

A seizure feels like being dragged deep under water. I feel like I can’t catch my breath. For me, [it] feels like electricity stuns and weakens every nerve ending in my body. It feels as though black ink is bleeding inward from every which way, causing my vision to slowly fade out. My verbal communication is a pile of babbling gravel.”

Seizures can last from a few seconds to a few minutes (usually under 5), depending on the type and severity of the event.

Seizure do’s and don’ts

People who have epilepsy may experience one or several kinds of seizure. Below, we look at the different kinds of generalized and focal seizures and give you tips on how to recognize them, as well as how best to support someone who is experiencing them.

Generalized seizures

1. Absence seizures. Also referred to as “petit mal,” meaning “small harm” or “little illness” in French, these are unlikely to look like seizures to the unsuspecting external observer.

The person having an absence seizure will appear to be distracted or absent (hence its name), staring blankly into the distance and blinking rapidly. This kind of seizure will only last a few seconds, and the person experiencing it will typically not realize that they even had it.

Absence seizures do not require any intervention. Just stay calm, and once the seizure is over, treat the person as you normally would.

2. Tonic-clonic seizures. These seizures are the ones that you will likely have seen depicted in television shows and movies.

They do not manifest in the exact same way in all individuals but usually involve the individual crying out, falling down, losing awareness, experiencing muscle spasms (hence “tonic,” which refers to shaking and jerking) and stiffening (hence “clonic,” which refers to muscular stiffness), and breathing rapidly and with difficulty.

These seizures are also called “grand mal,” meaning “great harm” or “great illness” in French. They may last up to a few minutes, and they leave the person dazed and physically exhausted.

If you witness someone experiencing a tonic-clonic seizure, your main priority should be to ensure that they are safe and do not get hurt. Make sure to:

  • cluttered room

    If someone is having a tonic-clonic seizure, your top priority should be to make sure that they do not get injured. Move them away from any heavy furniture and remove any potentially dangerous objects from their vicinity.

    Ease them to the ground if possible, to avoid a severe fall that may hurt them.

  • Put something soft (such as a folded jacket or sweater) under their head, to avoid head injuries.
  • Move them away (if possible) from large objects, including hard furniture, sharp edges, or hot surfaces (such as heaters), that may injure them.
  • Remove any small, hard objects or sharp objects (such as knives) that may surround them, to make sure that they do not get hurt.
  • Loosen any tight clothing or accessories around their neck (including ties and scarves), to make sure that they can breathe properly. Also, remove eyeglasses or sunglasses.
  • Similarly, remove any clothing items that may surround them, and which may accidentally wind around their neck and suffocate them.
  • As soon as you can, roll them onto their side. This is the first aid recovery position, which will allow the person to breathe more easily.

You must absolutely not:

  • Hold the person down or attempt to restrain them in any way; this is very dangerous for everyone involved, as a person experiencing a seizure cannot control their movements.
  • Attempt to put anything in their mouth. A popular myth suggests that inserting a wooden spoon will prevent the individual from swallowing their tongue or from biting it. No one can swallow their own tongue, and while a person experiencing a seizure may bite theirs, trying to insert anything into their mouths will only succeed in hurting their gums and teeth or making them choke.
  • Attempt to perform cardiopulmonary resuscitation; the person will typically regain normal breathing patterns once the seizure subsides.

It is also very important that you stay calm throughout and do not forget to time the seizure. This is a crucial step because, according to CDC guidelines, you must call an ambulance if the seizure lasts for longer than 5 minutes.

 

Focal seizures

1. Simple focal seizures. A person experiencing one of these may exhibit twitchiness – particularly in the face muscles – and may think that they are smelling or tasting something strange. Similar to the absence seizure, the simple focal seizure does not require any special intervention and normally lasts between a few seconds and a couple of minutes.

2. Complex focal seizures. This seizure type will make the person feel confused and disorientated, and they may not be able to respond clearly to questions or sustain any kind of interaction.

If you notice that someone is experiencing a complex focal seizure, stay calm, try to direct them to someplace safe (for example, away from moving cars), and speak to them gently and reassuringly. Do not leave them until the seizure has subsided – usually after about 2 minutes – and they have regained full awareness.

3. Secondary generalized seizures. These will typically start out as a regular focal seizure, only to evolve into a generalized, tonic-clonic seizure. In this case, you should follow the same guidelines as those outlined above.

What about non-epileptic seizures?

Non-epileptic seizures (NES), or “psychogenic non-epileptic seizures,” are not linked to abnormal electrical activity in the brain in the same way that epileptic seizures are. Instead, these are often caused by psychological factors, such as exposure to extreme stress, or are linked to psychiatric disorders.

These types of seizure are normally of three kinds:

woman feeling anxious

Other conditions and disorders can cause non-epileptic seizures. A panic attack, for instance, can manifest in a similar way to a regular seizure.

  • dissociative, which means that the person experiencing them has no awareness of, or control over, the event
  • panic attacks, which can make the person feel faint and be unable to breathe, and which make their heart race
  • brought on by a psychiatric disorder that makes the person to want to “trigger” or “stage” a seizure because they want to attract a degree of medical or social attention

Dissociative seizures and panic attacks are the most common NES. The general first aid guidelines for NES are usually the same as for epileptic seizures, and they focus on keeping the person safe from injury as the seizure unfolds.

For more information on seizures in general, the people who experience them, and what you can do to help, you can visit the Epilepsy Foundation website.

Source: What should you do if a friend has a seizure?

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 [BOOK] Computational Models of Brain and Behavior – Chapter 11: Multiscale Computer Modeling of Epilepsy – Google Books

Read Chapter 11: Multiscale Computer Modeling of Epilepsy

Εξώφυλλο

Computational Models of Brain and Behavior

 

John Wiley & Sons, 29 Νοε 2017584 σελίδες

A comprehensive Introduction to the world of brain and behavior computational models

This book provides a broad collection of articles covering different aspects of computational modeling efforts in psychology and neuroscience. Specifically, it discusses models that span different brain regions (hippocampus, amygdala, basal ganglia, visual cortex), different species (humans, rats, fruit flies), and different modeling methods (neural network, Bayesian, reinforcement learning, data fitting, and Hodgkin-Huxley models, among others).

Computational Models of Brain and Behavior is divided into four sections: (a) Models of brain disorders; (b) Neural models of behavioral processes; (c) Models of neural processes, brain regions and neurotransmitters, and (d) Neural modeling approaches. It provides in-depth coverage of models of psychiatric disorders, including depression, posttraumatic stress disorder (PTSD), schizophrenia, and dyslexia; models of neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and epilepsy; early sensory and perceptual processes; models of olfaction; higher/systems level models and low-level models; Pavlovian and instrumental conditioning; linking information theory to neurobiology; and more.

  • Covers computational approximations to intellectual disability in down syndrome
  • Discusses computational models of pharmacological and immunological treatment in Alzheimer’s disease
  • Examines neural circuit models of serotonergic system (from microcircuits to cognition)
  • Educates on information theory, memory, prediction, and timing in associative learning

Computational Models of Brain and Behavior is written for advanced undergraduate, Master’s and PhD-level students—as well as researchers involved in computational neuroscience modeling research.

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