Posts Tagged Epilepsy

[ARTICLE] Dramatic Weight Loss with Levetiracetam – Full Text

Summary

Background: Levetiracetam is considered a “weight-neutral” drug. We report 19 cases of significant weight loss associated with levetiracetam at a dose ranging from 500 to 2000 mg/day.

Methods: The population was divided into two groups. Group 1 includes patients in whom levetiracetam was the only possible cause of weight loss and Group 2 those in whom other factors may have played a role. Similar cases reported by the French national drug safety center were added (Group 3).

Results: Group 1 included 9 females and 3 males (weight loss ranging from 8.1% to 28.6%). Three patients had levetiracetam in monotherapy. Prior levetiracetam only three were overweight. One patient was hospitalized for a thorough assessment of weight loss. Seven patients reported reduced caloric intake due to decreased pleasure with food. The other five did not report any changes in feeding behavior. Group 2 included seven females with a weight loss ranging from 10% to 26.6%. One patient was on topiramate since two years prior to levetiracetam. Weight loss started with the introduction of levetiracetam. In 4 patients, there was a decreased dosage or cessation of a previous drug known to produce weight gain in some cases simultaneously to the introduction of levetiracetam, but in two of these patients these drugs had not produced any weight gain. Group 3 included only two patients (weight loss: 7 and 20 kg).

Conclusions: This study provides evidence that levetiracetam can cause significant weight loss. Women are at higher risk while initial weight is not a factor.

Levetiracetam (LEV) is an antiepileptic drug with a broad clinical spectrum effective in focal epilepsy as well as in idiopathic generalized epilepsy (Grunewald, 2005Di Bonaventura et al., 2005). The majority of adverse effects are of mild to moderate severity, the most commonly reported being asthenia, somnolence, headache, and dizziness (Genton et al., 2006). Less frequent events that may also occur are anorexia, nausea, dry mouth (Biton, 2002) and behavioral and psychiatric events (Dinkelacker et al., 2003Genton et al., 2006).

LEV is considered “weight-neutral” (Gidal et al., 2003Briggs and French, 2004). However, weight loss is listed in a study comparing LEV in adult vs ageing patients (Cramer et al., 2003) and four cases of considerable weight loss have been published with LEV used in cotherapy at a dose ranging from 2000 to 3000 mg/day (Hadjikoutis et al., 2003). In the light of our recent clinical experience, we report 19 cases of weight loss associated with LEV but at lower doses and in monotherapy in three patients. These 19 patients were divided in two soubgroups, with LEV as the likely contributing factor vs cases with confounding variables.[…]

 

Continue —> Dramatic Weight Loss with Levetiracetam – Gelisse – 2007 – Epilepsia – Wiley Online Library

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[WEB SITE] Comprehensive List of Epilepsy & Seizure Medications.

Understanding Epilepsy

Epilepsy makes your brain act abnormally and send unusual signals. This can result in seizures. Injury, sickness, and a number of other reasons can cause seizures, but recurring seizures are symptoms of epilepsy.

There are many different types of epileptic seizures. Several of them can be controlled with the right anti-seizure medications. In fact, 70 percent of people with epilepsy can control their seizures with proper medication.

If you are suffering from epilepsy, you’ll be glad to know there are many different anti-seizure drugs. However, the medication prescribed to you will depend on the type of epilepsy you have and several other factors.

Medications used for the treatment of seizures are known as anti-epileptic drugs, anti-seizure medications or AEDs. There are two types of AEDs: narrow-spectrum and broad-spectrum. Let’s have a look at all of the prescription AEDs in each category.

Here’s a comprehensive list of available epilepsy and anti seizure medications along with links to anti seizure medication prices that will help you save up to 90% off U.S. retail prices.

Narrow-Spectrum AEDs

If you regularly experience seizures in a specific part of your brain, narrow-spectrum AEDs will help. There are 17 narrow-spectrum AEDs, including:

Carbamazepine (Epitol, Equetro, Carbatrol ER, Tegretol)

Generic carbamazepine (Epitol, Equetro, Carbatrol ER, Tegretol) helps treat seizures taking place in the temporal lobe. It can also be used to help with refractory, partial, and secondary seizures. Carbamazepine interacts with a variety of other drugs, so it’s important to tell your doctor about any other medications you’re taking to avoid any harmful side effects.

Clobazam (Onfi)

Generic clobazam (Onfi) is used to help prevent secondary, partial, and absence seizures. This narrow-spectrum AED also falls into the benzodiazepine category. Drugs in this category are often used for anxiety and sedation. The Epilepsy Foundation states children as young as two years old can take Clobazam. However, in some rare cases, this drug can result in serious skin reactions.

Diazepam (Valium)

Generic diazepam is known as brand name, Valium to many of its users. This commonly prescribed drug is a benzodiazepine and is used to help treat prolonged or cluster seizures. It is also very effective in the short-term treatment of every type of seizure. This makes it a popular anti-seizure drug in emergency situations.

Tolerance to Diazepam usually occurs in a few weeks, which means doses must be increased over time. The side effects of this widely used drug include nausea, tiredness, depression, loss of appetite, and unsteady walking. Hyperactivity and drooling are also common side effects in children.

Divalproex (Depakote, Depakote ER)

Generic divalproex (Depakote, Depakote ER) is prescribed to treat multiple, absence, partial, and complex partial seizures. It slows down nerve circuits by increasing gamma-aminobutyric acid levels within your body. This slowing down of the nerve circuits helps control seizures.

Eslicarbazepine (Aptiom)

Generic eslicarbazepine, also known as brand name: Aptiom, is used in the treatment of partial-onset seizures. By blocking sodium channels, it’s able to slow down nerve firing sequences and help control certain seizures.

Ethosuximide (Zarontin)

Generic ethosuximide (Zarontin) is an anti-seizure drug is used to treat childhood, juvenile, and atypical absence seizures,

Gabapentin (Gralise, Horizant, Neurontin, Gabarone)

Generic gabapentin (Gralise, Horizant, Neurontin, Gabarone) has milder side effects than many other AEDs and is used in the treatment of partial seizures. Dizziness and fatigue are its most common side effects.

Lacosamide (Vimpat)

Generic lacosamide (Vimpat) is also used to treat partial seizures. This medication can be taken at home as an oral solution or oral tablet. An IV injection can also be received by a healthcare provider.

Methsuximide (Celontin)

Generic methsuximide (Celontin) is used to treat absence seizures when other medications or treatments don’t work. It works by slowing down your motor cortex. This makes it difficult for your brain to fire rapidly enough to start a seizure.

Oxcarbazepine (Oxtellar XR, Trileptal)

Generic oxcarbazepine (Oxtellar XR, Trileptal) is prescribed to help control focal seizures. It can be used to help treat adults and children as young as two years old.

Perampanel (Fycompa)

Generic perampanel (Fycompa) is used to help treat simple, complex,and refractory seizures. Doctors don’t fully understand how this anti-seizure drug works, but many believe it affects your brain’s glutamate receptors. Perampanel is effective, but it can have serious behavioral and psychiatric side effects.

Phenobarbital (Solfoton, Luminal)

Generic phenobarbital (Solfoton, Luminal) is one of the first seizure drugs ever used and is still prescribed for epilepsy to this day. It is used to treat tonic-clonic, partial, and generalized seizures. This drug is long-acting and effective at reducing convulsions related to seizures. It’s also a sedative, so its main side effects are drowsiness and tiredness.

Phenytoin (Dilantin)

Generic phenytoin (Dilantin) is another commonly used anti-seizure drug with a long history of use. The medication is used to treat simple complex, and refractory seizures. It works by stabilizing your neuronal membranes. The result is a calming effect on your brain’s nerve firings.

Pregabalin (Lyrica)

Generic pregabalin (Lyrica) is used alongside other medications for the treatment of partial-onset seizures. This means it’s an additional treatment only.

Rufinamide (Banzel)

Generic rufinamide (Banzel) is also used as additional treatment. It’s taken with other medications to help treat seizures caused by Lennox-Gastaut syndrome. Unfortunately, it can interact with several drugs and cause unusual heart rhythms. For these reasons, it’s seldom used.

Tiagabine (Gabitril)

Generic tiagabine (Gabitril) is also considered an additional treatment. It’s used to help treat simple and complex partial seizures.

Vigabatrin (Sabril)

Generic vigabatrin (Sabril) is sometimes prescribed along with other drugs to help treat complex partial seizures. However, the use of this drug is highly restricted due to its serious side effects. One of these side effects is permanent vision loss. Doctors and pharmacies must have a special registration in order to prescribe and dispense the drug.

Broad-Spectrum AEDs

If you suffer from two or more types of seizures, your doctor may prescribe a broad-spectrum AED for treatment. Unlike narrow-spectrum AEDs, broad-spectrum AEDs are designed to help treat and prevent seizures in several parts of the brain.

There are 11 broad-spectrum AEDs, including:

Clonazepam (Klonopin)

Generic clonazepam (Klonopin) is used to treat akinetic, myoclonic, absence, and several other types of seizures. It’s a long-acting benzodiazepine that’s popular for its ability to treat a diverse range of seizures.

Clorazepate (Tranxene-T)

Generic clorazepate, also known as brand name: Tranxene-T, clorazepate is also a benzodiazepine and used alongside other medications to help treat partial seizures.

Ezogabine (Potiga)

Generic ezogabine (Potiga) is an additional treatment used for complex partial, refractory, and generalized seizures. The secondary drug works by activating potassium channels and stabilizing the ring of your neurons.

This AED can damage your retina and cause long-term harm to your vision. For this reason, it’s only used as a last resort when other medications aren’t working. If you are prescribed Ezogabine, you will be required to have an eye exam twice a year. If the drug doesn’t help treat your seizures, your doctor will cancel the treatment and try another AED to prevent any eye problems.

Felbamate (Felbatol)

Genereic felbamate (Felbatol) is used to help control nearly every type of seizure. However, it can have serious side effects such as liver failure and anemia. Due to this, it’s only prescribed for people who haven’t had success with other treatments. Fellbamate can be used in combination with other medications or by itself as a single therapy.

Lamotrigine (Lamictal)

Generic lamotrigine or Lamotrigine Xr (Lamictal) has shown to help treat a wide variety of epileptic seizures. Unfortunately, use of the drug has been linked to Stevens-Johnson syndrome. This rare skin condition can include several serious symptoms such as the shedding of your skin.

Levetiracetam (Spritam, Keppra)

Generic levetiracetam (Spritam, Keppra) is often the first medication prescribed to treat absence, atypical, generalized, partial, a many other types of seizures. In fact, according to the Pharmacopoeia of Prophylactic Antiepileptic Drugs, it can be used to treat idiopathic, focal, symptomatic, and generalized epilepsy in adults and children of all ages. It’s effective and has fewer side effects than other epilepsy drugs.

Lorazepam (Ativan)

Generic lorazepam (Ativan) is a type of benzodiazepine used to treat critical, prolonged seizures.

Primidone (Mysoline)

Generic primidone (Mysoline) is prescribed to help treat juvenile myoclonic epilepsy. It also treats tonic-clonic, myoclonic, and focal seizures.

Topiramate (Trokendi XR, Qudexy XR, Topamax)

Generic topiramate (Trokendi XR, Qudexy XR, Topamax) is used by itself or alongside other AEDs to help treat a wide-variety of seizures in both children and adults.

Valproic acid (Stavzor, Depakene, Depacon, Depakote)

Generic valproic acid (Stavzor, Depakene, Depacon, Depakote) is a broad-spectrum AED that is commonly used and approved to help treat nearly all types of seizures. Like Topiramate, it can be used by itself as a single treatment or in conjunction with other anti-seizure medications.Valporic acid works by increasing your body’s GABA levels. This helps calm down and suppress random nerve firings.

Zonisamide (Zonegran)

Generic zonisamide (Zonegran) is sometimes prescribed to treat partial seizures and other forms of epilepsy. Unfortunately, its side effects can be serious. Some of these side effects can include weight loss, kidney stones, and cognitive issues.

Discuss AEDs with Your Doctor

Before you take an AED, discuss them with your doctor and learn about the different side effects they can cause. Use this reference as a starting point to learn more about seizure drugs. By doing so, you’ll be better prepared to work with your doctor and help choose the best AED options for you.

 

via Comprehensive List of Epilepsy & Seizure Medications – Alert News Today

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[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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ABOUT THE THOMAS HAYDN TRUST

The Thomas Haydn Trust is The Paediatric Epilepsy Charity that aims to serve the needs of Young People, Parents, Carers and Medical Professionals. But to know who we are you need to know why we are.

Providing local services and sharing the rewards globally is the core of THT’s work, weather newly diagnosed or not, you will find THT a valuable source of support, knowledge and news for the epilepsies.

The Thomas Haydn Trust was set up in the wake of Thomas Haydn Smith’s diagnosis of Lennox-Gastaut Syndrome – One of the Most severe forms of Childhood Onset Epilepsies, affecting 1 in 1,000,000 epilepsy sufferer’s worldwide.

In setting up THT our aim was to combat many of the hurdles that Thomas and his family come across while living with LGS. THT strives to ‘Give Something Back’ to organisations that help families and children with severe epilepsies.

We work towards our goals in the following manner:

Research

Raising the need profile for both basic and clinical research into Lennox-Gastaut Syndrome and other childhood Epilepsies.

Support

By providing a free and open forum for sufferers, family and carers’, allowing them to share experiences, build relationships and facilitate peer learning. THT also provides details of leading specialist support organisations of specific Epilepsy conditions – Supporting the specific needs of the child.

Education

Developing an ever-expending resource of research findings and educational materials for the public and medical professionals.

Funding

Where possible, fund individuals and organisations involved in support, development and care of families with sick children.

Awareness

Raising awareness of childhood Epilepsies through various mediums including the internet, press, radio and television. Highlighting the effects of LGS and other childhood onset Epilepsies through our live events – Raising awareness is the key principle on which THT works.

Empowerment

Promoting the advancement of individuals with Epilepsy to speak out against ignorance, predjudice and bigotry that still surrounds conditions of Epilepsy.

Networking

Developing links with other national and international organisations to create a coalition of information sharing networks.

via The Relationship Between Epilepsy and Sleep – Wattpad

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[WEB SITE] Wristband devices may improve detection and characterization of epileptic seizures

New research published in Epilepsia (http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1528-1167), a journal of the International League Against Epilepsy (ILAE), indicates that wristband devices may improve the detection and characterization of seizures in patients with epilepsy.

New devices are needed for monitoring epileptic seizures, especially those that can lead to sudden death. While rare, “sudden unexpected death in epilepsy” (SUDEP) is the most common cause of death in epilepsy, and it often occurs at night. The gold standard for monitoring seizures-video-electroencephalography- is available in epilepsy monitoring units but is an impractical procedure for daily life use. Therefore, clinicians often rely on patients and caregivers to report seizure counts, which are often inaccurate.

In their attempts to develop a better monitoring method, Giulia Regalia, PhD and Francesco Onorati, PhD, of Empatica Inc. in Milan, Italy and Cambridge, Massachusetts, and their colleagues examined the potential of automated, wearable systems to detect and characterize convulsive epileptic seizures. The researchers used three different wristbands to record two signals-called electrodermal activity and accelerometer signals-that usually exhibit marked changes upon the onset of convulsive seizures, obtaining 5928 hours of data from 69 patients, including 55 convulsive epileptic seizures from 22 patients.

The wristband detectors showed high sensitivity (95% of seizures were detected) while keeping the false alarm rate at a bearable level (on average, one false alarm every four days), which improves a pioneering 2012 study led by MIT professor Rosalind Picard, now chief scientist at Empatica.

In addition to detecting seizures, the method also revealed certain characteristics of the seizures, which may help alert clinicians and patients to seizures that are potentially dangerous and life-threatening.

“The present work provides significant improvements for convulsive seizure detection both in clinical and ambulatory real-life settings,” said Dr. Regalia. “Accurate seizure counts with real-time alerts to caregivers allows an early application of aid, which can be protective against SUDEP risk.” She noted that the wristband detectors do not require caregivers to be near patients continuously, which could significantly improve patients and caregivers’ quality of life.

Source: Wristband devices may improve detection and characterization of epileptic seizures

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[WEB SITE] Findings reveal how seizures can have lasting detrimental effects on memory

October 16, 2017

Although it’s been clear that seizures are linked to memory loss and other cognitive deficits in patients with Alzheimer’s disease, how this happens has been puzzling. In a study published in the journal Nature Medicine, a team of researchers reveals a mechanism that can explain how even relatively infrequent seizures can lead to long-lasting cognitive deficits in animal models. A better understanding of this new mechanism may lead to future strategies to reduce cognitive deficits in Alzheimer’s disease and other conditions associated with seizures, such as epilepsy.

“It’s been hard to reconcile how infrequent seizures can lead to persistent changes in memory in patients with Alzheimer’s disease,” said corresponding author Dr. Jeannie Chin, assistant professor of neuroscience at Baylor College of Medicine. “To solve this puzzle, we worked with a mouse model of Alzheimer’s disease focusing on the genetic changes that seizures might trigger in the memory center of the brain, the hippocampus, that could lead to loss of memory or other cognitive deficits.”

The researchers measured the levels of a number of proteins involved in memory and learning and found that levels of the protein deltaFosB strikingly increase in the hippocampus of Alzheimer’s disease mice that had seizures. DeltaFosB already is well known for its association with other neurological conditions linked to persistent brain activity of specific brain regions, such as addiction. In this study, the researchers found that after a seizure, the deltaFosB protein remains in the hippocampus for an unusually long time; its half-life – the time it takes for the amount of protein to decrease by half – is eight days. Most proteins have a half-life that is between hours and a day or two.

“Interestingly, because deltaFosB is a transcription factor, meaning that its job is to regulate the expression of other proteins, these findings led us to predict that the increased deltaFosB levels might be responsible for suppressing the production of proteins that are necessary for learning and memory,” Chin said. “In fact, we found that when the levels of deltaFosB increase, those of other proteins, such as calbindin, decrease. Calbindin also has been known for a long time to be involved in Alzheimer’s disease and epilepsy, but its mechanism of regulation was not known. We then hypothesized that deltaFosB might be regulating the production of calbindin.”

Further investigations supported the researchers’ hypothesis. The scientists showed that deltaFosB can bind to the gene calbindin suppressing the expression of the protein. When they either prevented deltaFosB activity or experimentally increased calbindin expression in the mice, calbindin levels were restored and the mice improved their memory. And when researchers experimentally increased deltaFosB levels in normal mice, calbindin expression was suppressed and the animals’ memory deteriorated, demonstrating that deltaFosB and calbindin are key regulators of memory.

Connecting pieces of the puzzle

“Our findings have helped us answer the question of how even infrequent seizures can have such lasting detrimental effects on memory,” Chin said. “We found that seizures can increase the levels of deltaFosB in the hippocampus, which results in a decrease in the levels of calbindin, a regulator of memory processes. DeltaFosB has a relatively long half-life, therefore even when seizures are infrequent, deltaFosB remains in the hippocampus for weeks acting like a brake, reducing the production of calbindin and other proteins, and disrupting the consequent brain activity involved in memory. The regulation of gene expression far outlasts the actual seizure event that triggered it.”

The scientists found the same changes in deltaFosB and calbindin levels in the hippocampus of Alzheimer’s disease patients and in the temporal lobe of epilepsy patients. However, they underscore that it is too soon to know whether regulating deltaFosB or calbindin could improve or prevent memory problems or other cognitive deficits in people with Alzheimer’s disease. However, “now that we know that the levels of deltaFosB and calbindin are effective markers of brain activity in the hippocampus and memory function, we propose that these markers could potentially help assess clinical therapies for Alzheimer’s and other diseases with seizures,” Chin said.

Source: Findings reveal how seizures can have lasting detrimental effects on memory

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[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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