Management of drug-resistant epilepsy

Last updated
Management of drug-resistant epilepsy
Other namesRefractory epilepsy
Specialty Neurology

Drug-resistant epilepsy (DRE), also known as refractory epilepsy, intractable epilepsy, or pharmacoresistant epilepsy refers to a state in which an individual with a diagnosis of epilepsy is unresponsive to multiple first line therapies. Based on the 2010 guidelines from the International League against Epilepsy (ILAE), DRE is officially diagnosed following a lack of therapeutic relief in the form of continued seizure burden after trialing at least two antiepileptic drugs (AEDs) at the appropriate dosage and duration. [1] [2] The probability that the next medication will achieve seizure freedom drops with every failed AED. For example, after two failed AEDs, the probability that the third will achieve seizure freedom is around 4%. [3] Drug-resistant epilepsy is commonly diagnosed after several years of uncontrolled seizures, however, in most cases, it is evident much earlier. Approximately 30% of people with epilepsy have a drug-resistant form. [4] Achieving seizure control in DRE patients is critical as uncontrolled seizures can lead to irreversible damage to the brain, cognitive impairment, and increased risk for sudden unexpected death in epilepsy called SUDEP. [5] [6] Indirect consequences of DRE include seizure related injuries and/or accidents, impairment in daily life, adverse medication effects, increased co-morbidities especially psychological, and increased economic burden, etc. [7]

Contents

Some clinical factors that are thought to be predictive of DRE include the female sex, focal epilepsy, developmental delay, status epilepticus, earlier age of onset of epilepsy, neurological deficits, having an abnormal EEG and/or imaging findings, genetic predisposition, association with the ABCB1 gene, and inborn errors of metabolism. [7] [8] Especially among pediatric populations there is a growing association between DRE and genetic conditions or developmental disorders such as Lennox-Gastaut or Dravet Syndrome.

There are numerous theories regarding the mechanism of action behind DRE many of which have been studied in human and/or animal models. However, it still remains unclear the exact pathogenesis of this condition. [7] [9]

Diagnostic evaluation

The first step is for physicians to refer their DRE patients to an epilepsy specialist in a comprehensive epilepsy center where further diagnostic work-up can be performed.

Prolonged EEG/Continuous video EEG/ Epilepsy Monitoring Unit monitoring

One of the first steps in management of drug resistant epilepsy is confirming the diagnosis by EEG. Typically patients are admitted to hospital for prolonged EEG monitoring with video technology used to capture clinical events as they occur. [10] Typically patients are taken off their anti-seizure medications in order to characterize the evolution of seizure symptoms and their relation with changes in electrical activity of brain. This is done while simultaneously minimizing the adverse consequences of seizures. Additional maneuvers to provoke seizures are also frequently performed, like sleep deprivation, photic stimulation, and hyperventilation. This study can take anywhere from 1–14 days. The length of the study depends on factors like baseline seizure frequency, the number and type of seizure medications the patient is taking prior to the study, institutional protocols etc. The goal is to record 3-4 typical seizures, though in some cases more or fewer seizures may need to be recorded. After this evaluation some patients may be determined to have non-epileptic causes of their symptoms, eg. syncope, psychogenic nonepileptic seizures, cardiac arrhythmia etc.

For patients who are confirmed to have epilepsy, this testing helps further elucidate the type of epilepsy (generalized vs focal), type of seizures (atonic, absence, GTC, etc.), and can be used for pre-surgical evaluation or to guide further management. Changes on EEG in relation to clinical seizure symptoms is used to determine the likely area of the brain responsible (symptomatic zone) and by extrapolation the area where seizure activity likely starts (seizure onset zone). In some specific cases, prolonged EEG may be done as an outpatient or ambulatory study where the patient goes home with an EEG set-up. This type of monitoring is usually limited to 2–3 days and patients are not taken off their AEDs. [11] [12]

Neuroimaging

MRI of brain is the most common first-line neuroimaging modality to be used in evaluation of a structural cause of epilepsy. A 3 Tesla MRI is generally recommended, as opposed to scanning on lower magnet strengths. MRI for evaluation of epilepsy often include T1 and T2 images that are optimized to appreciate gray-white matter differentiation and oblique coronal images along the axis of hippocampus. Identification of common lesions associated with epilepsy like focal cortical dysplasia, mesial temporal sclerosis, microencephalocele, and heterotopia require thorough review of images by trained clinicians as the changes can be very subtle and easily missed if not specifically evaluated for. Oftentimes, repeat MRI is required to elucidate an etiology to epilepsy and typically an epilepsy imaging protocol is followed to identify these subtle changes. There is ongoing quantitative analysis of standard MRI images to identify subtle lesions and use of stronger magnetic fields, like 7 Tesla MRI, for better delineation of anatomical details. Additionally, not all structural abnormalities seen on MRI correlate with epilepsy and may represent incidental findings. [11] [13] [14]

Positron emission tomography scan (PET) using the 18F-FDG radiotracer can also be used in evaluation of DRE. Its use in epilepsy evaluation is based on the premise that areas of the brain responsible for seizure onset also have persistent metabolic dysfunction and do not use glucose at the same rate as neurotypical areas of the brain. Specifically, during seizure activity (ictal) one would expect a hypermetabolic state with increased radiotracer uptake on PET scan while in between events (interictal) one would expect a hypometabolic state with lower radiotracer uptake on PET scan. Oftentimes findings on PET scan are often correlated with other diagnostic workup that has already/concurrently been obtained to further localize an epileptogenic area of the brain, particularly in the case of focal epilepsy. Other ligands like 11C-flumazenil, 11C-alpha-methyl-L-tryptophan, 11C-methionine, have also been used, mostly on research basis to help identify areas of seizure onset. [15] [16]

Single-Photon Emission Computerized Tomography (SPECT scan) is another radiotracer based imaging technique that uses an oxygen radio-isotope to assess blood flow in the brain. This imaging is performed during inpatient video EEG monitoring in which the tracer is injected into the patient's bloodstream as soon as a seizure start. Areas of the brain associated with seizure onset will have increased blood flow, hence, increased uptake of the tracer if injected at an appropriate time. Imaging is performed after seizure activity is over to assess areas showing a significant increase in blood flow at seizure onset. A major limitation with this technique is the logistics required when injecting the radiotracer and quality of the images produced. [16] [17] [11]

Magnetoencephalography (MEG): A newer non-invasive imaging technique that measures the magnetic field associated with neuronal firing in the brain. While each individual neuron's magnetic field is undetectable, when neurons are firing concurrently, such as during a seizure, the magnetic field generated is detected via MEG. This data provides real time brain mapping and has proven to be extremely effective in pre-surgical planning and localization of epilepsy. MEG is particularly useful in detect more superficial abnormalities and is more sensitive than other imaging modalities. [11] [18]

Neuropsychological testing

Neuropsychological testing involves a series of tests aimed at assessing higher order mental functions like memory, executive function, language, overall IQ, etc. in order to establish baseline cognitive function. If there is poor performance in measures of specific cognitive domains like verbal memory, naming, visual-spatial orientation; it may point to areas of brain that are dysfunctional and likely related to seizure onset. This testing could also indicate poor performance on most measures and suggest more widespread dysfunction in the brain. Besides helping assess the likely area of seizure onset, this testing can be informative post surgical intervention and/or epilepsy therapy. [11] [19]

Language Lateralization

If epilepsy surgery is being considered, testing is often performed to determine the hemisphere of the brain involved in language and memory function. This helps inform about potential risks to language and memory with surgery. There are two main tests available for this objective: the Wada test and fMRI.

The Wada test has been one of the most commonly used tests around the world since the 1960s. This is an invasive testing technique that requires neurointerventionalists, neuropsychologists, neurophysiologists, EEG technologists, and anesthesiologists. When conducting the wada test, a catheter is threaded from wrist or groin into the carotid artery and finally the middle cerebral artery. [20] An injection of sodium amytal is given to temporarily anesthetize 2/3rd of the cerebral hemisphere on one side. Neuropsychological testing is then done to assess language and memory function of the other hemisphere. Once the patient is fully recovered from the injection on the first side, the catheter is withdrawn and threaded up the contralateral middle cerebral artery with neuropsychological testing repeated. This testing informs the "reserve" for memory and language function in each hemisphere and the potential for impairment with resective surgery on a given side. In some cases additional testing with selective injection of the posterior cerebral artery (that supplies the mesial temporal region including hippoampus) can be done. [21]

The Wada test is increasingly being replaced by the noninvasive fMRI imaging technique. Functional MRI (fMRI) measures the change in blood flow and oxygenation in different parts of the brain in response to an activity. Different tasks or paradigms are presented to a patient while they are in an MRI scanner. These tasks are designed to activate areas involved in different language functions and post processing of the images helps identify areas that are activated during different language tasks.

Pharmacotherapy

While the term drug resistant epilepsy implies ineffectiveness of pharmacologic therapy, recent advances in the pharmaceutical industry have introduced new drugs that have proven to be effective in the management of DRE patients. Given the novel nature of these drugs, many of the sources utilized are primary/case studies.

Cenobamate

Approved by the FDA in 2019 for treatment of epilepsy in adults, Cenobamate is primarily used to treat patients with focal onset seizures. The mechanism of action of this drug is unclear, but is likely related to the inactivation of Na Channels and action as a GABA modulator. The dosing range for this drug is anywhere from 100-400 mg with a half-life of 55 hours. There have been at least three separate clinical trials involving Cenobamate with results showing a reduction in seizure burden by at least 50% in the experimental groups especially at higher doses of the drug. Of note, Cenobamate can interact with other medications especially other AEDs being taken and as such requires medication titration. [22] [23]

Fenfluramine

This drug was used at high doses as an obesity drug that was later recalled given adverse cardiac effects. Fenfluramine is now approved at lower doses as of 2020 for treatment of seizures in patients 2 years and older with Lennox-Gastaut and Dravet syndrome. Fenfluramine is an amphetamine derivative that acts as a serotonin agonist and on GABA and NMDA receptors. The dosing range is anywhere from 0.2-0.7 mg/kg/day with higher dosing being the most effective for seizure burden. [24] Among Dravet and LGS patients, it has been shown to be helpful with most seizure types including atonic, GTC, and tonic. This medication has also been reported to be helpful in behavioral and cognitive symptoms associated with intractable epilepsy. In specific, at higher doses there are reports of patients showing improvement in daily executive functioning and emotional regulation. No adverse cardiac events have been reported with the use of fenfluramine for epilepsy treatment with the main side effects being diarrhea, weight loss, and fatigue. [22] [25]

Cannabidiol

Cannabidiol has recently been emerging as an effective treatment for epilepsy without the psychoactive effects of the Cannabis Sativa plant it is derived from. It gained approval in 2019 for treatment of DRE associated with Dravet, LGS, and more recently seizures associated with Tuberous Sclerosis in patients over the age of 2 years old. The mechanism of action of Cannabidiol is unclear but hypothesized to be related to Ca channels, adenosine signaling, and overall modulation of neuronal hyperexcitability. Cannabidiol is often used concurrently with another AED, especially clobazam, although there is evidence of the efficacy of Cannabidiol when used on its own. Some studies suggest the efficacy of Cannabidiol for all forms of DRE regardless of the underlying etiology. [26] Similar to Fenfluramine, there has been evidence of improvements in cognition, emotional regulation, and communication in addition to seizure control for patients taking Cannabidiol. [22] [27]

Perampanel

First gained approval in the US in 2012 for the treatment of drug resistant focal epilepsy in patients 12 years and older. It is an antagonist at AMPA receptors with a dosing range from 4-12 mg/day. It is primarily used as an adjunctive treatment option and at higher doses is associated with adverse symptoms like dizziness, ataxias, and withdrawal symptoms. Perampanel has also been studied in the context of sleep and has been shown to help with sleep maintenance and reduction of daytime sleepiness. [28] [29] [30]

Diets

For over 100 years it has been known that a diet with a high fat content and a low carbohydrate content can reduce seizures. Radically curbing carbohydrate intake imitates starvation and forces the body to draw energy from ketone bodies that form when fat is metabolized instead of drawing its energy from sugar. This state is called ketosis and it changes several biochemical processes in the brain in a way that inhibits epileptic activity. On this basis there are several diets that are often recommended to children under 12 years old, but are also effective in adults for DRE management. [31]

Ketogenic diet

The ketogenic diet is the diet that is most commonly recommended by doctors for patients with epilepsy. In this diet the ratio of fat to carbohydrates and proteins is 4:1. That means that the fat content of the consumed food must be around 80%, the protein content must be around 15%, and the carbohydrate content must be around 5%. For comparison the average western diet consists of a carbohydrate content of over 50%. After one year on the ketogenic diet the success rate (seizure reduction over 50%) is between 30 and 50% and the dropout rate is around 45%. [32] [33] Although the ketogenic diet can be very effective, some families report that it's not compatible with daily life given its restrictive nature. It can be especially difficult for adolescents to follow as their autonomy increases. For this reason a fat ratio of 3: 1 instead of 4:1 can be recommended to make meals more palatable. Side effects of the ketogenic diet include constipation, fatigue, weight loss, and kidney stones (typically after long-term adherence). [34]

MCT-Ketogenic diet

In the 1960s, it was discovered that when medium-chain triglycerides (MCT) are metabolized more ketone bodies are produced than from metabolizing any other fat. This discovery sparked the introduction of the MCT-ketogenic diet, a modification of the ketogenic diet. In the MCT-ketogenic diet, MCT oil is added to ketogenic meals, [35] which allows the carbohydrate content to be increased. The efficacy of the MCT ketogenic diet does not differ significantly from the classic ketogenic diet however not all patients, especially pediatric populations, can tolerate the large amounts of MCT oil required. This diet can also be costly. [31] [36]

Modified Atkins

A modified Atkins diet was coined after the popular Atkins diet with the goal of reducing seizures through ketosis. In this diet, the fat content is slightly lower than in the ketogenic diet at around 60%, the protein content is around 30% and the carbohydrate content is around 10%. Several studies show that the modified Atkins diet is just as effective as the ketogenic diet. [37] Some physicians recommend the modified Atkins diet because they assume that patients will adhere to it on the long-term because it is more compatible with daily life and the meals are more enjoyable. [38]

Low Glycemic Index (LGI)

The aim of the LGI diet is to keep blood glucose levels at a stable state. Rapid fluctuations in glucose levels both high and low is thought to be a trigger for seizures in some patients with epilepsy. This diet permits 40-60 gram of carbohydrates daily but with the goal of a glycemic index of <50. This diet has been studied among pediatric populations as an effective form of management for DRE. [31] [39]

Surgery

In epilepsy surgery, a distinction can be made between resective and disconnective procedures. In a resective procedure the area of the brain that causes the seizures is removed. In a disconnective procedure the neural connections in the brain that allow the seizures to spread are disconnected. In most cases epilepsy surgery is only an option when the area of the brain that causes the seizures - the so-called epileptic focus can be clearly identified and is not responsible for critical functions such as language. Several imaging techniques such as magnetic resonance tomography and functional techniques like electrocorticography are used to demarcate the epileptic focus clearly. [40] Recording fMRI and EEG simultaneously is a noninvasive method detecting cerebral hemodynamic changes related to interictal epileptic discharges (IEDs) on scalp EEG. This has been shown through different studies to help diagnose different types of epilepsy. [40]

Lobe resection

Temporal lobe epilepsy (TLE) in which the epileptic focus is in the temporal lobe, is one of the most common types of epilepsy in adolescents and adults. Hence temporal lobe resection, during which the whole temporal lobe or just a part of the temporal lobe for example the hippocampus or the amygdala is removed, is the most common epilepsy surgery procedure. Between 40 and 60% of patients that undergo temporal lobe resection are continuously seizure free [41] [42] The surgery itself is very safe with a mortality of 0%. [43] [44] The risk for neurologic complications from a temporal lobe resection is around 3 to 7% [45] [46]

Lesionectomy

If the source of seizures is a lesion, for example a scar tissue from a brain injury a tumor or malformed blood vessels, this lesion can be removed surgically in a lesionectomy.[ citation needed ]

Corpus callosotomy

Corpus callosotomy is a palliative procedure for specially severe cases of epilepsy. This corpus callosum is a large bundle of nerve fibers that connects both brain halves with each other. To prevent the spreading of seizures from one brain hemisphere (brain half) to the other the corpus callosum can be split. This procedure is mostly carried out on patients with so-called drop attacks that come with a very high risk of injury and in which the epileptic focus is not clearly delimitable. It is very rare that a corpus callosotomy causes seizure freedom however in half of the patients the dangerous drop attacks are less severe. [47] After a corpus callosotomy among others there is the risk that language is temporarily or permanently impaired. The younger a patient is at the time of the corpus callosotomy, the better the prognosis.[ citation needed ]

Functional hemispherectomy

This procedure is a modern adaptation of the radical hemispherectomy in which one brain hemisphere is removed to prevent the spread of seizures from one brain hemisphere to the other. In the functional version only a part of the hemisphere is removed but the connections to the other brain hemisphere are cut through. This procedure is only performed on a small group of patients under the age of 13 that have severe damage or malformation of one hemisphere, patients with Sturge Weber syndrome or patients with Rasmussen's encephalitis. Surgical intervention is considered a viable option for infants with drug-resistant epilepsy, particularly when anti-seizure medications fail to achieve seizure control. For this population, surgery can lead to favorable outcomes in a substantial number of cases. [48] The functional hemispherectomy can achieve long-term seizure freedom in over 80% of patients however often at the price of hemiplegia and hemianopsy. The death rate is around 1 to 2% and 5% of patients develop a hydrocephalus that needs to be treated with a shunt. [49]

Multiple subpial transection

Multiple subpial transection (MST) is a palliative procedure that is considered when an epileptic focus can be identified but cannot be removed because it is in a functionally relevant brain region- a so-called eloquent region. In an MST nerve fibers are disconnected so that seizures cannot spread from the epileptic focus into the rest of the brain. Between 60 and 70% of patients experienced a seizure reduction of over 95% after an MST and the risk for neurologic deficits is around 19%. [50]

Vagus nerve stimulation

Vagus nerve stimulation (VNS) involves implanting a pacemaker-like generator below the skin in the chest area that intermittently sends electrical impulses to the left vagus nerve in the neck. The impulses are mediated to the brain by the vagus nerve and thereby help to inhibit electrical disturbances that cause seizures. The antiepileptic effect of vagus nerve stimulation increases over several months: after two years around half of VNS patients experience a reduction of their seizures by at least 50% [51] [52] and after 10 years the average seizure reduction is around 75% [53] Furthermore, in most patients mood (VNS has a significant anti-depressent effect and is approved for depression in some countries), alertness and quality-of-life are increased significantly within the first year of vagus nerve stimulation. [54] [55] VNS patients can induce an extra stimulation themselves with a VNS magnet when they noticed that a seizure is approaching and it has been shown that the majority of seizures can be interrupted this type of on-demand stimulation. [56] [57]

The procedure to implant a vagus nerve stimulator is very safe: no case of death related to VNS implantation surgery has ever occurred. Infection of the tissue pocket in which the generator is located that requires antibiotic treatment occurs in around 3% of patients. [58] [59] The most common side effect is hoarseness or change in voice. Headaches and shortness of breath are less common. In most cases, side effects only occur during activity of the stimulation (mostly every 3 to 5 minutes) and reduce over time. [60] In most cases VNS does not replace antiepileptic medication. Patients must continue their antiepileptic medication however in many cases the dose can be reduced over time so that patients experience fewer side effects of the medication. The battery of the VNS generator can, depending on the model and the settings, last between 3 and 10 years.[ citation needed ]

VNS with cardiac-based seizure detection

In 82% of epilepsy patients the heart rate increases quickly and suddenly upon a seizure [61] This is known as ictal tachycardia. Ictal tachycardia is so characteristic that it can be distinguished from the slow gradual increase of heart rate that occurs during physical activity. This way in the majority of epilepsy patients seizures can be detected in the ECG. In addition to classical VNS, some new VNS generators continuously monitor heart rate and identify fast and sudden heart rate increases associated with seizures with intelligent software. Then an automatic additional stimulation can be triggered to interrupt, prevent or alleviate the seizure. This new generator type was shown to detect and treat at least four out of five seizures and 60% of seizures were shown to be interrupted with this heart-rate triggered stimulation. [62] The earlier in the course of the seizure the stimulation occurred the quicker the seizure ended generally seizures were shown to be reduced by around 35% by stimulation [63] [64]

Other

Deep brain stimulation of the anterior nuclei of the thalamus is approved for DRE in some countries in Europe, but has been and continues to only be used in a very few patients. After 5 years of DBS a seizure reduction of 69% and a 50%-responder rate of 68% was reported in a randomized-double blinded trial. [65] The rate of serious device related events was 34% in this study.

Responsive neurostimulation (RNS) is approved for DRE in the US and involves stimulation directly to 1 or 2 seizure foci when abnormal electrocorticographic activity is detected by the devices software. After 2 years of RNS a seizure reduction of 53% was reported in a randomized-double blinded trial as well as a rate of serious device related events of 2.5%. [66]

Transcutaneous vagus nerve stimulation (tVNS) is approved for DRE in some European countries and involves externally stimulating the auricular branch of the vagus nerve in the ear. tVNS failed to demonstrate efficacy in a first randomized-double blinded trial: responder rates did not differ between active and control groups potentially indicating a placebo effect behind the 34% seizure reduction seen in the patients who completed the full follow-up period. [67]

Related Research Articles

<span class="mw-page-title-main">Epilepsy</span> Group of neurological disorders causing seizures

Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. An epileptic seizure is the clinical manifestation of an abnormal, excessive, and synchronized electrical discharge in the neurons. The occurrence of two or more unprovoked seizures defines epilepsy. The occurrence of just one seizure may warrant the definition in a more clinical usage where recurrence may be able to be prejudged. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain. These episodes can result in physical injuries, either directly, such as broken bones, or through causing accidents. In epilepsy, seizures tend to recur and may have no detectable underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy. People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to the alarming nature of their symptoms.

<span class="mw-page-title-main">Seizure</span> Period of symptoms due to excessive or synchronous neuronal brain activity

A seizure is a sudden change in behavior, movement and/or consciousness due to abnormal electrical activity in the brain. Seizures can look different in different people. It can be uncontrolled shaking of the whole body or a person spacing out for a few seconds. Most seizures last less than two minutes. They are then followed by confusion/drowsiness before the person returns to normal. If a seizure lasts longer than 5 minutes, it is a medical emergency and needs immediate treatment.

Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.

Absence seizures are one of several kinds of generalized seizures. In the past, absence epilepsy was referred to as "pyknolepsy," a term derived from the Greek word "pyknos," signifying "extremely frequent" or "grouped". These seizures are sometimes referred to as petit mal seizures ; however, usage of this terminology is no longer recommended. Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy. Absence seizures are most common in children. They affect both sides of the brain.

<span class="mw-page-title-main">Ketogenic diet</span> High-fat dietary therapy for epilepsy

The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate dietary therapy that in conventional medicine is used mainly to treat hard-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than carbohydrates.

<span class="mw-page-title-main">Lennox–Gastaut syndrome</span> Rare form of childhood-onset epilepsy

Lennox–Gastaut syndrome (LGS) is a complex, rare, and severe childhood-onset epilepsy syndrome. It is characterized by multiple and concurrent seizure types including tonic seizure, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG), which are very abnormal. Typically, it presents in children aged 3–5 years and most of the time persists into adulthood with slight changes in the electroclinical phenotype. It has been associated with perinatal injuries, congenital infections, brain malformations, brain tumors, genetic disorders such as tuberous sclerosis and numerous gene mutations. Sometimes LGS is observed after infantile epileptic spasm syndrome. The prognosis for LGS is marked by a 5% mortality in childhood and persistent seizures into adulthood.

<span class="mw-page-title-main">Vagus nerve stimulation</span> Medical treatment that involves delivering electrical impulses to the vagus nerve

Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. It is used as an add-on treatment for certain types of intractable epilepsy, cluster headaches, treatment-resistant depression and stroke rehabilitation.

<span class="mw-page-title-main">Temporal lobe epilepsy</span> Chronic focal seizure disorder

In the field of neurology, temporal lobe epilepsy is an enduring brain disorder that causes unprovoked seizures from the temporal lobe. Temporal lobe epilepsy is the most common type of focal onset epilepsy among adults. Seizure symptoms and behavior distinguish seizures arising from the medial temporal lobe from seizures arising from the lateral (neocortical) temporal lobe. Memory and psychiatric comorbidities may occur. Diagnosis relies on electroencephalographic (EEG) and neuroimaging studies. Anticonvulsant medications, epilepsy surgery and dietary treatments may improve seizure control.

Frontal lobe epilepsy (FLE) is a neurological disorder that is characterized by brief, recurring seizures arising in the frontal lobes of the brain, that often occur during sleep. It is the second most common type of epilepsy after temporal lobe epilepsy (TLE), and is related to the temporal form in that both forms are characterized by partial (focal) seizures.

Anterior temporal lobectomy (ATL) is the complete or partial removal of the anterior portion of the temporal lobe of the brain. The exact boundaries for removal can vary slightly in practice and between neurosurgeons. It is a treatment option for temporal lobe epilepsy for those in whom anticonvulsant medications do not control epileptic seizures, and who have frequent seizures, and who additionally qualify based on a WADA test to localize the dominant hemisphere for language module.

Abdominal epilepsy is a rare condition consisting of gastrointestinal disturbances caused by epileptiform seizure activity. It is most frequently found in children, though a few cases of it have been reported in adults. It has been described as a type of temporal lobe epilepsy. Responsiveness to anticonvulsants can aid in the diagnosis. Distinguishing features of abdominal epilepsy include (1) Abnormal laboratory, radiographic, and endoscopic findings revealing paroxysmal GI manifestations of unknown origin (2) CNS symptoms (3) Abnormal EEG. Most published medical literature dealing with abdominal epilepsy is in the form of individual case reports. A 2005 review article found a total of 36 cases described in the medical literature.

Epilepsy surgery involves a neurosurgical procedure where an area of the brain involved in seizures is either resected, ablated, disconnected or stimulated. The goal is to eliminate seizures or significantly reduce seizure burden. Approximately 60% of all people with epilepsy have focal epilepsy syndromes. In 20% to 30% of these patients, the condition is not adequately controlled with adequate trials of two anticonvulsive drugs, termed drug resistant epilepsy, or refractory epilepsy. Such patients are potential candidates for surgical epilepsy treatment.

Progressive Myoclonic Epilepsies (PME) are a rare group of inherited neurodegenerative diseases characterized by myoclonus, resistance to treatment, and neurological deterioration. The cause of PME depends largely on the type of PME. Most PMEs are caused by autosomal dominant or recessive and mitochondrial mutations. The location of the mutation also affects the inheritance and treatment of PME. Diagnosing PME is difficult due to their genetic heterogeneity and the lack of a genetic mutation identified in some patients. The prognosis depends largely on the worsening symptoms and failure to respond to treatment. There is no current cure for PME and treatment focuses on managing myoclonus and seizures through antiepileptic medication (AED).

<span class="mw-page-title-main">Rolandic epilepsy</span> Most common epilepsy syndrome in childhood, usually subsiding with age

Benign Rolandic epilepsy or self-limited epilepsy with centrotemporal spikes is the most common epilepsy syndrome in childhood. Most children will outgrow the syndrome, hence the label benign. The seizures, sometimes referred to as sylvian seizures, start around the central sulcus of the brain.

<span class="mw-page-title-main">Epilepsy in children</span>

Epilepsy is a neurological condition of recurrent episodes of unprovoked epileptic seizures. A seizure is an abnormal neuronal brain activity that can cause intellectual, emotional, and social consequences. Epilepsy affects children and adults of all ages and races, and is one of the most common neurological disorders of the nervous system. Epilepsy is more common among children than adults, affecting about 6 out of 1000 US children that are between the age of 0 to 5 years old. The epileptic seizures can be of different types depending on the part of the brain that was affected, seizures are classified in 2 main types partial seizure or generalized seizure.

Febrile infection-related epilepsy syndrome (FIRES), is onset of severe seizures following a febrile illness in someone who was previously healthy. The seizures may initially be focal; however, often become tonic-clonic. Complications often include intellectual disability, behavioral problems, and ongoing seizures.

<span class="mw-page-title-main">Fabrice Bartolomei</span> French neurophysiologist

Fabrice Bartolomei is a French neurophysiologist, and University Professor at Aix-Marseille University (AMU), leading the Service de Neurophysiologie Clinique of the Timone Hospital at the Assistance Publique - Hôpitaux de Marseille, and he is the medical director of the ‘Centre Saint-Paul - Hopital Henri Gastaut’. He is the coordinator of the clinical network CINAPSE that is dedicated to the management of adult and pediatric cases of severe epilepsy and leader of the Federation Hospitalo-Universitaire Epinext. He is also member of the research unit Institut de Neurosciences des Systèmes.

Musicogenic seizure, also known as music-induced seizure, is a rare type of seizure, with an estimated prevalence of 1 in 10,000,000 individuals, that arises from disorganized or abnormal brain electrical activity when a person hears or is exposed to a specific type of sound or musical stimuli. There are challenges when diagnosing a music-induced seizure due to the broad scope of triggers, and time delay between a stimulus and seizure. In addition, the causes of musicogenic seizures are not well-established as solely limited cases and research have been discovered and conducted respectively. Nevertheless, the current understanding of the mechanism behind musicogenic seizure is that music triggers the part of the brain that is responsible for evoking an emotion associated with that music. Dysfunction in this system leads to an abnormal release of dopamine, eventually inducing seizure.

Malignant migrating partial seizures of infancy (MMPSI) is a rare epileptic syndrome that onsets before 6 months of age, commonly in the first few weeks of life. Once seizures start, the site of seizure activity repeatedly migrates from one area of the brain to another, with few periods of remission in between. These seizures are 'focal' (updated term for 'partial'), meaning they do not affect both sides of the brain at the same time. These continuous seizures cause damage to the brain, hence the descriptor 'malignant.'

SLC6A1 epileptic encephalopathy is a genetic disorder characterised by the loss-of-function of one copy of the human SLC6A1 gene. SLC6A1 epileptic encephalopathy can typically manifest itself with early onset seizures and it can also be characterised by mild to severe learning disability. Not all manifestations of the conditions are present in one given patient.

References

  1. ↑ Kwan, Patrick; Arzimanoglou, Alexis; Berg, Anne T.; Brodie, Martin J.; Allen Hauser, W.; Mathern, Gary; Moshé, Solomon L.; Perucca, Emilio; Wiebe, Samuel (2010-06-01). "Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies". Epilepsia. 51 (6): 1069–1077. doi:10.1111/j.1528-1167.2009.02397.x. ISSN   1528-1167. PMID   19889013. S2CID   75283540.
  2. ↑ Bresnahan, Rebecca; Panebianco, Mariangela; Marson, Anthony G. (28 March 2019). "Brivaracetam add-on therapy for drug-resistant epilepsy". The Cochrane Database of Systematic Reviews. 3 (8): CD011501. doi:10.1002/14651858.CD011501.pub2. ISSN   1469-493X. PMC   6437881 . PMID   30920649.
  3. ↑ Kwan, Patrick; Brodie, Martin J. (2000-02-03). "Early Identification of Refractory Epilepsy". New England Journal of Medicine. 342 (5): 314–319. doi: 10.1056/NEJM200002033420503 . ISSN   0028-4793. PMID   10660394.
  4. ↑ Brodie, Martin J. (2013-05-01). "Road to refractory epilepsy: The Glasgow story". Epilepsia. 54: 5–8. doi: 10.1111/epi.12175 . ISSN   1528-1167. PMID   23646962.
  5. ↑ Hesdorffer, Dale C.; Tomson, Torbjorn; Benn, Emma; Sander, Josemir W.; Nilsson, Lena; Langan, Yvonne; Walczak, Thaddeus S.; Beghi, Ettore; Brodie, Martin J. (2011-06-01). "Combined analysis of risk factors for SUDEP". Epilepsia. 52 (6): 1150–1159. doi: 10.1111/j.1528-1167.2010.02952.x . ISSN   1528-1167. PMID   21671925.
  6. ↑ Langan, Y.; Nashef, L.; Sander, J. W. (2005-04-12). "Case-control study of SUDEP". Neurology. 64 (7): 1131–1133. doi:10.1212/01.WNL.0000156352.61328.CB. ISSN   0028-3878. PMID   15824334. S2CID   23573806.
  7. 1 2 3 Perucca, Emilio; Perucca, Piero; White, H Steve; Wirrell, Elaine C (2023). "Drug resistance in epilepsy". The Lancet Neurology. 22 (8): 723–734. doi:10.1016/S1474-4422(23)00151-5. PMID   37352888.
  8. ↑ Sultana, Bushra; Panzini, Marie-Andrée; Veilleux Carpentier, Ariane; Comtois, Jacynthe; Rioux, Bastien; Gore, Geneviève; Bauer, Prisca R.; Kwon, Churl-Su; Jetté, Nathalie; Josephson, Colin B.; Keezer, Mark R. (2021-04-27). "Incidence and Prevalence of Drug-Resistant Epilepsy: A Systematic Review and Meta-analysis". Neurology. 96 (17): 805–817. doi:10.1212/WNL.0000000000011839. hdl:1866/26896. ISSN   0028-3878. PMID   33722992.
  9. ↑ Łukawski, Krzysztof; Czuczwar, Stanisław J. (2021-09-02). "Understanding mechanisms of drug resistance in epilepsy and strategies for overcoming it". Expert Opinion on Drug Metabolism & Toxicology. 17 (9): 1075–1090. doi:10.1080/17425255.2021.1959912. ISSN   1742-5255. PMID   34310255.
  10. ↑ Cascino, Gregory D. (2002-06-27). "Video-EEG Monitoring in Adults". Epilepsia. 43: 80–93. doi:10.1046/j.1528-1157.43.s.3.14.x. PMID   12060010. S2CID   6618336.
  11. 1 2 3 4 5 Anyanwu, Chinekwu; Motamedi, Gholam (2018-03-21). "Diagnosis and Surgical Treatment of Drug-Resistant Epilepsy". Brain Sciences. 8 (4): 49. doi: 10.3390/brainsci8040049 . ISSN   2076-3425. PMC   5924385 . PMID   29561756.
  12. ↑ Noachtar, Soheyl; Rémi, Jan (2009). "The role of EEG in epilepsy: A critical review". Epilepsy & Behavior. 15 (1): 22–33. doi:10.1016/j.yebeh.2009.02.035. PMID   19248841.
  13. ↑ Quek, Amy M. L. (2012-05-01). "Autoimmune Epilepsy: Clinical Characteristics and Response to Immunotherapy". Archives of Neurology. 69 (5): 582–593. doi:10.1001/archneurol.2011.2985. ISSN   0003-9942. PMC   3601373 . PMID   22451162.
  14. ↑ Wang, Irene; Bernasconi, Andrea; Bernhardt, Boris; Blumenfeld, Hal; Cendes, Fernando; Chinvarun, Yotin; Jackson, Graeme; Morgan, Victoria; Rampp, Stefan; Vaudano, Anna Elisabetta; Federico, Paolo (2020). "MRI essentials in epileptology: a review from the ILAE Imaging Taskforce". Epileptic Disorders. 22 (4): 421–437. doi:10.1684/epd.2020.1174. ISSN   1294-9361. PMID   32763869.
  15. ↑ Niu, Na; Xing, Haiqun; Wu, Meiqi; Ma, Yanru; Liu, Yimin; Ba, Jiantao; Zhu, Shikun; Li, Fang; Huo, Li (2021). "Performance of PET imaging for the localization of epileptogenic zone in patients with epilepsy: a meta-analysis". European Radiology. 31 (8): 6353–6366. doi:10.1007/s00330-020-07645-4. ISSN   0938-7994. PMID   33523306.
  16. 1 2 Ponisio, Maria R.; Zempel, John M.; Day, Brian K.; Eisenman, Lawrence N.; Miller-Thomas, Michelle M.; Smyth, Matthew D.; Hogan, R. Edward (2021). "The Role of SPECT and PET in Epilepsy". American Journal of Roentgenology. 216 (3): 759–768. doi:10.2214/AJR.20.23336. ISSN   0361-803X. PMID   33474983.
  17. ↑ Yassin, Ahmed; El-Salem, Khalid; Al-Mistarehi, Abdel-Hameed; Momani, Aiman; Zein Alaabdin, Anas M.; Shah, Palak; Mountz, James Michael; Bagić, Anto I. (2021). Azhdarinia, Ali (ed.). "Use of Innovative SPECT Techniques in the Presurgical Evaluation of Patients with Nonlesional Extratemporal Drug-Resistant Epilepsy". Molecular Imaging. 2021. doi: 10.1155/2021/6614356 . ISSN   1535-3508. PMC   7953581 . PMID   33746629.
  18. ↑ Fred, Alfred Lenin; Kumar, Subbiahpillai Neelakantapillai; Kumar Haridhas, Ajay; Ghosh, Sayantan; Purushothaman Bhuvana, Harishita; Sim, Wei Khang Jeremy; Vimalan, Vijayaragavan; Givo, Fredin Arun Sedly; Jousmäki, Veikko; Padmanabhan, Parasuraman; Gulyás, Balázs (2022-06-15). "A Brief Introduction to Magnetoencephalography (MEG) and Its Clinical Applications". Brain Sciences. 12 (6): 788. doi: 10.3390/brainsci12060788 . ISSN   2076-3425. PMC   9221302 . PMID   35741673.
  19. ↑ Harcourt, Scott (2020). "The neuropsychology of epilepsy and suicide: A review". Aggression and Violent Behavior. 54: 101411. doi:10.1016/j.avb.2020.101411.
  20. ↑ Massot-Tarrús, Andreu; Mirsattari, Seyed M. (2022). "Roles of fMRI and Wada tests in the presurgical evaluation of language functions in temporal lobe epilepsy". Frontiers in Neurology. 13: 884730. doi: 10.3389/fneur.2022.884730 . ISSN   1664-2295. PMC   9562037 . PMID   36247757.
  21. ↑ Stabell, Kirsten E.; Bakke, Søren J.; Andresen, Sverre; Bjørnaes, Helge; Borchgrevink, Hans M.; Due-Tønnessen, Paulina; Heminghyt, Einar; Nome, Terje; Pedersen, Hans-Kristian; Ramm-Pettersen, Jon; Røste, Geir K.; Tennøe, Bjørn (July 2004). "Selective posterior cerebral artery amobarbital test: its role in presurgical memory assessment in temporal lobe epilepsy". Epilepsia. 45 (7): 817–825. doi: 10.1111/j.0013-9580.2004.59903.x . ISSN   0013-9580. PMID   15230707. S2CID   25909332.
  22. 1 2 3 Arenas Cabrera, Carmen; Cabezudo García, Pablo; Calvo Medina, Rocío; Galeano Bilbao, Benito; Martínez Agredano, Paula; Ruiz Giménez, Jesús; Rodríguez Uranga, Juan Jesús; Quiroga Subirana, Pablo (2024). "Avances y orientaciones en el tratamiento de la epilepsia farmacorresistente: revisión de los nuevos fármacos cenobamato, fenfluramina y cannabidiol por la Sociedad Andaluza de Epilepsia". Revista de Neurología (in Spanish). 79 (6): 161–173. doi:10.33588/rn.7906.2024086. ISSN   0210-0010. PMC   11469102 . PMID   39267402.
  23. ↑ Elkommos, Samia; Mula, Marco (2022-12-12). "Current and future pharmacotherapy options for drug-resistant epilepsy". Expert Opinion on Pharmacotherapy. 23 (18): 2023–2034. doi:10.1080/14656566.2022.2128670. ISSN   1465-6566. PMID   36154780.
  24. ↑ Xu, Yingchun; Chen, Deng; Liu, Ling (2024-03-25). "Optimal dose of fenfluramine in adjuvant treatment of drug-resistant epilepsy: evidence from randomized controlled trials". Frontiers in Neurology. 15. doi: 10.3389/fneur.2024.1371704 . ISSN   1664-2295. PMC   10999678 . PMID   38590719.
  25. ↑ Klein, Pavel; Friedman, Daniel; Kwan, Patrick (2024). "Recent Advances in Pharmacologic Treatments of Drug-Resistant Epilepsy: Breakthrough in Sight". CNS Drugs. 38 (12): 949–960. doi:10.1007/s40263-024-01130-y. ISSN   1172-7047. PMID   39433725.
  26. ↑ Espinosa-Jovel, Camilo; Riveros, Sandra; Bolaños-Almeida, Carlos; Salazar, Mateo Ramírez; Inga, Leidy Ceballos; Guío, Laura (2023). "Real-world evidence on the use of cannabidiol for the treatment of drug resistant epilepsy not related to Lennox-Gastaut syndrome, Dravet syndrome or Tuberous Sclerosis Complex". Seizure: European Journal of Epilepsy. 112: 72–76. doi:10.1016/j.seizure.2023.09.015. PMID   37769547.
  27. ↑ Calonge, Quentin; Besnard, Aurore; Bailly, Laurent; Damiano, Maria; Pichit, Phintip; Dupont, Sophie; Gourfinkel-An, Isabelle; Navarro, Vincent (2024). "Cannabidiol Treatment for Adult Patients with Drug-Resistant Epilepsies: A Real-World Study in a Tertiary Center". Brain and Behavior. 14 (11): e70122. doi:10.1002/brb3.70122. ISSN   2162-3279. PMC   11538088 . PMID   39501537.
  28. ↑ Filin, A. A.; Tardov, M. V.; Kunelskaya, N. L.; Vlasov, P. N. (2020-12-12). "The use of perampanel in drug-resistant focal epilepsy: its effect on sleep". Neurology, Neuropsychiatry, Psychosomatics. 12 (6): 49–53. doi:10.14412/2074-2711-2020-6-49-53. ISSN   2310-1342.
  29. ↑ Zhu, Chaofeng; Li, Juan; Wei, Dazhu; Wu, Luyan; Zhang, Yuying; Huang, Huapin; Lin, Wanhui (2023-11-14). "A nomogram to predict the treatment benefit of perampanel in drug-resistant epilepsy patients". Frontiers in Neurology. 14. doi: 10.3389/fneur.2023.1284171 . ISSN   1664-2295. PMC   10718189 . PMID   38093756.
  30. ↑ Bresnahan, Rebecca; Hill, Ruaraidh A; Wang, Jin (2023-04-14). Cochrane Epilepsy Group (ed.). "Perampanel add-on for drug-resistant focal epilepsy". Cochrane Database of Systematic Reviews. 2023 (4). doi:10.1002/14651858.CD010961.pub2. PMID   37059702.
  31. 1 2 3 Mustafa, Muhammad Saqlain; Shafique, Muhammad Ashir; Aheed, Bilal; Ashraf, Farheen; Ali, Syed Muhammad Sinaan; Iqbal, Muhammad Faheem; Haseeb, Abdul (2024). "The impact of ketogenic diet on drug-resistant epilepsy in children: A comprehensive review and meta-analysis". Irish Journal of Medical Science (1971 -). 193 (3): 1495–1503. doi:10.1007/s11845-024-03622-8. ISSN   0021-1265. PMID   38315271.
  32. ↑ Freeman, John M.; Vining, Eileen P. G.; Pillas, Diana J.; Pyzik, Paula L.; Casey, Jane C.; Lcsw; Kelly, and Millicent T. (1998-12-01). "The Efficacy of the Ketogenic Diet—1998: A Prospective Evaluation of Intervention in 150 Children". Pediatrics. 102 (6): 1358–1363. doi:10.1542/peds.102.6.1358. ISSN   0031-4005. PMID   9832569.
  33. ↑ Li, Hai-feng; Zou, Yan; Ding, Gangqiang (2013-12-01). "Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a Meta-analysis". Iranian Journal of Pediatrics. 23 (6): 613–620. ISSN   2008-2142. PMC   4025116 . PMID   24910737.
  34. ↑ Kossoff, Eric H.; Zupec-Kania, Beth A.; Rho, Jong M. (2009-08-01). "Ketogenic Diets: An Update for Child Neurologists". Journal of Child Neurology. 24 (8): 979–988. doi:10.1177/0883073809337162. ISSN   0883-0738. PMID   19535814. S2CID   11618891.
  35. ↑ Halle, Shirley (27 July 2014). "What is MCT Oil?" (in Dutch). Vitaa. Retrieved 22 March 2017.
  36. ↑ Anonymous Reviewer (2024). Review for "The use of ketogenic diets in children living with drug-resistant epilepsy, glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency: A scoping review". Vol. 37. pp. 827–846. doi:10.1111/jhn.13324/v2/review1.{{cite book}}: |work= ignored (help)
  37. ↑ GHAZAVI, Ahad; TONEKABONI, Seyed Hassan; KARIMZADEH, Parvaneh; NIKIBAKHSH, Ahmad Ali; KHAJEH, Ali; FAYYAZI, Afshin (2014-01-01). "The Ketogenic and Atkins Diets Effect on Intractable Epilepsy: A Comparison". Iranian Journal of Child Neurology. 8 (3): 12–17. ISSN   1735-4668. PMC   4135275 . PMID   25143768.
  38. ↑ Kossoff, EH; McGrogan, JR; Bluml, RM; Pillas, DJ; Rubenstein, JE; Vining, EP (February 2006). "A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy". Epilepsia. 47 (2): 421–4. doi: 10.1111/j.1528-1167.2006.00438.x . PMID   16499770. S2CID   30849940.
  39. ↑ Rohani, Pejman; Shervin Badv, Reza; Sohouli, Mohammad Hassan; Guimarães, Nathalia Sernizon (2024). "The efficacy of low glycemic index diet on seizure frequency in pediatric patients with epilepsy: A systematic review and meta-analysis". Seizure: European Journal of Epilepsy. 117: 150–158. doi:10.1016/j.seizure.2024.02.013. PMID   38422595.
  40. 1 2 Pittau, F.; Dubeau, F.; Gotman, J. (2012-05-08). "Contribution of EEG/fMRI to the definition of the epileptic focus". Neurology. 78 (19): 1479–1487. doi:10.1212/WNL.0b013e3182553bf7. ISSN   0028-3878. PMC   3345614 . PMID   22539574.
  41. ↑ Marks, William J. (2003-09-01). "Long-term Outcomes of Temporal Lobe Epilepsy Surgery". Epilepsy Currents. 3 (5): 178–180. doi:10.1046/j.1535-7597.2003.03509.x. ISSN   1535-7597. PMC   557956 . PMID   15902315.
  42. ↑ Jutila, L.; Immonen, A.; Mervaala, E.; Partanen, J.; Partanen, K.; Puranen, M.; Kälviäinen, R.; Alafuzoff, I.; Hurskainen, H. (2002-11-01). "Long term outcome of temporal lobe epilepsy surgery: analyses of 140 consecutive patients". Journal of Neurology, Neurosurgery & Psychiatry. 73 (5): 486–494. doi:10.1136/jnnp.73.5.486. ISSN   1468-330X. PMC   1738104 . PMID   12397139.
  43. ↑ McClelland S; III; Guo H; Okuyemi KS (2011-06-13). "POpulation-based analysis of morbidity and mortality following surgery for intractable temporal lobe epilepsy in the united states". Archives of Neurology. 68 (6): 725–729. doi: 10.1001/archneurol.2011.7 . ISSN   0003-9942. PMID   21320984.
  44. ↑ Fisch, Bruce (2011-11-01). "Anterior Temporal Lobectomy – How Safe Is It?". Epilepsy Currents. 11 (6): 186–188. doi:10.5698/1535-7511-11.6.186. ISSN   1535-7597. PMC   3220424 . PMID   22129637.
  45. ↑ Salanova, V.; Markand, O.; Worth, R. (2002-02-01). "Temporal Lobe Epilepsy Surgery: Outcome, Complications, and Late Mortality Rate in 215 Patients". Epilepsia. 43 (2): 170–174. doi: 10.1046/j.1528-1157.2002.33800.x . ISSN   1528-1167. PMID   11903464.
  46. ↑ Fisch, Bruce (2011-11-01). "Anterior Temporal Lobectomy – How Safe Is It?". Epilepsy Currents. 11 (6): 186–188. doi:10.5698/1535-7511-11.6.186. ISSN   1535-7597. PMC   3220424 . PMID   22129637.
  47. ↑ Maehara, Taketoshi; Shimizu, Hiroyuki (2001-01-23). "Surgical Outcome of Corpus Callosotomy in Patients with Drop Attacks". Epilepsia. 42 (1): 67–71. doi: 10.1046/j.1528-1157.2001.081422.x . ISSN   1528-1167. PMID   11207787.
  48. ↑ Tsou, Amy Y.; Kessler, Sudha Kilaru; Wu, Mingche; Abend, Nicholas S.; Massey, Shavonne L.; Treadwell, Jonathan R. (2023-01-03). "Surgical Treatments for Epilepsies in Children Aged 1–36 Months: A Systematic Review". Neurology. 100 (1): e1–e15. doi:10.1212/WNL.0000000000201012. ISSN   0028-3878. PMC   9827129 . PMID   36270898.
  49. ↑ Schramm, J.; Kuczaty, S.; Sassen, R.; Elger, C. E.; Lehe, M. von (2012-09-01). "Pediatric functional hemispherectomy: outcome in 92 patients". Acta Neurochirurgica. 154 (11): 2017–2028. doi:10.1007/s00701-012-1481-3. ISSN   0001-6268. PMID   22941395. S2CID   22259780.
  50. ↑ Spencer, Susan S.; Schramm, Johannes; Wyler, Allen; O'Connor, Michael; Orbach, Darren; Krauss, Gregory; Sperling, Michael; Devinsky, Orrin; Elger, Christian (2002-02-01). "Multiple Subpial Transection for Intractable Partial Epilepsy: An International Meta-analysis". Epilepsia. 43 (2): 141–145. doi: 10.1046/j.1528-1157.2002.28101.x . ISSN   1528-1167. PMID   11903459.
  51. ↑ Elliott, Robert E.; Morsi, Amr; Kalhorn, Stephen P.; Marcus, Joshua; Sellin, Jonathan; Kang, Matthew; Silverberg, Alyson; Rivera, Edwin; Geller, Eric (January 2011). "Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: Long-term outcomes and predictors of response". Epilepsy & Behavior. 20 (1): 57–63. doi:10.1016/j.yebeh.2010.10.017. PMID   21144802. S2CID   17965529.
  52. ↑ Orosz, Iren; McCormick, David; Zamponi, Nelia; Varadkar, Sophia; Feucht, Martha; Parain, Dominique; Griens, Roger; Vallée, Louis; Boon, Paul (2014-10-01). "Vagus nerve stimulation for drug-resistant epilepsy: A European long-term study up to 24 months in 347 children". Epilepsia. 55 (10): 1576–1584. doi: 10.1111/epi.12762 . ISSN   1528-1167. PMID   25231724. S2CID   25790247.
  53. ↑ Elliott, Robert E.; Morsi, Amr; Tanweer, Omar; Grobelny, Bartosz; Geller, Eric; Carlson, Chad; Devinsky, Orrin; Doyle, Werner K. (March 2011). "Efficacy of vagus nerve stimulation over time: Review of 65 consecutive patients with treatment-resistant epilepsy treated with VNS >10years". Epilepsy & Behavior. 20 (3): 478–483. doi:10.1016/j.yebeh.2010.12.042. PMID   21296622. S2CID   42406763.
  54. ↑ Ryvlin, Philippe; Gilliam, Frank G.; Nguyen, Dang K.; Colicchio, Gabriella; Iudice, Alfonso; Tinuper, Paolo; Zamponi, Nelia; Aguglia, Umberto; Wagner, Louis (2014-06-01). "The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial". Epilepsia. 55 (6): 893–900. doi:10.1111/epi.12611. ISSN   1528-1167. PMC   4283995 . PMID   24754318.
  55. ↑ Vonck, Kristl; Raedt, Robrecht; Naulaerts, Joke; De Vogelaere, Frederick; Thiery, Evert; Van Roost, Dirk; Aldenkamp, Bert; Miatton, Marijke; Boon, Paul (2014-09-01). "Vagus nerve stimulation…25 years later! What do we know about the effects on cognition?". Neuroscience & Biobehavioral Reviews. 45: 63–71. doi:10.1016/j.neubiorev.2014.05.005. PMID   24858008. S2CID   20048129.
  56. ↑ Fisher, R. S.; Eggleston, K. S.; Wright, C. W. (2015-01-01). "Vagus nerve stimulation magnet activation for seizures: a critical review". Acta Neurologica Scandinavica. 131 (1): 1–8. doi: 10.1111/ane.12288 . ISSN   1600-0404. PMID   25145652.
  57. ↑ Morris, George L.; Gloss, David; Buchhalter, Jeffrey; Mack, Kenneth J.; Nickels, Katherine; Harden, Cynthia (2013-01-01). "Evidence-Based Guideline Update: Vagus Nerve Stimulation for the Treatment of Epilepsy". Epilepsy Currents. 13 (6): 297–303. doi:10.5698/1535-7597-13.6.297. ISSN   1535-7597. PMC   3854750 . PMID   24348133.
  58. ↑ Ben-Menachem, Elinor (September 2001). "Vagus Nerve Stimulation, Side Effects, and Long-Term Safety : Journal of Clinical Neurophysiology". Journal of Clinical Neurophysiology. 18 (5): 415–418. doi:10.1097/00004691-200109000-00005. PMID   11709646. S2CID   1263798.
  59. ↑ Kahlow, Hannes; Olivecrona, Magnus (December 2013). "Complications of vagal nerve stimulation for drug-resistant epilepsy". Seizure. 22 (10): 827–833. doi: 10.1016/j.seizure.2013.06.011 . PMID   23867218.
  60. ↑ Ben-Menachem, Elinor (September 2001). "Vagus Nerve Stimulation, Side Effects, and Long-Term Safety : Journal of Clinical Neurophysiology". Journal of Clinical Neurophysiology. 18 (5): 415–418. doi:10.1097/00004691-200109000-00005. PMID   11709646. S2CID   1263798.
  61. ↑ Eggleston, Katherine S.; Olin, Bryan D.; Fisher, Robert S. (August 2014). "Ictal tachycardia: The head–heart connection". Seizure. 23 (7): 496–505. doi: 10.1016/j.seizure.2014.02.012 . PMID   24698385.
  62. ↑ Boon, Paul; Vonck, Kristl; Rijckevorsel, Kenou van; Tahry, Riem El; Elger, Christian E.; Mullatti, Nandini; Schulze-Bonhage, Andreas; Wagner, Louis; Diehl, Beate (2015). "A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation". Seizure. 32: 52–61. doi: 10.1016/j.seizure.2015.08.011 . hdl: 1854/LU-6985546 . PMID   26552564.
  63. ↑ Fisher, Robert S.; Afra, Pegah; Macken, Micheal; Minecan, Daniela N.; Bagić, Anto; Benbadis, Selim R.; Helmers, Sandra L.; Sinha, Saurabh R.; Slater, Jeremy (2016-02-01). "Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance—The U.S. E-37 Trial". Neuromodulation: Technology at the Neural Interface. 19 (2): 188–195. doi:10.1111/ner.12376. ISSN   1525-1403. PMC   5064739 . PMID   26663671.
  64. ↑ Boon, Paul; Vonck, Kristl; Rijckevorsel, Kenou van; Tahry, Riem El; Elger, Christian E.; Mullatti, Nandini; Schulze-Bonhage, Andreas; Wagner, Louis; Diehl, Beate (2015). "A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation". Seizure. 32: 52–61. doi: 10.1016/j.seizure.2015.08.011 . hdl: 1854/LU-6985546 . PMID   26552564.
  65. ↑ Salanova, Vicenta; Witt, Thomas; Worth, Robert; Henry, Thomas R.; Gross, Robert E.; Nazzaro, Jules M.; Labar, Douglas; Sperling, Michael R.; Sharan, Ashwini (2015-03-10). "Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy". Neurology. 84 (10): 1017–1025. doi:10.1212/WNL.0000000000001334. ISSN   0028-3878. PMC   4352097 . PMID   25663221.
  66. ↑ Bergey, Gregory K.; Morrell, Martha J.; Mizrahi, Eli M.; Goldman, Alica; King-Stephens, David; Nair, Dileep; Srinivasan, Shraddha; Jobst, Barbara; Gross, Robert E. (2015-02-24). "Long-term treatment with responsive brain stimulation in adults with refractory partial seizures". Neurology. 84 (8): 810–817. doi:10.1212/WNL.0000000000001280. ISSN   0028-3878. PMC   4339127 . PMID   25616485.
  67. ↑ Bauer, S.; Baier, H.; Baumgartner, C.; Bohlmann, K.; Fauser, S.; Graf, W.; Hillenbrand, B.; Hirsch, M.; Last, C. (2016). "Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02)". Brain Stimulation. 9 (3): 356–363. doi:10.1016/j.brs.2015.11.003. PMID   27033012. S2CID   13348339.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.