[WEB] Neurochecklists | Fully referenced checklist for Brain tumour related epilepsy (BTRE): treatment

Last reviewed on 4/9/2023

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• TUMOURS
• PRIMARY BRAIN TUMOURS
• Brain tumour related epilepsy (BTRE)
• Brain tumour related epilepsy (BTRE): treatment

First-line antiepileptic drugs (AEDs)³

• Valproate
• Lamotrigine
• Topiramate
• Lacosamide
• Levetiracetam
• Zonisamide

Add-on antiepileptic drugs (AEDs)⁴

Precautions: drug treatments to avoid

Precautions: contraindications to antiepileptic drug withdrawal³

Surgery: considerations⁷

Surgery: approaches⁷

Treatment of refractory low grade tumour-related seizures

References

1. van Breemen MS, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol 2007; 6:421-430. 
2. Rudà R, Bello L, Duffau H, Soffietti R. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments. Neuro Oncol 2012; 14(Suppl 4):iv55-iv64. 
3. Seidel S, Wehner T, Miller D, Wellmer J, Schlegel U, Grönheit W. Brain tumor related epilepsy: pathophysiological approaches and rational management of antiseizure medication. Neurol Res Pract 2022; 4:45.
4. Hauff NS, Storstein A. Seizure management and prophylaxis considerations in patients with brain tumors. Curr Oncol Rep 2023; 25:787-792.
5. Klinger NV, Shah AK, Mittal S. Management of brain tumor-related epilepsy. Neurol India 2017; 65(Supplement):S60-S70. 
6. Liang S, Fan X, Zhao M, et al. Clinical practice guidelines for the diagnosis and treatment of adult diffuse glioma-related epilepsy. Cancer Med 2019; 8:4527-4535. 
7. Giulioni M, Marucci G, Martinoni M, et al. Epilepsy associated tumors: review article. World J Clin Cases 2014; 2:623-641.
8. Ertürk Çetin Ö, İşler C, Uzan M, Özkara Ç. Epilepsy-related brain tumors. Seizure 2017; 44:93-97.
9. Ramantani G, Kadish NE, Anastasopoulos C, et al. Epilepsy surgery for glioneuronal tumors in childhood: avoid loss of time. Neurosurgery 2014; 74:648-657.
10. Rudà R, Soffietti R. What is new in the management of epilepsy in gliomas? Curr Treat Options Neurol 2015; 17:351.

Source:

[WEB PAGE] More epilepsy medicines linked to birth defects if taken during pregnancy

7 Jan 2021

Several epilepsy medicines carry risks when taken in pregnancy, a review, published today by the Medicines and Healthcare products Regulatory Agency (MHRA), has found.

The review, from the Commission on Human Medicines, looked at all the available safety data about 10 of the most commonly prescribed epilepsy medicines.

The medicine sodium valproate is known to cause an increased risk of birth defects and developmental problems in babies if taken during pregnancy. This prompted the review of the risks for other epilepsy medicines.

The review found that four out of the 10 epilepsy medicines increased the risk of a baby being born with a physical birth defect if taken during pregnancy. These were carbamazepine (brand name Tegretol), phenobarbital, phenytoin (brand name Epanutin) and topiramate (brand name Topamax).

Some of the medicines also increased the risk of children having learning or thinking difficulties later in life, or of babies being born smaller than average.

None of these medicines carried as high a risk if taken during pregnancy as sodium valproate, according to the review findings.

Lamotrigine (brand name Lamictal) and levetiracetam (brand name Keppra) were found to be safer in pregnancy than other epilepsy medicines.

A further 14 medicines were included in the review, but there was not enough evidence to reach a conclusion about their safety when used during pregnancy. More data are needed on these medicines to be able to comment on their safety during pregnancy.

Epilepsy Action stresses that it is important women do not stop or change how they take their epilepsy medicine without speaking to their doctor. Uncontrolled epilepsy can cause harm to both the mother and the unborn baby. The organisation advises anyone worried about their medicines to contact their epilepsy doctor or nurse.

Epilepsy Action is pushing for the swift circulation of these findings to healthcare professionals so they can help patients make informed choices. The organisation warns that mistakes made handling the safety information of sodium valproate must not be repeated.

Patricia was diagnosed with juvenile myoclonic epilepsy (JME) around 20 years old. She has been prescribed several epilepsy medicines to help control her seizures. One of her medicines was sodium valproate (Epilim).

Patricia has two children, Joseph, 20, and Amèlie, 11, who have both been affected by the medicine.

“I first learned about FACS (foetal anti-convulsant syndrome) and FVS (foetal valproate syndrome) in 2016, by which time Joseph was 15.

“I was devastated, particularly as we had not been warned about any of this, not when I was first prescribed them nor prior to becoming pregnant.

“It’s so frustrating to read women’s posts on forums, asking questions and posting photos of their babies, and knowing what I know. These women are being told they can take certain epilepsy medications during pregnancy and I find it so difficult to hear. It’s clear some of them still don’t know about the risks.

“I really hope that this review means that women can have conversations with their doctors and get all the detail they need to make their choices.”

Louise Cousins, director of External Affairs at Epilepsy Action, said: “It is imperative that this information is circulated to doctors and nurses widely and quickly. Past mistakes must not be repeated. We know that the consequences of women not knowing information such as this can be devastating. No woman or girl should be taking an anti-epileptic medication without them, or their family, being aware of the risks.

“Women with epilepsy often face difficult choices when they consider how to manage their condition through pregnancy. It is essential that they receive pre-conception counselling so they can work with their health professionals to make an informed choice.

“The review was unable to establish the risk in pregnancy of more epilepsy medications than those it was able to reach conclusions about. This is deeply concerning. We are urgently calling for more research looking into the risks of epilepsy medicines in pregnancy, including the risks of taking more than one medication at once – something many people with epilepsy have to do.

“We know that this new information may cause women with epilepsy and their families to feel worried. We urge anyone with concerns about medication they are taking, or have taken in the past, to speak to their doctor or nurse, or call the Epilepsy Action Helpline on 0808 800 5050.”

Epilepsy Action says this information could affect the choices of thousands of women with epilepsy, as well as raise concerns about the effects of these medicines if they’ve been taken during pregnancy in the past.

The organisation has written to Health Secretary Matt Hancock, calling for the reintroduction of pre-conception counselling for all women with epilepsy as an indicator in the Quality and Outcomes Framework (QOF). This will encourage GPs to talk to women about their options and the risks associated with these before becoming pregnant. Epilepsy Action has recently begun a new study with the University of Liverpool to design an ideal pathway for pre-conception counselling.

Epilepsy Action is also pushing for the recommendations of the First Do No Harm report, published following the Cumberlege review into three ‘public health scandals’, to be implemented in full. There is more information on epilepsy medicines and pregnancy on the Epilepsy Action website.

*NOTE (11 Jan 2021): An amend has been made to the information around lamotrigine and levetiracetam to clarify that they have been found to be ‘safer’ in pregnancy than other epilepsy medicines.*

You may also be interested in…

Government urged to issue apology over sodium valproate, Primodos and pelvic mesh ‘public health scandals’ by safety review

UPDATE (9 July 2020): Since the original story, the government has issued an apology to families affected by the public health scandals around the medical products sodium valproate, Primodos and pelvic mesh. You can read the full government response on the UK Parliament website.

Source

[WEB PAGE] Epilepsy – An in-depth report on the types, causes, diagnosis, and treatment of epilepsy

Highlights

What Is Epilepsy?

Epilepsy is a brain disorder that is marked by recurrent seizures. Seizures are episodes of disturbed brain function caused by abnormalities of the brain’s electrical activity. There are many types of seizures.

Causes

Epilepsy can affect people of all ages but is most common in young children and older adults. Some types of epilepsy are inherited and are due to genetic factors. Other possible causes of epilepsy include brain injuries due to head trauma or oxygen deprivation at birth. In many cases, the cause of epilepsy is unknown (idiopathic.)

Diagnosis

A health care provider will diagnose epilepsy based on a person’s medical history, description of seizures, and various diagnostic tools. The most important diagnostic tool is the electroencephalogram (EEG), which allows providers to record and analyze brain waves. Imaging tests such as computed tomography (CT) and magnetic resonance imaging (MRI) may also be used.

Treatment

The goal of epilepsy treatment is to control seizures. Many different types of anticonvulsant (anti-epileptic) drugs are available to treat epilepsy. Some people need only one drug, while others may need to take several drugs.

For people who have not been helped by medication, surgery or a neurostimulation device may be options. Dietary changes, such as the ketogenic diet, have shown promise in helping children with severe epilepsy.

Anti-epileptic drugs (AEDs) can cause many side effects. Pregnant women with epilepsy need to take special precautions, because some of these drugs (particularly valproate) can cause birth defects.

Introduction

Epilepsy is a brain disorder involving repeated, spontaneous seizures of any type. There are different types of epilepsy but what they all share are recurrent seizures caused by an uncontrolled electrical discharge from nerve cells in the cerebral cortex. This part of the brain controls higher mental functions, general movement and sensation, the functions of the internal organs in the abdominal cavity, perception, and behavioral reactions.[…]

For more visit site

[WEB PAGE] Seizures and epilepsy

Author(s): Rani Haley Lindberg, Devin Wells MDOriginally published: August 7, 2012 Last updated: April 5, 2016

Jump to:

• disease/disorder,
• essentials of assessment,
• rehabilitation management and treatments,
• cutting edge/emerging and unique concepts and practice,
• gaps in the evidencebased knowledge,
• references

disease/disorder:

Definition

Seizure is the transient onset of paroxysmal events due to abnormal electrical activity within the brain as a result of excessive or synchronous neuronal activity.¹

• Acute symptomatic seizures: seizures resulting from acute central nervous system (CNS) insult including but not limited to metabolic, toxic, structural, infectious, or inflammatory insults.²
• Unprovoked seizures: seizures that occur in the absence of active CNS insult or beyond the time interval estimated for acute seizures.²
• Seizures can be focal (with or without dyscognitive features) or generalized. Generalized seizures include absence, tonic-clonic, atonic, and myotonic seizures.
• Status epilepticus denotes that the seizure is prolonged or immediately recurrent without return of consciousness.

Epilepsy is a brain disorder in which there is a chronic underlying CNS disorder resulting in unprovoked, recurring seizures

Etiology

Seizure precipitants include but are not limited to the following:

• Traumatic brain injury
• Hypoxic-ischemic events in the brain
• Intracranial hemorrhage
• Infection of the central nervous system
• Metabolic disorder
• Congenital abnormalities of the brain
• Neurodegenerative disorders
• Drug withdrawal or intoxication
• Brain tumors/mass lesions
• Fever
• Primary or idiopathic epilepsy (unknown cause)

While seizures can be unprovoked, in some cases they may be triggered by factors such as fatigue, sleep deprivation, or flickering lights.

Epidemiology including risk factors and primary prevention

According to the World Health Organization 2015 update, there are approximately 50 million people world-wide who are living with epilepsy: a prevalence of 4 to 10 per 1000 people. Around 5% of the population will have at least 1 seizure within their lifespan.³ Incidence of neonatal seizures is 1-1.2% of live births. Younger children are at a higher risk if they have congenital, genetic, or developmental conditions; in adults, neoplastic, vascular, and degenerative etiologies are more common. The highest incidence of epilepsy occurs at the extremes of life. Men are at higher risk than women for epilepsy.

Focal seizures are the most common seizure type, yet generalized seizures are more common in children. Seizures developing 1 week post-TBI occurs in 14-53% of the moderate to severe TBI survivors. 50% of TBI survivors with penetrating brain injuries develop epilepsy. In individuals aged 15 to 24, TBI is the leading cause of epilepsy.

Patho-anatomy/physiology

An impairment of the biochemical processes at the neurotransmitter and ion channel level causes hyperexcitability and neuronal hypersynchrony. Seizures are a result of this abnormal and excessive neuronal activity because of an imbalance between excitatory and inhibitory forces within the brain.

The primary excitatory neurotransmitter in the brain is glutamate, and the primary inhibitory neurotransmitter is gamma-aminobutyric acid (GABA). Antiepileptic drugs (AEDs) facilitate neuronal inhibition and/or reduce excitation.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Individuals in whom the sole cause of a seizure is a correctable condition, for example a metabolic disturbance without an underlying structural lesion, are rarely at risk for future epilepsy or recurrent seizures in the absence of recurrence of the condition.

The risk of seizure recurrence in someone with an unprovoked or idiopathic initial seizure is estimated to be 30-70% in the first 12 months, depending on seizure type and etiology. Abnormal neurologic exam, postictal paralysis, abnormal electroencephalogram (EEG), and strong family history of seizures increase the risk of seizure recurrence.

Approximately 60-70% of individuals whose seizures are completely controlled can eventually discontinue antiepileptic therapy.

Specific secondary or associated conditions and complications

Consequences and complications associated with seizures and epilepsy include but are not limited to:

• Impairment of consciousness
• Physical injuries during the event
• Anoxic injury to the brain
• Learning disabilities
• Memory loss
• Language deficits
• Impaired self-esteem
• Fatigue
• Mood disorders (e.g., anxiety, depression, adjustment disorders)
• Loss of independence and limitations in participation, including specific work activities and driving.

Side effects of AEDs are common and include osteoporosis, weight gain, negative cognitive impairments, nausea, sedation, and/or ataxia.

2. essentials of assessment

History

A comprehensive history is necessary to confirm seizure activity, to characterize the seizure, and to identify risk factors for seizure. An accurate description of surrounding events, including witness interview, helps identify sources that elicit seizures, the presence of any aura, and ictal and postictal behaviors.

• Aura may include abnormal smell or taste, deja vu feeling, or an intense feeling that a seizure is imminent.
• Patients or witnesses may report: generalized convulsions, repetitive movements, staring spells, visual or auditory disturbances, or dysesthesias

History should also include a comprehensive review of medications, alcohol or drug use/abuse, family history, and thorough medical history, including history of head trauma, stroke, neurodegenerative diseases, and intracranial infections. In patients with confirmed epilepsy, history should assess seizure control and the functional/social impact of seizures.

Differential diagnosis includes but is not limited to transient ischemic attacks, vaso-vagal/syncopal episodes, delirium, migraine headaches, movement disorders, and psychological factors.

Physical examination

A careful neurologic examination in the interictal period, including assessment of cortical function and mental status, is essential. Presence of TBI or other premorbid neurological disorder can mask signs and symptoms of seizure.  Thus, observation for subtle clues and symptoms is essential to seizure diagnosis.

The physical manifestation of a seizure is dependent on its classification:

• Generalized tonic-clonic seizures: Abrupt onset with loss of consciousness; generalized muscle rigidity, followed by jerking/twitching movements. Often followed by a postictal phase characterized by deep sleep with deep respirations and gradual awakening accompanied by a headache.
• Focal seizures with dyscognitive features (complex partial seizures): altered consciousness without loss of consciousness often associated with repetitive behaviors or automatisms (lip smacking, snapping fingers, facial grimacing). The postictal phase includes confusion, somnolence, and headaches.
• Absence seizures (typically occurs during childhood): staring spell with impaired consciousness; during is typically 5-10 seconds.
• Subclinical seizures: abnormal electroencephalographic activity without physically symptoms or signs.

The physical exam should be comprehensive to assist in searching for an underlying cause of seizure, such as infection or a systemic disorder.

Functional assessment

Depending on the cause and duration of the seizure, there can be subsequent impairments in mobility, self-care, behavior, cognition, mood, self-esteem, learning abilities, and speech/language. In mesial temporal sclerosis, the most commonly diagnosed focal structural abnormality in patients with epilepsy, associated neuropsychiatric impairments may include decreased memory, cognition, depression, anxiety, and psychiatric comorbidities.

Laboratory studies

Laboratory tests include:

• Comprehensive metabolic panel including sodium, glucose, calcium, magnesium, renal and liver function levels
• Hematology studies
• Toxicology screens
• Serum prolactin level (elevated post seizure, must be drawn within 1 hour of the event)
• Lumbar puncture is indicated if there is suspicion of a central neurologic infectious process

Imaging

Neuroimaging studies are typically indicated for evaluation of the brain structure. Magnetic resonance imaging (MRI) is preferred over computerized tomography (CT)¹¹, given that it facilitates better identification of structural causes of epilepsy, such as mesial temporal sclerosis, cortical dysplasia, brain tumors, vascular malformations, TBI, cerebral infarction/hemorrhages, and infectious process.

An epilepsy protocol for the MRI should be performed, which would ideally include the following:

• Standard T1-weighted images.
• T2-weighted fast spin-echo sequences.
• Gradient echo (T2) sequences.
• Fluid-attenuated inversion recovery sequences.
• Three-dimensional (3D) volume acquisition sequences with high definition of the gray-white junction; 3D fast spoiled gradient recalled echo acquisition at the steady state.

Functional imaging techniques such as positron emission tomography (PET), single-photon emission computerized tomography (SPECT), functional magnetic resonance imaging (fMRI), and magnetic resonance spectroscopy (MRS) are helpful in localizing/mapping epileptic foci and can aide in surgical management of epilepsy.

Supplemental assessment tools

EEG is an essential diagnostic tool when evaluating seizures. Epileptiform abnormalities usually increase the likelihood that the patient will experience another seizure over the next 2 years. EEG abnormalities can be nonspecific and a normal EEG does not rule out epilepsy. Long-term video EEGs are helpful in recording multiple seizures. Epileptiform discharges are associated with epilepsy, while nonepileptiform abnormalities are nonspecific EEG abnormalities that do not support the diagnosis of epilepsy.

Neuropsychological testing can be used in nonoperative or postoperative epilepsy patients to assess level of cognitive functioning. Results can assist with recommendations for vocational and cognitive rehabilitation.

Early predictions of outcomes

In individuals with TBI resulting in loss of consciousness or amnesia lasting less than thirty minutes (mild injury), there is a 0.5% cumulative five-year probability of seizures. In moderate injury, or loss of consciousness for 30 minutes to 24 hours or skull fracture, there is a 1.2% probability and for severe injuries (loss of consciousness or amnesia >24hours, cerebral contusion, SDH) there is a 10% probability.¹³

In hospitalized TBI patients with initial GCS of 13 to 15, the 2 year incidence of epilepsy is 8%. For GCS 3 to 8, the 2 year incidence is 16.8%.¹²

Refractory epilepsy requiring multiple medications is more likely in those with focal seizures due to underlying structural abnormalities, multiple seizure types, or comorbid developmental delays.

Environmental

Seizures can be triggered by environmental factors such as loud noises and flashing lights.

Environmental safety considerations include avoiding heights/climbing activities, scuba diving, and swimming alone.

Social role and social support system

Seizures and epilepsy can significantly impact functional independence, learning abilities, employability, insurability/financial resources, self-esteem, mood, ability to drive or operate heavy equipment, and vocational skills.

Support systems should provide resources within the home and the community to provide these patients, families, and support network with education, and counseling about seizure triggers, physical and psychosocial consequences of seizures, and coping with seizure/epilepsy diagnosis.

Professional Issues

States differ in their requirements for reporting seizure/epilepsy diagnoses to the Office of Driver Services. Physicians should be knowledgeable of their local state law and regulations regarding drivers with an active history of epilepsy.⁴

3. rehabilitation management and treatments

Available or current treatment guidelines

The following are recommendations for seizure prophylaxis with antiepileptic drugs (AEDs) in patients with TBI:⁵

• Immediate seizures (within first 24 hours) post-TBI do not require any additional prophylaxis after 7 days.
• Early seizures (between days 1 and 7) post-TBI should be treated for at least 24 months with AEDs, unless there was a casual time-limited intracranial abnormality (hydrocephalus, active hemorrhage, or infectious process). Early seizures are associated with a higher incidence of intracranial bleeding. Incidence of early seizures post-TBI decreases significantly with seizure prophylaxis the first 7 days post-TBI.
• Late seizures (after 7 days) post TBI should be treated for at least 24 months.
• Any seizure post-TBI that is considered status epilepticus, requires treatment with AEDs for at least 12-24 months.⁶
• Individuals with frequent seizures during the first year post-trauma are less likely to have seizure remission.⁷

Recommendations for seizure prophylaxis for newly diagnosed brain tumors:⁸

• Anticonvulsant medications are not proven effective in preventing initial seizures. Because of a lack of efficacy and potential side effects, prophylactic anticonvulsants should not be routinely used in patients with newly diagnosed brain tumors.
• In patients with brain tumors who have not had a seizure, tapering and discontinuing anticonvulsants after the first postoperative week is appropriate, particularly in those patients who are medically stable and who are experiencing anticonvulsant-related side effects.

At different disease stages

New onset/acute:

• Initial seizure: Treat acute underlying cause (metabolic derangements, alcohol and drug withdrawal, intracranial hemorrhages, infectious process, hypoxic events, drug toxicity). If there is strong evidence of an epileptogenic focus, then AED treatment should be initiated.
• Initiate an AED after 2 or more unprovoked seizures.
• Choice of AED should take into consideration drug effectiveness for the seizure type, potential adverse effects including neurological/cognitive impairments, medication interactions, comorbid medical conditions, age and sex (pregnancy risk), lifestyle, cost, and patient preferences.
• Monotherapy is preferred. 10-15%of people need two AEDs to control seizure activity. Up to 80% of patients can become seizure free on AED treatment.
• First-line antiepileptic drugs include:
  • Generalized tonic-clonic seizures: valproic acid or lamotrigine
  • Focal seizures: carbamazepine, lamotrigine, or phenytoin
  • Absence seizures: valproic acid or ethosuximide for absence seizures
• Routine follow up of patients on AEDs should include AED serum level, blood counts, albumin level (for phenytoin), and hepatic and renal function monitoring.
• After a seizure-free period of 2-4 years, it is reasonable to consider discontinuation of AEDs. Tapering should be performed slowly; there is no well-defined accepted tapering schedule. It should be done over a 2-3 month period at minimum.
• Treatment for seizures resistant to AEDs include: Vagal nerve stimulators or surgical procedures⁹ such as anteromedial temporal resection, corpus callosotomy, functional hemispherectomy (hemispherotomy), and multiple subpial transection.
• Status epilepticus: Benzodiazepines are the first line of treatment followed by phenytoin, barbiturates, and propofol.

Coordination of care

Medical care should be coordinated with measures to address psychosocial consequences. Treatment team should include primary care physician, neurologist, physiatrist, neurosurgeon, psychiatry/psychology, physical therapy, occupation therapy, speech therapy, and vocational therapist.

Emerging/unique Interventions

Emerging and unique interventions include transcranial magnetic stimulation and deep brain stimulation and are discussed below.

4. cutting edge/emerging and unique concepts and practice

Cutting edge concepts and practice

Up to one third of patients do not have a response to current AED’s and therapies. ¹⁹

Clobazam is a benzodiazepine which is used for treatment of various types of epilepsy, though only approved for Lennox-Gastuat syndrome in the United States. It has less sedating effects that other benzodiazepines and has high safety profile and efficacy in refractory epilepsy. ¹⁷

Deep brain stimulation (DBS) is a newer area of study that is useful in treating pharmacologically refractory epilepsy.¹⁰ Stimulation of the anterior nuclei of the thalamus (ANT) has been shown to be useful in adjunctive treatment of refractory epilepsy; the FDA approved DBS in the ANT as treatment for severe and refractory partial-onset seizures. Other deep brain areas, such as the subthalamic nucleus, caudate nucleus, cerebellum, are being studies as it relates to DBS. More well-controlled, larger studies are needed for other deep brain structures.

Transcranial magnetic stimulation (TMS) is another area being studies for improvement in refractory cases of epilepsy. Low-frequency high intensity repetitive TMS has a significant antiepileptic effect when delivered to epileptogenic areas of the brain and can also reduce interictal epileptic discharge improving psychological conditions in patients.¹⁵

Responsive neurostimulator (RNS) is a device that when implanted in the cortical or subcortical epileptogenic areas of the brain detects abnormal activity and delivers electrical stimulation to inhibit seizures prior to the onset of symptoms. Clinical trials are ongoing currently, but data supports the RNS device as a therapy option for refractory partial seizures.¹⁶

Other treatment options that are being explored include Synchrotron radiation and lactate dehydrogenase inhibition.^18,19

5. gaps in the evidence-based knowledge

Gaps in the evidence-based knowledge

Although there are multiple resources providing recommendations regarding prophylaxis for seizures/epilepsy in high risk populations such as patients with CNS pathology, there are limited references providing a consensus to develop evidence-based guidelines for prevention and treatment.

references

1. Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005 Apr. 46(4):470-2.
2. Beghi E, Carpio A, Forsgren L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia. 2010;51:671-675.
3. Moran NF, Poole K, Bell G, et al. Epilepsy in the United Kingdom: seizure frequency and severity, anti-epileptic drug utilization and impact on life in 1652 people with epilepsy. Seizure. 2004;13:425-433.
4. Shareef YS, McKinnon JH, Gauthier SM, Noe KH, Sirven JI, Drazkowski JF. Counseling for driving restrictions in epilepsy and other causes of temporary impairment of consciousness: how are we doing? Epilepsy Behav. 2009;14:550-552.
5. Temkin NR. Risk factors for posttraumatic seizures in adults. Epilepsia. 2003;44 Suppl 10:18-20.
6. Christensen J, Pedersen MG, Pedersen CB, Sidenius P, Olsen J, Vestergaard M. Long-term risk of epilepsy after traumatic brain injury in children and young adults: a population-based cohort study. Lancet. 2009;373:1105-1110.
7. Emanuelson I, Uvebrant P. Occurence of epilepsy during first 10 years after traumatic brain injury acquired in childhood up to the age of 18 years in the south western Swedish population-based series. Brain Inj. 2009;23:612-616.1. 64p.
8. Kerrigan S, Grant R. Antiepileptic drugs for treating seizures in adults with brain tumors. Cochrane Database Syst Rev. 2011 Aug 10;(8):CD008586.
9. Wyllie E, Comair YG, Kotagal P, Bulacio J, Bingaman W, Ruggieri P. Seizure outcome after epilepsy surgery in children and adolescents. Ann Neurol. 1998;44:740-748.
10. Wakerley B, Schweder P, Green A, Aziz T. Possible seizure suppression via deep brain stimulation of the thalamic ventralis oralis posterior nucleus. J Clin Neurosci. 2011;18:972-973.
11. Salmenpera TM, Duncan JS. Imaging in epilepsy. Journal of Neurol Neurosurg Psychiatry. 2005(76): iii2-iii10.
12. EnglanderJ, Bushnik T, et al. Analyzing risk factors for late posttraumatic seizures: a prospective, multicenter investigation. Arch Phys Med Rehabil. 2003; 84 (3): 365
13. Annegers JF, Hauser WA, et al. A population-based study of seizures after traumatic brain injuries. N Engl J Med. 1998;338 (1): 20
14. SANTE Trial of Deep Brain Stimulation in Epilepsy Published; FDA Panel Recommends Approval in Close Vote. Medscape. Mar 19, 2010
15. Sun W, Mao W, et al. Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: A controlled clinical Study. Epilepsia 2012; 53: 1782-1789
16. Bergey G, Morrell M, et al. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology. 2015; 84: 810-817
17. Gauthier A, Mattson R. Clobazan: A safe, efficacious, and newly rediscovered therapeutic for epilepsy. CNS Neuroscience & Therapeutics; 2015; 21: 543-548.
18. Romanelli P, Bravin A, et al. New radiosurgical paradigms to treat epilepsy using synchrotron radiation. Epilepsy Toward the Next Decade. 2014; 231-236
19. Rho J, Inhibition of Lactate Dehydrogenase to Treat Epilepsy. N Engl J Med. 2015; 373:187-189
20. Sada N, Lee S, Katsu T, Otsuki T, Inoue T. Epilepsy treatment: targeting LDH enzymes with a stiripentol analog to treat epilepsy. Science 2015;347:1362-1367

Source: https://now.aapmr.org/seizures-and-epilepsy/

[NEWS] Funding boost for AI-based epilepsy monitoring

September 8th, 2020

Routinely recorded EEG is used to build a personalised model of the brain Credit: monsitj

University spinout company Neuronostics has received funding to develop its BioEP platform, an AI-based system for faster, more accurate diagnosis of epilepsy and to monitor response to treatment with anti-epileptic drugs (AEDs).

BioEP works by creating mathematical models of the brain using short segments of electroencephalogram (EEG) recordings. Computer simulations rapidly reveal the ease with which seizures can emerge and form the basis of the BioEP seizure risk score.

Neuronostics is developing BioEP in partnership with the University of Birmingham, where mathematician Professor John Terry, co-founder of the company, is Director of Centre for Systems Modelling & Quantitative Biomedicine.

Professor Terry’s research aims to improve diagnosis and treatment for people with epilepsy. He explains: “We build personalised models of the brain using EEG that is routinely collected when seeking to diagnose epilepsy. From these models the risk of epilepsy can be quickly determined. In contrast, multiple EEG recordings are often required to reach a clinical diagnosis at present. This is expensive, time-consuming, and exposes people with suspected epilepsy to risk.”

The funding, from the National Institute for Health Research (NIHR), will enable the research partnership to progress a prototype clinical platform that can provide a risk score showing the individual’s susceptibility to seizures. This measurement can be used in diagnosis, and as an objective assessment of response to treatment with AEDs, resulting in faster seizure control for people with epilepsy.

The clinical utility of the BioEP seizure risk score has already been demonstrated in a cohort of people with idiopathic generalized epilepsy.¹ Using just 20 seconds of an EEG recording that would be considered inconclusive in the current clinical pathway, BioEP achieved 72% diagnostic accuracy. This matches the accuracy achieved in the current diagnostic pathway, which typically takes a year, and involves multiple follow-ups.²

The company is interested to hear from commercial partners in EEG hardware manufacturing, digital EEG analysis, and companion diagnostics or prognostics, and research and clinical partners with interests in epilepsy, traumatic brain injury and dementia. For collaboration enquiries please email: info@neuronostics.com.

The NIHR funding was delivered through the AI in Health and Care Award, part of the NHS AI Lab, which was launched by the UK Government earlier this year to accelerate the adoption of Artificial Intelligence in health and care.

More information:
References
1. H Schmidt et al. A computational biomarker of idiopathic generalized epilepsy from resting state EEG Epilepsia 57: e200-e204 (2016).
2. S Smith. EEG in the diagnosis, classification, and management of patients with epilepsy Journal of Neurology, Neurosurgery & Psychiatry 76: ii2-ii7 (2005).

For further media information please contact: Ruth Ashton, Reputation & Communications Development Manager, University of Birmingham Enterprise, email: r.c.ashton@bham.ac.uk.

About Neuronostics

Neuronostics was established in 2018 and is focussed on developing clinical decision support tools and at home monitoring devices for people with suspected neurological conditions. Neuronostics is currently Medilink SW Start up of the Year and has been supported by grant funding in excess of £1M. Neuronostics’ first product—BioEP—is a revolutionary, patented, biomarker of the susceptibility to seizures in the human brain, informed by clinical EEG recordings.

About the University of Birmingham

The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 6,500 international students from over 150 countries.

About NIHR

The National Institute for Health Research (NIHR) is the nation’s largest funder of health and care research. The NIHR:
● Funds, supports and delivers high quality research that benefits the NHS, public health and social care
● Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
● Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
● Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
● Partners with other public funders, charities and industry to maximise the value of research to patients and the economy

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.

Provided by University of Birmingham

Source: https://sciencex.com/wire-news/361008258/funding-boost-for-ai-based-epilepsy-monitoring.html

[BOOK Chapter] Medication: Epilepsy – Abstract References Resources

Abstract

This chapter covers the use of medication in epilepsy, specific information about antiepileptic medication and what to do if there are issues or concerns about an individual’s medication.

References

1. Berg A (2008) Risk of recurrence after a first unprovoked seizure. Epilepsia 49(Suppl 1):13–18CrossRefGoogle Scholar
2. Brodie M, Barry S, Bamagous G, Norrie J, Kwan P (2012) Patterns of treatment response in newly diagnosed epilepsy. Neurology. 15:78(20)1548–1554Google Scholar
3. Epilepsy Action (2019) Travel advice for people with epilepsy. https://www.epilepsy.org.uk/info/daily-life/travelling-abroad. Accessed 03 Jan 2019
4. Epilepsy Society (2019) Generic and branded anti-epileptic drugs. https://www.epilepsysociety.org.uk/generic-and-branded-anti-epileptic-drugs. Accessed 03 Jan 2019
5. House of Commons and Social Care Committee (2019) Drugs policy: medicinal cannabis. https://publications.parliament.uk/pa/cm201719/cmselect/cmhealth/1821/1821.pdf. Accessed 03 Jan 2019
6. Medicines and Healthcare Products Regulatory Agency (2018) Valproate use by women and girls. Updated 2019. https://www.gov.uk/guidance/valproate-use-by-women-and-girls. Accessed 02 Jan 2020
7. Medicines for Children (2017) Frequently asked questions (FAQs). https://www.medicinesforchildren.org.uk/frequently-asked-questions-faqs. Accessed 03 Jan 2019
8. Mohanraj R, Brodie M (2006) Diagnosing refractory epilepsy: response to sequential treatment schedules. Eur J Neurol 13(3):277–282CrossRefGoogle Scholar
9. National Institute for Health and Care Excellence (NICE) (2012) Epilepsies: diagnosis and management. Clinical Guideline CG137. Updated 2019. https://www.nice.org.uk/guidance/cg137. Accessed 02 Jan 2020
10. National Institute for Clinical Excellence (NICE) (2016) Controlled drugs: safe use and management. NICE Guidance NG46. https://www.nice.org.uk/guidance/ng46. Accessed 02 Jan 2020
11. Shakespeare J, Sisodiya S (2019) Guidance document on valproate use in women and girls of childbearing years. https://www.rcog.org.uk/globalassets/documents/guidelines/valproate-guidance-march-2019.pdf. Accessed 02 Jan 2020

Resources

1. British National Formulary (BNF); Children’s British National Formulary (BNFC). https://bnf.nice.org.uk/
2. Epilepsy Society (2016) Contraception and Epilepsy. https://www.epilepsysociety.org.uk/contraception-and-epilepsy#.XiwkV2j7TIU. Accessed 25 Jan 2020
3. Medicines for Children (2017) Helping your child to swallow tablets. https://www.medicinesforchildren.org.uk/sites/default/files/contenttype/leaflet/pdf/Guide%20to%20swallowing%20tablets%2030.11.17.pdf. Accessed 25 Jan 2020
4. Medicines Healthcare products Regulatory Authority (MHRA) (2017) Branded anti-seizure medication information. https://www.gov.uk/drug-safety-update/antiepileptic-drugs-updated-advice-on-switching-between-different-manufacturers-products
5. NHS (2018) What is a controlled medicine (drug)? https://www.nhs.uk/common-health-questions/medicines/what-is-a-controlled-medicine-drug/. Accessed 02 Jan 2020

via Medication: Epilepsy | SpringerLink

[ARTICLE] Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience – Full Text

Abstract

Until the early 1990s, a limited number of antiepileptic drugs (AEDs) were available. Since then, a large variety of new AEDs have been developed and introduced, several of them offering new modes of action. One of these new AED families is described and reviewed in this article. Levetiracetam (LEV) and brivaracetam (BRV) are pyrrolidone derivate compounds binding at the presynaptic SV2A receptor site and are thus representative of AEDs with a unique mode of action. LEV was extensively investigated in randomized controlled trials and has a very promising efficacy both in focal and generalized epilepsies. Its pharmacokinetic profile is favorable and LEV does not undergo clinically relevant interactions. Adverse reactions comprise mainly asthenia, somnolence, and behavioral symptoms. It has now been established as a first-line antiepileptic drug. BRV has been recently introduced as an adjunct antiepileptic drug in focal epilepsy with a similarly promising pharmacokinetic profile and possibly increased tolerability concerning psychiatric adverse events. This review summarizes the essential preclinical and clinical data of LEV and BRV that is currently available and includes the experiences at a large tertiary referral epilepsy center.

Introduction

Since the introduction of bromides as the first effective antiepileptic drugs (AEDs),¹ chronic AED treatment that consisted of the sustained prevention of epileptic seizures has remained the standard of epilepsy therapy.² Before to the introduction of the newer generation of AEDs, a limited number of drugs were available that addressed the blockade of sodium channels, acting on gamma-aminobutyric acid (GABA) type A receptors, or interacting with calcium channels as the leading modes of action.³ With the introduction of the newer AEDs a heterogeneous group of drugs appeared, some of them offering new mechanisms of action² including the blockade of GABA aminotransferase (vigabatrin [VGB]), GABA re-uptake from the synaptic cleft (tiagabine [TGB]), the modulation of calcium channels (gabapentin [GBP], pregabalin [PGB]), the selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolproprionic acid (AMPA) receptor antagonism (perampanel [PER]), and the binding to the presynaptic SV2A receptor site which is the unique mode of action of levetiracetam (LEV) and brivaracetam (BRV), the AEDs this review will cover. The authors will summarize the development of both compounds as derivatives of piracetam, review the currently available preclinical and clinical data, and discuss the question of whether BRV has the potential to be recognized as being superior to LEV and if it can replace it as the standard AED with the main mode of action both AEDs reflect.[…]

 

Continue —-> Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience – Bernhard J. Steinhoff, Anke M. Staack, 2019

[Abstract] Pharmacology and epilepsy : update on the new antiepileptic drugs

Abstract

New antiepileptic drugs are regularly approved for treatment and offer large therapeutic opportunities. Efficacy of these drugs is relatively similar on-label with different mechanisms to be combined for a synergic effect. Treatments such as cannabidiol have benefitted from large media coverage despite limited clinical evidence so far. The objective of antiepileptic drugs is to stop the recurrence of epileptic seizures with as few adverse events as possible. When confronted to a difficult-to-treat epilepsy, referral to a specialised centre is strongly advised. The aim is to confirm that the diagnosis is correct, that the treatment is well adapted (indication, pharmacokinetic and compliance) and to evaluate the indication for non-pharmacological treatments such as epilepsy surgery.

 

via [Pharmacology and epilepsy : update on the new antiepileptic drugs]. – Abstract – Europe PMC

[BLOG POST] Which are the safest epilepsy drugs in pregnancy? – Neurochecklists Updates

Maternal use of antiepileptic agents during pregnancy and major congenital malformations in children

Bromley RL, Weston J, Marson AG.

JAMA 2017; 318:1700-1701.

Abstract

CLINICAL QUESTION:

Is maternal use of antiepileptic drugs during pregnancy associated with major congenital malformations in children?

BOTTOM LINE:

Certain antiepileptic drugs were associated with increased rates of congenital malformations (eg, spina bifida, cardiac anomalies). Lamotrigine (2.31% in 4195 pregnancies) and levetiracetam (1.77% in 817 pregnancies) were associated with the lowest risk and valproate was associated with the highest risk (10.93% in 2565 pregnancies) compared with the offspring of women without epilepsy (2.51% in 2154 pregnancies).

Also see

Weston J, Bromley R, Jackson CF, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev 2016; 11:CD010224.

Both references are cited in the neurochecklist:

Antiepileptic drugs (AEDs): teratogenicity

Abstract link 1

Abstract link 2

Drugs firms ‘creating ills for every pill’. Publik15 on Flickr. https://www.flickr.com/photos/publik15/3415531899

via Which are the safest epilepsy drugs in pregnancy? – Neurochecklists Updates

[BLOG POST] The 29 proven anti-epilepsy drugs…and their practical checklists