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Article structure

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Classification

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Seizure types

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An epileptic seizure is "a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain".[1]

There are three main types of seizures: partial, generalized, and unclassified. In terms of their origin within the brain, seizures may be described as either partial (focal) or generalized. Partial seizures only involve a localized part of the brain, whereas generalized seizures involve the the whole of both hemispheres. The term secondary generalisation may be used to describe a partial seizure that later spreads to the whole of the cortex and becomes generalized.

While most seizures can be neatly split into partial and generalized, some cannot. For example, a seizure that is generalized only within one hemisphere of the brain. Alternatively, there may be many focal points (multifocal seizures) that are distributed in a symmetrical or asymmetrical pattern.

Status epilepticus
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Epilepsy syndromes

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Signs and symptoms

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Causes

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Triggers

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  • Flickering light[2]
  • Thinking music[3]
  • Eating[4]
  • Praxis [Exercise?][5]
  • Somatosensory [Explain][6]
  • Proprioceptive [Explain][7]
  • Reading[8]
  • Exposure to hot water[9]
  • Being startled[10]

Mechanism

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  • DO11.10 has bravely volunteered to tack this subject.
Dump
  • The chemistry of neurons, channels (sodium, calcium), GABA.
  • The structure of how neurons link up and migrate to the appropriate part of the brain.
  • The concept of a seizure threshold.
  • The role of the corpus callosum in spreading a seizure between hemispheres.
  • What we learn from animal models.
  • A seizure is "excessive or synchronous neuronal activity in the brain". What makes it excessive (excite/inhibit)? Why does it become synchronous?
  • How does a partial-onset seizure spread to become generalised? Why do some remain partial?
  • How goes a general-onset seizure start without a focus?
  • Why are absence seizures such an exception (they have their own drugs, to some extent, and are one of the idiopathic epilepsies).
  • Are seizures damaging in themselves (controvesial)? Perhaps some more so than others (infantile spasms are one of the "catastrophic" epilepsy syndromes).
  • Why are some epilepsies "benign"?
  • What stops a seizure (self-limiting)? Why do some not stop (status)?

Diagnosis

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Treatment

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Chronic
  • Drugs are often first chosen based on the seizure type: partial-onset, generalised-onset, and absence seizures. Also, some rare epileptic syndromes have become associated with particular treatments (e.g., infantile spasms) and some drugs have achieved "orphan drug" status for certain epilepsies.
  • Monotherapy, polytherapy. Approval for "adjunctive use" or "initial monotherapy".
  • Difficult to arrange placebo-controlled trials for monotherapy. Alternative trial protocols are used.
  • No cure (other than surgery), nor preventative (anti-epileptogenic).
  • Most drugs have cognitive side effects, plus other effects.
  • Problems with some drugs and pregnancy (esp. valproate).
  • Modern drugs are more expensive but not necessarily any more effective. Supposed to be better tolerated, but few studies support this.
  • Ketogentic diet is as effective as any modern anticonvulsant but is traditionally reserved for refractory epilepsy in children and is limited by resources to monitor the diet.
  • Vagal nerve stimulator may help some but very rarely leads to seizure freedom. Can reduce seizure frequency but also (with use of a magnet switch) can be used to shorten a seizure in some people.
  • Surgery is rationed and only those likely to benefit are chosen. However, it has pretty good success rates and is the only cure.
  • Some surgery is palliative, not curative.
Emergency
Surgery

Prognosis

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  • Many childhood epilepsies disappear, esp. the idiopathic epilepsies.
  • Some epilepsies are regarded as "benign".
  • Some "catastrophic" epilepsies in infants have a terrible prognosis both for continued epilepsy and also mental function.
  • The brain tends to become calmer as we reach adulthood, which can naturally reduce seizure frequency. (hand waving here).
  • If someone becomes seizure-free on medication or post-surgery, then the medication may be gradually weaned and the epilepsy may have gone.
  • Uncontrolled epilepsy results in an increased risk of early death.
  • Sudden unexpected death in epilepsy (SUDEP).

Epidemiology

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Society

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  • Discuss legal implications, stigma, disability rights. Issues regarding how society handles the person with epilepsy and individual seizures. Briefly mention issues regarding photosensitive epilepsy.

History

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I'll have a go at drafting this section. Any contributory sources or facts or questions are welcome. -- Colin.

Here's a quickly thrown-together bunch of paragraphs on the history of epilepsy. Some of it is sourced to the AES History.[11] It is pretty rough at the moment.

Understanding

A set of law codes from ancient Babylon, known as the Code of Hammurabi and dating ca. 1760 BC, may contain the earliest written mention of epilepsy. Law 278 allows the return of a slave who develops epilepsy within a month of purchase.[12] Later Babylonian scholars inscribed their medical knowledge into stone tablets know as the Sakikku (meaning All Diseases). This dates from the reign of the Babylonian king Adad-apla-iddina of the Second Dynasty of Isin--reckoned to be between 1067 and 1046 BC. Many types of seizures are described, each attributed to a certain demon or departed spirit and given a prognosis.[13]

The earlised Chinese document to discuss epilepsy (specifically generalized convulsive seizures) comes from around 770-221 BC, in The Yellow Emperor's Classic of Internal Medicine, Huang Di Nei Ching.[14]

Hippocrates, On the Sacred Disease. Was "so-called". Superfluity of phlegm.

Galen, in 375 AD distinguished two forms of epilepsy. idiopathic epilepsy originated in the brain; symptomatic epilepsy from elsewhere in the body.

The ILAE's 1981 classification of seizure types and the 1989 classification of epilepsies are landmarks in our ability to describe and analyse the disease.

Throughout the 1970s and 1980s, researchers developed new ways to test drugs and understand the basic mechanisms of epilepsy. These included in vitro techniques for studying neurons; chronic epilepsy models in animals; and the breeding of genetic strains of animals highly susceptible to developing epilepsies.

Electrophysiology

Luigi Galvani discovered animal electricity (1791), and founded electrophysiology. Richard Caton discovered electrical activity in the brain (1875). Vladimir Vladimirovich Pravdich-Neminsky first recorded EEG in animals (1912). N. Cybulsky and X. Jelenska-Macieszyna recorded an EEG during an induced seizure in a dog (1914). In 1929, Hans Berger recorded EEG in humans and later studied EEG changes in epilepsy. This technology was rapidly applied to the diagnosis and treatment of epilepsy, and transformed our understanding of the disease. It was now possible to locate a seizure focus prior to surgery. By 1966, closed-circuit television enabled the routine simultaneous recording of EEG and clinical seizures.

Treatments

Many remedies were tried for epilepsy; all were ineffective until the discovery of potassium bromide. Sir Charles Locock (obstetrician who delivered Queen Victoria's babies) learned that bromide caused impotence and had tried it successfully on some women troubled by "sexual excitement". He believed it might therefore help with epilepsy (which many at the time associated with masturbation). He reported his results at a meeting of the Royal Medical and Chirurgical Society in London in 1957. The treatment took a while to catch on, but from 1870s it was the mainstay of medicinal therapy. Unfortunately, bromide was only weakly effective and quite unpleasantly toxic in high doses.

In 1912, the German drug company Bayer launched a new sedative and hypnotic called Luminal (phenobarbital). A young doctor, Alfred Hauptmann, gave this barbiturate drug to his epilepsy patients as tranquiliser and discovered it reduced their epileptic attacks. Some patients became seizure free and once bromide was removed from their regime, many improved physically and mentally.[15]Phenobarbital was the first really effective anticonvulsant and led to bromide's relegation to veterinary medicine. By 1918, phenobarbital was the dominant anticonvulsant, and remained so for 20 years. Its cheapness means that it remains the most widely used anticonvulsant in the developing world, though it is now considered only for second- or third-line use in more affluent countries.[16]

In 1937, two Boston neurologists, Tracy Putnam and H. Houston Merritt, devised the first animal experiments for identifying promising anticonvulsants from candidate drugs. Of the 19 drugs they planned to test, the first proved the most effective: sodium diphenyl hydantoinate, commonly known as phenytoin and marketed as Dilantin. By 1938, favourable patient trials led to the introduction of this important drug to clinical practice. Unlike phenobarbital, it did not produce sedation at theraputic doses, and is still regarded as an effective and useful anticonvulsant.

While many seizure types were susceptible to the new drugs, absence seizures proved more difficult to treat. A new animal model of epilepsy, where seizures were induced by the drug pentamethylenetetrazol (Metrazol), was used to identify that the drug trimethadione could be effective. William G. Lennox tested the drug on patients in 1945 and it was introduced in 1946. In 1955, trimethadione was replaced by the less toxic ethosuximide (Zarontin).

First synthesized in 1882, valproic acid was believed to be a metabolically inert solvent for organic compounds. In 1962, French researcher Pierre Eymard serendipitously discovered valproic acid's antiseizure activity while using it as a vehicle for a number of other compounds that were being screened for anti-seizure activity. Clinical trials in 1964 led to adoption in Europe in the late 1960s but the US took until 1978. Valproic acid is effective for treating a number of generalized seizure types, including absence seizures.[17]

Surgery for epilepsy began in earnest with Canadian neurosurgen Wilder Penfield in 1936. He and Herbert Jasper used EEG prior to surgery to identify the focus of the seizure and therefore the part to resect.

Brain imaging

Pneumoencephalography was used in the 1930s as a diagnostic procedure. It involved replacing the cerebrospinal fluid with air so that sufficient contrast could be achieved on x-ray. It was painful and stressful and only useful in a minority of cases. Huge improvement came in the early 1970s, when computerized tomography (CT) was invented. However, subtle changes to brain density were not picked up, and it wasn't until the 1980s that magnetic resonance imaging (MRI) enabled physicians to safely and precisely image the brain. MRI remains the definitive tool for identifying structural pathology in the brain.

Positron-emission tomography (PET) appeared in the late 1970s, and helped the investigation of epilepsy by highlighting areas of increased metabolic activity. Functional MRI (fMRI) is now also used for this purpose, and to identify vital brain regions that must be preserved during resective surgery.

Individuals: John Hughlings Jackson, Herbert Jasper, Wilder Penfield, H. Houston Merritt, William G. Lennox, Henri Gastaut.


Research

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Notes

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  1. ^ Engel J Jr. Report of the ILAE classification core group. Epilepsia. 2006 Sep;47(9):1558–68. PMID 16981873.
  2. ^ ILAE
  3. ^ ILAE
  4. ^ ILAE
  5. ^ ILAE
  6. ^ ILAE
  7. ^ ILAE
  8. ^ ILAE
  9. ^ ILAE
  10. ^ ILAE
  11. ^ Goldensohn ES, Porter RJ, Schwartzkroin PA. The American Epilepsy Society: an historic perspective on 50 years of advances in research (PDF). Epilepsia. 1997 Jan;38(1):124–50. PMID 9024195.
  12. ^ Temkin, 47. Not all scholars interpret the word bennu as epilepsy.
  13. ^ Wilson J, Reynolds E. Texts and documents. Translation and analysis of a cuneiform text forming part of a Babylonian treatise on epilepsy. Med Hist. 1990 Apr;34(2):185-98. PMID 2187129. Further reading: Marten Stol. Epilepsy in Babylonia. Brill Academic Publishers; 1993. ISBN 9072371631.
  14. ^ Lai CW, Lai YH. History of epilepsy in Chinese traditional medicine. Epilepsia. 1991 May-Jun;32(3):299-302. PMID 2044493. DOI:10.1111/j.1528-1157.1991.tb04655.x.
  15. ^ Scott, DF. The History of Epileptic Therapy. Taylor & Francis; 1993. pp59-65. ISBN 1850703914.
  16. ^ Kwan P, Brodie MJ. Phenobarbital for the treatment of epilepsy in the 21st century: a critical review. Epilepsia. 2004 Sep;45(9):1141-9. PMID 15329080.
  17. ^ Henry TR. The history of valproate in clinical neuroscience] (PDF). Psychopharmacol Bull. 2003;37 Suppl 2:5-16. PMID 14624229.

Bibliography

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Bibliography

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Books

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  • Engel J, Pedley TA, Aicardi J, Dichter MA, Moshe S. Epilepsy: A Comprehensive Textbook. 2nd ed. Lippincott Williams & Wilkins; 2007. ISBN 0781757770.
  • Arzimanoglou A, Guerrini R, Aicardi J. Aicardi's Epilepsy in Children. 3rd ed. Lippincott Williams & Wilkins; 2002. ISBN 0781726980.
  • Shorvon S, Perucca E, Fish D, Dodson WE, editors. The Treatment of Epilepsy. 2nd ed. Blackwell Science Ltd; 2004. ISBN 0632060468.
  • Levy RH, Mattson RH, Meldrum BS , Perucca E. Antiepileptic Drugs. 5th ed. Lippincott Williams & Wilkins; 2002. ISBN 0781723213.
  • Panayiotopoulos CP. A Clinical Guide to Epileptic Syndromes and Their Treatment. 2nd ed. London: Springer-Verlag; 2007. ISBN 1846286433.
  • Roger J, Dravet C, Bureau M, Genton P, Tassinari CA, Wolf P, editors. Epileptic Syndromes in Infancy, Childhood and Adolescence. 4th ed. John Libbey Eurotext; 2005. ISBN 2742005692.
  • Bromfield EG, Cavazos JE, Sirven JI, editors. An Introduction to Epilepsy. Bethesda (MD): National Institute of Neurological Disorders and Stroke; 2006.
    • Shame the text has no inline citations, only a list of references for each chapter. -- Colin.

Journals

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Epilepsy Currents is the journal of the AES. Freely available online to all readers.

Web sites

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Probably the most useful resource for international facts and figures. The campaign website also contains reports from around the world, though it doesn't seem to have moved on since 2005.
Has a few interesting resources. The History and the Social Consequences factsheets look promising but basic.
Has a large number of articles, literature reviews and other information pages for the professional. Some are reprints of work published in journals; others seem to be written for NSE.
The authority on classification and terminology. Useful glossary and extensive information on seizure types and syndromes.
Loads of clinical overviews of various topics. Not as highly regarded as established peer-reviewed print journals.

Clinical guildelines

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Comprises a number of PDF documents that contain a wealth of UK-focused data and guidelines built on evidence-based-medicine.
These Scottish guidelines, like the NICE equivalent for England & Wales, are thoroughly reviewed and evidence-based.
A substantial number of guidelines with an American flavour. Often jointly supported by the American Epilepsy Society.