Causes of Epilepsy and Seizures

Causes of Epilepsy and Seizures Contents (Jump to) Introduction to Epilepsy Seizures Causes of Epilepsy Conclusion References Figures Appendix Introduction to Epilepsy Epilepsy is the oldest known brain disorder dating back as early as 2080BC (Cascino et al., 1995). It was first identified as a disease by Dr Jon Hughlings Jackson in 1880 who defined it as â€Å"An occasional, sudden, massive, rapid and local discharge or the grey matter† (Scott, 1978). This definition has been confirmed 50 years later by Electroencephalography. A more recent definition was devised stating â€Å"Epilepsy is a neurological disorder in which the nerve cell activity in your brain is disturbed, causing a seizure during which you experience abnormal behaviour, symptoms and sensations, including loss of consciousness.†(Scambler, 1989) Worldwide, it is estimated that there are 65 million people living with epilepsy with almost 80% of the cases reported occurring in the developing world (Ngugi et al., 2010). Within the UK, the prevalence is between 1 in 40/70,000 which equates to 3% of the population will develop epilepsy in their lifetime. Recurrent seizures are the hallmark characteristic of an epileptic. If an individual has one seizure early in their lives then none thereafter, they are said to have had an epileptic seizure but do not suffer from epilepsy. (Duncan et al., 2006) Seizures A seizure is abnormally excessive neuronal activity localised to a particular area of the brain known as the cerebral cortex causing a disruption to normal brain function. These cortical discharges will transmit to the muscles causing convulsions or commonly referred to as a fit. Figure 1 Generalised seizure with neuronal activation in both hemisphere Classifying seizures is done based on the site of the brain which the seizure begins. This will be either; Partial – where the onset of seizure is localised to one part of the hemisphere (fig. 1), Generalised – where the onset of the seizure is across both hemispheres (fig. 2) or Secondary generalised – where a partial seizure later spreads to involve the majority of the 2 cerebral hemispheres (Duncan et al., 2006). Figure 2 Partial seizure with neuronal activation in one hemisphere The International League Against Epilepsy (ILAE) have defined 6 main types of seizures: Clonic, Tonic, Tonic-Clonic, myoclonic, absence and atonic (Solodar, 2014), with all having the shared characteristic of syncope. Tonic-clonic seizures (grand mal seizures) are the most common and typically last 30 seconds with an initial back arching motion (tonic phase), followed by severe shaking of body limbs (clonic phase) in which sufferers can become incontinent and bit their tongue (fig. 3). Myoclonic seizures consist of muscle spasms throughout the body, while absence seizures only display mild symptoms such as a slight head turn or repetitive eye blinking (Engel and Pedley, 2008). Figure 3 Tonic and Clonic phases of a seizure Causes of Epilepsy Majority of cases are termed idiopathic, meaning there is no known reason for the disorder in that individual. The difference in causes amongst the general population can be seen in figure 4. Genetic factors can causes epilepsy as can environmental factors. In general it is a combination of the two which go on to cause someone to become epileptic. Over 500 genes have been identified to be linked to the disorder if mutated with some making individuals more sensitive to environmental conditions that can initiate seizures (Sanchez-Carpintero Abad et al., 2007). Some symptomatic causes of epilepsy include; brain tumours, strokes, low oxygen during birth, head injuries during birth or during a person’s lifetime, infections such as meningitis or anything which causes damage to the brain (Chang and Lowenstein, 2003). Figure 4 Causes of epilepsy amongst the general population Conclusion Epilepsy is a condition which has a host of causes as have been highlighted. It is the category of seizure within the brain an individual has which will determine the type of seizure they have and the altered body state which is displayed. This can be a very distressing disorder for sufferers as they are unable to control when they have a seizure and could occur at a very dangerous time such as whilst driving. The effective management via medication, surgery or lifestyle changes can reduce a person’s chance of suffering future seizures. Unfortunately in the majority of cases, the cause is unknown. This makes it highly difficult to target the disease for a cure, therefore minimising the probability of a seizure is the next best thing. References CASCINO, G., HOPKINS, A. O. SHORVON, S. D. 1995. Epilepsy, London, Chapman Hall Medical. CHANG, B. S. LOWENSTEIN, D. H. 2003. Epilepsy. N Engl J Med, 349, 1257-66. DUNCAN, J. S., SANDER, J. W., SISODIYA, S. M. WALKER, M. C. 2006. Adult epilepsy. Lancet, 367, 1087-100. ENGEL, J., JR. PEDLEY, T. A. 2008. Epilepsy : a comprehensive textbook, Philadelphia, Pa. ; London, Wolters Kluwer/Lippincott Williams Wilkins. NGUGI, A. K., BOTTOMLEY, C., KLEINSCHMIDT, I., SANDER, J. W. NEWTON, C. R. 2010. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia, 51, 883-890. SANCHEZ-CARPINTERO ABAD, R., SANMARTI VILAPLANA, F. X. SERRATOSA FERNANDEZ, J. M. 2007. Genetic causes of epilepsy. Neurologist, 13, S47-51. SCAMBLER, G. 1989. Epilepsy, London, Tavistock / Routledge. SCOTT, D. 1978. About epilepsy, London, Duckworth. SOLODAR, J. 2014. Commentary: ILAE Definition of Epilepsy. Epilepsia, 55, 491. Figures ENGEL, J., JR. PEDLEY, T. A. 2008. Epilepsy : a comprehensive textbook, Philadelphia, Pa. ; London, Wolters Kluwer/Lippincott Williams Wilkins. – figures 1 2 http://www.doctortipster.com/10291-generalized-tonic-clonic-epilepsy-seizures-grand-mal-seizures-clinical-presentation.html figure 3 http://www.cureepilepsy.org/egi/about.asp figure 4 Appendix Reference Type: Book Record Number: 1988 Author: Cascino, Gregory, Hopkins, Anthony October and Shorvon, S. D. Year: 1995 Title: Epilepsy Place Published: London Publisher: Chapman Hall Medical Edition: 2nd ed / edited by Anthony Hopkins, Simon Shorvon and Gregory Cascino. Short Title: Epilepsy ISBN: 0412543303 :  ¹95.00 Accession Number: b9561325 Call Number: 616.853 20 British Library DSC 95/22799 British Library STI (B) GV 05 blsrissc Keywords: Epilepsy. Notes: GB9561325 bnb 2362 Previous ed.: 1987. Includes bibliographies and index. Research Notes: Useful book, especially for historical aspects. Uses different terminology for seizures than other material, possibly due to age of print Reference Type: Journal Article Record Number: 2037 Author: Chang, B. S. and Lowenstein, D. H. Year: 2003 Title: Epilepsy Journal: N Engl J Med Volume: 349 Issue: 13 Pages: 1257-66 Epub Date: 2003/09/26 Date: Sep 25 Short Title: Epilepsy Alternate Journal: The New England journal of medicine ISSN: 0028-4793 DOI: 10.1056/NEJMra022308 Accession Number: 14507951 Keywords: Cerebral Cortex/pathology/physiopathology Electroencephalography Epilepsy/classification/etiology/pathology/*physiopathology Hippocampus/pathology Humans Ion Channels/physiopathology Neuroglia/physiology Sclerosis Thalamus/physiopathology Notes: 1533-4406 Chang, Bernard S Lowenstein, Daniel H NS39950/NS/NINDS NIH HHS/United States Journal Article Research Support, U.S. Govt, P.H.S. Review United States N Engl J Med. 2003 Sep 25;349(13):1257-66. Research Notes: Good overview of the disorder with relevant sections around the causes Author Address: Comprehensive Epilepsy Center, Department of Neurology, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, USA. Database Provider: NLM Language: eng Reference Type: Journal Article Record Number: 10337 Author: Duncan, J. S., Sander, J. W., Sisodiya, S. M. and Walker, M. C. Year: 2006 Title: Adult epilepsy Journal: Lancet Volume: 367 Issue: 9516 Pages: 1087-100 Epub Date: 2006/04/04 Date: Apr 1 Short Title: Adult epilepsy Alternate Journal: Lancet ISSN: 0140-6736 DOI: 10.1016/s0140-6736(06)68477-8 Accession Number: 16581409 Keywords: Adult Aged Anticonvulsants/adverse effects/*therapeutic use Drug Resistance/*genetics Electroencephalography *Epilepsy/diagnosis/drug therapy/physiopathology Humans Incidence Infant Pharmacogenetics Abstract: The epilepsies are one of the most common serious brain disorders, can occur at all ages, and have many possible presentations and causes. Although incidence in childhood has fallen over the past three decades in developed countries, this reduction is matched by an increase in elderly people. Monogenic Mendelian epilepsies are rare. A clinical syndrome often has multiple possible genetic causes, and conversely, different mutations in one gene can lead to various epileptic syndromes. Most common epilepsies, however, are probably complex traits with environmental effects acting on inherited susceptibility, mediated by common variation in particular genes. Diagnosis of epilepsy remains clinical, and neurophysiological investigations assist with diagnosis of the syndrome. Brain imaging is making great progress in identifying the structural and functional causes and consequences of the epilepsies. Current antiepileptic drugs suppress seizures without influencing the underlying t endency to generate seizures, and are effective in 60-70% of individuals. Pharmacogenetic studies hold the promise of being able to better individualise treatment for each patient, with maximum possibility of benefit and minimum risk of adverse effects. For people with refractory focal epilepsy, neurosurgical resection offers the possibility of a life-changing cure. Potential new treatments include precise prediction of seizures and focal therapy with drug delivery, neural stimulation, and biological grafts. Notes: 1474-547x Duncan, John S Sander, Josemir W Sisodiya, Sanjay M Walker, Matthew C Journal Article Research Support, Non-U.S. Govt Review England Lancet. 2006 Apr 1;367(9516):1087-100. Research Notes: Very good overview with clear explanation around neuronal activity of seizures Author Address: Department of Clinical and Experimental Epilepsy, Institute of Neurology UCL, Queen Square, London WC1N 3BG, UK. [emailprotected] Database Provider: NLM Language: eng Reference Type: Book Record Number: 10529 Author: Engel, Jerome, Jr. and Pedley, Timothy A. Year: 2008 Title: Epilepsy : a comprehensive textbook Place Published: Philadelphia, Pa. ; London Publisher: Wolters Kluwer/Lippincott Williams Wilkins Pages: 2797 Edition: 2nd ed. Short Title: Epilepsy : a comprehensive textbook ISBN: 9780781757775 (set) :  ¹173.00 0781757770 (set) :  ¹173.00 Call Number: 616.853 22 British Library DSC m07/.34665 vol. 1 British Library STI (B) 616.853 British Library DSC m07/.34666 vol. 3 British Library DSC m07/.34664 vol. 2 Keywords: Epilepsy. Notes: GBA771698 bnb editors, Jerome Engel Jr., Timothy A. Pedley ; associate editors, Jean Aicardi [et al.]. Previous ed. : c1998. Includes bibliographical references and index. Formerly CIP. Uk Research Notes: Had everything covered in good detail. Reference Type: Journal Article Record Number: 10335 Author: Ngugi, Anthony K., Bottomley, Christian, Kleinschmidt, Immo, Sander, Josemir W. and Newton, Charles R. Year: 2010 Title: Estimation of the burden of active and life-time epilepsy: a meta-analytic approach Journal: Epilepsia Volume: 51 Issue: 5 Pages: 883-890 Short Title: Estimation of the burden of active and life-time epilepsy: a meta-analytic approach ISSN: 0013-9580 DOI: 10.1111/j.1528-1167.2009.02481.x Abstract: To estimate the burden of lifetime epilepsy (LTE) and active epilepsy (AE) and examine the influence of study characteristics on prevalence estimates. Notes: 10.1111/j.1528-1167.2009.02481.x Research Notes: Only really useful for prevalence related material URL: http://dx.doi.org/10.1111/j.1528-1167.2009.02481.x Name of Database: READCUBE Reference Type: Journal Article Record Number: 11373 Author: Sanchez-Carpintero Abad, R., Sanmarti Vilaplana, F. X. and Serratosa Fernandez, J. M. Year: 2007 Title: Genetic causes of epilepsy Journal: Neurologist Volume: 13 Issue: 6 Suppl 1 Pages: S47-51 Date: Nov Short Title: Genetic causes of epilepsy Alternate Journal: The neurologist ISSN: 1074-7931 (Print) 1074-7931 (Linking) DOI: 10.1097/NRL.0b013e31815bb07d Accession Number: 18090951 Keywords: Animals Cerebral Cortex/physiopathology Epilepsy/*etiology/*genetics/pathology Humans Ion Channel Gating/genetics Ion Channels/genetics/*physiology Abstract: BACKGROUND: The contribution of genetic factors to the origin of different epilepsies is a fact established by epidemiological, clinical, and molecular studies. These studies have made it possible to identify numerous mutations in different genes that cause or predispose to the development of certain types of epilepsy. REVIEW SUMMARY: The study of single-gene epilepsies has contributed relevant data regarding the pathophysiology of epilepsy. Most of these genes encode voltage- or ligand-gated ion channels. Other single-gene epilepsies are related to mutations that provoke alterations in neuronal maturation and migration during embryonic development. Nevertheless, the most common forms of epilepsy are not caused by single mutations but by a combination of polymorphisms, most of which are unknown, that generate an alteration in neuronal excitability. In some syndromes, genetic alterations and their consequences have made it possible to explain the therapeutic response to diff erent drugs. Therefore, the progress being made in genetics is changing the classification and diagnosis of epilepsy; moreover, it can sometimes influence the choice of treatment. CONCLUSION: The advances made in genetic knowledge of epilepsy have led to the description of new epilepsy syndromes and to a better characterization of known ones. However, the genes responsible for the most common forms of idiopathic epilepsy remain mostly unknown. This means that for the time being, in clinical practice, genetic diagnosis is limited to uncommon syndromes and to cases in which treatment decisions or genetic counseling can be derived from the diagnosis. Notes: Sanchez-Carpintero Abad, Rocio Sanmarti Vilaplana, Francesc X Serratosa Fernandez, Jose Maria eng Research Support, Non-U.S. Govt Review 2008/01/26 09:00 Neurologist. 2007 Nov;13(6 Suppl 1):S47-51. doi: 10.1097/NRL.0b013e31815bb07d. Research Notes: Very complicated to read. Poorly illustrated. URL: http://www.ncbi.nlm.nih.gov/pubmed/18090951 Author Address: Pediatric Neurology Unit, Department of Pediatrics, Clinica Universitaria de Navarra, Pamplona, Spain. [emailprotected] Reference Type: Book Record Number: 2015 Author: Scambler, Graham Year: 1989 Title: Epilepsy Place Published: London Publisher: Tavistock / Routledge Short Title: Epilepsy ISBN: 0415017580 (pbk) : No price 0415017572 (cased) : No price Accession Number: b8920431 Call Number: 362.1/96853 19 British Library DSC 89/23194 British Library HMNTS YK.1989.a.5440 Keywords: Epileptics Psychology. Notes: GB8920431 bnb 2054 Graham Scambler. The Experience of illness Bibliography: p124-130. _ Includes index. Research Notes: Written with the patient in mind but lacks specific scientific data Reference Type: Book Record Number: 2011 Author: Scott, Donald F. Year: 1978 Title: About Epilepsy : revised Edition Place Published: [S.l.] Publisher: Duckworth Edition: 3rd Ed. Short Title: About Epilepsy : revised Edition ISBN: 0715609467 Call Number: British Library DSC 79/5721 Research Notes: Very well written with good scientific data to back up claims. Reference Type: Journal Article Record Number: 10484 Author: Solodar, J. Year: 2014 Title: Commentary: ILAE Definition of Epilepsy Journal: Epilepsia Volume: 55 Issue: 4 Pages: 491 Date: Apr Short Title: Commentary: ILAE Definition of Epilepsy Alternate Journal: Epilepsia ISSN: 1528-1167 (Electronic) 0013-9580 (Linking) DOI: 10.1111/epi.12594 Accession Number: 24731170 Keywords: *Advisory Committees Epilepsy/*classification/*diagnosis Female Humans Male *Research Report *Societies, Medical Notes: Solodar, Jessica eng Comment 2014/04/16 06:00 Epilepsia. 2014 Apr;55(4):491. doi: 10.1111/epi.12594. Epub 2014 Apr 14. URL: http://www.ncbi.nlm.nih.gov/pubmed/24731170 Research Notes: Good summary of definitions around seizures and all terminology within epilepsy 1