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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, purposeless and synchronized electrical discharge in the brain cells called 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 immediate 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.
Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syndrome. In bipolar disorder, lamotrigine has not been shown to reliably treat acute depression; but for patients with bipolar disorder who are not currently symptomatic, it appears to be effective in reducing the risk of future episodes of depression.
Absence seizures are one of several kinds of generalized seizures. These seizures are sometimes referred to as petit mal seizures. 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.
Lennox–Gastaut syndrome (LGS) is a complex, rare, and severe childhood-onset epilepsy. It is characterized by multiple and concurrent seizure types, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG). Typically, it presents in children aged 3–5 years and can persist into adulthood. It has been associated with several gene mutations, perinatal injuries, congenital infections, brain tumors/malformations, and genetic disorders such as tuberous sclerosis and West syndrome. The prognosis for LGS is poor with a 5% mortality in childhood and persistent seizures into adulthood (80–90%).
Myoclonic epilepsy refers to a family of epilepsies that present with myoclonus. It starts in both sides of the body at once, and last for more than a second or two. When myoclonic jerks are occasionally associated with abnormal brain wave activity, it can be categorized as myoclonic seizure. If the abnormal brain wave activity is persistent and results from ongoing seizures, then a diagnosis of myoclonic epilepsy may be considered. Myoclonic seizures frequently occur in day-to-day life. During sleep, abrupt jerks and hiccups occurred.
Epileptic spasms is an uncommon-to-rare epileptic disorder in infants, children and adults. One of the other names of the disorder, West syndrome, is in memory of the English physician, William James West (1793–1848), who first described it in an article published in The Lancet in 1841. The original case actually described his own son, James Edwin West (1840–1860). Other names for it are "generalized flexion epilepsy", "infantile epileptic encephalopathy", "infantile myoclonic encephalopathy", "jackknife convulsions", "massive myoclonia" and "Salaam spasms". The term "infantile spasms" can be used to describe the specific seizure manifestation in the syndrome, but is also used as a synonym for the syndrome itself. West syndrome in modern usage is the triad of infantile spasms, a pathognomonic EEG pattern, and developmental regression – although the international definition requires only two out of these three elements.
Dravet syndrome, previously known as severe myoclonic epilepsy of infancy (SMEI), is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures or fever. It is very difficult to treat with anticonvulsant medications. It often begins before 1 year of age, with 6 months being the age that seizures, characterized by prolonged convulsions and triggered by fever, usually begin.
Idiopathic generalized epilepsy (IGE) is a group of epileptic disorders that are believed to have a strong underlying genetic basis. Patients with an IGE subtype are typically otherwise normal and have no structural brain abnormalities. People also often have a family history of epilepsy and seem to have a genetically predisposed risk of seizures. IGE tends to manifest itself between early childhood and adolescence although it can be eventually diagnosed later. The genetic cause of some IGE types is known, though inheritance does not always follow a simple monogenic mechanism.
Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a form of genetic generalized epilepsy, representing 5–10% of all epilepsy cases. Typically it first presents between the ages of 12 and 18 with myoclonic seizures. These events typically occur after awakening from sleep, during the evening or when sleep deprived. JME is also characterized by generalized tonic–clonic seizures, and a minority of patients have absence seizures. The genetics of JME are complex and rapidly evolving as over 20 chromosomal loci and multiple genes have been identified. Given the genetic and clinical heterogeneity of JME some authors have suggested that it should be thought of as a spectrum disorder.
Generalized epilepsy is a form of epilepsy characterised by generalised seizures with no apparent cause. Generalized seizures, as opposed to focal seizures, are a type of seizure that impairs consciousness and distorts the electrical activity of the whole or a larger portion of the brain. Generalized seizure occurs due to abnormalities in both hemispheres.
GLUT1 deficiency syndrome, also known as GLUT1-DS, De Vivo disease or Glucose transporter type 1 deficiency syndrome, is an autosomal dominant genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier. Glucose Transporter Type 1 Deficiency Syndrome has an estimated birth incidence of 1 in 90,000 to 1 in 24,300. This birth incidence translates to an estimated prevalence of 3,000 to 7,000 in the U.S.
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).
Ohtahara syndrome (OS), also known as early infantile epileptic encephalopathy (EIEE) is a progressive epileptic encephalopathy. The syndrome is outwardly characterized by tonic spasms and partial seizures within the first few months of life, and receives its more elaborate name from the pattern of burst activity on an electroencephalogram (EEG). It is an extremely debilitating progressive neurological disorder, involving intractable seizures and severe intellectual disabilities. No single cause has been identified, although in many cases structural brain damage is present.
Myoclonic astatic epilepsy (MAE), also known as myoclonic atonic epilepsy or Doose syndrome, is a generalized idiopathic epilepsy. MAE was first coined in 1970 by Dr. Hermann Doose. It is characterized by the development of myoclonic seizures and/or myoclonic astatic seizures. Some of the common monogenic causes include mutations in the genes SLC6A1 (3p25.3),CHD2 (15q26.1), AP2M1 (10q23.2). Myoclonic atonic epilepsy (MAE) is an intermittent childhood epilepsy syndrome. MAE is characterized by jerking muscle contractions followed by sudden muscle limpness. The onset of MAE is in early childhood. Almost all patients with MAE experienced their first seizures before the age of five years. Majority of children with MAE have normal development until the time of diagnosis, though few faces minor delay in development with speech delay. Boys tend to be affected more than girls. Genetics plays a significant role in the cause of this disorder. It is a rare childhood epilepsy, to be found in 1 to 2 out of 100 of all childhood-onset epilepsies. For the majority of MAE patients, the first seizure is a generalized tonic-clonic seizure. Even though generalized tonic-clonic seizures are the first seizure that occurred in MAE, few of the patients experienced absence seizures in their onset. For those children, whose onset is after four years they are more likely to experience absence seizures. There is an important role of Genetic in Doose Syndrome. These seizures occur more often in the early hours of the morning during sleep. The seizure response to the medication is very poor. Almost one-third have continuing seizures. The development of children progresses once seizures are controlled. Some children return to their regular functions. But few still remain with fluctuating grades of intellectual disability. Atypical absence often related with reduced muscle tone. Pure atonic seizures may also happen. Generalized tonic seizures are less frequently seen. Though Ancestor and natal history are typical. There is frequently a family history of seizures. The patients are having normal neurological examination and head size. This seizure is considered an 'epileptic encephalopathy. Current indication has suggested possible genetic links to the GEFS+ family. Though the frequency of seizures is more, and also poor cognition outcomes can be surprisingly good.
Epilepsy-intellectual disability in females also known as PCDH19 gene-related epilepsy or epileptic encephalopathy, early infantile, 9 (EIEE9), is a rare type of epilepsy that affects predominately females and is characterized by clusters of brief seizures, which start in infancy or early childhood, and is occasionally accompanied by varying degrees of cognitive impairment. The striking pattern of onset seizures at a young age, genetic testing and laboratory results, potential developmental delays or developmental regression and associated disorders, eases diagnosis.
Early myoclonic encephalopathy (EME) is a rare neonatal-onset epilepsy developmental and epileptic encephalopathy (DEE) with an onset at neonatal period or during the first 3 months of life. It is marked by the presence of myoclonic seizures but multiple seizure types may occur. The electroencephalographic recording is abnormal with eitherusually a suppression-burst pattern or other significantly abnormal patterns. On most occasions the seizures are drug-resistant. After several months, the seizure pattern may develop into infantile spasms syndrome. The neurological exam is abnormal with a significant risk of early death. Various genetic and metabolic disorders are responsible. At present, EME and Ohtahara syndrome are recorded as distinct patterns in the categorization of epilepsies but both neonatal-onset epilepsy syndromes are considered to be merged in one unique entity. It is a severe type of epilepsy syndrome associated with high level of resistance to treatment and a high risk for cognitive impairment. The myoclonic seizures could be seen in other epilepsy syndromes. Multiple types of childhood epilepsies are usually mentioned as myoclonic epilepsies when the myoclonic seizures are a predominant feature.
People with epilepsy may be classified into different syndromes based on specific clinical features. These features include the age at which seizures begin, the seizure types, and EEG findings, among others. Identifying an epilepsy syndrome is useful as it helps determine the underlying causes as well as deciding what anti-seizure medication should be tried. Epilepsy syndromes are more commonly diagnosed in infants and children. Some examples of epilepsy syndromes include benign rolandic epilepsy, childhood absence epilepsy and juvenile myoclonic epilepsy. Severe syndromes with diffuse brain dysfunction caused, at least partly, by some aspect of epilepsy, are also referred to as epileptic encephalopathies. These are associated with frequent seizures that are resistant to treatment and severe cognitive dysfunction, for instance Lennox-Gastaut syndrome and West syndrome.
SYNGAP1-related intellectual disability is a monogenetic developmental and epileptic encephalopathy that affects the central nervous system. Symptoms include intellectual disability, epilepsy, autism, sensory processing deficits, hypotonia and unstable gait.
CDKL5 deficiency disorder (CDD) is a rare genetic disorder caused by pathogenic variants in the gene CDKL5.
SLC13A5 citrate transporter disorder is a rare neurological disease, also known as SLC13A5 epilepsy and by other names. It is a spectrum disorder, discovered in 2014. It is one of the many subtypes of Ohtahara syndrome that have been linked to metabolic causes.
References
- ↑ Johannesen, Katrine M.; Gardella, Elena; Linnankivi, Tarja; Courage, Carolina; de Saint Martin, Anne; Lehesjoki, Anna-Elina; Mignot, Cyril; Afenjar, Alexandra; Lesca, Gaetan; Abi-Warde, Marie-Thérèse; Chelly, Jamel; Piton, Amélie; Merritt, J. Lawrence; Rodan, Lance H.; Tan, Wen-Hann; Bird, Lynne M.; Nespeca, Mark; Gleeson, Joseph G.; Yoo, Yongjin; Choi, Murim; Chae, Jong-Hee; Czapansky-Beilman, Desiree; Reichert, Sara Chadwick; Pendziwiat, Manuela; Verhoeven, Judith S.; Schelhaas, Helenius J.; Devinsky, Orrin; Christensen, Jakob; Specchio, Nicola; Trivisano, Marina; Weber, Yvonne G.; Nava, Caroline; Keren, Boris; Doummar, Diane; Schaefer, Elise; Hopkins, Sarah; Dubbs, Holly; Shaw, Jessica E.; Pisani, Laura; Myers, Candace T.; Tang, Sha; Tang, Shan; Pal, Deb K.; Millichap, John J.; Carvill, Gemma L.; Helbig, Kathrine L.; Mecarelli, Oriano; Striano, Pasquale; Helbig, Ingo; Rubboli, Guido; Mefford, Heather C.; Møller, Rikke S. (February 2018). "Defining the phenotypic spectrum of SLC6A1 mutations". Epilepsia. 59 (2): 389–402. doi:10.1111/epi.13986. PMC 7677605 . PMID 33241211.
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- 1 2 3 4 5 6 Goodspeed, Kimberly; Pérez-Palma, Eduardo; Iqbal, Sumaiya; Cooper, Dominique; Scimemi, Annalisa; Johannesen, Katrine M; Stefanski, Arthur; Demarest, Scott; Helbig, Katherine L; Kang, Jingqiong; Shaffo, Frances C; Prentice, Brandon; Brownstein, Catherine A; Lim, Byungchan; Helbig, Ingo; De Los Reyes, Emily; McKnight, Dianalee; Crunelli, Vincenzo; Campbell, Arthur J; Møller, Rikke S; Freed, Amber; Lal, Dennis (1 July 2020). "Current knowledge of SLC6A1-related neurodevelopmental disorders". Brain Communications. 2 (2): fcaa170. doi:10.1093/braincomms/fcaa170. PMC 7677605 . PMID 33241211.
- ↑ "Parent and Family Scientific Overview". SLC6A1 Connect. 19 March 2022.
- ↑ Poukas, VS; Pollard, JR; Anderson, CT (August 2011). "Rescue therapies for seizures". Current Neurology and Neuroscience Reports. 11 (4): 418–22. doi:10.1007/s11910-011-0207-x. PMID 21509498. S2CID 20170316.
- 1 2 3 Philadelphia, The Children's Hospital of (13 May 2020). "SLC6A1-Related Disorders". www.chop.edu.
- ↑ Palmer, S; Towne, MC; Pearl, PL; Pelletier, RC; Genetti, CA; Shi, J; Beggs, AH; Agrawal, PB; Brownstein, CA (November 2016). "SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures". Pediatric Neurology. 64: 77–79. doi:10.1016/j.pediatrneurol.2016.07.012. PMC 5223550 . PMID 27600546.