Related Research Articles
Epilepsy is a group of neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures are episodes that 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 have a tendency to recur and 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 their condition.
Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung disease, and kidney disease.
Polymicrogyria (PMG) is a condition that affects the development of the human brain by multiple small gyri (microgyri) creating excessive folding of the brain leading to an abnormally thick cortex. This abnormality can affect either one region of the brain or multiple regions.
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 insults, 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%).
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 named after 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.
Sudden Unexpected Death in Epilepsy (SUDEP) is a fatal complication of epilepsy. It is defined as the sudden and unexpected, non-traumatic and non-drowning death of a person with epilepsy, without a toxicological or anatomical cause of death detected during the post-mortem examination.
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, however it is usually around the sixth month of age that seizures begin, characterized by prolonged convulsions triggered by fever.
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 fairly common form of generalized epilepsy of presumed genetic origin, representing 5-10% of all epilepsy cases. This disorder typically first manifests itself between the ages of 12 and 18 with sudden brief involuntary single or multiple episodes of muscle(s) contractions caused by an abnormal excessive or synchronous neuronal activity in the brain. These events typically occur either early in the morning or upon sleep deprivation.
Autosomal dominant nocturnal frontal lobe epilepsy is an epileptic disorder that causes frequent violent seizures during sleep. These seizures often involve complex motor movements, such as hand clenching, arm raising/lowering, and knee bending. Vocalizations such as shouting, moaning, or crying are also common. ADNFLE is often misdiagnosed as nightmares. Attacks often occur in clusters and typically first manifest in childhood. There are four known loci for ADNFLE, three with known causative genes. These genes, CHRNA4, CHRNB2, and CHRNA2, encode various nicotinic acetylcholine receptor α and β subunits.
Unverricht–Lundborg disease is the most common form of an uncommon group of genetic epilepsy disorders called the progressive myoclonus epilepsies. It is caused due to a mutation in the cystatin B gene (CSTB). The disease is named after Heinrich Unverricht, who first described it in 1891, and Herman Bernhard Lundborg, who researched it in greater detail in 1901 and 1903. ULD onsets in children between the ages of 6 and 16; there are no known cases in which the person was older than 18. Most cases originate from the Baltic region of Europe, though many have been reported from countries in the Mediterranean.
CDKL5 is a gene that provides instructions for making a protein called cyclin-dependent kinase-like 5 also known as serine/threonine kinase 9 (STK9) that is essential for normal brain development. Mutations in the gene can cause deficiencies in the protein. The gene regulates neuronal morphology through cytoplasmic signaling and controlling gene expression. The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms at specific positions. Researchers are currently working to determine which proteins are targeted by the CDKL5 protein.
Progressive myoclonus epilepsy (PME) is a rare epilepsy syndrome caused by a variety of genetic disorders. The syndrome includes myoclonic seizures and tonic-clonic seizures together with progressive neurological decline.
Post-traumatic seizures (PTS) are seizures that result from traumatic brain injury (TBI), brain damage caused by physical trauma. PTS may be a risk factor for post-traumatic epilepsy (PTE), but a person who has a seizure or seizures due to traumatic brain injury does not necessarily have PTE, which is a form of epilepsy, a chronic condition in which seizures occur repeatedly. However, "PTS" and "PTE" may be used interchangeably in medical literature.
Spike-and-wave is a pattern of the electroencephalogram (EEG) typically observed during epileptic seizures. A spike-and-wave discharge is a regular, symmetrical, generalized EEG pattern seen particularly during absence epilepsy, also known as ‘petit mal’ epilepsy. The basic mechanisms underlying these patterns are complex and involve part of the cerebral cortex, the thalamocortical network, and intrinsic neuronal mechanisms. The first spike-and-wave pattern was recorded in the early twentieth century by Hans Berger. Many aspects of the pattern are still being researched and discovered, and still many aspects are uncertain. The spike-and-wave pattern is most commonly researched in absence epilepsy, but is common in several epilepsies such as Lennox-Gastaut syndrome (LGS) and Ohtahara syndrome. Antiepileptic drugs (AEDs) are commonly prescribed to treat epileptic seizures, and new ones are being discovered with fewer adverse effects. Today, most of the research is focused on the origin of the generalized bilateral spike-and-wave discharge. One proposal suggests that a thalamocortical (TC) loop is involved in the initiation spike-and-wave oscillations. Although there are several theories, the use of animal models has provided new insight on spike-and-wave discharge in humans.
Daniel H. Lowenstein, M.D., is the Robert B. and Ellinor Aird Professor of Neurology and Executive Vice Chancellor and Provost at the University of California, San Francisco (UCSF). He is known internationally for his work in the field of epilepsy including laboratory-based and clinical research, the clinical care of patients with epilepsy, and advocacy for the needs of patients and family members living with epilepsy. He has had an active role in medical education and in efforts to advance social justice, has held many leadership positions at both UCSF and Harvard Medical School, was the originator of the “Academy of Medical Educators” concept, and is the recipient of numerous teaching awards both at UCSF and nationally. He has served as the Dean for Medical Education at Harvard Medical School, and as President of the American Epilepsy Society. In 2017, he was elected to the National Academy of Medicine in recognition of his many contributions to American medicine.
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.
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.
Melodie Winawer is a board certified neurologist and the director of clinical neuroscience education at the Columbia University College of Physicians and Surgeons. Her primary research is the genetics of epilepsy, in which she examines how certain genes are risk factors for epilepsy. She is also a published author.
CDKL5 deficiency disorder (CDD) is a rare genetic disorder caused by pathogenic variants in the gene CDKL5.
References
- Winawer, M.R., Phenotype definition in epilepsy. Epilepsy Behav, 2006.
- Andermann, F., E. Kobayashi, and E. Andermann, Genetic focal epilepsies: state of the art and paths to the future. Epilepsia, 2005. 46 Suppl 10: p. 61-7.
- Gardiner, M., Genetics of idiopathic generalized epilepsies. Epilepsia, 2005. 46 Suppl 9: p. 15-20.
- Crino, P.B., H. Miyata, and H.V. Vinters, Neurodevelopmental disorders as a cause of seizures: neuropathologic, genetic, and mechanistic considerations. Brain Pathol, 2002. 12(2): p. 212-33.
- Szoeke, C.E., et al., Update on pharmacogenetics in epilepsy: a brief review. Lancet Neurol, 2006. 5(2): p. 189-96.
- Choi H, Winawer MR, Kalachikov S, Pedley TA, Hauser WA, Ottman R. Classification of partial seizure symptoms in genetic studies of the epilepsies. Neurology. 2006 Jun 13;66(11):1648-53.
- Freimer N, Sabatti C. The human phenome project. Nat Genet. 2003 May;34(1):15-21