Rasmussen's encephalitis is a rare inflammatory neurological disease, characterized by frequent and severe seizures, loss of motor skills and speech, hemiparesis (weakness on one side of the body), encephalitis (inflammation of the brain), and dementia. The illness affects a single cerebral hemisphere and generally occurs in children under the age of 15.
The condition mostly affects children, with an average age of 6 years. However, one in ten people with the condition develops it in adulthood.[ citation needed ]
There are two main stages, sometimes preceded by a 'prodromal stage' of a few months. In the acute stage, lasting four to eight months, the inflammation is active and the symptoms become progressively worse. These include weakness of one side of the body (hemiparesis), loss of vision for one side of the visual field (hemianopia), and cognitive difficulties (affecting learning, memory or language, for example). Epileptic seizures are also a major part of the illness, although these are often partial. Focal motor seizures or epilepsia partialis continua are particularly common, and may be very difficult to control with drugs.[ citation needed ]
In the chronic or residual stage, the inflammation is no longer active, but the affected individual is left with some or all of the symptoms because of the damage that the inflammation has caused. In the long term, most patients are left with some epilepsy, paralysis and cognitive problems, but the severity varies considerably. [1]
In Rasmussen's encephalitis, there is chronic inflammation of the brain, with infiltration of T lymphocytes into the brain tissue. In most cases, this affects only one cerebral hemisphere, either the left or the right. This inflammation causes permanent damage to the cells of the brain, leading to atrophy of the hemisphere; the epilepsy that this causes may itself contribute to the brain damage. The epilepsy might derive from a disturbed GABA release, [2] the main inhibitory neurotransmitter of the mammalian brain.
The cause of the inflammation is not known: infection by a virus has been suggested, but the evidence for this is inconclusive. [1] In the 1990s it was suggested that auto-antibodies against the glutamate receptor GluR3 were important in causing the disease, [3] but this is no longer thought to be the case. [4] However, more recent studies report the presence of autoantibodies against the NMDA-type glutamate receptor subunit GluRepsilon2 (anti-NR2A antibodies) in a subset of patients with Rasmussen's encephalitis. [5] There has also been some evidence that patients with RE express auto-antibodies against alpha 7 subunit of the nicotinic acetylcholine receptor. [6] By sequencing T cell receptors from various compartments it could be shown that RE patients present with peripheral CD8+ T-cell expansion which in some cases have been proven for years after disease onset. [7]
Rasmussen's encephalitis has been recorded with a neurovisceral porphyria, and acute intermittent porphyria. [8]
The diagnosis may be made on the clinical features alone, along with tests to rule out other possible causes. An EEG will usually show the electrical features of epilepsy and slowing of brain activity in the affected hemisphere, and MRI brain scans will show gradual shrinkage of the affected hemisphere with signs of inflammation or scarring. [9]
Brain biopsy can provide very strong confirmation of the diagnosis, but this is not always necessary. [9] [10]
During the acute stage, treatment is aimed at reducing the inflammation. As in other inflammatory diseases, steroids may be used first of all, either as a short course of high-dose treatment, or in a lower dose for long-term treatment. Intravenous immunoglobulin is also effective both in the short term and in the long term, particularly in adults where it has been proposed as first-line treatment. [11] Other similar treatments include plasmapheresis and tacrolimus, though there is less evidence for these. None of these treatments can prevent permanent disability from developing. [9] [12]
During the residual stage of the illness when there is no longer active inflammation, treatment is aimed at improving the remaining symptoms. Standard anti-epileptic drugs are usually ineffective in controlling seizures, and it may be necessary to surgically remove or disconnect the affected cerebral hemisphere, in an operation called hemispherectomy or via a corpus callosotomy. This usually results in further weakness, hemianopsia and cognitive problems, but the other side of the brain may be able to take over some of the function, particularly in young children. The operation may not be advisable if the left hemisphere is affected, since this hemisphere contains most of the parts of the brain that control language. However, hemispherectomy is often very effective in reducing seizures. [1] [9]
It is named for the neurosurgeon Theodore Rasmussen (1910–2002), who succeeded Wilder Penfield as head of the Montreal Neurological Institute, and served as Neurosurgeon-in-Chief at the Royal Victoria Hospital. [13] [14]
The Hemispherectomy Foundation was formed in 2008 to assist families with children who have Rasmussen's encephalitis and other conditions that require hemispherectomy. [15]
The RE Children's Project was founded in 2010 to increase awareness of Rasmussen's encephalitis. Its primary purpose is to support scientific research directed toward finding a cure for this disease.[ citation needed ]
Encephalomyelitis is inflammation of the brain and spinal cord. Various types of encephalomyelitis include:
Hemispherectomy is a neurosurgical procedure in which a cerebral hemisphere is removed or disconnected. It is used to treat a variety of refractory or drug-resistant seizure disorders (epilepsy).
Epilepsia partialis continua is a rare type of brain disorder in which a patient experiences recurrent motor epileptic seizures that are focal, and recur every few seconds or minutes for extended periods. It is sometimes called Kozhevnikov's epilepsia named after Russian psychiatrist Aleksei Yakovlevich Kozhevnikov who first described this type of epilepsy.
Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.
In the field of neurology, temporal lobe epilepsy is an enduring brain disorder that causes unprovoked seizures from the temporal lobe. Temporal lobe epilepsy is the most common type of focal onset epilepsy among adults. Seizure symptoms and behavior distinguish seizures arising from the medial temporal lobe from seizures arising from the lateral (neocortical) temporal lobe. Memory and psychiatric comorbidities may occur. Diagnosis relies on electroencephalographic (EEG) and neuroimaging studies. Anticonvulsant medications, epilepsy surgery and dietary treatments may improve seizure control.
Juvenile myoclonic epilepsy (JME), also known as Janz syndrome or impulsive petit mal, is a form of hereditary, idiopathic 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. It was first described by Théodore Herpin in 1857. Understanding of the genetics of JME has been rapidly evolving since the 1990s, and 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.
Epilepsy surgery involves a neurosurgical procedure where an area of the brain involved in seizures is either resected, ablated, disconnected or stimulated. The goal is to eliminate seizures or significantly reduce seizure burden. Approximately 60% of all people with epilepsy have focal epilepsy syndromes. In 15% to 20% of these patients, the condition is not adequately controlled with anticonvulsive drugs. Such patients are potential candidates for surgical epilepsy treatment.
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Leucine-rich, glioma inactivated 1, also known as LGI1, is a protein which in humans is encoded by the LGI1 gene. It may be a metastasis suppressor.
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James O. McNamara is an American neurologist and neuroscientist, known for his research of epileptogenesis, the process underlying development and progression of epilepsy. He is the Duke School of Medicine Professor of Neuroscience in the Departments of Neurobiology, Neurology, and Pharmacology and Cancer Biology at Duke University. He served as chair of the Department of Neurobiology at Duke from 2002 to 2011
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Svetlana Dambinova is a Russian neuroscientist, Doctor of Biological Sciences, Distinguished Professor at Laboratory of biomarkers at Medical Center "DeKalb", Atlanta, USA. Dambinova was awarded as Honored Worker of Science of the Republic of Buryatia (1996) and Russian Federation (1998). Known in the world for research of glutamate receptors. The Head of the project of the International Department of Neurology SPBGMU them. Acad. Pavlov's.
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