Rasmussen's encephalitis
Encyclopedia
Rasmussen's encephalitis, also known as chronic focal encephalitis (CFE), is a rare inflammatory neurological disorder
, characterized by frequent and severe seizure
s, loss of motor skill
s and speech, hemiparesis
(paralysis on one side of the body), encephalitis
(inflammation of the brain), and dementia
. The disorder, which affects a single cerebral hemisphere
, generally occurs in children under the age of 15.
, 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 cause of the inflammation is not known: infection by a virus
has been suggested, but the evidence for this is inconclusive. In the 1990s it was suggested that auto-antibodies against the glutamate receptor GluR3 were important in causing the disease, but this is no longer thought to be the case. 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.
Rasmussen's encephalitis has been recorded with a neurovisceral porphyria
, acute intermittent porphyria
and after ADEM (acute disseminated encephalomyelitis).
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 seizure
s 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.
In the chronic or residual stage, the inflammation is no longer active, but the sufferer is left with some or all of the symptoms because of the damage that the inflammation has caused.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.
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. Brain biopsy
can provide very strong confirmation of the diagnosis, but this is not always necessary.
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. Other similar treatments include plasmapheresis
and tacrolimus
, though there is less evidence for these. None of these treatments can prevent permanent disability from developing.
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
. This usually results in further weakness, hemianopia 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.
as head of the Montreal Neurological Institute, and served as Neurosurgeon-in-Chief at the Royal Victoria Hospital.
was formed in 2008 to assist families with children who have Rasmussen's Encephalitis and other conditions that require hemispherectomy.
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.
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
, characterized by frequent and severe seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, loss of motor skill
Motor skill
A motor skill is a learned sequence of movements that combine to produce a smooth, efficient action in order to master a particular task. The development of motor skill occurs in the motor cortex, the region of the cerebral cortex that controls voluntary muscle groups.- Development of motor skills...
s and speech, hemiparesis
Hemiparesis
Hemiparesis is weakness on one side of the body. It is less severe than hemiplegia - the total paralysis of the arm, leg, and trunk on one side of the body. Thus, the patient can move the impaired side of his body, but with reduced muscular strength....
(paralysis on one side of the body), encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
(inflammation of the brain), and dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
. The disorder, which affects a single cerebral hemisphere
Cerebral hemisphere
A cerebral hemisphere is one of the two regions of the eutherian brain that are delineated by the median plane, . The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres has an outer layer of grey matter called the cerebral cortex that is...
, generally occurs in children under the age of 15.
Causes and pathophysiology
In Rasmussen’s encephalitis, there is chronic inflammation of the brain, with infiltration of T lymphocytes into the brain tissue. This affects only one cerebral hemisphereCerebral hemisphere
A cerebral hemisphere is one of the two regions of the eutherian brain that are delineated by the median plane, . The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres has an outer layer of grey matter called the cerebral cortex that is...
, either the left or the right. This inflammation causes permanent damage to the cells of the brain, leading to atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
of the hemisphere; the epilepsy that this causes may itself contribute to the brain damage.
The cause of the inflammation is not known: infection by a virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
has been suggested, but the evidence for this is inconclusive. In the 1990s it was suggested that auto-antibodies against the glutamate receptor GluR3 were important in causing the disease, but this is no longer thought to be the case. 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.
Rasmussen's encephalitis has been recorded with a neurovisceral porphyria
Porphyria
Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway . They are broadly classified as acute porphyrias and cutaneous porphyrias, based on the site of the overproduction and accumulation of the porphyrins...
, acute intermittent porphyria
Acute intermittent porphyria
Acute intermittent porphyria is a rare autosomal dominant metabolic disorder affecting the production of heme, the oxygen-binding prosthetic group of hemoglobin. It is characterized by a deficiency of the enzyme porphobilinogen deaminase. Acute intermittent porphyria is the second most common...
and after ADEM (acute disseminated encephalomyelitis).
Clinical features
The condition mostly affects children, with an average age of 6 years. However, one in ten people with the condition develops it in adulthood.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
Hemiparesis
Hemiparesis is weakness on one side of the body. It is less severe than hemiplegia - the total paralysis of the arm, leg, and trunk on one side of the body. Thus, the patient can move the impaired side of his body, but with reduced muscular strength....
), loss of vision for one side of the visual field
Visual field
The term visual field is sometimes used as a synonym to field of view, though they do not designate the same thing. The visual field is the "spatial array of visual sensations available to observation in introspectionist psychological experiments", while 'field of view' "refers to the physical...
(hemianopia), and cognitive difficulties (affecting learning, memory or language, for example). Epileptic seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s are also a major part of the illness, although these are often partial. Focal motor seizures or epilepsia partialis continua
Epilepsia partialis continua
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 .-Presentation:During these seizures, there is repetitive focal myoclonus or Jacksonian...
are particularly common, and may be very difficult to control with drugs.
In the chronic or residual stage, the inflammation is no longer active, but the sufferer 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.
Investigations
The diagnosis may be made on the clinical features alone, along with tests to rule out other possible causes. An EEGEEG
EEG commonly refers to electroencephalography, a measurement of the electrical activity of the brain.EEG may also refer to:* Emperor Entertainment Group, a Hong Kong-based entertainment company...
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. Brain biopsy
Brain biopsy
Brain biopsy is the removal of a small piece of brain tissue for the diagnosis of abnormalities of the brain. It is used to diagnose Alzheimer's disease, tumors, infection, inflammation, and other brain disorders....
can provide very strong confirmation of the diagnosis, but this is not always necessary.
Treatment
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 immunoglobulinIntravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
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. Other similar treatments include plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
and tacrolimus
Tacrolimus
Tacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...
, though there is less evidence for these. None of these treatments can prevent permanent disability from developing.
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
Hemispherectomy
Hemispherectomy is a very rare surgical procedure where one cerebral hemisphere is removed or disabled. This procedure is used to treat a variety of seizure disorders where the source of the epilepsy is localized to a broad area of a single hemisphere of the brain...
. This usually results in further weakness, hemianopia 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.
Name of the disease
It is named for the neurosurgeon Theodore Rasmussen (1910–2002), who succeeded Wilder PenfieldWilder Penfield
Wilder Graves Penfield, OM, CC, CMG, FRS was an American born Canadian neurosurgeon. During his life he was called "the greatest living Canadian"...
as head of the Montreal Neurological Institute, and served as Neurosurgeon-in-Chief at the Royal Victoria Hospital.
Foundations
The Hemispherectomy FoundationHemispherectomy Foundation
The Hemispherectomy Foundation is a 501 non-profit organization founded to provide a support structure for children, and the families of children who have had or are preparing to have hemispherectomy brain surgery. The foundation also provides scholarships for college, trade schools, and summer...
was formed in 2008 to assist families with children who have Rasmussen's Encephalitis and other conditions that require hemispherectomy.
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.