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Rasmussen syndrome, also known as Rasmussen's encephalitis, is a rare progressive
autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...
neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
disease. It is characterized by frequent and severe
focal seizures Focal seizures are seizures that originate within brain networks limited to one hemisphere of the brain. In most cases, each seizure type has a consistent site of onset and characteristic patterns of spread, although some individuals experience mo ...
, progressive neurological decline,
hemiparesis Hemiparesis, also called unilateral paresis, is the weakness of one entire side of the body (''wikt:hemi-#Prefix, hemi-'' means "half"). Hemiplegia, in its most severe form, is the complete paralysis of one entire side of the body. Either hemipar ...
(weakness on one side of the body),
encephalitis Encephalitis is inflammation of the Human brain, brain. The severity can be variable with symptoms including reduction or alteration in consciousness, aphasia, headache, fever, confusion, a stiff neck, and vomiting. Complications may include se ...
, and unilateral
cerebral atrophy Cerebral atrophy is a common feature of many of the diseases that affect the brain. Atrophy of any tissue means a decrement in the size of the cell, which can be due to progressive loss of cytoplasmic proteins. In brain tissue, atrophy describes ...
. The disease primarily affects children under the age of 15, though adult cases have been reported. Originally described as a form of chronic focal motor epilepsy by Dr. A. Ya. Kozhevnikov in the 1880s and separately identified as focal seizures due to chronic localized encephalitis in the 1950s by Dr. Theodore Rasmussen. It is now classified to be a cytotoxic T-cell–mediated encephalitis.


Signs and symptoms

The hallmark symptoms are focal seizures, particularly Epilepsia Partialis Continua (EPC) a form of epilepsy characterized by continuous or near-continuous clonic movements in a localized body part. These seizures are typically resistant to standard anti-epileptic medications and often mark the early stage of the disease. This is often seen in the first main stage, sometimes preceded by a 'prodromal stage' of a few months. In the acute stage, which may last between four to eight months, the inflammation is active and symptoms worsen progressively. Children may initially present with subtle behavioral or academic changes before the onset of the drug-resistant focal seizures present. Over time as the disease advances, patients develop
hemiparesis Hemiparesis, also called unilateral paresis, is the weakness of one entire side of the body (''wikt:hemi-#Prefix, hemi-'' means "half"). Hemiplegia, in its most severe form, is the complete paralysis of one entire side of the body. Either hemipar ...
,
hemianopia Hemianopsia, or hemianopia, is a loss of vision or blindness ( anopsia) in half the visual field, usually on one side of the vertical midline. The most common causes of this damage are stroke, brain tumor, and trauma. This article deals only wi ...
(vision loss of one side of
visual field The visual field is "that portion of space in which objects are visible at the same moment during steady fixation of the gaze in one direction"; in ophthalmology and neurology the emphasis is mostly on the structure inside the visual field and it i ...
), and cognitive deficits, involving learning, memory or language. In this phase,
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...
often reveals hemispheric swelling and beginning signs of atrophy. The chronic or residual stage occurs after inflammation subsides. While the active immune damage lessens, the neurological deficits persist due to structural
brain damage Brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating trauma-induced damage. A common ...
. Patients are often left with long-term epilepsy, paralysis/motor impairment, and cognitive dysfunction, although the severity varies. Early diagnosis and treatment may lessen the long term disability in some cases. While Rasmussen's Encephalitis is most commonly diagnosed in children, with an average age of 6 years. However, approximately 10% of reported cases begin in adulthood.


Pathophysiology

Rasmussen's encephalitis is theorized as a T-cell-mediated autoimmune encephalitis, characterized by chronic, progressive inflammation limited to a single hemisphere of the brain.
Histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...
analysis of affected brain tissues reveals infiltration of cytotoxic CD8+ T lymphocytes, which target neurons and astrocytes. These immune cells release
granzyme B Granzyme B (GrB) is one of the serine protease granzymes most commonly found in the granules of natural killer cells (NK cells) and cytotoxic T cells. It is secreted by these cells along with the pore forming protein perforin to mediate apoptos ...
and
perforin Perforin-1 Perforin (PRF), encoded by the PRF1 gene, is a pore-forming toxic protein housed in the secretory granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Together, these cells are known as cytotoxic lymphocytes (CLs). ...
, a enzyme and protein that kill cells. This leads to direct neuronal apoptosis. The presence of activated microglia, identified through
HLA-DR HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. The complex of HLA-DR (Human Leukocyte Antigen – DR isotype) and peptide, generally between 9 and 30 amino acids in l ...
and
CD68 CD68 ( Cluster of Differentiation 68) is a protein highly expressed by cells in the monocyte lineage (e.g., monocytic phagocytes, osteoclasts), by circulating macrophages, and by tissue macrophages (e.g., Kupffer cells, microglia). Structure and ...
immunostaining In biochemistry, immunostaining is any use of an antibody-based method to detect a specific protein in a sample. The term "immunostaining" was originally used to refer to the immunohistochemical staining of tissue sections, as first described by ...
in brain biopsy samples, reflects a broader neuroinflammatory response that contributes to gliosis and progressive neuronal degeneration. This immune-mediated damage results in cortical atrophy, which is most pronounced in frontal and insular lobes, along with spreading posteriorly with disease progression. The exact trigger for this immune response remain unclear, several autoimmune hypotheses have been proposed. Early researchers suggested a role for antibodies against GluR3, a subunit of AMPA-type
glutamate receptors Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system an ...
but these findings have not been consistently replicated. Recent research has identified auto antibodies against the anti-NDMA receptor subunit GluRepsilon2 (NR2A), these are not consistently present across cases and may represent a secondary epiphenomenon rather than a primary pathogenic mechanism. There is limited evidence for auto antibodies targeting the
nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...
. Emerging immunological studies have shown that patients display persistent peripheral expansion of cloncally restricted CD8+ T cells, which are theorized to cross the
blood brain barrier Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is compo ...
and sustain cortical inflammation for years. Suggesting an antigen-drive, chronic immune response that initiates in the periphery and targets CNS antigen. The epilepsy observed in Rasmussen's encephalitis is a potential amplifier of immune-mediated damage, through mechanisms involving
excitotoxicity In excitotoxicity, neuron, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamic acid, glutamate become pathologically high, resulting in excessive stimulation of cell surface recept ...
and impaired
GABAergic In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter gamma-aminobutyric acid (GABA). For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic ...
inhibition. Rare associations with systemic autoimmune disorders, such as neurovisceral
porphyria Porphyria ( or ) is a group of disorders in which substances called porphyrins build up in the body, adversely affecting the skin or nervous system. The types that affect the nervous system are also known as Porphyria#Acute porphyrias, acute p ...
and
acute intermittent porphyria Acute intermittent porphyria (AIP) is a rare Metabolism, metabolic disorder affecting the production of heme resulting from a deficiency of the enzyme porphobilinogen deaminase. It is the most common of the acute porphyrias. Signs and symptoms Th ...
, have been reported in isolated cases.


Diagnosis

Early multidisciplinary diagnostic approach is essential as delayed diagnosis may lead to irreversible neurological decline. Diagnosis of Rasmussen's encephalitis is made through combination of clinical evaluation, electrophysiological findings, and neuroimaging, with invasive procedures deem not necessary.
Electroencephalography Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignal, bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in ...
(
EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neoc ...
) is a crucial diagnostic tool, revealing focal
epileptiform Epilepsy is a group of non-communicable neurological disorders characterized by a tendency for recurrent, unprovoked seizures. A seizure is a sudden burst of abnormal electrical activity in the brain that can cause a variety of symptoms, rang ...
discharge and slowing of background activity in affected hemisphere. Over time, these abnormalities often display more lateralized and severe form of epilepsy. Magnetic Resonance Imaging (MRI) showcase the progressive hemispheric atrophy, often beginning in the frontal or insular regions, then expanding posteriorly. In early phases, brain scans reveal cortical swelling and T2/
FLAIR Fluid-attenuated inversion recovery (FLAIR) is a magnetic resonance imaging sequence with an inversion recovery set to null fluids. For example, it can be used in brain imaging to suppress cerebrospinal fluid (CSF) effects on the image, so as to ...
hyperintensites consistent with inflammation. In later stages, this evolves into clear volume loss, ventricular enlargement, and gliosis.
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 tumors, infection, inflammation, and other brain disorders. By examining the tissue sample under a microscope, th ...
is not always required. It can provide definitive histopathology confirmation, especially atypical presentations ow when alternative diagnoses (tumors or other forms of encephalitis) are being considered. When retrieved the tissue analysis can also help rule out infections, neoplatic, or demyelinating processes.


Treatment

Treatment is typically divided into two phases: management of active inflammation in acute stage and control long-term neurological symptoms in the residual stage. During the acute stage, the primary goal is to suppress the autoimmune response and slow neurological decline. The first treatment usually include high dose
corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...
, either as intravenous
methylprednisolone Methylprednisolone (Depo-Medrol, Medrol, Solu-Medrol) is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used at high doses durin ...
pulses or as oral maintenance therapy. Intravenous immunoglobulin (IVIG) shown benefit in both pediatric and adult cases, often used monthly to modulate immune activity and reduce seizure frequency. Other immunotherapies such as
plasmapheresis Plasmapheresis (from the Greek language, Greek πλάσμα, ''plasma'', something molded, and ἀφαίρεσις ''aphairesis'', taking away) is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the ...
,
azathioprine Azathioprine, sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used for the treatment of rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus er ...
, clyclophosphamide,
mycophenolate mofetil Mycophenolic acid is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and live ...
, and
tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...
have been used at varying success, though clinical trials are still in progress. While these therapies can delay disease progression, they do not consistently prevent long term disability and responses varies between individuals. In chronic, or residual stage, the inflammatory activity subsides but neurological damage is often irreversible. Treatment shifts toward symptom management, especially seizure control. Unfortunately, standard anti-seizure medications are typically ineffective due to the focal drug resistant nature of the epilepsy. For many patients, functional hemispherectomy (surgical disconnection or removal of the affected hemisphere) becomes the most effective option to stop seizures. Variants such as anatomical hemispherectomy or hemispherotomy may be chosen based on age and severity of deficits. While hemispherectomy is associated with significant risks, such as permanent hemiplegia, hemianopia, and potential language loss if the dominant hemisphere is removed. It is often used as results in dramatic seizure reduction or remission for better quality of life. Early surgery in children, especially those under age 10, may offer better functional reorganization and recovery of language and cognitive skills by the contralateral hemisphere. Due to the severity of the procedure and its implications, some centers prioritizing early surgery and others favoring prolonged immunotherapy before considering invasive intervention.


History

It is named after Dr. Theodore Rasmussen (1910–2002), a pioneering
neurosurgeon Neurosurgery or neurological surgery, known in common parlance as brain surgery, is the medical specialty that focuses on the surgical treatment or rehabilitation of disorders which affect any portion of the nervous system including the brain, ...
who succeeded
Wilder Penfield Wilder Graves Penfield (January 26, 1891April 5, 1976) was an American-Canadian neurosurgeon. He expanded brain surgery's methods and techniques, including mapping the functions of various regions of the brain such as the cortical homunculus. ...
as head of the
Montreal Neurological Institute The McGill University Health Centre (MUHC; ) is one of two major healthcare networks in the city of Montreal, Quebec. It is affiliated with McGill University and one of the largest medical complexes in Montreal. It is the largest hospital system i ...
, and served as Neurosurgeon-in-Chief at the Royal Victoria Hospital. In the 1950s, Rasmussen and colleagues described a series of children presenting intractable focal seizures, progressive hemiparesis, and unilateral cerebral atrophy. Initially referred to as "focal seizures due to chronic localized encephalitis”. His clinical observations and early histopathological analyses, often based on tissue obtained from hemispherectomy procedures, led to recognition of the disorders as distinct clinical and neuropathological entity. Although Rasmussen brought modern recognition, similar cases had been described decades earlier by Dr. A. Ya. Kozhevnikov, a Russian neurologist in Siberia during the 1880s. Kozhevnikov reported chronic focal motor seizures now recognized as EPC, a defining symptom of Rasmussen’s encephalitis, in adult patients. The disorder was referred to in some literature as Kozhevnikov epilepsy, highlighting its motor manifestations. It wasn’t until the 1980s that researchers unified these clinical concepts and redefined the condition under the name Rasmussen’s syndrome (or encephalitis), recognizing the autoimmune and progressive nature of the disease beyond motor seizures alone.


Society

The Hemispherectomy Foundation 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.


References


External links

* {{NINDS, Rasmussens-encephalitis, Rasmussen's Encephalitis (Note: parts of this entry were copied from this
Public Domain The public domain (PD) consists of all the creative work to which no Exclusive exclusive intellectual property rights apply. Those rights may have expired, been forfeited, expressly Waiver, waived, or may be inapplicable. Because no one holds ...
source.) Encephalitis Disorders causing seizures Epilepsy types