Rasmussen encephalitis (RE) is a rare, disseminated, acquired, progressive disease first reported by Rasmussen et al. from the Montreal Neurological Institute in 1958, and had been named encephalitis because of the inflammatory changes suggested by the patient’s postoperative pathology; however, it was subsequently renamed Rasmussen syndrome (RS) by Gupta and Piatt et al. found signs of autoimmune damage within the tissue and vessel walls of one cerebral hemisphere, so it was renamed Rasmussen’s syndrome (RS). The disease begins in childhood as a chronic neurological disorder characterized by cognitive impairment, progressive hemiparesis and refractory epilepsy due to hemispheric damage, typically characterized by frequent partial epilepsy or persistent epilepsy with progressive hemiparesis of one limb and mental retardation, with severe cognitive impairment in the later stages of disease progression. diagnostic criteria for the disease, mainly through clinical manifestations, EEG, MRI, and brain crest fluid. In terms of treatment, antiepileptic drugs are ineffective, and immunosuppressants, immunoglobulins, and hormones are considered to have some effect, but only provide temporary remission and recurrence of epilepsy is inevitable. Unilateral hemispherectomy, especially functional hemispherectomy, is currently considered an effective treatment for Rasmussen’s syndrome.
In 1958, Rasmussen admitted three children with exceptional focal epilepsy whose postoperative brain histopathology was characterized mainly by inflammatory reactive lesions such as lymphocytic infiltration, microglia nodular proliferation, and peripheral vascular sleeve formation, similar to viral encephalitis, thus defining it as a new type of encephalitis and suggesting that its etiology may be related to viral infection. However, all studies on RS to date have failed to isolate viral replication from brain tissue of RS patients; therefore, the doctrine of RS viral infection is still debated. Although Rasmussen suggested that the occurrence of RS may be related to viral infection, because a clear pathogen has not been detected, many studies have turned to the cellular immune response after stress. by performing IgG immunocytochemical studies on postoperative tissues of RS, Farrell et al. found that the neuronal damage in brain tissue of RS patients was accompanied by microglia proliferation and T lymphocyte infiltration, according to which concluded that the blood-brain barrier is abnormal in RS patients, and pointed out that although direct evidence of viral infection has not been able to be found, T-lymphocyte infiltration suggests the possibility of viral infection, and autoimmune factors themselves can be caused by viral infection. The circulating autoantibody theory runs throughout the RS humoral immunity doctrine, and glutamate receptor studies occupy a major part. Glutamate is the predominant excitatory transmitter in the brain and regulates almost all functions in the brain by interacting with glutamate receptors. Glutamate receptors are divided into two categories, ionotropic and metabotropic, both of which are widely distributed in the central nervous system. Many studies have been reported on the relationship between glutamate, glutamate receptors and epilepsy, and the pathogenesis of RS has now been found to be closely related to autoimmunity. So far, a large number of studies have been conducted on the disease, and progress has been made not only in the above-mentioned theories, but also in the development of new hypotheses, such as the viral hypothesis, cytokine hypothesis, apoptosis hypothesis, enzyme and receptor hypothesis, all of which have enriched the understanding of RS.
The main clinical manifestations of RS are refractory epilepsy, progressive neurological deficits, and mental decline. The EEG shows focal slow waves with or without focal epileptic waves. Some patients have a course of inflammatory infection prior to onset, and most present with persistent partial epilepsy, while some patients present with complex partial seizures with or without automatism.
1. Course of RS
The typical clinical manifestations can be divided into 3 phases: (1) prodromal phase: characterized by hemiplegic convulsions, slow onset and gradual aggravation, accompanied by hemiplegic delayed paralysis; the prominent clinical symptom is uncontrollable seizures, partial seizures at the beginning of the disease, followed or not by generalized seizures. (2) Acute phase: characterized by progressive hemiparesis and frequent seizures, mostly simple partial seizures and complex partial seizures; progressive development of the disease leads to increasingly severe and frequent hemiparesis and seizures, and after 1 year patients all develop intractable epilepsy and persistent status epilepticus, accompanied by progressive motor impairment of one limb, hemianopia, cognitive decline, and if the main hemisphere is involved there may be simultaneous aphasia; this phase of Seizures in this period have the following characteristics: (1) various forms of seizures, the most common form is persistent partial epilepsy; (2) poor response to antiepileptic drugs. (3) Postictal phase: characterized by progressive mental decompensation, with psychiatric symptoms and mental retardation as the disease progresses; progressive psychiatric and neuropsychological damage, progressive atrophy of the cerebral hemispheres; seizure frequency may be reduced and coexist with neurological functional manifestations such as hemiparesis; brain imaging during this phase may show significant, often one-sided, brain lesions and brain atrophy.
2. Electroencephalogram
In the early stage of the disease, EEG is helpful for the diagnosis of RS, which shows polymorphic delta waves in the central and temporal leads. The following manifestations in the unilateral cerebral hemisphere are highly suggestive of RS: abnormal background activity and sleep spindle waves, focal slow activity, multifocal seizure discharges and subclinical seizure discharges.
3 Neuroimaging
The cranial CT shows signs of progressive atrophy of the diseased hemisphere and enlargement of the ipsilateral lateral ventricle and widening of the subarachnoid space, but it is difficult to detect early abnormal changes. MRI not only shows the atrophied hemisphere, but also abnormal signals of the cerebral cortex and white matter in the focal area, and early mild cortical edema in the focal area is found. If progressive hemispheric atrophy develops with the progression of the disease, RS should be highly suspected, but it still needs to be differentially diagnosed from certain metabolic encephalopathies; there are two forms of brain atrophy on MRI: one is diffuse, relatively uniform atrophy involving mainly the cerebral hemispheres; the other is focal atrophy on the background of diffuse atrophy.
4.Laboratory tests
No specific laboratory tests can support the diagnosis of RS, and 50% of patients have brain crest fluid cell and protein levels in the normal range.
Diagnosis
The diagnosis of RS is based on clinical, EEG and MRI, and in some patients, histopathological examination. Diagnosis is easier in chronic patients with a disease duration >1 year, while making an early diagnosis in the acute phase is more difficult. Early diagnosis is particularly important because of the significant effect of early immunosuppressive therapy. The diagnostic criteria proposed by Bien et al. are divided into two parts A and B. Part A: (1) focal epilepsy (with or without persistent limited epilepsy) and cortical damage on one side; (2) EEG showing slow waves with or without epileptiform discharges in one cerebral hemisphere; (3) MRI showing focal cortical atrophy in one cerebral hemisphere with at least one of the following: gray or white matter T2/ Part B: (i) persistent limited epilepsy or progressive cortical damage on one side; (ii) progressive focal atrophy of one hemisphere on MRI; (iii) histopathological examination of brain tissue with T-cell and microglia infiltration; RS can be excluded if there are more macrophages, B-cells or plasma cells or viral inclusions in the brain tissue. If brain tissue biopsy is not available, gadolinium-enhanced MRI and cranial CT may be performed to demonstrate the lack of gadolinium elevation and calcification to rule out other diseases that can cause hemiparesis.
Treatment
RS treatment has two goals: to reduce seizures and to stop progressive neurological damage.
1. antiepileptic drugs are poorly effective in treating persistent partial epilepsy, but are effective for other types of seizures.
2. Surgical treatment plays an important role in the treatment of RS epilepsy. Hemispherectomy is currently the most effective and the only method to cure RS radically, with complications such as hemiplegia, hemianopia and speech impairment (if the dominant hemisphere is removed). The timing of surgery is controversial, with some scholars preferring hemispherectomy in the early stages of the disease, while others believe that surgery should be performed when symptoms such as motor deficits, hemianopia, and aphasia appear during the course of the disease. The latter view is that not all children, especially those with late onset disease, will have the greatest degree of neurological damage. Those who advocate early surgery believe that the surgery will save the child from seizures and improve overall neurological function.
3. Immunosuppressive, immunomodulatory, and antiviral therapies have been used clinically, but their efficacy is also uncertain. Immunotherapy includes.
①Corticosteroid therapy.
② Intravenous immunoglobulin therapy.
(iii) corticosteroids + immunoglobulin.
④ plasma exchange (PEX) or protein AIgG immunosorbent (PAI).
⑤ Tacrolimus: an immunosuppressive agent that inhibits T-cell activity.
There are no clear guidelines for the choice of initial immunotherapy, and according to current data, hormones, intravenous application of gammaglobulin, PEX/PAI or tacrolimus are appropriate, but also not comparable to surgical treatment in stopping disease progression.