Diagnosis Of Rasmussen Encephalitis Research Articles

Rasmussen Encephalitis: A Rare Neurological Disorder

A case of Rasmussen encephalitis in a 8 year old child is reported here who presented with recurrent focal seizures and progressive weakness of left half of body. EEG showed electrical features of epilepsy. MRI brain showed cortical atrophy of one brain hemisphere. On the basis of clinical and radiological evidence, diagnosis of Rasmussen encephalitis was made which is a rare neurological disorder of childhood.

Diagnostic algorithm for children presenting with epilepsia partialis continua.

To characterize a cohort of children with epilepsia partialis continua (EPC) and develop a diagnostic algorithm incorporating key differential diagnoses. Children presenting with EPC to a tertiary pediatric neurology center between 2002 and 2019 were characterized. Fifty-four children fulfilled EPC criteria. Median age at onset was 7years (range 0.6-15), with median follow-up of 4.3years (range 0.2-16). The diagnosis was Rasmussen encephalitis (RE) in 30 of 54 (56%), a mitochondrial disorder in 12 of 54 (22.2%), and magnetic resonance imaging (MRI) lesion-positive focal epilepsy in 6 of 54 (11.1%). No diagnosis was made in 5 of 54 (9%). Children with mitochondrial disorders developed EPC earlier; each additional year at presentation reduced the odds of a mitochondrial diagnosis by 26% (P=.02). Preceding developmental concerns (odds ratio [OR] 22, P<.001), no seizures prior to EPC (OR 22, P<.001), bilateral slowing on electroencephalogram (EEG) (OR 26, P<.001), and increased cerebrospinal fluid (CSF) protein level (OR 16) predicted a mitochondrial disorder. Asymmetry or hemiatrophy was evident on MRI at presentation with EPC in 18 of 30 (60%) children with RE, and in the remainder at a median of 6months (range 3-15) after EPC onset. The first diagnostic test is brain MRI. Hemiatrophy may permit a diagnosis of RE with unilateral clinical and EEG findings. For children in whom a diagnosis of RE cannot be made on first scan but the clinical and radiological presentation resembles RE, repeat imaging every 6months is recommended to detect progressive unicortical hemiatrophy, and brain biopsy should be considered. Evidence of intrathecal inflammation (oligoclonal bands and raised neopterin) can be supportive. In children with bihemispheric EPC, rapid polymerase gamma testing is recommended and if negative, sequencing mtDNA and whole-exome sequencing on blood-derived DNA should be performed. Children presenting with EPC due to a mitochondrial disorder show clinical features distinguishing them from RE and structural epilepsies. A diagnostic algorithm for children with EPC will allow targeted investigation and timely diagnosis.

Arterial spin labeling hyperperfusion in Rasmussen's encephalitis: Is it due to focal brain inflammation or a postictal phenomenon?

Background and purposeThe study evaluated the utility of arterial spin labeling (ASL) perfusion imaging in Rasmussen's encephalitis (RE). Material and methodsThe hospital electronic database was searched using the search words “encephalitis,” “autoimmune encephalitis” and “Rasmussen's encephalitis” for the period of 1 Jan 2015 to 31 Jan 2017. Clinically diagnosed cases of RE for which epilepsy protocol magnetic resonance imaging (MRI) with perfusion imaging (ASL) performed on a 3T scanner were retrieved. The diagnosis of RE was based on Bien's criteria (Bien et al., 2005). We obtained patient's demographic details, clinical features, electrophysiological studies, and follow-up data from electronic hospital records. ResultsWe included nine patients with RE of whom seven patients showed increased perfusion, and two patients decreased perfusion. Among these patients, MRI changes of gyral hyperintensity without volume loss corresponded to regional ASL hyperperfusion in six patients and ASL hypoperfusion in one patient. Two patients who showed ASL hypoperfusion had corresponding atrophy on MRI. Eight patients of RE had epilepsia partialis continua (EPC) or daily seizures, and one patient was seizure-free post-surgery. Five patients showed a concordance of ASL hyperperfusion with clinical ictal onset zone. Among the seven patients with ASL hyperperfusion, the finding was concordant (complete or partial) with the electroencephalogram (EEG) ictal onset zone in six patients and with interictal epileptiform discharges (IED) in seven patients. ConclusionIncreased perfusion in ASL of the involved brain parenchyma in RE is a common MRI finding and may be due to either active inflammation of the brain involved or a seizure-related finding.

2. Follow-up of five cases with Rasmussen encephalitis with magnetoencephalography

Magnetoencephalography (MEG) recordings of interictal and/or ictal discharges can provide valuable information about the location of the epileptogenic area in the brain. Rasmussen Encephalitis (RE) is characterized by intractable epilepsy, progressive hemiparesis, and unilateral hemispheric atrophy. The progression of the symptoms to significant neurological impairment usually occurs within months to a few years. Five patients (mean age at first observation 7.6 ± 3 years) fitting Bien’s criteria for the diagnosis of RE were enrolled for the study and follow-up for at least 1.5 years (4–7 MEG measures per patient), in order to evaluate correlations between the evolution of clinical picture, neuroradiological and MEG findings. MEG data were visually inspected and interictal spikes were selected for the source localization by means of equivalent current dipoles (ECDs). Cortical thickness was evaluated from Magnetic Resonance Imaging (MRI). All patients showed ictal/interictal multifocality, reduction of background cortical magnetic activity, and progressive focal cortical atrophy on MRI of the affected hemisphere. Moreover, our preliminary data showed that dipole clusters were found mainly in the most atrophic cortical regions, suggesting a close relationship between MRI and MEG alterations.

Conservative management of Rasmussen's encephalitis in a Nigerian girl

Rasmussen's encephalitis (RE) is a rare disease of the brain characterized by focal seizures, unilateral cortical deficits, hemiparesis, and hemiatrophy of the contralateral cerebral hemisphere. The affected brain tissue shows a chronic inflammatory histopathology and an autoimmune reaction is suspected. Therapeutic strategies include anticonvulsants, immunomodulation and surgery. We present the first report of RE in a Nigerian. A 4-year-old girl presented with a 15-month history of recurrent involuntary jerky movements of the right upper limb and tonic deviation of the neck to the right side often associated with loss of consciousness. Seizures lasted 2 to 3 min and occurred every 2 to 3 h. She later developed right-sided weakness. On examination, she had right-sided spastic hemiparesis with astereognosis. The electroencephalograph showed theta and delta waves on the left cerebral hemisphere with epileptiform sharp and slow waves and phase reversal pattern. Brain computerized tomogram showed left hemispheric hemiatrophy with non-enhancing hypodense lesions in the left hemisphere. This was confirmed by brain magnetic resonance imaging, which showed left cerebral atrophy with associated left white matter hyperintensities on fluid-attenuated inversion recovery sequences. There was no enhancement with gadolinium. She improved on anticonvulsants. She fulfilled the European Consensus criteria for the diagnosis of RE. Electroencephalography and magnetic resonance imaging are important for the diagnosis of RE, a condition worth considering in patients with focal seizures and unilateral neurological deficits.

Evolution of MRI changes in Rasmussen's encephalitis

We studied the MRI findings in 16 patients with Rasmussen's encephalitis (RE), further analysed serial MRI changes in 11 of them and correlated it with clinical features. The diagnosis of RE was based on the European consensus statement (Brain, 128, 2005, 454). Details related to demographical, clinical, MRI observations were analysed. Forty MRIs of brain of 16 patients were reviewed. Eleven patients had undergone serial brain MRIs ranging from two to five occasions. All the patients had unihemispheric focal cortical atrophy, predominantly in the perisylvian region (n = 13). Other features were white matter signal changes (n = 14), and ipsilateral caudate (n = 6) and putamen (n = 4) atrophy. Signal alterations in putamen and caudate were noted in four each. In all the 11 patients with serial MRI, there was progression of cerebral atrophy and a trend towards increase in MRI staging. The MRI signal changes remained same in five patients, resolved in three patients, differential change in two patients and increased in one patient. Diffusion-weighted imaging showed facilitated diffusion (n = 5), and MR spectroscopy showed reduced N-acetyl-aspartate and elevated lactate (n = 2). Pattern recognition of MRI findings and the changes in serial MRI might serve as a surrogate marker of disease viz. unihemispheric progressive focal cortical atrophy and signal changes predominantly in the perisylvian distribution and caudate followed by putamen involvement. This might assist in understanding and monitoring of the disease progression.

Extrarolandic electroclinical findings in the evolution of adult-onset Rasmussen's encephalitis

Rasmussen's encephalitis (RE) is a rare immunomediated disorder characterized by unilateral hemispheric atrophy, drug-resistant focal epilepsy, and progressive neurological deficits. Its onset typically occurs in childhood, though it has also been reported in adult age (A-RE) with atypical clinical features. The aim of this study was to describe the electroclinical features in a group of seven patients with A-RE.We retrospectively studied seven women aged 23–43years (mean: 32.1years) with a diagnosis of RE according to commonly accepted diagnostic criteria. All the patients were clinically evaluated and underwent prolonged video-EEG monitoring, laboratory investigations, and high-resolution MRI follow-up.All the patients displayed an ictal electroclinical pattern whose evolution varied. We identified an early phase characterized by polymorphic ictal electroclinical manifestations (temporal semiology in five cases, frontal in one, and parietal in the remaining case) and a late phase clinically characterized by viscerosensitive phenomena followed by somatosensitive signs, experiential symptoms, and motor signs in all the cases. In the late phase, the ictal EEG pattern was characterized by monomorphic, pseudorhythmic, repetitive slow-wave theta activity over the frontal and central regions, with ipsilateral propagation and/or secondary spreading to contralateral perisylvian structures. Patients were treated with a combination of AEDs and immunotherapy (steroids and IVIg); epilepsy surgery was performed in 3 cases.Our results show that A-RE is characterized by early and late clinical- and EEG-different features which may reflect a progressive involvement of a specific “extrarolandic” network in the advanced phase of the disease and may suggest that the electroclinical expression of RE varies according to the different stages of the pathological process.

Clinico‐pathological investigations of Rasmussen encephalitis suggest multifocal disease progression and associated focal cortical dysplasia

Rasmussen encephalitis is a devastating neurological disorder characterised by seizures, brain inflammation, and progressive hemispheric atrophy. The objective of the current study was to systematically characterise patterns of structural lesions in children with Rasmussen encephalitis, referred for modified anatomical hemispherectomy at the Tsinghua University Epilepsy Center in Beijing. Seven consecutive patients were investigated with a mean age at operation of 4.5 years, who suffered from medically intractable seizures for a mean of 1.6 years. Foci of abnormally increased T2 signal intensity were observed in all patients. With the exception of one child, all patients presented with progressive unilateral cerebral atrophy. FDG-PET imaging revealed extensive regions of hypometabolism within the affected cerebral hemisphere in 3 of 4 patients. Diagnosis of Rasmussen encephalitis was confirmed histologically, demonstrating CD68 positive microglial nodules, as well as CD3 and CD8 positive Tlymphocytes invading the cerebral parenchyma. An intriguing observation was the heterogenous distribution of patterns of lesions throughout the affected hemisphere, suggesting multifocal manifestation and distinct sequences of disease progression, from discrete foci of inflammatory infiltrates (stage 1) to extensive cortical destruction (stage 4). Atypical hippocampal sclerosis (HS), with neuronal cell loss affecting most prominently the CA4 region (HS type 3 or end folium sclerosis), was evident in 5 of 7 cases. Four hippocampi also showed chronic inflammation. In addition, we observed associated focal cortical dysplasia (FCD; ILAE type IIId) in 4 of 7 children, supporting the concept of acquired and postmigratory FCD pathomechanisms. Postsurgical seizure freedom was achieved in all children with a mean follow-up period of 2.7 years and continuous antiepileptic medication.

Immunomodulatory therapy versus surgery for Rasmussen syndrome in early childhood

We examined seizure, cognitive, and motor outcomes in patients with Rasmussen syndrome or Rasmussen encephalitis (RS), after recent initiation of immunomodulatory therapies. Among 53 patients with a diagnosis of RS referred from all over Japan, 49 patients (male 22, female 27) with symptoms and findings characteristic of RS were evaluated. Regular intravenous immunoglobulin (IVIg) therapy was administered at a dose of 100mg/kg/day, etc. Regular steroid pulse therapy was conducted with methylprednisolone at a dose of 30mg/kg/day (children) or 1000mg/day (adults) for 3days. Tacrolimus was given at an initial dose of 0.1mg/kg/day (children). Mean onset age was 8.7±10.5years. Seizure-free rate was 71% after treatment by functional hemispherectomy (FH), and response rate for seizures was 81% by regular steroid pulse therapy, 42% by tacrolimus therapy, and 23% by regular IVIg therapy. Rate of patients with IQ higher than 80 (R80) was 50% by regular steroid pulse therapy, 43% by regular IVIg therapy, 29% by tacrolimus therapy, and 0% by FH. R80 after regular steroid pulse therapy was 100% in patients without MRI lesions, and 37% in those with advanced MRI lesions. Improvement of motor function (paresis) was observed only by immunomodulatory therapy. Motor function was aggravated in 100% of patients treated by FH, 62% by regular IVIg, and 10% by regular steroid pulse therapy. We suggest a new treatment strategy for RS using early immunomodulatory therapy: initiation of regular steroid pulse therapy after early diagnosis indicated by biomarkers, then switching to tacrolimus therapy after several months.

Rasmussen Encephalitis Followed by Other Autoimmune Disorders: Comorbidity or Chance Association? (P05.211)

Objective: To study patients with Rasmussen encephalitis (RE) and associated autoimmune disorders (AID). Background RE is a rare chronic inflammatory disease characterized by intractable focal epilepsy, often epilepsia partialis continua, progressing to hemiparesis, cognitive impairment, and unilateral cerebral atrophy. The etiology of RE remains unknown. We have previously reported the occurrence of two rare AID, Behcet9s disease and RE, in a father and son respectively. Design/Methods: Review of medical records of four individuals with a dual diagnosis of RE and other AID. Results: The diagnosis of RE in all four patients was based on previously reported criteria, and was pathologically confirmed in patients 2, 3 and 4. In family 1, a patient with RE onset at 2 years developed Hashimoto9s thyroiditis at 15 years; he also had a brother with Type 1 (autoimmune) diabetes mellitus. In family 2, the patient had RE onset at 3 years, and developed ulcerative colitis at 10 years. In family 3, the patient had RE at the age of 6 years, and developed Crohn9s disease at age 14. In family 4, the patient had RE onset at 14 years and onset of systemic lupus erythematosus at 31 years. In these four families, the second AID appeared several years after the onset of RE, with a mean interval of 11 years (median 10 years). Conclusions: We suggest that the incidence of a second AID in RE patients may be higher than by chance; however, the true frequency and relative risk are unknown. Our observations suggest that there may be a common predisposing factor for the development of autoimmune responses in these patients. Further study of the long term evolution of RE patients, as well as detailed family histories, and use of newer molecular techniques such as CGH microarray and whole exome sequencing, are warranted to clarify this. Disclosure: Dr. Amrom has nothing to disclose.

Diffusion tensor imaging and tractography of Rasmussen encephalitis

A 5-year-old girl presented with intractable seizures and nonfocal hemispheric slowing on EEG. Blood, urine, and CSF laboratory values were all normal. MR imaging of the brain demonstrated diffuse volume loss of the entire left hemisphere. Clinical and imaging findings were consistent with the diagnosis of Rasmussen encephalitis. Diffusion tensor imaging demonstrated increased ADC values and decreased fractional anisotropy (FA) of the affected (left) hemisphere. Tractography data showed decreased numbers of lines drawn in the affected hemisphere, with fewer lines drawn at higher FA thresholds, relative to the contralateral hemisphere, or to normal age-matched controls. Diffusion tensor imaging offers an adjunct MR imaging modality in diagnosis and monitoring of this rare condition.

Limited chronic focal encephalitis

To describe a more limited and less malignant form of Rasmussen encephalitis (RE). Three subjects (all women; 37, 31, and 32 years of age) developed childhood or late onset chronic focal encephalitis, with a relatively nonprogressive form of the disorder. In our patients, clinical features were dominated by partial seizures without marked focal motor deficit and in two with choreo-dystonic movements. The diagnosis of RE was supported by histologic examination and anatomic and functional MRI. These cases extend the phenotypic presentations of Rasmussen encephalitis and confirm Theodore Rasmussen's suggestion that there may be mild and nonprogressive forms of the disease.

Long term response to steroid therapy in Rasmussen encephalitis

Rasmussen encephalitis (RE) is a severe and progressive focal epilepsy of unknown origin that leads to deterioration of motor and cognitive function. In a previous study, we described positive effect of high doses of steroids during the first year after the onset of RE. The objective of this study was to evaluate this therapy at long term. We reviewed 11 patients (7 girls and 4 boys) with RE of the right hemisphere (7) and the left (4) at a follow-up of 9+/-2 years. Age at onset of RE ranged from 2 to 14 years. Six patients had no benefit from steroid therapy and underwent hemispherotomy. Five had significant reduction of seizure frequency with disappearance of epilepsia partialis continua, and improved motor function. Of these, two died of unexpected sudden death 5 and 7 years after seizure control. Two others with initial response experienced progressive recurrence of seizures 1 to 4 years after the end of steroid therapy and required hemispherotomy. Finally, only one patient exhibited total cessation of seizures with steroids for 3 years, but seizures progressively recurred although the frequency was moderate. Our data confirm that although steroid treatment can be useful when given early in the course of RE, long term relapse can occur among the good responders requiring delayed hemispheric disconnection.

Putaminal involvement in Rasmussen encephalitis

Rasmussen encephalitis (RE) is a rare devastating disease of childhood causing progressive neurological deficits and intractable seizures, typically affecting one hemisphere. Characteristic MRI features include progressive unihemispheric focal cortical atrophy and grey- or white-matter high-signal changes and basal ganglion involvement, particularly of the caudate nucleus. To analyse the pattern of involvement of different brain structures in a series of patients with RE and to attempt clinical correlation. We reviewed the medical records and neuroimaging data of 12 patients diagnosed with RE satisfying the European Consensus Statement diagnostic criteria. The disease manifested as seizures in all patients and was refractory; epilepsia partialis continua was a notable feature (nine patients). Hemiparesis of varying grades was noted in all but one patient; none had extrapyramidal signs. Neuroimaging showed cortical involvement in the insular/periinsular regions in 11 patients. Caudate atrophy was noted in ten patients. Putaminal atrophy was seen in nine patients, six of whom had additional hyperintense signal changes. Our study highlights frequent putaminal atrophy and signal changes in RE, which suggests a more extensive basal ganglion involvement than emphasized previously. Recognition of putaminal changes may be a useful additional tool in the radiological diagnosis of RE.

Neuropathological spectrum of Rasmussen encephalitis

Rasmussen encephalitis (RE) is a chronic epileptic disorder of unknown etiology, and is clinically characterized by progressive neurological deterioration, focal seizures often progressing to intractable epilepsy, cognitive decline and hemispheric atrophy. We report the spectrum of neuropathological changes seen in RE, and discuss the evolutionary mechanisms of this disease. Surgically obtained specimens from RE patients diagnosed during 2002-2004 at this institute were evaluated for the presence and extent of different histopathological features of RE. The H&E and immunohistochemistry stained slides were also evaluated for the type and distribution pattern of inflammatory infiltrates, along with a semiquantitative evaluation for the severity of inflammation. Four cases of RE were admitted during the study period, all of which presented with partial seizures with successive deterioration to intractable epilepsy. The age at onset varied between 5 and 10 years (mean 7.8 years), with three male and one female patients. Subsequently, all four patients underwent hemispherotomy. Histopathological features of perivascular lymphocytic infiltrate, neuronal loss, microglial nodules, and reactive astrocytosis, with or without evidence of neuronophagia confirmed a diagnosis of RE. These cases also had varying degrees of T-cell-rich (CD3-positive) inflammatory infiltrates and CD68-immunopositive microglial proliferation. It was observed that the severity of inflammation had a trend to inversely correlate with the duration of symptoms. It is proposed that an accurate evaluation and histopathological grading of these lesions may possibly have a role in patient prognostication.

Diagnostic imaging in 13 cases of Rasmussen's encephalitis: can early MRI suggest the diagnosis?

Rasmussen's encephalitis (RE) is a rare, progressive, chronic encephalitis characterised by drug-resistant epilepsy, progressive hemiparesis and mental impairment. It typically involves only one cerebral hemisphere, which becomes atrophic. We present neuroradiological findings in 13 children with RE. MRI was performed in all patients, fluorodeoxyglucose positron-emission tomography (PET) in three, Tc-99m hexamethylpropylenamine oxime single-photon emission computed tomography (SPECT) in two and proton MR spectroscopy ((1)HMRS) in two. MRI showed progression of the hemisphere atrophy, always prevalent in the region primarily involved (13 patients), spread of the abnormal signal in white matter (11) and cortex (10) and progression of atrophy of the head of the caudate nucleus (nine). Associated secondary changes were: atrophy of the contralateral cerebellar hemisphere (in four patients), the ipsilateral hippocampus (in five) and the brain stem (in five). The earliest CT and MRI abnormalities, seen between 1 day and 4 months after the first seizure (in 12 patients examined, nine of whom had MRI) in one cerebral hemisphere included: high signal on T2-weighted images in the cortex (seven patients) and white matter (nine), cortical atrophy usually involving the frontoinsular region, with mild or severe enlargement of the lateral ventricle (eight) and moderate atrophy of the head of the caudate nucleus (seven). Cortical swelling in the early stage of the disease was recognisable only in two patients. PET revealed hypometabolism, SPECT decreased perfusion, and (1)HMRS reduction of N-acetylaspartate in the affected hemisphere. PET and SPECT were usually performed in the late stages and did not provide specific findings. MRI thus demonstrates the progression of RE and may suggest the diagnosis in the early stages, often before the appearance of neurological deficits. Early diagnosis of RE may be crucial for selecting patients for aggressive medical therapy or major surgical interventions such as hemispherectomy.

Corneal thermal patterns in anterior uveitis.

<b>Objective: </b> To describe a more limited and less malignant form of Rasmussen encephalitis (RE). <b>Methods: </b> Three subjects (all women; 37, 31, and 32 years of age) developed childhood or late onset chronic focal encephalitis, with a relatively nonprogressive form of the disorder. <b>Results: </b> In our patients, clinical features were dominated by partial seizures without marked focal motor deficit and in two with choreo-dystonic movements. The diagnosis of RE was supported by histologic examination and anatomic and functional MRI. <b>Conclusions: </b> These cases extend the phenotypic presentations of Rasmussen encephalitis and confirm Theodore Rasmussen9s suggestion that there may be mild and nonprogressive forms of the disease.