Rasmussen's encephalitis: Early diagnostic criteria in children

Rasmussen's encephalitis (RE) is a rare chronic inflammatory brain disorder resulting in progressive neurodegeneration in one cerebral hemisphere. The inflammatory process is accompanied by progressive loss of function of the affected hemisphere, associated with drug-resistant partial epilepsy. The diagnosis is based on a range of clinical, electroencephalographic, radiological and biochemical arguments, without any specific formal marker, which makes the diagnosis of the disease complex, especially in its initial phase. Seizures are refractory to anti-seizures medication (ASM) and to classical immunomodulatory treatments. These treatments are also ineffective to stop the degenerative process. Only surgical treatment with hemispherotomy (surgical disconnection of a cerebral hemisphere) allows definitive cessation of seizures but this leads to definitive motor and cognitive deficits. The etiology of RE is not known, but there is strong evidence for an immunopathogenic mechanism involving T-cell mediated immunity. The emergence of biotherapies targeting against various cytokines offers potential therapeutic perspectives. This disease is currently a real challenge in terms of: (i) early diagnosis, before the constitution of marked hemispheric atrophy and the appearance of neurological and cognitive consequences; (ii) recognition of incomplete form; (iii) therapeutic management due to advances in the field of targeted treatment of inflammation; (iv) surgery and recovery possibilities.     

Neuroimaging follow-up in a case of Rasmussen's encephalitis with dyskinesias.

We describe a case of adult-onset biphasic Rasmussen's encephalitis who presented seizures and left dyskinesias at the onset and, after 1 year, language disorder. Serial MRI and [(18)F] FDG-PET scans were performed showing involvement of the right cerebral hemisphere in the first phase and of the contralateral one in the second.     

“Epilepsia partialis continua” due to multifocal encephalitis: Favourable outcome after immunoglobulin treatment

The case of a young woman with EPCK is described in which neoplastic and vascular disorders were excluded. Supported by EEG and PET, EPCK was imputed to multifocal encephalitis notwithstanding serological and CSF negativity. Cerebral biopsy confirmed the inflammatory nature of the affection, although the etiologic agent was not identified. High dose intravenous immunoglobulin therapy was followed by the prompt disappearance of EPCK and the remission of the other neurological deficits.

---

Sommario Viene descritto un caso di EPCK nel quale era stata esclusa una patologia neoplastica o vascolare dell'encefalo. L'EPCK è stata attribuita ad una encefalite multifocale, che ha trovato sostegno nei reperti EEG e PET, nonostante la negatività delle indagini sierologiche e liquorali. Una biopsia cerebrale ha confermato la natura flogistica dell'affezione, senza identificarne l'agente etiologico. La somministrazione endovenosa di immunoglobuline ad alto dosaggio è stata seguita da una rapida scomparsa della EPCK e da una remissione degli altri deficit neurologici.

     

Multiphasic presentation of Rasmussen's encephalitis

Rasmussen's encephalitis is a rare, chronic inflammatory disorder of unknown cause, characterised by drug‐resistant focal epilepsy that may rarely present in adolescence or adulthood. We present a case of Rasmussen's encephalitis with prominent recurrent fluctuation in symptoms and well‐documented fluctuating changes on MRI, adding to the spectrum of diversity of Rasmussen's encephalitis.     

Neuronal autoantibodies in patients with Rasmussen's encephalitis

Aim. Rasmussen's encephalitis (RE) is a rare disease with unknown pathophysiology. To disclose whether anti‐neuronal autoimmunity participates in the aetiology of RE, various neuronal autoantibodies (NAAbs) were investigated in sera of patients with RE and controls. Methods. The study included five patients who fulfilled the RE diagnostic criteria (clinical, EEG, and MRI findings) as the patient group, and 50 multiple sclerosis patients and 50 healthy subjects as the control groups. Sera were evaluated for various NAAbs by radioimmunoassay or cell‐based assays. All sera were also screened for uncharacterized antibodies to neuronal cell surface or synapse antigens by indirect immunofluorescence using hippocampal cell cultures. Results. The mean age at onset of seizures was 8.3±3.4 years (range: 4–13.5) and mean follow‐up time was 11.2±5.4 years (range: 5–19). All patients had unihemispheric atrophy of the cerebral cortex and epilepsia partialis continua. Two of the patients had moderate cognitive impairment, while the others were severely affected, as shown by neuropsychological testing. NAAb positivity was not detected in any of the patients. Conclusion. Immune aetiology is thought to have a role in RE, but the responsible players have not yet been elucidated. Our extensive antibody screening in a small number of patients does not support the presence of antigen‐specific anti‐neuronal autoimmunity in RE pathophysiology.     

Adult-Onset Rasmussen's Encephalitis: Anatomical-Electrographic-Clinical Features of 7 Italian Cases

Summary:  Purpose: A limited number of cases of adult-onset Rasmussen's encephalitis (A-RE) have been reported, but the features of the syndrome are still unclear. The aim of this study was to verify the clinical features of A-RE, and outline a noninvasive approach that may allow its early diagnosis and treatment.
Methods: Retrospective evaluation of extensive noninvasive work-up of seven patients with A-RE, including repeat clinical, neurophysiological, and neuroimaging investigations.
Results: The study identified two distinct patterns of disease presentation, one characterized by focal motor epilepsy (the "epileptic" phenotype), and the other by focal cortical myoclonus (the "myoclonic" phenotype). Unilateral neurological deficits and brain atrophy were progressive in both phenotypes, but they were more prominent and were detected earlier in the "epileptic" phenotype.
Conclusions: The anatomo-electroclinical features of these patients allowed a noninvasive diagnosis of A-RE and identification of two distinct disease phenotypes. Early noninvasive diagnosis can allow faster initiation of treatment.     

Electrophysiological findings in Rasmussen's syndrome

Background. Rasmussen syndrome is a rare, inflammatory and probably autoimmune disease presenting with epilepsia partialis continua which is generally in the form of myoclonic jerks and involves the upper extremities with or without head involvement. We sought to demonstrate the electrophysiological features in patients with Rasmussen syndrome. Methods. We performed continuous electrophysiological recordings of involuntary movement, as well as recordings of startle responses and long latency reflex in three patients with a diagnosis of Rasmussen syndrome. Results. Positive and negative myoclonus were recorded. Startle responses were found to be suppressed. However, long latency reflexes were high in amplitude and one patient even had a C reflex. Conclusion. Stimulus‐sensitive positive and negative cortical myoclonus are typical in epilepsia partialis continua of Rasmussen syndrome and degeneration of brainstem and reticulospinal pathways may develop in Rasmussen syndrome.     

Non‐ketotic hyperglycaemia presenting as epilepsia partialis continua

Epilepsia partialis continua is a rare epileptic syndrome observed in patients with brain structural lesions and metabolic disorders. We report a patient with non‐ketotic hyperglycaemia presenting as epilepsia partialis continua with reversible focal brain lesions. An 83‐year‐old woman visited our hospital due to sudden and repetitive left facial twitching lasting for two days. Initial laboratory data revealed serum glucose, osmolality, and sodium levels of 631 mg/dl, 310 mOsm/l, and 130 mEq/l, respectively. EEG was normal. Brain MRI showed low signal changes in the right frontal subcortical area and high signal changes in the surrounding right frontal cortical areas on T2‐weighted, fluid‐attenuated inversion recovery, and diffusion‐weighted images. No seizures recurred after correcting blood glucose levels, hydrating the patient, and infusing valproate (900 mg/day). Follow‐up MRI, six months later, showed complete resolution of the signal changes in the right frontal cortical and subcortical areas and no clinical seizures. When considering non‐ketotic hyperglycaemia with epilepsia partialis continua in an elderly patient, early diagnosis and administration of the appropriate therapy is very important in order to decrease morbidity.     

Rasmussen's encephalitis: Experience from a developing country based on a group of medically and surgically treated patients

PurposeTo describe the attributes of patients with Rasmussen's encephalitis (RE) seen in a tertiary epilepsy referral center in southern India and to enquire factors helpful in predicting responsiveness to immunotherapy.MethodsWe diagnosed RE based on the European consensus criteria. To assess the factors that could potentially predict the natural course and therapeutic outcome, we subcategorized our patients according to age at onset ( 6 years), duration from onset to presentation ( 2 years), immunotherapy versus surgery, and early (≤2 years from the onset) versus late surgery.ResultsThe median age at disease onset of 19 patients was 6.0 years (range 2.3–13 years). Epilepsia partialis continua (EPC) and hemiparesis were noted in 14 (73.6%) and 16 (84.2%) patients, respectively. One patient, who presented with dysarthria due to tongue EPC, did not have hemiparesis despite having had the disease for over 15 years. The MRI findings in majority conformed to stage 3 of Bien classification. While 9/10 patients treated by surgery achieved seizure-freedom, only 1/11 patients who received immunotherapy did so. One patient expired due to subsequent development of contralateral hemispheric disease following successful hemispherectomy. None of the factors such as age at onset, age at presentation, presence/absence of antecedents, seizure burden, MRI stage predicted responsiveness to immunotherapy.ConclusionThis study from a developing country, in addition to substantiating the well known characteristics of RE, noted the following unusual findings: isolated lingual EPC abolished by focal cortical resection, bilateral RE, putaminal atrophy and absence of hemiparesis despite long standing disease.     

Clinical course and variability of non-Rasmussen, nonstroke motor and sensory epilepsia partialis continua: a European survey and analysis of 65 cases

Purpose: To gain new insights into the clinical presentation, causes, treatment and prognosis of epilepsia partialis continua (EPC), and to develop hypotheses to be tested in a prospective investigation. Methods: In this retrospective multicenter study, all cases were included that fulfilled these criteria: constantly repeated fragments of epileptic seizures, with preserved consciousness, lasting ≥1 h and representing locally restricted motor or sensory epileptic activity. Single episodes were included when they lasted for a minimum of 1 day. EPC with Rasmussen syndrome and acute stroke were excluded. Key Findings: Three time courses with two subtypes each were distinguished, that is, EPC as a solitary event (de novo or in preexistent epilepsy); chronic repetitive nonprogressive EPC (with frequent or rare episodes); and chronic persistent nonprogressive EPC (primarily or evolving out of an episodic course). These were unrelated to etiologies (morphologic lesions 34%, inflammatory 29%, systemic disorders 9%, idiopathic 5%, unknown 23%). Precipitation and inhibition of seizures is a frequent feature of EPC. Levetiracetam and topiramate have improved the possibilities for pharmacotherapy. Topiramate seems to be particularly effective with dysontogenetic etiologies. Significance: The existence of several clearly distinct courses of nonprogressive EPC is a new finding. These distinctions will be further investigated in a prospective study with precise protocols for electroencephalography (EEG), imaging, and other studies. This should better establish the relation of motor and somatosensory EPC; further clarify the relations, pathogenesis, and significance of the different types and their etiologies; and possibly identify more semiologic variants. It should also provide more precise knowledge about therapy and modification of ictogenesis by external stimuli.     

Dual pathology in Rasmussen's encephalitis: A study of seven cases and review of the literature

Dual pathology has previously been reported in less than 10% of cases of Rasmussen's encephalitis (RE). Given the rarity of RE, it appears unlikely that dual pathology in RE is merely a coincidence. We therefore reviewed all cases of RE experienced in our institution to assess for an additional/associated pathology. A total of seven patients with RE were identified in our archives. Seven children (4 boys and 3 girls, age range: 3–16 years, mean: 9.5 years) with medically refractory epilepsy underwent surgical resection for intractable seizures. The surgical specimens were examined with routine neurohistological techniques, and immunohistochemistry was performed with an extensive panel of antibodies for viruses, lymphocytes, microglia/macrophages, human leukocyte antigen (HLA)‐DR, astrocytes, and neurons. Relevant literature was reviewed. Microscopically, all seven cases demonstrated the inflammatory pathology of RE in the cortex and white matter with leptomeningeal and perivascular lymphocytic infiltration, microglial nodules with/without neuronophagia, neuronal loss and gliosis. The HLA‐DR antibody was extremely helpful in highlighting the extent of microglial cell proliferation/activation that was not appreciable with standard histology. An unexpected finding in all seven cases was the presence of cortical dysplasia. In our series of seven cases, there was co‐occurrence of the inflammatory/destructive pathology of RE with malformative/dysplastic features in cortical architecture in 100% of cases, raising questions about the possible relationships between the two entities. Awareness of the possibility of dual pathology in RE is important for clinical and pathological diagnosis, and may affect the management and outcome of these patients. Immunohistochemistry is very helpful to make a definitive diagnosis of both pathologies.     

Epilepsia partialis continua in tick‐borne Russian spring‐summer encephalitis

Objectives – Epilepsia partialis continua (EPC) is characterized by localized continuous jerks, from time to time with spreading Jacksonian seizures and, more rarely, secondarily generalized tonic‐clonic seizures. EPC has numerous possible etiologies. In this paper we describe EPC in the tick‐borne Russian spring‐summer encephalitis (TBRSSE) and compare it with Rasmussen syndrome. Methods – We included patients with EPC in TBRSSE (between 2003 and 2010). The diagnosis was verified by immunology (antibodies against TBRSSE virus). The patients were followed 1–7 (mean 3.4) years. Results – We studied 10 patients (eight males, age 10–21 years) with MRI and video‐EEG. Nine developed EPC after acute TBRSSE (meningoencephalitic form), and one had a tick bite without clinical symptoms of encephalitis, but with subsequent EPC. All patients came from Ural and Siberia. The onset was at age 4–14 (mean 8.6 years). The interval from onset of TBRSSE or the tick bite to seizure onset was 1 day–4 years. We identified three phases of clinical course EPC in TBRSSE: (i) acute (meningoencephalitic/encephalitic); (ii) development of EPC; and (iii) chronic EPC. The effect of antiepileptic drugs differed according to seizure types. Conclusion – EPC caused by TBRSSE is relatively frequent in the Eastern parts of the Russian Federation but not west of the Ural. Unlike Rasmussen encephalitis, EPC with TBRSSE does not progress even in the long term. It appears as disabling but not fatal condition with a time course where three phases can be distinguished.     

Bilateral Rasmussen encephalitis: postmortem documentation in a five-year-old

A case of Rasmussen encephalitis with bilateral involvement and onset at age 2 years is reviewed. Rasmussen encephalitis is a rare progressive disease that causes intractable seizures, cognitive decline, and inflammatory changes in the brain. The neurologic involvement is characteristically unilateral. Bilateral involvement in this case was suspected within 5 months of presentation and was confirmed by bilateral frontal lobe biopsies. The severity and progression of the disease in this case was remarkable and resulted in the patient's death by age 5 years, despite numerous attempted therapeutic interventions. Autopsy findings confirmed the diagnosis of Rasmussen encephalitis with bilateral involvement.     

Abdominal epilepsia partialis continua in neurocysticercosis

Epilepsia partialis continua (EPC) of abdominal muscles is a rare entity with variable clinical localization and aetiology. A 25‐year‐old man presented with sudden onset of intermittent focal myoclonic movements involving the abdominal muscles on the right side exclusively, lasting from 20 minutes to an hour. Brain MRI revealed a ring‐enhancing lesion, suggestive of cysticercal granuloma over the left precentral gyrus. The patient fulfilled the revised diagnostic criteria for definitive diagnosis of neurocysticercosis. EEG did not show focal abnormalities during the events. Episodes of EPC were controlled with difficulty using 600 mg oxcarbazepine, 200 mg lacosamide, and 2,000 mg levetiracetam. The patient received antiparasitic therapy with albendazole (15 mg/kg for two weeks) and oral dexamethasone (0.1 mg/kg) for two weeks which was then tapered. The involvement of the primary motor cortex during ictal propagation may account for this curious phenomenon. This is the first report of abdominal EPC in a patient with inflammatory granuloma as a result of neurocysticercosis.     

Intraventricular Interferon-α Stops Seizures in Rasmussen's Encephalitis: A Case Report

Summary: A 3.5-year-old girl had epilepsia partialis continua of the right side. Clinical and laboratory findings were consistent with Rasmussen's encephalitis. Treatment with high-dose methylprednisolone led to temporary control of seizures, but for 2 years, the seizures remained refractory to phenobarbital, phenytoin, lorazepam, carbamazepine, valproic acid, vigaba-trin, gabapentin, and lamotrigine. A 6-week course, and later a 6-month course, of intraventricular interferon-α almost totally suppressed the seizures. Although moderately hemiparetic, the child has reasonable neurologic function with mild speech delay. She is receiving her third course of treatment, and seizures remain completely controlled.     

病毒性脑炎的头颅MRI表现

目的 研究头颅核磁共振（ＭＲＩ）对病毒性脑炎的早期诊断价值。方法 观察１０例病毒性脑炎患者头颅ＣＴ、ＭＲＩ表现,其中８例增强扫描。５例行快速液体衰减反转回复（ＦＬＡＩＲ）检查。结果 头颅ＭＲＩ较ＣＴ发现更多病灶,其病灶多不增强,ＦＬＡＩＲ技术可以更清发现病灶,其中单纯疱疹病毒性脑炎的ＭＲＩ更有其特征性表现。结论 头颅ＭＲＩ有助于病毒性脑炎的早期诊断同。     

Nationwide survey (incidence,clinical course,prognosis) of Rasmussen’s encephalitis

Purpose: Rasmussen’s encephalitis (RE) is a progressive and catastrophic epileptic disorder caused by chronic localized encephalitis. We performed a nationwide survey of RE to assess the clinical picture, treatment effect, and prognosis of Japanese RE patients. Subjects & methods: The subjects were 27 patients (male:12; female:15) from 13 medical facilities. All of them satisfied the clinical and neuroimaging criteria for RE, including 14 pathologically proven cases. Results: They were divided into the childhood-onset rapidly progressive type (CORP, n = 19), and late-onset slowly progressive type (LOSP, n = 8). The mean age at epilepsy onset was 4 years and 4 months in CORP, and 16 years in LOSP. The mean period between the onset age of epilepsy and development of frequent seizures was 1 year and 4 months in the former, and 3 years and 4 months in the latter. The immunomodulatory treatment including high-dose steroid (n = 14) and high-dose intravenous immunoglobulin therapies (IVIgG, n = 12) achieved more than a 50% reduction in the seizure frequency in 5 (36%) and 4 (33%) patients, respectively. Eight and seven patients underwent focal cortical resection and functional hemispherectomy, leading to significant improvement in 5 of the 8 patients and excellent seizure control in all 7 patients, respectively. Conclusion: Although the high-dose steroid and IVIG therapies may have alleviated the exacerbation of seizures in those with RE, they could not halt the disease progression. Functional hemispherectomy is still the only curative therapy for RE, despite the fact that the early introduction of this procedure remains controversial.