Rasmussen's Encephalitis Research Articles

HCMV infection and IFITM3 rs12252 are associated with Rasmussen's encephalitis disease progression.

ObjectiveRasmussen’s encephalitis (RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses such as human cytomegalovirus (HCMV) has been hypothesized to be a potential trigger for RE. Interferon‐induced transmembrane protein‐3 (IFITM3) single‐nucleotide polymorphism (SNP) rs12252 is associated with the severity of viral infection disease. This study aimed to address the possibility that HCMV infection and IFITM3 rs12252 might be associated with RE disease progression.MethodsThe expression of HCMV and IFITM3 was detected with immunohistochemical staining, in situ hybridization and immunofluorescence double staining. The genotype of IFITM3 rs12252 was detected using the Sanger sequencing method. A genetic association analysis was carried out for this SNP and HCMV antigen expression. The relationship between this SNP and the clinical characteristics of these patients was further analyzed. In in vitro study, HCMV replication in SH‐SY5Y cells with overexpressed IFITM3 variant was detected by immunofluorescence and real‐time RT‐PCR.ResultsElevated expression of HCMV and IFITM3 was observed in the brain tissue of RE patients. Moreover, the IFITM3 polymorphism rs12252‐C was found to associate with HCMV high detection and rapid disease progression in RE patients with the IFITM3 rs12252‐CC genotype. In vitro study showed the overexpressed IFITM3 variant was associated with HCMV high infection level.ConclusionThese results suggest that the IFITM3 rs12252‐C is associated with the disease progression of RE patients via facilitating persistent HCMV infection in brain tissue and provides new insight into understanding the pathogenesis of RE.

Rasmussen's encephalitis with persistent epilepsy in a young man.

Rasmussen's encephalitis (RE) is an uncommon cause of the seizure. Important key findings of RE include intractable seizure activity in children, progressive atrophy of the involved hemisphere, and small hemisphere with the large ventricle.

Rasmussen Encephalitis: Case Report and Review of the Literature

Rasmussen encephalitis (RE), also called Rasmussen syndrome, is a rare, progressive, chronic encephalitis affecting one hemisphere of the brain. It occurs mainly in children. However, around 10% of all cases are adolescents and adults. RE occurs usually in healthy individuals. It is estimated that no more than two new cases per year are identified in large epilepsy centers. Rasmussen’s encephalitis is characterized by intractable focal seizures, often in the form of epilepsia partialis continua (EPC) with motor and cognitive deterioration. Neuroimaging shows the progressive damage of the affected hemisphere, and histopathology is consistent with a T-cell dominated encephalitis with activated microglial cells and reactive astrogliosis. Cerebral hemispherectomy remains the only cure for seizures, but there are inevitable functional compromises. We report the rare case of an 8-year-old girl without any clinical history presented with recent left hemiparesis and seizures, and whose investigations based on the brain MRI and Electroencephalogram data, conducted to the diagnosis of Rasmussen’s encephalitis. Our management was exclusively medical, with a good outcome.

Neurological rehabilitation for a patient with chronic Rasmussen encephalitis: a case report.

ABSTRACTRasmussen encephalitis is a rare disease consisting of a chronic, slowly progressive inflammatory reaction of brain tissues. The objective of this study was to describe the case of an 18-year-old female patient, studying on the fourth grade of elementary school, and right-handed, who underwent left hemispherectomy in a neurological rehabilitation program. Her seizures began at 10 years of age and were unresponsive to drug treatment, with functional repercussions. She underwent hemispherectomy in March 2019, with 7 years of ongoing disease, and was admitted for the rehabilitation program with a multidisciplinary team in June 2020. The quality-of-life questionnaire (WHOQOL-BREF) was applied as a comparison measure before and after the rehabilitation program, along with measures of participation on the program activities. Despite the patient’s short time in a rehabilitation program, data show the importance of an interdisciplinary intervention through the establishment of specific and contextualized objectives in chronic patients.

Lessons learnt from 101 hemispherotomies in children with symptomatic epilepsy. Part I: seizure outcome

To evaluate variables that may predict the outcome after hemispherotomy basing on a retrospective study of a large consecutive pediatric cohort of patients from a single institution.One hundred and one patients with refractory seizures and variable decline in development (n=78) underwent hemispherotomy (med. age - 43 months, med. epilepsy history - 30 months). Developmental pathology was the anatomical substrate of disorder in 42 patients, while the infantile post-stroke scarring and gliosis was its origin in the majority of 43 cases with acquired etiology. The progressive pathology (the Rasmussen encephalitis, Sturge-Weber angiomatosis and tuberous sclerosis) was the etiology in 16 children. Left-sided hemisphere was impaired in 54 cases; some contralateral anatomical and potentially epileptogenic MRI-abnormalities were noted also in «healthy» hemisphere in ¼ of all cases. Eight patients needed second surgery to complete sectioning of undercut commissural fibers. FU is known in 91 patients (med. - 1.5 years) and 73 of them were free of seizures (80.2%), but only 30 of 40 patients with FU > 2 years were still SF (75%). All but one of re-do hemispherotomies were successful. AED-treatment was discontinued in 46 cases and tapered in other 27 patients. Up to 90% of kids demonstrated some improvement in behavior and cognition.Developmental pathology, infantile spasms and younger age onset of seizures are negative predictors for achievement of SF-status (p<0.05). Neither bilateral epileptic EEG-signs, nor MRI-abnormalities in «healthy» hemisphere had any relation to outcome, but focal seizure onset was associated positively with further SF-status (p = 0.03). Kids with multiple lobe unilateral CD do somewhat worse than their counterparts with hemimegalencephaly and acquired etiology. Post-hemispherotomy hemiparesis (either new or worsening of already existed one) has no relation either to the age at surgery, or to the age onset (p = 0.41). Children with left-sided lesions were less successful in every neurodevelopmental domain except maintaining expressive language. Patients with relapse or persisting seizures have good chances to become SF by re-doing hemispherotomy and should be evaluated for the possibly incomplete hemispheric isolation.Проанализировать влияние некоторых клинических факторов (семиология и частота приступов, возраст дебюта эпилепсии и ее длительность, этиология поражения и наличие аномалии в «здоровом» полушарии по данным магнитно-резонансной томографии) и способа дисконнекции пораженного полушария на исходы после гемисферотомии.Оперирован 101 ребенок. Медиана возраста на момент операции 43 мес, длительности эпилепсии 30 мес. У большинства (78) детей имелась задержка в развитии. В 25 наблюдениях на магнитно-резонансных томограммах имелись структурные нарушения и в противоположной, «здоровой», гемисфере. В 55 случаях произведена латеральная периинсулярная деафферентация, в 46 — вертикальная парасагиттальная дисконнекция (в 54 — слева, в 47 — справа). Повторно оперированы 8 пациентов в связи с продолжающимися приступами или их возобновлением (у всех — из-за неполной дисконнекции).Катамнез известен у 91 ребенка, с медианой продолжительности 1,5 года. Приступы прекратились у 73 (80,2%) человек, но только у 30 (75%) из 40 детей с катамнезом 2 года и более. В 80% случаев удалось отменить или упростить лечение антиэпилептическими препаратами (АЭП). Пороки развития мозга, инфантильные спазмы и ранняя манифестация эпилепсии оказались негативными предикторами в отношении вероятности полного прекращения приступов (p<0,05). Фокальное начало в приступах позитивным образом связано с вероятностью их полного прекращения после гемисферотомии (p=0,03). Вероятность появления нового или усугубление уже имевшегося гемипареза, а также его перманентности не связана ни с этиологией эпилепсии, ни с возрастом на момент операции или возрастом дебюта эпилепсии (p=0,41). Сторона поражения сказалась на развитии познавательных способностей и поведении (у детей с левополушарной гемисферотомией сохранились проблемы с их формированием), однако на формирование и развитие экспрессивной речи этот фактор не повлиял.У детей с эпилепсией, обусловленной структурным анатомическим поражением одного из полушарий мозга, гемисферотомия — единственная возможность помощи, если лечение антиэпилептическими препаратами неэффективно.

Neuropathology of Surgically Managed Epilepsy Specimens.

Epilepsy is characterized as recurrent seizures, and it is one of the most prevalent disorders of the human nervous system. A large and diverse profile of different syndromes and conditions can cause perturbations in neural networks that are associated with epilepsy. Advances in neuroimaging and electrophysiological monitoring have enhanced our ability to localize the neuropathological lesions that alter the neural networks giving rise to epilepsy, whereas advances in surgical management have resulted in excellent seizure control in many patients following resections. Histopathologic study using a variety of special stains, molecular analysis, and functional studies of these resected tissues has facilitated the neuropathological characterization of these lesions. Here, we review the neuropathology of common structural lesions that cause epilepsy and are amenable to neurosurgical resection, such as hippocampal sclerosis, focal cortical dysplasia, and its associated principal lesions, including long-term epilepsy-associated tumors, as well as other malformations of cortical development and Rasmussen encephalitis.

An Overview of The Role of Tumor Necrosis Factor-Alpha in Epileptogenesis and Its Terapeutic Implications.

The complex association between neuroinflammation and seizures has been widely investigated in recent years. As mediators of inflammatory response, cytokines like tumor necrosis factor-α (TNF-α) are potential therapeutic targets for epileptic disorders. TNF-α is a pleiotropic cytokine with a controversial role in epileptogenesis, seemingly capable to both favor the genesis of seizures and elicit neuromodulatory responses. Anti-TNF agents are a group of monoclonal antibodies engineered to inhibit the response to this cytokine for antinflammatory purposes. The clinical experience of the use of these drugs in neurological conditions like multiple sclerosis showed controversial results. Evidence in favor of the employment of anti-TNF agents for the treatment of epilepsy are still limited to certain forms of disorders, notably Rasmussen encephalitis, and in carefully selected patients.

Inflammation, ictogenesis, and epileptogenesis: An exploration through human disease.

Epilepsy is seen historically as a disease of aberrant neuronal signaling manifesting as seizures. With the discovery of numerous auto-antibodies and the subsequent growth in understanding of autoimmune encephalitis, there has been an increasing emphasis on the contribution of the innate and adaptive immune system to ictogenesis and epileptogenesis. Pathogenic antibodies, complement activation, CD8+ cytotoxic T cells, and microglial activation are seen, to various degrees, in different seizure-associated neuroinflammatory and autoimmune conditions. These aberrant immune responses are thought to cause disruptions in neuronal signaling, generation of acute symptomatic seizures, and, in some cases, the development of long-term autoimmune epilepsy. Although early treatment with immunomodulatory therapies improves outcomes in autoimmune encephalitides and autoimmune epilepsies, patient identification and treatment selection are not always clear-cut. This review examines the role of the different components of the immune system in various forms of seizure disorders including autoimmune encephalitis, autoimmune epilepsy, Rasmussen encephalitis, febrile infection-related epilepsy syndrome (FIRES), and new-onset refractory status epilepticus (NORSE). In particular, the pathophysiology and unique cytokine profiles seen in these disorders and their links with diagnosis, prognosis, and treatment decision-making are discussed.

Brain compensatory mechanisms enhance the recovery in the Rasmussen encephalitis child patient: a case was followed for 16 years.

Brain compensatory mechanisms enhance the recovery in the Rasmussen encephalitis child patient: a case was followed for 16 years.

Brain Inflammation and Seizures: Evolving Concepts and New Findings in the Last 2 Decades.

The concept of brain inflammation and its role in epilepsy has much evolved during the last 2 decades since my original Epilepsy Currents commentary,1 and even more since its first description in autoptic tissue from Rasmussen's encephalitis or in epilepsies developing after central nervous system (CNS) infections. The new vision stems from in-depth investigations carried out since 1999 in preclinical models of provoked seizures and acquired epilepsies and in human focal epilepsies.2 This commentary reports my subjective historical perspective of the progress in the field, also considering if predictions of the seminal findings were confirmed by the follow-up research, or if some original concepts were disproved. I will also discuss which aspects of this complex phenomenon need further investigations to help gather valuable insights for the clinical translation of the increasing experimental evidence.

An immunotherapy effect analysis in Rasmussen encephalitis

BackgroundImmune-mediated mechanisms substantially contribute to the Rasmussen encephalitis (RE) pathology, but for unknown reasons, immunotherapy is generally ineffective in patients who have already developed intractable epilepsy; overall laboratory data regarding the effect of immunotherapy on patients with RE are limited. We analyzed multiple samples from seven differently treated children with RE and evaluated the effects of immunotherapies on neuroinflammation. Immunotherapy was introduced to all patients at the time of intractable epilepsy and they all had to undergo hemispherothomy.MethodsImmunohistochemistry, flow cytometry, Luminex multiplex bead and enzyme-linked immunosorbent assay techniques were combined to determine: 1) inflammatory changes and lymphocyte subpopulations in 45 brain tissues; 2) lymphocyte subpopulations and the levels of 12 chemokines/cytokines in 24 cerebrospinal fluid (CSF) samples and 30 blood samples; and 3) the dynamics of these parameters in four RE patients from whom multiple samples were collected.ResultsSustained T cell-targeted therapy with cyclophosphamide, natalizumab, alemtuzumab, and intrathecal methotrexate (ITMTX), but not with azathioprine, substantially reduced inflammation in brain tissues. Despite the therapy, the distributions of CD8+ T cells and the levels of C-X-C motif ligand (CXCL) 10, CXCL13, and B cell activating factor (BAFF) in patients’ CSF remained increased compared to controls. A therapeutic approach combining alemtuzumab and ITMTX was the most effective in producing simultaneous reductions in histopathological inflammatory findings and in the numbers of activated CD8+ T cells in the brain tissue, as well as in the overall CD8+ T cell population and chemokine/cytokine production in the CSF.ConclusionsWe provide evidence that various T cell-targeted immunotherapies reduced inflammation in the brains of RE patients. The observation that intractable epilepsy persisted in all of the patients suggests a relative independence of seizure activity on the presence of T cells in the brain later in the disease course. Thus, new therapeutic targets must be identified. CXCL10, CXCL13 and BAFF levels were substantially increased in CSF from all patients and their significance in RE pathology remains to be addressed.

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.

Age-Dependent Reduction in Severity and Discrete Topographical Patterns in Rasmussen Encephalitis: A Link to Cortical Maturation?

BackgroundAutopsy studies in Rasmussen encephalitis reveal areas of sparing within the affected hemisphere. Clinical progression and inflammation are milder with an older onset. We sought to demonstrate radiological corroboration for these patterns. MethodsIn our retrospective study, 38 cases were dichotomized into severe pan-hemispheric (all lobes involved) and sub-hemispheric groups (others) to identify age demographics and other severity predictors. The extent and patterns of radiological pathology in the cortex and subcortical structures were assessed by structured visual grading. Relevant clinical data were also reported. ResultsChildren with pan-hemispheric involvement were younger at onset (P < 0.001) and were more likely to present with status epilepticus (odds ratio 8.5, 95% confidence interval 1.5 to 50.0, P = 0.022). A history of perinatal asphyxia/hospitalization (P < 0.001) and delayed milestones (P = 0.013) were encountered exclusively in this group, and progression to a low-amplitude record background on electroencephalography, suggesting that cortical damage was identified frequently (P = 0.038, odds ratio = 5.7, 95% confidence interval 1.3 to 25.0). Visual grading revealed significant differences among both cortical (P < 0.001) and subcortical (P < 0.001) regions. On multivariate analysis, the odds for pan-hemispheric disease decreased per year of age at onset (P = 0.022, odds ratio 0.51, 95% confidence interval 0.085 to 0.725). Epilepsy surgery (n = 14) was associated with Engel Class 1 seizure control (P < 0.001). Immunosuppressive therapy (n = 20) did not demonstrate a significant seizure remission (P = 0.157, odds ratio 0.39, 95% confidence interval 0.10 to 1.55). ConclusionsOur case series confirms the presence of specific topographical patterns of macroscopic radiological pathology over the affected hemisphere with a marked age-associated reduction in the odds for severe pan-hemispheric disease.

Epilepsy surgery for Rasmussen encephalitis: the UCLA experience.

Rasmussen encephalitis (RE) is a rare inflammatory neurological disorder typically involving one hemisphere and resulting in drug-resistant epilepsy and progressive neurological decline. Here, the authors present seizure outcomes in children who underwent epilepsy surgery for RE at a single institution. The records of consecutive patients who had undergone epilepsy surgery for RE at the UCLA Mattel Children's Hospital between 1982 and 2018 were retrospectively reviewed. Basic demographic information, seizure history, procedural notes, and postoperative seizure and functional outcome data were analyzed. The cohort included 44 patients, 41 of whom had sufficient data for analysis. Seizure freedom was achieved in 68%, 48%, and 22% of the patients at 1, 5, and 10 years, respectively. The median time to the first seizure for those who experienced seizure recurrence after surgery was 39 weeks (IQR 11-355 weeks). Anatomical hemispherectomy, as compared to functional hemispherectomy, was independently associated with a longer time to postoperative seizure recurrence (HR 0.078, p = 0.03). There was no statistically significant difference in postoperative seizure recurrence between patients with complete hemispherectomy and those who had less-than-hemispheric surgery. Following surgery, 68% of the patients could ambulate and 84% could speak regardless of operative intervention. A large proportion of RE patients will have seizure relapse after surgery, though patients with anatomical hemispherectomies may have a longer time to postoperative seizure recurrence. Overall, the long-term data in this study suggest that hemispheric surgery can be seen as palliative treatment for seizures rather than a cure for RE.

Pediatric Inflammatory and Autoimmune Neurologic Disorders at a Tertiary Medical Center.

To describe the spectrum of pediatric inflammatory neurologic diseases and compare the sensitivity of ancillary testing for these diagnoses. We analyzed clinical features and outcomes of 98 children with an immune-mediated central nervous system disorder. We compared sensitivities of each diagnostic modality. We identified the following diagnoses: acute cerebellar ataxia (n = 14; 14.3%), acute demyelinating encephalomyelitis (n = 13; 13.3%), multiple sclerosis (MS) (n = 18; 18.4%), anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDAR encephalitis) (n = 15; 15.3%), encephalitis not otherwise specified (n = 12; 12.2%), and "Other" (n = 26; 26.5%). "Other" included acute transverse myelitis, neuromyelitis optica, central nervous system lupus, primary central nervous system vasculitis, Rasmussen encephalitis, opsoclonus myoclonus ataxia syndrome, and clinically isolated syndrome. The mean age of onset of all diagnoses was 7.9 ± 5.5 years. The diagnostic sensitivity of magnetic resonance imaging (MRI) for acute demyelinating encephalomyelitis and multiple sclerosis was 92.3% and 94.4%, respectively. Cerebrospinal fluid was sensitive for multiple sclerosis in 92.3%, where 75% of patients had cerebrospinal fluid oligoclonal bands. Electroencephalogram (EEG) coupled with cerebrospinal fluid studies was highly sensitive for anti-NMDAR encephalitis (100%). EEG was sensitive for acute demyelinating encephalomyelitis and encephalitis not otherwise specified (77.8% and 80%). No diagnostic studies were sensitive for acute cerebellar ataxia. Seventy-three percent of patients with multiple sclerosis had residual deficits. Thirty-six percent of anti-NMDAR encephalitis patients were nonverbal and wheel-chair bound. We found that MRI is useful for detecting multiple sclerosis and acute demyelinating encephalomyelitis, cerebrospinal fluid is helpful in diagnosing multiple sclerosis and anti-NMDAR encephalitis, and EEG is often abnormal in suspected anti-NMDAR encephalitis, acute demyelinating encephalomyelitis, and encephalitis not otherwise specified. Neurologic outcome at follow-up was unfavorable in patients with multiple sclerosis and anti-NMDAR encephalitis.

Gliomatosis cerebri and Rasmussen's encephalitis: Two different entities causing refractory epilepsy. Comparison through two clinical cases

Background and importanceRasmussen's Encephalitis (RE) is a chronic and progressive childhood disease caused by an inflammatory disorder that affects a cerebral hemisphere. On the other hand, Gliomatosis Cerebri (GC) is a rare primary neoplastic glial process with a diffuse and infiltrative growth. Clinical presentationWe present two clinical cases with a history of continuous focal epilepsy refractory to antiepileptic drugs. They share similar clinical and radiologic features, but a different histopathological diagnosis. A brain biopsy was needed to distinguish GC from a RE. ConclusionThe debut of a drug-resistant epilepsy with focal seizures and an ipsilateral progressive hemiparesis suggests the diagnosis of RE. However, there are other entities such as GC, which, despite its rarity, should be considered in the differential diagnosis. So, in some cases, histological diagnosis is needed.

The Dilemma of Hemispherectomy for Rasmussen's Encephalitis in a Neurologically Intact Child

AbstractRasmussen's encephalitis is a rare drug-resistant focal epilepsy characterized by progressive hemiparesis, hemianopia, and cognitive decline. Hemispherectomy is currently the only known treatment that can be curative, though expected to cause postoperative motor and visual deficits in children and adolescents. To date, medical treatment with antiseizure medications and immunosuppressive agents can only offer partial, delayed, or temporary alleviation of symptoms. Hence, patients and families are often faced with the difficult decision to consider the possibility of seizure freedom at the cost of incurring permanent deficits. Here, we discussed the unique ethical issues when faced with a cure that can cause harm, and also discussed a shared decision-making approach guided by informed consent, principles of autonomy, and patient-centered values.

Risk factors and results of hemispherotomy reoperations in children.

The goal of this study was to perform an analysis of a single-center experience with hemispherotomy reoperations for refractory hemispheric pediatric epilepsy due to persistence of seizures after initial surgery. The authors also identify possible anatomical and neurophysiological reasons for hemispherotomy failure, as well as risk factors and surgical options for this subgroup of patients. A review was performed of the medical records in 18 consecutive cases in which candidates for redo hemispherotomy were treated between 2003 and 2018 at the authors' epilepsy surgery center. Fourteen patients underwent reoperation due to seizure recurrence and were studied herein, whereas in 3 the initial surgical procedure was stopped because of uncontrollable bleeding, and the remaining patient refused to undergo a reoperation in spite of seizure recurrence and went on to have a vagus nerve stimulation device placed. Among the 14 patients whose seizures recurred and in whom reoperations were done, the etiology of epilepsy consisted of 7 cases with malformations of cortical development (50%), 5 cases of Rasmussen encephalitis (35.8%), 1 case of porencephaly (7.1%), and 1 case of Sturge-Weber syndrome (7.1%). Eleven patients had radiological evidence of incomplete disconnection. After reoperation, 6 patients were Engel class IA, 1 was Engel II, 5 were Engel III, and 2 were Engel IV, within a mean follow-up of 48.4 months. Patients with malformations of cortical development have a higher risk of seizure recurrence, and these malformations comprised the main etiology in the reoperation series. Failure of an initial hemispherotomy usually occurs due to incomplete disconnection and needs to be extensively assessed. Outcomes of reoperation are most often favorable, with acceptable complication rates.

Double Pathology in Rasmussen Encephalitis.

Investigators from Children's Hospital Colorado and University of Colorado conducted a retrospective review of electronic medical records to identify all Rasmussen Encephalitis (RE) cases that had undergone surgery with subsequent pathologic evaluation at Children's Hospital Colorado during 2005-2019 to determine the frequency of double pathology.

How frequent is double pathology in Rasmussen encephalitis?

Rasmussen encephalitis (RE) is an uncommon, medically refractory cause of seizures that usually presents in childhood or adolescence resulting in unilateral hemispheric atrophy in most cases. The purported immune-mediated cause of the disease is supported by the characteristic histopathologic features of diffuse perivascular and intraparenchymal T-cell-predominant infiltrates, microglial activation with microglial nodules, and neuronophagia. A small number of reports have emerged, however, suggesting that double pathology (such as focal cortical dysplasia (FCD) or hippocampal sclerosis) may be present. We asked how often double pathology could be demonstrated in RE. A 15-year retrospective review of all RE cases seen at our pediatric tertiary care hospital yielded 11 patients, many of which had some degree of double pathology. The most diagnostically incontrovertible examples showed leptomeningeal neuronal heterotopia (n = 1) or leptomeningeal melanocytic nevus (n=1). Another coexistent feature was neuronal gigantism unassociated with hemimegaloencephaly, particularly prominent in layer II (n=2). Three additional cases showed dysmorphic neurons in the hippocampus (n=2) and dentate granule cell layer dispersion/bilamination (n=1). Finally, 2 cases had exaggerated radial arrangement of neurons FCD type Ia-like changes) (n=2), a condition known to have interobserver discordance. In summary, 7/11 of our RE cases showed prominent additional pathologies, 6 of which demonstrated disproportionately more severe inflammation, neuronophagia, or microglial activation in regions of double pathology. Our collection of cases shows that a majority of RE cases show double pathology. Although some of these cases can be reactive, the presence of maldevelopment in a subset raises the possibility of a causal relationship with RE. .