Rasmussen's Encephalitis Research Articles

Intravenous Corticosteroids as an Adjunctive Treatment for Refractory and Super-Refractory Status Epilepticus: An Observational Cohort Study

Status epilepticus (SE) represents a neurological emergency that leads to considerable morbidity and mortality. Following failure of first-line therapy, usually with benzodiazepines, there is no clear evidence to guide treatment of refractory SE, although a wide variety of approaches has been described anecdotally. The aim of this study was to assess the clinical response to corticosteroids in adults with refractory and super-refractory SE, describing, to the best of our knowledge, the first adult SE cohort treated with corticosteroids. We retrospectively analysed our adult SE registry (2006-2017), identifying 15 out of 987 episodes (1.5%) in which corticosteroids were prescribed de novo as adjuvant therapy to a variety of antiepileptic drug regimens. We analysed incident episodes and defined clinical response as SE ceasing within 1week of administration, without any other medical intervention. Out of 987 SE episodes, 15 (1.5%) were treated with de novo corticosteroids, corresponding to 12 patients, with increasing prevalence as the SE became refractory (10/411; 2.4% of episodes) and super-refractory (5/108; 4.6% of episodes). One patient (a woman with Rasmussen encephalitis) presented with four SE episodes over a period of 3years, so only her index SE episode was included in subsequent analyses. The episodes treated were predominantly of inflammatory origin (6/12), such as autoimmune or Rasmussen encephalitis. In five out of 12 (42%) of the considered incident episodes, SE resolved following corticosteroids (all within 3days). The outcome was better in this responders group (for 2/5 episodes, patients did not have a new handicap at discharge, versus 0/7 in non-responders). In patients with inflammatory and acute symptomatic causes, global prognosis was better than in those with progressive or neurodegenerative aetiologies (6/8 vs. 4/4 had a new handicap at discharge or died). Our observations seem to support the use of corticosteroids, especially for acute SE of putative inflammatory origin; these compounds, however, were prescribed infrequently.

Ipsilateral motor evoked potentials in a patient with unihemispheric cortical atrophy due to Rasmussen encephalitis.

The role of the ipsilaterally descending motor pathways in the recovery mechanisms after unilateral hemispheric damage is still poorly understood. Motor output reorganization was investigated in a 56-year-old male patient with acquired unilateral hemispheric atrophy due to Rasmussen encephalitis. In particular, the ipsilateral corticospinal pathways were explored using focal transcranial magnetic stimulation. In the first dorsal interosseous and wrist extensors muscles, the median amplitudes of the ipsilateral motor evoked potentials induced by transcranial magnetic stimulation in the patient were higher than those of 10 age-matched healthy control subjects. In the biceps brachii muscle, the median amplitudes of the ipsilateral motor evoked potentials were the second largest in the patient compared to the controls. This study demonstrated a reinforcement of ipsilateral motor projections from the unaffected motor cortex to the hemiparetic hand in a subject with acquired unihemispheric cortical damage.

Long-term seizure outcome in frontal lobe epilepsy surgery

PurposeThe purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery. MethodThis retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001–2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome. ResultsMean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I–II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357). ConclusionSurgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates.

Rasmussen's Encephalitis. A Case Report

Rasmussen's encephalitis (RE) is a rare but severe immune-mediated brain disorder leading to unilateral hemispheric atrophy, associated progressive neurological dysfunction with intellectual decline, and intractable seizures. It is a well-established cause of pharmacologically intractable epilepsy. The report is on a 17-month-old infant, treated at the Mario Catarino Rivas Hospital Honduras. Family history: grandfather epileptic secondary trauma from 20 years. Personal history: two previous emergency visits (at 16 months and 16 months 8 days) for convulsions for which she was admitted three days and was treated with valproic acid 30 mg/kg per day. The infant is admitted in the emergency, with a history of about three hours after onset of tonic convulsions, focused on left-side with drooling, oculogiros and relaxation of sphincters and fever of 38.5 ° C. Entered as convulsive syndrome in the study, however, as the days passed the number of seizures increased to 60 per day and was gradually presenting alterations in neurodevelopment. MRI reported leukoencephalopathy of undetermined origin and biopsy reported findings consistent with Rasmussen's syndrome. She was treated with immunoglobulin every two weeks for six doses after two months of hospitalization with achieved improvement. Currently, episodes of seizures have decreased significantly and almost not convulsing, she presented alterations in neurodevelopment.

Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping

Inflammatory disorders of the CNS are frequently accompanied by synaptic loss, which is thought to involve phagocytic microglia and complement components. However, the mechanisms accounting for aberrant synaptic connectivity in the context of CD8+ Tcell-driven neuronal damage are poorly understood. Here, we profiled the neuronal translatome in a murine model of encephalitis caused by CD8+ Tcells targeting antigenic neurons. Neuronal STAT1 signaling and downstream CCL2 expression were essential for apposition of phagocytes, ensuing synaptic loss and neurological disease. Analogous observations were made in the brains of Rasmussen's encephalitis patients. In this devastating CD8+ Tcell-driven autoimmune disease, neuronal STAT1 phosphorylation and CCL2 expression co-clustered with infiltrating CD8+ Tcells as well as phagocytes. Taken together, our findings uncover an active role of neurons in coordinating phagocyte-mediated synaptic loss and highlight neuronal STAT1 and CCL2 as critical steps in this process that are amenable to pharmacological interventions.

Clinico-radiological approach to cerebral hemiatrophy.

Cerebral hemiatrophy is an uncommon neuroimaging finding of diverse etiologies, conventionally classified into two broad categories: congenital and acquired. The authors propose an alternative pragmatic clinical approach to cerebral hemiatrophy, classifying its diverse etiologies into a single event insult such as an in utero stroke, or a progressive disorder from an inflammatory or neoplastic process, the latter of which needs urgent intervention and will be the focus of our review paper. Illustrative cases will also be presented to facilitate the understanding of the discussed disorders. A systematic approach, linking both clinical and neuroimaging features, is important to facilitate the diagnostic workup of cerebral hemiatrophy. This may potentially help avoid large-scale investigations. Determining the underlying aetiology of cerebral hemiatrophy may impact treatment and prognostication as some conditions such as Rasmussen encephalitis and Parry-Romberg syndrome may benefit from timely implementation of immunomodulatory therapy.

The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells.

Multiple sclerosis is an inflammatory demyelinating disease in which active demyelination and neurodegeneration are associated with lymphocyte infiltrates in the brain. However, so far little is known regarding the phenotype and function of these infiltrating lymphocyte populations. In this study, we performed an in-depth phenotypic characterization of T and B cell infiltrates in a large set of multiple sclerosis cases with different disease and lesion stages and compared the findings with those seen in inflammatory, non-inflammatory and normal human controls. In multiple sclerosis lesions, we found a dominance of CD8+ T cells and a prominent contribution of CD20+ B cells in all disease courses and lesion stages, including acute multiple sclerosis cases with very short disease duration, while CD4+ T cells were sparse. A dominance of CD8+ T cells was also seen in other inflammatory controls, such as Rasmussen's encephalitis and viral encephalitis, but the contribution of B cells in these diseases was modest. Phenotypic analysis of the CD8+ T cells suggested that part of the infiltrating cells in active lesions proliferate, show an activated cytotoxic phenotype and are in part destroyed by apoptosis. Further characterization of the remaining cells suggest that CD8+ T cells acquire features of tissue-resident memory cells, which may be focally reactivated in active lesions of acute, relapsing and progressive multiple sclerosis, while B cells, at least in part, gradually transform into plasma cells. The loss of surface molecules involved in the egress of leucocytes from inflamed tissue, such as S1P1 or CCR7, and the upregulation of CD103 expression may be responsible for the compartmentalization of the inflammatory response in established lesions. Similar phenotypic changes of tissue-infiltrating CD8+ T cells were also seen in Rasmussen's encephalitis. Our data underline the potential importance of CD8+ T lymphocytes and B cells in the inflammatory response in established multiple sclerosis lesions. Tissue-resident T and B cells may represent guardians of previous inflammatory brain disease, which can be reactivated and sustain the inflammatory response, when they are re-exposed to their specific antigen.

Electroencephalography Findings in Autoimmune and Neuroinflammation-Related Epilepsies

AbstractAutoimmune epilepsy occurs in association with localized central nervous system or systemic immune-mediated inflammation. Traditional anticonvulsant medications are frequently ineffective, and alternative approaches including immunomodulatory agents may be required. Identification of patients with autoimmune epilepsy may be challenging due to the variability of presentation and normal or nonspecific diagnostic results. Electroencephalography (EEG) features tend to include patterns of encephalopathy, generalized or focal interictal epileptiform abnormalities, or status epilepticus. Occasionally, specific EEG features may lend insight into the diagnosis. In this review article, we discuss EEG features of several suspected or proven immune-mediated pediatric epilepsies, including Rasmussen's encephalitis, idiopathic hemiconvulsion-hemiplegia syndrome, febrile infection-related epilepsy syndrome, epilepsies associated with autoantibodies to neuronal surface or intracellular antigens, and other systemic autoimmune diseases.

Mechanisms underlying lesion development and lesion distribution in CNS autoimmunity.

It is widely accepted that development of autoimmunity in the central nervous system (CNS) is triggered by autoreactive T cells, that are activated in the periphery and gain the capacity to migrate through endothelial cells at the blood-brain barrier (BBB) into the CNS. Upon local reactivation, an inflammatory cascade is initiated, that subsequently leads to a recruitment of additional immune cells ultimately causing demyelination and axonal damage. Even though the interaction of immune cells with the BBB has been in the focus of research for many years, the exact mechanisms of how immune cells enter and exit the CNS remains poorly understood. In this line, the factors deciding immune cell entry routes, lesion formation, cellular composition as well as distribution within the CNS have also not been elucidated. The following factors have been proposed to represent key determinants for lesion evaluation and distribution: (i) presence and density of (auto) antigens in the CNS, (ii) local immune milieu at sites of lesion development and resolution, (iii) trafficking routes and specific trafficking requirements, especially at the BBB and (iv) characteristics and phenotypes of CNS infiltrating cells and cell subsets (e.g. features of T helper subtypes or CD8 cells). The heterogeneity of lesion development within inflammatory demyelinating diseases remains poorly understood until today, but here especially orphan inflammatory CNS disorders such as neuromyelitis optica spectrum disorder (NMOSD), Rasmussen encephalitis or SUSAC syndrome might give important insights in critical determinants of lesion topography. Finally, investigating the interaction of T cells with the BBB using invitro approaches or tracking of T cells invivo in animals or even human patients, as well as the discovery of lymphatic vasculature in the CNS are teaching us new aspects during the development of CNS autoimmunity. In this review, we discuss recent findings which help to unravel mechanisms underlying lesion topography and might lead to new diagnostic or therapeutic approaches in neuroinflammatory disorders including multiple sclerosis (MS).

S132. Ipsilateral cerebellar atrophy and crossed ictal cerebellar diaschisis in a case of Rasmussen encephalitis

Rasmussen encephalitis is a rare hemispheric inflammatory disease with progressive course leading to intractable focal seizures and neurological deficits, which can evolve to epilepsia partialis continua, hemiplegia, aphasia and other symptoms. Neuroimaging classically reveals progressive hemispheric atrophy, based on sequential computed tomography (CT) and magnetic resonance imaging (MRI). Contralateral injury to the cerebellum is expected, represented either by atrophy in anatomical images or by hypometabolism in functional studies as positron emission tomography-computed tomography (PET-CT) or single-photon emission computed tomography (SPECT). The postulated mechanism is interruption to the cerebropontine-cerebellar pathway, with resultant involvement of cerebellum ipsilateral to motor deficits. We describe a case of Rasmussen encephalitis with unexpected cerebellar involvement, evidenced in MRI and ictal SPECT performed during preoperative evaluation. A 4-year-old boy had onset of focal clonic motor seizures involving right face and tongue seizures, which evolved to epilepsia partialis continua, progressive right hemiparesis and aphasia. Neuroimaging studies showed progressive left cerebral hemisphere and left cerebellum atrophy. Ictal spect disclosed right cerebellar diaschisis. The patient underwent left functional hemispherectomy. Pathology findings were compatible with Rasmussen’s encephalitis. Clinical follow-up reveals a patient that remains with no more seizures. Considering cerebral hemisphere and cerebellum fiber connections, one would expect cerebellar atrophy contralateral to the involved cerebral hemisphere, as previously demonstrated. In our case, functional assessment with ictal SPECT showed contralateral diaschisis, but MRI demonstrated ipsilateral atrophy of cerebellum. These findings did not compromise clinical and surgical prognosis and anatomopathological studies confirmed the diagnosis of Rasmussen encephalitis. The reason for ipsilateral cerebellar involvement in our patient is unclear, but it appears to be more an anatomical variation of neuronal circuits between cerebral cortex and cerebellum than a marker of different clinical course.

Humanized mouse model of Rasmussen's encephalitis supports the immune-mediated hypothesis.

Rasmussen's encephalitis (RE) is a chronic inflammatory brain disorder that causes frequent seizures and unilateral hemispheric atrophy with progressive neurological deficits. Hemispherectomy remains the only treatment that leads to seizure freedom for this refractory epileptic syndrome. The absence of an animal model of disease has been a major obstacle hampering the development of effective therapies. Here, we describe an experimental mouse model that shares several clinical and pathological features with the human disease. Immunodeficient mice injected with peripheral blood mononuclear cells from RE patients and monitored by video electroencephalography developed severe seizures of cortical origin and showed intense astrogliosis and accumulation of human IFN-γ- and granzyme B-expressing T lymphocytes in the brain compared with mice injected with immune cells from control subjects. We also provide evidence for the efficacy of α4 integrin blockade, an approved therapy for the treatment of multiple sclerosis and Crohn's disease, in reducing inflammatory markers associated with RE in the CNS. This model holds promise as a valuable tool for understanding the pathology of RE and for developing patient-tailored experimental therapeutics.

Blocking immune intrusion into the brain suppresses epilepsy in Rasmussen's encephalitis model.

Rasmussen's encephalitis (RE) is a neuroinflammatory disease that typically affects only one hemisphere of the brain, resulting in severe seizures. Sixty years after the disease was first described, the preferred and best treatment option for RE is grotesque and involves removing a hemisphere of the brain (hemispherectomy); therefore, a better understanding of this seizure disorder may provide additional, less invasive therapeutic options. In this issue of the JCI, Carmant and colleagues have developed an animal model of this focal seizure disorder. The model provides experimental insights into the pathogenesis of RE and potential new treatments for this disease.

Proliferative hippocampal activity in a group of patients with Rasmussen's encephalitis: Neuronal, glial, and BDNF tissue expression correlations

Rasmussen's encephalitis (RE) is a rare and devastating unilateral inflammatory brain disease that causes severe and intractable partial epilepsy. It has been shown that epilepsy and subsequent inflammation have deleterious influence on hippocampal cell survival and neurogenesis, but this still has not been systematically explored in human tissue. In this study, we investigated the correlation between inflammation and epilepsy as well as the rates of hippocampal gliogenesis and neurogenesis in a pediatric group of six patients with RE and six control cases. The dentate gyrus (DG) samples were obtained from patients who underwent surgery for intractable RE. Sections were processed for immunohistochemistry using antibodies against sex determining region Y-box 2 (Sox2), nestin, human protein encoded by MKI67 gen (Ki67), and brain-derived neurotrophic factor (BDNF). There was an increase in the number of Ki67-positive granule cells in the DG of patients with RE in comparison with the autopsy control group, but no statistical difference for Sox2-positive cells was observed between these groups. Nestin immunolabeling was less intense in the RE group while BDNF expression was increased. Neurons that were BDNF-positive were found in DG from patients with RE but not in the control group. In patients with RE, few nestin-positive cells in DG were also positive for BDNF, unlike in controls which showed no colocalization for these two markers. These results suggest a proliferation activity in the DG subfield of patients with RE, and also future studies are necessary to address the role of new cells in the hippocampus of patients with RE.

Preclinical to Clinical Translation of Studies of Transcranial Direct-Current Stimulation in the Treatment of Epilepsy: A Systematic Review.

Epilepsy is a chronic brain syndrome characterized by recurrent seizures resulting from excessive neuronal discharges. Despite the development of various new antiepileptic drugs, many patients are refractory to treatment and report side effects. Non-invasive methods of brain stimulation, such as transcranial direct current stimulation (tDCS), have been tested as alternative approaches to directly modulate the excitability of epileptogenic neural circuits. Although some pilot and initial clinical studies have shown positive results, there is still uncertainty regarding the next steps of investigation in this field. Therefore, we reviewed preclinical and clinical studies using the following framework: (1) preclinical studies that have been successfully translated to clinical studies, (2) preclinical studies that have failed to be translated to clinical studies, and (3) clinical findings that were not previously tested in preclinical studies. We searched PubMed, Web of Science, Embase, and SciELO (2002–2017) using the keywords “tDCS,” “epilepsy,” “clinical trials,” and “animal models.” Our initial search resulted in 64 articles. After applying inclusion and exclusion criteria, we screened 17 full-text articles to extract findings about the efficacy of tDCS, with respect to the therapeutic framework used and the resulting reduction in seizures and epileptiform patterns. We found that few preclinical findings have been translated into clinical research (number of sessions and effects on seizure frequency) and that most findings have not been tested clinically (effects of tDCS on status epilepticus and absence epilepsy, neuroprotective effects in the hippocampus, and combined use with specific medications). Finally, considering that clinical studies on tDCS have been conducted for several epileptic syndromes, most were not previously tested in preclinical studies (Rasmussen's encephalitis, drug resistant epilepsy, and hippocampal sclerosis-induced epilepsy). Overall, most studies report positive findings. However, it is important to underscore that a successful preclinical study may not indicate success in a clinical study, considering the differences highlighted herein. Although most studies report significant findings, there are still important insights from preclinical work that must be tested clinically. Understanding these factors may improve the evidence for the potential use of this technique as a clinical tool in the treatment of epilepsy.

The skull, the sinuses, and the seizures

A 50 year old gentleman presented with status epilepticus, which was treated with benzodiazepines and phenytoin. Past medical history was significant for an encephalitic illness during infancy, with infrequent seizures (generalized tonic, clonic) since then. Neurological exam was significant for right sided weakness, which recovered over few days. Residual deficits consisted of a right pronator drift. No hemiatrophy or neurocutaneous markers were noted. Brain imaging was performed (Fig 1). The most likely diagnosis isA.Sturge-Weber syndromeB.Silver-Russell syndromeC.Dyke-Davidoff-Masson syndromeD.Hemimegalencephaly 1. Answer: Dyke-Davidoff-Masson syndrome (DDMS). DDMS was first described in 1933, in nine patients with infantile hemiplegia [[1]Dyke C.G. Davidoff L.M. Masson C.B. Cerebral hemiatrophy and homolateral hypertrophy of the skull and sinuses.Surg Gynecol Obstet. 1933; 57: 588-600Google Scholar]. It is characterized by cerebral hemiatrophy, secondary to an insult to the developing brain either during the fetal period (congenital) or in early childhood (acquired). Etiological factors include infection, vascular insult (infarct, reduced arterial perfusion, hemorrhage), birth asphyxia, trauma, or prolonged febrile seizures. Diagnosis of DDMS in adulthood is uncommon. Clinically, DDMS tends to present with contralateral hemiplegia, contralateral hemiatrophy, seizures, and cognitive impairment. Dystonia, hemiparkinsonism, and mirror movements have also been reported. While the congenital form usually manifests in the perinatal or infancy period, presentation of the acquired form may be delayed into adolescence [1Dyke C.G. Davidoff L.M. Masson C.B. Cerebral hemiatrophy and homolateral hypertrophy of the skull and sinuses.Surg Gynecol Obstet. 1933; 57: 588-600Google Scholar, 2Atalar M.H. Icagasioglu D. Tas F. Cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome) in childhood: clinicoradiological analysis of 19 cases.Pediatr Int. 2007; 49: 70-75Crossref PubMed Scopus (44) Google Scholar]. Radiological findings of DDMS include cerebral hemiatrophy and ipsilateral ventricle dilatation. Compensatory calvarial changes include ipsilateral thickening of calvarium, enlarged diploic spaces and paranasal sinuses, elevation of the petrous ridge, sphenoid wing and orbital roof, reduced size of the anterior/middle cranial fossa, and displacement of the falcine attachment. In congenital DDMS, ipsilateral shift of midline structures with calvarial changes is noted, while ipsilateral prominent sulcal spaces are seen if the insult occurs after sulcation is complete [1Dyke C.G. Davidoff L.M. Masson C.B. Cerebral hemiatrophy and homolateral hypertrophy of the skull and sinuses.Surg Gynecol Obstet. 1933; 57: 588-600Google Scholar, 2Atalar M.H. Icagasioglu D. Tas F. Cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome) in childhood: clinicoradiological analysis of 19 cases.Pediatr Int. 2007; 49: 70-75Crossref PubMed Scopus (44) Google Scholar]. Crossed cerebrocerebellar diaschisis, ipsilateral basal ganglia and thalamus/mesencephalic hypoplasia, secondary to wallerian/transneuronal degeneration, have been reported in DDMS [3Demir Y. Sürücü E. Çilingir V. Bulut M.D. Tombul T. Dyke-Davidoff-Masson Syndrome with cerebral hypometabolism and unique crossed cerebellar diaschisis in 18F-FDG PET/CT.Clin Nucl Med. 2015; 40: 757-758Crossref PubMed Scopus (5) Google Scholar, 4Winkler D.T. Probst A. Wegmann W. Tolnay M. Dyke Davidoff Masson syndrome with crossed cerebellar atrophy: an old disease in a new millenium.Neuropathol Appl Neurobiol. 2001 Oct; 27: 403-405Crossref PubMed Scopus (14) Google Scholar]. Shen, et al. have described three radiological patterns, based on cortical/subcortical atrophy, presence of porencephalic cyst, and chronic infarction/necrosis in the middle cerebral artery territory [[5]Shen W.C. Chen C.C. Lee S.K. et al.Magnetic resonance imaging of cerebral hemiatrophy.J Formos Med Assoc. 1993; 92: 995-1000PubMed Google Scholar]. Differential diagnosis of DDMS includes Silver-Russell syndrome, Sturge-Weber syndrome (SWS), Rasmussen encephalitis, Fishman syndrome (FS), linear nevus syndrome (LNS), and hemimegalencephaly. SWS and Fishman syndrome are neurocutaneous disorders, with typical cutaneous lesions (facial cutaneous vascular malformations in SWS; unilateral cranial lipoma/lipodermoid of the eye in FS; facial nevus in LNS). Radiologically, SWS is characterized by tram-track calcifications, while cortex calcifications are seen in FS. Silver-Russell syndrome is characterized by a classical facial phenotype (triangular face, small pointed chin, broad forehead, thin mouth) and hemi-hypertrophy. In patients with Rasmussen encephalitis, hemispheric atrophy is noted but typical calvarial changes of DDMS are absent. Hemimegalencepahly is easily differentiated from DDMS by an enlarged cerebral hemisphere, with ipsilateral enlargement of lateral ventricle. Brain imaging in our patient showed diffuse atrophy of the left cerebral hemisphere [thinned gyri, widened sulci, enlarged ipsilateral ventricle (dashed arrows)] and ipsilateral calvarial changes [enlargement of the ipsilateral frontal sinus (white arrows), thickened calvarium (arrowheads)]. These changes are typical for acquired Dyke-Davidoff-Masson syndrome (DDMS). Saini M: Obtaining data, interpretation, preparation of manuscript. Tan NC: Revising manuscript.

Efectividad y seguridad de la cirugía para la epilepsia en niños. Experiencia de un hospital terciario en Ecuador

IntroductionThere is sufficient evidence on the usefulness of surgery as a therapeutic alternative for patients with drug-resistant epilepsy; however this treatment is underutilized, especially in developing countries. MethodsWe describe the outcomes of epilepsy surgery in 27 paediatric patients at Hospital Baca Ortiz in Quito, Ecuador. Our analysis considered the following variables: reduction in seizure frequency, surgery outcome according to the Engel classification, improvement in quality of life, and serious complications due to surgery. Results21 corpus callosotomies and 6 resective surgeries were performed. The mean seizure frequency decreased from 465 per month before surgery to 37.2 per month thereafter (p<.001); quality of life scale scores increased from 12.6 to 37.2 (p<.001), and quality of life improved in 72.7% of patients. Regarding resective surgery, 2 patients with temporal lobe epilepsy and one with posterior quadrant epilepsy achieved Engel class IA, and one patient undergoing hemispherotomy due to Rasmussen encephalitis achieved Engel class IIA. Two patients underwent surgery for hypothalamic hamartoma: one achieved Engel III and the other, Engel IA; however, the latter patient died in the medium term due to a postoperative complication. The other major complication was a case of hydrocephalus, which led to the death of a patient with refractory infantile spasms who underwent corpus callosotomy. ConclusionsFavourable outcomes were observed in 92.5% of patients.

Genital automatisms: Reappraisal of a remarkable but ignored symptom of focal seizures

ObjectivesGenital automatisms (GAs) are uncommon clinical phenomena of focal seizures. They are defined as repeated fondling, grabbing, or scratching of the genitals. The aim of this study was to determine the lateralizing and localizing value and associated clinical characteristics of GAs. MethodsThree hundred thirteen consecutive patients with drug-resistant seizures who were referred to our tertiary center for presurgical evaluation between 2009 and 2016 were investigated. The incidence of specific kinds of behavior, clinical semiology, associated symptoms/signs with corresponding ictal electroencephalography (EEG) findings, and their potential role in seizure localization and lateralization were evaluated. ResultsFifteen (4.8%) of 313 patients had GAs. Genital automatisms were identified in 19 (16.4%) of a total 116 seizures. Genital automatisms were observed to occur more often in men than in women (M/F: 10/5). Nine of fifteen patients (60%) had temporal lobe epilepsy (right/left: 4/5) and three (20%) had frontal lobe epilepsy (right/left: 1/2), whereas the remaining two patients could not be classified. One patient was diagnosed as having Rasmussen encephalitis. Genital automatisms were ipsilateral to epileptic focus in 12 patients and contralateral in only one patient according to ictal–interictal EEG and neuroimaging findings. Epileptic focus could not be lateralized in the last 2 patients. Genital automatisms were associated with unilateral hand automatisms such as postictal nose wiping or manual automatisms in 13 (86.7%) of 15 and contralateral dystonia was seen in 6 patients. All patients had amnesia of the performance of GAs. ConclusionGenital automatisms are more frequent in seizures originating from the temporal lobe, and they can also be seen in frontal lobe seizures. Genital automatisms seem to have a high lateralizing value to the ipsilateral hemisphere and are mostly concordant with other unilateral hand automatisms. Men exhibit GAs more often than women.

Diagnostic dilemmas of Rasmussen’s encephalitis in adults

Introduction. Rasmussen?s encephalitis (RE) represents a rare, progressive, and inflammatory disease of the brain. Its detection in adults is a great challenge in clinical medicine. The aim of this paper is to highlight the diagnostic dilemma of RE in adults. Case outline. A 46-year-old woman was hospitalized due to persistent intense diffuse headaches, followed by nausea and the urge for vomiting that made her wake up during the night. On several occasions, she had transitory speech and memory disorders, and right hand numbness. Magnetic resonance (MR) imaging findings were as follows: occipitoparietal left in the deep white matter, as well as subcortical T2/flair white matter hyperintensities, T1-hypointense change involving the corpus callosum. MR spectroscopy showed an increased level of choline/creatinine (Cr) (2.12), a reduction of N-acetylaspartate/ Cr (1.27), an increased level of myo-inositol/Cr (1.20), and the presence of lactate. The patient refused lumbar puncture. Due to the described changes close to the speech center, cerebral biopsy was not taken. Even after five years, MR and spectroscopic findings are unchanged, while the clinical condition remains stable and unchanged. Conclusion. This case highlights the diagnostic dilemmas that arise in adult-onset RE and suggests that this diagnosis should be considered in patients of any age with the appropriate clinical picture.

Adult–onset Rasmussen encephalitis with high anti N–methyl–D aspartate type glutamate receptor subunit antibody titer in serum and cerebrospinal fluid : Effects of high–dose intravenous methylprednisolone pulse therapy implemented eleven years after onset

Adult–onset Rasmussen encephalitis with high anti N–methyl–D aspartate type glutamate receptor subunit antibody titer in serum and cerebrospinal fluid : Effects of high–dose intravenous methylprednisolone pulse therapy implemented eleven years after onset

Phenotypic and functional complexity of brain-infiltrating T cells in Rasmussen encephalitis

Objective:To characterize the brain-infiltrating immune cell repertoire in Rasmussen encephalitis (RE) with special focus on the subsets, clonality, and their cytokine profile.Methods:The immune cell infiltrate of freshly isolated brain tissue from RE was phenotypically and functionally characterized using immunohistology, flow cytometry, and T-cell receptor (TCR) deep sequencing. Identification of clonally expanded T-cell clones (TCCs) was achieved by combining flow cytometry sorting of CD4+ and CD8+ T cells and high-throughput TCR Vβ-chain sequencing. The most abundant brain-infiltrating TCCs were isolated and functionally characterized.Results:We found that CD4+, CD8+, and also γδ T cells infiltrate the brain tissue in RE. Further analysis surprisingly revealed that not only brain-infiltrating CD8+ but also CD4+ T cells are clonally expanded in RE. All 3 subsets exhibited a Tc1/Th1 phenotype characterized by the production of interferon (IFN)-γ and TNF. Broad cytokine profiling at the clonal level showed strong production of IFN-γ and TNF and also secretion of interleukin (IL)-5, IL-13, and granzyme B, both in CD4+ and CD8+ T cells.Conclusions:CD8+ T cells were until now considered the central players in the immunopathogenesis of RE. Our study adds to previous findings and highlights that CD4+ TCCs and γδ T cells that secrete IFN-γ and TNF are also involved. These findings underline the complexity of T-cell immunity in RE and suggest a specific role for CD4+ T cells in orchestrating the CD8+ T-cell effector immune response.