Dynamic Contrast-enhanced MRI Quantification of Altered Vascular Permeability in Autoimmune Encephalitis.

Background Blood-brain barrier (BBB) permeability change is a possible pathologic mechanism of autoimmune encephalitis. Purpose To evaluate the change in BBB permeability in patients with autoimmune encephalitis as compared with healthy controls by using dynamic contrast-enhanced (DCE) MRI and to explore its predictive value for treatment response in patients. Materials and Methods This single-center retrospective study included consecutive patients with probable or possible autoimmune encephalitis and healthy controls who underwent DCE MRI between April 2020 and May 2021. Automatic volumetric segmentation was performed on three-dimensional T1-weighted images, and volume transfer constant (Ktrans) values were calculated at encephalitis-associated brain regions. Ktrans values were compared between the patients and controls, with adjustment for age and sex with use of a nonparametric approach. The Wilcoxon rank sum test was performed to compare Ktrans values of the good (improvement in modified Rankin Scale [mRS] score of at least two points or achievement of an mRS score of ≤2) and poor (improvement in mRS score of less than two points and achievement of an mRS score >2) treatment response groups among the patients. Results Thirty-eight patients with autoimmune encephalitis (median age, 38 years [IQR, 29-59 years]; 20 [53%] female) and 17 controls (median age, 71 years [IQR, 63-77 years]; 12 [71%] female) were included. All brain regions showed higher Ktrans values in patients as compared with controls (P < .001). The median difference in Ktrans between the patients and controls was largest in the right parahippocampal gyrus (25.1 × 10-4 min-1 [95% CI: 17.6, 43.4]). Among patients, the poor treatment response group had higher baseline Ktrans values in both cerebellar cortices (P = .03), the left cerebellar cortex (P = .02), right cerebellar cortex (P = .045), left cerebral cortex (P = .045), and left postcentral gyrus (P = .03) than the good treatment response group. Conclusion DCE MRI demonstrated that BBB permeability was increased in all brain regions in patients with autoimmune encephalitis as compared with controls, and baseline Ktrans values were higher in patients with poor treatment response in the cerebellar cortex, left cerebral cortex, and left postcentral gyrus as compared with the good response group. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Filippi and Rocca in this issue.

Cerebral Cortical Encephalitis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Cerebral cortical encephalitis (CCE) is a recently described myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) phenotype. In this observational retrospective study, we characterized 19 CCE patients (6.7% of our MOGAD cohort). Headache (n = 15, 79%), seizures (n = 13, 68%), and encephalopathy (n = 12, 63%) were frequent. Magnetic resonance imaging revealed unilateral (n = 12, 63%) or bilateral (n = 7, 37%) cortical T2 hyperintensity and leptomeningeal enhancement (n = 17, 89%). N-Methyl-D-aspartate receptor autoantibodies coexisted in 2 of 15 tested (13%). CCE pathology (n = 2) showed extensive subpial cortical demyelination (n = 2), microglial reactivity (n = 2), and inflammatory infiltrates (perivascular, n = 1; meningeal, n = 1). Most received high-dose steroids (n = 17, 89%), and all improved, but 3 had CCE relapses. This study highlights the CCE spectrum and provides insight into its pathogenesis. ANN NEUROL 2023;93:297-302.

Anti-metabolic glutamate receptor 5 encephalitis with gangliocytoma: a case and review of the literature.

BACKGROUND: There are very limited reports on anti-metabolic glutamate receptor5 (mGluR5) encephalitis, especially lacking of pediatric research. The disease was mostly accompanied by tumors, mainly Hodgkin's lymphoma. No reports of other tumors, such as gangliocytoma have been reported to associate with anti-mGluR5 encephalitis so far. CASE PRESENTATION AND LITERATURE REVIEWS: We reported a case of a 12-year-old boy with anti-mGluR5 encephalitis complicated with gangliocytoma. The patient suffered from mental disorders including auditory hallucination, and sleep disorders. His cranial magnetic resonance imaging (MRI) showed an abnormality in the right insular lobe. Autoimmune encephalitis antibodies testing was positive for mGluR5 IgG antibody both in cerebrospinal fluid and serum (1:3.2, 1:100 respectively). Abdominal CT indicated a mass in left retroperitoneal confirmed with gangliocytoma via pathology. The patient underwent resection of gangliocytoma. After first-line immunotherapy (glucocorticoid, gamma globulin), his condition was improved. Furthermore, we provide a summary of 6 pediatric cases of Anti-mGluR5 encephalitis. Most of them complicated with Hodgkin's lymphoma, except the case currently reported comorbid with gangliocytoma. The curative effect is satisfactory. CONCLUSIONS: We report the first patient with anti-mGlur5 encephalitis complicated with gangliocytoma. It suggests that in addition to paying attention to the common lymphoma associated with anti-mGlur5 encephalitis, we should also screen the possibility of other tumors for early detection of the cause, active treatment and prevention of recurrence.

Autoimmune encephalitis: what the radiologist needs to know.

Autoimmune encephalitis is a relatively novel nosological entity characterized by an immune-mediated damage of the central nervous system. While originally described as a paraneoplastic inflammatory phenomenon affecting limbic structures, numerous instances of non-paraneoplastic pathogenesis, as well as extra-limbic involvement, have been characterized. Given the wide spectrum of insidious clinical presentations ranging from cognitive impairment to psychiatric symptoms or seizures, it is crucial to raise awareness about this disease category. In fact, an early diagnosis can be dramatically beneficial for the prognosis both to achieve an early therapeutic intervention and to detect a potential underlying malignancy. In this scenario, the radiologist can be the first to pose the hypothesis of autoimmune encephalitis and refer the patient to a comprehensive diagnostic work-up - including clinical, serological, and neurophysiological assessments.In this article, we illustrate the main radiological characteristics of autoimmune encephalitis and its subtypes, including the typical limbic presentation, the features of extra-limbic involvement, and also peculiar imaging findings. In addition, we review the most relevant alternative diagnoses that should be considered, ranging from other encephalitides to neoplasms, vascular conditions, and post-seizure alterations. Finally, we discuss the most appropriate imaging diagnostic work-up, also proposing a suggested MRI protocol.

Febrile infection-related epilepsy syndrome with claustrum lesion: an underdiagnosed inflammatory encephalopathy.

OBJECTIVE: To summarize the clinical characteristics and prognosis of febrile infection-related epilepsy syndrome with claustrum lesions (FIRES-C). METHOD: Clinical data of FIRES-C patients were collected retrospectively. The study reviewed and analyzed their clinical manifestations, treatment strategies, and prognosis. RESULT: Twenty patients were enrolled, including 13 females and 7 males, with a median onset age of 20.5 years. All patients developed seizures after fever, with a median interval of 5 days. Brain MRI showed symmetric lesions in the claustrum in all patients. The median interval from seizure onset to abnormal MRI signals detection was 12.5 days. All patients had negative results for comprehensive tests of neurotropic viruses and antineuronal autoantibodies. Seventy percent of cases had been previously empirically diagnosed with autoimmune encephalitis or viral encephalitis before. All patients received anti-seizure medicine. Eleven patients (55%) received antiviral therapy. All patients received immunotherapy, including glucocorticoids (100%), intravenous immunoglobulin (IVIg) (65%), plasma exchange (PLEX) (10%), tocilizumab (10%), rituximab (5%), and cyclophosphamide (5%). Sixty percent of patients received long-term immunotherapy (≥ 3 months). The median follow-up was 11.5 months;60% of patients were diagnosed with refractory epilepsy. CONCLUSION: Bilateral claustrum lesion on MRI is a distinctive neuroimage feature for FIRES, which may serve as an indication for the initial clinical assessments. FIRES-C should be classified as a type of inflammatory encephalopathy characterized by a monophasic nature. Some FIRES-C patients respond to immunotherapy and antiseizure treatments but most experience refractory epilepsy as a long-term outcome.

MRI and pathology comparisons in Rasmussen's encephalitis: a multi-institutional examination of hemispherotomy outcomes relative to imaging and histological severity.

PURPOSE: Rasmussen encephalitis (RE) is a very rare chronic neurological disorder of unilateral inflammation of the cerebral cortex. Hemispherotomy provides the best chance at achieving seizure freedom in RE patients, but with significant risks and variable long-term outcomes. The goal of this study is to utilize our multicenter pediatric cohort to characterize if differences in pathology and/or imaging characterization of RE may provide a window into post-operative seizure outcomes, which in turn could guide decision-making for parents and healthcare providers. METHODS: This multi-institutional retrospective review of medical record, imaging, and pathology samples was approved by each individual institution's review board. Data was collected from all known pediatric cases of peri-insular functional hemispherotomy from the earliest available electronic medical records. Mean follow-up time was 4.9 years. Clinical outcomes were measured by last follow-up visit using both Engel and ILAE scoring systems. Relationships between categorical and continuous variables were analyzed with Pearson correlation values. RESULTS: Twenty-seven patients met study criteria. No statistically significant correlations existed between patient imaging and pathology data. Pathology stage, MRI brain imaging stages, and a combined assessment of pathology and imaging stages showed no statistically significant correlation to post-operative seizure freedom rates. Hemispherectomy Outcome Prediction Scale scoring demonstrated seizure freedom in only 71% of patients receiving a score of 1 and 36% of patients receiving a score of 2 which were substantially lower than predicted. CONCLUSIONS: Our analysis did not find evidence for either independent or combined analysis of imaging and pathology staging being predictive for post peri-insular hemispherotomy seizure outcomes, prompting the need for other biomarkers to be explored. Our data stands in contrast to the recently proposed Hemispherectomy Outcome Prediction Scale and does not externally validate this metric for an RE cohort.

Characterization of neuroinflammation pattern in anti-LGI1 encephalitis based on TSPO PET and symptom clustering analysis.

PURPOSE: TSPO PET with radioligand [18F]DPA-714 is an emerging molecular imaging technique that reflects cerebral inflammation and microglial activation, and it has been recently used in central nervous system diseases. In this study, we aimed to investigate the neuroinflammation pattern of anti-leucine-rich glioma-inactivated 1 (LGI1) protein autoimmune encephalitis (AIE) and to evaluate its possible correlation with clinical phenotypes. METHODS: Twenty patients with anti-LGI1 encephalitis from the autoimmune encephalitis cohort in Huashan Hospital and ten with other AIE and non-inflammatory diseases that underwent TSPO PET imaging were included in the current study. Increased regional [18F]DPA-714 retention in anti-LGI1 encephalitis was detected on a voxel basis using statistic parametric mapping analysis. Multiple correspondence analysis and hierarchical clustering were conducted for discriminate subgroups in anti-LGI1 encephalitis. Standardized uptake value ratios normalized to the cerebellum (SUVRc) were calculated for semiquantitative analysis of TSPO PET features between different LGI1-AIE subgroups. RESULTS: Increased regional retention of [18F]DPA-714 was identified in the bilateral hippocampus, caudate nucleus, and frontal cortex in LGI1-AIE patients. Two subgroups of LGI1-AIE patients were distinguished based on the top seven common symptoms. Patients in cluster 1 had a high frequency of facio-brachial dystonic seizures than those in cluster 2 (p = 0.004), whereas patients in cluster 2 had a higher frequency of general tonic-clonic (GTC) seizures than those in cluster 1 (p < 0.001). Supplementary motor area and superior frontal gyrus showed higher [18F]DPA-714 retention in cluster 2 patients compared with those in cluster 1 (p = 0.024; p = 0.04, respectively). CONCLUSIONS: Anti-LGI1 encephalitis had a distinctive molecular imaging pattern presented by TSPO PET scan. LGI1-AIE patients with higher retention of [18F]DPA-714 in the frontal cortex were more prone to present with GTC seizures. Further studies are required for verifying its value in clinical application.

Early and Aggressive Treatment May Modify Anti-Hu Associated Encephalitis Prognosis.

Anti-Hu encephalitis is a paraneoplastic syndrome in adults. In children, rare cases of anti-Hu encephalitis were reported mostly without underlying tumors and clinical outcome are usually severe. Here, we describe a 4-year-old girl who developed cerebellar syndrome with abnormal behavior. The brain magnetic resonance imaging showed several T2/fluid-attenuated inversion recovery bilateral brain lesions and autoimmune assessment showed positive anti-Hu antibodies. Computed tomography scan revealed ganglioneuroblastoma which was surgically removed 3 months after onset. Aggressive immunotherapy including dexamethasone, rituximab, and intravenous immunoglobulins were used and a marked neurological improvement soon after 9 months of onset was observed with the child being able to go back to school. The short delay between diagnosis and start of aggressive immunotherapy demonstrate the paramount importance of early diagnosis and early specific therapy after onset of symptoms.

Clinical and radiological spectrum of anti-myelin oligodendrocyte glycoprotein (MOG) antibody encephalitis: single-center observational study.

OBJECTIVE: The objective was to describe the clinical presentations, radiologic features, and outcomes of patients with autoimmune encephalitis associated with myelin oligodendrocyte glycoprotein antibody (MOG). BACKGROUND: During the past decade, the spectrum of the myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) has expanded. Recently, patients with MOG antibody encephalitis (MOG-E) who do not fulfill the criteria for ADEM have been reported. In this study, we aimed to describe the spectrum of MOG-E. METHODS: Sixty-four patients with MOGAD were screened for encephalitis-like presentation. We collected the clinical, radiological, laboratory, and outcome data of the patients who presented with encephalitis and compared it with the non-encephalitis group. RESULTS: We identified sixteen patients (nine males and seven females) with MOG-E. The median age of the encephalitis population was significantly lower than the non-encephalitis group (14.5 years (11.75-18) vs. 28 years (19.75-42), p = 0.0004). Twelve out of sixteen patients (75%) had fever at the time of encephalitis. Headache and seizure were present in 9/16 (56.2%) and 7/16 (43.75%) patients, respectively. FLAIR cortical hyperintensity was present in 10/16 (62.5%) patients. Supratentorial deep gray nuclei were involved in 10/16 (62.5%) patients. Three patients had tumefactive demyelination, and one patient had a leukodystrophy-like lesion. Twelve of 16 (75%) patients had a good clinical outcome. Patient with leukodystrophy pattern and other with generalized CNS atrophy showed a chronic progressive course. CONCLUSION: MOG-E can have heterogeneous radiological presentations. FLAIR cortical hyperintensity, tumefactive demyelination, and leukodystrophy-like presentations are novel radiological presentations associated with MOGAD. Though majority of MOG-E have a good clinical outcome, few patients can have chronic progressive disease even on immunosuppressive therapy.

Delayed onset of fatal encephalitis in a COVID-19 positive patient.

BACKGROUND: The SARS-nCoV-2019 epidemic has spread since December 2019, quickly gaining worldwide attention. Symptoms consist of fever, cough and breathing difficulties. An increasing number of studies are focusing on neurological manifestations. In addition to the typical ageusia and anosmia, up to 30% of cases can present headache, nausea and vomiting. More serious neurological manifestations, such as encephalitis, thrombosis and cerebral haemorrhage have been reported. CASE DESCRIPTION: We described the case of a 47-year-old man who tested positive for COVID-19 virus in early March 2020. After two negative nasopharyngeal swabs, 41 days after the diagnosis of COVID-19 infection, he developed intense headache with fever, and he was hospitalized. He had subsequent generalized epileptic seizures and intubation was necessary. Contrast Head MRI was negative for brain abscesses or tumours but detected severe vasogenic oedema of the white matter with 10 mm shift of the midline and compression of the right lateral ventricle. Massive cortisone support therapy was ineffective. We diagnosed brain death on day 43 from the infection diagnosis. DISCUSSION: COVID-19 virus can reach the brain, penetrating into the neuronal cells through the interaction between the spike protein S1 and the host ACE-2 receptor, expressed in the capillary endothelium. We believe that in this infection, the pro-inflammatory state induced by the cytokine storm can cause a cerebral cell-mediated response, with subsequent vasodilatation and brain oedema. CONCLUSION: To our knowledge, this is the first description of a delayed onset cell-mediated encephalitis caused by COVID-19 virus after more than 40 days from the diagnosis.

A novel classification model based on cerebral 18F-FDG uptake pattern facilitates the diagnosis of acute/subacute seropositive autoimmune encephalitis.

PURPOSE: To explore the intrinsic alteration of cerebral 18F-FDG metabolism in acute/subacute seropositive autoimmune encephalitis (AE) and to propose a universal classification model based on 18F-FDG metabolic patterns to predict AE. METHODS: Cerebral 18F-FDG PET images of 42 acute/subacute seropositive AE patients and 45 healthy controls (HCs) were compared using voxelwise and region of interest (ROI)-based schemes. The mean standardized uptake value ratios (SUVRs) of 59 subregions according to a modified Automated Anatomical Labeling (AAL) atlas were compared using a t-test. Subjects were randomly divided into a training set (70%) and a testing set (30%). Logistic regression models were built based on the SUVRs and the models were evaluated by determining their predictive value in the training and testing sets. RESULTS: The 18F-FDG uptake pattern in the AE group was characterized by increased SUVRs in the brainstem, cerebellum, basal ganglia, and temporal lobe, and decreased SUVRs in the occipital, and frontal regions with voxelwise analysis (false discovery rate [FDR] p<0.05). Utilizing ROI-based analysis, we identified 15 subareas that exhibited statistically significant changes in SUVRs among AE patients compared to HC (FDR p<0.05). Further, a logistic regression model incorporating SUVRs from the calcarine cortex, putamen, supramarginal gyrus, cerebelum_10, and hippocampus successfully enhanced the positive predictive value from 0.76 to 0.86 when compared to visual assessments. This model also demonstrated potent predictive ability, with AUC values of 0.94 and 0.91 observed for the training and testing sets, respectively. CONCLUSIONS: During the acute/subacute stages of seropositive AE, alterations in SUVRs appear to be concentrated within physiologically significant regions, ultimately defining the general cerebral metabolic pattern. By incorporating these key regions into a new classification model, we have improved the overall diagnostic efficiency of AE.

Decrease in the cortex/striatum metabolic ratio on [18F]-FDG PET: a biomarker of autoimmune encephalitis.

PURPOSE: The aim of this [18F]-FDG PET study was to determine the diagnostic value of the cortex/striatum metabolic ratio in a large cohort of patients suffering from autoimmune encephalitis (AE) and to search for correlations with the course of the disease. METHODS: We retrospectively collected clinical and paraclinical data of patients with AE, including brain 18F-FDG PET/CT. Whole-brain statistical analysis was performed using SPM8 software after activity parametrization to the striatum in comparison to healthy subjects. The discriminative performance of this metabolic ratio was evaluated in patients with AE using receiver operating characteristic curves against 44 healthy subjects and a control group of 688 patients with MCI. Relationship between cortex/striatum metabolic ratios and clinical/paraclinical data was assessed using univariate and multivariate analysis in patients with AE. RESULTS: Fifty-six patients with AE were included. In comparison to healthy subjects, voxel-based statistical analysis identified one large cluster (p-cluster < 0.05, FWE corrected) of widespread decreased cortex/striatum ratio in patients with AE. The mean metabolic ratio was significantly lower for AE patients (1.16 ± 0.13) than that for healthy subjects (1.39 ± 0.08; p < 0.001) and than that for MCI patients (1.32 ± 0.11; p < 0.001). A ratio threshold of 1.23 allowed to detect AE patients with a sensitivity of 71% and a specificity of 82% against MCI patients, and 98% against healthy subjects. A lower cortex/striatum metabolic ratio had a trend towards shorter delay before 18F-FDG PET/CT (p = 0.07) in multivariate analysis. CONCLUSION: The decrease in the cortex/striatal metabolic ratio has a good early diagnostic performance for the differentiation of AE patients from controls.

Usefulness of brain FDG PET/CT imaging in pediatric patients with suspected autoimmune encephalitis from a prospective study.

PURPOSE: Early diagnosis and treatment are of paramount importance for pediatric patients with autoimmune encephalitis (AE). The aim is to evaluate the usefulness of FDG PET/CT in pediatric patients with suspected AE from a prospective study. METHODS: The prospective study was conducted over a period of 23.5 months from May 14, 2019, to April 30, 2021. All patients (< 18-year-old) were hospitalized at the department of pediatric neurology and met the criteria of clinical suspected AE. The children underwent the tests of blood samplings, CSF, EEG, MRI, and 18F-FDG PET/CT. The criteria for FDG PET/CT diagnosis of AE were large lobar hypometabolism with or without focal hypermetabolism found on PET/CT. The clinical final diagnosis of AE includes seropositive and seronegative AE based on the diagnostic criteria. RESULTS: One hundred four pediatric inpatients (57 boys, 47 girls) were included, of which 58 children were diagnosed with AE (seropositive, 16; seronegative, 42), 45 children were diagnosed with non-AE, and one boy remained indeterminate diagnosis. Large lobar hypometabolism was found in 61 children, of which 54 (88.5%) children were finally diagnosed with AE. The sensitivity, specificity, and accuracy of FDG PET/CT for diagnosis of AE were 93.1%, 84.4%, and 89.3%, respectively, with a positive predictive value of 88.5% and a negative predictive value of 90.5%. The most common involved with hypometabolism was the parietal lobe, followed by occipital and frontal lobes, finally the temporal lobe on PET/CT in children with AE. CONCLUSION: Brain FDG PET/CT imaging has high specificity, sensitivity, and accuracy for diagnosis of AE in clinical suspected AE children. CLINICAL TRIALS: gov. NCT02969213. Registered 17 October 2016.

Deep Learning-Enabled Identification of Autoimmune Encephalitis on 3D Multi-Sequence MRI.

BACKGROUND: Autoimmune encephalitis (AE) is a noninfectious emergency with severe clinical attacks. It is difficult for the earlier diagnosis of acute AE due to the lack of antibody detection resources. PURPOSE: To construct a deep learning (DL) algorithm using multi-sequence magnetic resonance imaging (MRI) for the identification of acute AE. STUDY TYPE: Retrospective. POPULATION: One hundred and sixty AE patients (90 women; median age 36), 177 herpes simplex virus encephalitis (HSVE) (89 women; median age 39), and 184 healthy controls (HC) (95 women; median age 39) were included. Fifty-two patients from another site were enrolled for external validation. FIELD STRENGTH/SEQUENCE: 3.0 T; fast spin-echo (T1 WI, T2 WI, fluid attenuated inversion recovery imaging) and spin-echo echo-planar diffusion weighted imaging. ASSESSMENT: Five DL models based on individual or combined four MRI sequences to classify the datasets as AE, HSVE, or HC. Reader experiment was further carried out by radiologists. STATISTICAL TESTS: The discriminative performance of different models was assessed using the area under the receiver operating characteristic curve (AUC). The optimal threshold cut-off was identified when sensitivity and specificity were maximized (sensitivity + specificity - 1) in the validation set. Classification performance using confusion matrices was reported to evaluate the diagnostic value of the models and the radiologists' assessments before being assessed by the paired t-test (P < 0.05 was considered significant). RESULTS: In the internal test set, the fusion model achieved the significantly greatest diagnostic performance than single-sequence DL models with AUCs of 0.828, 0.884, and 0.899 for AE, HSVE, and HC, respectively. The model demonstrated a consistently high performance in the external validation set with AUCs of 0.831 (AE), 0.882 (HSVE), and 0.892 (HC). The fusion model also demonstrated significantly higher performance than all radiologists in identifying AE (accuracy between the fuse model vs. average radiologist: 83% vs. 72%). DATA CONCLUSION: The proposed DL algorithm derived from multi-sequence MRI provided desirable identification and classification of acute AE. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Clinical and imaging analysis to evaluate the response of patients with anti-DPPX encephalitis to immunotherapy.

BACKGROUND: To report the main spectrum and new clinical and imaging characteristics of dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, and to evaluate the effect of immunotherapy. METHODS: A retrospective analysis of nine patients with anti-DPPX encephalitis was performed, and all previously reported cases in the literature were reviewed. A cell-based indirect immunofluorescence assay using human embryonic kidney 293 cells transfected with DPPX was used. RESULTS: Nine patients were identified (median age, 51 years; range, 14-65 years) with prodromal fever, diarrhea, or weight loss, followed by rapid progressive encephalopathy characterized by cognitive disorder. One patient who received methylprednisolone therapy and a trial of tacrolimus showed substantial improvement and had no relapse by the 6-month follow-up. Our comprehensive literature review demonstrated that 53 cases were reported, of which more than half had prodromal weight loss (52.8%) and gastrointestinal disorders (58.5%). Cognitive disorders (74.6%) and brainstem/spinal cord disorders (75.5%) were the most common major symptoms. A greater proportion of Chinese patients than non-Chinese patients had abnormalities on brain magnetic resonance imaging specific for encephalitis (70.0% vs. 23.3%, P < 0.001). Our study is the first to report three patients with anti-DPPX encephalitis who had sleep disorders with rapid eye movement sleep behavior disorder, limb paralysis (two), severe pleocytosis, elevated protein levels (two) in the cerebrospinal fluid, and increased T2/FLAIR signal abnormalities in the bilateral hippocampus, temporal lobe, amygdala, basal ganglia, thalamus, centrum semiovale, and frontal and parietal lobes in seven patients (77.8%). CONCLUSION: Our study expands the clinical and imaging phenotypes of anti-DPPX encephalitis. Further studies elucidating the entire clinical spectrum of anti-DPPX encephalitis, its pathogenic mechanisms, and prognosis under long-term immunosuppressive therapy are warranted.

Non-invasive quantification of inflammation, axonal and myelin injury in multiple sclerosis.

The aim of this study was to determine the feasibility of diffusion basis spectrum imaging in multiple sclerosis at 7 T and to investigate the pathological substrates of tissue damage in lesions and normal-appearing white matter. To this end, 43 patients with multiple sclerosis (24 relapsing-remitting, 19 progressive), and 21 healthy control subjects were enrolled. White matter lesions were classified in T1-isointense, T1-hypointense and black holes. Mean values of diffusion basis spectrum imaging metrics (fibres, restricted and non-restricted fractions, axial and radial diffusivities and fractional anisotropy) were measured from whole brain white matter lesions and from both lesions and normal appearing white matter of the corpus callosum. Significant differences were found between T1-isointense and black holes (P ranging from 0.005 to <0.001) and between lesions' centre and rim (P < 0.001) for all the metrics. When comparing the three subject groups in terms of metrics derived from corpus callosum normal appearing white matter and T2-hyperintense lesions, a significant difference was found between healthy controls and relapsing-remitting patients for all metrics except restricted fraction and fractional anisotropy; between healthy controls and progressive patients for all metrics except restricted fraction and between relapsing-remitting and progressive multiple sclerosis patients for all metrics except fibres and restricted fractions (P ranging from 0.05 to <0.001 for all). Significant associations were found between corpus callosum normal-appearing white matter fibres fraction/non-restricted fraction and the Symbol Digit Modality Test (respectively, r = 0.35, P = 0.043; r = -0.35, P = 0.046), and between black holes radial diffusivity and Expanded Disability Status Score (r = 0.59, P = 0.002). We showed the feasibility of diffusion basis spectrum imaging metrics at 7 T, confirmed the role of the derived metrics in the characterization of lesions and normal appearing white matter tissue in different stages of the disease and demonstrated their clinical relevance. Thus, suggesting that diffusion basis spectrum imaging is a promising tool to investigate multiple sclerosis pathophysiology, monitor disease progression and treatment response.

Neuroimaging and neurological outcome of children with acute encephalitis.

AIM: To investigate the severity of acute phase magnetic resonance imaging (MRI) findings and severity of acute illness as risk factors for disability after recovery from encephalitis. METHOD: Children with encephalitis (n = 98; median age 6 years 10 months, interquartile range 3 years-11 years 6 months; 59 males, 39 females) treated in Turku University Hospital during the years 1995 to 2016 were identified in this retrospective cohort study. The acute phase (<2 months of symptom onset) brain MRIs were re-evaluated and classified based on the severity of neuroimaging finding by a neuroradiologist. Neurological outcome at discharge, at short-term (<3 months from discharge) follow-up, and at long-term (>1 year from discharge) follow-up was assessed from medical records using the Glasgow Outcome Scale. RESULTS: Long-term recovery was poor in 24 of 82 (29%) children with follow-up data. Two children died, eight had severe disability, and 14 had moderate disability. Acute phase MRI was available for re-evaluation from 74 of 82 patients with follow-up data. The increasing severity of MRI findings was associated with need for ventilator therapy and with poor recovery. INTERPRETATION: The risk for poor recovery in paediatric encephalitis is high, and it is associated with the severity of MRI findings. WHAT THIS PAPER ADDS: Poor long-term recovery was found in 29% of children with encephalitis. Severe disability measured by Glasgow Outcome Scale was found in 8%. The most severe neuroimaging findings were a risk factor for severe acute illness and poor long-term recovery.

Clinico-radiological characteristics of anti-myelin oligodendrocyte glycoprotein antibody-associated autoimmune encephalitis in children.

AIM: To investigate the clinical characteristics and prevalence of paediatric anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated autoimmune encephalitis. METHOD: A total of 94 paediatric patients (46 males, 48 females, median age 9 years 5 months, range: 8 months-17 years 8 months) with autoimmune encephalitis were recruited at Seoul National University Children's Hospital. We evaluated autoantibody status and identified patients with anti-MOG antibody-associated autoimmune encephalitis. Retrospective reviews of medical records were performed to describe clinical presentations, laboratory findings, treatments, and outcomes. RESULTS: Eight patients (five males, three females, median age 11 years 9 months) with anti-MOG antibody-associated encephalitis were identified (8.5% of those with autoimmune encephalitis), one of whom was copositive for anti-N-methyl-d-aspartate receptor (NMDAR) antibodies. Anti-NMDAR antibodies were identified in 23 patients (23 out of 94, 24.5%). Unilateral or bilateral cortical involvement was identified in five patients. Focal contrast enhancement was also identified in three of the five patients with cortical lesions. All patients showed favourable response to immunotherapy with a Modified Rankin Scale ≤2 at the last follow-up. Relapse was found in one patient and clinico-radiological remission was achieved with cyclic intravenous immunoglobulin therapy. INTERPRETATION: Anti-MOG antibody-associated encephalitis accounts for a significant proportion of clinically defined paediatric patients with autoimmune encephalitis. Anti-MOG antibody-associated encephalitis should be included in the clinical spectrum of anti-MOG-associated diseases.

Shigella-associated mild encephalitis with reversible splenial lesion in Hospital Center Delafontaine, Saint-Denis, France: a case report.

BACKGROUND: Mild encephalitis with reversible splenial lesion of the corpus callosum (MERS) is a clinical/radiological syndrome characterized by hyperintense signal changes in the splenium of the corpus callosum visible on diffusion weighted imaging (DWI) in the brain Magnetic Resonance Imaging (MRI) associated with various neurological symptoms. Progression is usually favorable with disappearance of the MRI brain lesion and regression of clinical symptoms over a few days to a few weeks. The exact pathophysiology remains unclear. MERS can be associated with various pathogens. CASE PRESENTATION: We report here a paediatric case of MERS associated with Shigella flexneri infection. A five-year-old boy with no relevant past medical history presented with symptoms such as headache, fever, profuse diarrhea and hallucinations. A brain Magnetic Resonance Imaging performed on Day 2 of the symptoms revealed hyperintense signal changes of the splenium of the corpus callosum in T2 FLAIR sequence. This infection had a favorable outcome after antibiotic therapy. No further recurrence of symptoms was observed and a follow-up clinical examination eight weeks later was normal. A follow-up brain Magnetic Resonance Imaging three months after discharge was also normal and the hyperintense signal changes of the splenium of the corpus callosum had disappeared completely. CONCLUSIONS: MERS is a clinical/radiological syndrome with a generally good prognosis. We believe that this is the first description of a case of Shigella-associated MERS. It is useful to know about this condition to help distinguish it from acute disseminated encephalomyelitis.

Clinical study of recurrent mild encephalitis/encephalopathy with a reversible splenial lesion in two cases.

BACKGROUND: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been reported worldwidely. However, the data about recurrent cases is limited. We aimed to analyze the clinical and radiographic features of recurrent MERS, and its possible mechanisms. CASE PRESENTATION: Two patients with clinically recurrent MERS were reported here, exhibiting neurological symptoms such as limbs weakness and numbness, stand/walk unsteadily, slurred speech and irritability, and typical lesions in the corpus callosum and white matter. One of them experienced another four episodes with a similar clinical course and magnetic resonance imaging findings over a period of 10 years. The Na levels in the present two patients were normal. DISCUSSION AND CONCLUSION: Combined with the patients reported previously, recurrence could be seen in both MERS type 1 and type 2 patients, from two to multiple times, with the latter possibly more common. It suggested that some genetic factors might be involved in MERS, especially for MERS type 2 or familial MERS.