anti-NMDAR Encephalitis Research Articles

Autoimmune encephalitis in Israeli children – A retrospective nationwide study

Immune-mediated or autoimmune encephalitis (AE) is a relatively new, rare and elusive form of encephalitis in children. We retrospectively collected seropositive children (0–18 years old) with well characterized antibodies through 3 reference laboratories in Israel. Clinical symptoms, MRI and EEG findings and treatment courses were described. A total of 16 patients were included in the study, with 10 females. Anti NMDA encephalitis was most common followed by anti HU and anti mGLuR1. Psychiatric symptoms, abnormal movements, seizures and behavioral changes were the most common presentation. Pathological MRI and EEG findings were described in 37% and 56% of children, respectively. Treatment with corticosteroids, Intravenous immunoglobulins (IVIG) was first line in most children. Following inadequate response children were treated with plasmapheresis and/or rituximab. Two patients relapsed following both first and second line protocols. In terms of long term prognosis, 9 children (56%) had one or more residual behavioral, psychiatric or neurologic findings. Three children required hospitalization for rehabilitation. AE remains a rare diagnosis with variable presenting symptoms, requiring a high index of suspicion. Consensus recommended treatment is generally effective in the pediatric population. Female gender was associated with a higher chance of severe disease. Larger cohorts would be needed to identify prognostic factors in the pediatric population.

MyD88-mediated signaling is critical for the generation of seizure responses and cognitive impairment in a model of anti-N-methyl-D-aspartate receptor encephalitis.

We previously demonstrated that interleukin-1 receptor-mediated immune activation contributes to seizure severity and memory loss in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. In the present study, we assessed the role of the myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in Toll-like receptor signaling, in the key phenotypic characteristics of anti-NMDAR encephalitis. Monoclonal anti-NMDAR antibodies or control antibodies were infused into the lateral ventricle of MyD88 knockout mice (MyD88-/-) and control C56BL/6J mice (wild type [WT]) via osmotic minipumps for 2 weeks. Seizure responses were measured by electroencephalography. Upon completion of the infusion, the motor, anxiety, and memory functions of the mice were assessed. Astrocytic (glial fibrillary acidic protein [GFAP]) and microglial (ionized calcium-binding adaptor molecule 1 [Iba-1]) activation and transcriptional activation for the principal inflammatory mediators involved in seizures were determined using immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. As shown before, 80% of WT mice infused with anti-NMDAR antibodies (n = 10) developed seizures (median = 11, interquartile range [IQR] = 3-25 in 2 weeks). In contrast, only three of 14 MyD88-/- mice (21.4%) had seizures (0, IQR = 0-.25, p = .01). The WT mice treated with antibodies also developed memory loss in the novel object recognition test, whereas such memory deficits were not apparent in MyD88-/- mice treated with anti-NMDAR antibodies (p = .03) or control antibodies (p = .04). Furthermore, in contrast to the WT mice exposed to anti-NMDAR antibodies, the MyD88-/- mice had a significantly lower induction of chemokine (C-C motif) ligand 2 (CCL2) in the hippocampus (p = .0001, Sidak tests). There were no significant changes in the expression of GFAP and Iba-1 in the MyD88-/- mice treated with anti-NMDAR or control antibodies. These findings suggest that MyD88-mediated signaling contributes to the seizure and memory phenotype in anti-NMDAR encephalitis and that CCL2 activation may participate in the expression of these features. The removal of MyD88 inflammation may be protective and therapeutically relevant.

Analysis of characteristics of movement disorders in patients with anti-N-methyl-D-aspartate receptor encephalitis.

Movement disorders (MDs) are common in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis but are poorly studied. This study aimed to investigate the clinical characteristics of MDs and the clinical differences between patients with and without MDs in anti-NMDAR encephalitis. A retrospective study was conducted on patients with anti-NMDAR encephalitis who were first diagnosed and treated in the First People's Hospital of Yunnan Province from January 2017 to September 2022. According to the presence or absence of MDs, all patients were divided into two groups, and the clinical manifestations, auxiliary examinations, and prognosis of the two groups were compared. Patients in the MDs group were further subgrouped by different ages (<12 years, 12-17 years, and ≥ 18 years) and genders, and the prevalence of each MD was compared in different age and gender groups. (1) In our study there were 64 patients, of whom 76.6% (49/64) presented with MDs; the median age of onset in patients with MDs was 21 (15,35) years and 65.3% (32/49) were female. The three most common MDs were orofacial dyskinesia (OFLD) (67.3%), dystonia (55.1%), and stereotypies (34.7%). Patients <12 years were more likely to experience chorea than patients in other age groups (p = 0.003). (2) Compared with the non-MDs group, patients in the MDs group showed higher rates of prodromal manifestations, autonomic dysfunction, consciousness disorders, as well as pulmonary infection and gastrointestinal dysfunction (all p < 0.05). Peripheral blood neutrophil to lymphocyte ratio (NLR) (p = 0.014), the proportion of cerebrospinal fluid (CSF) NMDAR antibody titers ≥1:32 (p = 0.047), ICU admission rate (p = 0.04), length of stay (p = 0.007), maximum mRS score in the course of disease (p = 0.001) and mRS score at discharge (p = 0.006) in the MDs group were significantly higher than the non-MDs group. MDs associated with anti-NMDAR encephalitis were predominantly hyperkinetic. Chorea occurred more commonly in patients aged <12 years. Patients with MDs were prone to autonomic dysfunction, consciousness disorders, pulmonary infection, and gastrointestinal dysfunction; they had more intense inflammation, more severe disease, and a poorer short-term prognosis.

Neuroleptic Intolerance and Residual Mutism in a Young Woman with Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis

We report a case of anti-NMDAR encephalitis and residual mutism in a 23-year-old woman who presented with neuroleptic intolerance. Admission to our department for investigation of her abnormal behavior revealed cerebrospinal fluid (CSF) positivity for anti-NMDAR antibodies, and the patient underwent immunotherapy. However, generalized tonic seizures developed, requiring mechanical ventilation in the intensive care unit. Antipsychotic drugs were also administered for involuntary movements and insomnia. Thereafter, a malignant syndrome of severe hyperCKemia (Max: 191,120 IU/L) and shock developed, requiring resuscitation and three sessions of hemodialysis. Subsequent rituximab therapy led to improvement, except for mutism, which had newly developed during resuscitation. Seven months after initial admission, the patient was discharged with independent gait. However, her mutism still persists. Temporary mutism has been reported to occur in this type of encephalitis, albeit rarely. The fact that remission was not observed in this case may have been due to cerebellar infarction occurring during resuscitation, but the true cause remains unclear. Malignant syndrome or rhabdomyolysis, as seen in this patient, has also sometimes been reported in this form of encephalitis when antipsychotic agents, especially dopamine receptor blockers, have been administered. Therefore, such agents should be administered with caution in patients with anti-NMDAR encephalitis. (Received August 17, 2023; Accepted October 24, 2023; Published March 1, 2024).

Contribution of cerebrospinal fluid antibody titers and sex to acute cerebral blood flow in patients with anti-NMDAR autoimmune encephalitis.

The objective of this study was to elucidate the contribution of cerebrospinal fluid (CSF) antibody titers (AT) and sex to acute cerebral blood flow (CBF) in patients diagnosed with anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE). Forty-five patients diagnosed with NMDAR AE were recruited from December 2016 to January 2023. The acute CBF in patients with NMDAR AE at the early stage of the disease was analyzed using arterial spin labeling. The groups were compared based on CSF AT and sex. The connectivity of the CBF in the region of interest was also compared between groups. The patients with different CSF AT exhibited varied brain regions with CBF abnormalities compared to the healthy subjects (p = 0.001, cluster-level FWE corrected). High antibody titers (HAT) in CSF contributed to more brain regions with CBF alterations in female patients than in female patients with low antibody titers (LAT) in CSF (p = 0.001, cluster-level FWE corrected). Female patients with HAT in CSF displayed more decreased CBF in the left post cingulum gyrus, left precuneus, left calcarine, and left middle cingulum gyrus than the male patients with the same AT in CSF (p = 0.001, cluster-level FWE corrected). All patients with NMDAR AE showed increased CBF in the left putamen (Putamen_L) and left amygdala (Amygdala_L) and decreased CBF in the right precuneus (Precuneus_R), which suggests that these are diagnostic CBF markers for NMDAR AE. CSF AT and sex contributed to CBF abnormalities in the patients diagnosed with NMDAR AE. Altered CBF might potentially serve as the diagnostic marker for NMDAR AE.

Clinical case of an atypical course of autoimmune anti-NMDA encephalitis

Autoimmune encephalitis with antibodies against NMDA receptor (anti-NMDA encephalitis) is a relatively newly described disease that occupies a leading position among encephalitis of various etiologies. The article presents diagnostic criteria for this disease and describes a case of an atypical course of confirmed anti-NMDA encephalitis. The peculiarities of this observation are the relatively mild course of the disease with the development of generalized seizures, mental and cognitive disorders at the onset of the disease. The difficulties in diagnosis and possible pathogenetic aspects of the disease are discussed.

Infrequent patterns in cerebrospinal fluid isofocusing test: Clinical significance and contribution of IgG index and Reiber diagram to their interpretation

Cerebrospinal fluid (CSF) isoelectrofocusing (IEF) is considered as the gold standard for detecting an intrathecal synthesis of IgG, which is a hallmark of multiple sclerosis (MS). This corresponds to the presence of CSF-restricted IgG oligoclonal bands (OCB) (typically type 2 pattern). Moreover, this technique can also detect a systemic immune reaction with passive transfer of IgG (type 3 and 4 patterns) for which the clinical relevance is less understood. The aim of our study was to determine the frequency and disease associations of IEF type 3 and 4 patterns and to investigate the potential usefulness of including quantitative data (IgG index and Reiber Diagram) in interpreting such IEF profiles.Among 544 patients who underwent CSF IEF (Hydragel CSF isofocusing kit, Sebia®, France) in our Laboratory during a six-year-period, those who presented type 3 or 4 patterns were selected. Clinical data and results of other immunological tests were analyzed for 27 patients followed in the Neurological Department.Frequencies of type 3 and type 4 patterns were relatively low (2.3 % and 3.4 % respectively). Among patients with type 3 pattern included in our study (n = 10), 5 were diagnosed with MS. For the 5 other patients, the diagnosis was a clinically isolated syndrome (CIS) (2 cases), a probable auto-immune encephalitis (2 cases) and a possible genetic neurodegenerative disease (1 case). MS patients had an IgG index >0.7 and fell into area 4 of Reiber diagram while non-MS patients had an IgG index <0.7 and fell into area 1, except the last case. Regarding type 4 pattern (n = 17), the diagnoses were as follows: MS (3), CIS (4), Neuromyelitis optica spectrum disorders with positive anti-AQP4 antibodies (3) and anti-NMDAR autoimmune encephalitis (1). The remaining cases had central nervous system impairment related to vascular, metabolic or tumoral etiologies (3) or peripheral nervous system impairment (3). In this group (type 4 pattern), IgG index was <0.7 in 15/17 cases. Interpretation using Reiber diagram showed an abnormal blood-brain barrier for 8/17 patients.Type 3 and 4 IEF patterns are infrequently observed in routine neurology practice. It is important for the diagnostic laboratory professional as well as for the neurologist to understand their clinical relevance. Our findings highlight the contribution of quantitative evaluation of CSF (IgG index, Reiber diagram) for the interpretation of such situations. Despite the small size of our study population, our results emphasize the importance of reporting the exact type of IEF pattern and not only the positivity or not of OCB.

Functional connectivity changes of the hippocampal subregions in anti-N-methyl-D-aspartate receptor encephalitis.

The hippocampus plays an important role in the pathophysiological mechanism of Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Nevertheless, the connection between the resting-state activity of the hippocampal subregions and neuropsychiatric disorders in patients remains unclear. This study aimed to explore the changes in functional connectivity (FC) in the hippocampal subregions of patients with anti-NMDAR encephalitis and its association with clinical symptoms and cognitive performance. Twenty-three patients with anti-NMDAR encephalitis and 23 healthy controls (HC) were recruited. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and completed clinical cognitive scales. Based on the Brainnetome Atlas, the rostral (anterior) and caudal (posterior) hippocampi of both the left and right hemispheres were selected as regions of interest (ROIs) for FC analysis. First, a one-sample t-test was used to observe the whole-brain connectivity distribution of hippocampal subregions within the patient and HC groups at a threshold of p < 0.05. The two-sample t-test was used to compare the differences in hippocampal ROIs connectivity between groups, followed by a partial correlation analysis between the FC values of brain regions with statistical differences and clinical variables. This study observed that the distribution of whole-brain functional connectivity in the rostral and caudal hippocampi aligned with the connectivity differences between the anterior and posterior hippocampi. Compared to the HC group, the patients showed significantly decreased FC between the bilateral rostral hippocampus and the left inferior orbitofrontal gyrus and between the right rostral hippocampus and the right cerebellum. However, a significant increase in FC was observed between the right rostral hippocampus and left superior temporal gyrus, the left caudal hippocampus and right superior frontal gyrus, and the right caudal hippocampus and left gyrus rectus. Partial correlation analysis showed that FC between the left inferior orbitofrontal gyrus and the right rostral hippocampus was significantly negatively correlated with the California Verbal Learning Test (CVLT) and Brief Visuospatial Memory Test (BVMT) scores. The FC between the right rostral hippocampus and the left superior temporal gyrus was negatively correlated with BVMT scores. FC abnormalities in the hippocampal subregions of patients with anti-NMDAR encephalitis were associated with cognitive impairment, emotional changes, and seizures. These results may help explain the pathophysiological mechanisms and clinical manifestations of anti-NMDAR encephalitis and NMDAR dysfunction-related diseases such as schizophrenia.

Anti-NMDA Receptor Encephalitis, Human Papillomavirus, and microRNA.

Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is a rare autoimmune disease, which is caused by antibodies attacking NMDA receptors in the brain. Previous studies revealed that this disorder might be induced by vaccination. Vaccination is the most useful strategy to prevent human or animal infectious diseases. Although vaccines can produce immunity against diseases, at low risk, they may trigger serious adverse events. Anti-NMDA receptor encephalitis has been studied to be related to the H1N1 (influenza A virus subtype H1N1), tetanus/diphtheria/ pertussis and polio vaccine, Japanese encephalitis, yellow fever, and coronavirus disease 2019 (COVID-19) vaccination. Several cases have been reported that anti-NMDA receptor encephalitis could also be triggered by the human papillomavirus (HPV) vaccine. However, there is a lack of studies to investigate the underlying mechanism. In this paper, the association between anti-NMDA receptor encephalitis and HPV vaccination is discussed in terms of their microRNA (miRNA) biomarkers. Phylogenetic tree and distance similarity analyses are used to explore the relationship between their miRNA biomarkers. The results show a higher degree of similarity between miRNA biomarkers associated with HPV and anti-NMDA receptor encephalitis or related vaccines when compared to the overall miRNAs. It indicates that while the risk of HPV triggering anti-NMDA receptor encephalitis is low, a connection between anti-NMDA receptor encephalitis and HPV vaccination cannot be ruled out. This finding suggests that in cases where individuals receiving HPV vaccination experience psychiatric or neurological symptoms, it should be considered to diagnose anti-NMDA receptor encephalitis, given the exclusion of other possible complications.

Pediatric anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis: Exploring psychosis, related risk factors, and hospital outcomes in a nationwide inpatient sample: A cross-sectional study.

Our study aims to examine the risk factors for comorbid psychosis in pediatric patients hospitalized for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and its impact on hospital outcomes. We conducted a cross-sectional study using the nationwide inpatient sample (NIS 2018-2019). We included 3,405 pediatric inpatients (age 6-17 years) with a primary discharge diagnosis of anti-NMDAR encephalitis. We used binomial logistic regression model to evaluate the odds ratio (OR) of variables (demographic and comorbidities) associated with comorbid psychosis. The prevalence of comorbid psychosis in anti-NMDAR encephalitis inpatients was 5.3%, and majorly constituted of adolescents (72.2%) and females (58.3%). In terms of race, Blacks (OR 2.41), and Hispanics (OR 1.80) had a higher risk of comorbid psychosis compared to Whites. Among comorbidities, encephalitis inpatients with depressive disorders (OR 4.60), sleep-wake disorders (OR 3.16), anxiety disorders (OR 2.11), neurodevelopmental disorders (OR 1.95), and disruptive behavior disorders (OR 2.15) had a higher risk of comorbid psychosis. Anti-NMDAR encephalitis inpatients with comorbid psychosis had a longer median length of stay at 24.6 days (vs. 9.8 days) and higher median charges at $262,796 (vs. $135,323) compared to those without psychotic presentation. Adolescents, females, and Blacks with encephalitis have a higher risk of psychotic presentation leading to hospitalization for anti-NMDAR encephalitis. Identification of demographic predictors and comorbidities can aid in early recognition and intervention to optimize care and potentially reduce the healthcare burden.

White matter microstructural alterations in patients with anti-N-methyl-D-aspartate receptor encephalitis: A tract-based spatial statistics study

BackgroundCognitive impairment is common in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis; however, neural mechanisms underlying this impairment remain unclear. Diffusion tensor imaging (DTI) is a potential method for studying the condition of white matter fibers in patients with anti-NMDAR encephalitis, allowing for an analysis of the neuroimaging mechanisms of cognitive impairment in conjunction with cognitive scales. This study aimed to explore white matter microstructural alterations and their correlation with cognitive function in patients with anti-NMDAR encephalitis. MethodsDTI data were collected from 22 patients with anti-NMDAR encephalitis (aged 29.00(19.75, 39.50) years; 12 males, 10 females) and 20 healthy controls (HCs) (aged 24.50(21.25, 32.00); 12 males, 8 females) matched for age, sex, and educational level. Changes in the white matter microstructure were analyzed using tract-based spatial statistics. Pearson correlation analysis was used to explore the correlation between white matter integrity and neuropsychological scores. ResultsCompared with HCs, patients with anti-NMDAR encephalitis showed decreased fractional anisotropy and increased mean diffusivity values in extensive white matter regions, which were associated with disease severity, memory, and executive and visuospatial functions. ConclusionWidespread impairment of the structural integrity of the white matter in the brain is significantly associated with cognitive dysfunction in patients with anti-NMDAR encephalitis, providing neuroimaging evidence for studying the underlying mechanisms.

Anti-N-methyl-D-aspartate Receptor Encephalitis after Herpes Simplex Virus Encephalitis

Abstract Encephalitis due to herpes simplex virus 1 (HSV1) has been described as a potential trigger for the development of anti-N-methyl-D-aspartate receptor (NMDAR) autoimmune encephalitis within few days to months. Here, we report one such case of anti-NMDAR encephalitis which was triggered by preceding HSV encephalitis. The patient had a history of headache and fever of 1–2-week duration, and cerebrospinal fluid and magnetic resonance imaging picture suggestive of HSV encephalitis. After 2 weeks of completion of 14-day course of acyclovir, he had symptoms of altered behavior, headache, and vomiting. The possibility of anti-N-methyl-D-aspartate (NMDA) encephalitis occurring after HSV encephalitis was considered. Serum for anti-NMDA antibody came positive, and he improved with treatment. A high index of suspicion and awareness of such a possibility can help in making the diagnosis and initiate early therapy.

Anti-NMDA Receptor Encephalitis Presenting with Language Impairment and Bradycardia

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is known to have various clinical symptoms, but usually shows acute behavioral changes, memory deficit, speech problems and dysregulation of autonomic nervous system. Recently, it has been found that NMDA receptors perform important roles not only in central nervous system but also in peripheral organs, like control the cardiac rhythm by located in the myocardium and cardiac conduction system. The authors would like to report a case of bradycardia accompanied by anti-NMDA receptor encephalitis.

Anti-NMDAR Encephalitis Clinical Practice Guideline: Improving Time to Diagnosis, Treatment, and Hospital Length of Stay.

A clinical practice guideline (CPG) was created to standardize evaluation and treatment for patients with suspected anti-methyl-d-aspartate receptor (NMDAR) autoimmune encephalitis (AE), the most common AE in children. The objective of this study was to evaluate the CPG effect on time to diagnosis, treatment, and hospital length of stay (LOS). Patients with an inpatient consult to pediatric rheumatology for AE during a 4-year period (period 2) after CPG implementation were identified. Data were extracted and compared with data over the preceding 4-year period (period 1). During period 1, fewer patients underwent diagnostic testing than during period 2 (34 vs 80). Number of patients diagnosed with AE did not differ from period 1 to that from period 2 (NMDAR AE 9 vs 8; seronegative AE 4 vs 5). The average time to diagnostic evaluation with lumbar puncture decreased from 5.4 to 1.5 days (p = 0.0082), and time to treatment decreased from 7.6 to 3.9 days (p = 0.018). LOS showed a trend toward improvement (40.4-29.2 days (p = 0.23)). Creation of a CPG for patients with suspected AE was associated with an improved time to diagnostic evaluation and treatment. With the CPG, more patients underwent AE testing, though total diagnoses remained the same.

Autoimmune Encephalitis. An Analysis of Three Cases

The diagnosis of diseases from the group of autoimmune encephalitis (AE) requires a detailed analysis of clinical data and correlation of results from a wide range of laboratory and instrumental research methods. This article presents three clinical cases of patients with AE. In one patient, AE was associated with a malignant neoplasm, in the second one – with the novel coronavirus infection, and in the third patient, no comorbid pathology was detected. The specific type of encephalitis was determined for each of the three patients. The diagnosis of “autoimmune limbic encephalitis” was established in two patients based on visualization of changes in the medial temporal structures in the magnetic resonance imaging of the brain, detection of pathological bioelectrical activity in the temporal lobe cortex in electroencephalography, and pleocytosis in cerebrospinal fluid. The diagnosis of “anti-NMDA receptor encephalitis” was made based on the detection of specific antibodies to the subunit of the corresponding receptor. Neurological deficit regression was observed in two patients after the application of combined immune therapy methods and in one patient without the use of immune therapy.

Are the new diagnoses needed in psychiatry, or is it enough for us to remember valentin magnan’s bouffée délirante? (To the article by E.V. Snedkov and co-authors ‘Is anti-NMDA receptor encephalitis real?’)

New clinical observations and new scientific data lead to the identification of new diseases. Anti-NMDA receptor encephalitis, which mainly develops in young women due to ovarian teratoma and other suspected etiological factors, manifested by numerous neurological and psychiatric symptoms that give an acute condition resembling primary mental disorders, and accompanied by the appearance of antibodies to NMDA receptors, is one example of this kind. Some experts are questioning whether anti-NMDA receptor encephalitis should be considered a separate neuropsychiatric disorder. This article analyses a recent publication by one of the groups opposing the new diagnosis.

Anti-NMDA receptor encephalitis as a reversible cause of acute psychoses: Diagnostic possibilities. (Comment on the article by E.V. Snedkov "Is anti-NMDA receptor encephalitis real? I. Diagnostic challenges")

Encephalitis with antibodies to NMDA receptors is a form of autoimmune encephalitis that most often debuts as an acute psychosis. Considering its curability and reversibility, encephalitis with antibodies to NMDA receptors must be included into differential diagnostic list for all the patients suffering first psychotic episode. However, to diagnose it, it is necessary to follow a step-by-step algorithm considering both clinical and instrumental and laboratory data. Confirming anti-NMDA-receptor encephalitis based solely on increased blood antibodies level often leads to false-positive diagnostics and errors in treatment of such patients. In this article, we discuss diagnostic features of encephalitis with antibodies to NMDA receptors,as well as other forms of autoimmune encephalitis that can initially manifest as acute psychoses.

Is anti-NMDA receptor encephalitis real? I. Diagnostic challenges

After conducting a thorough analysis of clinical, neurophysiological, neuroimmunological, neurobiological, and neuropathological research findings, the authors of the review question on the validity of the anti-NMDA receptor encephalitis concept. The review highlights the significance of studying sanogenetic mechanisms in medicine and warns against hasty interpretations of neurobiological data without clinical knowledge.

A 19-Month-Old Spanish Boy with Anti-NMDAR Encephalitis: Case Report and Review of Literature

Background and Aim: The classic definition of acute encephalitis consists of altered consciousness associated with fever, seizures or focal neurological alterations on neuroimaging or electroencephalography. However, there are particularities that may provide a glimpse of the probably autoimmune versus infectious etiology of the same neurological picture. Case presentation: A 19-month-old male starts with motor clumsiness and refusal to ambulation and leg claudication in the context of febrile pharyngotonsillitis. Simultaneously, first episode of forced gaze’s lateralization and cephalic deviation with right tonic movements and sucking. On examination: intense irritability with no contact, denial-type stereotypies, hemiparetic gait, pronation and adduction of the right arm and foot with frequent stumbling. Results: Neuroimaging tests, electroencephalogram, laboratory tests and antistreptolysin-O were normal, no pathological clinical exome and detection of antibodies in cerebrospinal fluid paired with serum. Such as diagnosis: acute autoimmune encephalitis due to anti-NMDA-R (N-methyl-D-aspartate Receptor) antibodies and movement disorder (choreoathetosis, hemidystonia). We initiate treatment with intramuscular penicillin and oral clobazam with erratic response. Fortunately, high doses of intravenous (iv) corticosteroids and immunoglobulins, oral corticotherapy and iv rituximab on our patient were used. Months later, clear improvement with autonomous ambulation without assistance, adequate manual opening and entire disappearance of dystonic-myoclonic movements. Conclusions: Choreoathetoid movements accompanied by irritability in an infectious context should lead us to think of Sydenham's chorea. However, new developments in the analysis of biological samples and a high index of suspicion may lead us to autoimmune pathology and the consequent early use of immunotherapy with optimal results.

Cortical atrophy in early-stage patients with anti-NMDA receptor encephalitis: a machine-learning MRI study with various feature extraction.

Conventional brain magnetic resonance imaging (MRI) of anti-N-methyl-D-aspartate-receptor encephalitis (NMDARE) is non-specific, thus showing little differential diagnostic value, especially for MRI-negative patients. To characterize patterns of structural alterations and facilitate the diagnosis of MRI-negative NMDARE patients, we build two support vector machine models (NMDARE versus healthy controls [HC] model and NMDARE versus viral encephalitis [VE] model) based on radiomics features extracted from brain MRI. A total of 109 MRI-negative NMDARE patients in the acute phase, 108 HCs and 84 acute MRI-negative VE cases were included for training. Another 29 NMDARE patients, 28 HCs and 26 VE cases were included for validation. Eighty features discriminated NMDARE patients from HCs, with area under the receiver operating characteristic curve (AUC) of 0.963 in validation set. NMDARE patients presented with significantly lower thickness, area, and volume and higher mean curvature than HCs. Potential atrophy predominately presented in the frontal lobe (cumulative weight = 4.3725, contribution rate of 29.86%), and temporal lobe (cumulative weight = 2.573, contribution rate of 17.57%). The NMDARE versus VE model achieved certain diagnostic power, with AUC of 0.879 in validation set. Our research shows potential atrophy across the entire cerebral cortex in acute NMDARE patients, and MRI machine learning model has a potential to facilitate the diagnosis MRI-negative NMDARE.