AntiNMDA
29.1K views | +0 today
Follow
 
Scooped by Nesrin Shaheen
onto AntiNMDA
Scoop.it!

Clinical spectrum of high-titre GAD65 antibodies | Journal of Neurology, Neurosurgery & Psychiatry

Introduction Glutamic acid decarboxylase-65 (GAD65) is an enzyme required for synthesis of gamma-aminobutyric acid, a major central nervous system inhibitory neurotransmitter.1 Antibodies targeting GAD65 are a biomarker of type 1 diabetes mellitus (T1DM). Low titres in serum lack clinical specificity for autoimmune neurological disease, and may be detected in patients with alternative neurological diagnoses, isolated T1DM or even healthy controls.2 3 In contrast, high-titre GAD65 antibodies, defined in our laboratory as more than 20 nmol/L in serum (over 1000-fold higher than the upper limit of normal), reportedly confer high clinical specificity for GAD65 neurological autoimmunity.2 GAD65 antibodies appear unlikely to be pathogenic given the intracellular location of GAD65, and may instead be a surrogate marker of cytotoxic T-cell-mediated disease in patients with associated neurological syndromes.1 Stiff-person spectrum disorders (SPSD) were first characterised by Moersch and Woltman in 1956 and later determined to be a prototypical presentation of GAD65 neurological autoimmunity.4–6 Other manifestations of GAD65 neurological autoimmunity that have since been described include cerebellar ataxia, epilepsy, limbic encephalitis (LE), cognitive impairment, myelopathy and/or brainstem dysfunction. These reports, however, are limited by small sample sizes or restriction to individual phenotypes, precluding complete disease characterisation.2 3 6–19 We, herein, evaluate the clinical manifestations, immunotherapy responses and outcomes of a large patient cohort with high-titre GAD65 antibodies who were systematically determined to have GAD65 neurological autoimmunity. Methods Patients provided written consent to the use of their records for research. Identification of patients with GAD65 neurological autoimmunity We retrospectively identified 323 patients with high-titre GAD65 antibodies (defined as >20 nmol/L in serum based on previous work demonstrating high clinical specificity for GAD65 neurological autoimmunity at this cut-off) detected in the Mayo Clinic Neuroimmunology Laboratory out of 380 514 samples submitted for anti-GAD65 testing from January 2003 to May 2018, using radioimmunoassay (RIA) as previously described.2 Their electronic medical records (EMRs) were then reviewed by two neurologists with fellowship training in Neuroimmunology/Autoimmune Neurology (AB and NLZ). Patients with non-neurological presentations (eg, GAD65 antibody detected as part of T1DM evaluation), as well as those with neurological presentations but a more likely alternative diagnosis than GAD65 neurological autoimmunity, were classified as not having GAD65 neurological autoimmunity; these patients were excluded from study analysis and summarised separately. Patients with no more likely alternative diagnosis but an atypical presentation for GAD65 neurological autoimmunity were also excluded from study analysis but described separately, to ensure potentially novel disease phenotypes were not overlooked. Remaining patients were classified as having GAD65 neurological autoimmunity, and data relating to their clinical presentation, neuroimaging, electrophysiological testing, laboratory findings, immunotherapy responses, and outcomes as measured by modified Rankin score (mRS)20 were extracted from their EMRs for analysis. Diagnosis of disease manifestations Diagnosis of disease manifestations in GAD65 neurological autoimmunity was based on clinical assessment by a Mayo Clinic physician with expertise in the disorder of interest, alongside EMR review by AB and NLZ as outlined above to ensure no more likely alternative diagnosis was present. Electrophysiological data (ie, auditory startle reflexes, exteroceptive responses and/or electromyography for SPSD as described previously,7 electroencephalography for epilepsy) were frequently gathered, but an abnormal electrophysiological study was not required for diagnosis given imperfect test clinical specificity.21 22 Patients with SPSD were classified as classical SPSD (trunk and limb involvement), partial SPSD (trunk or limb involvement), or SPSD with prominent exaggerated startle. LE was defined as medial temporal lobe T2-hyperintensity with subacute disease onset of less than 3 months. Cognitive impairment was diagnosed by the treating physician based on the Kokmen short test of mental status23 and/or formal neuropsychometric testing. Outcome measures Response to immunotherapy (corticosteroids, intravenous IG, plasma exchange (PLEX), rituximab, cyclophosphamide and/or autologous stem cell transplantation) was classified as no response, partial response, near-complete response (ie, minimal residual clinical signs/symptoms), or complete response (ie, no residual clinical signs/symptoms), as well as sustained (defined as benefit persisting for greater than 3 months) or non-sustained, based on review of the treating Mayo Clinic physician’s documentation by AB and NLZ. A poor outcome was defined as mRS >2 at last clinical follow-up. Statistical analyses Statistical analyses were performed using JMP Pro V.14.1.0. Continuous and categorical variables were reported as median (range) and number (percentage), respectively. Differences across multiple groups were assessed by the Kruskal-Wallis, Pearson’s χ2 or Fisher’s exact test for multiple categories, as appropriate. Associations with a poor outcome at last clinical follow-up were explored by univariate logistic regression analysis, while the simultaneous effect of multiple significant variables was assessed by multivariate logistic regression. A two-sided p<0.05 was considered statistically significant. Adjustment for multiple comparisons was not performed.24 The relationships among manifestations of GAD65 neurological autoimmunity were depicted using circular visualisation in R.25 Results One in three patients with high-titre GAD65 antibodies were classified as not having GAD65 neurological autoimmunity Of 323 patients with high-titre GAD65 antibodies, 37 (11%) had non-neurological presentations (eg, GAD65 antibody detected as part of T1DM evaluation) and were excluded from study analysis. Seventy-one of 323 patients (22%) were determined to have a more likely alternative diagnosis than GAD65 neurological autoimmunity after review of their EMR; these patients were excluded from study analysis but are summarised separately (online supplemental table 1). Three of 323 patients (1%) without more likely alternative diagnoses but presentations atypical for GAD65 neurological autoimmunity (hyperkinetic movement disorders) were also excluded from study analysis but are described separately (table 2). The remaining 212 of 323 patients (66%) were classified as having GAD65 neurological autoimmunity for study analysis. The median serum anti-GAD65 titre among patients classified as having a more likely alternative diagnosis was significantly lower compared with patients classified as having GAD65 neurological autoimmunity (149 nmol/L vs 534 nmol/L, p<0.0001), and was not significantly different compared with patients with non-neurological presentations (149 nmol/L vs 164 nmol/L, p=0.71). The process of classifying patients as having GAD65 neurological autoimmunity is depicted via flow diagram (figure 1). Supplemental material Figure 1 Flow diagram depicting patient selection for study inclusion. GAD65, glutamic acid decarboxylase-65. VIEW INLINE VIEW POPUP Table 2 Patients with high-titre GAD65 antibodies and hyperkinetic movement disorders Defining the core and secondary manifestations of GAD65 neurological autoimmunity Through EMR review, we found that SPSD, cerebellar ataxia, epilepsy without LE (simply referred to hereafter as epilepsy unless otherwise specified) and LE could all occur in isolation. These were thus designated core manifestations of GAD65 neurological autoimmunity. Patients with two or more core disease manifestations were designated overlap syndromes, with the exception of LE and epilepsy (all patients with LE had seizures). No patient had cognitive impairment, myelopathy or brainstem dysfunction reported in isolation (ie, in the absence of SPSD, cerebellar ataxia, epilepsy or LE). These co-occurring phenomena were thus designated secondary manifestations of GAD65 neurological autoimmunity. Core manifestations of GAD65 neurological autoimmunity are SPSD, cerebellar ataxia, epilepsy and LE The clinical characteristics, immunological/cancer associations and laboratory results of all 212 patients with GAD65 neurological autoimmunity are presented in table 1. The median age of symptom onset was 46 years (range: 5–83 years) and 163/212 (77%) were female. Concurrent systemic autoimmunity was documented in 125/212 (59%) patients with GAD65 neurological autoimmunity and was most often thyroid disease (72/212, 34%), T1DM (63/212, 30%), and/or pernicious anaemia (40/212, 19%). A diagnosis of cancer within 5 years of symptom onset was reported in 9/212 (4%). Stratification of these findings by core manifestation is included in table 1, and discussed in relevant sections below. VIEW INLINE VIEW POPUP Table 1 Characteristics of 212 patients with GAD65 neurological autoimmunity* Stiff-person spectrum disorders SPSD was the most common core manifestation and was often classical in presentation The most common core manifestation was SPSD, which was reported in 107/212 (50%). The majority (73/107, 68%) had classical SPSD. Partial SPSD was documented in 30/107 (28%), and a small minority were classified as SPSD with prominent exaggerated startle response (4/107, 4%). Electrophysiological findings supportive of SPSD were reported in 52/70 (74%). Common findings documented on clinical assessment included spasms (93/107, 87%), gait dysfunction attributed to SPSD (85/107, 79%) and hyperlordosis (49/107, 46%). Cerebellar ataxia Cerebellar ataxia was the second most common core manifestation and often affected gait Cerebellar ataxia was reported in 91/212 (43%). Gait ataxia was most frequently documented (76/91, 84%), followed by limb ataxia (63/91, 69%) and ataxic dysarthria (47/91, 52%). On brain MRI, cerebellar atrophy was observed in 24/91 (26%); no patient had cerebellar T2-hyperintensity or gadolinium enhancement indicative of cerebellitis. Rare paraneoplastic cases associated with cerebellar ataxia While a diagnosis of cancer within 5 years of symptom onset was reported in only 9/212 (4%), this ranged from 0/71 (0%) in SPSD to 6/55 (11%) in cerebellar ataxia (p=0.01). Cancers diagnosed included thyroid cancer, breast cancer, lung cancer, and thymoma (table 1). Epilepsy Epilepsy was classically temporal lobe in origin and occasionally musicogenic Epilepsy with or without LE was reported in 62/212 (29%). Seizures were focal-onset in 56/62 (90%) and unknown-onset in 6/62 (10%). Seizures most often localised to the medial temporal lobe (35/56, 63%). Other seizure localisations were temporal lobe not otherwise specified (11/56, 20%), temporal lobe involving Heschl’s gyrus (4/56, 7%), frontal lobe (3/56, 5%), tempoparietal region (1/56, 2%), temporal and occipital lobes (1/56, 2%), and hemispheric onset (1/56, 2%). Involvement of Heschl’s gyrus was presumed if music provoked seizures (three patients) or if the patient heard music during the seizure (one patient). Patients evaluated for seizure management were often medically refractory Seizures were medically refractory in the majority (42/57, 74%). However, medically refractory epilepsy was significantly more frequent among patients with epilepsy in isolation who were evaluated for seizure management (34/39, 87%), compared with patients with epilepsy as part of an overlap syndrome who may have presented for management of SPSD or cerebellar ataxia rather than epilepsy (8/18, 44%) (p=0.0007). Epilepsy surgery uniformly revealed gliosis and did not usually result in seizure freedom The most common neuroimaging finding prompting consideration of epilepsy surgery was mesial temporal sclerosis, or MTS (9/62, 15%). Eight of 62 patients (13%) underwent epilepsy surgery (unilateral anterior temporal lobectomy, 7 patients; unilateral anterolateral temporal/frontal lobe resections, 1 patient). Neuropathological data was available for 5/8 patients, all of whom had gliosis reported. Two of 5 had pathological evidence of chronic inflammation noted (mild leptomeningeal, focal superficial cortical and perivascular chronic inflammation, 1 patient; ‘patchy chronic inflammation’ as per Mayo Clinic physician interpretation of outside neuropathology report, 1 patient). No more likely alternative aetiology for seizures (eg, malformation of cortical development) was reported in any patient. At last follow-up after surgery, only 2/8 (25%) obtained seizure freedom (one patient had focal seizures with preserved awareness up to 9 months after surgery that ceased with intravenous IG over two further years of follow-up, 1 patient had focal seizures with impaired awareness up to ten years after surgery that ceased with addition of clobazam over two further years of follow-up). The remaining six patients continued to have disabling seizures (ie, seizures limiting daily activities, requiring acute medical evaluation and/or leading to injury) after surgery. Epilepsy was typically young-onset and chronic in disease duration On stratification by core disease manifestation (table 1), median age at symptom onset ranged from 24 years (range: 5–56 years) in epilepsy to 59 years (range: 14–83 years) in cerebellar ataxia (p<0.0001). We examined the age at symptom onset of individual core disease manifestations in patients with overlap syndromes, and similarly found that the median age ranged from 33 years (range: 11–60 years) for epilepsy onset to 53 years for both cerebellar ataxia onset (range: 26–69 years) and SPSD onset (range: 19–70 years) (p<0.0001). The median total symptom duration recorded ranged from 42 months (range: 3–171 months) in cerebellar ataxia to 137 months (range: 3–552 months) in epilepsy (p<0.0001). Epilepsy showed a trend toward less cerebrospinal fluid inflammation On review of laboratory results (table 1), median serum and cerebrospinal fluid (CSF) anti-GAD65 titre did not differ significantly across core manifestations of GAD65 neurological autoimmunity. Patients with epilepsy had the lowest median CSF anti-GAD65 titre (2.5 nmol/L) and the lowest frequency of elevated CSF IgG index (0/22, 0%) among core disease manifestations, but these differences did not reach statistical significance (p=0.10 and p=0.17, respectively). Limbic encephalitis Patients with epilepsy uncommonly had neuroimaging evidence of LE On MRI, medial temporal lobe T2-hyperintensity compatible with LE was seen in 10/62 (16%). These patients were classified separately as having LE and all had subacute-onset seizures/cognitive impairment. Only 1/10 (10%) were assessed at the Mayo Clinic within 3 months of disease onset, and 3/10 (30%) were assessed greater than 1 year after disease onset for management of sequelae of LE (ie, persistent seizures, cognitive difficulties). Secondary manifestations of GAD65 neurological autoimmunity include cognitive impairment, myelopathy and brainstem dysfunction Of the secondary disease manifestations cognitive impairment was the most common, being reported in 38/212 (18%). The predominant cognitive sphere impacted was short-term memory in 29/38 (76%), followed by working memory/attention in 6/38 (16%), and verbal fluency/expressive language in 3/38 (8%). Myelopathy was reported in 23/212 (11%), and manifested as upper motor neuron (UMN) signs (brisk tendon reflexes, extensor plantar responses and/or spasticity) in 19/23 (83%), followed by pyramidal weakness in 14/23 (61%) and bowel/bladder dysfunction in 4/23 (17%). No patient had spinal cord T2-hyperintensity or gadolinium enhancement indicative of myelitis. Concern for brainstem dysfunction was reported in 22/212 (10%) and was on the basis of oculomotor findings in all, including vertical misalignment (11/22, 50%), horizontal misalignment (7/22, 32%) and conjugate ophthalmoparesis (4/22, 18%). No patient had brainstem T2-hyperintensity or gadolinium enhancement indicative of brainstem encephalitis. Secondary manifestations of GAD65 neurological autoimmunity clustered with specific core manifestations Secondary disease manifestations clustered with specific core disease manifestations: cognitive impairment with epilepsy/LE (N=30/38, 79%), myelopathy with SPSD (N=18/23, 78%), and brainstem dysfunction with cerebellar ataxia (N=20/22, 91%). The relationships among core and secondary disease manifestations are depicted via chord diagram (figure 2). Figure 2 CHORD diagram depicting relationships among manifestations of GAD65 neurological autoimmunity in this chord diagram, Arcs representing the relationships among core manifestations (stiff-person spectrum disorder (SPSD), cerebellar ataxia, epilepsy and limbic encephalitis (LE)) and secondary manifestations (myelopathy, brainstem dysfunction and cognitive impairment) of GAD65 neurological autoimmunity are shown. The size of the Arc is proportional to the significance of the relationship. Orientation of disease manifestations around the CHORD diagram has been chosen to highlight significant overlap of neighbouring categories: cognitive impairment and epilepsy/LE, myelopathy and SPSD, and brainstem dysfunction and cerebellar ataxia. GAD65, glutamic acid decarboxylase-65. An atypical presentation of GAD65 neurological autoimmunity: hyperkinetic movement disorders Three patients had high-titre GAD65 antibodies but atypical presentations for GAD65 neurological autoimmunity (table 2). All had unilateral hyperkinetic movement disorders (dystonia, 2 patients; chorea, 1 patient). In patients with dystonia the onset was insidious, while in the patient with chorea onset was subacute. One patient with right lower extremity dystonia received intravenous IG and reported 90% improvement that was confirmed by the treating physician; however, dystonia recurred seven to 8 weeks after intravenous IG was discontinued due to intolerability. Responses to immunotherapy and outcomes in GAD65 neurological autoimmunity Responses to immunotherapy were stratified by core disease manifestation and are presented in table 3. Immunotherapy usage (corticosteroids, intravenous IG, PLEX, rituximab and cyclophosphamide) was not significantly different except for corticosteroid usage (p<0.0001). This was driven by infrequent corticosteroid usage in SPSD (7/44, 16%), the majority of whom received intravenous IG (38/44, 86%). VIEW INLINE VIEW POPUP Table 3 Responses to immunotherapy among 142 patients with GAD65 neurological autoimmunity Patients with epilepsy received immunotherapy later and were least immunotherapy responsive The median time from symptom onset to first immunotherapy ranged from 5 months (range: 1–22 months) in LE to 50.5 months (range: 1–324 months) in epilepsy (p<0.0001). The number of patients with sustained response to immunotherapy ranged from 5/20 (25%) in epilepsy to 32/44 (73%) in SPSD (p=0.002). Complete response to immunotherapy was rare Among all patients treated with immunotherapy, a complete response was reported in only 2/142 (1%); one patient had mild ataxic dysarthria that resolved after corticosteroids, and one patient had new-onset seizures with cortical-subcortical lesions on MRI that resolved after corticosteroids, intravenous IG and PLEX. In retrospect this patient’s clinicoradiographic presentation was concerning for co-existing for gamma-aminobutyric acid type A receptor encephalitis,26 but confirmatory testing for this antibody was not performed. Presence of cerebellar ataxia and serum GAD65 antibody titre >500 nmol/L predicted poor outcome Among patients with GAD65 neurological autoimmunity the mRS at last follow-up was as follows: 0, 2/212 (1%); 1, 28/212 (13%); 2, 61/212 (29%); 3, 65/212 (31%); 4, 49/212 (23%); 5, 3/212 (1%); 6, 4/212 (2%). Logistic regression analysis revealed that mRS >2 at first Mayo Clinic evaluation, cerebellar ataxia and serum GAD65 antibody titre >500 nmol/L were independent predictors of poor outcome (mRS >2) at last clinical follow-up (table 4). VIEW INLINE VIEW POPUP Table 4 Logistic regression analysis assessing predictors of poor outcome (MRS >2) at last clinical follow-up in 212 patients with GAD65 neurological autoimmunity Discussion This study of patients with GAD65 neurological autoimmunity provides numerous important insights into the disease. Through systematic review of all Mayo Clinic patients with high-titre GAD65 antibodies identified in our Neuroimmunology Laboratory over a 15-year period, we found that SPSD, cerebellar ataxia, epilepsy, and LE were core disease manifestations. Phenotypically, SPSD was usually classical in presentation, in keeping with previous studies.7 Cerebellar ataxia most often impacted gait, although limb and speech ataxia were also commonly reported. Among those with epilepsy, seizures typically originated from the temporal lobe. Interestingly, three patients had musicogenic epilepsy, suggesting patients with this rare form of reflex epilepsy should be considered for GAD65 antibody testing.27 28 With regard to immunotherapy-responsiveness, this differed significantly across core disease manifestations; SPSD was the most likely to respond to immunotherapy, while epilepsy was least immunotherapy responsive. We also determined that serum GAD65 antibody titre >500 nmol/L as well as cerebellar ataxia independently predicted poor outcome. An mRS >2 at first Mayo Clinic evaluation also independently predicted poor outcome, although the external validity of this finding to other centres requires further study. Across core disease manifestations the age of symptom onset was youngest for epilepsy, indicating that a prior epilepsy diagnosis in a patient presenting with features of SPSD or cerebellar ataxia may be a clue to GAD65 neurological autoimmunity. Medically-refractory epilepsy was reported in the majority but was significantly more frequent among those with epilepsy in isolation who were evaluated for seizure management, compared with those with epilepsy as part of an overlap syndrome who may have been evaluated for management of SPSD or cerebellar ataxia. This suggests that referral bias may skew toward more severe epilepsy in publications, a finding that should be part of a balanced prognostic discussion in newly-diagnosed GAD65 epilepsy patients. LE was least-represented in our cohort, which likely reflects the rarity of this presentation as well as the primarily outpatient tertiary care setting of this study; patients with severe presentations of LE might have been less likely to travel to our facility. A cancer diagnosed within 5 years of symptom onset, which is the timeframe within which an associated neurological disorder is typically considered paraneoplastic,29 only occurred in 9/212 (4%). However, this differed significantly across core disease manifestations, with the highest rates of cancer in patients with cerebellar ataxia (6/55, 11%) and LE (1/7, 14%) as noted previously.30 Cognitive impairment, brainstem dysfunction and myelopathy were frequent accompaniments of GAD65 neurological autoimmunity but did not occur in isolation, hence their designation as secondary disease manifestations. This finding emphasises that patients with high-titre GAD65 antibodies who only have cognitive impairment, myelopathy or brainstem dysfunction should be thoroughly evaluated for alternative etiologies, because such presentations in isolation are not typical of GAD65 neurological autoimmunity. Secondary disease manifestations clustered intuitively with core disease manifestations: cognitive impairment with epilepsy/LE, myelopathy with SPSD, and brainstem dysfunction with cerebellar ataxia. Cognitive impairment was typically amnestic in keeping with medial temporal lobe dysfunction, as would be expected given the high rate of co-occurrence with temporal lobe epilepsy and LE.31 32 Myelopathic findings were most often reported in SPSD and usually manifested as UMN findings (brisk reflexes, extensor plantar responses, mild UMN pattern of weakness), in keeping with previous reports.7 The frequent coexistence of brainstem dysfunction with cerebellar ataxia on the basis of oculomotor findings could reflect more diffuse posterior fossa inflammation (‘rhombencephalitis’) in some patients, as well as the difficulties parsing out whether such findings are brainstem or cerebellar in clinical practice.33 34 Three patients had hyperkinetic movement disorders, suggesting this phenotype may be part of the spectrum of GAD65 neurological autoimmunity.35 However, given the paucity of cases, thorough evaluation for other causes of a hyperkinetic movement disorder in a patient with high-titre GAD65 antibodies is recommended. On review of immunotherapy usage across core disease manifestations, only corticosteroid usage differed significantly. This was driven by the low usage of corticosteroids in patients with SPSD who instead largely received intravenous IG, which is likely due to randomised-controlled trial evidence for intravenous IG in SPSD.36 When evaluating immunotherapy-responsiveness, due to the retrospective nature of this study we were not able to implement standardised measures of disease severity when monitoring responses to immunotherapy. We thus chose to classify patients as having no response, partial response, near-complete response, or complete response to immunotherapy, based on the Mayo Clinic treating physician’s documentation. There is an element of subjectivity to this approach, but it has immediate translatability to clinical practice (eg, sustained response to immunotherapy is least often seen in epilepsy, response to immunotherapy is rarely complete) and is thus of clear utility to practitioners.37 Rates of sustained response to immunotherapy ranged from 73% in SPSD to only 25% in epilepsy, highlighting the recalcitrance of this disease manifestation.12 While the poor response to immunotherapy in patients with epilepsy and high-titre GAD65 antibodies may lead one to question whether or not anti-GAD65 is directly relevant to epilepsy aetiology, the high prevalence of epilepsy among these patients along with previously published series support a true disease association. Median time from symptom onset to first immunotherapy was longest for epilepsy (50.5 months), which may contribute to lack of immunotherapy-responsiveness. This delay to immunotherapy likely reflects epilepsy chronicity in GAD65 neurological autoimmunity, which in combination with the younger age of onset would explain the long median symptom duration recorded for epilepsy (137 months). The indolence of GAD65 epilepsy is unique compared with other autoimmune epilepsies, which usually present more rapidly.38 Inflammation was reported neuropathologically in only 2/5 patients with GAD65 epilepsy who underwent epilepsy surgery, and there was also a trend toward lower median CSF anti-GAD65 titre and less frequent elevated CSF IgG index among these patients compared with other core disease manifestations. Taken together, these findings may reflect a lack of inflammation in patients with chronic GAD65 epilepsy at the time they undergo clinical evaluation; whether a more prominent inflammatory response is present early on that may be more amenable to immunotherapy remains undetermined. With regard to patient outcomes we found that serum GAD65 antibody titre >500 nmol/L and cerebellar ataxia were independent predictors of poor outcome (mRS >2). The mRS was chosen as a measure of disease outcome given its frequent usage in scoring neurological disability and relative ease of determination, but may skew towards poor outcomes among patients with disease manifestations that prominently affect gait (ie, cerebellar ataxia). Despite this limitation of the mRS, its broad applicability means that predictors of a poor outcome as defined by mRS >2 are helpful when discussing disease prognosis. There are several limitations to this retrospective study. Clinical reporting of GAD65 antibodies in the Mayo Clinic Neuroimmunology Laboratory is based only on RIA, and so confirmation of high-titre GAD65 antibodies by a second assay (eg, rodent brain tissue indirect immunofluorescence, or TIIF) was not required for study inclusion. However, reporting of anti-GAD65 by TIIF is not routinely done, and so our approach is representative of clinical practice. Additionally, even serum positivity for anti-GAD65 by TIIF may occur in patients without GAD65 neurological autoimmunity,19 highlighting the challenge in determining what test methodology or cut-off best defines a clinically relevant high-titre GAD65 antibody result. Implementation of other test methodologies such as ELISA, immunoblot or cell-based assay to detect high-titre GAD65 antibodies in some laboratories has created the need for assay comparison studies, which is an area of active investigation in our laboratory. Based on our findings and that of the previous literature, high-titre GAD65 antibodies in serum are best viewed as necessary, but not sufficient for a diagnosis of GAD65 neurological autoimmunity.39 The presence of anti-GAD65 in CSF supports an autoimmune aetiology in the appropriate clinical context,39 which in keeping with our finding of anti-GAD65 CSF positivity in all patients who were classified as having GAD65 neurological autoimmunity. Calculation of intrathecal anti-GAD65 synthesis has recently been suggested as the most definitive laboratory evidence of GAD65 neurological autoimmunity.39 This calculation (which requires paired serum and CSF as well as albumin measurement to determine synthesis rate) is not performed in our testing laboratory, and was not required for study inclusion. While its calculation may aid in the determination of GAD65 neurological autoimmunity, it is not yet in widespread use and so systematic evaluation of its diagnostic utility in clinical practice is required. Given the lack of a diagnostic gold standard for GAD65 neurological autoimmunity that is independent of GAD65 antibody testing,39 rigorous clinical evaluation to rule out alternative diagnoses in patients with atypical features remains prudent. Prior to study analysis, we excluded one-third of patients with high-titre GAD65 antibodies who were classified as not having GAD65 neurological autoimmunity due to non-neurological presentations (eg, isolated T1DM) or more likely alternative neurological diagnoses. This seemingly high number of excluded patients could in part reflect referral bias at our specialised tertiary care centre, which may be enriched with patients who have atypical presentations for GAD65 neurological autoimmunity and are ultimately determined to have more likely alternative diagnoses. Additionally, it is possible that some patients who were considered to have a more likely alternative diagnosis for their neurological presentation may have had contributory GAD65 neurological autoimmunity (eg, SPSD potentially contributing to stiffness/spasms in a patient with myotonia congenita, GAD65 cerebellar dysfunction potentially contributing to episodic vestibular symptoms in patients diagnosed as having more common vestibular disorders such as vestibular neuritis or migraine, or GAD65 epilepsy potentially contributing to seizure aetiology in a patient with febrile seizures who developed MTS). However, rigorous efforts to only include patients with the disease of interest in studies such as this is critical to prevent ‘phenotype creep’, whereby neurological features of alternative diagnoses are mistakenly assumed to broaden the clinical spectrum of a neural antibody based solely on seropositivity by an imperfectly specific assay.40 Our finding that high-titre GAD65 antibodies in serum are suggestive of, but not pathognomonic for GAD65 neurological autoimmunity emphasises the importance of clinical-serological correlation when enrolling patients in future studies of this disease. References ↵McKeon A, Tracy JA. GAD65 neurological autoimmunity. Muscle Nerve 2017;56:15–27.doi:10.1002/mus.25565pmid:http://www.ncbi.nlm.nih.gov/pubmed/28063151OpenUrlPubMed ↵Walikonis JE, Lennon VA. Radioimmunoassay for glutamic acid decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. Mayo Clin Proc 1998;73:1161–6.doi:10.4065/73.12.1161pmid:http://www.ncbi.nlm.nih.gov/pubmed/9868413 ↵Munoz-Lopetegi A, de Bruijn M, Boukhrissi S. Neurologic syndromes related to anti-GAD65: clinical and serologic response to treatment. Neurol Neuroimmunol Neuroinflamm 2020;7:1.OpenUrl ↵Moersch FP, Woltman HW. Progressive fluctuating muscular rigidity and spasm ("stiff-man" syndrome); report of a case and some observations in 13 other cases. Proc Staff Meet Mayo Clin 1956;31:421–7.pmid:http://www.ncbi.nlm.nih.gov/pubmed/13350379OpenUrlPubMed ↵Solimena M, Folli F, Denis-Donini S, et al. Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N Engl J Med 1988;318:1012–20.doi:10.1056/NEJM198804213181602pmid:http://www.ncbi.nlm.nih.gov/pubmed/3281011 ↵Dalakas MC, Fujii M, Li M, et al. The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology 2000;55:1531–5.doi:10.1212/WNL.55.10.1531pmid:http://www.ncbi.nlm.nih.gov/pubmed/11094109OpenUrlCrossRefPubMed ↵McKeon A, Robinson MT, McEvoy KM, et al. Stiff-Man syndrome and variants: clinical course, treatments, and outcomes. Arch Neurol 2012;69:230–8.doi:10.1001/archneurol.2011.991pmid:http://www.ncbi.nlm.nih.gov/pubmed/22332190 ↵Honnorat J, Saiz A, Giometto B, et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol 2001;58:225–30.doi:10.1001/archneur.58.2.225pmid:http://www.ncbi.nlm.nih.gov/pubmed/11176960 ↵Martinez-Hernandez E, Ariño H, McKeon A, et al. Clinical and immunologic investigations in patients with stiff-person spectrum disorder. JAMA Neurol 2016;73:714–20.doi:10.1001/jamaneurol.2016.0133pmid:http://www.ncbi.nlm.nih.gov/pubmed/27065452OpenUrlPubMed ↵Peltola J, Kulmala P, Isojärvi J, et al. Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology 2000;55:46–50.doi:10.1212/WNL.55.1.46pmid:http://www.ncbi.nlm.nih.gov/pubmed/10891904OpenUrlPubMed ↵Liimatainen S, Peltola M, Sabater L, et al. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia 2010;51:760–7.doi:10.1111/j.1528-1167.2009.02325.xpmid:http://www.ncbi.nlm.nih.gov/pubmed/19817821OpenUrlPubMed ↵Joubert B, Belbezier A, Haesebaert J, et al. Long-Term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies. J Neurol 2020;267:2083–9.doi:10.1007/s00415-020-09807-2pmid:http://www.ncbi.nlm.nih.gov/pubmed/32221776OpenUrlPubMed ↵Malter MP, Helmstaedter C, Urbach H, et al. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 2010;67:470–8.doi:10.1002/ana.21917pmid:http://www.ncbi.nlm.nih.gov/pubmed/20437582 ↵Pittock SJ, Yoshikawa H, Ahlskog JE, et al. Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction. Mayo Clin Proc 2006;81:1207–14.doi:10.4065/81.9.1207pmid:http://www.ncbi.nlm.nih.gov/pubmed/16970217 ↵Arino H, Gresa-Arribas N, Blanco Y. Cerebellar ataxia and glutamic acid decarboxylase antibodies: immunologic profile and long-term effect of immunotherapy. JAMA Neurol 2014;71:1009–16.OpenUrlPubMed ↵Takagi M, Ishigaki Y, Uno K, et al. Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity: a case-control study. BMC Neurol 2013;13:76. doi:10.1186/1471-2377-13-76pmid:http://www.ncbi.nlm.nih.gov/pubmed/23835051OpenUrlPubMed ↵Ariño H, Gresa-Arribas N, Blanco Y, et al. Cerebellar ataxia and glutamic acid decarboxylase antibodies: immunologic profile and long-term effect of immunotherapy. JAMA Neurol 2014;71:1009–16.doi:10.1001/jamaneurol.2014.1011pmid:http://www.ncbi.nlm.nih.gov/pubmed/24934144OpenUrlPubMed ↵Muñiz-Castrillo S, Vogrig A, Joubert B, et al. Transient neurological symptoms preceding cerebellar ataxia with glutamic acid decarboxylase antibodies. Cerebellum 2020;19:715–21.doi:10.1007/s12311-020-01159-xpmid:http://www.ncbi.nlm.nih.gov/pubmed/32592031OpenUrlPubMed ↵Saiz A, Blanco Y, Sabater L, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 2008;131:2553–63.doi:10.1093/brain/awn183pmid:http://www.ncbi.nlm.nih.gov/pubmed/18687732 ↵Banks JL, Marotta CA. Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke 2007;38:1091–6.doi:10.1161/01.STR.0000258355.23810.c6pmid:http://www.ncbi.nlm.nih.gov/pubmed/17272767 ↵Sarva H, Deik A, Ullah A, et al. Clinical spectrum of stiff person syndrome: a review of recent reports. Tremor Other Hyperkinet Mov 2016;6:340.doi:10.5334/tohm.316pmid:http://www.ncbi.nlm.nih.gov/pubmed/26989571OpenUrlPubMed ↵Smith SJM. Eeg in the diagnosis, classification, and management of patients with epilepsy. J Neurol Neurosurg Psychiatry 2005;76:ii2–7.doi:10.1136/jnnp.2005.069245pmid:http://www.ncbi.nlm.nih.gov/pubmed/15961864OpenUrlFREE Full Text ↵Kokmen E, Naessens JM, Offord KP. A short test of mental status: description and preliminary results. Mayo Clin Proc 1987;62:281–8.doi:10.1016/S0025-6196(12)61905-3pmid:http://www.ncbi.nlm.nih.gov/pubmed/3561043 ↵Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology 1990;1:43–6.doi:10.1097/00001648-199001000-00010pmid:http://www.ncbi.nlm.nih.gov/pubmed/2081237OpenUrlCrossRefPubMed ↵Gu Z, Gu L, Eils R, et al. circlize implements and enhances circular visualization in R. Bioinformatics 2014;30:2811–2.doi:10.1093/bioinformatics/btu393pmid:http://www.ncbi.nlm.nih.gov/pubmed/24930139 ↵O'Connor K, Waters P, Komorowski L, et al. GABA receptor autoimmunity: a multicenter experience. Neurol Neuroimmunol Neuroinflamm 2019;6:e552. doi:10.1212/NXI.0000000000000552pmid:http://www.ncbi.nlm.nih.gov/pubmed/31119187 ↵Jesus-Ribeiro J, Bozorgi A, Alkhaldi M, et al. Autoimmune musicogenic epilepsy associated with anti-glutamic acid decarboxylase antibodies and stiff-person syndrome. Clin Case Rep 2020;8:61–4.doi:10.1002/ccr3.2538pmid:http://www.ncbi.nlm.nih.gov/pubmed/31998487OpenUrlPubMed ↵Nagahama Y, Kovach CK, Ciliberto M, et al. Localization of musicogenic epilepsy to Heschl's gyrus and superior temporal plane: case report. J Neurosurg 2018;129:157–64.doi:10.3171/2017.3.JNS162559pmid:http://www.ncbi.nlm.nih.gov/pubmed/28946181OpenUrlCrossRefPubMed ↵Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75:1135–40.doi:10.1136/jnnp.2003.034447pmid:http://www.ncbi.nlm.nih.gov/pubmed/15258215 ↵Ariño H, Höftberger R, Gresa-Arribas N, et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol 2015;72:874–81.doi:10.1001/jamaneurol.2015.0749pmid:http://www.ncbi.nlm.nih.gov/pubmed/26099072OpenUrlPubMed ↵Helmstaedter C, Kockelmann E. Cognitive outcomes in patients with chronic temporal lobe epilepsy. Epilepsia 2006;47:96–8.doi:10.1111/j.1528-1167.2006.00702.xpmid:http://www.ncbi.nlm.nih.gov/pubmed/17105474OpenUrlCrossRefPubMed ↵Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.doi:10.1016/S1474-4422(15)00401-9pmid:http://www.ncbi.nlm.nih.gov/pubmed/26906964OpenUrlCrossRefPubMed ↵Narayan RN, McKeon A, Fife TD. Autoimmune vestibulocerebellar syndromes. Semin Neurol 2020;40:097–115.doi:10.1055/s-0039-3402061pmid:http://www.ncbi.nlm.nih.gov/pubmed/31958862OpenUrlPubMed ↵Glisson CC. Approach to diplopia. Continuum 2019;25:1362–75.doi:10.1212/CON.0000000000000786pmid:http://www.ncbi.nlm.nih.gov/pubmed/31584541OpenUrlPubMed ↵O'Toole O, Lennon VA, Ahlskog JE, et al. Autoimmune chorea in adults. Neurology 2013;80:1133–44.doi:10.1212/WNL.0b013e3182886991pmid:http://www.ncbi.nlm.nih.gov/pubmed/23427325OpenUrlCrossRefPubMed ↵Dalakas MC, Fujii M, Li M, et al. High-Dose intravenous immune globulin for stiff-person syndrome. N Engl J Med 2001;345:1870–6.doi:10.1056/NEJMoa01167pmid:http://www.ncbi.nlm.nih.gov/pubmed/11756577 ↵Zalewski NL, Lennon VA, Lachance DH, et al. P/Q- and N-type calcium-channel antibodies: oncological, neurological, and serological accompaniments. Muscle Nerve 2016;54:220–7.doi:10.1002/mus.25027pmid:http://www.ncbi.nlm.nih.gov/pubmed/26789908OpenUrlPubMed ↵Dubey D, Pittock SJ, McKeon A. Antibody prevalence in epilepsy and encephalopathy score: increased specificity and applicability. Epilepsia 2019;60:367–9.doi:10.1111/epi.14649pmid:http://www.ncbi.nlm.nih.gov/pubmed/30727035OpenUrlPubMed ↵Graus F, Saiz A, Dalmau J. GAD antibodies in neurological disorders - insights and challenges. Nat Rev Neurol 2020;16:353–65.doi:10.1038/s41582-020-0359-xpmid:http://www.ncbi.nlm.nih.gov/pubmed/32457440OpenUrlPubMed ↵Budhram A, Mills JR, Shouman K, et al. False-positive anti-neuronal nuclear antibody type 1 in a patient with RFC1 repeat expansion: Preventing "phenotype creep" in autoimmune neurology. J Neurol Sci 2020;416:117018. doi:10.1016/j.jns.2020.117018pmid:http://www.ncbi.nlm.nih.gov/pubmed/32682126OpenUrlPubMed
No comment yet.
AntiNMDA
Your new post is loading...
Scooped by Nesrin Shaheen
Scoop.it!

Neural Antibody Testing for Autoimmune Encephalitis: A Canadian Single-Centre Experience | Canadian Journal of Neurological Sciences

Neural Antibody Testing for Autoimmune Encephalitis: A Canadian Single-Centre Experience - Volume 48 Issue 6
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Author Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis | Neurology

Author Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis | Neurology | AntiNMDA | Scoop.it
We appreciate the interest in our research.1 According to Pollak and colleagues,2 criteria of possible autoimmune psychosis (AP) are fulfilled if a patient has abrupt onset psychotic symptoms with at least one of the following: the presence of a tumor, movement disorder (dyskinesias, catatonia), adverse response to antipsychotics, “severe or disproportionate” cognitive dysfunction, decreased level of consciousness, unexplained seizures, and significant autonomic dysfunction.2 Fulfilment of these criteria should lead to additional tests such as EEG, MRI, and serum or CSF investigations. In our series of 105 patients with first episode of psychosis (FEP), 20% fulfilled these criteria but never developed AP.1 We confirm that 2 of 3 patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis presenting with FEP did not fulfill any of these criteria, including catatonia, which is a complex syndrome with its own set of 12 criteria that include echolalia.3 Thus, catatonia and echolalia should not be used as interchangeable terms.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Autoantibody-associated psychiatric symptoms and syndromes in adults: A narrative review and proposed diagnostic approach

Autoantibody-associated psychiatric symptoms and syndromes in adults: A narrative review and proposed diagnostic approach | AntiNMDA | Scoop.it
Autoimmune-mediated encephalitis is a disease that often encompasses psychiatric symptoms as its first clinical manifestation’s predominant and isolated characteristic. Novel guidelines even distinguish autoimmune psychosis from autoimmune encephalitis.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Vennada's Story: Recovery from Anti-NMDA Receptor Encephalitis

No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

The grey zone between autoimmune encephalitis and autoimmune‐associated epilepsy - Morano - - Epilepsia Open

The grey zone between autoimmune encephalitis and autoimmune‐associated epilepsy - Morano - - Epilepsia Open | AntiNMDA | Scoop.it
Click on the article title to read more.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

The role of dendritic cells and their interactions in the pathogenesis of antibody-associated autoimmune encephalitis | Journal of Neuroinflammation | Full Text

The role of dendritic cells and their interactions in the pathogenesis of antibody-associated autoimmune encephalitis | Journal of Neuroinflammation | Full Text | AntiNMDA | Scoop.it
Autoimmune encephalitis (AE) is an inflammatory brain disease which is frequently associated with antibodies (Abs) against cell-surface, synaptic or intracellular neuronal proteins. There is increasing evidence that dendritic cells (DCs) are implicated as key modulators in keeping the balance...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies | Read by QxMD

Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies | Read by QxMD | AntiNMDA | Scoop.it
RESULTS: Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case-control (n=11), case series (n=83), and case reports (n=103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called "cryptogenic NORSE". Among adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular, and degenerative conditions have been also described.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis

Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis | AntiNMDA | Scoop.it
Patients with autoimmune encephalitides, especially those with antibodies to the N-methyl-d-aspartate receptor (NMDAR), often present with prominent psychosis and respond well to immunotherapies. Although most patients progress to develop various neurological symptoms, it has been hypothesised...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Rituximab Treatment and Long-term Outcome of Patients With Autoimmune Encephalitis | Neurology Neuroimmunology & Neuroinflammation

Rituximab Treatment and Long-term Outcome of Patients With Autoimmune Encephalitis | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
Immunotherapeutic strategies for GAD65-AE remain highly controversial.27 Most patients are considered to require immunotherapy, and early immunotherapy has been found to be associated with a better outcome.10,28 However, the different neurologic manifestations of SPS, CA, and LE appear to respond...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Anti-NMDAR Encephalitis: Multidisciplinary Development of a Clinical Practice Guideline | American Academy of Pediatrics

Anti-NMDAR Encephalitis: Multidisciplinary Development of a Clinical Practice Guideline | American Academy of Pediatrics | AntiNMDA | Scoop.it
Knowledge about the diagnosis of autoimmune encephalitis (AE) is rapidly expanding. In the last 15 years, multiple new antibodies have been described. Anti-N-methyl-D-aspartate receptor (NMDAR)–antibody-mediated encephalitis, in particular, has been found to be common among teenagers and young adults1 and accounts for up to 86% of AE in patients aged <18 years.2 Other antibodies associated with AE (leucine-rich glioma-inactivated 1, contactin-associated protein-like 2, glutamic acid decarboxylase 65-kilodalton isoform, γ-aminobutyric acid A, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) are reported in children as case reports or series and with less clear typical clinical syndromes.3–9
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Comprehensive B-Cell Immune Repertoire Analysis of Anti-NMDAR Encephalitis and Anti-LGI1 Encephalitis

Comprehensive B-Cell Immune Repertoire Analysis of Anti-NMDAR Encephalitis and Anti-LGI1 Encephalitis | AntiNMDA | Scoop.it
Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) and anti-leucine-rich glioma-inactivated 1 encephalitis (anti-LGI1E) are the two most common types of antibody-mediated autoimmune encephalitis.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Neurological and cognitive outcomes after antibody‐negative autoimmune encephalitis in children - Gadian - - Developmental Medicine & Child Neurology

Neurological and cognitive outcomes after antibody‐negative autoimmune encephalitis in children - Gadian - - Developmental Medicine & Child Neurology | AntiNMDA | Scoop.it
AIM To characterize the neurological and cognitive outcomes in children with antibody-negative autoimmune encephalitis (Ab-negative AE). METHOD A cohort of children presenting to our institution ov...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Frontiers | Clinical Features and Outcomes in Pediatric Autoimmune Encephalitis Associated With CASPR2 Antibody | Pediatrics

Frontiers | Clinical Features and Outcomes in Pediatric Autoimmune Encephalitis Associated With CASPR2 Antibody | Pediatrics | AntiNMDA | Scoop.it
Background: Contactin-associated protein-like 2 (CASPR2) neurological autoimmunity has been associated with various clinical syndromes involving central and peripheral nervous system. CASPR2 antibody-associated autoimmune encephalitis is mostly reported in adults.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Frontiers | Risk Factors and Brain Metabolic Mechanism of Sleep Disorders in Autoimmune Encephalitis | Immunology

Frontiers | Risk Factors and Brain Metabolic Mechanism of Sleep Disorders in Autoimmune Encephalitis | Immunology | AntiNMDA | Scoop.it
BackgroundSleep disorders (SDs) in autoimmune encephalitis (AE) have received little attention and are poorly understood. We investigated the clinical characteristics, risk factors, and cerebral metabolic mechanism of SD in AE.MethodsClinical, laboratory, and imaging data were retrospectively...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

A peculiar case of psychosis: anti-NMDAr encephalitis | International Journal of Emergency Medicine | Full Text

A peculiar case of psychosis: anti-NMDAr encephalitis | International Journal of Emergency Medicine | Full Text | AntiNMDA | Scoop.it
Background Psychosis in pregnancy is rare and could be life-threatening. It requires prompt evaluation and proper management accordingly. Anti-N-methyl-d-aspartate receptor (anti-NMDAr) encephalitis following herpes simplex virus (HSV) infection is a rare cause of psychosis during pregnancy.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Acute Psychosis Due to Anti-N-Methyl D-Aspartate Receptor Encephalitis Following COVID-19 Vaccination: A Case Report - PMC

Acute Psychosis Due to Anti-N-Methyl D-Aspartate Receptor Encephalitis Following COVID-19 Vaccination: A Case Report - PMC | AntiNMDA | Scoop.it
Anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis has been reported after SARS-CoV-2 infection, but not after SARS-CoV-2 vaccination. We report the first known case of anti-NMDAR encephalitis after SARS-CoV-2 immunization in a young ...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Anti-NMDAR Autoantibodies Disrupt Ionotropic Receptor Signaling –

Anti-NMDAR Autoantibodies Disrupt Ionotropic Receptor Signaling – | AntiNMDA | Scoop.it
Vignesh Subramanian '24 Figure 1: The N-methyl-D-aspartate receptor (NMDAR) functions as an ion channel. N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels whose signaling enables higher-order functions, such as learning and memory, throughout the brain.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

A Brain on Fire: Laura's Battle with Autoimmune Encephalitis

A Brain on Fire: Laura's Battle with Autoimmune Encephalitis | AntiNMDA | Scoop.it
Laura Martin, a strong student and standout goalie at Transylvania University, hit a sudden wall as things turned worse. Diagnosis: Autoimmune Encephalitis.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Frontiers | Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis | Immunology

Frontiers | Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis | Immunology | AntiNMDA | Scoop.it
Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Frontiers | Acute Psychosis Due to Anti-N-Methyl D-Aspartate Receptor Encephalitis Following COVID-19 Vaccination: A Case Report | Neurology

Frontiers | Acute Psychosis Due to Anti-N-Methyl D-Aspartate Receptor Encephalitis Following COVID-19 Vaccination: A Case Report | Neurology | AntiNMDA | Scoop.it
Anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis has been reported after SARS-CoV-2 infection, but not after SARS-CoV-2 vaccination. We report the first known case of anti-NMDAR encephalitis after SARS-CoV-2 immunization in a young female presenting with acute psychosis,...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Lauren's Healing Story (Autoimmune Encephalitis) - Phoenix Helix

Lauren's Healing Story (Autoimmune Encephalitis) - Phoenix Helix | AntiNMDA | Scoop.it
When you have a disease only recently discovered and most doctors don't know it exists, it takes strong self-advocacy to get the help you need.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

CSF Findings in Acute NMDAR and LGI1 Antibody–Associated Autoimmune Encephalitis

CSF Findings in Acute NMDAR and LGI1 Antibody–Associated Autoimmune Encephalitis | AntiNMDA | Scoop.it
CSF in antibody-defined autoimmune encephalitis (AE) subtypes shows subtype-dependent degrees of inflammation ranging from rare and often mild to frequent and often robust. AEs with NMDA receptor antibodies (NMDAR-E) and leucine-rich glioma-inactivated ...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Physical Therapy Interventions and Outcome Measures for a Patient Diagnosed with Anti-NMDA Receptor Encephalitis

Physical Therapy Interventions and Outcome Measures for a Patient Diagnosed with Anti-NMDA Receptor Encephalitis | AntiNMDA | Scoop.it
Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common cause of
autoimmune encephalitis after acute demyelinating encephalitis. Patients usually present
with acute behavioral changes, psychosis, and abnormal limb movements and can also
...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Celebrating Excellence IU School of Medicine student solves her own mystery illness

Celebrating Excellence IU School of Medicine student solves her own mystery illness | AntiNMDA | Scoop.it
In 2019, Dana Mitchell, a fourth-year medical student at IU School of Medicine, was diagnosed with autoimmune encephalitis&mdash;a brain inflammation that wreaks neurological havoc. In search of a therapy that would provide lasting relief of her debilitating symptoms, Mitchell reviewed 40...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat | Neurology

Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat | Neurology | AntiNMDA | Scoop.it
Objective: This study was conducted to elucidate prevalence, clinical features, outcomes, and best treatment in patients with late-onset seizures due to autoimmune encephalitis (AE).Methods: This is a single-institution prospective cohort study (2012–2019) conducted at the Epilepsy Center at the...
No comment yet.