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Background and purpose: Management of idiopathic intracranial hypertension (IIH) is complex requiring multiple specialized disciplines. In practice, this creates considerable organizational and communicational challenges for healthcare professionals and patients. Thus, an interdisciplinary integrated outpatient clinic for IIH (comprising neurology, neuroophthalmology, neuroradiology, neurosurgery and endocrinology) was established with central coordination and a one‐stop concept. Here, the aim was to evaluate the effects of this one‐stop concept on objective clinical outcome. Methods: In a retrospective cohort study, the one‐stop era with integrated care (IC) (1 July 2021 to 31 December 2022) was compared to a reference group receiving standard care (SC) (1 July 2018 to 31 December 2019) regarding visual impairment/worsening and headache improvement/freedom 6 months after diagnosis. Multivariate binary logistic regression models were used to adjust for confounders. Results: Baseline characteristics of the IC group (n = 85) and SC group (n = 81) were comparable (female 90.6% vs. 90.1%; mean age 33.6 vs. 32.8 years; median body mass index 31.8 vs. 33.0; median cerebrospinal fluid opening pressure 32 vs. 34 cmH2O; at diagnosis, visual impairment was present in 71.8% vs. 69.1% and chronic headache in 55.3% vs. 56.8% in IC vs. SC). IC was associated with a higher likelihood of achieving both headache improvement (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.52–4.33, p < 0.001) and headache freedom (OR 1.75, 95% CI 1.11–3.09, p = 0.031). Regarding the risk of visual impairment and visual worsening IC was superior numerically but not statistically significantly (OR 0.87, 95% CI 0.69–1.16, p = 0.231, and OR 0.67, 95% CI 0.41–1.25, p = 0.354). Conclusions: Interdisciplinary integrated care of IIH is favourably associated with headache outcomes and potentially also visual outcomes. [ABSTRACT FROM AUTHOR]

Background: Employing a rebaselining concept may reduce noise in retinal layer thinning measured by optical coherence tomography (OCT). Methods: From an ongoing prospective observational study, we included patients with relapsing multiple sclerosis (RMS), who had OCT scans at disease-modifying treatment (DMT) start (baseline), 6–12 months after baseline (rebaseline), and ⩾12 months after rebaseline. Mean annualized percent loss (aL) rates (%/year) were calculated both from baseline and rebaseline for peripapillary-retinal-nerve-fiber-layer (aLpRNFLbaseline/aLpRNFLrebaseline) and macular-ganglion-cell-plus-inner-plexiform-layer (aLGCIPLbaseline/aLGCIPLrebaseline) by mixed-effects linear regression models. Results: We included 173 RMS patients (mean age 31.7 years (SD 8.8), 72.8% female, median disease duration 15 months (12-94) median baseline-to-last-follow-up-interval 37 months (18-71); 56.6% moderately effective DMT (M-DMT), 43.4% highly effective DMT (HE-DMT)). Both mean aLpRNFLbaseline and aLGCIPLbaseline significantly increased in association with relapse (0.51% and 0.26% per relapse, p < 0.001, respectively) and disability worsening (1.10% and 0.48%, p < 0.001, respectively) before baseline, but not with DMT class. Contrarily, neither aLpRNFLrebaseline nor aLGCIPLrebaseline was dependent on relapse or disability worsening before baseline, while HE-DMT significantly lowered aLpRNFLrebaseline (by 0.31%, p < 0.001) and aLGCIPLrebaseline (0.25%, p < 0.001) compared with M-DMT. Conclusions: Applying a rebaselining concept significantly improves differentiation of DMT effects on retinal layer thinning by avoiding carry-over confounding from previous disease activity. [ABSTRACT FROM AUTHOR]

Background: Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance. Methods: IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method. Results: The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab. Conclusion: Our findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease. [ABSTRACT FROM AUTHOR]

Objective: Assessing severity of antibody‐mediated encephalitis (AE) or paraneoplastic encephalitis (PE) requires valid and reliable scores to guide treatment decisions and predict outcome both in clinical routine and studies. We aimed to validate the prognostic value of the clinical assessment scale in autoimmune encephalitis (CASE) and the anti‐NMDAR‐encephalitis one‐year functional status (NEOS) score in patients suffering from AE and PE in a large monocentric cohort. Methods: We retrospectively applied the CASE and NEOS score to patients with definite AE and PE treated at a tertiary hospital. Correlations were established between the CASE and NEOS score and the modified Rankin scale (mRs). Multivariable analyses were calculated to identify predictors of outcome. Results: Thirty‐four patients (27 AE, 7 PE) were included. Correlations between mRS and CASE score were strongest in patients with AE compared to PE at all intervals, but in the subgroups (LGI1, NMDAR, GAD, miscellaneous surface antibodies, PE) the correlation was strongest in the interval after baseline. Patients with AE seemed to display better outcomes compared to PE, which was underlined by multivariable analysis. Improvement was mostly observed within 6–12 months after disease onset, after which little or no further improvement was noted with some exception for two patients with anti‐NMDARE who recovered substantially even after 12 months of treatment. The NEOS score significantly predicted the outcome at last follow‐up in patients with AE with a sensitivity of 79% at a cut‐off value of 2 points (AUC 0.79, 95% CI 0.58–0.99, p = 0.04). Interpretation: The CASE and NEOS score are suitable supplementary tools in addition to the mRS for capturing diverse symptoms, for grading and monitoring symptom severity. [ABSTRACT FROM AUTHOR]

Background and purpose: In idiopathic intracranial hypertension (IIH), magnetic resonance imaging (MRI) features are promising diagnostic markers, but the impact of rater experience and the specific referral question is unknown. Methods: From the Vienna Idiopathic Intracranial Hypertension database, patients were included with definitive IIH and routine cranial MRI performed during diagnostic work‐up. Frequencies of partial empty sella (ES), optic nerve sheath distension (ONSD), optic nerve tortuosity (ONT), posterior globe flattening (PGF) and transverse sinus stenosis (TSS) were compared in three settings: (i) real‐world rating, (ii) junior neuroradiologist without special IIH training and (iii) senior neuroradiologist with experience in IIH imaging (gold standard). Results: Magnetic resonance imaging scans of 84 IIH patients (88% female, mean age 33.5 years) were evaluated. By gold standard, ONSD was the most frequent (64.3%) followed by TSS (60.0%), ONT (46.4%), ES (44.4%) and PGF (23.8%). Compared to the gold standard, IIH features were described significantly less frequently in routine MRI reports (ONSD 28.6%, ONT 13.1%, PGF 4.8%, TSS 42.9%, p < 0.01 respectively) except for ES (42.9%, p = 0.9). A specific referral question regarding IIH increased detection rates in routine reports, but rates remained significantly lower than by gold standard. In contrast, a rating by a neuroradiologist without special training produced significantly higher frequencies of ONSD (81.0%, p < 0.01) and ONT (60.7%, p < 0.01) but not of ES (47.6%), PGF (29.8%) and TSS (68.1%). Conclusions: Idiopathic intracranial hypertension MRI features are underestimated in routine MRI reports and partly overcalled by less experienced neuroradiologists, driven by features less well known or methodologically difficult. Reevaluation of MRI scans by an experienced rater (and to a lesser degree a specific referral question) improves diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background and purpose: Following increasing demands of patients with suspected neurological symptoms after infection with severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2), the Department of Neurology at the Medical University of Vienna established a new outpatient clinic to systematically assess, diagnose, and document neurological complaints potentially associated with a prior SARS‐CoV‐2 infection. Methods: The data presented here include prospectively collected 156 outpatients from May 2021 to April 2022. Patients underwent semistandardized interviewing about symptoms with reported onset after SARS‐CoV‐2 infection, neurological examination, and comprehensive diagnostic workup. Results: Reported new onset symptoms after infection included fatigue (77.6%), subjective cognitive impairment (72.4%), headache (47.7%), loss of smell and/or taste (43.2%), and sleep disturbances (42.2%). Most patients had a mild coronavirus disease (COVID‐19) disease course (84%) and reported comorbidities (71%), of which the most frequent were psychiatric disorders (34%). Frequency of symptoms was not associated with age, sex, or severity of COVID‐19 course. A comprehensive diagnostic workup revealed no neurological abnormalities in the clinical examination, or electrophysiological or imaging assessments in the majority of patients (n = 143, 91.7%). Neuropsychological assessment of a subgroup of patients (n = 28, 17.9%) showed that cognitive impairments in executive functions and attention, anxiety, depression, and somatization symptoms were highly common. Conclusions: In this systematic registry, we identified fatigue, cognitive impairment, and headache as the most frequently reported persisting complaints after SARS‐CoV‐2 infection. Structural neurological findings were rare. We also suspect a link between the growing burden of the COVID‐19 pandemic on personal lives and the increase in reported neurological and psychiatric complaints. [ABSTRACT FROM AUTHOR]

Background: In idiopathic intracranial hypertension (IIH), certain MRI features are promising diagnostic markers, but whether these have prognostic value is currently unknown. Methods: We included patients from the Vienna-Idiopathic-Intracranial-Hypertension (VIIH) database with IIH according to Friedman criteria and cranial MRI performed at diagnosis. Presence of empty sella (ES), perioptic subarachnoid space distension (POSD) with or without optic nerve tortuosity (ONT), posterior globe flattening (PGF) and transverse sinus stenosis (TSS) was assessed and multivariable regression models regarding visual outcome (persistent visual impairment/visual worsening) and headache outcome (headache improvement/freedom of headache) were fitted. Results: We included 84 IIH patients (88.1% female, mean age 33.5 years, median body mass index 33.7). At baseline, visual impairment was present in 70.2% and headache in 84.5% (54.8% chronic). Persistent visual impairment occurred in 58.3%, visual worsening in 13.1%, headache improvement was achieved in 83.8%, freedom of headache in 26.2%. At least one MRI feature was found in 78.6% and 60.0% had ≥3 features with POSD most frequent (64.3%) followed by TSS (60.0%), ONT (46.4%), ES (44.0%) and PGF (23.8%). In multivariable models, there was no association of any single MRI feature or their number with visual impairment, visual worsening, headache improvement or freedom. Visual impairment at baseline predicted persistent visual impairment (odds ratio 6.3, p<0.001), but not visual worsening. Chronic headache at baseline was significantly associated with lower likelihood of headache freedom (odds ratio 0.48, p=0.013), but not with headache improvement. Conclusions: MRI features of IIH are neither prognostic of visual nor headache outcome. [ABSTRACT FROM AUTHOR]

Objective: To assess the prognostic impact of migraine headache in idiopathic intracranial hypertension (IIH). Background: Migraine headache is common in IIH, but it is unclear whether it has prognostic relevance. Methods: We investigated patients with IIH from the Vienna‐IIH‐database and differentiated migraine (IIH‐MIG) from non‐migraine headache (IIH‐nonMIG) and without headache (IIH‐noHA). Using multivariable models, we analyzed the impact of IIH‐MIG on headache and visual outcomes 12 months after diagnosis. Results: Among 97 patients (89% female, mean [SD] age 32.9 [11.1] years, median body mass index 32.0 kg/m2, median cerebrospinal fluid opening pressure 310 mm), 46% were assigned to IIH‐MIG, 37% to IIH‐nonMIG (11% tension‐type, 26% unclassifiable), and 17% to IIH‐noHA. Overall, headache improvement was achieved in 77% and freedom of headache in 28%. The IIH‐MIG group showed significantly lower rates for headache improvement (67% vs. 89% in IIH‐nonMIG, p = 0.019) and freedom of headache (11% vs. 33% in IIH‐nonMIG and 63% in IIH‐noHA, p = 0.015). These differences persisted when only analyzing patients with resolved papilledema at follow‐up. In contrast, visual worsening was significantly less common in IIH‐MIG (9% vs. 28% in IIH‐nonMIG and 31% in IIH‐noHA, p = 0.045). In multivariable models, IIH‐MIG was associated with a significantly lower likelihood of achieving headache improvement (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.40–0.78, p < 0.001) and freedom of headache (OR 0.29, 95% CI 0.12–0.46, p < 0.001), but also a lower risk for visual worsening (OR 0.26, 95% CI 0.04–0.82, p < 0.001). Conclusions: In IIH, migraine headache is associated with unfavorable outcomes for headache, even when papilledema has resolved, and possibly favorable visual outcome. [ABSTRACT FROM AUTHOR]

Background and purpose: This study was undertaken to investigate baseline peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness for prediction of disability accumulation in early relapsing multiple sclerosis (RMS). Methods: From a prospective observational study, we included patients with newly diagnosed RMS and obtained spectral‐domain optical coherence tomography scan within 90 days after RMS diagnosis. Impact of pRNFL and GCIPL thickness for prediction of disability accumulation (confirmed Expanded Disability Status Scale [EDSS] score ≥ 3.0) was tested by multivariate (adjusted hazard ratio [HR] with 95% confidence interval [CI]) Cox regression models. Results: We analyzed 231 MS patients (mean age = 30.3 years, SD = 8.1, 74% female) during a median observation period of 61 months (range = 12–93). Mean pRNFL thickness was 92.6 μm (SD = 12.1), and mean GCIPL thickness was 81.4 μm (SD = 11.8). EDSS ≥ 3 was reached by 28 patients (12.1%) after a median 49 months (range = 9–92). EDSS ≥ 3 was predicted with GCIPL < 77 μm (HR = 2.7, 95% CI = 1.6–4.2, p < 0.001) and pRNFL thickness ≤ 88 μm (HR = 2.0, 95% CI = 1.4–3.3, p < 0.001). Higher age (HR = 1.4 per 10 years, p < 0.001), incomplete remission of first clinical attack (HR = 2.2, p < 0.001), ≥10 magnetic resonance imaging (MRI) lesions (HR = 2.0, p < 0.001), and infratentorial MRI lesions (HR = 1.9, p < 0.001) were associated with increased risk of disability accumulation, whereas highly effective disease‐modifying treatment was protective (HR = 0.6, p < 0.001). Type of first clinical attack and presence of oligoclonal bands were not significantly associated. Conclusions: Retinal layer thickness (GCIPL more than pRNFL) is a useful predictor of future disability accumulation in RMS, independently adding to established markers. [ABSTRACT FROM AUTHOR]

Introduction: Botulinumtoxin associated muscle denervation (BNTMD) can be detected by magnet resonance imaging (MRI), MRI may provide further insights into the exact timeline of BNTMD and the potential impact and timing of physical exercise. We aimed to assess the time interval until detection of BNTMD by MRI and whether immediate physical exercise after intramuscular BNT injection has a measurable effect on clinical parameters and the intramuscular denervation dynamics illustrated by MRI. Materials and Methods: Eleven age-matched patients were randomized to an "exercise" or "no-exercise" group. Eighty mouse-units of incobotulinumtoxin were injected into the spastic biceps muscle. MRI of the injected region, hand-held dynamometry of elbow flexor strength and clinical rating scales (mAS, CGI-I) were conducted in predefined intervals. Results: We could not detect BNTMD within 24 h but 7 days after injection independent of group allocation (exercise n = 6, no-exercise n = 5). Denervation signs were more diffuse and spread into adjacent muscles in patients having received exercise. We could not detect differences concerning clinical measures between the two groups. Conclusions: Physical exercise might influence BNTMD dynamics and promote propagation of T2-MR muscle denervation signs from the injected site into adjacent muscles. Trial registration: clinicaltrialsregister.eu, Identifier 2017-003117-25. [ABSTRACT FROM AUTHOR]

Objective: To describe the neuropathological features of N‐methyl‐D‐aspartate receptor (NMDAR)‐encephalitis in an archival autopsy cohort. Methods: We examined four autopsies from patients with NMDAR‐encephalitis; two patients were untreated, three had comorbidities: small cell lung cancer, brain post‐transplant lymphoproliferative disease (PTLD), and overlapping demyelination. Results: The two untreated patients had inflammatory infiltrates predominantly composed of perivascular and parenchymal CD3+/CD8− T cells and CD79a+ B cells/plasma cells in basal ganglia, amygdala, and hippocampus with surrounding white matter. The hippocampi showed a significant decrease of NMDAR‐immunoreactivity that correlated with disease severity. The patient with NMDAR‐encephalitis and immunosuppression for kidney transplantation developed a brain monomorphic PTLD. Inflammatory changes were compatible with NMDAR‐encephalitis. Additionally, plasma cells accumulated in the vicinity of the necrotic tumor along with macrophages and activated microglia that strongly expressed pro‐inflammatory activation markers HLA‐DR, CD68, and IL18. The fourth patient developed demyelinating lesions in the setting of a relapse 4 years after NMDAR‐encephalitis. These lesions exhibited the hallmarks of classic multiple sclerosis with radially expanding lesions and remyelinated shadow plaques without complement or immunoglobulin deposition, compatible with a pattern I demyelination. Interpretation: The topographic distribution of inflammation in patients with NMDAR‐encephalitis reflects the clinical symptoms of movement disorders, abnormal behavior, and memory dysfunction with inflammation dominantly observed in basal ganglia, amygdala, and hippocampus, and loss of NMDAR‐immunoreactivity correlates with disease severity. Co‐occurring pathologies influence the spatial distribution, composition, and intensity of inflammation, which may modify patients' clinical presentation and outcome. ANN NEUROL 2021;90:725–737 [ABSTRACT FROM AUTHOR]

Objective: Anti-IgLON5 disease forms an interface between neuroinflammation and neurodegeneration and includes clinical phenotypes that are often similar to those of neurodegenerative diseases. An early diagnosis of patients with anti-IgLON5 disease and differentiation from neurodegenerative diseases is necessary and may have therapeutic implications. Methods: In our small sample size study we investigated oculomotor function as a differentiating factor between anti-IgLON5 disease and neurodegenerative disorders. We examined ocular motor and vestibular function in four patients suffering from anti-IgLON5 disease using video-oculography (VOG) and a computer-controlled rotational chair system (sampling rate 60 Hz) and compared the data with those from ten age-matched patients suffering from progressive supranuclear palsy (PSP) and healthy controls (CON). Results: Patients suffering from anti-IgLON5 disease differed from PSP most strikingly in terms of saccade velocity and accuracy, the presence of square wave jerks (SWJ) (anti-IgLON5 0/4 vs. PSP 9/10) and the clinical finding of supranuclear gaze palsy (anti-IgLON5 1/4). The presence of nystagmus, analysis of smooth pursuit eye movements, VOR and VOR suppression was reliable to differentiate between the two disease entities. Clear differences in all parameters, although not always significant, were found between all patients and CON. Discussion: We conclude that the use of VOG as a tool for clinical neurophysiological assessment can be helpful in differentiating between patients with PSP and patients with anti-IgLON5 disease. VOG could have particular value in patients with suspected PSP and lack of typical Parkinson's characteristics. future trials are indispensable to assess the potential of oculomotor function as a biomarker in anti-IgLON5 disease. [ABSTRACT FROM AUTHOR]

Background: Prospective observations of functional recovery are lacking in patients with autoimmune encephalitis defined by antibodies against synaptic proteins and neuronal cell surface receptors. Methods: Adult patients with a diagnosis of autoimmune encephalitis were included into a prospective registry. At 3, 6 and 12 months of follow-up, the patients' modified Rankin Scale (mRS) was obtained. Results: Patients were stratified into three groups according to their antibody (Ab) status: anti-NMDAR-Ab (n=12; group I), anti-LGI1/CASPR2-Ab (n=35; group II), and other antibodies (n=24; group III). A comparably higher proportion of patients in group I received plasma exchange/immunoadsorption and second line immunosuppressive treatments at baseline. A higher proportion of patients in group II presented with seizures. Group III mainly included patients with anti-GABABR-, anti-GAD65- and anti-GlyR-Ab. At baseline, one third of them had cancer. Patients in groups I and III had much higher median mRS scores at 3 months compared to patients in group II. A median mRS of 1 was found at all follow-up time points in group II. Conclusions: The different dynamics in the recovery of patients with certain autoimmune encephalitides have important implications for clinical trials. The high proportion of patients with significant disability at 3 months after diagnosis in groups I and III points to the need for improving treatment options. More distinct scores rather than the mRS are necessary to differentiate potential neurological improvements in patients with anti-LGI1-/CASPR2-encephalitis. [ABSTRACT FROM AUTHOR]

Background and purpose: Biomarkers reflecting the course of patients suffering from anti‐N‐methyl‐D‐aspartate receptor encephalitis (anti‐NMDARE) are urgently needed. Neurofilament light chains (NfL) have been studied as potential markers for neuroaxonal injury mainly in neuroinflammatory diseases, but so far there have been only in a few small reports on anti‐NMDARE. We aimed to compare the longitudinal course of cerebrospinal fluid (CSF)‐NfL levels and anti‐N‐methyl‐D‐aspartate receptor (anti‐NMDAR) antibodies with clinical parameters in six patients with anti‐NMDARE. Methods: Longitudinal measurement of CSF‐NfL levels and CSF anti‐NMDAR antibodies in six patients suffering from anti‐NMDARE was performed. Results: The major finding of this study is that most of our patients showed highly elevated NfL, with peak levels considerably delayed to clinical nadir. High NfL levels were associated with hippocampal atrophy but not with tumors detected. Furthermore, we did not find a clear relationship between NfL levels, CSF antibody titer, and CSF inflammatory markers. Conclusions: CSF‐NfL levels do not predict short‐term outcome but rather are associated with intensive care unit stay and extreme delta brushes. However, high CSF‐NFL levels were associated with long‐term outcome. Our data suggest early aggressive immunotherapy to avoid primary and secondary neuroaxonal damage. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis (AIE) poses a diagnostic challenge due to its heterogeneous clinical presentation, which overlaps with various neurological and psychiatric diseases. During the diagnostic work-up, cerebrospinal fluid (CSF) is routinely obtained, allowing for differential diagnostics as well as for the determination of antibody subclasses and specificities. In this monocentric cohort study, we describe initial and serial CSF findings of 33 patients diagnosed with antibody-associated AIE (LGI1 (n=8), NMDA (n=7), CASPR2 (n=3), IgLON5 (n=3), AMPAR (n=1), GAD65/67 (n=4), Yo (n=3), Ma-1/2 (n=2), CV2 (n=2)). Routine CSF parameters of 12.1% of AIE patients were in normal ranges, while 60.6% showed elevated protein levels and 45.4% had intrathecal oligoclonal bands (OCBs). Repeated CSF analyses showed a trend towards normalization of initial pathological CSF findings, while relapses were more likely to be associated with increased cell counts and total protein levels. OCB status conversion in anti-NMDARE patients coincided with clinical improvement. In summary, we show that in routine CSF analysis at diagnosis, a considerable number of patients with AIE did not exhibit alteration in the CSF and therefore, diagnosis may be delayed if antibody testing is not performed. Moreover, OCB status in anti-NMDAR AIE patients could represent a potential prognostic biomarker, however further studies are necessary to validate these exploratory findings. [ABSTRACT FROM AUTHOR]

Over the last years the clinical picture of autoimmune encephalitis has gained importance in neurology. The broad field of symptoms and syndromes poses a great challenge in diagnosis for clinicians. Early diagnosis and the initiation of the appropriate treatment is the most relevant step in the management of the patients. Over the last years advances in neuroimmunology have elucidated pathophysiological basis and improved treatment concepts. In this monocentric study we compare demographics, diagnostics, treatment options and outcomes with knowledge from literature. We present 38 patients suffering from autoimmune encephalitis. Antibodies were detected against NMDAR and LGI1 in seven patients, against GAD in 6 patients) one patient had coexisting antibodies against GABAA and GABAB), against CASPR2, IGLON5, YO, Glycine in 3 patients, against Ma-2 in 2 patients, against CV2 and AMPAR in 1 patient; two patients were diagnosed with hashimoto encephalitis with antibodies against TPO/TG. First, we compare baseline data of patients who were consecutively diagnosed with autoimmune encephalitis from a retrospective view. Further, we discuss when to stop immunosuppressive therapy since how long treatment should be performed after clinical stabilization or an acute relapse is still a matter of debate. Our experiences are comparable with data from literature. However, in contrary to other experts in the field we stop treatment and monitor patients very closely after tumor removal and after rehabilitation from first attack. [ABSTRACT FROM AUTHOR]

This review provides an overview on different antibody test methods that can be applied in cases of suspected paraneoplastic neurological syndromes (PNS) and anti-neuronal autoimmune encephalitis (AIE) in order to explain their diagnostic value, describe potential pitfalls and limitations, and discuss novel approaches aimed at discovering further autoantibodies. Onconeuronal antibodies are well-established biomarkers for PNS and may serve as specific tumor markers. The recommended procedure to detect onconeuronal antibodies is a combination of indirect immunohistochemistry on fixed rodent cerebellum and confirmation of the specificity by line assays. Simplification of this approach by only using line assays with recombinant proteins bears the risk to miss antibody-positive samples. Anti-neuronal surface antibodies are sensitive and specific biomarkers for AIE. Their identification requires the use of test methods that allow the recognition of conformation dependent epitopes. These commonly include cell-based assays and tissue based assays with unfixed rodent brain tissue. Tissue based assays can detect most of the currently known neuronal surface antibodies and thus enable broad screening of biological samples. A complementary testing on live neuronal cell cultures may confirm that the antibody recognizes a surface epitope. In patients with peripheral neuropathy, the screening may be expanded to teased nerve fibers to identify antibodies against the node of Ranvier. This method helps to identify a novel subgroup of peripheral autoimmune neuropathies, resulting in improved immunotherapy of these patients. Tissue based assays are useful to discover additional autoantibody targets that play a role in diverse autoimmune neurological syndromes. Antibody screening assays represent promising avenues of research to improve the diagnostic yield of current assays for antibody-associated autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

• This study investigates changes in disease-modifying treatment (DMT) prescriptions before and during the COVID-19 pandemic. • The average annualized number of DMT prescriptions in the preCOVID-19 era was 90.3/year and dropped to 74.8/year (−17.2%) in the COVID-19 era. • Use of alemtuzumab (−64%), antiCD20 (−49%), cladribine (−46%), and sphingosine-1-phosphate receptor modulators (−38%) was reduced. • Use of natalizumab increased by 24%, while lower efficacy DMT remained stable. Social distancing measures during the Covid-19 pandemic reduced access to health care and concerns were raised over the safety of immunosuppressive disease modifying treatments (DMT) for multiple sclerosis (MS). To investigate changes in DMT prescription before and during the pandemic in a large and well-characterized real-world cohort of MS patients. From the Vienna MS database (VMSD) we extracted MS patients who were initiated on a new DMT (both treatment-naïve and switching) between January 1st 2017 and December 31st 2021. Two time periods were defined: 1) the preCovid-19 era (January 1st 2017 to March 15th 2020, i.e. the day of the first lockdown in Austria) and the Covid-19 era (March 16th 2020 to December 31st 2021). Average annualized DMT prescription rates were descriptively compared between the two periods. The average annualized number of prescriptions in the preCovid-19 era was 90.3/year and dropped to 74.8/year (-17.2%) in the Covid-19 era, driven by a marked reduction to 41.7/year (-54%) in the first nine months of the Covid-19 era, partly offset by a rise to 101 in 2021. Use of alemtuzumab (-64%), antiCD20 (-49%), cladribine (-46%), and S1PM (-38%) was reduced, while natalizumab increased by 24%. Lower efficacy treatments remained stable. The pandemic coincides with a drop in DMT prescription, most markedly for immunosuppressive high-efficacy treatments, strongly suggesting the pandemic as the causal factor. If and how much this affects long-term outcome is yet to be determined. [ABSTRACT FROM AUTHOR]

Background: Employing a rebaselining concept may reduce noise in retinal layer thinning measured by optical coherence tomography (OCT)., Methods: From an ongoing prospective observational study, we included patients with relapsing multiple sclerosis (RMS), who had OCT scans at disease-modifying treatment (DMT) start (baseline), 6-12 months after baseline (rebaseline), and ⩾12 months after rebaseline. Mean annualized percent loss (aL) rates (%/year) were calculated both from baseline and rebaseline for peripapillary-retinal-nerve-fiber-layer (aLpRNFL baseline /aLpRNFL rebaseline ) and macular-ganglion-cell-plus-inner-plexiform-layer (aLGCIPL baseline /aLGCIPL rebaseline ) by mixed-effects linear regression models., Results: We included 173 RMS patients (mean age 31.7 years (SD 8.8), 72.8% female, median disease duration 15 months (12-94) median baseline-to-last-follow-up-interval 37 months (18-71); 56.6% moderately effective DMT (M-DMT), 43.4% highly effective DMT (HE-DMT)). Both mean aLpRNFL baseline and aLGCIPL baseline significantly increased in association with relapse (0.51% and 0.26% per relapse, p < 0.001, respectively) and disability worsening (1.10% and 0.48%, p < 0.001, respectively) before baseline, but not with DMT class. Contrarily, neither aLpRNFL rebaseline nor aLGCIPL rebaseline was dependent on relapse or disability worsening before baseline, while HE-DMT significantly lowered aLpRNFL rebaseline (by 0.31%, p < 0.001) and aLGCIPL rebaseline (0.25%, p < 0.001) compared with M-DMT., Conclusions: Applying a rebaselining concept significantly improves differentiation of DMT effects on retinal layer thinning by avoiding carry-over confounding from previous disease activity., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Gabriel Bsteh has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene/BMS, Lilly, MedWhizz, Merck, Novartis, Roche, Sanofi Genzyme and Teva, and received honoraria for consulting Biogen, Celgene/BMS, Merck, Novartis, Roche, Sanofi Genzyme, and Teva. He has received unrestricted research grants from Celgene/BMS and Novartis.Harald Hegen has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Bristol Myers Squibb, Horizon, Merck, Novartis, Sanofi Genzyme, Siemens and Teva, and received honoraria for consulting Biogen, Bristol Myers Squibb, Novartis, Roche, Sanofi Genzyme, and Teva. He is associate editor of Frontiers in Neurology.Nik Krajnc has participated in meetings sponsored by, received speaker honoraria or travel funding from Alexion, BMS/Celgene, Janssen-Cilag, Merck, Novartis, Roche and Sanofi Genzyme and held a grant for a Multiple Sclerosis Clinical Training Fellowship Programme from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).Fabian Föttinger has nothing to disclose.Patrick Altmann has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Merck, Roche, Sanofi Genzyme and Teva, and received honoraria for consulting from Biogen. He received a research grant from Quanterix International and was awarded a combined sponsorship from Biogen, Merck, Sanofi Genzyme, Roche, and Teva for a clinical study.Michael Auer has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Merck, Novartis, Sanofi Genzyme and Horizon Therapeutics.Klaus Berek has participated in meetings sponsored by and received travel funding from Biogen, Roche, Sanofi Genzyme, and Teva.Barbara Kornek has received honoraria for speaking and for consulting from Biogen, BMS-Celgene, Johnson & Johnson, Merck, Novartis, Roche, Teva, and Sanofi Genzyme outside of the submitted work. No conflict of interest with respect to the present study.Fritz Leutmezer has participated in meetings sponsored by, received speaker honoraria or travel funding from Actelion, Almirall, Biogen, Celgene, Johnson & Johnson, MedDay, Merck, Novartis, Roche, Sanofi Genzyme, and Teva, and received honoraria for consulting Biogen, Celgene, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.Stefan Macher declares no conflict of interest relevant to this study.Tobias Monschein has participated in meetings sponsored by or received travel funding from Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.Markus Ponleitner has participated in meetings sponsored by, received speaker or consulting honoraria or travel funding from Amicus, Merck, Novartis and Sanofi Genzyme.Paulus Rommer has received honoraria for consultancy/speaking from Alexion/Astra Zeneca, Allmiral, Amgen/Horizon, Amicus, Biogen, Merck, Novartis, Roche, Sandoz, Sanofi has received research grants from Amicus, Biogen, Merck, and Roche.Christiane Schmied declares no conflict of interest relevant to this study.Karin Zebenholzer received speaking honoraria or travel grants from Biogen, Celgene/BMS, Novartis, and Sanofi Genzyme.Gudrun Zulehner has participated in meetings sponsored by or received travel funding from Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.Tobias Zrzavy has participated in meetings sponsored by or received travel funding from Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.Florian Deisenhammer has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Almirall, Biogen, Celgene, Merck, Novartis, Roche, and Sanofi Genzyme. His institution received scientific grants from Biogen and Sanofi Genzyme.Franziska Di Pauli has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Biogen, Celgene BMS, Horizon, Johnson & Johnson, Merck, Novartis, Sanofi Genzyme, Teva, and Roche. Her institution has received research grants from Roche.Berthold Pemp has received honoraria for consulting from Novartis, has received honoraria for advisory boards/consulting from Chiesi and GenSight, and has received speaker honoraria from Novartis, Chiesi, and Santen.Thomas Berger has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, BMS/Celgene, Genesis, GSK, GW/Jazz Pharma, Horizon, Janssen-Cilag, MedDay, Merck, Novartis, Octapharma, Roche, Sandoz, Sanofi Genzyme, Teva, and UCB. His institution has received financial support in the past 12 months by unrestricted research grants (Biogen, Bayer, BMS/Celgene, Merck, Novartis, Roche, Sanofi Genzyme, Teva) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi Genzyme, and Teva.

Identification of patients with antibody-mediated encephalitis poses a diagnostic challenge, and any delay in that aspect will increase the interval until the initiation of immunotherapy and may negatively affect the patient´s clinical outcome. Within this review, we focus on therapeutic strategies in antibody-mediated encephalitis and propose how to proceed with patients who are suspected of having encephalitis of unknown origin. We further briefly outline differences in the treatment of paraneoplastic and antibody-mediated encephalitis according to its pathomechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings., Methods: We retrospectively investigated 3 AMPAR encephalitis patients with autoimmune global hippocampal amnesia using comprehensive cognitive and neuropsychologic assessment, antibody testing by in-house tissue-based and cell-based assays, and neuropathologic analysis of brain autopsy tissue including histology and immunohistochemistry., Results: Three patients presented with acute-to-subacute global amnesia without affection of cognitive performance, attention, concentration, or verbal function. None of the patients had epileptic seizures, change of behavior, personality changes, or psychiatric symptoms. The MRI was normal in 1 patient and showed increased fluid-attenuated inversion recovery/T2 signal in the hippocampus in the other 2 patients. Two patients showed complete remission after immunotherapy. The one patient who did not improve had an underlying adenocarcinoma of the lung and died 3.5 months after disease onset because of tumor progression. Neuropathologic analysis of the brain autopsy revealed unilateral hippocampal sclerosis accompanied by mild inflammatory infiltrates, predominantly composed of T lymphocytes, and decrease of AMPAR immunoreactivity., Conclusion: AMPAR antibodies usually associate with limbic encephalitis but may also present with immune responsive, acute-to-subacute, isolated hippocampal dysfunction without overt inflammatory CSF or MRI changes., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)