Successful plasmapheresis and immunoglobulin treatment for severe lipid storage myopathy: Doing the right thing for the wrong reason.

Three consecutive skeletal muscle biopsies during a several months time-frame, showing different degrees of neutral lipid storage. This is highlighted by Oil-red-O stains (D, E, F) and electron microscopy (G, H, I). Note the impact on mitochondrial morphology with so called 'parking lots (K, L). Zooming 'in and out' into the ultrastructure, using the nanotomy platform provides interesting detailled information (http://nanotomy.org). ​.

The Impact of Patient Support Programs on Adherence to Disease-Modifying Therapies of Patients with Relapsing-Remitting Multiple Sclerosis in Germany: A Non-Interventional, Prospective Study.

INTRODUCTION: Disease-modifying therapies (DMTs) in multiple sclerosis (MS) are chronic therapies, and patients are likely to face challenges in adhering to DMT dosing regimens over time. DMT manufacturers offer patient support programs (PSPs) to increase adherence. PSPs are managed offerings typically encompassing nurse services, phone services, online resources, or mobile offerings. This study evaluated whether PSPs have a positive impact on adherence to DMTs among patients with mild-to-moderate relapsing-remitting multiple sclerosis (RRMS) in Germany, independent of the treatment duration on DMT. METHODS: This was a non-interventional, prospective, cross-sectional, multi-center study with patient-reported outcomes. Patients reported their DMT adherence using patient adherence questionnaires at four visits during an observation period of 24 weeks; PSP participation for this period was reported at the last visit. The primary objective was to evaluate the impact of PSPs on adherence across different DMTs by comparing patients with PSP participation versus no participation; adherence was defined as not missing a single dose of DMT. RESULTS: One hundred eighty-four patients were analyzed (mean age: 44.6 years; 73.4% female; mean time on DMT: 7.2 years). Adherence across DMTs was significantly higher for PSP participants (92.9%) compared with non-participants (61.8%) (P = 0.0197). The observed rate of PSP participation (7.6%) was significantly lower than reported in earlier studies (P < 0.0001); PSP awareness among patients analyzed was low (22.3%). CONCLUSION: We consider this study to have shown that PSPs have a positive impact on adherence to DMTs in MS, independent of the treatment duration on DMT. The majority of PSP participants also believe in this positive effect. PSP participation and patient awareness were low, and real-world adherence levels were found to be higher with self-injectable DMTs than with oral DMTs. In summary, physicians should actively advise patients with MS to participate in PSPs and, together with their patients, consider achievable real-world adherence under different DMTs when deciding MS treatment strategies.

Lumbar puncture rapidly improves olfaction in patients with idiopathic intracranial hypertension: A cohort study.

BACKGROUND: A lumbar puncture constitutes an important diagnostic procedure in the evaluation of idiopathic intracranial hypertension. Chronic overflow of cerebrospinal fluid into the sheaths of the olfactory nerves appears to be related to olfactory impairment in these patients. Here, we asked whether cerebrospinal fluid drainage in idiopathic intracranial hypertension patients improves olfactory function. METHODS: Fourteen idiopathic intracranial hypertension patients and 14 neurologic control patients were investigated before and after lumbar puncture using the extended Sniffin' Sticks procedure. We assessed odor threshold, discrimination, and identification. In idiopathic intracranial hypertension patients, cerebrospinal fluid was drained until cerebrospinal fluid pressure had normalized. In addition, a third group of 14 healthy controls participated in the two smell tests at similar intervals. RESULTS: Relative to healthy controls, threshold, discrimination, and identification composite scores before lumbar puncture were significantly lower in idiopathic intracranial hypertension patients and also in neurologic controls. Following lumbar puncture, threshold, discrimination, and identification scores for neurologic controls remained unchanged whereas idiopathic intracranial hypertension patients showed robust improvement on the composite score as well as on all three subscores (all changes: p < 0.003), quickly regaining olfactory function in the normal range. Cerebrospinal fluid opening pressure was significantly correlated with improvement in threshold, discrimination, and identification score upon cerebrospinal fluid drainage (r = 0.609, p = 0.021). CONCLUSION: Olfactory impairment is an important, yet underappreciated, clinical feature of idiopathic intracranial hypertension. Lowering of increased intracranial pressure improves hyposmia. Our findings shed new light on the pathophysiology of cerebrospinal fluid circulation in idiopathic intracranial hypertension.

Olfactory and Gustatory Dysfunction in Patients With Autoimmune Encephalitis.

Objective: To test the hypothesis that olfactory (OF) and gustatory function (GF) is disturbed in patients with autoimmune encephalitides (AE). Methods: The orthonasal OF was tested in 32 patients with AE and 32 age- and sex-matched healthy controls (HC) with the standardized Threshold Discrimination Identification (TDI) score. This validated olfactory testing method yields individual scores for olfactory threshold (T), odor discrimination (D), and identification (I), along with a composite TDI score. The GF was determined by the Taste Strip Test (TST). Results: Overall, 24/32 (75%) of patients with AE, but none of 32 HC (p < 0.001) had olfactory dysfunction in TDI testing. The results of the threshold, discrimination and identification subtests were significantly reduced in patients with AE compared to HC (all p < 0.001). Assessed by TST, 5/19 (26.3%) of patients with AE, but none of 19 HC presented a significant limitation in GF (p < 0.001). The TDI score was correlated with the subjective estimation of the olfactory capacity on a visual analog scale (VAS; rs = 0.475, p = 0.008). Neither age, sex, modified Rankin Scale nor disease duration were associated with the composite TDI score. Conclusions: This is the first study investigating OF and GF in AE patients. According to unblinded assessment, patients with AE have a reduced olfactory and gustatory capacity compared to HC, suggesting that olfactory and gustatory dysfunction are hitherto unrecognized symptoms in AE. Further studies with larger number of AE patients would be of interest to verify our results.

7 Tesla MRI of Balo's concentric sclerosis versus multiple sclerosis lesions.

BACKGROUND: Baló's concentric sclerosis (BCS) is a rare condition characterized by concentrically layered white matter lesions. While its pathogenesis is unknown, hypoxia-induced tissue injury and chemotactic stimuli have been proposed as potential causes of BCS lesion formation. BCS has been suggested to be a variant of multiple sclerosis (MS). Here, we aimed to elucidate similarities and differences between BCS and MS by describing lesion morphology and localization in high-resolution 7 Tesla (7 T) magnetic resonance imaging (MRI) scans. METHODS: Ten patients with Baló-type lesions underwent 7 T MRI, and 10 relapsing remitting MS patients served as controls. The 7 T MR imaging protocol included 3D T1-weighted (T1w) magnetization-prepared rapid gradient echo, 2D high spatial resolution T2*-weighted (T2*w) fast low-angle shot and susceptibility-weighted imaging. RESULTS: Intralesional veins were visible in the center of all but one Baló-type lesion. Four Baló-type lesions displayed inhomogeneous intralesional T2*w signal intensities, which are suggestive of microhemorrhages or small ectatic venules. Eight of 10 BCS patients presented with 97 additional lesions, 36 of which (37%) had a central vein. Lesions involving the cortical gray matter and the U-fibers were not detected in BCS patients. CONCLUSION: Our findings support the hypothesis that BCS and MS share common pathogenetic mechanisms but patients present with different lesion phenotypes.

Objective assessment of a relative afferent pupillary defect by B-mode ultrasound.

PURPOSE: To evaluate B-mode ultrasound as a novel method for objective and quantitative assessment of a relative afferent pupillary defect (RAPD) in a prospective case-control study. METHODS: Seventeen patients with unilateral optic neuropathy and a clinically detectable RAPD and 17 age and sex matched healthy controls were examined with B-mode ultrasound using an Esaote-Mylab25 system according to current guidelines for orbital insonation. The swinging flashlight test was performed during ultrasound assessment with a standardized light stimulus using a penlight. RESULTS: B-mode ultrasound RAPD examination was doable in approximately 5 minutes only and was well tolerated by all participants. Compared to the unaffected contralateral eyes, eyes with RAPD showed lower absolute constriction amplitude of the pupillary diameter (mean [SD] 0.8 [0.4] vs. 2.1 [0.4] mm; p = 0.009) and a longer pupillary constriction time after ipsilateral light stimulus (mean [SD] 1240 [180] vs. 710 [200] ms; p = 0.008). In eyes affected by RAPD, visual acuity correlated with the absolute constriction amplitude (r = 0.75, p = 0.001). CONCLUSIONS: B-mode ultrasound enables fast, easy and objective quantification of a RAPD and can thus be applied in clinical practice to document a RAPD.

Tryptophan immunoadsorption during pregnancy and breastfeeding in patients with acute relapse of multiple sclerosis and neuromyelitis optica.

BACKGROUND: Up to every fourth woman with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) suffers a clinically relevant relapse during pregnancy. High doses of steroids bear some serious risks, especially within the first trimester of pregnancy. Immunoadsorption (IA) is an effective and more selective treatment option in disabling MS relapse than plasma exchange. Data on the use of IA during pregnancy and breastfeeding are scarce. METHODS: In this retrospective multicenter study, we analyzed the safety and efficacy of IA treatment in acute relapses during pregnancy or breastfeeding. The primary outcome parameter - change of acute relapse-related disability after IA - was assessed using Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). RESULTS: A total of 24 patients were analyzed, 23 with relapsing-remitting MS, and 1 with NMOSD. Twenty patients were treated with IA during pregnancy. Four patients received IA postnatally during the breastfeeding period. Treatment was started at a mean 22.5 [standard deviation (SD) 13.9] days after onset of relapse. Patients were treated with a series of 5.8 (mean, SD 0.7) IA treatments within 7-10 days. Sixteen patients received IA because of steroid-refractory relapse, eight were treated without preceding steroid pulse therapy. EDSS improved clinically relevant from 3.5 [median, interquartile range (IQR) 2] before IA to 2.5 (median, IQR 1.1) after IA, p < 0.001. In patients with ON, VA improved in four out of five patients. Altogether, in 83% of patients, a rapid and marked improvement of relapse-related symptoms was observed after IA with either a decrease of ⩾1 EDSS grade or improvement in VA ⩾20%. No clinically relevant side effect was reported in 138 IA treatments. CONCLUSIONS: Tryptophan-IA was found to be effective and well tolerated in MS/NMOSD relapses, both as an escalation option after insufficient response to steroid pulse therapy and as first-line relapse treatment during pregnancy and breastfeeding.

Fulminant rebound of relapsing-remitting multiple sclerosis after discontinuation of dimethyl fumarate: A case report.

BACKGROUND: Rebound phenomena after discontinuation of different treatments for relapsing-remitting multiple sclerosis (RRMS) have previously been described. Systematic database research in PubMed did not show any report with relapse directly associated with dimethyl fumarate (DMF) cessation. CASE PRESENTATION: Here, we report on a 38-year-old Caucasian male patient suffering from a relatively mild course of RRMS who developed a fulminant clinical rebound 2 months after discontinuation of DMF therapy. Radiological alterations presented impressively with primarily spinal involvement. The patient received intensive care and multiple immunomodulating therapies. CONCLUSION: We report on this case to raise neurologist's awareness of complications of basic therapy discontinuation in RRMS.

B-mode ultrasound assessment of pupillary function: Feasibility, reliability and normal values.

PURPOSE: To evaluate B-mode ultrasound as a novel method for the examination of pupillary function and to provide normal values for the pupillary reflex as assessed by B-mode ultrasound. METHODS: 100 subjects (49 female, 51 male, mean [range] age 51 [18-80 years]) with no history of ophthalmologic disease, no clinically detectable pupillary defects, and corrected visual acuity ≥ 0.8 were included in this prospective observational study. B-mode ultrasound was performed with the subjects eyes closed using an Esaote-Mylab25 system according to current guidelines for orbital insonation. A standardized light stimulus was applied. RESULTS: The mean ± standard deviation left and right pupillary diameters (PD) at rest were 4.7 ± 0.8 and 4.5 ± 0.8 mm. Following an ipsilateral light stimulus (Lstim), left and right constricted PD were 2.8 ± 0.6 and 2.7 ± 0.6 mm. Following a contralateral Lstim, left and right constricted PD were 2.7 ± 0.6 and 2.6 ± 0.5 mm. Left and right pupillary constriction time (PCT) following ipsilateral Lstim were 970 ± 261.6 and 967 ± 220 ms. Left and right PCT following a contralateral Lstim were 993.8 ± 192.6 and 963 ± 189.4 ms. Patient age was inversely correlated with PD at rest and with PD after ipsilateral and contralateral Lstim (all p<0.001), but not with PCT. CONCLUSIONS: B-mode ultrasound is a simple, rapid and objective method for the quantitative assessment of pupillary function, which may prove useful in a variety of settings where eyelid retraction is impeded or an infrared pupillometry device is unavailable.

High prevalence of neuronal surface autoantibodies associated with cognitive deficits in cancer patients.

The recent discovery of neuronal cell-surface antibodies profoundly expanded the clinical spectrum of paraneoplastic neurological syndromes. Many of these syndromes are associated with impaired cognitive function, a clinical symptom that is of increasing concern in cancer patients. However, the frequency of these antibodies in cancer patients and their relation to clinical syndromes is currently unknown. Here, we investigated the prevalence of neuronal cell-surface antibodies and associated paraneoplastic neurological syndromes in 323 patients with different cancer types and in 105 controls. Cerebrospinal fluid and serum samples were analysed for a large panel of anti-neuronal antibodies and all patients were screened for cognitive deficits. Blood-brain barrier integrity was assessed using the age-normalized albumin cerebrospinal fluid/serum ratio. Anti-neuronal autoantibodies were observed in 24.5% of cancer patients (in contrast to 3.1% in neurological control patients without cancer and 2.5% in healthy controls) and were almost exclusively detected in serum. The majority of antibodies were directed against cell-surface antigens (75.9%), most frequently IgA/IgM isotypes targeting the N-methyl-D-aspartate (NMDA) receptor. Cognitive deficits and cerebellar syndromes were significantly more prevalent in antibody-positive in comparison with antibody-negative patients (21 vs. 7%, p = 2.7 × 10-4; 11 vs. 2%, p = 3.0 × 10-3). Antibody-positive patients with cognitive deficits had a significantly increased albumin cerebrospinal fluid/serum ratio in comparison with antibody-positive patients with other neurological deficits, indicating blood-brain barrier dysfunction (49.1 × 10-3 vs. 12.0 × 10-3; p = 0.036). Our results show that anti-neuronal antibodies have a high prevalence in a wide range of different tumour types and are associated with distinct neurological deficits. Specifically, the results suggest a so far undefined cognitive paraneoplastic syndrome in patients with antibodies targeting neuronal surface antigens and concurrent blood-brain barrier dysfunction. Anti-neuronal antibodies might thus serve as a biomarker for potentially treatment-responsive cognitive impairments in cancer patients.

Olfactory dysfunction in patients with primary progressive MS.

OBJECTIVE: We tested the hypothesis that olfactory function is more impaired in patients with primary progressive MS (PPMS) than that in relapsing-remitting MS (RRMS). METHODS: Standardized olfactory testing was performed in 32 patients with PPMS, 32 patients with RRMS, and 32 healthy controls (HCs). Patients with olfactory dysfunction due to an alternative primary etiology were excluded. The validated olfactory testing method yielded individual scores for olfactory threshold, odor discrimination, and odor identification, along with a composite Threshold Discrimination Identification (TDI) score. RESULTS: Olfactory dysfunction was identified in 27 (84%) patients with PPMS, 10 (31%) patients with RRMS, and 1 (3%) HC. While age and sex were similar between PPMS and HCs, the TDI score and all olfactory subscores were significantly worse in patients with PPMS compared with HCs (all p < 0.001). After adjustment for differences in age, sex, Expanded Disability Status Scale (EDSS), and disease duration, odor discrimination, odor identification, and the composite TDI score were worse in patients with PPMS vs RRMS (p = 0.03, 0.04, and 0.02, respectively). Neither age, sex, EDSS, nor disease duration was significantly associated with the composite TDI score. CONCLUSIONS: Olfactory dysfunction was more frequent and severe in PPMS compared with RRMS, independent of disease duration and overall disability status. Further research on cellular level differences in olfactory neural pathways may lead to new insights about disease pathogenesis in MS.

A prospective study comparing tryptophan immunoadsorption with therapeutic plasma exchange for the treatment of chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare paralyzing inflammatory neuropathy with probably autoimmune origin. While plasma exchange (PE) constitutes a first-line treatment option for CIDP, there is only little known about the efficacy and safety of immunoadsorption (IA), a more selective apheresis procedure with assumed better tolerability. METHODS: In this prospective-randomized pilot trial, patients were randomly assigned to receive 6 sessions of PE (n = 10) or IA (n = 10) treating equal plasma volumes. To evaluate efficacy, we calculated the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score and the Medical Research Council (MRC) sum score at baseline (V1), after completion of 6 sessions (V2) as well as 4 weeks after completion (V3) in 9 patients per group (1 patient in each group did not complete follow-up). We additionally assessed safety and tolerability of treatments by monitoring adverse event and blood parameters. RESULTS: With IA, 6 out of 9 (66.7%) patients improved clinically, whereas with PE, 4 out of 9 (44.4%) patients improved, most of them immediately with completion of the apheresis treatment series. There was one adverse event (AE) out of 52 treatment sessions for the 9 patients in the IA group. In the PE group of 9 patients, there was 1 AE out of 51 sessions and a trend of greater fibrinogen reduction. No severe AE occurred in either group. CONCLUSION: The results of this pilot study suggest that IA is at least equally effective and safe compared to PE in CIDP patients.

Identification of neovascularization by contrast-enhanced ultrasound to detect unstable carotid stenosis.

BACKGROUND: Plaque neovascularization accompanies local inflammation and critically contributes to plaque instability. Correct identification of intraplaque neovascularization by contrast-enhanced ultrasound (CEUS) may provide an additional risk marker in carotid stenosis. This pilot study investigates the correlation between histological evaluation of carotid plaque specimens and pre-surgery CEUS to identify neovascularization. METHODS: 17 patients with high-grade internal carotid artery (ICA) stenosis were studied. CEUS was performed in all patients shortly before carotid endarterectomy. Neovascularization, infiltration of T cells and macrophages along with intraplaque hemorrhage were studied in excised plaques by immunohistochemistry. Ultrasound-based four-level and two-level classification systems for neovascularization were used. CEUS findings were compared with histological findings. RESULTS: Scores on the CEUS-based four-level and two-level classifications were robustly correlated with the density of intraplaque vessels (r = 0.635, p = 0.006 and r = 0.578, p = 0.015, respectively). Histological evaluation of regions with strong and prolonged intraplaque enhancement typically showed strong intraplaque neovascularization in conjunction with acute intraplaque hemorrhage. Moreover, higher grades of intraplaque neovascularization as determined by ultrasound were associated with a higher percentage of macrophage-rich areas. CONCLUSION: CEUS is a technique well suited to gauge the degree of neovascularization of carotid plaques. Future research will have to define the reliability and validity of CEUS in everyday clinical practice. Further, our study suggests that CEUS may also be useful to pick up features of vulnerable plaques such as acute intraplaque hemorrhages.

Does IIH Alter Brain Microstructures? - A DTI-Based Approach.

INTRODUCTION: To investigate the correlation of microstructural parameters with CSF pressure and macroscopic changes assessed by diffusion tensor imaging (DTI) in patients with idiopathic intracranial hypertension (IIH). METHODS: Twenty-three patients with IIH as well as age-, sex-, and body mass index (BMI)-matched controls underwent high resolution MR imaging of the optic nerve sheaths (ONS), pituitary gland, and ventricles. For DTI data a voxelwise permutation analysis was performed for the whole brain and ROI analysis was performed for the optic nerve and optic radiation. DTI measurements were correlated to morphometric measurements, CSF opening pressure, and headache intensity. The reliability of diagnostic performance of DTI parameters was assessed using ROC analysis. RESULTS: Analysis of DTI metrics revealed a significant reduction in the fractional anisotropy (FA) of the optic nerve in patients with IIH. In contrast, systematic regional variations between IIH patients and controls were neither observed in the whole brain analysis nor in the optic radiation. FA values of the optic nerve show significant correlations with the optic nerve sheath diameter (P = .003, r = -.589). The correlation of the alterations of the FA values of the optic radiation and the whole brain do not show a significant association to morphometric alterations in the ONS diameter and hypophysis height as well as to CSF opening pressure and headache intensity. CONCLUSIONS: The results indicate that IIH is associated with microstructural changes in the optic nerve. These alterations may be the direct consequence of chronically elevated intracranial pressure.

Longitudinal Testing of Olfactory and Gustatory Function in Patients with Multiple Sclerosis.

BACKGROUND: The aim of the study was to investigate changes of the olfactory and gustatory capacity in patients with multiple sclerosis (MS). METHODOLOGY: 20 MS patients were tested longitudinally for 3 years after initial testing. The Threshold Discrimination Identification test (TDI) was used for subjective olfactometry. Objective olfactometry was performed by registering olfactory evoked potentials (OEP) by EEG. The Taste Strip Test (TST) was used for gustatory testing. RESULTS: 45% of the patients showed olfactory dysfunction in the follow-up TDI test and 50% showed delayed OEP´s. 20% of the patients showed gustatory dysfunction on follow-up visit. The patients showed mild disease activity with 0,3 ± 0,5 relapses over the testing period and no significant change of their olfactory and gustatory capacity. The olfactory capacity for the discrimination of odors correlated inversely with the number of relapses (r = -0.5, p ≤ 0.05). The patients were aware of their olfactory deficit. CONCLUSIONS: Olfactory and gustatory dysfunction is a symptom in MS patients and may be a useful parameter to estimate disease progression in MS patients. As the discrimination of odors is processed in higher central regions of the central nervous system (CNS), the results suggest that olfactory dysfunction could be due to CNS damage.

Neurofascin (NF)155- and NF186-Specific T Cell Response in a Patient Developing a Central Pontocerebellar Demyelination after 10 Years of CIDP.

BACKGROUND: Information and pathobiological understanding about central demyelinating manifestation in patients, who primarily suffer from chronic inflammatory demyelinating polyneuropathy (CIDP), are scarce. METHODS: IFN-γ-response as well as antibodies against the (para)nodal antigens neurofascin (NF)155 and NF 186 had been tested by Elispot assay and ELISA before clinical manifestation and at follow-up. CASE DESCRIPTION AND RESULTS: The patient described here developed a subacute brainstem syndrome more than 10 years after diagnosis of CIDP under low-dose maintenance treatment of intravenous immunoglobulins (IVIG). MRI revealed enhancing right-sided pontocerebellar lesion. CSF examination showed mild pleocytosis and elevated protein, and negative oligoclonal bands. Further diagnostics exclude differential diagnoses such as tuberculoma, sarcoidosis, or metastasis. Specific IFN-γ response against NF155 and NF186 as measured by Elispot assay was elevated before clinical manifestation. NF155 and NF186 antibodies were negative. Escalation of IVIG treatment at 2 g/kg BW followed by 1.4 g/kg BW led to clinical remission albeit to a new asymptomatic central lesion. Follow-up NF155 and NF186-Elispot turned negative. CONCLUSION: The case reported here with a delayed central manifestation after an initially typical CIDP and NF155 and NF186 T cell responses does not resemble described cases of combined central and peripheral demyelination but may reflect a novel subtype within the great clinical heterogeneity of CIDP.

Immunoadsorption or plasma exchange in the treatment of autoimmune encephalitis: a pilot study.

Therapeutic apheresis has emerged as a major treatment option for autoantibody-associated inflammatory diseases of the nervous system. This includes patients with autoimmune encephalitides caused by antibodies against neuronal proteins. Plasma exchange (PE) and immunoadsorption (IA) constitute two possibilities to eliminate pathogenic antibodies from patients' plasma, but their efficacy and safety has not been prospectively assessed in larger patient groups of autoimmune encephalitides. In a prospective observational case control study, we, therefore, investigated the disease courses and treatment effects of 21 patients with autoimmune encephalitis associated with NMDAR, LGI1, CASPR2, GAD, mGluR5 and Hu antibodies. Patients were randomly assigned to receive PE (n = 11) or IA (n = 10). Symptoms were evaluated using the modified Rankin Scale (mRS). Side effects or adverse events were recorded. Both interventions, IA (p = 0.014) and PE (p = 0.01), resulted in significant reduction of the median mRS. With IA, 60 % of the patients improved clinically by at least 1 mRS score, none worsened. PE led to a comparable symptom reduction in 67 % of the cases. During 83 PE sessions, three adverse events were documented, while no side effects occurred under IA. Symptom improvement was significantly associated with younger age (r = -0.58), but not with disease duration. Therapeutic apheresis was most effective for neuronal surface antigens (83.3 %), followed by intracellular-synaptic antigens (66.7 %). Both IA and PE resulted in moderate to marked clinical improvement, with a low rate of adverse events. Apheresis is well tolerated and effective also as first-line therapy in autoimmune encephalitis, particularly in patients with antibodies targeting neuronal surfaces.