Cerebrospinal fluid findings in patients with neurological manifestations in post-COVID-19 syndrome

BACKGROUND: Information on cerebrospinal fluid (CSF) findings in patients with neurological manifestations in post-COVID-19 syndrome is scarce. METHODS: Retrospective evaluation of 84 CSF samples in patients fulfilling post-COVID-19 criteria in two neurological post-COVID-19 outpatient clinics. RESULTS: In 68% of samples, all CSF parameters were normal. The most frequent pathological CSF finding was elevation of total protein (median total protein 33.3 mg/dl [total range 18.5-116.2]) in 20 of 83 (24%) samples. The second most prevalent pathological finding was a blood-CSF barrier dysfunction as measured by elevation of QAlb (median QAlb 4.65 [2.4-13.2]) in 11/84 (13%). Pleocytosis was found in only 5/84 (6%) samples and was mild in all of them. CSF-restricted oligoclonal bands were found in 5/83 (6%) samples. Anti-neuronal autoantibodies in CSF were negative in most cases, whilst 12/68 (18%) samples were positive for anti-myelin autoantibodies in serum. PCR for herpesviridae (HSV-1/-2, VZV, EBV, CMV, HHV6) showed, if at all, only weakly positive results in CSF or EDTA whole blood/plasma. CONCLUSIONS: The majority of samples did not show any pathologies. The most frequent findings were elevation of total protein and blood-CSF barrier dysfunction with no signs of intrathecal inflammation. CSF analysis still keeps its value for exclusion of differential diagnoses

Effects of the COVID-19 pandemic on patients with NMO spectrum disorders and MOG-antibody-associated diseases: COPANMO(G)-Study

BACKGROUND AND OBJECTIVES: To evaluate the effects of the coronavirus disease 2019 (COVID-19) pandemic on the life of patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). METHODS: This multicenter, cross-sectional study included data of 187 patients recruited from 19 different German and Austrian Neuromyelitis Optica Study Group (NEMOS) centers between July 2021 and March 2022. The effects of the pandemic on immunotherapeutic treatment and access to care, the possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the potential effect of vaccination against SARS-CoV-2 on disease incidence and relapse risk were assessed using a patient questionnaire. Health-related quality of life (HRQoL) was measured with the EuroQoL Group 5-Dimension 5-Level Scale (EQ-5D-5L). Demographic and clinical characteristics were retrieved from the NEMOS database. RESULTS: One hundred eighty-seven patients (75% women; median age 47 [range 21-86] years; median disease duration 5.5 [range 0-67] years; median Expanded Disability Status Scale 2.0 [range 0-8.0]; 51% aquaporin-4 immunoglobulin G (AQP4-IgG)-positive, 36% myelin oligodendrocyte glycoprotein (MOG)-IgG-positive 13% double-seronegative) were analyzed. Most patients maintained excellent access to healthcare services throughout the pandemic. Immunotherapy was not changed in 88% of patients. Ninety-one percent of all patients were satisfied with medical care during the pandemic. Nearly two-thirds (64%) of patients rated their risk of infection with SARS-CoV-2 as low or moderate. Among this study sample, 23 patients (12%) knowingly acquired an infection with SARS-CoV-2 and predominantly had a nonsevere course of illness (n = 22/23, 96%). The SARS-CoV-2 vaccination rate was 89%, with 4 cases of confirmed attack or first manifestation of NMOSD/MOGAD occurring in temporal association with the vaccination (range 2-9 days). The reported HRQoL did not decline compared with a prepandemic assessment (mean EQ-5D-5L index value 0.76, 95% bootstrap confidence interval [CI] 0.72-0.80; mean EQ-VAS 66.5, 95% bootstrap CI 63.5-69.3). DISCUSSION: This study demonstrates that, overall, patients with NMOSD/MOGAD affiliated with specialized centers received ongoing medical care during the pandemic. Patients' satisfaction with medical care and HRQoL did not decrease

Clearance of JC polyomavirus from cerebrospinal fluid following treatment with interleukin-2 and pembrolizumab in an individual with progressive multifocal leukoencephalopathy and no underlying immune deficiency syndrome

A 71‐year‐old Caucasian man presented with dysarthria and fluctuating hypoesthesia of the right upper limb in early 2019. Brain magnetic resonance imaging (MRI) demonstrated T2/fluid attenuated inversion recovery hyperintense lesions in the left parietal cortical grey matter and adjacent white matter compatible with embolic stroke of undetermined source. Eight weeks later, symptoms had further progressed with loss of adequate communication, disturbance of fine motor skills, ataxia and neuropsychiatric symptoms. Widespread disease on brain MRI and the detection of JC polyomavirus (JCPyV) DNA from cerebrospinal fluid (CSF) confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML) [1]. Bone marrow biopsy revealed normal findings, and no underlying cause of reduced immunocompetence was identified. Despite rehabilitation, treatment with mirtazapine and two cycles of interleukin‐2 (IL‐2) (1 mio IE/m² sc once per day for 7 days) administered 2 weeks apart [1, 2], symptoms and MRI lesions further progressed, with complete immobility and severe dysphagia. Nine weeks after definite PML diagnosis and 4 weeks after the last IL‐2 dose, a total of three cycles of monthly infusions of pembrolizumab were applied. At the initiation of the third cycle of pembrolizumab, cognitive performance and fine motor skills had temporarily improved, and the patient had regained the ability to walk a few steps with assistance. On MRI, no increase in lesion load and no signs of an immune reconstitution inflammatory syndrome were noted. JCPyV DNA, after a decline that started already following the IL‐2 therapy, was no longer detected in CSF, collectively suggesting PML remission (Fig. 1). Enzyme‐linked immunosorbent assays revealed increasing JCPyV‐specific antibody titers in blood and CSF (AIJCPyV > 1.5 [3]). A pembrolizumab effect was indicated by reduced programmed cell death protein 1 (PD‐1) expression on peripheral CD4+ and CD8+ T cells after the treatment. Also, during the disease course of PML and following pembrolizumab treatment, proportions of innate immune cells (CD56dimCD16‐cytotoxic NK cells, CD14+ CD16 classical and CD14dim CD16+ non‐classical monocytes and CD11+ dendritic cells) and pro‐inflammatory cytokines and chemokine increased (Appendix S1, Table S1). Four weeks following the last infusion with pembrolizumab, aspiration pneumonia was suspected, and the patient received intravenous piperacillin/tazobactam 4/0.5 g three times per day for 7 days with temporary relief of symptoms. No causative bacteria were detected from blood cultures. Six weeks post‐pembrolizumab treatment, respiratory distress occurred again, and the general clinical condition further deteriorated. The patient and his legal custodians decided not to receive further hospital care, upon considering the severe and persistent disability, and the patient died shortly thereafter. As an autopsy was not performed, alternative causes of respiratory distress, such as autoimmune pneumonitis that might occur as an adverse event of pembrolizumab therapy, could not be ruled out