Neurology(R) neuroimmunology & neuroinflammation最新文献

{"title":"Demystifying MOGAD and Double Seronegative NMOSD Further With IL-6 Blockade.","authors":"Kok Pin Yong, Ho Jin Kim","doi":"10.1212/NXI.0000000000001110","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001110","url":null,"abstract":"Myelin oligodendrocyte glycoprotein-IgG (MOG-IgG)-associated disorder (MOGAD) is a recently de fi ned neuroimmunologic disorder a ff ecting the CNS, commonly presenting with acute disseminated encephalomyelitis in children and with optic neuritis and/or myelitis in adults. Although some patients, especially children, may exhibit a monophasic course, there are others who tend to run a highly relapsing course, potentially resulting in long-lasting neurologic disability, akin to those with neuromyelitis optica spectrum disorder (NMOSD). 1 In fact, up to almost half of patients with NMOSD without aquaporin-4 (AQP4-IgG) harbor MOG-IgG. 2 In addition, despite comprehensive testing for aquaporin-4 antibodies, there remains a proportion of patients who phenotypically resemble those with NMOSD but are seronegative for both AQP4-IgG and MOG-IgG. 3 Recent key phase II and III international, randomized, double-blind, placebo-controlled trials in patients with NMOSD, AQP4-IgG, drugs speci fi c immunopathogenic of humanized monoclonal antibody targeting interleukin-6 e cacy interleukin-6 of with","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/67/f2/NEURIMMINFL2021039476.PMC8674934.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39605559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF Neurofilament Light Chain Concentrations Predict Outcome in Bacterial Meningitis.","authors":"Nora Chekrouni,&nbsp;Thijs M van Soest,&nbsp;Matthijs C Brouwer,&nbsp;Eline A J Willemse,&nbsp;Charlotte E Teunissen,&nbsp;Diederik van de Beek","doi":"10.1212/NXI.0000000000001123","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001123","url":null,"abstract":"<p><strong>Background and objectives: </strong>Neurofilament light chain (NfL) is a biomarker for neuroaxonal damage and has been found to be elevated proportionally to the degree of neuronal damage in neurologic diseases. The objective of this study was to determine the prognostic accuracy of NfL concentrations on unfavorable outcome in adults with community-acquired bacterial meningitis.</p><p><strong>Methods: </strong>We measured NfL concentration CSF samples from a prospective cohort study of adults with community-acquired bacterial meningitis in The Netherlands and determined associations between NfL CSF concentrations, clinical characteristics, and outcome in multivariate analyses. We identified independent predictors of an unfavorable outcome (Glasgow Outcome Scale scores 1-4) by logistic regression.</p><p><strong>Results: </strong>CSF NfL concentrations were evaluated in 429 episodes of 425 patients with community-acquired bacterial meningitis. The median age of 429 episodes was 62 years (interquartile range, 50-69 years). Of note, 290 of 422 (68%) episodes presented with an altered mental status (Glasgow Coma Scale score < 14). Most common causative pathogens were <i>Streptococcus pneumoniae</i> (73%)<i>, Neisseria meningitidis</i> (7%), and <i>Listeria monocytogenes</i> (5%). The overall case fatality rate was 62 of 429 (15%), and unfavorable outcome occurred in 57 (37%) of 429 episodes. In multivariate analysis, predictors of unfavorable outcome were older age (OR 1.03, 95% CI 1.01-1.05), cranial nerve palsy (OR 4, 95% CI 1.6-10.3), high serum C-reactive protein concentration (OR 1.3, 95% CI 1.01-1.05), and high CSF NfL concentration (OR 1.5, 95% CI 1.07-2.00). CSF NfL concentrations were higher in patients presenting with focal cerebral deficits (717 pg/mL [416-1,401] vs 412 pg/mL [278-731]; <i>p</i> < 0.001). The area under the curve (AUC) for predicting unfavorable outcome in bacterial meningitis of CSF NfL concentration was 0.69 (95% CI, 0.64-0.74).</p><p><strong>Discussion: </strong>CSF NfL concentration is independently associated with unfavorable outcome in adults with community-acquired bacterial meningitis, suggesting that CSF NfL concentration may be a useful biomarker for prognostic assessment in bacterial meningitis.</p><p><strong>Classification of evidence: </strong>Can the level of NfL in CSF (the index test) predict unfavorable outcome in patients with bacterial meningitis, in a cohort of bacterial meningitis patients with a favorable and unfavorable outcome? This study provides Class II evidence that NfL level in CSF is a moderate predictor, with the AUC for predicting unfavorable outcome in bacterial meningitis being 0.69 (95% CI, 0.64-0.74).</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/3b/NEURIMMINFL2021039434.PMC8669658.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39723130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allosteric Modulation of NMDARs Reverses Patients' Autoantibody Effects in Mice.","authors":"Marija Radosevic,&nbsp;Jesús Planagumà,&nbsp;Francesco Mannara,&nbsp;Araceli Mellado,&nbsp;Esther Aguilar,&nbsp;Lidia Sabater,&nbsp;Jon Landa,&nbsp;Anna García-Serra,&nbsp;Estibaliz Maudes,&nbsp;Xavier Gasull,&nbsp;Mike Lewis,&nbsp;Josep Dalmau","doi":"10.1212/NXI.0000000000001122","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001122","url":null,"abstract":"<p><strong>Background and objectives: </strong>To demonstrate that an analog (SGE-301) of a brain-derived cholesterol metabolite, 24(S)-hydroxycholesterol, which is a selective positive allosteric modulator (PAM) of NMDA receptors (NMDARs), is able to reverse the memory and synaptic alterations caused by CSF from patients with anti-NMDAR encephalitis in an animal model of passive transfer of antibodies.</p><p><strong>Methods: </strong>Four groups of mice received (days 1-14) patients' or controls' CSF via osmotic pumps connected to the cerebroventricular system and from day 11 were treated with daily subcutaneous injections of SGE-301 or vehicle (no drug). Visuospatial memory, locomotor activity (LA), synaptic NMDAR cluster density, hippocampal long-term potentiation (LTP), and paired-pulse facilitation (PPF) were assessed on days 10, 13, 18, and 26 using reported techniques.</p><p><strong>Results: </strong>On day 10, mice infused with patients' CSF, but not controls' CSF, presented a significant visuospatial memory deficit, reduction of NMDAR clusters, and impairment of LTP, whereas LA and PPF were unaffected. These alterations persisted until day 18, the time of maximal deficits in this model. In contrast, mice that received patients' CSF but from day 11 were treated with SGE-301 showed memory recovery (day 13), and on day 18, all paradigms (memory, NMDAR clusters, and LTP) had reversed to values similar to those of controls. On day 26, no differences were observed among experimental groups.</p><p><strong>Discussion: </strong>An oxysterol biology-based PAM of NMDARs is able to reverse the synaptic and memory deficits caused by CSF from patients with anti-NMDAR encephalitis. These findings suggest a novel adjuvant treatment approach that deserves future clinical evaluation.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/d9/NEURIMMINFL2021039430.PMC8669659.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39723129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress Signal ULBP4, an NKG2D Ligand, Is Upregulated in Multiple Sclerosis and Shapes CD8⁺ T-Cell Behaviors.","authors":"Ana Carmena Moratalla,&nbsp;Yves Carpentier Solorio,&nbsp;Florent Lemaitre,&nbsp;Negar Farzam-Kia,&nbsp;Annie Levert,&nbsp;Stephanie E J Zandee,&nbsp;Boaz Lahav,&nbsp;Jean Victor Guimond,&nbsp;Elie Haddad,&nbsp;Marc Girard,&nbsp;Pierre Duquette,&nbsp;Catherine Larochelle,&nbsp;Alexandre Prat,&nbsp;Nathalie Arbour","doi":"10.1212/NXI.0000000000001119","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001119","url":null,"abstract":"<p><strong>Background and objectives: </strong>We posit the involvement of the natural killer group 2D (NKG2D) pathway in multiple sclerosis (MS) pathology via the presence of specific NKG2D ligands (NKG2DLs). We aim to evaluate the expression of NKG2DLs in the CNS and CSF of patients with MS and to identify cellular stressors inducing the expression of UL16-binding protein 4 (ULBP4), the only detectable NKG2DL. Finally, we evaluate the impact of ULBP4 on functions such as cytokine production and motility by CD8⁺ T lymphocytes, a subset largely expressing NKG2D, the cognate receptor.</p><p><strong>Methods: </strong>Human postmortem brain samples and CSF from patients with MS and controls were used to evaluate NKG2DL expression. In vitro assays using primary cultures of human astrocytes and neurons were performed to identify stressors inducing ULBP4 expression. Human CD8⁺ T lymphocytes from MS donors and age/sex-matched healthy controls were isolated to evaluate the functional impact of soluble ULBP4.</p><p><strong>Results: </strong>We detected mRNA coding for the 8 identified human NKG2DLs in brain samples from patients with MS and controls, but only ULBP4 protein expression was detectable by Western blot. ULBP4 levels were greater in patients with MS, particularly in active and chronic active lesions and normal-appearing white matter, compared with normal-appearing gray matter from MS donors and white and gray matter from controls. Soluble ULBP4 was also detected in CSF of patients with MS and controls, but a smaller shed/soluble form of 25 kDa was significantly elevated in CSF from female patients with MS compared with controls and male patients with MS. Our data indicate that soluble ULBP4 affects various functions of CD8⁺ T lymphocytes. First, it enhanced the production of the proinflammatory cytokines GM-CSF and interferon-γ (IFNγ). Second, it increased CD8⁺ T lymphocyte motility and favored a kinapse-like behavior when cultured in the presence of human astrocytes. CD8⁺ T lymphocytes from patients with MS were especially altered by the presence of soluble ULBP4 compared with healthy controls.</p><p><strong>Discussion: </strong>Our study provides new evidence for the involvement of NKG2D and its ligand ULBP4 in MS pathology. Our results point to ULBP4 as a viable target to specifically block 1 component of the NKG2D pathway without altering immune surveillance involving other NKG2DL.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/02/88/NEURIMMINFL2021039368.PMC8656234.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39698491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recovery From COVID-19 in Multiple Sclerosis: A Prospective and Longitudinal Cohort Study of the United Kingdom Multiple Sclerosis Register.","authors":"Afagh Garjani,&nbsp;Rodden M Middleton,&nbsp;Richard Nicholas,&nbsp;Nikos Evangelou","doi":"10.1212/NXI.0000000000001118","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001118","url":null,"abstract":"<p><strong>Background and objectives: </strong>To understand the course of recovery from coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) and to determine its predictors, including patients' pre-COVID-19 physical and mental health status.</p><p><strong>Methods: </strong>This prospective and longitudinal cohort study recruited patients with MS who reported COVID-19 from March 17, 2020, to March 19, 2021, as part of the United Kingdom MS Register (UKMSR) COVID-19 study. Participants used online questionnaires to regularly update their COVID-19 symptoms, recovery status, and duration of symptoms for those who fully recovered. Questionnaires were date stamped for estimation of COVID-19 symptom duration for those who had not recovered at their last follow-up. The UKMSR holds demographic and up-to-date clinical data on participants as well as their web-based Expanded Disability Status Scale (web-EDSS) and Hospital Anxiety and Depression Scale (HADS) scores. The association between these factors and recovery from COVID-19 was assessed using multivariable Cox regression analysis.</p><p><strong>Results: </strong>Of the 7,977 patients with MS who participated in the UKMSR COVID-19 study, 599 reported COVID-19 and prospectively updated their recovery status. Twenty-eight hospitalized participants were excluded. At least 165 participants (29.7%) had long-standing COVID-19 symptoms for ≥4 weeks and 69 (12.4%) for ≥12 weeks. Participants with pre-COVID-19 web-EDSS scores ≥7, participants with probable anxiety and/or depression (HADS scores ≥11) before COVID-19 onset, and women were less likely to report recovery from COVID-19.</p><p><strong>Discussion: </strong>Patients with MS are affected by postacute sequelae of COVID-19. Preexisting severe neurologic impairment or mental health problems appear to increase this risk. These findings can have implications in tailoring their post-COVID-19 rehabilitation.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/2f/NEURIMMINFL2021039246.PMC8631790.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39680001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgG4-Mediated Neurologic Autoimmunities: Understanding the Pathogenicity of IgG4, Ineffectiveness of IVIg, and Long-Lasting Benefits of Anti-B Cell Therapies.","authors":"Marinos C Dalakas","doi":"10.1212/NXI.0000000000001116","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001116","url":null,"abstract":"<p><strong>Background and objectives: </strong>Describe the unique functions of immunoglobulin G4 (IgG4) in IgG4-neurologic disorders (IgG4-ND) and explain why, in contrast to their IgG1-counterparts, they respond poorly to intravenous immune globulin (IVIg) but effectively to anti-B cell therapies.</p><p><strong>Methods: </strong>The IgG4 structure and isotype switch, B cells and plasmablasts relevant to IgG4 production, and IgG4-induced disruption of the targeted antigens are reviewed and compared with IgG1-mediated autoimmune ND, where IVIg inhibits IgG1-triggered inflammatory effects.</p><p><strong>Results: </strong>The main IgG4-ND include muscle-specific kinase myasthenia; nodal/paranodal chronic inflammatory demyelinating polyradiculoneuropathy with antibodies to neurofascin-155, contactin-1/caspr-1, or pan-neurofascins; antileucine-rich, glioma-inactivated-1 and contactin-associated protein-like 2 associated-limbic encephalitis, Morvan syndrome, or neuromyotonia; and anti-IgLON5 disorder. The IgG4, because of its unique structural features in the hinge region, has noninflammatory properties being functionally monovalent and bispecific, unable to engage in cross-linking and internalization of the targeted antigen. In contrast to IgG1 subclass which is bivalent and monospecific, IgG4 does not activate complement and cannot bind to inhibitory Fcγ receptor (FcγRIIb) to activate cellular and complement-mediated immune responses, the key functions inhibited by IVIg. Because IVIg contains only 0.7%-2.6% IgG4, its idiotypes are of IgG1 subclass and cannot effectively neutralize IgG4 or sufficiently enhance IgG4 catabolism by saturating FcRn. In contrast, rituximab, by targeting memory B cells and IgG4-producing CD20-positive short-lived plasma cells, induces long-lasting clinical benefits.</p><p><strong>Discussion: </strong>Rituximab is the preferred treatment in IgG4-ND patients with severe disease by effectively targeting the production of pathogenic IgG-4 antibodies. In contrast, IVIG is ineffective because it inhibits immunoinflammatory functions irrelevant to the mechanistic effects of IgG4 and contains IgG-1 idiotypes that cannot sufficiently neutralize or possibly catabolize IgG4. Controlled studies with anti-CD19/20 monoclonals that also activate FcγRIIb may be more promising in treating IgG4-ND.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/52/NEURIMMINFL2021039399.PMC8630661.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39678053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interim Analysis of Pregnancy Outcomes After Exposure to Dimethyl Fumarate in a Prospective International Registry.","authors":"Kerstin Hellwig,&nbsp;David Rog,&nbsp;Christopher McGuigan,&nbsp;Maria K Houtchens,&nbsp;Denise R Bruen,&nbsp;Oksana Mokliatchouk,&nbsp;Filipe Branco,&nbsp;Xiaomei Peng,&nbsp;Nicholas J Everage","doi":"10.1212/NXI.0000000000001114","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001114","url":null,"abstract":"<p><strong>Background and objectives: </strong>Oral delayed-release dimethyl fumarate (DMF) is not recommended during pregnancy and should only be used if the potential benefit justifies the potential fetal risk. Although DMF was well tolerated in clinical trials with consistent safety results in postmarketing surveillance, data are limited in pregnant women. The objective was to provide pregnancy outcomes and DMF exposure information from an interim analysis from a prospective, international registry (TecGistry; NCT01911767).</p><p><strong>Methods: </strong>Women exposed to DMF from the first day of their last menstrual period before conception or during pregnancy were evaluated. Data were obtained at enrollment; 6-7 months' gestation; 4 weeks after estimated due date; and 4, 12, and 52 weeks after birth. Outcomes included live births, gestational size, pregnancy loss, birth defects, and infant or maternal death after delivery. Outcomes were analyzed cumulatively from October 30, 2013 (the start of TecGistry), to April 8, 2020.</p><p><strong>Results: </strong>Of 345 enrolled patients, median (range) age was 32 (20-43) years. The mean (SD) duration of gestational weeks of DMF exposure was 4.9 (3.8). Most infants were full-term at birth (n = 249/274; 91%) and of average gestational size (n = 190/232; 82%). Of 351 outcomes, 277 were live births; 17 (5%) spontaneous abortions (95% confidence interval [CI] 2.6%-7.1%), including 1 (<1%) molar and 1 (<1%) ectopic pregnancy, were reported. There were 8 (2.9% [95% CI 1.3%-5.6%]) adjudicator-confirmed birth defects among the 277 live births.</p><p><strong>Discussion: </strong>Interim results from this large registry indicate that early DMF exposure was not significantly associated with adverse pregnancy outcomes. Outcomes are consistent with previous smaller reports and with the general population.</p><p><strong>Trial registration information: </strong>TecGistry; clinical trial registration number: NCT01911767.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/dc/NEURIMMINFL2021038953.PMC8611504.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39920105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No Signs of Neuroinflammation in Women With Chronic Fatigue Syndrome or Q Fever Fatigue Syndrome Using the TSPO Ligand [¹¹C]-PK11195.","authors":"Ruud Raijmakers,&nbsp;Megan Roerink,&nbsp;Stephan Keijmel,&nbsp;Leo Joosten,&nbsp;Mihai Netea,&nbsp;Jos van der Meer,&nbsp;Hans Knoop,&nbsp;Hans Klein,&nbsp;Chantal Bleeker-Rovers,&nbsp;Janine Doorduin","doi":"10.1212/NXI.0000000000001113","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001113","url":null,"abstract":"<p><strong>Background and objectives: </strong>The pathophysiology of chronic fatigue syndrome (CFS) and Q fever fatigue syndrome (QFS) remains elusive. Recent data suggest a role for neuroinflammation as defined by increased expression of translocator protein (TSPO). In the present study, we investigated whether there are signs of neuroinflammation in female patients with CFS and QFS compared with healthy women, using PET with the TSPO ligand ¹¹C-(<i>R</i>)-(2-chlorophenyl)-<i>N</i>-methyl-<i>N</i>-(1-methylpropyl)-3-isoquinoline-carbox-amide ([¹¹C]-PK11195).</p><p><strong>Methods: </strong>The study population consisted of patients with CFS (n = 9), patients with QFS (n = 10), and healthy subjects (HSs) (n = 9). All subjects were women, matched for age (±5 years) and neighborhood, aged between 18 and 59 years, who did not use any medication other than paracetamol or oral contraceptives, and were not vaccinated in the last 6 months. None of the subjects reported substance abuse in the past 3 months or reported signs of underlying psychiatric disease on the Mini-International Neuropsychiatric Interview. All subjects underwent a [¹¹C]-PK11195 PET scan, and the [¹¹C]-PK11195 binding potential (BP_ND) was calculated.</p><p><strong>Results: </strong>No statistically significant differences in BP_ND were found for patients with CFS or patients with QFS compared with HSs. BP_ND of [¹¹C]-PK11195 correlated with symptom severity scores in patients with QFS, but a negative correlation was found in patients with CFS.</p><p><strong>Discussion: </strong>In contrast to what was previously reported for CFS, we found no significant difference in BP_ND of [¹¹C]-PK11195 when comparing patients with CFS or QFS with healthy neighborhood controls. In this small series, we were unable to find signs of neuroinflammation in patients with CFS and QFS.</p><p><strong>Trial registration information: </strong>EudraCT number 2014-004448-37.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f8/a3/NEURIMMINFL2021039118.PMC8611501.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39920104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypogammaglobulinemia and Infections in Patients With Multiple Sclerosis Treated With Rituximab.","authors":"Marine Perriguey,&nbsp;Adil Maarouf,&nbsp;Jan-Patrick Stellmann,&nbsp;Audrey Rico,&nbsp;Clemence Boutiere,&nbsp;Sarah Demortiere,&nbsp;Pierre Durozard,&nbsp;Jean Pelletier,&nbsp;Bertrand Audoin","doi":"10.1212/NXI.0000000000001115","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001115","url":null,"abstract":"<p><strong>Background and objectives: </strong>To determine the frequency of hypogammaglobulinemia and infections in patients with multiple sclerosis (PwMS) receiving rituximab (RTX).</p><p><strong>Methods: </strong>This prospective observational study included all consecutive PwMS receiving RTX at the university hospital of Marseille, France, between 2015 and 2020. Patient visits occurred at least every 6 months.</p><p><strong>Results: </strong>We included 188 patients (151 with relapsing-remitting MS; the mean age was 43.4 years [SD 12.9], median disease duration 10 years [range 0-36], median Expanded Disability Status Scale 5 [range 0-8], median follow-up 3.5 years [range 1-5.8], and median number of RTX infusions 5 [range 1-9]). Overall, 317 symptomatic infections and 13 severe infections occurred in 133 of 188 (70.7%) and 11 of 188 (5.9%) patients, respectively. After 4 years, 24.4% of patients (95% CI 18.0-33.1) were free of any infection and 92.0% (95% CI 87.1-97.1) had not experienced a severe infection. At RTX onset, the immunoglobulin G (IgG) level was abnormal in 32 of 188 (17%) patients. After RTX, IgG level was <7, <6, <4 and <2 g/L for 83 (44%), 44 (23.4%), 8 (4.2%) and 1 (0.53%) patients, respectively. The risk of infection was associated with reduced IgG levels (multivariate Cox proportional hazards hazard ratio [HR] = 0.86, 95% CI 0.75-0.98, <i>p</i> = 0.03). The risk of reduced IgG level <6 g/L increased with age (HR = 1.36, 95% CI 1.05-1.75, <i>p</i> = 0.01).</p><p><strong>Discussion: </strong>In PwMS receiving RTX, reduced IgG level was frequent and interacted with the risk of infection.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/a4/NEURIMMINFL2021039267.PMC8611503.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39764350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Dietary Intervention on Serum Neurofilament Light Chain in Multiple Sclerosis.","authors":"Markus Bock,&nbsp;Falk Steffen,&nbsp;Frauke Zipp,&nbsp;Stefan Bittner","doi":"10.1212/NXI.0000000000001102","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001102","url":null,"abstract":"<p><strong>Background and objectives: </strong>Adapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for multiple sclerosis (MS), but information on their impact on neuroaxonal damage is lacking. Thus, we explored the impact of diets on serum neurofilament light chain (sNfL) levels in patients with relapsing-remitting MS.</p><p><strong>Methods: </strong>We retrospectively evaluated a prospective randomized controlled trial of 60 patients with MS who were on a common diet or ketogenic diet or fasting. We examined sNfL levels of 40 participants at baseline and at the end of the study after 6 months using single molecule array assay.</p><p><strong>Results: </strong>sNfL levels were investigated in 9 controls, 14 participants on CR, and 17 participants on AKD. Correlation analysis showed an association of sNfL with age and disease duration; an association was also found between sNfL and the Multiple Sclerosis Functional Composite. AKD significantly reduced sNfL levels at 6 months compared with the common diet group (<i>p</i> = 0.001).</p><p><strong>Discussion: </strong>For clinical or study use, consider that AKD may incline sNfL levels independent of relapse activity up to 3 months after initiation. At 6 months, AKD, which complements current therapies, reduced sNfL levels, therefore suggesting potential neuroprotective effects in MS. A single cycle of seven-day fasting did not affect sNfL. AKD may be an addition to the armamentarium to help clinicians support patients with MS in a personalized manner with tailored diet strategies.</p><p><strong>Trial registration information: </strong>Clinical trial registration number NCT01538355.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/ab/NEURIMMINFL2021038948.PMC8587737.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39612789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}