Explore the vast range of titles available.

Characteristics of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and cysteine-sparing NOTCH3 mutations are relatively unknown. This study compared clinical and imaging characteristics between patients with CADASIL and cysteine-sparing NOTCH3 mutations and those with CADASIL and cysteine-involving NOTCH3 mutations. We retrospectively reviewed medical records of patients with CADASIL admitted to the Asan Medical Center between September 1999 and September 2017. We compared clinical and brain magnetic resonance imaging (MRI) characteristics based on the presence or absence of cysteine-involving NOTCH3 gene mutations. We compared white matter change frequencies and grades in specific spatial regions between the groups according to age-related white matter change (ARWMC) scores. We evaluated the presence, number, and anatomical distributions of cerebral microbleeds according to the microbleed anatomical rating scale. We reviewed data from 79 patients (55 cysteine-involving, 24 cysteine-sparing NOTCH3 mutations). Clinical symptoms and signs did not differ significantly between the groups. The white matter change frequency and ARWMC scores (adjusted for age and stroke risk factors) in the anterior temporal lobes were lower in cysteine-sparing patients than in cysteine-involving patients. Frequencies and grades of the other brain region's white matter changes and cerebral microbleeds were similar between the groups.

Neuromyelitis optica spectrum disorder (NMOSD), driven by AQP4-IgG-producing B cells, is effectively managed with B cell depletion therapy (BCDT), such as rituximab (RTX). Although BCDT may reset the B cell compartment, its effects on B cell receptor (BCR) repertoire, clonality, isotype distribution, and somatic hypermutation (SHM) remain poorly understood. To examine how BCDT alters BCR features by comparing BCR repertoires between patients with NMOSD treated with RTX and azathioprine (AZA). From a prospective cohort, we recruited patients with NMOSD, including those on AZA (n = 11) and those 6-12 months post-RTX treatment (n = 9). Immunoglobulin heavy-chain libraries were generated from peripheral blood mononuclear cells and sequenced using Illumina MiSeq (2 × 300 bp). BCR features analyzed included isotype frequencies, D50 diversity index, top 10% clone fraction, SHM rates, and IGHV and IGHJ gene usage. Age (median 50 years) and disability scores were similar between the groups. In the RTX group, the median time since the last infusion was 9 months. RTX treatment led to a naïve B cell-dominant profile, with significantly reduced IgG1-IgG4 levels and unchanged IgA levels. Clonality was reduced, especially within the IgG isotype. SHM frequency was similar between groups, with no significant differences observed across individual isotypes. RTX also resulted in marked depletion of IGHV3-23, IGHV3-11, and IGHV3-73, along with IgG subclass-specific reductions in IGHV1-18, IGHV1-3, IGHV1-46, IGHV1-69, and IGHJ4. Six to twelve months after RTX treatment, patients with NMOSD display a rejuvenated BCR repertoire characterized by naïve B cell predominance, reduced class-switched clonality, and selective loss of V gene segments. These findings support the mechanism by which BCDT resets pathogenic memory B cells and offer benchmarks for monitoring B cell reconstitution in NMOSD.

Maintenance immunotherapy is effective in AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD), but how mechanistically distinct maintenance therapies organize the remission immune landscape and its relationship to neurological disability remains poorly defined. We performed integrated multiparameter flow cytometry and plasma cytokine profiling in serial remission samples (up to three per patient) from 28 patients receiving rituximab (RTX, n = 14) or azathioprine (AZA, n = 14). Between-treatment comparisons, within-treatment coupling analyses, and disability-associated immune analyses were conducted using age-adjusted patient-clustered regression models with prespecified false discovery rate control. RTX showed clear target engagement, characterized by profound B-cell depletion, gradual post-infusion reconstitution, and sustained reduction of natural killer T (NKT)-like cells. Beyond lineage depletion, RTX was associated with regulatory remodeling, including a memory-skewed regulatory T (Treg) phenotype and a lower effector-to-regulatory balance. In B-detectable RTX samples, the reconstituting B-cell compartment was transitional/naive-skewed with marked suppression of memory B cells. Although remission-phase cytokines were broadly low, interferon gamma-induced protein 10/CXC motif chemokine ligand 10 (IP-10/CXCL10) remained selectively elevated under RTX. Importantly, remission immune architecture differed by therapy: AZA showed a T cell immunoreceptor with Ig and ITIM domains (TIGIT)-linked regulatory disability axis, whereas RTX showed disability coupling to soluble inflammatory mediators, particularly interleukin-6 (IL-6) and IP-10. Mechanistically distinct maintenance therapies impose divergent remission immune architectures in NMOSD. These findings support a treatment-aware framework for biomarker interpretation and suggest that remission monitoring should consider therapy-specific immune networks rather than isolated immune markers.

Background Neuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing. Methods From a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups. Results Blood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups. Conclusions NMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual’s lifetime.

Although brain alterations have been reported in post-acute sequelae of SARS-CoV-2 (PASC), their prevalence and relationship to neurodegeneration remain unclear. We analyzed blood proteins and brain MRI from individuals approximately one year after mild COVID-19, categorized as Cog-PASC (with cognitive impairment), Other-PASC (without cognitive impairment), or non-PASC controls, across exploration, covariate-matched, and independent validation cohorts. In the exploration cohort, Cog-PASC showed elevated astroglial damage–associated proteins and structural and microstructural alterations across multiple cortical and subcortical regions, including cortical thinning in the cingulate and insular cortices, increased paramagnetic susceptibility in the hippocampus, and enlarged choroid plexus volume. In the age-, sex-, and education–matched cohort, cortical thinning and increased susceptibility in the cingulate remained significant. Blood proteomics revealed broader alterations involving oxidative stress responses and synaptic function in Cog-PASC, linked to neurodegenerative pathways. In the validation cohort, increased neuronal and astroglial damage-associated proteins, cortical thinning in the cingulate and insular cortices, and increased hippocampal susceptibility were demonstrated, along with enlarged choroid plexus, confirming the reproducibility of these neurodegeneration-associated alterations. These findings suggest distinct neurodegenerative processes in Cog-PASC not observed in other-PASC subtypes, even after mild COVID-19 infection. Post-acute sequelae of SARS-CoV-2 (PASC) have been linked to brain alterations, but association with cognitive problems are not well understood. Here, the authors analyze blood proteins and brain MRI data one year after mild COVID-19, revealing distinct neurodegenerative processes in PASC patients with cognitive problems, such as cortical thinning, brain iron deposition, enlarged choroid plexus, and increased blood neuronal/glial injury markers, compared to other-PASC.

Cognitive impairment (CI) is prevalent in central nervous system demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We developed a novel tablet-based modified digital Symbol Digit Modalities Test (MD-SDMT) with adjustable protocols that feature alternating symbol-digit combinations in each trial, lasting one or two minutes. We assessed 144 patients (99 with MS and 45 with NMOSD) using both MD-SDMT protocols and the traditional paper-based SDMT. We also gathered participants’ feedback through a questionnaire regarding their preferences and perceived reliability. The results showed strong correlations between MD-SDMT and paper-based SDMT scores (Pearsons correlation: 0.88 for 2 min; 0.85 for 1 min, both p < 0.001). Among the 120 respondents, the majority preferred the digitalized SDMT (55% for the 2 min, 39% for the 1 min) over the paper-based version (6%), with the 2 min MD-SDMT reported as the most reliable test. Notably, patients with NMOSD and older individuals exhibited a preference for the paper-based test, as compared to those with MS and younger patients. In summary, even with short test durations, the digitalized SDMT effectively evaluates cognitive function in MS and NMOSD patients, and is generally preferred over the paper-based method, although preferences may vary with patient characteristics.

BackgroundThe risk–benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD.MethodsThis retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes.ResultsThe mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab.ConclusionIn elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.

Sleep disturbances are common among patients with multiple sclerosis (PwMS), yet their longitudinal course and clinical determinants remain unclear. Here, we aimed to examine sleep quality in PwMS, investigate its association with quality of life, and evaluate its trajectory and clinical predictors over time. Between September 2022 and September 2023, PwMS who had not experienced a recent clinical relapse (within ≤ 2 months) were prospectively recruited. Sleep quality at baseline and after 6–12 months was measured using the Pittsburgh Sleep Quality Index (PSQI). Clinical factors associated with PSQI scores, and their longitudinal trajectories, were examined. A total of 118 patients with MS (median age, 46 years) were enrolled, with 54% identified as poor sleepers (PSQI > 5) at baseline and a comparable prevalence (53%) at follow-up. Poor sleep quality was associated independently with reduced quality of life. While PSQI scores remained generally stable over time in participants without clinical relapses during follow-up ( n  = 114), 23 (20.2%) exhibited a marked deterioration in sleep quality (PSQI score increase ≥ 3). Baseline optic Functional Systems scores (baseline: β = 0.226 (95% confidence interval, 0.021, 1.115), follow-up: β = 0.233, (0.038, 1.311)) and depression (baseline: β = 0.261, (1.031, 5.822), follow-up: β = 0.215, (0.473, 5.935)) independently predicted both baseline and future PSQI scores. In conclusion, poor sleep quality is common and persistent in PwMS, with depression and the severity of optic dysfunction identified as key predictors. These findings emphasize the need for targeted sleep management in MS care.

Cranial nerve involvement is a well-recognized feature in Guillain-Barré syndrome (GBS) but remains less well understood in chronic forms of autoimmune neuropathies. Earlier studies of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were conducted before updated diagnostic criteria and the recognition of autoimmune nodopathy (AN), which may limit the interpretation of their findings. We retrospectively analyzed 582 patients with chronic autoimmune neuropathies-CIDP (n = 431), multifocal motor neuropathy (MMN) (n = 64), anti-myelin-associated glycoprotein (MAG) neuropathy (n = 54), and AN (n = 33)-from 4 Korean and 1 UK centers. Patients with cranial nerve involvement were identified and described. CIDP patients with cranial nerve involvement (cranial+ CIDP) were compared with those without (cranial- CIDP). Cranial nerve involvement was observed in 8.8% (38/431) of CIDP and 24.2% (8/33) of AN patients but was absent in MMN (0/64) and anti-MAG neuropathy (0/54). Facial palsy was overall the most common manifestation (CIDP: 45%, AN: 50%). Patients with AN more frequently exhibited bilateral optic neuropathy (50%) and facial diplegia (38%), while CIDP patients more often showed trigeminal neuropathy and oculomotor nerve palsy (both 32%). Compared with cranial- CIDP, cranial+ CIDP patients were more often younger, of variant subtypes (especially multifocal), presented (sub)acutely with preceding infection/vaccination, followed by relapsing-remitting rather than progressive courses, and achieved greater improvement despite greater pre-treatment disability. Cranial nerve involvement serves as a diagnostic clue in chronic autoimmune neuropathies, particularly in identifying AN and CIDP. Cranial+ CIDP appears to represent a distinct subset with partial overlap to GBS, suggesting unique underlying mechanisms.