Journal of the Neurological Sciences最新文献

Background: The ASCLEPIOS/APLIOS/APOLITOS/ALITHIOS trials highlighted the benefits of ofatumumab in reducing relapse rates and disability progression in multiple sclerosis (MS). However, its effects on patients with severe disability status remains uncertain. This study aimed to clarify the outcomes of ofatumumab in MS patients with high Expanded Disability Status Scale (EDSS) scores and prolonged disease durations.

Methods: This is a retrospective cohort study of MS patients treated with ofatumumab at an MS center in Japan. At 12 months of treatment, patients with MS starting ofatumumab were classified into the treatment-responsive or treatment-resistant groups based on ofatumumab continuity, incidence of relapses with EDSS worsening, progression independent of relapse activity (PIRA). We used logistic regression analysis to identify factors associated with ofatumumab response.

Results: Seventy patients were included in the analysis; 39 (56 %) patients were relapsing-remitting (RR), and 31 (44 %) patients were secondary progressive (SP) MS. Mean age at ofatumumab initiation, age at onset, and disease duration were 48.0, 33.9, and 14.1 years, respectively. The median EDSS was 4.5 (3.0-6.5); 38(56 %) patients were classified as resistant. The resistant rates by disease type were 33 % (13/39) and 81 % (26/31) for RR and SP MS, respectively. On multivariate analysis, EDSS and No evidence of disease activity (NEDA) 3 were independent factors for ofatumumab responsiveness (OR, 1.74, 0.04; 95 % CI, 1.17-2.73, 0.00-0.47; p = 0.01, 0.04).

Conclusion: Ofatumumab may yield more favorable effects when initiated in patients with MS with lower EDSS scores.

Background: Few predictors of visual outcome after myelin oligodendrocyte glycoprotein (MOG) auto-antibody disease optic neuritis (ON) have been reliably elucidated. We evaluate whether between-study differences in ON neuroimaging regional enhancement features may underlie heterogeneity in reported visual prognosis.

Methods: PROSPERO (CRD42024580123). We systematically review within-study analyses correlating neuroimaging ON findings with visual outcome. Between studies, a meta-regression was conducted using ON segmental and regional inflammation (intraorbital, pre-chiasmal, intra- or post-chiasmal, and longitudinal extension) as predictors of final and change-from-baseline visual acuity (VA; LogMAR).

Results: We identified 26 reports (n = 1197 participants), eleven of which reported VA analyses or data stratified by enhancement region. Despite conflicting reports on the association between final VA and enhancement region, most studies report against this association. Meta-regression across all studies similarly determined that, at the study level, there was no significant association of any ON segment nor region with final or change-from-baseline VA. Risk of bias analysis indicated generally favourable quality across included studies.

Conclusion: Studies with poorer VA outcome did not significantly differ in the proportion of patients with various ON regional enhancement patterns. Future studies stratifying VA by neuroimaging findings with raw data reported are needed.

Background: Among white populations, a poly-specific antibody response against measles (M), rubella (R) and varicella zoster(Z) otherwise known as MRZR is seen in ∼70 % of MS and rarely in other demyelinating disorders. While the basis for MRZR is unclear, vaccination exposure / community acquired infections may have an influence on its frequency.

Objective: To determine the frequency and specificity of MRZR in MS and related disorders in a non- white population with historically low vaccinations and to contrast against oligoclonal bands (OCB).

Methods: In all, 167 consecutive patients (MS -96, MOGAD-33, AQP4-IgG + NMOSD-12 & double seronegative disorders[DSD] -26) were included. Clinical diagnosis, vaccination history and past infections contributing to MRZR were queried, OCB results were reviewed and MRZR measured.

Result: MRZR+ response was seen in 50 % MS, 21.2 % MOGAD, 8.3 %NMOSD and 3.8 % of DSN disease. Vaccination history was limited, a past history of Z was notably associated (p 0.005) with MRZR-Z+ and a high median antibody index was detected for Z and R (p 0.001) in MS. Among MRZR+ patients with MOGAD, a disseminated disease that included LETM (p 0.007), relapsing course (p 0.02), higher relapse rate (p 0.001) and lumbar puncture performed after 2 or more attacks(p 0.009) were significant. CSF specific OCB was more sensitive (71.9 %;95 %CI 61.8-80.6) and specific (94.4 %;95 %CI 86.2-98.4) than MRZR (sensitivity 50 % [95 %CI 39.62-60.4] and specificity 87.3 %(95 %CI 77.3-94.04) for MS patients.

Conclusion: In this south Indian cohort with historically low vaccination status, community acquired immunity may have in part influenced MRZR+ results, especially MRZR-Z. A chronic inflammatory state is a likely pre-requisite, that may not be disease specific, for MRZR positivity in immunologically overlapping CNS disorders such as MS, MOGAD and others.

Background and aims: We aimed to investigate long-term changes in carotid intima-media thickness (IMT) based on baseline blood pressure (BP) levels in non-cardioembolic stroke patients.

Methods: Patients aged 45-80 years with dyslipidemia who were not on statins before enrollment and had experienced a non-cardioembolic stroke were assigned to either the pravastatin group or the control group in a randomized trial. Patients were classified into three groups according to BP levels: normal BP (N-group: systolic BP [sBP] <140 mmHg and diastolic BP [dBP] <90 mmHg), highly elevated BP (G2 group: sBP ≥160 mmHg or dBP ≥100 mmHg), and mildly elevated BP (G1 group: the remaining patients). Mixed effect models were used to examine differences in slope of mean carotid IMT increases annually over the 5-year observation period among three groups, and for two groups divided based on whether they were above or below certain BP cut-off levels set at every 1 mmHg, ranging between 139 and 161 mmHg for sBP, and 89-101 mmHg for dBP.

Results: Of 792 patients, baseline mean carotid IMT in the G1-group (0.908 ± 0.152 mm) and G2-group (0.905 ± 0.145 mm) was significantly higher than the N-group (0.870 ± 0.153 mm) (P < 0.01, for both respectively). Although there was no significant difference in the increase among three groups (P = 0.091), the increase in patients above sBP 154, 159 and 160 mmHg or dBP 101 mmHg at baseline was higher than others (P < 0.05 for all).

Conclusions: High baseline BP correlated with a high baseline carotid IMT and its subsequent 5-year increase in non-cardioembolic stroke patients.

Clinical trial registration: http://www.

Clinicaltrials: gov.

Unique identifier: NCT00361530.

Background: A better knowledge of upper-extremity (UE) recovery in patients with stroke receiving usual care (UC) is crucial for informing clinicians on expected recovery and serves as reference for future studies.

Objectives: This systematic review and meta-analysis aimed to assess rate and amount of recovery of UE with UC in the subacute phase of stroke and identify covariates of UE recovery.

Methods: PRISMA-guidelines were used for search in PubMed, Cinahl and PEDro. Observational studies (OS) and UC groups of randomized control trials (RCT) of adults with subacute stroke and UE paresis were included, each reporting UE function at least at two time points. Placebo-, sham-controlled, dose-matched trials and trials with <10 participants were excluded.

Results: From 1220 records, 54 papers (19 OS and 35 RCTs) involving 2774 subacute stroke patients were included. Fugl-Meyer Assessment of Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT) were most frequently reported UE outcomes. Across RCTs, FMA-UE and ARAT improved 10 and 8 points, respectively, on average at 4-weeks from baseline. In OS, FMA-UE, improved 12 points at 12 weeks and 16 points at 24 weeks from baseline. Stroke severity, UE function, and lesion load of the cortico-spinal tract at baseline were associated with UE recovery.

Conclusions: UE function in subacute stroke showed improvements that exceeded the threshold for clinically important change across RCTs and OS. This review provides estimates of expected change in UC groups for sample size calculations and planning of future trials, thereby enhancing statistical power and comparability of findings.

Background: Recent literature suggests circadian rhythm influences cerebral perfusion parameters in adults experiencing an acute large vessel occlusion, but this has never been investigated in the pediatric and young adult populations.

Methods: We queried the United States RAPID Insights database (10/05/2018-09/29/2023) for unique patients between 2 and 25 years with computed tomography perfusion (CTP). Included scans had a minimum ischemic core volume (rCBF <30 %) of >0 cc and a Tmax volume of >0 cc. Intracerebral hemorrhage cases were excluded. Anterior circulation large vessel occlusion cases were segregated and reported separately. Imaging time was subdivided into three epochs: Night (23:00 h-06:59 h), Day (07:00 h-14:59 h), and Evening (15:00 h-22:59 h). Age was analyzed by pre-defined strata: 2-5, 6-11, 12-18, and 19-25 years. Perfusion parameters were stratified by age and time epochs. We used non-parametric testing for variables with non-normal distributions.

Results: We included 2415 CTP scans, with 307 identified as LVO. There were 637 patients 18 or younger, with 85 LVOs. In the overall cohort, LVOs had higher penumbral volumes (75.0 cc [25.0-156.0] vs 26.0 cc [8.0-78.0], p < 0.0001) and mismatch volumes (54.0 cc [18.0-120.0] vs 21.0 cc [7.0-62.0], p < 0.0001). In the LVO subgroup, there was a trend towards higher mismatch volumes at night (58.0 cc [IQR 19.5-139.8]) compared to evening (50.0 cc [IQR 18.8-114.3]) or daytime (55.0 cc [17.0-126.0]), but these differences were not significant (p = 0.72).

Conclusion: Contrary to reports in adults, we did not find a clear association between time of day and cerebral perfusion parameters among pediatric and young adult patients.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune mediated demyelinating neuropathy that can lead to secondary axonal degeneration and irreversible weakness and disability. Early effective treatment is therefore necessary to minimize the degree of axonal degeneration. Prior to 2024 the only FDA approved therapy for CIDP was intravenous immunoglobulin (IVIg). In 2024, efgartigimod (Vyvgart-Hytrulo), a FCRn inhibiting therapy (FIT) was approved for treatment of CIDP based on the phase II Adhere study. In the controlled setting of the phase II clinical study patients who were stable on IVIg were taken off treatment to ensure that their disease was active, and patients who worsened were then treated with efgartigimod. The responders were then randomized (in phase B) to either placebo or continued efgartigimod treatment. In the real world setting it is not feasible to stop IVIg and let patients worsen before starting a FIT, thus the transition from IVIG to efgartigimod in a real world setting was not studied in the pivotal trial. We have treated nine patients with FIT in our practice and report findings of four of those patients who had severe relapse of CIDP after treatment. Five of the other patients neither improved nor declined with FIT. This raises questions about the issues related to transitioning patients from IVIG to efgartigimod.

Background: Neuronal ceroid lipofuscinoses (NCLs) are progressive, autosomal recessive lysosomal storage disorders primarily affecting children, marked by seizures, cognitive decline, motor regression, and visual impairment. Limited genetic data exist for South Asian populations, with most studies relying on enzymatic assays or electron microscopy. This study explores the genetic spectrum of NCL and genotype-phenotype correlations in a cohort from South India.

Methods: A retrospective analysis was conducted on 56 genetically confirmed NCL patients diagnosed between January 2018 and June 2024 at a specialized neurological center in South India. Genetic analysis using next-generation sequencing (NGS) were performed, with variants classified as per ACMG guidelines. Clinical, electroencephalographic (EEG), imaging, and electron microscopy (EM) findings were reviewed, and genotype-phenotype correlations were analyzed.

Results: The cohort (33 males, 23 females) had a median age of onset of 36 months and a median disease duration of 65.5 months. Eight genetic subtypes were identified, with predominant mutations in TPP1 (19.64%), CLN6, MFSD8, and CLN8 (16.07% each). Seizures (75%), regression of milestones (87.5%), visual impairment (33.9%), and ataxia (57.1%) were common. EEG abnormalities were found in 76.3%, MRI revealed cerebellar atrophy in 89.13%, and thalamic T2 hypo-intensity in 91.3%. EM showed curvilinear and fingerprint profiles. Of the identified variants, 31 were previously reported, while 29 were novel.

Conclusion: This is the largest single-center NCL cohort in South Asia, highlighting a diverse genetic spectrum and significant novel variants, underscoring the importance of genetic testing for diagnosis and future therapies.

This review critically examines neuro-palliative care disparities in historically minoritized groups in the U.S., particularly in Asian, Black, and Latino communities. Addressing a gap in the 2022 American Academy of Neurology guidelines, this review synthesizes current literature and our clinical experiences as neurologists who identify as members of these communities in diverse care settings. We identify common barriers to palliative care access and acceptance, influenced by cultural heterogeneity, mistrust, and systemic disparities. The review offers targeted, actionable recommendations at the provider, healthcare system, and policy level to improve care and reduce disparities.