Neurology最新文献

Background and objectives: NOTCH2NLC-related neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease with characteristic white matter lesions (WMLs) visible on MRI. However, the distribution of WMLs and their clinical correlations remain poorly understood in NIID. This study aims to investigate the spatial and temporal distribution of WMLs in the brain of patients with NOTCH2NLC-related NIID.

Methods: We retrospectively evaluated patients diagnosed with NOTCH2NLC-related NIID in Zhongshan Hospital, Fudan University. Detailed clinical information, including retrospective MRI data, was collected. Spatial distribution of WMLs with fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) hyperintensities was quantified, and the relationship between WML distribution and clinical presentations was analyzed by the Fisher exact test. The volume of whole-brain WMLs was quantified using ITK-SNAP software. The relationship between phenotypes and WML volume was analyzed by the Student t test, Mann-Whitney test, or correlation analysis. WML development patterns were summarized based on the longitudinal observation of MRI characteristics.

Results: This study evaluated 45 patients with NOTCH2NLC-related NIID, with a median age of 66 years (range 55-82 years) and consisting of 30 women. Patients exhibited diverse clinical manifestations, with cognitive decline, autonomic dysfunction, and tremor being the 3 most frequent presentations. Severe WMLs were observed in 43 patients, with FLAIR hyperintensities predominantly in the corona radiata, centrum semiovale, and other brain regions. The presence of DWI hyperintensities was common in the corticomedullary junction (91.1%) and corpus callosum (53.3%). Analysis showed significant correlations between FLAIR hyperintensity volume and both age (r = 0.312, p = 0.042) and Montreal Cognitive Assessment scores (r = -0.371, p = 0.048). Longitudinal MRI retrospection in 7 patients over an average of 9.6 ± 2.9 years revealed 3 gradually progressed WML patterns: periventricular-subcortical, periventricular-dominant, and corticomedullary junction-dominant. In addition, 3 patients experienced rapid WML expansion associated with mitochondrial encephalomyopathy with lactic acidosis and stroke (MELAS)-like episodes.

Discussion: Our analysis revealed the radiologic characteristics and spatial distribution of WMLs and demonstrated significant correlations between FLAIR hyperintensity volume and age/cognitive levels in NIID. Long-term retrospection revealed 3 types of gradual WML expansion patterns while MELAS-like episodes cause rapid WML aggravation. Although results should be confirmed in a larger cohort, these insights enhance understanding of NIID's clinical-radiologic relationships and pathogenesis.

Background and objectives: Sex steroid hormones have been demonstrated to affect the immune system in multiple sclerosis (MS), and puberty may trigger MS activity. We aimed to evaluate the association between menarche and disease course in pediatric MS through comparison of relapse rates across premenarche, perimenarche, and postmenarche periods.

Methods: This is a retrospective analysis of a prospectively followed female cohort with pediatric-onset MS in the US Network of Pediatric MS Centers database. Perimenarche was considered the period from 1 year before to 1 year after the estimated menarche date based on menarche integer age. Relapses were collected prospectively. Negative binomial and repeated-measures Cox regression models were used to assess the association of pubertal development stage with relapse rate, adjusted for race, body mass index, and disease-modifying therapy (DMT).

Results: Of 736 participants (all female; mean onset age 14.4 ± 2.8 years; mean menarche age 11.6 ± 1.4 years), onset was in premenarche in 73, perimenarche in 112 (± 1 year of menarche), and postmenarche in 551. The median time of MS onset was 2.8 years after menarche. Most (86%) were exposed to DMT in follow-up. In adjusted negative binomial analysis, the annualized relapse rate during premenarche was 0.43, perimenarche was 0.65, and postmenarche was 0.43 (premenarche rate ratio [RR] 1.00 (95% CI 0.70-1.43) and perimenarche RR 1.52 (95% CI 1.16-1.99), compared with reference of postmenarche, p = 0.0049. In adjusted repeated-events Cox regression analysis, there was increased hazard to relapse in perimenarche and postmenarche compared with premenarche (perimenarche hazard ratio [HR] 1.78 [95% CI 1.17-2.70] and postmenarche HR 1.67 [95% CI 1.12-2.50], compared with reference of premenarche, p = 0.025). In this analysis, use of oral and infusion DMTs significantly lowered the relapse hazard compared with periods of no DMT use (injectable HR 0.98 [95% CI 0.83-1.15], oral HR 0.48 [95% CI 0.37-0.61], and infusion HR 0.24 [95% CI 0.18-0.31], compared with no DMT, p < 0.001).

Discussion: Onset of puberty may be a time of increase in disease activity and may require consideration of a change in therapeutic approach. Menarche age was used as a surrogate for puberty, and future studies measuring sex steroid hormones may be informative.

True seronegativity is extremely rare in Lyme neuroborreliosis (LNB) with reports only in patients with hematological malignancies or under treatment with chemotherapy and B-cell depleting therapies. In these instances, diagnosing LNB can be challenging. We report the case of a 63-year-old patient with 2 independent episodes of LNB. During the first episode with lymphocytic meningitis, anti-borrelial IgG and IgM were detected in serum and CSF. However, initial seropositivity converted to seronegative serum at 8 months of follow-up and remained seronegative during a second episode of LNB while on B-cell depleting treatment for multiple sclerosis. During this second episode, the patient reported painful meningoradiculoneuritis (Bannwarth syndrome), yet no anti-borrelial antibodies could be detected in serum or CSF. Borrelial PCR was positive in CSF, leading to the diagnosis of LNB. Symptoms resolved after antibiotic treatment. Cases of seronegative LNB can occur in the context of B-cell depleting agents. Standard antibiotic treatment is successful for LNB in the context of immunosuppressive treatment. Further diagnostic investigations with PCR or CXCL13 should be considered in cases with high clinical suspicion.

Since its introductory characterization by Kussmaul and Maier in 1866, the understanding of vasculitis has evolved significantly. Modern classification systems provide clear clinical and histopathologic definitions. Although early vasculitis cases likely included neuromuscular involvement, specific clinicopathologic descriptions of nerve vasculitis were lacking. We present early clinicopathologic descriptions of vasculitic neuropathy, as reported by the German physician Oskar Minkowski (1858-1931) and the French physicians Alix Joffroy (1844-1908) and Charles Achard (1860-1944).

Background and objectives: People with epilepsy are at risk of cardiac arrhythmias. Whether this association results from epilepsy, antiseizure medications (ASMs) such as sodium channel blockers (NABs), or other factors has not been systematically assessed. The aims of this study were to quantify the odds of cardiac conduction delays (CCDs) on electrocardiogram in older people with active epilepsy using vs not using NABs, to determine the prevalence of CCDs by NABs, and to examine the association of demographic and clinical factors with CCDs.

Methods: This was a cross-sectional study of the Canadian Longitudinal Study on Aging. We defined active epilepsy as self-reported epilepsy and taking ASM. Sodium channel blockers (NABs) were phenytoin, lamotrigine, carbamazepine, oxcarbazepine, or lacosamide. We compared CCDs between people with epilepsy using NABs and those not using NABs; determined the prevalence of CCDs by NAB type; and fitted a logistic regression model for each abnormal ECG outcome as a function of active epilepsy and NAB use while adjusting for demographics and clinical factors. Multiple imputations handled missing data (200 iterations).

Results: In total, 30,077 people, with mean age 63.0 (10.25) years and 50.9% female, were studied, including 141 people with active epilepsy who used NABs, 68 who did not use NABs, and 29,868 who did not have active epilepsy. Demographics between groups and relative to people without epilepsy were similar. People with active epilepsy taking NABs were more likely to have prolonged QRS (odds ratio [OR] = 2.85 [95% CI 1.09-7.43]) and any CCD (1.94 [1.03-3.63]) compared with those with active epilepsy without NAB. After adjusting for Framingham score and heart rate-lowering medications, NAB use was associated with prolonged QTc (OR = 1.52 [95% CI 1.06-2.18]) and any CCD (1.78 [1.16, 2.74]). The prevalence of any CCD was 36.1% [95% CI 24.2%-49.4%] for carbamazepine, 45.5% [31.7%-58.5%] for phenytoin, and 54.7% [28.9%-75.6%] lamotrigine. Epilepsy was not associated with any CCD.

Discussion: People with active epilepsy using NABs more commonly have CCDs. NAB use is associated with CCD, whereas active epilepsy is not.