BMC Neurology最新文献

Background: Hemophagocytic lymphohistiocytosis (HLH) is an inherited syndrome characterized by immune dysregulation. Central nervous system (CNS)-isolated disease is a rare presentation of familial HLH. We present a case of pediatric CNS-isolated HLH with a presentation complicated by unusual hemorrhagic intraparenchymal lesions.

Case presentation: A 15-year-old male presented with ataxia and MRI findings of multiple hemorrhagic lesions in his cerebral white matter, brainstem, and cerebellum, suggestive of vasculitis. After failing to improve with steroids and plasmapheresis, and progression to acute neurologic decompensation, new brainstem hemorrhages were noted. Further workup revealed 2 PRF1 mutations, confirming a diagnosis of familial CNS-HLH. He was later found to have a platelet granule defect, explaining his atypical neuroradiologic findings. The patient received treatment per the HLH-1994 protocol and underwent stem cell transplantation. Two years post-transplant, his perforin expression is nearly normal and his neurologic deficits have significantly improved.

Conclusions: This case illustrates the variability in presentation of isolated CNS-HLH. Although rare, it is important to include this diagnosis on the differential in patients with CNS hemorrhagic lesions. If initial diagnostic studies remain inconclusive or response to early treatments is poor, CNS-HLH should be considered, as delay in diagnosis and treatment significantly affects morbidity and mortality.

Determining the genetic contributions to Parkinson's disease (PD) across diverse ancestries is a high priority as this work can guide therapeutic development in a global setting. The genetics of PD spans the etiological risk spectrum, from rare, highly deleterious variants linked to monogenic forms with Mendelian patterns of inheritance, to common variation involved in sporadic disease. A major limitation in PD genomics research is lack of racial and ethnic diversity. Enrollment disparities have detrimental consequences on the generalizability of results and exacerbate existing inequities in care. The Black and African American Connections to Parkinson's Disease (BLAAC PD) study is part of the Global Parkinson's Genetics Program, supported by the Aligning Science Across Parkinson's initiative. The goal of the study is to investigate the genetic architecture underlying PD risk and progression in the Black and/or African American populations. This cross-sectional multicenter study in the United States has a recruitment target of up to 2,000 individuals with PD and up to 2,000 controls, all of Black and/or African American ancestry. The study design incorporates several strategies to reduce barriers to research participation. The multifaceted recruitment strategy aims to involve individuals with and without PD in various settings, emphasizing community outreach and engagement. The BLAAC PD study is an important first step toward informing understanding of the genetics of PD in a more diverse population.

Background: Our intent was to explore the mediating role of interstitial free water (FW) linking deep medullary vein (DMV) score to white matter hyperintensity (WMH) volume.

Methods: Our research team conducted a forward-looking analysis of initial clinical and imaging information gathered from 125 patients with cerebral small vessel disease. We identified six anatomic DMV regions on susceptibility weighted imaging (SWI) studies. Each region earned a score of 0-3, determined by the visual conditions of vessels, summing all six to generate a DMV score. We utilized fluid-attenuated inversion recovery (FLAIR) sequences to measure the volume of WMH. Additionally, we employed diffusion tensor imaging (DTI) to assess FW value.

Results: DMV score significantly positively correlated with FW value and with WMH volume (p < 0.05), and value of FW positively correlated with WMH volume (p < 0.05). The indirect effect of DMV score on WMH volume was mediated by FW (β = 0.281, 95% confidence interval [CI]: 0.178-0.388), whether adjusted for age and gender (β = 0.142, 95% CI: 0.058-0.240) or for age, gender and vascular risk factors (β = 0.141, 95% CI: 0.054-0.249).

Conclusion: DMV score correlate with WMH volume by virtue of FW increases in white matter.

Background: Increased intracranial pressure (ICP) in patients with idiopathic intracranial hypertension (IIH) affects the retinal microvasculature, which can be imaged and quantified by optical coherence tomography angiography (OCTA). We aimed to identify the mediating factor between ICP and OCTA parameters association in IIH patients.

Methods: IIH patients with active intracranial hypertension were enrolled. OCTA imaging was performed after ICP measurement. We quantified the branching complexity of the retinal arterioles and venules from the superficial vascular complex of the OCTA image. Eyes of IIH patients were stratified into eyes with papilledema (IIH-P) and eyes without papilledema (IIH-WP). All participants underwent visual acuity (VA) examination.

Results: One hundred and thirty-eight eyes from 70 IIH patients and 146 eyes from 73 controls were included. Compared to the control group, IIH patients and IIH-P had reduced arteriole complexity and increased venule complexity (p < 0.05). For IIH patients and IIH-P, increased retinal venule complexity correlated with increased ICP and reduced VA (p < 0.05); while decreased arteriole complexity only correlated with Frisen scores (p = 0.026). Papilledema mediated the effect (p < 0.001) between ICP and arteriole complexity while ICP had a direct effect (p < 0.001) on venule complexity.

Conclusion: Retinal venules imaged via OCTA may reflect ICP levels and may underpin the direct effect of increased ICP in IIH patients.

Background: Chronic overlapping pain conditions (COPCs), pain-related conditions that frequently occur together, may occur in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and could impact illness severity. This study aimed to identify comorbid COPCs in patients with ME/CFS and evaluate their impact on illness severity.

Methods: We used data from 923 participants in the Multi-Site Clinical Assessment of ME/CFS study, conducted in seven U.S. specialty clinics between 2012 and 2020, who completed the baseline assessment (595 ME/CFS and 328 healthy controls (HC)). COPCs included chronic low back pain (cLBP), chronic migraine/headache (cMHA), fibromyalgia (FM), interstitial cystitis/irritable bladder (IC/IB), irritable bowel syndrome (IBS), temporomandibular disorder (TMD). Illness severity was assessed through questionnaires measuring symptoms and functioning. Multivariate analysis of variance and analysis of covariance models were used for analyses. Log-binomial regression analyses were used to compute prevalence of COPCs and prevalence ratios (PR) between groups with 95% confidence intervals. Both unadjusted and adjusted results with age and sex are presented.

Results: 76% of participants with ME/CFS had at least one COPCs compared to 17.4% of HC. Among ME/CFS participants, cMHA was most prevalent (48.1%), followed by FM (45.0%), cLBP (33.1%), and IBS (31.6%). All individual COPCs, except TMD, were significantly more frequent in females than males. The unadjusted PR (ME/CFS compared to HC) was highest for FM [147.74 (95% confidence interval (CI) = 20.83-1047.75], followed by cLBP [39.45 (12.73-122.27)], and IC/IB [13.78 (1.88-101.24)]. The significance and order did not change after age and sex adjustment. The COPC comorbidities of cLBP and FM each had a significant impact on most health measures, particularly in pain attributes (Cohen's d effect size 0.8 or larger). While the impact of COPC comorbidities on non-pain attributes and quality of life measures was less pronounced than that on pain, statistically significant differences between ME/CFS participants with and without COPCs were still evident.

Conclusions: More than 75% of ME/CFS participants had one or more COPCs. Multiple COPCs further exacerbated illness severity, especially among females with ME/CFS. Assessment and management of COPCs may help improve the health and quality of life for patients with ME/CFS.

Background: Anti-dopamine receptor 2 (D2R) antibody encephalitis (D2R encephalitis) is a subtype of autoimmune encephalitis (AE). Lesions in affected patients primarily involve the basal ganglia, resulting in a range of psychiatric and movement disorders. A majority of cases reported to date have impacted children or adolescents, whereas we here describe a case of adult-onset D2R encephalitis.

Case presentation: A 30-year-old female patient affected by insomnia, recent memory impairment, bradykinesia, decreased responsivity, increased muscular tone of the extremities, and involuntary shaking of the right limb. Magnetic resonance imaging (MRI) of the basal ganglia did not reveal any notable findings, and both serum and cerebrospinal fluid were positive for antibodies specific for D2R. D2R encephalitis was diagnosed following the exclusion of other diseases. The patient's symptoms improved significantly with immunotherapeutic treatment, and she recovered fully over a 6-month follow-up period.

Conclusions: D2R is a new form of AE that can develop in adults and can be effectively treated via immunotherapy.

Background: Walking impairment after stroke is associated with substantial limitations in functional independence, quality of life, and long-term survival. People in the subacute phase after stroke who are unable to walk are most likely to benefit the greatest from use of overground robotic gait training (RGT). This study will provide preliminary evidence regarding the clinical use and efficacy of RGT during the subacute phase of stroke recovery as well as observational findings associated with the safety, tolerability, feasibility, and cost of delivering RGT during inpatient stroke rehabilitation.

Methods: This prospectively registered randomized controlled trial will enroll 54 patients admitted to inpatient rehabilitation within six months of stroke. Admitted patients will be screened at admission to inpatient rehabilitation for eligibility. Consented patients will be randomized based on stroke severity to receive either RGT or usual care for 90 minutes per week of gait training intervention during inpatient rehabilitation length of stay. Patients will complete assessments on walking and health outcomes at admission and discharge from inpatient rehabilitation and at 1- and 3-month follow-up. Intent-to-treat and per protocol analysis will be performed to evaluate safety [rate of adverse events, visual analog scale, and treatment completion rate], walking function [gait speed via 10-Meter Walk Test, Functional Ambulation Category, gait endurance via 6-Minute Walk Test] and health outcomes [Modified Rankin Scale, Stroke Rehabilitation Assessment of Movement, Continuity Assessment Record and Evaluation Tool, 5 Times Sit-to-Stand Test, Berg Balance Scale, and Stroke Impact Scale-16], and cost-analysis.

Discussion: This study will provide foundational evidence regarding the clinical use and efficacy of a RGT program during the subacute phase of stroke recovery with specific findings associated with the safety, tolerability, feasibility, and cost-analysis of delivering RGT during inpatient stroke rehabilitation.

Trial registration: NCT06430632.

Background: Synaptic degeneration, axonal injury, and white matter disintegration are among the pathological events in Alzheimer's disease (AD), for which growth-associated protein 43 (GAP-43) and diffusion tensor imaging (DTI) could be an indicator. In this study, the cerebrospinal fluid (CSF) GAP-43 clinical trajectories and their association with progression and AD hallmarks with white matter microstructural changes were evaluated.

Methods: A total number of 133 participants were enrolled in GAP-43 and DTI values were compared between groups, both cross-sectionally and longitudinally with two and four-year follow-ups. Subsequently, the correlation between GAP-43 levels in the CSF and DTI values was investigated using Spearman's correlation.

Results: The CSF level of GAP-43 is negatively correlated with the mean diffusivity measures in Fornix (Cres)/Stria terminals in early and late MCI (r_s=-0.478 p = 0.021 and r_s=-0.425 p = 0.038). Additionally, the CSF level of GAP-43 is negatively correlated with fractional anisotropy in the cingulum in late MCI (r_s=-0.437 p = 0.033). Moreover, the axial diffusivity in superior corona radiate (r_s=-0.562 p = 0.005 and r_s=-0.484 p = 0.036) and radial diffusivity in superior fronto-occipital fasciculus was negatively correlated with GAP-43 level in the early and mid-MCI participants (r_s=-0.520 p = 0.011 and r_s=-0.498 p = 0.030).

Conclusions: Presynaptic marker GAP-43 in combination with DTI can be used as a novel biomarker to identify microstructural synaptic degeneration in the early MCI. In addition, it can be used as a biomarker for tracking the progression of AD and monitoring treatment efficacy.

Background: Congenital agenesis of internal carotid artery (ICA) is a rare cerebrovascular variation entity. Most cases of congenital ICA agenesis are asymptomatic and discovered incidentally. Congenital ICA agenesis presenting as ischemic stroke is even rare.

Case presentation: An 80-year-old male patient was admitted to our hospital due to sudden dysarthria and left limb weakness for 3.5 h. Based on emergency physical examination and head computed tomography (CT) scan results, acute ischemic stroke (AIS) of right cerebral hemisphere was suspected. Following intravenous thrombolysis with recombinant tissue plasminogen activator, right congenital agenesis of ICA was confirmed by CT and digital subtraction angiography. Additionally, there was a severe right vertebral artery ostial (VAO) stenosis. After ruling out common causes of AIS such as haematological diseases, arterial dissection, organic heart disease, immunological abnormality and underlying possible malignancies, we hypothesize that the severe stenosis of the right VAO may have contributed to the development of AIS in this case.

Conclusions: We present a case of right congenital ICA agenesis in which severe stenosis of the right VAO may have played a role in the development of AIS. This case underscores a rare scenario where a lesion in the posterior circulation leads to an infarction in the anterior circulation in the setting of congenital ICA agenesis.