Journal of the Neurological Sciences最新文献

Background

The Myasthenia Gravis–Activities of Daily Living scale (MG-ADL) is an 8-item outcome measure to assess symptoms and functional limitations in myasthenia gravis (MG) patients. The MG-ADL score is an equally weighted level sum score that is used as primary outcome measures in clinical trials, in clinical practice, and as an end-point in health economic evaluation. This data analysis aims to obtain detailed knowledge of measurement properties of MG-ADL items and the MG-ADL score.

Methods

Cross-sectional data from a real-world prospective study (MRW) were combined with longitudinal data from the ADAPT trial. Outcome measures included were MG-ADL, Quantitative Myasthenia Gravis score (QMG), MG 15-item Quality of Life (MG-QOL15r) and EQ-5D-5L. Patients were categorized by their Myasthenia Gravis Foundation of America (MGFA) clinical classification. The following measurement properties were assessed: distributional characteristics, inter-item correlation, convergent, known groups and construct validity and internal factor structure.

Results

Correlations of items within MG-ADL dimensions were moderate, while MG-ADL correlations between comparable MG-QOL15r and QMG items were mixed. Known groups validity for the MG-ADL score was demonstrated for MGFA class. Mean MG-ADL item level scores by MGFA class demonstrated construct validity. PCA, including all four outcome measures, resulted in a nine factor solution.

Discussion

Psychometric properties of individual MG-ADL items were moderate to good. This study showed that the MG-ADL adequately captures the multidimensional heterogeneous nature of MG. This is, however, accompanied by mixed psychometric performance of the MG-ADL score, which may complicate health economic modelling.

Registration: MyRealWorld-MG was registered on November 25, 2019, with registration number NCT04176211. The ADAPT randomized clinical trial is registered at ClinicalTrials.gov (NCT03669588).

Background

The presence of inflammatory changes in the cerebrospinal fluid (CSF), including immunoglobulin intrathecal synthesis (IS), can support the diagnosis of autoimmune encephalitis (AE) and allow prompt treatment. The main aim of our study was to calculate the Kappa index as a marker of IS, in patients with AE.

Methods

Charts of patients undergoing a diagnostic work-up for suspected AE between 2009 and 2023 were reviewed and the Graus criteria applied. CSF and serum kappa free light chains were determined using the Freelite assay (The Binding Site Group) and the turbidimetric Optilite analyzer.

Results

We identified 34 patients with “definite” AE (9 anti-NMDAR AE and 25 limbic AE) and nine patients with “possible” AE. Five patients (15%) with definite AE had pleocytosis and twelve (34%) showed CSF-restricted oligoclonal bands (OCB) at isoelectric focusing. The Kappa index was >6 in 29.4% and > 3 in 50% of the definite AE patients. It was elevated (>3) in 36.4% of patients with definite AE who resulted negative to OCB testing and was the only altered parameter suggestive of an ongoing inflammatory process in the CNS in three definite AE patients with otherwise normal CSF findings (i.e. normal cell count and protein levels, no OCBs). In the possible AE group, one patient had a Kappa index >3 in the absence of OCB.

Conclusions

The Kappa index could be useful, as a more sensitive marker of IS and as a supportive marker of neuroinflammation, in the diagnostic work-up of suspected AE.

Objective

The COVID-19 pandemic extensively changed the United States residency application process, including transitioning interviews from in-person to virtually. This study aims to determine the effect of a neurology residency programs' social media presence on applicants and to identify aspects of the program's social media profile influencing students' decisions to apply.

Methods

This is an observational cross-sectional study of neurology residency applicants utilizing a 10-question survey distributed from October 2022 to March 2023. 115/176 (65%) applicants participated. Statistical tests were performed using SPSS Statistics. Categorical variables were presented as percentages of the total group. Categorical Likert Scale responses were assigned numerical values from one to five and presented as means.

Results

Most participants (87.8%) used social media to learn about neurology residency programs. Most participants (52.5) used both Instagram and X (formerly Twitter). Prominent factors affecting program selection were the number of posts and format, layout, or aesthetics of the social media profile. The most influential posts pertained to program culture, with the least influential posts highlighting specific residents. Social media presence had a small-moderate effect on selecting programs for application, and a small effect on ranking programs.

Conclusion

Overall, social media profiles have a small to moderate impact on the decision to apply to a specific neurology program, with less effect on the ranking process. These findings can assist residency programs in tailoring social media presence to better align with the preferences of applicants.

Introduction

Smartphone applications (apps) are instruments that assist with objective measurements during the clinical assessment of patients with movement disorders. We aim to test the hypothesis that Parkinson's disease (PD) patients will exhibit an increase in tapping variability and a decrease in tapping speed over a one-year period, compared to healthy controls (HC).

Methods

Data was prospectively collected from participants enrolled in our Cincinnati Cohort Biomarker Program, in 2021–2023. Participants diagnosed with PD and age-matched HC were examined over a one-year-interval with a tapping test performed with customized smartphone app. Tapping speed (taps/s), inter-tap intervals and variability (movement regularity), and sequence effect were measured.

Results

We included 295 PD patients and 62 HC. At baseline, PD subjects showed higher inter-tap variability than HC (coefficient-of-variation-CV, 37 ms [22–64] vs 26 ms [8–51]) (p = 0.007). Conversely, there was no difference in inter-tap intervals (411 ms [199–593] in PD versus 478 ms [243–618] in HC) and tapping speed (3.42[2.70–4.76] taps/s in PD versus 3.21 taps/s [2.57–4.54] in HC) (p > 0.05). Only PD subjects (n = 135), at the one-year follow-up, showed a decreased tapping speed vs baseline (3.44 taps/s [2.86–4.81] versus 3.39 taps/s [2.58,4.30]) (p = 0.036), without significant changes in inter-tap variability (CV, 32 ms [18,55] baseline versus 34 ms [22,59] follow-up) (p = 0.142). No changes were found in HC at the one-year follow up (all p values>0.05).

Conclusions

Inter-tap variability (dysrhythmia) but no inter-tap intervals or tapping speed are reliably distinctive feature of an app-based bradykinesia assessment in PD.

Patients with amyotrophic lateral sclerosis (ALS) do not develop oculomotor disturbances and vesicorectal dysfunction until end-stage disease owing to the survival of certain motor neurons (MNs), including oculomotor neurons and MNs within Onuf's nucleus. In sporadic ALS, adenosine deaminase acting on RNA 2 (ADAR2)-mediated editing of GluA2 mRNA at the Q/R site is compromised in lower MNs. We previously developed genetically modified mice with a conditional knockout of ADAR2 in cholinergic neurons (ADAR2^flox/flox/VAChT-Cre, Fast; AR2). These mice displayed slow and progressive lower motor neuron death with TAR DNA-binding protein 43 (TDP-43) pathology, attributable to insufficient editing at the GluA2 Q/R site due to ADAR2 deficiency. MN death was more common in fast-fatigable MNs owing to differential vulnerability under conditions of ADAR2 deficiency. Although facial and hypoglossal nerves were impaired in AR2 mice, cell death did not occur within the oculomotor nerve nucleus, as observed in patients with sporadic ALS. Since the basis for avoiding cystorectal damage in ALS is unknown, we compared the features of Onuf's nucleus MNs in 12-month-old AR2 mice with those in age-matched wild-type mice. Although the number of MNs was not significantly lower in AR2 mice, the neurons exhibited a shrunken morphology and TDP-43 pathology. Onuf's nucleus MNs could survive in an ADAR2-deficient state and mainly included fast fatigue-resistant (FR) and slow (S) MNs. In summary, FR and S MNs show increased resilience to ADAR2 deficiency, potentially participating in an important neuronal death avoidance mechanism in ALS.

Background

Guillain-Barré Syndrome (GBS) can lead to significant functional impairments, yet little is understood about the recovery phase and long-term consequences for patients in low- and medium-income countries.

Objective

To evaluate the functional status and identify factors influencing outcomes among patients with GBS in Colombia.

Methods

Telephone interviews were conducted with GBS patients enrolled in the Neuroviruses Emerging in the Americas Study between 2016 and 2020. The investigation encompassed access to health services and functional status assessments, utilizing the modified Rankin Scale (mRS), GBS Disability Score (GDS), Barthel Index (BI), and International Classification of Functioning (ICF). Univariate analysis, principal component analysis, linear discriminant analysis, and linear regression were employed to explore factors influencing functional status.

Results

Forty-five patients (mean age = 50[±22] years) with a median time from diagnosis of 28 months (IQR = 9–34) were included. Notably, 22% and 16% of patients did not receive rehabilitation services during the acute episode and post-discharge, respectively. Most patients demonstrated independence in basic daily activities (median BI = 100, IQR = 77.5–100), improvement in disability as the median mRS at follow-up was lower than at onset (1 [IQR = 0–3] vs. 4.5 [IQR = 4–5], p < 0.001), and most were able to walk without assistance (median GDS = 2, IQR = 0–2). A shorter period from disease onset to interview was associated with worse mRS (p = 0.015) and ICF (p = 0.019). Negative outcomes on GDS and ICF were linked to low socioeconomic status, ICF to the severity of weakness at onset, and BI to an older age.

Conclusions

This study underscores that the functional recovery of GBS patients in Colombia is influenced not only by the natural course of the disease but also by socioeconomic factors, emphasizing the crucial role of social determinants of health.

Background

Multiple sclerosis (MS) is a complex disease with substantial heritability estimates. Besides typical clinical manifestations such as motor and sensory deficits, MS is characterized by structural and functional brain abnormalities, and by cognitive impairment such as decreased working memory (WM) performance.

Objectives

We investigated the possible link between the polygenic risk for MS and WM performance in healthy adults (18–35 years). Additionally, we addressed the relationship between polygenic risk for MS and white matter fractional anisotropy (FA).

Methods

We generated a polygenic risk score (PRS) of MS susceptibility and investigated its association with WM performance in 3282 healthy adults (two subsamples, N₁ = 1803, N₂ = 1479). The association between MS-PRS and FA was studied in the second subsample. MS severity PRS associations were also investigated for the WM and FA measurements.

Results

MS-PRS was significantly associated with WM performance within the 10% lowest WM-performing individuals (p = 0.001; p_FDR = 0.018). It was not significantly associated with any of the investigated FA measurements. MS severity PRS was significantly associated with brain-wide mean FA (p = 0.041) and showed suggestive associations with additional FA measurements.

Conclusions

By identifying a genetic link between MS and WM performance this study contributes to the understanding of the genetic complexity of MS, and hopefully to the possible identification of molecular pathways linked to cognitive deficits in MS. It also contributes to the understanding of genetic associations with MS severity, as these associations seem to involve distinct biological pathways compared to genetic variants linked to the overall risk of developing MS.

Objectives

Target localization for deep brain stimulation (DBS) is a crucial step that influences the clinical benefit of the DBS procedure together with the reduction of side effects. In this work, we address the feasibility of DBS target localization in the globus pallidus internus (GPi) aided by intraoperative motor evoked potentials (MEP) with emphasis on the reduction of capsular side effects.

Material and methods

Micro-macroelectrode recordings were performed intraoperatively on 20 patients that underwent DBS treatment of the GPi (GPi-DBS). MEP were elicited intraoperatively by microelectrode stimulation during stereotactic DBS surgery. We studied the relationship between MEP thresholds and the internal capsule (IC) proximity.

Results

We found a significant correlation between intraoperative MEP thresholds and IC proximity.

Conclusions

We provide further evidence of the role of MEPs for DBS target localization in the GPi, which extends and confirms the usefulness of MEPs as previously reported by DBS target localization studies dealing with the subthalamic and thalamic nuclei. Our approach is advantageous in that it provides criteria to determine the DBS target without the need to rely on a patient's response while avoiding capsular effects.