Journal of Neurology最新文献

Introduction: The current literature on the prevalence and potential association between disease-modifying therapies (DMTs) and cancer risk in the MS population has yielded mixed findings.

Methods: This study aimed to estimate cancer prevalence and cancer risk in patients with MS (PwMS) under prolonged DMT exposure. Database search include: MEDLINE PUBMED, SCOPUS, and Google Scholar.

Results: A total of 13 studies involving 333,779 PwMS were included, reporting cancer events over periods ranging from 6 to 32 years. The aggregated pooled prevalence of cancer events in MS patients receiving disease-modifying therapies (DMTs) was 3.8% (95% CI 2.6, 5.2%), with substantial heterogeneity (I² = 99.7%, p = 0). Two studies compared cancer events in MS patients who received DMTs versus those who did not. The relative risk of cancer associated with DMTs was 0.8 (95% CI 0.59-1.31, I² = 93.6%, p = 0.53), indicating no significant increase in cancer risk due to DMTs. Breast and basal cell carcinomas had a high prevalence (18.4% and 11.3, respectively) in PwMS under DMTs.

Conclusion: This study reports a 3.8% pooled prevalence of cancer in PwMS receiving DMTs. The findings of this study suggest that DMTs alone do not increase cancer risk in PwMS. Breast cancer and basal cell carcinoma had the highest prevalence among the different types of cancer.

Fluid biomarkers play important roles in many aspects of neurodegenerative diseases, such as Huntington's disease (HD). However, a main question relates to how well levels of biomarkers measured in CSF are correlated with those measured in peripheral fluids, such as blood or saliva. In this study, we quantified levels of four neurodegenerative disease-related proteins, neurofilament light (NfL), total tau (t-tau), glial fibrillary acidic protein (GFAP) and YKL-40 in matched CSF, plasma and saliva samples from Huntingtin (HTT) gene-positive individuals (n = 21) using electrochemiluminescence assays. In addition, salivary levels of NfL, t-tau, and GFAP were quantified from a larger cohort (n = 95). We found both positive and negative correlations in the levels of these biomarkers among different biofluids. Most notably, in contrast to the significant positive correlations observed between CSF and plasma levels for NfL and GFAP, we detected significant negative correlations between the CSF and saliva levels of NfL and GFAP. With regard to clinical measures, both plasma and CSF levels of NfL were significantly positively correlated with Total Motor Score and chorea, whereas saliva levels of NfL showed significant correlations in the opposite direction. Additional correlations between salivary biomarkers with clinical data, adjusting for age, sex and CAG repeat length, confirmed that salivary NfL was significantly negatively associated with chorea scores in manifest HD, but not premanifest (PM), individuals. In contrast, salivary t-tau was positively associated with measures of cognition in PM participants. These findings suggest that salivary levels of NfL and t-tau proteins may exemplify non-invasive biomarkers for disease symptoms at different stages of illness. Further, these findings highlight the notion that different forms of disease proteins exist in different biological fluids.

Positional downbeat nystagmus (pDBN) is a common finding in dizzy patients, with etiologies ranging from benign paroxysmal positional vertigo (BPPV) to central vestibular lesions. Although peripheral pDBN often presents with distinct clinical features that differentiate it from BPPV, diagnosing its etiology can be challenging. A thorough clinical evaluation, including the physical characteristics of the nystagmus, response to positional maneuvers, and neurological findings, is often sufficient to diagnose conditions that provoke pDBN such as anterior canal BPPV, atypical posterior canal BPPV, and central causes. However, when the diagnosis remains uncertain, a brain MRI focusing on the posterior fossa is required. In human lesion models, the vestibulocerebellum (nodulus and uvula) is commonly implicated in pDBN. Central causes of positional vertigo include vascular events, tumors, immune mediated, toxicity, and demyelinating diseases. Ultimately, a significant number of cases will remain without a clear etiology despite extensive workup. Clinicians should be vigilant for signs suggesting central vestibular dysfunction at follow-up in cases of apparently refractory BPPV. The aim of this work is to provide a comprehensive overview of pDBN and offer a logical approach to its assessment, along with recommendations for future research directions.

Background: Conventional medical management, while essential, cannot address all multifaceted consequences of Parkinson's disease (PD). This pilot study explores the potential of a co-designed creative arts therapy on health-related quality of life, well-being, and pertinent non-motor symptoms.

Methods: We conducted an exploratory pilot study with a pre-post design using validated questionnaires. Eight individuals with PD participated in the program. The investigated intervention was a 10-week creative arts therapy with weekly 90-120-min sessions, guided by three creative therapists. Participants were allowed to autonomously select from multiple creative media based on their personal preferences. Explored co-primary outcomes included health-related quality of life (PDQ-39), well-being (ICECAP-A), anxiety/depression (HADS), executive functioning (BRIEF-A), resilience/mental flexibility (FIT-60), and self-efficacy (GSES). We used paired sample t tests for pre-post analysis of the co-primary outcomes and Wilcoxon signed-rank tests for PDQ-39 sub-scores. We also included aesthetic responsiveness (AReA) and healthcare consumption (IMCQ adapted for PD) questionnaires reported as descriptive statistics.

Results: The results showed a significant reduction in anxiety and an increase in well-being. We also observed a slight improvement in cognitive functioning. Finally, we noted a reduction in healthcare consumption (fewer visits at neurologists, specialized PD nurses, and allied healthcare professionals).

Conclusion: These findings cautiously suggest that our co-designed, multi-media creative arts therapy has the potential to increase well-being and reduce anxiety, while reducing healthcare consumption. These preliminary findings support the need for a larger, randomized controlled trial to explore the therapeutic potential of creative arts therapy in PD care.

Background: Huntington's disease (HD) is a rare neurodegenerative disease that causes progressive cognitive, physical, and psychiatric symptoms. Computerised cognitive training (CCT) is a novel intervention that aims to improve and maintain cognitive functions through repeated practice. The effects of CCT have yet to be established in HD. This randomised pilot trial examined the feasibility of a large scale trial to assess efficacy of multidomain CCT in pre-manifest and early-stage HD.

Methods: 28 participants were randomised to either at-home CCT (2 × 60 min sessions per week for 12 weeks; n = 13) or lifestyle education through monthly newsletters (n = 15). Participants completed cognitive tasks and questionnaires at baseline and follow up, either in person (n = 18) or via video teleconferencing (n = 10).

Results: All participants were retained at follow up, and adherence to CCT ranged from 96 to 100%, with 11/13 participants completing all sessions. Preliminary analyses showed evidence of a large effect of CCT on task switching and response inhibition, compared to lifestyle education. There was no evidence of specific benefit to other cognitive domains (processing speed, basic and divided attention, working memory), or psychosocial functions (subjective cognition, mood, health-related quality of life).

Discussion: Whilst retention and adherence rates were high, recruitment rates were low, suggesting that a large scale trial may be feasible with some modifications to increase recruitment rates, such as by reducing time burden associated with the study, and using a multi-site trial design. Potential effects on cognitive functioning warrant further investigation.

Clinical trial registration: The trial was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12622000908730).

Background: The presence of diffuse brain damage in normal-appearing white matter (NAWM) and gray matter (NAGM) in neuromyelitis optica spectrum disorder (NMOSD) remains controversial. We aimed to address this controversy by applying a multiparametric MRI approach. Additionally, the association between MRI metrics and clinical variables was explored.

Methods: In this cross-sectional study, we prospectively evaluated aquaporin-4-IgG positive NMOSD patients and healthy controls (HC) matched for age and sex. The clinical variables of interest were collected for each participant. The mean values of T1-w/T2-w ratio, magnetization transfer ratio (MTR), fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were obtained in NAWM, NAGM, as well as in global and hypointense lesion masks. Global lesions refer to those typically associated with aquaporin-4-IgG positive NMOSD. Hypointense lesions were defined as areas of hypointense signal in both T1-w and fluid-attenuated inversion recovery (FLAIR) images.

Results: In total, we included 105 participants (59 NMOSD patients and 46 HC). T1-w/T2-w ratio was lower in NAWM of NMOSD patients versus HC (1.83 ± 0.14 vs 1.89 ± 0.14; p = 0.029), while no significant differences were found in NAWM or NAGM across the other metrics: (p range: 0.079 to 0.973). Hypointense lesions showed lower T1-w/T2-w ratio, MTR, and FA, and higher diffusivity metrics as compared to global lesion masks (p < 0.001). T1-w/T2-w ratio in NAWM was inversely correlated with time to start immunosuppressive therapy (r =  - 0.278; p = 0.036) and with MD (r =  - 0.325; p = 0.014).

Conclusion: Microstructural integrity loss seems to be confined to focal tissue damage in NMOSD. Decreased T1-w/T2-w ratio in NAWM may reflect subclinical water accumulation due to astrocyte and blood-brain barrier dysfunction. Hypointense lesions have shown a severe degree of microstructural damage.

Introduction: The MAPT gene encodes Tau, a protein mainly expressed by neurons. Tau protein plays an important role in cerebral microtubule polymerization and stabilization, in axonal transport and synaptic plasticity. Heterozygous pathogenic variation in MAPT are involved in a spectrum of autosomal dominant neurodegenerative diseases known as taupathies, including Alzheimer's disease, Pick's disease, fronto-temporal dementia, cortico-basal degeneration and progressive supranuclear palsy. Taupathies are characterized by the constant presence of neuronal and/or glial aberrant Tau inclusions leading to atrophy and subsequent neuronal loss resulting in central nervous system degeneration. We report here two unrelated families in which segregates a MAPT-related neurodegenerative disorder marked by respiratory failure in the foreground.

Results: Nine individuals from two unrelated families were affected by a neurodegenerative disorder. Respiratory features were progressively worsening dyspnea-orthopnea with episodes of acute respiratory decompensation leading to hypercapnic coma or sudden death. A diaphragmatic paralysis was shown in three cases. Associated neurological signs were gait disturbances, bulbar signs including swallowing disorders and dysarthria, pyramidal signs, cognitive and behavioral disorders. ENMG inconstantly found signs of mild denervation. Post-mortem brain immuno-histochemical analysis in one patient revealed unusual composite neuronal Tau inclusions, significant neuronal loss and reactive gliosis, in cortical and subcortical regions, cranial nerves and anterior horn of spinal cord. The heterozygous missense variant c.2041C > T, p. (Pro681Ser) in MAPT was identified in both families by gene panel or exome sequencing.

Discussion: In the literature, four additional related patients carrying the same MAPT variant, in heterozygous state, also presented rapidly progressive respiratory failure and unusual composite neuronal Tau inclusions in anterior horn of spinal cord.

Conclusion: Our observation allows to extend the phenotypic spectrum associated with MAPT variants describing a rapidly progressive respiratory failure, with episodes of exacerbations and premature death.