Neurology and Therapy最新文献

Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disorder causing significant suffering and mental health problems for patients. Many patients with ALS have a severe psychological reaction to the serious diagnosis when they are first diagnosed. This study aims to investigate the impact of a brief mindfulness intervention on emotions, sleep, and quality of life (QOL) in patients with ALS who have recently been diagnosed.

Methods: This prospective intervention study enrolled patients who had been newly diagnosed with ALS. Participants received cognitive training and audio-led mindfulness exercises involving breathing awareness and body scan sessions for 10 days. The effectiveness of the intervention was evaluated by several scales.

Results: Ninety-one patients (aged 54.15 [10.10] years, 52 male/39 female [57.10%/42.90%]) were finally enrolled in the analysis. The Chinese Version Perceived Stress Scale (CPSS) (t = 2.05, P = 0.04) and Epworth Sleepiness Scale (ESS) (Z = -2.03, P = 0.04) scores significantly decreased, and the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ40) significantly increased (Z = -2.93, P < 0.01) following the brief mindfulness intervention. The Patient Health Questionnaire-9 (PHQ-9) (Z = -2.97, P < 0.01) and the 17-Item Hamilton Rating Scale for Depression (HAMD-17) (Z = -3.43, P < 0.01) were significantly reduced in patients with ALS diagnosed with depression. QOL was significantly improved in other patients with ALS (Z = -2.51, P = 0.01).

Conclusion: Our study indicated that a brief mindfulness intervention could be a potential way to reduce depression and improve daytime sleepiness, while also improving the QOL for newly diagnosed patients with ALS.

Introduction: Sphingosine-1-phosphate receptor (S1PR) modulators are effective therapies for multiple sclerosis (MS) that block lymphocyte egress from secondary lymphoid organs. This migration inhibition carries the risk of reduced infection-control as reported for the non-selective S1PR modulator, fingolimod. CXCL13:CXCR5-associated immune activities play a key role in protective antibody-based immunity but are also linked to inflammation in MS. Utilizing the ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, we aimed to determine whether selective S1PR modulation with ozanimod acts on the CXCL13:CXCR5 axis for modulating MS activity and whether this impacts anti-viral immune responses.

Methods: This 1-year observational study included 20 patients with MS receiving ozanimod and 10 healthy probands. CXCR5⁺ T cells, B cells, serum CXCL13, anti-SARS-CoV-2 serostatus, and SARS-CoV-2-spike protein (ProtS)-reactive T cell responses were measured at 3-month intervals.

Results: CXCR5⁺ T and B cell frequencies and serum CXCL13, but not anti-SARS-CoV-2 responses, declined after ozanimod initiation. Anti-SARS-CoV-2 antibody and ProtS-reactive T cell responses peaked after recall vaccinations and break-through infections. Notably, ProtS-reactive T cell frequencies shifted from CD4⁺ to CD8⁺ T cell responses in patients treated with ozanimod compared to controls.

Conclusion: Selective S1P receptor modulation with ozanimod affects the CXCL13:CXCR5 axis by reducing circulating CXCR5⁺ lymphocytes and serum CXCL13, which may contribute to reduce meningeal inflammation in MS. Moreover, the anti-SARS-CoV-2 immune defense appeared to be preserved during treatment with SARS-CoV-2-reactive CD8⁺ T cells, possibly compensating the lack of CD4⁺ T cell responses. Our immunological data may well apply to other viral infections and underscore the favorable safety and efficacy profile of ozanimod.

Introduction: Despite the availability of effective treatments, some patients with migraine in Japan do not receive appropriate medical management and treatment for migraine, potentially due to the lack of effective patient-doctor communication. This analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan)] 2nd study described the current state and challenges of patient-doctor communication in migraine treatment in Japan.

Methods: This analysis included adults with migraine who consulted doctors for headaches/migraine and reported details of their first consultation: their experiences with doctors regarding migraine diagnosis and treatments, migraine-related topics, and treatment goals discussed, and challenges in communication.

Results: Among the 6762 included respondents, 55.1% (3729/6762) consulted a general practitioner (GP) first for headaches. Of the 3192 respondents diagnosed with migraine and reported the diagnosing doctor's specialty (as GP, specialist, or non-headache specialist), specialists (64.0%; 2044/3192), followed by GPs (31.4%; 1001/3192), mostly commonly diagnosed migraine. In the first consultation, doctors told 48.0% (3249/6762) of respondents they had migraine. In the past year, 3854 respondents discussed migraine-related topics with doctors; most commonly, the use and effectiveness of prescription drugs, and headache symptoms, severity, and frequency [48.9% (1885/3854) to 67.8% (2612/3854)]. Specialists most commonly discussed migraine-related topics with respondents, but non-headache specialists, i.e., obstetricians and gynecologists, most commonly discussed menstrual-related migraine. A total of 1978 respondents had migraine-related topics they wanted to but could not discuss with doctors in the past year. Among them, 32.9% (651/1978) of respondents did not discuss the topics because the doctor did not ask. Although 96.6% (3724/3854) of respondents had treatment goals in mind, 36.0% (1388/3854) never discussed it with doctors.

Conclusion: Open and considerate patient-doctor communication and appropriate medical judgment are needed for timely and adequate medical management of migraine. Training doctors in effective communication techniques and considering a migraine diagnosis during consultations may be associated with better patient outcomes.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease, affects the optic nerves and spinal cord. Rituximab is often used off-label to treat NMOSD; however, comparator-controlled trial data are limited. Eculizumab is approved for treatment of anti-aquaporin-4 antibody-positive (AQP4-Ab+) NMOSD. Outcomes data for patients who switch from rituximab to eculizumab are limited.

Methods: This retrospective study used claims data from the IQVIA PharMetrics^® Plus database (1/1/2015-3/31/2022). Patients aged ≥ 18 years with NMOSD treated with rituximab were identified and split into two groups: patients with an eculizumab claim after rituximab (switch group, n = 20) and patients without an eculizumab claim (control group, n = 525). Hospitalization rates and duration were assessed 6 months before and 6 months after the switch date (switch group) or reference date (1-year post-rituximab initiation; control group).

Results: The percentage of patients hospitalized in the switch group decreased after transitioning to eculizumab (45.0% vs. 10.0%; p = 0.034) corresponding to a decreased mean number of hospitalizations per patient from 1.1 to 0.1 (p = 0.005). The percentage of patients hospitalized in the control group was similar before and after the reference date (10.1% vs. 9.3%; p = 0.755) corresponding to a mean number of hospitalizations per patient of 0.160 and 0.156 (p = 0.922), respectively. In the switch group, median (interquartile range [IQR]) hospitalization duration decreased from 8.5 (5.0-11.0) days before switching to eculizumab to 2.5 (2.2-2.8) days after switching (p < 0.001). Median (IQR) hospitalization duration in the control group was 4.0 (2.0-9.0) days before and 4.0 (2.0-6.0) days after the reference date.

Conclusion: Although the claims-based analysis and small patient numbers limit generalizability, we observed a reduction in hospitalizations number and length of stay in a cohort of patients with NMOSD who switched from rituximab to eculizumab.

Central post-stroke pain (CPSP) is an intractable neuropathic pain syndrome. Dual-target deep brain stimulation (DBS), which integrates sensory thalamic modulation and endogenous analgesic pathways, has emerged as a potential intervention; however, clinical evidence remains scarce. We report a 54-year-old woman who developed right-sided limb paresthesia progressing to persistent right hemibody pain following a left thalamic hemorrhage. Asymmetric DBS electrodes were implanted in the right periaqueductal gray (R-PAG) and left ventral posterior thalamus (L-VP). Longitudinal assessments utilized standardized scales-including the Visual Analog Scale (VAS), Douleur Neuropathique 4 (DN4) and Hamilton Depression Scale (HAMD). These evaluations demonstrated sustained improvements in pain intensity (VAS: 7 → 1), neuropathic symptoms (DN4: 4 → 1) and depressive symptoms (HAMD: 22 → 8) at the 12-month follow-up. Pain and transient numbness were mitigated by applying cyclic stimulation (5-min on/off intervals). This case highlights the potential of asymmetric dual-target DBS targeting both the PAG and VP to achieve multidimensional analgesia in CPSP and provides insights for optimizing patient selection and treatment strategies, including choices of targets, stimulation parameters and modalities. These findings enhance understanding of neural pathways in chronic pain modulation, specifically the interplay between sensory and emotional processing, and suggest a potential role for asymmetric DBS in treating neuropathic pain.

Introduction: Neurodegenerative dementia (ND) is characterized by progressive cognitive decline. The role of autoantibodies in ND remains controversial, as they may contribute to neurological damage or, under certain pathophysiological conditions, exert protective effects. In this study, we aimed to analyze the clinical characteristics of patients with autoantibody-positive ND and investigate potential molecular mechanisms using proteomics.

Methods: The study included 13 patients with autoantibody-positive ND (ND +), 13 with autoantibody-negative ND (ND -), and 13 cognitively normal controls. Differentially expressed proteins (DEPs) were identified through proteomic analysis. Bioinformatics approaches were employed to explore potential pathways and mechanisms. Multiple linear regression analysis was performed to examine the effects of DEPs on cognitive function and their interaction with autoantibody status.

Results: The ND + and ND - groups displayed similar overall cognitive status, levels of depression or anxiety symptoms, and mental and behavioral abnormalities. The ND + group demonstrated better daily living abilities and superior frontal lobe cognitive function. Proteomic analysis identified 162 DEPs associated with autoantibodies enriched in pathways related to endocytosis, endoplasmic reticulum protein processing, tight junctions, and cellular adhesion. In the ND + group, β-arrestin-1 (ARRB1, β = 3.31, 95% CI: 1.56-5.05) and calpain-2 (CAPN2, β = 0.32, 95% CI: 0.09-0.55) were positively associated with Frontal Assessment Battery (FAB) scores, whereas no such associations were observed in the ND - group. Conversely, in the ND- group, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1, β = - 2.38, 95% CI: -4.12 to-0.64) was negatively associated with FAB, with no corresponding effect in the ND + group.

Conclusion: This exploratory study provides preliminary evidence of distinct clinical and molecular signatures in autoantibody-positive neurodegeneration. ARRB1 and CAPN2 may contribute to cognitive resilience in this group, while UGGT1 appears associated with cognitive decline in autoantibody-negative cases. Owing to the limited sample size, these findings should be considered hypothesis-generating and warrant validation in larger, independent cohorts before consideration as biomarkers or therapeutic targets.

Introduction: Motor complications become major treatment challenges in patients with Parkinson's disease (PD). Istradefylline (IST) is used as an adjunct to levodopa in patients with PD exhibiting wearing-off (WO), but its impact on the onset of dyskinesia remains unclear. The objective of this study was to investigate the effect of IST on dyskinesia onset in patients with PD exhibiting WO.

Methods: In this 3-year, multicenter, randomized, open-label, parallel-group, controlled study, 214 patients with levodopa-treated PD exhibiting WO without pre-existing dyskinesia were randomized (1:1) to either adjunctive IST (IST group) or to adding another or increasing the dose of other anti-PD drugs (non-IST group). The primary endpoint was the time to onset of dyskinesia.

Results: Over 3 years, the incidence of dyskinesia was 37.9% and 41.1% in the IST and non-IST groups, respectively. The time to onset of dyskinesia was not significantly different between the IST versus non-IST groups (median: 1100.00 vs. 1082.00 days). When dividing patients by age, the rate of time to onset of dyskinesia was lower in the IST group in patients aged ≥ 68 years (median) and in the non-IST group for patients aged < 68 years and patients aged < 60 years at PD onset. The levodopa-equivalent daily dose (LEDD) was significantly lower throughout the study period, by 57 mg on average, in the IST group than in the non-IST group. Efficacy and safety indexes were not significantly different between the two groups.

Conclusion: Adjunctive IST showed no difference in the onset of dyskinesia compared with adding another or increasing the dose of other anti-PD drugs, and displayed equivalent efficacy and tolerability, while maintaining a lower LEDD in this long-term study of patients with PD exhibiting WO. These findings support the use of adjunctive IST as a viable treatment option for patients with PD exhibiting WO.

Trial registration: University hospital Medical Information Network clinical trials registry (UMIN000024536) and Japan Registry of Clinical Trials (jRCTs071180014).

Introduction: Antipsychotic medications are effective for people living with schizophrenia, but long-term treatment adherence remains challenging, leading to relapses and poor outcomes. Long-acting injectable antipsychotics (LAIs) may improve adherence and reduce relapses compared with oral antipsychotics. Barriers to the use of LAIs exist, yet practical recommendations to overcome them are lacking. Therefore, an expert consensus panel was formed to develop key recommendations using a modified Delphi panel method.

Methods: The panel chair and Interactive Forums, Inc., conducted a narrative literature review of English-language articles published in the 10 years before 02/02/2024. Panelists rated, discussed, and re-rated proposed statements during 2 online premeetings and 2 virtual group meetings in 2024. Consensus was defined as ≥ 75% agreement.

Results: The consensus panel initially included 9 experts and was expanded to 12, representing 6 countries and diverse psychiatric and lived experiences. In the first round, 31 recommendations were developed, with a high level of agreement; these were refined to 26 statements in the second round. Recommendations covered: (1) overcoming barriers to LAI initiation and use for the treatment of people with schizophrenia, and (2) procedures for initiation and switching, monitoring, and maintenance of LAIs for people with schizophrenia. The panel recommended that healthcare professionals (HCPs) consider LAIs proactively and initiate them early after a confirmed schizophrenia diagnosis. The importance of continued treatment with LAIs and their role in assessing nonadherence and treatment resistance were also highlighted. Further, the panel recommended that HCPs evaluate any personal biases about LAIs and engage in training/education to support goal setting and shared decision-making with patients and caregivers. Guidance on switching between antipsychotic formulations and maintaining treatment was also provided.

Conclusions: This expert consensus panel provided recommendations to guide HCPs on how to overcome barriers to LAI use and to implement, monitor, and maintain LAIs as routine schizophrenia treatment.

Epilepsy frequently requires treatment with antiseizure medications (ASM). With the progressive rise in life expectancy in this population, patients are more exposed to potential undesirable effects, some of them on bone tissue. Here, we review current knowledge concerning the impact of ASM on bone biology. Cytochrome P450 inductors decrease serum concentrations of active vitamin D, increasing parathyroid hormone (PTH) secretion and hence bone resorption. Valproic acid also reduces active vitamin D, but in addition activates osteoclasts and impairs osteoblastic function through different pathways. Although the mechanism remains unclear, topiramate is associated with reductions in bone mineral density and increased PTH. Levetiracetam has a very favorable bone profile. Lacosamide and lamotrigine have a preferable bone effect compared to other sodium channel blockers. These ASM with a lower impact on bone biology should be prioritized whenever possible. Every person with epilepsy receiving high-risk ASM should undergo fracture risk assessment.

Introduction: Studies suggest that early intervention with disease-modifying treatment for spinal muscular atrophy (SMA) might provide the best opportunity for optimal outcomes. One such treatment is onasemnogene abeparvovec, a gene replacement therapy with durable efficacy demonstrated in clinical trials, long-term studies, and real-world data (e.g., RESTORE registry).

Methods: A pooled post-hoc analysis was conducted to assess the early post-treatment impact of intravenous onasemnogene abeparvovec on motor function and event-free survival for symptomatic infants with SMA type 1 (i.e., non-sitters). Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores and event-free survival were evaluated for patients enrolled in the START, STR1VE-US, and STR1VE-EU clinical trials.

Results: The pooled analysis set included 67 patients. Mean (SD) CHOP INTEND score at baseline was 29.3 (9.58) points. Rapid increases in mean CHOP INTEND of 7.0, 9.7, and 11.8 points were observed at 1, 2, and 3 months post-dose, respectively. At 6 months post-dose, 54/59 infants (91.5%) treated with onasemnogene abeparvovec achieved a clinically significant ≥ 4-point improvement in CHOP INTEND score from baseline, with a mean (SD) CHOP INTEND score of 44.3 (9.92) points. Patients who received onasemnogene abeparvovec had longer ventilation-free survival compared with natural history, with a statistically significant separation from the natural history cohort being maintained throughout follow-up.

Conclusions: Rapid and clinically significant improvements in motor function were observed for onasemnogene abeparvovec-treated patients with symptomatic SMA type 1. Early diagnosis and treatment are essential for timely restoration and preservation of motor neurons and maximal motor function improvement.