Neurology and Therapy最新文献

This opinion paper on the acute treatment of migraine addresses the definition and recognition of acute migraine attacks, highlighting the variety of symptoms and manifestations. It describes the available treatments and guidelines, noting significant country-specific variations. The paper also discusses the prescribers' knowledge and updates, recognizing the segment-specific differences. Despite nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans being universally recommended as first-line treatments, their visibility in the field has diminished due to the promotion of newer medicines. The authors, a panel of 15 experts from six European countries, emphasize the underutilization of triptans and advocate for their prescription, and also their use in combination with NSAIDs, when NSAIDs alone are not sufficiently effective. The panel specifically considered the sumatriptan succinate-naproxen sodium combination, which was recently introduced in Europe and may be beneficial in patients not responding to NSAIDs, particularly for special patient groups, such as those with menstrual-related acute migraine or migraine attacks with prolonged pain or postdrome. Finally, the consensus highlights the need for individualized treatment plans and the importance of considering patient preferences and specific symptoms, integrating evidence-based recommendations with patient-centered care to optimize migraine management.

Introduction: Short-term use of dual antiplatelet therapy (DAPT) is superior to single antiplatelet therapy (SAPT) for early outcomes in acute ischemic stroke (AIS). However, the long-term effects of SAPT and DAPT remain unclear. This study aimed to evaluate long-term effects of DAPT and SAPT on clinical outcomes in patients with AIS.

Methods: A retrospective cohort study was conducted at three tertiary hospitals in Saudi Arabia, including 912 patients with AIS who received either DAPT (aspirin plus clopidogrel) or SAPT (aspirin or clopidogrel alone). The primary outcome was the incidence of net adverse clinical and cerebral events (NACCEs), which was defined as the incidence of any hemorrhagic transformation within 30 days, or stroke recurrence and/or all-cause mortality within 12 months of the index stroke.

Results: Of 4043 screened patients, 912 met the inclusion criteria, with a mean age of 65.47 years. Among them, 582 patients (63.8%) received DAPT. In the treatment selection model, patients with a more severe stroke presentation had lower odds of receiving DAPT. Over the 12-month period, there was no significant difference in the incidence of NACCEs between the DAPT and SAPT groups (p = 0.946). Additionally, the DAPT group showed a higher rate of stroke recurrence within the first 50 days post stroke. In contrast, the SAPT group had higher hemorrhagic transformation and mortality. However, none of these associations were statistically significant (p = 0.1075, 0.0865, and 0.3121, respectively). In the adjusted Cox models, DAPT was not independently associated with stroke recurrence, hemorrhagic transformation, all-cause mortality, or the composite NACCE endpoint (p > 0.05).

Conclusion: The addition of a second antiplatelet agent did not significantly reduce the long-term risk of stroke recurrence or mortality in patients with AIS over a 12-month period. Further studies are needed to assess long-term benefits and risks of DAPT in different stroke subpopulations.

Introduction: We evaluated continuous subcutaneously administered foslevodopa/foscarbidopa (LDp/CDp) in younger patients earlier within advanced Parkinson's disease (aPD).

Methods: This phase 3 trial included patients aged ≥ 30 years with levodopa-responsive PD, Mini-Mental State Examination score ≥ 24, and levodopa equivalent dose ≥ 400 mg/day. Patients were considered by the investigator as inadequately controlled on current oral/transdermal therapy and experienced ≥ 2.5 h/day "Off" time, with recognizable "On"/"Off" states. Patients were randomized (1:1) to LDp/CDp plus placebo capsules or orally administered immediate-release levodopa/carbidopa plus placebo infusion. This post hoc exploratory analysis focused on younger patients (≤ 65 years) earlier within aPD (Hoehn and Yahr stage ≤ 2 ["On" state], ≤ 5 years since motor fluctuations started). Outcomes included change from baseline (CFB) to week 12 in "Off" and "On" time, Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) II, 39-item PD Questionnaire (PDQ-39), and PD Sleep Scale-2 (PDSS-2).

Results: Twenty-six patients met subgroup criteria (LDp/CDp, n = 13; orally administered levodopa/carbidopa, n = 13). Despite small sample sizes, at week 12, LDp/CDp was associated with significantly greater improvements in "Off" time (mean [SD] CFB - 3.7 [3.1] vs - 1.6 [2.9] h; P = 0.0011), "On" time without troublesome dyskinesia (+ 3.9 [3.3] vs + 1.4 [3.8] h; P = 0.0011), and PDSS-2 (- 6.4 [4.6] vs - 1.8 [3.1]; P = 0.0220) vs orally administered levodopa/carbidopa. Mean (SD) CFB to week 12 (LDp/CDp vs orally administered levodopa/carbidopa) was + 4.2 (2.8) vs + 1.9 (4.6) h for "On" time without dyskinesia (P = 0.0878), - 3.0 (6.4) vs - 0.9 (3.5) for MDS-UPDRS II (P = 0.3539), and - 9.9 (7.4) vs - 1.9 (9.4) for PDQ-39 (P = 0.0534). For most assessments, treatment differences were numerically larger in the subgroup vs the overall population. Safety findings were consistent with the overall population.

Conclusions: LDp/CDp was associated with significantly greater improvements in motor function and sleep vs orally administered levodopa/carbidopa in younger patients earlier within aPD whose symptoms were inadequately controlled by oral/transdermal therapies. Larger real-world studies are needed to confirm findings.

Trial registration: ClinicalTrials.gov identifier, NCT04380142.

Importance: Tangier disease (TD) is an ultra-rare disease, characterised by progressive peripheral neuropathy with no established treatment.

Objectives: To determine whether miglustat improved the clinical status of a single patient with TD, and to investigate the possible mechanisms of miglustat in this patient.

Design, setting, and participants: An n-of-1 ABAB study, alternating on and off treatment for 6-month periods, total study duration of 2 years with an additional compassionate-access period of 21 months.

Exposure: Miglustat, an orphan drug licenced to treat Gaucher disease and Niemann-Pick disease, was repurposed.

Main outcomes and measures: The study was designed with two co-primary endpoints: (a) time taken to complete the nine-hole peg test (fine motor control and finger dexterity), and (b) hand strength: grip and three-point pinch strength tests. Secondary endpoints were quality-of-life measures and biomarkers.

Results: A 21-year-old (at baseline) left-handed male patient with TD, diagnosed at the age of 6 months, and disabling neuropathy was included in the study. Over 2 years, there was a small signal in our clinical measures that the drug may be beneficial. Compared with the 2 years prior to treatment, the patient had no relapse of neuropathy during his study period and further extension. During the 21-month treatment extension, he showed considerable improvement on primary endpoints. Biomarkers changed as expected based on the mechanism of action of miglustat. Nerve conduction studies showed a mild benefit. Importantly, the patient's reported experience suggested a meaningful benefit from miglustat.

Conclusions and relevance: Miglustat may be used to treat neurological complications of TD. This study showed that an n-of-1 study to inform a policy decision is practical and may offer hope to patients with rare diseases.

Trial registration: ClinicalTrials.gov Identifier: ISRCTN17945917. Registration date: 07/06/2021; 'retrospectively registered'.

Introduction: Caregivers provide essential support to patients with mild cognitive impairment (MCI). However, limited research has been conducted to validate instruments that assess their self-perceived competence in caregiving. This study aimed to assess the psychometric properties of the 7-item Sense of Competence Questionnaire (S-SCQ) in informal caregivers of patients with MCI.

Methods: A non-interventional, cross-sectional study was conducted in collaboration with the Spanish Confederation of Alzheimer's Disease, enrolling informal caregivers of patients with MCI. A non-parametric item response theory procedure (Mokken analysis) was performed to evaluate the S-SCQ's dimensional structure using scalability coefficients. Internal reliability was assessed using Cronbach's α. Concurrent validity was examined through Spearman's correlations between S-SCQ scores and measures of caregiver burden, psychological distress, resilience, and the caregiver-patient relationship.

Results: A total of 196 caregivers were studied. Caregivers had a mean age of 63.5 (SD 13.1) years, and most (63%) were female. The care recipients had a mean age of 72.9 (7.0) years, with a mean disease duration of 2.9 (2.2) years. The mean S-SCQ score was 26.1 (6.1). The S-SCQ demonstrated strong unidimensionality (H = 0.52) and good internal reliability (Cronbach's α = 0.86). Higher S-SCQ scores (greater sense of competence) correlated with lower caregiver burden (ρ = - 0.63, p < 0.001), reduced anxiety and depressive symptoms (ρ = - 0.32, p < 0.001), stronger caregiver-patient relationship (ρ = 0.72, p < 0.001), and greater resilience (ρ = 0.34, p < 0.001).

Conclusions: The S-SCQ is a reliable tool for assessing self-perceived competence in informal caregivers of patients with MCI. Its integration into clinical and research settings may offer an opportunity to enhance the early detection of caregiver burden and facilitate timely, targeted interventions.

Myasthenia gravis (MG) is a chronic, autoimmune, neurological condition characterized by fluctuating muscle weakness and fatigue, driven by autoantibodies against the neuromuscular junction (NMJ). Real-world evidence studies of patient registry data show that conventional treatments do not provide sufficient disease control for some patients and that, for them, significant health, quality of life, and economic burdens remain. In recent years, several new, targeted treatments for MG have become available. In light of this evolution of the MG treatment landscape, patients and clinicians have the opportunity to elevate their treatment goals, moving from previously accepted residual symptoms to targeting complete symptom resolution and prioritizing preservation of the NMJ to minimize damage. Patients with MG can now all aim for a fully functional life well into old age, but this requires a concerted and multi-stakeholder approach to disease management. Insights from other neurological diseases in which the availability of new therapies has sparked a shift in patient care could drive faster improvements in MG care. Here, we examine how the multiple sclerosis (MS) community evolved its approach to disease management with the availability of new treatments around a decade ago. In reflecting on the multi-faceted approach taken by the MS community to drive change and improve healthcare outcomes for patients with MS, we ask the questions 'What could constitute best practice care and good outcomes for patients with MG in the future?' and 'How do we, as an MG community, get there?'.

Introduction: Glucose at admission predicted poor outcome for patients with acute large vessel occlusion (LVO) undergoing endovascular therapy (EVT). Prior studies ignored continuous glucose monitoring after EVT. Therefore, we aim to evaluate the association between post-procedural glucose levels and outcomes in real-world settings.

Methods: This study was based on a multicenter cohort. Patients with LVO who underwent EVT within 24 h of symptom onset were enrolled. We analyzed post-procedural blood glucose based on preprandial blood glucose levels within 48 h after EVT recognizing disrupted normal dietary patterns and circadian rhythms due to severe symptoms of LVO. Primary clinical outcome was functional independence (90-day modified Rankin scale score 0-2). We evaluated the association between post-procedural glucose and functional independence using logistic regression and assessed whether stroke severity modified this association.

Results: A total of 693 patients were included. Multivariate logistic regression analysis showed that decreased average post-procedural glucose per unit was significantly related to functional independence (adjusted odds ratio [aOR]: 0.75, 95% confidence interval [CI] 0.68-0.83, P < 0.001). Hyperglycemia was defined as any preprandial blood glucose within 48 h after EVT ≥ 7.6 mmol/L based on the restricted cubic spline regression model. The hyperglycemia group was also significantly associated with functional independence (aOR: 0.54, 95% CI 0.36-0.82, P = 0.003), symptomatic intracranial hemorrhage (aOR: 2.16, 95% CI 1.08-4.34, P < 0.001), and 90-day mortality (aOR: 1.71, 95% CI 1.04-2.79, P = 0.033). Subgroup analysis specifically in individuals with severe stroke (defined as National Institutes of Health Stroke Scale [NIHSS] ≥ 15) showed that hyperglycemia was a risk factor for low functional independence.

Conclusion: Increased post-procedural glucose is associated with poor functional outcome after endovascular treatment and an increased risk of symptomatic intracranial hemorrhage after endovascular treatment, especially for those with more severe strokes.

Introduction: Neurofibromatosis type 1 with plexiform neurofibromas (NF1-PN) can cause substantial clinical morbidity, yet the overall humanistic burden in adults remains poorly characterized. This study assessed health-related quality of life (HRQoL), in addition to clinical characteristics, among adults with symptomatic NF1-PN.

Methods: A cross-sectional survey was conducted among adults with NF1-PN in the USA. The survey included the following patient-reported outcome (PRO) measures: PAin INtensity Scale for Plexiform Neurofibromas (PAINS-pNF), Pain Interference Index (PII-pNF), PN quality of life measure (PlexiQoL), Patient-Reported Outcomes Measurement Information System (PROMIS), Pediatric Quality of Life Inventory (PedsQL), Work Productivity and Activity Impairment (WPAI-CIQ), and EQ-5D-5L.

Results: Among 120 participants (mean age 41.8 years, 46.7% female), 80.0% reported experiencing pain and fatigue. Over half of patients reported moderate-to-severe chronic (51.7%) and spike (83.3%) tumor pain (PAINS-pNF: mean chronic pain = 3.6 ± 2.5; mean spike pain = 6.3 ± 3.2), with considerable interference with daily activities (PII-pNF: mean = 3.1 ± 1.6). PROMIS scores indicated worse outcomes than the general population for physical function (38.4 ± 7.7), depression (59.0 ± 9.2), anxiety (60.1 ± 9.5), and fatigue (59.0 ± 10.2). Only 12.5% were employed, with 50.8% reporting disability. Among employed individuals, work productivity loss averaged 39.3% ± 30.7. Overall daily activity impact was high (55.5% ± 22.5). The mean EQ-5D-5L utility score was 0.38 ± 0.39, with 69.2% reporting moderate-to-extreme pain/discomfort and 57.5% reporting moderate-to-extreme anxiety/depression.

Conclusion: Adults with symptomatic NF1-PN experience substantial disease burden across multiple domains, including high prevalence of pain, impaired physical and psychological functioning, reduced work productivity, and low health utility scores. These results highlight the need for integrated pharmacological, psychological, and rehabilitation interventions to support overall patient well-being.

Multiple sclerosis (MS) is a chronic sex-biased (3♀:1♂) immune-mediated demyelinating disease of the central nervous system (CNS). Disease-modifying therapies targeting the peripheral immune cells efficiently limit relapses in early MS but cannot abrogate the chronic progressive component of the disease. The exact cause of MS remains elusive but interactions between predisposing genetic and environmental risk factors result in aberrant activation of pro-inflammatory immune cells targeting the CNS, leading to the formation of multifocal demyelinating lesions in the brain and spinal cord. MS-related genetic polymorphisms and viral triggers are currently not amenable to intervention. In contrast, obesity and gut dysbiosis represent potential modifiable risk factors contributing to MS pathogenesis and disease course. Diet influences obesity and metabolic diseases, shapes gut microbiota composition, modulates oxidative stress, and affects biological aging and inflammatory processes. Dietary patterns have emerged as factors modifying MS risk, disease activity, and progression. Therapeutic dietary interventions represent a promising avenue to promote healthy aging and regulate neuroinflammatory and neurodegenerative processes in MS. Here we describe the impact of diet on MS course and review the nutritional interventions investigated in MS and its animal models, with a focus on the mechanisms implicated including the impact on the gut microbiota.