European Journal of Neurology最新文献

Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are effective for migraine prophylaxis; however, real-world evidence beyond 1 year remains limited.

Methods: This single-center, retrospective observational cohort study in Japan included 307 migraine patients who received CGRP mAbs (erenumab, galcanezumab, or fremanezumab) for ≥ 3 months between April 2022 and February 2025 for an effectiveness analysis. Outcomes included monthly migraine days (MMDs), ≥ 50% responder rates, adverse events (AEs), and treatment persistence. Patients were categorized as nonresponders or responders: early (≥ 50% MMD reduction by Month 3), late (Months 4-5), and ultralate (after Month 6).

Results: Significant MMD reductions were observed across 24 months. The ≥ 50% response rates were 45.9%, 57.0%, 63.6%, and 71.0% at 3, 6, 12, and 24 months, respectively. AEs occurred in 12.6% and were mild. Early responders had the lowest baseline MMDs and Migraine Disability Assessment (MIDAS) scores; nonresponders had the highest baseline MMDs and MIDAS scores and the highest rates of comorbid medication overuse headache (MOH) and psychiatric disorders. Compared with early responders, late and ultralate responders had higher baseline MMDs, higher MIDAS scores, higher rates of MOH, and more prior preventive failures. Additionally, ultralate responders presented the highest rates of photophobia and pulsatile headache and the fewest psychiatric comorbidities. Effectiveness appeared similar among the three CGRP mAbs. Treatment continuation rates were 68.3%, 58.0%, and 50.6% at 12, 18, and 24 months, respectively.

Conclusion: CGRP mAbs were associated with a long-term reduction in migraine frequency and favorable tolerability.

Background: Paramagnetic rim lesions (PRLs) are emerging MRI biomarkers of smoldering inflammation in multiple sclerosis with prognostic relevance¹. However, their prevalence in the early stages of the disease remains underexplored.

Objective: This prospective cohort study investigated the prevalence, anatomical distribution, and clinical significance of PRLs in newly diagnosed relapsing MS patients with high disease activity and explored their associations with conventional and non-conventional MRI measures, serum neurofilament light chain (sNfL), and clinical outcomes.

Methods: We enrolled treatment-naïve patients who had received an MS diagnosis in the previous 12 months. Patients underwent 3 T brain and spinal MRI including susceptibility-weighted imaging at baseline, 6, and 12 months, along with neurological and cognitive assessments and sNfL sampling.

Results: The cohort consisted of 21 patients, with a mean age of 31 and median disease duration of 9 months (IQR 4-17). Median EDSS score was 1.5. All patients presented with spinal cord lesions and 38% showed Gd + lesions. PRLs were detected in 76%, with a mean of 4.9 lesions per subject. Higher PRL burden correlated with greater T2 lesion volume and cortical lesion count, higher EDSS, reduced SDMT scores, and elevated baseline sNfL. PRLs remained stable over 12 months despite treatment; two new PRLs emerged at month 12. sNfL levels were higher in patients with ≥ 4 PRLs and decreased in all during follow-up.

Conclusions: Paramagnetic rim lesions (PRLs) are detectable early in RMS and correlate with a more severe clinical and radiological profile. The combined assessment of PRLs and CLs may improve disease monitoring and guide personalized treatment.

Background: Migraine and sleep disturbances share a bidirectional relationship, influencing each other's frequency and severity. The aim of this systematic review is to examine the effects of migraine-targeted interventions on both migraine outcomes and sleep parameters (including sleep quality and insomnia symptoms), as well as the effects of sleep-focused interventions on both sleep and migraine outcomes.

Methods: Following PRISMA 2020 guidelines, a systematic search was conducted across six databases (PubMed, Medline, Scopus, Embase, PsycINFO, CINAHL) for studies published until December 5, 2023. Eligible studies included Randomized Clinical Trials, Controlled Clinical Trials, and observational studies assessing migraine and/or sleep-targeted interventions in adults. The risk of bias was evaluated using RoB 2 and ROBINS-E tools.

Results: Twenty-three studies (1941 participants) were included. Pharmacological treatments such as erenumab, amitriptyline, propranolol, and onabotulinumtoxinA reduced migraine frequency and pain intensity, with variable effects on sleep quality. Melatonin showed no significant impact. Among non-pharmacological treatments, percutaneous electrical nerve stimulation, greater occipital nerve block, green light therapy, binaural beats, mindfulness, and dietary modifications improved both migraine symptoms and sleep. Digital Cognitive-Behavioral Therapy for Insomnia (CBT-I) significantly reduced headache days and improved sleep parameters, whereas evidence on standard CBT-I was mixed.

Limitations: Study heterogeneity, small sample sizes, and variability in outcome measures limit generalizability. Few studies focused on sleep-targeted interventions and their effects on migraine, highlighting a research gap.

Conclusions: Integrated approaches combining migraine and sleep interventions show promise for symptom management. Further research is needed to refine treatment strategies and assess long-term effects.

Registration: CRD42024617217.

Background: Neuroinflammatory and systemic immune mechanisms are increasingly recognized as contributors to migraine pathophysiology. However, peripheral markers of inflammation remain underexplored. This study aimed to evaluate systemic immune alterations in patients with migraine through complete blood count (CBC) parameters and derived inflammatory indices, comparing findings with healthy controls (HCs).

Methods: We conducted a cross-sectional analysis of peripheral blood samples, assessing leukocyte subtypes including absolute and relative (percentage-%) values, hemoglobin, and platelet levels. Inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), were calculated. Migraine features were collected.

Results: A total of 409 subjects were included: 179 HCs, 194 with episodic migraine (EM), and 36 with chronic migraine (CM). Regarding inflammatory indices, SII significantly differed among EM, CM, and HCs (p = 0.024). In particular, in post hoc analyses, it was significantly higher in CM (514.20 ± 250.57) vs. HCs (423.14 ± 221.69) (p = 0.019) and in CM compared to EM (448.28 ± 266.53, p = 0.044). Similarly, neutrophil% significantly differed among the three groups (p = 0.022), and was higher in patients with CM (58.69 ± 9.57) vs. HCs (54.81 ± 8.86, p = 0.019) and in patients with CM vs. EM (55.39 ± 9.77, p = 0.016). Lymphocyte% differed among the three groups (p = 0.047), and it was lower in CM (31.51 ± 8.27) vs. HCs (34.55 ± 8.24, p = 0.047).

Conclusions: Systemic immune dysregulation appears to be associated with migraine, particularly CM. Alterations in neutrophil and lymphocyte distributions, as well as increased SII, may represent peripheral correlates of central neuroinflammation. These findings suggest that simple, routinely available blood-derived markers could help identify inflammatory endophenotypes in migraine, warranting validation in larger, prospective studies.

Background: Parvovirus B19 (B19V) infection has been associated with neurological complications. Rarely, patients present with multiple mononeuropathy (MM). The present study aimed to better characterize the clinical, electrophysiological, and prognostic features of patients with B19V-related MM.

Methods: This retrospective, observational, multicenter study included patients with B19V-related MM diagnosed between January 2015 and January 2025 in seven university hospitals in France and Switzerland.

Results: Twenty-one patients were included. Twelve were female (57%). All were immunocompetent. The median age at symptom onset was 40 years [IQR: 31-44]. All patients experienced sensory symptoms, 19 (90%) reported neuropathic pain, nine (43%) developed motor weakness, and seven (33%) had cranial nerve involvement. The most frequently involved nerves were the median (14 patients, 67%), fibular (n = 13; 62%), and ulnar (n = 10; 48%) nerves. B19V IgM antibodies were present in 12/20 patients (60%), and all 21 patients were positive for IgG. B19V DNA was detected in blood by PCR in 20 patients (95%). Nerve biopsy showed necrotizing small-vessel vasculitis in one patient (17%), perivascular lymphocytic and macrophagic infiltrates in five (83%), and B19V DNA was detected by PCR in all four tested nerves. Most patients received immunomodulatory treatment (n = 19; 90%). MM relapse occurred in four patients (19%). A partial recovery was observed in 17/20 patients (85%), two remained stable (10%), and one achieved complete recovery (5%).

Conclusions: B19V infection should be systematically investigated in patients presenting with MM, especially in young individuals (including children) with predominantly sensory symptoms, predominant upper limb nerve involvement, and/or cranial nerve involvement.

Background: Cervical artery dissection (CeAD) is a major cause for stroke in young adults. A timely association with minor-to-moderate unimposing cervical trauma, which is often sports-related, is common in CeAD. Our goal was to assess whether physical activity puts patients at risk post-CeAD.

Methods: Pooled data from two prospective observational CeAD cohorts with in-person follow-up of at least 1-year post-CeAD were assessed. Changes in physical activity were recorded using patient-reported assessment of change in activity compared to pre-CeAD. Baecke score-derived sports index was applied to address the association between physical activity intensity and our outcomes. Outcomes were (1) recurrent dissection and (2) cerebral ischemia upon follow-up.

Results: A total of 648 CeAD patients were recorded. Physical activity-specific follow-up data were available in 333 (59.7%). The median follow-up duration was 6.5 (IQR 3.1, 10.9) years with 17/333 (5.1%) suffering CeAD recurrence and 22/33#3 (6.6%) experiencing cerebral ischemia. A total of 197 of 333 (59.2%) patients reported a change in physical activity post-CeAD (127 [64.5%] decrease, 70 [35.5%] increase). Neither overall change, increase, or decrease of physical activity was associated with recurrent CeAD or cerebral ischemia (p > 0.2 throughout). However, regular performance of higher-intensity sports, assessed via Baecke score-derived sports index, associated in trend to dissection recurrence (OR 3.43 [0.86, 13.64]; p = 0.080).

Conclusions: CeAD patients should be reassured that regaining physical activity after CeAD is safe. However, moderation on exertion should be discussed on an individual patient basis.

Background: Surgical intervention is recommended in idiopathic intracranial hypertension (IIH) for fulminant or treatment-refractory cases, yet data on outcomes remain limited, particularly regarding indication-specific effects. This study evaluated outcomes and indications for surgery in IIH, aiming to identify predictors of favorable or adverse results.

Methods: A retrospective multi-center study was conducted by the Danish-Austrian IIH Consortium (DASH-IIH). Databases from three centers (Vienna, Odense, Copenhagen) were screened for persons with IIH (pwIIH) fulfilling revised Friedman criteria who underwent surgery and had ≥ 6 months of follow-up. Outcomes at 6 months included visual function, headache improvement (≥ 50%), papilledema resolution, and severe adverse events. Multivariable regression was used to adjust for confounders.

Results: Of 1310 pwIIH, only 3.6% required surgery overall. Thirty-six pwIIH were included (100% female; mean age 32.5 years; median BMI 37.0; median CSF opening pressure 41 cmH₂O). Of these, 27 (75%) underwent CSF diversion and 9 (25%) optic nerve sheath fenestration (ONSF). The primary indication for surgery was acute visual deterioration in 83.3% and refractory headache in 16.7%. Visual function improved in 41.7%, papilledema resolved in 89.7%, and headache improved in 30.6%. No significant differences in outcomes were found between CSF diversion and ONSF. Importantly, no visual improvement occurred in cases operated for headache alone, and the odds of headache improvement were significantly lower in this group (OR 0.11, p = 0.012).

Conclusion: CSF diversion and ONSF are effective in IIH with acute visual threat, improving vision and, to a much lesser extent, headache. Refractory headache alone appears insufficient indication for surgical intervention.

Background: Painful diabetic neuropathy affects ~20%-40% of individuals with diabetes, driven by peripheral small nerve fiber damage and modulated by spinal cord and brain mechanisms. Corneal nerve imaging using corneal confocal microscopy (CCM) and skin biopsy to quantify intraepidermal nerve fiber density (IENFD) are objective measures of small nerve fiber damage.

Objectives: CCM and IENFD were assessed for their ability to distinguish painful from painless diabetic neuropathy.

Methods: Following PROSPERO-registered protocol and PRISMA guidelines, PubMed, Embase, and Web of Science were searched for studies on corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and IENFD in patients with painful and painless diabetic neuropathy. Standardized mean difference (SMD) with 95% confidence intervals (CI) was pooled using random-effects meta-analyses.

Results: Seven studies (n = 683) showed lower CNFD (SMD -0.50, 95% CI -0.96 to -0.03, p = 0.03) and CNFL (SMD -0.32, 95% CI -0.59 to -0.05, p = 0.02) in painful compared to painless DPN, with no difference in CNBD. Ten studies (n = 664) demonstrated lower IENFD in painful compared to painless DPN (SMD -0.31, 95% CI -0.59 to -0.02, p = 0.03, I² 69%). In three studies assessing both CCM and IENFD (n = 161), CNFD (p < 0.0001), CNBD (p = 0.01), CNFL (p = 0.0001), and IENFD (p = 0.008) were significantly lower in painful compared to painless DPN.

Conclusion: Both CCM and skin biopsy demonstrate small nerve fiber loss in painful compared to painless DPN, supporting their value in identifying alterations in small nerve fiber structure in painful DPN.

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by progressive muscle weakness due to SMN protein deficiency. While effective therapies exist, their impact on slowly progressive adult SMA patients remains unclear. Reliable biomarkers for monitoring disease progression and treatment response are urgently needed. This pilot study evaluated the utility of longitudinal quantitative muscle MRI (qMRI) to monitor disease progression in adult SMA patients treated with nusinersen over an extended period.

Methods: Nine adult patients with genetically confirmed 5q-SMA underwent whole-body muscle MRI and clinical assessment, including the Hammersmith Functional Motor Scale-Expanded (HFMS-EXP), Revised Upper Limb Module (RULM), and 6 min walk test (6MWT). Muscular fat fraction (mFF) was quantified in 20 muscles over a median follow-up of 54 months.

Results: Baseline mFF correlated strongly with clinical measures (HFMS-EXP: r = -0.90, p = 0.001; 6MWT: r = -0.96, p < 0.001), but not with age at onset or age at MRI. Over the observation period, a significant increase in mFF was detected (averaged annual increase of all studied muscles: 0.47%, p = 0.011), accentuated in the lower leg muscles. In contrast, clinical measures showed no consistent change. Consequently, no significant correlations were found between changes in mFF and clinical scores.

Conclusions: This study provides the longest reported longitudinal qMRI assessment in adult SMA patients treated with nusinersen, demonstrating that mFF progressively increases despite stable clinical scores. The results suggest that qMRI may be a sensitive and objective biomarker for detecting subtle disease progression in adult SMA, potentially surpassing clinical measures.

Introduction: Generalized myasthenia gravis (gMG) is a chronic autoimmune neuromuscular disorder characterized by fluctuating muscle weakness and exertional fatigue, often requiring long-term immunosuppressive or biologic treatment. Although international guidelines recommend achieving minimal manifestations as the primary treatment goal, the lack of a standardized measurement approach has limited its application in clinical settings and trials. Minimal Symptom Expression (MSE), defined as a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 0 or 1, has recently emerged as a practical, patient-centric endpoint that reflects minimal functional burden and aligns with regulatory priorities around patient-reported outcomes.

Results: This position paper examines the rationale for MSE as a clinically meaningful, actionable treatment target in gMG. We summarize the strengths of the underlying MG-ADL scale and highlight phase 3 trial data showing that MSE is attainable with biologic therapies, including complement and neonatal Fc receptor inhibitors. Data also suggest that achieving MSE correlates with improvements in physician-assessed outcomes and quality of life metrics. However, inconsistencies in how sustained MSE is defined and reported limit comparability across trials.

Conclusion: MSE, as a patient-centric endpoint, can be used alongside clinician-assessed measures and safety measures to support an integrated treatment goal that encompasses both efficacy and tolerability for the treatment of gMG. Future research should further define the clinical utility of MSE and sustained MSE and incorporate stakeholder input to validate MSE as a part of an integrated treatment goal in both clinical trials and real-world clinical practice.