Neurology最新文献

Spinocerebellar ataxia type 27B (SCA27B) is a recently identified autosomal dominant form of late-onset cerebellar ataxia (LOCA) caused by a guanine-adenine-adenine (GAA) > 250 intronic repeat expansion in the fibroblast growth factor 14 (FGF14) gene. Recent studies suggest that SCA27B may account for 10%-60% of undiagnosed patients with LOCA. Age at onset ranges from 40s to 70s, and clinical features include slowly progressive pancerebellar syndrome with prominent gait ataxia and cerebellar oculomotor abnormalities. Positive family history may be absent, particularly given the characteristically late onset of this condition. It is important to note that up to half of the patients with SCA27B report episodic symptoms, including imbalance, vertigo, visual disturbances, or dysarthria, which might initially manifest without clear interictal clinical or radiologic features of cerebellar ataxia. These features can result in the misdiagnosis of SCA27B. We present 2 patients with LOCA. Both patients initially received alternative working diagnoses, which were re-examined several years later only after symptoms and imaging findings progressed. First-line genetic testing for both patients was unrevealing because of the deep intronic location of the causative variant. Ultimately, whole-genome-based testing in one case and targeted FGF14 trinucleotide repeat analysis in the other revealed the diagnosis of SCA27B. These cases highlight SCA27B as a cause of episodic neurologic symptoms in an older adult population. Furthermore, these cases demonstrate the potential pitfalls of panel and exome-based genetic testing, given the important role of pathogenic intronic variants in the spectrum of neurogenetic disorders.

Background and objectives: Previous antiplatelet therapy (APT) may influence outcomes in patients undergoing direct endovascular therapy (EVT) for anterior circulation large vessel occlusion (LVO) stroke, but evidence on clinical benefits and safety is limited and inconsistent. We aimed to evaluate the effects of previous APT on the outcomes of direct EVT.

Methods: We conducted a retrospective analysis of consecutive patients treated at 20 high-volume stroke centers across 9 European countries and Israel (EVA-TRISP registry, 2015-2023). We included adults with anterior circulation LVO strokes, without previous use of IV thrombolysis (IVT) or anticoagulants. We compared outcomes of direct EVT patients stratified by previous APT regimen, using propensity score matching based on medical history and multilevel models to address confounders. The primary outcome was the 90-day modified Rankin Scale (mRS) score. The secondary efficacy outcomes were 90-day independence and the rate of successful reperfusion. The secondary safety outcomes were the rate of symptomatic intracranial hemorrhage (sICH) and mortality.

Results: Among 12,950 patients, 2,611 met the criteria and 1,308 were matched: 480 without previous APT and 828 with any previous APT, among whom 764 were on single APT and 64 on dual APT. The overall mean age was 75.8 ± 11.4 years, and 49.4% were female; the mean NIH Stroke Scale score was 13.1 ± 7.2 points, the successful reperfusion rate was 74.7%, and the median mRS score was 3 (interquartile range 2-4), with 38.8% of patients independent at 90 days. When compared with no previous APT, any previous APT was associated with a shift toward lower mRS scores at 90 days (odds ratio [OR] 1.30, CI 1.04-1.61, p = 0.018). Independence at 90 days was associated with any previous APT (OR 1.62, CI 1.22-2.16, p = 0.001). Any previous APT was not associated with successful reperfusion (OR 0.96, CI 0.69-1.35, p = 0.821), sICH (OR 1.06, CI 0.47-2.39, p = 0.880), or mortality (OR 0.89, CI 0.66-1.21, p = 0.821). There was no significant interaction between any previous APT and proximal/distal occlusion location (p = 0.213) or time-to-groin earlier/later than 6 hours (p = 0.743).

Discussion: In patients with anterior circulation LVO stroke treated with direct EVT and no previous anticoagulation, pretreatment with any APT was independently linked to better 90-day functional outcomes and higher independence, without increasing sICH risk.

Classification of evidence: This study provides Class III evidence that, in patients with anterior circulation LVO stroke treated with direct EVT, previous APT is associated with better 90-day functional outcomes compared with no previous APT.

Background and objectives: Neonatal encephalopathy (NE)-including hypoxic-ischemic encephalopathy (HIE)-is associated with significant morbidity and mortality worldwide. While data registries provide hypothesis-generating data, aid in quality improvement, and track management/outcomes over time, we recently demonstrated that only 4 of 1,281 (0.3%) variables were collected by all 22 international NE/HIE registries: birth weight, gestational age, and 1- and 5-minute Apgar scores. In response, our team set out to develop a set of common inpatient data elements to enable future harmonization of NE/HIE registry data.

Methods: Using a modified Delphi method, a panel of 14 international NE experts voted to separate the 1,281 variables from our previous study into "core elements," "supplemental elements," or those that "do not need to be collected." Based on the anonymous survey results, we created draft lists of core and supplemental common data elements (CDEs). These lists were further revised through group consensus meetings and external feedback from global registry leaders and attendants at 2 international conferences.

Results: The final data forms include 164 core elements and 225 supplemental elements stratified into 11 domains: demographics; pregnancy, labor, and delivery; delivery room; transport; acid-base; therapeutic hypothermia; neuromonitoring and seizures; neuroimaging; laboratory values (other than acid-base); hospital course; and discharge.

Discussion: The CDEs are the first of several important steps to further standardize research and reporting of NE/HIE investigations to perform more efficient and powerful clinical research in the field moving forward. Future studies need to establish a clinical and research definition of HIE and develop CDEs for collecting long-term, family-centered follow-up data postdischarge.

Functional neurological disorder (FND) is a neuropsychiatric disorder that manifests with involuntary neurologic symptoms because of a brain network dysfunction, arising from variable biopsychosocial etiologies. Symptoms have positive clinical features of inconsistency, like tremor entrainment or distractibility, and incongruence with typical or well-understood neurophysiology/neuroanatomy. FND is not a diagnosis of exclusion and diagnostic criteria are available for many FND phenotypes.

Background and objectives: Clinical phenotypes of neuropathies associated with contactin-associated protein-1 (CASPR1) or isolated CASPR1/contactin-1 (CNTN1)-complex-IgG are not well characterized, and we aimed to describe the same.

Methods: Patient sera positive for CASPR1 or CASPR1/CNTN1-complex-IgG by cell-based assay (CBA) at Mayo Clinic Neuroimmunology Laboratory (January 1, 2010-May 31, 2024) was identified retrospectively and prospectively. Clinical and paraclinical data were collected. CASPR1/CNTN1-complex-IgG-positive sera were tested using tissue indirect immunofluorescence assay, murine teased nerve fibers, and ELISAs for CASPR1 and CNTN1 to elucidate antigenic targets. Patients were compared with CNTN1-IgG and NF155-IgG4 autoimmune nodopathy cohorts.

Results: Among 17 CASPR1 or isolated CASPR1/CNTN1-complex-IgG-seropositive patients identified, 14 had clinical data (CASPR1-IgG = 8 [50% males, median age 50 years], CASPR1/CNTN1-complex-IgG = 6 [67% males, median age 42 years]). Neuropathic pain was more common in CASPR1-IgG (88% vs 33%), while sensory ataxia was more frequent in CASPR1/CNTN1-complex-IgG cases (100% vs 75%). All showed primarily demyelinating electrophysiology (1 CASPR1/CNTN1-complex-IgG case presented as chronic inflammatory sensory polyradiculopathy). Intravenous immunoglobulin (IVIg) refractoriness occurred in 63% of CASPR1-IgG and 40% of CASPR1/CNTN1-complex-IgG. Rituximab was effective in 6 of 7 (86%) treated patients. One patient with CASPR1/CNTN1-complex-IgG who was refractory to multiple immunotherapies underwent allogenic hematopoietic stem cell transplant after which she was off immunotherapies and is in sustained remission for the past 10 years. CASPR1-IgG patients progressed faster to nadir than NF155-IgG4 (p = 0.003). CASPR1/CNTN1-complex-IgG patients had more frequent asymmetric onset (p = 0.009) and greater long-term disability than NF155-IgG4 (p = 0.035). Five of the 7 CASPR1-IgG patients had IgG4 antibodies, compared with 2 of the 5 CASPR1/CNTN1-complex-IgG patients. Four isolated CASPR1/CNTN1-complex-IgG sera tested positive by tissue immunofluorescence assay; 3 also bound paranodes on teased nerve fibers. CASPR1-IgG cases had higher titers compared with CASPR1/CNTN1-complex-IgG cases by CBA. Three of the 5 CASPR1/CNTN1-complex-IgG cases had CASPR1-IgG reactivity by ELISA, while the other 2 were negative by both CASPR1 and CNTN1 ELISA.

Discussion: CASPR1-IgG and CASPR1/CNTN1-complex-IgG neuropathies, though rare, usually have a rapidly progressive course. Both are frequently IVIg-refractory and respond to rituximab. Compared with NF155-IgG4 nodopathies, CASPR1-IgG exhibits faster progression, while some CASPR1/CNTN1-complex-IgG nodopathies can cause greater long-term disability.

Background and objectives: fMRI has proven useful in dissecting the neurobiological underpinnings of migraine. However, the existing evidence is limited by small samples, use of suboptimal statistical thresholds, and different methods of clinical data acquisition. Given these limitations, we hypothesized that a large, well-characterized sample would allow a clearer distinction between resting-state functional connectivity (rs-FC) alterations specific to migraine and those related to migraine subtypes.

Methods: Adults with migraine and age-matched and sex-matched healthy controls (HCs) underwent a single 3T rs-fMRI scan. We compared rs-FC between migraine and HCs, and across migraine subtypes, using multi-voxel pattern and seed-based analysis. General linear models and analysis of covariance tests with Bonferroni-adjusted cluster-wise family-wise error correction (pFWE-Bonferroni ≤0.001) were applied. rs-FC measures, expressed as Z scores, were also compared across migraine subtypes using general linear models (pBonferroni < 0.05).

Results: We analyzed rs-fMRI data from 264 participants with migraine (mean age 42 ± 12 years, 234 women) and 151 HCs (mean age 41 ± 11 years, 130 women). The multi-voxel pattern analysis identified significant rs-FC differences in a cluster within the bilateral middle cingulate cortex when comparing participants with migraine to HCs (pFWE-Bonferroni <0.001). The seed-based analysis revealed that participants with migraine had increased rs-FC between the cluster in the bilateral middle cingulate cortex and both the right lateral occipital cortex and bilateral occipital pole (both pFWE-Bonferroni <0.001), compared with HCs. Furthermore, increased rs-FC was identified between the limbic lobe and the right occipital pole (pFWE-Bonferroni = 0.0014) and precuneus (pFWE-Bonferroni <0.001). The cingulate-occipital rs-FC was consistently increased in participants with migraine, irrespective of the migraine subtype (pBonferroni <0.001). In addition, ictal participants who were scanned during attacks exhibited an increased hypothalamic rs-FC with the bilateral precuneus, compared with HCs (pBonferroni <0.001). No significant associations emerged between rs-FC and clinical features in migraine.

Discussion: The identified rs-FC alterations between the middle cingulate cortex and occipital regions might represent a migraine-specific trait, suggesting an integration of nociceptive and visual processing. This discovery provides novel insights into the neurobiological underpinnings of migraine and proposes that altered cingulate-occipital rs-FC might serve as a potential biomarker for migraine.