Neurology最新文献

Background and objectives: Rapid advances in diagnostics and treatments are shifting child neurology practice, but child neurology training requirements have been much slower to change. Previous literature confirms strong support for modernization, but no formal consensus exists regarding maintaining or changing training. We aimed to develop a holistic consensus regarding the optimal training pathway and requirements using a modified Delphi process.

Methods: The authors invited 48 child neurologists as panelists, intentionally selecting to represent the diverse geography, practice type, subspecialties, and other demographics of child neurologists practicing in the United States. Panelists participated in an anonymized modified Delphi study with 4 rounds evaluating statements regarding current training requirements, core rotation durations, and mandatory subspecialty rotations with the option to agree or disagree. Statements were derived from current Accreditation Council of Graduate Medical Education, American Board of Psychiatry and Neurology, and American Board of Pediatrics requirements for child neurology training and recent literature. Statements that did not reach a predefined level of consensus (≥75% agreement or disagreement on a 7-point Likert scale) were re-queried or modified for subsequent rounds. Panelists had access to all previous anonymized results and comments. The final modifications were presented in round 4 as a comprehensive training proposal.

Results: Twenty-seven panelists agreed to participate, with most completing all 4 rounds. In round 1, consensus was reached on 45 of 118 (38%) items; round 2, 28 of 87 (32%); round 3, 16 of 25 (64%); and round 4, 1 of 1 (100%). There was consensus regarding the age scope of practice and certain subspecialties that should be required, but no initial consensus regarding time-based requirements. By round 4, consensus emerged for the following rotations-months: neonatal and pediatric intensive care-4, adolescent medicine-0.5, emergency medicine-1.5, inpatient pediatrics-3, outpatient pediatrics-3.5, inpatient child neurology-9.5, outpatient child neurology-6, inpatient adult neurology-3, outpatient adult neurology-2, genetics-2, EEG/neurophysiology-2, neuroimaging-1, child psychiatry-1, and electives-7.5. The consensus schedule consists of 46.5 total months of requirements.

Discussion: This study suggests that, despite diverging views prevalent among child neurologists, a diverse panel can, through a multiround Delphi process, arrive at consensus regarding many core features of the child neurology training structure and certification requirements.

Background and objectives: Stereo-EEG-guided radiofrequency thermocoagulation (RFTHC) has been proposed as relatively safe from a cognitive perspective; however, there is a lack of evidence based on neuropsychological assessments supporting this. This study is the first prospective evaluation of neuropsychological outcomes associated with stereo-EEG-guided RFTHC in patients with focal drug-resistant epilepsy.

Methods: This cohort study involved prospective recruitment of consecutive patients undergoing stereo-EEG from 2 Australian centers. A comprehensive neuropsychological assessment was administered before implantation and 3 months after RFTHC (M = 104.51 days, SD = 29.25). Outcomes across cognitive domains were assessed at a group level with repeated measures t tests. Factorial repeated measures analyses of variance compared memory and language outcomes according to whether dominant mesial temporal lobe (mTL) structures were coagulated. Reliable change indices (RCIs) were computed to explore psychometrically reliable changes at an individual level.

Results: The sample comprised 39 patients who underwent stereo-EEG (M = 37.08 ± 9.67 years, range = 17-56 years, 54% female). Nineteen (49%) had a language dominant epileptogenic zone (EZ), 16 (41%) a nondominant EZ, and 4 (10%) a bilateral EZ. All patients underwent RFTHC with a mean of 11.87 (SD = 6.82, range = 2-29) coagulation sites. Ten patients (26%) had RFTHC within the dominant mTL. At a group level, RFTHC was not associated with a significant decline on any neuropsychological measures (all comparisons p > 0.05). Subgroup analyses revealed a decline in delayed verbal recall after RFTHC of dominant mTL structures (F(1,37) = 4.46, p = 0.04, η_p² = 0.11, 95% CI [0-0.30]; medium to large effect), although it did not remain statistically significant after correction for false discovery rate. No statistically significant group differences were observed on visual memory or language measures post-RFTHC (all comparisons p > 0.05). RCI revealed that after RFTHC within the dominant mTL, 20% of patients experienced a decline in verbal memory and 10% in visual memory. By contrast, 7% declined in verbal memory and 10% in visual memory post-RFTHC outside the dominant mTL.

Discussion: While these findings support the current view that RFTHC is cognitively benign for most cases, the results raise the question of a verbal memory decline after coagulation of the dominant mTL. Individualized neuropsychological counseling before stereo-EEG is essential to avoid unanticipated deficits.

Background and objectives: CSF biomarkers of Aβ42 and phosphorylated tau (p-tau181) are used clinically for the detection of Alzheimer disease (AD) pathology during life. CSF biomarker validation studies have largely used clinical diagnoses and/or amyloid PET imaging as the reference standard. The few existing CSF-to-autopsy studies have been restricted to late-stage AD. This CSF-to-autopsy study investigated associations between CSF biomarkers of AD and AD neuropathologic changes among brain donors who had normal cognition at the time of lumbar puncture (LP).

Methods: This was a retrospective study of brain donors from the National Alzheimer's Coordinating Center who had normal cognition at the time of LP and who had measurements of CSF Aβ42 and p-tau181 performed with Lumipulse assays. All brain donors were from Washington University Knight ADRC. Staging of AD neuropathologic change (ADNC) was made based on National Institute on Aging-Alzheimer's Association criteria. For this study, participants were divided into 2 categories: "AD-" (no AD/low ADNC) and "AD+" (intermediate/high ADNC). Accuracy of each biomarker for discriminating AD status was evaluated using area under the curve (AUC) statistics generated using predicted probabilities from binary logistic regressions that controlled for age, sex, APOE ε4, and interval between LP and death.

Results: The average age at LP was 79.3 years (SD = 5.6), and the average age at death was 87.1 years (SD = 6.5). Of the 49 brain donors, 24 (49%) were male and 47 (95.9%) were White. 20 (40.8%) had autopsy-confirmed AD. The average interval from LP until death was 7.76 years (SD = 4.31). CSF p-tau181/Aβ42 was the optimal predictor of AD, having excellent discrimination accuracy (AUC = 0.97, 95% CI 0.94-1.00, p = 0.003). CSF p-tau181 alone had the second-best discrimination accuracy (AUC = 0.92, 95% CI 0.84-1.00, p = 0.001), followed by CSF Aβ42 alone (AUC = 0.92, 95% CI 0.85-1.00, p = 0.007), while CSF t-tau had the numerically lowest discrimination accuracy (AUC = 0.87, 95% CI 0.76-0.97, p = 0.005). Effects remained after controlling for prevalent comorbid neuropathologies. CSF p-tau181/Aβ42 was strongly associated with CERAD ratings of neuritic amyloid plaque scores and Braak staging of NFTs.

Discussion: This study supports Lumipulse-measured CSF Aβ42 and p-tau181 and, particularly, the ratio of p-tau181 to Aβ42, for the early detection of AD pathophysiologic processes.

Classification of evidence: This study provides Class II evidence that Lumipulse measures of p-tau181/Aβ42 in the CSF accurately discriminated cognitively normal participants with and without Alzheimer disease neuropathologic change.

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of several malignancies, with improved survival. These monoclonal antibodies target immune checkpoints, including cytotoxic T-lymphocyte-associated protein 4 (ipilimumab and tremelimumab), programmed death 1 (nivolumab, pembrolizumab, cemiplimab, and dostarlimab), programmed death ligand 1 (atezolizumab, avelumab, and durvalumab), and lymphocyte activation gene 3 (relatlimab), and effectively augment the immune response against tumor cells. Releasing the brakes on the immune system has consequences, however, in the form of immune-related adverse events (irAEs), which may affect any organ. Neurologic irAEs represent 1%-3% of all irAEs, with immune-mediated myopathy (ICI myopathy) being the most common manifestation. Recent large patient series and systematic reviews have established the key features and highlighted new insights into ICI myopathy. ICI myopathy is characterized by an acute or subacute onset of oculobulbar and/or proximal limb weakness, with or without associated respiratory insufficiency and myocarditis. Creatine kinase elevation is common. Oculobulbar presentations with or without respiratory failure may be misattributed to neuromuscular junction disorders, particularly because acetylcholine receptor antibodies are present in up to 40% of patients; however, an electrodiagnostic evidence of a defect of neuromuscular transmission is often absent even in patients with severe weakness, highlighting that the myopathic process is the driving force behind these presentations. Muscle histopathology commonly demonstrates a unique signature of multifocal clusters of necrotic and regenerating fibers, differentiating ICI myopathy from other autoimmune myopathies. Transcriptomic analysis has uncovered distinct subgroups within ICI myopathy, revealing varying degrees of type 1 and type 2 interferon pathway activation alongside notable upregulation of the interleukin (IL)-6 pathway in affected muscle tissue. This discovery presents a promising avenue for intervention through the use of therapies that suppress the interferon pathway and target IL-6 or its receptor. Despite clinical improvements with immunomodulatory therapy, with corticosteroids the mainstay of treatment, mortality remains high, particularly in those with associated myocarditis or respiratory failure requiring intubation, where mortality occurs in up to 50%. ICI withdrawal can lead to cancer progression and death, highlighting a need for improved approaches to ICI rechallenge, performed in limited patients with variable success to date.

Given the relatively low incidence, high prehospital death rate, substantial geographical differences, and complex disease origin (combination of genetic and environmental risk factors), epidemiologic research on subarachnoid hemorrhage (SAH) and its risk factors is challenging. In practice, we are more or less forced to exploit compromised study designs and nonrepresentative data in such circumstances where it is almost impossible to gather comprehensive data through an optimal design. For example, hospital-based patient cohorts, administrative data repositories, and short-term population-based studies from small geographical regions are often used to research the incidence, case fatality, and risk factors of SAH, regardless of their inherent and self-evident limitations. Since studies on the epidemiology of SAH focus largely on identifying possible risk factors that could aid in disease diagnostics, treatment, and prevention, we aimed to review recent evidence on modifiable risk factors for SAH. In this context, we also try to explain the methodological reasons behind some of the conflicting results and to discuss the primary strengths and limitations of different study designs used in the field of SAH epidemiology. Based on our findings, smoking, high blood pressure, and possibly low physical activity are the only risk factors with high-quality evidence supporting their causal role in SAH. In addition, since all 3 commonly used study designs in SAH epidemiology, namely, hospital-based, population-based, and administrative register-based studies, have their own strengths and limitations, the most robust risk factor estimates and other epidemiologic measures of SAH can likely be established by combining various overlapping and high-quality sources of information in the future.

Background and objectives: There is growing evidence that sleep disturbances are associated with cognitive impairment risk, but their association with the incidence of motoric cognitive risk syndrome (MCR)-a predementia syndrome characterized by slow gait speed and cognitive complaints-is unknown. We aimed to examine the association of sleep disturbances, overall and specific subtypes, with (1) incident and (2) prevalent MCR in older adults.

Methods: Community-residing adults aged 65 years and older without dementia were recruited from population lists and included in Central Control of Mobility and Aging, a prospective cohort study, in Albert Einstein College of Medicine, Bronx, NY. We included participants with available data for MCR and Pittsburgh Sleep Quality Index (PSQI). MCR was defined as cognitive complaints reported on standardized questionnaires and slow gait speed as recorded on an electronic treadmill and was adjudicated at baseline and annual follow-up visits. Participants were divided into "good" sleepers (≤5) and "poor" sleepers (>5) based on an established PSQI cut score. Among participants without MCR at baseline, Cox proportional hazard models adjusted for (1) age, sex, and education and (2) further for comorbidity index, Geriatric Depression Scale score, and global cognitive score were used to examine the association of baseline sleep disturbances with MCR incidence. Association between poor sleep quality and prevalent MCR at baseline in the overall population was explored using multivariate logistic regression analysis.

Results: 445 participants were included (56.9% women, mean age: 75.9 years [75.3; 76.5]). In MCR-free participants at baseline (n = 403), 36 developed incident MCR over a mean follow-up of 2.9 years. Poor sleepers had a higher risk of incident MCR (HR = 2.7 [1.2; 5.2]) compared with good sleepers, but this association was not significant after adjustment for depressive symptoms (adjusted hazard ratio [aHR] = 1.6 [0.7-3.4]). Among the 7 PSQI components, only sleep-related daytime dysfunction (excessive sleepiness and lower enthusiasm) showed a significant risk of MCR in fully adjusted models (aHR = 3.3 [1.5-7.4]). Prevalent MCR was not associated with poor sleep quality (OR [95% CI] = 1.1 [0.5-2.3]).

Discussion: Overall poor sleep quality was associated with incident MCR, but not with prevalent MCR. Specifically, older adults with sleep-related daytime dysfunction are at increased risk of developing MCR. Further studies are needed to validate mechanisms of this relationship.