Neurology. Clinical practice最新文献

Objectives: The aim of this study was to evaluate the contribution of metagenomic next-generation sequencing (mNGS) in critically ill patients with encephalitis of unknown etiology.

Methods: This retrospective study (2016-2023) was conducted in a tertiary care referral neuro-ICU at La Pitié-Salpêtrière Hospital (Paris, France). The inclusion criteria were encephalitis with unknown etiology and mNGS performed on CSF, brain biopsy, and/or autopsy. We assessed the yield of mNGS and whether specific treatments were initiated. Neurologic outcome at 1 year was assessed using the Glasgow Outcome Scale-Extended (GOSE-1: death; GOSE-8: upper good recovery).

Results: A total of 49 patients were included, of whom 44.9% were immunosuppressed. At 1 year, 38.8% had a GOSE score 4-8 and 47.7% died. mNGS was performed on the CSF of 40 of 49 patients (81.6%) and on brain biopsy of 19 of 49 patients (38.8%), including 12 patients who underwent both CSF and biopsy testing. Among the 40 mNGS analyses performed on the CSF, 7 (17.5%) yielded positive results but only 1 (2.5%) was likely causative. Conversely, 7 of 19 mNGS analyses (36.8%) on biopsies were positive and causative. Regarding the yield of mNGS in the entire cohort, 15 of 49 patients (30.6%) had a positive result but only 7 of 49 (14.3%) were causative (dengue virus, measles virus, rubella virus, Nocardia spp, HHV6, astrovirus, and orthobunyavirus), all from brain biopsies of immunocompromised patients. Conversely, 8 of 49 mNGS analyses (16.3%) were noncausative (polyomavirus, HHV8, HHV7, EBV, 2 pegiviruses, and 2 rhinoviruses). Specific treatments were initiated in 4 of 7 patients (57%). Among the 34 patients with a negative mNGS result, 5 (14.7%) were diagnosed with infectious encephalitis using conventional methods.

Conclusion: In critically ill patients with encephalitis of unknown etiology, mNGS performed on brain biopsy could reduce diagnostic uncertainty.

Background and objectives: The Inflation Reduction Act (IRA) introduced major reforms to Medicare Part D, including an annual out-of-pocket (OOP) maximum and the Medicare Prescription Payment Plan (MPPP), which allows beneficiaries to spread OOP costs over monthly payments. The IRA's Part D provisions, as well as wider use of direct-to-consumer (DTC) pharmacies, could reduce OOP costs for self-administered disease-modifying therapies (DMTs) among Medicare beneficiaries with multiple sclerosis (MS). This study estimated OOP costs for self-administered DMTs under the IRA's Part D provisions and through DTC pharmacies.

Methods: We calculated OOP costs for brand-name and generic DMTs under Part D in the pre-IRA (2023) and post-IRA (2025) periods. We also assessed the impact of voluntary enrollment in the MPPP in 2025. Finally, we examined OOP costs for generic DMTs purchased through DTC pharmacies.

Results: Before the IRA (2023), annual OOP costs ranged from $6,275 to $8,883 for brand-name DMTs; after the IRA (2025), annual OOP costs decreased by 68%-77% because all brand-name DMT users reached the annual OOP maximum ($2,000 in 2025). OOP costs were heavily frontloaded as lumpsum payments unless beneficiaries enrolled in the MPPP, which could lead to monthly payments as low as $167 for DMTs in 2025 (a reduction of over 90% in monthly OOP costs for January). Generic DMTs had annual OOP costs ranging from $212 to $7,855 before the IRA (2023) and $212 to $2,000 after the IRA (2025). Purchasing generic DMTs through DTC pharmacies resulted in annual OOP costs ranging from $133 to $39,984 and could lead to lower costs for some beneficiaries.

Discussion: Annual OOP costs for self-administered DMTs among Medicare beneficiaries with MS decreased significantly beginning January 1, 2025, because of the IRA's annual OOP maximum. Beneficiaries who voluntarily enroll in the MPPP will also be able to spread OOP costs over more manageable monthly payments. Direct cash purchase of some generic DMTs through DTC pharmacies could lead to lower OOP costs, but these payments will not count toward beneficiaries' deductible or annual OOP maximum. Neurologists have a critical role in ensuring that their Medicare patients with MS are aware of the option to enroll in the MPPP and the possibility of obtaining generic DMTs through DTC pharmacies.

Background and objectives: Numerous observational studies are available to asymptomatic individuals at risk to carry or known carriers of pathogenic variations associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS-FTD) spectrum disorders. Little is known about such individuals' motivations for participation or the impact on their emotional well-being.

Methods: Asymptomatic at-risk adults, with or without genetic status known, were recruited through social media advocacy groups and by National Society of Genetic Counselors ALS-FTD special interest group members. Interviews were conducted through secure videoconferencing. Two coders independently analyzed interview transcripts, followed by thematic content analysis.

Results: Twelve participants (9 status-aware and 3 status-unaware) were interviewed, representing experience with 11 observational studies. Some motivations for participation aligned with previous literature, including altruism, health focus, and intellectual interest. Motivations unique to this population stemmed from the hereditary nature of the disease, including fear of future disease onset and the desire to establish a relationship with a specialized clinical care team, reflecting individual, familial, and societal factors. Benefits of participation included meeting these motivational goals, social connection and support, psychological well-being, and practical benefits. Challenges to participation fell into research-related (e.g., struggles with the observational nature of research), disease-related (e.g., anxiety about disease risk), and logistical (e.g., travel and study procedures) categories. Compared with status-unaware participants, status-aware participants more frequently cited individual motivators for research participation and encountered more research-related challenges when their participation did not align with their anticipated personal health benefits. Interviewees found relationships with providers through research to be rewarding but noted confusion between research and clinical care as a significant challenge.

Discussion: Participation in observational research helps address unmet emotional and medical needs for asymptomatic individuals who are at risk of ALS-FTD spectrum disorders. However, some of these needs are beyond the scope of research, highlighting the need for new models of clinical care for at-risk individuals.

Background and objectives: Approximately one-third of children with epilepsy develop intractable epilepsy and require multiple-day hospital admission for EEG and neuroimaging to determine other interventions for seizure reduction (Phase 1). Of note, children with epilepsy are at increased risk of autism spectrum disorder (ASD); however, prolonged hospitalization may be difficult due to developmental delays, sensory sensitivities, and challenging behavior. Challenging behavior during or reluctance to complete admission may lead to delayed or incomplete information about seizures and interfere with treatment. To address this need, we created a multidisciplinary team and a novel program, the Phase 1 ASD and epilepsy intervention program. We used quality improvement (QI) methodology, and our aim was to increase the percentage of patients with ASD and epilepsy who participated in a treatment program before Phase 1 admission from 0% to 80% in the first year.

Methods: Participants included children with ASD and epilepsy who were referred for Phase 1 at a large children's hospital with a level 4 epilepsy center. After referral, caregivers were called to complete an intake and gather information about the child's development, preferences, and needs for admission. The program includes individualized planning for admission based on the child's needs, team communication about patient characteristics and needs, and behavior intervention. The intervention was implemented and monitored using QI methodology.

Results: All children with ASD referred for Phase 1 were enrolled in the program, and we achieved a centerline shift in the first 2 years, which has been sustained for 5 years (68 of 81 participants, 83.9%). The age of patients ranged from 2 to 18, with a mean age of 10.7 years. Seventy percent were male, and 66.7% were White. All children who participated completed the multiple-day EEG and all required medical procedures.

Discussion: Our work demonstrates the feasibility of the program, which is now standard of care at our hospital. Similar interventions can be implemented for Phase 2 admissions or other medical procedures. Children with ASD who participate in a multidisciplinary intervention program can successfully complete potentially challenging hospital admissions, allowing them equitable access to critical care.

Background and objectives: In cervical spondylotic myelopathy (CSM), compression may not be evident in the neutral position, potentially leading to misdiagnosis and delayed treatment. We sought to assess the utility of flexion-extension MRI in revealing occult spondylotic compression in undifferentiated myelopathies with spinal cord T2 hyperintensity.

Methods: Adult patients with clinical myelopathy and cervical spinal cord T2 hyperintensities who had undergone flexion-extension cervical spine MRI over a >10-year period (December 31, 2012, to October 24, 2023) were retrospectively identified. Demographic, clinical, and radiologic data were collected and analyzed.

Results: Ninety patients who underwent flexion-extension MRI for possible CSM were identified. The median age was 58 years (range, 30-81), with 47 of 90 patients (52%) being male. CSM was the final diagnosis in 65 (85% had insidious onset; 12% had reverse Lhermitte phenomenon). Before flexion-extension MRI, 39 of 65 with CSM had an initially uncertain diagnosis and 26 of 65 (40%) were initially given alternative diagnoses, including 19 of 65 (29%) who received immunotherapy and one who underwent spinal cord biopsy. The median delay to diagnosis in these patients was 15 months (range, 0.5-155). Positional compression on flexion-extension MRI at sites of T2 signal hyperintensity was more likely with a final diagnosis of CSM (55/65 [85%]) than with an alternative myelopathy etiology (3/25 [12%]: multiple sclerosis, 2; progressive lateral sclerosis, 1) (p < 0.0001). The odds ratio for CSM in the presence of positional cord compression was 40.3 (95% CI 10.58-137.4; Fisher exact test p < 0.0001). The dynamic changes noted in CSM during flexion-extension MRI included the following: worse in extension, 47 (85%); worse in flexion, 4 (7.5%); worse in both, 4 (7.5%). Decompressive surgery was completed at Mayo Clinic in 46 of 65 patients with CSM (71%). Most reported symptomatic improvement alone (29/43, 67%), nearly a quarter (10/43, 23%) reported improvement in some symptoms but worsening of others, a minority (4/43, 9%) noted only symptom stability, and none described worsening alone (0/43, 0%); 3 were lost to follow-up.

Discussion: Flexion-extension MRI is a cost-effective, accessible technique that can reveal occult CSM or provide clarity when the diagnosis is uncertain, and its use may reduce misdiagnosis and allow earlier treatment of unrecognized CSM.

Background and objectives: Focal cortical dysplasia (FCD) is the most common cause of surgically treatable drug-resistant epilepsy (DRE) in children. Surgical outcomes are poorly defined in early-onset FCD-DRE. The purpose of this study was to evaluate clinical and presurgical characteristics relating to surgical outcomes in early-life (seizure onset <4 months old) FCD-DRE.

Methods: A multicenter prospective cohort was analyzed from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database to identify patients with pathologically confirmed FCD-DRE and seizure onset younger than 4 months old. Clinical characteristics, presurgical workup, and surgical intervention and outcomes data were collected and analyzed. Primary outcome was to evaluate whether earlier surgery is associated with seizure freedom; secondary outcomes evaluated clinical/presurgical predictors of seizure freedom and safety.

Results: Thirty-one patients with FCD-DRE were identified from 18 PERC centers. Median age at seizure onset was 2.4 months (interquartile range 1.2-3.6 months). Four patients had focal to bilateral tonic-clonic seizures (FBTCS); 35% (n = 11) had epileptic spasms. Median age at phase 1 referral was 2.0 years (0.7-4.0 years). Median age at surgery was 2.6 years (1.1-5.5 years). Pathology was type II, 65% (n = 20); type I, 26% (n = 8); and type III, 6% (n = 2). Seizure freedom was achieved in 65% (n = 20) with median follow-up 2.5 years (1.3-4 years). Age at seizure onset/referral/surgery, surgery type, and experiencing FBTCS were not associated with seizure-free outcome. Type IIB pathology had 89% (n = 8) seizure-free outcome. Epileptic spasms had 45% seizure-free outcome. Transient neurologic deficits occurred in 2 patients, and an expected neurologic deficit in 1 (visual field cut from occipital lobectomy). There were no deaths.

Discussion: This study finds high rates of seizure-free outcome in epilepsy surgery for early-onset FCD-DRE across all pathologies and procedures with minimal complication rates and no deaths. Focal cortical dysplasia type IIB is associated with very high rates of seizure-free outcome. Epileptic spasms were associated with lower seizure-free outcome. The study also fails to confirm a high rate of multilobar unilateral hypoplasia with severe epilepsy in children, a type I FCD variant that has been reported as a common etiology of early-life FCD.

Objectives: To describe the neuroimaging findings of patients after successful antiparasitic treatment for subarachnoid and intraventricular neurocysticercosis (NCC).

Methods: In this retrospective case series, we reviewed brain MRIs for 6 patients cared for between 2015 and 2021 with confirmed subarachnoid or intraventricular NCC who were successfully treated, defined as a negative Taenia solium antigen and quantitative PCR from CSF.

Results: On post-treatment MRIs obtained between 0 months and over 4 years after completion of therapy, all patients had persistently abnormal neuroimaging findings, including residual enhancing cysts and leptomeningeal and vascular enhancement, despite continued clinical improvement.

Discussion: Persistent post-treatment MRI abnormalities are common in patients with NCC and do not necessarily warrant additional antiparasitic therapy. Although MRI remains a valuable tool for assessing overall treatment response, complete normalization of neuroimaging findings is uncommon in subarachnoid and intraventricular NCC.

Neurologic disorders, now a leading cause of disease burden globally, have further added to the growing concerns of access to care, especially given the anticipated 19% shortfall of neurologists. There is a pressing need to improve access and decrease appointment wait times. We led a departmental initiative to bridge the access gap. We focused on template management, leveraging advanced practice providers (APPs), and provision of timely access for new patients. Over 2 years, the total patient volume and the new patient volume increased by 34% and 32%, respectively. Visits per clinic session grew by 21% for APPs. The number of new patients seen within 10 days grew from 19% to 42% (123% increase) for internal referrals and from 21% to 43% (100% increase) for all referrals. This article reviews our strategies in improving patient access.

Background and objectives: The socioeconomic and demographic factors affecting the prescription of migraine medications are underexplored. Understanding these factors is critical to addressing health. We used our tertiary headache center's prescription database to assess the demographic and socioeconomic factors associated with the prescription of acute and preventive migraine medications and the factors affecting the rollout of novel migraine medications.

Methods: We performed a retrospective cohort analysis using aggregated deidentified data of patients who had received care through the Stanford Headache Clinic using data adapted from the Stanford deidentified instance of the Observational Medical Outcomes Partnership Common Data Model. We included patients in California who had received a diagnosis of chronic migraine and had received at least 1 prescription from our clinic between 2018 and 2022. The types and volumes of prescriptions were assessed, as well as demographic factors (age, sex, race ethnicity, and zip code income quartile).

Results: A total of 4,213 patients met inclusion criteria, of whom 3,349 (79.5%) were women and 863 (20.5%) were men, with a mean age of 44.6 ± 14.7 years. Our group was predominantly White and non-Hispanic/non-Latino (2,381/4213, 56.5%) and came from zip codes whose median income ranged from $77,250 to $236,912 (2046/3298, 62.0%). Age, sex, and race-ethnicity were all found to be statistically significant factors in the selection of both acute and preventive medications for patients. Zip code income quartile played a limited role in prescription variation for both acute and preventive medications. Race-ethnicity was also a statistically significant factor for those who received a prescription for a calcitonin gene-related peptide (CGRP) monoclonal antibody and a gepant. Similarly, sex, race-ethnicity, and zip code income quartile were all factors in the rollout of the CGRP monoclonal antibodies and gepants (all p < 0.05), but age was not (p = 0.722 and p = 0.057, respectively). The second and third zip code income quartiles had the lowest prescription rates of the CGRP monoclonal antibodies and gepants during their rollout.

Discussion: Disparities in sex, race-ethnicity, and zip code income quartile were found among those who received medications and which acute and preventive migraine medications were prescribed. This may reflect that some groups may have received less headache-specific care before establishing with our clinic. Future research will seek to better illuminate the underlying reasons for this more clearly to enable solutions and ensure equitable care.

Background and objectives: Atypical psychosis, characterized by severe delusions, paranoia, and auditory or somatic hallucinations, is a notable complication of continuous subcutaneous infusion (CSCI) of foslevodopa/foscarbidopa therapy in Parkinson disease (PD). The aim of this study was to identify clinical predictors of CSCI-induced psychosis to understand its potential mechanisms and evaluate predictive measures for early detection and management.

Methods: This retrospective cohort study included patients with PD treated with CSCI (n = 23) and an independent PD database cohort (n = 94) from Osaka University Hospital. In the CSCI cohort, clinical data such as psychosis information and answers from Parkinson's Disease Questionnaire (PDQ39) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Current Symptoms (QUIP-CS) were collected. Statistical analyses included independent t tests and linear regression to identify predictors of atypical psychosis within a year of CSCI initiation. In the PD database cohort, potential relationships between QUIP-CS scores and other clinical parameters were explored using correlational analyses.

Results: Among the 23 patients, 6 developed atypical psychosis, all occurring within 6 months, with 4 of them discontinuing CSCI. Patients who developed atypical psychosis had significantly higher QUIP-CS scores before CSCI (adjusted p = 0.0032). Linear regression identified QUIP-CS as the sole predictor of atypical psychosis onset (coefficient = 0.199, p < 0.001). Among the PDQ39 subitems, item 27 showed a significant correlation with QUIP-CS scores (r = 0.722, adjusted p = 0.0128). Furthermore, a composite score comprising PDQ39 items 20, 27, 29, 31, and 36 (PDQ39_sub5) showed an even stronger correlation with QUIP-CS scores (r = 0.770, p = 0.0000704). This association was independently confirmed in the PD database cohort (r = 0.415, p = 0.00003). Finally, PDQ39_sub5 effectively stratified survival curves for psychosis onset in the CSCI cohort (p = 0.008).

Discussion: CSCI-induced psychosis is distinct from visual hallucinations observed in typical PD psychosis and likely involves mechanisms in mesolimbic circuits and impulsive-compulsive behaviors associated with dopamine dysregulation. While QUIP-CS is rarely used in clinical practice, widely used PDQ39_sub5 offers a practical way to identify individual psychosis risk. These findings potentially offer tailored strategies to predict and manage atypical psychosis in patients with PD receiving advanced dopaminergic therapies.