Neurology. Clinical practice最新文献

Background and objectives: Susac syndrome (SuS) is a rare autoimmune disorder characterized by the classic clinical triad of encephalopathy, sensorineural hearing loss, and branch retinal artery occlusion (BRAO). Maintenance immunotherapy is important in most cases to prevent new attacks that can cause significant disability. However, owing to the rarity of SuS, there are few large studies evaluating the efficacy of immunotherapies in SuS. In this large case series, we evaluated the association of utilized immunotherapies and relapse rates in the management of SuS from a large multicenter cohort.

Methods: Retrospective data analysis of 54 patients with definite or probable SuS diagnoses who were evaluated and managed at 2 academic medical centers in the United States. The percentage with relapse and annualized relapse rate (ARR) were calculated for each immunotherapy.

Results: The median age at diagnosis of SuS was 36.5 years (interquartile range 30-46 years), and 61% were female. On maintenance immunotherapy, the relapse rate and median ARR were as follows: mycophenolate mofetil 40% (12 of 30 with a median duration of 1.08 years; ARR 0), low or intermediate dose IV immunoglobulin (IVIG) 42.3% (11 of 26 with a median duration of 0.75 years; ARR 0.1), high dose IVIG 11.7% (2 of 17 with a median duration of 0.58 years; ARR 0), cyclophosphamide 36.3% (8 of 22 with a median duration 0.5 years; ARR 0), rituximab 38% (8 of 21 with a median duration of 1.58 years; ARR 0), azathioprine 60% (3 of 5 with a median duration of 1.33 years; ARR 0.1), methotrexate 66.6% (2 of 3 with a median duration of 5.5 years, ARR 0.1), infliximab 0% (0 of 1 with duration of 0.66 years; ARR 0), maintenance plasma exchange 0% (0 of 1 with duration of 1.25 years; ARR 0), and tocilizumab 0% (0 of 1 with duration of 0.91; ARR 0).

Discussion: Our relatively large cohort of patients with SuS shows a variety of maintenance immunotherapies are used with varying response rates. Among our patients, a number of refractory cases required aggressive and combination of immunotherapies.

Background and objectives: Plasma biomarkers provide new tools for evaluating patients with mild cognitive impairment (MCI) for Alzheimer disease (AD) pathology. Such tools are needed for anti-amyloid therapies that require efficient and accurate diagnostic evaluation to identify potential treatment candidates. This study sought to develop and evaluate the clinical performance of a multimarker combination of plasma beta-amyloid 42/40 (Aβ42/40), ptau-217, and APOE genotype to predict amyloid PET positivity in a diverse cohort of patients at a memory clinic and evaluate >4,000 results from "real-world" specimens submitted for high-throughput clinical testing.

Methods: Study participants were from the 1Florida AD Research Center. Demographics, clinical evaluations, and amyloid PET scan data were provided along with plasma specimens for model development in the intended-use cohort (MCI/AD: n = 215). Aβ42/40 and ApoE4 proteotype (reflecting high-risk APOE ɛ4 alleles) were measured by mass spectrometry and ptau-217 by immunoassay. A likelihood score model was determined for each biomarker separately and in combination. Model performance was optimized using 2 cutpoints, 1 for high and 1 for low likelihood of PET positivity, to attain ≥90% specificity and sensitivity. These cutpoints were applied to categorize 4,326 real-world specimens and an expanded cohort stratified by cognitive status (normal cognition [NC], MCI, AD).

Results: For the intended-use cohort (46.0% prevalence of PET positivity), a combination of Aβ42/40, ptau-217, and APOE4 allele count provided the best model with a receiver operating characteristic area under the curve of 0.942 and with 2 cutpoints fixed at 91% sensitivity and 91% specificity, yielding a high cutpoint with 88% positive predictive value and 87% accuracy and a low cutpoint with 91% negative predictive value and 85% accuracy. Incorporating the APOE4 allele count also reduced the percentage of patients with indeterminate risk from 15% to 10%. The cutpoints categorized the real-world clinical specimens as having 42% high, 51% low, and 7% indeterminate likelihood of PET positivity and differentiated between NC, MCI, and AD dementia cognitive status in the expanded cohort.

Discussion: Combining plasma biomarkers Aβ42/40, ptau-217, and APOE4 allele count is a scalable approach for evaluating patients with MCI for suspected AD pathology.

Background and objectives: Muscular dystrophies are characterized by progressive muscle weakness and degeneration. Identifying cases and abstracting data from electronic medical records (EMRs) is helpful for surveillance and research. However, manual EMR abstraction is laborious. We studied 2 approaches to accelerate EMR abstraction: large language models (LLMs) and International Classification of Diseases (ICD) code meta-analysis.

Methods: In our cross-sectional study, EMRs from 22 individuals with Duchenne muscular dystrophy (DMD) and 22 individuals with limb-girdle muscular dystrophy (LGMD) were exported into a data shelter and manually annotated using MedTator. Annotations were guided by a schema focused on 4 key features of muscular dystrophy: first symptoms, ambulatory status, serum creatine kinase (CK) levels, and genetic test results. Five LLMs were fed a series of prompts and examples, and then, clinic notes from each of the 44 cases were inputted for model analysis. Inter-rater agreement (IAA) and F1 scores were calculated for manual annotations, and the F1 score for LLMs compared with manual annotations was calculated. We then analyzed a separate set of 77 DMD and 59 LGMD cases to determine whether the number of health care encounters with a muscular dystrophy-related ICD code could predict diagnostic certainty based on MD STARnet criteria.

Results: IAA for manual annotations varied between 80% (for annotation of symptoms) and 100% (for CK values). The highest performing LLM was Llama 3-8b, which yielded the following accuracies: 46.8% for "first symptoms," 56.9% for "ambulatory status," 69.2% for "CK values," and 68.4% for "genetic test results." Among 77 individuals with DMD, all patients with 20 or more encounters linked to relevant ICD codes had definite or probable diagnoses, whereas among 59 individuals with LGMD, all patients with 25 or more encounters linked to relevant ICD codes had definite or probable diagnoses.

Discussion: LLMs promise to accelerate EMR abstraction for rare diseases such as muscular dystrophy, but F1 scores for LLMs currently lag manual abstractions for unstructured data. Llama 3-8b demonstrated superior performance to the 4 other models tested. Metadata such as ICD code counts may help prioritize high-yield cases for surveillance and research purposes.

Background and objectives: Postanoxic myoclonus is a well-recognized phenomenon after cardiac arrest and often indicates poor prognosis. Other spontaneous movements, such as tonic eyelid opening, have also been documented, but spontaneous chewing movements remain poorly characterized. The aim of this study was to systematically analyze the electrophysiologic features of postanoxic chewing movements, propose a standardized nomenclature, discuss potential pathophysiology, and evaluate their prognostic significance.

Methods: We retrospectively reviewed clinical data from post-cardiac arrest patients who exhibited suspicious chewing movements during continuous video-EEG (vEEG) monitoring between January 2021 and December 2024. Chewing movements were analyzed for duration, frequency, and correlation with EEG findings. Demographic, clinical, management, and outcome data were also collected. A thorough literature review was conducted.

Results: Twelve patients (mean age: 62.3 ± 10.5 years) who experienced out-of-hospital cardiac arrest exhibited repetitive chewing movements. Detailed analysis of video recordings and bedside observations identified these movements as rhythmic tongue elevations against the upper palate with minimal jaw activity, producing chewing artifacts on EEG. These episodes lasted 4-5 seconds and were periodic in 2 patients. Video-EEG revealed that in 8 patients, the movements followed EEG bursts by 1-1.5 seconds, whereas in 4 patients, they occurred spontaneously without corresponding cortical activity. The movements were transient, with a median duration of 24 hours, and resolved within 72 hours despite persistent burst-suppression patterns. Brain MRI in 3 patients demonstrated diffuse anoxic/hypoxic cortical injury with relative brainstem preservation. All patients died after cardiac arrest, with a median survival of 5 days.

Discussion: We propose the term postanoxic oral automatism (PAOA) to describe a distinct, transient oral motor phenomenon characterized by repetitive, chewing-like tongue movements in comatose patients after cardiac arrest. Unlike previous reports confined to burst-suppression EEG patterns, our findings show that PAOA can occur in both burst-suppression and background-suppression EEG backgrounds. These movements likely result from disinhibition of brainstem central pattern generators responsible for rhythmic orofacial activity and may signify severe cortical dysfunction. Although PAOA is associated with poor prognosis, its independent predictive value remains unclear.

Background and objectives: Historically, researchers and clinicians have assumed that patients engage and initiate treatment for Tourette syndrome to reduce tic severity. As a result, current gold-standard assessment methods and intervention studies focus on global tic reduction. However, initial community-engaged work suggests that patients seek tic treatment for reasons beyond symptom reduction (e.g., impairment), and a host of previous research has shown an inconclusive relationship between tic severity and impairment. The aim of this study was to qualitatively examine patient-reported tic-related impairment using an open-ended prompt exploring the ways that tics get in the way or make life hard.

Methods: Data were collected from 2 treatment trials examining various methods of delivering Comprehensive Behavioral Intervention for Tics. In total, 69 participants aged 8-57 years were included in this study. Responses to prompts were coded using an inductive, iterative approach by 3 researchers with expertise in tic disorders.

Results: Six major themes (social interference, task interference, physical experiences, tic-related emotional distress, activity restriction, and sleep interference/fatigue) and 14 minor themes were extracted from the data.

Discussion: Results represent an initial step in identifying, measuring, and addressing patient-centered goals in tic treatment.

Background and objective: The aim of this study was to assess the localizing and lateralizing significance of initial, mid-ictal, and ictal-end head position in versive seizures with secondary generalization.

Methods: We analyzed video-EEG recordings of 65 patients with focal epilepsy for various head position changes during version evolving into secondary generalized tonic-clonic (GTC) seizure. We calculated the latency of version from seizure onset and the latency of secondary generalization from version. We excluded patients with generalized epilepsy.

Results: The latency of version from seizure onset (T1) was 46.7 ± 8.8 sec and 24.1 ± 8.2 sec in temporal and frontal lobe groups, respectively (p < 0.0001). Occipital seizures had the longest latency of 77.8 ± 42.9 sec (p = 0.0002). The latency of secondary GTC seizures (T4) from initial version was 15.7 ± 3.2 sec in the temporal lobe group, compared with 18.3 ± 5.7 sec in the frontal lobe group (p = 0.03) and 18.8 ± 9.3 sec (p = 0.13) in the parietal lobe group. Occipital seizures had the shortest latency at 9.8 ± 3.9 sec (p = 0.0001). In 57 of 65 patients, the head position evolved to a primary midline position from the initial version. In 24 of 65 patients, the head position further evolved to an ictal-end position by the end of the GTC phase. In these 24 patients, the ictal-end head position was contralateral to the direction of initial version in 100% of cases, and hence ipsilateral to the epileptogenic zone. In total, 13 of these 24 patients also had corresponding ipsilateral ictal-end clonic movement.

Discussion: Latency of onset of the initial version has a localizing significance for the epileptogenic zone, with the shortest latency for frontal seizures and the longest for occipital seizures. This is consistent with the relative distance of the frontal eye field from these seizure-onset zones. An ictal-end head position contralateral to the initial version occurs in approximately 37% of focal epilepsies and is always ipsilateral to the epileptogenic zone.

Background and objectives: The Up-LIFT Trial demonstrated that in-clinic rehabilitation augmented by noninvasive spinal cord stimulation (ARC^EX Therapy) safely and effectively improved upper extremity strength and function in people with chronic incomplete cervical spinal cord injury (SCI). As a follow-up study, LIFT Home, a single-arm interventional trial, investigated the safety, usability, and benefits of ARC^EX Therapy during home use.

Methods: Seventeen participants from the Up-LIFT Trial continued with ARC^EX Therapy at home for 1 month. Primary endpoints evaluated the safety and feasibility of at-home ARC^EX Therapy. Secondary efficacy outcomes included the Capabilities of Upper Extremity Test (CUE-T); the Graded Redefined Assessment of Strength, Sensation, and Performance; pinch and grasp forces; and global impression of change scores. Additional post hoc analysis examined the effect of different periods of time without treatment, and the potential of home-based therapy to maintain or extend improvements achieved in-clinic. Finally, quality of life and independence were assessed through participant-reported surveys.

Results: There were no serious adverse events related to the device or major usability issues that interfered with home-based treatment. Compliance with the prescribed therapy was high and mirrored in-clinic therapy dosages, with participants completing 12.3 ± 2.9 sessions each lasting 59 ± 10 minutes on average. Average CUE-T scores and pinch forces significantly improved (Δ2.2 ± 4.1, p = 0.025 and Δ6.9 N ± 15.5, p = 0.020, respectively), as did pain interference with day-to-day activities (International SCI Pain Data Set subscore Δ-0.6 ± 1.2, p = 0.019), psychological health (World Health Organization Quality of Life-BREF subscore Δ3.4 ± 5.8, p = 0.025), and self-care ability (Spinal Cord Independence Measure III subscore Δ0.2 ± 0.4, p = 0.042). Improvements were most apparent in individuals who responded to prior in-clinic ARC ^EX Therapy. Notably, post hoc analysis revealed that functional decline following periods of inactivity can be reversed, and in-clinic progress can be further enhanced with at-home ARC^EX Therapy.

Discussion: This study suggests ARC^EX Therapy can be safely used at home to continue to improve strength and function. It is important that at-home therapy may be essential to maintain intervention-related in-clinic gains.

Trial registration information: The LIFT Home Trial was registered on clinicaltrials.gov (NCT05284201, clinicaltrials.gov/study/NCT05284201) on September 03, 2022. The first participant was enrolled on March 03, 2022.

Background and objectives: Determining whether a patient should discontinue antiseizure medication after a period of seizure-freedom is often challenging. Risk prediction tools can support shared decision-making. End-user stakeholder engagement throughout the tool development process is critical. We examined clinician views regarding potential novel graphically based seizure risk prediction tools.

Methods: We conducted 6 qualitative 1-hour focus groups of 3-5 providers who see patients with epilepsy (total N = 25). We used purposive sampling as informed by previous literature to include both epileptologists and general adult neurologists from geographically diverse settings. We obtained feedback from respondents regarding several possible novel seizure risk prediction tools and asked for any other suggested risk prediction formats. Interviews were transcribed verbatim and analyzed by independent readers using both deductive (researcher-driven) and inductive (response-based) reasoning.

Results: Although some respondents favored numerical-only calculator outputs, others favored graphical outputs, such as cumulative incidence functions (displaying risk across time) for themselves and pictographs (static patient icons colored to represent how many patients might have a seizure) to share with patients, including a comparison between continuation vs discontinuation (not available in existing calculators). Although responses were mixed, some respondents typically felt that CIs surrounding predictions would be cluttering and not improve their gist graph understanding. Other suggested output formats could include "stoplight" summary displays or decision charts.

Discussion: Our results provide vital feedback to direct future risk prediction tool development efforts. Although some preferred numerical-only presentations for their simplicity, others cited that graphical displays have many advantages regarding clarity and amount of information. Future studies will also require patient input.

Background: The transition from pediatric to adult health care for people with epilepsy is a critical period that requires careful planning to ensure optimal patient well-being. Adolescents with epilepsy face health-related and social challenges (e.g., psychiatric disorders, treatment nonadherence, family planning, and medico-legal issues).

Recent findings: The TÉCUM (Transition en Épilepsie Complexe de l'Université de Montréal) program aims to establish a sustainable model of transition care. Key initiatives include patient-oriented symposia (covering medical and social topics), a website that is a hub for available public and community resources, and a standardized online questionnaire to assess patient psychosocial well-being and transition readiness to tailor interventions.

Implications for practice: Our innovative program has established new educational initiatives for patients and their families and measures to ensure optimal management of their epilepsy as well as their psychosocial needs. We anticipate that the TÉCUM program will positively influence adolescents and young adults with epilepsy across Canada.

Background and objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that commonly leads to respiratory failure. Early respiratory interventions that may improve symptoms and outcomes are underused when prescribed. We sought to characterize patient perspectives and preferences for respiratory care to enable identification of implementation strategies to improve the uptake of ALS respiratory interventions.

Methods: A prospective multicenter mixed-methods observational study was conducted using semistructured interviews of participants recently diagnosed with ALS at 4 academic centers in the United States. Eligible patients were those with an ALS diagnosis in the previous 12 months, forced vital capacity <80% predicted normal, or presence of dyspnea or orthopnea.

Results: Twenty-four patients with ALS were interviewed. Ten participants were using some form of respiratory therapy, including 8 using noninvasive ventilation (NIV). The most endorsed factors related to openness to initiate respiratory therapy were a doctor's recommendation and abnormal pulmonary function test results. The most commonly endorsed preferences for learning about a respiratory device included kinesthetic and reading. Descriptions of lung volume recruitment were received with more openness than of NIV. For those not prescribed NIV, reasons for hesitancy to start NIV included fear of mask discomfort, claustrophobia, and lack of perceived benefit. Perceptions about NIV differed in participants identifying as "proactive" rather than "reactive" with their health.

Discussion: Patients in the first year after ALS diagnosis have variable receptiveness to respiratory care. These patients place different weights on the factors supporting NIV and may have different educational needs about respiratory interventions. Implementation strategies for respiratory care interventions in ALS should consider patients' motivations for adopting interventions such as NIV, provide multiple educational formats, and identify barriers to incorporating home respiratory care.