Neurology. Clinical practice最新文献

Background: Cognitive motor dissociation (CMD) occurs when patients with severe brain injury follow commands on task-based functional MRI or EEG assessment despite demonstrating no behavioral evidence of language function. Recognizing the value of identifying patients with CMD, evidence-based guidelines published in the United States and Europe now recommend that these assessments are conducted as part of clinical care for select patients.

Recent findings: We describe our institutionally supported approach for clinical assessment of CMD and report lessons learned so that other centers can more easily implement these evaluations. Among the key lessons are the need to consider ethical implications of CMD assessment; establish standardized local protocols for patient selection, data acquisition, analysis, and interpretation; and develop effective strategies for communication of test results.

Implications for practice: Independent validation of methods to assess CMD is not available. Our approach for clinical CMD assessment is intended to be flexible, allowing for iterative improvements as the evidence base grows.

Background and objectives: SCN2A-related disorders (SCN2A-RDs) entail severe impairments in multiple domains that could serve as nonseizure outcomes in clinical trials. This study evaluated the fitness for purpose of several clinical instruments with both standardized and alternative scoring and with some measures used out of their intended age range for assessing communication in SCN2A-affected participants.

Methods: Parents of SCN2A-affected children were recruited through FamilieSCN2A Foundation outreach for a combined cross-sectional and longitudinal study. They completed assessments of their children at study entry and 6 and 12 months later. Assessments included the Vineland Adaptive Behavior Scale (VABS-3), Adaptive Behavior Assessment System (ABAS), Communication Matrix, and Communication and Symbolic Behavior Scale (CSBS). Analyses examined floor and ceiling effects, inter-rater and test-retest reliability, discrimination among different levels of functional impairment, and sensitivity to clinical aspects of SCN2A-RDs.

Results: Of 65 participants (28 females, median age 6.4 years, IQR 4.1-10.5), 56 (86%) had epilepsy. Eleven (17%) used speech as their primary communication mode; 84% were considered ineffective communicators. The mean Vineland composite standardized score (SS) was 34 (IQR 26-46). Cross-sectionally, standardized scores decreased with increasing age. There were substantial floor effects for receptive (75%) and expressive (83%) communication. SSs discriminated poorly between verbal vs nonverbal and communicative vs noncommunicative participants and were not sensitive to features reflecting epilepsy severity (e.g., epileptic spasms and number of current medications). By contrast, Vineland growth scale value (GSV) and ABAS, Matrix, and CSBS raw scores had minimal floor effects; most increased with age. These alternative scores distinguished clearly between participants with different levels of communication and were sensitive to aspects of epilepsy severity. Longitudinally, SSs decreased, but other scores remained relatively stable over a year.

Discussion: SCN2A-RD is characterized by severe-to-profound impairment with a SS <4 SDs of the norm-referenced mean. Owing to severe floor effects and their insensitivity to markers of communication function, age-standardized scores (e.g., Vineland SS) are not fit for purpose in clinical trials or other settings for evaluating nonseizure outcomes such as communication. GSVs and alternative scoring and assessments have much better measurement profiles in all these regards and should be considered in future precision medicine trials for SCN2A-RDs and other similar rare diseases.

Background and objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to the loss of motor function and muscle strength. Nonpharmacologic neuromodulative therapeutic approaches such as active exercise may contribute to preserve motor functions in ALS, but this hypothesis remains debated. The present meta-analysis first aimed to evaluate the effect of active exercise on function and muscle strength preservation. Moreover, since the responsiveness to induced neuroplasticity of patients with ALS is being discussed, the second objective was to review the analogous effects of noninvasive brain stimulation (NIBS).

Methods: Following PRISMA guidelines, we systematically reviewed PubMed, CENTRAL, NIH PMC, PEDro, ScienceDirect, and Web of Science databases from the period between January 10 and July 1, 2023. Criteria limited inclusion to randomized controlled trials comparing active exercise (aerobic or resistance) with usual care or NIBS with sham. The primary outcome was assessed based on functional assessment scores reported on validated clinical scales, and the secondary outcome analysis included muscle strength and neurophysiologic changes. Methodologic quality of the selected studies was assessed using the Physiotherapy Evidence-Based (PEDro) scale. Relative risk (RR) and heterogeneity (I²) were calculated with Revman software, and evidence quality was estimated by the GRADE quality scale.

Results: Thirteen studies were included. Analysis involved 393 patients among whom 164 underwent active exercise and 155 received usual care, 41 received NIBS and 33 underwent sham stimulations. The nature of active exercise was consistent across studies but varied in frequency. NIBS parameters were consistent for stimulation sites and session frequency. Function was significantly preserved in 5 of 9 studies on active exercise and 2 of 4 NIBS trials. Meta-analysis on functional scales indicated a moderate quality of evidence for the effectiveness of active exercises (RR = 0.61 [0.18, 1.04] with I² = 69%) compared with usual care and very low quality of evidence for NIBS (RR = -1.41 [-0.44, 3.26] with I² = 89%). Only 1 NIBS study revealed neuroplastic changes in the brain.

Discussion: Active exercise likely slows functional loss in ALS, but the effects of NIBS need further investigation to support their neuroprotective effectiveness. Moreover, both interventions require further neurophysiologic investigation to elucidate ALS neuroplasticity.

Trial registration information: This review has been registered in PROSPERO (CRD42023408121).

Background and objectives: Patients with liver failure experience long hospitalizations and acute neurologic complications. Encephalopathy limits the bedside examination, rendering presenting signs of acute brain injury less specific. Seizures are common. Brain MRI is the gold standard for detecting acute brain injury, but intensive medical needs may preclude immediate transfer for imaging. EEG is a bedside test applied in cases of seizure or encephalopathy. We hypothesized that EEG variables can predict MRI signs of acute brain injury in children hospitalized with liver failure.

Methods: In this retrospective cohort analysis, records were collected for patients admitted to a MedStar hospital between 2014 and 2022 with ICD-9/10 codes related to liver failure, who underwent brain MRI and EEG testing during the same admission. Exclusion criteria included age older than 24 years and >7 days elapsing between EEG and MRI testing. Clinical data of interest from chart review, reinterpreted MRI scans, reinterpreted EEG tracings, and quantitative EEG variables were compiled into a database. Quantitative EEG variables were processed using MNE-Python.

Results: Of 746 records screened, 52 patients met inclusion criteria comprising 63 EEG-MRI pairs. Univariate analysis of all quantitative EEG variables of interest showed depressed theta-alpha variability (TAV) when paired MRI involved abnormal restricted diffusivity in cortical or deep gray matter structures (TAV 0.705, SD 0.310; p < 0.001) compared with MRI with no abnormal restricted diffusivity (TAV 0.895, SD 0.095). Multilinear regression analysis including potential confounders demonstrated independent association of depressed TAV with this MRI finding, with an odds ratio of 4.0317 (95% CI 1.3868-11.7165; AUROC 0.83).

Discussion: Depressed TAV on EEG is associated with increased odds of abnormal restricted diffusivity in gray matter on brain MRI in children and young adults hospitalized with liver failure. This MRI finding is seen in scenarios where changes to medical management are time-sensitive (i.e., acute stroke and PRES) or where prognostic discussion may be influenced by MRI findings (hypoxic-ischemic injury). TAV thus has a potential role as an automated, bedside decision support tool for clinicians deciding on the urgency of brain MRI in critically ill patients.

Purpose of review: Dysphagia, or difficulty swallowing, affects several individuals globally and can contribute to a reduced quality of life and partial medication adherence, especially in patients with epilepsy. There is also a lack of awareness and understanding of dysphagia among both health care providers and patients. This review examines the interplay between dysphagia and epilepsy treatment and the potential for optimizing diagnosis and intervention.

Recent findings: Dysphagia, although a prevalent condition, is often underdiagnosed or misdiagnosed. Managing dysphagia involves patient and caregiver education on medication management techniques, lifestyle changes, and collaboration with a multidisciplinary health care team. There are also several modalities to screen and evaluate for dysphagia by using technology, using questionnaires, and asking probing questions. In patients with epilepsy, dysphagia can make swallowing certain formulations of antiseizure medications (ASMs) difficult or impossible-so, there is a need for tailored management strategies if discontinuing the medication is not feasible. Alternative formulations such as soluble, liquid, granular, or powder alternatives have been recognized as valuable options in addressing partial adherence due to dysphagia.

Summary: Patients with dysphagia may have varying symptoms, making it challenging for clinicians to accurately identify the condition. To address this issue, various questionnaires and assessments have been developed to uncover swallowing difficulties. Administration of alternate ASM formulations must consider options available for each individual.

Background and objectives: Few estimates of the long-term health system costs of Parkinson disease by phase of disease are available. We estimated 10-year and phase-based net health system costs of Parkinson disease before and after case ascertainment.

Methods: Using population-based linked administrative databases from Ontario, Canada, we identified 43,149 community-dwelling persons with incident Parkinson disease aged 40 years and older between 2009 and 2018 using a validated algorithm. These individuals were matched 1:1 to controls without Parkinson disease based on demographics and a propensity score. We calculated phase-based, net health system costs from the provincial government perspective during the preascertainment (3 years before index), initial (1 year after index), early continuing (>1-6 years after index), later continuing (>6-10 years after index), and terminal (1 year before death, if applicable) phases (standardized to 2020 $CAD and calculated on an annual basis). By applying survival probabilities to monthly cost estimates, we also determined 10-year net health system costs, stratified by sex and age.

Results: Annual mean net costs of Parkinson disease were lowest in the preascertainment phase ($212 CAD, 95% CI [$20-$404]), intermediate in the initial phase ($4,576 (95% CI [$4,217-$4,935]), and higher in the early continuing phase ($7,078, 95% CI [$6,717-$7,438]). The later continuing phase ($12,500, 95% CI [$12,060-$12,940]) and the terminal phase ($13,933, 95% CI [$13,123-$14,743]) showed the highest costs. The 10-year net cost of Parkinson disease was $82,153 (95% CI [$77,965-$86,341]) and was significantly higher in women ($89,773, 95% CI [$83,306-$96,240]) than in men ($76,469, 95% CI [$70,983-$81,953]) and older individuals ($92,197, 95% CI [$87,087-$97,307]), compared with younger individuals ($62,580, 95% CI [$55,346-$69,814]). Over the 10-year period, hospital, nursing home, and home care were the largest contributors to costs of Parkinson disease.

Discussion: Health system costs of Parkinson disease are substantial, particularly in the later phases. Interventions to reduce avoidable use of hospital and nursing home services by persons living with Parkinson disease may provide better quality of life and be cost saving from the health system perspective.

Purpose of review: The potential diagnostic value of radiographic, horizontal, conjugate gaze deviation (Rad h-CGD) was first recognized in 2003 by Simon et al. Thereafter, interest grew related to its potential use as a marker of different neurologic and vestibular disorders. Over the past 20 years, we have identified clinical correlates of Rad h-CGD including those caused by supratentorial and infratentorial lesions. We propose clinicians and radiologists will better diagnose and manage patients by knowing the different diagnostic possibilities for Rad h-CGD.

Findings: We report different clinical correlates of Rad h-CGD relevant for localizing and lateralizing lesions. We measured the angle of deviation and correlated it with the clinical findings and underlying mechanisms. We then reviewed important data from the previous literature relevant to the localization of each lesion and combined it with our experience into the design of a practical algorithm to interpret Rad h-CGD.

Summary: Using Rad h-CGD provides useful information about the diagnosis and localization and may reveal subtle ocular findings not clear on physical examination. However, Rad h-CGD alone cannot distinguish between supratentorial and infratentorial lesions, and therefore, the clinical context is critical. Moreover, although Rad h-CGD occurs with strokes due to large vessel occlusion, it could also be seen with an acute vestibular syndrome, secondary to a peripheral vestibular neuritis. Other possibilities include ischemic events in the cerebellum, brainstem, and labyrinth.

Background and objectives: We evaluated the performance of 3 large language models (LLMs) in generating patient education materials (PEMs) and enhancing the readability of prewritten PEMs on idiopathic intracranial hypertension (IIH).

Methods: This cross-sectional comparative study compared 3 LLMs, ChatGPT-3.5, ChatGPT-4, and Google Bard, for their ability to generate PEMs on IIH using 3 prompts. Prompt A (control prompt): "Can you write a patient-targeted health information handout on idiopathic intracranial hypertension that is easily understandable by the average American?", Prompt B (modifier statement + control prompt): "Given patient education materials are recommended to be written at a 6th-grade reading level, using the SMOG readability formula, can you write a patient-targeted health information handout on idiopathic intracranial hypertension that is easily understandable by the average American?", and Prompt C: "Given patient education materials are recommended to be written at a 6th-grade reading level, using the SMOG readability formula, can you rewrite the following text to a 6th-grade reading level: [insert text]." We compared generated and rewritten PEMs, along with the first 20 googled eligible PEMs on IIH, on readability (Simple Measure of Gobbledygook [SMOG] and Flesch-Kincaid Grade Level [FKGL]), quality (DISCERN and Patient Education Materials Assessment tool [PEMAT]), and accuracy (Likert misinformation scale).

Results: Generated PEMs were of high quality, understandability, and accuracy (median DISCERN score ≥4, PEMAT understandability ≥70%, Likert misinformation scale = 1). Only ChatGPT-4 was able to generate PEMs at the specified 6th-grade reading level (SMOG: 5.5 ± 0.6, FKGL: 5.6 ± 0.7). Original published PEMs were rewritten to below a 6th-grade reading level with Prompt C, without a decrease in quality, understandability, or accuracy only by ChatGPT-4 (SMOG: 5.6 ± 0.6, FKGL: 5.7 ± 0.8, p < 0.001, DISCERN ≥4, Likert misinformation = 1).

Discussion: In conclusion, LLMs, particularly ChatGPT-4, can produce high-quality, readable PEMs on IIH. They can also serve as supplementary tools to improve the readability of prewritten PEMs while maintaining quality and accuracy.

Background and objectives: Headache syndromes are highly prevalent, disabling, and costly. Our goals were to (1) describe headache care delivery and costs in a system and (2) identify opportunities for the system to collect, organize, or analyze health care data to facilitate value-based headache care delivery.

Methods: We performed a descriptive, retrospective cohort study using data from a large integrated health system (July 2018-July 2021). We assigned individuals into a reference (REF) or headache group based on headache-related ICD diagnoses. The primary exposure variable, applied to the headache group, was the headache specialty seen most after the incident headache diagnosis: primary care (PC), neurology (NEU), or headache subspecialist (HS). Outcomes of interest were per member per month all-cause costs, per episode costs, all-cause utilization, and headache utilization. Variables included age, sex, insurance contract, and the Adjusted Clinical Groups (ACG) concurrent risk score. We calculated univariate statistics for clinical indicators and outcomes for each group. For outcome variables, we also report these statistics after adjustment for ACG risk score.

Results: We identified 22,700 (14%) individuals in the headache groups and 138,818 (86%) individuals in the reference group (REF). Within the headache groups, 84% received care from PC, 14% from NEU, and 2% from HS. The average ACG risk scores increased across exposure groups. In both unadjusted and after risk adjustment analyses, total cost of care (TCOC) was highest in NEU and HS, and the largest drivers of TCOC were outpatient facility costs, followed by inpatient facility costs. HS had the highest pharmacy and professional costs. After risk adjustment, all-cause inpatient admissions and headache-related ED visits were roughly similar, although there was increasing use of outpatient PC and NEU visits across exposure groups.

Discussion: Individuals seen by a NEU or HS had higher medical morbidity, higher health care utilization, and higher costs than those who receive care from PC. Outcome data were either not available or not structured to determine the value of neurologic expertise in headache care or within a particular headache care pathway. To clarify neurology's value in primary headache disorders, we encourage health system leaders to adopt an economic evaluation framework.

Background and objectives: Recent studies have suggested that antibiotics could be a contributing factor to Parkinson disease (PD), but validation in other population cohorts, such as Asians, is needed. This study examined the association between exposure to antibiotics and PD risk in the Korean population.

Methods: Using the National Health Insurance Service (NHIS) database, this population-level cohort research study from Korea included 298,379 people aged 40 years and older who underwent a national health examination in 2004-2005. Cumulative antibiotic exposure days were investigated over 4 years (2002-2005), and new cases of PD were followed for 14 years (2006-2019). Various covariates, such as infectious diseases, were considered in the analysis. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) and CIs for the PD risk from antibiotic exposure.

Results: PD risk was statistically significantly higher in those exposed to antibiotics for ≥121 days than in those not exposed to antibiotics (aHR, 1.29; 95% CI 1.07-1.55). In addition, compared with those exposed to antibiotics for 1-14 days, those exposed to antibiotics for ≥121 days had a higher risk of PD (aHR, 1.37; 95% CI 1.17-1.61). The results of sensitivity analyses that applied washout periods or extended antibiotic exposure periods were consistent with those of the main analyses.

Discussion: Extended usage of antibiotics was linked to a higher incidence of PD, even after controlling for several risk variables. Further research is needed to warrant the causation and mechanisms of antibiotic exposure and PD.