Neurology. Clinical practice最新文献

Background: Neuroprognostication for disorders of consciousness (DoC) after severe acute brain injury is a major challenge, and the conventional clinical approach struggles to keep pace with a rapidly evolving literature. Lacking specialization, and fragmented between providers, conventional neuroprognostication is variable, frequently incongruent with guidelines, and prone to error, contributing to avoidable mortality and morbidity.

Recent findings: We review the limitations of the conventional approach to neuroprognostication and DoC care, and propose a paradigm entitled the Recovery of Consciousness Via Evidence-Based Medicine and Research (RECOVER) program to address them. The aim of the RECOVER program is to provide specialized, comprehensive, and longitudinal care that synthesizes interdisciplinary perspectives, provides continuity to patients and families, and improves the future of DoC care through research and education.

Implications for practice: This model, if broadly adopted, may help establish neuroprognostication as a new subspecialty that improves the care of this vulnerable patient population.

Background and objectives: To compare long-term seizure control in patients with long-term VNS (vagal nerve stimulator) stimulation (VNS-on) with those who discontinued VNS after >3 years (VNS-off).

Methods: Patients with refractory epilepsy with VNS therapy for >3 years (and follow-up for >2 years after VNS discontinuation for VNS-off patients) were included. Patients with brain surgery <3 years after VNS were excluded. We compared the percentage of patients with ≥50% seizure reduction (50% responder rate) and change in seizure frequency within and between groups in follow-up.

Results: Thirty-three VNS-on and 16 VNS-off patients were evaluated. VNS-on patients underwent stimulation for 9.7 years (mean). VNS-off patients had VNS treatment for 6.5 years (mean), discontinued treatment, then had additional 8.0 years (mean) follow-up. 50% responder rates were similar between groups (VNS-on: 54.5% vs VNS-off at last-on: 37.5%, p = 0.26; vs VNS-off at the last follow-up: 62.5%, p = 0.60). VNS-on patients had a significant reduction in seizure frequency at the last follow-up compared with baseline (median [Mdn] = -4.5 seizures/month, interquartile range [IQR] = 14.0, 56% reduction, p = 0.013). VNS-off patients also showed significant seizure reduction while still continuing VNS therapy (Mdn = -1.0 seizures/month, IQR = 13.0, 35% reduction, p = 0.020) and, after discontinuing therapy, at the last follow-up compared with baseline (Mdn = -3.2, IQR = 11.0, 52% reduction, p = 0.020). The 2 groups were comparable in seizure frequency change both at the last-on visit (absolute change, p = 0.62; relative change, p = 0.50) at the last follow-up (absolute change, p = 0.67; relative change, p = 0.76).

Discussion: Patients who discontinued VNS therapy and those who continued therapy had similar response during active treatment and similar long-term outcomes, suggesting that factors such as the natural disease course and/or medication treatment strongly affect long-term outcomes.

Background and objectives: Patients with acute symptomatic seizures (ASyS) and acute epileptiform findings on EEG are common. They are often prescribed long-term antiseizure medications (ASMs); it is unknown whether or when this is necessary. Primary outcome was late unprovoked seizure occurrence and association with ASM taper. The secondary outcome was EEG pattern evolution over time.

Methods: This is a retrospective cohort study of patients from 2015 to 2021 with ASyS (clinical or electrographic) and/or epileptiform findings on index hospitalization EEGs who were discharged on ASMs and had subsequent follow-up including an outpatient EEG at Yale New Haven Hospital. All patients were seen in our postacute symptomatic seizure (PASS) clinic after hospital discharge. We also developed a simple predictive score, Epilepsy-PASS (EPI-PASS), using variables independently associated with seizure recurrence based on stepwise regression; each of the 3 identified variables was assigned a score of 0 (absent) or 1 (present), for a total score of 0-3.

Results: Of 190 patients screened, 58 were excluded, leaving a final cohort of 112 patients. Twenty-four percent (27/112) patients developed a late unprovoked seizure (i.e., epilepsy). Independent predictors of epilepsy were persistence of epileptiform abnormalities on follow-up EEGs [56% developed epilepsy vs 19% without, 0.002, OR 7.18 (1.36-37.88)], clinical ASyS [32% vs 13%, p = 0.002, OR 7.45 (2.31-54.36)], and cortical involvement on imaging [40% vs 11%, p = 0.003, OR 7.63 (1.96-29.58)]. None of the 23 patients with none of these predictors (0 points on EPI-PASS) developed epilepsy, vs 13% with 1 predictor (EPI-PASS = 1) and 46% with 2 or 3 predictors (EPI-PASS = 2-3) at 1-year follow-up. ASM taper was not associated with seizure recurrence. Abnormal EEG findings in the index hospitalization usually resolved [54/69 (78%) patients] on subsequent EEGs.

Discussion: Most patients with clinical ASyS or acute epileptiform EEG findings do not require long-term ASMs. Index hospitalization EEG findings usually resolve, but if they do not, there is a >50% chance of developing epilepsy. Other predictors of epilepsy are cortical involvement on imaging and clinical ASyS. A simple 4-point scale using these 3 predictors (EPI-PASS) may help predict the risk of developing epilepsy but requires independent validation.

Background and objectives: Given the paucity of high-quality safety/efficacy data on acute stroke therapies in patients with premorbid disability, they risk being routinely excluded from such therapies. We examined utilization of endovascular thrombectomy (EVT), associated workflow, and poststroke outcomes among patients with vs without premorbid disability.

Methods: We used national registry data on thrombolysis/EVT for the Czech Republic from 1 January 2016 to 31 December 2020. Premorbid disability was defined as prestroke modified Rankin Scale score (mRS) ≥3. We compared proportions of patients with vs without premorbid disability who received EVT and examined workflow times. We compared ΔmRS-change in mRS from prestroke to 3 months-in patients with vs without premorbid disability, in addition to intracerebral hemorrhage (ICH), mortality, and discharge NIHSS (National Institutes of Health Stroke Scale score), adjusting for age, sex, baseline NIHSS, and comorbidities, and verified using propensity score weighting (PSW) and matching for differences in treatment assignment. We stratified by age group (<65, 65-74, 75-84, ≥85 years) to explore outcome heterogeneity with vs without premorbid disability.

Results: Among 22,405 patients with ischemic stroke who received thrombolysis/EVT/both, 1,712 (7.6%) had prestroke mRS ≥ 3. Patients with prestroke disability were less likely to receive EVT vs those without (10.1% vs 20.7%, aOR: 0.30, 95% CI 0.24-0.36). When treated, they had longer door-to-arterial puncture times (median: 75 minutes, IQR: 58-100 vs 54, IQR: 27-77, adjusted difference: 12.5, 95% CI 2.68-22.3). Patients with prestroke disability receiving thrombolysis/EVT/both had worse ΔmRS (adjusted rate ratio, aIRR on PSW: 1.57, 95% CI 1.43-1.72), rates of 3-month mRS 5-6, discharge NIHSS, and mortality (aOR-PSW [mortality]: 2.54, 95% CI 1.92-3.34), while ICH did not significantly differ. 32.1% of patients with prestroke disability receiving thrombolysis/EVT/both successfully returned to prestroke state, but this proportion ranged from 19.6% for those older than 85 years to 66.0% for those younger than 65 years. Regardless of premorbid disability, EVT was associated with better outcomes including lower ΔmRS (aIRR-PSW: 0.87, 95% CI 0.83-0.91) and mortality, with no interaction of treatment effect by premorbid disability status (e.g., mortality p_interaction = 0.73). EVT recipients with premorbid disability did not differ significantly for several outcomes including ΔmRS (aIRR: 0.99, 95% CI 0.84-1.17) but were more likely to have 3-month mRS 5-6 (70.1% vs 39.5% without premorbid disability, aOR: 1.85, 95% CI 1.12-3.04).

Discussion: Patients with premorbid disability were less likely to receive EVT, had slower treatment times, and had worse outcomes compared with patients without premorbid disability. However, regardless of premorbid disability, patient

Background: Approximately 6.9 million American individuals have Alzheimer dementia and 50% have mild disease. Lecanemab, an approved antiamyloid antibody, is associated with modest reduction in functional decline in patients with mild dementia or mild cognitive impairment. In Clarity-AD, 239 (26.6%) of patients experienced amyloid-related imaging abnormalities (ARIAs) overall (i.e., ARIAs associated with hemorrhages or edema). The complexity of treatment and risks of adverse events necessitate a multidisciplinary collaborative approach.

Recent findings: With limited treatment options, lecanemab approval generated significant interest among clinicians, patients, and families. Lecanemab treatment requires biweekly infusions along with ongoing imaging tests, laboratory monitoring, patient assessment, drug interaction screening, and cognitive function monitoring. Processes to support patient selection, access, and safety are important given the monitoring requirements and total cost of care.

Implications for practice: The planning process for lecanemab can serve as a blueprint to support safe and effective management of therapeutic innovation in neurology and other areas.

Background and objectives: We determined inter-modality (in-person vs telemedicine examination) and inter-rater agreement for telemedicine assessments (2 different examiners) using the Telemedicine Buffalo Concussion Physical Examination (Tele-BCPE), a standardized concussion examination designed for remote use.

Methods: Patients referred for an initial evaluation for concussion were invited to participate. Participants had a brief initial assessment by the treating neurologist. After a patient granted informed consent to participate in the study, the treating neurologist obtained a concussion-related history before leaving the examination room. Using the Tele-BCPE, 2 virtual examinations in no specific sequence were then performed from nearby rooms by the treating neurologist and another neurologist. After the 2 telemedicine examinations, the treating physician returned to the examination room to perform the in-person examination. Intraclass correlation coefficients (ICC) determined inter-modality validity (in-person vs remote examination by the same examiner) and inter-rater reliability (between remote examinations done by 2 examiners) of overall scores of the Tele-BCPE within the comparison datasets. Cohen's kappa, κ, measured levels of agreement of dichotomous ratings (abnormality present vs absent) on individual components of the Tele-BCPE to determine inter-modality and inter-rater agreement.

Results: For total scores of the Tele-BCPE, both inter-modality agreement (ICC = 0.95 [95% CI 0.86-0.98, p < 0.001]) and inter-rater agreement (ICC = 0.88 [95% CI 0.71-0.95, p < 0.001]) were reliable (ICC >0.70). There was at least substantial inter-modality agreement (κ ≥ 0.61) for 25 of 29 examination elements. For inter-rater agreement (2 telemedicine examinations), there was at least substantial agreement for 8 of 29 examination elements.

Discussion: Our study demonstrates that the Tele-BCPE yielded consistent clinical results, whether conducted in-person or virtually by the same examiner, or when performed virtually by 2 different examiners. The Tele-BCPE is a valid indicator of neurologic examination findings as determined by an in-person concussion assessment. The Tele-BCPE may also be performed with excellent levels of reliability by neurologists with different training and backgrounds in the virtual setting. These findings suggest that a combination of in-person and telemedicine modalities, or involvement of 2 telemedicine examiners for the same patient, can provide consistent concussion assessments across the continuum of care.

Background and objectives: The published data about mechanical thrombectomy (MT) in cancer patients is sparse. We present our institutional experience in this clinical scenario, and a meta-analysis.

Methods: The baseline data, procedural data, clinical and radiological outcomes of MT were analyzed and compared among three groups of stroke patients: controls, patients with active malignancy (AM), and patients with history of malignancy (HOM). A meta-analysis of 12 studies was conducted to address the differences between controls and AM patients regarding selected outcomes.

Results: The 3 groups (controls, AM, HOM) showed significant differences regarding previous history of stroke or TIA (7.8% vs 10.5% vs 38.5%, p = 0.006), alcohol consumption (0.9% vs 10.5% vs 0.0%, p = 0.04), thrombophilia (1.7% vs 15.8% vs 7.7%, p = 0.009), deep venous thrombosis (0.4 vs 26.3% vs 7.7%, p = 0.005). The AM group had significantly higher rates of sICH (3.5% [controls] vs 21.1% [AM] vs 0.0% [HOM], p = 0.007), and mortality at 3 months (27.5% [controls] vs 61.5% [AM] vs 40.0% [HOM] vs, p = 0.032). The control and HOM groups had significantly better functional independence at 3 months (52.1% [controls] vs 15.4% [AM] vs 60.0% [HOM], p = 0.032).In the meta-analysis, the AM arm showed significantly higher mortality during hospitalization (n = 6, OR 95% CI = 3.03 [1.62, 5.64]), and at 3 months (n = 10, OR 95% CI = 4.33 [2.80, 6.68]), and significantly lower rates of 3 months functional independence (mRS = 0-2) (n = 10, OR 95% CI = 0.47 [0.32, 0.70]). No significant difference was found in sICH rates (n = 6, pooled OR 95% CI = 2.03 [0.83, 4.95]).

Discussion: Endovascular MT is technically successful and reasonably safe in treating AIS from LVO in active malignancy patients. However, the causes and implications of sICH require further investigation. Despite technical success, these patients experience poor clinical outcomes, and the long-term benefits of MT remain uncertain.

Background and objectives: Endovascular therapy (EVT) for stroke has emerged as an important therapy for selected stroke patients, and shorter times to clot removal improve functional outcomes. EVT requires the close coordination of multiple departments and poses unique challenges to care coordination in large hospitals. We present the results of our quality improvement project that aimed to improve our door-to-groin puncture (DTP) times for patients who undergo EVT after direct presentation to our emergency department.

Methods: We conducted time-motion studies to understand the full process of an EVT activation and conducted Gemba walks in multiple hospitals. We also reviewed the literature and interviewed stakeholders to create interventions that were implemented over 4 Plan-Do-Study-Act (PDSA) cycles. We retrospectively collected data starting from baseline and during every PDSA cycle. During each cycle, we studied the impact of the interventions, adjusted the interventions, and generated further interventions. A variety of interventions were introduced targeting all aspects of the EVT process. This included parallel processing to reduce waiting time, standardization of protocols and training of staff, behavioral prompts in the form of a stroke clock, and push systems to empower staff to facilitate the forward movement of the patient. A novel role-based communication app to facilitate group communications was also used.

Results: Eighty-eight patients spanning across 22 months were analyzed. After the final PDSA cycle, the median DTP time was reduced by 36.5% compared with baseline (130 minutes (interquartile range [IQR] 111-140) to 82.5 minutes (IQR 74.8-100)). There were improvements in all phases of the EVT process with the largest time savings occurring in EVT decision to patient arrival at the angiosuite. Interventions that were most impactful are described.

Discussion: EVT is a complex process involving multiple processes and local factors. Analysis of the process from all angles and intervening on multiple small aspects can add up to significant improvements in DTP times.

Background and objectives: Cognitive impairment is experienced by up to 80% of people with Parkinson disease (PD). Little is known regarding the subjective experience and frequency of bothersome cognitive problems across the range of disease duration as expressed directly in patients' own words. We describe the types and frequency of bothersome cognitive symptoms reported verbatim by patients with PD.

Methods: Through the online Fox Insight study and the Parkinson Disease Patient Report of Problems, we asked patients with PD to self-report by keyboard entry up to five most bothersome problems and how these problems affect their functioning. Human-in-the-loop curation, natural language processing, and machine learning were used to categorize responses into 8 cognitive symptoms: memory, concentration/attention, cognitive slowing, language/word finding, mental alertness/awareness, visuospatial abilities, executive abilities/working memory, and cognitive impairment not otherwise specified. Associations between cognitive symptoms and demographic and disease-related variables were examined in our cross-sectional cohort using multivariate logistic regression.

Results: Among 25,192 participants (55% men) of median age 67 years and 3 years since diagnosis (YSD), 8,001 (32%) reported a cognitive symptom at baseline. The 3 most frequently reported symptoms were memory (13%), language/word finding (12%), and concentration/attention (9%). Depression was significantly associated with bothersome cognitive problems in all domains except visuospatial abilities. Predictors of reporting any cognitive symptom in PD were depression (adjusted OR 1.5), increasing MDS-UPDRS Part II score (OR 1.4 per 10-point increment), higher education (OR 1.2 per year), and YSD 1, 2, 6-7, and 8-9 vs 0 YSD. Among individuals with at least one cognitive symptom, posterior cortical-related cognitive symptoms (i.e., visuospatial, memory, and language) were reported by 17% (n = 4325), frontostriatal-related symptoms (i.e., executive abilities, concentration/attention) by 7% (n = 1,827), and both by 14.2% (n = 1,020). Odds of reporting posterior cortical symptoms vs frontostriatal symptoms increased with age and MDS-UPDRS part II score, but not depression.

Discussion: Nearly one-third of participants with PD, even early in the disease course, report cognitive symptoms as among their most bothersome problems. Online verbatim reporting analyzed by human-in-the-loop curation, natural language processing, and machine learning is feasible on a large scale and allows a detailed examination of the nature and distribution of cognitive symptoms in PD.