Neurology最新文献

Objectives: Anticoagulants and thrombolytics may interact with anti-amyloid monoclonal antibodies (mAbs) to increase intracranial hemorrhage risk, so expert guidance recommends against their co-prescription. We aimed to estimate how many people with mild cognitive impairment (MCI) or dementia develop a new cardiovascular indication for anticoagulant and thrombolytic drugs.

Methods: In a longitudinal cohort of adults aged 65 years or older from the Health and Retirement Study (2010-2020) with linked Medicare claims and no previous indication for anticoagulants, cognition was categorized as normal, MCI, or dementia. We fit separate Fine-Gray survival models accounting for competing risk of death to estimate 1-year incidence of atrial fibrillation (AF), deep vein thrombosis (DVT), pulmonary embolism (PE), acute myocardial infarction (AMI), and stroke.

Results: Among 12,373 participants (mean age 73 years, 59% female), the 1-year risk in those with MCI was 1.7% for AF, 1.2% for DVT, 0.4% for PE, 1.2% for AMI, 2.0% for stroke, and 5.7% for any indication. In those with dementia, the 1-year risk was 1.7% for AF, 1.8% for DVT, 0.3% for PE, 1.0% for AMI, 2.4% for stroke, and 6.7% for any indication.

Discussion: Our findings inform shared decision making about the tradeoffs of anti-amyloid mAbs but should be validated in populations with confirmed treatment eligibility.

Background and objectives: Antiseizure medications (ASMs) undergo marked pharmacokinetic alterations during pregnancy and postpartum. Suboptimal ASM management can lead to adverse maternal and child outcomes. However, there is scant literature to guide how to adjust ASM dosing. This study analyzed how ASMs were dosed in a large observational cohort study of pregnant women with epilepsy (PWWE) who had favorable seizure outcomes.

Methods: Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) was a prospective, observational cohort study that enrolled PWWE 2012-2016 across 20 US epilepsy centers. Inclusion criteria were PWWE, ages 14-45 years, and <20 weeks' gestational age. Seizures and ASM type(s) and doses were documented in a daily diary. Our analysis included ASM doses in pregnancy through early postpartum (6 weeks post-delivery). For each ASM, we analyzed percent participants who underwent ≥1 dose change in pregnancy and postpartum, time of first dose change after enrollment, time to subsequent changes, amount of each dose adjustment, and percent of conception dose at delivery and 6-week postpartum.

Results: A total of 299 participants (median 31 [range 17-46] years) were eligible for analysis. Median enrollment was 14-weeks gestation. Dose increases were made in 246/363 (67.8%) of ASMs during pregnancy beginning median 32 days post-enrollment; dose decreases were made within 6 weeks post-delivery for 171/357 (47.9%) of ASMs beginning median 3 days postpartum. For lamotrigine, 128/146 (87.7%) participants had doses increased, by 100 mg/d (median), reaching 191% of conception dose (mean) by delivery. Postpartum, 103/146 (70.5%) had dose tapers, by 100 mg/d (median), to 116% of conception dose (mean) by 6 weeks. For levetiracetam, 70/125 (56.0%) participants had doses increased, by 500 mg/d (median), reaching 177% of conception dose (mean) by delivery. Postpartum, 43/125 (34.4%) had dose tapers, by 500 mg/d (median), to 136% of conception dose (mean) by 6 weeks. For other ASMs, 10/14 had doses increased in pregnancy and 8/14 were tapered early postpartum.

Discussion: Previous MONEAD analyses showed no difference in seizure control between pregnant and nonpregnant women with epilepsy. We detail how ASMs were managed in pregnancy and early postpartum to achieve this favorable outcome. These findings can be useful for the management of PWWE. Limitations of this study include limited data in the first trimester, enrollment from epilepsy centers, and limited number of participants on a wider variety of ASMs.

Trial registration information: ClinicalTrials.gov Identifier: NCT01730170. Study Details | Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) | ClinicalTrials.gov. First submitted: November 9, 2012. First patient enrolled: December 19, 2012.

Background and objectives: Aging is associated with changes in circadian rhythms. Rest-activity rhythms (RARs) measured using accelerometers are markers of circadian rhythms. Altered circadian rhythms may be risk factors of neurocognitive outcomes; however, results are mixed, and previous studies were often conducted in homogeneous populations. We aimed to assess the association between circadian RARs and incident dementia in a racially diverse sample of older adults.

Methods: This was a retrospective examination of data from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort study conducted at 4 US centers. ARIC participants who wore the Zio XT® long-term continuous monitoring patch in 2016-17 for ≥3 days and were free of prevalent dementia were included. RARs were derived from investigational accelerometer data from the patch. Nonparametric RARs included relative amplitude (rhythm strength), intradaily variability (rhythm fragmentation), and interdaily stability (rhythm consistency). Cosinor RARs included measures of rhythm strength (amplitude, mesor) and circadian timing (acrophase). Dementia cases were adjudicated through 2020 using in-person and phone assessments, hospitalization codes, and death certifications. Cox proportional hazards models were used.

Results: Of the 2,183 participants (mean ± SD age 79 ± 4.5 years, 58% female, 24% Black), 176 (8%) developed dementia. The median follow-up time was 3 years, and the mean Zio XT Patch wear time was 12 days. After multivariable adjustment, each 1-SD decrement in relative amplitude and 1-SD increment in intradaily variability were associated with 54% (95% CI 32%-78%) and 19% (95% CI 2%-38%) greater risk of dementia, respectively. Amplitude and mesor were associated with elevated dementia risk after multivariable adjustment (hazard ratios per 1-SD decrement: 1.43 [95% CI 1.15-1.78] and 1.33 [95% CI 1.08-1.63], respectively). A later acrophase was associated with 1.45 times (95% CI 1.01-2.07) greater risk of dementia compared with a normal acrophase.

Discussion: Using accelerometer data from a commonly used ambulatory ECG monitor, weaker and more fragmented circadian RARs and later peak activity time were prospectively associated with elevated dementia risk in older Black and White adults. Limitations of our study include the lack of dementia subtype data and objective sleep disorder measurements. Further research to determine whether circadian rhythm interventions can reduce dementia risk is warranted.

Background and objectives: Epilepsy surgery outcomes after intracranial EEG remain suboptimal necessitating the discovery of additional biomarkers to define the epileptogenic zone. Fast ripples (FRs) are a promising, new interictal epilepsy biomarker. By analyzing a multicenter data set consisting of overnight stereo-EEG (SEEG) recordings, we aimed at validating FRs as an accurate marker of the epileptogenic zone. We hypothesized that removing ≥60% of total FR events would significantly increase the odds of good postsurgical outcome (Engel class I). In addition, we compared FRs with spikes, and spikes co-occurring with FRs (spike-FRs) as surgery outcome predictors.

Methods: This retrospective cohort study included consecutive patients from 4 epilepsy surgery centers in Canada, Finland, and Denmark, who underwent SEEG followed by resective surgery or a preplanned ablation procedure separate from the SEEG and had at least 1 year of follow-up. We detected FRs and spikes automatically from overnight SEEG recordings edited for artifacts. To calculate resection ratios of the detected events, we determined resected SEEG contacts by superimposing the peri-implantation and postresection images. We evaluated postsurgical seizure outcomes from medical records.

Results: Of the 73 included patients (mean age 23 ± 12 years, 41% female), 46 had good and 27 had poor (Engel classes II-IV) outcome at the latest follow-up. Patients with FR resection ratio ≥0.6 were more likely to achieve good postsurgical outcome (p < 0.001, diagnostic odds ratio [DOR] 10, 95% CI 2.7-39). Of those with ≥0.6 FR resection ratio, 26 of 29 (90%, 95% CI 74%-96%) achieved good outcome, whereas of those with <0.6 FR resection ratio, 24 of 44 (55%, 95% CI 46%-63%) had poor outcome, with overall accuracy of 68% (95% CI 57%-79%). In addition, the spike-FR resection ratio ≥0.6 was associated with good postsurgical outcome (p = 0.007, DOR 4.1, 95% CI 1.4-12, accuracy 64%, 95% CI 52%-75%), whereas the spike resection ratio ≥0.6 was not.

Discussion: In accordance with our hypothesis, the FR resection ratio ≥0.6 significantly increased the odds of attaining good postsurgical seizure outcome. Although the FR resection ratio ≥0.6 accurately predicted good postsurgical outcome, resecting <0.6 of FRs did not necessarily mean poor outcome. As predictors of postsurgical outcome, spikes fared poorly, whereas spike-FRs were comparable with FRs.

Objectives: Neuronal autoantibodies are linked to cognitive impairment in neurologic diseases and can be associated with tumors. In patients with cancer, IgA/IgM N-Methyl-D-Aspartate receptor (NMDAR) autoantibodies are most common, yet their clinical relevance is unclear. We assessed cognitive function in cancer patients with serum NMDAR autoantibodies and compared the results with matched controls.

Methods: For this cross-sectional case-control study in Germany, we recruited 1,055 patients with cancer and tested for neuronal serum autoantibodies. Cognitive assessment was performed blinded to antibody status and after excluding patients with potential confounders of cognitive dysfunction. The tests included verbal memory (Rey Auditory Verbal Learning Test), visuospatial memory (Rey-Osterrieth Complex Figure), and working memory.

Results: Fifty-six patients with IgA/IgM NMDAR autoantibodies (median age 61.0 years [28.0-86.0], 35.7% female) were matched 1:1 to autoantibody-negative patients by age, sex, cancer type, and stage. Autoantibody-positive patients showed impairments in verbal memory (mean score ± SD: 9.7 ± 3.6 vs 11.4 ± 3.2; p = 0.01; Cohen d = 0.49), visuospatial memory (19.4 ± 7.0 vs 22.6 ± 5.6; p = 0.01; d = 0.50), and working memory (6.2 ± 1.9 vs 7.0 ± 2.1; p = 0.04; d = 0.40). Memory function decreased with increasing IgA NMDAR autoantibody levels. Both groups performed similarly on measures of attention, executive function, and verbal fluency.

Discussion: Serum NMDAR autoantibodies are associated with isolated memory deficits in patients with cancer and might serve as a potential biomarker for cancer-related cognitive impairment.

A 41-year-old, left-handed man was admitted to the hospital for workup of a 3-week history of headache, constant vertigo, diplopia, and left hemiparesis. An initial diagnosis was made, and the patient was treated with symptomatic improvement. He was discharged and then presented a few weeks later with recurrence of his symptoms which required additional diagnostic workup. This ultimately led to a diagnosis of a rare disorder. In this case report, we outline his clinical course and our reasoning at each step which led to our eventual definitive diagnosis.