Clinical neurology:

OBJECTIVE: Dravet syndrome (DS) is a developmental and epileptic encephalopathy with a wide spectrum of comorbidities comprising sleep disorders, reported in up to 85% of cases. For this, a sleep study is recommended in patients with a sleep complaint. However, no data are available on sleep architecture in DS or on the impact of seizures on sleep quality and macrostructure. We aim to investigate the impact of epileptic phenomena on sleep in DS.

Clinical development of novel antiseizure medications (ASMs) would benefit from an early proof of principle (POP) model. The photosensitivity model, which uses the photoparoxysmal electroencephalographic response (PPR) as a surrogate of seizures, is currently the only human model that allows POP trials of investigational compounds after a single drug administration. Typically, trials in this model are performed as single-blinded, placebo-controlled phase IIa POP studies, evaluating a range of doses in small groups of epilepsy patients. In the second part of this review, based on the background information provided in Part 1, we analyze the outcome of all published trials performed over roughly 50 years. Many of the 35 drugs tested in the model were also examined in traditional add-on trials in patients with epilepsy, thus allowing analysis of the predictivity of the model. Drugs were categorized into three groups: drugs that suppressed PPR; drugs that exerted no effect on PPR; and drugs that increased PPR, indicating a proconvulsant effect. For the vast majority of drugs, the model correctly predicted the drugs' activity during long-term studies in patients with different types of epilepsy, including focal onset epilepsies. For some investigational compounds, the model detected proconvulsant activity that had not been observed in preclinical animal experiments and phase I studies in healthy volunteers, demonstrating the value of the model for adverse event assessment in patients with epilepsy. Limitations of the model are that it does not predict the extent of drug resistance of patients' seizures during chronic administration or efficacy differentiation of the novel drug from existing ASMs. Photosensitive POP trials are a useful tool to quantitatively predict drug efficacy and in aiding dose selection for subsequent larger phase IIb trials with chronic drug administration.

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline and functional loss in older adults. Obstructive sleep apnea (OSA) is common in older adults, can increase cerebrovascular disease risk, and is linked to medial temporal lobe (MTL) degeneration and cognitive impairment. However, the interaction between OSA features and CSVD burden and their combined effect on MTL structure and function are not well understood. This study tested the hypothesis that CSVD burden is a candidate mechanism linking OSA to MTL degeneration and impaired memory in older adults.

No abstract available

BACKGROUND AND OBJECTIVES: This single-center retrospective cohort study sought to characterize the clinical spectrum of small vessel predominant primary CNS vasculitis (sv-PCNSV) and to investigate the impact of early intensive immunosuppressive therapy on remission.

IMPORTANCE: In 2019, an alleged "mystery" neurological illness emerged in New Brunswick, Canada. Despite extensive media attention, no case description has been published to date.

BackgroundReal-world data on the long-term trends in risk factors, acute antithrombotic strategies, medication adherence, and their impact on the prognosis of minor ischemic stroke (MIS) or transient ischemic attack (TIA) are limited.MethodsWe analyzed cases of acute MIS (National Institutes of Health Stroke Scale score ≤ 3) and TIA from the China National Stroke Registries (CNSRs), a series of multicenter, nationwide hospital-based registries in China. Stroke risk factors, acute antithrombotic strategies, and adherence to secondary prevention were compared between CNSR I (2007-2008) and CNSR III (2015-2018). The main outcomes were stroke recurrence, disability (modified Rankin Scale 3-5), and all-cause mortality at 3, 6, and 12 months of follow-up.ResultsIn total, 15,352 patients with acute MIS or TIA were included, including 7,013 patients from CNSR I and 8,339 patients from CNSR III. Over the past decade, there has been a 10-fold increase in the acute use of dual antiplatelet therapy (3.15% in CNSR I vs. 31.75% in CNSR III) and a 7-fold increase in statin adherence at the 12-month follow-up (10.56% in CNSR I vs. 71.15% in CNSR III). It was also observed that the adjusted cumulative incidence of stroke recurrence (15.38% [15.29%-15.47%] vs. 8.29% [8.27%-8.32%]), disability rates (11.29% [11.12%-11.46%] vs. 4.38% [4.32%-4.44%]), and all-cause mortality (8.17% [8.04%-8.30%] vs. 1.86% [1.83%-1.89%]) at the 12-month follow-up showed a marked decline over the decade. Risk factors such as age (per 10 years), diabetes, and prior stroke were linked to a higher risk of 12-month stroke recurrence in CNSR I (CNSR I: OR and 95%CI, 1.25[1.17-1.33] for age per 10 years; 1.40[1.18-1.66] for diabetes; and 1.96[1.68-2.27] for prior stroke), and these associations remained significant after 10 years (CNSR III: OR and 95%CI, 1.15[1.08-1.24] for age per 10 years; 1.35[1.13-1.61] for diabetes; and 1.54[1.29-1.84] for prior stroke).ConclusionThe past decade has witnessed significant advancements in both acute antithrombotic strategies and medication adherence, accompanied by marked reductions in stroke recurrence, disability, and mortality. These improvements highlight a positive shift toward more effective evidence-based care for patients with MIS or TIA.

Dystonia is a movement disorder with varied clinical features and diverse etiologies. Here we present a revision of the 2013 consensus definition and classification of dystonia in light of subsequent publications and experience with its application during the last decade. A panel of movement disorder specialists with expertise in dystonia reviewed the original document and proposed some revision. There was broad consensus to retain the definition of dystonia with only minor clarifications to the wording. Dystonia is defined as a movement disorder characterized by sustained or intermittent abnormal movements, postures, or both. Dystonic movements and postures are typically patterned and repetitive and may be tremulous or jerky. They are often initiated or worsened by voluntary action and frequently associated with overflow movements. The two-axis structure for classification of the many different presentations of dystonia was also retained, with some revision. Axis I summarizes key clinical characteristics of dystonia, including age at onset, family history, body distribution, temporal dimensions, phenomenology, and whether dystonia is isolated or combined with other neurological or medical problems. Axis II organizes information regarding its etiological basis, including genetic, acquired, and anatomical, and common disease mechanisms. This consensus provides an update to the original definition and classification of dystonia with the aim of facilitating its clinical recognition and management. The revision retains the essence of the original proposal and aims particularly to provide a structure facilitating a uniform implementation. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

BACKGROUND AND OBJECTIVES: Insight into -related pathways is important to unravel pathophysiology and identify therapeutic targets against late-life cognitive decline. We aimed to estimate mediators of 4 on cognition and dementia through different disease markers on structural in vivo brain imaging.

BACKGROUND AND OBJECTIVES: Older adults are expected to have higher readmission rates after seizure-related hospitalization. We sought to define the 30-day readmission rate for older adults after seizure hospitalization and to examine whether occurrence, timing, or specialization of follow-up with primary or neuro-related care is associated with lower readmission risk.

No abstract available

Stroke remains a leading cause of long-term disability and mortality worldwide, necessitating novel therapeutic strategies to enhance recovery. Traditional rehabilitation approaches, including physical therapy and pharmacological interventions, often provide limited functional improvement. Neuromodulation has emerged as a promising strategy to promote post-stroke recovery by enhancing neuroplasticity and functional reorganization. Among various neuromodulatory techniques, chemogenetics, particularly Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), offers precise, cell-type-specific, and temporally controlled modulation of neuronal and glial activity. This review explores the mechanisms and therapeutic potential of chemogenetic modulation in stroke recovery. Preclinical studies have demonstrated that activation of excitatory DREADDs (hM3Dq) in neurons located within the peri-infarct area or contralateral M1 has been shown to enhance neuroplasticity, facilitate axonal sprouting, and lead to improved behavioral recovery following stroke. Conversely, stimulation of inhibitory DREADDs (hM4Di) suppresses stroke-induced excitotoxicity, mitigates peri-infarct spreading depolarizations (PIDs), and modulates neuroinflammatory responses. By targeting specific neuronal and glial populations, chemogenetics enables phase-specific interventions-early inhibition to minimize damage during the acute phase and late excitation to promote plasticity during the recovery phase. Despite its advantages over traditional neuromodulation techniques, such as optogenetics and deep brain stimulation, several challenges remain before chemogenetics can be translated into clinical applications. These include optimizing viral vector delivery, improving ligand specificity, minimizing off-target effects, and ensuring long-term receptor stability. Furthermore, integrating chemogenetics with existing stroke rehabilitation strategies, including brain-computer interfaces and physical therapy, may enhance functional recovery by facilitating adaptive neuroplasticity. Future research should focus on refining chemogenetic tools to enable clinical application. By offering a highly selective, reversible, and minimally invasive approach, chemogenetics holds great potential for revolutionizing post-stroke therapy and advancing personalized neuromodulation strategies.

An 89-year-old man presented with a 3-year history of chronic daily headaches that significantly worsened over the past 4 months. Initially episodic, the left-sided headaches became continuous and were accompanied by systemic symptoms such as weight loss and elevated inflammatory markers, specifically C-reactive protein and erythrocyte sedimentation rate. Over subsequent weeks, the neurologic examination revealed new-onset left-sided ophthalmoplegia, ptosis, and marked visual acuity loss. This article explores the differential diagnosis for such a complex clinical presentation and highlights how a systematic diagnostic approach can guide clinicians toward the correct diagnosis.

CONCLUSIONS: A higher DII was associated with an increased risk of PPD in Chinese women. The present finding reinforces the importance of limiting pro-inflammatory food consumed and adopting an anti-inflammatory diet to decrease the risk of PPD.

BACKGROUND: Food insecurity is a risk factor for depressive symptoms during pregnancy, while resilience and social support are protective. This study evaluated models testing the collective influence of food insecurity, resilience, and social support on depressive symptoms among pregnant individuals.

CONCLUSIONS: Baclofen up to 50-60 mg/day may increase percent days abstinent and reduce craving, but may increase dropout due to adverse events. Clinicians should carefully consider individual patient factors when prescribing baclofen to patients with AUD.

BACKGROUND AND OBJECTIVES: People living with HIV (PWH) have increased rates of ischemic stroke even after antiretroviral therapy (ART) and viral suppression. Cerebral white matter hyperintensities (WMHs) on brain MRI are associated with an increased risk of stroke and cognitive impairment. This study sought to characterize and quantify brain WMHs during acute HIV infection and after early ART initiation compared with people without HIV.

OBJECTIVE: An emerging approach in surgery is to propose prehabilitation programs to strengthen the patient's functional abilities before surgical interventions, thus helping them cope better with its consequences. In drug-resistant language-dominant temporal lobe epilepsy (LdTLE), surgical treatment carries a risk of increasing cognitive deficits, notably word-finding difficulties (anomia) and verbal memory difficulties that negatively impact personal, social, and occupational activities. In this study, we invited 15 LdTLE patients to enroll in a speech and language prehabilitation program adapted to the specifics of their difficulties, organized daily during the preoperative period.

The fertility effects of antiseizure medications (ASMs) have been highlighted in females of reproductive age; however, the effects in males have not been extensively analyzed. This review aims to summarize the existing evidence of how ASMs affect sexual hormones and functions in males with epilepsy. We searched the Embase, PubMed, and MEDLINE databases in January 2024 to identify studies measuring sexual hormones, sexual function, or sperm parameters of males with epilepsy taking any ASM except valproic acid who were compared to a control group. A systematic review summarizing the effects of valproic acid on sexual function was published in 2018; therefore, we excluded valproic acid to avoid duplicating existing evidence. Risk of bias assessments were specific to the study type and included the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, NIH Quality Assessment Tool for Before-After (Pre-Post) Studies, and Cochrane Risk of Bias-2 tool for randomized trials. The systematic review included 32 studies, and the meta-analysis included 22 studies. Using random effect models, we calculated mean differences or rate ratios for studies assessing the association between ASMs and male sexual hormones or functions. Analyses were run for each combination of individual ASM or ASM characteristic, outcome, and comparison group. Males taking oxcarbazepine had significantly higher levels of testosterone, luteinizing hormone, and follicle-stimulating hormone compared to healthy controls. Conversely, there was no evidence of differences in any outcomes between levetiracetam or lamotrigine and comparison groups. Analyses that included untreated males with epilepsy rarely differed from males taking ASMs, highlighting the potential importance of epilepsy on altered sex hormones and functions. However, results should be interpreted cautiously, as many analyses included only a few studies and had high heterogeneity.

BACKGROUND: Emotion regulation deficits are prevalent in most psychiatric conditions; in particular in affective and personality disorders. The insula cortex is an intersection of emotion regulation, (expressive suppression vs. cognitive reappraisal), affective disorders, and traits predisposing dysfunctional personality. In this study, we tested the interrelation of emotion regulation strategies, brain structure, and narcissistic personality traits in a sub-clinical cohort.