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Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. The impacts of antihypertensive drugs and blood pressure (BP) on ALS are currently debatable. Objective To evaluate the causal relationship involving antihypertensive drugs, BP, and ALS through a Mendelian randomization (MR) analysis. Methods The causal relationship between BP and ALS was evaluated by a bidirectional two-sample MR analysis. Then, a sensitivity analysis was performed using a secondary BP genome-wide association study. The drug-target MR was employed to evaluate the impact of antihypertensive drugs on ALS. Furthermore, we used cis-expression quantitative trait loci (cis-eQTLs) data from brain tissue and blood to validate the positive results by a summary-based MR method. Results We found that an increment in systolic BP (SBP) could elevate the risk of ALS (inverse-variance weighted [IVW] odds ratio [OR] = 1.003; 95% confidence interval [95%CI]: 1.001–1.006; per 10-mmHg increment) and ALS might be protected by angiotensin-converting enzyme inhibitors (ACEIs; OR = 0.970; 95%CI: 0.956–0.984; p = 1.96 × 10−5; per 10-mmHg decrement). A causal relationship was not observed between diastolic BP and other antihypertensive drugs in ALS. Conclusion In the present study, genetic support for elevated SBP serves as a risk factor for ALS. Besides, ACEIs hold promise as a candidate for ALS.

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Abstract Background Prior to October 2022, stroke patients in Piaui lacked access to both stroke unit care and thrombolytic treatment, until the implementation of a telemedicine-based stroke care program. Objective To conduct a descriptive analysis of patients suspected of stroke who received telemedicine-based care in Piauí during the first year of the program's implementation. Methods We conducted a retrospective analysis of 868 patients treated from October 2022 to September 2023 under the state-wide stroke care program, which includes 6 Stroke Treatment Centers distributed around the state. Utilizing data from the JOIN telemedicine platform, the analysis focused on patient demographics, stroke types, treatment timelines, and outcomes of thrombolytic treatment. Results The cohort included 868 patients, with a mean age of 67.2 years, out of whom 55.5% were male. Chronic hypertension was reported in 57.8% and diabetes in 22.5% of the patients. The average onset-to-door time was 3.3 hours, door-to-computed tomography time was 23 minutes, and door-to-needle time averaged 67 minutes. Thrombolysis was administered to 15.6% of all stroke cases, with 31.8% among those being ischemic strokes. Among patients who arrived within the thrombolytic time window, the rate was 27.3%. Conclusion The introduction of a telemedicine-based stroke care program in Piauí has significantly enhanced access to essential stroke treatments, demonstrating its effectiveness in overcoming healthcare disparities. The initiative's success underscores the potential of telemedicine as a scalable model for improving stroke care in regions with limited healthcare resources. Future efforts will focus on reducing treatment times and expanding stroke care infrastructure to ensure comprehensive patient care.

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Abstract Background Since the advent of 18F-2-fluoro-2-deoxy-D-glucose ([18F]FDG, henceforth, FDG) in the 1970s as a neurochemical tracer, FDG positron emission tomography (PET) has been used for research in dementia and to help diagnose dementing neurodegenerative disorders. However, FDG PET is still unavailable in most centers, especially those in low- and middle-income countries, and there is limited data on biomarkers from patients in diverse populations, such Latin Americans. Objective To analyze the main indications and how the use of FDG PET helped improve the diagnosis of dementia in a specialized center in Recife, one of the largest cities in Northeastern Brazil. Methods We retrospectively analyzed data from 62 individuals under follow-up at our center between 2018 and 2023 who had a clinical diagnosis of dementia or mild cognitive impairment and underwent FDG PET scans. Results In 21/29 (72.4%) patients, FDG PET helped investigate the types of atypical neurodegenerative dementias; in 14/24 (58.3%), it clarified the clinical question in the investigation of early-onset dementia syndromes; and, in 9 cases, it was performed to differentiate between degenerative and non-degenerative dementias. Conclusion These numbers may set the foundation for further longitudinal analyses and collaborative studies including participants from Northeastern Brazil.

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Abstract Background Migraine causes intense pain, significant disability, deficits in attention and memory, slowed information processing, and cognitive disorders. However, it is unclear how migraine, cardiovascular, and cerebral issues impact daily life or relate to future adverse events. Objective To evaluate the brain activity and autonomic regulation in untreated migraine patients. Methods In the present case-control study, we compared untreated migraine patients with healthy controls. The participants underwent cognitive testing (Stroop Color Test, Trail Making Test, Addenbrooke's Cognitive Examination, and Reaction Time Test), brain activity measurement (MindWave Mobile), and autonomic regulation assessment via heart rate variability (Polar V800). Results No differences were found between the groups in terms of cognitive test scores. However, the healthy controls consistently showed increased variation in brain activity during the cognitive tests, while migraine patients exhibited decreased activity across all tests (p < 0.05). During the Stroop Color Test, the controls showed a positive change in brain activity (Δ = 5.12 ± 3.64) while the migraine patients showed a negative change (Δ = −5.41 ± 2.21). In addition, the control group demonstrated a normal autonomic response, with increased sympathetic activity (low-frequency [LF] band: 70.2–84.4 Hz) and decreased parasympathetic activity (high-frequency [HF] band: 29.6–15.6 Hz) during cognitive tasks (p < 0.05). In contrast, the migraine group showed imbalanced autonomic regulation, characterized by minimal changes in both sympathetic (LF band: 74.0–74.8 Hz) and parasympathetic activity (HF band: 25.9–25.1 Hz) (p > 0.05). Conclusion Despite the similar cognitive test scores, migraine patients exhibited reduced variation in brain activity during cognitive tests and an imbalanced autonomic regulation, characterized by decreased sympathetic activity and increased parasympathetic activity.

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Abstract Background Spinal cord injury (SCI) results in changes in autonomic function, impacting an individual's movement, sensory perception, and overall quality of life. Phyllanthin, a lignan from Phyllanthus amarus, is known for its neuronal protective effects. Objective To evaluate the potential of phyllanthin identified in P. amarus methanolic extract (PAME) against SCI in experimental rats. Methods The lignan was identified in PAME using high-performance liquid chromatography (HPLC). Spinal cord injury was induced in Sprague-Dawley rats using the laminectomy clip compression method. Rats received either a vehicle (distilled water) or methylprednisolone (30 mg/kg) or PAME (50, 100, and 200 mg/kg) orally for 4 weeks after SCI. Behavioral, histological, and molecular parameters were assessed to evaluate the neuroprotective effects of phyllanthin. Results During the HPLC analysis of PAME, phyllanthin was present at a retention time of 25.30 minutes with 75.22% weight per weight (w/w). The administration of standardized PAME (100 and 200 mg/kg) effectively ameliorated the alterations induced by SCI in thermal and mechano-tactile hyperalgesia, locomotor activity, and nerve conduction velocity (p < 0.05 each). The SCI-induced elevation in spinal interleukins (ILs: IL-1β and IL-6) and tumor necrosis factor alpha (TNF-α) protein levels was also effectively (p < 0.05) reduced by PAME. The PAME treatment markedly (p < 0.05) ameliorated SCI-induced alterations in protein expressions of B-cell leukemia/lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax), and caspase-3 in the spinal cord. Aberrations, such as inflammatory infiltration, edema, congestion, and necrosis induced in the spinal cord, were also effectively reduced by the PAME treatment (p < 0.05). Conclusion Phyllanthin identified in P. amarus showed neuroprotective potential against SCI by moderating impairments in behavioral (allodynia, hyperalgesia, and nerve conduction velocity) parameters, elevated inflammatory mediators (IL-1β, IL-6, and TNF-α), and deactivating the apoptotic signaling (Bax/caspase-3) pathway.

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Abstract Background Multiple sclerosis (MS) is the main cause of nontraumatic neurological disabilities in the population under 50 years of age. Objective To evaluate the most prevalent symptoms in a national sample of people with MS and to analyze their correlation with disease characteristics, demographics, quality of life, employment status, and use of social benefits. Methods Cross-sectional, online, self-reported survey, concerning demographic and clinical data, employment status, and use of social benefits. Results A total of 466 patients answered the survey. The median age at onset was 30 years, the current age, of 39, and disease duration was 8 years. Furthermore, the median patient determined disease steps (PDDS) was 2, which indicates minor to moderate disability. The median MS impact and walking scale scores were 31 and 20%, which denotes minor to moderate quality of life and mobility compromise. Among the participants, 43% suffered fatigue and 51% reported not sleeping well. Unemployed patients had delayed diagnosis and higher disability rates. Furthermore, half of the unemployed patients are receiving some social benefit, compared with only 6.5% of the employed patients. Conclusion The current study presents symptom prevalence in a national sample of patients with MS and discloses that those with a diagnosis delay and more disability have higher rates of unemployment and use of social benefits. Strategies for earlier diagnosis and better treatment plans can not only reduce patient disability but, possibly, increase employment retention and reduce the use of social benefits.

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Abstract Background Recent studies have reported that endovascular thrombectomy (ET) may improve neurological outcomes in large-core stroke. Objective We performed a systematic review and meta-analysis to compare the pooled efficacy and safety of ET and of the best medical treatment among patients with large-core stroke. Methods We searched the PubMed/MEDLINE, Scopus, and Cochrane databases from inception to November 2023. The inclusion criteria were randomized controlled trials (RCTs) comparing ET and the best medical treatment available among patients with large-core stroke (Alberta Stroke Program Early Computed Tomography Score [ASPECTS] < 6 or ischemic core > 50 mL on perfusion imaging) within 24 hours of symptom onset. Results We included 6 RTCs comprising 1,887 patients (ET group: n = 945). Endovascular thrombectomy was associated with good neurological outcomes (odds ratio [OR]: 2.92; 95% confidence interval [95%CI]: 2.17–3.93), or independent walking (OR: 2.22; 95%CI: 1.72–2.86). Trial sequential analysis confirmed a robust statistical significance for good neurological outcomes favoring ET. Endovascular thrombectomy was associated with higher risks of developing intracranial bleeding (OR: 2.65; 95%CI: 1.35–5.22) and symptomatic intracranial bleeding (OR: 1.83; 95%CI: 1.14–2.94). There were no differences between the groups regarding mortality or decompressive craniectomy. Patients submitted to non-contrast computed tomography (CT) with CT angiography (CTA) scans were analyzed separately and showed good neurological outcomes, comparable to those of the patients submitted to other imaging modalities (OR: 3.24; 95%CI: 1.52–6.92). Conclusion Endovascular thrombectomy was associated with good neurological outcomes and independent walking in patients with large-core acute ischemic stroke. However, it was also associated with an increased risk of developing intracranial bleeding. Non-contrast head CT with CTA scans may be appropriate for screening patients to undergo ET.

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Abstract Tenecteplase (TNK) is a genetically engineered variant of alteplase, showing promise for acute ischemic stroke treatment. With a longer half-life and higher fibrin specificity, TNK enables more targeted and efficient clot dissolution. Clinical trials demonstrate potential advantages, including improved reperfusion rates and functional outcomes with lower systemic bleeding. Though not officially approved for this purpose by all regulatory agencies, TNK is used off-label and in acute stroke guidelines due to its ease of administration and effectiveness. The 0.25 mg/kg dosage within 4.5 hours of symptom onset was shown to be consistently effective and safe. Further trials are expected to identify patient subgroups that benefit most from TNK treatment. The present narrative review assesses the existing literature and evidence regarding the use of tenecteplase for the treatment of acute ischemic stroke.

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Abstract Non-cerebral palsy motor impairments have been increasing over time, especially in preterm-born children, with a variety of labels, including, but not limited to, developmental coordination disorder and minor neurological dysfunction. They may not only negatively affect the child in their daily life activities, but are also associated with cognitive, emotional, and behavioral disorders, as well as decreased academic performance. Since there is a paucity of literature on non-cerebral palsy motor impairment, the main objective of the present study is to assess minor neurological dysfunction in the context of neurodevelopment. We reviewed the medical literature using the following search terms: preterm infants; follow-up; non-cerebral palsy motor impairment or disability; minor neurological dysfunction; developmental coordination disorder; neurological soft signs; and Touwen Neurological Examination. We compiled evidence-based data on minor neurological dysfunction critical domains, diagnosis, etiological factors and the influence of age and puberty in minor neurological signs. We also listed the cohort studies that used the Touwen Neurological Examination for premature or term-born follow-up, including those that suggest an association between minor neurological dysfunction and developmental coordination disorder as a motor impairment beyond cerebral palsy. Moreover, we found significant evidence of a correlation involving minor neurological dysfunction and cognitive, behavioral, and learning abilities, which, all in all, means that these children particularly deserve special attention regarding social, educational and healthcare resources. Furthermore, since motor activity seems to play an important role in the physical, mental, and neurological health of typical children, different approaches to education could have a positive impact on neurological development.

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Abstract The Brazilian Ministry of Health has issued new recommendations for the management of patients with acute ischemic stroke. The protocol covers aspects related to diagnosis, treatment, and patient monitoring, expanding the available treatment options for patients treated within the Brazilian Public Health System (Sistema Único de Saúde – SUS, in Portuguese). This article discusses some of the recommendations presented in the current Clinical Practice Protocol, aiming to spread awareness of the document's updates and assist healthcare professionals and services in implementing these recommendations.

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Abstract The licensing of lecanemab and donanemab, disease-modifying immunotherapies for Alzheimer's disease (AD) targeting β-amyloid pathology, has been met with difference in opinion about efficacy, adverse effects, and cost-effectiveness. Here we summarize the current situation and make the case for cautious adoption of these treatments into clinical practice. This opinion is predicated on four main observations: 1) these treatments impact the core pathologies of AD and result in meaningful benefits; 2) while adverse effects can be serious, these are proving manageable in clinical practice; 3) upscaling services to deliver these agents is likely to provide wider benefits for diagnosing and treating dementia and facilitating the adoption of future treatments from the dementia drug pipeline; and 4) factoring in both the wider societal cost of care and potential for continued accrual of long term benefits will be likely to bring these treatments within acceptable cost-effectiveness thresholds.

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Abstract Two antiamyloid monoclonal antibodies (mAbs), lecanemab and donanemab, were recently launched for treatment of Alzheimer's disease (AD). These mAbs remove amyloid protein from the brain and cause statistically significant improvement in cognitive/functional tests, meaning a change in evolution of AD. This is important to reinforce the amyloid cascade hypothesis and to further concentrate studies on the pathways from the deposition of the beta-amyloid protein to synaptic loss and neuronal death. However, it is necessary to evaluate whether the results are clinically important. Analysis of the clinical trials showed that the statistically significant differences over placebo did not reach the minimum clinically important difference that would be meaningful for patients, caregivers and clinicians. Besides, the incidence of adverse events is high and potentially severe. Although there are reasons to celebrate this first step towards disease-modifying therapies for AD, lecanemab and donanemab should not be used to treat AD in clinical pratice.

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Abstract We herein present aspects of the biography of Professor Paul Hoffmann, covering his main works, mainly the article describing the cutaneous silent period, a new technique when it was published in 1922, with a review of its importance, its role in clinical neurophysiology, and its clinical application.