Resumen en Inglés:

Abstract Background Amyotrophic lateral sclerosis (ALS) is a multifaceted neurodegenerative disorder with a poor prognosis. Weight loss and malnutrition emerge as significant clinical features during disease progression. Objective To explore how demographic and clinical characteristics relate to survival in ALS patients, emphasizing the role of weight loss percentage at the time of diagnosis. Methods We conducted a retrospective study that used the database of a multidisciplinary ALS care center in the city of Natal, Brazil. Results A total of 132 patients were included in the study. The mean age of the participants at symptom onset was of 56.9 years, and most of them were male (59.8%). Older age, bulbar onset, and faster disease progression were associated with weight loss ≥ 10% at diagnosis. Among 132 patients, 72% experienced death or tracheostomy, with a median survival of 34 months. Survival was notably reduced in patients aged ≥ 60 years, those with significant weight loss, rapid disease progression, or those submitted to gastrostomy. Weight loss and the rate of disease progression were the strongest predictors of reduced survival. Potential factors relating gastrostomy with reduced survival are discussed. Conclusion The present study highlights the critical impact of weight loss and disease progression on survival in ALS patients, emphasizing the importance of early nutritional and clinical interventions. These findings underscore the need for comprehensive, multidisciplinary care strategies to address key prognostic factors and improve outcomes in ALS patients.

Resumen en Inglés:

Abstract Background Chagas disease is an important cause of heart failure (HF) and stroke, affecting over 6 million people. High-intensity transient signals (HITS) are detected on transcranial Doppler (TCD) in patients with Chagas disease, but the effect of antithrombotic treatment on HITS is unknown. Objective To evaluate whether acetylsalicylic acid (ASA) reduces the frequency and number of HITS in patients with Chagasic HF. Methods Proof-of-principle pilot prospective, randomized, open, blinded endpoint (PROBE) clinical trial, in which patients with both Chagas and HITS were randomized 2:1 to ASA 300 mg for 7 days and standard HF treatment or standard HF treatment alone (control group). The primary outcome was the proportion of HITS after one week, analyzed using the Chi-squared test. Results A total of 373 patients with HF were evaluated, with HITS occurring in 22/190 (12%) Chagasic patients and in 16/183 (8%) non-Chagasic patients (p = 0.531). Twelve of the 22 (54%) Chagasic patients were randomized to treatment with (n = 8) or without ASA (n = 4). Two patients in the control group (50%) persisted with HITS after 7 days of treatment, compared to none in the ASA group, p = 0.028. The median number of HITS decreased from 3.5 to 0 with ASA (p = 0.012) and 4.0 to 0.5 in the control group (p = 0.095), with no significant between-group difference (p = 0.262). No adverse events were reported. Conclusion In the present pilot clinical trial, ASA reduced the proportion of HITS in patients with Chagas disease HF.

Resumen en Inglés:

Abstract Background Intracranial germ cell tumors (iGCTs) often lead to endocrine-metabolic complications; however, their long-term effects are not well understood and characterized. Objective To evaluate endocrine-metabolic dysfunction before and after iGCTs treatment. Methods The present retrospective study included 99 patients with iGCTs treated at a tertiary hospital. Endocrine and metabolic parameters were assessed before and after treatment. Results A male sex predominance was observed (81.8%). The leading site was pineal (44.4%), and 67.7% of the tumors were classified as germinoma. Radiotherapy was performed in 82.8% of the cases (58.5% cranial and 41.5% craniospinal). At diagnosis, the incidences of gonadotropin-independent precocious puberty and diabetes insipidus were 15.2% and 48.2%, respectively. Significant endocrine-metabolic changes in patients with iGCTs were observed after treatment, as 72.3% of patients required hormone replacement, 60% had growth hormone deficiency, and dyslipidemia was observed in 49.2% of patients. Overweight increased from 24.2 to 35.4% after treatment, while obesity increased from 10.1 to 15.4%. There was an increase in growth hormone deficiency, hypothyroidism, and hypogonadism, while prolactin levels significantly decreased after treatment. An older age at diagnosis was associated with a lower risk of hypocortisolism (p = 0.005). Regarding sex, females had lower height Z-scores and a higher frequency of growth hormone deficiency compared with males. Tumor-related mortality was reported in 22.2% of patients, occurring on average 2.2 years postdiagnosis. Conclusion The high prevalence of endocrine-metabolic complications following radiotherapy highlights the necessity of ongoing monitoring. The treatment demonstrated significant efficacy, as reflected by the notable survival rates. Early intervention is crucial for improving the long-term quality of life.

Resumen en Inglés:

Abstract Background Cefepime is an antibiotic widely used for severe infections in hospital . However, its use can lead to encephalopathy, which is detected by electroencephalogram (EEG). Objective To establish the socioclinical pattern of cefepime encephalopathy and its correlation with EEG. Methods Forty-one medical records of patients diagnosed with cefepime-induced encephalopathy were analyzed according to the criteria established by Naranjo et al.,1 with socioclinical parameters being evaluated. Results All EEG tracings in the presence of cefepime-induced encephalopathy had generalized periodic discharges (GPD), and 70.7% of the exams met the criteria for a nonconvulsive status epilepticus. With the withdrawal of cefepime, 85.3% of patients had clinical improvement. Conclusion Encephalopathy caused by cefepime is a clinical manifestation that should be considered among patients using this antibiotic, with a wide spectrum of manifestations. The use of EEG imaging is critical for diagnosis.

Resumen en Inglés:

Abstract Background Mechanical thrombectomy (MT) is a key therapy for acute ischemic stroke (AIS), improving survival and functional outcomes. However, the variability in results highlights the need for predictive markers to refine patient selection. Biomarkers reflecting inflammation and metabolic stress are gaining recognition for their role in AIS and MT outcomes. Objective To systematically review and synthesize the evidence on biomarkers associated with clinical outcomes in AIS patients undergoing MT. Specific aims include evaluating their relationship with functional recovery (mRS), mortality, infarct volume, hemorrhagic transformation, and complications such as malignant brain edema (MBE) and delayed cerebral ischemia (DCI). Methods A systematic review of the literature was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to identify studies evaluating biomarkers in MT. The PubMed and Embase databases were searched using the following terms: (Marker OR biomarker*) AND (Mechanical Thrombectomy OR endovascular) AND Stroke. Results Of 2,834 articles identified, 86 met inclusion criteria. Several biomarkers, such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), adenosine deaminase (ADA), neuron-specific enolase (NSE), and matrix metalloproteinase-9 (MMP-9), were consistently associated with worse functional outcomes, increased mortality, and higher risk of complications including hemorrhagic transformation and MBE. Conclusion Multiple biomarkers demonstrate prognostic value in AIS patients undergoing MT. These findings may support risk stratification and individualized care, though further prospective studies are needed to integrate these biomarkers into the clinical practice.

Resumen en Inglés:

Abstract Background Chronic pain is highly prevalent in frail older adults, resulting in reduced mobility and poor quality of life. However, research on the experience of chronic pain among frail older adults is scarce. Objective To compare the experience of chronic pain among frail, prefrail, and non-frail older adults, and to identify associations involving pain measures and frailty syndrome. Methods We conducted a cross-sectional study with older adults aged ≥ 60 years presenting chronic pain. The participants were recruited by convenience in specialized outpatient services at public hospitals. Frailty syndrome was identified through the frailty phenotype. The experience of pain was compared among the groups, and we conducted a multivariate logistic regression analysis adjusted for covariates. Results Out of the 135 participants, 36.3% were non-frail, 38.5%, prefrail, and 25.2%, frail. Frail older adults presented severe pain more frequently (p = 0.009) and had worse scores for neuropathic pain (mean: 4.1; 95%CI: 3.2–5.1) and depression associated with chronic pain (mean: 9.7; 95%CI: 7.9–11.5) compared with non-frail older adults (p < 0.001). Moreover, frail older adults presented worse multidimensional pain scores (mean: 59.4; 95%CI: 51.7–67.2) compared with non-frail (p = 0.001) and prefrail older adults (p = 0.017). Frail older adults were 3.5-fold as likely to present neuropathic pain, and they presented a 7-fold higher risk of severe pain than non-frail and prefrail older adults. Conclusion Frail older adults present severe chronic pain and experience neuropathic pain more frequently. Comprehensive chronic pain assessment and management in this population is critical to achieve active and healthy aging.

Resumen en Inglés:

Abstract Background Mitochondrial dysfunction plays a crucial role in neuropsychiatric disorders, including delirium. Objective To explore the causal links between mitochondrial-related druggable genes, cerebrospinal fluid metabolites, and delirium. Methods Summary-level data on mitochondrial-related druggable genes, expression quantitative trait loci (eQTLs), 338 cerebrospinal fluid (CSF) metabolites, and delirium data were obtained from publicly accessible genome-wide association studies. A two-sample Mendelian randomization (MR) was applied to assess the causal effects of blood cis-eQTL of mitochondrial-related druggable genes on delirium. Sensitivity analyses were also undertaken to ensure the MR results' reliability. We assessed whether cerebrospinal fluid metabolites mediate the causal relationship between druggable mitochondrial genes and delirium. Results A total of 12 mitochondrial-related druggable genes (8 protective and 4 risk) were identified to be associated with delirium risk (p < 0.05). Furthermore, 20 CSF metabolites were significantly associated with delirium, 9 positively and 11 negatively. Sensitivity analyses showed no evidence of heterogeneity or horizontal pleiotropy. Mediation analysis indicated that 3-hydroxyoctanoate partially mediated the causal association between sterol carrier protein 2 (SCP2) and delirium, accounting for approximately 19.23% of the total effect. Conclusion The present work reveals that mitochondrial-related genes and CSF metabolites may play causal roles in delirium and highlights SCP2–3-hydroxyoctanoate as a novel molecular axis. These findings expand current knowledge of delirium pathogenesis and offer a potential molecular target for diagnosis and therapy. Further experimental validation and population-diverse studies are needed to confirm these findings.

Resumen en Inglés:

Abstract Background Post coronavirus disease (COVID) syndrome is a frequent condition, resulting from the persistence of symptoms or the development of new ones, after 12 weeks of acute severe acute respiratory syndrome coronavirus 2 infection. The impact on sleep was observed worldwide, whether in the acute phase due to the direct effect of the infection or due to changes in patients' circadian cycle imposed by new routines during quarantine, dysfunctional habits, and social isolation. Objective Given the persistence of sleep-related symptoms in patients with long-term COVID syndrome, we decided to follow-up and reassess these patients after 1 year. Methods The present is an observational, longitudinal, and prospective clinical study. The study took place in two stages: the first assessment between October 2020 and September 2021, with reassessment after 1 year. Participants underwent the application of the Geriatric Depression Scale (GDS) or the Beck Inventory, Addenbrooke's Cognitive Examination - Revised (ACE-R) and Mini-Mental State Examination (MMSE). The evaluation of sleep disorders involved a comprehensive clinical history obtained through a structured questionnaire. Results Of the 46 cases with sleep complaints, 7 refused to return for a new assessment. Thus, 39 patients were included, of which 9 persisted with insomnia (23.07%) and 2 patients persisted with central hypersomnia (5.12%). The persistence of cognitive complaints was also higher in patients with insomnia when compared with those without it (N = 5; 56%, p = 0.001). Conclusion Given the persistence of patients with insomnia and central hypersomnia, the damage to the central nervous system may be lasting, reinforcing the need for follow-up.

Resumen en Inglés:

Abstract Obesity is a complex metabolic disorder with significant implications for both individual and public health. It has been strongly linked to chronic headache conditions, including migraines and idiopathic intracranial hypertension (IIH). Individuals with obesity who suffer from migraine are at increased risk of chronification, while weight reduction has been associated with improvement in IIH-related headaches, likely due to a decrease in cerebrospinal fluid pressure. These observations underscore the importance of weight management strategies as a therapeutic consideration in patients with obesity and headache disorders. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are pharmacological agents that mimic the hormone's endogenous activity. Analysis of selected studies highlights that these agents have emerged as a promising therapeutic option. The aim of this narrative review is to examine the role of GLP-1 RAs in the management of headaches, particularly in the context of IIH, migraine, and the gut–brain axis. Additionally, this review addresses the challenges associated with the use of this pharmaceutical class, including the potential for headaches as adverse effect, and identifies existing knowledge gaps that may guide future research.

Resumen en Inglés:

Abstract Essential tremor (ET) is the most prevalent movement disorder globally, affecting about 1% of the general population and 5% of those aged over 65 years. Characterized by involuntary, rhythmic oscillations, it primarily manifests as postural and kinetic tremors, predominantly in the upper limbs. Genetic studies, neuropathological examinations, neurophysiological assessments, and various neuroimaging techniques have demonstrated functional, neurotransmitter-related, and structural abnormalities within the cerebello-thalamo-cortical circuit. These findings collectively portray ET as a neurodegenerative syndrome with diverse etiologies and clinical manifestations, highlighting the involvement of the cerebellum.

Resumen en Inglés:

Abstract Benzodiazepine (BZD) receptor agonists, commonly known as Z-drugs, are non-BZD hypnotics primarily prescribed for the treatment of insomnia. Their use is recommended for no longer than four weeks to minimize the risk of adverse effects, including dependence and withdrawal. However, these guidelines are frequently disregarded, and the abuse of and dependence on Z-drugs has emerged as a growing public health concern in Brazil. The present article reviews the current evidence on Z-drug use disorder—including dependence and withdrawal—and proposes clinical guidelines for the management of discontinuation. The recommendations were developed based on a systematic review of the literature and refined using the Delphi methodology. The consensus was developed by a multidisciplinary task force, with coordination and voting led by a steering committee. An advisory committee, consisting of neurologists from the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN, in Portuguese) and psychiatrists specializing in substance-use disorders, contributed to the selection and organization of the scientific literature and took part in the voting process. Key recommendations were established: 1) prior to discontinuation, a comprehensive assessment of mental status, psychiatric and sleep comorbidities, and the degree of pharmacological dependence is essential; 2) gradual tapering is advised; 3) non-pharmacological interventions, such as cognitive behavioral therapy for insomnia, are recommended, and acceptance and commitment therapy, which is optional, may be incorporated; 4) for zolpidem withdrawal, adjunctive pharmacotherapy, which is optional, may include trazodone, other antidepressants, quetiapine or other antipsychotics, alpha-2-delta (α2δ) ligands, or alternative hypnotics (such as ramelteon, zopiclone, and eszopiclone); 5) forZ-drug discontinuation, intermediate-or long-acting BZDs are recommended; and 6) short- or ultra-short-acting BZDs and immediate-release melatonin are not recommended.

Resumen en Inglés:

Abstract Cervical radiculopathy (CR) is a common condition encountered in the general population, usually related to a musculoskeletal degenerative condition. Conventional electroneuromyography (ENMG) consists of nerve conduction studies (NCS) and needle electromyography (EMG), and it is regarded as the most specific diagnostic evaluation in this scenario. Although CR is commonly encountered in clinical practice, ENMG as a diagnostic tool is not often discussed in neurology residency programs. Electromyography has demonstrated modest sensitivity (50–71%) but excellent specificity (approaching 100%) for the diagnosis of CR. It can also provide valuable information about lesion chronicity. In EMG, acute lesions typically present with denervation potentials and reduced recruitment, but with preserved motor unit action potential (MUAP) morphology. In contrast, chronic lesions are characterized by remodeling, with MUAPs showing increased duration, amplitude, and number of phases, in addition to reduced recruitment. The present review aims to provide an overview of the roles of NCS and EMG, while also introducing key terminology commonly encountered in the interpretation of these diagnostic modalities.

Resumen en Inglés:

Abstract We review the contributions of Georges Guinon, an eminent pupil of Professor Jean-Martin Charcot, to the clinical description of Gilles de La Tourette syndrome, including phenomenological definitions and the occurrence of psychiatric findings such as obsessive-compulsive behavior.