Abstract Alzheimer's disease (AD), diabetic cognitive impairment (DCI), and vascular dementia (VD) are considered the most common causes of severe cognitive impairment in clinical practice. Numerous factors can influence their progression, and many studies have recently revealed that metabolic disorders play crucial roles in the progression of cognitive impairment. Mounting evidence indicate that the regulation of lipid metabolism is a major factor in maintaining brain homeostasis. Generally, abnormalities in lipid metabolism can affect amyloid-beta (Aβ) deposition, tau hyperphosphorylation, and insulin resistance through lipid metabolic signaling cascades; affect the neuronal membrane structure, neurotransmitter synthesis and release; and promote synapse growth, which can impact neural signal transmission and exacerbate disease progression in individuals with cognitive impairment, including AD, DCI, and VD. Moreover, apolipoprotein E (APOE), a key protein in lipid transport, is involved in the occurrence and development of the aforementioned diseases by regulating lipid metabolism. The present article mainly discusses how lipid metabolic disorders in the brain microenvironment are involved in regulating the progression of cognitive impairment, and it explores the regulatory effects of targeting the key lipid transport protein APOE in the context of the role of lipid metabolism in the common pathogenesis of three diseases—Aβ deposition, tau hyperphosphorylation, and insulin resistance—which will help elucidate the potential of targeting lipid metabolism for the treatment of cognitive impairment.

Resumo Os pioneiros da Neurologia no Japão foram os professores Hiroshi Kawahara e Kinnosuke Miura. Kawahara publicou a primeira descrição de paralisia bulbar progressiva e escreveu o primeiro livro-texto de Neurologia no Japão. Já Miura publicou estudos sobre esclerose lateral amiotrófica, além de participar da fundação da Sociedade Japonesa de Neurologia. A influência da Neurologia europeia, particularmente francesa e alemã, nas figuras dos Professores Jean-Martin Charcot e Erwin Bälz foi fundamental na consolidação da Neurologia no Japão.

Abstract The pioneers of neurology in Japan were professors Hiroshi Kawahara and Kinnosuke Miura. Kawahara published the first description of progressive bulbar palsy and wrote the first neurology textbook in Japan. Miura, on the other hand, published studies about amyotrophic lateral sclerosis, in addition to participating in the founding of the Japanese Society of Neurology. The influence of European neurology, particularly French and German, in the figures of Professor Jean-Martin Charcot and Professor Erwin Bälz, was fundamental in the consolidation of neurology in Japan.

Abstract Background Tafamidis is a kinetic stabilizer that binds to the transthyretin (TTR) gene, inhibiting its dissociation. It is the only disease-modifying treatment for hereditary TTR amyloidosis with peripheral neuropathy (ATTRv-PN) available in the National Therapeutic Form (Formulário Terapêutico Nacional, FTN, in Portuguese) of the Brazilian Unified Health System (Sistema Único de Saúde, SUS, in Portuguese). Objective To assess if the efficacy and safety of tafamidis in the Brazilian real-world experience are comparable to the results of clinical trials. Methods We retrospectively studied all patients with ATTRv-PN evaluated at our center from September 2011 to March 2022 (data cut-off) who were initiated on tafamidis and had at least 1 follow up visit 6 months after the initiation of the drug treatment. Neurologic and functional outcomes were compared from day 1 (D1) of the tafamidis treatment (baseline) to the last follow-up. Results In total, 33 patients were included, 18 (55%) of whom were female. All patients were carriers of the V30M mutation of ATTRv-PN, and 20 (61%) presented early onset (EO) ATTRv-PN. At baseline, the median age of the sample was of 40 (interquartile range [IQR]: 36–68) years, the median Neuropathy Impairment Score (NIS) was of 10 (6–24) points, and the median body mass index (BMI) was of 26 (23–28) kg/m2. The mean follow-up time was of 3.4 years. At the last follow-up, the BMI, the neurological impairment, and the level of disability slightly worsened compared with baseline, while the findings of the nerve conduction studies remained stable. These same results were observed across EO and late-onset (LO) ATTRv-PN patients. A total of 25 (75.8%) patients were considered responders, and 8 (24.2%), non-responders. Conclusion The efficacy and safety of tafamidis reported in clinical trials is expandable to the Brazilian real-world scenario in EO and late-onset (LO) ATTRv-PN.

Abstract Background The movement disorder known as hemifacial spasm is characterized by involuntary contractions of the muscles that are innervated by the facial nerve. The treatment of choice for this condition is botulinum toxin injections. Objective To analyze the botulinum toxin dosage in patients undergoing treatment for hemifacial spasm during a 14-year period. Methods A retrospective study of medical records from patients treated at the Neurology Service of Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, from 2010 to 2024, was performed. Results A total of 151 patients met the inclusion criteria. The dose of botulinum toxin revealed a statistically significant increase during the first 3.46 years of follow-up. In the long-term, a trend toward dose stabilization was identified. The median latency for the onset of effect was 4 days, while the median duration of effect was 3 months. All side effects were temporary, with the most common being hemifacial weakness (17.9%) and palpebral ptosis (3.3%). Most patients presented primary hemifacial spasm (88.1%), with a neurovascular conflict identified in 24.1% of cases. Conclusion The increase in botulinum toxin dosage during the first years may be explained by dosage adjustment to control hemifacial spasm with the lowest possible doses. A prolonged interval between applications may also be associated with this increase. Dose stabilization tends to be achieved over time, indicating disease control.

Resumo Antecedentes A cirurgia de epilepsia é reconhecida por sua eficácia no controle de crises em um número significativo de pacientes com epilepsia resistente a medicamentos. Apesar disso, persiste uma deficiência notável na referência desses pacientes para monitoramento por vídeo-eletroencefalograma (EEG) e avaliação cirúrgica. Para avaliar essa lacuna, a Adequação Canadense da Cirurgia de Epilepsia (Canadian Appropriateness of Epilepsy Surgery CASES, na sigla em inglês), uma ferramenta online para avaliação de cirurgia de epilepsia (www.epilepsycases.com), foi desenvolvida para auxiliar médicos no processo de selecionar pacientes com epilepsia refratária para avaliações cirúrgicas. Objetivo Avaliar a utilidade da CASES na identificação de candidatos para cirurgia de epilepsia, facilitando assim os processos de decisão terapêutica para pacientes com epilepsia resistente a medicamentos. Métodos Foi realizada uma análise transversal usando a plataforma CASES para estimar a necessidade de avaliação cirúrgica entre indivíduos com epilepsia. Os participantes foram selecionados dentre aqueles em atendimento na Clínica de Epilepsia do Serviço de Neurologia, Hospital de Clínicas de Porto Alegre, durante um período de 3 meses. O estudo incluiu uma coorte de 211 pacientes. Os dados foram sistematicamente extraídos dos prontuários médicos dos pacientes ou coletados durante consultas clínicas. Resultados Da coorte avaliada, 59,6% foram identificados como potenciais candidatos para monitoramento por vídeo-EEG e subsequente avaliação cirúrgica. Fatores significativamente associados com recomendações para vídeo-EEG e avaliação cirúrgica incluíram a frequência de crises, o número de drogas anticrise (DACs) testadas e a ocorrência de efeitos adversos relacionados aos medicamentos. Conclusão A CASES mostrou um potencial significativo em orientar as recomendações para monitoramento por vídeo-EEG e facilitar o encaminhamento de pacientes para avaliação cirúrgica. Ferramentas como essas podem não apenas melhorar os tratamentos e resultados dos pacientes, mas também contribuir para economias de custo no manejo da epilepsia a curto e longo prazo. medicamentos disso vídeoeletroencefalograma vídeo eletroencefalograma EEG (EEG lacuna Canadian inglês, inglês , inglês) www.epilepsycases.com, wwwepilepsycasescom www.epilepsycases.com www epilepsycases (www.epilepsycases.com) cirúrgicas Neurologia Alegre meses 21 clínicas avaliada 596 59 6 59,6 vídeoEEG DACs (DACs prazo (www.epilepsycases.com 2 5 59,

Abstract Background Epilepsy surgery is recognized for its effectiveness in controlling seizures in a significant number of patients with drug-resistant epilepsy. Despite this, there remains a notable deficiency in referring these patients for video-electroencephalogram (EEG) monitoring and surgical evaluation. Addressing this gap, the Canadian Appropriateness of Epilepsy Surgery (CASES), an online tool for epilepsy surgery evaluation (www.epilepsycases.com), was developed to aid physicians in the referral process of patients with refractory epilepsy to surgical assessments. Objective The present study aimed to evaluate the utility of CASES in identifying candidates for epilepsy surgery, thereby facilitating clinical decision-making for patients with drug-resistant epilepsy. Methods A cross-sectional analysis was conducted using the CASES platform to assess surgical candidacy among individuals with epilepsy. Participants were selected among those receiving care at the Epilepsy Clinic of the Neurology Service, Hospital de Clínicas de Porto Alegre, Brazil, over a 3-month period. The study cohort included 211 patients. Data were systematically extracted from patient medical records or collected during clinical appointments. Results Of the evaluated cohort, 59.6% were identified as potential candidates for video-EEG monitoring and subsequent surgical evaluation. Factors significantly associated with recommendations for video-EEG and surgical assessment included seizure frequency, the number of antiseizure medications (ASMs) trialed, and the occurrence of drug-related adverse effects. Conclusion The CASES showed significant potential in guiding recommendations for video-EEG monitoring and facilitating referrals for epilepsy surgery. This tool may not only enhance patient treatments and outcomes but also contribute to cost savings in epilepsy management in both the short and long term. drugresistant drug resistant videoelectroencephalogram video electroencephalogram EEG (EEG gap CASES, , (CASES) www.epilepsycases.com, wwwepilepsycasescom www.epilepsycases.com www epilepsycases com (www.epilepsycases.com) assessments decisionmaking decision making crosssectional cross sectional Service Alegre Brazil 3month month 3 period 21 appointments 596 59 6 59.6 videoEEG frequency ASMs (ASMs trialed drugrelated related effects term (CASES (www.epilepsycases.com 2 5 59.

Resumo Com base na minha atividade de neurologista clínico com mais de 50 anos de experiência no atendimento de pacientes com doença de Alzheimer (DA), foco neste artigo de revisão nos dois aspectos fundamentais da doença para o médico: o diagnóstico e o tratamento. Os critérios diagnósticos de 1984 permaneceram estáveis por mais de um quarto de século quando foram substituídos em 2011. Desde então, muitas descobertas foram feitas, especialmente de biomarcadores que têm grande impacto no diagnóstico da DA. Recentemente, biomarcadores de DA tornaram-se disponíveis no plasma, o que certamente causará uma grande mudança no diagnóstico da DA biológica, termo que ainda necessita de cuidados e informações para a sociedade antes de ser utilizado na prática clínica. Três anticorpos monoclonais contra o peptídeo β-amiloide também foram aprovados recentemente e dois deles mostraram efeito pequeno, mas estatisticamente significativo, no resultado clínico. Esses anticorpos monoclonais tiveram maior efeito na redução de placas amiloides no cérebro avaliadas por tomografia por emissão de pósitrons (positron emission tomography, PET, em inglês) e na concentração de biomarcadores no líquido cefalorraquidiano (peptídeo β-amiloide com 42 aminoácidos e proteína tau hiperfosforilada) do que nas avaliações neuropsicológicas e funcionais. Mesmo este pequeno efeito clínico poderá ser encorajador para o desenvolvimento de novas pesquisas, particularmente auxiliado pela maior facilidade de diagnóstico e monitoramento da evolução da fisiopatologia da DA com biomarcadores plasmáticos eficientes para diagnóstico ou controle evolutivo. Recentemente, novos critérios diagnósticos para a DA foram apresentados pela Alzheimer's Association causando controvérsia quanto ao seu emprego na prática clínica. 5 DA, , (DA) médico tratamento 198 2011 então feitas Recentemente tornaramse tornaram se plasma biológica clínica βamiloide β amiloide significativo positron tomography PET inglês 4 hiperfosforilada funcionais pesquisas evolutivo Alzheimers s (DA 19 201 1 20 2

Abstract Based on my work as a clinical neurologist with more than 50 years of experience in caring for patients with Alzheimer's disease (AD), I focus, in this review article, on the disease's two fundamental aspects for the doctor: diagnosis and treatment. The 1984 diagnostic criteria had been stable for more than a quarter of a century when it was replaced in 2011. Since then, there have been many discoveries, especially of biomarkers that have a heavy impact on the diagnosis of AD. Recently, AD biomarkers have become available in plasma, which certainly will cause a major change in the diagnosis of biological AD, a term that still needs care and information to society before being used in clinical practice. Three monoclonal antibodies against β-amyloid peptide have also been recently approved, and two of these have shown a small but statistically significant effect on clinical outcome. These monoclonal antibodies have had a greater effect on the reduction of amyloid plaques in the brain assessed by positron emission tomography (PET), and on the concentration of biomarkers in the cerebrospinal fluid (β-amyloid peptide with 42 amino acids and hyperphosphorylated tau protein) than in the neuropsychological and functional assessments. Even this small clinical effect will be encouraging for the development of new research, particularly helped by the greater ease of diagnosis and monitoring of the evolution of AD pathophysiology with plasma biomarkers. Recently, new diagnostic criteria for AD were presented by the Alzheimer's Association, causing controversy about their use in clinical practice. 5 Alzheimers Alzheimer s , (AD) focus article diseases doctor treatment 198 2011 then discoveries Recently practice βamyloid β approved outcome PET, PET (PET) 4 protein assessments research Association (AD 19 201 (PET 1 20 2

Resumo Antecedentes A migrânea é uma cefaleia primária que afeta 14,4% da população global. Os mecanismos fisiopatológicos da migrânea envolvem a interação entre a ativação hipotalâmica, depressão cortical alastrante, estimulação trigeminal e componentes inflamatórios com inflamação neurogênica ou neuroinflamação. Objetivo Avaliar a frequência da variante genética IL1A -899C > T (rs1800587) em pacientes com migrânea e controles saudáveis, bem como sua associação com as manifestações clínicas da migrânea. Métodos Realizamos um estudo do tipo caso-controle com 92 pacientes com migrânea e 88 indivíduos saudáveis pareados por idade, sexo, índice de massa corporal (IMC) e etnia. Dados demográficos, antropométricos e clínicos foram obtidos. A variante IL1A -889C > T (rs1800587) foi identificada por meio de reação em cadeia da polimerase em tempo real. Resultados O estudo foi composto predominantemente por mulheres e indivíduos caucasianos, sem diferenças significativas em termos de idade, sexo, etnia e IMC entre os grupos de migrânea e controle. No grupo de migrânea, 57,6% apresentavam migrânea episódica e 45,7% tinham aura. Encontrou-se uma associação entre os pacientes portadores do genótipo CT e a presença de aura (CT: 57,7%; TT: 27,5%; p = 0,027), e os portadores dos genótipos CT e TT apresentaram taxas mais altas de osmofobia quando comparados com os portadores do genótipo CC (p = 0,003). A variante IL1A -889C > T não esteve associada à suscetibilidade à migrânea, a sua forma crônica ou episódica, bem como a outros sintomas relacionados à migrânea. Conclusão O polimorfismo genético IL1A -889C > T foi associado com aura e osmofobia em indivíduos com migrânea. 144 14 4 14,4 global hipotalâmica alastrante neuroinflamação ILA IL 899C C rs1800587 rs (rs1800587 casocontrole caso controle 9 8 idade sexo (IMC demográficos obtidos 889C real caucasianos 576 57 6 57,6 457 45 7 45,7 Encontrouse Encontrou se (CT 57,7% 577 27,5% 275 27 5 0,027, 0027 0,027 , 0 027 0,027) 0,003. 0003 0,003 . 003 0,003) 1 14, rs180058 (rs180058 57, 45, 57,7 27,5 2 002 0,02 02 000 0,00 00 rs18005 (rs18005 27, 0,0 rs1800 (rs1800 0, rs180 (rs180 rs18 (rs18 rs1 (rs1 (rs

Abstract Background Migraine belongs to the group of primary headaches, affecting 14.4% of the global population. The pathophysiological mechanisms of migraine involve the interplay between hypothalamic activation, cortical spreading depression, trigeminal stimulation, and inflammatory components with neurogenic inflammation or neuroinflammation. Objective To assess the frequency of the IL1A -899C > T (rs1800587) genetic variant in patients with migraine and healthy controls, as well as its association with the clinical manifestations of migraine. Methods We conducted a case-control study involving 92 migraine patients and 88 healthy controls matched for age, sex, body mass index (BMI), and ethnicity. Demographic, anthropometric, and clinical data were obtained. The IL1A -889C > T (rs1800587) variant was identified using real-time polymerase chain reaction. Results The study comprised predominantly women and Caucasian individuals, with no significant differences in terms of age, sex, ethnicity, or BMI observed between the migraine and control groups. Within the migraine group, 57.6% had episodic migraines, and 45.7% experienced aura. The patients carrying the CT genotype showed stronger associations with the presence of aura (CT: 57.7%; TT: 27.5%; p = 0.027), and those carrying the CT and TT genotypes showed higher osmophobia rates when compared with the CC genotype (p = 0.003). The IL1A -889C > T genetic variant was not associated with migraine susceptibility, be it chronic or episodic, nor to other symptoms associated with migraine. Conclusion The IL1A -889C > T genetic variant was associated with aura and osmophobia in migraine patients. headaches 144 14 4 14.4 population activation depression stimulation neuroinflammation ILA IL A 899C C rs1800587 rs (rs1800587 casecontrol case 9 8 age sex BMI, , (BMI) ethnicity Demographic anthropometric obtained 889C realtime real time reaction individuals groups 576 57 6 57.6 migraines 457 45 7 45.7 (CT 57.7% 577 27.5% 275 27 5 0.027, 0027 0.027 0 027 0.027) 0.003. 0003 0.003 . 003 0.003) susceptibility 1 14. rs180058 (rs180058 (BMI 57. 45. 57.7 27.5 2 002 0.02 02 000 0.00 00 rs18005 (rs18005 27. 0.0 rs1800 (rs1800 0. rs180 (rs180 rs18 (rs18 rs1 (rs1 (rs

Resumo Antecedentes A compreensão das alterações do sistema nervoso autônomo (SNA) na fase crônica do acidente vascular cerebral isquêmico (AVCi) ainda é insuficiente. A variabilidade da frequência cardíaca (VFC) fornece uma abordagem não invasiva para avaliar a função autonômica. Objetivo Comparar os parâmetros da VFC durante o ciclo sono-vigília entre participantes saudáveis e com AVCi crônico. Métodos Estudo retrospectivo transversal baseado em registros clínicos e registros de eletrocardiograma de 24 horas de 179 pacientes com AVCi confirmado e 184 controles pareados por idade e sexo. As variações do índice de atividade autonômica total (VTAI) e do índice de atividade parassimpática (VPAI) foram usados para calcular a variação circadiana. As comparações foram feitas usando testes não paramétricos. Análise discriminante canônica (CDA) e análise de variância (ANOVA) de três vias foram usadas para análises multivariadas. Um nível de confiança de 95% foi estabelecido para a significância estatística. Resultados O grupo controle exibiu maior variabilidade nos parâmetros de domínio do tempo e da frequência durante as horas de vigília: desvio padrão dos intervalos NN (SDNN, p < 0,001) e das médias dos intervalos NN (SDANN, p < 0,001), assim como a banda de baixa frequência (LF, p < 0,001). Durante o sono, a diferença foi maior na banda de alta frequência (HF, p < 0,001) e a razão baixa/alta frequência (LF/HF) foi menor (p < 0,001). O VPAI e VTAI mostraram menor variabilidade nos pacientes com AVC (p < 0,001). Conclusão Os pacientes com AVCi apresentaram atividade vagal cardíaca diminuída, medida pela VFC. Isto pode resultar de desequilíbrios nos sistemas simpático e parassimpático que mudam durante as fases do sono. Em pacientes com AVCi, esses desequilíbrios podem permanecer meses após a lesão inicial. SNA (SNA (AVCi insuficiente (VFC sonovigília sono vigília crônico 2 17 18 sexo (VTAI (VPAI circadiana paramétricos CDA (CDA ANOVA (ANOVA multivariadas 95 estatística SDNN, SDNN (SDNN 0,001 0001 0 001 SDANN, SDANN (SDANN 0,001, , LF, LF (LF 0,001. . HF, HF (HF baixaalta LF/HF LFHF (LF/HF diminuída inicial 1 9 0,00 000 00 0,0 0,

Abstract Background Alterations of the autonomic nervous system (ANS) in the chronic stage of ischemic stroke (IS) are not well understood. Heart rate variability (HRV) provides a noninvasive approach to assess autonomic function. Objective To compare the HRV parameters during the sleep-wake cycle between patients with IS in the chronic stage and healthy subjects. Methods We conducted a retrospective transversal study based on clinical records and 24-hour electrocardiogram (EKG) monitoring registries of 179 patients with a confirmed IS diagnosis and 184 age- and sex-matched healthy subjects. Circadian variation was calculated according to the variation of the total autonomic activity (VTAI) and the parasympathetic activity (VPAI) indexes. Comparisons were performed using nonparametric tests. Multivariable analyses were performed with canonical discriminant analysis (CDA) and a three-way analysis of variance (ANOVA). Statistical significance was established with a confidence level of 95%. Results During waking hours, the healthy group exhibited higher variability in the time domain and frequency domain parameters: standard deviation of NN intervals (SDNN, p < 0.001) and of the average NN intervals (SDANN, p < 0.001), as well as low-frequency (LF) band (p < 0.001). During sleep, the difference was higher in the high-frequency (HF) band (p < 0.001), and lower in the low-/high-frequency ratio (LF/HF, p < 0.001). Both VPAI and VTAI showed less significant difference in IS patients (p < 0.001). Conclusion There was diminished heart vagal activity among IS patients, as measured through HRV. During sleep, this is likely caused by an imbalance in the sympathetic and parasympathetic systems shifting through the sleep phases. These imbalances could persist over time in patients with IS, lasting months after the initial injury. ANS (ANS (IS understood (HRV function sleepwake wake subjects 24hour hour 24 EKG (EKG 17 18 age sexmatched sex matched (VTAI (VPAI indexes tests CDA (CDA threeway three way ANOVA. ANOVA . (ANOVA) 95 95% hours SDNN, SDNN (SDNN 0.001 0001 0 001 SDANN, SDANN (SDANN 0.001, , lowfrequency low LF (LF 0.001. highfrequency high HF (HF low/highfrequency lowhighfrequency /high LF/HF, LFHF (LF/HF phases injury 2 1 (ANOVA 9 0.00 000 00 LF/HF 0.0 0.

Resumo Antecedentes A atrofia muscular espinhal (AME-5q) é uma doença neurodegenerativa caracterizada por atrofia muscular progressiva, hipotonia e fraqueza. Na AME 1 os sintomas iniciam-se no primeiro semestre de vida. Terapias modificadoras de doença foram aprovadas e demonstram melhores resultados quanto mais cedo forem iniciadas. Objetivo Descrever a segurança e a eficácia clínica das terapias modificadoras de doença quanto às funções motora, respiratória e bulbar. Os pacientes com AME 1 foram divididos em 2 grupos: os que faziam uso exclusivamente de nusinersena (grupo 1) e os que transacionaram para onasemnogene abeparvovec (OA) (grupo 2). Métodos Durante 18 meses, os pacientes foram avaliados utilizando a escala Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), marcos do desenvolvimento, necessidade e duração da ventilação, necessidade de suporte nutricional, consistência dos alimentos e sinais de disfagia. Dividiram-se dez pacientes entre os grupos; no grupo 1, a idade média para início do nusinersena foi de 53,6 (12–115) meses e, no grupo 2, a idade foi de 7 (1–12) meses para o nusinersena e 15,2 (10–19) meses para OA. Resultado Nossos resultados indicam que 70% dos pacientes atingiram algum marco motor, com o grupo 1 aumentando 10,2 pontos na escala CHOP-INTEND, e o grupo 2 aumentando 33. Ademais, 90% dos pacientes não apresentaram declínio respiratório e 30% mantiveram alimentação oral. Não houve efeitos adversos graves ou mortes. Conclusão Ambos os grupos apresentaram melhoria na função motora e estabilização da função respiratória e bulbar, com a diferença entre os grupos sendo possivelmente relacionada com o início mais precoce do tratamento. Assim, este estudo fornece informações valiosas sobre a segurança e eficácia clínica destas terapias para pacientes com AME 1. AME5q AMEq 5q q (AME-5q progressiva fraqueza iniciamse iniciam se vida iniciadas bulbar OA (OA 2. . 2) Childrens Children s CHOPINTEND, CHOPINTEND CHOP INTEND , (CHOP-INTEND) desenvolvimento ventilação nutricional disfagia Dividiramse Dividiram 536 53 6 53, 12–115 12115 12 115 (12–115 1–12 112 (1–12 152 15 15, 10–19 1019 10 19 (10–19 70 motor 102 10, INTEND, CHOP-INTEND 33 Ademais 90 30 oral mortes tratamento Assim (CHOP-INTEND 5 12–11 1211 11 (12–11 1–1 (1–1 10–1 101 (10–1 3 9 12–1 121 (12–1 1– (1– 10– (10– 12– (12– (1 (10 (12 (

Abstract Background Spinal muscular atrophy (SMA-5q) is a neurodegenerative disease characterized by progressive muscle atrophy, hypotonia, and weakness, with SMA 1 presenting symptoms within the first 6 months of life. Disease-modifying therapies have been approved, with better outcomes with earlier treatment. Objective To describe the safety and clinical efficacy of disease-modifying therapies based on SMN1 and SMN2 gene strategies concerning motor, respiratory, and bulbar function. Patients with SMA 1 were divided into 2 groups: those exclusively on nusinersen (group 1) and those transitioning to onasemnogene abeparvovec (OA) (group 2). Methods Over 18 months, patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scale, developmental milestones, ventilation needs and duration, nutritional support needs, consistency of food, and signs of dysphagia. There were ten patients, divided between the groups; in group 1, the average age for starting nusinersen was 53.6 (12–115) months, and, in group 2, the age was 7 (1–12) months for nusinersen and 15.2 (10–19) months for OA. Results Our results indicate that 70% of patients reached some motor milestones, with group 1 increasing by 10.2 points on the CHOP-INTEND scale, while group 2 increased by 33 points. Additionally, 90% of the patients experienced no respiratory decline, and 30% maintained oral feeding. No serious adverse effects or deaths were recorded. Conclusion Both groups showed improvement in motor function and stabilization of respiratory and bulbar function, with the difference between the groups possibly being related to the earlier treatment initiation. Thus, the present study provides valuable insights into the real-world safety and clinical efficacy of disease-modifying therapies for SMA 1 patients. SMA5q SMAq 5q q (SMA-5q hypotonia weakness life Diseasemodifying Disease modifying approved diseasemodifying SMN OA (OA 2. . 2) Childrens Children s CHOPINTEND CHOP INTEND (CHOP-INTEND scale milestones duration food dysphagia 536 53 53. 12–115 12115 12 115 (12–115 1–12 112 (1–12 152 15 15. 10–19 1019 10 19 (10–19 70 102 10. 3 Additionally 90 decline 30 feeding recorded initiation Thus realworld real world 5 12–11 1211 11 (12–11 1–1 (1–1 10–1 101 (10–1 9 12–1 121 (12–1 1– (1– 10– (10– 12– (12– (1 (10 (12 (

Resumo Antecedentes O diagnóstico precoce da doença de Alzheimer (DA) e do comprometimento cognitivo leve (CCL) continua sendo um desafio significativo na neurologia, com métodos convencionais frequentemente limitados pela subjetividade e variabilidade na interpretação. A integração da aprendizagem profunda com a inteligência artificial (IA) na análise de imagens de ressonância magnética surge como uma abordagem transformadora, oferecendo o potencial para insights diagnósticos imparciais e altamente precisos. Objetivo Uma metanálise foi projetada para analisar a precisão diagnóstica do aprendizado profundo de imagens de ressonância magnética em modelos de DA e CCL. Métodos Uma metanálise foi realizada nos bancos de dados das bibliotecas PubMed, Embase e Cochrane seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com foco na precisão diagnóstica do aprendizado profundo. Posteriormente, a qualidade metodológica foi avaliada por meio do checklist QUADAS-2. Medidas diagnósticas, incluindo sensibilidade, especificidade, razões de verossimilhança, razão de chances diagnósticas e área sob a curva característica de operação do receptor (area under the receiver operating characteristic curve [AUROC]) foram analisadas, juntamente com análises de subgrupo para ressonância magnética ponderada em T1 e não ponderada em T1. Resultados Um total de 18 estudos elegíveis foram identificados. O coeficiente de correlação de Spearman foi de -0,6506. A metanálise mostrou que a sensibilidade e a especificidade combinadas, a razão de verossimilhança positiva, a razão de verossimilhança negativa e a razão de chances de diagnóstico foram 0,84, 0,86, 6,0, 0,19 e 32, respectivamente. A AUROC foi de 0,92. O ponto quiescente do resumo hierárquico da característica de operação do receptor (hierarchical summary of receiver operating characteristic [HSROC]) foi 3,463. Notavelmente, as imagens de 12 estudos foram adquiridas apenas por ressonância magnética ponderada em T1, e as dos outros 6 foram obtidas apenas por ressonância magnética não ponderada em T1. Conclusão Em geral, a aprendizagem profunda da ressonância magnética para o diagnóstico de DA e CCL mostrou boa sensibilidade e especificidade e contribuiu para melhorar a precisão diagnóstica. (DA (CCL neurologia interpretação IA (IA transformadora precisos PubMed MetaAnalyses Meta Analyses PRISMA, PRISMA , (PRISMA) Posteriormente QUADAS2. QUADAS2 QUADAS 2. 2 QUADAS-2 area [AUROC] analisadas T 1 identificados 0,6506. 06506 0 6506 -0,6506 combinadas positiva 084 84 0,84 086 86 0,86 60 6,0 019 19 0,1 32 respectivamente 092 92 0,92 hierarchical HSROC [HSROC] 3463 3 463 3,463 Notavelmente geral (PRISMA QUADAS- [AUROC 0,6506 0650 650 -0,650 08 8 0,8 6, 01 0, 09 9 0,9 [HSROC 346 46 3,46 0,650 065 65 -0,65 34 4 3,4 0,65 06 -0,6 3, 0,6 -0, -0 -

Abstract Background The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains a significant challenge in neurology, with conventional methods often limited by subjectivity and variability in interpretation. Integrating deep learning with artificial intelligence (AI) in magnetic resonance imaging (MRI) analysis emerges as a transformative approach, offering the potential for unbiased, highly accurate diagnostic insights. Objective A meta-analysis was designed to analyze the diagnostic accuracy of deep learning of MRI images on AD and MCI models. Methods A meta-analysis was performed across PubMed, Embase, and Cochrane library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on the diagnostic accuracy of deep learning. Subsequently, methodological quality was assessed using the QUADAS-2 checklist. Diagnostic measures, including sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristic curve (AUROC) were analyzed, alongside subgroup analyses for T1-weighted and non-T1-weighted MRI. Results A total of 18 eligible studies were identified. The Spearman correlation coefficient was -0.6506. Meta-analysis showed that the combined sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.84, 0.86, 6.0, 0.19, and 32, respectively. The AUROC was 0.92. The quiescent point of hierarchical summary of receiver operating characteristic (HSROC) was 3.463. Notably, the images of 12 studies were acquired by T1-weighted MRI alone, and those of the other 6 were gathered by non-T1-weighted MRI alone. Conclusion Overall, deep learning of MRI for the diagnosis of AD and MCI showed good sensitivity and specificity and contributed to improving diagnostic accuracy. Alzheimers Alzheimer s (AD (MCI neurology interpretation AI (AI (MRI approach unbiased insights metaanalysis meta models PubMed Embase MetaAnalyses Meta Analyses PRISMA (PRISMA guidelines Subsequently QUADAS2 QUADAS 2 QUADAS- checklist measures ratios (AUROC analyzed T1weighted Tweighted T1 weighted T nonT1weighted nonTweighted non 1 identified 0.6506. 06506 0 6506 -0.6506 Metaanalysis 084 84 0.84 086 86 0.86 60 6.0 019 19 0.19 32 respectively 092 92 0.92 HSROC (HSROC 3463 3 463 3.463 Notably alone Overall nonT 0.6506 0650 650 -0.650 08 8 0.8 6. 01 0.1 09 9 0.9 346 46 3.46 0.650 065 65 -0.65 0. 34 4 3.4 0.65 06 -0.6 3. 0.6 -0. -0 -

Resumo Antecedentes Pacientes com doença grave por coronavírus-19 (COVID-19) podem necessitar do uso de ventilação mecânica (VM) invasiva por um período prolongado. Parâmetros agressivos de VM têm sido associados a alterações na pressão intracraniana (PIC) em pacientes com doenças intracranianas agudas. Elevações significativas da PIC podem comprometer a complacência intracraniana (CIC) e a hemodinâmica cerebrovascular (HVC). No entanto, os efeitos desses parâmetros em indivíduos sem doenças neurológicas ainda não foram sistematicamente avaliados. Objetivo Avaliar a CIC em pacientes em VM com COVID-19 comparados com outros diagnósticos, para melhor caracterizar os efeitos da VM e COVID-19 sobre a CIC. Também foi feita a comparação entre a CIC em pacientes com COVID-19 sem VM e voluntários saudáveis, para avaliar o efeito isolado da COVID-19 sobre a ICC. Métodos Trata-se de um estudo exploratório, observacional com amostra por conveniência. A CIC foi avaliada com um dispositivo não invasivo de monitoramento da PIC. A relação P2/P1 foi calculada dividindo-se a amplitude desses dois pontos, sendo definida como "anormal" quando P2 > P1. A análise estatística foi realizada usando um modelo linear misto com efeitos aleatórios para comparar a relação P2/P1 nos quatro grupos no primeiro dia de monitoramento. Resultados Uma amostra de conveniência com 78 voluntários (15 COVID-19 em VM, 15 sem COVID-19 em VM, 24 com COVID em respiração espontânea e 24 saudáveis) foram prospectivamente incluídos. Não houve diferença nas razões P2/P1 entre pacientes em VM com e sem COVID-19, nem entre pacientes sem VM com COVID-19 ou saudáveis. No entanto, a relação P2/P1 foi maior em pacientes com COVID-19 com uso de VM do que naqueles sem. Conclusão Os dados dessa análise exploratória sugerem que a COVID-19 não prejudica a CIC. coronavírus19 coronavírus 19 coronavírus-1 COVID19 (COVID-19 (VM prolongado (PIC agudas (CIC HVC. HVC . (HVC) entanto avaliados COVID-1 diagnósticos saudáveis ICC Tratase Trata se exploratório P2P1 PP P1 P P2/P dividindose dividindo pontos anormal "anormal 7 (1 1 2 incluídos COVID19, 19, coronavírus1 coronavírus- COVID1 (COVID-1 (HVC COVID- P2P ( (COVID- (COVID

Abstract Background Patients with severe coronavirus disease-19 (COVID-19) may require the use of invasive mechanical ventilation (MV) for prolonged periods. Aggressive MV parameters have been associated with changes in intracranial pressure (ICP) in patients with acute intracranial disorders. Significant ICP elevation could compromise intracranial compliance (ICC) and cerebrovascular hemodynamics (CVH). However, the effects of these parameters in individuals without neurological disorders have not yet been evaluated. Objective To evaluate ICC in patients on MV with COVID-19 infection compared to other diagnoses, to better characterize the effects of MV and COVID-19 upon ICC. We also compared between the ICC in patients with COVID-19 who did not require MV and healthy volunteers, to assess the isolated effect of COVID-19 upon ICC. Methods This was an exploratory, observational study with a convenience sample. The ICC was evaluated with a noninvasive ICP monitoring device. The P2/P1 ratio was calculated by dividing the amplitude of these two points, being defined as "abnormal" when P2 > P1. The statistical analysis was performed using a mixed linear model with random effects to compare the P2/P1 ratio in all four groups on the first monitoring day. Results A convenience sample of 78 subjects (15 MV-COVID-19, 15 MV non-COVID-19, 24 non-MV-COVID-19, and 24 healthy participants) was prospectively enrolled. There was no difference in P2/P1 ratios between MV patients with and without COVID-19, nor between non-MV patients with COVID-19 and healthy volunteers. However, the P2/P1 ratio was higher in COVID-19 patients with MV use than in those without it. Conclusion This exploratory analysis suggests that COVID-19 does not impair ICC. disease19 disease 19 disease-1 COVID19 COVID (COVID-19 (MV periods (ICP (ICC CVH. CVH . (CVH) However COVID-1 diagnoses volunteers device P2P1 PP P1 P P2/P points abnormal "abnormal day 7 (1 MVCOVID19, MVCOVID19 MVCOVID 19, MV-COVID-19 1 nonCOVID19, nonCOVID19 nonCOVID non non-COVID-19 2 nonMVCOVID19, nonMVCOVID19 nonMVCOVID non-MV-COVID-19 participants enrolled COVID19, nonMV it disease1 disease- COVID1 (COVID-1 (CVH COVID- P2P ( MVCOVID1 MV-COVID-1 nonCOVID1 non-COVID-1 nonMVCOVID1 non-MV-COVID-1 (COVID- MV-COVID- non-COVID- non-MV-COVID- (COVID MV-COVID non-COVID non-MV-COVID