The new era of artificial intelligence in neuroradiology: current research and promising tools.

Radiology has a number of characteristics that make it an especially suitable medical discipline for early artificial intelligence (AI) adoption. These include having a well-established digital workflow, standardized protocols for image storage, and numerous well-defined interpretive activities. The more than 200 commercial radiologic AI-based products recently approved by the Food and Drug Administration (FDA) to assist radiologists in a number of narrow image-analysis tasks such as image enhancement, workflow triage, and quantification, corroborate this observation. However, in order to leverage AI to boost efficacy and efficiency, and to overcome substantial obstacles to widespread successful clinical use of these products, radiologists should become familiarized with the emerging applications in their particular areas of expertise. In light of this, in this article we survey the existing literature on the application of AI-based techniques in neuroradiology, focusing on conditions such as vascular diseases, epilepsy, and demyelinating and neurodegenerative conditions. We also introduce some of the algorithms behind the applications, briefly discuss a few of the challenges of generalization in the use of AI models in neuroradiology, and skate over the most relevant commercially available solutions adopted in clinical practice. If well designed, AI algorithms have the potential to radically improve radiology, strengthening image analysis, enhancing the value of quantitative imaging techniques, and mitigating diagnostic errors.

A radiologia tem uma série de características que a torna uma disciplina médica especialmente adequada à adoção precoce da inteligência artificial (IA), incluindo um fluxo de trabalho digital bem estabelecido, protocolos padronizados para armazenamento de imagens e inúmeras atividades interpretativas bem definidas. Tal adequação é corroborada pelos mais de 200 produtos radiológicos comerciais baseados em IA recentemente aprovados pelo Food and Drug Administration (FDA) para auxiliar os radiologistas em uma série de tarefas restritas de análise de imagens, como quantificação, triagem de fluxo de trabalho e aprimoramento da qualidade das imagens. Entretanto, para o aumento da eficácia e eficiência da IA, além de uma utilização clínica bem-sucedida dos produtos que utilizam essa tecnologia, os radiologistas devem estar atualizados com as aplicações em suas áreas específicas de atuação. Assim, neste artigo, pesquisamos na literatura existente aplicações baseadas em IA em neurorradiologia, mais especificamente em condições como doenças vasculares, epilepsia, condições desmielinizantes e neurodegenerativas. Também abordamos os principais algoritmos por trás de tais aplicações, discutimos alguns dos desafios na generalização no uso desses modelos e introduzimos as soluções comercialmente disponíveis mais relevantes adotadas na prática clínica. Se cautelosamente desenvolvidos, os algoritmos de IA têm o potencial de melhorar radicalmente a radiologia, aperfeiçoando a análise de imagens, aumentando o valor das técnicas de imagem quantitativas e mitigando erros de diagnóstico.

T1/T2-weighted ratio: A feasible MRI biomarker in multiple sclerosis.

T1/T2-weighted ratio is a novel magnetic resonance imaging (MRI) biomarker based on conventional sequences, related to microstructural integrity and with increasing use in multiple sclerosis (MS) research. Different from other advanced MRI techniques, this method has the advantage of being based on routinely acquired MRI sequences, a feature that enables analysis of retrospective cohorts with considerable clinical value. This article provides an overview of this method, describing the previous cross-sectional and longitudinal findings in the main MS clinical phenotypes and in different brain tissues: focal white matter (WM) lesions, normal-appearing white matter (NAWM), cortical gray matter (GM), and deep normal-appearing gray matter (NAGM). We also discuss the clinical associations, possible reasons for conflicting results, correlations with other MRI-based measures, and histopathological associations. We highlight the limitations of the biomarker itself and the methodology of each study. Finally, we update the reader on its potential use as an imaging biomarker in research.

Misdiagnosis in multiple sclerosis in a Brazilian reference center: Clinical, radiological, laboratory profile and failures in the diagnostic process-Cohort study.

BACKGROUND: Multiple sclerosis misdiagnosis remains a problem despite the well-validated McDonald 2017. For proper evaluation of errors in the diagnostic process that lead to misdiagnosis, it is adequate to incorporate patients who are already under regular follow-up at reference centers of demyelinating diseases. OBJECTIVES: To evaluate multiple sclerosis misdiagnosis in patients who are on follow-up at a reference center of demyelinating diseases in Brazil. METHODS: We designed an observational study including patients in regular follow-up, who were diagnosed with multiple sclerosis at our specialized outpatient clinic in the Hospital of Clinics in the University of Sao Paulo, from 1996 to 2021, and were reassessed for misdiagnosis in 2022. We evaluated demographic information, clinical profile, and complementary exams and classified participants as "established multiple sclerosis," "non-multiple sclerosis, diagnosed," and "non-multiple sclerosis, undiagnosed." Failures in the diagnostic process were assessed by the modified Diagnostic Error Evaluation and Research tool. RESULTS: A total of 201 patients were included. After analysis, 191/201 (95.02%) participants were confirmed as "established multiple sclerosis," 5/201 (2.49%) were defined as "non-multiple sclerosis, diagnosed," and 5/201 (2.49%) were defined as "non-multiple sclerosis, undiagnosed." CONCLUSIONS: Multiple sclerosis misdiagnosis persists in reference centers, emphasizing the need for careful interpretation of clinical findings to prevent errors.

AQP4-IgG NMOSD, MOGAD, and double-seronegative NMOSD: is it possible to depict the antibody subtype using magnetic resonance imaging?

BACKGROUND: There is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands. OBJECTIVE: To investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients. METHODS: A cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images. RESULTS: In total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003). CONCLUSION: The pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis.

ANTECEDENTES: Há sobreposição clínica e radiológica entre as doenças desmielinizantes. No entanto, seus mecanismos fisiopatológicos são diferentes e apresentam prognósticos e demandas de tratamento distintos. OBJETIVO: Investigar as características de imagens de RM dos pacientes com doença associada à glicoproteína de oligodendrócito de mielina (MOGAD), a doenças do espectro da neuromielite óptica positivas para antiaquaporina-4 imunoglobulina G (AQP4-IgG NMOSD), e pacientes duplamente soronegativos. MéTODOS: Estudo retrospectivo e transversal para analisar as características e frequência das lesões do sistema nervoso central (SNC). Dois neurorradiologistas avaliaram consensualmente as imagens do cérebro, das órbitas e da medula espinhal. RESULTADOS: Ao todo, foram incluídos 68 pacientes(25 com AQP4-IgG NMOSD, 28 com MOGAD e 15 duplo-soronegativos). Há diferenças na apresentação clínica entre os grupos. O grupo MOGAD demonstrou menor frequência de comprometimento do cérebro (39.2%) comparado com o AQP4-IgG NMOSD (p = 0.002), com predomínio da distribuição das lesões nas regiões subcortical/justacortical, mesencéfalo, pedúnculos cerebelares médios e cerebelo. O grupo duplo-soronegativo demonstrou maior frequência de comprometimento do cérebro (80%), com lesões de maiores dimensões e com morfologia tumefeita, além de neurite óptica com maior extensão (p = 0.006). O grupo AQP4-IgG NMOSD demonstrou neurite óptica com predomínio na região óptico-quiasmática e as lesões encefálicas acometeram predominantemente as regiões hipotalâmica e área postrema (MOGAD versus AQP4-IgG NMOSD p = 0.013). Além disso, foram observadas mais lesões na medula espinhal (78.3%) e a presença da "bright spotty lesion" foi um achado primordial para a sua diferenciação com os pacientes MOGAD (p = 0.003). CONCLUSãO: A análise pormenorizada das características das lesões por RM dos pacientes com doenças desmielinizantes imunomediadas fornece informações fundamentais que auxiliam os médicos no diagnóstico diferencial em um momento oportuno.

AQP4-IgG NMOSD, MOGAD, and double-seronegative NMOSD: is it possible to depict the antibody subtype using magnetic resonance imaging? / NMOSD AQP4-IgG, MOGAD e NMOSD duplo soronegativo: é possível caracterizar o tipo de anticorpo pela ressonância magnética?

Abstract Background There is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands. Objective To investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients. Methods A cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images. Results In total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003). Conclusion The pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis.

Resumo Antecedentes Há sobreposição clínica e radiológica entre as doenças desmielinizantes. No entanto, seus mecanismos fisiopatológicos são diferentes e apresentam prognósticos e demandas de tratamento distintos. Objetivo Investigar as características de imagens de RM dos pacientes com doença associada à glicoproteína de oligodendrócito de mielina (MOGAD), a doenças do espectro da neuromielite óptica positivas para antiaquaporina-4 imunoglobulina G (AQP4-IgG NMOSD), e pacientes duplamente soronegativos. Métodos Estudo retrospectivo e transversal para analisar as características e frequência das lesões do sistema nervoso central (SNC). Dois neurorradiologistas avaliaram consensualmente as imagens do cérebro, das órbitas e da medula espinhal. Resultados Ao todo, foram incluídos 68 pacientes(25 com AQP4-IgG NMOSD, 28 com MOGAD e 15 duplo-soronegativos). Há diferenças na apresentação clínica entre os grupos. O grupo MOGAD demonstrou menor frequência de comprometimento do cérebro (39.2%) comparado com o AQP4-IgG NMOSD (p = 0.002), com predomínio da distribuição das lesões nas regiões subcortical/justacortical, mesencéfalo, pedúnculos cerebelares médios e cerebelo. O grupo duplo-soronegativo demonstrou maior frequência de comprometimento do cérebro (80%), com lesões de maiores dimensões e com morfologia tumefeita, além de neurite óptica com maior extensão (p = 0.006). O grupo AQP4-IgG NMOSD demonstrou neurite óptica com predomínio na região óptico-quiasmática e as lesões encefálicas acometeram predominantemente as regiões hipotalâmica e área postrema (MOGAD versus AQP4-IgG NMOSD p = 0.013). Além disso, foram observadas mais lesões na medula espinhal (78.3%) e a presença da "bright spotty lesion" foi um achado primordial para a sua diferenciação com os pacientes MOGAD (p = 0.003). Conclusão A análise pormenorizada das características das lesões por RM dos pacientes com doenças desmielinizantes imunomediadas fornece informações fundamentais que auxiliam os médicos no diagnóstico diferencial em um momento oportuno.

Neuromyelitis optica spectrum disorders: a review with a focus on children and adolescents.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, ∼ 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population.

O espectro da neuromielite óptica (ENMO) é uma rara e grave doença inflamatória do sistema nervoso central (SNC), fortemente associada ao anticorpo anti-aquaporina 4 (AQP4-IgG) e que afeta preferencialmente mulheres jovens de etnias não-caucasianas. No entanto, aproximadamente de 5 a 10% de todos os casos se iniciam na infância. Crianças e adolescentes compartilham as mesmas características clínicas, radiológicas e laboratoriais dos adultos. Além disso, o mesmo critério diagnóstico de ENMO é aplicado para pacientes com início na infância. No entanto, dados da população pediátrica são escassos. Em pacientes pediátricos soronegativos, existe uma alta frequência de positividade ao anticorpo contra a glicoproteína na mielina do oligodendrócito (MOG-IgG), indicando outra patologia; porém, a distinção clínica entre as duas doenças é desafiadora. Três medicações (eculizumabe, inebilizumabe e satralizumabe) foram recentemente aprovadas para pacientes adultos com AQP4-IgG. Apenas um dos ensaios pivotais do satralizumabe recrutou adolescentes. Novos ensaios clínicos em pacientes pediátricos com ENMO são necessários para avaliar a segurança e eficácia destas drogas nesta população.

Neuromyelitis optica spectrum disorders: a review with a focus on children and adolescents / Espectro da neuromielite óptica: uma revisão com ênfase em crianças e adolescentes

Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, ~ 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population.

Resumo O espectro da neuromielite óptica (ENMO) é uma rara e grave doença inflamatória do sistema nervoso central (SNC), fortemente associada ao anticorpo anti-aquaporina 4 (AQP4-IgG) e que afeta preferencialmente mulheres jovens de etnias não-caucasianas. No entanto, aproximadamente de 5 a 10% de todos os casos se iniciam na infância. Crianças e adolescentes compartilham as mesmas características clínicas, radiológicas e laboratoriais dos adultos. Além disso, o mesmo critério diagnóstico de ENMO é aplicado para pacientes com início na infância. No entanto, dados da população pediátrica são escassos. Em pacientes pediátricos soronegativos, existe uma alta frequência de positividade ao anticorpo contra a glicoproteína na mielina do oligodendrócito (MOG-IgG), indicando outra patologia; porém, a distinção clínica entre as duas doenças é desafiadora. Três medicações (eculizumabe, inebilizumabe e satralizumabe) foram recentemente aprovadas para pacientes adultos com AQP4-IgG. Apenas um dos ensaios pivotais do satralizumabe recrutou adolescentes. Novos ensaios clínicos em pacientes pediátricos com ENMO são necessários para avaliar a segurança e eficácia destas drogas nesta população.

Asymptomatic MRI lesions in pediatric-onset AQP4-IgG positive NMOSD.

BACKGROUND AND PURPOSE: Around 5% of all Neuromyelitis Optica Spectrum Disorders (NMOSD) cases start before 18 years of age. Clinical and radiological manifestations of AQP4-IgG positive NMOSD were revised in 2015, and the importance of neuroimaging in the diagnosis is well recognized. Neuroimaging findings in pediatric-onset NMOSD were scarcely described, and longitudinal evaluation of NMOSD lesions was only accessed in a few adult-onset cohorts. METHODS: This study evaluated brain, spinal cord, and optic nerve MRI of sixteen pediatric-onset AQP4-IgG positive NMOSD through a qualitative evaluation of lesion evolution. Lesions were classified as symptomatic or asymptomatic in acute or chronic phase (> 30 days from last attack) MRI. RESULTS: Seventy MRI scans and 54 subsequent exams were evaluated. Most NMOSD lesions (74.5%) reduced, remained stable, or developed atrophy/cavitation. New brain lesions or enlargement of existing brain lesions were found in two patients (12.5%) without any clinical symptom and in five patients (31.2%) in the course of an attack from other topography (optic neuritis or acute myelitis). One patient (6.3%) presented an asymptomatic spinal cord lesion irrespective of clinical manifestation. No asymptomatic lesion was described in optic nerve MRI. In acute phase exams, longitudinally extensive transverse myelitis (13/19 vs 8/24; p = 0.033), cervical myelitis (15/19 vs 10/24, p = 0.028), lumbar myelitis (5/19 vs 0/24; p = 0.012), and a higher number of segments [median 8 (range 4-17) vs 3.5 (range 1-14); p = 0.003] were affected. CONCLUSIONS: Asymptomatic brain and spinal cord lesions can occur in pediatric-onset NMOSD, especially in the course of acute optic neuritis or myelitis. More longitudinal studies are necessary to guide recommendations on neuroimaging frequency in pediatric patients with AQP4-IgG NMOSD.

Nighttime Sleep Characteristics and White Matter Integrity in Young Adults.

Purpose: Sleep is essential for life and plays a key role for optimal physiology, brain functioning, and health. Evidence suggests a relation between sleep and cerebral white matter integrity. Human studies report that sleep duration shows a U-shaped association with brain functioning. We hypothesized that participants with longer or shorter sleep time in the nighttime period show altered microstructural white matter integrity. Participants and Methods: Seventy-three young adult participants were evaluated. Sleep-wake cycle parameters were assessed objectively using actigraphy. Diffusion tensor imaging studies were performed to assess white matter integrity using fractional anisotropy and mean, axial, and radial diffusivities. Relations between white matter microstructure indexes and sleep parameters were investigated through tract-based spatial statistics. Participants were grouped according to their nocturnal total sleep time: 27 in the Reference sleep group (6.5-8.0 h), 23 in the Short sleep group (<6.5 h) and 23 in the Long sleep group (>8.0 h). Results: Compared with the Reference sleep group, participants in the Long sleep group showed lower fractional anisotropy (p < 0.05) and higher radial diffusivity (p < 0.05) values in white matter tracts linked to sleep regulation (corona radiata, body of the corpus callosum, superior longitudinal fasciculus, and anterior thalamic radiation). Conclusion: This pattern of reduced fractional anisotropy and increased radial diffusivity in the Long sleep group indicates an association between sleep duration and lower integrity of myelin sheaths. Because myelin is continuously remodeled in the brain, nighttime sleep characteristics appear to be a key player for its quality and maintenance.

Mechanisms of myelin repair, MRI techniques and therapeutic opportunities in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The remyelination process requires the activation, migration and differentiation of oligodendrocyte progenitor cells (OPC) in demyelinated areas. The metabolic dysfunction in chronic demyelinating lesions impairs the activation of OPCs, the myelin debris clearance by microglia decreases with age, along with diminished secretion of factors promoting OPC differentiation. Conventional magnetic resonance imaging (MRI) sequences have limited ability to differentiate unmyelinated and remyelinated lesions. Advanced MRI sequences based on magnetization transfer ratio (MTR), myelin water fraction (MWF) and diffusion tensor imaging (DTI) have been used to evaluate remyelination in clinical trials. More recently, the q-space myelin map (qMM) has been used on experimental and exploratory clinical studies. The improvement of myelin-specific MRI sequences with high reliability and standardization among centers will allow a more accurate evaluation of new therapies to improve remyelination. These new remyelination promoting treatments alone or in combination with current options may reduce the risk of long-term disability in MS.

Reduced quality of life in a pediatric-onset Neuromyelitis optica spectrum disorders cohort.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is a severe condition associated with high disability and low quality of life (QoL) in adults. Since this evaluation had been rarely perfomed in children, this study aimed to describe QoL in pediatric-onset NMOSD with positive aquaporin4 antibody (AQP4-IgG) patients. METHODS: This was a cross-section evaluation of patients and parents' proxy QoL from individuals enrolled in a longitudinal cohort of AQP4-IgG positive NMOSD with onset ≤ 18 years of age. RESULTS: Eighteen patients were included, sixteen girls. The mean (SD) age at disease onset was 11.5 (3.6) years. Eleven of patients experienced disability during a mean (SD) of 8.3 (5.3) years of follow-up. NMOSD had impact in QoL in 10 patients, being associated with higher EDSS and poor academic performance at last follow-up. Results from the PedsQL inventory for 13 patients and 10 parents disclosed low QoL specially in emotional functioning. CONCLUSION: This study indicates impaired quality of life, high disability and high impact of the disease in daily life of adolescents and young adults with pediatric onset NMOSD.

Assessing cognitive control and the reward system in overweight young adults using sensitivity to incentives and white matter integrity.

Cognitive control and incentive sensitivity are related to overeating and obesity. Optimal white matter integrity is relevant for an efficient interaction among reward-related brain regions. However, its relationship with sensitivity to incentives remains controversial. The aim of this study was to assess the incentive sensitivity and its relationship to white matter integrity in normal-weight and overweight groups. Seventy-six young adults participated in this study: 31 were normal-weight (body mass index [BMI] 18.5 to < 25.0 kg/m2, 14 females) and 45 were overweight (BMI ≥ 25.0 kg/m2, 22 females). Incentive sensitivity was assessed using an antisaccade task that evaluates the effect of incentives (neutral, reward, and loss avoidance) on cognitive control performance. Diffusion tensor imaging studies were performed to assess white matter integrity. The relationship between white matter microstructure and incentive sensitivity was investigated through tract-based spatial statistics. Behavioral antisaccade results showed that normal-weight participants presented higher accuracy (78.0 vs. 66.7%, p = 0.01) for loss avoidance incentive compared to overweight participants. Diffusion tensor imaging analysis revealed a positive relationship between fractional anisotropy and loss avoidance accuracy in the normal-weight group (p < 0.05). No relationship reached significance in the overweight group. These results support the hypothesis that white matter integrity is relevant for performance in an incentivized antisaccade task.

Longitudinal analysis of verbal episodic memory in patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: A 4.5-year follow-up study was conducted to characterize baseline verbal episodic memory (VEM) and its behavior and to assess the effects of relapsing-remitting multiple sclerosis (RRMS) on this domain. METHODS: Twenty-nine patients with RRMS underwent two neuropsychological assessments performed an average of 4.5 years apart. Twenty-six control participants underwent a single neuropsychological assessment. A significance level of p < 0.005 was adopted to denote a significant difference between the groups on the Mann Whitney and Wilcoxon paired statistical analyses. RESULTS: No statistical difference was found in the results of the VEM tests between the first and second neuropsychological assessments of the patients. However, a statistical difference was evident between the patient and control groups in the results of the VEM tests. CONCLUSION: The patient group showed changes in the VEM relative to the control group. After approximately 4.5 years of disease, the patient performance on the VEM stabilized or improved.

Longitudinal analysis of verbal episodic memory in patients with relapsing-remitting multiple sclerosis / Análise longitudinal da memória episódica verbal em pacientes com esclerose múltipla remitente-recorrente

ABSTRACT Objective: A 4.5-year follow-up study was conducted to characterize baseline verbal episodic memory (VEM) and its behavior and to assess the effects of relapsing-remitting multiple sclerosis (RRMS) on this domain. Methods: Twenty-nine patients with RRMS underwent two neuropsychological assessments performed an average of 4.5 years apart. Twenty-six control participants underwent a single neuropsychological assessment. A significance level of p < 0.005 was adopted to denote a significant difference between the groups on the Mann Whitney and Wilcoxon paired statistical analyses. Results: No statistical difference was found in the results of the VEM tests between the first and second neuropsychological assessments of the patients. However, a statistical difference was evident between the patient and control groups in the results of the VEM tests. Conclusion: The patient group showed changes in the VEM relative to the control group. After approximately 4.5 years of disease, the patient performance on the VEM stabilized or improved.

RESUMO Objetivo: Neste estudo, propomos a caracterização da Memória Episódica Verbal (MEV) basal e o seu comportamento após o período de 4,5 anos de doença, a fim de avaliar o efeito da EMRR neste domínio. Métodos: Vinte e nove pacientes com EMRR foram submetidos a duas avaliações neuropsicológicas realizadas entre um intervalo de tempo médio de 4,5 anos. Vinte e seis controles foram submetidos à avaliação neuropsicológica única. Considerou-se nível de significância p <0,005 para delinear diferença significante entre os grupos nas análises estatísticas Mann Whitney e Wilcoxon pareado. Resultados: Não houve diferença estatística nos resultados dos testes de MEV entre a primeira e segunda avaliação neuropsicológica realizada pelos pacientes. Houve discrepância estatística nos resultados dos testes de MEV entre o grupo dos pacientes e controles. Conclusão: O grupo de pacientes apresentou alterações de MEV quando comparado aos controles. Após 4,5 anos aproximadamente os pacientes estabilizaram ou melhoraram seu desempenho em MEV.

The protective effects of high-education levels on cognition in different stages of multiple sclerosis.

BACKGROUND: Low-education attainment is associated with worse cognitive performance in multiple sclerosis (MS) patients, and possibly with a lower cognitive reserve and/or increased inflammatory activity. Cognitive reserve refers to the capability of a source of intellectual enrichment in attenuating a negative effect of a disease-related factor; while the inflammatory activity is often related to T2-lesion load (T2-LL) increase. OBJECTIVE: To disentangle the effects of cognitive reserve and an increased T2-LL in MS-patients with low-education levels. METHODS: The study included 136 MS patients and 65 healthy-controls, divided in low-education (12 years or less of school education without obtaining any technical superior degree) and high-education (more than 12 years of school education with technical or superior degree) groups. An extensive battery of neuropsychological tests was applied examining intelligence quotient and six cognitive domains. Test results were z-scored and subjects with z-scores ≤ -1.5 in two or more domains were considered cognitively impaired. To test the factors associated with worse cognitive performance, regression models were applied using average cognition as target; education level, Expanded Disability Status Scale (EDSS), T2-LL, disease duration, age of disease onset, age and gender as predictors. We also tested the correlation between T2-LL and cognition in the groups. To investigate the role of education level as a source of intellectual enrichment/cognitive reserve in different stages of MS, we sub-divided the MS patients in three groups according to the disease duration (less than 5 years, between 5 and 10 years and more than 10 years). RESULTS: Worse average cognition was associated with low-education level, higher T2-LL and male gender. A higher frequency of cognitively impaired patients was observed in MS patients with low-education level, in all stages of the disease. In patients with a disease duration shorter than five years, there was a lower correlation between worse average cognition and T2-LL in the high-education level group, compared to the patients with low-education level; in MS patients with longer disease duration, we observed a stronger correlation between lesion burden and cognitive impairment in both groups. CONCLUSION: Education attainment is a source of intellectual enrichment and can enhance the cognitive reserve in MS patients. The protective effect of a high-education level was stronger in patients with less than five years of disease, suggesting a stronger role of cognitive reserve in short-term disease. In long-term disease we observed a greater impact of increased inflammatory activity on cognition.

Causes, effects and connectivity changes in MS-related cognitive decline / Causas, efeitos e alterações de conectividade no declínio relacionado à esclerose múltipla

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.

Declínio cognitivo é uma situação frequente mas ainda pouco compreendida na esclerose múltipla (EM). Atualmente, não são totalmente conhecidos os principais determinantes da disfunção cognitiva na doença, tendo sido apontadas fortes associações entre danos à substância cinzenta e declínio cognitivo. Estudos multiparamétricos mostram que os diferentes fatores patológicos da EM participam como causas interdependentes de atrofia da substância cinzenta e dano cerebral permanente. Eles são associados a efeitos funcionais intermediários (detectados por RM funcional) representando um equilíbrio entre desconexão cerebral e alterações (mal) adaptativas. Portanto, uma abordagem de imagem mais abrangente é necessária, com o objetivo de encontrar associações entre alterações estruturais e a organização funcional cerebral. Para melhor compreender o declínio cognitivo na EM, esse artigo propões uma revisão dos principais métodos de imagem por RM e suas correlações com função cognitiva, discutindo as múltiplas faces patológicas da EM e seu impacto na eficiência das redes neurais.

Causes, effects and connectivity changes in MS-related cognitive decline.

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.

Declínio cognitivo é uma situação frequente mas ainda pouco compreendida na esclerose múltipla (EM). Atualmente, não são totalmente conhecidos os principais determinantes da disfunção cognitiva na doença, tendo sido apontadas fortes associações entre danos à substância cinzenta e declínio cognitivo. Estudos multiparamétricos mostram que os diferentes fatores patológicos da EM participam como causas interdependentes de atrofia da substância cinzenta e dano cerebral permanente. Eles são associados a efeitos funcionais intermediários (detectados por RM funcional) representando um equilíbrio entre desconexão cerebral e alterações (mal) adaptativas. Portanto, uma abordagem de imagem mais abrangente é necessária, com o objetivo de encontrar associações entre alterações estruturais e a organização funcional cerebral. Para melhor compreender o declínio cognitivo na EM, esse artigo propões uma revisão dos principais métodos de imagem por RM e suas correlações com função cognitiva, discutindo as múltiplas faces patológicas da EM e seu impacto na eficiência das redes neurais.

Toxic leukoencephalopathies, including drug, medication, environmental, and radiation-induced encephalopathic syndromes.

Toxic leukoencephalopathies can be secondary to the exposure to a wide variety of exogenous agents, including cranial irradiation, chemotherapy, antiepileptic agents, drugs of abuse, and environmental toxins. There is no typical clinical picture, and patients can present with a wide array of signs and symptoms. Involvement of white matter is a key finding in this scenario, although in some circumstances other high metabolic areas of the central nervous system can also be affected. Magnetic resonance (MR) imaging usually discloses bilateral and symmetric white matter areas of hyperintense signal on T2-weighted and fluid-attenuated inversion recovery images, and signs of restricted diffusion are associated in the acute stage. In most cases, the changes are reversible, especially with prompt recognition of the disease and discontinuation of the noxious agent. Either the MR or clinical features may be similar to several nontoxic entities, such as demyelinating diseases, leukodystrophies, hepatic encephalopathy, vascular disease, hypoxic-ischemic states, and others. A high index of suspicion should be maintained whenever a patient presents recent onset of neurologic deficit, searching the risk of exposure to a neurotoxic agent. Getting to know the most frequent MR appearances and mechanisms of action of causative agents may help to make an early diagnosis and begin therapy, improving outcome. In this review, some of the most important causes of leukoencephalopathies are presented; as well as other 2 related conditions: strokelike migraine attacks after radiation therapy syndrome and reversible splenial lesions.

Segmented corpus callosum diffusivity correlates with the Expanded Disability Status Scale score in the early stages of relapsing-remitting multiple sclerosis.

OBJECTIVE: The aim of this study was to characterize the microscopic damage to the corpus callosum in relapsing-remitting multiple sclerosis (RRMS) with diffusion tensor imaging and to investigate the correlation of this damage with disability. The diffusion tensor imaging parameters of fractional anisotropy and mean diffusivity provide information about the integrity of cell membranes, offering two more specific indices, namely the axial and radial diffusivities, which are useful for discriminating axon loss from demyelination. METHOD: Brain magnetic resonance imaging exams of 30 relapsing-remitting multiple sclerosis patients and 30 age- and sex-matched healthy controls were acquired in a 3T scanner. The axial diffusivities, radial diffusivities, fractional anisotropy, and mean diffusivity of five segments of the corpus callosum, correlated to the Expanded Disability Status Scale score, were obtained. RESULTS: All corpus callosum segments showed increased radial diffusivities and mean diffusivity, as well as decreased fractional anisotropy, in the relapsing-remitting multiple sclerosis group. The axial diffusivity was increased in the posterior midbody and splenium. The Expanded Disability Status Scale scores correlated more strongly with axial diffusivities and mean diffusivity, with an isolated correlation with radial diffusivities in the posterior midbody of the corpus callosum. There was no significant correlation with lesion loads. CONCLUSION: Neurological dysfunction in relapsing-remitting multiple sclerosis can be influenced by commissural disconnection, and the diffusion indices of diffusion tensor imaging are potential biomarkers of disability that can be assessed during follow-up.