Impairment of daily occupations in multiple sclerosis: analysis of neuroimaging, general and social cognition, and reserve.

BACKGROUND: Multiple Sclerosis (MS) can impact performance of daily occupations in both relapsing-remitting (RRMS) and secondary-progressive (SPMS) clinical courses. Work force participation decreases with advancing physical disability but the influence of non-motor factors, neuroimaging, and reserve have been scarcely investigated. We aimed to evaluate MRI, clinical, and cognitive (social and general) factors associated with impairment in different daily occupations and address whether cognitive and brain reserve have a positive impact on the ability to maintain these activities. METHODS: We prospectively enrolled persons with MS (PwMS) who underwent clinical examination (Expanded Disability Status Scale - EDSS; Timed 25-Foot Walk Test - T25FW; and the Nine Hole Peg Test - 9HPT), general neuropsychological assessment (Brief Repeatable Battery of Neuropsychological Tests - BRBN, including the Symbol Digit Modalities Test - SDMT), social cognition evaluation (Reading the Mind in the Eyes Test), cognitive reserve questionnaire, and MRI (FreeSurfer). We also enrolled healthy subjects for comparison as a control group. Daily occupations (employment, money management, and driving abilities) were assessed in all individuals with questionnaires. RESULTS: We included 62 PwMS (32 RRMS and 30 SPMS; mean age 42.8 years; median educational time 12.75 years) and 67 controls (mean age 39.7; median educational time 12.0 years) which were similar regarding demographics, education, and socioeconomic status (p > 0.1). Most PwMS (67.7%) had work-restrictions. They also reported fewer money management and driving abilities than controls (p < 0.001). Work-restriction was associated with physical disability (p = 0.006), SDMT and BRBN performance (p = 0.035 and p = 0.031, respectively), and T2-lesion volume (p = 0.022), with large effect sizes (d > 0.75). After hierarchical linear regression, money management was associated with hand dexterity, general and social cognition, and cognitive reserve (p < 0.03). Variables associated with driving abilities included fatigue, verbal fluency, striatum volume, and brain reserve (p < 0.05). CONCLUSIONS: PwMS have more frequent work-restrictions and impairment in money management and driving abilities compared to controls. Cognitive function, physical disability, and MS-lesion burden are strongly associated with work-restriction. Social cognition can also influence financial capacity. Cognitive and brain reserve can help retain some of these daily occupations.

Are we ready to define cognitive worsening in MS? How different cutoffs detect future cognitive worsening after six years of follow-up.

BACKGROUND: Although cognitive evaluation has been incorporated in recent MS clinical trials, the definition of cognitive progression is not clear and recent data are questioning the 4-point cutoff using the SDMT at the individual level. We aimed to evaluate the behavior of cognitive performance over time using different cutoffs. METHODS: Cognitive performance over six years was analyzed in a cohort of 42 relapsing-remitting MS patients and 30 controls using verbal/visual memory and information processing speed tests. Fixed cutoffs were: 10% and 20% change (all tests) and a 4- and 8-point change (SDMT). The relative cutoff established by regression-based models was a 1SD change. RESULTS: The distributions of "worsening", "stability", and "improvement" showed low concordance rates across the cutoffs (p < 0.001 for most comparisons). Most patients classified with worsening initially using fixed cutoffs had subsequent improvement in all cognitive tests, yielding a low sensitivity to predict later cognitive worsening. Using the relative cutoff, the proportion of patients with subsequent improvement was noticeably smaller. CONCLUSIONS: Fixed cutoffs classify a high proportion of patients with cognitive improvement. Most patients categorized with worsening initially presented subsequent improvement. Instead, the relative cutoff generally had a better performance. These data raise concerns about how we are defining cognitive worsening so far, especially at the individual level.

Diagnosis of Alzheimer's disease: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

Este artigo apresenta o consenso realizado pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia sobre os critérios diagnósticos da Doença de Alzheimer (DA) no Brasil. Foi realizada uma revisão da literatura e dos critérios clínicos e de pesquisa para DA, sendo propostos protocolos para o diagnóstico de DA em níveis de atenção primária, secundária e terciária. Dentro deste cenário clínico, são apresentados os critérios diagnósticos para DA típica e atípica, além de instrumentos de avaliação clínica, cognitiva e funcional; bem como propedêutica complementar com exames laboratoriais e de neuroimagem. A utilização de biomarcadores é também apresentada, tanto para o diagnóstico clínico em situações específicas quanto para pesquisa.

Diagnóstico da doença de Alzheimer: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Diagnosis of Alzheimer's disease: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO Este artigo apresenta o consenso realizado pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia sobre os critérios diagnósticos da Doença de Alzheimer (DA) no Brasil. Foi realizada uma revisão da literatura e dos critérios clínicos e de pesquisa para DA, sendo propostos protocolos para o diagnóstico de DA em níveis de atenção primária, secundária e terciária. Dentro deste cenário clínico, são apresentados os critérios diagnósticos para DA típica e atípica, além de instrumentos de avaliação clínica, cognitiva e funcional; bem como propedêutica complementar com exames laboratoriais e de neuroimagem. A utilização de biomarcadores é também apresentada, tanto para o diagnóstico clínico em situações específicas quanto para pesquisa.

ABSTRACT This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

Neuropsychiatric Symptoms in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease: A 12-Month Follow-Up Study.

Introduction: Neuropsychiatric symptoms in patients with frontotemporal dementia (FTD) are highly prevalent and may complicate clinical managements. Objective: To test whether the Neuropsychiatry Inventory (NPI) could detect change in neuropsychiatric symptoms and caregiver's distress in patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) from baseline to a 12-month follow-up and to investigate possible predictors of change in NPI scores. Methods: The sample consisted of 31 patients diagnosed with bvFTD and 28 patients with AD and their caregivers. The Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination Revised (ACE-R), the INECO Frontal Screening (IFS), the Frontal Assessment Battery (FAB), the Executive Interview (EXIT-25) and the NPI were applied. Descriptive statistics, Mann-Whitney U test, Wilcoxon test, Chi square (χ2) test and Linear Regression Analysis were used. Results: NPI total and caregiver distress scores were statistically higher among bvFTD patients at both assessment points. MMSE, ACE-R scores significantly declined and NPI Total and Distress scores significantly increased in both groups. In the bvFTD group, age was the only independent predictor variable for the NPI total score at follow up. In the AD group, ACE-R and EXIT-25, conjunctively, were associated with the NPI total score at follow up. Conclusions: In 12 months, cognition declined and neuropsychiatric symptoms increased in bvFTD and AD groups. In the AD group only, cognitive impairment was a significant predictor of change in neuropsychiatric symptoms.

Associations between cognitive and clinical disability across MS subtypes: The role of the underlying brain damage.

BACKGROUND: Cognitive impairment (CI) is present in all stages and subtypes of multiple sclerosis (MS). However, the majority of studies examined relapsing-remitting (RRMS) patients, and did not address cognitive phenotyping. Is still not clear whether patients with progressive MS (PMS) have a distinct pattern of CI compared to RRMS. In addition, there is conflicting data regarding the correlation between clinical and cognitive disability. OBJECTIVE: To investigate the differences of CI between PMS and RRMS patients, evaluating cognitive phenotypes. We also aimed to analyze the association between physical and cognitive disability with MRI measures of grey-matter atrophy and lesion burden. METHODS: Thirty patients with PMS and twenty-four with RRMS underwent neurological, neuropsychological (BRB-N, Boston Naming, and Tower of London), and MRI assessments (3T). Brain volume evaluations were performed using FreeSurfer. Principal Components Analysis on neuropsychological yielded six principal cognitive domains. Cognitive deficits were classified according to three categories: no CI, impairment in isolated cognitive domain, or impairment in combined domains. RESULTS: In the overall sample, the most frequently impaired cognitive domains were information processing speed (IPS) and visual memory. PMS patients had a higher prevalence of verbal memory and verbal fluency deficits, and more frequent impairment in combined cognitive domains compared to RRMS individuals. After multivariable regression analysis with clinical variables, EDSS was associated with most cognitive domains. Nevertheless, after including T1-lesion volume in the model, it was the most consistent predictor of cognitive performance. To further analyze the interaction between EDSS and T1-lesions, we performed GLM analysis with EDSS and T1-hypointense lesion volume as covariates, and T1-lesion volume adjusted better the model for verbal memory (p = 0.013), IPS (p = 0.021) and total number of impaired cognitive domains (p = 0.021). CONCLUSIONS: RRMS and PMS patients tend to have a similar neuropsychological profile in general, but the extent of CI was greater in PMS patients. Worse cognitive performance was associated with increased physical disability, but this correlation was no longer significant after controlling for T1-lesion volume, suggesting that the underlying MS pathology might be involved in this relationship. Thalamic and T1-lesion volumes were the most consistent MRI predictors associated with cognitive disability.

Disease Progression in Frontotemporal Dementia and Alzheimer Disease: The Contribution of Staging Scales.

INTRODUCTION: There is a shortage of validated instruments to estimate disease progression in frontotemporal dementia (FTD). OBJECTIVES: To evaluate the ability of the FTD Rating Scale (FTD-FRS) to detect functional and behavioral changes in patients diagnosed with the behavioral variant of FTD (bvFTD), primary progressive aphasia (PPA), and Alzheimer disease (AD) after 12 months of the initial evaluation, compared to the Clinical Dementia Rating scale-frontotemporal lobar degeneration (CDR-FTLD) and the original Clinical Dementia Rating scale (CDR). METHODS: The sample consisted of 70 individuals, aged 40+ years, with at least 2 years of schooling, 31 with the diagnosis of bvFTD, 12 with PPA (8 with semantic variant and 4 with non-fluent variant), and 27 with AD. The FTD-FRS, the CDR, and the 2 additional CDR-FTLD items were completed by a clinician, based on the information provided by the caregiver with frequent contact with the patient. The Addenbrooke Cognitive Examination-Revised was completed by patients. After 12 months, the same protocol was applied. RESULTS: The FTD-FRS, CDR-FTLD, and CDR detected significant decline after 12 months in the 3 clinical groups (exception: FTD-FRS for PPA). The CDR was less sensitive to severe disease stages. CONCLUSIONS: The FTD-FRS and the CDR-FTLD are especially useful tools for dementia staging in AD and in the FTD spectrum.

Exploring the performance of outcome measures in MS for predicting cognitive and clinical progression in the following years.

BACKGROUND: The demand for better outcome measures in multiple sclerosis (MS) management has been increasingly recognized. Nevertheless, the prognostic impacts of available outcome measures for long-term clinical and especially cognitive disability have not been thoroughly investigated. We, therefore, aimed to explore the sustainability and long-term predictive value of outcome measures in MS. METHODS: We studied a cohort of 42 relapsing-remitting MS patients and 30 healthy subjects. Evaluations were performed at baseline and after two (Y2) and six years (Y6), and included neurological and neuropsychological evaluation (BRBN), MRI (3T), and quality of life assessment. Combined clinical and cognitive measures were evaluated, such as minimal and no evidence of disease activity (MEDA and NEDA, respectively). We performed logistic regression with bootstrapping and calculated the diagnostic properties to identify patients who reached six-year clinical and/or cognitive worsening. RESULTS: NEDA status was observed in up to 30.8% of patients at Y2, but only in 5% at Y6, and did not preclude cognitive decline (SDMT and BRBN). The absence of MRI activity and MEDA status at Y2 were associated with less EDSS worsening in the following years but without impact on cognition. The absence of deterioration on combined clinical/cognitive measures at Y2 (e.g., T25W+ 9HPT + BRBN) was associated with better outcomes in the following years (clinical and cognitive), with moderate to large effect sizes. For the identification of clinical worsening at Y6, best accuracies were found for MEDA (70.6%), and clinical worsening (71.4%), but only MEDA remained in the final model after multivariable logistic regression analysis (OR = 6.81, p = 0.017). For combined clinical and cognitive worsening at Y6, only T25W+ 9HPT + BRBN remained in the final model (OR = 8.5, p = 0.017). CONCLUSIONS: Early MS inflammatory disease activity is associated with future clinical disability. Nevertheless, NEDA was difficult to sustain in the long-term and did not preclude cognitive deterioration. Clinical and cognitive measures combined predicted outcomes better than each one isolated. Our data suggest that the evaluation of more than one cognitive domain yields a better predictive outcome measure.

Cognitive trajectories in relapsing-remitting multiple sclerosis: A longitudinal 6-year study.

BACKGROUND: Information concerning longitudinal cognitive trajectories in multiple sclerosis (MS) is relatively scarce. Moreover, it is unclear which factors are associated with cognitive decline and what is the clinical impact of cognitive impairment (CI) in the long run. OBJECTIVE: To investigate cognitive trajectories in relapsing-remitting multiple sclerosis (RRMS) patients, analyzing clinical and magnetic resonance imaging (MRI) predictors of cognitive decline. METHODS: We enrolled 42 patients and 30 controls. They underwent brain MRI and clinical/neuropsychological evaluation at baseline and after 1, 2, and 6 years. We evaluated cognitive domains with principal component analysis and performed multivariable regression analyzing predictors of clinical/cognitive deterioration. We also performed repeated measures analysis to assess whether clinical progression was different according to CI at baseline. RESULTS: A total of 23 (62.2%) patients deteriorated in combined cognitive domains after 6 years, most in processing speed and memory. The number of baseline impaired cognitive domains was strongly associated with 6-year cognitive (R2 = 0.452; p < 0.001) and Expanded Disability Status Scale (EDSS) deterioration (R2 = 0.263; p < 0.001). Patients with baseline CI in combined domains had worse clinical progression. CONCLUSION: Isolated CI tends to become more widespread, affecting memory and processing speed alongside. The extent of baseline CI was the best predictor of both clinical and cognitive deterioration after 6 years.

The Effect of Pelvic Floor Muscle Contraction on Detrusor Overactivity Pressure in Neurogenic and Nonneurogenic Women During Urodynamic Study: A Cross-Sectional Study.

OBJECTIVE: The aims of this study were to investigate whether detrusor overactivity can be influenced by a pelvic floor muscle contraction in multiple sclerosis-associated overactive bladder and idiopathic overactive bladder volunteers and to compare urodynamic findings between the two groups. DESIGN: Eighteen women with multiple sclerosis-associated overactive bladder and 17 women with overactive bladder responded the overactive bladder V8 questionnaire and performed urodynamic study with electromyography of pelvic floor muscle to confirm the presence of a 15-sec pelvic floor muscle contraction during a detrusor overactivity, when present. Variables were the following: overactive bladder-V8 questionnaire, maximum cystometric capacity, volume at first detrusor overactivity, maximum detrusor overactivity amplitude, and percentage of detrusor overactivity pressure reduction. RESULTS: All participants had a reduction in detrusor overactivity pressure when pelvic floor muscle contraction was requested. Multiple sclerosis-associated overactive bladder group showed significant higher detrusor overactivity amplitude than overactive bladder group (P = 0.02). Overactive bladder group had their detrusor overactivity pressure reduced in a greater extent when compared with multiple sclerosis-associated overactive bladder group (P = 0.01). CONCLUSIONS: The results suggest that pelvic floor muscle contraction is able to reduce detrusor overactivity pressure in multiple sclerosis-associated overactive bladder and overactive bladder population.

Clinical and MRI correlates of CSF neurofilament light chain levels in relapsing and progressive MS.

BACKGOUND: A major aim in MS field has been the search for biomarkers that enable accurate detection of neuronal damage. Besides MRI, recent studies have shown that neuroaxonal damage can also be tracked by neurofilament detection. Nevertheless, before widespread implementation, a better understanding of the principal contributors for this biomarker is of paramount importance. Therefore, we analyzed neurofilament light chain (NfL) in relapsing (RMS) and progressive MS (PMS), addressing which MRI and clinical variables are better related to this biomarker. METHODS: Forty-seven MS patients underwent MRI (3T) and cerebrospinal fluid (CSF) sampling. We measured NfL concentrations using ELISA (UmanDiagnostics) and performed multivariable regression analysis to assess the contribution of clinical and MRI metrics to NfL. RESULTS: NfL correlated with previous clinical activity in RMS (p < 0.001). In RMS, NfL also correlated with Gad+ and cortical lesion volumes. However, after multivariable analysis, only cortical lesions and relapses in previous 12 months remained in the final model (R2 = 0.610; p = 0.009 and p = 0.00008, respectively). In PMS, T1-hypointense lesion volume was the only predictor after multivariate analysis (R2 = 0.564; p = 0.012). CONCLUSIONS: CSF NfL levels are increased in RMS and associated with relapses and cortical lesions. Although NfL levels were correlated with Gad+ lesion volume, this association did not persist in multivariable analysis after controlling for previous clinical activity. We encourage controlling for previous clinical activity when testing the association of NfL with MRI. In PMS, the major contributor to NfL was T1-hypointense lesion volume.

Clinical characteristics of 153 Brazilian patients with neuromyelitis optica spectrum disorder (NMOSD).

BACKGROUND: The 2015 criteria for diagnosing neuromyelitis optica spectrum disorder (NMOSD) have encouraged several groups across the world to report on their patients using these criteria. The disease typically manifests with severe relapses of optic neuritis, longitudinally extensive myelitis and/or brainstem syndromes, often leading to severe disability. Some patients are seropositive for antibodies against aquaporin-4 (AQP4), others are positive for anti-myelin oligodendrocyte glycoprotein (MOG), while a few are negative for both biomarkers. The disease is complex, and only now are specific therapeutic clinical trials being carried out. The present study adds to the literature through detailed clinical data from 153 medical records of Brazilian patients. METHODS: Retrospective assessment of medical records from nine specialized units in Brazil. RESULTS: NMOSD was more prevalent in females (4.1:1), who had significantly fewer relapses than males (p = 0.007) but presented similar levels of disability over time. African ancestry was associated with higher levels of disability throughout the disease course (p < 0.001), although the number of relapses was similar to that observed in white patients. Concomitant autoimmune diseases were relatively rare in this population (6.5%). Positivity for anti-AQP4 antibodies was identified in 62% of the patients tested, while 3% presented anti-MOG antibodies. Anti-AQP4 antibodies were not associated to worse disease course. The last medical record showed that six patients had died and 13 were wheelchair-bound. Seventy percent of the patients did not respond to first-line therapy (azathioprine and/or corticosteroids), and five patients continued to relapse even after four different courses of treatment. CONCLUSION: The present study adds to the reports from other countries presenting original data on Brazilian patients diagnosed with NMOSD according to the 2015 criteria.

The Accuracy of INECO Frontal Screening in the Diagnosis of Executive Dysfunction in Frontotemporal Dementia and Alzheimer Disease.

INTRODUCTION: Executive dysfunction is a common symptom in neurodegenerative disorders and is in need of easy-to-apply screening tools that might identify it. The aims of the present study were to examine some of the psychometric characteristics of the Brazilian version of the INECO frontal screening (IFS), and to investigate its accuracy to diagnose executive dysfunction in dementia and its accuracy to differentiate Alzheimer disease (AD) from the behavioral variant of frontotemporal dementia (bvFTD). METHODS: Patients diagnosed with bvFTD (n=18) and AD (n=20), and 15 healthy controls completed a neuropsychological battery, the Neuropsychiatric Inventory, the Cornell Scale for Depression in Dementia, the Clinical Dementia Rating, and the IFS. RESULTS: The IFS had acceptable internal consistency (α=0.714) and was significantly correlated with general cognitive measures and with neuropsychological tests. The IFS had adequate accuracy to differentiate patients with dementia from healthy controls (AUC=0.768, cutoff=19.75, sensitivity=0.80, specificity=0.63), but low accuracy to differentiate bvFTD from AD (AUC=0.594, cutoff=16.75, sensitivity=0.667, specificity=0.600). CONCLUSION: The present study suggested that the IFS may be used to screen for executive dysfunction in dementia. Nonetheless, it should be used with caution in the differential diagnosis between AD and bvFTD.

Apathy and functional disability in behavioral variant frontotemporal dementia.

Background: Behavioral variant frontotemporal dementia (bvFTD) has profound consequences on patients and their families. In this multicenter study, we investigated the contribution of cognitive and neuropsychiatric factors to everyday function at different levels of overall functional impairment. Methods: In a retrospective cross-sectional study, 109 patients with bvFTD from 4 specialist frontotemporal dementia centers (Australia, England, India, and Brazil) were included. The measures administered evaluated everyday function (Disability Assessment for Dementia [DAD]), dementia staging (Clinical Dementia Rating [CDR]), general cognition (Addenbrooke's Cognitive Examination-revised [ACE-R]), and neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI]). Patients were then subdivided according to functional impairment on the DAD into mild, moderate, severe, and very severe subgroups. Three separate multiple linear regression analyses were run, where (1) total DAD, (2) basic activities of daily living (BADL), and (3) instrumental activities of daily living (IADL) scores were dependent variables; ACE-R total score and selected NPI domains (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) were used as independent variables. Age, sex, education, and country of origin were controlled for in the analyses. Results: Cognitive deficits were similar across the mild, moderate, and severe subgroups but significantly worse in the very severe subgroup. NPI domain scores (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) did not differ across the DAD subgroups. In the multiple regression analyses, a model including ACE-R and NPI apathy explained 32.5% of the variance for total DAD scores. For IADL, 35.6% of the variance was explained by the ACE-R only. No model emerged for BADL scores. Conclusions: Cognitive deficits and apathy are key contributors to functional disability in bvFTD but factors underlying impairment in BADLs remain unclear. Treatments targeting reduction of disability need to address apathy and cognitive impairment to ensure greater efficacy, especially in regards to IADLs.

Normative values of the Brief Repeatable Battery of Neuropsychological Tests in a Brazilian population sample: discrete and regression-based norms.

Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.

Normative values of the Brief Repeatable Battery of Neuropsychological Tests in a Brazilian population sample: discrete and regression-based norms / Valores normativos da Brief Repeatable Battery of Neuropsychological Tests (BRB-N) em uma amostra da população Brasileira: dados discretos e contínuos

ABSTRACT Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.

RESUMO Objetivo Disfunção cognitiva é comum em pacientes com esclerose múltipla. Por isto, a Brief Repeatable Battery of Neuropsychological Tests (BRB-N) foi desenvolvida para avaliar as funções cognitivas mais frequentemente alteradas na doença. Entretanto, estão faltando dados normativos desta bateria no Brasil. Assim, nosso objetivo foi fornecer valores normativos contínuos e discretos da BRB-N para a população brasileira. Métodos Foram recrutados 285 indivíduos sadios da comunidade em 10 centros do Brasil e aplicada a versão A em 237 e a versão B em 48 sujeitos. Normas contínuas foram calculadas com análise de regressão múltipla. Resultados Escores brutos médios e 5°percentil para cada subteste são fornecidos, estratificados por idade e nível educacional. Os escores brutos dos sujeitos sadios foram convertidos em escores de escalas e postos em regressão quanto a idade, sexo e educação, fornecendo equações que podem ser usadas para calcular escores previsíveis. Conclusão Nossos dados normativos permitem um uso mais amplo da BRB-N na prática clínica e na pesquisa, fornecendo normas para dados discretos e contínuos. Normas para dados discretos deveriam ser usadas com cuidado e escores demograficamente ajustados são geralmente preferidos quando interpretando dados neuropsicológicos.

Validity and Reliability of the Frontotemporal Dementia Rating Scale (FTD-FRS) for the Progression and Staging of Dementia in Brazilian Patients.

INTRODUCTION: Few studies on instruments for staging frontotemporal dementia (FTD) have been conducted. OBJECTIVE: The objective of this study was to analyze the factor structure, internal consistency, reliability, and convergent validity of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS). METHODS: A total of 97 individuals aged 40 years and above with >2 years' education took part in the study, 31 patients diagnosed with behavioral variant FTD (bvFTD), 8 patients with primary progressive aphasia, 28 with Alzheimer disease, 8 with mild cognitive impairment, and a control group of 22 healthy subjects. The FTD-FRS was completed by family members or caregivers, and Neurologists completed the 8-item Clinical Dementia Rating for Frontotemporal Lobar Degeneration (CDR-FTLD) scale (6 original domains plus Language and Behavior). The Alzheimer disease and FTD patients had equivalent disease severity level. RESULTS: The internal consistency of the FTD-FRS, estimated by Cronbach α, was 0.975 whereas test-retest reliability was 0.977. Scree plot and exploratory factor (Varimax rotation) analyses revealed the existence of 4 factors, with eigenvalues >1, which together explained 77.13% of the total variance with values of 1.28 to 17.52. The domains of the Brazilian version of the FTD-FRS scale correlated with the domains of the CDR-FTLD. CONCLUSIONS: The present study is the first to document the factorial structure of the FTD-FRS and its convergent validity with the CDR-FTLD. These tools are key to determine dementia severity in FTD. The Brazilian FTD-FRS demonstrated adequate psychometric properties for use in Brazil. This instrument may contribute to disease staging in FTD and may help to document intervention-related changes.

Is inpatient ictal video-electroencephalographic monitoring mandatory in mesial temporal lobe epilepsy with unilateral hippocampal sclerosis? A prospective study.

OBJECTIVE: To compare surgical outcome in mesial temporal lobe epilepsy (MTLE) patients with unilateral hippocampal sclerosis (MTLE-HS) who had or did not have preoperative video-electroencephalographic monitoring (VEEG). METHODS: A prospective study was undertaken with 166 consecutive pharmacoresistant unilateral MTLE-HS patients. All patients were investigated with detailed seizure semiology, serial routine outpatient EEG, magnetic resonance imaging, neuropsychological evaluation, and if necessary, other examinations. Postoperative follow-up ranged between 2 and 16 years. Patients were divided into: (1) patients operated on based on routine outpatient EEG information, with >80% of EEGs with unilateral interictal epileptiform discharges (IEDs) ipsilateral to HS or ictal events (n = 71); and (2) patients submitted to preoperative VEEG (n = 95). To avoid the bias generated by ictal recordings, we performed a subanalysis of: (1) patients without preoperatively ictal recordings (n = 80) and (2) patients with ictal recordings in VEEG or routine outpatient EEG (n = 86). RESULTS: Groups were similar regarding gender, age at surgery, seizure onset, preoperative seizure frequency, and duration of follow-up. Overall, 136/166 (81.92%) were classified as Engel I seizure outcome, with no difference between groups; 76.84% and 88.73% of patients with and without VEEG, respectively, had Engel I postoperative seizure outcome (P = .77). The time lag until surgery was shorter in the group without VEEG (80 vs 38 months; P = .01). Considering ictal recordings, 76.74% of patients with seizures recorded and 87.50% without ictal recordings had Engel I outcome (P = .11). SIGNIFICANCE: We performed the first prospective study in a tertiary epilepsy center comparing surgical outcomes in unilateral MTLE-HS patients investigated preoperatively with and without VEEG. Based on the surgical outcome, VEEG is not imperative in patients with unilateral MTLE-HS who have compatible semiology and clearly ipsilateralized IEDs evaluated by a multidisciplinary and experienced epilepsy group.