Ensemble-imbalance-based classification for amyotrophic lateral sclerosis prognostic prediction: identifying short-survival patients at diagnosis.

Prognosticating Amyotrophic Lateral Sclerosis (ALS) presents a formidable challenge due to patients exhibiting different onset sites, progression rates, and survival times. In this study, we have developed and evaluated Machine Learning (ML) algorithms that integrate Ensemble and Imbalance Learning techniques to classify patients into Short and Non-Short survival groups based on data collected during diagnosis. We aimed to identify individuals at high risk of mortality within 24 months of symptom onset through analysis of patient data commonly encountered in daily clinical practice. Our Ensemble-Imbalance approach underwent evaluation employing six ML algorithms as base classifiers. Remarkably, our results outperformed those of individual algorithms, achieving a Balanced Accuracy of 88% and a Sensitivity of 96%. Additionally, we used the Shapley Additive Explanations framework to elucidate the decision-making process of the top-performing model, pinpointing the most important features and their correlations with the target prediction. Furthermore, we presented helpful tools to visualize and compare patient similarities, offering valuable insights. Confirming the obtained results, our approach could aid physicians in devising personalized treatment plans at the time of diagnosis or serve as an inclusion/exclusion criterion in clinical trials.

"Clock dial pattern", a radiologic clue to neuro-chikungunya diagnosis: a case series.

BACKGROUND: Chikungunya is a mosquito-borne disease caused by the chikungunya virus (CHIKV) and can lead to neurological complications in severe cases. OBJECTIVE: This study examined neuroimaging patterns in chikungunya cases during two outbreaks in Brazil to identify specific patterns for diagnosis and treatment of neuro-chikungunya. METHODS: Eight patients with confirmed chikungunya and neurological involvement were included. Clinical examinations and MRI scans were performed, and findings were analyzed by neuroradiologists. Data on age, sex, neurological symptoms, diagnostic tests, MRI findings, and clinical outcomes were recorded. RESULTS: Patients showed different neuroimaging patterns. Six patients exhibited a "clock dial pattern" with hyperintense dotted lesions in the spinal cord periphery. One patient had thickening and enhancement of anterior nerve roots. Brain MRI revealed multiple hyperintense lesions in the white matter, particularly in the medulla oblongata, in six patients. One patient had a normal brain MRI. CONCLUSION: The "clock dial pattern" observed in spinal cord MRI may be indicative of chikungunya-related nervous system lesions. Isolated involvement of spinal cord white matter in chikungunya can help differentiate it from other viral infections. Additionally, distinct brainstem involvement in chikungunya-associated encephalitis, particularly in the rostral region, sets it apart from other arboviral infections. Recognizing these neuroimaging patterns can contribute to early diagnosis and appropriate management of neuro-chikungunya.

ANTECEDENTES: A chikungunya é uma doença transmitida por mosquitos causada pelo vírus chikungunya (CHIKV) e pode levar a complicações neurológicas em casos graves. OBJETIVO: Este estudo examinou padrões de neuroimagem em casos de chikungunya durante dois surtos no Brasil para identificar padrões específicos para o diagnóstico e tratamento de neurochikungunya. MéTODOS: Oito pacientes com chikungunya confirmada e envolvimento neurológico foram incluídos. Exames clínicos e ressonâncias magnéticas (RM) foram realizados, e os achados foram analisados por neurorradiologistas. Dados sobre idade, sexo, sintomas neurológicos, testes diagnósticos, achados de RM e desfechos clínicos foram registrados. RESULTADOS: Os pacientes apresentaram diferentes padrões de neuroimagem. Seis pacientes apresentaram um "padrão de mostrador de relógio" com lesões pontilhadas hiperintensas na periferia da medula espinhal. Um paciente apresentou espessamento e realce das raízes nervosas anteriores. A RM do cérebro revelou múltiplas lesões hiperintensas na substância branca, especialmente no bulbo em seis pacientes. Um paciente apresentou uma RM cerebral normal. CONCLUSãO: O "padrão de mostrador de relógio" observado na RM da medula espinhal pode ser indicativo de lesões do sistema nervoso relacionadas à chikungunya. O envolvimento isolado da substância branca da medula espinhal na chikungunya pode ajudar a diferenciá-la de outras infecções virais. Além disso, o envolvimento distinto do tronco cerebral na encefalite associada à chikungunya, especialmente na região rostral, a distingue de outras infecções por arbovírus. O reconhecimento desses padrões de neuroimagem pode contribuir para o diagnóstico precoce e manejo adequado da neurochikungunya.

"Clock dial pattern", a radiologic clue to neuro-chikungunya diagnosis: a case series / "Padrão em ponteiro de relógio", uma dica radiológica para o diagnóstico de neurochikungunya: série de casos

Abstract Background Chikungunya is a mosquito-borne disease caused by the chikungunya virus (CHIKV) and can lead to neurological complications in severe cases. Objective This study examined neuroimaging patterns in chikungunya cases during two outbreaks in Brazil to identify specific patterns for diagnosis and treatment of neuro-chikungunya. Methods Eight patients with confirmed chikungunya and neurological involvement were included. Clinical examinations and MRI scans were performed, and findings were analyzed by neuroradiologists. Data on age, sex, neurological symptoms, diagnostic tests, MRI findings, and clinical outcomes were recorded. Results Patients showed different neuroimaging patterns. Six patients exhibited a "clock dial pattern" with hyperintense dotted lesions in the spinal cord periphery. One patient had thickening and enhancement of anterior nerve roots. Brain MRI revealed multiple hyperintense lesions in the white matter, particularly in the medulla oblongata, in six patients. One patient had a normal brain MRI. Conclusion The "clock dial pattern" observed in spinal cord MRI may be indicative of chikungunya-related nervous system lesions. Isolated involvement of spinal cord white matter in chikungunya can help differentiate it from other viral infections. Additionally, distinct brainstem involvement in chikungunya-associated encephalitis, particularly in the rostral region, sets it apart from other arboviral infections. Recognizing these neuroimaging patterns can contribute to early diagnosis and appropriate management of neuro-chikungunya.

Resumo Antecedentes A chikungunya é uma doença transmitida por mosquitos causada pelo vírus chikungunya (CHIKV) e pode levar a complicações neurológicas em casos graves. Objetivo Este estudo examinou padrões de neuroimagem em casos de chikungunya durante dois surtos no Brasil para identificar padrões específicos para o diagnóstico e tratamento de neurochikungunya. Métodos Oito pacientes com chikungunya confirmada e envolvimento neurológico foram incluídos. Exames clínicos e ressonâncias magnéticas (RM) foram realizados, e os achados foram analisados por neurorradiologistas. Dados sobre idade, sexo, sintomas neurológicos, testes diagnósticos, achados de RM e desfechos clínicos foram registrados. Resultados Os pacientes apresentaram diferentes padrões de neuroimagem. Seis pacientes apresentaram um "padrão de mostrador de relógio" com lesões pontilhadas hiperintensas na periferia da medula espinhal. Um paciente apresentou espessamento e realce das raízes nervosas anteriores. A RM do cérebro revelou múltiplas lesões hiperintensas na substância branca, especialmente no bulbo em seis pacientes. Um paciente apresentou uma RM cerebral normal. Conclusão O "padrão de mostrador de relógio" observado na RM da medula espinhal pode ser indicativo de lesões do sistema nervoso relacionadas à chikungunya. O envolvimento isolado da substância branca da medula espinhal na chikungunya pode ajudar a diferenciá-la de outras infecções virais. Além disso, o envolvimento distinto do tronco cerebral na encefalite associada à chikungunya, especialmente na região rostral, a distingue de outras infecções por arbovírus. O reconhecimento desses padrões de neuroimagem pode contribuir para o diagnóstico precoce e manejo adequado da neurochikungunya.

Definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in amyotrophic lateral sclerosis (ALS): Consensus from ALS and Motor Neuron Disease Scientific Department of the Brazilian Academy of Neurology.

The spectrum of neuropsychiatric phenomena observed in amyotrophic lateral sclerosis (ALS) is wide and not fully understood. Disorders of laughter and crying stand among the most common manifestations. The aim of this study is to report the results of an educational consensus organized by the Brazilian Academy of Neurology to evaluate the definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in ALS patients. Twelve members of the Brazilian Academy of Neurology - considered to be experts in the field - were recruited to answer 12 questions about the subject. After exchanging revisions, a first draft was prepared. A face-to-face meeting was held in Fortaleza, Brazil on 9.23.22 to discuss it. The revised version was subsequently emailed to all members of the ALS Scientific Department from the Brazilian Academy of Neurology and the final revised version submitted for publication. The prevalence of pseudobulbar affect/pathological laughter and crying (PBA/PLC) in ALS patients from 15 combined studies and 3906 patients was 27.4% (N = 1070), ranging from 11.4% to 71%. Bulbar onset is a risk factor but there are limited studies evaluating the differences in prevalence among the different motor neuron diseases subtypes, including patients with and without frontotemporal dementia. Antidepressants and a combination of dextromethorphan and quinidine (not available in Brazil) are possible therapeutic options. This group of panelists acknowledge the multiple gaps in the current literature and reinforces the need for further studies.

O espectro de fenômenos neuropsiquiátricos observados na ELA é amplo e não completamente entendido. Desordens do riso e do choro estão entre as manifestações mais comuns. O objetivo deste estudo é relatar os resultados de um Consenso organizado pela Academia Brasileira de Neurologia para avaliar definições, fenomenologia, diagnóstico, e manejo dos distúrbios do riso e do choro em pacientes com ELA. Doze membros da Academia Brasileira de Neurologia ­ considerados experts na área ­ foram recrutados para responder 12 questões na temática. Depois da verificação das revisões, um primeiro manuscrito foi preparado. Após, foi realizado um encontro presencial em Fortaleza, Brasil, em 23/09/2022, para discussão do conteúdo. A versão revisada foi posteriormente enviada por e-mail para todos os membros do Departamento Científico de DNM/ELA da Academia Brasileira de Neurologia e a versão final revisada foi submetida para publicação. A prevalência da síndrome pseudobulbar em pacientes com ELA em 15 estudos combinados com 3906 pacientes foi de 27,4% (n = 1070), variando entre 11,4% e 71%. Início bulbar é um fator de risco, mas há limitados estudos avaliando as diferenças em prevalência entre os diferentes subtipos de Doença do Neurônio Motor, incluindo pacientes com e sem Demência Frontotemporal. Antidepressivos e uma combinação de dextrometorfana e quinidina (indisponíveis no Brasil) são opções terapêuticas possíveis. Esse grupo de panelistas reconhece as múltiplas demandas não atendidas na literatura atual e reforça a necessidade de futuros estudos.

A geographical study on amyotrophic lateral sclerosis in Rio Grande Do Norte, Brazil, from 2005 to 2018.

OBJECTIVE: amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disorder with variable incidence and prevalence worldwide. However, clinical-epidemiological studies on ALS are scarce in Brazil. Thus, this study investigated whether ALS incidence had uniform spatial distribution in population-based cluster analysis in Rio Grande do Norte state (Brazil), from 2005 to 2018. METHODS: new cases of ALS were identified in a database of the ALS multidisciplinary care center of the Onofre Lopes University Hospital in Natal (Rio Grande do Norte, Brazil). Approaches were based on incidence (empirical Bayes estimator and Moran's I analysis) and cluster analyses (Moran scatter plot and spatial correlogram). RESULTS: a total of 177 patients (59% males) participated in the study; the mean age of ALS onset was 57 years. Mean annual incidence of ALS was 0.3769 per 100,000 inhabitants (95% confidence interval of 0.0889), higher in males than in females (0.4516 per 100,000 vs. 0.3044 per 100,000). According to spatial statistics, patients were homogeneously distributed throughout the studied area. CONCLUSION: a low estimate was observed compared with other populations. Results did not indicate areas of increased risk or significant spatial geographic dependence, suggesting a random ALS incidence in Rio Grande do Norte.

Clinical Neurophysiology of Zika Virus-Related Disorders of the Peripheral Nervous System in Adults.

SUMMARY: During the 2013 to 2016 outbreak in the Pacific and Americas, Zika virus infection resulted not only in febrile and cutaneous manifestations but also in (severe) neurologic complications. These included both central and peripheral nervous system disorders. The most frequent was Guillain-Barré syndrome that typically developed 1 to 2 weeks after the acute infection. Later, other peripheral nervous system syndromes were recognized in association with the viral infection, broadening the spectrum of Zika virus-related peripheral nervous system syndromes. In the current article, the authors review all available clinical neurophysiology data on Guillain-Barré syndrome and other peripheral nervous system syndromes in an attempt to characterize the major patterns of involvement related to Zika virus. The authors also highlight the clinical usefulness of nerve conduction studies and needle EMG in the investigation of suspected Zika virus-related Guillain-Barré syndrome.

Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy.

Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease's severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.

Antecedent infections in Guillain-Barré syndrome in endemic areas of arbovirus transmission: A multinational case-control study.

Half of the world's population is at risk of arthropod-borne virus (arbovirus) infections. Several arbovirus infections have been associated with Guillain-Barré syndrome (GBS). We investigated whether arboviruses are driving GBS beyond epidemic phases of transmission and studied the antibody response to glycolipids. The protocol of the International Guillain-Barré syndrome Outcome Study (IGOS), an observational prospective cohort study, was adapted to a case-control design. Serum samples were tested for a recent infection with Zika virus (ZIKV), dengue virus (DENV), chikungunya (CHIKV) virus, hepatitis E virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Campylobacter jejuni, and Mycoplasma pneumoniae, and for antibodies to glycolipids. Forty-nine patients were included from Brazil (63%), Argentina (14%), and Malaysia (22%). Evidence of a recent infection was found in 27/49 (55%) patients: C jejuni (n = 15, 31%), M pneumoniae (n = 5, 10%), CHIKV (n = 2, 4%), EBV (n = 1, 2%), C jejuni and M pneumoniae (n = 2, 4%), CMV and DENV (n = 1, 2%), and C jejuni and DENV (n = 1, 2%). In 22 patients, 35 paired controls were collected. Odds ratio for recent infections did not significantly differ between cases and controls. No typical anti-ganglioside antibody binding was associated with recent arbovirus infection. We conclude that arbovirus infections occur in GBS patients outside of epidemic viral transmission, although not significantly more than in controls. Broad infection and anti-ganglioside antibody serology are important to establish the most likely pathogenic trigger in GBS patients. Larger studies are necessary to determine the association between arboviruses and GBS.

Clinical Features of COVID-19 on Patients With Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND OBJECTIVES: To describe the clinical features and disease outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: The Neuroimmunology Brazilian Study Group has set up the report of severe acute respiratory syndrome (SARS-CoV2) cases in patients with NMOSD (pwNMOSD) using a designed web-based case report form. All neuroimmunology outpatient centers and individual neurologists were invited to register their patients across the country. Data collected between March 19 and July 25, 2020, were uploaded at the REDONE.br platform. Inclusion criteria were as follows: (1) NMOSD diagnosis according to the 2015 International Panel Criteria and (2) confirmed SARS-CoV2 infection (reverse transcription-polymerase chain reaction or serology) or clinical suspicion of COVID-19, diagnosed according to Center for Disease Control / Council of State and Territorial Epidemiologists (CDC/CSTE) case definition. Demographic and NMOSD-related clinical data, comorbidities, disease-modifying therapy (DMT), COVID-19 clinical features, and severity were described. RESULTS: Among the 2,061 pwNMOSD followed up by Brazilian neurologists involved on the registry of COVID-19 in pwNMOSD at the REDONE.br platform, 34 patients (29 women) aged 37 years (range 8-77), with disease onset at 31 years (range 4-69) and disease duration of 6 years (range 0.2-20.5), developed COVID-19 (18 confirmed and 16 probable cases). Most patients exhibited mild disease, being treated at home (77%); 4 patients required admission at intensive care units (severe cases); and 1 patient died. Five of 34 (15%) presented neurologic manifestations (relapse or pseudoexacerbation) during or after SARS-CoV2 infection. DISCUSSION: Most NMOSD patients with COVID-19 presented mild disease forms. However, pwNMOSD had much higher odds of hospitalization and intensive care unit admission comparing with the general Brazilian population. The frequency of death was not clearly different. NMOSD disability, DMT type, and comorbidities were not associated with COVID-19 outcome. SARS-CoV2 infection was demonstrated as a risk factor for NMOSD relapses. Collaborative studies using shared NMOSD data are needed to suitably define factors related to COVID-19 severity and neurologic manifestations.

Genetic epidemiology of familial ALS in Brazil.

Many genes associated with familial forms of the amyotrophic lateral sclerosis (fALS) have been identified in European and North American cohorts. However, little is known about the genetic bases of fALS in Latin America and Brazil, in particular. To address this question, we recruited 107 patients with fALS from 93 unrelated families from Southeastern, Southern, and Northeastern regions of the country. A 3-step diagnostic approach was used: 1) Triplet repeat primed polymerase chain reaction to search for C9orf72 expansions, then 2) fragment digestion to search for the c.166 C>T VAPB variant, and finally, 3) whole exome sequencing for those who tested negative. We identified the genetic cause for fALS in 70% of the families. VAPB and C9orf72 were the most frequent genes (30% and 22%, respectively), followed by SOD1, TARDBP, ANXA11, and FUS. Five novel variants in known ALS genes were found, including the SOD1 Val120Leu and ANXA11 Asp40Tyr, which were seen in 2 unrelated families each. In conclusion, VAPB and then C9orf72 are the genes most commonly related to fALS in Brazil.

CAG repeats ≥ 34 in Ataxin-1 gene are associated with amyotrophic lateral sclerosis in a Brazilian cohort.

Little is known about the genetic basis of amyotrophic lateral sclerosis (ALS) outside Europe and US. In this study, we investigated whether intermediate CAG expansions at ATXN1 were associated to ALS in the Brazilian population. To accomplish that, representative samples from 411 unrelated patients and 436 neurologically normal controls from 6 centers spread over the territory were genotyped to quantify ATXN1 expansions. We found that ATXN1 intermediate-length expansion (≥34 CAG repeats) are associated with the disease (odds ratio = 2.19, 95% CI = 1.081-4.441, p = .026). Most ATXN1-positive patients had classical phenotype, but some of them presented predominant lower motor neuron involvement. None of them had associated ataxia. Frontotemporal dementia was concomitantly found in 12.5% of patients carrying the intermediate ATXN1 expansion. Further studies are needed to validate these findings and to understand the pathophysiological mechanisms that connect ataxin-1 and ALS.

Association of Copper Status with Lipid Profile and Functional Status in Patients with Amyotrophic Lateral Sclerosis.

Oxidative stress is one of the main mechanisms associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). Copper can affect cellular oxidation and lipid metabolism. The aim of this study was to evaluate the association of copper status with lipid profile and functional status in patients with ALS. A cross-sectional study was carried out including 27 patients with ALS (case group) and 26 healthy individuals (control group). Copper status was evaluated by habitual dietary copper intake, plasma copper, and serum ceruloplasmin concentrations. The lipid profile included analysis of serum total cholesterol (TC), LDL-cholesterol (LDL-c), HDL-cholesterol (HDL-c), and triglycerides (TGL). The functional status of patients with ALS was assessed by the ALS Functional Rating Scale-Revised (ALSFRS-R). In the case group, plasma copper was lower compared with the control group (133.9 versus 164.1 µg/dL, p=0.0001) and was positively correlated with HDL-c (rs=0.398, p=0.044). In the control group, plasma copper was positively correlated with serum ceruloplasmin (rs=0.646, p < 0.001), TC (rs=0.446, p=0.025), LDL-c (rs=0.445, p=0.029), and HDL-c (rs=0.479, p=0.015), and serum ceruloplasmin was positively correlated only with LDL-c (rs=0.407, p=0.043). In the case group, dietary copper intake (B=-0.373, p < 0.001), plasma copper (B=-0.005, p=0.033), and TC (B=-0.312, p=0.001) were inversely associated with the functional status of patients with ALS. In contrast, serum ceruloplasmin (B=0.016, p=0.044), LDL-c (B=0.314, p=0.001), HDL-c (B=0.308, p=0.001), and TGL (B=0.062; p=0.001) were positively associated with their functional status. In conclusion, this study suggests a disturbance of copper status and its connection with the lipid profile in patients with ALS. Furthermore, copper status and lipid profile may influence the functional status of patients with ALS, standing out as potential biomarkers of disease severity.

Intermediate-length CAG repeat in ATXN2 is associated with increased risk for amyotrophic lateral sclerosis in Brazilian patients.

Intermediate-length cytosine-adenine-guanine nucleotide repeat expansions in the ATXN2 gene (which encodes for the protein Ataxin-2) have been linked to increased risk for amyotrophic lateral sclerosis (ALS) in different populations. There is no such study in the Brazilian population, which has a mixed ethnic background. We have thus selected 459 patients with ALS (372 Sporadic ALS and 87 Familial ALS) and 468 control subjects from 6 Brazilian centers to investigate this point. We performed polymerase chain reaction to determine the length of the ATXN2 alleles. Polymerase chain reaction products were resolved using capillary electrophoresis on ABI 3500 × l capillary sequencer. We found that ATXN2 intermediate-length expansions (larger than 26 repeats) were associated with an increased risk for ALS (odds ratio = 2.56, 95% confidence interval: 1.29-5.08, p = 0.005). Phenotype in patients with and without ATXN2 expansions was similar. Our findings support the hypothesis that ATXN2 plays an important role in the pathogenesis of ALS also in the Brazilian population.

Guillain, Barraquer and I.

The year 2016 was the centennial anniversary of the recognition of the Guillain-Barré syndrome, which was first described by George Guillain, Jean-Alexandre Barré and André Strohl. In celebration of the centennial, this historical review describes aspects of the contributions of Guillain and the Spanish neurologist, Barraquer-Bordas and a brief account of the Fourth International Neurological Congress, which brought together Guillain and Barraquer-Bordas. There were many outstanding Brazilian physicians at that meeting. Finally, the author describes his interaction with Barraquer-Bordas and provides an account of his influence in shaping a generation of Brazilian neurologists, including himself.

The frequency of the C9orf72 expansion in a Brazilian population.

G4C2 hexanucleotide repeat expansions in the C9orf72 gene seem to be the cause of numerous cases of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). In this study, we investigated the presence of the G4C2 repeat expansion in 463 Brazilian probands, of whom 404 had ALS/motor neuron disease and 67 FTD, and in 63 healthy controls in the southeastern region of Brazil. The highest frequencies of the C9orf72 mutation were in the ALS-FTD group (50% of familial and 17.6% of sporadic cases), although it was also present in 5% of pure ALS/motor neuron disease patients (11.8% of familial and 3.6% of sporadic cases) and in 7.1% of pure familial FTD. Among G4C2 repeat mutation carriers, 68.8% of the subjects who developed dementia symptoms were females. This frequency was significantly higher than the percentage reached by men with C9orf72 expansion who had this phenotype (p = 0.047). No abnormal repeat expansion was found in control groups. Inclusion of the C9orf72 genetic test in the molecular panels for Brazilian populations with these neurodegenerative diseases should be strongly considered.

Guillain, Barraquer and I / Guillain, Barraquer e eu

ABSTRACT The year 2016 was the centennial anniversary of the recognition of the Guillain-Barré syndrome, which was first described by George Guillain, Jean-Alexandre Barré and André Strohl. In celebration of the centennial, this historical review describes aspects of the contributions of Guillain and the Spanish neurologist, Barraquer-Bordas and a brief account of the Fourth International Neurological Congress, which brought together Guillain and Barraquer-Bordas. There were many outstanding Brazilian physicians at that meeting. Finally, the author describes his interaction with Barraquer-Bordas and provides an account of his influence in shaping a generation of Brazilian neurologists, including himself.

RESUMO O ano de 2016 foi o aniversário do centenário do reconhecimento da síndrome de Guillain-Barré (GBS), que foi descrita pela primeira vez por George Guillain, Jean-Alexandre Barré e André Strohl. Em comemoração ao centenário, esta revisão histórica descreve aspectos das contribuições de Guillain e Barraquer-Bordas e uma breve descrição do IV Congresso Neurológico Internacional, que reuniu Guillain e o neurologista espanhol Barraquer-Bordas. Naquela reunião houve participação também de excelentes médicos brasileiros. Finalmente, o autor descreve sua interação com Barraquer-Bordas e fornece uma descrição de sua influência na formação de uma geração de neurologistas brasileiros, incluindo ele próprio.

Dietary intake and zinc status in amyotrophic lateral sclerosis patients.

BACKGROUND: There is considerable evidence that abnormal zinc homeostasis is related to amyotrophic lateral sclerosis (ALS) pathogenesis, and malnutrition is an independent prognostic factor for worsened survival of ALS patients. OBJECTIVE: To evaluate the dietary intake and zinc status in patients with ALS, treated in a specialized outpatient facility in Natal, Brazil. METHODS: Twenty patients with ALS (case group) and 37 healthy subjects (control group) were included. Clinical and anthropometric assessments were carried out and dietary intake was obtained from two 24-hour recalls. Plasma and urinary zinc concentrations were determined by atomic absorption spectrophotometry. RESULTS: Most of the participants were eutrophic. Mean energy, protein, carbohydrate and fat intake was significantly lower for the case group. There was greater prevalence of inadequate zinc intake in the case group (35%) compared to controls (27%). Mean plasma zinc was significantly lower in the case group than in controls (77.13 ± 22.21 vs 87.84 ± 17.44 µgZn/dl). Urinary zinc did not differ significantly between cases and controls. In the case group, plasma and urinary zinc concentrations were below reference values in 50.0% and 52.6% of patients, respectively. CONCLUSION: A large portion of patients with ALS exhibited poor dietary intake and changes in body zinc status. The zinc deficiency found in half of the ALS patients may contribute to a worsened prognosis and should be the target of nutritional intervention that aims to correct this deficiency.