Unraveling the genetic landscape of undiagnosed cerebellar ataxia in Brazilian patients.

INTRODUCTION: Hereditary ataxias (HAs) encompass a diverse and genetically intricate group of rare neurodegenerative disorders, presenting diagnostic challenges. Whole-exome sequencing (WES) has significantly improved diagnostic success. This study aimed to elucidate genetic causes of cerebellar ataxia within a diverse Brazilian cohort. METHODS: Biological samples were collected from individuals with sporadic or familial cerebellar ataxia, spanning various ages and phenotypes, excluding common SCAs and Friedreich ataxia. RFC1 biallelic AAGGG repeat expansion was screened in all patients. For AAGGG-negative cases, WES targeting 441 ataxia-related genes was performed, followed by ExpansionHunter analysis for repeat expansions, including the recently described GGC-ZFHX3. Variant classification adhered to ClinGen guidelines, yielding definitive or probable diagnoses. RESULTS: The study involved 76 diverse Brazilian families. 16 % received definitive diagnoses, and another 16 % received probable ones. RFC1-related ataxia was predominant, with two definitive cases, followed by KIF1A (one definitive and one probable) and SYNE-1 (two probable). Early-onset cases exhibited higher diagnostic rates. ExpansionHunter improved diagnosis by 4 %.We did not detected GGC-ZFHX3 repeat expansion in this cohort. CONCLUSION: This study highlights diagnostic complexities in cerebellar ataxia, even with advanced genetic methods. RFC1, KIF1A, and SYNE1 emerged as prevalent mutations. ZFHX3 repeat expansion seem to be rare in Brazilian population. Early-onset cases showed higher diagnostic success. WES coupled with ExpansionHunter holds promise as a primary diagnostic tool, emphasizing the need for broader NGS accessibility in Brazil.

Sjogren's syndrome: a neurological perspective.

Sjogren's syndrome (SS) is a complex autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands, resulting in sicca symptoms. Additionally, SS presents with neurological manifestations that significantly impact the nervous system. This review aims to provide a comprehensive overview of the neurological aspects of SSj, covering both the peripheral and central nervous system involvement, while emphasizing diagnosis, treatment, and prognosis.

A síndrome de Sjogren (SS) é uma doença autoimune complexa caracterizada pela infiltração linfocítica das glândulas salivares e lacrimais, resultando em sintomas sicca. Além disso, a SS apresenta manifestações neurológicas que afetam significativamente o sistema nervoso. Esta revisão tem como objetivo fornecer uma visão abrangente dos aspectos neurológicos da SSj, abordando tanto o envolvimento do sistema nervoso periférico quanto do central, com ênfase no diagnóstico, tratamento e prognóstico.

Frequency of GAA-FGF14 Ataxia in a Large Cohort of Brazilian Patients With Unsolved Adult-Onset Cerebellar Ataxia.

Objectives: Intronic FGF14 GAA repeat expansions have recently been found to be a common cause of hereditary ataxia (GAA-FGF14 ataxia; SCA27B). The global epidemiology and regional prevalence of this newly reported disorder remain to be established. In this study, we investigated the frequency of GAA-FGF14 ataxia in a large cohort of Brazilian patients with unsolved adult-onset ataxia. Methods: We recruited 93 index patients with genetically unsolved adult-onset ataxia despite extensive genetic investigation and genotyped the FGF14 repeat locus. Patients were recruited across 4 different regions of Brazil. Results: Of the 93 index patients, 8 (9%) carried an FGF14 (GAA)≥250 expansion. The expansion was also identified in 1 affected relative. Seven patients were of European descent, 1 was of African descent, and 1was of admixed American ancestry. One patient carrying a (GAA)376 expansion developed ataxia at age 28 years, confirming that GAA-FGF14 ataxia can occur before the age of 30 years. One patient displayed episodic symptoms, while none had downbeat nystagmus. Cerebellar atrophy was observed on brain MRI in 7 of 8 patients (87%). Discussion: Our results suggest that GAA-FGF14 ataxia is a common cause of adult-onset ataxia in the Brazilian population, although larger studies are needed to fully define its epidemiology.

Brazilian autoimmune encephalitis network (BrAIN): antibody profile and clinical characteristics from a multicenter study.

Background: The frequency of antibodies in autoimmune encephalitis (AIE) may vary in different populations, however, data from developing countries are lacking. To describe the clinical profile of AIE in Brazil, and to evaluate seasonality and predictors of AIE in adult and pediatric patients. Methods: We evaluated patients with possible AIE from 17 centers of the Brazilian Autoimmune Encephalitis Network (BrAIN) between 2018 and 2022. CSF and serum were tested with TBAs and CBAs. Data on clinical presentation, complementary investigation, and treatment were compiled. Seasonality and predictors of AIE in adult and pediatric populations were analyzed. Results: Of the 564 patients, 145 (25.7%) were confirmed as seropositive, 69 (12.23%) were seronegative according to Graus, and 58% received immunotherapy. The median delay to diagnosis confirmation was 5.97 ± 10.3 months. No seasonality variation was observed after 55 months of enrolment. The following antibodies were found: anti-NMDAR (n=79, 54%), anti-MOG (n=14, 9%), anti-LGI1(n=12, 8%), anti-GAD (n=11, 7%), anti-GlyR (n=7, 4%), anti-Caspr2 (n=6, 4%), anti-AMPAR (n=4, 2%), anti-GABA-BR (n=4, 2%), anti-GABA-AR (n=2, 1%), anti-IgLON5 (n=1, 1%), and others (n=5, 3%). Predictors of seropositive AIE in the pediatric population (n=42) were decreased level of consciousness (p=0.04), and chorea (p=0.002). Among adults (n=103), predictors of seropositive AIE were movement disorders (p=0.0001), seizures (p=0.0001), autonomic instability (p=0.026), and memory impairment (p=0.001). Conclusion: Most common antibodies in Brazilian patients are anti-NMDAR, followed by anti-MOG and anti-LGI1. Only 26% of the possible AIE patients harbor antibodies, and 12% were seronegative AIE. Patients had a 6-month delay in diagnosis and no seasonality was found. Findings highlight the barriers to treating AIE in developing countries and indicate an opportunity for cost-effect analysis. In this scenario, some clinical manifestations help predict seropositive AIE such as decreased level of consciousness, chorea, and dystonia among children, and movement disorders and memory impairment among adults.

Diagnosis and management of Parkinson's disease dementia and dementia with Lewy bodies: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) represent the second most common type of degenerative dementia in patients aged 65 years and older, leading to progressive cognitive dysfunction and impaired quality of life. This study aims to provide a consensus based on a systematic Brazilian literature review and a comprehensive international review concerning PDD and DLB. Moreover, we sought to report on and give recommendations about the best diagnostic approaches focusing on primary and secondary care. Based on the available data, we recommend clinicians to apply at least one brief global cognitive instrument to assess PDD, such as the Mini-Mental State Examination and preferably the Montreal Cognitive Assessment and the Addenbrooke's Cognitive Examination-Revised. Validated instruments to accurately assess functional abilities in Brazilian PD patients are still incipient. Further studies should focus on biomarkers with Brazilian cohorts.

A demência da doença de Parkinson (DDP) e a demência com corpos de Lewy (DCL) representam a segunda causa mais comum de demência neurodegenerativa em pessoas com mais de 65 anos, ocasionando progressivo declínio cognitivo e comprometimento da qualidade de vida. O presente estudo tem como objetivo prover um consenso de especialistas sobre a DDP e DCL, baseado em revisão sistemática da literatura brasileira e revisão não-sistemática de literatura internacional. Ademais, tal estudo visa promover informação e conceder recomendações sobre abordagem diagnóstica, com foco nos níveis de atenção primária e secundária em saúde. Com base nos dados disponíveis, recomendamos que os profissionais realizem pelo menos um breve instrumento cognitivo global, como o Mini-Exame do Estado Mental, contudo de preferência optem pela Avaliação Cognitiva de Montreal e o Exame Cognitivo de Addenbrooke-Revisado. Observa-se uma carência de instrumentos validados para a avaliação precisa das habilidades funcionais em pacientes brasileiros com DDP e DCL. Além disso, mais estudos focando em biomarcadores com coortes brasileiras também são necessários.

Guidelines for Parkinson's disease treatment: consensus from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology - motor symptoms.

The treatment of Parkinson's disease (PD) is challenging, especially since it is considered highly individualized. The Brazilian Academy of Neurology has recognized the need to disseminate knowledge about the management of PD treatment, adapting the best evidence to the Brazilian reality. Thus, the main published treatment guidelines were reviewed based on the recommendations of group from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology.

The history behind ALS type 8: from the first phenotype description to the discovery of VAPB mutation.

Over the past 68 years, the Finkel type late-onset adult autosomal dominant spinal muscular atrophy (SMA) that is allelic with amyotrophic lateral sclerosis-8 (ALS8) gained a genotype-phenotype correlation among the motor neuron diseases through the work of groups led by Zatz and Marques Jr.

Professor Faustino Esposel: Neurology, football and spiritualism.

Faustino Monteiro Esposel was a renowned neurologist from Rio de Janeiro, born on October 24, 1888. Together with his mentor, Professor Antônio Austregésilo Rodrigues Lima - the founder of modern Brazilian Neurology -, Professor Esposel described one of the rival signs of the Babinski sign, known as the Austregésilo-Esposel sign, in a study published in the renowned journal L'Encéphale in 1912. This article aims to summarize the life story of this illustrious neurologist as well as to highlight his achievements "beyond medicine".

Use of non-invasive stimulation in movement disorders: a critical review.

BACKGROUND: Noninvasive stimulation has been widely used in the past 30 years to study and treat a large number of neurological diseases, including movement disorders. OBJECTIVE: In this critical review, we illustrate the rationale for use of these techniques in movement disorders and summarize the best medical evidence based on the main clinical trials performed to date. METHODS: A nationally representative group of experts performed a comprehensive review of the literature in order to analyze the key clinical decision-making factors driving transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in movement disorders. Classes of evidence and recommendations were described for each disease. RESULTS: Despite unavoidable heterogeneities and low effect size, TMS is likely to be effective for treating motor symptoms and depression in Parkinson's disease (PD). The efficacy in other movement disorders is unclear. TMS is possibly effective for focal hand dystonia, essential tremor and cerebellar ataxia. Additionally, it is likely to be ineffective in reducing tics in Tourette syndrome. Lastly, tDCS is likely to be effective in improving gait in PD. CONCLUSIONS: There is encouraging evidence for the use of noninvasive stimulation on a subset of symptoms in selected movement disorders, although the means to optimize protocols for improving positive outcomes in routine clinical practice remain undetermined. Similarly, the best stimulation paradigms and responder profile need to be investigated in large clinical trials with established therapeutic and assessment paradigms that could also allow genuine long-term benefits to be determined.

Evidence and practices of the use of next generation sequencing in patients with undiagnosed autosomal dominant cerebellar ataxias: a review.

Autosomal dominant cerebellar ataxias (ADCA) are heterogeneous diseases with a highly variable phenotype and genotype. They can be divided into episodic ataxia and spinocerebellar ataxia (SCA); the latter is considered the prototype of the ADCA. Most of the ADCA are caused by polyglutamine expansions, mainly SCA 1, 2, 3, 6, 7, 17 and Dentatorubral-pallidoluysian atrophy (DRPLA). However, 30% of patients remain undiagnosed after testing for these most common SCA. Recently, several studies have demonstrated that the new generation of sequencing methods are useful for the diagnose of these patients. This review focus on searching evidence on the literature, its usefulness in clinical practice and future perspectives.

Wilson's disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI.

INTRODUCTION: Brain magnetic resonance imaging (MRI) studies on Wilson's disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce. METHODS: Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: D: -penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P. RESULTS: MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis. CONCLUSIONS: From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P.

Parkinsonism and Belly Dancer Syndrome in a Patient with Schizophrenia.

Background: Belly dancer syndrome (BDS) and parkinsonian features are rarely described in association as a drug-induced movement disorder. Phenomenology shown: A 62-year-old woman with paranoid schizophrenia presented with bradykinesia, rigidity, rest, and postural tremor, as well as dyskinetic abdominal movements. Educational value: Our case highlights that drug-induced parkinsonism can be associated with other rare movement disorders, such as BDS, with subsequent greater morbidity.

Dupuytren, Ledderhose, and Peyronie Diseases After Primidone Use For Essential Tremor.

INTRODUCTION: Dupuytren, Ledderhose, and Peyronie diseases are chronic fibrotic conditions related to progressive fibrosis of the palmar fascia, plantar fascia, and tunica albuginea, respectively. These conditions have been associated with antiepileptic drug use, mainly phenobarbital and primidone. CASE REPORT: A 71-year-old man developed simultaneous Dupuytren, Ledderhose, and Peyronie diseases after primidone use for essential tremor. CONCLUSIONS: There are a few reports associating barbiturate use to connective tissue disorders, and some suggest that drug withdrawal may result in a better prognosis. Therefore, physicians must be aware of such adverse events when caring for patients on long-term barbiturate use.

Mild cognitive impairment in Parkinson's disease: Characterization and impact on quality of life according to subtype.

AIM: Mild cognitive impairment (MCI) was initially described as a risk factor for Alzheimer's disease. Because of differences in baseline cognitive abilities, MCI in Parkinson's disease (PD; PD-MCI) requires distinct neuropsychological criteria for diagnosis and follow up. In addition to representing a risk factor for PD-related dementia, PD-MCI results in higher morbidity, which can be reduced through early detection. The aim of the present study was to gather data regarding MCI subtypes from neuropsychological profiles and clinical features in PD patients, to evaluate its impact on patients' quality of life according to subtype, and to compare the data with a control (Co) group. METHOD: A total of 149 individuals were selected: 81 controls and 60 patients diagnosed with PD according to the United Kingdom Parkinson's Disease Society Brain Bank criteria. All individuals were submitted to neurological and neuropsychological assessments. RESULTS: The amnestic subtype of MCI was the most common in both the PD and Co groups. PD patients showed greater impairment in MCI than the Co group. The amnestic subtype of PD-MCI was associated with a lower quality of life compared with the non-amnestic group. CONCLUSIONS: The PD group showed worse cognitive performance than the Co group. The amnestic subtype of PD-MCI was associated with the greatest impairment of quality of life. Geriatr Gerontol Int 2019; 19: 497-502.

Paraneoplastic cerebellar degeneration as initial presentation of renal cell carcinoma.

BACKGROUND: Paraneoplastic cerebellar degeneration is usually associated with gynecological and breast cancer, lung cancer, and Hodgkin's lymphoma. Renal cell carcinoma has rarely been described as an underlying malignancy in these cases. CASE PRESENTATION: We report the case of a 75 year-old woman who develop cerebellar ataxia following a respiratory viral infection. During investigation, around 1 year afterward, she noticed constitutional symptoms suggestive of malignancy. Renal carcinoma was found and the hypothesis of paraneoplastic cerebellar degeneration was considered. CONCLUSIONS: As no specific antineuronal antibodies have been described in the setting of renal cell carcinoma, paraneoplastic cerebellar degeneration should be considered when the tumor is detected and other causes are excluded. Immunotherapy should be prescribed as soon as possible.

Mania as the first manifestation of Wilson's disease.

BACKGROUND: Although mental changes are frequent in Wilson's disease, severe psychiatric disorders occur uncommonly and usually accompany the neurological picture. There are few reports in the literature of Wilson's disease patients with typical bipolar affective disorder (BPAD). CASE REPORT: The authors report the case of a patient with Wilson's disease whose initial manifestation was a manic episode followed by depression. Tremor in the upper limbs appeared one year after the onset of symptoms. The diagnosis of Wilson's disease was established three years after the first symptoms appeared, based on the neuropsychiatric picture, the detection of Kayser-Fleischer rings and the results of diagnostic tests indicating chronic liver disease and copper excess. ATP7B genotyping and magnetic resonance imaging of the brain with proton spectroscopy study were also performed. The patient became asymptomatic two years after starting treatment with penicillamine and remained non-symptomatic controlled during the eight-year follow-up period, without any specific treatment for the BPAD. CONCLUSIONS: To our knowledge, this is a singular report of a case of Wilson's disease in which a manic episode preceded the onset of neurological symptoms. The association between Wilson's disease and bipolar disorder is discussed.

Association between Parkinson's disease and glucocerebrosidase mutations in Brazil.

OBJECTIVE: To evaluate the association between parkinsonism and mutations in the glucocerebrosidase gene (GBA) in Brazilian patients. METHODS: We searched for three GBA common mutations (N370S, L444P and G377S) in 65 Brazilian patients affected by PD with disease onset before the age of 55 and compared the results to 267 age- and sex-matched controls. RESULTS: GBA mutations were detected at a significantly higher frequency among Parkinson's disease patients (2/65=3%), when compared to the control group (0/267): P=0.0379. CONCLUSION: These results provide further evidence for GBA mutations being a possible hereditary risk factor for PD.

Prevalence of cardiovascular risk factors among elderly Brazilians over eighty with ischemic stroke.

INTRODUCTION: An ischemic stroke is usually a catastrophic event, mostly in the elderly. Cardiovascular involvement is the leading cause of ischemic stroke in this age population and hence the knowledge about its risk factors is important for the definition of specific policies of prevention. PURPOSE: To evaluate the prevalence of cardiovascular risk factors in patients with age equal to or above 80 in a hospital population with ischemic stroke. METHOD: Retrospective study of consecutive patients diagnosed with ischemic stroke admitted to a tertiary health facility. RESULTS: From September 2004 to March 2006, 215 patients were studied. There was a female preponderance (p<0.01). Among patients over eighty, 72% had hypertension and atrial fibrillation was more common among the oldest old (p<0.01). CONCLUSION: Hypertension and atrial fibrillation should be treated aggressively in the elderly. Anticoagulants should be considered more often in these patients.

Sjogren's syndrome: a neurological perspective / Síndrome de Sjogren: uma perspectiva neurológica

Abstract Sjogren's syndrome (SS) is a complex autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands, resulting in sicca symptoms. Additionally, SS presents with neurological manifestations that significantly impact the nervous system. This review aims to provide a comprehensive overview of the neurological aspects of SSj, covering both the peripheral and central nervous system involvement, while emphasizing diagnosis, treatment, and prognosis.

Resumo A síndrome de Sjogren (SS) é uma doença autoimune complexa caracterizada pela infiltração linfocítica das glândulas salivares e lacrimais, resultando em sintomas sicca. Além disso, a SS apresenta manifestações neurológicas que afetam significativamente o sistema nervoso. Esta revisão tem como objetivo fornecer uma visão abrangente dos aspectos neurológicos da SSj, abordando tanto o envolvimento do sistema nervoso periférico quanto do central, com ênfase no diagnóstico, tratamento e prognóstico.

[Spontaneous carotid and vertebral arteries dissection in a multiethnic population]. / Dissecção espontânea das artérias carótidas e vertebrais em uma população multiétnica.

Spontaneous dissection of the carotid and vertebral arteries (SDCVA) is considered a rare cause of stroke, particularly in countries with multiethnic population. The objective was to evaluate the clinical and neuroimaging features of patients with SDCVA from a multiethnic population. Sixty-six patients diagnosed with SDCVA were studied at two tertiary hospitals at São Paulo. An initial questionnaire was completed and patients were followed prospectively. Among the patients studied, 82% were caucasian, 53% were male and the average age was 41.7 years old. The most frequent cardiovascular risk factors found were systemic hypertension and tobacco use. Other aspects evaluated were history of previous migraine, initial treatment and prognosis. In conclusion, although the population studied was multiethnic, there was a marked predominance of caucasians. The analysis of clinical and neuroimaging data from patients with SDCVA allows a better understanding of the disease, leading to an earlier diagnosis and more appropriate treatment.