Prevalência de disfagia orofaríngea nas paraparesias espásticas hereditárias

Hereditary spastic paraplegias (HSP) are a group of genetic diseases characterized by lower limb spasticity with or without additional neurological features. Swallowing dysfunction is poorly studied in HSP and its presence can lead to significant respiratory and nutritional complications. Objectives: The aim of this study was to evaluate the frequency and clinical characteristics of dysphagia in different types of HSP. Methods: A two-center cross-sectional prevalence study was performed. Genetically confirmed HSP patients were evaluated using the Northwestern Dysphagia Patient Check Sheet and the Functional Oral Intake Scale. In addition, self-perception of dysphagia was assessed by the Eat Assessment Tool-10 and the Swallowing Disturbance Questionnaire. Results: Thirty-six patients with spastic paraplegia type 4 (SPG4), five with SPG11, four with SPG5, four with cerebrotendinous xanthomatosis (CTX), three with SPG7, and two with SPG3A were evaluated. Mild to moderate oropharyngeal dysphagia was present in 3/5 (60%) of SPG11 and 2/4 (50%) of CTX patients. A single SPG4 (2%) and a single SPG7 (33%) patient had mild oropharyngeal dysphagia. All other evaluated patients presented with normal or functional swallowing. Conclusions: Clinically significant oropharyngeal dysphagia was only present in complicated forms of HSP Patients with SPG11 and CTX had the highest risks for dysphagia, suggesting that surveillance of swallowing function should be part of the management of patients with these disorders.As paraparesias espásticas hereditárias (PEH) são um grupo de doenças genéticas caracterizado por espasticidade dos membros inferiores com ou sem características neurológicas adicionais. A disfunção da deglutição é pouco estudada nas PEH e sua presença pode levar a complicações respiratórias e nutricionais significativas. Objetivo: O objetivo deste estudo foi avaliar a frequência e a caracterização clínica da disfagia em diferentes tipos de PEH. Métodos: Foi realizado um estudo transversal em dois centros. Os pacientes com PEH confirmados geneticamente foram avaliados pelo Northwestern Dysphagia Patient Check Sheet e pela Escala Funcional de Ingestão Oral. Além disso, a autopercepção da disfagia foi avaliada pelo Eat Assessment Tool-10 e pelo Swallowing Disturbance Questionnaire. Resultados: Trinta e seis pacientes com paraplegia espástica tipo 4 (SPG4), cinco com SPG11, quatro com SPG5, quatro com xantomatose cerebrotendinosa (CTX), três com SPG7 e dois com SPG3A foram avaliados. Disfagia orofaríngea leve a moderada estava presente em 3/5 (60%) dos pacientes com SPG11 e 2/4 (50%) dos pacientes com CTX. Um único SPG4 (2%) e um único SPG7 (33%) apresentaram disfagia orofaríngea leve. Todos os outros pacientes avaliados apresentaram deglutição normal ou funcional. Conclusão: Disfagia orofaríngea clinicamente significativa estava presente apenas nas formas complicadas de PEH. A SPG11 e CTX apresentaram maiores riscos de disfagia, sugerindo que a avaliação da deglutição deve fazer parte do manejo dos pacientes com essas condições

Are cognitive changes in hereditary spastic paraplegias restricted to complicated forms?

Background: Little is known about the cognitive profile of Hereditary Spastic Paraplegias (HSP), where most scientific attention has been given to motor features related to corticospinal tract degeneration. Objectives: We aimed to perform a broad characterization of the cognitive functions of patients with pure and complicated HSP as well as to determine the frequency of abnormal cognitive performances in the studied subtypes. Methods: A two-center cross-sectional case-control study was performed. All individuals underwent cognitive assessment through screening tests (Mini Mental State Examination—MEEM and Montreal Cognitive Assessment—MOCA) and tests to assess specific cognitive functions (Verbal fluency with phonological restriction—FAS; Verbal categorical fluency—FAS-cat and Rey's Verbal Auditory Learning Test -RAVLT). Results: Fifty four patients with genetically confirmed HSP diagnosis, 36 with spastic paraplegia type 4 (SPG4), 5 SPG11, 4 SPG5, 4 cerebrotendinous xanthomatosis (CTX), 3 SPG7 and 2 SPG3A, and 10 healthy, unrelated control subjects, with similar age, sex, and education participated in the study. SPG4 patients had worse performances in MOCA, FAS, FAS-cat, and RAVLT when compared to controls. Most SPG4 patients presented cognitive changes not compatible with dementia, performing poorly in memory, attention and executive functions. SPG5 patients scored lower in executive functions and memory, and SPG7 patients performed poorly on memory tasks. All evaluated cognitive functions were markedly altered in CTX and SPG11 patients. Conclusions: Cognitive abnormalities are frequent in HSP, being more severe in complicated forms. However, cognitive impairments of pure HSPs might impact patients' lives, decreasing families' socioeconomic status and contributing to the overall disease burden

Dysarthria in hereditary spastic paraplegia type 4

Objective: To describe the speech pattern of patients with hereditary Spastic Paraplegia type 4 (SPG4) and correlated it with their clinical data. Methods: Cross-sectional study was carried out in two university hospitals in Brazil. Two groups participated in the study: the case group (n = 28) with a confirmed genetic diagnosis for SPG4 and a control group (n = 17) matched for sex and age. The speech assessment of both groups included: speech task recording, acoustic analysis, and auditory-perceptual analysis. In addition, disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Results: In the auditory-perceptual analysis, 53.5% (n = 15) of individuals with SPG4 were dysarthric, with mild to moderate changes in the subsystems of phonation and articulation. On acoustic analysis, SPG4 subjects’ performances were worse in measurements related to breathing (maximum phonation time) and articulation (speech rate, articulation rate). The articulation variables (speech rate, articulation rate) are related to the age of onset of the first motor symptom. Conclusion: Dysarthria in SPG4 is frequent and mild, and it did not evolve in conjunction with more advanced motor diseases. This data suggest that diagnosed patients should be screened and referred for speech therapy evaluation and those pathophysiological mechanisms of speech involvement may differ from the length-dependent degeneration of the corticospinal tract

Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias

The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). A multicenter historical cohort was performed at five centers in Brazil, in which probands and affected relatives' data from consecutive families with childhood-onset HSP (onset < 12 years-old) were reviewed from 2011 to 2020. One hundred and six individuals (83 families) with suspicion of childhood-onset HSP were evaluated, being 68 (50 families) with solved genetic diagnosis, 6 (5 families) with candidate variants in HSP-related genes and 32 (28 families) with unsolved genetic diagnosis. The most common childhood-onset subtype was SPG4, 11/50 (22%) families with solved genetic diagnosis; followed by SPG3A, 8/50 (16%). Missense pathogenic variants in SPAST were found in 54.5% of probands, favoring the association of this type of variant to childhood-onset SPG4. Survival curves to major handicap and cross-sectional Spastic Paraplegia Rating Scale progressions confirmed the slow neurological deterioration in SPG4 and SPG3A. Most common complicating features and twenty variants not previously described in HSP-related genes were reported. These results are fundamental to understand the molecular and clinical epidemiology of childhood-onset HSP, which might help on differential diagnosis, patient care and guiding future collaborative trials for these rare diseases

Are Cognitive Changes in Hereditary Spastic Paraplegias Restricted to Complicated Forms?

Background: Little is known about the cognitive profile of Hereditary Spastic Paraplegias (HSP), where most scientific attention has been given to motor features related to corticospinal tract degeneration.Objectives: We aimed to perform a broad characterization of the cognitive functions of patients with pure and complicated HSP as well as to determine the frequency of abnormal cognitive performances in the studied subtypes.Methods: A two-center cross-sectional case-control study was performed. All individuals underwent cognitive assessment through screening tests (Mini Mental State Examination—MEEM and Montreal Cognitive Assessment—MOCA) and tests to assess specific cognitive functions (Verbal fluency with phonological restriction—FAS; Verbal categorical fluency—FAS-cat and Rey's Verbal Auditory Learning Test -RAVLT).Results: Fifty four patients with genetically confirmed HSP diagnosis, 36 with spastic paraplegia type 4 (SPG4), 5 SPG11, 4 SPG5, 4 cerebrotendinous xanthomatosis (CTX), 3 SPG7 and 2 SPG3A, and 10 healthy, unrelated control subjects, with similar age, sex, and education participated in the study. SPG4 patients had worse performances in MOCA, FAS, FAS-cat, and RAVLT when compared to controls. Most SPG4 patients presented cognitive changes not compatible with dementia, performing poorly in memory, attention and executive functions. SPG5 patients scored lower in executive functions and memory, and SPG7 patients performed poorly on memory tasks. All evaluated cognitive functions were markedly altered in CTX and SPG11 patients.Conclusions: Cognitive abnormalities are frequent in HSP, being more severe in complicated forms. However, cognitive impairments of pure HSPs might impact patients' lives, decreasing families' socioeconomic status and contributing to the overall disease burden

Autonomic assessment in patients with hereditary spastic paraplegia SPG4

Orientador: Marcondes Cavalcante França JuniorDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: As mutações no gene SPAST são a causa mais comum de paraparesia espástica hereditária (PEH-SPG4), a qual se caracteriza por fraqueza progressiva nos membros inferiores, espasticidade e hiperreflexia. Existem poucos estudos acerca das manifestações não motoras nesta doença e nenhum a respeito do envolvimento do sistema nervoso autonômico. Portanto, o objetivo deste trabalho foi determinar a frequência e padrão das manifestações autonômicas em pacientes com PEH-SPG4, além de determinar a relevância clínica e os possíveis fatores associados a estas manifestações. Métodos: Foram incluídos 34 pacientes com diagnóstico molecular confirmado de PEH-SPG4 em um estudo transversal multicêntrico. A versão adaptada e validada para o português da escala Scales for Outcomes in Parkinson¿s Disease Autonomic Questionnaire (SCOPA-AUT) foi aplicada para quantificar a gravidade dos sintomas autonômicos em todos estes indivíduos. Em 26 deles, realizamos a avaliação neurofisiológica detalhada (variabilidade da frequência, resposta simpática cutânea ¿ RSC e estudo quantitativo do reflexo axonal sudomotor ¿ QSART). Os resultados obtidos foram comparados com 44 indivíduos saudáveis pareados em idade e sexo. Resultados: No grupo de PEH-SPG4, havia 18 homens, com idade média de 47,7 ± 12,6 anos. A pontuação da SCOPA-AUT foi similar entre pacientes e controles (p=0,238). Apenas a pontuação do domínio urinário da escala foi significativamente maior entre os pacientes (4 vs 2,5; p=0,05). Ausência da RSC em mãos e pés foi mais frequente em pacientes (20% vs 0%; p<0,001 e 64% vs 0%; p=0,006 respectivamente). A resposta do QSART foi menor em todas regiões registradas no grupo PEH-SPG4. Discussão: Os nossos resultados indicam que os pacientes com PEH-SPG4 apresentam disfunção sudomotora ocasionada pelo dano às fibras finas pós-ganglionares colinérgicas. A neurodegeneração nos pacientes com PEH-SPG4 se estende ao sistema nervoso periféricoAbstract: Introduction: SPAST mutations are the most common cause of hereditary spastic paraplegia (SPG4-HSP), which is characterized by progressive lower limb weakness, spasticity and hyperreflexia. There are few studies about non-motor manifestations in this disease and none about autonomic involvement. Therefore, our aim was to determine the frequency and pattern of autonomic complaints in patients with SPG4-HSP, as well as to determine the clinical relevance and the possible factors associated with these manifestations. Materials and Methods: We recruited 34 molecularly confirmed SPG4 patients in a multicenter cross-sectional study, of which 26 underwent detailed neurophysiologic testing (heart rate variability, Sympathetic skin response - SSR and Quantitative Sudomotor Axonal Reflex Test - QSART). The Scales for Outcomes in Parkinson¿s Disease Autonomic Questionnaire (SCOPA-AUT) was applied to quantify the severity of autonomic symptoms. Results were compared with 44 age and gender-matched healthy controls using non-parametric tests. P-values <0.05 were considered significant. Results: In the SPG4-HSP group, there were 18 men, with a mean age of 47.7 ± 12.6 years old. SCOPA-AUT scores were similar between patients and controls (p=0.238). Only the urinary domain subscore was significantly higher among patients (4 vs 2.5, p=0.05). Absent SSR in the hands and feet were more frequent among patients (20% vs 0%, p<0.001 and 64% vs 0%, p=0.006 respectively). QSART responses were also smaller throughout all recording regions in the SPG4-HSP group. Discussion: Our results indicate that SPG4-HSP patients have sudomotor dysfunction caused by damaged small postganglionic cholinergic fibers. Damage in SPG4-HSP extends to the peripheral nervous systemMestradoFisiopatologia MédicaMestra em Ciências2013/01766-7CAPESFAPES