Reabilitação fisioterapêutica em pacientes com síndrome da pessoa rígida: revisão integrativa / Physiotherapy rehabilitation in patients with stiff person syndrome: integrative review

Introdução: A Síndrome da Pessoa Rígida é uma doença neuroimunológica rara do sistema nervoso central caracterizada por espasmos dolorosos e rigidez progressiva que envolvem os músculos proximais dos membros e axiais do tronco. A forma clássica tem início insidioso com piora gradual ao longo do tempo e muitas vezes leva à incapacidade permanente. Objetivo: Analisar os estudos publicados na literatura científica que utilizaram a reabilitação fisioterapêutica como proposta de tratamento dos sintomas motores na Síndrome da Pessoa Rígida. Método: Trata-se de uma revisão integrativa da literatura realizada no período de julho a dezembro de 2022 nas bases de dados PubMed, SciELO, LILACS e BVS. Resultados: Foram encontrados 12 artigos publicados entre o período de 2002 a 2021, que discorriam sobre o tratamento fisioterapêutico nesta população. O número escasso de estudos se dá pela raridade da patologia que dificulta a realização de ensaios clínicos robustos. Os artigos selecionados eram relatos de casos de um ou mais indivíduos, com enfoque nas intervenções realizadas de acordo com cada queixa funcional apresentada, sendo estas a dor, fraqueza muscular, hipomobilidade articular, rigidez, instabilidade postural, alterações na marcha e limitações nas atividades de vida diária. Conclusão: A reabilitação fisioterapêutica faz parte do tratamento sintomatológico e tem como finalidade, auxiliar na manutenção da funcionalidade e qualidade de vida, minimizando as repercussões motoras que são desencadeadas pela síndrome.

Introduction: Stiff Person Syndrome is a rare neuroimmunological disease of the central nervous system characterized by painful spasms and progressive rigidity involving the proximal muscles of the limbs and axial muscles of the trunk. The classic form has an insidious onset with gradual worsening over time and often leads to permanent disability. Objective: To analyze the studies published in the scientific literature that used hysiotherapeutic rehabilitation as a proposal for treating motor symptoms in Stiff Person Syndrome. Method: This is an integrative review of the literature carried out from July to December 2022 in the PubMed, SciELO, LILACS and VHL databases. Results: 12 articles published between 2002 and 2021 were found, which discussed physiotherapeutic treatment in this population. The scarce number of studies is due to the rarity of the pathology, which makes it difficult to carry out robust clinical trials. The selected articles were case reports of one or more individuals, focusing on interventions carried out according to each functional complaint presented, these being pain, muscle weakness, joint hypomobility, stiffness, postural instability, changes in gait and limitations in walking activities. daily life. Conclusion: Physiotherapy rehabilitation is part of symptomatological treatment and aims to help maintain functionality and quality of life, minimizing the motor repercussions that are triggered by the syndrome.

Neurofilament light chain as a biomarker for acute hepatic porphyrias.

Background: Acute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and prognostic value of serum neurofilament light chain (NfL) as potential biomarker for AHP. Methods: We conducted a cross-sectional observational study to evaluate NfL levels in patients with AHP. They were divided in different groups: normal health individuals; patients with definitive diagnosis of AHP during acute episodes; patients with AHP and infrequent attacks; patients with AHP and recurrent attacks; asymptomatic individuals with positive genetic testing and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels elevated 4 or more times ("high excretors"); asymptomatic individuals with exclusive positive genetic test; control group with Hereditary Amyloidosis related to Transthyretin with Polyneuropathy (ATTRv-PN). Results: During acute attacks, serum NfL levels were 68 times higher compared to normal controls and disclosed a strong correlation with ALA and PBG levels; also exhibited elevated levels in patients with chronic symptoms regardless of the number of disease attacks compared to healthy controls, and at similar levels to patients with ATTRv-PN, which is a model of progressive neuropathy. Conclusion: This study represents the first to establish NfL as a biomarker for AHP, disclosing NfL as a sensitive biomarker for axonal damage and chronic symptom occurrence. This study not only underscores that neurological damage associated with the disease in any patient, irrespective of the number of attacks, but also reinforces the progressive and profoundly debilitating nature of acute and chronic symptoms observed in individuals with AHP.

Myasthenia gravis in the complex scenario of LRBA-related immune dysregulation / Miastenia gravis no cenário clínico complexo das imunodesregulações relacionadas ao gene LRBA

Autoimmune diseases have been progressively recognized as a potential complication of primary immunodeficiency, especially for some genetic subtypes of common variable immunodeficiency. Although often associated with other autoimmune disorders, autoimmune myasthenia gravis is occasionally identified as a neuromuscular complication of primary immunodeficiency. We report the case of a Brazilian woman with common variable immunodeficiency-8 due to an LRBA variant, in which myasthenia gravis was identified in association with anti-acetylcholine receptor antibody. Marked clinical improvement occurred after intravenous immunoglobulin therapy.

Doenças autoimunes foram progressivamente reconhecidas como complicações potenciais das imunodeficiências primárias, especialmente para alguns subtipos genéticos das imunodeficiências comuns variáveis. Embora se associe comumente a outras doenças autoimunes, a Miastenia gravis autoimune adquirida foi raramente associada como complicação neuromuscular de imunodeficiências primárias. É descrito neste artigo o caso de paciente brasileira do sexo feminino com diagnóstico de Imunodeficiência Comum Variável tipo 8 por variante no gene LRBA, na qual foi identificada Miastenia gravis em associação a anticorpos antirreceptor de acetilcolina. Ela evoluiu com marcante melhora clínica após a introdução de terapêutica com imunoglobulina endovenosa.

Adult-onset non-5q proximal spinal muscular atrophy: a comprehensive review / Atrofia muscular espinhal não-5q proximal de início no adulto: uma revisão abrangente

Abstract Background: Adult-onset spinal muscular atrophy (SMA) represents an expanding group of inherited neurodegenerative disorders in clinical practice. Objective: This review aims to synthesize the main clinical, genetic, radiological, biochemical, and neurophysiological aspects related to the classical and recently described forms of proximal SMA. Methods: The authors performed a non-systematic critical review summarizing adult-onset proximal SMA presentations. Results: Previously limited to cases of SMN1-related SMA type 4 (adult form), this group has now more than 15 different clinical conditions that have in common the symmetrical and progressive compromise of lower motor neurons starting in adulthood or elderly stage. New clinical and genetic subtypes of adult-onset proximal SMA have been recognized and are currently target of wide neuroradiological, pathological, and genetic studies. Conclusions: This new complex group of rare disorders typically present with lower motor neuron disease in association with other neurological or systemic signs of impairment, which are relatively specific and typical for each genetic subtype.

RESUMO Antecedentes: Atrofia muscular espinhal (AME) de início no adulto representa um grupo de doenças neurodegenerativas hereditárias em expansão na prática clínica. Objetivo: Este artigo de revisão sintetiza os principais aspectos clínicos, genéticos, radiológicos, bioquímicos e neurofisiológicos relacionados às formas clássicas e recentemente descritas de AME proximal do adulto. Métodos: Os autores realizaram uma revisão crítica não sistemática descrevendo as principais apresentações de AME proximal de início no adulto. Resultados: Previamente restrito às apresentações de AME tipo 4 associada ao gene SMN1, este grupo atualmente envolve mais de 15 diferentes condições clínicas que compartilham entre si a presença de comprometimento progressivo e simétrico do neurônio motor inferior se iniciando no adulto ou no idoso. Novos subtipos clínicos e genéticos de AME proximal de início no adulto foram reconhecidas e são alvos atuais de estudos direcionados a aspectos neurorradiológicos, patológicos e genéticos. Conclusões: Este novo grupo complexo de doenças raras tipicamente se apresenta com doença do neurônio motor inferior em associação com outros sinais de comprometimento neurológico ou sistêmico, os quais apresentam padrões relativamente específicos para cada subtipo genético.

Leigh syndrome caused by mitochondrial DNA-maintenance defects revealed by whole exome sequencing.

Leigh syndrome represents a complex inherited neurometabolic and neurodegenerative disorder associated with different clinical, genetic and neuroimaging findings in the context of bilateral symmetrical lesions involving the brainstem and basal ganglia. Heterogeneous neurological manifestations such as spasticity, cerebellar ataxia, dystonia, choreoathetosis and parkinsonism are associated with multisystemic and ophthalmological abnormalities due to >75 different monogenic causes. Here, we describe the clinical and genetic features of a Brazilian cohort of patients with Leigh Syndrome in which muscle biopsy analysis showed mitochondrial DNA defects and determine the utility of whole exome sequencing for a final genetic diagnostic in this cohort.

Leukodystrophy with disorders of sex development due to WT1 mutations.

BACKGROUND: Hypomyelinating leukodystrophies represent an expanding group of neurogenetic disorders characterized primarily by central nervous system hypomyelination and variable neurological and non-neurological involvement. Hypomyelinating disorders have been rarely associated with gonadal dysfunction, being mainly represented by hypogonadotrophic hypogonadism in 4H syndrome. WT1 gene-associated disorders are classically associated with complex phenotypes including early carcinogenic risk for gonadoblastoma and Wilms' tumor, chronic renal failure, nephrotic syndrome and sex developmental disorders in intersex disorders and ambiguous genitalia. METHODS: The authors describe three non-related Brazilian patients with hypomyelinating leukodystrophy associated with complex neurological and systemic dysfunction with WT1 gene mutations. RESULTS: All described patients presented with similar neuroimaging features including thin corpus callosum, mild to moderate cerebellar atrophy and diffuse periventricular and profound hypomyelinating leukodystrophy involving supratentorial white matter with classical compromise linked to inherited non-somatic WT1 gene mutations in a similar pattern to Denys-Drash syndrome, including nephrotic syndrome with different glomerular disease, chronic renal failure, intersex disorder with ambiguous genitalia, and early occurrence of specific tumors, such as Wilms' tumor and gonadoblastoma. CONCLUSIONS: Clinicians must include WT1 gene mutations in the differential diagnosis of hypomyelinating leukodystrophy with nephrotic syndrome, chronic renal failure, ambiguous genitalia or sex developmental disorders.