ABSTRACT
BACKGROUND AND OBJECTIVES: Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders characterized by progressive pyramidal tract involvement. SPG76 is a recently identified form of HSP, caused by biallelic calpain-1 (CAPN1) variants. The most frequently described MRI abnormality in SPG76 is mild cerebellar atrophy and non-specific white matter abnormalities were reported in only one case. Following the identification of prominent white matter abnormalities in a subject with CAPN1 variants, which delayed the diagnosis, we aimed to verify the presence of MRI patterns of white matter involvement specific to this HSP. METHODS: We performed a retrospective radiological qualitative analysis of 15 subjects with SPG76 (4 previously unreported) initially screened for white matter involvement. Moreover, we performed quantitative analyses in our proband with available longitudinal studies. RESULTS: We observed bilateral, periventricular white matter involvement in 12 subjects (80%), associated with multifocal subcortical abnormalities in 5 of them (33.3%). Three subjects (20%) presented only multifocal subcortical involvement. Longitudinal quantitative analyses of our proband revealed increase in multifocal white matter lesion count and increased area of periventricular white matter involvement over time. DISCUSSION: SPG76 should be added to the list of HSPs with associated white matter abnormalities. We identified periventricular white matter involvement in subjects with SPG76, variably associated with multifocal subcortical white matter abnormalities. These findings, in the presence of progressive spastic paraparesis, can mislead the diagnostic process towards an acquired white matter disorder.
Subject(s)
Paraparesis, Spastic , Spastic Paraplegia, Hereditary , White Matter , Humans , White Matter/diagnostic imaging , White Matter/pathology , Retrospective Studies , Spastic Paraplegia, Hereditary/diagnostic imaging , Spastic Paraplegia, Hereditary/genetics , Magnetic Resonance ImagingABSTRACT
Pruritus represents one of the main clinical complaints in medical practice, and leads to significant impairment of life quality and some discomfort. Although the knowledge of its main primary and secondary etiologies is well-established in Internal Medicine, especially in Hepatology, its pathophysiological basis and specific therapeutic-directed approaches are still very complex and need a proper systematization for comprehension. This review aims to present the main current themes regarding the main clinical, pathophysiological, therapeutical and management aspects of cholestasis-associated pruritus. METHODS: The authors performed a wide review of practical clinical guidelines, review articles and original articles from manuscripts published and indexed in PubMed. CONCLUSIONS: Pruritus in cholestasis represents a complex symptom in clinical practice and can be secondary to different pathophysiological mechanisms; its early recognition allows a proper therapeutic approach in most cases.
O prurido representa uma das principais queixas clínicas na prática médica e origina importante comprometimento da qualidade de vida, além de desconforto. Apesar de suas principais etiologias primárias e secundárias serem de conhecimento bem estabelecido na Clínica Médica, em especial na Hepatologia, suas bases fisiopatológicas e os princípios da terapêutica específica direcionada são bastante complexos e necessitam uma sistematização adequada para sua compreensão apropriada. Esta revisão objetiva abordar os principais temas atuais referentes às bases clínicas, fisiopatológicas, terapêuticas e de manejo do prurido relacionados à colestase. Os autores realizaram ampla revisão em diretrizes clínicas práticas, artigos de revisão e publicações originais de artigos publicados e indexados na base PubMed. O prurido na colestase representa um sintoma complexo na prática clínica e pode decorrer de diferentes mecanismos fisiopatológicos secundários. Seu reconhecimento precoce possibilita a abordagem terapêutica apropriada na maioria dos casos.
Subject(s)
Humans , Antipruritics/therapeutic use , Cholestasis/complications , Pruritus/etiology , Pruritus/therapy , Skin/innervation , Neuralgia/physiopathologyABSTRACT
Sialidosis is a rare lysosomal storage disease with a wide clinical spectrum ranging from nearly asymptomatic to severe presentations. We present two Brazilian siblings with sialidosis, the first patient with sialidosis type I, and the second with sialidosis type II. Our report reinforces the relevance of ophthalmologic evaluation in patients with early and late-onset ataxias, if an association with myoclonus or dysmorphic features is present or not. Also, we demonstrate that sialidosis might represent a single genetic entity with variable clinical expression through these two siblings.
