RESUMO

Cerebrotendinous Xanthomatosis represents a rare and underdiagnosed inherited neurometabolic disorder due to homozygous or compound heterozygous variants involving the CYP27A1 gene. This bile acid metabolism disorder represents a key potentially treatable neurogenetic condition due to the wide spectrum of neurological presentations in which it most commonly occurs. Cerebellar ataxia, peripheral neuropathy, spastic paraparesis, epilepsy, parkinsonism, cognitive decline, intellectual disability, and neuropsychiatric disturbances represent some of the most common neurological signs observed in this condition. Despite representing key features to increase diagnostic index suspicion, multisystemic involvement does not represent an obligatory feature and can also be under evaluated during diagnostic work-up. Chenodeoxycholic acid represents a well-known successful therapy for this inherited metabolic disease, however its unavailability in several contexts, high costs and common use in patients at late stages of disease course limit more favorable neurological outcomes for most individuals. This review article aims to discuss and highlight the most recent and updated knowledge regarding clinical, pathophysiological, neuroimaging, genetic and therapeutic aspects related to Cerebrotendinous Xanthomatosis.

RESUMO

BACKGROUND: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant spinocerebellar ataxia caused by pathological expansion of CAG trinucleotide repeats in the ATN1 gene. Most cases were described in patients from Japanese ancestry who presented with adult-onset progressive cerebellar ataxia associated with cognitive impairment, choreoathetosis and other movement disorders. DRPLA has been rarely described in Brazilian patients. METHODS: We performed a retrospective observational multicentric study including six different Neurology Centers in Brazil. All patients with genetically confirmed diagnosis of DRPLA had their medical records evaluated and clinical, genetic and neuroimaging features were analyzed. RESULTS: We describe of eight Brazilian patients (5 male, 3 female) from four nuclear families with genetically confirmed DRPLA. The most common neurological features included cerebellar ataxia (n = 7), dementia (n = 3), chorea (n = 2), psychiatric disturbances (n = 2), progressive myoclonic epilepsy (n = 2) and severe bulbar signs (n = 1). Progressive myoclonic epilepsy was observed in two juvenile-onset cases before 20-year. A large CAG trinucleotide length was observed in the two juvenile-onset cases and genetic anticipation was observed in all cases. Neuroimaging studies disclosed cerebellar atrophy (n = 6), as well as brainstem and cerebellar atrophy (n = 2) and leukoencephalopathy (n = 1). CONCLUSION: The patients described herein reinforce that clinical features of DRPLA are highly influenced by age of onset, genetic anticipation and CAG repetition lengths. There is a large complex spectrum of neurological features associated with DRPLA, varying from pure cerebellar ataxia to dementia associated with other movement disorders (myoclonus, choreoathetosis). DRPLA is an unusual cause of cerebellar ataxia and neurodegeneration in Brazilian patients.

Assuntos

Povo Asiático/genética , Epilepsias Mioclônicas Progressivas/etnologia , Epilepsias Mioclônicas Progressivas/genética , Proteínas do Tecido Nervoso/genética , Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Brasil , Ataxia Cerebelar/etnologia , Ataxia Cerebelar/genética , Criança , Demência/etnologia , Demência/genética , Feminino , Humanos , Japão/etnologia , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etnologia , Transtornos dos Movimentos/genética , Neuroimagem , Estudos Retrospectivos , Adulto Jovem

RESUMO

Acute hepatic porphyria represents a rare, underdiagnosed group of inherited metabolic disorders due to hereditary defects of heme group biosynthesis pathway. Most patients have their definite diagnosis after several years of complex and disabling clinical manifestations and commonly after life-threatening acute neurovisceral episodes or severe motor handicap. Many key studies in the last two decades have been performed and led to the discovery of novel possible diagnostic and prognostic biomarkers and to the development of new therapeutic purposes, including small interfering RNA-based therapy, specifically driven to inhibit selectively delta-aminolevulinic acid synthase production and decrease the recurrence number of severe acute presentation for most patients. Several distinct mechanisms have been identified to contribute to the several neuromuscular signs and symptoms. This review article aims to present the current knowledge regarding the main pathophysiological mechanisms involved with the acute and chronic presentation of acute hepatic porphyria and to highlight the relevance of such content for clinical practice and in decision making about therapeutic options.

RESUMO

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rare, progressive, and fatal neurodegenerative disease due to upper and lower motor neuron involvement with symptoms classically occurring in adulthood with an increasing recognition of juvenile presentations and childhood neurodegenerative disorders caused by genetic variants in genes related to Amyotrophic Lateral Sclerosis. The main objective of this study is detail clinical, radiological, neurophysiological, and genetic findings of a Brazilian cohort of patients with a recent described condition known as Spastic Tetraplegia and Axial Hypotonia (STAHP) due to SOD1 deficiency and compare with other cases described in the literature and discuss whether the clinical picture related to SOD1 protein deficiency is a new entity or may be represent a very early-onset form of Amyotrophic Lateral Sclerosis. METHODS: We conducted a case series report which included retrospective data from five Brazilian patients with SOD1 protein deficiency of a Brazilian reference center for Neuromuscular Disorders. Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population. RESULTS: All 5 patients presented with a childhood-onset neurodegenerative disorders characterized by spastic tetraplegia with axial hypotonia in all cases, with gestational history showing polyhydramnios in 4/5 and intrauterine growth restriction in 3/5 patients, with most patients initially presenting a normal motor development until the six month of life or during the first year followed by a rapidly progressive motor decline with severe dysphagia and respiratory insufficiency in all patients accompanied by cognitive impairment in 3/5 patients. All patients were homozygous for the c.335dupG (p.Cys112Trpfs*11) mutation in the SOD1 gene with completely decreased enzyme activity. CONCLUSIONS: This case series is the biggest data collection of the new recent clinical entity described as Spastic Tetraplegia and Axial Hypotonia (STAHP) due to SOD1 deficiency.

Assuntos

Esclerose Lateral Amiotrófica , Hipotonia Muscular , Superóxido Dismutase-1 , Adulto , Esclerose Lateral Amiotrófica/genética , Criança , Humanos , Hipotonia Muscular/genética , Mutação/genética , Quadriplegia/genética , Estudos Retrospectivos , Superóxido Dismutase-1/genética

RESUMO

PURPOSE OF REVIEW: The aims of this review are to discuss the imaging modalities used to assess muscle changes in myopathies, to provide an overview of the inherited myopathies focusing on their patterns of muscle involvement in magnetic resonance imaging (MR), and to propose up-to-date imaging-based diagnostic algorithms that can help in the diagnostic workup. CONCLUSION: Familiarization with the most common and specific patterns of muscular involvement in inherited myopathies is very important for radiologists and neurologists, as imaging plays a significant role in diagnosis and follow-up of these patients. KEY POINTS: • Imaging is an increasingly important tool for diagnosis and follow-up in the setting of inherited myopathies. • Knowledge of the most common imaging patterns of muscle involvement in inherited myopathies is valuable for both radiologists and neurologists. • In this review, we present imaging-based algorithms that can help in the diagnostic workup of myopathies.

Assuntos

Doenças Musculares , Algoritmos , Humanos , Imageamento por Ressonância Magnética , Músculos , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/genética , Radiologistas

Assuntos

Alcaptonúria/diagnóstico , Doenças Ósseas Metabólicas/diagnóstico por imagem , Vértebras Cervicais/diagnóstico por imagem , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Ocronose/diagnóstico , Compressão da Medula Espinal/diagnóstico por imagem , Espondilose/diagnóstico por imagem , Adulto , Alcaptonúria/complicações , Alcaptonúria/urina , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Ácido Homogentísico/urina , Humanos , Deslocamento do Disco Intervertebral/etiologia , Deslocamento do Disco Intervertebral/fisiopatologia , Masculino , Ocronose/complicações , Ocronose/urina , Doenças da Esclera/etiologia , Doenças da Esclera/patologia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/fisiopatologia , Espondilose/etiologia , Espondilose/fisiopatologia , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia

RESUMO

Genetic leukoencephalopathies represent an expanding group of inherited disorders associated with involvement of brain white matter. Cystic degeneration has been previously described with some acquired or inherited leukoencephalopathies. We describe a 6-month-old Brazilian boy with a 2-month history of severe and rapidly progressive developmental and psychomotor regression and seizures. Neurological examination showed spastic tetraparesis and lethargy. Neuroimaging showed diffuse and symmetric cavitating cystic leukoencephalopathy. Whole-exome sequencing revealed compound heterozygous mutations in the NFU1 gene, providing definite genetic diagnosis of multiple mitochondrial dysfunction syndrome type 1. We report a rare presentation of early-onset cystic leukoencephalopathy in the context of multiple mitochondrial dysfunction syndrome type 1.