Assuntos
Autoanticorpos/sangue , Encefalopatias/imunologia , Proteínas ELAV/imunologia , Neoplasias Pulmonares/complicações , Tumores Neuroendócrinos/complicações , Encefalopatias/complicações , Encefalopatias/diagnóstico por imagem , Encefalopatias/terapia , Diagnóstico Diferencial , Humanos , Sistema Límbico/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/imunologia , Tumores Neuroendócrinos/terapiaAssuntos
Síndrome de Churg-Strauss/complicações , Doenças Desmielinizantes/complicações , Polineuropatias/complicações , Síndrome de Churg-Strauss/patologia , Síndrome de Churg-Strauss/fisiopatologia , Síndrome de Churg-Strauss/terapia , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/fisiopatologia , Doenças Desmielinizantes/terapia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/patologia , Polineuropatias/fisiopatologia , Polineuropatias/terapia , Nervo Sural/patologia , Nervo Sural/fisiopatologiaRESUMO
Non-invasive and simple to measure biomarkers are still an unmet need for myotonic dystrophy type 1 (DM1). Indeed, muscle biopsies can be extremely informative, but their invasive nature limits their application. Extracellular microRNAs are emerging humoral biomarkers and preliminary studies identified a group of miRNAs that are deregulated in the plasma or serum of small groups of DM1 patients. Here we adopted very stringent selection and normalization criteria to validate or disprove these miRNAs in 103 DM1 patients and 111 matched controls. We confirmed that 8 miRNAs out of 12 were significantly deregulated in DM1 patients: miR-1, miR-27b, miR-133a, miR-133b, miR-206, miR-140-3p, miR-454 and miR-574. The levels of these miRNAs, alone or in combination, discriminated DM1 from controls significantly, and correlated with both skeletal muscle strength and creatine kinase values. Interestingly, miR-133b levels were significantly higher in DM1 female patients. Finally, the identified miRNAs were also deregulated in the plasma of a small group (n = 30) of DM2 patients. In conclusion, this study proposes that miRNAs might be useful as DM1 humoral biomarkers.
Assuntos
MicroRNAs/sangue , Distrofia Miotônica/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisAssuntos
Transtornos da Motilidade Ocular/complicações , Síndrome de Zellweger/complicações , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação/genética , Transtornos da Motilidade Ocular/genética , Fator 2 da Biogênese de Peroxissomos , Tempo de Reação/fisiologia , Síndrome de Zellweger/genéticaAssuntos
Apraxias/congênito , Ataxia Cerebelar/complicações , Ataxia Cerebelar/diagnóstico , Síndrome de Cogan/complicações , Síndrome de Cogan/diagnóstico , Apraxias/complicações , Apraxias/diagnóstico , Criança , Eletromiografia , Feminino , Humanos , Itália , Imageamento por Ressonância Magnética , Masculino , IrmãosAssuntos
Encéfalo/patologia , Xantomatose Cerebrotendinosa/diagnóstico , Xantomatose Cerebrotendinosa/patologia , Ácido Quenodesoxicólico/uso terapêutico , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Xantomatose Cerebrotendinosa/tratamento farmacológicoAssuntos
Proteínas de Transporte de Cátions/genética , Terapia por Quelação/métodos , Doenças Metabólicas/genética , Mutação/genética , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/genética , Feminino , Humanos , Estudos Longitudinais , Doenças Metabólicas/complicações , Pessoa de Meia-Idade , Transtornos Parkinsonianos/complicações , Transportador 8 de ZincoRESUMO
Polyneuropathy has been reported in cerebrotendinous xanthomatosis (CTX), although its nature and possible association with certain genotypes and phenotypes are unclear. The effect of chronic administration of chenodeoxycholic acid (CDCA) on peripheral nerve conduction parameters is still debated. We report clinical, laboratory, and electrophysiological findings in 35 CTX patients. Twenty-six subjects (74.2 %) showed peripheral nerve abnormalities. Polyneuropathy was predominantly axonal (76.9 % of patients) and generally mild. No correlation was found between its presence and clinical or biochemical data. In polyneuropathic patients, CDCA treatment improved electrophysiological conduction parameters, irrespective of the duration of therapy. Improvement mainly concerned nerve conduction velocities, whereas most nerve amplitudes remained unchanged. This means that CDCA treatment did not influence the number of axons activated by maximum electrical stimulation but increased the conduction of the still-excitable fibers. Our findings may suggest that CDCA treatment promotes myelin synthesis in nerve fibers with residual unaffected axons. The effect of therapy may therefore depend largely on the extent of irreversible structural damage to axons.
Assuntos
Ácido Quenodesoxicólico/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Polineuropatias/tratamento farmacológico , Polineuropatias/etiologia , Xantomatose Cerebrotendinosa/complicações , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Adolescente , Adulto , Idoso , Colestanotriol 26-Mono-Oxigenase/genética , Colestanol/sangue , Eletromiografia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Condução Nervosa/efeitos dos fármacos , Condução Nervosa/genética , Exame Neurológico , Estatísticas não Paramétricas , Xantomatose Cerebrotendinosa/genética , Adulto JovemRESUMO
Cerebrotendinous xanthomatosis (CTX) is a rare neurometabolic disease due to defective activity of sterol 27-hydroxylase, with plasma and tissue cholestanol storage. Clinical phenotype is characterized by both systemic manifestations and neurological signs. Therapy with chenodeoxycholic acid (CDCA) suppresses abnormal bile acid synthesis. The purpose of the study was to assess the frequency and clinical relevance of spasticity in the CTX phenotype and to study the usefulness of transcranial magnetic stimulation (TMS) in detecting corticospinal tract damage and monitoring the effects of replacement therapy. Twenty-four CTX patients underwent clinical evaluation including general disability scores, pyramidal and cerebellar function scales, assessment of serum cholestanol and TMS. Nine patients who started CDCA therapy at baseline received clinical and neurophysiological follow up. All patients showed signs of pyramidal damage which were relevant for clinical disability in 18 out of 24 cases (75%), resulting in spastic paraparesis. TMS revealed corticospinal alterations even in subjects with mild clinical signs of corticospinal tract involvement. After CDCA treatment, serum cholestanol decreased to normal concentrations in all patients. Clinical picture was unchanged in seven out of nine cases; in two others pyramidal signs disappeared. A reduction in abnormal neurophysiological parameters was found. Spastic paraparesis is the most frequent and relevant neurological feature in CTX patients. Replacement treatment with CDCA can prevent the progression of pyramidal damage, especially if started early in the course of the disease. TMS represents a sensitive indicator of corticospinal tract dysfunction and subclinical improvements in pyramidal function after CDCA therapy.
Assuntos
Potencial Evocado Motor/fisiologia , Espasticidade Muscular/etiologia , Espasticidade Muscular/fisiopatologia , Xantomatose Cerebrotendinosa/complicações , Xantomatose Cerebrotendinosa/fisiopatologia , Adolescente , Adulto , Ácido Quenodesoxicólico/uso terapêutico , Avaliação da Deficiência , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Magnética Transcraniana , Xantomatose Cerebrotendinosa/tratamento farmacológico , Adulto JovemRESUMO
OBJECTIVE: To quantify total and regional brain damage in subjects with cerebrotendinous xanthomatosis (CTX) using MR based quantitative measures. BACKGROUND: CTX is a rare inherited disorder characterised by progressive neurological impairment. Appropriate therapy can slow disease progression. Measures of brain volume changes have been used in several neurological disorders due to their value in assessing disease outcome and monitoring patients' evolution. METHODS: 24 CTX patients underwent conventional MRI to measure total and regional brain volumes. In five CTX patients who started therapy at baseline, clinical and MRI examinations were repeated after 2 years. Clinical disability, overall cognitive performance and cerebellar function were evaluated using the modified Rankin Scale (RS), Mini Mental Status Examination (MMSE) and cerebellar functional system score (CB-FSS). RESULTS: Measures of normalised brain, cortical and cerebellar volumes were lower in CTX patients than in healthy controls (p<0.01). Instead, there were no differences in normalised white matter volumes between the two groups (p=0.1). At regional analysis, a significant volume decrease was found in each cortical region (p<0.01 for all regions). Normalised cortical volumes correlated closely with age (r=-0.9, p<0.0001), RS (r=-0.65, p<0.001) and MMSE (r=-0.60, p<0.01). Normalised cerebellar volumes correlated closely with CB-FSS scores (r=-0.58, p<0.01). In the five CTX patients followed over time, the annual brain volume decrease was -1.1 ± 0.2%. CONCLUSIONS: Cortical volume, rather than white matter volume, is diffusely decreased in CTX patients and correlates closely with the patient's clinical status. These data provide evidence for the presence of clinically relevant neuronal-axonal damage in the brains of CTX patients.
Assuntos
Cerebelo/patologia , Córtex Cerebral/patologia , Imageamento por Ressonância Magnética , Xantomatose Cerebrotendinosa/patologia , Adolescente , Adulto , Atrofia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas Mielinizadas/patologia , Neurônios/patologia , Testes Neuropsicológicos , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease, because of sterol 27-hydroxylase deficiency. Clinical manifestations of CTX are tendon xanthomas, juvenile cataracts, osteoporosis, diarrhoea and multiple progressive neurological dysfunctions. More than 300 patients with CTX have been reported to date worldwide and about fifty different mutations identified in CYP27A1 gene. This study describes the clinical and laboratory findings of seven new patients. METHODS: We report the molecular and clinical characterization of seven new Italian patients with CTX carrying four novel mutations. RESULTS: We identified four novel mutations located in different exons, in particular in the region of exons 2-5 of the CYP27A1 gene. Phenotypical expression did not differ from classical CTX presentation except for absence of tendon xanthomas in two patients.