RESUMO
Magnetic resonance imaging (MRI), with diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR), is a useful diagnostic investigation for Creutzfeldt-Jakob disease (CJD). Amendment of the diagnostic criteria for sporadic CJD (sCJD) to include defined MRI alterations has just recently been proposed. We analyzed MRI scans with FLAIR and/or DWI available of 29 patients with the E200K or the V210I mutation, and a control group of 29 sCJD patients to compare the MRI lesion profile and evaluate the applicability of new MRI criteria to genetic CJD patients. FLAIR images of all 29 patients and controls and DWI images of 15 genetic CJD and 13 sCJD were rated by 2 neuroradiologists blinded to diagnosis and genetic testing. In genetic CJD (gCJD) patients, hyperintensities on FLAIR could be found in the putamen in 55% and the caudate nucleus in 66% and on DWI in 33% and 60%, respectively. Lesion profile and frequency of hyperintensities did not differ significantly from the findings in sCJD. New diagnostic MRI criteria yield similar sensitivity for gCJD and sCJD, being 79% and 72%, respectively. MRI provides useful information in E200K and V210I gCJD patients. The alterations strongly resembled those seen in sCJD, once again demonstrating the similarity of the clinical syndrome in patients with these particular mutations.
Assuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico , Imageamento por Ressonância Magnética/métodos , Príons , Síndrome de Creutzfeldt-Jakob/genética , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Mutação , Príons/genética , Sensibilidade e EspecificidadeRESUMO
Nemaline myopathy (NM) is a muscle disorder with broad clinical and genetic heterogeneity. The clinical presentation of affected individuals ranges from severe perinatal muscle weakness to milder childhood-onset forms, and the disease course and prognosis depends on the gene and mutation type. To date, 14 causative genes have been identified, and ACTA1 accounts for more than half of the severe NM cases. ACTA1 encodes α-actin, one of the principal components of the contractile units in skeletal muscle. We established a homogenous cohort of ten unreported families with severe NM, and we provide clinical, genetic, histological, and ultrastructural data. The patients manifested antenatal or neonatal muscle weakness requiring permanent respiratory assistance, and most deceased within the first months of life. DNA sequencing identified known or novel ACTA1 mutations in all. Morphological analyses of the muscle biopsy specimens showed characteristic features of NM histopathology including cytoplasmic and intranuclear rods, cytoplasmic bodies, and major myofibrillar disorganization. We also detected structural anomalies of the perinuclear space, emphasizing a physiological contribution of skeletal muscle α-actin to nuclear shape. In-depth investigations of the nuclei confirmed an abnormal localization of lamin A/C, Nesprin-1, and Nesprin-2, forming the main constituents of the nuclear lamina and the LINC complex and ensuring nuclear envelope integrity. To validate the relevance of our findings, we examined muscle samples from three previously reported ACTA1 cases, and we identified the same set of structural aberrations. Moreover, we measured an increased expression of cardiac α-actin in the muscle samples from the patients with longer lifespan, indicating a potential compensatory effect. Overall, this study expands the genetic and morphological spectrum of severe ACTA1-related nemaline myopathy, improves molecular diagnosis, highlights the enlargement of the perinuclear space as an ultrastructural hallmark, and indicates a potential genotype/phenotype correlation.
Assuntos
Miopatias da Nemalina , Actinas/genética , Actinas/metabolismo , Biópsia , Criança , Feminino , Humanos , Debilidade Muscular/metabolismo , Músculo Esquelético/patologia , Mutação/genética , Miopatias da Nemalina/genética , Miopatias da Nemalina/patologia , Membrana Nuclear/metabolismo , Membrana Nuclear/patologia , GravidezRESUMO
CADASIL is the most common cause of hereditary stroke and vascular dementia. Published information about this disease in South America is scant. We describe clinical and demographic characteristics of 13 patients (10 families) with CADASIL from Argentina.Methods Medical records, diagnostic tests and family history of patients with CADASIL were reviewed.Results Thirteen patients with CADASIL (10 families) were included. All patients had European ancestry. Initial presentation was stroke in most patients (n = 11). Stroke patients later developed cognitive complaints (n = 9), migraine with aura (n = 1), apathy (n = 4) and depression (n = 6). External capsule and temporal lobe involvement on MRI were characteristic imaging findings. Two patients died after intracerebral hemorrhage.Conclusion This is the first report of non-related patients with CADASIL in South America addressing ancestry. Since European ancestry is not highly prevalent in all South American countries, there may be variable incidence of CADASIL within this region.
Assuntos
Encéfalo/patologia , CADASIL/complicações , CADASIL/diagnóstico , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Argentina , Biópsia , CADASIL/etnologia , Doenças Arteriais Cerebrais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/etnologia , População BrancaRESUMO
CADASIL is the most common cause of hereditary stroke and vascular dementia. Published information about this disease in South America is scant. We describe clinical and demographic characteristics of 13 patients (10 families) with CADASIL from Argentina.Methods Medical records, diagnostic tests and family history of patients with CADASIL were reviewed.Results Thirteen patients with CADASIL (10 families) were included. All patients had European ancestry. Initial presentation was stroke in most patients (n = 11). Stroke patients later developed cognitive complaints (n = 9), migraine with aura (n = 1), apathy (n = 4) and depression (n = 6). External capsule and temporal lobe involvement on MRI were characteristic imaging findings. Two patients died after intracerebral hemorrhage.Conclusion This is the first report of non-related patients with CADASIL in South America addressing ancestry. Since European ancestry is not highly prevalent in all South American countries, there may be variable incidence of CADASIL within this region.
CADASIL é a causa mais frequente de acidente vascular cerebral e demência hereditários. São poucas as publicações sobre esta doença na América do Sul. Aqui descrevemos dados clínicos e demográficos de 13 pacientes (10 famílias) da Argentina com CADASIL.Métodos Prontuários médicos testes diagnósticos e história familiar de pacientes com CADASIL foram revisados.Resultados Treze pacientes com CADASIL (10 famílias) foram incluídos. Todos os pacientes tinha ancestralidade europeia. A apresentação inicial foi acidente vascular cerebral na maioria dos pacientes (n = 11). Pacientes com acidente vascular cerebral depois desenvolveram alterações cognitivas (n = 9), enxaqueca com aura (n = 1), apatia (n = 4) e depressão (n = 6). Os achados de imagem característicos da RM foram na cápsula externa e no lobo temporal. Dois pacientes morreram por hemorragia intracerebral.Conclusão Este é o primeiro relato de série de casos de pessoas não relacionadas entre si que apresentavam CADASIL na América do Sul, discutindo ancestralidade. Uma vez que a ascendência europeia tem prevalência variada em diferentes países da América do Sul, é possível que esta seja uma variável de incidência de CADASIL nesta região.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encéfalo/patologia , CADASIL , Acidente Vascular Cerebral/etiologia , Argentina , Biópsia , CADASIL , Doenças Arteriais Cerebrais , População Branca , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Acidente Vascular Cerebral/etnologiaRESUMO
La neuropatía periférica correspondiente al síndrome de ataxia telangiectasia es poco conocida. Se presenta un caso en un niño de 9 años de edad, con antecedentes familiares de padre, madre y hermanos con telangiectasias conjuntivales. A la edad de tres años comienza con signos centrales, caídas frecuentes, babeo y temblores en miembros superiores, estrabismo convergente de ojo derecho y nistagmus lateral y vertical. Al examen neurológico se encuentra hipotrofia muscular en ambas piernas, con caída de ambos antepiés, arreflexia en miembros inferiores y sensibilidad superficial y profunda conservada. Se detectó atrofia cerebelosa por tomografía computada y la velocidad de conducción motora estaba ligeramente disminuida. El resto de los exámenes fueron normales. No se detectaron alteraciones de la inmunidad humoral ni celular. La biopsia de nervio safeno externo mostró disminución de fibras mielínicas gruesas y medianas, variables según los fascículos, hasta alrededor de un 40 por ciento, con aisladas fibras en degeneración actual, sin evidencias de regeneración axonal. En los cortes semifinos y en el estudio ultraestructural se confirmaron los hallazgos ópticos y las fibras remanentes no mostraron alteraciones axonales ni en las células de Schwann. Estos hallazgos son compatibles con afectación de las neuromas sensitivas primarias del ganglio de la raíz dorsal, como ha sido previamente descripto en esta enfermedad y son comparables a las lesiones vistas en otras afectaciones ganglionares (degeneraciones espino-cerebelosas-Friedreich); por lo tanto, desde el punto de vista neurológico y neuropatológico, creemos conveniente ubicar este síndrome dentro de las degeneraciones espino-cerebelosas, como ya fuera propuesto por E. Boder y R. P. Sedgwick