RESUMO
The aim was to study brain involvement in myotonic dystrophy type 1 by single photon emission tomography (SPECT) and positron emission tomography (PET). 58 DM1 patients were subjected to SPECT; 17 to both SPECT and PET. SPECT patients were grouped as 'normally perfused' and 'abnormally perfused'; PET patients as 'normal performers' and 'abnormal performers'. To quantify hypoperfusion and/or hypometabolism, we used a semi-quantitative scale. To localize focal hypoperfusion/hypometabolism, nine cerebral areas of involvement were identified. The Chi-square, Wilcoxon, McNemar tests were used for statistics. SPECT showed abnormalities in 52/58 patients. PET showed an abnormal glucidic uptake in 15/17. Hypoperfusion was mild/moderate in 50/58 patients, mostly involving the left supratentorial areas. Abnormal glucidic uptake was mainly observed in the left frontal lobe. Abnormalities in blood perfusion and/or glucose metabolism are frequent in DM1. These abnormalities involve the left more often than the right hemisphere, the frontal lobe more than other lobes. Such abnormalities are more often cortical than subcortical.
Assuntos
Distrofia Miotônica/diagnóstico por imagem , Distrofia Miotônica/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Mitochondrial myopathies are regulated by two genomes: the nuclear DNA, and the mitochondrial DNA. While, so far, most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial DNA, a new field of investigation is that of syndromes due to mutations in the nuclear DNA. These latter disorders have mendelian inheritance. RESULTS: Three representative cases have been selected: one with COX deficiency and a Leigh syndrome due to a SURF1 gene mutation, one due to a defect of Coenzyme Q synthesis and one with dominant optic atrophy due to a mutation in the OPA1 gene. CONCLUSIONS: Future developments will show that many neurodegenerative disorders are due to mutations of nuclear genes controlling mitochondrial function, fusion and fission.
Assuntos
Núcleo Celular , DNA/genética , Genoma/genética , Doenças Mitocondriais/genética , Criança , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Lactente , Doença de Leigh/diagnóstico , Doença de Leigh/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Doenças Mitocondriais/diagnóstico , Proteínas Mitocondriais/genética , Mutação/genética , Atrofia Óptica/diagnóstico , Atrofia Óptica/genética , Prostaglandina-Endoperóxido Sintases/deficiência , Prostaglandina-Endoperóxido Sintases/genética , Ubiquinona/genéticaRESUMO
The objective of this study was to determine the degree of brain involvement in a cohort of myotonic dystrophy type 1 and type 2 (DM1, DM2) patients by brain studies and functional tests and to compare the results of the two groups. DM1, DM2 are multisystemic disorders due to polynucleotide expansions. Previous studies on brain involvement by neuroimaging and functional methods have led to contradictory results. Fifty molecularly defined DM1 patients and 14 DM2 patients, were recruited for the study. Age at recruitment, age at disease onset, disease duration and educational level were recorded. Neuromuscular assessment was done by MIRS. An extensive neuropsychological battery was performed in 48/50 DM1 and in a control group of 44 healthy matched subjects. Forty six of 50 DM1 and 12/14 DM2 underwent brain MRI; 21/50 DM1 and 9/14 DM2 underwent brain perfusion SPECT, with semiquantitative analysis of the results. MRI images were classified by ARWMC (age-related white matter changes) score, in order to quantify recurrence, localization and patterns of distribution of white matter hyperintense lesions (WMHLs) in our two cohorts. MRI results were matched to SPECT and to neuropsychological results. Thirty-seven of 46 DM1 and 10/12 DM2 had abnormal MRI imaging, showing scattered supratentorial, bilateral, symmetrical focal or diffuse WMHLs. A typical temporo-insular diffuse subcortical pattern was seen in DM1 subjects only, with no correlation with cognitive involvement. Major cognitive involvement was seen in the case of diffuse frontal lesions. A relationship with CTG expansion size was documented for DM1 subjects. SPECT showed minimal hypoperfusion in the posterior cortex planes in DM1 and, to a lesser extent, in DM2. Very mild degrees of involvement in the DM2 cohort were seen. Neuroimaging and functional investigations confirmed a more severe involvement of the brain in DM1 compared to DM2. A temporo-insular diffuse lesional pattern, specific for DM1, was found on MRI. This confirms greater expansion size as a risk factor for more extensive brain involvement in DM1.