Brain lesion in congenital myotonic dystrophy

Congenital myotonic dystrophy (CMyD) affects the brain, causing mental changes and psychomotor retardation. However, the pathophysiology of the brain dysfunctions in CMyD remain to be clarified. We described two cases of CMyD with brain abnormalities. Case 1 was diagnosed as having ventricular dilation at 17 days after birth, and died at 3 years and 6 months. Case 2 was diagnosed as having ventricular dilation at birth, and died at 1 year and 3 months. Pathologically, both cases showed remote hypoxic ischemic brain damage and leptomeningeal glioneuronal heterotopia (LGH). In our patients, the white matter changes may have been caused by perinatal asphyxia, and LGH by embryological abnormalities. Taken our data and those of previous reports together, it is suggested that cerebral abnormalities in CMyD are ascribed to both hypoxic ischemic changes and histogenetic abnormalities.     

Proton magnetic resonance spectroscopy of brain in congenital myotonic dystrophy

Volume selective proton magnetic resonance spectroscopy of brain was performed on a 1.5 T magnet in 5 patients with congenital muscular dystrophy and compared to the results in 46 healthy children and 1 healthy adult. Peaks of N-acetyl aspartate, choline, and creatine but not lactate, were observed in both groups on proton magnetic resonance spectroscopy. Spectroscopy of controls revealed an increase with advancing age in the ratio of N-acetyl aspartate/choline and N-acetyl aspartate/creatine and a decrease in the choline/creatine ratio. In patients with congenital myotonic dystrophy, the N-acetyl aspartate/choline ratio did not increase with advancing age, but the N-acetyl aspartate/creatine ratio did. The choline/creatine ratio decreased with advancing age, which matched the results of controls. At any age older than 4 years, the N-acetyl aspartate/choline and N-acetyl aspartate/creatine ratios were lower in patients with congenital myotonic dystrophy than in controls. The choline/creatine ratio did not differ between congenital myotonic dystrophy and controls. These results suggest that in patients with congenital myotonic dystrophy N-acetyl aspartate decreases and there exists a developmental disorder of neurons in brain.     

Brain proton magnetic resonance spectroscopy and brain atrophy in myotonic dystrophy

OBJECTIVES: To evaluate by magnetic resonance spectroscopy the age-related cerebral alterations present in myotonic dystrophy (MD) and to compare these results with those obtained by magnetic resonance imaging. DESIGN: Twenty-one patients (aged 16-63 years) with MD were compared with 16 age-matched healthy control subjects. RESULTS: In magnetic resonance spectroscopy, the mean (+/- SD) ratio of N-acetylaspartate to creatine and phosphocreatine in the patients with MD (1.09 +/- 0.32) was significantly lower than that in the control subjects (1.93 +/- 0.43) (P<.001). The mean ratio of N-acetylaspartate to choline-containing compounds in the patients with MD (1.70 +/- 0.44) was also significantly lower than that in the control subjects (2.75 +/- 0.53) (P<.001). These changes could be observed already in the younger patients. In magnetic resonance imaging, the mean brain area was significantly decreased and the mean ventricular space was significantly increased in patients with MD compared with the control subjects. Although we have confirmed brain atrophy in patients with MD in previous reports, a regression analysis indicated that the brain shrinks progressively with age in patients with this disorder and in control subjects, resulting in overlapping values for younger subjects. CONCLUSION: Magnetic resonance spectroscopy indicates that the cerebral abnormalities in patients with MD may be present at an early stage, when the results of magnetic resonance imaging studies are still equivocal.     

Brain 1H magnetic resonance spectroscopic differences in myotonic dystrophy type 2 and type 1

To evaluate cerebral metabolism and intergroup differences in closely matched patients with myotonic dystrophy type 2 (DM2, n = 15) and type 1 (DM1, n = 14), we performed (1)H magnetic resonance spectroscopic (MRS) analyses of the occipital and temporoparietal cortical regions as well as of subcortical frontal white matter. Relative to healthy subjects, the concentration of N-acetylaspartate was significantly reduced in all tested brain regions in both disease groups. In the DM1 patients we also observed a concomitant depletion of creatine and choline levels, particularly in the frontal white matter. A discriminant analysis based on the (1)H-MRS data distinguished between the DM2, DM1, and control groups with an overall accuracy of 88%. (1)H-MRS indicates that neurochemical alterations involving gray and white matter occur in patients with DM2 and DM1. Although structural abnormalities (cerebral atrophy, white matter lesions) are similar in DM2 and DM1, changes in cerebral metabolites can differentiate these disease groups, suggesting that the diseases differ in their neurocellular pathology.     

Cystinuria with congenital myotonic dystrophy

Two brothers with congenital myotonic dystrophy also had cystinuria with large renal stones. This report is the first to document the concurrence of cystinuria and congenital myotonic dystrophy. It is uncertain whether these two conditions are coincidental or share a common pathogenesis.     

Central nervous system magnetic resonance imaging findings in myotonic dystrophy

We evaluated findings in 14 patients with myotonic dystrophy (MD) using magnetic resonance imaging of the brain and compared them with those in age-matched controls with headache. There was an increased incidence of ventriculomegaly and a lumpy and/or thick pattern of periventricular hyperintensity in patients with MD as compared with the age-matched controls. These white matter abnormalities do not appear to be etiologically specific, but some possible explanations for these frequent findings in MD are discussed.     

Cerebral abnormalities in congenital myotonic dystrophy

The brain structure of 14 infants born with congenital myotonic dystrophy at 2 hospitals was evaluated by cranial ultrasonography, and the findings were correlated with clinical and neuropathologic data. Ventricular dilation was diagnosed in 11 infants (78%). Seven infants died during the neonatal period; all had ventricular dilation which remained essentially static. In the ultrasound scans of the 5 infants with ventricular dilation. Of the 7 survivors, 4 had ventricular dilation born at 1 hospital, 4 had widening of the interhemispheric fissure. Macrocephaly, a previously unrecognized finding in congenital myotonic dystrophy, was present in 10 infants (71%), 8 of whom presented with ventricular dilation. None had clinical evidence of increased intracranial pressure. There was no ventricular obstruction in the 4 brains examined pathologically. Histologic examination revealed minor expression of neuronal migrational disturbances in each patient. Macrocephaly together with the ultrasonographic and neuropathologic findings in our patients suggest that these abnormalities may originate in an external hydrocephalus.     

Occlusive hydrocephalus in congenital myotonic dystrophy

A case of congenital myotonic dystrophy is reported which was complicated by the development of a hydrocephalus that needed ventricular-peritoneal shunting at the age of 4 months. Although dilatation of cerebral ventricles is a common feature in these patients, an occlusive hydrocephalus has not so far been reported.     

Heterotopic neurons in congenital myotonic dystrophy with mental retardation

We studied heterotopic abnormalities of the brain and spinal cord of a 48-year-old mentally retarded man with congenital myotonic dystrophy. He presented with a 2-year history of progressive muscular weakness in the trunk and he developed dyspnea on effort and orthopnea 4 months pro to death. He died of acute renal failure and severe congestive heart failure. The characteristic neuropathological finding was a number of heterotopic neurons in the cerebrum. In the molecular layer of the cerebral cortex, medium-sized neurons, pyramid-shaped large neurons, and horizontal cells were noted. Many neurons were also distributed sporadically in the subcortical white matter. In the spinal cord, abnormally situated neurons were present in be posterior and lateral columns near the gray matter. These findings suggest that intrauterine maturational disturbance occurs during the period of migration and organization of neurons in the brain and spinal cord.     

Cranial magnetic resonance imaging in genetically proven myotonic dystrophy type 1 and 2

Abstract. Cranial magnetic resonance imaging (MRI) in 19 German patients with genetically proven myotonic dystrophy Type 1 (DM1, n = 10) or Type 2 (DM2, n = 9) showed pathological findings consisting of white matter lesions (WML) and/or brain atrophy in 9/10 DM1 and 8/9 DM2 patients. Anterior temporal WML (ATWML) were exclusively seen in DM1 patients. Our findings indicate a high frequency of central nervous system (CNS) involvement in both disorders. However, temporopolar pathology, previously associated with intellectual dysfunction, seems to be restricted to DM1.     

Steinert's myotonic dystrophy and Thomsen's congenital myotonia. Observation of a family (author's transl)

The nosographic relationship between Thomsen's and Steinert's disease is still uncertain. There is not agreement in the literature whether these are two different diseases or just different stages in the evolution of a single one. Four members of a family in two generations have been studied: two have a typical Steinert's, one a Thomsen's disease and one a clinical pattern that cannot be clearly considered neither of the first nor of the second type. In this patient a generalized muscular hypertrophy was followed, at the age of 54, by a generalized impairment of the muscular trophism and evolved into a severe wasting. This may be interpreted as an evolution of Thomsen's into a Steinert's disease. Furthermore, the presence in the same family of cases of both Thomsen's and Steinert's disease supports the hypothesis of a single disease. The present study suggests that Thomsen's and Steinert's diseases could be two clinical varieties of a single disease in different stages of development. This conclusion is supported by the similarity in the electromyographic patterns and in the histological picture from muscle biopsy of all patients examined.     

Muscle magnetic resonance imaging in patients with congenital muscular dystrophy and Ullrich phenotype

The aim of this study was to evaluate muscle magnetic resonance imaging findings in patients with congenital muscular dystrophy and Ullrich phenotype. Fifteen children with congenital muscular dystrophy and Ullrich phenotype were included in the study. All patients had collagen VI studies in muscle and, when family structure was informative, linkage studies to the collagen 6 loci. Three of the 15 patients had reduced collagen in muscle. One of the three was from an informative family and linked to one of the collagen 6 loci. Another patient was linked to one of the collagen 6 loci but had normal expression of collagen in muscle. The remaining 11 all had normal collagen expression in muscle. Only two of these 11 were from informative families and linkage to collagen 6 loci was excluded in them. All patients had muscle magnetic resonance imaging of their leg muscles using transverse T1 sequences. With the exception of the two patients in whom linkage to the collagen 6 loci was excluded, the other 13 patients showed the same pattern of selective involvement on magnetic resonance imaging of thigh muscles. This consisted of relative sparing of sartorius, gracilis, adductor longus and rectus. This pattern was also found in the case linked COL6A1/A2 locus but with normal collagen. This finding, and the striking clinical and magnetic resonance imaging concordance between patients with normal and reduced collagen VI in muscle suggest that collagen VI could still be the culprit in several cases with normal collagen expression, or alternatively a primary defect in a protein that closely interacts with collagen VI. Mutation analysis of the collagen 6 genes in cases with normal collagen VI expression is needed to resolve this issue.