| In a patient with connatal pelizaeus-merzbacher disease with the same mutation in the proteolipid protein gene as in jimpy(msd) mice the immunohistochemical study of the brain demonstrated deficiencies of myelin and proteolipid protein despite good expression of myelin basic protein. The mechanism of myelination is partly disturbed by the mutation; therefore jimpy(msd) mice can be used as a suitable model for further studies in connatal pelizaeus-merzbacher disease. ( info) |
2/292. A de novo splice donor site mutation causes in-frame deletion of 14 amino acids in the proteolipid protein in pelizaeus-merzbacher disease. pelizaeus-merzbacher disease (PMD) is a leukodystrophy associated with mutations in the proteolipid protein (PLP) gene. Jimpy is a mouse model of human PMD, and a splice site mutation in Jimpy causes the deletion of exon 5 from the PLP mRNA, producing a truncated form of PLP. We describe a de novo point mutation at the 5' splice donor site of exon 5 in a 17-year-old male with PMD, which results in the skipping of 42 base pairs of exon 5. The mutation removes only 14 amino acids in-frame of PLP. This is a novel splice donor site mutation in the human PLP gene. Moreover, the results indicate that the 14-amino acid deletion in the PLP is responsible for oligodendrocyte cell death and the development of PMD. ( info) |
3/292. MRI appearances of metachromatic leukodystrophy. BACKGROUND: The leukodystrophies constitute a wide spectrum of cerebral disorders of varying etiology. The imaging appearances on CT and MRI are recognizable as abnormalities of white matter; however, it may be impossible to arrive at the correct diagnosis based on imaging studies alone. patients AND methods: Three patients of varying age and clinical symptomatology diagnosed with metachromatic leukodystrophy (MLD) had remarkably similar MRI appearances. A "tigroid" or "leopard-skin" appearance was demonstrated within deep white matter in each case. RESULTS: All of the patients had biochemical confirmation of MLD. CONCLUSION: Although the "tigroid" pattern previously was considered to be pathognomonic of pelizaeus-merzbacher disease, the diagnosis of MLD must now be considered when these MRI appearances are encountered. ( info) |
4/292. MRI features of Balo's concentric sclerosis. We report MRI findings in a 56-year-old woman with Balo's concentric sclerosis (BCS) who initially presented with a progressive hemiparesis. MRI showed two lesions with a concentric pattern in the left frontoparietal region and a laminated, arcuate pattern in the right frontal region. These patterns were best seen in post-contrast images and were consistent with BCS. In addition, there were several small cerebral multiple sclerosis-like plaques. The clinical symptoms improved and the MR findings regressed after corticosteroid therapy. The patient had completely recovered 12 months later, except for mild right hand numbness. MRI showed further regression of the lesions, but the concentric pattern was still present. This case demonstrated that BCS can run a benign prolonged course and may persist for a long time. Concentric or laminated contrast enhancement in the acute phase may suggest that bands of demyelination in BCS occur synchronously rather than successively. ( info) |
| A 3-yr-old boy received valproic acid (VPA) for recurrent seizures. He developed coma and acute liver failure that were attributed to VPA toxicity, and underwent emergency orthotopic liver transplantation (OLTx). Despite good graft function, his neurological state worsened and led to death a few months later. The diagnosis of Alpers-Huttenlocher syndrome (AHS) was suspected, subsequently to liver Tx, in view of ongoing neurologic deterioration and magnetic resonance imaging (MRI) findings. The syndrome, recessively inherited, associates brain degeneration with liver failure, and is now considered a mitochondrial disease. Enzyme activity deficiencies of the respiratory chain were identified in muscle mitochondria, as well as morphologic abnormalities of mitochondria in the explanted liver. Guidelines for diagnosis are presented, in order to differentiate the liver failure in AHS from that induced by genuine VPA toxicity. It is recommended to avoid liver Tx in patients with AHS given the fatal neurological course of the disease. ( info) |
| We report two cases of Balo's concentric sclerosis that demonstrate the typical magnetic resonance imaging (MRI) findings of concentric rings of demyelination involving the superficial and deep white matter and sparing the cortex. In both cases biopsy was not performed as MRI findings and multi-mode evoked potential studies were consistent with demyelinating illness. The theories regarding the pathogenesis of this peculiar appearance are briefly reviewed. ( info) |
7/292. Evidence that Alpers-Huttenlocher syndrome could be a mitochondrial disease. We report an 11-year-old boy with a slight developmental delay and epilepsy. After he was placed on valproate, he developed hepatic failure and increasing neurologic symptoms, including epilepsia partialis continua, and died. autopsy findings in liver and cerebrum were consistent with progressive neuronal degeneration of childhood with liver disease, also called Alpers-Huttenlocher syndrome. Ragged red fibers and cytochrome c oxidase negative fibers were present in muscle. These results suggest that Alpers-Huttenlocher syndrome, at least in some patients, is a mitochondrial disease. ( info) |
8/292. Fatal deterioration of neurological disease after orthotopic liver transplantation for valproic acid-induced liver damage. We describe a 12-year-old girl with an early onset neurologic disease of slow progressiveness and electro-encephalography showing epileptic activity. The girl developed fulminant liver failure 5 months after the start of valproic acid treatment. Repeated mitochondrial assays failed to prove a mitochondrial disorder, but muscle biopsies were slightly pathological. Liver histology indicated acute-on-chronic liver disease. Six weeks after a successful orthotopic liver transplantation her neurological condition deteriorated rapidly, soon leading to generalized cortical disease and death. Post-mortem brain examination showed advanced central nervous destruction. We suggest that this is a late-onset Huttenlocher variant of Alpers' syndrome, where fulminant liver failure can be triggered by valproic acid, and orthotopic liver transplantation can subsequently trigger a fatal neurologic deterioration. Our case illustrates that when a referral center receives a previously unknown patient with hepatocellular insufficiency, it might be impossible to differentiate between fulminant vs. acute-on-chronic liver failure, and the decision whether to perform a liver transplantation or not would become difficult. ( info) |
9/292. Recurrent myelinoclastic diffuse sclerosis: a case report of a child with Schilder's variant of multiple sclerosis. Myelinoclastic diffuse sclerosis (MDS, Schilder's disease) is a rare CNS demyelinating disorder affecting mainly children and usually presenting as an intracranial mass lesion. We report the first case of recurrent intracranial MDS where the third episode of demyelination involved the cervical spinal cord. This may represent a subset of the disease, which should be considered as Schilder's variant (childhood form) of multiple sclerosis. ( info) |
10/292. Pathognomonic MR imaging findings in Balo concentric sclerosis. Irregular, concentric zones of increased signal on T2-weighted cranial MR imaging studies may strongly suggest Balo concentric sclerosis (BCS), a rare but recognized variant of multiple sclerosis. Differentiating BCS from multiple sclerosis or neoplasm can be difficult clinically, but MR imaging findings noted in this case may be pathognomonic. ( info) |