Leigh syndrome: serial MR imaging and clinical follow-up.

BACKGROUND AND PURPOSE: Subacute necrotizing encephalomyelopathy, or Leigh syndrome (LS), is a progressive neurodegenerative disorder characterized by symmetrical spongiform lesions in the brain with onset usually in infancy or early childhood. Little is known of the developing process of the brain lesions in LS that are particularly relevant to the occurrence of fatal respiratory failure. Our purpose was to determine whether fatal respiratory failure can be predicted before death on the basis of clinical characteristics or findings on longitudinal MR images of the brain. METHODS: Clinical records and serial MR studies of eight patients with LS aged 3 months to 12 years who met the diagnostic criteria for LS were reviewed retrospectively, with special reference to a correlation between loss of respiratory control and MR abnormalities. Both T1- and T2-weighted images were obtained at the onset of disease or when clinical symptoms worsened. RESULTS: Serial MR images were divided into three groups on the basis of the following findings: 1) symmetrical basal ganglia lesions before brain stem involvement (n = 4); 2) initial involvement of the brain stem (n = 2); and 3) cerebral white matter lesions followed by brain stem lesions (n = 2). Lesions of the lower brain stem were always present when patients had near fatal respiratory failure. However, upper brain stem lesions were transient and were found in parallel to reversible respiratory disorder. Fatal respiratory failure was unpredictable from clinical or neuroradiologic findings. CONCLUSION: Brain stem lesions are associated with the loss of respiratory control in patients with LS, but the time at which fatal respiratory failure will occur is unpredictable.

Acute encephalopathy associated with nontyphoidal salmonellosis.

The importance of an acute encephalopathy associated with nontyphoidal salmonellosis has recently been recognized, but the disease entity has been poorly established. In this study, we describe two encephalopathic patients associated with nontyphoidal salmonellosis. The patients exhibited a rapid evolution of coma after the onset of lethargy or seizure. Fever and diarrhea due to salmonellosis preceded these events. Secondary factors inducing encephalopathies, such as severe dehydration, sepsis, meningitis, electrolyte or metabolic disturbances, acute renal failure, and multiple organ failure, were excluded in the differential diagnosis at the onset of encephalopathic features. These clinical findings and rapid development of encephalopathic features from localized intestinal infection without any significant abnormalities in a variety of blood tests may suggest a toxic etiology. However, endotoxin was not found in serum from both patients. From these results, we conclude that nontyphoidal salmonellosis can cause a toxic encephalopathy syndrome, like shigellosis or verocytotoxin-producing Escherichia coli infection.

[Two early-childhood cases of optic neuritis].

We reported two early-childhood cases suffering from acute optic neuritis (ON). Case 1 was a 3-year-old girl, who had a preceding upper respiratory infection, headache, nausea and subsequent sudden visual disturbance. Cranial MRI revealed multiple T2-elongated lesions in the white matter. She showed two neurological relapses including ON, leading to the diagnosis of clinically probable multiple sclerosis (MS). Case 2 was a 2-year-old boy, who had an acute onset of visual disturbance without any other neurological deficits. MRI with Gd-DTPA enhancement revealed not only a disorder of optic nerves but involvement of the white matter in the acute phase. It has been suggested that there may be a broad spectrum of demyelinating disorders between ON and MS even in early-childhood. Therefore, we should bear in mind to the subsequent progression to MS in childhood ON cases with silent brain lesions.

An inhibitory factor for cell-free protein synthesis from Salmonella enteritidis exhibits cytopathic activity against Chinese hamster ovary cells.

A factor inhibiting cell-free protein synthesis was purified from Salmonella enteritidis cell lysate by sequential ammonium sulfate precipitation, chromatography on anion exchange and hydrophobic interaction columns, and polyacrylamide disc gel electrophoresis. The purified factor, which was named SIPS (Salmonella inhibitor of protein synthesis), inhibited in vitro protein synthesis in rabbit reticulocyte lysate and had a molecular mass of 38 kDa, estimated by PAGE under denaturing conditions. SIPS was also cytopathic for Chinese hamster ovary cells. The N-terminal amino acid sequence (20 residues) of SIPS was found to be identical to that of mature L-asparaginase II of Escherichia coli. Indeed, the purified SIPS exhibited asparaginase activity, E. coli L-asparaginase II had cytopathic activity and inhibited in vitro protein synthesis. The results suggest that at least a part of cytotoxicity and inhibition of cell-free protein synthesis caused by S. enteritidis is a property of the bacterial L-asparaginase.

Proteolipid protein gene duplications causing Pelizaeus-Merzbacher disease: molecular mechanism and phenotypic manifestations.

Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder characterized by dysmyelination of the central nervous system (CNS) caused by mutations involving the proteolipid protein gene (PLP). In addition to point and frameshift mutations in the coding region, duplications involving the entire PLP have been recognized recently as a major genetic abnormality causing PMD. We devised an interphase fluorescence in situ hybridization (FISH) assay to establish an efficient screening test for PLP duplication. Thirteen patients from 11 Japanese PMD families were determined to have PLP duplications. This molecular diagnostic FISH test also readily detected female carriers. Molecular analysis revealed that the size of the duplication and location of the breakpoints showed striking variation. Fiber FISH demonstrated that the duplication is tandem in nature. Haplotype analysis indicated an intrachromosomal origin for the duplication. These results suggest that an unequal sister chromatid exchange in male meiosis is likely to be the major mechanism leading to the formation of the duplication. Patients with the duplication commonly present with a mild PMD phenotype. Two patients with an exceptionally severe clinical phenotype carried large duplications, suggesting that either the larger duplicated segment incorporates additional dosage-sensitive genes or that the location of the duplication junction may affect the phenotype.