Rou-Shayn Chen

MELAS syndrome with mitochondrial tRNA(Leu(UUR)) gene mutation in a Chinese family.

The clinical features of a patient in a Chinese family with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) are reported. The study revealed that hearing and visual impairments and miscarriages may be early clinical presentations in MELAS. A heteroplasmic A to G transition in the tRNA(Leu(UUR)) gene was noted at the nucleotide pair 3243 in the mitochondrial DNA of muscle, blood, and hair follicles of the proband and his maternal relatives. Quantitative analysis of the mutated mitochondrial DNA revealed variable proportions in different tissues and subjects of maternal lineage in the family. Muscle tissue contained a higher proportion of the mutant mitochondria than other tissues examined. The function of the reproductive system of the proband seems to be impaired. In one clinically healthy sibling, the 3243rd point mutation was found in sperm mitochondrial DNA, although sperm motility was not affected. It seems that biochemical defects in mitochondrial respiration and oxidative phosphorylation are tissue specific expressions of the 3243rd point mutation in the mitochondrial DNA of the affected target tissues.

Chronic Carbon Disulfide Encephalopathy

To understand central nervous damage after long-term exposure to carbon disulfide (CS2), 10 patients who had polyneuropathy with various neuropsychiatric symptoms in a viscose rayon plant were studied. Clinical and laboratory examinations including electroencephalography (EEG), brain computed tomography (CT), brain magnetic resonance images (MRI), and carotid duplex sonography were carried out. Clinically, headache, unpleasant dreams, memory impairment, fatigue, anorexia and emotional lability were common in these patients while 2 patients had stroke episodes. EEGs were all normal. Brain CT scan showed mild cortical atrophy in 3 and low density lesions in the basal ganglia in 3. Brain MRI studies also disclosed mild cortical atrophy in 4 and multiple lesions involving the basal ganglia and corona radiata in 4. Carotid duplex sonography revealed mild atherosclerosis with plaques (< 20% stenosis) of extracranial vessels in 6. However there was no significant difference in flow velocities and flow volumes in the extracranial carotid arteries between patients and the normal controls. Interestingly, 2 patients had multiple brain lesions in the subcortical white matter but without strokes. In conclusion, encephalopathy with possible strokes may occur after chronic exposure to CS2, as well as polyneuropathy. The lesions usually involve the basal ganglia and subcortical white matter. Furthermore, MRI study may detect brain lesions particularly in the subcortical white matter areas before the occurrence of stroke.

Polyneuropathy induced by carbon disulphide in viscose rayon workers.

OBJECTIVES--To understand the prevalence of polyneuropathy and correlations among the clinical manifestations, electrophysiological findings, and degree of exposure to carbon disulphide (CS2) in workers who were exposed to variable concentrations of CS2 in a viscose rayon factory. METHODS--All the 163 workers received a detailed physical and neurological evaluation. Fixed point air samples were analysed for CS2. Nerve conduction velocity was studied in 26 workers with symptoms similar to neuropathy. RESULTS--Nine workers (53%) with overt polyneuropathy from the fibre cutting department and 19 workers (13%) with oligosymptoms similar to polyneuropathy from various jobs were noted. The fixed point air concentrations of CS2 were 150-300 ppm in the cutting areas and 15 to 100 ppm in the spinning areas. The estimated eight hour time weighted averages in the fibre cutting areas were 40-67 ppm. The occurrence of polyneuropathy was generally correlated with the degree of exposure to CS2. Nerve conduction velocities (NCVs) were significantly different in the overt polyneuropathy and subclinical polyneuropathy groups from the normal controls. The sensitive indicators for CS2 polyneuropathy were distal latency, motor NCV, and amplitude of sensory nerve action potentials in sensory NCVs. CONCLUSION--The outbreak of polyneuropathy was attributed to higher concentrations of CS2 in fibre cutting areas. Even in other jobs with relatively lower concentrations of CS2, the hazard of subclinical polyneuropathy cannot be overlooked.

Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson’s disease in Taiwan

Background and purpose:  The association between glucocerebrosidase (GBA) mutations and Parkinson’s disease (PD) is attracting increased attention worldwide. In patients of Chinese ethnicity, other than the common L444P mutation, a few mutations have been reported. However, the contribution of GBA to PD can be answered only by a thorough investigation of its mutations in a unique large population.

Overlapping syndrome of MERRF and MELAS: molecular and neuroradiological studies

We describe a 42‐year‐old woman with overlapping syndrome of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes) and MERRF (myoclonus epilepsy and ragged‐red fibers). Clinically, she had episodic headache, stroke‐like episode with left hemiparesis and lactic acidosis commonly found in MELAS syndrome. However, myoclonus seizure, and ataxia with dyssynergic gait characteristic of MERRF were also noted. Computed tomographic scans showed a right temporo‐parietal hypodense lesion. The lesion disappeared 20 months later, even magnetic resonance images also failed to reveal this abnormality. A molecular analysis of mitochondrial DNA was conducted by using restriction endonucleases Apa I and Nae I. A transition from A to G was found at the nucleotide position 3243, but not found at the 8344th nucleotide pair. In this report, we document the fluctuating CT changes and emphasize the importance of molecular analysis in patients with overlapping syndrome of mitochondrial encephalomyopathies.

Random mitotic segregation of mitochondrial DNA in MELAS syndrome.

We describe the heterogeneity of clinical features and molecular genetic characteristics of the probands and other members in two families with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes (MELAS) syndrome. A point mutation at the 3243rd nucleotide position of mtDNA was found only in some of the maternal lineage members of the two families. Furthermore, the proportions of mutant mtDNA were varied and found only in some tissues of the individuals. Intriguingly, in some subjects, the mutant mtDNA was found in blood cells or hair follicles but was absent in muscles. The data do not support the notion of a selective advantage of wild‐type mtDNA to rapidly replicating cells. We suggest that a rapid replicative segregation may occur in early embryogenesis.

Mitochondrial DNA variants as genetic risk factors for Parkinson disease

Investigation of the relationship between mitochondrial DNA (mtDNA) variants and Parkinson disease (PD) remains an issue awaiting more supportive evidence. Moreover, an affirming cellular model study is also lacking.

Random X chromosome methylation patterns in the carriers with clinical phenotypic expressions of X-linked recessive bulbospinal neuronopathy.

Objectives ‐ We report the unusual phenotypic expression in 2 female carriers of a family with X‐linked recessive bulbospinal neuronopathy (X‐BSN). We analyze the methylation pattern of the androgen receptor (AR) gene to inspect the possibility of non‐random X chromosome inactivation to be the underlying mechanism. Material and methods ‐ Twenty‐three members in 3 generations of a Taiwanese family were examined and studied for genomic DNA analysis. We analyzed the sequence of the first exon of the AR gene to identify the numbers of CAG repeats, and to determine the methylation pattern by using the restriction enzymes Hpa II and Hha I. Results ‐ There were 3 probands and 5 carriers and 2 of the carriers manifested clinical symptoms. Sequence analysis revealed that the numbers of trinucleotide repeats ranged from 42 to 45 in one allele of the X‐chromosome in the 5 female carriers. The restriction pattern of the Hpa II and Hha I recognizable sites of the X‐chromosome indicated a random methylation. Conclusion ‐ Our data suggest that molecular genetic studies are important in confirming the diagnosis of X‐BSN and early detection of female carriers, and the random or non‐random methylation pattern of the X‐chromosome is not a determining factor for partial expression of the abnormal AR gene in some carriers.

Asymmetric dystonia with frontal white matter lesions in Wilson's disease

Asymmetrical manifestation of dystonia was investigated in 26 patients with Wilsons disease with modified dystonia rating scale and correlated with the asymmetricity of CT and/or MRI findings. Ten patients (eight men and two women) had dystonia. The age of disease onset ranged from 11 to 30 years with a mean of 18.6 ± 5.2 years. The duration of the illness was from 2 to 15 years (mean 7.0; S.D. 3.6). Six patients had subcortical white matter lesions in the frontal and/or parietal lobes, as well as lesions in the basal ganglia. Five patients, who had asymmetrical white matter lesions in the frontal lobes and symmetrical lesions in the basal ganglia and the thalamus, developed more severe contralateral dystonia. The other four patients with symmetric lesions in the basal ganglia and the thalamus had nearly‐symmetrical dystonia. One patient with symmetrical lesions in the frontal lobes and the basal ganglia also had symmetrical manifestation of dystonia. We suggest that the interruption of the loop between the thalamus and premotor cortex by subcortical white matter lesions may enhance contralateral dystonia.

The evolution of contrast enhancement in granulomatous amebic encephalitis

Abstract In the literature, variable enhanced patterns in cases of granulomatous amebic encephalitis (GAE) have been reported. The reason for this variety is still unknown. We report a case of GAE in whom serial images showed different enhanced patterns as the lesions evolved. The enhanced pattern was nodular or gyriform at its early stage, became ring-like as the lesions enlarged and at its late stage, developed into a heterogeneous pattern. We concluded that the variable enhanced patterns seen in GAE might correspond to the evolution of the lesions. Realizing the serial changes may help us in the early diagnosis and treatment of this fatal disease.