Diffuse posterior leukoencephalopathy in MELAS without stroke-like episodes: A case report.

RATIONALE: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is the most common subtype of mitochondrial encephalopathy. In the past, it was believed that most hereditary white matter lesions were lysosome storage disorders or peroxisome diseases. However, in recent years, white matter lesions have been increasingly regarded as a common feature of patients with mitochondrial diseases. In addition to stroke-like lesions, about half of the patients with MELAS reported white matter lesions in the brain. PATIENT CONCERNS: Herein, we provide a case of A 48-year-old female who presented with episodic loss of consciousness with twitching of extremities. Previous medical history revealed 10 years of history of epilepsy, 10 years of history of diabetes, a history of hearing loss, and unknown etiology. Ancillary findings included brain magnetic fluid-attenuated inversion recovery showed symmetrical lesions in the bilateral parietal lobe with high signal intensity at the edge, and high signal intensity in the bilateral occipital lobe, paraventricular white matter, corona radiata, and the center of semiovale. DIAGNOSES: Mitochondrial deoxyribonucleic acid gene sequencing returned A3243G point mutation and it supports the diagnosis of intracranial hypertension. INTERVENTIONS: Considered the diagnosis of symptomatic epilepsy, the patient was treated with mechanical ventilation, midazolam, and levetiracetam, and the limb twitching symptoms were controlled. The patient was comatose, chronically bedridden, with gastrointestinal dysfunction, and was treated prophylactically with antibiotics against infection, parenteral nutrition, and other supportive measures. B vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone were given, and mechanical ventilation and midazolam were stopped after 8 days. He was discharged from the hospital on 30 days and continued symptomatic treatment with B-vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone, and antiepileptic treatment with levetiracetam, with outpatient follow-up. OUTCOMES: No further seizures were recorded and the patient recovered well. LESSONS: MELAS syndrome without stroke-like episodes of diffuse posterior cerebral white matter lesions is rare in clinical practice, and the possibility of MELAS syndrome should be considered in symmetric posterior cerebral white matter lesions.

Bone morphogenetic protein 9 serves a protective role in response to ischemic­reperfusion in the brain by promoting ERK activation.

The aim of the present study was to investigate the expression and function mechanism of bone morphogenetic protein 9 (BMP9) in cerebral ischemia­reperfusion (I/R) injuries in vivo and in vitro. A total of 40 Sprague­Dawley rats were randomly divided into four groups (n=10): i) Normal control; ii) sham surgery group, the procedure without occlusion; iii) I/R group, right middle cerebral artery occlusion (MCAO) followed by reperfusion; and iv) adenoviral vector (Ad)­BMP9 + I/R group, Ad­BMP9 intracerebroventricular injection was performed 2 days prior to MCAO. Neurological deficit score and infarct volume were measured at 24 h following reperfusion. To further test the mechanism of BMP9, astrocytes were isolated and treated with Ad­BMP9, Ad­BMP9 + extracellular signal­regulated kinase (ERK) inhibitor PD098059, Ad­BMP9 + c­Jun N­terminal kinase inhibitor SP600125 and Ad­BMP9 + p38 inhibitor SB203580 for 24 h, followed by undergoing oxygen­glucose deprivation and reoxygenation (OGD/R) treatment. Cell viability and death were assessed by 3­(4,5­dimethylthiazol­2yl)­5­(3­carboxymethoxyphenyl)­(4­sulfophenyl)­2H­tetrazolium and lactate dehydrogenase release, respectively. Gene expression was determined by quantitative polymerase chain reaction and western blotting. BMP9 was identified to be upregulated at mRNA and protein levels in cerebral I/R animal and cell models. BMP9 pretreatment significantly reduced the neurological score and infarct volume compared with I/R rats. In astrocytes, overexpression of BMP9 significantly decreased cell death and improved cell viability, an effect which may be mediated by the ERK signaling pathway, as ERK was activated by BMP9 and the use of PD098059 partially reversed the protective effect of BMP9. Pretreatment with BMP­9 may be a promising treatment option for prevention of cerebral I/R injuries.

Systematic analysis of microarray datasets to identify Parkinson's disease­associated pathways and genes.

In order to investigate commonly disturbed genes and pathways in various brain regions of patients with Parkinson's disease (PD), microarray datasets from previous studies were collected and systematically analyzed. Different normalization methods were applied to microarray datasets from different platforms. A strategy combining gene co­expression networks and clinical information was adopted, using weighted gene co­expression network analysis (WGCNA) to screen for commonly disturbed genes in different brain regions of patients with PD. Functional enrichment analysis of commonly disturbed genes was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Co­pathway relationships were identified with Pearson's correlation coefficient tests and a hypergeometric distribution­based test. Common genes in pathway pairs were selected out and regarded as risk genes. A total of 17 microarray datasets from 7 platforms were retained for further analysis. Five gene coexpression modules were identified, containing 9,745, 736, 233, 101 and 93 genes, respectively. One module was significantly correlated with PD samples and thus the 736 genes it contained were considered to be candidate PD­associated genes. Functional enrichment analysis demonstrated that these genes were implicated in oxidative phosphorylation and PD. A total of 44 pathway pairs and 52 risk genes were revealed, and a risk gene pathway relationship network was constructed. Eight modules were identified and were revealed to be associated with PD, cancers and metabolism. A number of disturbed pathways and risk genes were unveiled in PD, and these findings may help advance understanding of PD pathogenesis.

SNCA rs3822086 C>T Polymorphism Increases the Susceptibility to Parkinson's Disease in a Chinese Han Population.

OBJECTIVE: Protofibrils of alpha-synuclein mediate neuronal cell death and propagate Parkinson's disease (PD). In this study, we investigated the relationship between the rs3822086 C>T polymorphism located in the fourth intron of the alpha-synuclein (SNCA) gene and susceptibility to PD in a Chinese Han population. METHODS: 146 PD patients and 144 sex- and age-matched healthy individuals (control group) were selected for this study. The SNCA rs3822086 polymorphism was examined in all 300 study subjects by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The genotype and allele frequencies of the SNCA rs3822086 polymorphism showed significant differences between the PD group and control group (TT: 25.3% vs. 18.8%, p=0.035; CT+TT: 77.4% vs. 66.0%, p=0.031; T allele: 51.4% vs. 42.4%, p=0.030; respectively). Stratified analyses based on gender indicated that male PD patients exhibited higher genotype and allele frequencies of the SNCA rs3822086 polymorphism compared to healthy male controls (TT: 26.7% vs. 13.2%, p=0.011; CC+CT: 73.3% vs. 86.8%, p=0.024; T allele: 51.2% vs. 37.9%, p=0.012; respectively). Age-stratified analyses indicated that the genotype and allele frequencies of the SNCA rs3822086 polymorphism were significantly higher in PD patients older than 60 years in comparison to healthy controls (TT: 32.2% vs. 20.5%, p=0.014; CT+TT: 77.0% vs. 60.2%, p=0.017; T allele: 54.6% vs. 40.3%, p=0.008; respectively). CONCLUSION: Our findings demonstrate that the SNCA rs3822086 C>T polymorphism correlates with increased susceptibility to PD among the Chinese Han population.