Somatic mitochondrial DNA mutations in different grades of glioma.

Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.

Safety and Use of MLC601/MLC901 (NeuroAiDTM) in Primary Intracerebral Hemorrhage: A Cohort Study from the NeuroAiD Safe Treatment Registry.

BACKGROUND: MLC601/MLC901 (NeuroAiD™) is a combination of natural products shown to be safe and to aid neurological recovery after brain injuries, especially ischemic stroke. Few studies have investigated NeuroAiD in primary intracerebral hemorrhage (ICH). The NeuroAiD Safe Treatment (NeST) Registry explores NeuroAiD use in the real-world setting. This cohort study aimed to assess its use and safety in ICH. METHODS: The online NeST Registry of subjects with ICH given NeuroAiD prospectively collected clinical data at baseline and monthly visits (V) 1 to 3. Outcome measures included compliance, side effects, Glasgow Coma Scale (GCS), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Short Orientation-Memory-Concentration Test (SOMCT). RESULTS: Sixty-six subjects were included. NeuroAiD was well-tolerated with fair compliance over three months. Two non-serious side effects were reported. Mean scores significantly improved on all outcome scales. The proportion of subjects with favorable outcomes significantly improved from baseline to V3: NIHSS 0-4, from 12% to 59% (p < 0.0001); GCS 13-15, from 64% to 88% (p = 0.007); mRS 0-1, from 9% to 37% (p = 0.004); and SOMCT score 0-8, from 44% to 68% (p = 0.029). CONCLUSIONS: NeuroAiD in the real-world setting was safe and showed potential for a sustained positive effect on neurological recovery after ICH.

Late Temporal Lobe Extensive Osteoradionecrosis Post Radiation for Nasopharyngeal Carcinoma: Case Series.

Osteoradionecrosis is one of the most serious complications of radiotherapy for nasopharyngeal carcinoma. We report three cases of osteoradionecrosis in temporal lobe who presented differently few years after completion of radiotherapy. Cranial magnetic resonance image showed lesions in temporal lobe either unilateral or bilateral with mass effect. One of the cases even showed disease progression few years after the initial diagnosis of osteoradionecrosis. Diagnosis of osteoradionecrosis for all three patients was confirmed by biopsy.

Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress.

The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress.

Sphenoethmoid sinusitis in a child resulting in a disastrous intracranial sequela.

Localized sphenoethmoid sinusitis in children is a rare occurrence. It is usually overlooked because of the misconception that the sinuses are not developed. We describe a case of localized acute sphenoid and right posterior ethmoid sinusitis that presented as right frontobasal subdural empyema and multiple deep cerebral abscesses. Morbidity from subdural empyema in children is high. Early diagnosis and treatment based on recognition that the etiology might involve the paranasal sinuses affects the overall prognosis.