Leigh syndrome followed by parkinsonism in an adult with homozygous c.626C > T mutation in MTFMT

Objective : To report the clinical, radiologic, biochemical, and molecular characteristics in a 46-year-old participant with adult-onset Leigh syndrome (LS), followed by parkinsonism. Methods : Case description with diagnostic workup included blood and CSF analysis, skeletal muscle investigations, blue native polyacrylamide gel electrophoresis, whole exome sequencing targeting nuclear genes involved in mitochondrial transcription and translation, cerebral MRI, 123I-FP-CIT brain single-photon emission computed tomography (SPECT), and C-11 raclopride positron emission tomography (PET). Results : The participant was found to have a defect in the oxidative phosphorylation caused by a c.626C>T mutation in the gene coding for mitochondrial methionyl-tRNA formyltransferase (MTFMT), which is a pathogenic mutation affecting intramitochondrial protein translation. The proband had a normal concentration of lactate in blood and no abnormal microscopic findings in skeletal muscle. Cerebral MRI showed bilateral lesions in the striatum, mesencephalon, pons, and medial thalamus. Lactate concentration in CSF was increased. FP-CIT SPECT and C-11 raclopride PET demonstrated a defect in the dopaminergic system. Conclusions : We report on a case with adult-onset LS related to a MTFMT mutation. Two years after the onset of symptoms of LS, the proband developed a parkinson-like disease. The c.626C>T mutation is the most common pathogenic mutation found in 22 patients reported earlier in the literature with a defect in MTFMT. The age of the previously reported cases varied between 14 months and 24 years. Our report expands the phenotypical spectrum of MTFMT-related neurologic disease and provides clinical evidence for involvement of MTFMT in extrapyramidal syndromes

"Silver" mode for the heavy Higgs search in the presence of a fourth SM family

We investigate the possible enhancement to the discovery of the heavy Higgs boson through the possible fourth SM family heavy neutrino. Using the channel h-> v4 v4->mu W mu W, it is found that for certain ranges of Higgs boson and v4 masses LHC could discover both of them simultaneously with 1 fb^-1 integrated luminosity

Variability of physiological brain perfusion in healthy subjects – A systematic review of modifiers. Considerations for multi-center ASL studies

Quantitative measurements of brain perfusion are influenced by perfusion-modifiers. Standardization of measurement conditions and correction for important modifiers is essential to improve accuracy and to facilitate the interpretation of perfusion-derived parameters. An extensive literature search was carried out for factors influencing quantitative measurements of perfusion in the human brain unrelated to medication use. A total of 58 perfusion modifiers were categorized into four groups. Several factors (e.g., caffeine, aging, and blood gases) were found to induce a considerable effect on brain perfusion that was consistent across different studies; for other factors, the modifying effect was found to be debatable, due to contradictory results or lack of evidence. Using the results of this review, we propose a standard operating procedure, based on practices already implemented in several research centers. Also, a theory of ‘deep MRI physiotyping’ is inferred from the combined knowledge of factors influencing brain perfusion as a strategy to reduce variance by taking both personal information and the presence or absence of perfusion modifiers into account. We hypothesize that this will allow to personalize the concept of normality, as well as to reach more rigorous and earlier diagnoses of brain disorders

Delayed intravenous thrombolysis based on MRI mismatch in posterior circulation stroke

The current time-based approach for patient selection for intravenous (IV) thrombolysis in an acute stroke setting neglects the individual variation of cerebral blood flow impairment. This approach restricts the eligible patient population. In the last decade, advanced imaging and especially MRI diffusion- and perfusion-weighted imaging (DWI-PWI) techniques have been used to select patients for IV thrombolysis outside the current 4.5 h time window. Most of these studies focus on the anterior (carotid artery) cerebral circulation only. We report the case of an acute ischemic stroke due to a dissection of the right vertebral artery and occlusion of the posterior inferior cerebellar artery with good clinical outcome. The patient received IV thrombolysis far beyond the current established time window. This decision was based upon a marked MRI DWI-PWI mismatch zone in the posterior circulation territory