Visual memory failure presages conversion to MELAS phenotype.

OBJECTIVE: To examine the correlation between verbal and visual memory function and correlation with brain metabolites (lactate and N-Acetylaspartate, NAA) in individuals with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). METHODS: Memory performance and brain metabolites (ventricular lactate, occipital lactate, and occipital NAA) were examined in 18 MELAS, 58 m.3243A > G carriers, and 20 familial controls. Measures included the Selective Reminding Test (verbal memory), Benton Visuospatial Retention Test (visual memory), and MR Spectroscopy (NAA, Lactate). ANOVA, chi-squared/Fisher's exact tests, paired t-tests, Pearson correlations, and Spearman correlations were used. RESULTS: When compared to carriers and controls, MELAS patients had the: (1) most impaired memory functions (Visual: p = 0.0003; Verbal: p = 0.02), (2) greatest visual than verbal memory impairment, (3) highest brain lactate levels (p < 0.0001), and (4) lowest brain NAA levels (p = 0.0003). Occipital and ventricular lactate to NAA ratios correlated significantly with visual memory performance (p ≤ 0.001). Higher lactate levels (p ≤ 0.01) and lower NAA levels (p = 0.0009) correlated specifically with greater visual memory dysfunction in MELAS. There was little or no correlation with verbal memory. INTERPRETATION: Individuals with MELAS are at increased risk for impaired memory. Although verbal and visual memory are both affected, visual memory is preferentially affected and more clearly associated with brain metabolite levels. Preferential involvement of posterior brain regions is a distinctive clinical signature of MELAS. We now report a distinctive cognitive phenotype that targets visual memory more prominently and earlier than verbal memory. We speculate that this finding in carriers presages a conversion to the MELAS phenotype.

Reversible cerebral vasoconstriction syndrome in children: an update.

Headaches are one of the most common neurologic complaints leading to emergency room visits in pediatric patients. Of the different type of headache presentations, thunderclap headaches require a particularly urgent work-up. In children, recurrent thunderclap headaches are more often associated with reversible cerebral vasoconstriction syndrome (RCVS) than other etiologies such as subarachnoid hemorrhage. RCVS is a vascular disorder of incompletely understood etiology, characterized by diffuse vasoconstriction of the cerebral arterial vasculature, and commonly associated with recurrent severe headaches. Patients may experience focal neurological deficits, due to hemorrhages, infarcts, and even posterior reversible encephalopathy syndrome . Although RCVS has been best characterized in adults, it does occur in children. This review summarizes the presentation of RCVS in children and highlights some of the differences with the adult population.

Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity.

Mitochondrial disorders represent a large collection of rare syndromes that are difficult to manage both because we do not fully understand biochemical pathogenesis and because we currently lack facile markers of severity. The m.3243A>G variant is the most common heteroplasmic mitochondrial DNA mutation and underlies a spectrum of diseases, notably mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS). To identify robust circulating markers of m.3243A>G disease, we first performed discovery proteomics, targeted metabolomics, and untargeted metabolomics on plasma from a deeply phenotyped cohort (102 patients, 32 controls). In a validation phase, we measured concentrations of prioritized metabolites in an independent cohort using distinct methods. We validated 20 analytes (1 protein, 19 metabolites) that distinguish patients with MELAS from controls. The collection includes classic (lactate, alanine) and more recently identified (GDF-15, α-hydroxybutyrate) mitochondrial markers. By mining untargeted mass-spectra we uncovered 3 less well-studied metabolite families: N-lactoyl-amino acids, ß-hydroxy acylcarnitines, and ß-hydroxy fatty acids. Many of these 20 analytes correlate strongly with established measures of severity, including Karnofsky status, and mechanistically, nearly all markers are attributable to an elevated NADH/NAD+ ratio, or NADH-reductive stress. Our work defines a panel of organelle function tests related to NADH-reductive stress that should enable classification and monitoring of mitochondrial disease.

Theoretical and experimental study of temperature effect on electronic and optical properties of TiO2: comparing rutile and anatase.

To gain fundamental understanding of the high-temperature optical gas-sensing and light-energy conversion materials, we comparatively investigate the temperature effects on the band gap and optical properties of rutile and anatase TiO2 experimentally and theoretically. Given that the electronic structures of rutile and anatase are fundamentally different, i.e. direct band gap in rutile and indirect gap in anatase, it is not clear whether these materials exhibit different electronic structure renormalizations with temperature. Using ab initio methods, we show that the electron-phonon interaction is the dominant factor for temperature band gap renormalization compared to the thermal expansion. As a result of different contributions from the acoustic and optical phonons, the band gap is found to widen with temperature up to 300 K, and to narrow at higher temperatures. Our calculations suggest that the band gap is narrowed by about 147 meV and 128 meV at 1000 K for rutile and anatase, respectively. Experimentally, for rutile and anatase TiO2 thin films we conducted UV-Vis transmission measurements at different temperatures, and analyzed band gaps from the Tauc plots. For both TiO2 phases, the band gap is found to decrease for temperature above 300 K quantitatively, agreeing with our theoretical results. The temperature effects on the dielectric functions, the refractive index, the extinction coefficient as well as the optical conductivity are also investigated. Rutile and anatase show generally similar optical properties, but differences exist in the long wavelength regime above 600 nm, where we found that the dielectric function of rutile decreases while that of anatase increases with temperature increase.

These are not the trends you are looking for: poorly calibrated single-pass electrofishing data can bias estimates of trends in fish abundance.

There is increasing interest in the potential of single-pass and timed electrofishing to assess status and trends in fish populations. However, where capture probability varies over time, there is a risk that uncalibrated electrofishing data could fail to detect, or provide biased estimates of trends. This study analysed a long-term electrofishing dataset collected over 50 years in an intensively studied catchment where egg deposition and emigrant production declined by c. 82% and 35% over the same time. The electrofishing data were used to illustrate the effects of changing capture probability on estimated trends in juvenile Atlantic salmon Salmo salar abundance. Temporal variability in capture probability was modelled. Trends in abundance were then estimated from uncalibrated single-pass electrofishing count data and compared with estimates from data calibrated for capture probability. The calibrated data revealed significant declines in S. salar fry (age 0) and parr (age ≥ 1) abundance. However, the trend estimates from the uncalibrated data were positively biased and not significant. Exploration of alternative (realistic) scenarios with different trends in true abundance and capture probability suggests that uncalibrated electrofishing data can provide very misleading estimates of trends. The problem is exacerbated in data where capture probability is low. It is recommended that single-pass and timed electrofishing methods should not be used to assess trends in fish populations without regular (annual) calibration.

A spatio-temporal statistical model of maximum daily river temperatures to inform the management of Scotland's Atlantic salmon rivers under climate change.

The thermal suitability of riverine habitats for cold water adapted species may be reduced under climate change. Riparian tree planting is a practical climate change mitigation measure, but it is often unclear where to focus effort for maximum benefit. Recent developments in data collection, monitoring and statistical methods have facilitated the development of increasingly sophisticated river temperature models capable of predicting spatial variability at large scales appropriate to management. In parallel, improvements in temporal river temperature models have increased the accuracy of temperature predictions at individual sites. This study developed a novel large scale spatio-temporal model of maximum daily river temperature (Twmax) for Scotland that predicts variability in both river temperature and climate sensitivity. Twmax was modelled as a linear function of maximum daily air temperature (Tamax), with the slope and intercept allowed to vary as a smooth function of day of the year (DoY) and further modified by landscape covariates including elevation, channel orientation and riparian woodland. Spatial correlation in Twmax was modelled at two scales; (1) river network (2) regional. Temporal correlation was addressed through an autoregressive (AR1) error structure for observations within sites. Additional site level variability was modelled with random effects. The resulting model was used to map (1) spatial variability in predicted Twmax under current (but extreme) climate conditions (2) the sensitivity of rivers to climate variability and (3) the effects of riparian tree planting. These visualisations provide innovative tools for informing fisheries and land-use management under current and future climate.

Reversible Cerebral Vasoconstriction Syndrome in Pediatrics: A Case Series and Review.

Reversible cerebral vasoconstriction syndrome is a transient vasculopathy associated with severe headaches and stroke. In most cases of reversible cerebral vasoconstriction syndrome, there is a precipitating event or trigger, such as pregnancy, serotonin agonist treatment or illicit drug use. The authors present 2 pediatric cases of reversible cerebral vasoconstriction syndrome and review the previous 11 pediatric cases in the literature. In many instances, the clinical and radiographic features are similar in both pediatric and adult cases. In the pediatric group, reported potential triggers include trauma (1/13), exercise (2/13), water to the face (3/13), hypertension (3/13), and medication or substance use (4/13). One surprising difference is that 11 out of 13 pediatric patients with reversible cerebral vasoconstriction syndrome are male while most cases in adults are female. Many of the pediatric patients with reversible cerebral vasoconstriction syndrome were treated with a calcium channel blocker and the overall outcome of pediatric reversible cerebral vasoconstriction syndrome was good, with most patients experiencing a full recovery.

Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-Like Episodes (MELAS): A Case Report and Critical Reappraisal of Treatment Options.

IMPORTANCE: Stroke-like episodes signal progression and significant disability in the mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes syndrome. Arginine is widely used as a treatment for stroke-like episode, although there is little evidence for this intervention. We discuss the management of a patient with mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes who presented with a stroke-like episode. OBSERVATION: During a seizure, which triggers the stroke-like episode, neurons are forced to utilize glycolysis as a source of adenosine triphosphate. Glycolytic by-products are damaging to the neuron. Breakdown of the blood-brain barrier leads to vasogenic edema. CONCLUSION: Treatment of stroke-like episode should include anticonvulsants interictally to prevent seizures and dexamethasone ictally to help repair the blood-brain barrier.

Astn2, a novel member of the astrotactin gene family, regulates the trafficking of ASTN1 during glial-guided neuronal migration.

Glial-guided neuronal migration is a key step in the development of laminar architecture of cortical regions of the mammalian brain. We previously reported that neuronal protein astrotactin (ASTN1) functions as a neuron-glial ligand during CNS glial-guided migration. Here, we identify a new Astn family member, Astn2, that is expressed at high levels in migrating, cerebellar granule neurons, along with Astn1, at developmental stages when glial-guided migration is ongoing. Biochemical and flow cytometry experiments show that ASTN2 forms a complex with ASTN1 and regulates surface expression of ASTN1. Live imaging of Venus-tagged ASTN1 in migrating cerebellar granule cells reveals the intracellular trafficking of ASTN1-Venus, with ASTN1-Venus accumulating in the forward aspect of the leading process where new sites of adhesion will form. Treatment of migrating neurons with Dynasore, a soluble noncompetitive inhibitor of Dynamin, rapidly arrests the migration of immature granule cells in a reversible manner, suggesting the critical importance of receptor trafficking to neuronal locomotion along Bergmann glial fibers in the developing cerebellum. Together, these findings suggest that ASTN2 regulates the levels of ASTN1 in the plasma membrane and that the release of neuronal adhesions to the glial fiber during neuronal locomotion involves the intracellular trafficking of ASTN1.

Sickle cell anemia with moyamoya disease: outcomes after EDAS procedure.

Moyamoya disease is a relatively uncommon neurovascular complication of sickle cell anemia. We report a case series of six patients with sickle cell anemia who developed moyamoya disease and underwent encephaloduroarteriosynangiosis procedures. These six patients presented with either cerebrovascular accidents, transient ischemic attacks, or seizures, and subsequent magnetic resonance imaging scans were suggestive of moyamoya-like changes in the cerebral vasculature. Conventional cerebral angiography was used to confirm the diagnosis in all six patients. Four of six patients manifested a cerebrovascular accident before surgery, and two of these patients were compliant on a transfusion protocol at the time of their cerebrovascular accident. Bilateral (n = 4) or unilateral (n = 2) encephaloduroarteriosynangiosis procedures were performed without any complications. The patient who was stroke-free preoperatively had a cerebrovascular accident 2 weeks after the procedure; otherwise, all patients have remained free of neurovascular complications with an average follow-up of 33 months. Collateral anastomoses between external and internal carotid arteries were established by magnetic resonance angiography in three patients. The encephaloduroarteriosynangiosis procedure is a safe and effective treatment option in patients with sickle cell anemia who develop moyamoya disease.