Dyslexia and cognitive impairment in adult patients with myotonic dystrophy type 1: a clinical prospective analysis.

BACKGROUND: Cognitive impairments in patients with myotonic dystrophy type 1 (DM1) have often been described, however, there are only few studies differentiating between partial performance disorders and mental retardation in common. This study focused on the evaluation of reading performance and the frequency of dyslexia in adult DM1 patients. METHODS: We performed a prospective cohort study including genetically confirmed adult DM1 patients registered in the DM registry of Germany or the internal database of the Friedrich-Baur-Institute, Munich, Germany. For the assessment of the patients' reading and spelling performance, we used the standardized and validated test 'Salzburger Lese- und Rechtschreibtest' (SLRT II). The 'CFT-20 R Grundintelligenztest Skala 2' in revised ("R") version (CFT 20-R), determining the intelligence level, was appropriate to differentiate between dyslexia and general mental retardation. The diagnosis of dyslexia, the combined reading and spelling disorder, was based on the guidelines for diagnosis and therapy of children and adolescents with dyslexia 2015 (S3-guideline) providing (1) the criterion of the divergence from age level and (2) the criterion of IQ-divergence. RESULTS: Fifty-seven DM1 patients participated in our study. Evaluating the reading performance, 16 patients fulfilled the divergence criteria of the age level and 2 patients the IQ-divergence criteria. In total, the diagnosis of a reading disorder was given in 18 DM1 patients (31.6 %). In 11 out of these 18 patients with a reading disorder, a relevant impairment of spelling performance was observed with at least three spelling errors. As there are no normative values for adults in spelling performance, we assume a combined reading disorder and dyslexia, in those 11 DM1 patients (19.3 %). Regarding the separate analyses of the test procedures, in the SLRT II the performance was below average in 40.4 % of all patients for 'word reading' and in 61.4 % of all patients for 'pseudoword reading'. There was a significant positive correlation between the CTG expansion size and a reading disorder (p=0.027). The average IQ of 17 examined DM1 patients was in the lower normal range (86.1 ± 19.1). 54.5 % of patients with reading disorder had a normal IQ. CONCLUSION: The calculated prevalence of dyslexia in the DM1 study cohort was 19.3 % and thus considerably increased compared to the normal German population. As dyslexia is not equivalent to a general cognitive impairment, it is important not to miss dyslexic features in cognitive inconspicuous DM1 patients. Case-by-case one should consider a differential diagnostic approach, as individualized therapies can be offered to support dyslexic patients in their performance.

Anticonvulsant actions of furosemide in vitro.

Anticonvulsant properties of furosemide have been suggested to reduce neuronal synchronization via its inhibitory effect on the Na+/K+/2Cl- co-transport system. We have studied effects of furosemide on spontaneous epileptiform activity and analysed effects of furosemide on amplitudes of stimulus-induced population-spikes, on stimulus-induced K+ changes, on extracellular pH changes at rest and during stimulation, and on changes in the extracellular space-volume. We used three different in vitro models of epilepsy in the combined hippocampal-entorhinal cortex slice preparation. Furosemide reversibly suppressed low Ca2+-induced epileptiform activity in hippocampus proper and blocked or significantly reduced different types of epileptiform discharges in the low Mg2+ model and the 4-aminopyridine model. Amplitudes of evoked field potentials underwent an initial slight increase followed by a significant reduction after prolonged treatment with furosemide. Stimulus-induced increases in extracellular potassium were also significantly reduced. Furosemide caused an alkaline shift at rest. Stimulus-induced pH transients changed from a biphasic alkalotic-acidotic sequence to a monophasic alkalotic shift. Stimulation-induced shrinkage of extracellular space-volume was reduced by furosemide, whereas no effect on baseline extracellular space-volume was seen. We conclude, that furosemide possesses strong anticonvulsive effects in various in vitro models of epilepsy. The anticonvulsive properties of furosemide cannot be explained by its effects on extracellular pH changes but appear in part to be mediated via a reduced excitability with consequent reduction of activity-induced potassium rises. Finally, partial inhibition of activity-induced extracellular space shrinkage may contribute to its anticonvulsant properties.

Measurement of acidic aerosol species in eastern Europe: implications for air pollution epidemiology.

A large number of studies have indicated associations between particulate air pollution and adverse health outcomes. Wintertime air pollution in particular has been associated with increased mortality. Identification of causal constituents of inhalable particulate matter has been elusive, although one candidate has been the acidity of the aerosol. Here we report measurements of acidic aerosol species made for approximately 1.5 years in Erfurt, Germany, and Sokolov, Czech Republic. In both locations, the burning of high-sulfur coal is the primary source of ambient air pollution. Twenty-four-hour average measurements were made for PM10, [particulate matter with an aerodynamic diameter (da) < or = 10 microns], as well as fine particle (da < 2.5 microns) H+ and SO4(2-) for the entire study. Additionally, separate day and night measurements of fine particle H+, SO4(2-), NO3-, and NH4+ and the gases, SO2, HNO3, HONO, and NH3 were collected with an annular denuder/filter pack system over a 7-month (late winter-summer) period with additional measurements during pollution episodes the following winter. At both sites, 24-hr SO2 (mean concentrations of 52 micrograms/m3, with peak levels of > 585 micrograms/m3) and PM10 (mean concentration 60 micrograms m3) concentrations were quite high. However, aerosol SO4(2-) concentrations (mean concentration of approximately 10 micrograms/m3) were not as great as expected given the high SO2 concentrations, and acidity was very low (mean concentration of < 1 microgram/m3, with peak levels of only 7 micrograms/m3). Low acidity is likely to be the result of NH3 neutralization and slow conversion of SO2 to SO4(2-).(ABSTRACT TRUNCATED AT 250 WORDS)

Prehospital thrombolysis in acute myocardial infarction.

The benefit and risk of prehospital thrombolysis for acute myocardial infarction (AMI) were evaluated in a double-blind randomized trial. Patients presenting less than 4 hours after symptom onset received 2 million units of urokinase as an intravenous bolus either before (group A, n = 40) or after (group B, n = 38) hospital admission. The mean time interval from onset of symptoms to thrombolytic therapy was 85 +/- 51 minutes in group A and 137 +/- 50 minutes in group B (p less than 0.0005). In 91% of the patients, thrombolytic therapy was administered less than 3 hours after symptom onset. Complication rates during the pre- and in-hospital period were low and did not differ between groups. Three patients died (1 in group A, 2 in group B) from reinfarction 7 to 14 days after admission. Left-sided cardiac catheterization before discharge revealed a patency rate in the infarct-related artery of 61% in group A and 67% in group B (difference not significant). Global left ventricular function and regional wall motion at the infarct site did not differ significantly between group A and B (ejection fraction 51 +/- 10%, n = 28 vs 53 +/- 14%, n = 28; wall motion -2.3 +/- 1.3 vs -2.2 +/- 1.1 standard deviation, respectively). Also, peak creatine kinase did not differ significantly (838 +/- 634 U/liter in group A vs 924 +/- 595 U/liter in group B). Prehospital thrombolysis using a bolus injection of urokinase has a low risk when performed by a trained physician with a mobile care unit. The saving of 45 minutes in the early stage of an acute infarction through prehospital thrombolysis did not appear to be important for salvage of myocardial function.