Mitochondrial Disease and Hearing Loss in Children: A Systematic Review.

OBJECTIVES: Hearing loss is a clinical symptom, frequently mentioned in the context of mitochondrial disease. With no cure available for mitochondrial disease, supportive treatment of clinical symptoms like hearing loss is of the utmost importance. The aim of this study was to summarize current knowledge on hearing loss in genetically proven mitochondrial disease in children and deduce possible and necessary consequences in patient care. METHODS: Systematic literature review, including Medline, Embase, and Cochrane library. Review protocol was established and registered prior to conduction (International prospective register of systematic reviews-PROSPERO: CRD42020165356). Conduction of this review was done in accordance with MOOSE criteria. RESULTS: A total of 23 articles, meeting predefined criteria and providing sufficient information on 75 individuals with childhood onset hearing loss was included for analysis. Both cochlear and retro-cochlear origin of hearing loss can be identified among different types of mitochondrial disease. Analysis was hindered by inhomogeneous reporting and methodical limitations. CONCLUSION: Overall, the findings do not allow for a general statement on hearing loss in children with mitochondrial disease. Retro-cochlear hearing loss seems to be found more often than expected. A common feature appears to be progression of hearing loss over time. However, hearing loss in these patients shows manifold characteristics. Therefore, awareness of mitochondrial disease as a possible causative background is important for otolaryngologists. Future attempts rely on standardized reporting and long-term follow-up. LEVEL OF EVIDENCE: NA Laryngoscope, 132:2459-2472, 2022.

Evidence for a dysfunction of left posterior reading areas in German dyslexic readers.

The brain activity during a sentence reading task and a visual control task was examined with fMRI in 13 German dyslexic readers and 15 age-matched fluent readers (age: 14-16 years). These participants came from a longitudinal study and the dyslexic readers exhibited a persistent reading fluency deficit from early on. For the first time with German dyslexic readers, and in correspondence with the majority of functional imaging studies, we found reduced dyslexic activation in the left occipitotemporal cortex and in a small region of the left supramarginal gyrus. Enhanced activation was found in left inferior frontal and subcortical regions.

A placebo-controlled study of lofexidine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.

This study evaluated the efficacy and safety of Lofexidine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with lofexidine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. Fourty-four medication-free subjects (41 boys and three girls; mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, lofexidine was associated with a mean improvement of 41% in the total score on the teacher-rated ADHD Rating Scale compared to 7% improvement for placebo. Eleven of 22 subjects who received lofexidine were blindly rated on the Clinical Global Scale-Improvement as either much improved or very much improved compared to none of 22 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 29% in the lofexidine group and 18% in the placebo group, which was not a significant difference. On the Continuous Performance Test, commission errors decreased by 25% and omission errors by 20% in the lofexidine group, compared with increases of 33% in commission errors and of 36% in omission errors in the placebo group. Tic severity decreased by 27% in the lofexidine group, compared to 0% in the placebo group. One lofexidine subject with sedation withdrew at week 4. Lofexidine was associated with insignificant decreases in blood pressure and pulse. Lofexidine appears to be a safe and effective treatment for children with tic disorders and ADHD.

The intensity-pitch relation revisited: monopolar versus bipolar cochlear stimulation.

OBJECTIVE/HYPOTHESIS: The very high speech perception scores now being achieved with cochlear implants have led to demands for similar levels of achievement in music perception and perception in noisy environments. One of the crucial factors in these fields is pitch perception. The aim of the present study was to investigate the extent to which pitch perception is influenced by the intensity of the stimulus, through the use of different stimulation modes (monopolar, bipolar) and different electrodes (lateral and perimodiolar). STUDY DESIGN: Sixteen postlingually deafened patients with an average implant use of 3.1 years were included in this study. All patients were using a Cochlear (CI24M, CI24R, CI24RE) cochlear implant. METHODS: Subjects were asked to compare the pitch of an intensity-constant reference tone with the pitch of a test tone of varying intensity. The test was repeated for apical, mediocochlear, and basal channel locations, and also for monopolar and bipolar stimulation. RESULTS: It was found that in monopolar stimulation 87.5% and in bipolar stimulation 85.7% of the patients perceived a clear pitch change with changing intensity of the stimulus (Spearman correlation coefficients r < -0.3 or r > 0.3, respectively). A total of 73.1% of these patients perceived lower pitches with increasing intensity, 26.9% reported the opposite effect. No statistically significant difference in the intensity-pitch correlation could be found between mono- and bipolar stimulation. Neither the mean dynamic range nor the type of electrode used was found to be related to the correlation coefficient. CONCLUSION: Although the majority of today's cochlear implant recipients perform well and the intensity-pitch relation in cochlear implant recipients is still poorly understood, rising demands on speech-coding strategies may soon make a compensation of the pitch shifts desirable. Although the results of our study tend to argue against a peripheral mechanism, the exact origin of this phenomenon remains unclear.

Developmental dyslexia: gray matter abnormalities in the occipitotemporal cortex.

Functional neuroimaging studies have consistently demonstrated less activation of the left occipitotemporal cortex in dyslexic readers. This region is considered critical for skilled reading and damage to it in adult readers leads to severe deficits in reading ability. In contrast to these findings, structural abnormalities in the occipitotemporal cortex were not consistently found to date. We used optimized Voxel Based Morphometry with T1 weighted MR images to investigate gray matter volume in 13 dyslexic and 15 nonimpaired reading adolescents (age 14-16). Less gray matter volume for dyslexic readers was found in the left and right fusiform gyrus, the bilateral anterior cerebellum and in the right supramarginal gyrus. Decreased gray matter volume in the left and right fusiform gyrus of dyslexic readers highlights the importance of this brain region for developmental dyslexia. The structural abnormalities in the right occipitotemporal cortex suggest that dyslexia may be such a persistent disorder because an occipitotemporal reading area, critical for skilled reading, cannot develop in any hemisphere. The extended areas of reduced gray matter volume in dyslexic readers in the cerebellum suggest that structural abnormalities in the cerebellum are also strongly associated with dyslexia and warrant further investigation.

Taxi vs. taksi: on orthographic word recognition in the left ventral occipitotemporal cortex.

The importance of the left occipitotemporal cortex for visual word processing is highlighted by numerous functional neuroimaging studies, but the precise function of the visual word form area (VWFA) in this brain region is still under debate. The present functional magnetic resonance imaging study varied orthographic familiarity independent from phonological-semantic familiarity by presenting orthographically familiar and orthographically unfamiliar forms (pseudohomophones) of the same words in a phonological lexical decision task. Consistent with orthographic word recognition in the VWFA, we found lower activation for familiar compared with unfamiliar forms, but no difference between pseudohomophones and pseudowords. This orthographic familiarity effect in the VWFA differed from the phonological familiarity effect in left frontal regions, where phonologically unfamiliar pseudowords led to higher activation than phonologically familiar pseudohomophones. We suggest that the VWFA not only computes letter string representations but also hosts word-specific orthographic representations. These representations function as recognition units with the effect that letter strings that readily match with stored representations lead to less activation that letter strings that do not.

Experimental realization of one-way quantum computing with two-photon four-qubit cluster states.

We report an experimental realization of one-way quantum computing on a two-photon four-qubit cluster state. This is accomplished by developing a two-photon cluster state source entangled both in polarization and spatial modes. With this special source, we implemented a highly efficient Grover's search algorithm and high-fidelity two-qubit quantum gates. Our experiment demonstrates that such cluster states could serve as an ideal source and a building block for rapid and precise optical quantum computation.

Comparison of cyanamide and placebo in the treatment of alcohol dependence of adolescents.

AIMS: About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that cyanamide may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term cyanamide treatment in alcohol dependence of adolescents. METHODS: In this, double-blind, placebo-controlled study, we recruited 26 patients, aged 16-19 years, with chronic (frequent and regular) or episodic (frequent, but irregular) alcohol dependence. Patients were randomly allocated treatment with cyanamide (200 mg daily) or a placebo for 90 days. Patients were assessed on the day the treatment was started, and on days 30 and 90, by interview, self-report, questionnaire and laboratory screening. Patients were classified as abstinent, relapsing or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure. RESULTS: The cyanamide (n = 13) and placebo (n = 13) groups were well matched in terms of baseline demographic and alcohol-related variables. Mean cumulative abstinence duration was significantly greater in the cyanamide group than in the placebo group. Apart from occasional diarrhoea, there was no difference in side effects between groups. CONCLUSIONS: Cyanamide seems to be an effective and well tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for the treatment of some adolescent alcohol-dependent patients. Because of reported hepatotoxic, haematological and dermatological side effects, patients should be observed continuously by experienced clinicians. Further studies are necessary to prove the efficacy of cyanamide in adolescents.

The visual word form area and the frequency with which words are encountered: evidence from a parametric fMRI study.

Cohen and Dehaene et al. proposed that the Visual Word Form Area (VWFA) in the left midfusiform gyrus, contrary to its name, is limited to the extraction of an abstract letter string and not involved in proper visual word recognition. We examined this prelexical function of the VWFA by a parametric block design with five levels of written word frequency. The lowest level was represented by pseudowords and the highest level by words of very high frequency. Contrary to the assumed prelexical function of the VWFA, increasing frequency was associated with decreasing brain activation in a large posterior cluster of the left hemisphere including middle and posterior fusiform regions. The same negative relation between frequency and activation was found in several left frontal clusters. The relation of increasing frequency and decreasing activation in occipitotemporal regions corresponds to a similar relation in the same brain regions found by studies which experimentally manipulated object or face familiarity. This convergence suggests that fusiform regions are specialized for extracting and storing abstract patterns when processing visual objects and these patterns serve as recognition units in subsequent encounters with the same objects.