Implications of intracochlear decomposition gas formation in non-putrefied cadavers.

Introduction: Postmortem computed tomography (pmCT) prior to forensic autopsy has become increasingly important in recent decades, especially in forensic documentation of single injuries, injury patterns, and causes of death. Postmortem decomposition gas formation can also be detected in pmCT scans, which might affect cochlear implant research in postmortem human temporal bones (TBs). Material and methods: Fifty non-putrefied hanging fatalities within a 2-year period (January 2017 to December 2019) were included with 100 TBs. Each body underwent whole-body pmCT prior to forensic autopsy. PmCT scans were analyzed with respect to the presence of intracochlear gas despite the lack of putrefaction at autopsy by an experienced fellow neurotologist. Results: PmCT revealed gas formation in two individuals despite the lack of head trauma and putrefaction at postmortem examination and autopsy. Both individuals showed enclosed gas in the vestibule and the cochlea on both sides. Discussion: Intracochlear gas formation, most likely related to decomposition, may occur despite the lack of putrefaction at postmortem examination and autopsy and can be detected by pmCT. This finding seems to be rather rare in non-traumatic death cases but might affect cochlear pressure research in postmortem human TB.

Developmental surface dyslexia and dysgraphia in a child with corpus callosum agenesis: an approach to diagnosis and treatment.

We present a case study detailing cognitive performance, functional neuroimaging, and effects of a hypothesis-driven treatment in a 10-year-old girl diagnosed with complete, isolated corpus callosum agenesis. Despite having average overall intellectual abilities, the girl exhibited profound surface dyslexia and dysgraphia. Spelling treatment significantly and persistently improved her spelling of trained irregular words, and this improvement generalized to reading accuracy and speed of trained words. Diffusion weighted imaging revealed strengthened intrahemispheric white matter connectivity of the left temporal cortex after treatment and identified interhemispheric connectivity between the occipital lobes, likely facilitated by a pathway crossing the midline via the posterior commissure. This case underlines the corpus callosum's critical role in lexical reading and writing. It demonstrates that spelling treatment may enhance interhemispheric connectivity in corpus callosum agenesis through alternative pathways, boosting the development of a more efficient functional organization of the visual word form area within the left temporo-occipital cortex.

Preservation of Residual Hearing: Long-Term Results With a Mid-Scala Electrode.

OBJECTIVE: The long-term preservation of residual hearing after cochlear implantation has become a major goal over the past few years. The aim of the present study was to evaluate residual hearing in the long-term follow-up using mid-scala electrodes. METHODS: In this retrospective, single-center study, we collected data from 27 patients who were implanted between 2014 and 2015 with residual hearing in the low-frequency range using a mid-scala electrode. Measurements of the hearing thresholds were carried out directly postoperatively (day 1 after surgery) and in the long-term follow-up 43.7 ± 6.9 months. The calculation of the extent of audiological hearing preservation was determined using the HEARRING group formula by Skarsynski. RESULTS: Postoperative preservation of residual hearing was achieved in 69.2% of the cases in the low-frequency range between 250 Hz and 1 kHz, of which 89.5% of the patients had frequencies that suggested using electroacoustic stimulation (EAS). In the long-term follow-up, 30.8% of the patients showed residual hearing; however, 57.1% had apparently benefited from EAS. CONCLUSION: Preservation of residual hearing is feasible in the long term using mid-scala electrodes. Postoperatively, there is over the half of patients who benefit from an EAS strategy. The long-term follow-up shows a certain decrease in residual hearing. However, these results are comparable to studies relating to other types of electrodes. Further research should be conducted in future to better evaluate hearing loss in long-term follow-up, compared to direct postoperative audiological results.

ARID1B controls transcriptional programs of axon projection in an organoid model of the human corpus callosum.

Mutations in ARID1B, a member of the mSWI/SNF complex, cause severe neurodevelopmental phenotypes with elusive mechanisms in humans. The most common structural abnormality in the brain of ARID1B patients is agenesis of the corpus callosum (ACC), characterized by the absence of an interhemispheric white matter tract that connects distant cortical regions. Here, we find that neurons expressing SATB2, a determinant of callosal projection neuron (CPN) identity, show impaired maturation in ARID1B+/- neural organoids. Molecularly, a reduction in chromatin accessibility of genomic regions targeted by TCF-like, NFI-like, and ARID-like transcription factors drives the differential expression of genes required for corpus callosum (CC) development. Through an in vitro model of the CC tract, we demonstrate that this transcriptional dysregulation impairs the formation of long-range axonal projections, causing structural underconnectivity. Our study uncovers new functions of the mSWI/SNF during human corticogenesis, identifying cell-autonomous axonogenesis defects in SATB2+ neurons as a cause of ACC in ARID1B patients.

The effect of prenatal maternal distress on offspring brain development: A systematic review.

BACKGROUND: Prenatal maternal distress can negatively affect pregnancy outcomes, yet its impact on the offspring's brain structure and function remains unclear. This systematic review summarizes the available literature on the relationship between prenatal maternal distress and brain development in fetuses and infants up to 12 months of age. METHODS: We searched Central, Embase, MEDLINE, PsycINFO, and PSYNDEXplus for studies published between database inception and December 2023. Studies were included if prenatal maternal anxiety, stress, and/or depression was assessed, neuroimaging was used to examine the offspring, and the offspring's brain was imaged within the first year of life. The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-II. RESULTS: Out of the 1516 studies retrieved, 71 met our inclusion criteria. Although the studies varied greatly in their methodology, the results generally pointed to structural and functional aberrations in the limbic system, prefrontal cortex, and insula in fetuses and infants prenatally exposed to maternal distress. CONCLUSIONS: The hippocampus, amygdala, and prefrontal cortex have a high density of glucocorticoid receptors, which play a key role in adapting to stressors and maintaining stress-related homeostasis. We thus conclude that in utero exposure to maternal distress prompts these brain regions to adapt by undergoing structural and functional changes, with the consequence that these alterations increase the risk for developing a neuropsychiatric illness later on. Future research should investigate the effect of providing psychological support for pregnant women on the offspring's early brain development.

Rituximab treatment in pediatric-onset multiple sclerosis.

BACKGROUND AND PURPOSE: Rituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk-benefit profile of RTX in pediatric-onset multiple sclerosis are scarce. METHODS: In this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review. Annualized relapse rates, Expanded Disability Status Scale scores and magnetic resonance imaging parameters (new T2 lesions and contrast-enhancing lesions) were assessed before and during RTX treatment. The proportion of patients who remained free from clinical and disease activity (NEDA-3) during RTX treatment was calculated. Side effects such as infusion-related reactions, infections and laboratory abnormalities were assessed. RESULTS: Sixty-one patients received RTX during a median (interquartile range) follow-up period of 20.9 (35.6) months. The annualized relapse rate decreased from 0.6 (95% confidence interval [CI] 0.38-0.92) to 0.03 (95% CI 0.02-0.14). The annual rate of new T2 lesions decreased from 1.25 (95% CI 0.70-2.48) to 0.08 (95% CI 0.03-0.25) and annual rates of new contrast-enhancing lesions decreased from 0.86 (95% CI 0.30-3.96) to 0. Overall, 70% of patients displayed no evidence of disease activity (NEDA-3). Adverse events were observed in 67% of patients. Six patients discontinued treatment due to ongoing disease activity or adverse events. CONCLUSION: Our study provides class IV evidence that RTX reduces clinical and radiological activity in pediatric-onset multiple sclerosis.

Differences in the swallowing process of newborns and healthy preterm infants: first results with a non-invasive bioimpedance and electromyography measurement system.

PURPOSE: Preterm infants (PI) have difficulty coordinating sucking, swallowing and breathing, and there is a risk of aspiration. The causes of this are not yet sufficiently understood. The aim of this study was to test a novel measurement device to measure breathing and pharyngeal processes involved in swallowing externally in everyday life to identify possible differences in neonates (NB) and PI. METHODS: Forty healthy NB were studied at 4-8 weeks of age (mean: 6.7 weeks) and 20 healthy PI (mean gestational age 30.5 weeks) at postmenstrual age (PMA) 34/35 weeks (mean PMA 35.1 weeks) during a single feeding. Surface electrodes were used to measure bioimpedance and electromyography reflecting swallow-related changes in the pharynx and muscle activation of the tongue and submental muscles. A respiratory belt was combined with recording of the depth of chest movements and the occurrence of pauses in breathing. RESULTS: Velocity and extent of pharyngeal closure did not differ significantly across the feeding period (velocity: p=0.09, closure: p=0.17), but during the first two suck-swallow bursts PI had greater velocity (p<0.001*) and extent of pharyngeal closure (p=0.004*) than NB. The duration of swallowing phases was significantly longer in PIs (p<0.001*), their muscle activation decreased faster (p<0.001*), and they had more pauses in breathing than NBs. CONCLUSIONS: The novel measurement device allowed, for the first time in everyday life, the measurement of factors influencing swallowing and breath-swallow coordination in NBs and PIs. PIs showed differences from NBs most likely due to differences in muscle strength and condition.

Cortical thickness in the right medial frontal gyrus predicts planning performance in healthy children and adolescents.

The ability to plan is an important part of the set of the cognitive skills called "executive functions." To be able to plan actions in advance is of great importance in everyday life and constitutes one of the major key features for academic as well as economic success. The present study aimed to investigate the neuroanatomical correlates of planning in normally developing children, as measured by the cortical thickness of the prefrontal cortex. Eighteen healthy children and adolescents underwent structural MRI examinations and the Tower of London (ToL) task. A multiple regression analysis revealed that the cortical thickness of the right caudal middle frontal gyrus (cMFG) was a significant predictor of planning performance. Neither the cortical thickness of any other prefrontal area nor gender were significantly associated with performance in the ToL task. The results of the present exploratory study suggest that the cortical thickness of the right, but not the left cMFG, is positively correlated with performance in the ToL task. We, therefore, conclude that increased cortical thickness may be more beneficial for higher-order processes, such as information integration, than for lower-order processes, such as the analysis of external information.

Larger corpus callosum volume is favorable for theory of mind development in healthy children.

While previous research has demonstrated a link between the corpus callosum (CC) and theory of mind (ToM) abilities in individuals with corpus callosum agenesis (ACC), the relationship between CC volume and ToM remains unclear in healthy children. The present study examined whether CC volume influences children's performance on ToM tasks that assess their understanding of pretense, emotion recognition, and false beliefs. Forty children aged 6-12 years underwent structural magnetic resonance imaging (MRI) and a cognitive test battery. We found that larger mid-anterior and central subsections of the CC significantly correlated with better ToM abilities. We could also demonstrate age- and sex-related effects, as the CC-ToM relationship differed between younger (6-8 years) and older (9-12 years) children, and between female and male participants. Importantly, the older children drove the association between the CC mid-anterior and central subsection volumes and ToM abilities. This study is the first to demonstrate that CC size is associated with ToM abilities in healthy children, underlining the idea that the CC plays a vital role in their socio-cognitive development. CC subsection volumes may thus not only serve as a measure of heterogeneity in neurodevelopmental populations known to exhibit socio-cognitive deficits, but also in typically developing children.

Triple Semi-Circular Canal Occlusion and Cochlear Implantation: A Treatment Option for Single-Sided Menière's Disease with Functional Deafness-A Case Series.

The surgical options for patients with single-sided Menière's disease and functional deafness are challenging. Our case series reports the outcomes of surgical treatments of patients with single-sided Menière's disease and functional deafness. These patients have undergone a one-staged occlusion of all semi-circular canals and cochlear implantation. Five patients (four female and one male; 62 ± 8.2 years with a range from 50 to 72 years) with single-sided Menière's disease and functional deafness were included in this study. In all cases, the patients suffered from frequent rotational vertigo episodes for many years. Other treatment options (e.g., medication) had not yet been successful. Preoperatively, the Dizziness Handicap Inventory (DHI) of all patients indicated severe emotional, physical, and functional deficits. Patients showed a functional (near-total) deafness of the affected ear in all cases. All patients were supplied with cochlear implants in combination with a triple occlusion of all semi-circular canals in a one-stage procedure. After a short period of increased dizziness following surgery and after the activation of the cochlear implant and CI rehabilitation (auditory-verbal therapy), vertigo control and an adequate audiological outcome were achieved. The DHI showed a constant decrease after surgery. The combination of a triple semi-circular canal occlusion and cochlear implantation can be an efficient treatment for patients with single-sided Menière's disease.

Humoral Immune Response Following SARS-CoV-2 mRNA Vaccination and Infection in Pediatric-Onset Multiple Sclerosis.

OBJECTIVE: Currently, there are no data available on SARS-CoV-2 vaccine responses in pediatric-onset multiple sclerosis (POMS), and little is known about the course of SARS-CoV-2 infection in this age group. We therefore investigated humoral immune responses after COVID-19 vaccination and/or infection in POMS. METHODS: We retrospectively analyzed seroconversion rates and SARS-CoV-2-specific antibody levels in 30 POMS and one pediatric CIS patient treated with no disease-modifying therapy (no DMT), immunomodulatory DMT (IM-DMT), or immunosuppressive DMT (IS-DMT) from two Austrian MS centers. RESULTS: The median age at MS onset was 15.39 years (interquartile range [IQR]: 1.97). The median age at the first COVID-19 vaccination was 17.43 years (IQR: 2.76). After two vaccine doses, seroconversion (≥0.8 BAU/ml) was reached in 25 of 28 patients (89.3%). All patients with no DMT or IM-DMT generated robust immune responses to vaccination (seroconversion: no DMT: 6/6, IM-DMT: 7/7 [100%]; median titers: no DMT: 2075 BAU [IQR: 1268.50], IM-DMT: 2500 BAU [IQR: 0]). In the IS-DMT group, seroconversion was achieved in 12 of 14 patients (80%), and median titers were 50.8 BAU (IQR 254.63). Titers were significantly higher in no DMT versus IS-DMT (P = 0.012) and in IM-DMT versus IS-DMT (P = 0.001). Infection with SARS-CoV-2 occurred in 11 of 31 patients, and symptoms were mild in all cases. One relapse occurred after infection, but no relapses were documented after vaccination. CONCLUSIONS: Generally, mRNA vaccinations were well tolerated in POMS patients with and without DMT. Immune response was significantly reduced in patients treated with IS-DMT. No unexpected adverse events or relapses related to vaccinations were observed.

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can change the normal trajectory of human fetal brain development and may lead to long-lasting neurodevelopmental changes in the form of fetal alcohol spectrum disorders. Currently, early prenatal patterns of alcohol-related central nervous system changes are unclear and it is unknown if small amounts of PAE may result in early detectable brain anomalies. This super-resolution fetal magnetic resonance imaging (MRI) study aimed to identify regional effects of PAE on human brain structure. Fetuses were prospectively assessed using atlas-based semi-automated 3-dimensional tissue segmentation based on 1.5 T and 3 T fetal brain MRI examinations. After expectant mothers completed anonymized PRAMS and TACE questionnaires for PAE, fetuses without gross macroscopic brain abnormalities were identified and analyzed. Linear mixed-effects modeling of regional brain volumes was conducted and multiple comparisons were corrected using the Benjamini-Hochberg procedure. In total, 500 pregnant women were recruited with 51 reporting gestational alcohol consumption. After excluding confounding comorbidities, 24 fetuses (26 observations) were identified with PAE and 52 age-matched controls without PAE were analyzed. Patients with PAE showed significantly larger volumes of the corpus callosum (P ≤ 0.001) and smaller volumes of the periventricular zone (P = 0.001). Even minor (1-3 standard drinks per week) PAE changed the neurodevelopmental trajectory.

Visuospatial processing skills following unilateral arterial ischemic stroke in childhood.

Due to the rare occurrence of childhood stroke, its impact on later cognitive functioning remains unclear. While it is often assumed that children recover better than adults, recent studies suggest that childhood stroke can negatively affect a wide range of cognitive domains, such as attention, language, and processing speed, among others. We examined the effect of unilateral stroke on children's visuoconstructive ability and visual memory. Seventeen children with left- or right-sided arterial ischemic stroke were tested using subtests of the Hamburg-Wechsler Intelligenztest für Kinder and the Rey-Osterrieth Complex Figure (ROCF). The ROCF was evaluated both quantitatively and qualitatively with the help of two separate scoring methods. We found that lesion laterality and age at stroke impacted childhood stroke patients' ability to recall certain elements of the figure. Regarding lesion laterality, left-sided stroke patients had more difficulties recalling internal details than right-sided stroke patients. In terms of age, patients with stroke onset before the age of 5 years remembered fewer structural elements than patients with stroke onset after the age of 5 years did. Moreover, the qualitative scoring method better differentiated between individuals and between groups than the more commonly used quantitative method. The results of this study not only highlight the importance of a qualitative assessment of the ROCF but could also aid clinicians in testing stroke patients more accurately and tailoring subsequent therapy to the patient's individual needs.

Fetal temporal sulcus depth asymmetry has prognostic value for language development.

In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymmetry can not only be observed in adults, but is already recognizable in the fetal brain. As the STS lies adjacent to brain areas important for language, STS depth asymmetry may represent an anatomical marker for language abilities. This study investigated the prognostic value of STS depth asymmetry in healthy fetuses for later language abilities, language localization, and language-related white matter tracts. Less right lateralization of the fetal STS depth was significantly associated with better verbal abilities, with fetal STS depth asymmetry explaining more than 40% of variance in verbal skills 6-13 years later. Furthermore, less right fetal STS depth asymmetry correlated with increased left language localization during childhood. We hypothesize that earlier and/or more localized fetal development of the left temporal cortex is accompanied by an earlier development of the left STS and is favorable for early language learning. If the findings of this pilot study hold true in larger samples of healthy children and in different clinical populations, fetal STS asymmetry has the potential to become a diagnostic biomarker of the maturity and integrity of neural correlates of language.

Sex differences in neural processing of speech in neonates.

The large majority of studies shows that girls develop their language skills faster than boys in the first few years of life. Are girls born with this advantage in language development? The present study used fNIRS in neonates to investigate sex differences in neural processing of speech within the first days of life. We found that speech stimuli elicited significantly more brain activity than non-speech stimuli in both groups of male and female neonates. However, whereas girls showed significant HbO changes to speech stimuli only within the left hemisphere, boys exhibited simultaneous neural activations in both hemispheres, with a larger and more significant fronto-temporal cluster in the right hemisphere. Furthermore, in boys, the variation in time-to-peak latencies was considerably greater than in girls. These findings suggest an earlier maturation of language-related brain areas in girls and highlight the importance of sex-specific investigations of neural language networks in infants.

Myelomeningocele-Chiari II malformation-Neurological predictability based on fetal and postnatal magnetic resonance imaging.

OBJECTIVE: This systematic comparison between pre- and postnatal imaging findings and postnatal motor outcome assesses the reliability of MRI accuracy in the prognostication of the future long-term (mean, 11.4 years) ambulatory status in a historic group of postnatally repaired myelomeningocele (MMC) cases. METHODS: A retrospective, single-center study of 34 postnatally repaired MMC patients was performed. We used fetal and postnatal magnetic resonance imaging (MRI) to compare the fetal and postnatal radiological lesion level to each other and to the postnatal ambulatory level as a standard of reference and analyzed Chiari II malformation characteristics. RESULTS: In 13/15 (87%) and 29/31 (94%) cases, the functional level was equal to or better than the prenatal and postnatal radiological lesion level. A radiological lesion level agreement within two segments could be achieved in 13/15 (87%) patients. A worse than expected functional level occurred in cases with Myelocele (2/3 patients), coexistent crowding of the posterior fossa (2/3 patients) and/or abnormal white matter architecture, represented by callosal dysgenesis (1/3 patients). In all patients (2/2) with a radiological disagreement of more than two segments, segmentation disorders and scoliosis were observed. CONCLUSION: Fetal and postnatal MRI are predictive of the long-term ambulatory status in postnatally repaired MMC patients.

The duration of intrauterine development influences discrimination of speech prosody in infants.

Auditory speech discrimination is essential for normal language development. Children born preterm are at greater risk of language developmental delays. Using functional near-infrared spectroscopy at term-equivalent age, the present study investigated early discrimination of speech prosody in 62 neonates born between week 23 and 41 of gestational age (GA). We found a significant positive correlation between GA at birth and neural discrimination of forward versus backward speech at term-equivalent age. Cluster analysis identified a critical threshold at around week 32 of GA, pointing out the existence of subgroups. Infants born before week 32 of GA exhibited a significantly different pattern of hemodynamic response to speech stimuli compared to infants born at or after week 32 of GA. Thus, children born before the GA of 32 weeks are especially vulnerable to early speech discrimination deficits. To support their early language development, we therefore suggest a close follow-up and additional speech and language therapy especially in the group of children born before week 32 of GA.

The Prenatal Morphomechanic Impact of Agenesis of the Corpus Callosum on Human Brain Structure and Asymmetry.

Genetic, molecular, and physical forces together impact brain morphogenesis. The early impact of deficient midline crossing in agenesis of the Corpus Callosum (ACC) on prenatal human brain development and architecture is widely unknown. Here we analyze the changes of brain structure in 46 fetuses with ACC in vivo to identify their deviations from normal development. Cases of complete ACC show an increase in the thickness of the cerebral wall in the frontomedial regions and a reduction in the temporal, insular, medial occipital and lateral parietal regions, already present at midgestation. ACC is associated with a more symmetric configuration of the temporal lobes and increased frequency of atypical asymmetry patterns, indicating an early morphomechanic effect of callosal growth on human brain development affecting the thickness of the pallium along a ventro-dorsal gradient. Altered prenatal brain architecture in ACC emphasizes the importance of conformational forces introduced by emerging interhemispheric connectivity on the establishment of polygenically determined brain asymmetries.

The Prenatal Origins of Human Brain Asymmetry: Lessons Learned from a Cohort of Fetuses with Body Lateralization Defects.

Knowledge about structural brain asymmetries of human fetuses with body lateralization defects-congenital diseases in which visceral organs are partially or completely incorrectly positioned-can improve our understanding of the developmental origins of hemispheric brain asymmetry. This study investigated structural brain asymmetry in 21 fetuses, which were diagnosed with different types of lateralization defects; 5 fetuses with ciliopathies and 26 age-matched healthy control cases, between 22 and 34 gestational weeks of age. For this purpose, a database of 4007 fetal magnetic resonance imagings (MRIs) was accessed and searched for the corresponding diagnoses. Specific temporal lobe brain asymmetry indices were quantified using in vivo, super-resolution-processed MR brain imaging data. Results revealed that the perisylvian fetal structural brain lateralization patterns and asymmetry indices did not differ between cases with lateralization defects, ciliopathies, and normal controls. Molecular mechanisms involved in the definition of the right/left body axis-including cilium-dependent lateralization processes-appear to occur independently from those involved in the early establishment of structural human brain asymmetries. Atypically inverted early structural brain asymmetries are similarly rare in individuals with lateralization defects and may have a complex, multifactorial, and neurodevelopmental background with currently unknown postnatal functional consequences.

Minimizing Intracochlear Pressure: Influence of the Insertion Sheath.

OBJECTIVE: Atraumatic cochlear implantation (CI) and insertion of the electrode in particular are major goals of recent CI surgery. Perimodiolar electrode arrays need a stylet or exosheath for insertion. The sheath can influence the intracochlear pressure changes during insertion of the electrode. The aim of this study was to modify the insertion sheath to optimize intracochlear pressure changes. METHODS: In an artifical cochlear model, 7 different modified insertion sheaths were used. The intracochlear pressure was measured with a micro-optical sensor in the apical part of the model cochlea. RESULTS: Significant lower intracochlear pressure changes were observed when the apical part of the insertion sheath was either shortened or tapered. Modification of the stopper does influence the intracochlear pressure significantly. CONCLUSION: Modification of the insertion sheath leads to lower intracochlear pressure gain. The differences and impact on intracochlear pressure changes found in this study underline the importance of even subtle modifications of the electrode insertion technique.