Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults.

Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~ 31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain.

Repeated complete atrioventricular block during remifentanil administration in a pediatric patient with brain tumor and acute hydrocephalus: a case report.

BACKGROUND: Remifentanil, an ultra-short-acting µ-opioid receptor agonist, is commonly used for anesthetic management due to excellent adjustability. Remifentanil is known to cause sinus bradycardia, however, because it has a direct negative chronotropic effect on the cardiac conduction system and there is an indirect negative chronotropic effect via the parasympathetic nervous system. CASE PRESENTATION: An 8-year-old Japanese boy was diagnosed with acute hydrocephalus due to a brain tumor in the fourth ventricle and underwent emergency surgery. Imaging examination showed brainstem compression. Endoscopic third ventriculostomy and ventriculoperitoneal shunt surgery were scheduled. Remifentanil was started during induction of general anesthesia, but electrocardiogram showed sinus bradycardia, then Wenckebach-type atrioventricular block, and then complete atrioventricular block. Remifentanil was immediately discontinued, and we administered atropine sulfate. Complete atrioventricular block was restored to sinus rhythm. When remifentanil was restarted, however, the electrocardiogram again showed sinus bradycardia, Wenckebach-type atrioventricular block, and then complete atrioventricular block. Remifentanil was again immediately discontinued, we administered adrenaline, and then complete atrioventricular block was restored to sinus rhythm. Fentanyl was used instead of remifentanil with continuous infusion of dopamine. There has since been no further occurrence of complete atrioventricular block. CONCLUSIONS: This is the first known case of complete atrioventricular block in a pediatric patient with increased intracranial pressure seemingly caused by administration of remifentanil.

"Bloomy rind sign" in varicella-zoster virus brainstem meningoencephalitis.

The bloomy rind sign, characterized by band-like abnormalities along the surface of the brainstem on magnetic resonance imaging without contrast enhancement, has been considered a specific imaging marker for leptomeningeal metastasis from lung adenocarcinoma. In this study, we describe the case of an 85-year-old male with a 3-week history of headache, fever, and progressive cognitive impairment. The patient was diagnosed with varicella-zoster virus brainstem meningoencephalitis and magnetic resonance imaging revealed hyperintensities along the brainstem surface on fluid-attenuated inversion recovery and diffusion-weighted imaging that mimicked a bloomy rind sign. However, the patient showed no signs of lung cancer or meningeal carcinomatosis. This case suggests that the bloomy rind sign is not exclusive to leptomeningeal metastasis but can also be observed in other conditions, such as central nervous system infections.

Do auditory brainstem implants favor the development of sensory integration and cognitive functions?

BACKGROUND: Information about the development of cognitive skills and the effect of sensory integration in children using auditory brainstem implants (ABIs) is still limited. OBJECTIVE: This study primarily aims to investigate the relationship between sensory processing skills and attention and memory abilities in children with ABI, and secondarily aims to examine the effects of implant duration on sensory processing and cognitive skills in these children. METHODS: The study included 25 children between the ages of 6 and 10 years (mean age: 14 girls and 11 boys) with inner ear and/or auditory nerve anomalies using auditory brainstem implants. Visual-Aural Digit Span Test B, Marking Test, Dunn Sensory Profile Questionnaire were applied to all children. RESULTS: The sensory processing skills of children are statistically significant and positive, and moderately related to their cognitive skills. As the duration of implant use increases, better attention and memory performances have been observed (p < .05). CONCLUSION: The study demonstrated the positive impact of sensory processing on the development of memory and attention skills in children with ABI. It will contribute to evaluating the effectiveness of attention, memory, and sensory integration skills, and aiding in the development of more effective educational strategies for these children.

A single-cell transcriptomic map of the developing Atoh1 lineage identifies neural fate decisions and neuronal diversity in the hindbrain.

Proneural transcription factors establish molecular cascades to orchestrate neuronal diversity. One such transcription factor, Atonal homolog 1 (Atoh1), gives rise to cerebellar excitatory neurons and over 30 distinct nuclei in the brainstem critical for hearing, breathing, and balance. Although Atoh1 lineage neurons have been qualitatively described, the transcriptional programs that drive their fate decisions and the full extent of their diversity remain unknown. Here, we analyzed single-cell RNA sequencing and ATOH1 DNA binding in Atoh1 lineage neurons of the developing mouse hindbrain. This high-resolution dataset identified markers for specific brainstem nuclei and demonstrated that transcriptionally heterogeneous progenitors require ATOH1 for proper migration. Moreover, we identified a sizable population of proliferating unipolar brush cell progenitors in the mouse Atoh1 lineage, previously described in humans as the origin of one medulloblastoma subtype. Collectively, our data provide insights into the developing mouse hindbrain and markers for functional assessment of understudied neuronal populations.

Neuronal network controlling REM sleep.

Rapid eye movement sleep is a state characterized by concomitant occurrence of rapid eye movements, electroencephalographic activation and muscle atonia. In this review, we provide up to date knowledge on the neuronal network controlling its onset and maintenance. It is now accepted that muscle atonia during rapid eye movement sleep is due to activation of glutamatergic neurons localized in the pontine sublaterodorsal tegmental nucleus. These neurons directly project and excite glycinergic/γ-aminobutyric acid-ergic pre-motoneurons localized in the ventromedial medulla. The sublaterodorsal tegmental nucleus rapid eye movement-on neurons are inactivated during wakefulness and non-rapid eye movement by rapid eye movement-off γ-aminobutyric acid-ergic neurons localized in the ventrolateral periaqueductal grey and the adjacent dorsal deep mesencephalic reticular nucleus. Melanin-concentrating hormone and γ-aminobutyric acid-ergic rapid eye movement sleep-on neurons localized in the lateral hypothalamus would inhibit these rapid eye movement sleep-off neurons initiating the state. Finally, the activation of a few limbic cortical structures during rapid eye movement sleep by the claustrum and the supramammillary nucleus as well as that of the basolateral amygdala would be involved in the function(s) of rapid eye movement sleep. In summary, rapid eye movement sleep is generated by a brainstem generator controlled by forebrain structures involved in autonomic control.

[Brainstem auditory evoked responses in horses with hearing loss and during general anesthesia]. / Hör- und Hirnstammfunktionsprüfung beim Pferd: Resultate bei ausgewählten klinischen Szenarien.

INTRODUCTION: The brainstem auditory evoked response (BAER) is a diagnostic approach to examine the hearing system of horses objectively. The aim of this BAER examination was the diagnosis of conductive or sensorineural hearing loss or deafness in horses with external otitis, head trauma, headshaking, tinnitus or skittish horses with eye disease. Brainstem dysfunction is induced by intracranial hypotension. BAER was used in horses with colic surgery which had a low arterial blood pressure during general anesthesia. The endoscopic finding of the guttural pouch was the ipsilateral mild to severe hypertrophy of the tympanostylohyoideum in horses with external otitis or head trauma. The otoscopic examination of standing sedated horses was done before BAER. The cartilagineous and osseous part of the external ear canal in horses with external otitis were obstructed with exsudate and tympanic membranes were not visible. Horses with right sided external otitis: right moderate to severe conductive hearing loss (significantly prolonged latencies of I, III, V and interpeak latencies I-III, I-V, III-V; thresholds of hearing levels 60 to 80 dB right); horses with left sided external otitis: left severe conductive hearing loss (no correct identification of BAER peaks, latencies not measurable, 80 dB); horse with left sided head trauma: severe left sided conductive hearing loss (blood in the left external ear canal, no visible tympanic membrane, no correct identification of BAER peaks, latencies not measurable, 80 dB); horses with head shaking: mild sensorineural hearing loss on both sides (on both sides osseous parts II/III with keratin scales of the junction, visible tympanic membranes, significantly prolonged V, I-III, I-V, 40 dB); moderate to severe skittish horses with chronic eye disease (mostly left sided equine recurrent uveitis): moderate sensorineural hearing loss on both sides (normal otoscopical findings, significantly prolonged latencies and interpeak latencies left; I-V, III-V right, 60 dB, pathological involvement in the auditory pathway of the brainstem between the cochlear nucleus and colliculus caudalis); horse with a tinnitus on both sides: mild sensorineural hearing loss on both sides (normal otoscopical findings, prolonged V, I-III, I-V, III-V, 40 dB, pathology of auditory nerve, cochlear nucleus and above the level of this nucleus); American paint horses: sensorineurale deafness on both sides (normal otoscopical findings, absent BAER peaks, isoelectric lines and 80 dB on both sides). The prolonged latencies of I, III and V including interpeak latencies I-III only left and I-V and III-V on both sides in horses with laparotomy during general anesthesia were associated with low arterial blood pressure (62 mmHg, median). These findings could demonstrate a hypotension in the brainstem too. The BAER could be a technical tool during general anesthesia for normalizing the arterial blood pressure and brainstem function to prevent imbalance of body movements after general anesthesia.

INTRODUCTION: L'examen objectif de l'audition chez le cheval est réalisé par la mesure des Potentiels Évoqués Auditifs (PEA) ou Brainstem Auditory-Evoked Response (BAER). L'objectif de ces examens est de diagnostiquer une surdité de transmission ou neurosensorielle ou une surdité chez les chevaux souffrant d'otite externe, de traumatisme crânien, de headshaking, d'acouphènes ou chez des chevaux craintifs souffrant d'une maladie oculaire. Étant donné que l'audiométrie du tronc cérébral vérifie également la fonction du tronc cérébral, des chevaux ayant subi une laparotomie et une déshydratation préopératoire ont été examinés pour détecter un dysfonctionnement du tronc cérébral dû à une baisse de la pression artérielle. L'otoscopie et l'audiométrie du tronc cérébral (système AEP Corona) ont été réalisées. Les résultats de l'otoscopie chez les chevaux atteints d'otite externe: Pars cartilaginea et ossea degré III, tympan non visible. Les résultats de l'endoscopie des poches gutturales chez les chevaux atteints d'otite externe exsudative ou de traumatisme crânien: toujours une augmentation ou une hypertrophie ipsilatérale du tympanostylohyoïdien. Les résultats de la BAER des chevaux atteints d' une otite externe à droite sont les suivants: surdité de transmission moyenne à sévère à droite (ondes I, III, V significativement prolongées, latences interpicales I-III, I-V, III-V par rapport au groupe de contrôle, valeurs limites au-dessus du seuil auditif normal 60 à 80 dB); chevaux atteints d'otite externe à gauche: surdité de transmission de haut niveau à gauche (ondes non identifiables, 80 dB à gauche); chevaux avec une fistule auriculaire à droite: surdité de perception bilatérale de bas niveau (allongement significatif des ondes III, V et des latences interpicales des deux côtés, 40 dB); cheval avec traumatisme crânien à gauche: surdité de transmission de degré élevé (à gauche, sang dans le conduit auditif externe, tympan non visible, ondes non identifiables, 80 dB); chevaux avec headshaking: surdité de perception de degré faible (des deux côtés, pars ossea de degré II, tympans visibles, allongement significatif V, I-III, I-V, 40 dB); chevaux présentant une peur et une maladie oculaire: surdité moyenne, neurosensorielle (otoscopie normale, allongement significatif de toutes les ondes et des latences interpeak à gauche, I-V, III-V à droite, 60 dB, vitesse pathologique de conduction des voies auditives dans le tronc cérébral); American Paint Horses: surdité neurosensorielle (otoscopie normale, ligne isoélectrique bilatérale des HA, 80 dB). Les ondes I, III et V prolongées et les latences interpicales I-III, I-V et III-V chez les chevaux ayant subi une laparotomie sont associées à la baisse de la pression artérielle (62 mmHg, médiane) pendant l'anesthésie générale et indiquent une hypotension dans le tronc cérébral. Pendant l'anesthésie générale, l'audiométrie du tronc cérébral offre une possibilité particulière de détecter le dysfonctionnement du tronc cérébral, de réguler la pression artérielle et de garantir un lever sans problème avec un équilibre auditif et visuel de la posture après l'anesthésie générale.

The spectrum of anti-GQ1B antibody syndrome: beyond Miller Fisher syndrome and Bickerstaff brainstem encephalitis.

INTRODUCTION: Since the initial identification of Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE),significant milestones have been achieved in understanding these diseases.Discoveries of common serum antibodies (IgG anti-GQ1b), antecedent infections, neurophysiological data, andneuroimaging suggested a shared autoimmune pathogenetic mechanism rather than distinct pathogenesis, leadingto the hypothesis that both diseases are part of a unified syndrome, termed "Fisher-Bickerstaff syndrome". The subsequent identification of atypical anti-GQ1b-positive forms expanded the classification to a broader condition known as "Anti-GQ1b-Antibody syndrome". METHODS: An exhaustive literature review was conducted, analyzing a substantial body of research spanning from the initialdescriptions of the syndrome's components to recent developments in diagnostic classification and researchperspectives. RESULTS: Anti-GQ1b syndrome encompasses a continuous spectrum of conditions defined by a common serological profilewith varying degrees of peripheral (PNS) and central nervous system (CNS) involvement. MFS and BBE represent theopposite ends of this spectrum, with MFS primarily affecting the PNS and BBE predominantly involving the CNS.Recently identified atypical forms, such as acute ophthalmoparesis, acute ataxic neuropathy withoutophthalmoparesis, Guillain-Barré syndrome (GBS) with ophthalmoparesis, MFS-GBS and BBE-GBS overlap syndromes,have broadened this spectrum. CONCLUSION: This work aims to provide an extensive, detailed, and updated overview of all aspects of the anti-GQ1b syndromewith the intention of serving as a stepping stone for further shaping thereof. Special attention was given to therecently identified atypical forms, underscoring their significance in redefining the boundaries of the syndrome.

Hearing Assessment of Free-Ranging Owls and Implications for Wildlife Rehabilitation: 31 Cases (2014-2023).

Owls, members of the avian order Strigiformes, are nocturnal birds of prey that are found worldwide except for Antarctica. Traumatized, free-ranging owls are commonly presented to veterinary hospitals and wildlife rehabilitation facilities with the goal of providing medical care and rehabilitation to enable release back into their natural habitat. Minimal guidelines exist for the release of wildlife, and whereas a need for functional vision is described in raptors, assessing and evaluating hearing is usually not mentioned. This can be problematic for nocturnal predators because hearing is the primary sense utilized by owls when hunting and navigating in their dark environment. The brainstem auditory evoked response (BAER) test is a minimally invasive, objective assessment of hearing commonly used in companion animals. To the authors' knowledge, routine or standardized BAER evaluation has not been reported in traumatized, free-ranging owls. In the following retrospective study, 31 free-ranging owls presented to the University of Georgia Veterinary Teaching Hospital for known or suspected trauma or being found in a debilitated state underwent BAER testing to assess for the presence of complete sensorineural hearing loss. Similar to assessment of hearing in companion animals, the BAER test was elicited using a broad click stimulus delivered at 85 dB nHL. In all owls, qualitative assessment and peak latency measurements of the BAER test reflected hearing ability. This study highlights the importance of hearing in nocturnal raptors, how BAER testing can aid in decision making regarding rehabilitation, and provides a foundation for further investigation of hearing loss in traumatized owls. We suggest that veterinarians working with free-ranging owls in a rehabilitation setting should consider BAER testing as part of routine diagnostic testing.

A novel copy number variant in the murine Cdh23 gene gives rise to profound deafness and vestibular dysfunction.

Hearing loss is the most common congenital sensory deficit worldwide and exhibits high genetic heterogeneity, making molecular diagnoses elusive for most individuals. Detecting novel mutations that contribute to hearing loss is crucial to providing accurate personalized diagnoses, tailored interventions, and improving prognosis. Copy number variants (CNVs) are structural mutations that are understudied, potential contributors to hearing loss. Here, we present the Abnormal Wobbly Gait (AWG) mouse, the first documented mutant exhibiting waltzer-like locomotor dysfunction, hyperactivity, circling behaviour, and profound deafness caused by a spontaneous CNV deletion in cadherin 23 (Cdh23). We were unable to identify the causative mutation through a conventional whole-genome sequencing (WGS) and variant detection pipeline, but instead found a linked variant in hexokinase 1 (Hk1) that was insufficient to recapitulate the AWG phenotype when introduced into C57BL/6J mice using CRISPR-Cas9. Investigating nearby deafness-associated genes revealed a pronounced downregulation of Cdh23 mRNA and a complete absence of full-length CDH23 protein, which is critical for the development and maintenance of inner ear hair cells, in whole head extracts from AWG neonates. Manual inspection of WGS read depth plots of the Cdh23 locus revealed a putative 10.4 kb genomic deletion of exons 11 and 12 that was validated by PCR and Sanger sequencing. This study underscores the imperative to refine variant detection strategies to permit identification of pathogenic CNVs easily missed by conventional variant calling to enhance diagnostic precision and ultimately improve clinical outcomes for individuals with genetically heterogenous disorders such as hearing loss.

A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata.

Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9-month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50-mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double-blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4-week loading dose of 200 mg QD or placebo for 9 months (placebo-controlled phase); they then entered the active-therapy extension and received ritlecitinib 50 mg QD (with a 4-week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I-V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans.

Neuromyelitis optica spectrum disorder with acute brainstem manifestations as initial symptoms.

Objective: To explore the clinical features and prognosis of patients with neuromyelitis optica spectrum disorder (NMOSD) initially presenting with acute brainstem symptoms. Methods: The clinical data of NMOSD patients admitted to two medical centers were collected. The clinical characteristics, laboratory data, neuroimaging features and prognoses of patients with NMOSD with acute brainstem manifestations as initial symptoms (NMOSD-BSMIS) were analyzed. The clinical features and prognosis of patients with NMOSD-BSMIS and patients with NMOSD with other manifestations as initial symptoms (NMOSD-OMIS) were compared. Results: Fifty-two patients (18.37 %, 52/283) initially presented with acute brainstem symptoms. Intractable nausea, vomiting or hiccups, diplopia, vertigo, headache, and facial hypoesthesia were the initial symptoms in most of the patients. The percentage of patients who were positive for serum aquaporin 4 (AQP4)-IgG antibodies was 81.63 % (40/49). MRI revealed that the lesions were usually located in the postrema, dorsal medulla oblongata, pons and other areas around the fourth ventricle. The early-stage misdiagnosis rate was 46.15 %. Compared with those in the non-misdiagnosed group, the age of onset of patients in the NMOSD-BSMIS group was older, and the proportion of patients admitted to the neurology department as the first department was lower in the misdiagnosed group. The annual relapse rate of patients who underwent NMOSD-BSMIS was significantly greater than that of patients who underwent NMOSD-OMIS (P < 0.01). Conclusions: NMOSD patients can initially present with different brainstem symptoms. The early misdiagnosis rate of NMOSD-BSMIS is high. Moreover, if patients are older or initially admitted to nonneurological departments, they are more likely to be misdiagnosed. Moreover, the annual recurrence rate of NMOSD-BSMIS is greater in the early stage.

NMDAR dysfunction and the regulation of dopaminergic transmission in schizophrenia.

A substantial body of evidence implicates dysfunction in N-methyl-d-aspartate receptors (NMDARs) in the pathophysiology of schizophrenia. This article illustrates how NMDAR dysfunction may give rise to many of the neurobiological phenomena frequently associated with schizophrenia with a particular focus on how NMDAR dysfunction affects the thalamic reticular nucleus (nRT) and pedunculopontine tegmental nucleus (PPTg). Furthermore, this article presents a model for schizophrenia illustrating how dysfunction in the nRT may interrupt prefrontal regulation of midbrain dopaminergic neurons, and how dysfunction in the PPTg may drive increased, irregular burst firing.

Hypertrophic olivary degeneration secondary to a Guillain Mollaret triangle cavernoma: Two case report.

Hypertrophic olivary degeneration (HOD) is a rare form of transsynaptic degeneration. It is caused by a damage at the Guillain-Mollaret triangle (GMT), which is defined by three anatomical structures: the dentate nucleus, the red nucleus, and the inferior olivary nucleus (ION). Clinically, it may be revealed by palatal myoclonus. On MRI, it appears as a unilateral or bilateral enlargement of the inferior olivary nucleus which shows a high signal intensity on T2-weighted images, with sometimes a cerebellar atrophy. Here we report 2 cases of healthy patients which present hemorrhagic brainstem cavernomas, complicated later by the development of palatal myoclonus and cerebellar ataxia, with MRI features corresponding to an (HOD) secondary to a (GMT) cavernoma. The purpose is to explain the mechanism of (HOD) subsequent to lesion in (GMT), and to describe magnetic resonance imaging features.

Prospective Evaluation of a Modified Apnea Test in Brain Death Candidates that Does Not Require Disconnection from the Ventilator.

BACKGROUND: The apnea test (AT) is an important component in the determination of brain death/death by neurologic criteria (BD/DNC) and often entails disconnecting the patient from the ventilator followed by tracheal oxygen insufflation to ensure adequate oxygenation. To rate the test as positive, most international guidelines state that a lack of spontaneous breathing must be demonstrated when the arterial partial pressure of carbon dioxide (PaCO2) ≥ 60 mm Hg. However, the loss of positive end-expiratory pressure that is associated with disconnection from the ventilator may cause rapid desaturation. This, in turn, can lead to cardiopulmonary instability (especially in patients with pulmonary impairment and diseases such as acute respiratory distress syndrome), putting patients at increased risk. Therefore, this prospective study aimed to investigate whether a modified version of the AT (mAT), in which the patient remains connected to the ventilator, is a safer yet still valid alternative. METHODS: The mAT was performed in all 140 BD/DNC candidates registered between January 2019 and December 2022: after 10 min of preoxygenation, (1) positive end-expiratory pressure was increased by 2 mbar (1.5 mm Hg), (2) ventilation mode was switched to continuous positive airway pressure, and (3) apnea back-up mode was turned off (flow trigger 10 L/min). The mAT was considered positive when spontaneous breathing did not occur upon PaCO2 increase to ≥ 60 mm Hg (baseline 35-45 mm Hg). Clinical complications during/after mAT were documented. RESULTS: The mAT was possible in 139/140 patients and had a median duration of 15 min (interquartile range 13-19 min). Severe complications were not evident. In 51 patients, the post-mAT arterial partial pressure of oxygen (PaO2) was lower than the pre-mAT PaO2, whereas it was the same or higher in 88 cases. In patients with pulmonary impairment, apneic oxygenation during the mAT improved PaO2. In 123 cases, there was a transient drop in blood pressure at the end of or after the mAT, whereas in 12 cases, the mean arterial pressure dropped below 60 mm Hg. CONCLUSIONS: The mAT is a safe and protective means of identifying patients who no longer have an intact central respiratory drive, which is a critical factor in the diagnosis of BD/DNC. Clinical trial registration DRKS, DRKS00017803, retrospectively registered 23.11.2020, https://drks.de/search/de/trial/DRKS00017803.

Auditory brainstem response to paired clicks as a candidate marker of cochlear synaptopathy in humans.

OBJECTIVE: This study aimed to evaluate whether auditory brainstem response (ABR) using a paired-click stimulation paradigm could serve as a tool for detecting cochlear synaptopathy (CS). METHODS: The ABRs to single-clicks and paired-clicks with various inter-click intervals (ICIs) and scores for word intelligibility in degraded listening conditions were obtained from 57 adults with normal hearing. The wave I peak amplitude and root mean square values for the post-wave I response within a range delayed from the wave I peak (referred to as the RMSpost-w1) were calculated for the single- and second-click responses. RESULTS: The wave I peak amplitudes did not correlate with age except for the second-click responses at an ICI of 7 ms, and the word intelligibility scores. However, we found that the RMSpost-w1 values for the second-click responses significantly decreased with increasing age. Moreover, the RMSpost-w1 values for the second-click responses at an ICI of 5 ms correlated significantly with the scores for word intelligibility in degraded listening conditions. CONCLUSIONS: The magnitude of the post-wave I response for the second-click response could serve as a tool for detecting CS in humans. SIGNIFICANCE: Our findings shed new light on the analytical methods of ABR for quantifying CS.

Evaluation of newborn hearing screening program in Jordan.

Introduction: The Newborn Hearing Screening (NHS) program was officially launched in Jordan in 2021. Since its inception, no studies have examined the effectiveness of the program. This study seeks to assess the effectiveness and outcomes of the NHS program in Jordan. Methods: A retrospective cross-sectional study was conducted to investigate the program coverage rate, referral rate, loss to follow-up rate and the hearing status of newborns who successfully completed the necessary diagnostic assessment. Live births in all hospitals administered by the Ministry of Health (MoH) in Jordan from July 2021 to November 2023 were included. Results: Out of 25,825 newborns delivered, 99.4% (25,682) were screened. A referral rate of 0.7% (189) was recorded. Approximately 61.9% of those referred (n = 117) had normal hearing, while 31.7% (60 infants) were diagnosed with hearing loss. The prevalence of congenital hearing loss was 0.14%, and the mean age for identifying hearing loss was 11 months. Discussion: The current status of the NHS program in Jordan is promising. The program has achieved most benchmarks recommended by the Joint Committee on Infant Hearing (JCIH), demonstrating encouraging outcomes. There is a need to investigate and address the factors causing delays in the identification of hearing loss in Jordan.

Auditory brainstem response findings in autism spectrum disorder speech delay population.

OBJECTIVES: Evaluate pediatric auditory brainstem response (ABR) findings in children with Autism Spectrum Disorder (ASD) after the 2013 DSM-5 update. STUDY DESIGN: This was an IRB-approved, six-year retrospective chart review evaluating ABR results from pediatric patients with speech delay. Diagnosis of ASD and other neurodevelopmental abnormalities were collected for patient stratification. METHODS: From 2017 to 2023, 148 pediatric patients with speech delay were identified through diagnosis of speech delay and underwent ABR testing. Patients were then separated into two groups: Neurotypical (N = 79) and ASD (N = 69). ABR results were obtained through chart review and waveform and interpeak latency (IPL) results were recorded. Differences in waveform and IPL results were determined via Pearson's chi-square test, with multivariate analysis accounting for race, sex, and age. RESULTS: 28 patients with ASD (40.6 %) had at least one waveform/IPL prolongation. Analysis showed an increased incidence of waveform III (p = 0.028) and IPL III-V (p = 0.03) prolongation in the ASD group compared to their neurotypical counterparts. Waveform III prolongation was noted more in females with ASD (p = 0.001) than in males. No statistically significant difference when comparing race and age was found, except in the 2-3 age range (p = 0.003). CONCLUSIONS: There were higher percentages of prolongation for all waveforms and IPLs in the ASD group versus neurotypical, though not as high as previously reported. Race and age did not appear to be factors in ABR findings though more data is needed to make clinical associations.

Comparisons of Audiologic Characteristics in Patients with Continuous and Intermittent Tinnitus.

BACKGROUND: No studies to date have compared audiologic characteristics in patients with continuous and intermittent tinnitus. The present study classified tinnitus patients into continuous and intermittent groups based on tinnitus duration and compared their audiologic characteristics. METHODS: This study enrolled 604 patients with tinnitus from January 2019 to December 2022. Clinical manifestations, PTA results, the frequency and loudness of tinnitus, ABR, DPOAE, and TEOAE tests were compared in patients with continuous and intermittent tinnitus. RESULTS: Of the 604 patients, 231 (38.2%) had continuous and 373 (61.8%) had intermittent tinnitus. There were no significant between-group differences in otologic symptoms, tinnitus onomatopoeia. PTA showed that hearing thresholds, except at 125 Hz, were significantly higher in patients with continuous rather than intermittent tinnitus. The loudness of tinnitus was significantly greater in patients with continuous rather than intermittent tinnitus. ABR tests showed that the absolute latency of wave V was significantly longer in continuous than in intermittent tinnitus. Signal-to-noise ratios on TEOAE tests were significantly lower in patients with continuous rather than intermittent tinnitus at all frequencies tested (1, 1.5, 2, 3, and 4 kHz). Response rates to sound stimuli at all frequencies, except for 1 kHz, were significantly lower on DPOAE tests in patients with continuous rather than intermittent tinnitus. CONCLUSIONS: Continuous tinnitus is more common in males, more persistent over time, and is associated with a higher rate of hearing loss. In contrast, intermittent tinnitus is more common in women, appears acutely, and is associated with a relatively lower rate of hearing loss. Based on the findings of the current paper, it seems that audiologic characteristics may differ between patients with continuous and intermittent tinnitus.

Brainstem dominant form of X-linked adrenoleukodystrophy with a novel ABCD1 missense variant: A case report and literature review.

BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder attributed to ABCD1 mutations. Case reports with predominant brainstem involvement are rare. CASE PRESENTATION: In this study, we reported a plateau male worker of X-ALD characterized by progressive weakness accompanied by gait instability, mild nystagmus, and constipation. After 2 years of onset, a brain Magnetic Resonance Image (MRI) scan showed no abnormality but genetic analysis revealed a heterozygous mutation (c.1534G>A) in the ABCD1 gene. After 7 years of onset, although the patient was given aggressive dietary and symptomatic treatment in the course of the disease, a brain MRI scan showed predominantly brainstem damage, but serum concentrations of very long-chain fatty acids were normal, and he had been bedridden for almost 2 years with severe bladder dysfunction, forcing him to undergo cystostomy. The patient was discharged with improved urinary retention and renal function. CONCLUSIONS: We reported an X-ALD patient with a novel ABCD1 variation characterized by brainstem damage and retrospectively summarized the clinical manifestation, MRI features, and genetic features of X-ALD patients with brainstem damage.