Voice Improvement After Essential Tremor Treatment via Focused Ultrasound and Deep Brain Stimulation.

OBJECTIVES: The primary objective of this study was to determine whether two neurosurgical procedures, deep brain stimulation (DBS) and focused ultrasound (FUS), to treat essential tremor (ET) of the upper limb also reduce vocal tremor (VT) in patients with comorbid dysphonia. METHODS: Twelve patients with ET and concomitant VT scheduled for neurosurgical intervention (FUS or DBS) or returning for follow-up after DBS implantation were assessed. FUS patients were assessed pre- and post-intervention and DBS patients were assessed with the electrodes turned on and off post-implantation. Three voice recordings of a sustained /a/ were obtained for each participant condition. Percent fundamental frequency variability (FFV) was calculated for each recorded sustained vowel. Additionally, blinded expert perceptual VT rating (VTR) was performed to assess subjective changes in tremors. RESULTS: Of the 12 patients, seven underwent unilateral FUS, and five underwent bilateral DBS. Mean FFV without neurosurgical intervention was 18.3%, SD = 7.8 and with neurosurgical intervention was 6.3%, SD = 3.0 (t (70) =8.7, p < 0.001). Mean FFV decreased in the FUS cohort from 22.0%, SD = 7.1 pre-ablation to 6.7%, SD = 2.4 post-ablation (t (40) = 7.7, p < 0.001). Mean FFV also decreased in the DBS cohort from 15.7%, SD = 7.0 to 6.0%, SD = 3.3 when stimulation was turned on (t (28)=5.7 p < 0.001). In the FUS group, mean VTR decreased from 4.0 to 1.4 post-ablation (Z = 7.8, p < 0.001). In the DBS group, mean VTR decreased from 3.3 to 2.1 with stimulation (Z = 4.1, p < 0.001). CONCLUSION: Neurosurgical interventions for ET (bilateral DBS and unilateral FUS) demonstrate acoustic and perceptual benefits for VT. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:367-373, 2024.

Postoperative Serum Cortisol and Cushing Disease Recurrence in Patients With Corticotroph Adenomas.

CONTEXT: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized. OBJECTIVE: To analyze postoperative serum cortisol and recurrence rates in Cushing disease. METHODS: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables. RESULTS: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001). CONCLUSION: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.

Postoperative Radiotherapy and Facial Nerve Outcomes Following Nerve Repair: A Systematic Review.

OBJECTIVE: To compare outcomes of facial nerve repair or grafting following facial nerve-sacrificing procedures among patients treated with and without postoperative radiotherapy (RT). DATA SOURCES: PubMed, OVID, Conference Papers Index, Cochrane Library, ClinicalTrials.gov. REVIEW METHODS: Databases were searched using terms including "facial nerve," "graft," "repair," and "radiotherapy." Abstracts mentioning facial nerve repair and evaluation of facial nerve function were included for full-text review. Studies that utilized the House-Brackmann or similar validated scale for evaluation of postoperative facial nerve function were selected for review. All identified studies were included in a pooled t test analysis. RESULTS: Twelve studies with 142 patients were included in the systematic review. All 12 studies individually demonstrated no significant difference in facial nerve outcomes between patients who received postoperative radiation and patients who did not. A pooled t test of data from all studies also demonstrated no significant difference in postoperative facial nerve function between the postoperative RT and non-RT groups (t stat = 0.92, p = .36). CONCLUSION: This analysis, including 12 studies, demonstrated that among patients undergoing facial nerve grafting or repair, there was no significant difference in postoperative facial nerve function between postoperative RT and non-RT patients. Due to the small sample size and variability in study methods, further studies directly comparing outcomes between patients with and without postoperative RT would be beneficial.

Columellar Scar Following Open Rhinoplasty Using Absorbable Suture Versus Nonabsorbable Suture: A Meta-Analysis.

Objective: This meta-analysis seeks to determine whether a difference in long-term scar outcomes exists between absorbable and nonabsorbable sutures for closure of the columellar incision after open rhinoplasty. Review Methods: PubMed, OVID Medline, Conference Papers Index, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using terms including "suture," "sutures," "absorbable," "columella," "columellar," "transcolumellar," "trans-columellar," "rhinoplasty," "septorhinoplasty," "scar," "scars," and "scarring," as well as associated MeSH terms. Results: Six studies with 435 patients were included for systematic review and meta-analysis, with five studies included in meta-analysis for patient-reported outcomes, and six studies included for physician-reported outcomes. There was no significant difference in scar appearance between the absorbable suture group and nonabsorbable group among both patient-reported and physician-reported outcomes. Conclusion: This meta-analysis of six studies meeting inclusion criteria does not demonstrate a significant difference in long-term scar appearance based on suture type after open rhinoplasty.

Autoimmune Associated Vocal Fold Lesions: A Systematic Review.

OBJECTIVE: While Autoimmune Associated Vocal Fold Lesions (AaVFLs) have been described in many reports, there is no consensus on best practices in management. The purpose of this systematic review is to clarify the characteristics and treatment of dysphonia in the setting of AaVFLs. STUDY DESIGN: Systematic review METHODS: Pubmed and OVIDMedline and Google Scholar were searched, including terms related to (1) Vocal fold/cord, rheumatoid node/nodule, bamboo nodes/nodules, laryngeal deposits/nodes/nodules and (2) Autoimmune diseases/syndromes, connective tissue disease. RESULTS: Twenty-one studies with 83 patients diagnosed with AaVFLs were included. AaVFLs occurred predominantly in females in the 4th or 5th decade of life, with an overall mean age of 39.8 (SD = 12.8). Autoimmune or connective tissue disease was established prior to presentation to an otolaryngologist in 75.9% (44/58) of patients. Bilateral lesions were present in 83.8% (57/68) of patients. Treatment modalities included medical therapy alone (28.1%), voice therapy alone (17.5%), surgical treatment alone (7.0%), combination of medical and voice therapy (33.3%), and combination of surgical, medical and voice therapy (7.0%). All patients treated with voice therapy had voice improvement; lower rates were seen with solo medical (4/14 improved, 28.6%) or surgical therapy (3/6 improved, 50%). CONCLUSION: AaVFLs occur predominantly in women in their 30's to 50's and are associated with a variety of autoimmune conditions. A significant number of patients (25%) present to the Otolaryngologist without an established autoimmune diagnosis. While treatment outcomes are not robustly reported, a significant number of patients with AAVFLs treated with voice therapy alone or voice therapy in combination with other treatment modalities (medical or surgical) experience subjective improvement in voice quality and function.

Malignant Transformation in Glottic Dysplasia Treated With Photoangiolytic LASER - A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review and meta-analysis seeks to characterize the rate of malignant progression among patients with laryngeal dysplasia treated with photoangiolytic laser and compare to prior systematic reviews of conventional surgical approaches. METHODS: OVIDMedline, Pubmed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Google Scholar were searched, including terms related to patients with vocal fold dysplasia who were treated by angiolytic laser ablation. Some articles already known to authors or identified through hand searching were included. RESULTS: Six articles with 155 cases were included. Two studies used potassium titanyl phosphate exclusively, one solely used the pulsed dye laser, and three studies utilized both laser types during the study period. The pooled overall mean of malignant progression for patients with laryngeal dysplasia treated with photoangiolytic laser was 12%, as calculated by conducting a meta-analysis of single arm proportion. CONCLUSION: Laryngeal dysplasia is a premalignant lesion which confers a risk of progression to malignancy. After biopsy to establish the diagnosis there are multiple surgical techniques available for treatment with the goal of lesion eradication and voice preservation. In our review, there is a low malignant transformation rate for patients treated via with photoangiolytic laser.

Audiometric Outcomes After Surgical Repair of Congenital Aural Atresia: Does Age Matter?

OBJECTIVE: To determine if there is an age-based difference in audiometric outcomes for patients undergoing primary congenital aural atresia (CAA) repair. STUDY DESIGN: Retrospective chart review. SETTING: Single academic, high-volume, tertiary care hospital. PATIENTS: Individuals undergoing primary CAA repair by a single surgeon between 2004 and 2020. INTERVENTIONS: CAA repair. MAIN OUTCOME MEASURES: Preoperative and postoperative four tone (500, 1,000, 2,000, 4,000 Hz) air-conduction pure-tone average (PTA), bone-conduction PTA, air-bone gap and speech reception threshold, and preoperative to postoperative change in values. RESULTS: We identified 247 patients (262 ears) who underwent repair. The mean and median ages were approximately 12 and 8.5 years, respectively, both of which served as cutoff ages to compare younger versus older patients. The average preoperative to postoperative improvement values in air-conduction PTA, air-bone gap, and speech reception threshold for individuals younger than 12 years were 26.6 ± 10.2, 23.8 ± 12.6, and 30.1 ± 12.1 dB hearing level (HL), respectively, and those for individuals 12 years or older were 25.9 ± 15.7, 26.2 ± 10.3, and 31.3 ± 12.8 dB HL, respectively. For individuals younger than 8.5 years, the values were 25.8 ± 9.5, 24.9 ± 9.4, and 30.0 ± 10.6 dB HL, respectively, and those for individuals 8.5 years or older were 27.1 ± 13.5, 25.7 ± 11.0, and 30.0 ± 14.6 dB HL, respectively. The improvement did not differ significantly between the younger and older groups, using both cutoff ages. There was no difference in revision surgery rates or complications between groups. CONCLUSION: An individual at any age can enjoy audiometric improvement from atresia repair.

Vocal Fold Paralysis Following COVID-19 Vaccination: Query of VAERS Database.

OBJECTIVE: Vocal fold paresis or paralysis (VFP) may severely affect quality of life due to dysphonia and respiratory distress. As an increasing percentage of the United States population receives the COVID-19 vaccination, the objective of this study is to determine the correlation of COVID-19 postvaccination recurrent laryngeal neuropathy and resulting VFP. METHODS: The Vaccine Adverse Event Reporting System database was queried for patients exhibiting symptoms of VFP following COVID-19 vaccination. Patient demographics and clinical information including presenting symptoms, time of symptom onset, time of diagnosis and laterality. RESULTS: Twenty patients were found to have laryngoscopy confirmed VFP following COVID-19 vaccination. Vaccinations for Pfizer-BioNTech, Moderna, and Janssen were reported. Of those reported, 13 patients were female (65.0%) and seven were male (35.0%), with a mean age of 61.8 years. The most common presenting symptom was a hoarse voice (30.0%). A majority of these cases were unilateral in nature (64.0%). Mean time from vaccination to symptom onset was 12.1 days and mean time from vaccination to diagnosis was 37.6 days. CONCLUSION: For patients presenting with voice or swallowing complaints after receiving the COVID-19 vaccine, prompt evaluation by an otolaryngologist should occur. However, the potential VFP side effect of vaccination is very rarely cited in the literature and largely outweighed by the benefits of vaccination. Further research is needed to delineate the exact pathophysiology of this complication and determine whether a causal relationship exists.

Characterization of a paradoxical post-operative increase in serum cortisol in Cushing disease.

PURPOSE: In Cushing disease, early post-operative serum cortisol fluctuations have not been adequately characterized, and their association with initial remission and recurrence is unclear. METHODS: A retrospective cohort study of patients with Cushing disease was conducted at two institutions. A "riser" was defined a priori as a paradoxical increase in serum cortisol with an immediate incremental increase in serum cortisol over three consecutive cortisol draws separated by roughly 6-h (definition 1). Post hoc analyses used a definition of two consecutive increases (definition 2). Risers were compared to non-risers for initial remission and time-to-recurrence. RESULTS: A total of 505 patients with Cushing disease were screened, and 469 had adequate data for group assignment. Analysis of post-operative cortisol showed a subgroup of "risers" with a frequency of 3.6% for definition 1 and 42.6% for definition 2. In these patients, cortisol levels were significantly higher until approximately 36 h post-operatively, and cortisol had a significantly longer mean serum half-life. In the post hoc analysis, definition 2 risers had a lower remission rate compared to non-risers (162/196, 82.7%, versus 243/264, 92.0%) with an odds ratio of 0.41 (0.23-0.73; p = 0.003). For both definitions, recurrence was similar between groups. CONCLUSIONS: We found that almost half of Cushing disease patients experienced a temporary increase in serum cortisol level during the early post-operative period. Serum cortisol half-life was longer, and the remission rates were lower, however, recurrence rates were similar to non-risers.

Patient and Observer Graded Rhinoplasty Scar Outcomes: A Randomized Controlled Trial of Fast Absorbing Versus Permanent Columellar Suture Closure.

Background: When performing an open rhinoplasty, surgeons commonly use nonabsorbable skin sutures to close the columellar incision. These are believed to minimize scarring. However, removal can be associated with patient discomfort and outcomes may not be superior to using absorbable sutures. Objective: To compare difference in scar appearance for columellar closure after rhinoplasty with absorbable and nonabsorbable sutures. Methods: We performed a prospective randomized control trial with 61 patients. Forty-one patients completed follow-up and were included in final analysis: 23 whose columellar incision was closed with absorbable sutures and 18 with nonabsorbable sutures. A blinded surgeon performed Stony Brook Evaluation Scale (SBES) and a patient performed Patient Scar Assessment Questionnaire (PSAQ) was completed for each suture type. Results: Our results did not reject the null hypothesis that there is no difference in SBES or PSAQ scores between absorbable and nonabsorbable suture types. Conclusions: No difference was detected in scar outcomes between absorbable and nonabsorbable sutures for closure of the columellar incision created during an open rhinoplasty as rated by both patients and blinded clinicians.

Congenital Aural Stenosis With Cholesteatoma.

OBJECTIVE: Compare surgical and audiological outcomes of patients with congenital aural stenosis (CAS) with cholesteatoma to patients with CAS without cholesteatoma and patients with complete congenital aural atresia (CCAA). STUDY DESIGN: Retrospective case series. SETTING: Tertiary care hospital. PATIENTS: Patients with CAS (with and without cholesteatoma) and CCAA. INTERVENTION: Surgery for CAS/CAA. MAIN OUTCOME MEASURES: Patients with CAS and CAA undergoing surgical repair from June 2004 to July 2020 were identified from an institutional database. Included patients were divided by presence of a canal cholesteatoma. Clinical history, pre- and postoperative audiometric data, and clinical outcomes were compared. RESULTS: Of the 283 patients (300 ears), 18 (19 ears) had a canal cholesteatoma. When compared to ears without cholesteatoma (CCAA ears plus CAS ears without cholesteatoma), ears with cholesteatoma were more likely to be younger (9.2 ±â€Š6.6 vs. 11.5 ±â€Š9.2; p = 0.015), female (66.7% vs. 38.1%; p = 0.02; OR 3.2, 95% CI 1.18-8.9), and have normal/Grade I microtia (47.4% vs. 9.6%; p < 0.0001; OR 0.12, 95% CI 0.044-0.32), but not a history of draining ear (5.3% vs. 0%; p = 0.05; OR 0.06, 95% CI 0.004-0.999). Preoperative audiometric data demonstrated a lower mean air-bone gap (45.8 dB vs. 52.3 dB; p = 0.009) and better speech reception threshold (48.7 dB vs. 57.4 dB; p = 0.0004) in cholesteatoma ears. Postoperatively, ears with cholesteatoma were more likely to close the ABG within 20 dB (p = 0.001; OR 0.19, 95% CI 0.072-0.52). No patient in the cholesteatoma group developed post-operative bony/soft-tissue stenosis (0% vs. 9.7%; p = 0.65; OR 1.61; 0.21-12.6) or required revision surgery (0% vs. 11%; p = 0.38; OR 2.46, 0.32-19). CONCLUSIONS: Patients with CAS and cholesteatoma have better audiometric outcomes and likely a more durable repair with a decreased need for revision possibly secondary to greater embryologic development of the meatus, ear canal, and middle ear space despite the cholesteatoma.

Reciprocal Copy Number Variations at 22q11.2 Produce Distinct and Convergent Neurobehavioral Impairments Relevant for Schizophrenia and Autism Spectrum Disorder.

BACKGROUND: 22q11.2 deletions and duplications are copy number variations (CNVs) that predispose to developmental neuropsychiatric disorders. Both CNVs are associated with autism spectrum disorder (ASD), while the deletion confers disproportionate risk for schizophrenia. Neurobehavioral profiles associated with these reciprocal CNVs in conjunction with brain imaging measures have not been reported. METHODS: We profiled the impact of 22q11.2 CNVs on neurobehavioral measures relevant to ASD and psychosis in 106 22q11.2 deletion carriers, 38 22q11.2 duplication carriers, and 82 demographically matched healthy control subjects. To determine whether brain-behavior relationships were altered in CNV carriers, we further tested for interactions between group and regional brain structure on neurobehavioral domains. RESULTS: Cognitive deficits were observed in both CNV groups, with the lowest IQs in deletion carriers. ASD and dimensionally measured ASD traits were elevated in both CNV groups; however, duplication carriers exhibited increased stereotypies compared to deletion carriers. Moreover, discriminant analysis using ASD subdomains distinguished between CNV cases with 76% accuracy. Both psychotic disorder diagnosis and dimensionally measured positive and negative symptoms were elevated in deletion carriers. Finally, healthy control subjects showed an inverse relationship between processing speed and cortical thickness in heteromodal association areas, which was absent in both CNV groups. CONCLUSIONS: 22q11.2 CNVs differentially modulate intellectual functioning and psychosis-related symptomatology but converge on broad ASD-related symptomatology. However, subtle differences in ASD profiles distinguish CNV groups. Processing speed impairments, coupled with the lack of normative relationship between processing speed and cortical thickness in CNV carriers, implicate aberrant development of the cortical mantle in the pathology underlying impaired processing speed ability.

Mapping Subcortical Brain Alterations in 22q11.2 Deletion Syndrome: Effects of Deletion Size and Convergence With Idiopathic Neuropsychiatric Illness.

OBJECTIVE: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. METHODS: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female). RESULTS: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. CONCLUSIONS: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study.

22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

Ultrasound Guidance for Implantation of Hypoglossal Nerve Stimulator in a Breast Implant Patient.

The hypoglossal nerve stimulator (HGNS) is an effective treatment for obstructive sleep apnea in qualified patients. The implantation is typically performed without direct visualization or image guidance. A surgical approach utilizing ultrasound guidance has proved useful for patients with silicone breast implants, which may be at risk of rupture during insertion of the device. This surgical modification expands the population that can benefit from HGNS to now include patients with breast implants. Laryngoscope, 2651-2653, 2018.

Risky Decision Making in Neurofibromatosis Type 1: An Exploratory Study.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a monogenic disorder affecting cognitive function. About one third of children with NF1 have attentional disorders, and the cognitive phenotype is characterized by impairment in prefrontally-mediated functions. Mouse models of NF1 show irregularities in GABA release and striatal dopamine metabolism. We hypothesized that youth with NF1 would show abnormal behavior and neural activity on a task of risk-taking reliant on prefrontal-striatal circuits. METHODS: Youth with NF1 (N=29) and demographically comparable healthy controls (N=22), ages 8-19, were administered a developmentally sensitive gambling task, in which they chose between low-risk gambles with a high probability of obtaining a small reward, and high-risk gambles with a low probability of obtaining a large reward. We used functional magnetic resonance imaging (fMRI) to investigate neural activity associated with risky decision making, as well as age-associated changes in these behavioral and neural processes. RESULTS: Behaviorally, youth with NF1 tended to make fewer risky decisions than controls. Neuroimaging analyses revealed significantly reduced neural activity across multiple brain regions involved in higher-order semantic processing and motivation (i.e., anterior cingulate, paracingulate, supramarginal, and angular gyri) in patients with NF1 relative to controls during the task. We also observed atypical age-associated changes in neural activity in patients with NF1, such that during risk taking, neural activity tended to decrease with age in controls, whereas it tended to increase with age in patients with NF1. CONCLUSIONS: Findings suggest that developmental trajectories of neural activity during risky decision-making may be disrupted in youth with NF1.

Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry.

Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion < control < duplication). In contrast, gene dosage varied negatively with mean cortical thickness (deletion > control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in subregions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development.SIGNIFICANCE STATEMENT Probing naturally occurring reciprocal copy number variation in the genome may help us understand mechanisms underlying deviations from typical brain and cognitive development. The 22q11.2 genomic region is particularly susceptible to chromosomal rearrangements and contains many genes crucial for neuronal development and migration. Not surprisingly, reciprocal genomic imbalances at this locus confer some of the highest known genetic risks for developmental neuropsychiatric disorders. Here we provide the first evidence that brain morphology differs meaningfully as a function of reciprocal genomic variation at the 22q11.2 locus. Cortical thickness and surface area were affected in opposite directions with more widespread effects of gene dosage on cortical surface area.

Categorical versus dimensional approaches to autism-associated intermediate phenotypes in 22q11.2 microdeletion syndrome.

BACKGROUND: 22q11.2 Microdeletion syndrome (22q11DS) is associated with elevated rates of autism spectrum disorders (ASDs), although the diagnosis is controversial. In order to determine whether there is a biological substrate of ASD in 22q11DS, we examined neurocognitive and structural neuroanatomic differences between those with 22q11DS and an ASD diagnosis (22q11DS-ASD+) and those with 22q11DS without ASD (22q11DS-ASD-); we then determined whether these differences were better characterized within a categorical or dimensional framework. METHODS: We collected multiple neurocognitive measures and high-resolution T1-weighted scans on 116 individuals (29 22q11DS-ASD+, 32 22q11DS-ASD-, 55 typically developing controls) between 6 and 26 years of age. Measures of subcortical volume, cortical thickness (CT), and surface area were extracted using the FreeSurfer image analysis suite. Group differences in neurocognitive and neuroanatomic measures were assessed; regression analyses were then performed to determine whether a categorical or dimensional measure of ASD was a better predictor of neurocognitive impairment and/or neuroanatomic abnormalities observed in 22q11DS-ASD+. RESULTS: In comparison to 22q11DS-ASD-, 22q11DS-ASD+ participants exhibited decreased bilateral hippocampal CT and decreased right amygdala volumes. Those with 22q11DS-ASD+ also showed slowed processing speed and impairments in visuospatial and facial memory. Neurocognitive impairments fit a dimensional model of ASD, whereas reductions in parahippocampal CT were best explained by a categorical measure of ASD. CONCLUSIONS: A combination of categorical and dimensional measures of ASD may provide the most comprehensive understanding of ASDs in 22q11DS.