Interleaved Propofol-Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy. OBJECTIVES: The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery. METHODS: Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events. RESULTS: Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. CONCLUSIONS: Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Electrophysiology-aided DBS targeting the ventral intermediate nucleus in an essential tremor patient with MRI-incompatible lead: A case report.

Essential tremor (ET) is a common disease in the elderly population. Severe, medication-refractory ET may require surgical intervention via ablation or deep brain stimulation (DBS). Thalamic Vim (Ventral intermediate nucleus), targeted indirectly using atlas-based coordinates, is the classical target in these procedures. We present a case of an ET patient with a non-MR-compatible cardiac orphaned leads who was a candidate for DBS surgery. Due to the lead constraints of MR use, we used a head computed tomography (CT) with contrast media as the reference exam to define the AC, PC, and midline, and to register and indirectly target the Vim. For target validation, we used intraoperative electrophysiological recordings and intraoperative CT. We implanted bilateral directional leads at the target location. We used the-essential-tremor-rating-assessment-scale (TETRAS) pre and postoperatively to clinically evaluate tremor. Intraoperative micro-electrode recordings (MERs) showed individual tremor cells and a robust increase in normalized root mean square (NRMS) indicating entry to the Vim. Postoperative visualization using lead-DBS along with dramatic clinical improvements show that we were able to accurately target the Vim. Our results show that CT-only registration and planning for thalamic Vim DBS is feasible, and that MERs and intraoperative CT are useful adjuncts for Vim target validation.

Asleep DBS under ketamine sedation: Proof of concept.

BACKGROUND: Deep brain stimulation (DBS) is commonly and safely performed for selective Parkinson's disease patients. Many centers perform DBS lead positioning exclusively under local anesthesia, to optimize brain microelectrode recordings (MER) and testing of stimulation-related therapeutic and side effects. These measures enable physiological identification of the DBS borders and subdomains based on electrophysiological properties like firing rates and patterns, intra-operative evaluation of therapeutic window, and improvement of lead placement accuracy. Nevertheless, due to the challenges of awake surgery, some centers use sedation or general anesthesia, despite the distortion of discharge properties and interference with clinical testing, resulting in potential impact on surgical outcomes. Thus, there is a need for a novel anesthesia regimen that enables sedation without compromising intra-operative monitoring. OBJECTIVE: This open-label study investigates the use of low-dose ketamine for conscious sedation during microelectrode recordings and lead positioning in subthalamic nucleus (STN) DBS for Parkinson's disease patients. METHODS: Three anesthetic regimens were retrospectively compared in 38 surgeries (74 MER trajectories, 5962 recording sites) across three DBS centers: 1) Interleaved propofol-ketamine (PK), 2) Interleaved propofol-awake (PA), and 3) Fully awake (AA). RESULTS: All anesthesia regimens achieved satisfactory MER. Detection of STN borders and subdomains by expert electrophysiologist was similar between the groups. Electrophysiological signature of the STN under ketamine was not inferior to either control group. All patients completed stimulation testing. CONCLUSIONS: This study supports a low-dose ketamine anesthesia regimen for DBS which allows microelectrode recordings and stimulation testing that are not inferior to those conducted under awake and propofol-awake regimens and may optimize patient experience. A prospective double-blind study that would also compare patients' satisfaction level and clinical outcome should be performed to confirm these findings.

A practical method for real-time detection of pedicle wall breaching during funneling.

BACKGROUND: A reliable, real-time method for the detection of pedicle wall breaching during funnelling in spine deformity surgery could be accessible to any surgeon assisted with neuromonitoring. METHODS: Fifty-six consecutive patients (1066 pedicles), who were submitted to spinal deformity surgery from December 2013 to July 2015 were included in the study group. A control group of 13 consecutive patients (226 pedicles) with spinal deformity surgery were operated on from January to December 2013 and were excluded from finder stimulation. In the study cohort, continuous stimulation during funnelling was delivered via a finder and subsequently a compound muscle action potential (CMAP) threshold was determined. Following funnelling, manual inspection of the pedicular internal walls was performed. The CMAP thresholds were compared with the results of palpation to determine the sensitivity and specificity of the technique for detecting pedicular breaching. To cover common ranges of damage, the medial and lateral breaches were compared and the concave-apical breaches compared to the non-apical or convex-apical breaches. In addition, a pedicle screw test was estimated for all patients. RESULTS: ROC analysis showed 9 mA cut-off to have a sensitivity of 88.0% and a specificity of 89.5% for predicting pedicular breaching, with an area under the curve of 0.92 (95% confidence interval 0.90-0.94; P < 0.001). Using 9 mA threshold as an alert criterion, funnelling at the concave-apical pedicles showed significantly more true and false positive alerts and fewer true negative alerts when compared with the non-apical and convex-apical pedicles (P < 0.001). Medial breaches had significantly lower stimulation thresholds than lateral breaches (P < 0.001). Thresholds of screw-testing were significantly higher for study than for control-patients (P = 0.002). CONCLUSIONS: Finder stimulation has a considerably higher sensitivity and specificity for prediction of pedicular breaching, most prominent for medial breaches. Screw-testing displayed significantly better results in patients undergoing the finder stimulation technique, as compared with the control group. The main advantages of our method are its high safety level and low cost, which may be critical in less affluent countries. LEVEL OF EVIDENCE: III.

Conservative management for pediatric patients with chiari 1 anomaly: A retrospective study.

OBJECTIVE: To better understand the natural history of non-surgical management of chiari 1 anomaly. PATIENTS AND METHODS: After obtaining approval of the institutional review board, medical records and radiological exams of patients treated for CM1 at our institution between the years 2010 and 2016 were reviewed. Twenty-nine patients total were included in our study. RESULTS: The average age of our patient population was 8.5 years old at the time of diagnosis. The average tonsillar herniation on first MRI was 9.4 mm (+/- 4.6) and the average tonsillar herniation on second MRI was 10.4 mm (+/- 4.8). The average follow up time of our sample of patients was 26 months. Of the 29 patients in our study 9 (31 %) had symptomatic presentation. Interestingly, four of our patients (13.8 %) presented with epilepsy. CONCLUSIONS: Our findings support the previous work that nonoperative management is best in asymptomatic or mildly symptomatic chiari patients.

The cause of brachial plexopathy in robot-assisted transaxillary thyroidectomy-A neurophysiological investigation.

OBJECTIVES/HYPOTHESIS: During robot-assisted transaxillary thyroidectomy, the patient's arm is maintained in an overhead flexed position for a prolonged time, which poses a risk of postoperative brachial plexopathy. The aim of the study was to identify the causes of brachial plexopathy and to assess the benefit of intraoperative neurophysiological monitoring (IONM) in preventing positional brachial plexopathy in this setting. STUDY DESIGN: Retrospective case series. METHODS: The computerized database of a tertiary medical center was searched for all consecutive patients who underwent robot-assisted transaxillary thyroidectomy between 2012 and 2014. Clinical, operative, and outcome parameters were collected from the medical files. Findings were compared between patients operated with and without IONM. RESULTS: The cohort included 30 patients, 14 operated with IONM and 16 without. Three events of impending brachial plexopathy were detected in the monitored group. The monitored group had significantly better shoulder movement (P = .003), a lower rate of hypoesthesia (P = .011), less pain (P = .001) in the early postoperative period than the nonmonitored group and higher quality of life in the early postoperative period (P = .012). The monitored group was significantly younger than the nonmonitored one (P = .02) and had a significantly larger diameter of thyroid nodule than the nonmonitored group (P = .043). CONCLUSIONS: IONM during robot-assisted transaxillary thyroidectomy may improve short-term postoperative pain and shoulder movement and longer-term quality of life. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2187-2193, 2016.

Hyperactive auditory processing in Williams syndrome: Evidence from auditory evoked potentials.

The neurophysiologic aberrations underlying the auditory hypersensitivity in Williams syndrome (WS) are not well defined. The P1-N1-P2 obligatory complex and mismatch negativity (MMN) response were investigated in 18 participants with WS, and the results were compared with those of 18 age- and gender-matched typically developing (TD) controls. Results revealed significantly higher amplitudes of both the P1-N1-P2 obligatory complex and the MMN response in the WS participants than in the TD controls. The P1-N1-P2 complex showed an age-dependent reduction in the TD but not in the WS participants. Moreover, high P1-N1-P2 complex was associated with low verbal comprehension scores in WS. This investigation demonstrates that central auditory processing is hyperactive in WS. The increase in auditory brain responses of both the obligatory complex and MMN response suggests aberrant processes of auditory encoding and discrimination in WS. Results also imply that auditory processing may be subjected to a delayed or diverse maturation and may affect the development of high cognitive functioning in WS.

Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects.

The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age.

Biological effects of COMT haplotypes and psychosis risk in 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common genetic syndrome associated with schizophrenia. The catechol-O-methyltransferase (COMT) gene is located in the obligatory deletion region, and possible associations between COMT variants and neuropsychiatric manifestations in 22q11.2DS have been reported. The purpose of the current study was to evaluate the effect of COMT hemizygosity and molecular haplotypes on gene expression and enzyme activity and its association with psychotic symptoms in 22q11.2DS. METHODS: Lymphoblast samples were drawn from 53 individuals with 22q11.2DS and 16 typically developing control subjects. We measured COMT messenger (m)RNA and protein expression and enzyme activity using standard procedures. The presence of a psychotic disorder and cognitive deficits were also evaluated using structured testing. RESULTS: There was an approximately 50% reduction in COMT mRNA, protein, and enzyme activity levels in 22q11.2DS samples. Haplotype analysis revealed clear phenotypic differences between various Val-containing haplotypes on COMT-3' untranslated region extended mRNA, soluble COMT and membrane-bound proteins, and enzyme activity. The G variant of rs165599, a 3' untranslated region single nucleotide polymorphism, was associated with low levels of COMT expression and with the presence of psychosis and lower performance IQ scores in our 22q11.2DS sample. Finally, we demonstrate that the COMT rs74745580 "T" mutation is associated with absent soluble COMT expression and very low COMT activity in two 22q11.2DS individuals. CONCLUSIONS: Our findings confirm a robust effect of COMT hemizygosity on COMT activity and show complex interactions of variants within the COMT gene that influence COMT biology and confound conclusions based on associations with the Val158Met genotype alone.

Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes.

22q11.2 deletion syndrome (22q11.2DS) is a common genetic risk factor for the development of schizophrenia. We investigated two neurophysiological endophenotypes of schizophrenia - P50 sensory gating and mismatch negativity in 22q11.2DS subject and evaluated their association with catechol O-methyltransferase (COMT) and proline dehydrogenase (PRODH) genetic variants. We also assessed the association of neurophysiological measures with schizophrenia-like symptomatology in 22q11.2DS. Fifty-nine subjects, 41 with 22q11.2DS and 18 typically developing controls, participated in the study. The participants with 22q11.2DS were genotyped for the COMT Val(158)Met (rs4680) and PRODH Gln(19)Pro (rs2008720) and Arg(185)Trp (rs4819756) polymorphisms. Following psychiatric evaluation, all the participants underwent neurophysiological recordings and executive function assessment. The 22q11.2DS group showed poorer sensory gating of the P50 response than the controls. Within the 22q11.2DS group, the COMT Met allele was associated with poorer sensory gating, while both the COMT Met allele and the PRODH Pro-Arg haplotype were associated with smaller mismatch negativity amplitudes. Smaller mismatch negativity amplitudes predicted greater impairment of executive functions and greater severity of schizophrenia-like negative symptoms in 22q11.2DS. The current study demonstrates that sensory gating impairments that are typical of schizophrenia are found in 22q11.2DS subjects. Our results further suggest that COMT and PRODH genetic variations contribute to sensory gating and mismatch negativity schizophrenia-like impairments in 22q11.2DS, possibly via dopaminergic/glutamatergic networks. The associations of mismatch negativity impairments with increased severity of schizophrenia-like negative symptoms and poorer executive functions performance in our 22q11.2DS sample suggest that mismatch negativity is a potential endophenotype for schizophrenia in 22q11.2DS.

Genotype-phenotype correlation in 22q11.2 deletion syndrome.

BACKGROUND: The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion. METHODS: Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation. RESULTS: Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2%) carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted.Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes. CONCLUSIONS: MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms.Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.

The feasibility and safety of S-adenosyl-L-methionine (SAMe) for the treatment of neuropsychiatric symptoms in 22q11.2 deletion syndrome: a double-blind placebo-controlled trial.

The goal of this trial was to assess the feasibility and safety of using S-adenosyl-L-methionine (SAMe) to treat depressive disorder, attention deficit/hyperactivity disorder (ADHD) and cognitive deficits in individuals with the 22q11.2 deletion syndrome (22q11.2DS). SAMe supposedly enhances the activity of the COMT enzyme. Because individuals with 22q11.2DS have only one copy of the gene responsible for the enzyme, COMT haploinsufficiency may be associated with their psychiatric morbidity and cognitive deficits. We assessed twelve 22q11.2DS individuals with depressive disorder or ADHD in a randomized double-blind cross-over placebo-controlled trial, using SAMe 800 mg bid. Individuals were evaluated for treatment safety and effectiveness during the trial and upon completion at sixth week. Compared to placebo, there were no significant differences in the rate of reported side effects between SAMe and placebo. Despite a general concern that SAMe might induce mania in vulnerable individuals, no manic or psychotic symptoms were exhibited during the SAMe treatment. Individuals with 22q11.2DS with comorbid depressive disorder with or without psychotic symptoms (n = 5) had a larger numerical improvement on relevant clinical scales compared to placebo. No treatment effect was found on ADHD symptoms in subjects who suffered from 22q11.2DS with comorbid ADHD (n = 7). Cognitive performance did not improve or deteriorate following treatment with SAMe compared to placebo. In conclusion SAMe treatment up to 1,600 mg/day for 6 weeks in 22q11.2DS individuals appears to be safe, well tolerated and with no serious side effects. No significant benefit in depressive or ADHD symptoms was detected.

Cochlear hearing loss in patients with Laron syndrome.

The aim of this prospective clinical study was to test auditory function in patients with Laron syndrome, either untreated or treated with insulin-like growth factor I (IGF-I). The study group consisted of 11 patients with Laron syndrome: 5 untreated adults, 5 children and young adults treated with replacement IGF-I starting at bone age <2 years, and 1 adolescent who started replacement therapy at bone age 4.6 years. The auditory evaluation included pure tone and speech audiometry, tympanometry and acoustic reflexes, otoacoustic emissions, loudness dynamics, auditory brain stem responses and a hyperacusis questionnaire. All untreated patients and the patient who started treatment late had various degrees of sensorineural hearing loss and auditory hypersensitivity; acoustic middle ear reflexes were absent in most of them. All treated children had normal hearing and no auditory hypersensitivity; most had recordable middle ear acoustic reflexes. In conclusion, auditory defects seem to be associated with Laron syndrome and may be prevented by starting treatment with IGF-I at an early developmental age.

Phenotypic psychiatric characterization of children with Williams syndrome and response of those with ADHD to methylphenidate treatment.

Williams syndrome (WS) is associated with cognitive deficits, special behavioral phenotype, and high rates of psychiatric disorders. The aims of the present study were: (1) To compare the rates of psychiatric disorders and repetitive behaviors in children with WS to children with idiopathic developmental disability (DDs); (2) To longitudinally assess the change in psychiatric disorders during adolescence in WS; (3) To assess retrospectively the effectiveness and safety of methylphenidate (MPH) treatment in WS children with ADHD. The study consisted of a cohort of 38 children and adolescents (age 13.1 ± 5.2 years) with WS and a sample of age-matched DDs (age 15.0 ± 3.1 years). A current follow-up evaluation was conducted after 5.6 ± 1.6 years for 25 subjects (65.8%) of the WS cohort. The rate of most psychiatric disorders was found similar in children with WS and DD controls. Specific phobia, especially from noises, obsessive-compulsive symptoms (e.g., aggressive obsessions and repetitive questions), and stereotypic behaviors (e.g., glancing), were more common in WS than DDs. In a longitudinal follow-up of the WS children, we found a decrease in the rate of anxiety disorders. In addition, a clinically significant improvement was reported in 72.2% of WS children with ADHD following MPH treatment. Sadness/unhappiness was the most common side effect associated with MPH treatment in WS, occurring in 2/3 of treated individuals. The present study further elucidates the neuropsychiatric phenotype of WS. Our results also suggest that MPH treatment for ADHD in WS warrants future prospective controlled trials.

The effect of methylphenidate on prefrontal cognitive functioning, inattention, and hyperactivity in velocardiofacial syndrome.

OBJECTIVE: Methylphenidate (MPH) is commonly used to treat attention-deficit/hyperactivity disorder (ADHD) in all children, including those with velocardiofacial syndrome (VCFS). Yet concerns have been raised regarding its safety and efficacy in VCFS. The goal of this study was to examine the safety and efficacy of MPH in children with VCFS. METHODS: Thirty-four children and adolescents with VCFS and ADHD participated in a randomized, controlled trial with a 2:1 ratio of MPH versus placebo. All subjects underwent a cardiological evaluation before and after MPH administration. The primary outcome measure was prefrontal cognitive performance following a single dose of MPH or placebo. A follow-up assessment was conducted after a 6-month treatment with MPH. RESULTS: Compared with placebo, single MPH administration was associated with a more robust improvement in prefrontal cognitive performance, including achievements in the Hearts and Flowers executive function task and the visual continuous performance task. After 6 months of treatment, a 40% reduction in severity of ADHD symptoms was reported by parents on the Revised Conners Rating Scale. All subjects treated with MPH reported at least one side effect, but it did not necessitate discontinuation of treatment. MPH induced an increase in heart rate and blood pressure that was usually minor, but was clinically significant in two cases. No differences in response to MPH were observed between catechol-O-methyltransferase Met versus Val carriers. CONCLUSION: The use of MPH in children with VCFS appears to be effective and relatively safe. A comprehensive cardiovascular evaluation for children with VCFS before and during stimulant treatment is recommended.

A comparative study of hearing loss in two microdeletion syndromes: velocardiofacial (22q11.2 deletion) and Williams (7q11.23 deletion) syndromes.

OBJECTIVE: To comprehensively assess auditory impairments in velocardiofacial syndrome (VCFS) and Williams syndrome (WS). STUDY DESIGN: Audiologic measurements were conducted with 62 subjects with VCFS and 44 subjects with WS, as well as two control groups consisting of 22 subjects with idiopathic developmental disability and 23 typically developing controls. An association between severity of hearing loss in VCFS and the (158)Val/Met polymorphism of the catechol-O-methyltransferase gene (COMT) was explored. RESULTS: Hearing was significantly more impaired in the VCFS and WS groups compared with the developmental disability and typically developing groups. Audiologic abnormalities identified in both the VCFS and WS groups included high-tone hearing loss (predominantly sensorineural or mixed type), loss of acoustic reflex, and middle ear pathologies. In both the VCFS and WS groups, hearing loss severity was positively correlated with age. In the VCFS group, hearing loss was more severe in the subgroup carrying the COMT Val allele compared with the subgroup carrying the COMT Met allele. CONCLUSIONS: Hearing impairments, including sensorineural hearing loss and acoustic reflex dysfunction, are very common in both VCFS and WS. Hearing loss is less severe in subjects with the COMT Met allele, possibly due to the protective effect of dopamine on the hearing system.

Auditory and visual processing in Williams syndrome.

Williams syndrome is a neurodevelopmental disorder caused by a deletion on chromosome 7. It is characterized by a range of medical problems in addition to severe impairments in visuospatial processing and oversensitivity to sounds, including hypersensitivity to sounds (hyperacusis) and extreme fear from sounds (phonophobia). In spite of impairments in visuospatial processing, object and face processing abilities are relatively preserved in WS.The present review discusses the growing research in the field linking the unique sensory phenotype in WS with underlying structural and functional brain abnormalities. In addition, possible associations between the genetic defect and the abnormal sensory processing are presented. Because Williams syndrome is etiologically homogeneous, it may serve as a model to promote understanding of visuospatial and auditory processing in humans. The findings may also have important implications for other developmental psychopathologies, such as autism, schizophrenia and attention deficit hyperactivity disorder.

Hyperactive auditory efferent system and lack of acoustic reflexes in Williams syndrome.

The auditory efferent system and acoustic reflexes have been investigated in patients with Williams syndrome (WS). Twenty-one patients aged 6-26 years with a genetically confirmed diagnosis of WS and with reported hyperacusis were compared with 21 normally developing age-matched subjects. The medial olivocochlear (MOC) efferent system was tested by stimulation of the contralateral ear with increasing levels of white noise, while recording transient evoked otoacoustic emissions (TEOAE) in the ipsilateral ear. The suppression effect on the amplitudes of the TEOAE was computed for each contralateral stimulus level. This measure reflects the strength of the MOC efferent system. In addition, the thresholds of ipsilateral and contralateral acoustic reflexes in response to 1, 2 and 4 kHz tones as well as to broadband stimuli were also recorded. Results showed that patients with WS had a significantly higher suppression effect of the MOC reflex on TEOAE. Ipsilateral and contralateral acoustic reflexes to tonal and broadband stimuli presented at maximum stimulus intensities were absent in 62-86% of the patients with WS. In the remainder, acoustic reflexes were elicited at lower auditory sensation thresholds than in controls. Hyperexcitability of the MOC efferent system coupled with absence of acoustic reflexes may contribute to the hyperacusis in WS and the consequent high-tone hearing loss induced by environmental noise. Both measures can be used for objective detection and thus, intervention of hyperacusis in the early stages of life.