11C-Methionine uptake in meningiomas after stereotactic radiotherapy.

OBJECTIVE: 11C-Methionine positron emission tomography (MET-PET) is used for stereotactic radiotherapy planning in meningioma patients. The role of MET-PET during subsequent follow-up (FU) is unclear. We analyzed the uptake of 11C-Methionine before and after stereotactic radiotherapy (SRT) in patients with a complex meningioma and investigated if there was a difference between patients with progressive disease (PD) and stable disease (SD) during FU. METHODS: This retrospective study investigates 62 MET-PETs in 29 complex meningioma patients. Standardized uptake value (SUV)max and SUVpeak tumor-to-normal ratios (T/N-ratios) were calculated, comparing the tumor region with both the mirroring intracranial area and the right frontal gray matter. The difference in 11C-Methionine uptake pre- and post-SRT was analyzed, as well as the change in uptake between PD or SD. RESULTS: Median (IQR) FU duration was 67 months (50.5-91.0). The uptake of 11C-Methionine in meningiomas remained increased after SRT. Neither a statistically significant difference between MET-PETs before and after SRT was encountered, nor a significant difference in one of the four T/N-ratios between patients with SD versus PD with median (IQR) SUVmax T/NR front 2.65 (2.13-3.68) vs 2.97 (1.55-3.54) [p = 0.66]; SUVmax T/Nmirror 2.92 (2.19-3.71) vs 2.95 (1.74-3.60) [p = 0.61]; SUVpeak T/NR front 2.35 (1.64-3.40) vs 2.25 (1.44-3.74) [p = 0.80]; SUVpeak T/Nmirror 2.38 (1.91-3.36) vs 2.35 (1.56-3.72) [p = 0.95]. CONCLUSIONS: Our data do not support use of MET-PET during FU of complex intracranial meningiomas after SRT. MET-PET could not differentiate between progressive or stable disease.

Tinnitus: an underreported condition following microvascular decompression for hemifacial spasm.

PURPOSE: While hearing loss is a well-known condition following microvascular decompression (MVD) for hemifacial spasm (HFS), tinnitus is an underreported one. This study aims to identify prevalence, characteristics, severity, and predictors of tinnitus following MVD for HFS. METHODS: A single-center cohort of 55 HFS patients completed a questionnaire approximately 5 years following MVD. Data encompassed tinnitus presence, side, type, onset, and severity measured by a 10-point Visual Analogue Scale (VAS). Descriptive, correlation, and logistic regression analyses were conducted. RESULTS  : At surgery, participants' median age was 58 years (IQR 52-65). The median duration of HFS symptoms before surgery was 5 years (IQR 3-8), slightly predominant on the left (60%). Postoperative tinnitus was reported by 20 patients (36%), versus nine (16%) that reported preoperative tinnitus. Postoperative tinnitus was ipsilateral on the surgical side in 13 patients (65%), bilateral in six (30%), and contralateral in one (5%). Among patients with bilateral postoperative tinnitus, 33% did not have this preoperatively. Tinnitus was continuous in 70% of cases and pulsatile in 30%. Onset of new tinnitus was in 58% immediately or within days, in 25% within three months, and in 17% between three months and one year after surgery. The mean severity of postoperative tinnitus was 5.1 points on the VAS. Preoperative tinnitus and presence of arachnoid adhesions had suggestive associations with postoperative tinnitus in initial analyses (p = 0.005 and p = 0.065). However, preoperative tinnitus was the only significant predictor of postoperative tinnitus (p = 0.011). CONCLUSION: Tinnitus is a common condition following MVD for HFS, with a moderate overall severity. Causes behind postoperative tinnitus remain obscure but could be related to those of postoperative hearing loss in this patient population. Clinicians should be aware of tinnitus following MVD and vigilantly monitor its occurrence, to facilitate prevention efforts and optimize outcome for HFS patients undergoing MVD.

Assessing Facial Palsy: Does Feedback Improve Assessment Using the eFACE and Sunnybrook Facial Grading System?

OBJECTIVE(S): To explore learning effects when applying the clinician-graded electronic facial function scale (eFACE) and the Sunnybrook Facial Grading System (Sunnybrook). METHODS: Surgeons, facial rehabilitation therapists, and medical students were randomly allocated to the eFACE (n = 7) or Sunnybrook (n = 6) and graded 60 videos (Massachusetts Eye and Ear Infirmary open-source standard set); 10 persons with normal facial function and 50 patients with a wide variation of facial palsy severity. Participants received an introduction and individual feedback after each set of 10 videos. Scores were compared to the reference score provided with the set. Multilevel analysis was performed to analyze learning effect. RESULTS: A learning effect was only found for the eFACE, with significant difference scores in set 1 and 2 compared to set 6, and no significant difference scores in the following sets. The difference score was associated with the reference score (severity of facial palsy) for eFACE (ß = -0.19; SE = 0.04; p < 0.001) and Sunnybrook (ß = -0.15; SE = 0.04; p < 0.001). Age of participants was also associated with the difference score in the eFACE group (ß = 0.18; SE = 0.03; p < 0.001). No differences in scores were found between groups of participants. CONCLUSION: The eFACE showed a learning effect of feedback while the Sunnybrook did not. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

The Relevance of Intraoperative Clinical and Accelerometric Measurements for Thalamotomy Outcome.

Thalamotomy alleviates medication-refractory tremors in patients with movement disorders such as Parkinson's Disease (PD), Essential tremor (ET), and Holmes tremor (HT). However, limited data are available on tremor intensity during different thalamotomy stages. Also, the predictive value of the intraoperative tremor status for treatment outcomes remains unclear. Therefore, we aimed to quantify tremor status during thalamotomy and postoperatively. Data were gathered between January 2020 and June 2023 during consecutive unilateral thalamotomy procedures in patients with PD (n = 13), ET (n = 8), and HT (n = 3). MDS-UPDRS scores and tri-axial accelerometry data were obtained during rest, postural, and intention tremor tests. Measurements were performed intraoperatively (1) before lesioning-probe insertion, (2) directly after lesioning-probe insertion, (3) during coagulation, (4) directly after coagulation, and (5) 4-6 months post-surgery. Accelerometric data were recorded continuously during the coagulation process. Outcome measures included MDS-UPDRS tremor scores and accelerometric parameters (peak frequency, tremor amplitude, and area under the curve of power (AUCP)). Tremor intensity was assessed for the insertion effect (1-2), during coagulation (3), post-coagulation effect (1-4), and postoperative effect (1-5). Following insertion and coagulation, tremor intensity improved significantly compared to baseline (p < 0.001). The insertion effect clearly correlated with the postoperative effect (ρ = 0.863, p < 0.001). Both tremor amplitude and AUCP declined gradually during coagulation. Peak frequency did not change significantly intraoperatively. In conclusion, the study data show that both the intraoperative insertion effect and the post-coagulation effect are good predictors for thalamotomy outcomes.

A Novel Accelerometry Method to Perioperatively Quantify Essential Tremor Based on Fahn-Tolosa-Marin Criteria.

The disease status, progression, and treatment effect of essential tremor (ET) patients are currently assessed with clinical scores, such as the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM). The use of objective and rater-independent monitoring of tremors may improve clinical care for patients with ET. Therefore, the focus of this study is to develop an objective accelerometry-based method to quantify ET, based on FTM criteria. Thirteen patients with ET and thirteen matched healthy participants underwent FTM tests to rate tremor severity, paired with tri-axial accelerometric measurements at the index fingers. Analogue FTM assessments were performed by four independent raters based on video recordings. Quantitative measures were derived from the accelerometric data, e.g., the area under the curve of power in the 4-8 Hz frequency band (AUCP) and maximal tremor amplitude. As such, accelerometric tremor scores were computed, using thresholds based on healthy measurements and FTM criteria. Agreement between accelerometric and clinical FTM scores was analyzed with Cohen's kappa coefficient. It was assessed whether there was a relationship between mean FTM scores and the natural logarithm (ln) of the accelerometric outcome measures using linear regression. The agreement between accelerometric and FTM scores was substantial for resting and intention tremor tests (≥72.7%). However, the agreement between accelerometric postural tremor data and clinical FTM ratings (κ = 0.459) was low, although their logarithmic (ln) relationship was substantial (R2 ≥ 0.724). Accelerometric test-retest reliability was good to excellent (ICC ≥ 0.753). This pilot study shows that tremors can be quantified with accelerometry, using healthy thresholds and FTM criteria. The test-retest reliability of the accelerometric tremor scoring algorithm indicates that our low-cost accelerometry-based approach is a promising one. The proposed easy-to-use technology could diminish the rater dependency of FTM scores and enable physicians to monitor ET patients more objectively in clinical, intraoperative, and home settings.

Supine MDS-UPDRS-III Assessment: An Explorative Study.

The Movement Disorder Society Unified Parkinson's Disease Rating Scale-part III (MDS-UPDRS-III) is designed to be applied in the sitting position. However, to evaluate the clinical effect during stereotactic neurosurgery or to assess bedridden patients with Parkinson's disease (PD), the MDS-UPDRS-III is often used in a supine position. This explorative study evaluates the agreement of the MDS-UPDRS-III in the sitting and the supine positions. In 23 PD patients, the MDS-UPDRS-III was applied in both positions while accelerometric measurements were performed. Video recordings of the assessments were evaluated by two certified raters. Agreement between the sitting and supine MDS-UPDRS-III was studied using Cohen's kappa coefficient. Relationships between the MDS-UPDRS-III tremor scores and accelerometric amplitudes were calculated for both positions with linear regression. A fair to substantial agreement was found for MDS-UPDRS-III scores of individual items in the sitting and supine positions, while combining all tests resulted in a substantial agreement. The inter-rater reliability was fair to moderate for both positions. A logarithmic relationship between tremor scores and accelerometric amplitude was revealed for both the sitting and supine positions. Nevertheless, these data are insufficient to fully support the supine application of the MDS-UPDRS-III. Several recommendations are made to address the sensitivity of the scale to inter-rater variability. In conclusion, although an overall substantial agreement between sitting and supine MDS-UPDRS-III is confirmed, its application in the supine position is not endorsed for the whole range of its individual items. Caution is warranted in interpreting the supine MDS-UPDRS-III, pending additional research.

Use of NEedle Versus suRFACE Recording Electrodes for Detection of Intraoperative Motor Warnings: A Non-Inferiority Trial. The NERFACE Study Part II.

In the NERFACE study part I, the characteristics of muscle transcranial electrical stimulation motor evoked potentials (mTc-MEPs) recorded from the tibialis anterior (TA) muscles with surface and subcutaneous needle electrodes were compared. The aim of this study (NERFACE part II) was to investigate whether the use of surface electrodes was non-inferior to the use of subcutaneous needle electrodes in detecting mTc-MEP warnings during spinal cord monitoring. mTc-MEPs were simultaneously recorded from TA muscles with surface and subcutaneous needle electrodes. Monitoring outcomes (no warning, reversible warning, irreversible warning, complete loss of mTc-MEP amplitude) and neurological outcomes (no, transient, or permanent new motor deficits) were collected. The non-inferiority margin was 5%. In total, 210 (86.8%) out of 242 consecutive patients were included. There was a perfect agreement between both recording electrode types for the detection of mTc-MEP warnings. For both electrode types, the proportion of patients with a warning was 0.12 (25/210) (difference, 0.0% (one-sided 95% CI, 0.014)), indicating non-inferiority of the surface electrode. Moreover, reversible warnings for both electrode types were never followed by permanent new motor deficits, whereas among the 10 patients with irreversible warnings or complete loss of amplitude, more than half developed transient or permanent new motor deficits. In conclusion, the use of surface electrodes was non-inferior to the use of subcutaneous needle electrodes for the detection of mTc-MEP warnings recorded over the TA muscles.

Short-Term Neck Pain After Posterior Foraminotomy Compared with Anterior Discectomy with Fusion for Cervical Foraminal Radiculopathy: A Secondary Analysis of the FACET Randomized Controlled Trial.

BACKGROUND: Short-term neck pain after posterior cervical foraminotomy (posterior surgery) compared with anterior cervical discectomy with fusion (anterior surgery) treating cervical radiculopathy has only been assessed once, retrospectively, to our knowledge. The aim of this study was to prospectively evaluate the course of neck pain for 6 weeks after both treatments. METHODS: This is a secondary analysis of the multicenter Foraminotomy ACDF Cost-Effectiveness Trial (FACET), conducted from January 2016 to May 2020. Of 389 patients who had single-level, 1-sided cervical radiculopathy and were screened for eligibility, 265 were randomly assigned to undergo posterior surgery (n = 132) or anterior surgery (n = 133). The primary outcome of the present analysis was neck pain, assessed weekly for 6 weeks using the visual analog scale (VAS), on a scale of 0 to 100. The secondary outcomes were arm pain, neck disability, work ability, quality of life, treatment satisfaction, motor and sensory changes, and hospital length of stay. Data were analyzed with mixed model analysis in intention-to-treat samples using 2-sided 95% confidence intervals (CIs). RESULTS: In the first postoperative week, the mean VAS for neck pain was 56.2 mm (95% CI, 51.7 to 60.8 mm) after posterior surgery and 46.7 mm (95% CI, 42.2 to 51.2 mm) after anterior surgery. The mean between-group difference was 9.5 mm (95% CI, 3.3 to 15.7 mm), which gradually decreased to 2.3 mm (95% CI, -3.6 to 8.1 mm) at postoperative week 6. As of postoperative week 5, there was no significant difference between groups. Responder analyses confirmed this result. Secondary outcomes showed small differences between groups. CONCLUSIONS: Insight into the course of neck pain during the first 6 weeks after posterior compared with anterior surgery is provided. Despite initially more neck pain after posterior surgery, patients swiftly improved and, as of postoperative week 5, results similar to those after anterior surgery were observed. Our findings should enable improved patient counseling and enhanced shared decision-making between physicians and patients with cervical radiculopathy, where more neck pain in the first postoperative weeks should be balanced against the benefits of posterior surgery. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Comparing Motor-Evoked Potential Characteristics of NEedle versus suRFACE Recording Electrodes during Spinal Cord Monitoring-The NERFACE Study Part I.

Muscle-recorded transcranial electrical stimulation motor-evoked potentials (mTc-MEPs) are used to assess the spinal cord integrity. They are commonly recorded with subcutaneous needle or surface electrodes, but the different characteristics of mTc-MEP signals recorded with the two types of electrodes have not been formally compared yet. In this study, mTc-MEPs were simultaneously recorded from the tibialis anterior (TA) muscles using surface and subcutaneous needle electrodes in 242 consecutive patients. Elicitability, motor thresholds, amplitude, area under the curve (AUC), signal-to-noise ratio (SNR), and the variability between mTc-MEP amplitudes were compared. Whereas amplitude and AUC were significantly higher in subcutaneous needle recordings (p < 0.01), motor thresholds and elicitability were similar for surface and subcutaneous needle recordings. Moreover, the SNRs were >2 in more than 99.5% of the surface and subcutaneous needle recordings, and the variability between consecutive amplitudes was not significantly different between the two recording electrode types (p = 0.34). Surface electrodes appear to be a good alternative to needle electrodes for spinal cord monitoring. They are non-invasive, can record signals at similar threshold intensities, have adequately high SNRs, and record signals with equivalent variability. Whether surface electrodes are non-inferior to subcutaneous needle electrodes in detecting motor warnings is investigated in part II of the NERFACE study.

Noninferiority of Posterior Cervical Foraminotomy vs Anterior Cervical Discectomy With Fusion for Procedural Success and Reduction in Arm Pain Among Patients With Cervical Radiculopathy at 1 Year: The FACET Randomized Clinical Trial.

Importance: The choice between posterior cervical foraminotomy (posterior surgery) and anterior cervical discectomy with fusion (anterior surgery) for cervical foraminal radiculopathy remains controversial. Objective: To investigate the noninferiority of posterior vs anterior surgery in patients with cervical foraminal radiculopathy with regard to clinical outcomes after 1 year. Design, Setting, and Participants: This multicenter investigator-blinded noninferiority randomized clinical trial was conducted from January 2016 to May 2020 with a total follow-up of 2 years. Patients were included from 9 hospitals in the Netherlands. Of 389 adult patients with 1-sided single-level cervical foraminal radiculopathy screened for eligibility, 124 declined to participate or did not meet eligibility criteria. Patients with pure axial neck pain without radicular pain were not eligible. Of 265 patients randomized (132 to posterior and 133 to anterior), 15 were lost to follow-up and 228 were included in the 1-year analysis (110 in posterior and 118 in anterior). Interventions: Patients were randomly assigned 1:1 to posterior foraminotomy or anterior cervical discectomy with fusion. Main Outcomes and Measures: Primary outcomes were proportion of success using Odom criteria and decrease in arm pain using a visual analogue scale from 0 to 100 with a noninferiority margin of 10% (assuming advantages with posterior surgery over anterior surgery that would justify a tolerable loss of efficacy of 10%). Secondary outcomes were neck pain, disability, quality of life, work status, treatment satisfaction, reoperations, and complications. Analyses were performed with 2-proportion z tests at 1-sided .05 significance levels with Bonferroni corrections. Results: Among 265 included patients, the mean (SD) age was 51.2 (8.3) years; 133 patients (50%) were female and 132 (50%) were male. Patients were randomly assigned to posterior (132) or anterior (133) surgery. The proportion of success was 0.88 (86 of 98) in the posterior surgery group and 0.76 (81 of 106) in the anterior surgery group (difference, -0.11 percentage points; 1-sided 95% CI, -0.01) and the between-group difference in arm pain was -2.8 (1-sided 95% CI, -9.4) at 1-year follow-up, indicating noninferiority of posterior surgery. Decrease in arm pain had a between-group difference of 3.4 (1-sided 95% CI, 11.8), crossing the noninferiority margin with 1.8 points. All secondary outcomes had 2-sided 95% CIs clustered around 0 with small between-group differences. Conclusions and Relevance: In this randomized clinical trial, posterior surgery was noninferior to anterior surgery for patients with cervical radiculopathy regarding success rate and arm pain at 1 year. Decrease in arm pain and secondary outcomes had small between-group differences. These results may be used to enhance shared decision-making. Trial Registration: Netherlands Trial Register Identifier: NTR5536.

The Accuracy of Patient-Specific Spinal Drill Guides Is Non-Inferior to Computer-Assisted Surgery: The Results of a Split-Spine Randomized Controlled Trial.

In recent years, patient-specific spinal drill guides (3DPGs) have gained widespread popularity. Several studies have shown that the accuracy of screw insertion with these guides is superior to that obtained using the freehand insertion technique, but there are no studies that make a comparison with computer-assisted surgery (CAS). The aim of this study was to determine whether the accuracy of insertion of spinal screws using 3DPGs is non-inferior to insertion via CAS. A randomized controlled split-spine study was performed in which 3DPG and CAS were randomly assigned to the left or right sides of the spines of patients undergoing fixation surgery. The 3D measured accuracy of screw insertion was the primary study outcome parameter. Sixty screws inserted in 10 patients who completed the study protocol were used for the non-inferiority analysis. The non-inferiority of 3DPG was demonstrated for entry-point accuracy, as the upper margin of the 95% CI (−1.01 mm−0.49 mm) for the difference between the means did not cross the predetermined non-inferiority margin of 1 mm (p < 0.05). We also demonstrated non-inferiority of 3D angular accuracy (p < 0.05), with a 95% CI for the true difference of −2.30°−1.35°, not crossing the predetermined non-inferiority margin of 3° (p < 0.05). The results of this randomized controlled trial (RCT) showed that 3DPGs provide a non-inferior alternative to CAS in terms of screw insertion accuracy and have considerable potential as a navigational technique in spinal fixation.

Intraoperative Quantification of MDS-UPDRS Tremor Measurements Using 3D Accelerometry: A Pilot Study.

The most frequently used method for evaluating tremor in Parkinson's disease (PD) is currently the internationally standardized Movement Disorder Society­Unified PD Rating Scale (MDS-UPDRS). However, the MDS-UPDRS is associated with limitations, such as its inherent subjectivity and reliance on experienced raters. Objective motor measurements using accelerometry may overcome the shortcomings of visually scored scales. Therefore, the current study focuses on translating the MDS-UPDRS tremor tests into an objective scoring method using 3D accelerometry. An algorithm to measure and classify tremor according to MDS-UPDRS criteria is proposed. For this study, 28 PD patients undergoing neurosurgical treatment and 26 healthy control subjects were included. Both groups underwent MDS-UPDRS tests to rate tremor severity, while accelerometric measurements were performed at the index fingers. All measurements were performed in an off-medication state. Quantitative measures were calculated from the 3D acceleration data, such as tremor amplitude and area-under-the-curve of power in the 4−6 Hz range. Agreement between MDS-UPDRS tremor scores and objective accelerometric scores was investigated. The trends were consistent with the logarithmic relationship between tremor amplitude and MDS-UPDRS score reported in previous studies. The accelerometric scores showed a substantial concordance (>69.6%) with the MDS-UPDRS ratings. However, accelerometric kinetic tremor measures poorly associated with the given MDS-UPDRS scores (R2 < 0.3), mainly due to the noise between 4 and 6 Hz found in the healthy controls. This study shows that MDS-UDPRS tremor tests can be translated to objective accelerometric measurements. However, discrepancies were found between accelerometric kinetic tremor measures and MDS-UDPRS ratings. This technology has the potential to reduce rater dependency of MDS-UPDRS measurements and allow more objective intraoperative monitoring of tremor.

Fluorescence-guided detection of pituitary neuroendocrine tumor (PitNET) tissue during endoscopic transsphenoidal surgery available agents, their potential, and technical aspects.

Differentiation of pituitary neuroendocrine tumor (PitNET) tissue from surrounding normal tissue during surgery is challenging. A number of fluorescent agents is available for visualization of tissue discrepancy, with the potential of improving total tumor resection. This review evaluates the availability, clinical and technical applicability of the various fluorescent agents within the field of pituitary surgery. According to PRISMA guidelines, a systematic review was performed to identify reports describing results of in vivo application of fluorescent agents. In this review, 15 publications were included. Sodium Fluorescein (FNa) was considered in two studies. The first study reported noticeable fluorescence in adenoma tissue, the second demonstrated the strongest fluorescence in non-functioning pituitary adenomas. 5-Aminolevulinic acid (5-ALA) was investigated in three studies. One study compared laser-based optical biopsy system (OBS) with photo-diagnostic filter (PD) and found that the OBS was able to detect all microadenomas, even when MRI was negative. The second study retrospectively analyzed twelve pituitary adenomas and found only one positive for fluorescence. The third investigated fifteen pituitary adenomas of which one displayed vague fluorescence. Indocyanine green (ICG) was researched in four studies with variable results. Second-Window ICG yielded no significant difference between functioning and non-functioning adenomas in one study, while a second study displayed 4 times higher fluorescence in tumor tissue than in normal tissue. In three studies, OTL38 showed potential in non-functioning pituitary adenomas. At present, evidence for fluorescent agents to benefit total resection of PitNETs is lacking. OTL38 can potentially serve as a selective fluorescent agent in non-functioning pituitary adenomas in the near future.

Detraining Slows and Maintenance Training Over 6 Years Halts Parkinsonian Symptoms-Progression.

Introduction: There are scant data to demonstrate that the long-term non-pharmaceutical interventions can slow the progression of motor and non-motor symptoms and lower drug dose in Parkinson's disease (PD). Methods: After randomization, the Exercise-only (E, n = 19) group completed an initial 3-week-long, 15-session supervised, high-intensity sensorimotor agility exercise program designed to improve the postural stability. The Exercise + Maintenance (E + M, n = 22) group completed the 3-week program and continued the same program three times per week for 6 years. The no exercise and no maintenance control (C, n = 26) group continued habitual living. In each patient, 11 outcomes were measured before and after the 3-week initial exercise program and then, at 3, 6, 12, 18, 24, 36, 48, 60, and 72 months. Results: The longitudinal linear mixed effects modeling of each variable was fitted with maximum likelihood estimation and adjusted for baseline and covariates. The exercise program strongly improved the primary outcome, Motor Experiences of Daily Living, by ~7 points and all secondary outcomes [body mass index (BMI), disease and no disease-specific quality of life, depression, mobility, and standing balance]. In E group, the detraining effects lasted up to 12 months. E+M group further improved the initial exercise-induced gains up to 3 months and the gains were sustained until year 6. In C group, the symptoms worsened steadily. By year 6, levodopa (L-dopa) equivalents increased in all the groups but least in E + M group. Conclusion: A short-term, high-intensity sensorimotor agility exercise program improved the PD symptoms up to a year during detraining but the subsequent 6-year maintenance program was needed to further increase or sustain the initial improvements in the symptoms, quality of life, and drug dose.

Children's gradient sensitivity to phonological mismatch: considering the dynamics of looking behavior and pupil dilation.

In a preferential looking paradigm, we studied how children's looking behavior and pupillary response were modulated by the degree of phonological mismatch between the correct label of a target referent and its manipulated form. We manipulated degree of mismatch by introducing one or more featural changes to the target label. Both looking behavior and pupillary response were sensitive to degree of mismatch, corroborating previous studies that found differential responses in one or the other measure. Using time-course analyses, we present for the first time results demonstrating full separability among conditions (detecting difference not only between one vs. more, but also between two and three featural changes). Furthermore, the correct labels and small featural changes were associated with stable target preference, while large featural changes were associated with oscillating looking behavior, suggesting significant shifts in looking preference over time. These findings further support and extend the notion that early words are represented in great detail, containing subphonemic information.

Pupillometry registers toddlers' sensitivity to degrees of mispronunciation.

This study introduces a method ideally suited for investigating toddlers' ability to detect mispronunciations in lexical representations: pupillometry. Previous research has established that the magnitude of pupil dilation reflects differing levels of cognitive effort. Building on those findings, we use pupil dilation to study the level of detail encoded in lexical representations with 30-month-old children whose lexicons allow for a featurally balanced stimulus set. In each trial, we present a picture followed by a corresponding auditory label. By systematically manipulating the number of feature changes in the onset of the label (e.g., baby∼daby∼faby∼shaby), we tested whether featural distance predicts the degree of pupil dilation. Our findings support the existence of a relationship between featural distance and pupil dilation. First, mispronounced words are associated with a larger degree of dilation than correct forms. Second, words that deviate more from the correct form are related to a larger dilation than words that deviate less. This pattern indicates that toddlers are sensitive to the degree of mispronunciation, and as such it corroborates previous work that found word recognition modulated by sub-segmental detail and by the degree of mismatch. Thus, we establish that pupillometry provides a viable alternative to paradigms that require overt behavioral response in increasing our understanding of the development of lexical representations.

Sensitivity to Phonological Universals: The Case of Stops and Fricatives.

Linguistic evidence suggests that syllables like bdam (with stop-stop clusters) are less preferred than bzam (with stop-fricative combinations). Here, we demonstrate that English speakers manifest similar preferences despite no direct experience with either structure. Experiment 1 elicited syllable count for auditory materials (e.g., does bzam have one syllable or two?); Experiment 2 examined the AX discrimination of auditory stimuli (e.g., is bzam = bezam?); whereas Experiment 3 repeated this task using printed materials. Results showed that syllables that are dispreferred across languages (e.g., bdam) were prone to misidentification relative to preferred syllables (e.g., bzam). The emergence of this pattern irrespective of stimulus modality--for auditory and printed materials--suggests that misidentification does not solely stem from a phonetic failure. Further, the effect remained significant after controlling for various statistical properties of the materials. These results suggest that speakers possess broad linguistic preferences that extend to syllables they have never encountered before.

[Prevalence of celiac disease in Turner syndrome]. / Coeliakia prevalenciája Turner-szindrómában.

INTRODUCTION AND AIM: Percentage of coeliac disease among patients with Turner syndrome is given differently in a few publication. The aim of the study was to assess prevalence of celiac disease in Turner syndrome. PATIENTS AND METHODS: Serological screening of coeliac disease were performed in 63 patients with Turner syndrome during the last 11.5 years (since 1994). Serological investigations were repeated yearly since 2003 in all patients, and the results of screening of new patients were completed. Theirs first case of coeliac disease was announced in 2004 in Gyermekgyógyászat (Hun). Further positive serological results were found after publication of the first case. RESULTS: Positive results were found in seven of 63 patients (two EmA and five antitransglutaminase IgA positivity). Intestinal biopsy was applied in all 7 cases. Coeliac disease was revealed by histologic analysis in the five cases - 5/63 (7.9%). CONCLUSION: The prevalence of coeliac disease in Turner syndrome seems to be higher than in general population. This can play role in the insufficient effect of growth hormone therapy in the affected patients. The high prevalence indicates that the connection between these disorders can not be coincidental. Their cases and the available data from the publications indicate that screening of coeliac disease in patients with Turner syndrome should be performed and intestinal biopsy is recommended in positive cases.