Differences in Tic Severity Among Adolescent Girls and Boys with Tourette Syndrome During the Pandemic.

Limited data are available regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on adolescents with Tourette syndrome (TS). We sought to compare sex differences in tic severity experienced by adolescents before and during the COVID-19 pandemic. We extracted from the electronic health record and retrospectively reviewed Yale Global Tic Severity Scores (YGTSS) from adolescents (ages 13 through 17) with TS presenting to our clinic before (36 months) and during (24 months) the pandemic. A total of 373 unique adolescent patient encounters (prepandemic: 199; pandemic: 173) were identified. Compared with prepandemic, girls accounted for a significantly greater proportion of visits during the pandemic (p < 0.001). Prepandemic, tic severity did not differ between girls and boys. During the pandemic, compared with girls, boys had less clinically severe tics (p = 0.003). During the pandemic, older girls, but not boys, had less clinically severe tics (ρ =- 0.32, p = 0.003). These findings provide evidence that, regarding tic severity assessed with YGTSS, the experiences of adolescent girls and boys with TS have differed during the pandemic.

From urges to tics in children with Tourette syndrome: associations with supplementary motor area GABA and right motor cortex physiology.

Tourette syndrome (TS) is a childhood-onset disorder in which tics are often preceded by premonitory sensory urges. More severe urges correlate with worse tics and can render behavioral therapies less effective. The supplementary motor area (SMA) is a prefrontal region believed to influence tic performance. To determine whether cortical physiological properties correlate with urges and tics, we evaluated, in 8-12-year-old right-handed TS children (n = 17), correlations of urge and tic severity scores and compared both to cortical excitability (CE) and short- and long-interval cortical inhibition (SICI and LICI) in both left and right M1. We also modeled these M1 transcranial magnetic stimulation measures with SMA gamma-amino butyric acid (GABA) levels in TS and typically developing control children (n = 16). Urge intensity correlated strongly with tic scores. More severe urges correlated with lower CE and less LICI in both right and left M1. Unexpectedly, in right M1, lower CE and less LICI correlated with less severe tics. We found that SMA GABA modulation of right, but not left, M1 CE and LICI differed in TS. We conclude that in young children with TS, lower right M1 CE and LICI, modulated by SMA GABA, may reflect compensatory mechanisms to diminish tics in response to premonitory urges.

Altered frontal-mediated inhibition and white matter connectivity in pediatric chronic tic disorders.

Tics are unique from most movement disorders, in that they are partially suppressible. As part of the inhibitory motor network, the pre-supplementary motor area is engaged in motor control and may be involved in tic physiology. We used dual-site transcranial magnetic stimulation to assess inhibitory connectivity between right pre-supplementary motor area and left primary motor cortex, which has previously been demonstrated in healthy adults. We also used diffusion tensor imaging to investigate white matter connectivity in children with chronic tics. Twelve children with chronic tic disorder and fourteen typically developing controls underwent MRI with diffusion tensor imaging indices analysis followed by single and paired-pulse transcranial magnetic stimulation with conditioning pulse over the right pre-supplementary motor area followed by left motor cortex test pulse. Neurophysiologic and imaging data relationships to measures of tic severity and suppressibility were also evaluated in tic patients. Pre-supplementary motor area-mediated inhibition of left motor cortex was present in healthy control children but not in chronic tic disorder participants. Less inhibition correlated with worse tic suppressibility (ρ = - 0.73, p = 0.047). Imaging analysis showed increased fractional anisotropy in the right superior longitudinal fasciculus, corpus callosum, corona radiata and posterior limb of the internal capsule (p < 0.05) in tic participants, which correlated with lower self-reported tic suppressibility (ρ = - 0.70, p = 0.05). Physiologic data revealed impaired frontal-mediated motor cortex inhibition in chronic tic participants, and imaging analysis showed abnormalities in motor pathways. Collectively, the neurophysiologic and neuroanatomic data correlate with tic suppressibility, supporting the relevancy to tic pathophysiology.

Supercritical focusing coherent anti-Stokes Raman scattering microscopy for high-resolution vibrational imaging.

We report the development of, to the best of our knowledge, a novel supercritical focusing coherent anti-Stokes Raman scattering (SCF-CARS) microscopy for high-resolution vibrational imaging. Two optimized phase patterns with a combination of concentric rings with an alternative 0 and π phase are generated by using a spatial light modulator and applied to the pump beam for minimizing its focal spot size. One of the phase patterns is for both the lateral and axial resolution enhancement, and the other can further improve the lateral resolution, but it sacrifices the axial resolution to some extent. We demonstrate this high-resolution SCF-CARS microscopy technique by imaging the polymethyl methacrylate (PMMA) nano-cylinder on a microscope slide and glass-air interface, as well as biomedical samples, for example, tooth.

Functional Neuroanatomy of Secondary Self-Injurious Behavior.

BACKGROUND: Secondary self-injurious behavior (SSIB) is underreported and predominantly not associated with suicide. In both adults and children, SSIB can cause intractable self-harm and is associated with a variety of clinical disorders, particularly those involving dysfunctional motor control. METHODS: We performed a literature review evaluating the clinical efficacy of deep-brain stimulation (DBS) as modulating SSIB observations and review current progress in preclinical SSIB animal studies. RESULTS: Neuromodulation is an effective therapeutic option for several movement disorders. Interestingly, this approach is emerging as a potentially effective treatment for movement disorder-associated SSIB (secondary); however, it is important to understand the neuroanatomy, clinical appraisal, and outcome data when considering surgical therapy for SSIB. CONCLUSION: The current review examines the literature encompassing animal models and human case studies while identifying existing hypotheses from cytoarchitectonic-based targeting to neurotransmitter-based pathways. This review also highlights the need for awareness of an underrecognized pathology that may be amenable to DBS.

Preliminary evaluation of child self-rating using the Child Tourette Syndrome Impairment Scale.

AIM: To evaluate and compare how children with Tourette syndrome and parents rate tic and non-tic behavioral related impairment in home, school, and social domains; to compare these with clinician tic ratings; and to identify factors that may predict greater impairment. METHOD: In a sample of 85 Tourette syndrome and 92 healthy control families, the Child Tourette Syndrome Impairment Scale, designed for parent-report and which includes 37 items rated for tic and non-tic impairment, was administered to parents and, with the referent modified, to children ages 9 to 17 years. Tic severity was rated using the Yale Global Tic Severity Scale (YGTSS). Analyses utilized descriptive and multivariate statistics. RESULTS: Tourette syndrome children's and parents' impairment ratings were higher than HC (p<0.001) and correlated moderately (r=0.46 to 0.54; p<0.001). Children's and parents' tic impairment ratings correlated with YGTSS (r=0.36 to 0.37; p<0.001). Parents' average ratings were higher than children's for 19 tic and all 37 non-tic impairment items. For 29 items, children self-rated impairment higher for tics than non-tics. Diagnoses of attention-deficit-hyperactivity disorder and obsessive-compulsive disorder had larger effects on parent impairment ratings. INTERPRETATION: The Child Tourette Syndrome Impairment Scale appears informative for child self-rating in Tourette syndrome.

CNS, lung, and lymph node involvement in Gaucher disease type 3 after 11 years of therapy: clinical, histopathologic, and biochemical findings.

A Caucasian male with Gaucher disease type 3, treated with continuous enzyme therapy (ET) for 11 years, experienced progressive mesenteric and retroperitoneal lymphadenopathy, lung disease, and neurological involvement leading to death at an age of 12.5 years. Autopsy showed significant pathology of the brain, lymph nodes, and lungs. Liver and spleen glucosylceramide (GluCer) and glucosylsphingosine (GluS) levels were nearly normal and storage cells were cleared. Clusters of macrophages and very elevated GluCer and GluS levels were in the lungs, and brain parenchymal and perivascular regions. Compared to normal brain GluCer (GC 18:0), GluCer species with long fatty acid acyl chains were increased in the patient's brain. This profile was similar to that in the patient's lungs, suggesting that these lipids were present in brain perivascular macrophages. In the patient's brain, generalized astrogliosis, and enhanced LC3, ubiquitin, and Tau signals were identified in the regions surrounding macrophage clusters, indicating proinflammation, altered autophagy, and neurodegeneration. These findings highlight the altered phenotypes resulting from increased longevity due to ET, as well as those in poorly accessible compartments of brain and lung, which manifested progressive disease involvement despite ET.

Complete characterization of RNA biomarker fingerprints using a multi-modal ATR-FTIR and SERS approach for label-free early breast cancer diagnosis.

Breast cancer is a prevalent form of cancer worldwide, and the current standard screening method, mammography, often requires invasive biopsy procedures for further assessment. Recent research has explored microRNAs (miRNAs) in circulating blood as potential biomarkers for early breast cancer diagnosis. In this study, we employed a multi-modal spectroscopy approach, combining attenuated total reflection Fourier transform infrared (ATR-FTIR) and surface-enhanced Raman scattering (SERS) to comprehensively characterize the full-spectrum fingerprints of RNA biomarkers in the blood serum of breast cancer patients. The sensitivity of conventional FTIR and Raman spectroscopy was enhanced by ATR-FTIR and SERS through the utilization of a diamond ATR crystal and silver-coated silicon nanopillars, respectively. Moreover, a wider measurement wavelength range was achieved with the multi-modal approach than with a single spectroscopic method alone. We have shown the results on 91 clinical samples, which comprised 44 malignant and 47 benign cases. Principal component analysis (PCA) was performed on the ATR-FTIR, SERS, and multi-modal data. From the peak analysis, we gained insights into biomolecular absorption and scattering-related features, which aid in the differentiation of malignant and benign samples. Applying 32 machine learning algorithms to the PCA results, we identified key molecular fingerprints and demonstrated that the multi-modal approach outperforms individual techniques, achieving higher average validation accuracy (95.1%), blind test accuracy (91.6%), specificity (94.7%), sensitivity (95.5%), and F-score (94.8%). The support vector machine (SVM) model showed the best area under the curve (AUC) characterization value of 0.9979, indicating excellent performance. These findings highlight the potential of the multi-modal spectroscopy approach as an accurate, reliable, and rapid method for distinguishing between malignant and benign breast tumors in women. Such a label-free approach holds promise for improving early breast cancer diagnosis and patient outcomes.

Accelerated Theta Burst Transcranial Magnetic Stimulation for Refractory Depression in Autism Spectrum Disorder.

PURPOSE: Major depressive disorder (MDD) disproportionately affects those living with autism spectrum disorder (ASD) and is associated with significant impairment and treatment recidivism. METHODS: We studied the use of accelerated theta burst stimulation (ATBS) for the treatment of refractory MDD in ASD (3 treatments daily x 10 days). This prospective open-label 12-week trial included 10 subjects with a mean age of 21.5 years, randomized to receive unilateral or bilateral stimulation of the dorsolateral prefrontal cortex. RESULTS: One participant dropped out of the study due to intolerability. In both treatment arms, depressive symptoms, scored on the Hamilton Depression Rating Scale scores, diminished substantially. At 12 weeks post-treatment, full remission was sustained in 5 subjects and partial remission in 3 subjects. Treatment with ATBS, regardless of the site of stimulation, was associated with a significant, substantial, and sustained improvement in depressive symptomatology via the primary outcome measure, the Hamilton Depression Rating Scale. Additional secondary measures, including self-report depression scales, fluid cognition, and sleep quality, also showed significant improvement. No serious adverse events occurred during the study. Mild transient headaches were infrequently reported, which are expected side effects of ATBS. CONCLUSION: Overall, ATBS treatment was highly effective and well-tolerated in individuals with ASD and co-occurring MDD. The findings support the need for a larger, sham-controlled randomized controlled trial to further evaluate efficacy of ATBS in this population.

Emerging Subspecialties: Pediatric Movement Disorders Neurology.

Pediatric movement disorders (PMD) neurologists care for infants, children, and adolescents with conditions that disrupt typical movement; serving as important subspecialist child neurologists in both academic and private practice settings. In contrast to adult movement disorders neurologists whose "bread and butter" is hypokinetic Parkinson disease, PMD subspecialty practice is often dominated by hyperkinetic movement disorders including tics, dystonia, chorea, tremor, and myoclonus. PMD neurology practice intersects with a variety of subspecialties, including neonatology, developmental pediatrics, rehabilitation medicine, epilepsy, child & adolescent psychiatry, psychology, orthopedics, genetics & metabolism, and neurosurgery. Over the past several decades, significant advancements in the PMD field have included operationalizing definitions for distinct movement disorders, recognizing the spectrum of clinical phenotypes, expanding research on genetic and neuroimmunologic causes of movement disorders, and advancing available treatments. Subspecialty training in PMD provides trainees with advanced clinical, diagnostic, procedural, and management skills that reflect the complexities of contemporary practice. The child neurologist who is fascinated by the intricacies of child motor development, appreciates the power of observation skills coupled with a thoughtful physical examination, and is excited by the challenge of the unknown may be well-suited to a career as a PMD specialist.

Frontal Cortex Hyperactivation and Gamma Desynchrony in Fragile X Syndrome: Correlates of Auditory Hypersensitivity.

Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation. Studying the neural mechanisms underlying sound sensitivity in FXS using scalp electroencephalography (EEG) is challenging because the temporal and frontal regions have overlapping neural projections that are difficult to differentiate. To overcome this challenge, we conducted EEG source analysis on a group of 36 individuals with FXS and 39 matched healthy controls. Our goal was to characterize the spatial and temporal properties of the response to an auditory chirp stimulus. Our results showed that males with FXS exhibit excessive activation in the frontal cortex in response to the stimulus onset, which may reflect changes in top-down modulation of auditory processing. Additionally, during the chirp stimulus, individuals with FXS demonstrated a reduction in typical gamma phase synchrony, along with an increase in asynchronous gamma power, across multiple regions, most strongly in temporal cortex. Consistent with these findings, we observed a decrease in the signal-to-noise ratio, estimated by the ratio of synchronous to asynchronous gamma activity, in individuals with FXS. Furthermore, this ratio was highly correlated with performance in an auditory attention task. Compared to controls, males with FXS demonstrated elevated bidirectional frontotemporal information flow at chirp onset. The evidence indicates that both temporal lobe hyperexcitability and disruptions in top-down regulation play a role in auditory sensitivity disturbances in FXS. These findings have the potential to guide the development of therapeutic targets and back-translation strategies.

Safety and efficacy of intra-erythrocyte dexamethasone sodium phosphate in children with ataxia telangiectasia (ATTeST): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Ataxia telangiectasia is a multisystem disorder with progressive neurodegeneration. Corticosteroids can improve neurological functioning in patients with the disorder but adrenal suppression and symptom recurrence on treatment discontinuation has limited their use, prompting the development of novel steroid delivery systems. The aim of the ATTeST study was to evaluate the efficacy and safety of intra-erythrocyte delivery of dexamethasone sodium phosphate compared with placebo in children with ataxia telangiectasia. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 trial was done at 22 centres in 12 countries (Australia, Belgium, Germany, India, Israel, Italy, Norway, Poland, Spain, Tunisia, the UK, and the USA). Eligible participants were children aged 6 years or older weighing more than 15 kg who met clinical criteria for ataxia telangiectasia but who had preserved autonomous gait. Participants were randomly assigned (1:1:1) to low-dose (approximately 5-10 mg), or high-dose (approximately 14-22 mg) intra-erythrocyte dexamethasone sodium phosphate, or placebo, using an independent interactive web response system, with minimisation for sex and age (6-9 years vs ≥10 years). Intravenous intra-erythrocyte dexamethasone sodium phosphate was administered once a month for 6 months. Participants, employees of the sponsor, investigators, all raters of efficacy endpoints, and central reviewers were masked to treatment assignment and dose allocations. The primary efficacy endpoint was change in the modified International Cooperative Ataxia Rating Scale (mICARS) from baseline to month 6, assessed in the modified intention-to-treat (mITT) population, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline efficacy assessment. This trial is registered with Clinicaltrials.gov (NCT02770807) and is complete. FINDINGS: Between March 2, 2017, and May 13, 2021, 239 children were assessed for eligibility, of whom 176 were randomly assigned. One patient assigned to high-dose intra-erythrocyte dexamethasone sodium phosphate did not initiate treatment. 175 patients received at least one dose of treatment (59 patients received the low dose and 57 received the high dose of intra-erythrocyte dexamethasone sodium phosphate, and 59 received placebo). The mITT population comprised 164 participants (56 children in the low-dose group, 54 children in the high-dose group, and 54 in the placebo group). Compared with the placebo group, no differences were identified with regard to change in mICARS score from baseline to 6 months in the low-dose group (least squares mean difference -1·37 [95% CI -2·932 to 0·190]) or the high-dose group (-1·40 [-2·957 to 0·152]; p=0·0765). Adverse events were reported in 43 (73%) of 59 participants in the low-dose group, 47 (82%) of 57 participants in the high-dose group, and 43 (73%) of 59 participants in the placebo group. Serious adverse events were observed in six (10%) of 59 participants in the low-dose group, seven (12%) of 57 participants in the high-dose group, and seven (12%) of 59 participants in the placebo group. There were no reports of hyperglycaemia, hypertension, hirsutism, or Cushingoid appearance in any of the treatment groups, nor any treatment-related deaths. INTERPRETATION: Although there were no safety concerns, the primary efficacy endpoint was not met, possibly related to delays in treatment reducing the number of participants who received treatment as outlined in the protocol, and potentially different treatment effects according to age. Studies of intra-erythrocyte delivery of dexamethasone sodium phosphate will continue in participants aged 6-9 years, on the basis of findings from subgroup analyses from this trial. FUNDING: EryDel and Quince Therapeutics.

Spectrum of Pediatric to Early Adulthood POLR3A-Associated Movement Disorders.

Background: POLR3A pathogenic variants are associated with hypomyelination, hypodontia, hypogonadism, and movement disorders. Cases: We describe the range of movement disorders seen in six patients (four female, two male) with POLR3A variants [three novel (c.2214del, c.3775G>A, c.3905G>T) and six previously reported (c.760C>T, c.1771-7C>G, c.1909+22G>A, c.2005C>T, c.2422C>T, c.3337-11T>C)]. Patient 1 presented with a neonatal progeroid syndrome and developed parkinsonism, dystonia, ataxia, and spasticity. Patient 2 presented with infant-onset rapidly progressive chorea, and dystonia. Three patients (patients 3, 5, 6) presented predominantly with ataxia in combination with spasticity and dystonia. Patient 4 developed segmental dystonia during adolescence and ataxia in early adulthood. Four patients had vertical gaze impairment. The most common brain MRI abnormality was T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain. Conclusion: POLR3A-related disorders exhibit significant phenotypic pleomorphism. Vertical gaze dysfunction and T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain may be useful signs suggestive of this condition.

Adolescent Gender Differences in Tic- and Non-Tic-Related Impairments in Tourette Syndrome.

We aimed to compare tic- and non-tic-related impairment experienced by adolescent girls and boys (ages 13 through 17) with Tourette syndrome and associations with age. We extracted from the electronic health record child and parental responses to the mini-Child Tourette Syndrome Impairment Scale (mini-CTIM) and other questionnaire data reflective of tic- and non-tic-related impairment of adolescents with Tourette syndrome presenting to our clinic over a 12-month period. We identified a total of 132 (49 female, 83 male) unique adolescent encounters. Mini-CTIM scores did not differ significantly between genders. Tic- and non-tic-related impairment were lower in older boys, but not older girls. Obsessive-compulsive symptoms correlated with parent-reported non-tic-related impairment experienced by adolescent girls but not boys. During adolescence, tic- and non-tic-related impairments may be less likely to improve with age in girls. Future longitudinal studies are needed to confirm this finding.

Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome.

The FMR1 gene is inactive in Fragile X syndrome (FXS), resulting in low levels of FMRP and consequent neurochemical, synaptic, and local circuit neurophysiological alterations in the fmr1 KO mouse. In FXS patients, electrophysiological studies have demonstrated a marked reduction in global alpha activity and regional increases in gamma oscillations associated with intellectual disability and sensory hypersensitivity. Since alpha activity is associated with a thalamocortical function with widely distributed modulatory effects on neocortical excitability, insight into alpha physiology may provide insight into systems-level disease mechanisms. Herein, we took a data-driven approach to clarify the temporal and spatial properties of alpha and theta activity in participants with FXS. High-resolution resting-state EEG data were collected from participants affected by FXS (n = 65) and matched controls (n = 70). We used a multivariate technique to empirically classify neural oscillatory bands based on their coherent spatiotemporal patterns. Participants with FXS demonstrated: 1) redistribution of lower-frequency boundaries indicating a "slower" dominant alpha rhythm, 2) an anteriorization of alpha frequency activity, and 3) a correlation of increased individualized alpha power measurements with auditory neurosensory dysfunction. These findings suggest an important role for alterations in thalamocortical physiology for the well-established neocortical hyper-excitability in FXS and, thus, a role for neural systems level disruption to cortical hyperexcitability that has been studied primarily at the local circuit level in animal models.

Chronic striatal cholinergic interneuron excitation induces clinically-relevant dystonic behavior in mice.

Dystonia is common, debilitating, often medically refractory, and difficult to diagnose. The gold standard for both clinical and mouse model dystonia evaluation is subjective assessment, ideally by expert consensus. However, this subjectivity makes translational quantification of clinically-relevant dystonia metrics across species nearly impossible. Many mouse models of genetic dystonias display abnormal striatal cholinergic interneuron excitation, but few display subjectively dystonic features. Therefore, whether striatal cholinergic interneuron pathology causes dystonia remains unknown. To address these critical limitations, we first demonstrate that objectively quantifiable leg adduction variability correlates with leg dystonia severity in people. We then show that chemogenetic excitation of striatal cholinergic interneurons in mice causes comparable leg adduction variability in mice. This clinically-relevant dystonic behavior in mice does not occur with acute excitation, but rather develops after 14 days of ongoing striatal cholinergic interneuron excitation. This requirement for prolonged excitation recapitulates the clinically observed phenomena of a delay between an inciting brain injury and subsequent dystonia manifestation and demonstrates a causative link between chronic striatal cholinergic interneuron excitation and clinically-relevant dystonic behavior in mice. Therefore, these results support targeting striatal ChIs for dystonia drug development and suggests early treatment in the window following injury but prior to dystonia onset. One Sentence Summary: Chronic excitation of dorsal striatal cholinergic interneuron causes clinically-relevant dystonic phenotypes in mice.

Novel PRRT2 mutation in an African-American family with paroxysmal kinesigenic dyskinesia.

BACKGROUND: Recently, heterozygous mutations in PRRT2 (Chr 16p11.2) have been identified in Han Chinese, Japanese and Caucasians with paroxysmal kinesigenic dyskinesia. In previous work, a paroxysmal kinesigenic dyskinesia locus was mapped to Chr 16p11.2 - q11.2 in a multiplex African-American family. METHODS: Sanger sequencing was used to analyze all four PRRT2 exons for sequence variants in 13 probands (9 Caucasian, 1 Caucasian-Thai, 1 Vietnamese and 2 African-American) with some form of paroxysmal dyskinesia. RESULTS: One patient of mixed Caucasian-Thai background and one African-American family harbored the previously described hotspot mutation in PRRT2 (c.649dupC, p.R217Pfs*8). Another African-American family was found to have a novel mutation (c.776dupG, p.E260*). Both of these variants are likely to cause loss-of-function via nonsense-mediated decay of mutant PRRT2 transcripts. All affected individuals had classic paroxysmal kinesigenic dyskinesia phenotypes. CONCLUSIONS: Heterozygous PRRT2 gene mutations also cause paroxysmal kinesigenic dyskinesia in African-Americans. The c.649dupC hotspot mutation in PRRT2 is common across racial groups.

Safety and tolerability of theta-burst transcranial magnetic stimulation in children.

AIM: Theta-burst stimulation (TBS) is a lower intensity, high-frequency repetitive transcranial magnetic stimulation technique developed recently for quantifying and modulating cerebral cortical function. Nearly all published studies have involved adults. The aim of this study was to obtain safety data as a basis for evaluating potential risks versus benefits of TBS research in children. METHOD: Forty participants under 18 years: 16 with Tourette syndrome (five females, 11 males; mean age 12y, SD 2y 10mo) and 24 typically developing children (12 females, 12 males; mean age 12y 11mo, SD 2y 10mo) underwent intermittent or continuous TBS over the left motor cortex. Open questions, a structured 16-question review of systems, and visual analog mood scale (VAMS) were administered before and after TBS. A Wilcoxon signed-rank sum test was used to analyze differences in VAMS scores before and after TBS. RESULTS: There were no serious adverse events. Five of the 40 children reported mild, self-limited adverse events: a subjective sensation of finger twitching (n=1), neck stiffness (n=1), and mild headache (n=3). The total adverse event rate was 11.6%. There was no significant change in VAMS score in either group after one session of TBS. INTERPRETATION: A single session of TBS in children appears to be safe and well tolerated.

The Phenomenology of Tics and Tic-Like Behavior in TikTok.

BACKGROUND: Pediatricians and pediatric subspecialists worldwide have reported a marked increase in functional (conversion) disorders with tic-like behaviors during the COVID-19 pandemic. These patients often report frequent viewing of Tourette syndrome (TS) TikTok videos, suggesting disease modeling. We aimed to evaluate tic phenomenology in videos posted on TikTok. METHODS: The 100 most-viewed videos under #tourettes in TikTok were randomly assigned to two of three primary reviewers (<2 years independent practice), all pediatric neurologists specializing in movement disorders, for extraction and classification of tic phenomenology. Initial disagreements were solved by consensus. If not resolved, one of five senior reviewers (>2 years independent pediatric movement disorder practice) served as a tiebreaker. In addition, two primary and one senior reviewer rated each video on a Likert scale from 1 = "All the tics are typical of TS" to 5 = "None of the tics are typical of TS". Median scores and Spearman correlation between primary and senior reviewers were calculated. RESULTS: Six videos without tic-like behaviors were excluded. Most videos depicted coprophenomena (coprolalia: 53.2%; copropraxia: 20.2%), often with unusual characteristics. Frequently, videos demonstrated atypical phenomenology such as very strong influence by the environment (motor: 54.3%; phonic: 54.3%), aggression (19.1%), throwing objects (22.3%), self-injurious behaviors (27.7%), and long phrases (>3 words; 45.7%). Most videos portrayed atypical, nontic behaviors (median [IQR] Likert ratings: 5 [4-5]). Primary vs. senior rater scores demonstrated moderate agreement (r = 0.46; P < 0.001). CONCLUSIONS: TS symptom portrayals on highly viewed TikTok videos are predominantly not representative or typical of TS.

EEG Correlates of Active Stopping and Preparation for Stopping in Chronic Tic Disorder.

Motor inhibition is an important cognitive process involved in tic suppression. As the right frontal lobe contains important inhibitory network nodes, we characterized right superior, middle, and inferior frontal gyral (RSFG, RMFG, RIFG) event-related oscillations during motor inhibition in youth with chronic tic disorders (CTD) versus controls. Fourteen children with CTD and 13 controls (10-17 years old) completed an anticipated-response stop signal task while dense-array electroencephalography was recorded. Between-group differences in spectral power changes (3-50 Hz) were explored after source localization and multiple comparisons correction. Two epochs within the stop signal task were studied: (1) preparatory phase early in the trial before motor execution/inhibition and (2) active inhibition phase after stop signal presentation. Correlation analyses between electrophysiologic data and clinical rating scales for tic, obsessive-compulsive symptoms, and inattention/hyperactivity were performed. There were no behavioral or electrophysiological differences during active stopping. During stop preparation, CTD participants showed greater event-related desynchronization (ERD) in the RSFG (γ-band), RMFG (ß, γ-bands), and RIFG (θ, α, ß, γ-bands). Higher RSFG γ-ERD correlated with lower tic severity (r = 0.66, p = 0.04). Our findings suggest RSFG γ-ERD may represent a mechanism that allows CTD patients to keep tics under control and achieve behavioral performance similar to peers.