Motor Skills and Neurological Soft Signs: Are They Only Clinical Differences or Reflection of Distinct Etiopathogenesis in Tic Disorder and Primary Stereotypic Movement Disorder?

Motor Skills and Neurological Soft Signs: Are They Only Clinical Differences or Reflection of Distinct Etiopathogenesis in Tic Disorder and Primary Stereotypic Movement Disorder? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Motor Skills and Neurological Soft Signs: Are They Only Clinical Differences or Reflection of Distinct Etiopathogenesis in Tic Disorder and Primary Stereotypic Movement Disorder? Ecem Selin Akbas Aliyev, Dilek Ünal This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4986441/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract While Tic Disorders (TD) and Stereotypic Movement Disorder (SMD) are commonly comorbid in pediatric clinics, their clinical and etiological differences remain poorly understood. We aimed to investigate the clinical features that differentiate between TD and primary SMD by evaluating neurological soft signs (NSS) and motor skills. The Kiddie-Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version DSM-5 (K-SADS-PL) and Sociodemographic and Clinical Data Form were administered to the children and their parents. The clinician completed the Yale Global Tic Severity Scale (YGTSS), Repetitive Behavior Scale-Revised (RBS-R) and Neurological Evaluation Scale (NES). The Nine-Hole Peg Test was used for fine motor skills, the 1-Minute Sit-to-Stand Test for gross motor skills, the Flamingo Balance Test for static balance, and the Finger-to-Nose Test for bilateral coordination. Parents completed the Conners Parent Rating Scale-Revised Short Form (CPRS-RSF) and the Developmental Coordination Disorder Questionnaire-Revised (DCDQ-R). Our sample consisted of 20 TD, 20 primary SMD, 13 ADHD patients, and 20 healthy controls (HCs). Sequencing of the complex motor acts scores of NES were significantly higher in the SMD group than in HCs. The primary SMD group demonstrated significantly lower dominant hand performance on the Nine-Hole Peg Test than the TD group. Children with primary SMD had significantly lower scores of 1-minute sit-to-stand test; higher total and subscale scores of DCDQ-R and higher developmental coordination disorder risk than HCs. Our findings offer valuable insights into the distinct etiopathogenesis of TD and primary SMD, providing a foundation for future neurobiological research. Tic Disorder Stereotypic Movement Disorder Motor Skills Psychomotor Performance Figures Figure 1 INTRODUCTION Tics are defined as sudden, rapid, repetitive, non-rhythmic motor movements and vocalizations, that typically occur in bursts, fluctuating in intensity and frequency [ 1 ]. Stereotypies are repetitive, involuntary, rhythmic, coordinated, and purposeless behaviors [ 2 ]. They can be seen during normal development as a physiological and temporary finding, and stereotypies are divided into two main groups, primary and secondary, depending on whether they are accompanied by a developmental disorder or neurological disease [ 3 ]. Stereotypies are more prevalent in individuals with TD compared to the general population [ 4 , 5 ]. The co-occurence of TD and stereotypic movement disorder (SMD) is believed to stem from dysfunction in the cortico-striato-thalamo-cortical (CSTC) pathway related to habitual behaviors [ 6 ]. Tics and stereotypies share similarities, such as the presence of motor or vocal components and behavioral repetition [ 7 ]. Although common neuroanatomical regions are mentioned, they differ in their age of onset, frequently involved body regions, and clinical features [ 8 ]. Neurological soft signs (NSS) are abnormal motor or sensory findings observed in the absence of a neurological disorder of identifiable origin [ 9 ]. Neuroimaging studies indicate that NSS result from the interaction of various brain regions instead of a single origin. NSS have been categorized based on their neuroanatomical correlates, commonly including sensorimotor integration, motor coordination, sequencing of complex motor acts, and primitive reflexes [ 10 ]. The frequency of NSS, has been shown to increase in children diagnosed with psychiatric disorders which are also commonly found in the healthy population [ 11 , 12 ]. Both TD and primary SMD also frequently exhibit NSS [ 13 – 15 ]. Children with neurodevelopmental disorders generally display more motor skill problems than their healthy peers [ 16 ]. While many studies indicate motor skill impairments in TD, findings in the literature have been inconsistent [ 17 – 22 ]. Reasons for these conflicts include age heterogeneity in samples, failure to exclude comorbidities and medication effects, and variations in assessment methods [ 22 ]. Although motor skill problems have been shown in children with primary stereotypy, knowledge of this subject is limited [ 15 , 23 ]. Research on the differential diagnosis of tics and stereotypies has emphasized the phenomenological distinction [ 8 ]. To our knowledge, no previous studies have investigated how TD and primary SMD differ regarding accompanying clinical features. We hypothesized that disruptions at different stages of neuronal development are involved in the etiology of tics and stereotypies and that the NSS and motor skill problems accompanying TD and primary SMD will exhibit differences that can provide valuable insights into these distinct neurobiological mechanisms. METHODS Participants The research group comprised children aged 6-12 years who were admitted to the Department of Child and Adolescent Psychiatry from March to July 2022 and met the inclusion criteria. The healthy control (HC) group consisted of age- and gender-matched children who visited our outpatient clinic within the same period and had no psychiatric disorders. Since there are no sample studies with significant results of patients with TD and primary SMD in the literature, an alpha level of 0.05 for detecting a large effect size of d=0.4 for One-way ANOVA was calculated with G-power 3.1.9.6 analysis to create 80% power for a sample size of 76. A total of 83 children were reached within the specified time interval, but 73 participants were included in the analysis as children who could not complete the tests were eliminated. The flowchart of sampling is given in Figure 1. Inclusion criteria for the research group were; (1) current diagnosis of TD (Tourette syndrome, transient tic disorder, chronic motor or vocal tic disorder), primary SMD, or ADHD, (2) showing the movement disorder symptoms at the time of assessment (for the TD and primary SMD groups), (3) being between 6-12 years. Exclusion criteria included; (1) diagnoses of autism spectrum disorder (ASD), anxiety disorders, depression, posttraumatic stress disorder, obsessive compulsive disorder, psychotic disorder, eating disorder, substance use disorder according to DSM-5; (2) intellectual disability identified through clinical evaluation; (3) acute or chronic neurological, genetic, inflammatory disease; (4) hearing or vision loss; (5) history of hypoxic birth or severe prematurity (≤28 weeks); (6) acute or chronic medication use. Patients with ADHD were not excluded from the TD and SMD groups because of high comorbidity rates. An ADHD control group was added for this reason. To verify the inclusion and exclusion criteria, children received a psychiatric assessment by a child and adolescent psychiatrist, with diagnoses verified by a senior supervisor psychiatrist. Procedures After completing the Sociodemographic and Clinical Data Form created by the researchers, the Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Life-time (K-SADS-PL) which is validated and reliable in Turkish was administered for differential diagnosis. Yale Global Tic Severity Scale (YGTSS), Repetitive Behavior Scale-Revised (RBS-R), Neurological Evaluation Scale (NES) were also applied by the clinician across groups. Parents rated the Conners’ Parent Rating Scale-Revised Short Form (CPRS-RSF), Revised Developmental Coordination Disorder Questionnaire (DCDQ-R). To comprehensively evaluate the motor skills of the all participants, clinicians conducted four motor skills tests: Nine-Hole Peg Test, Flamingo Balance Test, 1-Minute Sit-to-Stand Test, Finger to Nose Test. Materials Yale Global Tic Severity Scale (YGTSS): This scale, completed by the clinician based on a semi-structured interview, evaluates the tics present in the last week according to the child's and parent's report [24]. It then grades the number, frequency, severity, complexity, and interference with daily activities for motor and vocal tics separately. A higher scale score indicates greater severity. A Turkish validity and reliability study of the scale was conducted [25]. Repetitive Behavior Scale-Revised (RBS-R): The RBS-R is a clinical rating scale developed to assess repetitive behaviors and the severity of these behaviors [26]. The validity and reliability of its Turkish translation has been performed [27]. The RBS-R consists of six subscales including stereotypic behavior, self-injurious behavior, behavior, ritualistic behavior, sameness/uniformity behavior and restricted interests. As the score obtained from the scale increases, it is accepted that the severity of repetitive behaviors seen in children increases. Neurological Evaluation Scale (NES): The NES, developed by Buchanan and Heinrichs in 1989, assesses impairments in four areas: sensorimotor integration (audiovisual integration, stereognosis, graphesthesia, extinction, right-left confusion), motor coordination (rapid alternating movement, tandem walk, finger-thumb opposition, finger-to-nose test, rhythm tapping), sequencing of complex motor acts (fist-ring test, fist-edge-palm test, Ozeretski test) and others (adventitious overflow, Romberg, tremor, memory, mirror movements, synkinesis, convergence, gaze impersistence, glabellar reflex, snout reflex, grasp reflex, suck reflex) [28]. The scale consists of 26 items, 14 evaluated separately for each half of the body. The instructions are given and scored by the clinician. Since it evaluates biological parameters, there is no difference between cultures; therefore, there is no need for validity and reliability studies [29]. In the items indicating lateralization and assessing the right and left half of the body separately, the results of the side with the higher score were used [30, 31]. Conners’ Parent Rating Scale-Revised Short Form (CPRS-RSF): This likert-type scale used to measure ADHD symptom domains and symptom severity has subscales including attention deficit/cognitive problems, hyperactivity, oppositional defiance and ADHD index [32]. Kaner et al. conducted its Turkish validity and reliability study [33]. Revised Developmental Coordination Disorder Questionnaire (DCDQ-R): The DCDQ-R is the only scale with a good level of evidence according to the Developmental Coordination Disorder (DCD) diagnosis and treatment guidelines [34]. The scale consists of control during movement, fine motor/handwriting and general coordination subscales. In addition, it has cut-off scores for children aged 5-8 years, 8-12 years and 10-15 years, and according to the scores obtained, it is concluded that “indication of DCD or suspect DCD” or “probably not DCD”. The Turkish validity and reliability study of the test was conducted [35]. Nine-Hole Peg Test : The measurement tool used to measure manual dexterity consisted of nine small sticks made in standard sizes and a board with nine holes on which they were placed. The child was asked to place and remove the sticks from the board quickly. The placement and removal times were recorded using a stopwatch, first for the dominant hand and then for the non-dominant hand separately [36]. Flamingo Balance Test : In this test to assess static balance, the child was instructed to stand on his/her preferred foot for 60 seconds. As the child lost balance, the timer was stopped and restarted when the balance was regained. The clinician recorded the number of restarts [37]. 1-Minute Sit-to-Stand Test : The clinician instructed the child to sit and stand on a height-adjustable chair, recording the number of sit-ups and stand-ups in 1 minute with a timer. This measurement tool was used to assess lower extremity function [38, 39]. Finger to Nose Test : In this test, which measures bilateral coordination, the clinician instructed the child to close his/her eyes, arms out to the sides and raise to shoulder level, touch the tip of his/her nose with the tip of the index finger with the hand in a fist position except for the index finger, and use one right and one left hand while doing so [40, 41]. Data analyses The Statistical Package for Social Sciences (SPSS) version 22.0 was used for statistical analysis of the data. In descriptive analyses, means and standard deviations were used for continuous variables with normal distribution; medians and interquartile ranges (IQRs) were used for continuous variables with non-normal distribution; numbers and percentages were used for categorical variables. The normality of the distribution was evaluated with Shapiro-Wilk statistics. Group differences for sociodemographic variables, scale scores and performance-based measures were examined using the One-Way ANOVA or Kruskal-Wallis tests for continuous variables and Chi-square (χ2) test for categorical variables. Pairwise group comparisons were made with the Mann-Whitney U tests with Bonferonni correction. The Spearman's nonparametric correlation test was used to investigate the relationship between continuous variables. In all analyses, a p value less than 0.05 was expected for statistical significance. Effect sizes for significant results were also reported. RESULTS The Sociodemographic and Clinical Characteristics of the Study Sample Within the study period, we enrolled 20 children with TD (n = 17, 85% male), 20 with primary SMD (n = 14, 70% male), 13 with ADHD (n = 10, 76,9% male) and 20 healthy controls (HCs) (n = 12, 60% male). The mean ages of participants in group of TD, primary SMD, ADHD and HC were 8,3 (SD = 2), 7,6 (SD = 1), 8.2 (SD = 1) and 8.9 (SD = 2) years, respectively. The groups did not differ significantly in terms of mean age (F = 2,344, p = 0.081, One-way ANOVA) or sex (χ²=3.332, p = 0.343, df = 3). No significant differences emerged between groups regarding other sociodemographic and familial variables (Supplementary Table 1). Furthermore, there were no significant differences between the four groups regarding the perinatal factors, medical history, developmental stages, and school-related factors. Hand, foot, and eye preferences as well as cerebral dominance did not differ significantly among the groups (p > 0.05). The TD group consisted of children with transient tic disorder (n = 5, 25%), chronic motor or vocal tic disorder (n = 10, 50%) and Tourette’s Syndrome (TS) (n = 5, 25%). Supplementary Table 2 shows the comparison between TD and SMD groups regarding the age of onset of symptoms, age at diagnosis and ADHD comorbidity. Group Differences on Clinical Assessment Scales Table 1 shows the comparison of the four groups in terms of clinical assessment scales. For the NES, sequencing of the complex motor acts scores was significantly higher in the SMD group than in the HC group (U = 98.500, p = 0.005). Fist-ring test and Ozeretski test scores were significantly higher for the primary SMD patients compared to HCs (U = 95.000, p = 0.002 and U = 119.500, p = 0.008; respectively). Other NES scores did not differ between study groups. We found significant differences between the DCDQ-R scores of the groups (Table 1 ). The post-hoc analyses showed that control during movement scores were significantly lower only in the SMD group compared to HCs (U = 98.500, p = 0.006). In terms of fine motor/handwriting and general coordination subscales and total scale scores, all three patient groups had significantly lower scores than HCs. Based on parent DCDQ-R ratings, 10% of children with TD, 20% of children with primary SMD, 15.4% of children with ADHD were characterized as having “indication of DCD or suspect DCD”. Table 1 Comparison of clinical assessment scales between study groups. Median (IQR) TD (n = 20) SMD (n = 20) ADHD (n = 13) HC (n = 20) KW/p E.S. NES Sensorimotor integration 2.0 (2) 3.5 (2) 2.0 (3) 2.0 (5) 2.777/0.427 - Motor incoordination 0.5 (2) 0.5 (2) 1.0 (3) 0.0 (1) 2.566/0.463 - Sequencing of complex motor acts 1.0 (3) 2.0 (4) 2.0 (3) 1.0 (2) 9.406/0.024* 0.092 Fist-ring test 0.5 (1) 1.0 (2) 1.0 (2) 0.0 (1) 10.536/0.015* 0.109 Ozeretski test 0.0 (0) 0.5 (2) 0.0 (1) 0.0 (0) 9.096/0.028* 0.088 Fist-edge-palm test 0.0 (2) 1.0 (2) 1.0 (1) 0.0 (1) 3.496/0.321 - Others 4.0 (4) 4.0 (4) 3.0 (4) 3.0 (5) 2.075/0.557 - Total 9.0 (6) 10.5 (9) 7.0 (9) 7.5 (9) 5.111/0.164 - DCDQ-R Control during movement 27.0 (5) 25.0 (8) 25.0 (6) 28.5 (3) 8.420/0.038* 0.078 Fine motor/Handwriting 16.0 (4) 16.5 (5) 16.0 (3) 20 .0(3) 12.295/0.006* 0.134 General Coordination 20.5 (3) 20.0 (6) 19.0 (5) 23.0 (4) 15.855/0.001* 0.186 Total 65.0 (9) 60.5 (14) 62.0 (11) 70.0 (8) 17.815/0.000* 0.215 NES: Neurological Evaluation Scale, DCDQ-R: Revised Developmental Coordination Disorder Questionnaire, IQR: Interquartile Range, TD: Tic Disorder, SMD: Stereotypic Movement Disorder, ADHD: Attention Deficit Hyperactivity Disorder, HC: Healthy Control, KW: Kruskal-Wallis Test, *p < 0.05, E.S.: Effect Size According to the evaluation of the TD group with YGTSS, mean scores for motor and vocal tics were 6.7 (SD = 4.4) and 5.0 (SD = 4.9), respectively. The mean global impairment score was 0.9 (SD = 0.9) and the total score of YGTSS was 12.6 (SD = 6.8). In the primary SMD group, mean scores for RBS-R stereotypic behavior subscale and RBS-R total score were 3.4 (SD = 2.5) and 5.4 (SD = 6.9), respectively. The mean CPRS-RSF total scores of the four groups were 31.0 (SD = 18.1) for TD, 28.5 (SD = 17.9) for primary SMD, 40.0 (SD = 14.8) for ADHD and 8.6 (SD = 8.2) for HC. Group Differences on Motor Skill Tests Descriptive statistics and group comparisons for the motor skill tests are shown in Table 2 . The Nine-hole peg test scores differed among 4 groups. The dominant hand performance of the children in the primary SMD group was significantly lower than in the TD group (U = 97.000, p = 0.005, Cohen’s d = 0.79). Although the difference in terms of nondominant hand performance did not reach significance, children with SMD were slower than children with TD (U = 116.000, p = 0.023). These four groups did not differ significantly regarding the Flamingo Balance Test, finger-to-nose test (Table 2 ). Comparison of four groups’ 1-minute sit-to-stand test scores found a statistically significant difference. The scores of children with primary SMD were significantly lower than HCs (U = 90.500, p = 0.003, Bonferonni corrected). In post-hoc analysis, other pairwise comparisons did not yield significant differences. Table 2 Comparison of motor skill performance between study groups. Median (IQR) TD (n = 20) SMD (n = 20) ADHD (n = 13) HC (n = 20) KW/p E.S. Nine-hole peg test Dominant hand 23.0 (4) 27.0 (7) 25.0 (6) 23.0 (9) 9.015/0.029* 0.087 Nondominant hand 26.0 (3) 32.5 (12) 26.0 (6) 26.0 (9) 7.250/0.064 - 1-minute sit-to-stand test 27.0 (7) 24.0 (6) 29.0 (10) 29.0 (6) 9.565/0.023* 0.095 Flamingo balance test 5.0 (4) 7.0 (7) 4.0 (6) 5.0 (5) 6.068/0.108 - Finger-to-nose test 4.0 (0) 4.0 (0) 4.0 (0) 4.0 (0) 2.670/0.445 - IQR: Interquartile Range, TD: Tic Disorder, SMD: Stereotypic Movement Disorder, ADHD: Attention Deficit, HC: Healthy Control, KW: Kruskal-Wallis Test, *p < 0.05, E.S.: Effect Size Correlational Analyses Bivariate correlations in the TD group revealed that YGTSS- Total Score, Total Tic Score and Global Impairment Score were not significantly correlated with NES, Nine-Hole Peg Test, Flamingo Balance Test, 1-minute sit-to-stand test, finger-to-nose test, and DCDQ-R scores (Spearman’s correlation, p > 0.05). In the primary SMD group, no statistically significant differences emerged in the correlation analyses between RBS-R scores and NES, CPRS-RSF, Nine-Hole Peg Test, Flamingo Balance Test, 1-minute sit-to-stand test, finger-to-nose test or DCDQ-R scores (Spearman’s correlation, p > 0.05). Across all four study groups, pairwise correlation analyses showed no significant relationships between CPRS-RSF scores and any motor performance tests, NES, or DCDQ-R (Spearman’s correlation, p > 0.05). DISCUSSION Our study is the first to compare children aged 6–12 years diagnosed with TD and primary SMD with age- and gender-matched children with ADHD and HCs regarding sociodemographic and clinical characteristics, NSS, fine and gross motor skills, balance, and coordination. We made an effort to exclude confounding factors and obtain more accurate results about elucidating etiopathogenesis by creating groups with homogenous sociodemographic characteristics, no medication use, and no psychiatric comorbidity. The age range enabled us to perform clinical evaluation early after the onset of symptoms before developing adaptive neurobiological mechanisms in the brain. We found that children with primary SMD had lower fine motor skill performance than those with TD. Additionally, the primary SMD group, but not the TD group, showed lower gross motor skills and a higher DCD risk than HCs, with higher NES scores in the sequencing of complex motor acts. Other strengths of the study include using valid and reliable measurement tools for motor skills and NSS in Turkish and evaluations across various areas such as fine and gross motor skills, balance, coordination, and functional exercise capacity. We reduced the risk of misinterpretation by excluding psychiatric comorbidities, global developmental delay, hearing and visual problems, and neurological and genetic diseases that may affect motor skills. Due to the common ADHD comorbidity in TD and SMD patients, this was not an exclusion criterion; we included a separate ADHD group to control for the confounding effects. NSS can also be observed in typically developing children and may indicate impaired cortical inhibition that controls motor functions when persistent into late childhood [ 42 ]. Reports of NSS in individuals with schizophrenia, bipolar disorder, and ADHD highlight potential neurodevelopmental issues [ 43 – 45 ]. In a research conducted with 122 healthy adults with no family history of psychiatric disorders, NES score > 1 was recorded in 54.1% of the sample [ 46 ]. In our study, the median value of the HC group’s total NES score was 8. The fact that NSS was observed in healthy children who did not meet the diagnostic criteria for any psychiatric disorder is compatible with the information in the literature [ 46 ]. This finding indicates that there may be an impairment in the neural development process in the normal population who do not show signs of neurodevelopmental disorders. Furthermore, the observation of NSS in healthy children underscores the significant differences between the SMD group and HCs, adding to the gravity of our findings. The literature on NSS in SMD is mainly derived from ASD studies, and sensory integration and motor coordination problems are higher in this population [ 47 ]. Mahone et al. found higher NSS scores in children with primary complex motor stereotypy compared to HCs, indicating a risk of motor dysfunction despite the relative absence of comorbidities that may affect motor function [ 15 ]. A striking point in our findings was the significant difference in the sequencing of complex motor acts scores of the NES corresponds neuroanatomically to prefrontal cortex [ 10 ]. Kaneko et al. demonstrated that the quantitative assessment system developed using NSS tests can objectively assess neurodevelopmental delay in children with neurodevelopmental disorders [ 48 ]. Thus, our findings suggesting prefrontal cortex-related test impairments in the primary SMD group indicate potential disruptions in prefrontal cortex development. Neuroimaging studies indicate that TD patients exhibit dysfunction in brain regions associated with movement planning and coordination within the CSTC pathway [ 49 , 50 ]. Although numerous studies have examined fine motor skill deficits in TD, conflicting findings make it challenging to draw definitive conclusions [ 22 ]. One study found poor fine motor performance in children with TS, linking lower performance to tic severity and predicting tic severity in adulthood based on dominant hand performance [ 18 ]. However, our study found no impairments, possibly due to excluding severe cases with psychiatric comorbidities. Notably, our participants did not have chronic medical or neurological conditions, nor were they on psychiatric medications. These results align with Buse et al.'s research indicating that motor skill deficits in TS may not be directly attributable to tics but to treatment-related factors and psychiatric comorbidities [ 19 ]. From another point of view, the absence of fine motor impairments in our TD group might also reflect compensatory neurobiological mechanisms. Functional neuroimaging studies suggest that the need to suppress tics enhances cognitive control over motor activities, facilitating better symptom regulation and linking to structural changes in the prefrontal cortex [ 51 ]. Our knowledge of fine motor skill problems in school-aged children with primary SMD is limited. Valente et al. evaluated 26 preschool children with SMD and found impaired manual dexterity in 58% of the sample [ 23 ]. Our study is the first to utilize both clinician-administered objective measurement tools and parent-reported scales to assess fine motor skill impairments in school-aged children diagnosed with SMD. Compared to children with TD, our primary SMD patients exhibited lower performance in fine motor speed and skill, for which frontal, sensorimotor, and premotor cortex were responsible [ 52 ]. No previous studies have directly compared these two movement disorders regarding fine motor skills. Neurodevelopmental disorders have common points not only clinically but also neurobiologically [ 53 ]. According to the “ neurodevelopmental burden hypothesis ”, earlier onset and increased severity of disorders correlate with greater overall neurodevelopmental impairment, with a spectrum of severity ranging from ASD to late-onset neurodevelopmental disorder [ 54 ]. From this point of view, our results may indicate that primary SMD has a heavier neurodevelopmental burden than TD, which may be rooted in an earlier insult to the neurodevelopment process of these neural circuits. In our study, the TD and SMD groups did not differ from each other or HCs in static balance and bilateral coordination. Previous research has documented a low prevalence of balance impairments in TD, aligning with our findings [ 55 ]. The development of the cerebellum, the primary brain region associated with balance, occurs late in the prenatal brain development process. The lack of postural balance impairments in the TD group might be attributed to disruptions in developmental processes prior to cerebellum development [ 56 ]. Impaired balance performance has been reported in preschool children with SMD compared to healthy peers [ 23 ]. However, the normal static balance performance observed in our SMD group may be because our sample consisted of school-age children. Longitudinal studies indicate that brain structural abnormalities arise from developmental delays rather than impairments [ 57 ]. Additionally, considering the results of Valente et al. [ 25 ], our study suggests school-aged children with primary SMD may catch up with their neurodevelopmentally normal peers, although this observation presents a limitation of our cross-sectional study. Our study found that children with SMD had the lowest functional exercise capacity and lower extremity muscle strength. The significant difference between children with SMD and HCs was independent of stereotypy severity and was observed in groups matched for sociodemographic and developmental characteristics. Furthermore, none of the children had acute infection or respiratory distress that could affect 1-minute sit-stand test performance. Research has shown that visuospatial working memory plays a role in gross motor skills, likely due to the involvement of neural networks responsible for planning and movement control [ 58 ]. Functional neuroimaging has linked various brain regions—including the frontal, parietal, and occipital cortices, cerebellum, thalamus, and insula—to visuospatial working memory [ 59 – 61 ]. Lower gross motor performance in children with SMD may indicate underlying visuospatial working memory deficits. Future studies combining motor skill assessments with neuropsychological evaluations may clarify this relationship. All three patient groups scored significantly lower than HCs on the DCDQ-R total score, fine motor/handwriting score, and general coordination score, supporting the literature that suggests motor dysfunction is more prevalent in children with neurodevelopmental disorders [ 16 ]. The SMD group also exhibited a higher risk for DCD. Mahone et al. found "probable" DCD in 14% and "suspect" DCD in 17% of 52 children with complex motor stereotypy, aligning with our rates [ 15 ]. In a study in which DCD comorbidity was found in 19 (45%) of 42 children with primary motor stereotypy, Freeman et al. concluded that tics and stereotypies may involve different brain mechanisms [ 62 ]. Similarly, our findings contribute to the literature supporting a different etiopathogenesis between tics and stereotypies. In conclusion, our findings revealed NSS and motor skill differences in a homogeneous study sample that may be a reflection of different impaction process on neurodevelopment for TD and primary SMD. However, our cross-sectional study was conducted with a clinical sample, which may have reduced the generalizability of the results to the population. Also, this research did not study molecular mechanisms and neural circuits beyond these clinical differences. Future studies overcoming these challenges may illuminate the etiology and treatment options for these two frequent neurodevelopmental disorders. Declarations Funding: No funding was received to assist with the preparation of this manuscript. Conflict of interest: The authors declare no conflict of interest. Availability of data and material: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Code availability: Not applicable Authors’ contributions: ESAA: conceptualization, data curation, investigation, methodology, resources, writing, original draft preparation, reviewing, and editing. DÜ: conceptualization, methodology, project administration, supervision, review, and editing. Ethics approval: Approval was granted for this study from the Hacettepe University Faculty of Medicine Non-Interventional Clinical Research Ethics Board (March 1, 2022/No: GO 22/76). The study procedure was held in accordance with the Declaration of Helsinki. Informed consent: Parents/legal guardians of all participants provided written consent and verbal assent was obtained from the children themselves, according to their age and understanding. The participants were informed about the purpose of the study, the procedures involved, and their right to withdraw from the study at any time without consequence. The informed consent form included information on data privacy, confidentiality, and data storage. Consent for publication: Parents/legal guardians of all participants provided informed consent for publication of their anonymized data. Identifiable details of the participants were not included in the manuscript or any accompanying materials. The authors confirm that all authors have reviewed and approved the final manuscript. References American Psychiatric Association, D. and A.P. Association, Diagnostic and statistical manual of mental disorders: DSM-5 . Vol. 5. 2013: American psychiatric association Washington, DC. Singer, H.S., Stereotypic movement disorders. Handbook of clinical neurology, 2011. 100 : p. 631-639. Singer, H.S., Motor stereotypies. Semin Pediatr Neurol, 2009. 16 (2): p. 77-81. Baizabal-Carvallo, J.F. and J. Jankovic, Beyond tics: movement disorders in patients with Tourette syndrome. J Neural Transm (Vienna), 2021. 128 (8): p. 1177-1183. 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Heinrichs, The Neurological Evaluation Scale (NES): a structured instrument for the assessment of neurological signs in schizophrenia. Psychiatry Res, 1989. 27 (3): p. 335-50. Kenar, A.N.I. and H. Herken, Neuropsychologic functions and soft neurologic signs in adult ADHD/Eriskin dikkat eksikligi ve hiperaktivite bozuklugunda silik norolojik belirtiler ve noropsikolojik islev duzeyleri. Anadolu Psikiyatri Dergisi, 2014. 15 (4): p. 318-328. Sanders, R.D., et al., Factor structure of neurologic examination abnormalities in unmedicated schizophrenia. Psychiatry research, 2000. 95 (3): p. 237-243. Sanders, R.D., et al., Confirmatory factor analysis of the Neurological Evaluation Scale in unmedicated schizophrenia. Psychiatry Research, 2005. 133 (1): p. 65-71. Conners, C.K., et al., The revised Conners' Parent Rating Scale (CPRS-R): factor structure, reliability, and criterion validity. Journal of abnormal child psychology, 1998. 26 : p. 257-268. Kaner, S., S. Buyukozturk, and E. Iseri, Conners parent rating scale-revised short: Turkish standardization study/Conners anababa dereceleme olcegi-yenilenmis kisa: Turkiye stardardizasyon calismasi. Archives of Neuropsychiatry, 2013. 50 (2): p. 100-110. Wilson, B., et al., The developmental coordination disorder questionnaire 2007 (DCDQ’07). Administrative manual for the DCDQ107 with psychometric properties, 2007. 10 : p. 267-72. Yildirim, C.K., et al., Cross-cultural adaptation of the Developmental Coordination Disorder Questionnaire in Turkish children. Perceptual and motor skills, 2019. 126 (1): p. 40-49. Smith, Y.A., E. Hong, and C. Presson, Normative and validation studies of the Nine-hole Peg Test with children. Perceptual and motor skills, 2000. 90 (3): p. 823-843. Barabas, A., K. Bretz, and R. Kaske. Stabilometry of the flamingo balance test . in ISBS-Conference Proceedings Archive . 1996. Reychler, G., et al., Assessment of validity and reliability of the 1-minute sit-to-stand test to measure the heart rate response to exercise in healthy children. JAMA pediatrics, 2019. 173 (7): p. 692-693. Combret, Y., et al., Measurement properties of the one-minute sit-to-stand test in children and adolescents with cystic fibrosis: A multicenter randomized cross-over trial. PloS one, 2021. 16 (2): p. e0246781. Bruininks, R.H., Bruininks-oseretsky test of motor proficiency: BOT-2 . 2005: NCS Pearson/AGS Minneapolis, MN:. Köse, B., Bruininks-Oseretsky motor yeterlik testi 2 kısa formunun Türkçe uyarlaması ve özgül öğrenme güçlüğü olan çocuklarda geçerlilik ve güvenilirliği. 2018. Martins, I., et al., A longitudinal study of neurological soft signs from late childhood into early adulthood. Developmental Medicine & Child Neurology, 2008. 50 (8): p. 602-607. Fountoulakis, K.N., et al., Neurological soft signs significantly differentiate schizophrenia patients from healthy controls. Acta neuropsychiatrica, 2018. 30 (2): p. 97-105. Goswami, U., et al., Neuropsychological dysfunction, soft neurological signs and social disability in euthymic patients with bipolar disorder. The British Journal of Psychiatry, 2006. 188 (4): p. 366-373. Patankar, V., et al., Neurological soft signs in children with attention deficit hyperactivity disorder. Indian Journal of psychiatry, 2012. 54 (2): p. 159. Fountoulakis, K.N., et al., Prevalence and correlates of neurological soft signs in healthy controls without family history of any mental disorder: A neurodevelopmental variation rather than a specific risk factor? International Journal of Developmental Neuroscience, 2018. 68 : p. 59-65. D'Agati, E., et al., Scientific Evidence for the Evaluation of Neurological Soft Signs as Atypical Neurodevelopment Markers in Childhood Neuropsychiatric Disorders. J Psychiatr Pract, 2018. 24 (4): p. 230-238. Kaneko, M., Y. Yamashita, and K. Iramina, Quantitative evaluation system of soft neurological signs for children with attention deficit hyperactivity disorder. Sensors, 2016. 16 (1): p. 116. Biswal, B., et al., Abnormal cerebral activation associated with a motor task in Tourette syndrome. AJNR Am J Neuroradiol, 1998. 19 (8): p. 1509-12. Braun, A.R., et al., The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls. Neuropsychopharmacology, 1993. 9 (4): p. 277-91. Jackson, S.R., et al., Compensatory neural reorganization in Tourette syndrome. Current Biology, 2011. 21 (7): p. 580-585. Kim, S.G., et al., Functional magnetic resonance imaging of motor cortex: hemispheric asymmetry and handedness. Science, 1993. 261 (5121): p. 615-7. Kern, J.K., et al., Shared Brain Connectivity Issues, Symptoms, and Comorbidities in Autism Spectrum Disorder, Attention Deficit/Hyperactivity Disorder, and Tourette Syndrome. Brain Connect, 2015. 5 (6): p. 321-35. Morris-Rosendahl, D.J. and M.A. Crocq, Neurodevelopmental disorders-the history and future of a diagnostic concept . Dialogues Clin Neurosci, 2020. 22 (1): p. 65-72. Baglioni, V., et al., Motor ability and visual-motor integration in children affected by tic disorder. Prev. Res, 2013. 2 : p. 22-26. Borsani, E., et al., Correlation between human nervous system development and acquisition of fetal skills: An overview. Brain and development, 2019. 41 (3): p. 225-233. Shaw, P., et al., Cortical development in typically developing children with symptoms of hyperactivity and impulsivity: support for a dimensional view of attention deficit hyperactivity disorder. Am J Psychiatry, 2011. 168 (2): p. 143-51. van Der Fels, I.M., et al., Relations between gross motor skills and executive functions, controlling for the role of information processing and lapses of attention in 8-10 year old children. PLoS One, 2019. 14 (10): p. e0224219. Nelson, C.A., et al., Functional neuroanatomy of spatial working memory in children. Developmental psychology, 2000. 36 (1): p. 109. van Ewijk, H., et al., Neural correlates of visuospatial working memory in attention-deficit/hyperactivity disorder and healthy controls. Psychiatry Research: Neuroimaging, 2015. 233 (2): p. 233-242. Kwon, H., A.L. Reiss, and V. Menon, Neural basis of protracted developmental changes in visuo-spatial working memory. Proceedings of the National Academy of Sciences, 2002. 99 (20): p. 13336-13341. Freeman, R.D., A. Soltanifar, and S. Baer, Stereotypic movement disorder: easily missed. Dev Med Child Neurol, 2010. 52 (8): p. 733-8. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4986441","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":349769641,"identity":"ba3fc2a9-efca-4267-b319-5908d1e4143d","order_by":0,"name":"Ecem Selin Akbas Aliyev","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIie2PMUsDMRTHc3vEtVBoP4FwpfAWj/SDuCQE4mJ3hwPP5VyK/SRdD8cngU65Zo10Md+gbr1FzAk6CKntJpjf8t7w//F/j5BE4i9C6feaISdFP+/xWIUERfVKdYJCiP5a4pwv2ue3/S0bXSw1on+ybPWgQ0tZXMWUQfsoh9TIKTjFUZitbIwIylrNq5hjaT7MahSNozmKeisBg5JVOqqMLZ123TveNdbugrKRYP1hJW8XMDirkAPekKAgA/dLy8Rs1CVdy0njVH+Y5OBCCz/wy8jM9cu+ZGOw2vuuZjOw1/51Vxbx938iPpP82HjP7JRwIpFI/A8+ABY8bXQ+K17fAAAAAElFTkSuQmCC","orcid":"","institution":"Turkish Ministry of Health, Ankara Etlik City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ecem","middleName":"Selin Akbas","lastName":"Aliyev","suffix":""},{"id":349769644,"identity":"0b5209bb-8245-4972-9c05-fd57e41e1ae4","order_by":1,"name":"Dilek Ünal","email":"","orcid":"","institution":"Hacettepe University","correspondingAuthor":false,"prefix":"","firstName":"Dilek","middleName":"","lastName":"Ünal","suffix":""}],"badges":[],"createdAt":"2024-08-27 18:51:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4986441/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4986441/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66867675,"identity":"1e3b8db8-b412-4a20-a426-b33f3c5de531","added_by":"auto","created_at":"2024-10-17 09:22:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":298469,"visible":true,"origin":"","legend":"\u003cp\u003eSampling process according to STROBE flowchart. Btw: between, TD: Tic Disorders, SMD: Stereotypic Movement Disorder, ADHD: Attention Deficit Hyperactivity Disorder, HC: Healthy Control, K-SADS-PL: The Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Life-time, GAD: Generalized Anxiety Disorder, OCD: Obsessive Compulsive Disorder, ASD: Autism Spectrum Disorder\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4986441/v1/8a562cb927b384e39e6ff39e.png"},{"id":66870030,"identity":"b1b8df2b-a8f6-4844-929f-3d2191e71b3f","added_by":"auto","created_at":"2024-10-17 09:38:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":940164,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4986441/v1/debf53b1-7750-4220-a438-0c4aed5aaa88.pdf"},{"id":66867676,"identity":"ed285c96-9620-4a1c-a494-b0bf294c5fd7","added_by":"auto","created_at":"2024-10-17 09:22:25","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":19665,"visible":true,"origin":"","legend":"","description":"","filename":"supplementaryinformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-4986441/v1/6f75f189f6877eacb40a4621.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Motor Skills and Neurological Soft Signs: Are They Only Clinical Differences or Reflection of Distinct Etiopathogenesis in Tic Disorder and Primary Stereotypic Movement Disorder?","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003e \u003cem\u003eTics\u003c/em\u003e are defined as sudden, rapid, repetitive, non-rhythmic motor movements and vocalizations, that typically occur in bursts, fluctuating in intensity and frequency [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. \u003cem\u003eStereotypies\u003c/em\u003e are repetitive, involuntary, rhythmic, coordinated, and purposeless behaviors [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. They can be seen during normal development as a physiological and temporary finding, and stereotypies are divided into two main groups, primary and secondary, depending on whether they are accompanied by a developmental disorder or neurological disease [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Stereotypies are more prevalent in individuals with TD compared to the general population [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The co-occurence of TD and stereotypic movement disorder (SMD) is believed to stem from dysfunction in the cortico-striato-thalamo-cortical (CSTC) pathway related to habitual behaviors [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Tics and stereotypies share similarities, such as the presence of motor or vocal components and behavioral repetition [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Although common neuroanatomical regions are mentioned, they differ in their age of onset, frequently involved body regions, and clinical features [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eNeurological soft signs\u003c/em\u003e (NSS) are abnormal motor or sensory findings observed in the absence of a neurological disorder of identifiable origin [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Neuroimaging studies indicate that NSS result from the interaction of various brain regions instead of a single origin. NSS have been categorized based on their neuroanatomical correlates, commonly including sensorimotor integration, motor coordination, sequencing of complex motor acts, and primitive reflexes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The frequency of NSS, has been shown to increase in children diagnosed with psychiatric disorders which are also commonly found in the healthy population [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Both TD and primary SMD also frequently exhibit NSS [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eChildren with neurodevelopmental disorders generally display more motor skill problems than their healthy peers [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. While many studies indicate motor skill impairments in TD, findings in the literature have been inconsistent [\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Reasons for these conflicts include age heterogeneity in samples, failure to exclude comorbidities and medication effects, and variations in assessment methods [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Although motor skill problems have been shown in children with primary stereotypy, knowledge of this subject is limited [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eResearch on the differential diagnosis of tics and stereotypies has emphasized the phenomenological distinction [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. To our knowledge, no previous studies have investigated how TD and primary SMD differ regarding accompanying clinical features. We hypothesized that disruptions at different stages of neuronal development are involved in the etiology of tics and stereotypies and that the NSS and motor skill problems accompanying TD and primary SMD will exhibit differences that can provide valuable insights into these distinct neurobiological mechanisms.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research group comprised children aged 6-12 years who were admitted to the Department of Child and Adolescent Psychiatry from March to July 2022 and met the inclusion criteria. The healthy control (HC) group consisted of age- and gender-matched children who visited our outpatient clinic within the same period and had no psychiatric disorders. Since there are no sample studies with significant results of patients with TD and primary SMD in the literature, an alpha level of 0.05 for detecting a large effect size of d=0.4 for One-way ANOVA was calculated with G-power 3.1.9.6 analysis to create 80% power for a sample size of 76. A total of 83 children were reached within the specified time interval, but 73 participants were included in the analysis as children who could not complete the tests were eliminated. The flowchart of sampling is given in Figure 1.\u003c/p\u003e\n\u003cp\u003eInclusion criteria for the research group were; (1) current diagnosis of TD (Tourette syndrome, transient tic disorder, chronic motor or vocal tic disorder), primary SMD, or ADHD, (2) showing the movement disorder symptoms at the time of assessment (for the TD and primary SMD groups), (3) being between 6-12 years. Exclusion criteria included; (1) diagnoses of autism spectrum disorder (ASD), anxiety disorders, depression, posttraumatic stress disorder, obsessive compulsive disorder, psychotic disorder, eating disorder, substance use disorder according to DSM-5; (2) intellectual disability identified through clinical evaluation; (3) acute or chronic neurological, genetic, inflammatory disease; (4) hearing or vision loss; (5) history of hypoxic birth or severe prematurity (\u0026le;28 weeks); (6) acute or chronic medication use. Patients with ADHD were not excluded from the TD and SMD groups because of high comorbidity rates. An ADHD control group was added for this reason. To verify the inclusion and exclusion criteria, children received a psychiatric assessment by a child and adolescent psychiatrist, with diagnoses verified by a senior supervisor psychiatrist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProcedures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter completing the Sociodemographic and Clinical Data Form created by the researchers, the Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Life-time (K-SADS-PL) which is validated and reliable in Turkish was administered for differential diagnosis. Yale Global Tic Severity Scale (YGTSS), Repetitive Behavior Scale-Revised (RBS-R), Neurological Evaluation Scale (NES) were also applied by the clinician across groups. Parents rated the Conners\u0026rsquo; Parent Rating Scale-Revised Short Form (CPRS-RSF), Revised Developmental Coordination Disorder Questionnaire (DCDQ-R).\u0026nbsp;To comprehensively evaluate the motor skills of the all participants, clinicians conducted four motor skills tests: Nine-Hole Peg Test, Flamingo Balance Test, 1-Minute Sit-to-Stand Test, Finger to Nose Test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYale Global Tic Severity Scale (YGTSS):\u003c/strong\u003e This scale, completed by the clinician based on a semi-structured interview, evaluates the tics present in the last week according to the child\u0026apos;s and parent\u0026apos;s report [24]. It then grades the number, frequency, severity, complexity, and interference with daily activities for motor and vocal tics separately. A higher scale score indicates greater severity. A Turkish validity and reliability study of the scale was conducted [25].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRepetitive Behavior Scale-Revised (RBS-R):\u003c/strong\u003e The RBS-R is a clinical rating scale developed to assess repetitive behaviors and the severity of these behaviors [26]. The validity and reliability of its Turkish translation has been performed [27]. The RBS-R consists of six subscales including stereotypic behavior, self-injurious behavior, behavior, ritualistic behavior, sameness/uniformity behavior and restricted interests. As the score obtained from the scale increases, it is accepted that the severity of repetitive behaviors seen in children increases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNeurological Evaluation Scale (NES):\u003c/strong\u003e The NES, developed by Buchanan and Heinrichs in 1989, assesses impairments in four areas: sensorimotor integration (audiovisual integration, stereognosis, graphesthesia, extinction, right-left confusion), motor coordination (rapid alternating movement, tandem walk, finger-thumb opposition, finger-to-nose test, rhythm tapping), sequencing of complex motor acts (fist-ring test, fist-edge-palm test, Ozeretski test) and others (adventitious overflow, Romberg, tremor, memory, mirror movements, synkinesis, convergence, gaze impersistence, glabellar reflex, snout reflex, grasp reflex, suck reflex) [28]. The scale consists of 26 items, 14 evaluated separately for each half of the body. The instructions are given and scored by the clinician. Since it evaluates biological parameters, there is no difference between cultures; therefore, there is no need for validity and reliability studies [29]. In the items indicating lateralization and assessing the right and left half of the body separately, the results of the side with the higher score were used [30, 31].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConners\u0026rsquo; Parent Rating Scale-Revised Short Form (CPRS-RSF):\u0026nbsp;\u003c/strong\u003eThis likert-type scale used to measure ADHD symptom domains and symptom severity has subscales including attention deficit/cognitive problems, hyperactivity, oppositional defiance and ADHD index\u0026nbsp;[32]. Kaner et al. conducted its\u0026nbsp;Turkish validity and reliability study\u0026nbsp;[33].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRevised Developmental Coordination Disorder Questionnaire (DCDQ-R):\u003c/strong\u003e The DCDQ-R is the only scale with a good level of evidence according to the Developmental Coordination Disorder (DCD) diagnosis and treatment guidelines [34]. The scale consists of control during movement, fine motor/handwriting and general coordination subscales. In addition, it has cut-off scores for children aged 5-8 years, 8-12 years and 10-15 years, and according to the scores obtained, it is concluded that \u0026ldquo;indication of DCD or suspect DCD\u0026rdquo; or \u0026ldquo;probably not DCD\u0026rdquo;. The Turkish validity and reliability study of the test was conducted [35].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNine-Hole Peg Test\u003c/strong\u003e: The measurement tool used to measure manual dexterity consisted of nine small sticks made in standard sizes and a board with nine holes on which they were placed. The child was asked to place and remove the sticks from the board quickly. The placement and removal times were recorded using a stopwatch, first for the dominant hand and then for the non-dominant hand separately\u0026nbsp;[36].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFlamingo Balance Test\u003c/strong\u003e: In this test to assess static balance, the child was instructed to stand on his/her preferred foot for 60 seconds. As the child lost balance, the timer was stopped and restarted when the balance was regained. The clinician recorded the number of restarts\u0026nbsp;[37].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1-Minute Sit-to-Stand Test\u003c/strong\u003e: The clinician instructed the child to sit and stand on a height-adjustable chair, recording the number of sit-ups and stand-ups in 1 minute with a timer. This measurement tool was used to assess lower extremity function\u0026nbsp;[38, 39].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinger to Nose Test\u003c/strong\u003e: In this test, which measures bilateral coordination, the clinician instructed the child to close his/her eyes, arms out to the sides and raise to shoulder level, touch the tip of his/her nose with the tip of the index finger with the hand in a fist position except for the index finger, and use one right and one left hand while doing so\u0026nbsp;[40, 41].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Statistical Package for Social Sciences (SPSS) version 22.0 was used for statistical analysis of the data. In descriptive analyses, means and standard deviations were used for continuous variables with normal distribution; medians and interquartile ranges (IQRs) were used for continuous variables with non-normal distribution; numbers and percentages were used for categorical variables. The normality of the distribution was evaluated with Shapiro-Wilk statistics. Group differences for sociodemographic variables, scale scores and performance-based measures were examined using the One-Way ANOVA or Kruskal-Wallis tests for continuous variables and Chi-square (\u0026chi;2) test for categorical variables. Pairwise group comparisons were made with the Mann-Whitney \u003cem\u003eU\u003c/em\u003e tests with Bonferonni correction. The Spearman\u0026apos;s nonparametric correlation test was used to investigate the relationship between continuous variables. In all analyses, a p value less than 0.05 was expected for statistical significance. Effect sizes for significant results were also reported.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eThe Sociodemographic and Clinical Characteristics of the Study Sample\u003c/h2\u003e \u003cp\u003eWithin the study period, we enrolled 20 children with TD (n\u0026thinsp;=\u0026thinsp;17, 85% male), 20 with primary SMD (n\u0026thinsp;=\u0026thinsp;14, 70% male), 13 with ADHD (n\u0026thinsp;=\u0026thinsp;10, 76,9% male) and 20 healthy controls (HCs) (n\u0026thinsp;=\u0026thinsp;12, 60% male). The mean ages of participants in group of TD, primary SMD, ADHD and HC were 8,3 (SD\u0026thinsp;=\u0026thinsp;2), 7,6 (SD\u0026thinsp;=\u0026thinsp;1), 8.2 (SD\u0026thinsp;=\u0026thinsp;1) and 8.9 (SD\u0026thinsp;=\u0026thinsp;2) years, respectively. The groups did not differ significantly in terms of mean age (F\u0026thinsp;=\u0026thinsp;2,344, p\u0026thinsp;=\u0026thinsp;0.081, One-way ANOVA) or sex (χ\u0026sup2;=3.332, p\u0026thinsp;=\u0026thinsp;0.343, df\u0026thinsp;=\u0026thinsp;3). No significant differences emerged between groups regarding other sociodemographic and familial variables (Supplementary Table\u0026nbsp;1). Furthermore, there were no significant differences between the four groups regarding the perinatal factors, medical history, developmental stages, and school-related factors. Hand, foot, and eye preferences as well as cerebral dominance did not differ significantly among the groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eThe TD group consisted of children with transient tic disorder (n\u0026thinsp;=\u0026thinsp;5, 25%), chronic motor or vocal tic disorder (n\u0026thinsp;=\u0026thinsp;10, 50%) and Tourette\u0026rsquo;s Syndrome (TS) (n\u0026thinsp;=\u0026thinsp;5, 25%). Supplementary Table\u0026nbsp;2 shows the comparison between TD and SMD groups regarding the age of onset of symptoms, age at diagnosis and ADHD comorbidity.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eGroup Differences on Clinical Assessment Scales\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the comparison of the four groups in terms of clinical assessment scales. For the NES, sequencing of the complex motor acts scores was significantly higher in the SMD group than in the HC group (U\u0026thinsp;=\u0026thinsp;98.500, p\u0026thinsp;=\u0026thinsp;0.005). Fist-ring test and Ozeretski test scores were significantly higher for the primary SMD patients compared to HCs (U\u0026thinsp;=\u0026thinsp;95.000, p\u0026thinsp;=\u0026thinsp;0.002 and U\u0026thinsp;=\u0026thinsp;119.500, p\u0026thinsp;=\u0026thinsp;0.008; respectively). Other NES scores did not differ between study groups. We found significant differences between the DCDQ-R scores of the groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The post-hoc analyses showed that control during movement scores were significantly lower only in the SMD group compared to HCs (U\u0026thinsp;=\u0026thinsp;98.500, p\u0026thinsp;=\u0026thinsp;0.006). In terms of fine motor/handwriting and general coordination subscales and total scale scores, all three patient groups had significantly lower scores than HCs. Based on parent DCDQ-R ratings, 10% of children with TD, 20% of children with primary SMD, 15.4% of children with ADHD were characterized as having \u0026ldquo;indication of DCD or suspect DCD\u0026rdquo;.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical assessment scales between study groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTD (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSMD (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eADHD (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHC (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eKW/p\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eE.S.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eNES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSensorimotor integration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.5 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.0 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.0 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.777/0.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eMotor incoordination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.0 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.566/0.463\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSequencing of complex motor acts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.0 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.406/0.024*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFist-ring test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.536/0.015*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.109\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOzeretski test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.096/0.028*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFist-edge-palm test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.496/0.321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.0 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.075/0.557\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.5 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.0 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.5 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.111/0.164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eDCDQ-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eControl during movement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.0 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.0 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e28.5 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8.420/0.038*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eFine motor/Handwriting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.5 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.0 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20 .0(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.295/0.006*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGeneral Coordination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.5 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.0 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e23.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15.855/0.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.186\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.0 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.5 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62.0 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e70.0 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17.815/0.000*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eNES: Neurological Evaluation Scale, DCDQ-R: Revised Developmental Coordination Disorder Questionnaire, IQR: Interquartile Range, TD: Tic Disorder, SMD: Stereotypic Movement Disorder, ADHD: Attention Deficit Hyperactivity Disorder, HC: Healthy Control, KW: Kruskal-Wallis Test, *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, E.S.: Effect Size\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e According to the evaluation of the TD group with YGTSS, mean scores for motor and vocal tics were 6.7 (SD\u0026thinsp;=\u0026thinsp;4.4) and 5.0 (SD\u0026thinsp;=\u0026thinsp;4.9), respectively. The mean global impairment score was 0.9 (SD\u0026thinsp;=\u0026thinsp;0.9) and the total score of YGTSS was 12.6 (SD\u0026thinsp;=\u0026thinsp;6.8). In the primary SMD group, mean scores for RBS-R stereotypic behavior subscale and RBS-R total score were 3.4 (SD\u0026thinsp;=\u0026thinsp;2.5) and 5.4 (SD\u0026thinsp;=\u0026thinsp;6.9), respectively. The mean CPRS-RSF total scores of the four groups were 31.0 (SD\u0026thinsp;=\u0026thinsp;18.1) for TD, 28.5 (SD\u0026thinsp;=\u0026thinsp;17.9) for primary SMD, 40.0 (SD\u0026thinsp;=\u0026thinsp;14.8) for ADHD and 8.6 (SD\u0026thinsp;=\u0026thinsp;8.2) for HC.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eGroup Differences on Motor Skill Tests\u003c/h2\u003e \u003cp\u003eDescriptive statistics and group comparisons for the motor skill tests are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The Nine-hole peg test scores differed among 4 groups. The dominant hand performance of the children in the primary SMD group was significantly lower than in the TD group (U\u0026thinsp;=\u0026thinsp;97.000, p\u0026thinsp;=\u0026thinsp;0.005, Cohen\u0026rsquo;s d\u0026thinsp;=\u0026thinsp;0.79). Although the difference in terms of nondominant hand performance did not reach significance, children with SMD were slower than children with TD (U\u0026thinsp;=\u0026thinsp;116.000, p\u0026thinsp;=\u0026thinsp;0.023). These four groups did not differ significantly regarding the Flamingo Balance Test, finger-to-nose test (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Comparison of four groups\u0026rsquo; 1-minute sit-to-stand test scores found a statistically significant difference. The scores of children with primary SMD were significantly lower than HCs (U\u0026thinsp;=\u0026thinsp;90.500, p\u0026thinsp;=\u0026thinsp;0.003, Bonferonni corrected). In post-hoc analysis, other pairwise comparisons did not yield significant differences.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of motor skill performance between study groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTD (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSMD (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eADHD (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHC (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eKW/p\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eE.S.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNine-hole peg test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDominant hand\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.0 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.0 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.015/0.029*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNondominant hand\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.0 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.5 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26.0 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.250/0.064\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e1-minute sit-to-stand test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.0 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.0 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.565/0.023*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFlamingo balance test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.0 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.0 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.068/0.108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFinger-to-nose test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.670/0.445\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eIQR: Interquartile Range, TD: Tic Disorder, SMD: Stereotypic Movement Disorder, ADHD: Attention Deficit, HC: Healthy Control, KW: Kruskal-Wallis Test, *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, E.S.: Effect Size\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCorrelational Analyses\u003c/h2\u003e \u003cp\u003eBivariate correlations in the TD group revealed that YGTSS- Total Score, Total Tic Score and Global Impairment Score were not significantly correlated with NES, Nine-Hole Peg Test, Flamingo Balance Test, 1-minute sit-to-stand test, finger-to-nose test, and DCDQ-R scores (Spearman\u0026rsquo;s correlation, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In the primary SMD group, no statistically significant differences emerged in the correlation analyses between RBS-R scores and NES, CPRS-RSF, Nine-Hole Peg Test, Flamingo Balance Test, 1-minute sit-to-stand test, finger-to-nose test or DCDQ-R scores (Spearman\u0026rsquo;s correlation, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Across all four study groups, pairwise correlation analyses showed no significant relationships between CPRS-RSF scores and any motor performance tests, NES, or DCDQ-R (Spearman\u0026rsquo;s correlation, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOur study is the first to compare children aged 6\u0026ndash;12 years diagnosed with TD and primary SMD with age- and gender-matched children with ADHD and HCs regarding sociodemographic and clinical characteristics, NSS, fine and gross motor skills, balance, and coordination. We made an effort to exclude confounding factors and obtain more accurate results about elucidating etiopathogenesis by creating groups with homogenous sociodemographic characteristics, no medication use, and no psychiatric comorbidity. The age range enabled us to perform clinical evaluation early after the onset of symptoms before developing adaptive neurobiological mechanisms in the brain. We found that children with primary SMD had lower fine motor skill performance than those with TD. Additionally, the primary SMD group, but not the TD group, showed lower gross motor skills and a higher DCD risk than HCs, with higher NES scores in the sequencing of complex motor acts.\u003c/p\u003e \u003cp\u003eOther strengths of the study include using valid and reliable measurement tools for motor skills and NSS in Turkish and evaluations across various areas such as fine and gross motor skills, balance, coordination, and functional exercise capacity. We reduced the risk of misinterpretation by excluding psychiatric comorbidities, global developmental delay, hearing and visual problems, and neurological and genetic diseases that may affect motor skills. Due to the common ADHD comorbidity in TD and SMD patients, this was not an exclusion criterion; we included a separate ADHD group to control for the confounding effects.\u003c/p\u003e \u003cp\u003eNSS can also be observed in typically developing children and may indicate impaired cortical inhibition that controls motor functions when persistent into late childhood [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Reports of NSS in individuals with schizophrenia, bipolar disorder, and ADHD highlight potential neurodevelopmental issues [\u003cspan additionalcitationids=\"CR44\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. In a research conducted with 122 healthy adults with no family history of psychiatric disorders, NES score\u0026thinsp;\u0026gt;\u0026thinsp;1 was recorded in 54.1% of the sample [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. In our study, the median value of the HC group\u0026rsquo;s total NES score was 8. The fact that NSS was observed in healthy children who did not meet the diagnostic criteria for any psychiatric disorder is compatible with the information in the literature [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. This finding indicates that there may be an impairment in the neural development process in the normal population who do not show signs of neurodevelopmental disorders. Furthermore, the observation of NSS in healthy children underscores the significant differences between the SMD group and HCs, adding to the gravity of our findings.\u003c/p\u003e \u003cp\u003eThe literature on NSS in SMD is mainly derived from ASD studies, and sensory integration and motor coordination problems are higher in this population [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Mahone et al. found higher NSS scores in children with primary complex motor stereotypy compared to HCs, indicating a risk of motor dysfunction despite the relative absence of comorbidities that may affect motor function [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A striking point in our findings was the significant difference in the sequencing of complex motor acts scores of the NES corresponds neuroanatomically to prefrontal cortex [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Kaneko et al. demonstrated that the quantitative assessment system developed using NSS tests can objectively assess neurodevelopmental delay in children with neurodevelopmental disorders [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Thus, our findings suggesting prefrontal cortex-related test impairments in the primary SMD group indicate potential disruptions in prefrontal cortex development.\u003c/p\u003e \u003cp\u003eNeuroimaging studies indicate that TD patients exhibit dysfunction in brain regions associated with movement planning and coordination within the CSTC pathway [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Although numerous studies have examined fine motor skill deficits in TD, conflicting findings make it challenging to draw definitive conclusions [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. One study found poor fine motor performance in children with TS, linking lower performance to tic severity and predicting tic severity in adulthood based on dominant hand performance [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, our study found no impairments, possibly due to excluding severe cases with psychiatric comorbidities. Notably, our participants did not have chronic medical or neurological conditions, nor were they on psychiatric medications. These results align with Buse et al.'s research indicating that motor skill deficits in TS may not be directly attributable to tics but to treatment-related factors and psychiatric comorbidities [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. From another point of view, the absence of fine motor impairments in our TD group might also reflect compensatory neurobiological mechanisms. Functional neuroimaging studies suggest that the need to suppress tics enhances cognitive control over motor activities, facilitating better symptom regulation and linking to structural changes in the prefrontal cortex [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur knowledge of fine motor skill problems in school-aged children with primary SMD is limited. Valente et al. evaluated 26 preschool children with SMD and found impaired manual dexterity in 58% of the sample [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Our study is the first to utilize both clinician-administered objective measurement tools and parent-reported scales to assess fine motor skill impairments in school-aged children diagnosed with SMD. Compared to children with TD, our primary SMD patients exhibited lower performance in fine motor speed and skill, for which frontal, sensorimotor, and premotor cortex were responsible [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. No previous studies have directly compared these two movement disorders regarding fine motor skills. Neurodevelopmental disorders have common points not only clinically but also neurobiologically [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. According to the \u0026ldquo;\u003cem\u003eneurodevelopmental burden hypothesis\u003c/em\u003e\u0026rdquo;, earlier onset and increased severity of disorders correlate with greater overall neurodevelopmental impairment, with a spectrum of severity ranging from ASD to late-onset neurodevelopmental disorder [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. From this point of view, our results may indicate that primary SMD has a heavier neurodevelopmental burden than TD, which may be rooted in an earlier insult to the neurodevelopment process of these neural circuits.\u003c/p\u003e \u003cp\u003eIn our study, the TD and SMD groups did not differ from each other or HCs in static balance and bilateral coordination. Previous research has documented a low prevalence of balance impairments in TD, aligning with our findings [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. The development of the cerebellum, the primary brain region associated with balance, occurs late in the prenatal brain development process. The lack of postural balance impairments in the TD group might be attributed to disruptions in developmental processes prior to cerebellum development [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. Impaired balance performance has been reported in preschool children with SMD compared to healthy peers [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, the normal static balance performance observed in our SMD group may be because our sample consisted of school-age children. Longitudinal studies indicate that brain structural abnormalities arise from developmental delays rather than impairments [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Additionally, considering the results of Valente et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], our study suggests school-aged children with primary SMD may catch up with their neurodevelopmentally normal peers, although this observation presents a limitation of our cross-sectional study.\u003c/p\u003e \u003cp\u003eOur study found that children with SMD had the lowest functional exercise capacity and lower extremity muscle strength. The significant difference between children with SMD and HCs was independent of stereotypy severity and was observed in groups matched for sociodemographic and developmental characteristics. Furthermore, none of the children had acute infection or respiratory distress that could affect 1-minute sit-stand test performance. Research has shown that visuospatial working memory plays a role in gross motor skills, likely due to the involvement of neural networks responsible for planning and movement control [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. Functional neuroimaging has linked various brain regions\u0026mdash;including the frontal, parietal, and occipital cortices, cerebellum, thalamus, and insula\u0026mdash;to visuospatial working memory [\u003cspan additionalcitationids=\"CR60\" citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]. Lower gross motor performance in children with SMD may indicate underlying visuospatial working memory deficits. Future studies combining motor skill assessments with neuropsychological evaluations may clarify this relationship.\u003c/p\u003e \u003cp\u003eAll three patient groups scored significantly lower than HCs on the DCDQ-R total score, fine motor/handwriting score, and general coordination score, supporting the literature that suggests motor dysfunction is more prevalent in children with neurodevelopmental disorders [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The SMD group also exhibited a higher risk for DCD. Mahone et al. found \"probable\" DCD in 14% and \"suspect\" DCD in 17% of 52 children with complex motor stereotypy, aligning with our rates [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In a study in which DCD comorbidity was found in 19 (45%) of 42 children with primary motor stereotypy, Freeman et al. concluded that tics and stereotypies may involve different brain mechanisms [\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]. Similarly, our findings contribute to the literature supporting a different etiopathogenesis between tics and stereotypies.\u003c/p\u003e \u003cp\u003eIn conclusion, our findings revealed NSS and motor skill differences in a homogeneous study sample that may be a reflection of different impaction process on neurodevelopment for TD and primary SMD. However, our cross-sectional study was conducted with a clinical sample, which may have reduced the generalizability of the results to the population. Also, this research did not study molecular mechanisms and neural circuits beyond these clinical differences. Future studies overcoming these challenges may illuminate the etiology and treatment options for these two frequent neurodevelopmental disorders.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNo funding was received to assist with the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e The authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u003c/strong\u003e The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions:\u0026nbsp;\u003c/strong\u003eESAA: conceptualization, data curation, investigation, methodology, resources, writing, original draft preparation, reviewing, and editing. DÜ: conceptualization, methodology, project administration, supervision, review, and editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eApproval was granted for this study from the Hacettepe University Faculty of Medicine Non-Interventional Clinical Research Ethics Board (March 1, 2022/No: GO 22/76). The study procedure was held in accordance with the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent:\u0026nbsp;\u003c/strong\u003eParents/legal guardians of all participants provided written consent and verbal assent was obtained from the children themselves, according to their age and understanding. The participants were informed about the purpose of the study, the procedures involved, and their right to withdraw from the study at any time without consequence. The informed consent form included information on data privacy, confidentiality, and data storage.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eParents/legal guardians of all participants provided informed consent for publication of their anonymized data. Identifiable details of the participants were not included in the manuscript or any accompanying materials. The authors confirm that all authors have reviewed and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAmerican Psychiatric Association, D. and A.P. Association, \u003cem\u003eDiagnostic and statistical manual of mental disorders: DSM-5\u003c/em\u003e. Vol. 5. 2013: American psychiatric association Washington, DC.\u003c/li\u003e\n\u003cli\u003eSinger, H.S., \u003cem\u003eStereotypic movement disorders.\u003c/em\u003e Handbook of clinical neurology, 2011. \u003cstrong\u003e100\u003c/strong\u003e: p. 631-639.\u003c/li\u003e\n\u003cli\u003eSinger, H.S., \u003cem\u003eMotor stereotypies.\u003c/em\u003e Semin Pediatr Neurol, 2009. \u003cstrong\u003e16\u003c/strong\u003e(2): p. 77-81.\u003c/li\u003e\n\u003cli\u003eBaizabal-Carvallo, J.F. and J. 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Reiss, and V. Menon, \u003cem\u003eNeural basis of protracted developmental changes in visuo-spatial working memory.\u003c/em\u003e Proceedings of the National Academy of Sciences, 2002. \u003cstrong\u003e99\u003c/strong\u003e(20): p. 13336-13341.\u003c/li\u003e\n\u003cli\u003eFreeman, R.D., A. Soltanifar, and S. Baer, \u003cem\u003eStereotypic movement disorder: easily missed.\u003c/em\u003e Dev Med Child Neurol, 2010. \u003cstrong\u003e52\u003c/strong\u003e(8): p. 733-8.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tic Disorder, Stereotypic Movement Disorder, Motor Skills, Psychomotor Performance","lastPublishedDoi":"10.21203/rs.3.rs-4986441/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4986441/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWhile Tic Disorders (TD) and Stereotypic Movement Disorder (SMD) are commonly comorbid in pediatric clinics, their clinical and etiological differences remain poorly understood. We aimed to investigate the clinical features that differentiate between TD and primary SMD by evaluating neurological soft signs (NSS) and motor skills. The Kiddie-Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version DSM-5 (K-SADS-PL) and Sociodemographic and Clinical Data Form were administered to the children and their parents. The clinician completed the Yale Global Tic Severity Scale (YGTSS), Repetitive Behavior Scale-Revised (RBS-R) and Neurological Evaluation Scale (NES). The Nine-Hole Peg Test was used for fine motor skills, the 1-Minute Sit-to-Stand Test for gross motor skills, the Flamingo Balance Test for static balance, and the Finger-to-Nose Test for bilateral coordination. Parents completed the Conners Parent Rating Scale-Revised Short Form (CPRS-RSF) and the Developmental Coordination Disorder Questionnaire-Revised (DCDQ-R). Our sample consisted of 20 TD, 20 primary SMD, 13 ADHD patients, and 20 healthy controls (HCs). Sequencing of the complex motor acts scores of NES were significantly higher in the SMD group than in HCs. The primary SMD group demonstrated significantly lower dominant hand performance on the Nine-Hole Peg Test than the TD group. Children with primary SMD had significantly lower scores of 1-minute sit-to-stand test; higher total and subscale scores of DCDQ-R and higher developmental coordination disorder risk than HCs. Our findings offer valuable insights into the distinct etiopathogenesis of TD and primary SMD, providing a foundation for future neurobiological research.\u003c/p\u003e","manuscriptTitle":"Motor Skills and Neurological Soft Signs: Are They Only Clinical Differences or Reflection of Distinct Etiopathogenesis in Tic Disorder and Primary Stereotypic Movement Disorder?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-17 09:22:21","doi":"10.21203/rs.3.rs-4986441/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d36c3265-f347-427d-ad66-3c7c56924aaa","owner":[],"postedDate":"October 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-17T09:22:23+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-17 09:22:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4986441","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4986441","identity":"rs-4986441","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}