Sociodemographic and clinical characteristics of childhood tic disorders Perihan Cam Ray1, Gonca Gül Çelik1, Ayşegül Tahiroğlu1, Çağlar Charles Daniel Jaicks1, Ayşe Avcı2 1Çukurova University Faculty of Medicine, Department of Child and Adolescent Psychiatry, Adana, Turkey. 2Çağ University, Department of Psychology, Mersin, Turkey Cukurova Medical Journal 2019;44(Suppl 1):251-262. Abstract Öz Purpose: In this study, we aimed to investigate the sociodemographic and clinical characteristics of children and adolescents diagnosed with tic disorders. Materials and Methods: The study population included 187 children with tic disorders, aged between 4 and 18 years. The data were obtained by using Yale Global Tic Severity Scale (YGTSS), Screen for Child Anxiety and Related Disorders, Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL). The demographic information, history of familial diseases were recorded. Results: The study included 37 girls (mean 10.9 ± 2.5 years) and 150 boys (mean 10.9 ± 2.7 years) with a mean age of 10.9 ± 2.6 years. Of all cases, 135 were classified as Tourette Syndrome (n=135; 72.2%), 50 as motor tics (n=50; 26.7 %) and 2 as others tic disorders (n=2; 1.1%) ) according to the diagnostic tic disorders subtype. There was no significant difference between the two groups in terms of mean age and first symptom age according to the subtype of tic disorder. In 91% of the cases, the age of onset of tics was 12 years or younger. The rate of having at least one comorbidity, mean number of comorbidities and comorbid ADHD rates were significantly higher among boys than girls. The most common comorbid diagnoses were ADHD (n=142, 75.9%), OCD (n= 08, 57.8%) and anxiety disorder (n=57, 30.4%). Conclusion: In our study, male cases, early onset and multiple comorbid diagnoses were found to be significantly higher in childhood tic disorders. Objective: In this study, it was aimed to investigate the sociodemographic data, clinical features and other accompanying mental disorders of children and adolescents diagnosed with tic disorder. Materials and Methods: A total of 187 patients aged 4-18 years with a diagnosis of Tic Disorder were included in the study. The Turkish version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Now and Lifetime Version was used to screen for psychiatric symptoms. Demographic information and familial disease histories of the cases were recorded. Results: 37 girls (mean age 10.9±2.5 years) and 150 boys (mean age 10.9±2.7 years) with a mean age of 10.9±2.6 years were included in the study. According to the Tic Disorder subtype, 135 (72.2%) of the cases were diagnosed with Tourette Syndrome, 26.7% (n=50) motor tic disorder, and 2 (1.1%) another tic disorder. There was no significant difference between the two groups in terms of the mean age of the cases according to the Tic Disorder subtype and the age of the first symptom. The age of onset of tics in 91% of the cases was 12 years or younger. The rate of having at least one comorbidity, the mean number of comorbidities, and the rate of attention deficit hyperactivity disorder (ADHD) comorbidity were significantly higher among boys than girls. The most common comorbidities were ADHD (n=142, 75.9%), obsessive compulsive disorder (OCD) (n=108, 57.8%) and anxiety disorder (n=57, 30.4%). Conclusion: In our study, male cases, early onset and multiple comorbidities were found to be significantly higher in childhood tic disorders. Keywords: Tic disorders, Tourette Syndrome, phenomenology, childhood. Key words: Tic disorders, Tourette’s Syndrome, phenomenology, childhood.
INTRODUCTION Tics are defined as sudden, repetitive, non-rhythmic, rapid, irregular movements and sounds, and tic disorders are neurodevelopmental disorders that begin in childhood1. Tic disorders are classified according to the types of tics present and their duration. According to the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5), they are grouped as chronic motor or vocal tic disorder (KVMT), Tourette syndrome (TS), transient tic disorders, and unspecified tic disorders. TS is a tic disorder characterized by more than one motor and at least one vocal tic, persisting for more than 1 year, and including tics occurring before the age of 18. KVMT, multiple motor tics or vocal tics occurring before the age of 18 and persisting for more than 1 year; transient tic disorder includes motor and vocal tics lasting less than 1 year1. The prevalence of tic disorders is reported to be approximately 15-20% in school-age children for transient tic disorders, approximately 1.6% for KVMT in children, and approximately 0.5-1% for TS2,3,4,5,6. Tics are more common in boys than girls, with a rate of about 3 to 4/14,6,7,8,9,10. It is stated that tics are generally associated with a sensory phenomenon that can be defined as an itching sensation, pressure, increased internal tension or urge to act, and increased somatic hypersensitivity to external stimuli and most commonly involve the head, neck, and upper body11,12. Symptoms usually begin with mild motor tics at 4-10 years of age, followed by more complex motor and vocal tics. It has been reported that it decreases and continues into adulthood in the remaining one third7,13,14,15,16,17. In clinical and community-based studies of children with tic disorders, it has been shown that children often have a comorbidity, especially when TS alone is a rare condition, and only 8-15% of children with TS have pure TS without comorbidity or co-morbid psychopathology. It is stated that the comorbidity can reach 80-90% 3,7,17,18,19,20,21. Considering clinical and epidemiological studies, it has been shown in many studies that attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD) are the most common comorbid conditions and occur in approximately 50% of children with tic disorders7,9,10 ,15,17,18,21-23. It is stated that approximately 30% of children have a triad of tic disorder, ADHD and OCD17. In genetic, neuroimaging, neurophysiological and neurochemical studies on tic disorders and especially the etiology of TS, tics are thought to be related to cortical and subcortical region dysfunctions, including basal ganglia, thalamus and frontal cortex24,25,26, these regions play an important role in the formation of tics. It is associated with parallel cortico-striato-thalamo-cortical (PRTC) circuits27,28. In TS, dopaminergic, GamaAminobutyric Acid-GABAergic and serotonergic animal models have been developed, generally targeting the basal ganglia. In this study, it was planned to investigate the sociodemographic data, clinical features and other accompanying mental disorders of children and adolescents diagnosed with tic disorder. It is thought that at the beginning of the benefits expected from the study, it will be a guide for clinicians in clarifying the phenotypic appearance and choosing treatment based on the clinical features of childhood tic disorders. MATERIALS AND METHODS A total of 187 cases, 37 girls and 150 boys, aged 4-18 years, diagnosed with Tic Disorder and evaluated in the Çukurova University Faculty of Medicine, Pediatric Psychiatry Outpatient Clinic between November 2012 and December 2013 were included in the study. Approval for this study was obtained from the Ethics Committee of Çukurova University Faculty of Medicine (Date: 8 November 2012, No: 13). At the stage of sample selection, detailed information about the study was given to eligible cases and families. Volunteers were included in the study after written informed consent was obtained from the subjects and their families. Demographic information, infection and rheumatic disease history of the cases were recorded. Cases diagnosed with pervasive developmental disorder, psychotic disorders, and mental retardation were excluded from the study. Scales Interview Schedule for Affective Disorders and Schizophrenia for School-Age Children Now and Lifetime Version Turkish version CDSG-SY (K-SADS-PL) This scale, which is applied to screen for mental symptoms, is DSM-III-R and DSM-IV Volume/Volume in children and adolescents. 44 Year/Year 2019 Clinical features of childhood tic disorders is a semi-structured interview form used to detect psychopathologies according to 253 diagnostic criteria. Turkish validity-reliability study of the scale developed by Kaufman et al. (1997) Gökler et al. made by29,30. Yale General Tic Severity Rating Scale-YGTSS (YGTSS) It is an 11-item scale used for tic symptom severity and completed by the clinician. The characteristics of motor and vocal tics are evaluated in 5 different dimensions: number, frequency, intensity, complexity and inhibition. Each subscale score is in the range of 0-5 and is calculated separately for movement and vocal tic scores. Accordingly, the individual’s total score for movement tics can be between 0-25, and the total score for vocal tics can be between 0-25. The functional impairment score is in the range of 0-50 points, and is included in the total YGTS score without affecting the movement and vocal tic scores. The YGTS total score range is between 0-100. This scale was developed by Leckman et al. It was developed by Zaimoğlu et al. made by31,32. Laboratory examinations Hemoglobin, hematocrit, RBC (red blood cell count), MCV (mean erythrocyte volume), MPV (mean platelet volume), neutrophil, basophil, euzonophile, lymphocyte ratios, ferritin, which are routinely requested from the patients who applied to our outpatient clinic and studied from antecubital venous blood samples , serum antistreptolysin-O (ASO) levels were studied in the central laboratory of Çukurova University Faculty of Medicine. Quantitative measurement of ASO was made by turbidimetric method. Statistical analysis Statistical analyzes of study data were performed with SPSS version 16.00. The normal distribution of continuous variables was investigated using the Shapiro-Wilks test. Since the normal distribution could not be determined in continuous variables, independent groups numerical variables analysis non-parametric tests were used (MannWhitney U-test). Numerical variables are given as mean ± standard deviation. Categorical variables were analyzed using the Chi-Square test. The categorical variables are summarized as numbers and percentages. The relationship between continuous variables was examined with the Pearson correlation coefficient. The critical value of p=0.05 was used to analyze its statistical significance. RESULTS: The study included 37 girls (mean: 10.9±2.5 years), and 150 boys (mean: 10.9±2.7 years), aged 4-18 years (mean: 10.9±2.6 years), diagnosed with tic disorder. A total of 187 cases were included. Of the female cases, 26 (70.3%) TS, 9 (24.3%) MT, 2 (5.4%) Other TB; 109 (72.7%) of the male cases were diagnosed as TS and 41 (27.3%) of them were diagnosed as MT. There was no significant difference between the genders in terms of the frequency of tic disorder subtypes and the ratio of TS and MT diagnoses, which constitute the majority of the sample (p=0.771). On the other hand, the rate of having at least one comorbidity and the mean number of comorbidities and ADHD comorbidities were significantly higher among boys than girls. (respectively; p=0.0001, 0.028, p=0.001). The data and general characteristics of the cases by gender are presented in Table 1. According to the Tic Disorder subtype, 135 (72.2%) of the cases were diagnosed with TS, 26.7% (n=50) with motor tic disorder, and 2 (1.1%) with another tic disorder. Since it was thought that it would be more appropriate in terms of statistical analysis, all diagnoses except TS were grouped under the name of DTD and analyzes comparing the two groups were included. When the cases were analyzed in terms of comorbidities according to the tic disorder subtype, the only significant result was; OCD comorbidity was detected at a higher rate in the DTD group (p=0.046). Analysis results for tic disorder subtypes are shown in Table 2. Table 1. Comparison of Cases by Gender Female Male P Age of First Symptom* 7.9±2.4 7.2±2.7 0.095 Number of comorbidities* 1.8±1.1 2.3±0.9 0.028+ Comorbidity** Any comorbidity 32(86.5) 148 (98.7) 0.0001 + ADHD 20(54.1) 122 (81.3) 0.001+ OCD 23(62.2) 85 (56.7) 0.544 Anxiety Disorder. 13(35.1) 44 (29.3) 0.492 Çam Ray et al. Cukurova Medical Journal 254 Tic Disorder Type** TS 26(70.3) 109 (72.7) 0.771 DTB 11(29.7) 41 (27.3) Motor Tics** K-Shoulder 14(37.8) 32 (21.3) 0.037+ K-Block 4( 10.8) 6 (4.0) 0.099 YGTRS scores* Motor tic-Disruption 23.6±13.0 27.3±9.9 0.047+ Laboratory* ASO 218.3±252.1 273.3±216.7 0.033+ Ferritin 24.8±11.4 33.3±19.8 0.035+ Neutrophil 53.8±15.0 49.5±10.0 0.007 + Lymphocyte 33.5±11.1 37.7±8.8 0.004+ Monocyte 6.3±1.9 7.2±2.1 0.030+ RBC 4.6±0.3 4.8±0.3 0.025+ * Mean ± Standard Deviation; ** Given as n (%). + p<0.05; ADHD: attention deficit hyperactivity disorder, OCD: obsessive compulsive disorder, TS: Tourette’s Syndrome, DTB: Other non-Tourette tic disorders, F: complex, AB: antibiotic, YGTRS: Yale General Tic Severity Rating Scale, ASO: Antistreptolysin-O, RBC : red blood cell count Table 2. Characteristics of the cases and distribution of tics by tic disorder subtype DTB TS p Age* 10.9±2.5 10.9±2.7 0.845 Age at first symptom* 7.7±2.7 7.1±2.7 0.687 Comorbidities** OCD 72 (53.3) 36 (69.2) 0.046+ Clinical Features** Antibiotic Prophylaxis in the Family 23 (46.0) 2 (11.1) 0.008+ Hypoxia During Birth 32 (24.8) 3 (6.2) 0.006+ Motor Tics** B-Neck 15 (28.8) 64 (47.4) 0.021+ B-Eye 33 (63.5) 110 (81.5) 0.009+ B-Nose 16 (30.8) 68 (49.6) 0.016+ B-Mouth 20 (38.5) 74 (54.8) 0.045+ B-Face 9 (17.3) 40 ( 29.6) 0.086+ B-Shoulder 8 (15.4) 63 (46.7) 0.0001+ B-Arm 7 (13.5) 36 (26.7) 0.055 B-Abdominal 1 (1.9) 16 (11.9) 0.034+ B-Other – 8 (5.9) 0.073 K-Breast 6 (11.5) 41 (30.4) 0.008+ K-Shoulder 5 (9.6) 41 (30.4) 0.003+ K-Arm 7 (13.5) 40 (29.6) 0.022+ K-Text 9 (6.7) 0.056 K-Leg 3 (5.8) 17 (12.6) 0.176 K-Bending 3 (5.8) 21 (15.6) 0.073 K-Compulsive 7 (13.5) 38 ( 28.1) 0.035+ K-Ezyme 1 (1.9) 14 (10.4) 0.057 Vowel Tics K-Word – 14 (10.4) 0.016+ K-Syllabic 1 (1.9) 26 (19.3) 0.003+ K-Echolalia – 17 (12.6) 0.007 + K-Caprolali – 21 (15.6) 0.003+ K-Palali – 11 (8.1) 0.034+ K-Strange Sound – 9 (6.7) 0.056 * Mean ± Standard Deviation ; ** Given as n (%). + p<0.05, B: Simple, F: Complex; DTD: Other tic disorders other than Tourette’s, OCD: obsessive-compulsive disorder Skin/Volume 44 Years/Year 2019 Clinical features of childhood tic disorders 255 Table 3. Tic scores and laboratory analysis analyzes by age at first symptom 3-9 years 10-18 P Motor Tick Scores* Complex Tics 2.7±2.2 2.2±2.5 0.046** Severity 3.1±0.8 2.8±0.8 0.053 Voice Tick Scores* Complex Tics 0.7±1.2 0.3±0.9 0.055 Count 1.4±1.1 1.0±1.0 0.084 Disability 1.3±1.2 0.9±1.0 0.064 Impairment 15.7±12.8 12.1±11.6 0.059 Overall Scores* General Impairment 45.1±19.7 38.1±17.0 0.031** Motor Tick Score 14.5±4.2 13.3±4.2 0.087 Audible Tick Score 8.3±6.2 6.6±5.9 0.121 Total Score 68.6±28.9 58.1± 25.1 0.023** Laboratory Studies* Neutrophil 49.2±11.4 52.7±11.3 0.024** Lymphocyte 38.1±10.0 34.6±7.9 0.011** Basophil 0.8±0.7 0.9±0.5 0.057 Hematocrit 38.3±2.8 39.3±3.6 0.043** *Mean ± Standard Deviation , **p<0.05 55.4% of our cases started under the age of 9, 35.6% between the ages of 9-12 and 9% above the age of 12. When the groups with first symptom age of 3-9 years and 10-18 years of age were compared according to YGTRS; K-motor tic (p=0.046), general impairment (p=0.031) and total scores (p=0.023) were significantly higher in the 3-9 age group compared to the other group. The comparison of the groups formed according to the age of onset of symptoms is shown in Table 3. While 180 of the cases (96.3%) had at least one co-diagnosis, no co-diagnosis was found in only 7 (3.7%) cases. Cases with no comorbidity had higher YBTSS scale BM neck and CM-shoulder tics ratios, and motor tic severity score averages were higher than cases with at least one comorbidity (respectively; p=0.002, p=0.042, p=0.001). The findings of the comparison of cases with and without comorbidity are presented in Table 4. Table 4. Data of the cases according to whether they have co-diagnosis Co-diagnosis (+) Co-diagnosis (-) p Stories Related to Immunity** Frequent Infection 140 (78.7) 2 (28.6) 0.002+ AB Prophylaxis 128 (71.9) 3 (42.9) 0.097 Motor Tics** B-Neck 72 (40.0) 7 (100) 0.002+ B-Shoulder 66 (36.7) 5 (71.4) 0.063 K-Shoulder 42 (23.3) 4 (57.1) 0.042+ Motor Tick Scores* Frequency 3.6±1.1 4.4±0.7 0.097 Severity 3.0±0.8 4.0±0.5 0.001+ Voice Tick Scores* Intensity 1.8±1.4 2.8±1.2 0.073 Overall Scores* General Impairment 42.4±18.9 44.2±18.8 0.799 Motor Tick Score 13.8±4.4 16.0±3.5 0.173 Audible Tick Score 8.0±6.9 10.1±4.4 0.317 Total Score 64.7±27.8 70.2±24.1 0.497 Laboratory Examinations* Lymphocyte 37.2±9.2 26.2±11.4 0.023+ MPV 7.9±1.2 9.1±1.1 0.018+ * Mean ± Standard Deviation; ** Given as n (%). + p<0.05; B: Simple, C: Complex, AB: antibiotic, MPV: mean platelet volume. Pine Ray et al. Cukurova Medical Journal 256 It was determined that 142 of the cases (75.9%) were diagnosed with ADHD as well as tic disorder. OCD comorbidity was present in 57.8% (n=108) and anxiety disorder comorbidity in 30.4% (n=57) of the cases. The results of the analyzes made by dividing the cases with and without ADHD comorbidity into two groups; the mean age of those with this comorbidity was significantly younger than those without (p=0.022). When the general tic scores were examined in terms of OCD comorbidity, there was no significant difference between those with and without OCD comorbidity. The comparison of cases with and without ADHD and OCD comorbidity is shown in Table 5. Table 5. Comparison of Groups with and Without ADHD and OCD Comorbidity ADHD Comorbidity p OCD Comorbidity p Yes No Yes No Age* 10.6±2.6 11.6±2.5 0.022+ Age* 11.2±2.7 10.5±2. 5 0.049+ Comorbid* 2.5±0.8 1.3±0.9 0.0001+ Comorbid* 2.4±0.9 1.8±1.0 0.000+ Motor Tics** Motor Tics** K-Neck 38(26.8) 6(13.3) 0.064 F-Compulsion 36 ( 33.3) 9 (11.4) 0.001+ K-Volume 40(28.2) 7(15.6) 0.089 Voice Tics** K-Block 5(3.5) 5(11.1) 0.049+ B-Voice 70 (64.8) 62 (78.5) 0.043+ T-(F)-Head/Neck 83(58.5) 17(37.8) 0.015+ Motor Tick Score* Motor Tick Score* Severity 2.9±0.8 3.1±0.8 0.057 Disability 2.1±0.9 1.7±1.0 0.004+ Audible Tick Score* Overall Scores * Number 1.2±1.1 1.4±1.0 0.051 General Impairment 43.5±18.8 39.5±18.9 0.239 Frequency 2.0±1.8 2.4±1.7 0.090 Motor Tick Score 14.1±4.3 13.2±4.4 0.109 Severity 1.7±1.4 2.1±1.3 0.066 Audible Tick Score 8.0±6.1 8.5±8.8 0.841 Total Score 66.4±27.4 60.6±28.4 0.212 Laboratory* Ferritin 33.3±19.8 26.2±13.2 0.073 Lymphocyte 37.7±9.7 34.2±8.2 0.052 RBC 4.8±0.3 4.7±0.3 0.082 * Mean ± Standard Deviation;** n (% ) are given. + p<0.05, ADHD: attention deficit hyperactivity disorder, OCD: obsessive compulsive disorder, B: Simple, F: Complex, RBC: red blood cell count. Compared to the others, the frequency of BM-nose, KM-neck and KM-dystonia tics were found to be lower in patients with anxiety disorders. Comparison of cases with and without anxiety disorder comorbidity is shown in Table 6. Pregnancy and birth histories of the cases, their family history of mental illness and whether they had seizures were recorded. In 30 (38.5%) of 78 cases with sufficient information, there was a history of anemia in the mother during the intrauterine period. There was no significant difference between the two groups in terms of overall tic scores. Birth weight of 88.1% (N=149) of 169 cases whose information was reached was 2.5-4 kg; 7.6% (n=13) of them were less than 2.5 kg; 4.1% of them (n=7) were over 4kg. Thirty-five (19.8%) of 177 cases had a history of hypoxia at birth. When the two groups were compared in terms of tic overall scores; tic general deterioration scores of those with a history of hypoxia (respectively; 47.8±17.6; 40.7±18.7; p=0.035), general motor tic score (respectively; 15.0±4.8; 13.5± 4.2; p=0.029) and grand total scores (respectively; 76.0±26.4; 61.6±27.1; p=0.037) were significantly higher than the others. Seizure history in 18 (10.3%) of 175 cases; EEG disorder was present in 16 (17.8%) of 90 cases. There was no statistically significant difference in terms of tic general scores of those with normal or impaired EEG. There was a history of enuresis in 39 (22.5%) out of a total of 173 cases. Speech disorder was present in 22 (23.4%) of 94 cases with sufficient information. 3 (13.6%) of those with a history of speech disorder had CM copropraxia, but it was not seen in the other group (p=0.001). The rates of KS-echolalia were also higher in those with a history of speech disorder than in those without (p=0.017). Of 168 cases, 141 (83.9%) had a family history of mental illness. A family history of OCD-/tic disorder was defined in 122 (73.1%) of 167 patients, for whom sufficient information was obtained. There was no significant difference between the two groups in terms of overall tic scores. Volume/Volume 44 Year/Year 2019 Clinical features of childhood tic disorders 257 Table 6. Comparison of groups with and without anxiety disorder comorbidity, see Anxiety. (+) Anxiety see. (-) p Comorbid* 2.7±1.0 2.0±0.8 0.0001+ Motor Tics** B-Nose 15 (26.3) 61 (53.1) 0.001+ B-Face 10 (17.5) 39 (30.0) 0.075 N-Neck 8 (14.0) 36 (27.7) 0.043+ K-Dystonic 3 (5.3) 21 (16.2) 0.040+ K-Twist 2 (3.5) 16 (12.3) 0.060 Vocal Tics** K-Syllable 4 (7.0) 23 (17.7) 0.056 Motor Tick Score * Complexity 2.1±1.2 2.4±1.3 0.070 Disability 1.7±0.8 2.1±1.0 0.024+ Impairment 22.7±9.7 28.2±10.8 0.001+ Overall Scores* General Impairment 37.4±16.3 44.8±19.5 0.026+ Total Score 57.9±24.1 68.0±28.6 0.041+ Laboratory Studies* Ferritin 27.4±16.8 33.4±19.2 0.051 MCV 81.5±6.3 79.4±8.5 0.042+ * Mean ± Standard Deviation; ** Given as n (%). + p<0.05, B: Simple, F: Complex; MCV: mean erythrocyte volume DISCUSSION According to the results of our study, male cases, early onset and multiple comorbidities are observed in childhood tic disorders. The mean age of 187 patients included in the study was 10.9±2.6 years, 37 of which were girls and 150 were boys. Similar to our study, in a study that included 126 children and adolescents aged 5-17 years, the mean age of the participants was 10.7 years, with men making up 78.6% of the sample33. The fact that the number of males is higher here is consistent with the information that males are affected more frequently than females in the literature studies4,5,34 and this rate is approximately 4 times7,9. Similar to the rates of 66.7% and 73.7% TS and 26.3% and 33.3% other tic disorders reported in studies involving children and adolescents with tic disorders35,36; 72.2% of our cases were diagnosed with Tourette Syndrome and 26.7% with DBT. In our study, boys (56.1%) were diagnosed with TS at a higher rate than girls (17.5%). In addition, when the cases in the TS and DBT groups were compared according to the tic disorder subtypes; There was no significant difference between the two groups in terms of mean age, age at presentation, and age at first symptom. Consistent with the information that various comorbid psychiatric disorders frequently accompany tic disorders, and especially children with TS in current studies7,18,22,37, 96.3% of our cases had at least one comorbidity, while only 3.7% of them had any comorbidity. He had no co-diagnosis. In studies conducted with children with tic disorders in our country, it has been reported that more than 80% of the cases have at least one comorbidity 35,36. In the group with at least one comorbidity, the mean age at presentation was found to be lower than the group without comorbidity, although it was not statistically significant. In the literature, it has been stated that the comorbid diagnosis symptoms in tic disorders generally manifest before the tics become clinically noticeable, and most comorbid conditions are between the ages of 4-10 15,16,17. It can be thought that the cases present earlier, as they cause psychopathological, social and academic disorders, which are caused by both tics and comorbidities, and even more so in some studies. In addition, it has been reported that comorbidity is associated with worse functional outcomes16,17 and the presence of comorbidity significantly increases the risk of mortality38. Unlike studies that reported that tic severity was associated with premature urges, the presence of copro-, echo-, and palifenomen, and the number of comorbidities39, overall tic scores were reported by Çam Ray et al. In terms of Cukurova Medical Journal 258, there was no significant difference between those with at least one comorbidity and those without. The motor complex tic score, tic general impairment score, and tic total score were significantly higher in cases with the age of first symptom between 3-9 years of age, compared to the group whose age at first symptom was between 10-18 years; motor tic severity score, vocal complex tic score, and vocal tic impairment score were slightly higher. Our findings show that the mean age of onset of tics is 6.4 years7,9, 90-95% of TS cases begin between 4-13 years of age13, and tic severity peaks between 8-12 years of age 13,14,15. appears to be consistent with studies reporting that tics have disappeared or improved significantly9,15,19. However, in a study conducted with children and adolescents aged 5-17 years, there was no significant difference in YGTS scores33. Similar to the studies in the literature reporting that ADHD is the most common comorbid disorder in individuals with TS, the most common comorbidity among our cases was ADHD with a rate of 75.9%10,15,17. Similarly, ADHD was reported as the most common comorbidity, with 60% and 61.2%, respectively, in samples of 3500 children and adolescents diagnosed with TS from 64 different centers from 22 countries and 5060 children and adolescents from 27 countries7,37. In studies conducted in our country, the rates of ADHD in children with tic disorders were found to be 40.4%, 25.0% and 14.2%, lower than our study35,36,40. The difference in these rates can be explained by characteristics such as the number of the sample group, age and gender. Similar to the available data, there was no significant difference in tic severity between individuals with TS with or without ADHD, in our study, no significant difference was found between those with and without ADHD comorbidity in terms of general tic scores23,37,41,42. In our study, the mean age and admission age of the cases with ADHD were found to be lower than those without ADHD. Our data coincide with studies in which ADHD symptoms generally start before the onset of tics and ADHD comorbidity is more effective in terms of psychopathology and impairment in functionality than the severity of the tic, when TS and ADHD coexist 23,37,41,42. Similar to previous studies; ADHD comorbidity was significantly more common among boys than girls in statistical analyzes43. In addition, it has been reported that the rate of having at least one comorbidity and the mean number of comorbidities are significantly higher in boys compared to girls, and that the comorbidity score in boys is significantly higher than in girls7. On the other hand, considering that ADHD is more common among males in our study, it may be compatible with studies showing that tic disorders accompanied by ADHD have more comorbidities7,22,23. It is also stated that gender differences are likely to be a factor specific not only to ADHD comorbidity but also to tic disorders43. OCD co-diagnosis of 57.8% in our cases in terms of OCD comorbidity rate is consistent with the information reported in current studies that approximately 50-60% of TS patients have obsessive compulsive symptoms or OCD7,9,14,23,39. In addition, the rates of OCD comorbidity in our study were lower than 75% reported in children with TS and higher than 19.3% and 18.8% reported in children with tic disorders35,36,40. In contrast to studies in which OCD with comorbid tics started at an early age,44 patients with OCD had a higher mean age and age at presentation than patients with OCD without tic. There was no significant difference between the comorbidity of OCD in terms of age at first symptom. The frequency of OCD comorbidity was significantly higher among the patients with DTB compared to the patients with TS. It was determined that there was no significant difference between those with and without OCD comorbidity in terms of general tic scores, but those without OCD had slightly higher motor tic severity score and vocal tic score score than those with OCD. However, in the literature, it has been reported that TS patients with OCD comorbidity have more severe tics than TS patients without OCD21,23,42. One of the interesting results of the study is that, contrary to expectations, the severity of tics is low in cases accompanied by OCD. In this, the possibility that the compulsion-like behaviors interpreted in OCD overlaps with the motor movements that are actually tics comes to mind. In general, it was found that tic severity and comorbid diseases were associated with high tic severity, and comorbid self-harming behavior had the highest effect on tic severity, followed by anger, depression, anxiety, OCD, and finally ADHD7. Unlike our findings, the coexistence of OCD and tic coexistence obsessive compulsive tic Skin/Volume 44 Year/Year 2019 Clinical features of childhood tic disorders 259 revealed the concept of the disorder, and earlier symptom onset, male gender, and a higher probability of having sensory phenomena were reported44 ,45,46. The mean number of comorbidities was found to be significantly higher in those with ADHD, OCD, and anxiety disorder comorbidities compared to those without. In our data, it has been reported that the presence of OCD in patients with TS increases the rate of comorbid other diseases23,44,47 and in the presence of ADHD in patients with TS or CMT with ADHD, it has been reported that it increases the rate of having more comorbid psychiatric symptoms and other comorbid diseases23,34,41. It is an interesting point, and important in terms of phenomenology, that it has been stated that comorbid OCD significantly increases the presence of internalized disorders such as mood disorders and anxiety disorders23,47, while ADHD increases the risk of externalized disorders such as OCD23. It has been reported that impulse control problems such as depression, anger control and sexual inappropriate behaviors, personality disorders, self-harming behavior and sleep problems affect these patients more in TS patients with ADHD and/or OCD compared to patients without these comorbidities7,22, 34.47. Although the common genetic and environmental etiopathogenesis of TS, ADHD and childhood-onset OCD patients has not been fully elucidated by the studies in the literature, neurobiological studies draw attention to cortico-striatothalamocortical pathways48. In particular, the association of Sydenham’s chorea, OCD and tic disorder with the basal ganglia of the brain and related cortical and thalamic regions, the common phenotypic features of OCD and tic disorders were remarkable, and hypotheses and evidence regarding their relationship with the pediatric acute-onset neuropsychiatric syndrome (PANS), on which autoimmune mechanisms are blamed. presented49. In a study conducted with 1374 children and adults with TS, a lifetime diagnosis of anxiety disorder was reported as 31.4% and a diagnosis of depression at 22.9%, and the prevalence rates for anxiety were reported to be significantly higher in those with TS + OCD than in those with TS + ADHD39. In our study, 30.5% of our cases had anxiety disorders, similar to these rates. In our study, 23.4% of 94 cases had a history of articulation defects and/or speech disorders in the form of stuttering. This rate was higher than the prevalences reported for speech disorders in the population. 13.6% of those with a history of speech disorder had CM copropraxia, and the rates of KS-echolalia were high. These data may be compatible with studies reporting that developmental stuttering is associated with involuntary movements, complex and simple motor tics, and that there is a relationship between stuttering and Tourette’s syndrome50,51. 10.3% of 175 cases had a history of seizures; EEG disorder was present in 17.8% of 90 cases with EEG recordings. This data was obtained from Toros et al. (2002)40 In the EEG examinations of 28 cases, 14.3% nonspecific EEG findings were consistent with pathological EEG findings supported by clinical findings in 7.1%. Tik bozukluklarının etiyolojisinde, komorbidite varlığı ve semptom şiddeti üzerine perinatal olayların ve psikososyal stresin olası etkileri üzerinde önemle durulmuştur. Olgularımızda hipoksi , annede gebelikte anemi ve bebekte düşük doğum ağırlığı öyküsü belirgindi. Perinatal faktörlerin etkilerinin araştırıldığı bir çalışmada, annenin sigara içimi ve düşük doğum ağırlığının TS başlangıcı, komorbidite varlığı ve semptom şiddeti için en tutarlı ilişkili faktörler olarak bildirilmiş ve mekanizma tam bilinmese de, bunların erken beyin hasarı sonucu dopaminerjik sistem değişikliklerine bağlı olabileceği belirtilmektedir52. 168 olgunun % 83,9 ailede ruhsal hastalık, 167 olgunun % 73,1’inde ailede OKB ve/veya tik bozukluğu öyküsü vardı öyküsü vardı. Ülkemizde yapılmış çalışmalarda bildirilen birinci derece akrabalarında en az bir ruhsal bozukluğa sahip olma oranı olan % 32,5, tik bozukluğu olan hastaların % 17,5’inde ailesinde KVMT ve TS’lerin % 14,3’ünde ailesinde OKB ve % 7,2’sinde ailesinde motor tik öyküsü bildirilmektedir35,40. Bu oranların çalışmamızda daha yüksek olması, bildirilen oranın sadece birinci derece akrabaları değil, geniş ailedeki oranları içermesi ile ilgili olabileceği düşünülmektedir. Ailesel genetik çalışmalar, OKB ve TS’deki genetik bozuklukların benzerlik gösterdiği53, TS’li hastalarda, OKB’nin veya subklinik OKB’nin varlığının, birinci derece akrabalarında komorbid DEHB ve TS birlikteliğinin bulunması riskini belirgin oranda arttırdığını belirtilmektedir64. Yazında komorbiditelerin tipi, tikler ve tik-ilişkili davranışlar TS fenomenolojisini ve tedavisini karmaşıklaştırdığı görülebilmektedir. Araştırmamızın önemi, çocukluk çağı tik bozukluklarının fenomenolojik açıdan değerlendirilmesidir. Çam Ray ve ark. Cukurova Medical Journal 260 Çalışmamızda, erkek olgu, erken başlangıç, DEHB, OKB gibi tanıların sık olduğu, eş tanı sıklığının yüksek olduğu saptanmıştır. DEHB en sık eşlik eden tanı olması olguların tedavi için başvuru yaşını belirgin olarak düşürmektedir. Çalışmanın ilgi çekici sonuçlarından biri de beklenenin aksine OKB nin eşlik ettiği olgularda tik şiddetinin düşük olmasıdır. Yine eşlik eden tanılardan kekemelik ve enurezis öyküleri tik bozukluklarındaki nörogelişimsel gecikmelerle uyumlu görünmektedir ve özellikle kekemelik, tik ve OKB’yi içeren bozuklukların bazal ganglion patolojisi ile ilişkilendirilmeleri ortak etyolojiye dikkat çekmektedir. Tik bozukluklarında başlangıç yaşı, komorbidite cinsiyet, motor tiklerin karmaşıklığı, ailesel ruhsal ve gelişimsel öykülerin mevcut klinik görünüm ve olası tedavi seçenekleri üzerinde belirleyici olabileceği düşünülmektedir. Yazar Katkıları: Çalışma konsepti/Tasarımı: PRÇ, GGÇ, AT; Veri toplama: PRÇ, GGÇ, AT; Veri analizi ve yorumlama: GGÇ, AT, AA; Yazı taslağı: PRÇ, ÇDC, GGÇ; İçeriğin eleştirel incelenmesi: GGÇ, AA, AT; Son onay ve sorumluluk: RÇR, GGÇ, AT, ÇCDJ, AA; Teknik ve malzeme desteği: -; Süpervizyon: GGÇ, AT; Fon sağlama (mevcut ise): yok. Bilgilendirilmiş Onam: Katılımcılardan yazılı onam alınmıştır. Hakem Değerlendirmesi: Dış bağımsız. Çıkar Çatışması: Yazarlar çıkar çatışması beyan etmemişlerdir. Finansal Destek: Yazarlar finansal destek beyan etmemişlerdir. Author Contributions: Concept/Design : PRÇ, GGÇ, AT; Data acquisition: PRÇ, GGÇ, AT; Data analysis and interpretation: GGÇ, AT, AA; Drafting manuscript: PRÇ, ÇDC, GGÇ; Critical revision of manuscript: GGÇ, AA, AT; Final approval and accountability: RÇR, GGÇ, AT, ÇCDJ, AA; Technical or material support: -; Supervision: GGÇ, AT; Securing funding (if available): n/a. Informed Consent: Written consent was obtained from the participants. Peer-review: Externally peer-reviewed. Conflict of Interest: Authors declared no conflict of interest. Financial Disclosure: Authors declared no financial support KAYNAKLAR 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 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