Functional Tic-Like Behaviors: A Common Comorbidity in Patients with Tourette Syndrome.

BACKGROUND: Comorbid functional tic-like behaviors (FTB) have been described only rarely in patients with Tourette syndrome (TS). OBJECTIVES: We present the first large sample of patients suffering from TS and FTB to raise awareness of this clinical presentation and to guide how to differentiate one from the other. METHODS: We analyzed clinical data of 71 patients (n = 27 [38.0%] female, mean age: 21.5, range: 11-55) with TS + FTB. RESULTS: In the majority of patients, FTB started abruptly on average 15 years after tic onset with "treatment-resistant" complex movements and ("coprophenomena-like") vocalizations preceded by timely related psychological stressors. Psychological evaluation revealed evidence for internal conflicts (79%), emotional dysregulation (56%), and maintaining factors (70%). About one third of patients had a positive history for further medically unexplained symptoms. Compared to a large TS sample (n = 1032), patients with TS + FTB were more likely to be female, and presented significantly more common with "coprophenomena-like" symptoms, atypical influential factors, atypical descriptions of premonitory sensations, and higher rates of comorbid obsessive-compulsive disorder and "self-injurious" behavior. CONCLUSIONS: Based on our data it can be assumed that FTB is a common comorbidity in TS, similar to functional overlay in other movement disorders and epilepsy. Before classifying a patient as suffering from treatment-resistant TS, FTB should be ruled out.

Non-just-right experiences are more closely related to OCD than tics in Tourette patients.

Complex tics and obsessive or compulsive behaviour can be difficult to differentiate diagnostically. The majority of adult patients with Tourette syndrome report experiencing premonitory urges before tics. Some of these experiences have been linked to non-just-right experiences (NJRE), which are frequently reported by patients with obsessive-compulsive disorder or behaviours (OCD/OCB). We aimed to assess whether NJRE are more closely related to tics and tic-associated premonitory urges or whether they are more closely associated with OCD. A total of N = 111 patients (mean age = 34.77 + /-12.93; N = 37 female) with a confirmed diagnosis of Tourette syndrome completed the premonitory urges for tic disorders scale (PUTS), the revised non-just-right experiences scale (NJRE-QR), and questionnaires regarding their tic severity, and comorbid OCD/OCB. A multi-trait-multi-methods matrix was calculated to examine associations amongst scales measuring tic-related and OCB-related phenomena. The PUTS correlated overall higher with tic questionnaires than with OCD/OCB questionnaires. The NJRE correlated higher with OCD symptoms than with tic severity. The results indicate that non-just-right experiences are more closely associated with comorbid OCB than with tics in patients with Tourette syndrome.

Premonitory Urge and Tic Severity, Comorbidities, and Quality of Life in Chronic Tic Disorders.

Background: Tics are intimately associated with premonitory urges (PU) but knowledge about urges is still limited, with small sample sizes often limiting the generalizability of findings. Objectives: This study addressed the following open questions: (1) is tic severity associated with urge severity, (2) how common is relief, (3) which comorbidities are associated with urges, (4) are urges, tics, and comorbidities associated with lower quality of life, and (5) can complex and simple, motor and vocal tics be differentiated based on PU? Methods: N = 291 patients who reported a confirmed diagnosis of chronic primary tic disorder (age = 18-65, 24% female) filled out an online survey assessing demographic data, comorbid conditions, location, quality and intensity of PU, as well as quality of life. Every tic was recorded, and whether the patient experienced a PU, the frequency, intensity, and quality of that urge. Results: PU and tic severity were significantly associated, and 85% of urge-related tics were followed by relief. A diagnosis of attention deficit/hyperactivity disorder (ADHD) or depression, female gender, and older age increased the likelihood of experiencing PU, while more obsessive compulsive (OCD) symptoms and younger age were associated with higher urge intensities. PU, complex vocal tics, ADHD, OCD, anxiety, and depression were related to lower quality of life. Motor and vocal, complex and simple tics did not differ regarding PU intensity, frequency, and quality, or relief. Conclusions: The results shed light on the relationship between PU, tics, comorbidities, age, gender, and quality of life in tic disorders.

The Rush Video-Based Tic Rating Scale-Revised: A Practice-Oriented Revision.

Background: The Modified Rush Video-Based Tic Rating Scale (MRVS) is the most widely used video-based scale for assessing tic severity in patients with Tourette syndrome (TS). However, shortcomings of the MRVS, including a lack of clear instructions, a time-consuming recording procedure, and weak correlations with the gold standard for tic assessment, the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS), limits its use in research settings, although video assessments are generally considered objective, reliable, and time-saving measurements. Objectives: We aimed to revise the MRVS (MRVS-R) to simplify and standardize the assessment procedure and improve the correlation with the YGTSS-TTS. Methods: We used 102 videos of patients with TS or persistent motor tic disorder filmed according to the MRVS. We compared the tic frequency assessed by MRVS with frequencies according to MRVS-R based on a 5-min (instead of a 10-min) video to investigate whether reducing the recording time leads to significant changes. In addition, we adapted the MRVS to the YGTSS and defined new anchor values for motor and phonic tic frequency based on frequency distributions as assessed in our sample. Finally, we compared the MRVS-R and MRVS regarding psychometric properties and correlation with the YGTSS-TTS. Results: Cutting video recording time in half did not significantly affect assessments of motor and phonic tic frequencies. Psychometric properties were acceptable. Most important, proposed revisions of the MRVS improved correlation with the YGTSS-TTS. Conclusions: The MRVS-R is a simplified version of the MRVS with comparable psychometric qualities, but higher correlations with the YGTSS-TTS.

CANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders - Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study.

Preliminary data suggest that cannabis-based medicines might be a promising new treatment for patients with Tourette syndrome (TS)/chronic tic disorders (CTD) resulting in an improvement of tics, comorbidities, and quality of life. This randomized, multicenter, placebo-controlled, phase IIIb study aimed to examine efficacy and safety of the cannabis extract nabiximols in adults with TS/CTD (n = 97, randomized 2:1 to nabiximols:placebo). The primary efficacy endpoint was defined as a tic reduction of ≥ 25% according to the Total Tic Score of the Yale Global Tic Severity Scale after 13 weeks of treatment. Although a much larger number of patients in the nabiximols compared to the placebo group (14/64 (21·9%) vs. 3/33 (9·1%)) met the responder criterion, superiority of nabiximols could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Additionally exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder suggesting that these subgroups may benefit better from treatment with cannabis-based medication. There were no relevant safety issues. Our data further support the role of cannabinoids in the treatment of patients with chronic tic disorders.

Prevalence and clinical correlates of misophonia symptoms in the general population of Germany.

Introduction: Misophonia refers to a phenomenon in which affected individuals have a selective intolerance to sounds of mostly oral or nasal origin. This intolerance is typically associated with strong emotional reactions such as anger, irritation, and disgust. The aim of this study was to conduct the first large epidemiological survey to determine the prevalence of misophonia symptoms in the adult population in Germany. Methods: We conducted a large-scale representative population survey between December 2020 and March 2021. For this purpose, a sample of 2,519 people were visited in their households and assessed with the Misophonia Questionnaire (MQ) and the Amsterdam Misophonia Questionnaire (AMISOS-R) to document misophonic symptoms. The primary estimate of clinical misophonia symptoms prevalence was based on the MQ Severity Scale and a secondary estimate was based on the AMISOS-R. The survey further included self-ratings to measure perfectionism, not-just-right experience (NJRE), autonomous sensory meridian response (ASMR) and general health as well as demographic data. Results: Five percent of the sample scored equal or above the MQ Severity Scale threshold for clinical misophonia symptoms (5.9% based on AMISOS-R). Individuals with clinical misophonia symptoms had a higher rate of perfectionism, a higher occurrence of NJRE, higher susceptibility to ASMR, and a worse general health status than those scoring below the cut-off-score. All those factors also independently predicted the severity of misophonia symptoms in a multiple regression model. Conclusion: Misophonia is a frequent condition and should further be examined as an independent diagnostic entity.

Implications for blinding in clinical trials with THC-containing cannabinoids based on the CANNA-TICS trial.

Randomized double-blind placebo-controlled trials (RCTs) are regarded as the gold standard for clinical trials. While there are established standards to avoid unblinding, in RCTs using tetrahydrocannabinol (THC) containing cannabinoids, however, accidental unblinding and intentional self-unbinding must be considered as a particular issue, since THC tests are widely available. To investigate unblinding rates in an RCT using a THC-containing cannabinoid, we re-contacted 54 out of 97 participants of the CANNA-TICS trial who had participated in our study center in Hannover. Of the 54 participants, 53 could be reached. Of these, one participant (2%) stated that she had unblinded herself intentionally during the treatment phase, and another three patients (6%) reported intentional unblinding after the end of the treatment. Noteworthy, two patients provided discrepant information and denied self-unblinding during the interview, although during study/clinic visits they had reported having done so. Thus, based on all available information, three participants (6%) unblinded themselves intentionally during the treatment phase and another three (6%) after the end of the treatment. Accidental unblinding during the treatment phase was reported by 4/54 participants (7%) (during study visits). Since one participant reported both intentional self-unblinding (during the interview) and accidental unblinding (during a study visit), the total unblinding rate was 17% (n = 9). Of these, seven participants (13%) reported unblinding during the treatment phase. When asked in the interview whether they knew that self-unblinding would have been possible, only 34% (n = 18/53) of participants stated that they had been aware of this possibility. Thus, altogether 33% (n = 6/18) of those being informed about the possibility of self-unblinding did so and half of them (3/18, 17 %) during the treatment phase. It can be expected that in parallel to increasing knowledge of medicinal and recreational use of cannabinoids, more and more people will also be informed about the availability of THC tests. Hence, in future RCTs using THC-containing cannabinoids, researchers have to take the possibility of accidental and intentional unblinding into consideration, when designing the study.

Premonitory Urges Reconsidered: Urge Location Corresponds to Tic Location in Patients With Primary Tic Disorders.

OBJECTIVE: In patients with Tourette syndrome and other primary tic disorders (PTDs), tics are typically preceded by premonitory urges (PUs). To date, only a few studies have investigated the location and frequency of PUs, and contrary to clinical experience, the results suggest that PUs are not located in the same anatomic region as the tics. This study aimed to further explore PU location and frequency in detail, differentiating the kind and complexity of the corresponding tics, in a large sample of patients with PTD. METHODS: A total of 291 adult (≥ 18 years) patients with a confirmed diagnosis of chronic PTD were included. The study was conducted online, assement included tics and the general characterization of PUs and a sophisticated body drawing for locating PUs. RESULTS: We found that PUs were located in the same body area as, or in direct proximity to, the corresponding tic. Most frequently, PUs were located in the face and at the head (62.1%). Compared with simple tics, complex (motor and vocal) tics were more often preceded by a PU; but there was no difference in PU frequency observed between motor tics and vocal tics. PUs were more often experienced at the front than at the back of the body (73% vs. 27%), while there was no difference between the right and left sides (41.6% vs. 41.3%). CONCLUSION: The strong association between PU and tic location further supports the hypothesis that PUs represent the core of PTD. Accordingly, future therapies should focus on treating PUs to achieve greater tic reduction.

ONLINE-TICS: Internet-Delivered Behavioral Treatment for Patients with Chronic Tic Disorders.

Comprehensive Behavioral Intervention for Tics (CBIT) is considered a first-line therapy for tics. However, availability of CBIT is extremely limited due to a lack of qualified therapists. This study is a multicenter (n = 5), randomized, controlled, observer-blind trial including 161 adult patients with chronic tic disorders (CTD) to provide data on efficacy and safety of an internet-delivered, completely therapist-independent CBIT intervention (iCBIT Minddistrict®) in the treatment of tics compared to placebo and face-to-face (f2f) CBIT. Using a linear mixed model with the change to baseline of Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) as a dependent variable, we found a clear trend towards significance for superiority of iCBIT (n = 67) over placebo (n = 70) (-1.28 (-2.58; 0.01); p = 0.053). In addition, the difference in tic reduction between iCBIT and placebo increased, resulting in a significant difference 3 (-2.25 (-3.75; -0.75), p = 0.003) and 6 months (-2.71 (-4.27; -1.16), p < 0.001) after the end of treatment. Key secondary analysis indicated non-inferiority of iCBIT in comparison to f2f CBIT (n = 24). No safety signals were detected. Although the primary endpoint was narrowly missed, it is strongly suggested that iCBIT is superior compared to placebo. Remarkably, treatment effects of iCBIT even increased over time.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part II: psychological interventions.

Part II of the European clinical guidelines for Tourette syndrome and other tic disorders (ECAP journal, 2011) provides updated information and recommendations for psychological interventions for individuals with tic disorders, created by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain original studies of psychological interventions for tic disorders, published since the initial European clinical guidelines were issued. Relevant studies were identified using computerized searches of the MEDLINE and PsycINFO databases for the years 2011-2019 and a manual search for the years 2019-2021. Based on clinical consensus, psychoeducation is recommended as an initial intervention regardless of symptom severity. According to a systematic literature search, most evidence was found for Habit Reversal Training (HRT), primarily the expanded package Comprehensive Behavioral Intervention for Tics (CBIT). Evidence was also found for Exposure and Response Prevention (ERP), but to a lesser degree of certainty than HRT/CBIT due to fewer studies. Currently, cognitive interventions and third-wave interventions are not recommended as stand-alone treatments for tic disorders. Several novel treatment delivery formats are currently being evaluated, of which videoconference delivery of HRT/CBIT has the most evidence to date. To summarize, when psychoeducation alone is insufficient, both HRT/CBIT and ERP are recommended as first-line interventions for tic disorders. As part of the development of the clinical guidelines, a survey is reported from ESSTS members and other tic disorder experts on preference, use and availability of psychological interventions for tic disorders.

Stop that! It's not Tourette's but a new type of mass sociogenic illness.

We report the first outbreak of a new type of mass sociogenic illness that in contrast to all previously reported episodes is spread solely via social media. Accordingly, we suggest the more specific term 'mass social media-induced illness'. In Germany, the current outbreak of mass social media-induced illness is initiated by a 'virtual' index case, who is the second most successful YouTube creator in Germany and enjoys enormous popularity among young people. Affected teenagers present with similar or identical functional 'Tourette-like' behaviours, which can be clearly differentiated from tics in Tourette syndrome. Functional 'Tourette-like' symptoms can be regarded as the 'modern' form of the well-known motor variant of mass sociogenic illness. Moreover, they can be viewed as the 21st century expression of a culture-bound stress reaction of our post-modern society emphasizing the uniqueness of individuals and valuing their alleged exceptionality, thus promoting attention-seeking behaviours and aggravating the permanent identity crisis of modern man. We wish to raise awareness of the current global Tourette-like mass social media-induced illness outbreak. A large number of young people across different countries are affected, with considerable impact on health care systems and society as a whole, since spread via social media is no longer restricted to specific locations such as local communities or school environments spread via social media is no longer restricted to specific locations such as schools or towns.

Validation of the Rage Attack Questionnaire-Revised (RAQ-R) in a Mixed Psychiatric Population.

Rage Attacks (RA) represent a clinically relevant symptom in patients with different psychiatric disorders. However, only recently the Rage Attack Questionnaire Revised (RAQ-R, 22 items, range, 0-66) has been developed as a new instrument for the assessment of RA. This study aimed to validate the RAQ-R in a large mixed psychiatric and psychosomatic sample. We tested internal consistency, convergent and discriminant validity as well as factor structure. In order to further explore the relationship of RA to other psychiatric symptoms, we calculated Pearson correlations between the RAQ-R and several other self-assessments including measurements for general psychological distress, quality of life, depression, anxiety, attention deficit/hyperactivity disorder (ADHD), impulsivity, and self-regulation abilities. Most relevant predictors of RA were examined in a multiple regression with stepwise elimination. In order to assess the manifestation of RA in different psychiatric disorders, group differences between diagnostic categories and healthy controls were calculated. Additionally, psychiatric patients were compared to patients with Tourette syndrome along RAQ-R scores. Data from healthy subjects and patients with Tourette syndrome were obtained from a previous study of our group. In this study, we included 156 patients with a wide and typical spectrum of psychiatric diseases. The RAQ-R was found to have excellent internal consistency and strong construct validity in this sample (Cronbach's α = 0.97, Average Variance Extracted = 0.58). Thus, the RAQ-R was shown to be a psychometrically sound assessment of RA in patients with different psychiatric disorders. Close constructs to RA were found to be aggression and hostility (r = 0.68) as well as low frustration tolerance and impulse control (r = 0.69). Compared to healthy controls, RA were significantly more common in the psychiatric sample (p < 0.001). More specifically, RAQ-R scores in all diagnostic categories assessed were higher compared to controls. Highest scores and effect sizes were found in patients with ADHD and borderline personality disorder (p < 0.001). Our results suggest that RA are a common and relevant symptom in many psychiatric disorders. As depression and RA showed only a moderate relation, RA should be distinguished from the concept of anger attacks, which are described as a core symptom of depression.

Yale Global Tic Severity Scale (YGTSS): Psychometric Quality of the Gold Standard for Tic Assessment Based on the Large-Scale EMTICS Study.

The Yale Global Tic Severity Scale (YGTSS) is a clinician-rated instrument considered as the gold standard for assessing tics in patients with Tourette's Syndrome and other tic disorders. Previous psychometric investigations of the YGTSS exhibit different limitations such as small sample sizes and insufficient methods. To overcome these shortcomings, we used a subsample of the large-scale "European Multicentre Tics in Children Study" (EMTICS) including 706 children and adolescents with a chronic tic disorder and investigated convergent, discriminant and factorial validity, as well as internal consistency of the YGTSS. Our results confirm acceptable convergent and good to very good discriminant validity, respectively, indicated by a sufficiently high correlation of the YGTSS total tic score with the Clinical Global Impression Scale for tics (r s = 0.65) and only low to medium correlations with clinical severity ratings of attention deficit/hyperactivity symptoms (r s = 0.24), obsessive-compulsive symptoms (r s = 27) as well as internalizing symptoms (r s = 0.27). Internal consistency was found to be acceptable (Ω = 0.58 for YGTSS total tic score). A confirmatory factor analysis supports the concept of the two factors "motor tics" and "phonic tics," but still demonstrated just a marginal model fit (root mean square error of approximation = 0.09 [0.08; 0.10], comparative fit index = 0.90, and Tucker Lewis index = 0.87). A subsequent analysis of local misspecifications revealed correlated measurement errors, suggesting opportunities for improvement regarding the item wording. In conclusion, our results indicate acceptable psychometric quality of the YGTSS. However, taking the wide use and importance of the YGTSS into account, our results suggest the need for further investigations and improvements of the YGTSS. In addition, our results show limitations of the global severity score as a sum score indicating that the separate use of the total tic score and the impairment rating is more beneficial.

The CANNA-TICS Study Protocol: A Randomized Multi-Center Double-Blind Placebo Controlled Trial to Demonstrate the Efficacy and Safety of Nabiximols in the Treatment of Adults With Chronic Tic Disorders.

Background: Gilles de la Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by motor and vocal tics. First-line treatments for tics are antipsychotics and tic-specific behavioral therapies. However, due to a lack of trained therapists and adverse events of antipsychotic medication many patients seek alternative treatment options including cannabis. Based on the favorable results obtained from case studies on different cannabis-based medicines as well as two small randomized controlled trials using delta-9-tetrahydrocannabinol (THC), we hypothesize that the cannabis extract nabiximols can be regarded as a promising new and safe treatment strategy in TS. Objective: To test in a double blind randomized clinical trial, whether treatment with the cannabis extract nabiximols is superior to placebo in patients with chronic tic disorders. Patients and Methods: This is a multicenter, randomized, double-blind, placebo controlled, parallel-group, phase IIIb trial, which aims to enroll 96 adult patients with chronic tic disorders (TS or chronic motor tic disorder) across 6 centers throughout Germany. Patients will be randomized with a 2:1 ratio into a nabiximols and a placebo arm. The primary efficacy endpoint is defined as tic reduction of at least 30% (compared to baseline) according to the Total Tic Score of the Yale Global Tic Severity Scale (YGTSS-TTS) after 13 weeks of treatment. In addition, several secondary endpoints will be assessed including changes in different psychiatric comorbidities, quality of life, driving ability, and safety assessments. Discussion: This will be the first large, controlled study investigating efficacy and safety of a cannabis-based medicine in patients with TS. Based on available data using different cannabis-based medicines, we expect not only a reduction of tics, but also an improvement of psychiatric comorbidities. If the cannabis extract nabiximols is proven to be safe and effective, it will be a valuable alternative treatment option. The results of this study will be of high health-economic relevance, because a substantial number of patients uses cannabis (illegally) as self-medication. Conclusion: The CANNA-TICS trial will clarify whether nabiximols is efficacious and safe in the treatment of patients with chronic tic disorders. Clinical Trial Registration: This trial is registered at clinicaltrialsregister.eu (Eudra-CT 2016-000564-42) and clinicaltrials.gov (NCT03087201).

N-Acetylcysteine for Pediatric Obsessive-Compulsive Disorder: A Small Pilot Study.

Background: Many children and adults with Obsessive-Compulsive Disorder (OCD) fail to respond to first-line pharmacological and behavioral treatments. Glutamate dysfunction may contribute to the development of OCD. N-acetylcysteine (NAC), a glutamate modulating drug, has shown to be a promising agent in adults with OCD. Methods: We conducted a double-blind, placebo-controlled clinical trial from July 2012 to January 2017. Children ages 8 to 17 years with OCD were assigned to receive NAC (up to 2700 mg/day) or the matching placebo for a period of 12 weeks. Children were required to be on stable psychiatric treatment (both medication and therapy) but were not required to be treatment-refractory. The primary outcome was OCD symptom severity as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We used linear mixed models to analyze the effect of NAC compared to placebo. Results: Due to poor recruitment and eventual expiration of the study medication, enrollment was stopped at 11 children out of a planned sample size of 40. Nonetheless, NAC was associated with significant reduction in CY-BOCS total score compared to placebo (Satterthwaite's test: t (37) = 2.36, p = 0.024) with effects separating from placebo beginning at week 8. Mean CY-BOCS total score decreased in the NAC group from 21.4 ± 4.65 at baseline to 14.4 ± 5.55 at week 12. In the placebo group, mean CY-BOCS total score remained unchanged (21.3 ± 4.65). In the NAC group, 1 out of 5 participants achieved >35% improvement in CY-BOCS total score, while none of the six patients in placebo group reached this improvement level. NAC and placebo were well tolerated. One mild adverse event was reported in each group. Conclusions: Our trial suggests that there may be some initial improvement in OCD symptom severity with NAC treatment. NAC was well tolerated in the study population. Future trials should employ multiple sites and have a larger study population to further confirm any benefits of NAC.

Treatment of Gilles de la Tourette Syndrome with Cannabis-Based Medicine: Results from a Retrospective Analysis and Online Survey.

Introduction: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder that is characterized by motor and vocal tics and psychiatric comorbidities, including attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive behavior/disorder (OCB/OCD). From anecdotal reports and preliminary controlled studies, it is suggested that cannabis-based medicine (CBM) may improve tics and comorbidities in adults with GTS. This study was designed to further investigate efficacy and safety of CBM in GTS and specifically compare effects of different CBM. Materials and Methods: First, we performed a retrospective data analysis including all those adult patients seen at our clinic, who had used CBM for the treatment of GTS at some time. All these patients were asked to complete an online survey (second study part) to receive more detailed data about treatment with CBM. Results: From medical records, we identified 98 patients who had used CBM (most often street cannabis followed by nabiximols, dronabinol, medicinal cannabis) for the treatment of GTS: Of the 38 patients who were able to judge, 66% preferred treatment with medicinal cannabis, 18% dronabinol, 11% nabiximols, and 5% street cannabis. Altogether, CBM resulted in a subjective improvement of tics (of about 60% in 85% of treated cases), comorbidities (55% of treated cases, most often OCB/OCD, ADHD, and sleeping disorders), and quality of life (93%). The effects of CBM appear to persist in the long term. Adverse events occurred in half of the patients, but they were rated as tolerable. Dosages of all CBM varied markedly. Patients assessed cannabis (with a preference for tetrahydrocannabinol [THC]-rich strains) as more effective and better tolerated compared with nabiximols and dronabinol. These data were confirmed by results obtained from the online survey (n=40). Conclusion: From our results, it is further supported that CBM might be effective and safe in the treatment of tics and comorbidities at least in a subgroup of adult patients with GTS. In our sample, patients favored THC-rich cannabis over dronabinol and nabiximols, which might be related to the entourage effect of cannabis. However, several limitations of the study have to be taken into considerations such as the open uncontrolled design and the retrospective data analysis.

Tic disorders revisited: introduction of the term "tic spectrum disorders".

Although the DSM-5 chronic motor tic disorder (CMTD) and Tourette syndrome (TS) are distinct diagnostic categories, there is no genetic or phenotypic evidence that supports this diagnostic categorization. The aim of this study was to compare patients with both diagnoses along a number of clinical characteristics to provide further diagnostic clarity. Our sample consisted of 1018 patients (including adult and child patients) suffering from chronic tic disorders. Tic severity was assessed via Shapiro Tourette-Syndrome Severity Scale (STSS). Lifetime prevalence of other comorbid conditions was assessed in a semi-structured clinical interview. The data were gained through retrospective chart analysis. The two groups did not differ significantly in any of the clinical or demographic variables. Patients only differed in tic severity, with CMTD patients (n = 40) having lower mean tic severity (STSS = 2.0 vs. 2.8; p < 0.001), prevalence of complex motor tics (27.5% vs. 55.9%; p < 0.01), copropraxia (0% vs. 16.2%; p < 0.01) and echopraxia (10.0% vs. 23.8%; p < 0.05), and a markedly lower comorbidity score (1.9 vs. 2.7; p < 0.001) as compared to TS patients (n = 978). Our results suggest that both disorders exist along a symptom severity continuum of which TS constitutes a more severe and CMTD a less severe form. We therefore suggest the introduction of the term "tic spectrum disorders", instead of using different diagnostic categories.

Vaporized Cannabis Is Effective and Well-Tolerated in an Adolescent with Tourette Syndrome.

We present the case of a 12-year-old boy diagnosed with Tourette syndrome, who was successfully treated with a combination of vaporized medicinal cannabis and oral pure tetrahydrocannabinol (THC). Due to severe motor tics resulting in insomnia, the parents - both of whom were medical doctors - decided to initiate treatment with 0.02 g vaporized cannabis (Bedrocan with a THC content of 22% and a cannabidiol content of 1%; corresponding to a dose equivalent to 4.4 mg THC) without prior consultation of a Tourette expert. This treatment resulted - according to the parents' report - in an immediate and nearly complete remission of the tics. Due to a further increase in tics, the parents therefore decided to implement a regular treatment with a combination of vaporized medicinal cannabis (up to 0.1 g cannabis per day, varieties Bedrocan and Amnesia Haze, corresponding to 22 mg THC/day) plus orally administered oil-based THC drops (maximum daily dose = 12.5 mg THC) resulting in a marked tic reduction. During a visit in our clinic, we were able to observe the reported beneficial effects 30 min after vaporization of 0.15 g cannabis (Amnesia Haze, equivalent to 33 mg THC; in addition, 7 mg oral THC were taken at home 6 h before the visit): tics, premonitory urges, and overall impairment significantly improved according to self-ratings, parent and clinician questionnaires. Importantly, no adverse events were reported. From this single case study, it is suggested that cannabis-based medicines and their combination (such as oral THC plus vaporized medicinal cannabis) are effective and safe in the treatment of severe tics in minors with TS. However, long-term follow-up is needed to confirm the beneficial treatment effects. We want to emphasize that in this boy treatment with cannabis was initiated by the parents before a consultation in our clinic has taken place. In our opinion, treatment with cannabis-based medicine in children should be regarded as a last-line treatment, when well-established treatments have failed to improve tics.