[Attention deficit/hyperactivity disorder (ADHD) and Tourette disorder (TD): between comorbidity and differential diagnosis]. / Trastorno por déficit de atención/hiperactividad (TDAH) y trastorno de Tourette (TT): entre la comorbilidad y el diagnóstico diferencial.

Tourette Disorder (TD) and attention deficit hyperactivity disorder (ADHD) are both major neuropsychiatric conditions that usually begin during infancy This revision aims to collaborate with pediatricians, who are often confronted with the question of co-morbidity or differential diagnosis between ADHD and TD. The question becomes urgent when the clinician must decide if he/she can start ADHD or TD treatment. We encourage our colleagues to revise our findings, based in bimolecular and neuroanatomic shared issues in addition to updated epidemiological findings. The clinician will find an original proposed algorithm that they can use when the shared symptoms are present in a little patient. TD and ADHD must be intervened early, so we can get better outcomes. The consequences of letting the symptoms increase can generate sequels and handicaps, that can interfere with the quality of life and functionality not only during infancy and adolescence but also in adult life.

El Trastorno de Tourette (TT) y el Trastorno por déficit de atención / hiperactividad (TDAH) son entidades neuropsiquiátricas que usualmente inician en la infancia. Esta revisión busca colaborar con los clínicos, quienes suelen confrontarse al dilema de saber si existe una comorbilidad o un diagnóstico diferencial, ya que esta pregunta cobra vital importancia en el momento de decidir el tratamiento. Invitamos al colega a revisar nuestros hallazgos, soportados por bases moleculares, fisiológicas y neuroanatómicas, además de los datos epidemiológicos. Al final, brindamos una propuesta de algoritmo diagnóstico que podrá utilizar cuando se encuentre ante síntomas compartidos entre los dos diagnósticos. El TDAH y el TT deben ser intervenidos tempranamente, para mejorar la calidad de vida y funcionalidad del paciente y prevenir secuelas, no solo en niños, niñas y adolescentes (NNA), también a lo largo de la vida.

Tic Status in Tourette Syndrome Due to Depletion of the Deep Brain Stimulation Battery.

In this case report, a patient with Tourette syndrome was admitted to the emergency department with nonrhythmic, continuous, generalized hyperkinetic movements associated with muscle contractions in the trunk, neck, and upper and lower limbs caused by depletion of the deep brain stimulation battery.

Potential relationship between Tourette syndrome and gut microbiome.

OBJECTIVE: In this article, the author aims to discuss and review the relationship between gut microbiota and Tourette syndrome, and whether the change in gut microbiota can affect the severity of Tourette syndrome. SOURCES: Literature from PubMed, Google Scholar, and China National Knowledge Infrastructure was mainly reviewed. Both original studies and review articles were discussed. The articles were required to be published as of May 2022. SUMMARY OF THE FINDINGS: Current studies on the gut microbiome have found that the gut microbiome and brain seem to interact. It is named the brain-gut-axis. The relationship between the brain-gut axis and neurological and psychiatric disorders has been a topic of intense interest. Tourette syndrome is a chronic neurological disease that seriously affects the quality of life of children, and there appears to be an increase in Ruminococcaceae and Bacteroides in the gut of patients with Tourette syndrome. After clinical observation and animal experiments, there appear to be particular gut microbiota changes in Tourette syndrome. It provides a new possible idea for the treatment of Tourette syndrome. Probiotics and fecal microbial transplantation have been tried to treat Tourette syndrome, especially Tourette syndrome which is not sensitive to drugs, and some results have been achieved. CONCLUSIONS: The relationship between gut microbiota and Tourette syndrome and how to alleviate Tourette syndrome by improving gut microbiota are new topics, more in-depth and larger sample size research is still needed.

Comparative efficacy, tolerability, and acceptability of pharmacological interventions for the treatment of children, adolescents, and young adults with Tourette's syndrome: a systematic review and network meta-analysis.

BACKGROUND: In clinical practice guidelines there is no consensus about the medications that should be initially offered to children and young people with Tourette's syndrome. To provide a rigorous evidence base that could help guide decision making and guideline development, we aimed to compare the efficacy, tolerability, and acceptability of pharmacological interventions for Tourette's syndrome. METHODS: For this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Embase, PsycINFO, PubMed, Web of Science, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov, for published and unpublished studies from database inception to Nov 19, 2021. We included double-blind randomised controlled trials of any medication administered as a monotherapy for at least 1 week against another medication or placebo in children and adolescents (aged ≥4 years and ≤18 years), adults (>18 years), or both, diagnosed with Tourette's syndrome according to standardised criteria. We excluded studies that exclusively recruited participants with comorbid attention-deficit hyperactivity disorder or obsessive-compulsive disorder. The primary outcome was change in severity of tic symptoms (efficacy). Secondary outcomes were treatment discontinuations due to adverse events (tolerability) and for any reason (acceptability). Pharmacological interventions were examined considering medication categories and medications individually in separate analyses. Summary data were extracted and pooled with a random-effects network meta-analysis to calculate standardised mean differences for efficacy and odds ratios for tolerability and acceptability, with 95% CIs. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was pre-registered in PROSPERO (CRD42022296975). FINDINGS: Of the 12 088 records identified through the database search, 88 records representing 39 randomised controlled trials were included in the network meta-analysis; these 39 randomised controlled trials comprised 4578 participants (mean age 11·8 [SD 4·5] years; 3676 [80·8%] male participants) and evaluated 23 individual medications distributed across six medication categories. When considering medication categories, first-generation (standardised mean difference [SMD] -0·65 [95% CI -0·79 to -0·51]; low certainty of evidence) and second-generation (-0·71 [-0·88 to -0·54]; moderate certainty of evidence) antipsychotic drugs, as well as α-2 agonists (-0·21 [-0·39 to -0·03]; moderate certainty of evidence), were more efficacious than placebo. First-generation and second-generation antipsychotic drugs did not differ from each other (SMD 0·06 [95% CI -0·14 to 0·25]; low certainty of evidence). However, both first-generation (SMD 0·44 [95% CI 0·21 to 0·66]) and second-generation (0·49 [0·25 to 0·74]) antipsychotic drugs outperformed α-2 agonists, with moderate certainty of evidence. Similar findings were observed when individual medications were considered: aripiprazole (SMD -0·60 [95% CI -0·83 to -0·38]), haloperidol (-0·51 [-0·88 to -0·14]), olanzapine (-0·83 [-1·49 to -0·18]), pimozide (-0·48 [-0·84 to -0·12]), risperidone (-0·66 [-0·98 to -0·34]), and clonidine (-0·20 [-0·37 to -0·02]) all outperformed placebo, with moderate certainty of evidence. Antipsychotic medications did not differ from each other, but there was low to very low certainty of evidence for these comparisons. However, aripiprazole (SMD -0·40 [95% CI -0·69 to -0·12]) and risperidone (-0·46 [-0·82 to -0·11]) outperformed clonidine, with moderate certainty of evidence. Heterogeneity or inconsistency only emerged for a few comparisons. In terms of tolerability and acceptability, there were no relevant findings for any of the efficacious medication categories or individual medications against each other or placebo, but there was low to very low certainty of evidence associated with these comparisons. INTERPRETATION: Our analyses show that antipsychotic drugs are the most efficacious intervention for Tourette's syndrome, while α-2 agonists are also more efficacious than placebo and could be chosen by those who elect not to take antipsychotic drugs. Shared decision making about the degree of tic-related severity and distress or impairment, the trade-offs of efficacy and safety between antipsychotic drugs and α-2 agonists, and other highly relevant individual factors that could not be addressed in the present analysis, should guide the choice of medication for children and young people with Tourette's syndrome. FUNDING: None.

Tourette's Syndrome cervical dystonia induced occipital neuralgia remedied by peripheral nerve stimulation: A case report / Síndrome de Tourette, distonia cervical induzida por neuralgia occipital remediada por estimulação nervosa periférica: relato de caso

BACKGROUND: Dystonia is uncommon in Tourette's syndrome, and occipital neuralgia secondary to Tourette's dystonia is more rare, affecting quality of life. Occipital peripheral nerve stimulation (PNS) is an excellent alternative by being adjustable and minimally invasive. Our case demonstrates occipital PNS as an effective option for refractory Tourette's dystonia. CASE PRESENTATION: A thirty-four-year-old male with poorly controlled Tourette's cervical dystonia presented with severe occipital neuralgia. Various medications were prescribed including propranolol and amitriptyline, and bilateral third-occipital nerve rhizotomies and occipital nerve blocks were trialed. Distal nerve blocks at the occipital protuberance were most effective. Therefore, an occipital PNS trial was done, and a PNS was implanted with no complications. Upon follow-up, the patient reported drastic pain reduction. CONCLUSION: Our case illustrates neuromodulation benefits for a rare presentation of refractory occipital neuralgia secondary to Tourette's-related dystonia. Occipital PNS should be considered for refractory cases because it is safe, easy to implant, and effective.

FUNDAMENTO: A distonia é incomum na síndrome de Tourette, e a neuralgia occipital secundária à distonia de Tourette é mais rara, afetando a qualidade de vida. A estimulação do nervo periférico occipital (SNP) é uma excelente alternativa por ser ajustável e minimamente invasiva. Nosso caso demonstra o SNP occipital como uma opção eficaz para a distonia de Tourette refratária. APRESENTAÇÃO DO CASO: Um homem de 34 anos com distonia cervical de Tourette mal controlada apresentou neuralgia occipital grave. Vários medicamentos foram prescritos, incluindo propranolol e amitriptilina, e foram testadas rizotomias bilaterais do nervo terceiro-occipital e bloqueios do nervo occipital. Os bloqueios dos nervos distais na protuberância occipital foram mais eficazes. Portanto, foi feito um ensaio de PNS occipital e um PNS foi implantado sem complicações. Após o acompanhamento, o paciente relatou redução drástica da dor. CONCLUSÃO: Nosso caso ilustra os benefícios da neuromodulação para uma apresentação rara de neuralgia occipital refratária secundária à distonia relacionada a Tourette. O PNS occipital deve ser considerado para casos refratários porque é seguro, fácil de implantar e eficaz.

Identity-by-descent analysis of a large Tourette's syndrome pedigree from Costa Rica implicates genes involved in neuronal development and signal transduction.

Tourette Syndrome (TS) is a heritable, early-onset neuropsychiatric disorder that typically begins in early childhood. Identifying rare genetic variants that make a significant contribution to risk in affected families may provide important insights into the molecular aetiology of this complex and heterogeneous syndrome. Here we present a whole-genome sequencing (WGS) analysis from the 11-generation pedigree (>500 individuals) of a densely affected Costa Rican family which shares ancestry from six founder pairs. By conducting an identity-by-descent (IBD) analysis using WGS data from 19 individuals from the extended pedigree we have identified putative risk haplotypes that were not seen in controls, and can be linked with four of the six founder pairs. Rare coding and non-coding variants present on the haplotypes and only seen in haplotype carriers show an enrichment in pathways such as regulation of locomotion and signal transduction, suggesting common mechanisms by which the haplotype-specific variants may be contributing to TS-risk in this pedigree. In particular we have identified a rare deleterious missense variation in RAPGEF1 on a chromosome 9 haplotype and two ultra-rare deleterious intronic variants in ERBB4 and IKZF2 on the same chromosome 2 haplotype. All three genes play a role in neurodevelopment. This study, using WGS data in a pedigree-based approach, shows the importance of investigating both coding and non-coding variants to identify genes that may contribute to disease risk. Together, the genes and variants identified on the IBD haplotypes represent biologically relevant targets for investigation in other pedigree and population-based TS data.

Treatments for Tourette syndrome in children and young adults: a systematic review / Tratamento da síndrome de Tourette em crianças e jovens adultos: uma revisão sistemática

INTRODUCTION: Tourette's Syndrome (TS) is a neurodevelopmental disorder characterized by motor and / or vocal tics for more than 12 months. TS affects about 0.8% of pediatric patients and is associated with great functional impairment and psychological distress. The present study aims to list and compare the effectiveness of therapies used in children and young people with TS. METHODS: PubMed / MEDLINE, Cochrane Library, ScienceDirect, SciELO and Lilacs were used from September 2020 to April 2021 to search for randomized clinical trials with pharmacological, behavioral, physical or alternative interventions for tics in children and young people with ST. RESULTS: 13 clinical trials were included, of which six pharmacological, six behavioral and one of other conformation. The global score on the Yale Global Tic Severity Scale showed evidence in favor of Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT). Evidence from two studies suggests that antipsychotic medications improve tic scores. Evidence from other interventions has shown no conclusive benefit. CONCLUSIONS: The present study identified benefits with the use of antipsychotics. The study also found that HRT and CBIT showed improvement in reducing the severity of tics, in addition to not having any adverse effects. These therapies showed significant clinical improvement, but there is no comparison between the use of these isolated approaches in relation to their use associated with medications. In view of the different forms of therapy, further studies are needed to identify the effectiveness and the profile of adverse effects of these interventions.

INTRODUÇÃO: A Síndrome de Tourette (ST) é um distúrbio do neurodesenvolvimento caracterizado por tiques motores e/ou vocais por mais de 12 meses. A ST afeta cerca de 0,8% dos pacientes pediátricos e associa-se a grande comprometimento funcional e sofrimento psíquico. O presente estudo tem como objetivo listar e comparar a eficácia das terapias utilizadas em crianças e jovens com ST. MÉTODOS: PubMed/MEDLINE, Cochrane Library, ScienceDirect, SciELO e Lilacs foram usados desde setembro de 2020 até abril de 2021 para a busca de ensaios clínicos randomizados com intervenções farmacológicas, comportamentais, físicas ou alternativas para tiques em crianças e jovens com ST. RESULTADOS: 13 ensaios clínicos foram incluídos, dos quais seis farmacológicos, seis comportamentais e um de outra conformação. A pontuação global na Yale Global Tic Severity Scale, apresentou evidências a favor do Treinamento de Reversão de Hábito (TRH) e Intervenção Comportamental Abrangente para Tiques (ICAT). As evidências de dois estudos sugerem que medicamentos antipsicóticos melhoram os escores de tiques. Evidências de outras intervenções não mostraram nenhum benefício conclusivo. CONCLUSÕES: O presente estudo identificou benefícios com o uso do antipsicóticos. O estudo também identificou que a TRH e a ICAT apresentaram melhora na redução da gravidade dos tiques, além de não apresentarem efeitos adversos. Essas terapias mostraram importante melhora clínica, mas não há comparação entre o uso dessas abordagens isoladas em relação ao seu uso associado com medicamentos. Diante das diferentes formas de terapia, mais estudos são necessários para identificar a eficácia e o perfil de efeitos adversos dessas intervenções.

Beyond tics: movement disorders in patients with Tourette syndrome.

BACKGROUND: Tics are the hallmark of Tourette syndrome (TS). However, TS patients may have a particular vulnerability to develop other movement disorders (MDs), such as dystonia, chorea, stereotypy, and other hyperkinetic disorders that may be wrongly attributed to tics. MATERIALS AND METHODS: We studied a cohort of 201 patients with motor and phonic tics associated with TS to determine if they have additional, co-existent, MDs. RESULTS: There were 67 (33.3%) patients with comorbid non-tic MDs. Phenomenology-wise, piano-playing movements resembling chorea or myoclonus, were the most common non-tic movement, observed in 11% of cases, followed by stereotypies (8.0%), tremor, dystonia and parkinsonism, 5.0% each. Drug-induced was the most common etiology (6.0%), followed by functional movement disorders (5.0%) and tardive phenomena (5.0%). No clear etiology was identified in most patients. Piano-playing movements, were associated with a younger age at onset (P = 0.004) and younger age at presentation (P < 0.001). Patients with drug-induced movements and tardive phenomena had a lower frequency of craniofacial tics. FMDs, and idiopathic MDS showed no specific associations with TS. Tic severity was not a predictor of any co-existent MD. CONCLUSION: About a third of patients with TS present with comorbid MDs which should be differentiated and distinguished from tics as their etiopathogenesis and treatment may be different.

[A pediatric cohort with Gilles de la Tourette syndrome]. / Descripción de una cohorte pediátrica con síndrome de Gilles de la Tourette.

INTRODUCTION: Tourette Syndrome (TS) is a common disorder with chronic motor and phonic tics, associated with neuropsychiatric comorbidities. OBJECTIVE: To characterize clinical-demographic variables, comor bidities, and management in a pediatric cohort with TS and compare them according to sex. PATIENTS AND METHOD: A retrospective cohort of patients < 18 years old with TS followed up between 2000 and 2018 was evaluated. Clinical records were reviewed obtaining variables of age, sex, reason for consul tation, age of onset, type and complexity of tics, follow-up time, family history, obsessive behaviors, neuropsychiatric and psychopathological comorbidity, neurological disorders, and pediatric mor bidity. Studies and treatments performed, and management used were also recorded. RESULTS: 126 patients were included, aged between 4-18 years, 103 males (sex F:M ratio = 4.5:1), with a follow-up of 4.8 ± 1.9 years. The mean age of tic onset and TS diagnosis was 6.5 ± 2.2 and 9.4 ± 2.7 years, res pectively, and a diagnostic latency of 2.8 ± 2.2 years. The first consultation in the total of girls was due to tics, in contrast to the boys of whom 14.6% (n = 15) consulted due to comorbidities. There was 38.9% of tics and 8,7% of TS. Neuropsychiatric comorbidities were frequent, recorded in 69.8%, with Attention Deficit Disorder (43.6%) and Obsessive-Compulsive Disorder (20.6%) standing out.110 cases (87.3%), received pharmacological therapy and 54.4% required three or more drugs at some point in their evolution. Only in 16 cases (12.7%), no pharmacological therapy was required, only psychoeducation in 7 (5.6%) cases, and behavioral therapy in 9 cases (7.1%). CONCLUSIONS: The cli nical characteristics of our children with TS are similar to international descriptions, highlighting that in the group of boys, the first consultation could be due to comorbidity, recognizing later the presence of tics. Although psychoeducation and behavioral therapies are recommended as first-line management, most of the patients in this group required pharmacological therapy.

Síndrome de Tourette: Tratamiento farmacológico en pacientes pediátricos, una puesta al día / Tourette's Syndrome: An Update on Pharmacological Treatment in Paediatric Patients

El síndrome de Tourette (ST) se caracteriza por tics motores y fónicos, destacando las dificultades de su manejo farmacológico. El objetivo de este artículo es describir los resultados de una revisión bibliográfica de las alternativas de tratamiento farmacológico existentes en la actualidad para el ST pediátrico. Metodología: Se realizó una búsqueda bibliográfica en base de datos PubMed utilizando los términos meSH "Tourette syndrome", "Tics", "Therapeutics" y "Children" entre los años 1950 y 2020, tras priorización y exclusión se obtuvo un total de 64 artículos. Resultados: Los artículos muestran 21 alternativas terapéuticas, que se detallan en dos niveles según eficacia y efectos adversos. Conclusiones: Existen múltiples alternativas farmacológicas, algunas con efectos adversos que pueden llegar a determinar la imposibilidad de continuar el tratamiento. Esta sigue siendo un área abierta de investigación en la búsqueda de alternativas que disminuyan estos efectos.

Abstract. Introduction: Tourette syndrome (TS) is characterized by motor and phonic tics, and the difficulties of its pharmacological management. The objective of this article is to describe the results of a bibliographic review of the pharmacological treatment alternatives that currently exist for pediatric TS. Methods: A bibliographic search was carried out in the PubMed database using the meSH terms "Tourette syndrome", "Tics", "Therapeutics" and "Children" between 1950 and 2020, after prioritization and exclusion, a total of 64 articles were selected. Results: The articles show 21 therapeutic alternatives, which are categorized into two levels according to efficacy and adverse effects. Conclusions: There are multiple pharmacological alternatives, some with adverse effects that may make it impossible to continue treatment. This continues to be an open area of investigation in the search for alternatives that minimize these side effects.

Trichotillomania is more related to Tourette disorder than to obsessive-compulsive disorder

Objective: Trichotillomania (TTM) is characterized by the pulling out of one's hair. TTM was classified as an impulse control disorder in DSM-IV, but is now classified in the obsessive-compulsive related disorders section of DSM-5. Classification for TTM remains an open question, especially considering its impact on treatment of the disorder. In this review, we questioned the relation of TTM to tic disorder and obsessive-compulsive disorder (OCD). Method: We reviewed relevant MEDLINE-indexed articles on clinical, neuropsychological, neurobiological, and therapeutic aspects of trichotillomania, OCD, and tic disorders. Results: Our review found a closer relationship between TTM and tic disorder from neurobiological (especially imaging) and therapeutic standpoints. Conclusion: We sought to challenge the DSM-5 classification of TTM and to compare TTM with both OCD and tic disorder. Some discrepancies between TTM and tic disorders notwithstanding, several arguments are in favor of a closer relationship between these two disorders than between TTM and OCD, especially when considering implications for therapy. This consideration is essential for patients.

De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder with a genetic risk component, yet identification of high-confidence risk genes has been challenging. In recent years, risk gene discovery in other complex psychiatric disorders has been achieved by studying rare de novo (DN) coding variants. METHODS: We performed whole-exome sequencing in 222 OCD parent-child trios (184 trios after quality control), comparing DN variant frequencies with 777 previously sequenced unaffected trios. We estimated the contribution of DN mutations to OCD risk and the number of genes involved. Finally, we looked for gene enrichment in other datasets and canonical pathways. RESULTS: DN likely gene disrupting and predicted damaging missense variants are enriched in OCD probands (rate ratio, 1.52; p = .0005) and contribute to risk. We identified 2 high-confidence risk genes, each containing 2 DN damaging variants in unrelated probands: CHD8 and SCUBE1. We estimate that 34% of DN damaging variants in OCD contribute to risk and that DN damaging variants in approximately 335 genes contribute to risk in 22% of OCD cases. Furthermore, genes harboring DN damaging variants in OCD are enriched for those reported in neurodevelopmental disorders, particularly Tourette's disorder and autism spectrum disorder. An exploratory network analysis reveals significant functional connectivity and enrichment in canonical pathways, biological processes, and disease networks. CONCLUSIONS: Our findings show a pathway toward systematic gene discovery in OCD via identification of DN damaging variants. Sequencing larger cohorts of OCD parent-child trios will reveal more OCD risk genes and will provide needed insights into underlying disease biology.

Trichotillomania is more related to Tourette disorder than to obsessive-compulsive disorder.

OBJECTIVE: Trichotillomania (TTM) is characterized by the pulling out of one's hair. TTM was classified as an impulse control disorder in DSM-IV, but is now classified in the obsessive-compulsive related disorders section of DSM-5. Classification for TTM remains an open question, especially considering its impact on treatment of the disorder. In this review, we questioned the relation of TTM to tic disorder and obsessive-compulsive disorder (OCD). METHOD: We reviewed relevant MEDLINE-indexed articles on clinical, neuropsychological, neurobiological, and therapeutic aspects of trichotillomania, OCD, and tic disorders. RESULTS: Our review found a closer relationship between TTM and tic disorder from neurobiological (especially imaging) and therapeutic standpoints. CONCLUSION: We sought to challenge the DSM-5 classification of TTM and to compare TTM with both OCD and tic disorder. Some discrepancies between TTM and tic disorders notwithstanding, several arguments are in favor of a closer relationship between these two disorders than between TTM and OCD, especially when considering implications for therapy. This consideration is essential for patients.