Tics and stereotypies: A comparative clinical review.

Tics and stereotypies are the most common pathological repetitive complex motor behaviors occurring during the neurodevelopmental period. Although they may appear transiently during development without acquiring a pathological status, when they become chronic they may be distressing, socially impairing, or even, in the case of malignant tics, potentially physically harmful. Despite a certain similarity in their phenomenology, physicians should be able to distinguish them for their different variability over time, topographical distribution, association with sensory manifestations, and relationship with environmental triggers. The complex phenomenology of tics and stereotypies is constantly enriched by the characterization of novel variants, e.g. tics triggered by auditory stimuli in association with misophonia and stereotypies associated with intense imagery activity. Their pathophysiology remains partially elusive, but both animal model and brain imaging studies confirm the involvement of all the three major loops (sensorimotor, associative and limbic) within the cortico-basal ganglia circuitry. From a management perspective, the greatest advances witnessed in the last decade involve the diffusion of behavioral strategies (e.g. habit reversal training or response interruption and redirection), including the development of protocols for telehealth on online training in order to optimise access. In the context of severe tics, e.g. in refractory Tourette syndrome, there is increasing experience with deep brain stimulation of the intralaminar thalamic nuclei or the globus pallidus internus, although more research is needed to fine tune target choice and stimulation setting definition.

Clinical Presentation and Prognosis of Common Movement Disorders.

Great progress has been made in expanding our understanding of the natural history of movement disorders, leading to impressive advancements in their medical and surgical management. Movement disorders are a diverse group of diseases, varying widely in clinical characteristics and evolution. Some are monosymptomatic while others have associated motor and nonmotor features. Some are static while others follow a progressive course. This chapter will review common primary and secondary movement disorders: Parkinson disease and other forms of Parkinsonism, essential tremor and its differential diagnoses, dystonia and tic disorders. Herein, we will provide an overview of the clinical presentation and prognosis of the primary and secondary movement disorders most relevant to discussions of surgical candidacy.

Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a lamininopathy associated with tics, obsessive compulsive traits and myopia due to cell adhesion and migration defects.

BACKGROUND: Laminins are heterotrimeric complexes, consisting of α, ß and γ subunits that form a major component of basement membranes and extracellular matrix. Laminin complexes have different, but often overlapping, distributions and functions. METHODS: Under our clinical protocol, NCT00068224, we have performed extensive clinical and neuropsychiatric phenotyping, neuroimaging and molecular analysis in patients with laminin α1 (LAMA1)-associated lamininopathy. We investigated the consequence of mutations in LAMA1 using patient-derived fibroblasts and neuronal cells derived from neuronal stem cells. RESULTS: In this paper we describe individuals with biallelic mutations in LAMA1, all of whom had the cerebellar dysplasia, myopia and retinal dystrophy, in addition to obsessive compulsive traits, tics and anxiety. Patient-derived fibroblasts have impaired adhesion, reduced migration, abnormal morphology and increased apoptosis due to impaired activation of Cdc42, a member of the Rho family of GTPases that is involved in cytoskeletal dynamics. LAMA1 knockdown in human neuronal cells also showed abnormal morphology and filopodia formation, supporting the importance of LAMA1 in neuronal migration, and marking these cells potentially useful tools for disease modelling and therapeutic target discovery. CONCLUSION: This paper broadens the phenotypes associated with LAMA1 mutations. We demonstrate that LAMA1 deficiency can lead to alteration in cytoskeletal dynamics, which may invariably lead to alteration in dendrite growth and axonal formation. Estimation of disease prevalence based on population studies in LAMA1 reveals a prevalence of 1-20 in 1 000 000. TRIAL REGISTRATION NUMBER: NCT00068224.

Phenomenology and natural history of Tourette syndrome: brief summary or research / Fenomenologia e história natural da síndrome de Tourette: breve resumo da pesquisa

The phenomenology of Tourette syndrome is complex. Although overt motor and vocal tics are the defining features of Tourette syndrome, many individuals report experiencing sensory "urges," which are often difficult to describe. The natural history of this condition is also variable, with some individuals experiencing a marked reduction in tics by the end of the second decade of life while others go on to have a lifelong condition. The aim of this thesis was three-fold: (1) to develop a valid and reliable clinical rating instrument; (2) to investigate the sensory phenomena associated with Tourette syndrome; and (3) to document the course of tic severity over the course of the first two decades of life. Each of these three studies involved groups of patients with Tourette syndrome or a chronic tic disorder and each of these studies has been published in a peer-reviewed journal. The Yale Global Tic Severity Scale (YGTSS) has excellent psychometric properties that have been independently replicated. It has also emerged as the most widely used clinician-rated tic severity scale in randomized clinical trials around the world. Sensory phenomena, particularly premonitory urges, are commonly reported among individuals with Tourette syndrome by the age of 10 years. There is considerable overlap with the sensory phenomena described by individuals with Obsessive-Compulsive Disorder. Tics usually have their onset in the first decade of life. They then follow a waxing and waning course and a changing repertoire of tics. As documented in the third study, for a majority of patients the period of worst tic severity usually falls between the ages of 7 and 15 years of age, after which tic severity gradually declines. This falloff in tic symptoms is consistent with available epidemiological data that indicate a much lower prevalence of Tourette syndrome among adults than children. This decline in tic severity has been confirmed in subsequent studies...

A fenomenologia da síndrome de Tourette (ST) é complexa. Apesar de tiques motores e vocais serem as características definidoras da síndrome, muitas pessoas relatam ter urgências premonitórias (fenômenos sensoriais) de difícil descrição. A história natural da ST também é variável, com alguns indivíduos que experimentam uma redução acentuada nos tiques até o final da segunda década de vida, enquanto outros permanecem com sintomas ao longo de toda a vida adulta. Os objetivos principais desta tese são três: (1) desenvolver um instrumento de avaliação clínica com boa validade e confiabilidade para ST; (2) investigar os fenômenos sensoriais (FS) associados a ST; e (3) documentar o curso da gravidade dos tiques durante as duas primeiras décadas de vida. Para atingir esses objetivos incluíram-se grupos de pacientes clinicamente bem caracterizados e de artigos científicos publicados em periódicos internacionais de alto impacto. A Escala de Gravidade Global de tiques de Yale (YGTSS) apresentou excelentes propriedades psicométricas, o que foi replicado em estudos independentes. Também emergiu como a escala de gravidade mais utilizada em ensaios clínicos randomizados para ST em todo o mundo. Os FS, particularmente urgências premonitórias, são comumente relatados entre os indivíduos com ST com a partir da idade de 10 anos. Há uma sobreposição considerável com os FS descritos por indivíduos com Transtorno Obsessivo- Compulsivo (TOC). Os tiques costumam ter seu início na primeira década de vida e, então, seguem um curso flutuante com mudança do seu repertório. Conforme documentado no terceiro estudo, para a maioria dos pacientes, o período de pior gravidade dos tiques ocorre geralmente entre 7 e 15 anos de idade, após o qual a gravidade declina gradualmente. Esta queda dos sintomas de tiques é consistente com os dados epidemiológicos disponíveis que indicam uma prevalência muito menor de ST entre adultos do que crianças. Em resumo, há um esforço para incremento...

The DRD4 gene and severity of tics and comorbid symptoms: main effects and interactions with delivery complications.

In this study, we investigated the role of the dopamine receptor D4 (DRD4) 48-base pairs (bp) variable number of tandem repeats (VNTR) and perinatal adversities regarding severity of tics and comorbid symptoms in children with tic disorders. We genotyped 110 children with tics with regard to the 48-bp VNTR and assessed presence of prenatal smoking exposure, and pregnancy and delivery complications by parent questionnaires. We examined associations between 2, 3, 4, and 7 repeat (R) alleles and severity of tics and comorbid obsessive-compulsive, depressive, anxious, and autistic symptoms. Through linear regressions, we investigated whether perinatal adversities and the 2R, 3R, 4R, and 7R alleles would interact with severity ratings of tics or comorbid symptoms as outcome. Presence of a 2R allele was related to more severe obsessive-compulsive symptoms, and presence of a 3R allele to increased severity of autistic features. Pregnancy complications were associated with decreased obsessive-compulsive symptom severity, and prenatal smoking exposure to more severe depressive and autistic symptoms. In children without a 3R allele delivery complications were associated with more severe tics, but in children with a 3R variant an inverse relation between delivery complications and tic severity was found. Moreover, the relation between delivery complications and internalizing symptom severity appeared to be most pronounced in children with a 2R allele. In conclusion, this study provides evidence for a role of the 48-bp VNTR in the etiology of tic and associated disorders, and for interactions with delivery complications regarding severity of tics and co-occurring internalizing symptoms.

Neurological disorders in children and adolescents.

OBJECTIVE: To ascertain the prevalence of active epilepsy, febrile seizures (FS), cerebral palsy (CP) and tic disorders (TD) in aged 19 years or less. METHODS: This was a cross-sectional observational study conducted as a two-stage door-to-door survey of a stratified randomly selected population in 2003-04. Trained field workers screened the population followed by case examination by the field neurologist. RESULTS: A total of 16979 (male 8898, female 8081) subjects aged

Candidate locus for chorea and tic disorders at 15q?

Cases of chromosomal aberrations are known to be associated with specific phenotypic abnormalities, including tics and chorea. We report the case of a 10-year-old caucasian boy with tics, chorea, and a de novo chromosome 15 paracentric inversion, 46,XY,inv(15) (q13;q22.3) identified with G-banding chromosome analysis (trypsin-Giemsa staining). Subsequent fluorescence in situ hybridization with locus-specific small nuclear ribonucleoprotein polypeptide N gene probe confirmed that the breakpoints of the inversion were distal to 15q12. Mutation analysis showed no mutation or polymorphism in the thyroid transcription factor 1 gene (TITF1). The results suggest that 15q is a region to explore for candidate genes of etiologic importance in the development of tics and chorea.

Los tics en la infancia / Tics in childhood

Los tics en la infancia constituyen una manifestación patológica muy frecuente. Son movimientos involuntarios, sin finalidad concreta y favorecidos pro factores emocionales. Existen tres grupos importantes que deben ser conocidos: tics transitorios, tics motores crónicos y tics múltiples o síndrome de Gilles de la Tourette. Los criterioe diagnósticos de los tics crónicos múltiples han variado con el transcurso de los años, hasta llegar a simplificarse por motivos de mayor conocimiento etiopatogénico. Es un síndrome con una incidencia relativamente frecuente. En este artículo se hace hincapié en el núcleo patológico obsesión-compulsivo, formas monosintomáticas y en la etiopatogenia orgánica del síndrome. Se citan las nuevas investigaciones con unas perspectivas de futuro apasionantes

[Facial myokomias in brain stem tumors]. / Gesichtsmyokymien bei Hirnstammtumoren.

Four cases of brain-stem tumor were described, in which myokymias were electromyographically derived from the region of several cerebral nerves. An attempt is made to interpret the effects of twitching by reference to the electromyogram. Myokymias are a positive indication of organic brain stem damage. The use subtle techniques of electromyographic examination shows that this muscular hyperkinesis is not so infrequent a symptom as is generally believed.