European Society for the Study of Tourette Syndrome (ESSTS)
Conference details: 8-10 June, Warsaw, Poland.
Report by: Jeremy Stern, Consultant Neurologist, St George’s Hospital.
Conflict of interest statement: The author declares that there are no conflicts of interest.
First Published online: 22/11/16
Tics are more intensively investigated than you may think. The annual ESSTS conference recently took place in Warsaw and last year the first World Congress on the topic was held in London with over 400 delegates.
Around 1% of children have Tourette Syndrome (TS) with higher rates in SEN education. Tics are more commonly seen in the context of transient tics disorders in up to 15-20% of boys, and in persisting chronic multiple tics. TS is defined by chronic multiple motor and at least one vocal tic which can be simple or complex. It is highly associated with other comorbidities including OCD and ADHD. Severity varies but effects on quality of life can be dramatic. At the meeting Nafar Peretz from Israel presented a study of 46 young people, 80% had mild depression and 9% experienced suicidal ideation. The average case starts at around the ages of 5-7 and improves into adolescence but many are outside these parameters and there is surprisingly little longitudinal data, an important Danish study of over 300 children seen over 5 years was presented by Camilla Groth, largely confirming the current view.
Genetics is the hottest area, updates were given by Perry Paschou from Democritos University, Greece, Jeremiah Scarf from Harvard and Zeynep Turner from Copenhagen. TS is highly heritable with first degree relatives having a rate of 10-20% each for TS, chronic tics and OCD. The investigational methods of the 1980s and 90s frustrated the expectation of a single gene. To date only two major genes have been identified in very small numbers of patients – SLITRK1 and L-histadine decarboxylase. Similar to other complex traits including neuropsychiatric conditions, the current direction is to use contemporary methods to reveal the missing heredity residing in polygenic and epigenetic mechanisms. GWAS is foremost and there are also studies of DNA methylation, copy number variants and the basal ganglia transcriptome (over 800 upregulated genes). An overlap with the genetics of OCD, ADHD and autism is emerging with evidence for a distinct genetic architecture for TS with and without comorbidities. This work depends on large numbers of cases, with a total worldwide count of 12,500 predicted for next year. This is still relatively small – in bipolar disorder bank on 1 gene per 1000 cases. So far there are many regions of interest but few possibly confirmed susceptibility genes, including NRXN1.
Professor James Leckman from Yale gave a keynote lecture integrating advances in aetiology including genetics and environmental factors. The latter include maternal smoking and neuro-immunological mechanisms. He received lifetime achievement awards from both ESSTS and the UK charity, Tourettes Action. The potential for vulnerability and exacerbations of TS relating to Group A Streptococcal infections and basal ganglia antibodies (present in 25% of TS cases) did not feature heavily in this meeting but remains an enigma. There is an ongoing multicentre European study hoping to demonstrate a link (EMTICS). There is currently no good evidence for treatment with antibiotics or IVIG.
Moving to neurobiology, the consensus hypothesis is of a neurodevelopmental disorder with subtle atrophy of the basal ganglia thalamocortical circuits. Some of the most important findings are reduced caudate volumes on MRI and an abnormal distribution of GABAergic basal ganglia interneurons in a small number of post-mortem brains. This is now beginning to be more convincingly tested in animal models using rodents and monkeys. They can’t be asked if they experience the typical premonitory sensation of a human tic but the face validity of a tic-like movement or vocalisation is now possible. Izhar Bar-Gad from Israel has led in this field, using bicuculline injections into the striatum and the work is converging with human deep brain stimulation (DBS) recordings showing abnormal striatal inhibition. He explained an emerging concept of striatal somatotopy determining the bodily location of tics, with vocal tics possibly having a distinct limbic circuit anatomy, and cortical inputs influencing the timing of tic expression.
Kirsten Müller-Vahl from Hannover reviewed pharmacotherapy. Neuroleptics suppress tics and can be useful but with variable effects and are the basis of a dopaminergic theory of tics, with some support from functional imaging. Probably the most commonly used agent is the partial D2 agonist aripiprazole and the best investigated is risperidone in a field where clinical trials are difficult. Other neurotransmitters may also be important. MRS of the glutaminergic system was explored by Siyan Fan (Utrecht) and Ahmad Seif Kanaan (Hannover) who are both PhD students funded by the TS-Eurotrain initiative. Ahmad received the Professor Mary Robertson Award for his research. The adrenergic agent Clonidine is used mostly in children with comorbid ADHD. There is modest evidence for a number of other drugs. Current investigational agents include cannabinoids (the basal ganglia are rich in CB1 receptors), acomprosate, ecopipam (D1 antagonist) and a study compound which is an inverse agonist of the presynaptic histamine H3 receptor.
Tom Foltynie from Queen Square reviewed the growing experience of DBS for TS. There are now approaching 150 documented cases, but few controlled data and a multiplicity of neurosurgical targets- predominantly thalamic and GPi. An international registry is collecting data to attempt to make sense of this and the London RCT of anteromedial limbic GPi with stimulator on/off crossover had recently reported on 13 patients with positive results and safety record. Interestingly blinding in this context is problematic- it causes stress that exacerbates tics. It seems that these patients are unusually prone to infective complications. Longer term Italian data with a thalamic target was less positive at 5 years than 2 years and there are clearly individual cases with a less beneficial response.
Behavioural treatments for tics (habit reversal training as part of Comprehensive Behavioural Intervention for Tics (CBIT), from the US, exposure response prevention (ERP) from the Netherlands are evidence based but not generally available due to lack of resources for clinical psychologists. This is leading to exploration using telemedicine with a demonstration from Judy Grejsen from Denmark, and also possible web-based options with no therapist.
This is a selection of the work presented to represent the current main themes, much has been left out, from the benefits of kick-boxing, the philosophy of self-will and involuntary movements to further imaging and animal work. Next year’s ESSTS meeting will be in Seville, 14-16th June.