In recent years the number of scientific meetings dedicated to TS has increased to a fairly regular flow. Every five years the American Tourette Syndrome Association (TSA) hold the biggest of these, and this organisation has also been crucial in stimulating and funding research. There have been five so far, Professor Mary Robertson has attended them all. In June I went to my second, in New York. There were over 250 delegates from around the world. The core of the meeting comprised lectures giving us the current state of play, new progress since the last meeting in Cleveland in 2004, and importantly a view to the future. In addition there were poster sessions where individual researchers present their work in progress and "roundtable sessions" allowing a more interactive format on selected topics.

Also in June the yearly International Movement Disorder Society Symposium was held in Paris, but I wasn't there. Several posters concerning TS were presented.

To set the scene for our new research blog I'll briefly summarise the broad messages I took away from New York. In this entry I will generally not be crediting individual researchers by name.

1) Genetics

It has long been known that in most cases TS appears to be inherited with other family members having either TS, tics or obsessionality. However it has not proved possible to track down the genes involved, probably because there are several that cause vulnerability to TS. The current approach is Genome Wide Association Study (GWAS). Using new technology it is possible to screen for hundreds of thousands of minor genetic variations and blood from over 1000 TS cases has been analysed in this way. The advantage of this approach is that we don't need to know what we are looking for in advance, the disadvantage is the huge number of TS cases needed to get powerful results. Currently more are being sought and that may include some from the UK (the work is in the US).

Preliminary results have identified 7 possible regions of DNA that may be significant and this is being further investigated. Previous results from 2007 using pairs of siblings one with TS and one without TS but only looking at less than 400 variations in DNA also identified a region of interest on chromosome number 2 that is still being looked at.

2) Neural circuitry and Neurosurgery

One of the mysteries of TS is what is actually happening in the brain to cause the symptoms as people with TS have no obvious abnormalities of the structure of the brain on brain scans or post-mortem examination (although very few brains have been examined in this way- if you would like to donate your brain after you have died then the office can give you details!). On the other hand there may be some subtle abnormalities of the size of certain parts of the brain including circuits that control movement (called the basal ganglia) and connections between the left and right brain (called the corpus callosum).

The emerging concept is that TS is not caused by an abnormality of one part of the brain (as for instance happens in a stroke whose effects are focal) but of malfunction of the whole circuits that control movement and are also involved in emotion (so can also cause OCD). An important publication of the last few years was a post-mortem study showing certain kinds of brain cells ("parvalbumin positive") are reduced in a part of this circuit called the caudate nucleus. These cells have regulatory and control functions on the whole circuit and could be abnormal due to an abnormality of the development of the brain.

Whilst normal clinical brain scans (MRI or CT) do not show any problem in people with TS, research scans showing the function of the brain are capable of showing differences although these are very hard to interpret. This can include the activity of different parts of the brain in terms of firing of brain cells and release of certain neurotransmitter chemicals. One presentation at the meeting showed a new approach of looking at the development of connectivity of different parts of the brain- children with TS seemed to be lagging behind by about 3 years.

The new treatment of Deep Brain Stimulation (DBS) may be a way to correct the malfunctioning circuits, by the surgical insertion of stimulator wires into the brain- early results are very encouraging but this is still an experimental treatment and not routinely performed in the UK.

3) Epidemiology (how common is TS)

TS was thought to be rare until the 1970s but by the 1980s it was though to affect 1 in every 2000 people. Over the last 20 years it has become apparent that it is actually more common than that. It affects about 1% of schoolchildren, although some of these are very mild they can still have associated features like OCD and ADHD. The amount of TS found depends on how it is counted.

Recent and new epidemiology data was presented. Firstly a couple of very large American studies which both seemed to underestimate the amount of TS. A telephone survey in which 64 000 random telephone calls were made- only 0.3% had a diagnosis of TS made by a doctor (so there must be a lot who had TS but did not have a diagnosis because it was mild or because they hadn't seen a doctor). The other study was of Medicaid and private insurance companies in the US- also showing a low rate of TS of 0.5 per 1000 amongst 10 million children! This seems to be because in America neurology doctors are not paid if they see a psychiatry patient and TS is classified as a mental disorder, so the doctors naturally call it something else! Let's hope President Obama succeeds in reforming the system there.

An excellent study from Sweden was presented (by Anne-Liis von Knorring, you can find the summary on the internet). This took a different approach predicted to identify higher numbers- looking at children in school and seeing how many actually have TS. She had a figure of around 0.5% overall but the interesting feature was that when association with OCD and ADHD was looked at, this comorbidity was most common in TS and chronic vocal tics, less common in Chronic Multiple Tics (CMT, persistent tics but no vocal tics) and not very common in Transient Tic Disorder (tics that disappear with age, very common in boys- seen far more often than TS).

4) Neuroimmunology

TS probably can't be explained by genes alone- but we don't have a very good understanding of other important factors. One theory is that throat infections with a bacteria called streptococcus (which is very common in children, about 30% have it at some time) may sometimes trigger off an immune response that attacks the brain (autoimmunity) causing TS or related disorders in genetically vulnerable individuals. An antibody called "anti basal ganglia antibody" or ABGA has been identified in a subgroup of patients who have a sudden onset of a TS like condition after throat infection and ABGA is also found in about 25% of people with "normal" TS, but the significance of this is highly controversial. It may mean that antibiotics or treatments affecting the immune system may be helpful for people with TS but there is not good proof of this so far.

Presentations at the meeting on this topic included one by British (alright, originally South African) speaker Professor Gavin Giovannoni who has been supported by Tourettes Action. We heard closely argued data from several other speakers and overall the jury is still out- I won't go into detail here but we will cover future developments on the blog.

5) Drug treatments and animal models

For most patients with severe tics in the UK the main treatment is with drugs. The effect of drugs tend to be a bit variable from person to person and as we all know they are not usually anywhere near 100% effective. The characteristics of TS make it difficult to conduct good clinical trials, providing the solid evidence needed to decide which are the best treatments. We know that small trials are often positive and this can be disproved with the larger trials ("placebo controlled, double blind) that are difficult to conduct. Many drugs have been tried but we usually recommend clonidine or dopamine blocking drugs (like sulpiride or aripiprazole). 

I am afraid this most important field is essentially a little stagnant at the moment. In general drug companies are not interested in developing drugs for TS. The Government funding body in the US (NIH) rejected applications for larger trials for TS, and this may be because of the emphasis that has been put on people succeeding despite having tics, and TS not being life-threatening. It seems unlikely that very much more reliable, effective and tolerable drugs are immediately on the way although people with TS may benefit from drug development for other conditions- novel drugs in other areas of neuropsychiatry could also provide something new for TS, if we can persuade the medical authorities of the need to allow off-license prescribing.

Another problem is the absence of a good animal model- meaning an animal system that through genetic engineering or brain surgery seems to resemble a person with TS either in a literal sense or in certain measurable characteristics, or in any case to the extent that drugs can be tested in the animal to predict if they will work for humans who actually have the disease. However at the meeting we did also hear about progress with animal models, this kind of work could be important in future.

6) Behavioural treatments

This area has increased rapidly in importance in the last few years, but in the UK we are badly lagging behind.

It has been known for some time that certain behavioural techniques delivered by experienced clinical psychologists can be as helpful for tics as drugs. These include habit retraining therapy (HRT) and exposure response prevention (ERP). The basic principle of HRT is for troublesome tics to be countered by a competing physical movement, and for ERP for suppression of tics in response to premonitory sensations (the feeling or urge that most patients have prior to ticcing, that gets better when they tic in response). The old view that suppressing tics is bad has been replaced by the current concept that suppressing tics actually makes the urge to tic reduce over time.

There are recent trials using a new acronym CBIT which is Comprehensive Behavioural Intervention for Tics. It consists of several elements: psychoeducation, HRT, functional intervention (identifying exacerbating and relieving factors), a reward system (for complying with CBIT, not for tic reduction) and relaxation training.

At the meeting we heard the results of the child CBIT study, and the adult results are awaited. Over 50% of children had a good response compared to 18% in the control group who received only the education and support elements.

We know that access to clinical psychologists is very patchy in the UK and worse than that there are hardly any psychologists who are experienced in these specialised techniques for tics. Tourettes Action is concerned about this. One possible but inadequate solution is to have a look at the books written by Douglas Woods and colleagues, available on Amazon, Doug is one of the primary researchers on these studies and the books for parents and for adults as well as therapists outlines principles that may help in self-management.

6) Impact of TS

People in the UK may be interested to see this survey of American TSA members including 670 adults, 740 parents and 420 children.

Some selected stats:

10 % adults quit job because of tics

17% avoided job interview

21% asked to leave a public place

Regarding treatments:

Children:

• Medication (83%)
• Diet Alteration (30%)
• Fatty Acids- Omega 3 (24%)
• Behavioural / CBT
• Psychotherapy
• Vitamins
• Support Group
• Mineral supplements
• Meditation
• Massage therapy
• Others.....

Adults:

• Medication (95%)
• Diet Alteration
• Support Groups
• Meditation
• Psychotherapy
• Massage therapy
• Vitamins
• Behavioural / CBT
• Chiropractic
• Fatty Acids- Omega 3

And drugs:

Children:

• Clonidine (50%)
• Guanfacine
• Risperidone
• Sertraline
• Aripiprazole (20%)
• Pimozide
• Clonzaepam
• Escitalopram
• Haloperidol (10%)

Adults:

• Haloperidol 40%
• Clonidine
• Risperidone
• Pimozide
• Fluoxetine
• Paroxetine
• Alprazolam
• Escitalopram
• Guanfacine

Interesting as we tend to avoid haloperidol in the UK due to side effects- newer drugs are preferred.

So I hope this summary of the New York meeting is interesting- it will be longest entry in the blog for a long time to come. Watch out for updates on new reports of interest....