Tuesday, August 30, 2005

PDS in old age

Do older people show less symptoms of PDS or are there fewer to have PDS? I gave a talk at the Oxford Dysfluency Conference, where I showed that the attendance of therapy is declining with age. I argued that the effect is not due to the fact that fewer older people stutter, but due to other reasons: see my post. But a few people said that there is a decline in age. But I havent found any very convincing articles yet. I just looked at the internet and couldnt find anything in 5 minutes. (So it cannot exist. :-)

I also have conceptual problems to believe it as it doesnt fit in well with my understanding of PDS. If it's really a defect somewhere, then how can old age make it better? Or if there are compensationary systems, then shouldnt young people be more likely to stutter less? The only reason I can come up with is that the neurotransmitter balance is changing, which then affects the severity of PDS symptoms. So if there is clear research showing that older people stutter less, then this seems to point to a dependence on the neurotransmitter systems. Well, I guess you can also argue that people calm down and have less energy to stutter!

Sunday, August 28, 2005

Why are you so scared?

Over the last weeks, I have been reading a German discussion forum. I was amazed to discover how many were very scared of speaking situations, and tried everything possible to avoid them. One person is getting married this weekend, and the whole forum including him and his wife spent so much time trying to come up with tricks so that he doesn't have to speak.

I know what it feels like to be in such a state. I was the same when I was young(er). But strangely enough, after the age of 20 I am not scared at all at any situation, even though I do stutter in most of the situations. I am still wondering why? Is it because I attended therapy and met other people with PDS? Or is it just an hormonal change and my true personality shines through? :-)

Anyway, reading the posts has made aware again that the handicap arising from PDS is NOT JUST dysfluency, but for many (especially those that never had contact with other people with PDS) can impact life very dramatically. But their current (and my past) behaviour is completely irrational. You have the choice: being scared like hell or worrying for a week before the speaking situation and then stuttering, or not worrying and stuttering. Isn't the choice obvious? I guess the solution is "to do what you fear", and the fear will dissolve if the fear is irrational. In fact, I believe that many people with PDS can reduce their fear substantially by attending group therapy, and speak or "stutter" in a safe environment. Making you mentally fluent is easier than physically fluent.

To finish off, let me tell you what might have made me fear less: A dream! One day I was dreaming about being chased by a few people. I was always running away and I always ended up on the top of a cliff line. Obviously, there was no escape route, and the closer they came the more scared I got. But one day I realized that I was dreaming, and being a physicist I realized: "Hey, inside dreams the laws of physics don't apply!!!!!" So I decided to fly away! This happened in several dreams. So I could always fly away, but after a while I got bored by running away. So then one night I realized again that I was dreaming and I told myself: "I am so sick of running away. Let them kill me. Physics doesn't apply. But would be cool to see what would happen if you get killed in your own dream." So instead of flying away, I turned around and stood there waiting for them to come closer. And then they got scared and run away. And I started chasing them!! From then onwards, I hardly had nightmares anymore... :-)

Friday, August 26, 2005

Visitor from Kuwait!

I just noticed that my blog had a visitor from Kuwait. There are very very few people from Asia. I would be interested to know what is happening regarding PDS in Arabic countries. Maybe there is a stuttering oil sheik who can sponsor my blog! :-) If you are from Asia, please post a comment or send me an email. I would love to hear from you.

Thursday, August 25, 2005

Between speech and language?

What can happen, will happen somewhere sometime! A quote from my old physics professor at university. You can modify the statement to: What works, will break down somewhere sometime! This realisation leads to be a beautiful analogy between body disorders and body functions. For example in the brain, every brain function must give rise to at least one brain disorder. So the spectrum of brain disorders is a reflection of the functions of the brain. So how about PDS?

The intriguing thing is that PDS does not seem to be a fundamental malfunction of language nor of speech. Virtually all people with PDS have the ability to speak completely fluently at times and in certain situations. If you mix their fluent speech samples with samples of normal speakers, I bet with you that a listener will not be able to distinguish between the two groups. So we do have the ability to speak, and we are not like some people who cannot pronounce certain sounds or control their speech rate. Concerning language, no-one to my knowledge has ever shown that people with PDS have clear language deficits (like in dyslexia), but possibly very subtle ones.

But to what brain function does PDS link if not language or speech? My answer is that PDS is not a total breakdown of a brain function, but only an unstable underperforming brain function. Moreover, PDS is probably not about a specific brain function, but about the malfunctioning interplay between different brain functions, probably the integration between different information from different brain regions. In a sense, it is in between speech and language.

I am finished with drugs

I have been writing a lot about drugs for treating PDS, and this post is going to be the last for a while.

My blog is getting a bit too interactive! Yesterday I received an email by a prospective participant of the Paraglone study. For the sake of science, I should probably not speculate about the study until its end. However, as the study is very likely a double blind study, I guess writing on a blog about the subject and "experimental subjects" reading the posts does not bias the results?

Holger Stenzel provided me with more information on drugs & PDS, only enhancing his junkie status! :-) I am just kidding. In my opinion, he deals with the issue in a frightfully rational and responsible way. He told me and I read about his experience with two drugs: Risperidone and Olanzapine. He took the medication under the supervision of a neurologist. He discontinued use of Risperidone after only a brief period, and has been taking Olanzapine for two and a half years, but is now only taking it every second day. He has spoken about his experience in German discussion forums, and made his reports available to researchers and pharmaceutical companies. To summarise, he says that he has been noticeably more fluent (he talks about a reduction of 30%) but with some side effects. He also said that the German discussion forums have been quite ideological about his reports/work. I have read his posts, but I wholeheartedly support him, as his descriptions and review of the literature strikes me as very objective and informed. In fact, I was wondering myself whether, given the opportunity, I would try a drug myself.

Holger has also sent me links to two interesting articles: on Olazapine, and a review by Maguire and others.

He also told me about this on-going "pilot study of the efficacy and safety of Aripiprazole in the treatment of stuttering (co-PI), 2004 to 2005." (check here) Aripiprazole was developed by Britol-Myers Squibb Company to treat schizophrenia. Its effects are novel in the sense that it is not only antagonistic to dopamine receptors, but can be partially agonistic in case of lower-than-normal activity. Therefore, a stabilisation of the neurotransmitter system is expected.

The Department of Psychiatry and Human Behavior from the University of California at Irvine has a budget of $5 million dollar to work together with pharmaceutical companies on Phase I-III Clinical Trials, among them on PDS.

Monday, August 22, 2005

Timeline of Pagoclone study

Several of you have asked me about whether I know the timeline of the Pagoclone study: see Indevus' website, and a previous post.

I have been told that the study is starting now, and expected to be finished within less than a year. So we are looking at late Spring or Summer 2006 for the earliest date of the results to be made public.

General speaking, the pharmaceutical industry is under pressure to publish the results even if it turns out to be negative.

So we need to wait.........

Friday, August 19, 2005

Tom's Top 10 on drugs

Here are some thought provoking statements about using drug for PDS treatment.

1) Drugs will never cure PDS.

2) Studies will show that some drugs reduce stuttering symptoms in the majority of people with PDS.

3) Drugs will be less effective for some, probably allowing scientists to divide people with PDS into subclasses which would be a very significant finding.

4) Studies will also show that there are no long-lasting effects once drug use is discontinued.

5) The most useful and effective use will be temporally limited to a few hours i.e. taken before an important presentation or job interview.

6) The drugs will have no significant side effects.

7) The class(es) of drugs most effective will give us a better understanding of the nature and causes of PDS.

8) Drugs that do not alleviate symptoms but might help to unlearn bad habits, learn new habits or prevent relapse will become as important as drugs alleviating symptoms.

9) Pharmaceutical companies might jump on the band wagon depending on the strength of the business cases. Leading to more money for *real and no nonsense* scientific research and to aggressive marketing, and in the process to an over-emphasizing of the real usefulness.

10) The use of drugs that act more with the fear/anxiety aspects or that will be taken over long periods of time will stay problematic both medically and ethically.

The German stuttering junkie

Holger Stenzel has posted an interesting comment in German, so I decided to translate it in English so you can read it.

I have never met Holger, but several people kind of jokingly refer to him as the German stuttering junkie :-), as he is very knowledgable on this issue, has been and is discussing the issue in German discussion groups and, I think, also wrote about his experience with some of the drugs, but I couldnt find anything on google.

Here is the text.

"The good and bad days effect seems to be shared by many people with PDS according to testimony.

My personal symptoms are also marked by constantly changing phases of better or worse fluency. I find it very difficult to causally link them to other factors. Except that good days in terms of fluency seems to go hand in hand with better cognitive performance in word retrieval and concentration, and during bad days I often experience that any attempt to speak creates havoc in my brain.

It is plausible that the effect is related to specific constellations of the neurotransmitter metabolism. Finding the underlying biochemical mechanism could provide the necessary basis to develop drugs that would so-to-speak keep the good days permamently. This approach should be feasible and would be an important step in a medical treatment of stuttering.

Currently, neuropharmaceutical understanding of stuttering is not sufficiently good. An inhibiting factor is the very limited ability of test any drug for speech and cognition using animal models. Gerry Maguire et al.'s dopamine [Note: a neurotransmitter] hypothesis is a first step and based on clinical studies of the drug Risperidon and Olanzapin. The dopamine antagonists are the first class of drugs with proven fluency enhancing effects.

A rather unintended discovery was the dramatic reduction in symptoms with some people with PDS taking a derivate of the substance Cyclopyrrolon, Pagoclone. The outcomes of the Phase 2 study by Indevus Pharmaceuticals Inc. are eagerly anticipated. Pagoclone is said to act as an antagist and modulate GABA-A [Note: see here]. The inhibitionary effect of GABA is due to hyperpolarisation. A stream of negatively charges ions blocks the depolarisation of the neuron needed to release the action potential. And that is how GABA reduces the electrical excitibality of neurons. Indevus is the first pharmaceutical company to have apply for a patent for a drug for PDS: see here.

Best wishes from Germany!

Holger Stenzel

(Source: Holger Stenzel, translated by Tom Weidig)

Tuesday, August 16, 2005

Fluctuation over time

Today, it is just a quick post. The post is about the fluctuation of the severity of stuttering over time. Many people including myself experience moments of greater fluency and unfortunately moments of disastrous disfluency. Why? A scientific theory must explain this phenomena. We all go through periods where we are in best form, be it intellectually, mood-wise, or like in sports. Or, for example, people with hearing difficulties also fluctuate in their ability to hear. So this fluctuation in fluency should not come as a surprise, but still the question is what is the exact mechanism that makes us more or less fluent.

Sometimes it could just be day form, but sometimes it seems to be a situation that changes severity dramatically. I am wondering whether much research has been done on this issue. Does the severity have cycles like increasing slowly, peaking and then going down slowly? Or is it more erratic? Changing dramatically within one day. And how much does it fluctuate? Which factors correlate with a change in fluency?


By the way, I am currently in Munich, and writing this post from the computer of a friend of mine. She actually promised me to read my blog. So if you are reading this: Hello Heike! Do you like my blog? :-)

Saturday, August 13, 2005

Too busy to write

I am too busy to write... until next Wednesday....

I have to organise a party for tommorrow evening and then I am off to Munich.


Friday, August 05, 2005

Neurotransmitters and PDS

Swallow one pill and your stuttering is gone! An attractive thought for most of us who have PDS. No tedious speech exercises or frightening exploration of our inner soul. Over the years many drugs have been tried out to reduce stuttering with mixed results. Some drugs seem to be able to reduce stuttering but not eliminate all dysfluencies. But, the effect is very dependent on the person, and side effects can be severe. In this post, I want to explain why drugs can have an impact on stuttering severity. But please take my expose in with a pinch of salt, I am not an expert.

Broadly speaking, many drugs impact stuttering by directly or indirectly changing the level of (certain types of) neurotransmitters in the brain. Thus, the issue is really about understanding how a change in the level of neurotransmitters can affect stuttering. Neurotransmitters are molecules that relay and modulate the electrical signals between neurons and are therefore able to inhibit or increase the activity of neurons. The mechanism is as follows. Neurons have long arms which end close to other neurons. When a neuron fires an electrical signal, the signal travels along the long arm. At its end due to the electrical signal, neurotransmitters are released and they dock to the receptors on the membrane of the other neuron. This docking provokes changes in the other neuron influencing its probability to fire a signal. Different regions of the brain have different sensitivities to the different types of neurotransmitters. This sensitivity comes from the number of receptors for a specific type of neurotransmitters the membrane of the neurons in that region have.

When I think about neurotransmitters acting on the brain, I think about the weather acting on a big city. Remember I compare the brain to a big city, with many different objects interacting with each other. And the neurotransmitters are the weather that changes the interaction of the objects. For example, during heavy rain fall, the motorways have more traffic jams because the tyres have less grip on the road. Or during suneshine, people are having less stress and work more efficiently. I think of PDS as a defect underground transport system either due to genetics (e.g. a blueprint for underground trains or how to build tunnes is missing) or developmental issues (e.g. the tunnels was never built due to an earthquake or no cash). You can now see how the weather (i.e. the neurotransmitters) can impact the functioning of the city without an underground system. Nice weather makes it easier to function without an underground system. Bad weather like heavy rainfall (i.e. different levels of neurotransmitters due to stress or panic) makes the absence of an underground system much worse. A drug that gives you nice weather makes you stutter less.

After this crude introduction, I will be able to discuss the Pagoclone pharmaceutical study in more detail in my next post.

Thursday, August 04, 2005

Quality stamp against evaluation

A lot of efforts are going into evaluating different therapies. As I have said before, evaluating the efficacy of a therapy is a very tricky business. And comparing therapies is even more difficult. There are many theoretical issues. Let me list a few. The profile of the clients might be different. The quality of therapist might influence the therapy. Can you punish a therapy where the clients did not follow the instructions. The enormous efforts needed to get a sample big enough for reliable statistics. Defining the correct outcome measures. The time period over which the clients need to be monitored. These are a few of the issues from the top of my head. I agree that criticizing is always much easier than making constructive suggestion for improvement! But let me just re-emphasize that I myself had done a statistical study on patients' data of the KST.

Due to the enormous difficulties to have a controlled environment to do measure therapy efficacy, I believe that national associations must be realistic and go the route of quality control rather than evaluation. Instead of evaluating the success of a therapy, the associations could give out a "quality stamp", a kind of seal of approval. Therapies must fufill certain quality criteria to obtain the "quality stamp". My suggestions would be, for example: The therapy is fully documented. The patients are informed about the latest understanding of PDS. The patients are told that a cure as such is unlikely but a significant improvement with hard work is possible. The therapy has a maintenance phase of at least one year. The therapy or therapist must exist for at least one year. And so on.

So what is your opinion? I think such an approach is doable, even though much work and lobbying would need to be done...

Wednesday, August 03, 2005

Battle of the Therapies

Which form of therapy is the best? Answering such an explosive question is not easy, and might even be impossible when including practical considerations on costs, logistics, therapist-dependent-outcome and even defining outcome measures. I do not know of any published serious research comparing different therapies with enough clients to do decent statistics.

To my knowledge, PEVOS from the Demosthenes Institute of the German Stuttering Association is the only such attempt currently running. The Demosthenes institute deals with educational and research issues on PDS. PEVOS stands for "project of evaluation of stuttering therapies". The linked webpage is in German. They have written an English article for a forum discussion at the ISAD 2003: look here.

They write in the abstract: "On the initiative of the German self-help organisation the PEVOS program was developed to evaluate different stuttering therapies over a time period of two years after therapy. The concept was designed by a group of therapists and scientists and was tested since 2001. In the test-phase data were collected from ten therapists with 100 clients. Fluency data were obtained by telephone calls. Functional outcomes and changes in attitudes and emotions were measured with questionnaires. Results of the test-phase¹s evaluation including the first two assessments will be presented, organisational problems and possible solutions will be discussed."

Their results do not suprise me, and confirm what many have found before. The clients have on average significantly improved in fluency. Unfortunately, they do not have long-term data yet. At least one-year data is needed to evaluate the success of a therapy. They have also not compared between therapies for example, but such a comparison might not be very meaningful until long-term data is available. They are refreshingly frank about the difficulties that they faced. They conclude: "In addition the program is very time-consuming and therefore expensive. PEVOS has been financed by the German stuttering association during the test-phase and its follow-ups. Several unsuccessful attempts have been made to secure funding for the main implementation of PEVOS. Considering these failed attempts it is necessary to think the concept over: it must be considered that therapists and/or professional associations of therapists contribute to the costs. At the same time it must be considered how the program could be less time-consuming." Unfortunately, the issues (e.g. of data collection) will only get worse as time from end of therapy (to get the long-term data) will increase. And I can think of other important theoretical issues that they have not even discussed... It is very very tricky to do the research sensibly... But they should be applauded for their efforts and courage to launch such a project! I am more of an advocat for a "quality stamp" approach by national assocations than evaluation which is difficult, tricky and messy. Such an approach would entail a checklist of features a "good" therapy should have: giving information on PDS, maintenance phase, no claim of a cure, etc.

The article was as of End of 2003. A new statistical study of the current PEVOS data (which should include more long-term data) is underway, and new results should be out in a few months.