Tuesday, October 30, 2007

European Symposium on Fluency Disorders

There is a new conference coming up in Belgium in April 2008: the European Symposium on Fluency Disorders: see here for more information and a detailed program of speakers. The conference is organised by Kurt Eggers who works as a lecturer and clinician at the Lessius University College. I met him at the Oxford Dysfluency Conference in 2005, I think. He is currently doing a PhD on the role of temperament in stuttering and his PhD supervisor is Luc de Nil.

I will attend. It is only 2 and a half hours away from Luxembourg. The most interesting speakers for me are Luc de Nil with a summary of past brain research, and Nicole Ambrose on possible genetic factors for subtyping. Some talks are given via video conference link which is an interesting concept. I'll be curious how it works out!

Sunday, October 28, 2007

Crackpot award for Bodehamer

I have decided to continue my crackpot awards: see here, and here. But I am now going to include anyone who proclaims theories on stuttering that are completely ignoring well-established neuroscience facts on stuttering from the last 10 years. I mainly think here about structural and functional brain differences in young and adult people who stutter, and about genetics. Bob Bodehamer is a "good" example:
The cause: There could be several causes for blocking including genetic predispositions and/or developmental problems. However, our concern is not primarily about the first cause of blocking. Our concern is with what has continued the behavior. We believe that it is the meanings placed around those early experiences of struggling to speak that have become well learned which continues the behavior. This explains how most children grow out of stuttering while some don't - it is about the meanings that the child placed around the behavior.
This statement is just plain non-sense in the light of the most recent research. He permits that these first blocks could be triggered by genetics, and these blocks are enough to learn bad habits which results in long-term stuttering. So what happens to the genes afterwards? Are they self-destructing and not play a role anymore? Also, brain scans clearly show that the brain structure of adults and young people who stutter is different than fluent speakers. There is a physical manifestation. People who stutter do not have misplaced meaning, they have misplaced brain structures. In fact, what is happening is that the physical cause STAYS THERE even for children who recover, and provokes learned behaviours for those who don't.

He should stop playing the theoretician. Science is not theology, his day job as a Southern Baptist pastor. The empirical reality informs the theory, and not the other way around. I just hope he at least does not think that the Earth was created 7000 years ago. If he wants to contribute constructively, he should acknowledge that stuttering has a clear physical component. And no-one is disputing that the effects are also learned behaviour. And here is where he can use his NLP to minimize the effects, but I doubt it is any more effective than other treatments.

Saturday, October 27, 2007

Shameless advertising

This is just so bad and fits perfectly with what I alluded to in my tirade on media portrail of stuttering: see here.

I am wondering whether she is still using the device. Would be great to have her write a post on this! So if anyone knows her, let her know that I would love to hear from her.

Friday, October 26, 2007

Trial Start: DCM vs Lidcombe

Good news from Marie-Christen Franken! She has now received funding for a large-scale trial to compare the demands & capacities treatment to the Lidcombe treatment. And they have already enrolled children.

They have already published a pilot study: see here. Based on a relatively small sample and no long-term outcome measure (both are essential for a good trial!), they could not see a difference between both treatments:
This pilot study compared two treatments for stuttering in preschool-age children.Thirty children were randomly assigned to either a Lidcombe Program (LP) treatment or a Demands and Capacities Model (DCM) treatment. Stuttering frequencies and severity ratings were obtained immediately before and after treatment (12 weeks). The stuttering frequencies and severity ratings significantly decreased for both treatment groups. No differences between groups were found. Parents of children in both groups were cooperative in many respects, and there were no differences between them on scales that measured their satisfaction with the two treatments. The findings suggest that randomized controlled trials of LP versus DCM treatments are feasible, and they underline the need for experimental analyses of the two treatments. EDUCATIONAL OBJECTIVES: The reader will be able to: (1) describe the principles and methods of Lidcombe treatment for early stuttering; (2) delineate principles and methods of Demands and Capacities Model treatment; and (3) summarize results of an investigation that compared these programs' relative effects in a pilot study.

I am very curious what will come out. My guess is no big difference between both treatments. Though I am concerned that the statistics and research design like in the Lidcombe trial will be flawed. Another interesting twist would be to have a third non-treatment arm.

Tuesday, October 23, 2007

Meeting Marc Shell at Harvard

As you can see Marc Shell has changed a bit over the years. I guess this is what happens when you become a professor of comparative literature at Harvard University. Marc even has his own wikipedia entry, and of course he stutters. He recently wrote a book on stuttering, literature and his own experience called Stutter.
I met up with him on my East Coast stop-over from my California trip back to Europe. Boston was my first stop. The day started badly. I had arranged two meetings with two professors and they both canceled at the last minute, but then agreed to meet up upon my insistence. In the morning, I had a meeting with a professor at Harvard Business School who also wrote a book on venture capital, like myself. Mine is called Exposed to the J-curve. In the afternoon, I was supposed to meet up with Marc at 4:30. In the mean-time, I was sitting in a coffee shop at Harvard Square soaking in the atmosphere with free WiFi. And I played chess against the scrubby "chess master" outside in order to uncover him, but much to my surprise he was a true chess master with international rating and I lost all my games and money! I also have international rating and played in the World Junior Championship for Luxembourg but I am not at master level. Then I went to the English department, but Marc Shell didn't show up. I was just about to leave when the secretary run after me and called me back.

We had a good discussion on stuttering and on stuttering research. We especially talked about how more money could be channeled for stuttering research. Though I have to admit that at first it was a bit surreal to watch Marc Shell in action when the discussion turned from daily talk to intellectual. His words were chosen in such a way that my mind went blank. I mean I heard his words but didn't understand what he was saying. When science meets the arts... I noticed that his words are more loaded with specific meaning. So when I say functional I mean something that has a function, but he probably gives it a more specific meaning in the context of a given theory. He also comes up with many interesting subtle connections and ideas which make logical sense but are often not necessarily of relevance to explain the basic aspects of a phenomena.

Monday, October 22, 2007

Phase III Pagoclone trial delayed?

I know how interested every here is in stuttering medication, especially Pagoclone and its clinical trials. Some time ago, I posted a press release from Indevus about their intention to start a Phase III clinical trial in the first half of 2007: see here.

However, as of October 2007, I do not know of any evidence that the Phase III trials have already started, except the existence of waiting lists for the trial. (If you are currently part of such a trial, please let us know.) I can only speculate on this delay. First, any kind of project is often delayed by a few months for any reason. And therefore there is no reason to be concerned. Second, Indevus might have become more hesitant, and are having second thoughts. Such a re-evaluation might be in terms of efficacy, or in terms of a business decision. A re-evaluation also often happen irrespective of efficacy concerns after changes in management, the board of directors, or general strategy. For example, if Pagoclone only applies to a minority, the profit estimates might be severely affected. Such trials are very expensive, often in the tens of million dollars. On the other hand, an approved drug would have significant revenues. Indevus might also underestimate the potential market even as a "minority" drug, and therefore find the risks too high. One concern might also be their cash burn rate, i.e. they spend money without getting money back soon, and they might be looking for a partner like a venture capital fund or another pharmaceutical company to share the risks: see this intriguing conference call one year ago. As I said, I am only speculating by putting myself in their situation, based on public knowledge and based on my understanding of corporate thinking.

We will find out in the next months. However, should Indevus decide against a Phase III trial, which I hope they won't, do not expect a press release. Indevus has already stopped Pagoclone as an anti-anxiety drug and for premature ejaculation, I believe, and a third U-turn would reflect badly on them. A more likely scenario is that they postpone and delay release as long as possible, and the news appears somewhere in an annual report on page 130 in terms of a lack of provisions for Pagoclone. For example, the year-end 2007 balance sheet will be audited in March. So, the longer the trial is delayed, the higher the probability that they have indeed changed their mind.

On a side note, a detailed article on the Phase II clinical studies has not been presented at any conference or published in a peer-review journal, as far as I know. The only information comes from the Indevus press-release and conference calls to analysts: see here. However, at some point, such an academic discussion with a closer look at the data must happen.

Let's hope that this post is a storm in a teacup! Let me know when some of you are participating in a Phase III trial.

Sunday, October 21, 2007

Trying out medication: Week 4

Here is the four-week report on taking Zyprexa: see here and here for earlier reports:
Four weeks into the Zyprexa Zydis and so far, so good. The first week or so was very tiring indeed, my energy levels were sapped and I was very sedated. After about 10 days my energy levels resumed and I felt fine. My facial ticks/secondaries are all but gone, as I don't have to struggle so much to get the words out. In the past my stomach used to get into knots from forcing out the words, this has also stopped as the words seem to flow better. I no longer think about speech all the time, its a refreshing change after 30+ yrs as my mind seems clearer and I can focus more. I am less anxious in speaking situations. I am still a stammerer, don't think that this drug is a "magic cure" because its not, what it enables me to do is relax and seems to make the speech timing improve as I don't have the blocks anymore when initiating speech. Weight gain has been slight - I would say about 5-6lbs, however my weight fluctuates by 2-3lbs per week up and down anyway, and I can exercise off this weight gain without any worries. To sum up....."So far so good"........ My doctor said that when he saw me after 3 weeks, he could see an improvement in my speech and my eye contact. I will be having a blood test at 6 week and may well increase the dosage to 10mg as long as the sedation effect is not too much. I imagine that this treatment works better on some sub-types than others, and its working so far. I will let you know what the blood tests show in 2 weeks.

Friday, October 19, 2007

The second brain paper

The second article is now in press at NeuroImage. The main author is Soo-Eun Chang, a post-doc in Christy Ludlow's group at NIH (National Institute of Health) in Bethesda close to Washington DC. She is a speech and language pathologist by training. I had the pleasure to meet up with her and Christy for lunch on Wednesday before I took the plane back to Old Europe. Our discussion topics included their work and stuttering medication.

Here is their abstract of Brain anatomy differences in childhood stuttering by Soo-Eun Chang, Kirk I. Erickson, Nicoline G. Ambrose, Mark A. Hasegawa-Johnson, and Christy L. Ludlow:
Previous imaging studies in adults with persistent stuttering found left white matter deficiencies and reversed right-left asymmetries compared to fluent controls. We hypothesized that similar differences might be present indicating brain development differences in children at risk of stuttering. Optimized voxel-based morphometry compared gray matter volume (GMV) and diffusion tensor imaging measured fractional anisotropy (FA) in white matter tracts in 3 groups: children with persistent stuttering, children recovered from stuttering, and fluent peers. Both the persistent stuttering and recovered groups had reduced GMV from normal in speech-relevant regions: the left inferior frontal gyrus, and bilateral temporal regions. Reduced FA was found in the left white matter tracts underlying the motor regions for face and larynx in the persistent stuttering group. Contrary to previous findings in adults who stutter, no increases were found in the right hemisphere speech regions in stuttering or recovered children and no differences in right-left asymmetries. Instead, a risk for childhood stuttering was associated with deficiencies in left gray matter volume while reduced white matter integrity in the left hemisphere speech system was associated with persistent stuttering. Anatomical increases in right hemisphere structures previously found in adults who stutter may have resulted from a life-time of stuttering. These findings point to the importance of considering the role of neuroplasticity during development when studying persistent forms of developmental disorders in adults.

We'll find out whether Neanderthals stutter

Check out this interesting article: Neanderthals May Have Had Genes for Speech. The scientists have found FOXP2, a gene that in humans is known to relate to grammar/speech, in Neanderthal DNA. It is fascinating that we can now look at ancient DNA.

Once we have singled out the stuttering genes, we can also look at whether Neanderthals have these genes. Maybe they got extinct, because they were stuttering much more that modern humans!!!

Meeting the Inghams in Santa Barbara

The weekend before last I drove up North to Santa Barbara to meet up with the Inghams. They are both professors in speech science at UCLA at Santa Barbara and clearly among the leading scientists in stuttering research. They were so kind to invite me to stay at their place. They have a fantastic house in the hills of Santa Barbara. Roger Ingham showed me around in his BMW with the words "I like it much better than my Ferrari that I had before"... :-)

We had very good scientific discussions but also engaged in gossip. They were not too enthusiastic on medication to reduce stuttering due to lack of good evidence. I was questioning how this fits in with several reports (see previous blog posts) from people who stutter who took a medication and said they improved. The discrepancy might be due the existence of sub types. Or because the gains are not overt, but internal. I argued that stuttering is not just a malfunctioning of communication of the message from the person who stutteres to the listener, but that stuttering also affects the mental creation and therefore quality of the message. People who stutter either spent a lot of efforts avoiding or generating fluent speech or dealing with secondary symptoms and states of anxiety. This leaves them much less room to create good messages. I am so much better at creating messages when I stutter less and am not under time pressure. And, the medication might make this easier. Or, there were no improvements apart from placebo-enduced and due to weak methodology.

I also discussed with Roger Ingham his past, current and future research. He has a multi-million research grant and still works very closely with the brain researchers around Peter Fox in San Antonio (Texas). The Inghams go to Texas and stay there for longer periods of time, though they did not express great admiration for San Antonio's beauty. Regarding research, they are clearly moving in the direction of theory testing using methods like TMS (knocking out brain regions temporarily) to test causality, and dual tasks and fluency-enhancing setups to control the driving variables of stuttering better.

Thursday, October 18, 2007

Two breakthrough brain studies!

There is a new article out based on brain imaging work from two top neuroscientists Kate Watkins and Smith at Oxford on the brain of young people: see here and the abstract below:
Using functional and diffusion imaging, we examined brain structure and function in the motor and language areas in a group of young people who stutter. During speech production, irrespective of fluency or auditory feedback, the people who stuttered showed overactivity relative to controls in the anterior insula, cerebellum and midbrain bilaterally and underactivity in the ventral premotor, Rolandic opercular and sensorimotor cortex bilaterally and Heschl's gyrus on the left. These results are consistent with a recent meta-analysis of functional imaging studies in developmental stuttering. Two additional findings emerged from our study. First, we found overactivity in the midbrain, which was at the level of the substantia nigra and extended to the pedunculopontine nucleus, red nucleus and subthalamic nucleus. This overactivity is consistent with suggestions in previous studies of abnormal function of the basal ganglia or excessive dopamine in people who stutter. Second, we found underactivity of the cortical motor and premotor areas associated with articulation and speech production. Analysis of the diffusion data revealed that the integrity of the white matter underlying the underactive areas in ventral premotor cortex was reduced in people who stutter. The white matter tracts in this area via connections with posterior superior temporal and inferior parietal cortex provide a substrate for the integration of articulatory planning and sensory feedback, and via connections with primary motor cortex, a substrate for execution of articulatory movements. Our data support the conclusion that stuttering is a disorder related primarily to disruption in the cortical and subcortical neural systems supporting the selection, initiation and execution of motor sequences necessary for fluent speech production.
Another similar study will come out very soon. Studying and finding similar things. I'll talk about it as soon as it is published.

These two studies are especially significant as they studied young people's brains which should be less affected by years of stuttering. There is now very convincing evidence that brains of people who stutter are structurally different. WE HAVE DIFFERENT BRAINS!

Tuesday, October 16, 2007

Who says stuttering has no benefit?

There are not only costs to stuttering. Today, I drove down from Princeton to Washington DC on the 95 South. The speed limit is 65mph, which is infinitely slow for a European driver who is used to 90mph. So I was stretching the limits a bit, and much to my surprise a police car gets behind me and makes me tstop. Do you know what I did? I on purpose stuttered as much as I could. Where are you heading to? "Ehhhhh, WWWWWWWasshhh, WWWWaashhhh.." and so on. He was very confused and his face said "Why did I stop this freak?". I got off with a warning. Somehow he didn't want to spend too much time on me.. And who says stuttering has no benefits? :-)

Friday, October 12, 2007

Judy's Online Conference

Here is a link to Judy's online conference 2007. Many different people write articles on many different topics on stuttering: some interesting, some informative, some personal, some the same old stuff, and some misguided! Judge for yourself.

Meeting Jeff Blitz

The rocket scientist, that is myself, met up with Jeff Blitz, the director and writer of Rocket Science in Westwood on Sunday morning for breakfast. Luckily, Jeff also stutters so I had the opportunity to meet my first Hollywood director. He was not accompanied by blonde girls or bodyguards. I met Jeff at the opening of the research center at UCI Medical Center. So if you young, stutter and see no hope for a future career, don't worry: you can still become a Hollywood director, a quantum physicist, a UK pop star (Gareth Gates), a top sprinter (Ben Johnson), guitarist of Wet Wet Wet (Graeme Duffin), professor of comparative literature at Harvard (Marc Shell). I wonder if we also have a famous serial killer or mafia boss in our ranks. Did you make fun of my stuttering? Or if you don't want to be any of the above at least they will meet up with you as you stutter, too!

Jeff is the "older" person on the right with the main cast and the film producer. To be fair, Jeff looks younger in reality, but this is the only picture I could find of him. You definitely need to check out the movie website for previews. The main character is a teenage boy who stutters and joins the debating society. It is good to know that someone who stutters wrote the script and knows what it feels like to stutter. I haven't seen the movie yet, but I am convinced that it is one of the most faithful portrayal of stuttering so far. Jeff spoke about the challenge to present his movies in front of audiences during Q&A sessions. You should also check out his most famous movie, Spellbound, which received many awards including an Oscar nomination for best documentary. And this BBC interview.

Thursday, October 04, 2007

The Center for the Medical Treatment of Stuttering (CMTS)

I am currently in Orange County / LA, and I will attend tonight's opening ceremony of The Center For The Medical Treatment of Stuttering at UCI Medical Center, which is headed by Gerald Maguire who is a psychiatrist and the world leading (and only) clinician/researcher on stuttering medication. The center was made possible by a 1 million dollar endowment from Granville Kirkup. The focus of the center is on treating people who stutter using medication, on the research into stuttering medication, and on teaching. They will put out a press release to which I will link.

The center is a really great initiative to explore new avenues in the treatment and understanding of stuttering. The area of stuttering medication is still in its infancy, but shows promises at least for some patients. It's still early days, and some, especially from the traditional stuttering community, are quite skeptical and critical. However, it is also fair to say that most critics do not really know much about neuropharmacology and act out of instinct, and most importantly do not offer effective long-term treatments themselves. I get tens of emails from people who are looking for new avenues as traditional approaches have not helped them a lot. I am not saying stuttering medication is the answer for everyone or a cure for some. But we must explore new approaches.

Jerry has invited me to the opening, and I have been offering him free advice when needed on various issues from statistics, scientific methodology, fundraising to website design. But I'll keep an open mind, and I am not endorsing stuttering medication. I just do not know enough about them, and lack first-person experience. However, I fully endorse the idea that we must spend much more efforts on exploring this new avenue. In the same way, as we should with genetics and brain research into stuttering.

Monday, October 01, 2007

Trying out Medication: Week 1

Here is his experience after one week on Olazapine:

It's a week since I started on the Zyprexa Zydis and the Zantac (generic used). I have been tired, the first 4/5 days were very tiring, it seems better now, less tired. (the 'spaced out' feelings have gone). There has been no noticeably gain in weight, maybe a pound or so, but my weight can fluctuate by 1 or 2 pounds a day anyway.....I have not been able to exercise much this week as I have been so tired, however I am now over this and will exercise from now onwards. I will have a blood test in a couple of weeks to check my levels.

The facial ticks are all but eliminated, I am surprised that this happened so quickly. I feel less/hardly any stress in talking situations and indeed have intentionally put myself into more speaking situations as my confidence has grown. My stuttering has dropped considerably and I am only in week 1 of the treatment. There are hardly any blocks anymore and if it continues at this rate, I will be all but fluent soon - I'd never use the word "cured".

The fact that I am taking the drug may well have given me increased confidence and the upward spiral of confidence has occurred as opposed to the usual downward spiral that we usually experience, so it is self perpetuating. I liken the drugs to a pair of glasses for my eyesight, while I wear the glasses/take the zyprexa it will help my eyesight/speech, however if I take the glasses off/stop the treatment, the symptoms are still there.

Trying out medication: Week 0

I am starting a series on one of your fellow readers who is trying out whether medication is helping his stuttering. (I have edited the report and took out names.)

I am a 39 year old male that has always stuttered. I am married with 3 children, all of which are fluent. I have good and bad days, however over the years it seems to have got worse and I use a good deal of avoidance when entering speaking situations. I suffer mainly from blocks as opposed to repetitions and have major problems with introductions and my name (and other factual things I cannot change).

I have had conventional speech therapy as a young adult and in 2000 I did the McGuire programme. The costal breathing was great, it worked for a while and I was 100% fluent, well I say fluent, thats fluent to people on the outside, as I was thinking/living and indeed breathing stammering 24/7 365 days a year. After the Maguire programme, I got worse and worse as it was hard to go from "fluent" to worse than I was before the programme. I have tried hypotherapy and various CD/MP3's that offer a "cure" - If someone told me that I would be fluent by standing on one leg and chanting, I may have tried that too!!!

I have been doing a good deal of research and after consultation at the stuttering centre at UCI California I decided to take Zyprexa Zydis (olazapine) and Zantac to help offset the weight gain. Pagoclone is still on clinical trials and the drug will not be available until 2010/2011, so I will give the Zyprexa a chance. Prior to going on the drugs, I have intentionally dropped 10lbs in weight (I weigh 200lbs and am 6ft 2" tall) and embarked on a healthy exercise campaign to offset any weight issues that Zyprexa may cause. In addition I had blood tests to get a base line for my fats/lipids/bloodwork.

I took my first medication on Saturday and am now a 300 pound diabetic fluent person!!.....just kidding.....I will be monitoring my weight and will also bloodwork to see if anything changes. The first morning after the drugs, I was very tired, however this is to be expected at the start of taking the drug. As a result, I will make sure that I not be using threshing machinery/flying aeroplanes at 2.30am !!!

If the Zyprexa Zydis does not work or the side effects are too much, I would switch to Abilify which has less side effects but has not been so widely tested for stammering. I will keep a regular update on here so people can see the effects of the drug and also how it affects me in other ways.