tag:blogger.com,1999:blog-12602489.post5376845345044717061..comments2024-03-24T15:07:18.773+01:00Comments on The Stuttering Brain: Stuttering: a disconnection syndromeTom Weidighttp://www.blogger.com/profile/02084153394215001999noreply@blogger.comBlogger8125tag:blogger.com,1999:blog-12602489.post-3123925717847635982010-06-21T19:59:13.697+02:002010-06-21T19:59:13.697+02:00- Thanks, Silva.
- You're welcome, Tom.- Thanks, Silva.<br />- You're welcome, Tom.Silvahttp://gagueira.wordpress.com/noreply@blogger.comtag:blogger.com,1999:blog-12602489.post-87204224672945946602010-06-21T05:11:22.660+02:002010-06-21T05:11:22.660+02:00Does anyone think that a bigger disconnect (i.e.,w...Does anyone think that a bigger disconnect (i.e.,weaker myelin sheath) has a correlation for stuttering severity? It is a naive simplification but seems to make sense to me. They should do imaging with mild and severe PWS to find out.Anonymoushttps://www.blogger.com/profile/01588816545658108691noreply@blogger.comtag:blogger.com,1999:blog-12602489.post-25577538327277131472010-06-20T19:12:48.738+02:002010-06-20T19:12:48.738+02:00>> Does anyone think the lysosomal enzyme ab...>> Does anyone think the lysosomal enzyme abnormality leads to a physical white matter deficit? <br /><br />Yes, that's entirely possible. The type of cells that are most affected by the dysfunctional lysosomal cycle might well be prominently present or critically involved in the proper development and functioning of certain fiber connections. Due to the inability of those cells to clean themselves properly, their development and functioning could be stopped or reduced.<br /><br />However, these mutation are only present in a small share of the stuttering population. So it's very unlikely that the brain imaging's sample contains more than 5-10% of the people with these genes...<br /><br />>> And if so how would enzyme replacement therapy fix a physical structural abnormality? Would it eventually grow the white matter connections??<br /><br />I am not sure, but I would not be surprised if the cells are just under-developed. If it's like a plant that is not watered enough and is not flowering well, it will do much better with more water. If the mutation "kills" cells because the cleaning is critical, there is little chance.Tom Weidighttps://www.blogger.com/profile/02084153394215001999noreply@blogger.comtag:blogger.com,1999:blog-12602489.post-9805770531322107092010-06-20T04:08:32.790+02:002010-06-20T04:08:32.790+02:00The author replies: We thank Büchel and Watkins fo...The author replies: We thank Büchel and Watkins for drawing attention to the extensive literature on brain imaging in stuttering. In addition to diffusion tensor imaging, a variety of imaging methods, including positron-emission tomography,1 voxel-based morphometry,2 and functional MRI,3 have consistently shown differences in the brains of patients who stutter, as compared with control subjects. However, because of the significant plasticity of the brain, it is often not possible to know whether these differences are the cause of stuttering or the result of stuttering. Although the mutations that we have identified suggest an effect on lysosomal function, the effect of these mutations on neuronal-cell biology must still be explored. Therefore, morphologic differences in stuttering can be viewed as a phenotype associated with the disorder. Although we agree that knowledge from imaging studies is and will continue to be illustrative, we also believe that knowledge of causative genetic and molecular differences provides a very different and more fundamental level of understanding of this enigmatic disorder.<br /><br />Dennis Drayna, Ph.D. <br />National Institutes of Health <br />Bethesda, MD <br />drayna@nidcd.nih.gov<br /><br />Since publication of his article, the author reports no further potential conflict of interest.Silvahttp://gagueira.wordpress.com/noreply@blogger.comtag:blogger.com,1999:blog-12602489.post-1280240177861449372010-06-20T04:07:12.823+02:002010-06-20T04:07:12.823+02:00to the Editor: In the report by Kang et al. (Feb. ...to the Editor: In the report by Kang et al. (Feb. 25 issue)1 regarding genetic abnormalities in the lysosomal enzyme–targeting pathway in persistent developmental stuttering, it would have been important to relate the results to recent neuroimaging findings in patients with this disorder. Contrary to the authors' statement that "the underlying causes of stuttering are unknown," studies using diffusion tensor imaging, a technique sensitive to subtle abnormalities in brain white matter, have consistently revealed left-hemisphere white-matter abnormalities in patients with this disorder.2,3,4 Together with studies showing a speech-timing abnormality in such patients, these data strongly suggest adisconnection syndrome. The observed mutations in the genes encoding the alpha and beta subunit (GNPTAB) and the gamma subunit (GNPTAG) of GlcNAc-1-phophotransferase and the likely evidence of lysosomal dysfunction in patients with persistent developmental stuttering now provide a possible neurochemical basis for white-matter abnormalities, because lysosomes participate in protein trafficking,5 which is crucial for the biogenesis and maintenance of myelin sheaths.6 Consequently, it is not surprising that a hallmark of mucolipidosis types II and III, disorders caused by mutations in GNPTAB and GNPTAG, is the severe white-matter abnormality documented on magnetic resonance imaging (MRI).<br /><br /><br />Christian Büchel, M.D. <br />University Medical Center Hamburg-Eppendorf <br />Hamburg, Germany <br />buechel@uke.de<br /><br /><br />Kate E. Watkins, Ph.D. <br />University of Oxford <br />Oxford, United Kingdom<br /><br />No potential conflict of interest relevant to this letter was reported.Silvanoreply@blogger.comtag:blogger.com,1999:blog-12602489.post-34394812437077208052010-06-19T20:54:59.243+02:002010-06-19T20:54:59.243+02:00Have StutterTalk start another petition demanding ...Have StutterTalk start another petition demanding this paper be made available for public debate.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-12602489.post-10147731536450982762010-06-19T20:11:11.235+02:002010-06-19T20:11:11.235+02:00strengthen the white matter connections rather.. t...strengthen the white matter connections rather.. the myelin sheathig88sirhttps://www.blogger.com/profile/14118519918762348922noreply@blogger.comtag:blogger.com,1999:blog-12602489.post-9684810069557802512010-06-19T20:08:01.630+02:002010-06-19T20:08:01.630+02:00Does anyone think the lysosomal enzyme abnormality...Does anyone think the lysosomal enzyme abnormality leads to a physical white matter deficit? And if so how would enzyme replacement therapy fix a physical structural abnormality? Would it eventually grow the white matter connections??ig88sirhttps://www.blogger.com/profile/14118519918762348922noreply@blogger.com