National Spasmodic Dysphonia Association

Focal White Matter Changes in Spasmodic Dysphonia: A Combined Diffusion Tensor Imaging and Neuropathological Study

Authors: Kristina Simonyan, Fernanda Tovar-Moll, John Ostuni, Mark Hallett, Victor F. Kalasinsky, Michael R. Lewin-Smith, Elisabeth J. Rushing, Alexander O. Vortmeyer, Christy L. Ludlow

The full article on this study was published in Brain (2008): 131(2), 447-459,

Abstract
Spasmodic dysphonia is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are well characterized, the pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in these patients as determined by a combined approach of diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to identify brain changes and to target those brain regions for neuropathological examination. DTI showed right-sided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in the white matter along the corticobulbar/corticospinal tract in 20 spasmodic dysphonia patients compared to 20 healthy subjects. In addition, water diffusivity was bilaterally increased in the lentiform nucleus, ventral thalamus and cerebellar white and grey matter in the patients. These brain changes were substantiated with focal histopathological abnormalities presented as a loss of axonal density and myelin content in the right genu of the internal capsule and clusters of mineral depositions, containing calcium, phosphorus and iron, in the parenchyma and vessel walls of the posterior limb of the internal capsule, putamen, globus pallidus and cerebellum in the postmortem brain tissue from one patient compared to three controls. The specificity of these brain abnormalities is confirmed by their localization, limited only to the corticobulbar/corticospinal tract and its main input/output structures. We also found positive correlation between the diffusivity changes and clinical symptoms of spasmodic dysphonia (r=0.509, p=0.037). These brain abnormalities may alter the central control of voluntary voice production and, therefore, may underlie the pathophysiology of this disorder.

Lay Summary of Research
Spasmodic Dysphonia (SD) is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are known, the brain abnormalities underlying this voice disorder remain unknown. Using magnetic resonance imaging (MRI) available in most hospitals, no brain abnormalities are seen in persons with SD. However, when some specialized techniques were used, referred to as Diffusion Tensor Imaging (DTI), we found structural brain differences in patients with SD in comparison with normal speakers. This study compared 20 SD patients and 20 healthy subjects using this specialized technique. The connecting pathways in the brain from the cortex down to the brain stem region, where the neurons controlling the laryngeal muscles can be found, were measured on both sides of the brain. In this study, the connecting pathway on the right side of the brain from the cortex to the brainstem showed some thinning suggesting that some of the fibers from cortical neurons going to the brainstem were either injured or losing their myelin covering.

We also studied a brain that was donated by an SD patient and their family and compared it with brains of people who had normal speech. No gross abnormalities could be seen in the brain of the SD patient in comparison with the three controls. However, when we closely examined the region that showed abnormalities on brain imaging with DTI, we found some thinning in the same region?the right internal capsule, which carries fibers from the laryngeal motor cortical region towards the brainstem motor nuclei for laryngeal muscle control. In addition, in regions of the basal ganglia, thalamus and cerebellum we also found clusters of mineral accumulations, which contained calcium, phosphorus, and iron. This indicates that some abnormal processes have occurred in the brains of persons with SD but does not tell us what caused those abnormalities.

This study is important because it is the first time we have found abnormalities that may underlie the development of the voice disorder in persons with spasmodic dysphonia. The next step will be to determine what has caused these abnormalities to occur. Studies of abnormalities in proteins that may have produced the build up of these deposits in the brain will be required to unravel the cause of SD.

The National Spasmodic Dysphonia Association announced its new research program in 2007. We had a call for research applications for new investigator startup grants or post-doctoral study on research aimed at increasing the understanding of Spasmodic Dysphonia.

These small grants will be awarded to new or established investigators in the amounts of $10,000 and $20,000 per year. This funding usually serves as ?seed money? providing the funds needed for preliminary data before generating even greater funding from the National Institutes of Health.

The recipient(s) will be announced after the grants are reviewed and ranked by the new NSDA Scientific Advisory Board and then funding is approved by the Board of Directors. We were pleased to receive quality applications this first round and hope to distribute $50,000 this inaugural year.

To assist in the implementation of the new research program, the NSDA has established a new Scientific Advisory Board.

The Board is charged with:

? Reviewing the research grants on an annual basis and making recommendations for funding to the NSDA Board of Directors;

? Advising the NSDA Board of Directors as to the state of research in Spasmodic Dysphonia including what directions should be pursued and possible mechanisms that could be utilized;

? Stimulating interest in research in SD.

In addition, the Chairperson of the Scientific Advisory Board will serve as chief advisor to the NSDA on all research matters that would further the goals and purposes of the Association and call meetings of the Advisory Board at his/her discretion or upon request of the NSDA Executive Committee.

The following people have agreed to serve on the Scientific Advisory Board:

Christy Ludlow, Ph.D., Chair
National Institutes of Neurological Disorders and Stroke, NIH, Bethesda, MD

Gerald Berke, M.D.
UCLA, Los Angeles, CA

Craig Evinger, Ph.D.
SUNY Stony Brook, Stony Brook, NY

Chris Sapienza, Ph.D.
University of Florida, Gainesville, FL

Carlie Tanner, Ph.D.
Parkinson?s Disease Institute, Sunnyvale, CA

This is a major step forward for the NSDA and for the understanding of Spasmodic Dysphonia.

The National Spasmodic Dysphonia Association is pleased to announce its collaboration with WE MOVE on a case study entitled Case Study: The Use of Botulinum Toxin in the Treatment of Spasmodic Dysphonia as part of their initiative The Role of Chemodenervation in the Management of Hyperkinetic Movement Disorders. This case, in addition to four exercises on the foundations of chemodenervation and five other condition-specific cases, may be accessed through the WE MOVE Movement Disorder Virtual University CME Classrooms.

The case study on the use of botulinum toxin in the treatment of spasmodic dysphonia examines the different types of SD, the tools used in the assessment of this condition and the commonly employed doses of botulinum toxin type A in the treatment of adductor-type spasmodic dysphonia. The case was authored by Stephen Bansberg, M.D. Assistant Professor of Otolaryngology at the Mayo Clinic College of Medicine.

This activity is designated by WE MOVE for up to 1.0 hour of AMA PRATM Category 1 credit. WE MOVE gratefully acknowledges an unrestricted educational grant from Allergan, Inc., through which we are able to produce this activity and provide CME credit to physicians.

To participate in this free CME activity, log onto to the WE MOVE Movement Disorder Virtual University CME Classrooms and click on the lesson's title, linked to the activity at www.mdvu.org/classrooms/cme.

About WE MOVE
WE MOVE is a not-for-profit (501 C3) organization dedicated to educating and informing patients, professionals and the public about the latest clinical advances, management and treatment options for neurologic movement disorders. The Movement Disorder Virtual University is the healthcare professional?s source for movement disorder news, resources and educational activities.

Easier Done than Said...Living with a Broken Voice is a new book written by those who suffer from SD, and professionals who work with SD patients. It is a compendium of shared experiences from within the SD community.

This book is designed to:

? Provide comfort and guidance to those who are struggling to understand spasmodic dysphonia;

? Explain to family, friends, co-workers, and other interested parties the challenges faced by people with spasmodic dysphonia; and

? Bring spasmodic dysphonia to the general public?s attention.

For those who have been coping with SD for years, we hope this book will provide you with some new ideas to address current issues you might be facing. For those who are recently diagnosed or who are still seeking answers to this strange ailment, we hope this book will serve as a useful reference guide as you begin your journey through life with SD. For friends, family members, or co-workers of those with SD, we hope this book will help you to better understand the plight of people dealing with SD.

Author Karen Feeley has been living with SD since 1997 and has been an active member of the NSDA since 2001.

We expect the new book to be premiered at the 2008 Symposium in Salt Lake City, UT, on March 29 and author Karen Feeley will speaking about the process of writing the book and reading excerpts from it.

Easier Done than Said...Living with a Broken Voice will be available on April 1 and you can pre-order a copy by clicking here. It will be shipped after April 1, 2008.

Congratulations to NSDA Member Emily Lim who recently published a new children's book entitled The Prince and Pauper Bear. Emily shared, "This story was inspired by my personal struggles of coping with Spasmodic Dysphonia for the past nine years."

The Prince Bear and Pauper Bear is the first story I have ever written. There are parts of me in the wo main characters. Prince Bear was me before I was stricken with the condition, while Pauper Bear resembles me after. Like me, Pauper Bear discovers goodness and kindness from different people and is given a second chance," she said.

Wanting to repay the support and kindness she has received, Emily decided to pay it forward. She has generously donated a limited quantity of her book to the NSDA with proceeds supporting the organization. Click here to order it.

The NSDA, working with the Dystonia Advocacy Coalition (DAC), needs your help to obtain additional dystonia research funding through the Department of Defense and the Congressionally Directed Research Funds. We have been working with key members of Congress to try to get dystonia added to the list of disorders that are supported through this program.

We are asking veterans to help us explore the possible connection between service-related illnesses and injuries and dystonia by completing a Dystonia Veterans Survey.