5/30/2005
ALS Can Affect More than Motor Neurons, Researchers Conclude at a Workshop on FTD
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| Front row, left to right Organizing Committee for the FTD Workshop Gloria Grace, London, ON, Lucie Bruijn, ALSA VP & Science Director, Cathy Lomen-Hoerth, San Francisco, CA, and Morris Freedman, Toronto, ON. Back row Nigel Leigh, London, UK, Paul Ince, Sheffield, UK, and Michael Strong, London, ON. |
The spectrum of cognitive change associated with amyotrophic lateral sclerosis, as well as implications for families trying to cope, were addressed by researchers from around the world who convened in London, Ontario, Canada May 15-17, 2005 for a workshop on the topic sponsored and funded in part by The ALS Association (ALSA). The goal was to reach consensus on what is known about the biology of intellectual function affected by ALS, and what are the priorities for investigation. The conclusion of the researchers is that ALS is most likely a single disorder that can affect the nervous system broadly. This is in contrast to the idea that ALS only damages the motor system. The varied symptoms of ALS including motor and cognitive changes merely reflect where in the brain and spinal cord the damage is done.
Cognitive change is definitely possible with ALS, and though the behavioral effects are often mild, or indeed absent, the loss of motor function that is the hallmark of the disease can be accompanied by marked alteration in reasoning and social interaction that can further disable a patient and burden families already under enormous stress.
Workshop organizer Michael Strong, M.D, of the London Health Sciences Centre, Ontario, this year’s recipient of the Essey award from ALSA, called the conference “a meeting that fundamentally changes a field.”
“It has been an excellent forum for discussion,” said Lucie Bruijn, Ph.D., ALSA science director and vice president. "The interaction between clinicians, pathologists, cell biologists and geneticist all focusing on this issue is invaluable,” Bruijn said.
Frontotemporal dementia is a type of disorder in cognition that is more subtle than the dementia of Alzheimer’s disease. It tends to affect social behavior, mood, and the ability to process or produce speech, rather than memory. The brain region affected lies above the eyes and behind the temples.
Questionnaires and paper and pencil tests by neuropsychologists can reveal cognitive changes that patients may deny and that family members may not have grasped. But most of these tests are not optimized to detect the particular changes most commonly associated with ALS, workshop presenters said. New and simpler tests are needed, and are already being developed. ALSA funded researcher Cathy Lomen-Hoerth, M.D., Ph.D., of the University of California, San Francisco, presented data on this issue, as did Stanley Appel, M.D., at Baylor University in Houston.
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Dr. Michael Strong |
Another crucial issue is the specific damage taking place within the nervous system in the disease. Pathologists can find abnormal deposits of protein in neurons of the brain and spinal cord, in regions that carry out the functions that are altered by ALS. These deposits are in one sense similar to the pathology in Parkinson’s disease and Alzheimer’s disease, as well as a host of degenerative disorders of the nervous system. All the diseases show protein aggregates as pathology. For ALS, the identity of the abnormal deposits associated with cognitive change is still unknown. Research needs to determine the exact protein aggregating in ALS, workshop presenters said.
ALS patients who come to autopsy also show visible shriveling of the frontal and temporal brain regions. These changes can be detected in living patients by modern imaging techniques that are ever improving the ability to gauge the action of the brain at work. Sharing software and expertise will accelerate the ability of investigators to assess brain function and follow patient progress, as well as unravel the fundamental disease process. Researchers need to follow patients over the course of ALS, which can be challenging given the increasing disability coming with the disease.
Tantalizing evidence on genetic factors that might influence when and how cognitive change appears in ALS was also presented at the workshop by John Hardy. It is likely that a person’s genes will influence how the disease will play out in that person’s nervous system said workshop presenter Paul Ince. Future research needs to focus on the genetic underpinnings of the disease, said Bruijn.
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| ALSA VP & Science Director Lucie Bruijn with David Cameron, National Executive Director, ALS Society of Canada |
Workshop presenter Morris Freedman, M.D., of the University of Toronto, Canada pointed out that very few clinical trials have tested drugs that might help patients with frontotemporal dementia. Well-designed clinical trials are urgently needed. Strong noted that single centers will not be enough and that multiple centers are required to gather adequate data to find effective treatment of the behavioral change and frontotemporal dementia associated with ALS.
Other sponsors of the workshop were the ALS Society of Canada and of Windsor/Essex County, as well as the Michael Halls Endowment. The steering committee for the workshop included Bruijn, Strong, Freedman, Lomen-Hoerth, and Pamela Shaw, M.D., of the University of Sheffield, U.K., Gloria Grace, Ph.D., London Health Sciences Centre, Ontario, Canada, and Nigel Leigh, M.D., Ph.D., King’s College, London, U.K.
Proceedings of the workshop will be published, and several tangible action items were discussed. Future meetings will convene to ensure progress in understanding FTD and how to manage it.
