Peter A. LeWitt, MD
Dr. LeWitt is the Director of the Parkinson Disease and Movement Disorder Program at Henry Ford Hospital, West Bloomfield, Michigan.
For most neurology subspecialties, the past quarter-century was only the latest chapter of a productive history extending through the mid-19th century, but for movement disorders, these years were formative. Before then, movement disorder specialists were few in number, and their medical literature was far more scanty than it is now, with multiple journals and texts now devoted to this topic. Twenty-five years ago, the international society devoted to Parkinson disease and other movement disorders was only a recent arrival. Fortunately, two charismatic and brilliant leaders—the American neurologist Stanley Fahn, MD, and the British neurologist C. David Marsden, MBBS—came forward to inspire a generation of trainees with their broad interests in bridging clinical neurology, experimental neuroscience, and patient advocacy. Today, the impact of these pioneers is still felt by a growing community of movement disorder clinicians and researchers who have transformed movement disorders from an earlier realm of descriptive neurology into a vibrant field exploring disease mechanisms and therapeutics, as well as an expanding array of clinical insights.
When Neurology Reviews was founded in 1993, the majority of significant developments in movement disorders concerned Parkinson’s disease. Strategies to improve upon dopaminergic therapy were being tested in clinical trials, along with ventures into pallidotomy as a neurosurgical treatment. Animal models of parkinsonism and neurochemical analysis of brain and putative biomarkers provided scientific guidance for trials of disease modification. Another milestone from the 1990s was discovery of the first gene leading to autosomal-dominant parkinsonism. This rare mutation in the structural protein alpha-synuclein had a much broader impact on Parkinson’s disease research in that it provided important information about the sporadic disorder’s final common pathway of pathogenesis. Today, alpha-synuclein is the focus of therapeutic intervention utilizing immunologic therapies to halt disease progression. Over the past quarter-century, more than two dozen additional gene mutations associated with parkinsonism have been discovered. These mutations provide additional insight into disease mechanisms. Beyond the science and clinical insights that have propelled advances in understanding Parkinson’s disease and its related disorders, the growth of the patient advocacy and caregiver movement has also been remarkable in expanding what is needed to improve daily life with this disorder.
Since 1993, other movement disorders have also profited from the tremendous growth of molecular neuroscience and its applications. Novel neuroimaging techniques like functional MRI, computation of neural pathways, and scanning using PET and SPECT have helped work out the brain mechanisms of several disorders. Genetic probing of familial disorders like dystonia and myoclonus have helped to unravel the neurochemistry of what has gone wrong to cause certain movement disorders. In turn, transgenic animal models using these human genetic mutations have allowed exploration of what might be done to fix the problems. These developments could have huge implications for making progress in the therapies of the future, since the most common categories of movement disorders—dystonia, myoclonus, ataxia, tremor, restless legs syndrome, Tourette syndrome, choreic disorders, and paroxysmal movement disorders—all can have hereditary patterns. Genetic testing can be valuable for choosing at-risk individuals for participation in trials of disease-modifying drugs for Huntington’s disease, for example, and this strategy may be the way of the future for other late-life emergent disorders. In the past decade, several gene therapy studies have been carried out in patients with Parkinson’s disease. The promise of this approach and the recent gene editing and RNA interference approaches, all part of the molecular biology revolution of the past 25 years, may further change the landscape of movement disorder therapeutics ahead.
Today, movement disorder specialists routinely use therapeutic approaches that were in their infancy in 1993. Botulinum toxin selective denervation has had a major impact by improving quality of life for patients affected with a wide range of movement disorders: dystonic necks, hands, and feet; involuntary facial movements and voice aberrations; tics; spasticity; and drooling. Deep brain stimulation is a routine option for many patients with tremor, Parkinson’s disease, and dystonia. Developments in this field have refined the choice of targets for stimulation and the possibility of treating other disorders with these techniques, like Tourette syndrome. A nonsurgical approach to abolishing tremor, MRI-guided focused ultrasound, recently was approved. In the background of these advances is the increasing knowledge of movement disorders that practitioners have to offer many patients with disorders that in the past were merely neurologic curiosities. Through clinical trial research and serendipity (the major treatment options for essential tremor arose this way), there is an expanding search for repurposing older medications and harnessing new biotechnology to target the mechanisms leading to various movement disorders.
It is impressive how much the neurologic discipline of movement disorders has changed in response to the new era of electronic communications and other technologies. In the past quarter-century, medical students, residents, and practicing neurologists have had instant access to a curriculum that includes resources such as video-recorded movement disorders. Clinical trials are being revolutionized by electronic technologies that record information in ways that improve upon human ratings. A patient with Parkinson’s disease, essential tremor, or restless legs syndrome can now have symptoms monitored remotely by wearable devices that offer a real-world view on how a new therapy is performing. But perhaps the greatest revolution in the recent past has been increasing confidence that progressive disabilities caused by movement disorders might be halted by emerging insights into disease mechanisms. There has been tremendous growth of interest among the basic neuroscience community in human diseases affecting motor control. More than half of research presentations at recent international Parkinson’s disease and movement disorder conferences reflect this trend. These efforts support an optimistic view that, over the next quarter-century, the most challenging movement disorder problems of today will experience as much progress as in the past 25 years.