Although the issue has not gained many headlines, a great deal of energy is being expended by movement disorders neurologists to develop a new way of thinking about Parkinson’s disease. This effort has been prompted by two major trends: a growing recognition that traditional definitions are inadequate, and an assortment of new scientific discoveries that compel us to broaden our understanding of what exactly constitutes Parkinson’s disease.
To neurologists, the classic definition of Parkinson’s disease in patients consists of a combination of clinical (i.e., symptoms and physical examination findings) abnormalities: tremor, muscle rigidity, a characteristic impairment of voluntary movement (reduced in speed, size and quantity), and posture and balance problems. These features are collectively known as the syndrome of parkinsonism.
In Parkinson’s disease, this syndrome is associated with disappearance of most of the nerve cells, as seen under a microscope during an autopsy, in an area of the brain called the substantia nigra. Surviving cells contain distinctive abnormal structures called Lewy bodies. However, neurologists have determined over the last 60 years that there are many other causes for parkinsonism that do not show these pathologic findings. Meanwhile, the latter may be found in individuals who showed no signs of parkinsonism during life. In other words, neither the clinical or pathological definitions we have traditionally used have proved to be entirely reliable in describing Parkinson’s disease.
At the same time and as the limitations of old definitions have become obvious, scientific discoveries have yielded new information that must be accounted for by any new definitions. Numerous studies over the last 25 years have focused on a wide assortment of nonmotor manifestations of Parkinson’s disease. We have come to accept that having Parkinson’s disease entails not only the motor symptoms listed above, but often a variety of problems disrupting thought, mood, basic bodily functions (via the autonomic nervous system), sensation (especially smell), sleep, and other nervous system activities. Simultaneously, pathologists have noted that brain abnormalities outside the substantia nigra explain many of these symptoms.
Having expanded the spectrum of symptoms that people with Parkinson’s disease experience, neurologists came to realize that many of these nonmotor symptoms can make their presence felt years, and sometimes decades, before the motor symptoms. In particular, losing the sense of smell, depression, constipation, and REM-sleep behavior disorder (a tendency to act out dreams during sleep) may be the first evidence of developing Parkinson’s disease. Meanwhile, tremendous advances in the science of genetics have determined that a number of specific mutations may cause Parkinson’s disease.
These are the knowledge gains that have encouraged movement disorder specialists to rethink long-held concepts about Parkinson’s disease. Recent publications have described the formulation of a new definition, with multiple stages of diagnosis, based on a sequence of phases of development:
– the prephysiological phase: when people have a predisposition to Parkinson’s, especially genetic, but before anything actually goes wrong
– the preclinical phase: when nerve cell damage has started, but before symptoms develop
– the premotor phase: when people have nonmotor symptoms, but before parkinsonism develops
– the prediagnostic phase: when motor symptoms have started, but have not reached the number or severity required to establish a diagnosis
– Parkinson’s disease: when there is finally enough evidence of the motor manifestations to meet the traditional definition
This is the current state for the art of defining this disease. Even though it has been nearly 200 years since James Parkinson first wrote about the disease that came to bear his name, neurologists still struggle with some of the most basic concepts of diagnosis, such as when does start? When can someone be said to have Parkinson’s disease? These issues remain to be fully settled.
Why do neurologists devote so much effort to this exercise? One of the main reasons is excitement about opportunities that early recognition of Parkinson’s disease presents. Each of the phases outlined above opens channels to different kinds of research. Expanding our horizons about what Parkinson’s disease encompasses, from a narrow definition based solely on the motor manifestations to embracing all the nonmotor manifestations we now recognize, has already paid dividends. Identifying patients in the premotor phase of Parkinson’s disease allows us to study Parkinson’s disease in its earliest stages. For example, following a group of people with REM-sleep behavior disorder and no motor symptoms has, for the first time, afforded scientists the opportunity to study traditional motor Parkinson’s disease before and as it develops. More promising still is the potential to intervene in Parkinson’s disease with future treatments aimed at stopping the disease process in its tracks, before motor symptoms develop.
Based on a talk given by Dr. Riley at InMotion on April 2, 2015