Young Onset Parkinsons Disease

Young-Onset Parkinson's Disease: Reproduced with the permission of William Koller, M.D., Ph.D. and Jean Hubble, M.D.
Facts and Figures Parkinson's disease (PD) is an ailment affecting primarily the elderly, with the majority of patients diagnosed at 60 years of age or older. Yet, the clinical and pathological features of PD may occur in younger individuals. Whether younger-onset PD is truly the same illness as that of older individuals is not known.

In individuals of all ages, the diagnosis of PD is based only on the clinical features of tremor, muscle rigidity, and overall slowness in movement (bradykinesia). No single feature of the physician's examination, no blood test, no X-ray finding distinguishes PD in younger versus older patients. Doctors and researchers have tried to understand why PD sometimes occurs at an early age. Much work has also been directed at attempting to learn whether younger individuals prognosis and response to therapy differs from that of older patients. For the purpose of studying these issues, researchers have arbitrarily defined young-onset PD as those cases in which symptoms appear before the age of 40. Cases of PD commencing before age 20 may have certain distinguishing features including a strong tendency for the illness to be familial. Therefore, much of the information in this chapter is based on information gained in investigations of PD specifically in the 20-39 year-old age group.

PD affects about 1 in 100 Americans over the age of 60 years. The illness is much rarer at younger ages. The exact number of cases in younger individuals is difficult to estimate. To obtain such statistics, door-to-door surveys in the manner of a census-taking would have to be performed. It is said that of patients seen in PD clinics in the United States, about 5% have their initial symptoms before age 40 years. The number of young-onset PD cases in Japan may be twice as great as the number in the United States; however, the reason for this geographic difference is not known.

Some physicians report that they have been seeing more cases of young-onset PD in recent years. This has been difficult to establish with certainty; in part, this observation may be due to a greater awareness of PD on the part of physicians and the general public.

Young-onset and Typical PD: A Comparison The diagnosis of PD is based on the patient's symptoms (individual complaints or problems) and clinical signs (findings of physician's examination). Conflicting reports exist regarding which signs or symptoms may reliably differentiate PD in younger individuals from that occurring in older patients. The following sections provide a general overview of the clinical features of young-onset compared to older-onset PD.

Dystonia Thirty to 50% of young-onset cases begin with dystonia, an uncontrollable stiffening or "drawing-up" of a muscle group or limb. Foot or leg dystonia is particularly common in young-onset PD. In addition, dystonia may tend to more readily occur in the younger patient when the effects of levodopa (Sinemet) wear off between doses.

Tremor In contrast to dystonia, tremor appears to be slightly less common in the younger patient compared to the older patient. Tremor is quite common in older onset PD occurring in about 70% of patients as an initial symptom. In one study of a large family with young-onset PD, tremor occurred in only 8 of 41 patients with PD. However, this family is not necessarily representative of all young-onset cases. Tremor, nonetheless, can be one of the most troublesome PD symptoms. P.H. is a 35 year-old flight attendant who began to notice hand tremor about 1 year ago. The tremor has become more prominent over recent months and while it does not limit his ability to work, write, or perform other hand movements, he finds the tremor to be embarrassing in public, an embarrassment shared by many young-onset patients.

Family History The cause of PD is unknown. The theory that individuals may inherit a tendency to develop PD greatly interests researchers. If it can be proven, this theory may ultimately lead to understanding the cause of this illness. It appears that individuals with very early onset PD (starting before age 21 years) frequently have family members with the same condition. However, there appears to be about the same number of relatives affected in older-onset PD as in PD commencing between 21 and 39 years of age. One reason that young-onset PD patients may appear to have PD "running" in their family relates to their age. Compared to older patients, younger individuals are more apt to have living family members from the preceding generation including their parents (individuals aged 60-80 years). Recognizing that PD occurs in approximately 1 out of 100 individuals over age 60 years, it is not surprising that many young-onset PD patients can identify other family members with the illness.

Mental Symptoms "Cognition" refers to an individual's mental state and includes the ability to reason, remember, and exercise appropriate judgement. Difficulties with cognition are common in any elderly population, but PD patients appear to be at a greater risk for the development of such problems. Researchers have wondered whether patients with PD starting earlier in life are at greater or lesser risk for the development of cognitive problems compared to those with typical older-onset PD. This has been a difficult issue to study because aging, itself, influences cognition. Complicating the matter further, PD medicines can also cause or worsen cognitive problems. Thus, it may not be proper to compare the mental state of a newly diagnosed young-onset patient with a newly diagnosed patient over sixty. On the other hand, it is not appropriate to compare two sixty year-old patients, one with PD symptoms for one year and the other with symptoms for 21 years. Keeping in mind all the limitations in studying this problem, it seems that patients with symptoms before forty have the same or a lower risk of developing cognitive difficulties compared to older patients. Depression appears to be quite common in patients with PD. It may even occur prior to the onset of the usual PD symptoms of tremor, rigidity and slowed movements. It has been suggested that young-onset PD patients have depression more frequently and earlier in the course of the illness than to older-onset patients; however, this has not been well established.

Treatment Complications One of the possible complications of long-term levodopa use is dyskinesia: involuntary movements usually occurring when a dose of levodopa is at its peak effect. There are various types of dyskinesia. The most common is chorea, which is a fidgeting, wiggling, or twisting movement of the face, arms, or legs. Sudden brief body jerks (myoclonus) can also occur as a dyskinetic movement related to levodopa. Another form of dyskinesia is dystonia, a drawing-up or tightening of muscles. Like other dyskinesias, dystonia can occur when a dose of levodopa is having its maximal effect. As mentioned earlier, dystonia is also common as an initial symptom in young-onset PD and can be totally unrelated to levodopa treatment or occur when the effects of levodopa are minimal. There has been much study of the occurrence of dyskinesia in young-onset PD. Virtually all the research indicates that levodopa-induced dyskinesia is more common in young-onset PD compared to older-onset cases. In one study, 20% of younger patients developed dyskinesia by the sixth month of levodopa treatment. By the fifth year of levodopa therapy, 96% of patients with disease onset prior to age forty had developed dyskinesia compared to 64% in the older-onset group. It has also been suggested that dyskinesias occur at relatively lower doses of levodopa in younger patients.

In addition to dyskinesia, it appears that younger-onset PD patients are more likely to experience motor fluctuations. These are swings in motor function throughout the day, usually related to the administration of levodopa. For instance, the patient may awaken in the morning with slowed movements and tremor and then have improved movement, tremor reduction and, perhaps, dyskinesia after taking a levodopa tablet; tremor and slowness then reappear prior to the next dose of levodopa. Researchers found that such fluctuations occurred in over 60% of young-onset PD patients by the third year of levodopa therapy compared with 24% of older-onset patients.

For R.A., a 55 year-old homemaker who has carried the diagnosis of PD for approximately 16 years, dyskinesia manifests as uncontrollable twisting movements of her left arm and leg, occurring about 30 minutes after each dose of levodopa and lasting for about one hour. As mentioned above, however, these periods alternate with episodes of slowness, stiffness and tremor experienced for about 20% of her total waking day. It should be noted, nonetheless, that even with these problems she is able to continue her usual activities of housekeeping, rearing two teenagers and participating in community volunteer work.

New therapies are constantly being sought for the treatment of PD. Several investigational drugs are currently being studied and surgical remedies are also being explored. Each new treatment approach must be carefully tested and proven to be effective before becoming generally available. In addition, R.A. and other young-onset patients experiencing dyskinesia to an unacceptable degree might try changing the dosing, timing, or strength of levodopa. The newly available controlled-release levodopa preparation might also provide R.A. with more sustained benefit and some physicians are prescribing the use of liquid levodopa (Sinemet), a preparation composed of Sinemet CR tablets, water, and citric acid mixed, under a physician's guidance, by the patient him/herself at home. This preparation was initially developed by Dr. Matt Kurth of Barrow Neurological Institute and has been reviewed in Neurology Journals. Finally, medicines such as bromocriptine or pergolide might be added to the therapy in an effort to smooth out motor fluctuations.

The need for improved PD therapy is accentuated by the fact that young-onset PD patients are more likely to develop levodopa-related complications such as dyskinesia and fluctuations. Strategies to delay the need for levodopa therapy are being explored. Both medicinal and non-medicinal antiparkinson therapies to serve as levodopa substitutes or adjuncts are now under investigation.

Prognosis Despite the tendency for higher rates of levodopa complications in young-onset patients, overall prognosis appears to be better than in older-onset PD. In part, this may be due to other medical conditions such as arthritis which are common in the elderly and can further compromise the older PD patient's ability to move. These inherent differences in the physical condition of older and younger patients, however, do not seem to offer a total explanation for the difference in disease progression between the two groups. One measure of disease progression is disability, which refers to an individual's limitation in performing day-to-day activities. In one study, older-onset PD patients had about 80% greater disability compared to younger-onset patients when assessed during their fifth year of levodopa therapy.

Causes While the cause of PD remains uncertain, scientists speculate that it may be the result of inherited tendencies and/or the culmination of one or more environmental toxin exposure(s). As mentioned earlier, young-onset patients seem to have more PD in their families than older patients. P.H., the 35-year old flight attendent discussed previously, for example, may have noted his tremor a bit earlier than most because his father had PD and his mother has a slight tremor of the hand and head.

If a chemical or toxin in the environment is solely responsible for PD, it would seem reasonable to expect that individuals with earlier onset symptoms would have a history of a greater or more sustained exposure compared to older patients. In addition, younger patients would be anticipated to recollect such exposures more accurately than older patients. So far, a lifestyle feature or occupational exposure distinguishing young-onset from older-onset PD has not been found. It has been reported that younger patients more frequently have a rural background compared to older patients. However, this has not been corroborated in all investigations. If this rural link is ultimately proven to be correct, herbicides and pesticides might be considered as likely culprits in at least some cases of young-onset PD.

Differential Diagnosis The list of medical conditions which the physician must consider based on the patient's symptoms is termed the differential diagnosis. Few conditions, other than PD, can mimic the symptoms of an older-onset PD patient. However, the differential diagnosis is important in the younger patient with parkinsonian symptoms, particularly if a treatable alternative diagnosis can be established.

As mentioned earlier, there is no bloodtest or X-ray to confirm the diagnosis of PD. The tests which a doctor may schedule are usually directed at excluding alternative diagnoses. At the initial doctors visit, bloodtests are frequently run to provide the doctor with information about the patient's general state of health. More specifically, the bloodtests are used to exclude an illness called Wilson's disease. This is a condition in which copper is improperly stored within the body; dystonia and tremor are frequent symptoms of Wilson's disease. It is imperative that this disease be properly diagnosed because it is a treatable condition, while left untreated the illness can be devastating. Furthermore, Wilson's disease is inherited, therefore the correct diagnosis can help other family members as well.

There are other familial conditions that can resemble young-onset PD. Unfortunately, effective remedies have not been found for these conditions. It is sometimes important to attempt to corroborate these diagnoses because such corroboration may shed light on the patient's potential response to levodopa and other standard PD medications. It may also guide genetic counseling since other family members may be at risk for the illness. In an effort to establish these diagnoses, the doctor may ask the patient to undergo a brain imaging study such as a CT or an MRI scan. In very rare instances, parkinson-like symptoms occur due to stroke or tumor, which could also be detected by brain imaging scans.

Exposure to certain drugs and toxins such as carbon monoxide can result in conditions resembling PD. The diagnosis is usually made based on the patient's history, although blood tests may be helpful in some cases.

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