Abstract: Young onset Parkinson’s disease (YOPD) is defined as idiopathic Parkinson’s disease (IPPD) occurring in people between 21 and 40 years of age; it strikes approximately 5% of Parkinson’s patients. YOPD has earlier onset of motor complications than later onset Parkinson’s disease. Motor complications and disease progression are responsible for devastating morbidity. Current medical and surgical treatments can dramatically ameliorate motor complications and help maintain function and employment. Patient education, support, and advocacy provided by nursing staff can influence the treatment options for these patients, having a significant effect on the future course of the disease. This case history documents the course of a YOPD patient with unusually severe motor complications. He is the only patient at Puget Sound Neurology ever to develop rhabdomyolysis due to dyskinesias. Following bilateral subthalamic nucleus deep brain stimulation, his Parkinson’s symptoms have improved dramatically, and his motor complications are significantly improved.
Young onset Parkinson’s disease (YOPD) is defined as idiopathic Parkinson’s disease (IPPD) presenting in individuals between 21 and 40 years of age. It presents in the same manner as IPPD in older individuals (Paulson & Stern, 1997). The cardinal symptoms of Parkinson’s dis ease at any age are almost always unilateral at onset (Fahn, Greene, Ford, & Bressman, 1997) and include the classic signs and symptoms of resting tremor, rigidity, and/or bradykinesia (Paulson & Stern, 1997). Symptoms typically progress to the unaffected side over time; however, the side on which symptoms began remains more affected. The current consensus is that the pathophysiology of YOPD is identical to that of IPPD and that the younger age represents the low end of a bell-shaped curve pertaining to the age at which IPPD presents (Paulson & Stern). IPPD results from a loss of neurons in the substantia nigra. It is estimated that patients have lost approximately 80% of their striatal dopamine- producing cells at the time of diagnosis (Langston, Koller, & Giron, 1992).
Because of the chronic, progressive nature of Parkinson’s disease, patients benefit from teaching and support that nurses have to offer (Vernon & Jenkins, 1995). Nurses have the opportunity to provide not only care but also patient education and to refer them to support groups appropriate for their specific needs (Lin, Woelfel, & Light, 1985). They can also provide information and guidance around work-related issues, psychosocial issues involved in becoming disabled at a young age, and the associated depression (Calne, 2003).
The standard pharmacologie treatment for YOPD is dopaminergic medications. While levodopa treatment is the gold standard in terms of potency and effectiveness, it leads to response fluctuations and dyskinesias, portrayed as abnormal movements usually seen at peak dose (Clarke & Guttman, 2002). Dopamine agonists take longer for full efficacy to be achieved and may not be associated with as desirable a level of control. However, multiple studies have created a consensus that dopamine agonists delay motor complications, which is especially important in YOPD patients (Olanow, Watts, & Koller, 2001). For this reason, most Parkinson’s disease specialists attempt treatment with dopamine agonists before initiating levodopa. Acceptable control may be maintained for up to 2 years using dopamine agonists alone (Poewe, 1998).
YOPD patients should understand that levodopa does not cause motor complications and dyskinesias. Rather, they are the result of disease progression, in conjunction with the “hammering” of the stria tal area with dopamine replacement (Factor, 2001). Therefore, patients should not withhold levodopa therapy when they require it to maintain function. Levodopa, in fact, is the only anti-pa rkinsonian medication shown to reduce mortality rates of IPPD patients (Rajput, 2001). It is therefore important to use levodopa when necessary and maintain the dosage as low as possible. This can be accomplished by combining levodopa with dopamine agonists (Poewe, 1998). Patients who require higher dosages of levodopa for longer duration are more likely to develop severe motor complications than those who are able to maintain lower dosages of levodopa. Patients often desire and seek the positive effects of high doses of levodopa because of its rapid onset and superior efficacy. However, they must understand the devastating consequences of these high doses in the future.
YOPD patients benefit from understanding the concept of “therapeutic window” of levodopa as soon as it is initiated. When exogenous levodopa is introduced, the therapeutic window is wide. Symptoms dramatically improve, usually with few or no side effects. However, the window narrows with disease progression, causing motor fluctuations, including wearing off of medication, dyskinesias, sudden and severe wearing off, and muscle cramping (Riley & Lang, 1993). It is important to introduce treatment options that will help maintain the therapeutic window. Those options include treating initially with dopamine agonists and keeping levodopa doses as low as possible.
Carefully planned and executed exercise and other rehabilitative therapies for YOPD patients are essential (Cornelia, Stebbins, Brown- Toms, & Goetz, 1994). Especially important are those that strengthen the axial muscle group, as well as walking and balance exercises. Tai chi is a slow-moving martial art, which emphasizes balance. Balance exercises help improve postural instability and balance problems, which often do not respond well to medications (Olanow & Koller, 1998). If appropriate exercise is initiated as early as possible, some of the gait problems, particularly those related to stooped posture, may be prevented (Olanow & Koller). Exercise not only helps preserve balance, it also strengthens muscles, enhances the neurological pathways that make exercise possible, helps maintain appropriate weight, and promotes optimal health (Carter, 1995).
Patients with YOPD should understand the implications of the disease and motor complications on their employment. Their deficits may result in difficulty completing motor tasks, slower walking, social embarrassment, and issues with driving if motor symptoms are severe (Shrag, Hovris, Morley, Quinn, & Jahanshahi, 2003). Patients may be directed to vocational rehabilitation to facilitate employment options, which can be maintained with Parkinson’s- related motor complications.
YOPD patients may benefit from surgical options (Tornquist, 2001). Over the last 10 years, surgical options have progressed dramatically. Lesioning techniques were the only surgical option approved for Parkinson’s disease until 2002. In January of 2002, the Food and Drug Administration approved deep brain stimulation of the subthalamic nucleus and the globus pallidus. These procedures can improve some symptoms of Parkinson’s disease, as well as ameliorate motor complications. In addition, when the subthalamic nucleus is chosen as a target, substantial medication reduction is usually possible (Benabid et al., 2000).
Dietary management in Parkinson’s disease is important. Patients with YOPD are at increased risk for poor nutrition, as well as constipation, because of decreased gastrointestinal motility (Nutt & Carter, 1990). In patients with advanced disease, there is amino acid competition for levodopa absorption, which can cause erratic responses to levodopa (Nutt, Woddard, Hammerstad, Carter, & Anderson, 1984). While no specific diet is required, a balanced diet with adequate fiber is encouraged. Protein intake may be timed either 2 hours before or 1 hour after levodopa administration, to allow for adequate protein intake, without interfering with levodopa absorption.
The cost of medications can be a significant issue in patients with YOPD. The disability caused by YOPD renders many patients unable to work, limiting the availability of medical insurance plans that cover expensive, newer medications. These medications, particularly dopamine antagonists and catechol-O-methyltransferase (COMT) inhibitors, help delay motor complications. The most potent strength of carbidopa/levodopa (the 25/250 dosage form) is the most inexpensive Parkinsonian medication available. Tragically many patients must rely on that option, because it is the only affordable one. Patients can be made aware of all available cost savings options, such as patient assistance programs, introductory promotions, and samples when available.
SLJ presented in the clinic in February 1999 at 51 years of age. Details of his previous medical history were available by patient report only. He developed a resting tremor in his right upper extremity in 1984, at the age of 36 years. This was followed by muscle stiffness and a shuffling gait within 2 years. He began taking levodopa about 1986 and began to develop rapid wearing off and inconsistent effects of levodopa about 1992. Dyskinesias began in 1993 and were severe by 1995, when he was 48 years old.
When he came, to the clinic in February 1999, he was experiencing dyskinesias for most of the day. He had begun titrating liquid carbidopa/levodopa, in doses of 100 mg of levodopa approximately every 2 hours. He took approximately 10 doses per day. With this regime, he would experience dyskinesias at the onset o\f action, notice an effect within hour, and have an “on” time for about 1 hour. Towards the end of that hour, he would again notice dyskinesias; then he would abruptly go “off.” He also experienced a consistent period of depression during his “off” periods. His UPDRS scale at the time of his consult was 45 (Paulson & Stern, 1997), and he was in a dyskinetic state at that time. He was considered to be in stage 3, per the modified Hoehn and Yahr scale (Paulson & Stern). His cognitive functioning was intact at the time of his initial consult. He reported no cognitive decline or thought disorders. However, he did report a significantly depressed mood when he was “off.” The depression would lift dramatically during his “on” time.
During his initial consult, he received the following interventions. His understanding of his illness was supplemented through education. In particular, the relationship between the timing and amount of his levodopa dosages and his “off” time and dyskinesias was explained. The crucial importance of exercise was strongly emphasized, to strengthen the feedback mechanism of the motor control system. He was invited to participate in the local YOPD support group, to provide social support and further education about his disease. Pramipexole was initiated, to be slowly titrated to 0.75 mg tid. The concept of COMT inhibitors was discussed, to be utilized after he reached a therapeutic dose of a dopamine agonist.
He returned for a follow-up visit approximately 7 weeks following his initial consult. His UPDRS score was 35 when “on” and 44 when “off.” He had reduced his liquid carbidopa/levodopa to 75 mg every 2 hours and had successfully titrated pramipexole to 0.75 mg tid. He was noting more “on” time, as well as a considerably improved mood. He had discovered that emotion or excitement often triggered his dyskinesias. Because he was still experiencing significant dyskinesias, amantadine was initiated at 100 mg tid.
During his follow-up on June 2,1999, his UPDRS score was 25 when “on” and 33 when “off.” He reported a 50% improvement of Ws dyskinesias with the treatment of amantadine. He had experienced mild hallucinations shortly after initiating the amantadine, in the form of “vague movements of objects”; however, they were non- threatening, and he understood that they were medication-related. Having kept a calendar of his symptoms every day for a month, he noted that his most severe “off” periods were associated with eating fish, pork, and beef proteins. He did not have an “off” episode with vegetable protein. He had gained 11 pounds since his previous visit, and it was thought that the reason was the improvement of Ws dyskinesias, which decreased his caloric expenditure.
Six months later, his condition was worse. His UPDRS scale was 40 when “off” and 36 when “on.” He had increased Ws liquid carbidopa/ levodopa to 100 mg every 2 hours. He described abrupt wearing off and had only about 45 minutes between the time he took levodopa and development of dyskinesias. The amantadine had lost some of its effectiveness. He could be very functional during his “on” periods, but they were decreasing in length, and Ws “off” episodes were more debilitating. He had lost 17 pounds over the previous 6 weeks. His vital signs showed a postural drop of 104/60 mm Hg sitting to 80/60 mm Hg standing; however, he deWed symptoms of postural hypotension. He was encouraged to increase fluid and salt intake, remain seated for 20 to 30 minutes after meals, and sit at the edge of the bed for 5 to 7 minutes before rising. Entacopone was added, to be given with every other dose of levodopa. His UPDRS scale during that visit had increased to 42, at the time that he was “off.”
Two weeks after beginning entacopone, he noted a dramatic improvement of his symptoms and was able to reduce his carbidopa/ levodopa by about 15% and maintain quality “on” time. His levodopa dose had gone from 1500 to 1250 mg per day. He was no longer experiencing abrupt wearing off. His dyskinesias were still dramatic, but had not increased. He was interested in making further changes, which could potentially improve his dyskinesias. His dopamine agonist was changed from pramipexole to ropinerole at 4 mg tid as a trial, in an attempt to further decrease his dyskinesias.
Five weeks later, his condition had improved. He found that he had maintained the same level of effectiveness from the ropinerole as with pramipexole, with fewer dyskinesias. He was using carbidopa/ levodopa 25/250 solution and had reduced his dosage to 800-900 mg per day of levodopa. He was adding an entacopone 200-mg tablet every morning to his carbidopa/levodopa, and tablet with his 2 pm and 8 pm dosages. He had observed that taking of the entacopone with his afternoon carbidopa/levodopa doses further decreased his dyskinesias. He had decreased his ropinerole dosage to 4 mg bid. He felt that the ropinerole had helped his symptoms of freezing and turning in bed, as well as fine motor activity. He was still going “off,” but was not experiencing the abrupt wearing off he had previously. He continued to experience dyskinesias, but they were less severe. His UPDRS scale was 23 when “on” and 32 when “off.”
At that visit, his ropinerole was changed to 2 mg qid, rather than 4 mg bid, and he was taught to march in place before arising, which helped alleviate his postural blood pressure drops. He was also re-educated to keep well hydrated with water and electrolyte- containing sports drinks to help maintain his hydration.
Over the following 9 months, his condition deteriorated. He displayed significant postural instability, he began experiencing “on-off” phenomena, and his dyskinesias became worse than they had ever been. He had stopped his amantadine, because he thought that it had lost its effectiveness. It was noted during one of his follow- up visits that he had no hair on ITIS arms or legs, because it had been rubbed off by his clothing during his violent movements. Multiple adjustments of his medications were attempted to help improve his functioning, but were not successful.
In October 2000, an emergency room physician called our office and informed us that SL] had presented there with a severe exacerbation of his dyskinesias and an elevated CPK, and it was determined that he had developed rhabdomyolysis. He had experienced intractable and violent dyskinesias over the last few days. He had gradually tapered his carbidopa/levodopa, but the dyskinesias did not improve. The morning before his admission, he had discontinued all his medications. His dyskinesias and muscle spasms were so violent that his roommate described sitting on him to keep him from falling out of bed. At home, they had attempted to treat his dyskinesias with fairly large doses of lorazepam; a total of 10 mg in a 24-hour period, which had not significantly helped his dyskinesias. He was admitted into a monitored bed. He was given fluids, as well as intravenous lorazepam, in an attempt to improve his dyskinesias. He was started on quetiapine and carbidopa/ levodopa 12.5/50 ( of a 25/100) every 2 to 3 hours. His CPK peaked at 728, then normalized.
He was discharged on October 6, 2000. His discharge medications were carbidopa/levodopa 25/100, tablet up to every 2 hours, pramipexole to be titrated to 0.75 mg up to 6 times a day, lorazepam up to 1 mg every 8 hours, and quetiapine 25 at hs to attempt to treat his dyskinesias. The decision to use quetiapine was based on published studies reporting low-dose clozapine to treat levodopa- induced dyskinesias in Parkinson’s patients (Pierelli et al, 1998; Rascol, 2000). It was thought that clozapine was useful in treating Parkinson’s dyskinesias because of the rapid dissociation from the D2 receptors, which would allow improved accommodation of available dopamine (Kapur & seeman, 2000). The disadvantage of clozapine was the potential hematological complications and the requirements for blood monitoring. Because quetiapine also exhibits fast dissociation of the D2 receptors (Kapur & seeman), it was hypothesized that quetiapine would improve dyskinesias, without the risks associated with clozapine.
At his follow-up visit, his motor fluctuations were much improved. His amantadine had been restarted and was effective. He was taking carbidopa/levodopa 25/250 tablet every 2 to 3 hours, entacopone 200 mg daily with his first dose of carbidopa/levodopa, pramipexole 0.75 mg 6 times per day, amantadine 100 mg rid, quetiapine 25 mg at hs, and lorazepam up to 2 mg at hs. He reported that the quetiapine significantly helped his nightmares and activity during the night. His dyskinesias were still severe, and he was having postural symptoms when he stood up. His blood pressure was 100/50 mm Hg when sitting and 76/50 mm Hg standing. His weight was 145 pounds, which was a decrease from his normal weight but represented no further weight loss. He was educated to attempt to take no more than a carbidopa/levodopa 25/250 at one time. His quetiapine was increased to 50 mg up to bid, to attempt to control dyskinesias. He was encouraged to salt his food arid drink fluids such as Gatorade to help maintain his hydration and blood pressure.
Over the next several months, his condition remained severe, but did not worsen. He continued to experience severe postural hypotension. Although his dyskinesias and “off” periods were severe, he was able to maintain activities of daily living. He was also able to engage in his hobbies, which included fishing and working on cars.
In December 2001, he called to say that his symptoms had worsened. His dyskinesias were extremely severe and nearing the level at which he was hospitalized. He had apparently been taken to the hospital because of erratic driving during a period in which he had exceptionally violent dyskinesias. In public places, people would shy away from him because of his movements. Amantadine had lost much of its effe\ctiveness. He was able to sleep only 3 to 4 hours during the night and would wake up experiencing severe rigidity and tremor.
He returned to the office on January 3,2002. An attempt was made to place him on carbidopa/levodopa CR along with entacapone, to provide less dramatic pulses of levodopa. A referral was made for him to be placed in a research protocol. A UPDRS scale rating was impossible because of his violent dyskinesias. A few days later, he called to say that he was worse still. His dyskinesias were very severe, and he reported passing out several times a day. The carbidopa/levodopa CR was ineffective, even with the entacopone, so he had returned to the carbidopa/levodopa 25/250. He had discontinued his pramipexole, because he was under the impression that he would have to, in order to be considered for a protocol. He also had discontinued his quetiapine, because he had run out of it. His blood pressure was 80/60 mm Hg sitting and 60/40 mm Hg standing. He was given samples of quetiapine, ropinirole, and midodrine 5 mg tid was prescribed for postural hypotension. He was again counseled to get up slowly, push fluids, and eat salty foods.
Over the next month, he and his caretaker worked on a medication management program in which he took of a tablet of a carbidopa/ levodopa 25/250, every 1 to 2 hours, 10 to 12 times a day. He would follow every other dose of carbidopa/levodopa dose with ropinerole 2 mg and use quetiapine as needed, based on the level of the dyskinesias. His quetiapine dosage ranged from 25 to 125 mg per day. This management strategy dramatically improved his “on” time and decreased his dyskinesias. Over the next several months, he gained 18 pounds. His “on” time increased, “off” time decreased, and his dykinesias improved. His UPDRS scale decreased to 33 when “on” and 38 when “off.” He did not enroll in the clinical trial.
In the spring of 2002, he moved to a town approximately 50 miles away, which made it more difficult to obtain samples of ropinerole and quetiapine, which were so important to control the level of his dyskinesias. He was unable to afford them. His routine was to revert to carbidopa/levodopa 25/250 in large amounts, become severely dyskinetic with severe postural hypotension, and then come into the clinic when he could find a ride. Patient assistance programs were not an option, because he had an insurance policy that provided drugs. However, brand name drugs were covered at only 50%, and he was unable to afford the copayments. For that reason, he was maintained as much as possible on samples from the office.
In the spring of 2003, he had a left-side STN deep brain stimulator placed, followed by the right-side STN deep brain stimulator in September 2003. The surgery has been extremely successful in helping him decrease his carbidopa/levodopa intake, and he is now taking 500 to 750 mg per day. He has only very mild peak-dose dyskinesias, but they are not disabling. He is able to sleep through the night, without awakening. His tremor, rigidity, and gait have improved dramatically.
Young onset Parkinson’s disease has the potential for profound disability at a young age. It frequently destroys careers and livelihood and severely diminishes quality of life. A total treatment approach that utilizes patient education, advocacy, medical management, exercise, dietary assistance, and possible surgical options can significantly decrease the morbidity involved with this devastating disease. Nurses play a key role in providing effective services for these patients.
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Questions or comments about this article may be directed to Sharon K. Jung, ARNP CNRN, by phone at 253/284-4488 or by e-mail at [email protected] She is a nurse practitioner at Puget Sound Neurology, Tacoma, WA.
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