A 55-year-old right-handed man was diagnosed with Parkinson's disease in 2001 (onset at the age of 46 years). The first symptoms of the disease were rest tremor in the left hand and slight rigidity in the left upper extremity. Brain MRI at the time of the diagnosis showed no pathological findings. Antiparkinsonian medication was started at the time of the diagnosis. Medication changes over the course of the disease are presented in table . The patient had graduated from high school, corresponding to 12 years of formal education, and had various occupations after school including working as a janitor and a survey interviewer, before retiring due to motor symptoms of the disease 2 years after the diagnosis.
Changes in the antiparkinsonian medication and the behavior of the patient
Approximately 5 years after the diagnosis, the patient gradually developed a gambling problem mostly for coin-operated slot machines. Before the diagnosis, the patient had no gambling problems and no experience in slot machine gambling. Earlier, while working as an interviewer in casinos, he remembered being ‘surprised’ that some people could get addicted to gambling. At the time of the brain PET imaging in 2010, he played more than 10 h/week on slot machines and spent more than 1,000 €/month on electronic machine gambling. His gambling had caused him significant debts. In 2010, pathological gambling was confirmed according to DSM-IV criteria. Maladaptive gambling behavior was indicated by 7 out of 10 DSM-IV items (cutoff ≥5 items) and the South Oaks Gambling Screen (SOGS) score was 8 out of 20 (cutoff ≥5 points). The questionnaire for impulsive-compulsive disorders in Parkinson's disease (QUIP) indicated pathological gambling (5 out of 5 items, cutoff ≥2 items), but did not indicate any other impulse control disorders.
Together with slot machine gambling, the patient developed punding-like compulsory behavior, which involved picking wild berries. From the year 2006 onwards, he gradually spent more and more time picking berries. In 2010, the patient saw himself as being obsessed with picking wild berries together with the problematic gambling habit. In the autumn of 2010 alone, he picked hundreds of liters of lingonberries. He described going to the woods early in the morning, losing his sense of time and place (similar to gambling), and stayed in the woods for up to 12 h. While picking, he felt no urge to gamble. He started picking berries before dawn, parking his car next to the woods and using the headlights of his car to find berries. In 2011, due to motor fluctuations and sudden off-periods, he had to regularly interrupt berry picking and return to his car for levodopa dosing.
The patient had shown no interest in arts or poetry before the diagnosis and dopamine replacement therapy, which was confirmed by his family and friends. Seven years after the diagnosis (2 years after gambling and punding started), he started writing poems. He predominantly wrote early in the morning (3–7 a.m.) before taking morning medications. The themes of his poems were a mixture of love, disease and nature. His poetry was considered interesting by a commercial publisher, and his first poetry book was published 1 year later, and the second book was published in 2010. He showed no interest in other forms of art, such as visual arts or music.
At the time of the PET imaging in 2010, the patient was on Hoehn and Yahr stage 2.0, and his total Unified Parkinson's Disease Rating Scale (UPDRS) score was 53 [UPDRS I = 2 (out of 16), UPDRS II = 12 (out of 52), UPDRS III = 36 (out of 108), UPDRS IV = 3 (out of 23)]. Blood count, plasma glucose, plasma alanine aminotransferase, plasma gamma-glutamyl transferase, fasting plasma creatinine and plasma carbohydrate-deficient transferring (CDT) were normal. Urine drug testing for cannabis, cocaine, opiates, phencyclidine, methadone, dextropropoxyphene and benzodiazepines was negative. Brain 1.5T MRI continued to show no pathological findings. The patient underwent a structured interview (SCID-I) by a consultant psychiatrist, which did not reveal any lifetime Axis-I psychiatric disorders or ADHD. The patient scored 10 points (out of 63) in Beck Depression Inventory, indicating that he did not suffer from clinically significant depression. Temperament and character inventory (TCI) scores were 27/40 (27 out of 40) for novelty seeking, 16/35 for harm avoidance, 20/24 for reward dependence, 5/8 for persistence, 36/44 for self-directedness, 34/42 for cooperativeness and 7/33 for self-transcendence. Barratt Impulsiveness Scale (BIS-11) total score was 76, and subscores were 18 (range 8–32) for attentional, 23 (11–44) for motor and 35 (11–44) for non-planning impulsiveness.
F]fluorodopa-PET was performed with an ECAT EXACT HR+ scanner in 3D mode, injected dose 168 MBq, 90-min scanning, Patlak analysis with occipital cortex as reference, antiparkinsonian medications had been discontinued for 12 h prior to tracer injection, and carbidopa 150 mg had been given orally 1 h prior to injection, as described previously [9
]. Striatal deficit in tracer uptake was seen especially in the putamen contralateral to the predominant symptoms of the disease, which was in line with the diagnosis of idiopathic Parkinson's disease [right caudate Ki
) 7.41, left caudate 9.35, right putamen 2.99, left putamen 4.21, right ventral striatum 10.10, left ventral striatum 10.40, right medial orbitofrontal cortex (mOFC) 2.26, and left mOFC 2.36]. As compared to the other subjects of our previously reported study of Parkinson's disease patients without known increase in creativity, with or without impulse control disorders, the left [whole group Ki
median (range) 8.40 (6.46–10.40) 10–3
] and right ventral striatal [8.77 (7.31–10.10)], and the left caudate [7.39 (4.87–9.35)], [18
F]fluorodopa uptake of the present patient was the highest of the group (n = 19, one patient with self-reported increase in creativity was excluded from the analysis) [9
After PET imaging, cabergoline was rapidly stopped due to pathological gambling. Soon after the stopping of cabergoline, pathological gambling behavior decreased without significant changes in punding or poetic creativity. In parallel with cabergoline discontinuation, his motor symptoms increased and restless legs symptoms appeared. The levodopa dose was therefore markedly increased in 2010 and low-dose pramipexole for restless legs syndrome was initiated (table ). The patient felt that after cabergoline was stopped, his gambling was under control. Within 1 year of cabergoline discontinuation and levodopa dose increase in 2010, he developed significant motor fluctuations and is currently under consideration for deep brain stimulation.
Is the co-existence of the three behavioral changes coincidental in our patient? The possible linkage between impulsive-compulsive behaviors and artistic creativity in this patient led us to preliminarily investigate the phenomenon in a population of Parkinson's disease patients. We performed a postal survey inquiring the issue from January to August 2011. The survey was sent to 376 patients from our previous study [10
] (patients who had indicated that they were willing to participate in further studies), which investigated the prevalence of impulse control disorders in Finnish patients with Parkinson's disease. The survey included the QUIP together with questions regarding possible artistic creativity before and after the diagnosis of Parkinson's disease. A total of 296 (78.7%) of 376 patients returned the survey, but 6 patients were excluded because of inadequate data. Overall, 38.7% (n = 108 of 279) of the patients screened positive for at least one impulse control disorder in QUIP and 19.3% (n = 54 of 280) of the patients reported increased artistic creativity after the diagnosis of Parkinson's disease. Impulse control disorders as screened with QUIP were significantly more frequent in patients reporting increased creativity after the diagnosis than in patients without creativity increase (54.7 vs. 34.6%, respectively; n = 270, χ2
= 7.31, d.f. = 1, p = 0.007). Moreover, 33.3% (18 of the 54) of the patients with an increase in creativity subjectively linked the enhanced creativity directly to dopamine replacement therapy. The prevalence of creativity or impulse control disorders did not vary according to the side of predominant motor symptoms or to the type of medication used by the patient.