ILLUSTRATIVE CASE STUDIES
Case 1: Tranquility restored after surgery
Case 1 is a highly active, charismatic person, who is prepared to take risks. His natural
hyperthymia has brought him considerable professional success. In 2000, at the age of 44,
he was diagnosed with PD. Two years after being prescribed dopaminergic medication (5mgs
of pergolide combined with 150 mg of levodopa), he developed a pathological gambling
habit. This was accompanied by an internet addiction, nocturnal hyperactivity and an
unbridled libido. This hypersexuality had a negative impact on his family life, and the
gambling had such serious financial consequences that he voluntarily had himself banned
from entering casinos in 2003. During this period, several attempts were made to adjust his
medication. However, none of these succeeded in completely eradicating his behavioral
problems. While he was no longer gambling by the time he was hospitalized in 2007 with a
view to undergoing surgery, a profile of potentially dangerous hyperdopaminergic behavior
persisted with, in particular, a pursuit of the rush obtained from excessive speed at the
wheel and the making of rash purchases. He was being treated at the time with 3mgs of
pergolide and 500 mg of levodopa (Figure 3). The improvement of motor symptoms
resulting from STN stimulation permitted the complete discontinuation of dopamine
agonists and the reduction of levodopa dosages (to 300 mg/day). One year after surgery, all
hyperdopaminergic behaviors had disappeared, in the absence of any onset of apathy,
depression or anxiety (Figure 3). The patient’s behavioral profile had been normalized to his
complete satisfaction. “I was living like a mad man. I was irrational and unstable. I should
have been locked up. But that’s all over now– I’m free from all those vices. I have no more
unhealthy thoughts, no more sick needs. Now I am at peace in all respects.”
Case 2: post-operative relapse of manic state
A 56 year old male with a disease-duration of 12 years was examined in 2007 with a view to
surgical intervention. The previous year, while being treated with a combination of
pramipexole 3 mg and 1600 mg of levodopa, he experienced a classic manic episode, with
heightened irritability and psychotic symptoms which included paranoia, loss of identity,
mistrust and feelings of abandonment. In addition, nocturnal hyperactivity and addictive
behaviors affecting do-it-yourself, shopping and sexual activity had serious consequences on
the patient’s family life (Figure 4). These behavioral problems were alleviated by reducing
the dosage of pramipexole, while maintaining that of levodopa. The behavioral assessment
carried out at the pre-operative consultation revealed that although none of his symptoms
attained pathological levels, the patient continued to function in an overall
hyperdopaminergic mode. The patient was offered STN stimulation due to disabling motor
fluctuations. A rapid improvement of motor symptoms was noted, permitting the
discontinuation of dopamine agonists and a considerable reduction in dosages of remaining
medication. However, the onset of a severe restless leg syndrome resulting in insomnia
necessitated the prescription of tramadol controlled release 200 mg, clonazepam 2 mg and
100 mg LP of levodopa-carbidopa controlled release at bed-time. The inefficacy of this
combination led to the introduction of a dopamine agonist (piribedil 300 mg). Stimulation
parameters remained unchanged. This treatment gained control of the restless leg
syndrome, but on the patient’s return home, his family noticed worrying behavioral changes.
Patient became impulsive and started to take risks when driving. He seemed irritable and
muddled, was verbally aggressive and even purchased a top of the range car on a whim. It
was at this point that we saw the patient, who himself made the link between his behavior
and a manic episode in 2006 (Figure 4). Piribedil dosages were reduced to 200 mg/day and
shortly afterwards, a progressive return to normal was noted in terms of behavior. One year
after surgery, his treatment remains unchanged and a moderate hyperactivity persists,
affecting do-it-yourself and creativity levels. There has, however, been no relapse to the
former manic state. Although this patient’s behavior remains highly sensitive to medication,
dopamine agonists are essential to offset the severe restless leg syndrome, making
management of this patient difficult.
Case 3: Preoperative non-motor fluctuations and postoperative non-motor withdrawal state
A 58 year old female patient was offered surgery for severe motor fluctuations which
developed after 8 years of PD. Before surgery on 1500mg/day levodopa and 4,5 mg of
pramipexole she presented with a dopaminergic compulsive medication use, accompanied
by severe fluctuations of mood. During OFF periods, she experienced feelings of anxiety,
leading on occasion to full panic attacks, accompanied by sensations of suffocation. She felt
a great distress, which she expressed by weeping and shouting; she also spoke of ending her
life. “It’s hell….I cannot live like this any longer…people are sick of me….I’d be better off
ending it all…” During these episodes, she would withdraw from other people and had no
wish to speak. During ON periods, on the other hand, her mood would lift. “I feel alive
again…I want to do all sorts of things…” (Figures 5 and 6) The positive effect of subthalamic
stimulation noted after surgery enabled discontinuation of the dopamine agonist, while a 75
mg/day dosage of levodopa was maintained. Five months after undergoing surgery, the
patient developed a severe hypodopaminergic syndrome, with depression, apathy, anxiety
and irritability. Her condition was reminiscent of her preoperative severe OFF-period mood
state but instead of being intermittent, these non-motor psychic symptoms had become
permanent. Indeed, the patient gave up all activity, her anxiety had returned. She was
unable to be alone and was experiencing considerable mental suffering: “Living like this is
not a life…at least before I had the ON periods…” In response to this situation, dopamine
agonist treatment was undertaken (300 mg of piribedil, combined with 3 mg of bromazepam
and 20 mg of paroxetine at bedtime). Apathy, anxiety and suicidal thoughts rapidly
disappeared. The patient was once again able to gain pleasure from her activities. One year
on from surgery her behavioral profile had normalized (Figure 6).
Figure 3: CASE 1 behavioral assessments prior to surgery, with treatment consisting of 5mg
of pergolide and 150 mg of levodopa (plus benzerazide), and following surgery with patient
on 300 mg of levodopa and stimulation parameters as follows: Right STN monopolar, contact
2 negative, 3.5V/60µs/160 Hz ; Left STN monopolar, contact 6 negative, 3V/60 µs/ 160Hz.
Red lines indicate scores for severity of symptoms (0=absence; 1= slight; 2=moderate;
3=pronounced; 4= severe)
Figure 4: CASE 2 behavioral assessments during both hypo-manic episodes: in 2006 (prior to
surgery), with treatment consisting of 3 mg of pramipexol and 1600 mg of levodopa (plus
benzerazide); and in 2008 (following surgery), when it consisted of 200 mg of tramadol
controlled release, 2 mg of clonazepam, 100 mg of levodopa controlled release (plus
carbidopa) at bedtime, and 300 mg of piribedil. Stimulation parameters were as follows:
Right STN, monopolar, contact 2 negative, 1.7 V/ 60 µs/130 HZ; Left STN, monopolar, contact
6 negative, 2.5 V/60 s/130 HZ. Red lines indicate scores for severity of symptoms
(0=absence; 1= slight; 2=moderate; 3=pronounced; 4= severe)
Figure 5: Case 3 Preoperative non-motor fluctuations involving asthenia and affective state
using Norris Visual Analogic Scale, apathy (SAS, cut-off for apathy ≥14) and anxiety (BAI, 2235 scores indicates moderate anxiety, ≥ 36 severe anxiety).
Preoperative non-motor fluctuations
VAS asthenia
/80
4.1
64.8
VAS affective
state /80
5.8
Apathy scale
/42
9
58.9
OFF
19
Beck anxiety
inventory /63
15
37
0
ON
20
40
60
Figure 6: Case 3 behavioral assessments prior to surgery (on 1500mg/day levodopa + 4.5mg
pramipexole) and one year following surgery (on 300 mg of piribedil, 300mg levodopa, 3 mg
bromazepam, 20 mg paroxetine). Red lines indicate scores for severity of symptoms
(0=absence; 1= slight; 2=moderate; 3=pronounced; 4= severe)