Disambiguating the Psychiatric Sequelae of Parkinson’s Disease, Deep Brain Stimulation, and Life Events: Case Report and Literature Review

“Mr. R,” a 66-year-old white man with a 15-year history of Parkinson’s disease, was evaluated for surgical implantation of electrodes for deep brain stimulation (DBS). Initial neuropsychological testing showed nearly normal cognitive functioning with an isolated mild to moderate impairment on one measure of semantic verbal fluency. Mr. R’s history and presurgical evaluation revealed no contraindications for surgery; he did not meet criteria for mild cognitive impairment, dementia, or any Parkinson-plus syndromes, such as Lewy body dementia. No psychiatric concerns were noted by his neurology providers, so he was not scheduled for additional psychological or psychiatric evaluation prior to surgery. Because of his motor fluctuations and medication-induced dyskinesia, he was considered to be a good candidate for DBS.

Mr. R underwent staged bilateral DBS surgery targeting the subthalamic nucleus (STN). Leads were placed using microelectrode recording. The left STN and right STN leads were implanted a week apart, and coordinates were consistent with acceptable lead placement. The indirect coordinates relative to the midcommissural point were as follows: for the left STN, 10.95 mm lateral, 3.38 mm posterior, and 7.86 mm inferior; for the right STN, 10.92 mm lateral, 1.66 mm posterior, 6.88 mm inferior (consistent with the right electrode being anterior, slightly medial, and superior relative to the left electrode). Relative to consensus coordinates for the STN (11–13 mm lateral to midline, 3–4 mm posterior to the midcommissural point, and 4–5 mm ventral to the intercommissural plane) (1), the left electrode was therefore medial and inferior, and the inferior contacts would be expected to be ventral to the STN and therefore situated in the substantia nigra on both sides. Direct visualization confirmed this (Figure 1).

The programmable implantable pulse generator was placed 11 days later, and initial programming was completed 11 days after placement of the generator. (For initial programming settings, see Table S1 in the online data supplement that accompanies the online edition of this article.) Over the next 3 months, the patient had an excellent response to DBS, and no changes were made to his stimulation settings. His carbidopa-levodopa dosage was decreased by 80%. Regarding his behavior, Mr. R reported having more energy, his wife noted that he was more helpful with chores, and his daughter said, “It’s like having a teenage boy in the house.” This initial “hypomanic” state was the first indication of developing adverse behavioral effects. The patient and family were asked to watch his behavior and report any concerns immediately.

Four and a half months after initial programming of the pulse generator, Mr. R reported more dyskinesia, prompting a decrease in his regular carbidopa-levodopa dosage and discontinuation of his entacapone and extended-release carbidopa-levodopa.

Two weeks later, he was seen emergently because his wife reported “acting-out and angry behavior.” On the way to his appointment, he became very agitated and crushed his eyeglasses, resulting in multiple facial lacerations. Given that turning off stimulation completely would have a profound negative impact on motor function, his DBS device was reprogrammed to use a more dorsal left electrode contact. This change was effected in order to shift stimulation away from the ventromedial aspect of the STN and substantia nigra. Unfortunately, this change worsened his motor control; bradykinesia and tremor were more pronounced. Therefore, pulse width and frequency of stimulation were increased (Figure 2). Two days later, Mr. R reported that his anger had resolved. Over the next 8 months, Mr. R did well and made only minor changes to the amplitude using the patient programmer (see Table S1 in the online data supplement). (In this clinic, most patients are provided the opportunity to increase stimulation by 0.1–0.2 V per day for rigidity, bradykinesia, or tremor and to decrease stimulation as much as needed to mitigate dyskinesia or problematic side effects. Patients are encouraged to make gradual adjustments, and the programmer determines the range within which a patient can make changes.)

Seventeen months after initial programming, Mr. R developed irritability, anger outbursts, cognitive decline, paranoid delusions, and visual hallucinations. He also complained of worsening memory and verbal fluency. His wife described him as disinhibited and “not himself” and reported that the formerly reticent man was now voluble. He exhibited paranoia, believing that his neighborhood was suddenly unsafe and that teenagers were breaking into his home. He tried to get his gun to protect his family. His behavior became reckless and unpredictable. His daughter reported that while she was driving along a cliff road with no guardrail, he swung his cane at her in an attempt to “get a rise out of her.” His family became so concerned for the patient’s and others’ safety that they hid his firearms.

Mr. R was seen immediately in the DBS clinic. As there were no recent programming changes to correlate with his behavioral changes, he was referred to psychiatry. Three weeks later, prior to his psychiatric evaluation, he began to note an improvement in mood and behavior despite there having been no programming changes at the previous visit. He was experiencing more pronounced bradykinesia, so he underwent reprogramming in the off-medication state, with retesting of each contact for symptomatic benefit and side effect profile. The electrode configuration was changed to double monopolar bilaterally (Figure 3) (also see Table S1 in the online data supplement).

Mr. R was evaluated by psychiatry 1 week after reprogramming, 4 weeks after he was referred. As noted, his mood and behavior had already improved prior to reprogramming. During the psychiatric evaluation, Mr. R and his wife denied any new symptoms other than cognitive decline. He denied a history of mood symptoms or formal psychiatric history except for mild untreated depressive symptoms while in college. Mr. R and his wife disclosed that 4 months before starting DBS, Mr. R had been involved in a motor vehicle collision at work. After the collision, he disclosed to his supervisor his diagnosis of Parkinson’s disease, which he had hidden for more than a decade. Working in a physically demanding profession, he requested accommodations for his Parkinson’s disease. He reports that his supervisor subjected him to increased job stress, forcing him into retirement against his wishes. Soon afterward, he filed a lawsuit against his employer. The transition to retirement was very difficult for the couple. Mr. R’s wife worked from home, and they fought over many minor domestic issues, such as whether or not the blinds could be opened during the day. During this period, he was having difficulty coping with the stress of his job loss, his lawsuit against his employer, and daily conflict with his wife. On the day when Mr. R swung his cane at his daughter while she was driving, he had been drinking alcohol excessively. Mr. R had continued to be agitated and difficult to manage for a few weeks after that incident. His wife said that he had been so difficult to manage that the family was considering placing him in a nursing home.

On mental status examination, Mr. R demonstrated a flat affect and limited verbal interaction. No other abnormalities were noted. His wife explained that this was normal, “how he is.” He was given the diagnoses of adjustment disorder with disturbance of emotions and conduct; alcohol use disorder; and mild cognitive disorder.

He underwent repeat neuropsychological testing 2 weeks later. His overall performance on cognitive function was average, with slight declines noted in the domains of perceptual reasoning, working memory, processing speed, executive function, phonemic fluency, and nondominant hand fine motor coordination. In contrast, his verbal comprehension improved, and he showed stable performance in tasks of attention, confrontation naming, semantic fluency, and visuospatial and visual memory.

With this second episode of behavior change, there was no direct correlation between the changes in his mood and behavior and the timing of DBS programming changes. His behavior change was therefore attributed primarily to the psychological impact of multiple stressors, including worsening Parkinson’s disease symptoms, his job loss and the lawsuit he was filing against his employer, and the difficult transition to being at home, where his wife worked full-time. Additionally, at least one behavioral incident could be attributed to alcohol intoxication.

Mr. R restricted his alcohol use, developed new hobbies, and he and his wife began to compromise at home. Both Mr. R and his wife reported that communication between them significantly improved. His depressive symptoms improved, and there were no residual behavioral concerns. His wife described him as “so much better.” The improvement persisted, and he has been doing well at all follow-up appointments.