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Jen-Rei, Thien, Keong, Leng, Phokaewvarangkul, and Bhidayasiri: Peak-Dose Ballism Associated with Declining Implantable Pulse Generator Battery Life in Deep Brain Stimulation for Parkinson’s Disease
Deep brain stimulation (DBS) is performed in patients with Parkinson’s disease (PD) whose motor fluctuations and dyskinesias are difficult to control with PD medications alone [1]. However, DBS has complications of its own, with dyskinesia and unwanted involuntary movements experienced by some patients [2]. This case report highlights an unusual presentation of peak-dose ballism associated with DBS powered by an implantable pulse generator (IPG) that was approaching the end of its battery life.
A 62-year-old Malaysian woman with a 14-year history of PD underwent bilateral subthalamic nucleus DBS surgery in April 2015 (model 3389, Activa PC, Medtronics Inc.; Juncos, Puerto Rico) for intractable tremor and motor fluctuations. She had excellent results following DBS, becoming capable of independent walking and having improved ability to perform normal daily activities (segment 1, Supplementary Video 1 in the onlineonly Data Supplement).
Eight months after her surgery, she unfortunately experienced a fall in her bedroom resulting in a right hip fracture. Right hip arthroplasty was performed; however, she remained wheelchair bound thereafter. Although she did not regain full mobility following the surgery, her PD symptoms remained stable, controlled by DBS and levodopa/carbidopa/entacapone (LCE) 150/37.5/200 mg three times a day and pramipexole extended-release (ER) 1.5 mg daily with a total levodopa equivalent daily dose (LEDD) of 750 mg/day. Over the next four years, her symptoms remained stable with monopolar stimulation. Her latest settings in August 2019, prior to this presentation, were contact C+3-, 2.8 V, 60 μs, 130 Hz on the left electrode and contact C+11-, 2.2 V, 60 μs, 130 Hz on the right electrode (Table 1).
In October 2019, she experienced a sudden onset of abnormal movements, manifesting as peak-dose ballism, worsening on the right side, associated with dystonic posturing of the left arm (segment 2, Supplementary Video 1 in the online-only Data Supplement). These episodes were unlike the peak-dose dyskinesias that she had experienced in the past. The ballistic movements developed one hour after her dopaminergic medications, with each episode lasting approximately 20 to 30 minutes. She denied any episodes of wearing off.
Her DBS settings and medications were reviewed. Electrode impedances were found to be within the normal range. However, the IPG battery life was 2.8 V, indicating a status of “Increase Battery Monitoring.” A brain CT scan confirmed the correct position of the DBS leads without any structural lesions (Table 1).
To address the peak-dose ballistic movements, the voltage setting was gradually reduced by 0.1–0.2 V daily in the hope of resolving the ballistic movements. However, her ballistic movements (peak dose dyskinesia) persisted at stimulation settings as low as contact C+3-, 1.0 V, 60 μs, 130 Hz on the left electrode and contact C+11-, 1.5 V, 60 μs, 130 Hz on the right electrode. With the low stimulation settings, her “off” period became prolonged, manifesting as worsening tremors and reading difficulty. In response to these prolonged ‘off’ periods, levodopa/carbidopa was increased to 100/25 mg 1 tablet 4 times daily and pramipexole ER 0.375 mg 2 times a day, with a total LEDD of 476 mg. As the ballistic movements persisted, we decided to turn off her IPG stimulation as the voltage was only 1.0 V and 1.5 V on the left and right electrodes, respectively. With her IPG turned off, her ballistic movements ceased, but the “off” periods became more noticeable, as evidenced by an increase in the MDS UPDRS-III (Movement Disorder Society sponsored revision of the Unified Parkinson’s Disease Rating Scale-Part III) score from 63 to 75. Further adjustments of her dopaminergic medications were made to ameliorate her ‘off’ symptoms, including an increase of levodopa/carbidopa to 100/25 mg 1.5 tablets 4 times daily together with pramipexole ER 0.375 mg twice daily, giving a total LEDD of 676 mg. However, she began to experience generalized peak-dose levodopa dyskinesia (Table 1).
In November 2019, the patient decided to change her IPG in view of her motor complications. Currently, the patient’s condition remains satisfactory at IPG settings at contact C+3- of 2.1 V, 60 μs, 130 Hz on left electrode and at contact C+11- of 1.6 V, 60 μs, 130 Hz on right electrode and medications consisting of one levodopa/carbidopa 100/25 mg tablet 4 times daily and pramipexole ER 0.375 mg twice daily, with a total LEDD of 476 mg (Table 1). The IPG settings and medications are similar to those just prior to IPG replacement (segment 3, Supplementary Video 1 in the online-only Data Supplement).
Several studies have described rebound symptoms associated with unexpected battery depletion, including bradykinesia, rigidity, freezing and instability, tremor, status dystonicus, persistent depression, unilateral or bilateral restless legs, returning or increased obsessive compulsive disorder symptoms, fatigue, anxiety, depression, increased emotionality, difficulty thinking, lack of energy and panic attacks. The majority of symptoms listed are hypokinetic movement disorder symptoms and mood disorders. Peak-dose dyskinesia or ballism has not been described in these studies [3-7].
We initially postulated that the peak-dose dyskinesia occurring in our patient was a result of disinhibition of the striatothalamo-cortical pathway due to the inconsistent voltage output of the IPG. Interestingly, however, when the stimulation was reduced to a minimal voltage of 1.0 V and 1.5 V with a frequency of 130 Hz and pulse width of 60 μs, peak-dose dyskinesia still occurred, perhaps because the low-dose stimulation resulted in disinhibition of the striato-thalamo-cortical pathway in addition to medication-induced dyskinesia.
Several factors affect battery life in an IPG, including deviceto-device variation, battery voltage effects on current drain, battery usage, battery chemistry, impedance fluctuations, interpolation error, usage patterns and self-discharge [7]. At the time when the patient developed problematic peak-dose ballism, the battery life of her IPG was classified as “To Increase Battery Monitoring,” which suggests that rebound symptoms can occur before the battery is completely depleted. Anticipating battery life is a critical clinical issue since sudden interruption of DBS therapy, as experienced by our patient, can result in medical emergencies. In this case, the patient had bilateral ballistic movements due to the deteriorating IPG, which may have led to serious traumatic injuries. This type of observation is virtually impossible to identify in a large study, as it is rare and unexpected. However, neurologists should be aware of the wide range of complications that may arise in patients when their battery is almost or completely depleted.

Supplementary Material

The online-only Data Supplement is available with this article at https://doi.org/10.14802/jmd.20078.

Video 1.

Segment 1: The patient is cheerful in “on” period with DBS settings left subthalamic nucleus -2, case +ve, 2.9 V, freqeuncy 130 Hz and pulse width 60 μs and right subthalamic nucleus -11, case +ve, 1.3 V, frequency 130 HZ and pulse width 60 μs. Segment 2: The patient in “on” period with DBS settings left subthalamic nucleus -3, case +ve, 1 V, frequency 130 Hz and pulse width 60 μs, and right subthalamic nucleus -11, case +ve, 1.5 V, frequency 130 Hz, and pulse width 60 μs, when the IPG battery near end of life. The video shows peak dose ballism, worse on the right that resolved upon turning off the DBS. Segment 3: Post operative replacement of DBS-IPG with left subthalamic nucleus -3, case +ve, 2.1 V, frequency 130 Hz, and pulse width 60 μs, and right subthalamic nucleus -11, case +ve, 1.6 V, frequency 130 Hz, and pulse width 60 μs, without peak dose dyskinesia.

Notes

Conflicts of Interest

Prof. Roongroj Bhidayasiri has received consultancy, and/or honoraria/lecture fees from Abbot, Boehringer-Ingelheim, Britannia Pharmaceuticals, GlaxoSmithKline, Ipsen Pharmaceuticals, Novartis, and Teva-Lundbeck; he has received research funding from the Newton Fund, UK Government, Thailand Research Fund, Crown Property Bureau, Chulalongkorn University, and National Science and Technology Development Agency.

Author Contributions

Conceptualisation: Denzel Chong Jen-Rei, Lim Thien Thien, Lee Hock Keong, Hoe Wei Leng. Data curation: Denzel Chong Jen-Rei, Lim Thien Thien, Lee Hock Keong, Hoe Wei Leng. Formal analysis: Denzel Chong JenRei, Lim Thien Thien. Investigation: Denzel Chong Jen-Rei, Lim Thien Thien, Hoe Wei Leng. Methodology: Denzel Chong Jen-Rei, Lim Thien Thien. Project administration: Denzel Chong Jen-Rei, Lim Thien Thien. Resources: Lim Thien Thien, Lee Hock Keong, Hoe Wei Leng. Software: Denzel Chong Jen-Rei, Lim Thien Thien. Supervision: Denzel Chong Jen-Rei, Lim Thien Thien. Validation: Denzel Chong Jen-Rei, Lim Thien Thien. Visualisation: Denzel Chong Jen-Rei, Lim Thien Thien. Writing—original draft: Denzel Chong Jen-Rei, Lim Thien Thien. Writing—review & editing: Denzel Chong Jen-Rei, Lim Thien Thien, Onanong Phokaewvarangkul, Roongroj Bhidayasiri.

Ethical Standards

The authors confirm the the approval of an institutional review board was not required for this work. Informed conset was obtained from the patient for publishing this case report.

Acknowledgments

None.

Table 1.
Motor effects and motor complications in relation to deep brain stimulation settings and medications from August 2019 till November 2019
Left subthalamic nucleus
Right subthalamic nucleus
MDS UPDRS-III MDS UPDRS-IV* Medications Total LEDD (mg/day)
Lead position Voltage (V) Pulse width (μs) Frequency (Hz) Motor effects Lead position Voltage (V) Pulse width (μs) Frequency (Hz) Motor effects
Aug-19 C+3- 2.8 60 130 No wearing off C+11- 2.2 60 130 No wearing off 67 4.1: 0/4 4.4: 0/4 Levodopa/carbidopa 100/25 mg 0.5 tablet TDS 226
No dyskinesias No dyskinesias 4.2: 0/4 4.5: 0/4
4.3: 0/4 4.6: 0/4 Pramipexole ER 0.375 mg BD
Total: 0/24
October 2019 (battery near end of life at 2.8 V) C+3- 2.9 60 130 Right peak-dose ballism +++ C+11- 2.4 60 130 Left peak-dose ballism + 74 4.1: 3/4 4.4: 3/4 Levodopa/carbidopa 100/25 mg 0.5 tablet QID 276
No wearing off No wearing off 4.2: 4/4 4.5: 2/4
4.3: 0/4 4.6: 0/4 Pramipexole ER 0.375 mg BD
Total: 12/24
October 2019 (stimulation down) C+3- 1.0 60 130 Right peak-dose ballism +++ and prolonged “off” period C+11- 1.5 60 130 Left peak-dose ballism + and prolonged “off” period 63 4.1: 2/4 4.4: 3/4 Levodopa/carbidopa 100/25 mg 1 tablet QID 476
4.2: 3/4 4.5: 2/4
4.3: 2/4 4.6: 1/4 Pramipexole ER 0.375 mg BD
Total: 13/24
October 2019 stimulation off Off Peak-dose generalized dyskinesia and wearing off Off Peak-dose generalized dyskinesia and wearing off 75 4.1: 2/4 4.4: 2/4 Levodopa/carbidopa 100/25 mg 1.5 tablet QID 676
4.2: 2/4 4.5: 1/4
4.3: 3/4 4.6: 1/4 Pramipexole ER 0.375 mg BD
Total: 11/24
Nov-19 C+3- 2.1 60 130 No dyskinesia or wearing off seen C+11- 1.6 60 130 No dyskinesia or wearing off seen 62 4.1: 0/4 4.4: 0/4 Levodopa/carbidopa 100/25 mg 1 tablet QID 476
4.2: 0/4 4.5: 0/4
4.3: 0/4 4.6: 0/4 Pramipexole ER 0.375 mg BD
Total: 0

*subscore items: 4.1, time spent with dyskinesias; 4.2, functional impact of dyskinesias; 4.3, time spent in off state; 4.4, functional impact of fluctuations; 4.5, complexity of motor fluctuations; 4.6, painful off-state dystonia. +: mild ballism, ++: moderate ballism, +++: severe ballism. MDS UPDRS: Movement Disorder Society sponsored revision of the Unified Parkinson’s Disease Rating Scale, LEDD: levodopa equivalent daily dose, ER: extended-release.

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