Stimulation-Induced Dyskinesia, Interleaving Settings, and Management of Subthalamic Nucleus Deep Brain Stimulation in DYT1 Dystonia

DYT1 dystonia is a primary dystonia with potential for significant symptomatic improvement after bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi). GPi is the historical target of choice for this disease. This chapter presents a case of an adolescent with disabling generalized DYT1 dystonia who underwent bilateral subthalamic nucleus (STN) DBS as part of a prospective clinical trial. While limb and cervical dystonia dramatically improved with DBS, programming was limited by stimulation-induced bilateral limb dyskinesia, including in the left arm, which was previously unaffected by dystonia. After years of evolving symptoms and complex programming, bilateral interleaved settings using both a contact in motor STN and the most dorsal DBS contact in the zona incerta resulted in sustained, near-complete resolution of dystonia without side effects. This case illustrates the use of the STN as an effective DBS target for primary dystonia, although complex programming was necessary to mitigate stimulation-induced dyskinesia.

Patient Selection Criteria for Deep Brain Stimulation for Dystonia

Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. A recent revision now classifies dystonia into two axes: (1) clinical characteristics (age at onset, temporal pattern, body distribution, whether focal, segmental, or generalized; and associated features) and (2) etiology, whether idiopathic/genetic or secondary to other neurological/medical diseases. Pharmacological treatments for dystonia remain generally unsatisfactory and consist of various combinations of levodopa, anticholinergics, muscle-relaxing drugs as well as botulinum toxin injections in focal and segmental dystonia. Overall in outcomes are poor because of limited efficacy and the potential for significant side effects such as sedation and cognitive impairment. A humanitarian-device exemption from the Food and Drug Administration was issued for the treatment of medically refractory symptoms of generalized dystonia with the use of DBS. Bilateral GPi DBS surgery is effective for both generalized and focal dystonia including cervical dystonia and tardive dystonia. DBS may be the best available treatment for disabling symptoms of generalized, cervical, tardive, and other dystonia that have failed to respond to oral drugs and botulinum toxin injections (when applicable) as long as contractures have not developed, because in this situation, DBS will be ineffective. Rigorous patient selection and careful management of comorbidities are essential for favorable outcomes.

Postural Instability and Gait Disorder After Subthalamic Nucleus Deep Brain Stimulation

Parkinson disease (PD) patients who have undergone surgery and develop festinating gait and postural instability are challenging to diagnose and treat. This chapter describes the case of an early-onset PD patient who underwent deep brain stimulation (DBS) 4 years after disease onset due to motor and nonmotor fluctuations and medication side effects (impulse control disorder). A year after surgery, the patient developed gait and balance problems in the on-medication/on-stimulation states that resolved after turning stimulation off or withdrawing medication for 12 hours. However, other symptoms, including as bradykinesia, rigidity, and tremor, reappeared. Troubleshooting involved magnetic resonance imaging to evaluate electrode placement and complete screening of all contacts with successful reprogramming and medication adjustments. The pathophysiology of balance problems is discussed, including the synergistic effects of subthalamic nucleus DBS and dopaminergic treatment, which may lead to increased postural sway and lower limb dystonia.

Freezing of Gait After Bilateral Globus Pallidus Interna Deep Brain Stimulation in Generalized Dystonia

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a safe and long-term effective treatment for medication-refractory dystonia. However, complications and side effects may occur. Freezing of gait (FOG) is a rare phenomenon in patients with dystonia, although very frequently this complication is observed in patients with Parkinson disease (PD). FOG can be disabling and may severely impair quality of life, even when episodic. This chapter reports on a case of a 49-year-old left-handed man presenting with FOG, impairment in balance, and walking difficulty. These issues emerged 3 years after successful bilateral GPi DBS for primary generalized dystonia.

Subthalamic Nucleus Deep Brain Stimulation May Improve Pain in the Setting of Parkinson Disease

More than 50% of patients with Parkinson disease (PD) can have chronic pain. PD pain has been associated with reduced quality of life scores on validated measures. The most common source of PD pain is musculoskeletal in origin. This pain may manifest as rigidity, cramps, shoulder discomfort, spinal or hand and foot deformities, dystonic pain, or nonradicular back pain. Our case illustrates improvement in chronic pain following bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery in a 45-year-old patient with PD. Approximately 1 year after PD onset, he developed constant pain and tremor in his left upper extremity, which gradually worsened over time. Initially, carbidopa/levodopa completely alleviated both his arm tremor and pain. Over the next several years, he developed off periods that were associated with bothersome tremor and pain, and on periods that were associated with prominent neck and left arm dyskinesia, both of which were associated with significant pain. At age 60 years, after 15 years of PD, he underwent bilateral STN DBS implantation. Following DBS, he had significant improvement in his left arm tremor, rigidity, motor fluctuations, and pain. He also had a 70% reduction in his dopaminergic medication and complete resolution of dyskinesia and neck pain.

Medication-Refractory Parkinsonian Tremor Requiring Dual Lead Implantation for Tremor Control

A 52-year-old man with Parkinson disease (PD) of 9 years’ duration was referred to the DBS clinic for medication-refractory severe unilateral rest and re-emergent tremor and frequent motor fluctuations. He was approved for DBS, with debate over the optimal target to treat severe tremor and fluctuations (subthalamic nucleus [STN] plus/minus the ventral intermediate [Vim] thalamus) and unilateral versus bilateral implantation. The committee decided to perform unilateral STN lead placement first, to provide benefit for both motor fluctuation and tremor, with the option of adding Vim concurrently if required. Intraoperatively, there was incomplete tremor capture, so a second lead was placed in Vim with success. Subsequent DBS programming achieved marked improvement of tremor and fluctuations at low stimulation, although side effects necessitated bipolar configurations in both leads. The patient reported excellent sustained tremor suppression at 2-year follow-up, although motor fluctuations recurred. This case illustrates that for intraoperative stimulation-refractory PD tremor, consideration can be given to adding a second Vim DBS target (dual DBS targets).

Target Selection for Parkinson Disease With Medication-Refractory Unilateral Resting Tremor

A 67-year-old, right-handed man had a 7-year history of right-dominant, severe medication-refractory resting and action-postural tremor, rigidity, bradykinesia, and impairment of postural reflexes, with his symptoms poorly responsive to oral antiparkinsonian medication. His parkinsonian symptoms with the exception of tremor responded to levodopa infusion. His most bothersome symptom was tremor, and implantation of a left subthalamic nucleus (STN) deep brain stimulation (DBS) lead was pursued with possible posterior subthalamic area (PSA) DBS if the tremor suppression by STN was not intraoperatively sufficient. Ultimately, the STN DBS lead provided reasonable tremor suppression during the operation, and there was no need for PSA DBS. After the surgery, his tremor and other parkinsonian symptoms were well-controlled. This case highlights that unilateral STN DBS is a reasonable indication for medication-refractory parkinsonian tremor with significant laterality of bothersome symptoms, although other options may also be considered.

Symptomatic Cystic Lesion Following Deep Brain Stimulation Surgery

Deep brain stimulation therapy is an effective therapy for selected patients with movement disorders. The procedure is relatively safe, but complications related to the surgical procedure or implanted hardware can occur. The common complications include hemorrhage, infarct, infection, and confusion. Noninfectious cyst formation around the DBS lead is a rare but potential complication of this procedure, which can occur several weeks to months after DBS lead implantation. This chapter describes a case of noninfectious cyst formation at the tip of DBS lead in a patient with essential tremor. Clinical presentation, role of imaging, and the management options for this rare complication are discussed. This case also illustrates the importance of post-DBS imaging in suspected cases with new or unexplained symptoms.

Tardive Dystonia and Dyskinesia Responsive to Deep Brain Stimulation

Tardive disorders encompass phenomenologically diverse delayed-onset persistent involuntary motor symptoms associated with exposure to dopamine receptor blocking agents. Two common tardive disorders encountered in the clinical setting include tardive dyskinesia and tardive dystonia. This chapter presents a patient with severe refractory tardive dyskinesia and also tardive dystonia, manifesting as frequent and disabling retropulsion. He initially underwent bilateral globus pallidus interna (GPi) deep brain stimulation (DBS) but was found to have lead migration secondary to his severe hyperkinetic movements. He had persistent symptoms despite lead revision and ultimately required bilateral subthalamic nucleus (STN) rescue DBS implantation. The rescue procedure was synergistic with the initial GPi DBS and markedly improved his symptoms. Severe tardive dyskinesia and dystonia may respond to bilateral GPi DBS, and if necessary, rescue STN DBS can be added.

Deep Brain Stimulation for Dystonia

The past two decades have revealed substantial benefits of bilateral pallidal deep brain stimulation (DBS) in patients with medication-refractory primary dystonia. There is a growing body of evidence now describing not only short-term but also long-term benefits up to 10 years following DBS. These benefits are often sustained, requiring minimal long-term modification. Pallidal programming for dystonia may be complex owing to the gradual onset of benefits and often delayed development of side effects. There is a relative scarcity of evidence-based recommendations for standardized programming methods. This chapter reviews essential factors to consider for appropriate patient selection and discusses strategies for initial and follow-up programming. Finally, the chapter describes the potential short-term and long-term adverse effects, while considering various strategies to mitigate them.