In the latest review article in our Clinical Therapeutics series, a 72-year-old man with Parkinson’s disease is referred for consideration of deep-brain stimulation, which involves the implantation of electrodes in one of the nuclei of the basal ganglia and can result in significant improvement in some symptoms of Parkinson’s disease.
Parkinson’s disease typically develops between the ages of 55 and 65 years and occurs in 1 to 2% of persons over the age of 60 years. Approximately 0.3% of the general population is affected, and the prevalence is higher among men than women, with a ratio of 1.6 to 1.0.
• What are classic manifestations of Parkinson’s disease?
Motor manifestations of the disorder commonly include a resting tremor, a soft voice, small handwriting (micrographia), stiffness (rigidity), slowness of movements (bradykinesia), shuffling steps, and difficulties with balance. A classic symptom is resting tremor, although 20% of patients do not have it. Parkinson’s disease also has a multitude of nonmotor manifestations, including disturbances of mood (e.g., depression, anxiety, and apathy), cognition (e.g., frontal-lobe dysfunction, memory difficulties, and dementia), and sleep (e.g., apnea and sleep disorders), as well as autonomic dysfunction (e.g., sexual dysfunction, digestive problems, and orthostasis).
• What medication-related complications typically develop in patients with Parkinson’s disease?
Typically, patients with Parkinson’s disease have a robust response to one or more medications. However, after 5 years of therapy, medication-related complications develop in a majority of patients. Such complications include dyskinesia and “on-off” fluctuations, in which a sudden, sometimes unpredictable loss of benefit from medication occurs, characterized by reduced mobility, tremor, rigidity, and other motor and nonmotor manifestations. Some symptoms (e.g., difficulties with gait, balance, speech, swallowing, or cognition) may become progressively resistant to carbidopa-levodopa and other pharmacologic therapies.
Morning Report Questions
Q: Which patients are candidates for deep-brain stimulation?
A: Deep-brain stimulation was approved by the Food and Drug Administration (FDA) in 2002 “as an adjunctive therapy in reducing some of the symptoms of advanced, levodopa-responsive Parkinson’s disease that are not adequately controlled by medication.” Most centers select patients for deep-brain stimulation on the basis of the nature of the patient’s symptoms and the likelihood of a response to the therapy. Typically, levodopa-responsive symptoms, tremor, on-off fluctuations, and dyskinesia are most likely to improve with deep-brain stimulation, whereas impairments in gait, balance, and speech are less likely to improve and may in some cases worsen. Patients should be considered for deep-brain stimulation only if adequate trials of multiple medications for Parkinson’s disease (e.g., carbidopa-levodopa, dopamine agonists, monoamine oxidase inhibitors, and amantadine) have been unsuccessful.
Q: What adverse events are associated with the use of deep-brain stimulation?
A: Among the most worrisome adverse events associated with placement of leads for deep-brain stimulation are infection and intracranial hemorrhage. In recent large series, rates of infection requiring further surgery have ranged from 1.2 to 15.2%. Infections most often require device removal and a period of antibiotic treatment before consideration of device replacement. In an extensive literature review, the overall rate of intracranial hemorrhage was calculated to be 5.0%; symptomatic hemorrhage occurred in 2.1% of patients, and hemorrhage causing permanent deficit or death occurred in 1.1%. Postprocedural seizures have also been reported, with an estimated incidence of 2.4% in one review of the literature. Neurologic side effects of deep-brain stimulation include cognitive impairment, memory deficits, difficulties with speech, disequilibrium, dysphagia, and motor and sensory disturbances. Emotional or psychological side effects have included mania, depression, apathy, laughter, crying, panic, fear, anxiety, and suicidal ideation.