Parkinson Disease (Paralysis Agitans)

Risk

• Advanced age

• 1% of population >65 y

• No difference in distribution by gender

Perioperative Risks

• Hemodynamic instability, hypotension, arrhythmias

• Aspiration and upper airway obstruction from poor coordination of upper airway muscles

• Laryngospasm

• Postop confusion and hallucinations

Worry About

• Exacerbation of PD symptoms triggered by dopamine antagonists such as metoclopramide; also phenothiazines, butyrophenones

• Potential drug interactions: MAOIs; meperidine

Overview

• Pathophysiology: Symptoms result from the loss of dopaminergic cells in the pars compacta region of the substantia nigra reticulata. This loss upsets the normal balance between dopaminergic inhibition and cholinergic excitation.

• At least two of the following clinical manifestations are required for the diagnosis of PD: postural instability, bradykinesia, resting tremor, and rigidity. Other common features include depression, anxiety, sensory abnormalities, anosmia, autonomic dysfunction, cognitive impairment, and sleep disturbances.

Etiology

• Etiology unknown; possible genetic predisposition; possible neurotoxin involvement.

Usual Treatment

• Pharmacologic: The goal of current medical therapies is to maintain motor function and quality of life by restoring the dopaminergic/cholinergic balance in the striatum and blocking the effect of Ach.

  • Dopamine precursors

    • l-Dopa (a prodrug converted to dopamine in the brain): Mainstay of therapy, ameliorates all major clinical features of parkinsonism. Often helpful for hyperkinesias. Levodopa treatment is characterized by “on” periods of symptom amelioration and possible dyskinesias followed by “off” periods with decreasing therapeutic levels of dopamine and return of symptoms.

    • Carbidopa: Inhibits dopa decarboxylase, the enzyme responsible for the conversion of levodopa to DA. Limits breakdown of levodopa outside the CNS and increases the effectiveness of levodopa while also minimizing side effects.

    • Sinemet: Combination of carbidopa/levodopa.

  • DAs: Less effective than levodopa in relieving signs/symptoms of PD but less likely to cause dyskinesia and the on-off phenomenon. These drugs include ergot alkaloids (bromocriptine, cabergoline, lisuride), and nonergot alkaloids (pramipexole, ropinirole, rotigotine).

  • Anticholinergics: Trihexyphenidyl benztropine—more helpful for tremor and rigidity; generally less effective than DA drugs.

  • Antivirals: Amantadine—given for mild parkinsonism. Used alone or in combination with anti-Ach. Unclear mechanism of action. Improves all clinical features of PD.

  • MAO-B inhibitors: Selegiline—inhibits breakdown of DA and enhances antiparkinsonian effect of levodopa. May reduce the on-off phenomenon.

  • COMT inhibitors: Entacapone and tolcapone—help sustain plasma levels of levodopa. Decreases the dose and response fluctuations due to carbidopa/levodopa (Sinemet).

Surgical

• Lesioning: Historically, surgical intervention was primarily limited to lesioning of deep brain structures. The idea was that permanent lesioning would remove stimuli due to abnormal CNS activity (thalamotomy, used to treat tremor; pallidotomy, used to treat levodopa-induced dyskinesia/antiparkinsonian effects).

• Although affording some clinical benefits, such operations were also shown to result in permanent side effects, such as paresis, confusion, quadrantanopsia, gait disturbances, dysarthria, and hypersalivation.

• Such surgeries were associated with high complication rates and no possibility of lowering anti-PD drugs. These procedures are rarely performed today, having been replaced by DBS.

• DBS: In the late 1980s it was discovered intraop that high-frequency electrical stimulation could produce the same functional effect as surgical lesioning. This introduced DBS as a primary treatment modality. DBS has revolutionized the treatment of PD.

• The CNS targets of DBS include the ventralis intermedius nucleus (VIM), the subthalamic nucleus (STN), and the globus pallidus (GPi). However, the effects of VIM DBS on the other symptoms of PD (akinesia, rigidity, bradykinesia, etc.) are short-lived or nonexistent. GPi or STN DBS is used to treat these other symptoms.

Assessment Points