BOSTON — Drug changes—by the physician or the patient—and infections are the most likely culprits behind motor fluctuations that land a patient with Parkinson's disease in the emergency department.

“The first thing to do is look for infections or other medical issues, and check to see if there have been any medication changes,” said Dr. Stewart Factor said at the annual meeting of the American Academy of Neurology.

Urinary tract or upper respiratory infections can trigger dyskinesias by altering the sensitivity to medication, said Dr. Factor of Emory University, Atlanta.

He cited the case of a 60-year-old woman whose “off” periods confined her to a wheelchair. She had sudden rapid cycling from virtual immobility to severe dyskinesia that made it difficult to breathe, and reported a fever of 101° F for 3 days. In the ED, she displayed decreased breath sounds and crackles on the left side. A chest radiograph confirmed lower left lobe pneumonia. She responded well to intravenous antibiotics and fluids, but the dyskinetic cycling continued despite holding her carbidopa-levodopa and decreasing her pergolide by half. Only after 48 hours, when she became afebrile and the pneumonia had improved, was it possible to restart her medication, Dr. Factor said.

A second patient arrived at the ED short of breath, dehydrated, and diaphoretic, with a sudden, severe escalation of choreiform dyskinesia that had been going on for several hours. His leg movements were so extreme, he had severe bruising from hitting them against the bed rails in the ED. His creatine kinase was more than 21,000 U/L, and his white blood cell count was elevated. Questioning revealed he'd taken extra carbidopa-levodopa. “He had planned on going dancing that night and he didn't want to go 'off',” Dr. Factor said. In the ED, his medications were withheld for 12 hours, and he received intravenous fluids. He was discharged when his creatine kinase was normal, and restarted his drugs.

“People who self-medicate love to be 'on,' even if it increases their dyskinesia,” Dr. Factor said. “It's so much better than the alternative for them.” Patients may have run out of their drugs, or recently added a new drug that was increased too rapidly or stopped suddenly.

Psychiatric symptoms also cause patients to change their drug regimen, he added, citing the case of a woman with Parkinson's-related psychosis. She'd been prescribed 100 mg/day of quetiapine after a suicide attempt, but the dose was cut to 50 mg several years later. After the drop, “she heard the voice of God telling her to stop her medications, and became severely immobile,” Dr. Factor said. Psychiatric symptoms resolved after quetiapine was increased from 50 mg to 400 mg.

Abrupt stop of dopaminergic medications can lead to Parkinson's hyperpyrexia syndrome (PHS). Its clinical features are nearly identical to neuroleptic malignant syndrome: severe rigidity with tremor progressing to immobility. Within 72–96 hours, most patients develop fever (up to 107° F) and altered state of consciousness (from agitation and confusion to stupor and coma), plus autonomic dysregulation (tachycardia, tachypnea, labile blood pressure, urinary incontinence, or diaphoresis). There will always be leukocytosis and elevated creatine kinase. PHS is rare but serious—about 30% don't fully recover, and about 4% die.

PHS is usually tied to abrupt stop of drugs, including drug holidays, noncompliance, unsure diagnosis, or sudden alteration of drug regimen.

Tips for Calming Patients' Motor Fluctuations

The primary goal should always be to identify and treat any constitutional illness, said Dr. Stewart Factor. But if no underlying illness is present, drug therapy must be focused on breaking the motor cycle and then tailoring medical therapy to the patient's needs.

“Alteration in Parkinson's medications must be individualized with the goal of trying to maintain a more constant peripheral level of levodopa,” he said.

For prolonged “off” periods, consider the following approaches:

▸ Use more frequent carbidopa-levodopa (C/L) doses.

▸ Make quick-absorb C/L by dissolving tablets in tap water with ascorbic acid and dividing into hourly doses.

▸ Try adding a dopamine agonist.

▸ Use parenteral injection of apomorphine hydrochloride. “This drug when administered subcutaneously has a rapid onset, usually within 10 minutes, and a short duration of about 1 hour,” Dr. Factor said. “It has been used to rescue patients from intractable off periods, consistently improves off periods, and its effectiveness can be maintained for years.”

▸ Try controlled-release C/L.

For peak-dose choreiform dyskinesias, consider these strategies:

▸ Lower the dose of C/L or hold the medication until the symptoms improve.

▸ Try a mild sedative (lorazepam, alprazolam, or clonazepam) in the meantime. “This is particularly useful when dyskinesias are worse at night, and can be utilized in the ED while waiting for the dopaminergic medications to wear off,” he said.

▸ Controlled-release C/L may be a better choice, because its peak plasma level is lower than the standard formulation. This may worsen diphasic dyskinesias, however, especially if given in the evening.

▸ Do not give patients any of the typical neuroleptics such as haloperidol or prochlorperazine, because they can ultimately worsen Parkinson's.

Infections, Drug Changes Cause the Biggest Problems for PD