Anti-seizure drug levetiracetam worsens woman’s Parkinson’s
Case report shows need for monitoring Parkinson's patients, researchers say
Treatment with the anti-seizure medication levetiracetam led to a worsening of Parkinson’s disease symptoms for a woman in Saudi Arabia, according to a case report.
The woman was given levetiracetam to prevent seizures after she fell and hit her head, but she soon after experienced deteriorating neurological and motor function. Once levetiracetam was discontinued, the woman’s clinical status improved.
“The use of Levetiracetam in patients with Parkinson’s disease can rarely lead to acute exacerbation of Parkinson’s symptoms and worsening of outcome,” the researchers wrote. “Close monitoring of patients with Parkinson’s disease is recommended when prescribing anti-epileptics.”
The report, “Parkinson’s disease exacerbation following Levetiracetam administration: an unusual phenomenon,” was published in Oxford Medical Case Reports.
Parkinson’s disease is a neurodegenerative condition characterized by the progressive loss of nerve cells responsible for producing a brain-signaling chemical (neurotransmitter) called dopamine, leading to a wide range of motor and nonmotor symptoms.
Modulating dopamine
Levetiracetam is approved in the U.S. for controlling seizures in people with certain types of epilepsy. It works by binding to a brain protein called synaptic vesicle protein 2A, in turn modulating the release of various neurotransmitters, including dopamine.
Some studies have evaluated whether levetiracetam could ease dyskinesia, or involuntary muscle movements caused by levodopa treatment, in people with Parkinson’s. Those studies yielded inconsistent results, and the medication aggravated Parkinson’s symptoms for some patients.
In the case report, scientists focused on a 77-year-old woman in Saudi Arabia whose Parkinson’s disease was exacerbated by levetiracetam. She’d been diagnosed with Parkinson’s more than a decade prior, and her disease was well controlled with a regimen of levodopa/carbidopa.
She came to the researchers’ clinic feeling dizzy after a fall that caused her to lose consciousness for two minutes. She did not have a history of seizures or sudden headaches.
A physical exam found the patient generally stable. Her score on the Glasgow Coma Scale (GCS) — a neurological assessment of how alert and oriented a person is — was 15 out of 15, reflecting that she was fully awake and responsive. The only notable finding was muscle stiffness with cogwheel rigidity, a feature of Parkinson’s in which muscles are stiff and move in a jerky fashion.
Brain imaging showed signs of diffuse subarachnoid hemorrhage, or extensive bleeding in the space surrounding the brain. Because this degree of bleeding can lead to epilepsy, the clinicians started her on levetiracetam to prevent seizures.
Four days later, the woman’s GCS dropped to a 9 out of 15, reflecting a worsening neurological status. She also showed signs of worsening Parkinson’s motor symptoms, including muscle weakness, progressive muscle stiffness, tremor, and overactive muscle reflexes.
An electroencephalogram, which measures the electrical activity in the brain, didn’t show any signs of seizures, and other brain imaging studies looked normal.
After all other possible causes of Parkinson’s exacerbations were ruled out, the doctors gradually weaned the patient off of levetiracetam until the treatment was discontinued completely.
This led to significant clinical improvements over the next few days, including a resolution of muscle stiffness, tremors, and other neurological changes, and she was discharged from the hospital.
Given the possible association between levetiracetam and Parkinson’s exacerbations, “an alternative anti-seizure agent can be considered in patients with Parkinson’s Disease,” the researchers wrote.
They noted, however, that a number of other anti-epileptic medications have also been associated with Parkinson’s development, and thus could also pose a risk of making a patient’s symptoms worse.
One anti-epileptic medication, zonisamide (sold as Zonegran in the U.S.), has appeared to be well tolerated by Parkinson’s patients in clinical studies, and evidence suggests that it could ease Parkinson’s motor symptoms. The medication has been approved in Japan under the brand name Trerief as an add-on Parkinson’s therapy since 2009.
“Hence, it is plausible that the administration of this treatment may yield favorable outcomes in individuals diagnosed with Parkinson’s disease who … necessitate the use of antiepileptic medications for … seizure prevention,” the researchers wrote.
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