Parkinson’s disease (PD) is a progressive neurological disorder defined by motor symptoms, such as resting tremor, bradykinesia (slowness of movement), and rigidity (muscle stiffness). These symptoms develop due to the loss of dopamine-producing neurons in the brain’s substantia nigra. A seizure, in contrast, is an episode of abnormal, uncontrolled electrical activity causing temporary changes in movement, behavior, or consciousness. This article explores the connection between PD and seizures, as both conditions affect brain function and movement.
The Direct Relationship Between Parkinson’s and Seizures
Parkinson’s disease is not considered a direct cause of typical epileptic seizures, unlike conditions such as traumatic brain injury or stroke. The primary pathology of PD—the selective loss of dopaminergic neurons—does not inherently trigger the sudden, hypersynchronous electrical discharge characteristic of a seizure. Seizures are episodic and generally last only a few minutes, contrasting with the persistent and gradually worsening nature of Parkinson’s motor symptoms.
Despite this, epidemiological studies consistently show that individuals with PD have a statistically higher risk of developing seizures compared to the general population. For example, one large-scale cohort study found that patients with PD had an approximately 1.7-fold increased risk of incident epileptic seizures. This significant correlation suggests that the underlying disease process creates a brain environment more susceptible to abnormal electrical activity.
Shared Biological Mechanisms and Increased Risk
The correlation between Parkinson’s disease and increased seizure risk is partly explained by shared neurobiological pathways and the widespread nature of neurodegeneration in PD. Although the disease begins in the substantia nigra, it eventually affects other brain regions, including the cerebral cortex, where seizures often originate. This broader neurodegeneration can lead to structural changes that increase neuronal excitability.
The accumulation of misfolded alpha-synuclein protein, a hallmark of PD, may contribute to this increased susceptibility by affecting synaptic function and neuronal communication. This protein aggregation can disrupt the balance of neurotransmitters essential for regulating electrical activity in the brain. Specifically, changes in the balance between the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate may lower the brain’s seizure threshold.
The depletion of dopamine, which is central to PD, has also been implicated in seizure modulation, as its loss can make epileptic seizures more likely. Chronic neuroinflammation, oxidative stress, and mitochondrial dysfunction are common pathological features in both PD and epilepsy, suggesting an overlap in underlying disease mechanisms. This shared pathology creates an environment of hyperexcitability, where neurons are more easily triggered into synchronized firing.
Medication Effects on Seizure Threshold
In many cases, the most common link between PD and seizure activity is iatrogenic, meaning it is related to the medications used to manage the disorder. Several dopaminergic drugs and other Parkinson’s treatments are known to lower the seizure threshold in susceptible individuals. This can occur even if the patient does not have a prior history of epilepsy.
Amantadine, often used to treat dyskinesia, is one PD medication that can acutely lower the seizure threshold. High doses of levodopa, the most effective drug for PD, or the use of certain dopamine agonists have also been documented to potentially induce or exacerbate seizure activity. Medications like selegiline, a monoamine oxidase B (MAO-B) inhibitor, are also known agents that can reduce the seizure threshold.
Careful dosing and monitoring are necessary when initiating new treatments or adjusting existing ones, especially in patients who have a history of seizures or other risk factors. Neurologists must weigh the therapeutic benefits against the proconvulsant potential of specific PD drugs.
Distinguishing Seizures from Parkinson’s Motor Symptoms
A significant challenge is differentiating a true epileptic seizure from the involuntary movements common in advanced Parkinson’s disease. PD motor symptoms include severe tremors, which are rhythmic movements usually occurring at rest. They also include dyskinesia, which are writhing, involuntary movements often caused by long-term levodopa use.
In contrast, a focal seizure can sometimes mimic these movements but is characterized by a sudden onset and offset. A key distinguishing feature of many seizures is the alteration or complete loss of awareness or consciousness during the event. A major seizure is often followed by a post-ictal state, a period of confusion, drowsiness, or exhaustion that can last minutes to hours.
Parkinsonian tremors usually stop or decrease during intentional movement, whereas seizure-related movements are generally uncontrolled. Observing whether the movement is symmetrical or involves a sudden, uncontrolled jerking of the entire body can also help differentiate the two. A definitive diagnosis requires a neurologist, who can use an electroencephalogram (EEG) to detect the abnormal electrical activity characteristic of a seizure.