Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized primarily by motor symptoms like tremor, rigidity, and slowed movement. While PD itself is not generally considered a direct cause of seizures, research indicates that individuals with PD face a higher risk of experiencing seizures compared to the general population. This increased risk stems from a variety of interconnected factors, including shared underlying pathology, the effects of certain treatments, and the presence of co-occurring conditions.
Parkinson’s Disease and Seizures The Direct Link
Typical idiopathic Parkinson’s disease, the most common form, is primarily defined by the loss of dopamine-producing neurons in the substantia nigra pars compacta. This neurodegeneration mainly affects the motor circuits connecting the basal ganglia to the cortex, which explains the characteristic movement difficulties. Seizures, in contrast, result from sudden, abnormal, and excessive electrical activity originating from hyperexcitable neurons, most often in the cerebral cortex. The primary pathology of PD is therefore anatomically and functionally distinct from the typical origin of epileptic activity.
The classic understanding of PD pathology focuses on the subcortical motor system, while seizures are a cortical phenomenon. However, the progressive nature of PD involves more widespread pathology, including the accumulation of alpha-synuclein protein into Lewy bodies that can spread beyond the substantia nigra to cortical areas in advanced stages. This broader neurodegeneration and the resulting disruption of neurotransmitter balance, particularly the loss of dopamine, may contribute to a state of increased neuronal excitability. Dopamine depletion can alter the balance between excitatory and inhibitory signals in the brain, potentially lowering the threshold required for a seizure to occur.
Research suggests that this neurodegenerative process alone may be associated with an increased risk of incident epileptic seizures, even when accounting for other common risk factors. The shared involvement of mechanisms like neuroinflammation, oxidative stress, and mitochondrial dysfunction in both PD and epilepsy further hints at common underlying neurobiological vulnerability. Nevertheless, the motor symptoms of PD are fundamentally different from the uncontrolled electrical discharges that characterize a seizure event. This distinction reinforces the idea that classical PD is a risk factor, not a direct instigator, of seizures.
Atypical Parkinsonism and Associated Seizure Risk
A significant exception to the general lack of direct causation involves conditions that mimic PD but have distinct underlying pathologies, collectively known as atypical parkinsonism or Parkinsonism-plus syndromes. These conditions, such as Dementia with Lewy Bodies (DLB), are associated with a greater and more direct risk of seizures. DLB is characterized by widespread alpha-synuclein pathology that involves the cerebral cortex early in the disease, which directly increases the likelihood of seizures and non-convulsive status epilepticus.
Certain genetic forms of parkinsonism also show a clear link to epilepsy, especially those with an early-onset presentation. For example, mutations in genes like PRKN (Parkin) or PINK1, responsible for some cases of early-onset PD, have been found in individuals who also have a history of seizures or epilepsy. These specific genetic errors often relate to mitochondrial function or protein recycling, which are processes implicated in both neurodegeneration and neuronal hyperexcitability.
The presence of widespread pathology, particularly in the cortex, appears to be the unifying factor linking atypical parkinsonism to seizures. In cases of DLB, a high percentage of patients with parkinsonism and epilepsy also have a diagnosis of dementia, supporting a shared pathophysiological mechanism related to extensive neurodegeneration. This contrasts with the pathology of typical idiopathic PD, which is initially more confined to the subcortical motor structures.
Medication Interactions and Lowered Seizure Threshold
The pharmacological treatment of Parkinson’s disease introduces complexity, as certain dopaminergic medications can influence the brain’s seizure threshold. Drugs that lower this threshold increase a person’s susceptibility to a seizure event. While anti-Parkinson’s medications are generally safe, they may trigger seizures in individuals who are already susceptible, such as those with a pre-existing or underlying seizure disorder.
The primary treatment, levodopa/carbidopa, can be implicated in rare cases, particularly when used in high doses. Carbidopa, which is combined with levodopa to prevent its premature breakdown, can bind to and deplete Vitamin B6 (pyridoxal 5′-phosphate). B6 is a cofactor necessary for the synthesis of the inhibitory neurotransmitter GABA. A severe B6 deficiency caused by this interaction can reduce the brain’s inhibitory activity, leading to a lowered seizure threshold.
Although less common, other dopaminergic agents like Amantadine, which influences glutamate neurotransmission, or some MAO-B inhibitors, which affect dopamine levels, may also be proconvulsant in certain situations or in individuals with a high predisposition. The risk is highly dependent on the individual patient’s underlying susceptibility and the dose of the medication. Clinicians must carefully consider a patient’s history of epilepsy or other proconvulsive factors when initiating or adjusting PD therapy.
Seizure Risk Factors Independent of PD Pathology
Beyond the specific neurobiology and drug effects of Parkinson’s disease, the patient demographic—typically older adults—is prone to various other conditions that increase seizure risk. These co-morbidities often coincide with PD, but their effect on seizure risk is independent of the PD-related pathology.
These co-morbidities are potent seizure triggers:
- Cerebrovascular disease, such as a prior stroke, is a common cause of seizures in older individuals.
- Metabolic imbalances, including hypoglycemia (low blood sugar) or severe electrolyte disturbances, such as hyponatremia (low sodium).
- Systemic infections or severe infections of the central nervous system, which can induce seizures by causing inflammation or fever.
- Pre-existing epilepsy, where the two conditions simply co-exist.
When a person with PD experiences a seizure, the cause must be investigated thoroughly. It may be related to age-related vascular changes, an acute medical issue, or a pre-existing neurological condition rather than the Parkinson’s disease process itself.