Alternative Therapies

ARE SEIZURES BAD FOR THE BRAIN?
By Souhel Najjar, M.D.

Medically refractory partial seizures are characterized by cell loss and gliosis (scar cells) with consequences for nerve cell reorganization, excitability, memory and cognitive functions. Several studies provide solid evidence for long-term alterations of neuronal excitability and cognitive capacity associated with repeated seizures during development. The data raise concerns about the long-term cognitive consequences of repetitive seizures, especially in, but not limited to, developing brains.

Some epilepsy types are more specifically associated with such nerve cell reorganization, and more pronounced nerve cell loss such as mesial temporal lobe epilepsies (MTEs). A radiological and pathological signature of MTE, hippocampal sclerosis is the prime example of how repeated seizures induce neuronal reorganization and nerve cell loss. Hippocampal sclerosis is often associated with refractory seizures that result in memory impairment. Interestingly, a fully developed hippocampal sclerosis is infrequently observed following even a single prolonged febrile seizure, which might suggest the presence of a preexisting vulnerability for this condition.

Other recent studies show definitive evidence of long term effects of even brief but repetitive febrile seizures (FS) on memory during early brain development in rats. Absence seizures (also known as petit mal seizures), are not considered harmful to nerve cells since these seizures do not produce massive excitation of the neurons. It is worth noting that recurrent seizures in refractory epilepsies may result in various personality changes and other psychopathological conditions (20%- 50%).

These changes are more often encountered in temporal lobe epilepsies. The temporal lobes contain vital limbic system structures (hippocampus and amygdala) that are closely involved in emotional behavior. Repeated seizures in refractory partial epilepsies can cause pathological changes that affect these structures, which can result in personality disorders, affective disorders (depression 18%, anxiety 20%, fear, paroxysmal irritability 30%, and euphoric moods), and even psychosis (8-10%). The strongest risk factors for psychosis in epilepsy are those that indicate severity of epilepsy, including long duration of active epilepsy, multiple seizure types, and poor response to drug treatment.

Mechanisms mediating the harmful effects of repeated seizures

Excessive nerve cell excitation due to potentiation of N-methyl-D-aspartate (NMDA) receptors (excitatory receptors), appears to be the main culprit that irreversibly damages nerve cells. Numerous studies show that NMDA receptors play a prominent role in the neuropathology and the pathogenesis of epilepsy. Several studies show that NMDA provoked seizures, induced early in the developing rat brain, are followed with subsequent deficits in spatial learning and an increased susceptibility to seizures in adulthood. Furthermore, the activation of intrinsic inflammatory cells (so-called microglial cells), the production of inflammatory/toxic molecules (so-called cytokines) by these cells, the breakdown of blood-brain barrier, and calcium dysregulation, are well-documented abnormalities in epileptic tissue, and may play a role in nerve cell injury. The above data suggest that early effective medical, and at times surgical, treatment for refractory epilepsy is essential to limit potential irreversible nerve cell injury, and its related progressive neurological, cognitive, and neuropsychiatric effects caused by repeated seizures.