Living with epilepsy presents unique challenges that can impact every aspect of its sufferers’ daily lives, including their most fundamental sense of security and independence. Often shrouded in mystery, epilepsy is a complex, chronic disorder of the brain’s electrical system characterized by sudden, recurrent brain seizures that can involve sensory disturbance, loss of consciousness, staring spells, or convulsions. During a seizure, neurons may fire as many as 500 times a second, much faster than normal. In some people, this happens only occasionally. But for others, it may happen many times per day.
Around 1 percent of the U.S. population has active epilepsy; around 30 percent are children (CDC, 2010). While the number of people who suffer from epilepsy may be comparatively small, there is no sure cure. And treatments, which typically focus primarily on medications, often yield mixed results. For more than 30 percent of people with epilepsy, drugs are either ineffective or only partially effective, which means they must seek a non-pharmacological solution such as meditation.
What causes epileptic seizures?
Epileptic seizures are triggered by electrical misfires in the brain — clusters of nerve cells, or neurons signaling abnormally. These abnormal electrical storms cause the brief, sudden changes in movement, behavior or consciousness known as seizures, which may last from a few seconds to a few minutes. Seizures are referred to as symptomatic when they can be linked to identifiable diseases or brain abnormalities and cryptogenic when no cause can be found. Idiopathic seizures are diagnosed when an unknown genetic or hereditary cause is suspected.
What causes these electrical storms?
Epileptic seizures can potentially be triggered by any event that disturbs normal brain activity. Seizures may have either acute or remote causes: acute if, for example, an active brain disease such as Alzheimer’s is causing seizures; remote if a brain abnormality was caused by a previous injury or event. For example, if a child with active meningitis experiences seizures they, they’re diagnosed as acute symptomatic seizures, but if the child develops seizures 2 years later, she would be diagnosed with remote symptomatic epilepsy.
There are at least 40 known types of epilepsy, but in nearly two-thirds of epilepsy cases, no direct cause was identified (CDC, 2012). Epileptic syndromes often have diverse primary causes that may be genetic, developmental or acquired.
Known causes of epilepsy include:
- Brain chemistry
- Genetic factors
- Head trauma
- Prenatal injuries
- Birth abnormalities and congenital conditions
- Environmental causes
- Other disorders
Head trauma, birth abnormalities and association with other disorders
In some cases, the brain’s attempts to repair itself after a head injury, stroke, or other event may inadvertently generate abnormal neural connections that lead to epilepsy. Abnormalities in brain wiring that occur during early brain development may disturb neuronal activity and lead to epilepsy; for example, lack of oxygen, hemorrhage, brain malformations, low levels of blood sugar, blood calcium, blood magnesium or other electrolyte disturbances. Epilepsy is associated with congenital conditions such as Down syndrome; Angelman’s syndrome, tuberous sclerosis, neurofibromatosis and autism.
Epilepsy is also associated with other disorders, including metabolic disorders, brain tumors, Alzheimer’s, stroke, cerebral palsy, and infectious diseases such as meningitis, viral encephalitis, AIDS.
Genetic causes of epilepsy
Some types of epilepsy tend to run in families, and some have been traced to an abnormality with a specific gene. Often, these genetic abnormalities cause subtle changes in the way the body processes calcium, potassium, sodium, and other chemicals. In some cases, genes are not a direct cause of epilepsy but still influence the disease process; for example, genes can affect the way someone processes drugs or can produce clusters of malformed neurons in the brain.
Brain function — from the excitability of the membranes surrounding our cells to our levels of neurotransmitters — is controlled by individual genes that, when damaged or mutant, may lead to seizures. For example, progressive myoclonus epilepsy has been linked to over 50 different mutations of the EPM2A gene that helps break down protein. A severe form of this syndrome called Lafora disease is linked to mutations in EPM2A and the gene NHLRC1, which is involved in breaking down carbohydrates (Jansen et al, 2012). Mutations of the gene SCN1A, which is involved in regulating sodium within cells, have been linked to many epilepsy syndromes, including Dravet Syndrome (Mulley et al, 2005). And the list goes on. In fact, so far, we’re aware of mutations in over 70 genes that define the biological pathways leading to epilepsy and some researchers estimate that more than 500 genes may play a role in this disorder. However, it is increasingly clear that, in many forms of epilepsy, genetic abnormalities play only a partial role, perhaps by increasing a person’s susceptibility to seizures that are triggered by an environmental factor (NIH, 2012).
The role of brain chemistry in causing epilepsy
An imbalance between excitatory and inhibitory neurotransmitters (brain chemicals) can cause epilepsy. Some people with epilepsy may have too much of a neurotransmitter that increases impulse transmission (an excitatory neurotransmitter) and others may have too little of a neurotransmitter that reduce transmission (an inhibitory neurotransmitter).
We’ve long known that chemically blocking the amino acid gamma-aminobutyric acid (GABA) triggers epileptic seizure in animals. GABA, the primary inhibitory neurotransmitter in the cerebral cortex, is responsible for maintaining the inhibitory tone that counterbalances neuronal excitation; that is, it slows electrical transmission between nerve cells. Low levels of GABA in the brain have been found to cause epilepsy in some people and increase the risk for seizure (Bradford, 1995; Gale, 1992). GABA regulates the activity of other neurotransmitters (including serotonin, norepinephrine, epinephrine and dopamine) and has a calming, anti-anxiety, anticonvulsant effect on the brain.
Studies analyzing the changes in amino acid content in animal and human brain tissue following onset of epileptic seizure have found that, in some cases, imbalances in GABA and the amino acid glutamate may work in tandem to cause epileptic seizures (Bradford, 1995). Glutamate, the most common excitatory transmitter in the brain, promotes neural firing and enhances electrical flow among brain cells. Glutamate is also known to play a role in early brain development, which may help explain some cases of childhood epilepsy. Glutamate transporters are known to play an important role in regulating excitability in a baby’s developing neocortex and, without this control, hyperexcitability ensues in the form of seizures (Demarque et al, 2004).
Synaptically released glutamate (glutamate released as neurons fire) has been found to play a major role in the initiation and spread of seizure activity, regardless of the primary cause of the seizure (Chapman, 2000). It can reduce GABA’s ability to inhibit or regulate electrical activity in the hippocampus (Min et al, 1999), the brain area responsible for storing and indexing memories.
GABAergic neurons help control glutamatergic neurons, but when a seizure occurs, GABAergic neurons are destroyed, which leads to decreased GABA activity, and more seizures (Scharfman, 2008). In fact, anticonvulsant drugs prescribed for epilepsy modulate the amount of GABA in the brain in order to counterbalance the excitotoxcity elicited by too much glutamate. However, GABA receptors are highly plastic and can change after seizures, rendering an anticonvulsant ineffective.
Because our brains are continually adapting to changes in stimuli, a small change in neuronal activity, if repeated, may eventually lead to full-blown epilepsy, a process referred to as electrical kindling. Glutamate and GABA are centrally involved in the kindling process, especially in the hippocampus, the memory warehouse. This is one of the overlapping pathways for epilepsy and Alzheimer’s dementia that may help explain why some Alzheimer’s patients suffer epileptic seizures (Noebels, 2011).
The cell membrane surrounding each neuron, which allows the neuron to generate electrical impulses, is a critical determinant of nerve cell function and seizure control. Studies have shown that a disruption in certain processes, such as an abnormality with molecules of sodium or calcium moving in and out of membranes, may lead to epilepsy (NIH, 2012; Scharfman. 2007). An acute or sudden imbalance in electrolytes such as calcium, sodium, potassium or chloride can depolarize these nerve cells, which discharges action potentials and can lead to seizures. Studies have found that abnormalities in neurons’ sodium channels can increase the release of the excitatory glutamate, which, in turn, can lead to excitotoxcity, and ultimately a seizure (Scharfman, 2008).
Epilepsy may also be caused by changes in brain cells called glia cells. While glia do not conduct nerve impulses, they regulate concentrations of chemicals in the brain (e.g., sodium or calcium) that can change the way neurons signal each other (Scharfman, 2008).
In some cases, epileptic seizures are triggered by an unhealthy lifestyle that includes, for example, sleep deprivation, use of street drugs, and excessive alcohol consumption. But other factors, such as hormonal imbalances, and environmental exposure to substances such as lead, carbon monoxide or toxic chemicals can cause seizures, as well.
Psychoemotional problems can contribute to causing and exacerbating epilepsy, and as you’re about to see, epilepsy shares some common pathological pathways with mental health disorders like stress, anxiety and depression that may provide more insight into how these disorders affect work in tandem to cause seizures.
The Role of Stress, Anxiety and Depression
Epilepsy commonly co-occurs with mental health disorders such as depression and anxiety, which further decreases quality of life for the person who is struggling with seizures.
Many people with epilepsy can identify a precipitating factor that triggers or exacerbates their seizures. Sleep deprivation and fatigue are among them, but stress is, by far, the most frequent precipitator (Frucht et al, 2000). One survey of epilepsy patients found that 64 percent of patients believed stress increased the frequency of seizures and over half of those found it necessary to seek stress reduction techniques (Hauta et al, 2003).
One important factor linked to both depression and anxiety is perceived stigma (Adewuya et al, 2005; Jacoby et al, 2005). High rates of perceived stigma are also common in about half of those with epilepsy, especially in younger age groups (Baker et al, 2001a, 2001b).
Oxidative stress is a destructive process in which free radicals or reactive oxygen molecules react with the components of cells (e.g., proteins or fats and nucleic acids such as DNA), ultimately damaging those cells. Chronic stress, or an inability to cope with stress, increases the body’s level of oxidative stress (Liu, Mori, 1999). (For more about oxidative stress, see How Stress Impacts the Immune System< and How Meditation Boosts Immunity, From the Cellular Level Up)
Oxidative stress is emerging as a mechanism that may play a role in causing seizure-induced brain damage. Coincidentally, seizures are common in people with mitochondrial diseases and disorders (e.g., Alzheimer’s, autism), any disease in which involves dysfunctional mitochondria — diseases with an energy problem. Mitochondria, the part of the cell often called the “cell’s powerhouse,” generates over 90 percent of the body’s energy. So oxidative stress may be both a consequence and a cause of epileptic seizures (Patel, 2002).
The association between epilepsy and depression is especially strong; in fact, depression is the most common mental health disorder in patients with epilepsy.
By the same token, patients with depression are at higher risk of developing epilepsy than are people who don’t have depression. Some quick statistics:
- 1 in 3 people with epilepsy also have depression (Kanner, 2005).
- People with a history of depression are 3 to 7 times more likely to develop epilepsy than the average person (Kanner, 2005).
- 20 to 55 percent of people with recurrent seizures have depression; 3 to 9 percent of people with well-controlled seizures have depression (Gilliam et al, 2004).
- An estimated 30 – 50 percent of people with refractory (intractable or difficult to treat) epilepsy have Major Depression; in fact, depression actually has a stronger correlation with quality of life than seizure frequency.
For decades, depression was thought to be a “psychosocial complication” of epilepsy, but recent research shows that the connection between epilepsy and depression may be a two-way street — depression and epilepsy may share a common pathology. For example, studies of rats genetically prone to epilepsy have found abnormal secretion in the brain of neurotransmitters such as serotonin, norepinephrine, GABA and dopamine. The abnormal secretion patterns of serotonin and norepinephrine were similar to abnormal patterns for these neurotransmitters in patients with depression (Kanner, 2005).
Depression and epilepsy share other common pathological pathways. Several studies have found frontal lobe disturbances in patients who have both temporal lobe epilepsy and depression (Bromfield et al, 1990; Horner et al, 1996; Hempel et al, 1996; Jokeit et al, 1997). Others have documented actual structural cortical changes in the frontal lobes of depressed patients, including decreases in cortical thickness, neuron size and density (Rajkowska, 1999). And atrophy of the hippocampus, which is among the most frequently identified abnormalities in people with epilepsy, is also common in people with depression. Neuroimaging studies of patients with both epilepsy and depression have found a correlation between the severity of depression and epilepsy and severity of brain structural abnormalities (Gilliam et al, 2000; Quiske et al, 2000; Schmitz et al, 1997).
Such common pathways between depression and epilepsy might also account for recent data suggesting that patients with a history of depression may not respond as well to medication or surgery for treatment of their seizures. One study of 90 patients who didn’t respond to anti-epileptic medication and underwent brain surgery to remove seizure-focus tissue found that those with a lifetime history of depression were less likely to become seizure-free. They also found that depression could be a biological marker for a more severe form of epilepsy (Kanner, 2005).
Anxiety can occur before, during or after seizures for people with epilepsy, often due to concerns such as fear of accidents, losing control, or social embarrassment.
Some quick statistics:
- Patients with epilepsy have panic attacks up to 6 times more frequently than control populations (Beyenburg et al, 2007).
- Seizure frequency has been linked with severity of anxiety in some (Jacoby et al, 1996), suggesting that as the burden of epilepsy increases, so does the anxiety.
- The risk of anxiety disorders is higher in focal epilepsies (especially temporal lobe) than in generalized epilepsies.
- Onset of epilepsy late in life has been linked with higher levels of anxiety (Baker et al, 2001).
The amygdala, a temporal lobe structure in the brain’s emotional limbic system, has long been recognized for its central role in producing emotions and emotional reactions. Changes in neuronal excitability in the amygdala are characteristic features of anxiety and depression, but they also play a pivotal role in temporal lobe epilepsy. The amygdala is heavily involved in provoking anxiety symptoms, as well as epileptic discharges in temporal lobe epilepsy.
Both structural and fMRI studies have confirmed amygdala abnormalities in some people with anxiety or panic disorders (Cendes et al, 1994; Satishchandra et al, 2003; Drevets et al, 2004). More than half of patients with MRI-confirmed amygdala atrophy on the same side as the seizure focus have some form of seizure-related fear and anxiety (Paesschen, 2001). Patients with temporal lobe epilepsy and seizure-related anxiety symptoms have also both been found to have reduced amygdala volume (Cendes et al, 1994).
The central role of GABA receptors and other neurotransmitter systems (especially serotonin, dopamine, noradrenaline) in both epilepsy and anxiety disorders suggests other common pathways between the two disorders (Beyenburg et al, 2007; Lydiard et al, 2003; Charney et al, 2003). Neuronal excitability in the amygdala is regulated by GABAergic transmission, right? Well, the mechanisms that regulate GABA release in the amygdala are severely impaired by stress, which can trigger amygdala hyperexcitability in anxiety and other stress-related disorders and may help explain the stress-induced exacerbation of seizure activity in people with epilepsy (Aroniadou-Anderjaska, 2007).
Not only can meditation can help ease the psychological burden of epilepsy, evidence suggests that it may impact the physiological roots of epilepsy, as well.
- Aroniadou-Anderjaska, F. Qashu, M. F. M. Braga. Amino Acids. Mechanisms regulating GABAergic inhibitory transmission in the basolateral amygdala: implications for epilepsy and anxiety disorders. April 2007, Volume 32, Issue 3, pp 305-315.
Adewuya AO, Ola BA. Prevalence of and risk factors for anxiety and depressive disorders in Nigerian adolescents with epilepsy. Epilepsy Behav 2005;6:342–7.
Baker GA, Jacoby A, Buck D, Brooks J, Potts P, Chadwick DW. The quality of life of older people with epilepsy: findings from a UK community study. Seizure 2001;10:92–9.
Baker GA, Jacoby A, Buck D, Brooks J, Potts P, Chadwick DW. The quality of life of older people with epilepsy: findings from a UK community study. Seizure 2001;10:92–9.
Baker GA, Brooks J, Buck D, Jacoby A. The stigma of epilepsy: a European perspective. Epilepsia 2000;41:98–104.
Beyenburg S, Stoffel-Wagner B, Bauer J, et al. Neuroactive steroids and seizure susceptibility. Epilepsy Res 2001;44:141–53.  Lydiard RB. The role of GABA in anxiety disorders. J Clin Psychiatry 2003;64(Suppl. 3):21–7.
Bradford, H.F.. Glutamate, GABA and Epilepsy. Progress in Neurobiology. Vol 47, 6. December 1995. 477-511.
Bromfield E, Altshuler L, Leiderman D. Cerebral metabolism and depression in patients with complex partial seizures. Epilepsia. 1990;31:625.
CDC. Current trends prevalence of self-reported epilepsy—United States, 1986–1990. MMWR 1994;43:810–1, 817–8.
Cendes F, Andermann F, Gloor P, et al. Relationship between atrophy of the amygdala and ictal fear in temporal lobe epilepsy. Brain 1994;117:739–46.
Chapman, Astrid G.. Glutamate and Epilepsy. Journal of Nutrition April 1, 2000 vol. 130 no. 4.
Charney DS. Neuroanatomical circuits modulating fear and anxiety behaviors. Acta Psychiatr Scand 2003(Suppl. 417):38–50.
Demarque M, Villeneuve N, Manent JB, Becq H, Represa A, Ben-Ari Y, Aniksztejn L. Glutamate Transporters Prevent the Generation of Seizures in the Developing Rat Neocortex. J Neurosci 2004;24(13):3289–3294.
Drevets WC. Neuroimaging studies of mood disorders. Biol Psychiatry 2000;48:813–29.
Frucht, M., Quigg, M., Schwaner, C., Fountain, N.B.. Distribution of Seizure Precipitants Among Epilepsy Syndromes. Epilepsia, (2000) 41: 1534–1539.
Gale, K.. Department of Pharmacology, Georgetown University Medical Center, Washington, D.C.. GABA and epilepsy: basic concepts from preclinical research. Epilepsia.1992, 33 Suppl 5:S3-12.
Gilliam, F. G., Santos, J., Vahle, V., Carter, J., Brown, K. and Hecimovic, H. (2004), Depression in Epilepsy: Ignoring Clinical Expression of Neuronal Network Dysfunction?. Epilepsia, 45: 28–33.
Gilliam F, Maton B, Martin RC, et al. Extent of 1H spectroscopy abnormalities independently predicts mood status and quality of life in temporal lobe epilepsy. Epilepsia. 2000;41(suppl):54.
Sheryl R Hauta,, Mary Vouyiouklisa, Shlomo Shinnara. Stress and epilepsy: a patient perception survey. Epilepsy & Behavior. Volume 4, Issue 5, October 2003, Pages 511–514.
Horner MD, Flashman LA, Freides D, Epstein CM, Bakay RA. Temporal lobe epilepsy and performance on the Wisconsin card sorting test. J Clin Exp Neuropsychol. 1996;18:310–113.
Hempel A, Risse GL, Mercer K, Gates J. Neuropsychological evidence of frontal lobe dysfunction in patients with temporal lobe epilepsy. Epilepsia. 1996;37(suppl 5):119.
Jacoby A, Baker GA, Steen N, Potts P, Chadwick DW. The clinical course of epilepsy and its psychosocial correlates: finding from a U.K. community study. Epilepsia 1996;37:148–61.
Jacoby A, Snape D, Baker GA. Epilepsy and social identity: the stigma of a chronic neurological disorder. Lancet Neurol 2005;4:171–8.
Jansen, Anna C, Andermann, Eva. Progressive Myoclonus Epilepsy, Lafora Type. Bookshelf ID: NBK1389PMID: 20301563. Posting: December 28, 2007; Last Update: November 3, 2011.
Jokeit H, Seitz RJ, Markowitsch HJ, Neumann N, Witte OW, Ebner A. Prefrontal asymmetric interictal glucose hypometabolism and cognitive impairment in patients with temporal lobe epilepsy. Brain. 1997;12:2283–2294.
Kalynchuk LE. Long-term amygdala kindling in rats as a model for the study of interictal emotionality in temporal lobe epilepsy. Neurosci Biobehav Rev 2000;24:691–704.
Kanner A, Jobe, P.C., Ettinger, A.. In presentations given at the American Association for the Advancement of Science Annual Conference, March 9, 2005.
Kim, DH, Moon YS, Kim HS, et al. Effect of Zen meditation on serum nitric oxide activity and lipid peroxidation. Prog Neuropsychopharmacol Biol Psychiatry 2005;29(2):327–31.
Liu J, Mori A. Stress, aging, and brain oxidative damage. Neurochem Res Nov;1999 24(11):1479– 1497.
Lydiard RB. The role of GABA in anxiety disorders. J Clin Psychiatry 2003;64(Suppl. 3):21–7.
Meldrum, B. S. (1995). Excitatory Amino Acid Receptors and Their Role in Epilepsy and Cerebral Ischemia. Annals of the New York Academy of Sciences, 757: 492–505.
Ming-Yuan Min, Zare Melyan, and Dimitri M. Kullmann. Synaptically released glutamate reduces γ-aminobutyric acid (GABA)ergic inhibition in the hippocampus via kainate receptors. Proc Natl Acad Sci U S A. 1999 August 17; 96(17): 9932–9937.
John C. Mulley, Ingrid E. Scheffer, Steven Petrou, Leanne M. Dibbens, Samuel F. Berkovic, and Louise A. Harkin. SCN1A Mutations and Epilepsy. Human Mutation. 25:535-542 (2005).
National Institutes of Health (NIH). Seizures and Epilepsy: Hope Through Research. Last retrieved March 2012.
Noebels, Jeffrey L.. A Perfect Storm: Converging Paths of Epilepsy and Alzheimer’s Dementia Intersect in the Hippocampal Formation. Epilepsia. 2011 January; 52(Suppl 1): 39–46.
Patel, Manisha N.. Oxidative Stress, Mitochondrial Dysfunction, and Epilepsy. Free Radical Research. 2002, Vol. 36, No. 11 , Pages 1139-1146.
Paesschen WV, King MD, Duncan JS, Connelly A. The amygdala and temporal lobe simple partial seizures: a prospective and quantitative MRI study. Epilepsia 2001;42:857–62.
Quiske A, Helmstaedter C, Lux S, et al. Depression in patients with temporal lobe epilepsy is related to mesial temporal sclerosis. Epilepsy Res. 2000;39:121–125.
Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, Overholser JC, Roth BL, Stockmeier CA. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999;45:1085–1098.
Satishchandra P, Krishnamoorthy ES, van Elst LT, et al. Mesial temporal structures and comorbid anxiety in refractory partial epilepsy. J Neuropsychiatry Clin Neurosci 2003;15:450–2.
Scharfman, Helen E.. 30th Annual Postgradute Review Course, Columbia University, December 2007 March 2008.
Schmitz EB, Moriarty J, Costa JC, Ring HA, Ell PJ, Trimble MR. Psychiatric profiles and patterns of cerebral blood flow in focal epilepsy: interactions between depression, obsessionality, and perfusion related to the laterality of the epilepsy. J Neurol Neurosurg Psychiatry. 1997;62:458–463.
Treiman, D.M.. GABAergic Mechanisms in epilepsy. Epilepsia. 2001; 42 Suppl 3:8-12.