Epilepsy as an autoimmune disorder

Epilepsy should be evaluated in case management for neuroinflammation that reduces neuronal thresholds of excitability, and more evidence that this can be due to autoimmunity was just published in JAMA Neurology. The authors note that...

"Epilepsy is a debilitating condition, often with neither a known etiology nor an effective treatment. Autoimmune mechanisms have been increasingly identified."

They conducted a study investigating the relationship between epilepsy and common autoimmune diseases by examining data for 2,518,034 subjects showing the relationship between epilepsy and these twelve common autoimmune diseases: type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn's disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome, myasthenia gravis, and celiac disease. Considering the brain destabilizing effects of neuroinflammation present in many autoimmune conditions it's not surprising that their data showed a strong association:

"The risk of epilepsy was significantly heightened among patients with autoimmune diseases (odds ratio, 3.8) and was especially pronounced in children (5.2). Elevated risk was consistently observed across all 12 autoimmune diseases."

That's a 380% increase in risk in general and a 520% increase in children. Medscape Medical News quotes lead investigator Kenneth Mandl, MD, MPH, from Intelligent Health Laboratory, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts:

"We need to expand our thinking when it comes to clinical management of these conditions."

The authors conclude:

"Epilepsy and autoimmune disease frequently co-occur; patients with either condition should undergo surveillance for the other. The potential role of autoimmunity must be given due consideration in epilepsy so that we are not overlooking a treatable cause." 

Considering that low progesterone can contribute to loss of immune intolerance, a paper just published in Clinical Neurophysiology discussing the anticonvulsant effects of progesterone and its metabolites is worth noting:

"Progesterone is an anticonvulsant neurosteroid. It is reduced by the unidirectional enzyme 5α-reductase to 5α-dihydroprogesterone (DHP) and subsequently reduced by the bidirectional enzyme 3α,5α- hydroxysteroidoxidoreductase to 3α,5α-tetrahydroprogesterone (THP, also called “allopregnanolone”). Progesterone, DHP and THP have protective effects in models of traumatic brain injury, and slows epileptogenesis in kindling models. It is possible that these pregnanes could be anticonvulsant. Since anticonvulsant drugs cannot prevent epileptogenesis, endogenous hormones or their analogues remain attractive potential therapies to improve prognoses after a first seizure...We hypothesize that progesterone, DHP, and THP may alter epileptogenic processes by reducing tonic hyper-excitability." 

Also just published in Clinical Neurophysiology is a study showing that the omega-3 fatty acid DHA (docosahexanoic acid), already known to be critical for brain development and function and a modulator of chronic low grade inflammation, has anticonvulsant properties.

"Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n−3 PUFA), which has previously shown to have anticonvulsant activity rats. The purpose of the present experiment was: (1) to confirm that sub-chronic DHA raises thresholds in the maximal pentylenetetrazole (PTZ) model, and (2) to determine whether that increase is correlated with an increase in serum and brain DHA."

Maximal pentylenetetrazole (PTZ) is a rat model of seizure activity. Interestingly, their results showed that increases of serum DHA reduced seizures (increased seizure latency) without increasing brain DHA, system a global chronic inflammation modulating effect:

"In the maximal PTZ model, DHA significantly increased seizure latency by approximately 3 fold, as compared to vehicle-injected controls. This increase in seizure latency was associated with an increase in serum unesterified DHA levels. Total brain DHA and brain unesterified DHA, however, were not significantly different between treatment and control groups."