I recently attended a meeting regarding vagus nerve stimulation (VNS) for use in patients with drug-resistant epilepsy. As we know, seizures are caused by over excitation or excessive depolarization of neurons in the brain. Patients with seizures are treated with antiepileptic drugs, but the chance of becoming seizure-free decreases dramatically with each antiepileptic failed eventually resulting in drug-resistant epilepsy (Kwan & Brodie, 2000).
The vagus nerve (cranial nerve X) is involved in parasympathetic control of the heart, lungs, and digestive tract. Incidentally an increased heart rate is associated with epileptic seizures (Fisher, etal., 2015). This is where VNS comes in. A wire is coiled around the vagus nerve and attached to a device. The device detects changes in heart rate and then sends a signal through the wire to the vagus nerve, stimulating a cascade of events that interrupts the seizure. This treatment is highly effective in restoring the quality of life back to patients with epilepsy. Although it may not guarantee seizure freedom in severe cases, it can decrease the severity and length of seizure activity. It has also been shown to lower the risk of sudden death in epilepsy patients over time (Ryvlin, et al., 2018). But is this the only way to handle drug-resistant epilepsy?
More information is coming to light about the importance of the gut microbiome and its involvement in numerous physiological processes and conditions such as obesity and depression. Could it be that it also influences epilepsy? The vagus nerve is a component in the microbiome-gut-brain axis and is often activated by gut microorganisms. We know that activation of the vagus nerve during a period of over excitation creates downstream effects within the brain which stops epileptic seizures. We also know that whether a neurotransmitter is excitatory or inhibitory is fully dependent on the receptor. Recently, dysbiosis in the gut microbiome has been seen to influence epilepsy and restored homeostasis has been seen to improve epilepsy. Could the signals sent by the gut microbiota be contributing to the over excitation of neurons resulting in seizures? A patient with Crohn’s disease and epilepsy was treated with a donor fecal matter transplant (FMT) for Crohn’s, but became seizure-free (He, et al., 2017).
Vagal nerve stimulation provides a huge benefit to patients suffering from drug resistant epilepsy, but it may just be the start. It seems that gut microbiota are becoming more important than we initially thought and could be the answer to many conditions, including epilepsy.
References:
Fisher, R. S., Afra, P., Macken, M., Minecan, D. N., Bagić, A., Benbadis, S. R., … Najimipour, B. (2015). Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance-The U.S. E-37 Trial. Neuromodulation: Technology at the Neural Interface, 19(2), 188–195. doi: 10.1111/ner.12376
He, Z., Cui, B.-T., Zhang, T., Li, P., Long, C.-Y., Ji, G.-Z., & Zhang, F.-M. (2017). Fecal microbiota transplantation cured epilepsy in a case with Crohn’s disease: The first report. World Journal of Gastroenterology, 23(19), 3565. doi: 10.3748/wjg.v23.i19.3565
Kwan, P., & Brodie, M. J. (2000). Early Identification of Refractory Epilepsy. New England Journal of Medicine, 342(5), 314–319. doi: 10.1056/nejm200002033420503
Ryvlin, P., So, E. L., Gordon, C. M., Hesdorffer, D. C., Sperling, M. R., Devinsky, O., … Friedman, D. (2018). Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with VNS therapy. Epilepsia, 59(3), 562–572. doi: 10.1111/epi.14002
Sara,
ReplyDeleteI found your post to be very interesting. As a person who lives with daily seizures your post immediately jumped out at me. I find it very interesting that doctors are looking at a link between the gut microbiome and epilepsy. In many cases of juvenile epilepsy parents are asked to put their children on a ketogenic diet to see whether that will help with seizure reduction (Emory University, 2005). One study I researched found that “After 6 months of treatment, 2 patients were seizure free, 3 had ≥ 90% seizure reduction, 5 had a reduction of 50–89%, and 10 had < 50% reduction. All 10 responders showed an improvement in EEG. Compared with baseline, fecal microbial profiles showed lower alpha diversity after KD therapy and revealed significantly decreased abundance of Firmicutes and increased levels of Bacteroidetes. We also observed that Clostridiales, Ruminococcaceae, Rikenellaceae, Lachnospiraceae, and Alistipes were enriched in the non-responsive group” (Zhang, et al, 2018). While I have heard that the keto diet was very beneficial for some before reading this, I did not know why. Scientists have now shown the reason a keto diet may work for some is actually the alteration some genes involved in energy metabolism in the brain (Emory University, 2005)
While this seems to be a very promising line of research on the control of epilepsy I do not believe the gut microbiome is the cause of epilepsy, perhaps more of a perpetuating factor. Many forms of epilepsy are genetic or arise from a blow to the head. We do not officially know the “cause” of epilepsy. Following a ketogenic diet may prove to control some forms of epilepsy, but unfortunately that is more likely the case in juvenile genetic epilepsy versus those with epilepsy following brain damage. It is exciting we may be able to alter the genes in the brain with a simple diet but there still needs to be much more research into what is causing epilepsy before we can develop any sort of cure.
Emory University Health Sciences Center. "Ketogenic Diet Prevents Seizures By Enhancing Brain Energy Production, Increasing Neuron Stability." ScienceDaily. ScienceDaily, 15 November 2005. .
Zhang, Y., Zhou, S., Zhou, Y., Yu, L., Zhang, L., & Wang, Y. (2018). Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy research, 145, 163-168.