keto + epilepsy


Epilepsy is a chronic neurological disorder that is associated with a confusion in the usual electrical bustle within the brain. The main indicator of this disorder results in repeated seizures, which can range from summary lapses to severe and prolonged convulsions.

Epilepsy will vary in severity and impact from person to person. There are over 40 different types of seizures that people can experience. The description is based on which part of the brain is affected: - Partial (or focal) seizures: affects a small fragment of the brain - Generalized seizures: affect both sides of the brain

Epilepsy is classed as one of the common neurological disorders as it affects 50 million people worldwide, occurring at any age.

What Causes Epilepsy?

There exist several causes of epilepsy including genetic, environmental, and physiological factors (1). All of which modify neuronal capacity or broker functional changes within the brain. The most common ideal of epilepsy, which affects 6 out of 10 people, is known as idiopathic epilepsy (2). The exact means for this type of epilepsy remains unknown, with genetic factors appearing to be key (3). The bearing of a family history is known to enhance an individual’s risk for maturing epilepsy (4).

For all other types of epilepsy that exists, genetics is believed to be secondary to an environmental or physiological factor (1). The term epileptogenesis is what is given to describe the offshoot of the estate of epilepsy (5).

Such causes include:

  • Brain damage (6)

  • Severe head injury (7)

  • Stroke (8)

  • An disease in the skull i.e. meningitis (9)

  • Brain tumors (10)

  • Certain genetic syndromes (1, 2)

Is There a Cure for Epilepsy?

At present, there is currently no known cure for epilepsy. However, there does exist some very effective medication known as Anti-Epileptic Drugs (AEDs). It is estimated that around 70% of individuals with epilepsy can control seizures with these drugs (11)

. There does exist a group of the population with epilepsy that do not respond well to AEDs and are believed to have drug resistant epilepsy. Otherwise known as intractable or refractory epilepsy. In the case of these individuals, other forms of treatment are sought (12).

The History of the Ketogenic Diet (KD) for Use in Epilepsy

The use of the ketogenic diet to treat epilepsy dates as far back as Hippocrates time (13). The primary way to induce ketosis at that time was using fasting or starvation. Since then, modern reports put the utility of the KD in processing primes epilepsy starting in the 1920s (14). It was within this time that it was found that the level of ketosis could be induced with carbohydrate restriction and higher levels of fat narrowing.

How Can the Ketogenic Diet Help Patients with Epilepsy?

Although the KD is an established treatment alternative in epilepsy centers around the world, the mechanisms underlying its clinical efficacy remain unknown.

Over the past two decades, the understanding into the mechanism has begun to grow.

Proposed mechanisms for the anticonvulsant possessions of the ketogenic diet are believed to be due to:

  • Ketone bodies

  • Limited glucose

  • A rise in fatty acids

  • Enhanced bioenergetic reserves (15)

It is believed that the ketone mass produced with the ketogenic diet provide the anticonvulsant possessions (16) as well as reducing neuronal excitability in the mind. However, the exact link between ketone consistency and the anticonvulsant efficacy of the ketogenic diet is not fully understood.

Another theory is that KD increases anticonvulsant action because of to its effect on certain neurotransmitters (17). Namely it is idea that the ketone wealth alters the brain handling of the main excitatory and inhibitory neurotransmitters, GABA and glutamate.

Are Higher Ketone Levels Better for Seizure Control?

The level of ketones doesn’t always appear to correlate with seizure control (18). For example, group substantiating just a mild ketosis level (0.5-1mmol/L) could have just as good seizure control as those with a higher ketone level (4-6mmol/L).

Although the optimal ketone body level has not been classified, it is known that infusion of glucose does cause the return of seizures as quickly as one hour (19). It appears that as well as the state of ketosis and the neuroprotective role that ketone bodies generally display, the lower glucose levels, as well as other circulating fatty acids i.e. PUFAs also contribute to the anti-seizure effect (20).

The Effect of the Ketogenic Diet in Children:

The use of the ketogenic diet has most extensively been used in children for those with refractory epilepsy. There now exist several studies, which confirm a response rate of approximately 50% in children with refractory epilepsy (21). In 2008, the first randomised controlled trial was undertaken to look at the specific efficacy of the ketogenic diet in children compared to a control (21).

The study collected data from 54 children on the KD and 49 on the control group. The results showed that after 3 months, 38% of children in the ketogenic group had greater than 50% seizure reduction compared to just 6% in the control group (21).

The same research group went on to conduct another similar study which this time reported data at 3, 6 and 12-month time points. At 12 months, they reported similar improvements in seizure control confirming that the KD for use in refractory epilepsy in children is an acceptable treatment of choice (22).

In 2009, the first blinded, crossover design study was carried out in children. This type of design meant that both the physicians and the parents of the children didn’t know what group they belonged to i.e. the ketogenic or the control group (23).

Both groups consumed the ketogenic diet but one group was given a solution of saccharin (a sweetener not known to stop ketosis) or a solution of glucose (known to inhibit ketosis). A trend towards improved seizures in the saccharin group was reported.

The International Ketogenic Diet Study Group, which consists of 26 neurologists and dietitians, has deemed the KD an effective nonpharmacologic treatment for intractable epilepsy (24).

The Effect of the Ketogenic Diet in Adults:

Unlike in children, the use of the KD in adults has been a lot more limited. The main reason is there is a perceived lack of tolerability and compliance in adults. As such, there remains very few well designed or randomised controlled trials within adults following a ketogenic diet.

A meta-analysis study carried out in 2014, looked to summarise the main studies that have been conducted in adults (25). A total of 12 studies were identified which included data on 270 patients. Three different types of the ketogenic diet were looked at (the classical, other forms of ketogenic and the Modified Atkins).

It was reported that better compliance came with that of the Modified Atkins Approach (56% vs 45%). However, better seizure control was noted with the classical ketogenic approach in comparison to the Modified Atkins approach (42% vs 34%) (25).

It has been found that for those adults (with drug resistant epilepsy) who comply with the diet, around 30% report 50% or more reduction in seizures (25).

Take-Home Message:

Again, as noted from the International Ketogenic Diet Study group, there is a recommendation to strongly consider the use of the ketogenic diet in patients of any age who have failed up to three medications (24).

It can be stated that the use of the ketogenic diet is a proven therapy option for the use in children given the strong clinical data (22).

Although the data is limited in adults, for those with drug resistant epilepsy, this could be a very good treatment of choice. The major barrier is to establish a ketogenic approach that will result in good compliance.

Whilst we can see that the diet does appear to offer significant anticonvulsant for those with refractory epilepsy, more work is needed to truly understand the exact mechanism of action that is at play. Having this then means that more and better therapeutic modalities could be developed in the future.

REFERENCES

(1) Epilepsy - Symptoms and causes. (n.d.). Retrieved September 7, 2018, from http://www.mayoclinic.org/diseases-conditions/epilepsy/symptoms-causes/syc-20350093.

(2) Idiopathic generalized epilepsies. (n.d.). Retrieved September 7, 2018, from https://www.epilepsy.com/learn/professionals/about-epilepsy-seizures/idiopathic-generalized-epilepsies.

(3) Steinlein, O. K. (2008). Genetics and epilepsy. Dialogues in Clinical Neuroscience, 10(1), 29–38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181863/.

(4) Poduri, A., & Lowenstein, D. (2011). Epilepsy genetics—past, present, and future. Current Opinion in Genetics & Development, 21(3), 325–332. https://doi.org/10.1016/j.gde.2011.01.005

(5) Goldberg, E. M., & Coulter, D. A. (2013). Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction. Nature Reviews. Neuroscience, 14(5), 337–349. https://doi.org/10.1038/nrn3482.

(6) Engel, J. (2018). Epileptogenesis, traumatic brain injury, and biomarkers. Neurobiology of Disease. https://doi.org/10.1016/j.nbd.2018.04.002

(7) Englander, J., Cifu, D. X., & Diaz-Arrastia, R. (2014). Seizures after traumatic brain injury. Archives of Physical Medicine and Rehabilitation, 95(6), 1223–1224. https://doi.org/10.1016/j.apmr.2013.06.002.

(8) Reddy, D. S., Bhimani, A., Kuruba, R., Park, M. J., & Sohrabji, F. (2017). Prospects of modeling poststroke epileptogenesis. Journal of Neuroscience Research, 95(4), 1000–1016. https://doi.org/10.1002/jnr.23836

(9) Vezzani, A., Fujinami, R. S., White, H. S., Preux, P.-M., Blümcke, I., Sander, J. W., & Löscher, W. (2016). Infections, inflammation and epilepsy. Acta Neuropathologica, 131(2), 211–234. https://doi.org/10.1007/s00401-015-1481-5.

(10) ENGLOT, D. J., CHANG, E. F., & VECHT, C. J. (2016). Epilepsy and brain tumors. Handbook of Clinical Neurology, 134, 267–285. https://doi.org/10.1016/B978-0-12-802997-8.00016-5.

(11) Goldenberg, M. M. (2010). Overview of drugs used for epilepsy and seizures. Pharmacy and Therapeutics, 35(7), 392–415. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912003/.

(12) Krauss, G. L., & Sperling, M. R. (2011). Treating patients with medically resistant epilepsy. Neurology. Clinical Practice, 1(1), 14–23. https://doi.org/10.1212/CPJ.0b013e31823d07d1.

(13) Hartman, A. L., Rubenstein, J. E., & Kossoff, E. H. (2013). Intermittent fasting: A “new” historical strategy for controlling seizures? Epilepsy Research, 104(3), 275–279. https://doi.org/10.1016/j.eplepsyres.2012.10.011.

(14) Wheless, J. W. (2008). History of the ketogenic diet. Epilepsia, 49 Suppl 8, 3–5. https://doi.org/10.1111/j.1528-1167.2008.01821.x.

(15) Youngson, N. A., Morris, M. J., & Ballard, J. W. O. (2017). The mechanisms mediating the antiepileptic effects of the ketogenic diet, and potential opportunities for improvement with metabolism-altering drugs. Seizure, 52, 15–19. https://doi.org/10.1016/j.seizure.2017.09.005.

(16) Zhang, Y., Xu, J., Zhang, K., Yang, W., & Li, B. (2018). The anticonvulsant effects of ketogenic diet on epileptic seizures and potential mechanisms. Current Neuropharmacology, 16(1), 66–70. https://doi.org/10.2174/1570159X15666170517153509.

(17) de Lima, P. A., de Brito Sampaio, L. P., & Damasceno, N. R. T. (2014). Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy. Clinics, 69(10), 699–705. https://doi.org/10.6061/clinics/2014(10)09.

(18) Danial, N. N., Hartman, A. L., Stafstrom, C. E., & Thio, L. L. (2013). How does the ketogenic diet work? Four potential mechanisms. Journal of Child Neurology, 28(8), 1027–1033. https://doi.org/10.1177/0883073813487598.

(19) Schauwecker, P. E. (2012). The effects of glycemic control on seizures and seizure-induced excitotoxic cell death. BMC Neuroscience, 13, 94. https://doi.org/10.1186/1471-2202-13-94.

(20) Taha, A. Y., Burnham, W. M., & Auvin, S. (2010). Polyunsaturated fatty acids and epilepsy: polyunsaturated fatty acids and epilepsy. Epilepsia, 51(8), 1348–1358. https://doi.org/10.1111/j.1528-1167.2010.02654.x.

(21) Sharma, S., & Jain, P. (2014). The ketogenic diet and other dietary treatments for refractory epilepsy in children. Annals of Indian Academy of Neurology, 17(3), 253–258. https://doi.org/10.4103/0972-2327.138471.

(22) Barañano, K. W., & Hartman, A. L. (2008). The ketogenic diet: uses in epilepsy and other neurologic illnesses. Current Treatment Options in Neurology, 10(6), 410–419. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898565/.

(23) Freeman, J. M., Vining, E. P. G., Kossoff, E. H., Pyzik, P. L., Ye, X., & Goodman, S. N. (2009). A blinded, crossover study of the efficacy of the ketogenic diet. Epilepsia, 50(2), 322–325. https://doi.org/10.1111/j.1528-1167.2008.01740.x.

(24) Kossoff, E. H., Zupec‐Kania, B. A., Auvin, S., Ballaban‐Gil, K. R., Christina Bergqvist, A. G., Blackford, R., … Wirrell, E. C. (2018). Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open, 3(2), 175–192. https://doi.org/10.1002/epi4.12225.

(25) Klein, P., Tyrlikova, I., & Mathews, G. C. (2014). Dietary treatment in adults with refractory epilepsy: a review. Neurology, 83(21), 1978–1985. https://doi.org/10.1212/WNL.0000000000001004.


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