Accepted Manuscript

Is ketogenic diet truly effective in mitochondrial epilepsy?

Josef Finsterer , MD, PhD Sonam Kothari , MBBS

PII: S0887-8994(14)00283-5

DOI: 10.1016/j.pediatrneurol.2014.05.007

Reference: PNU 8361

To appear in: Pediatric Neurology

Received Date: 25 April 2014

Revised Date: 4 May 2014

Accepted Date: 8 May 2014

Please cite this article as: Finsterer J, Kothari S, Is ketogenic diet truly effective in mitochondrialepilepsy?, Pediatric Neurology (2014), doi: 10.1016/j.pediatrneurol.2014.05.007.

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Is ketogenic diet truly effective in mitochondrial epilepsy? Josef Finsterer, MD, PhD [1], Sonam Kothari, MBBS [2] [1] Krankenanstalt Rudolfstiftung, Vienna, Austria [2] NIMHANS, Bangalore, India Number of words (abstract): none Number of words (including references): 501 Number of references: 5 Number of tables: 0 Number of figures: 0 Key words: mitochondrial, respiratory chain, epilepsy, seizure, ketogenic diet, heteroplasmy Corresponding author: Josef Finsterer, MD, PhD Postfach 20 1180 Vienna Austria, Europe Tel. +43-1-71165-92085 Fax. +43-1-4781711 E-mail: fifigs1@yahoo.de

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Letter to the Editor With interest we read the article by Stereade et al.[1] about the effect of ketogenic diet (KD) in one MELAS-patient. We have the following comments and concerns. There are reports showing a beneficial effect of KD in treating epilepsy in 75% of mitochondrial disorders.[2] In reverse, other studies have shown that seizures may recur after 3 months on the average in 82% of children under KD.[3] For how long was the patient followed up? Did seizure frequency increase after discontinuation of KD? The patient was under KD for >1y.[1] How strictly did she follow the KD regimen? Did the patient ever stop KD or forgot it? In case she discontinued KD, did clinical manifestations deteriorate again? Was she tested for compliance by any metabolic parameter? How can the authors be sure that improvement of epilepsy resulted from KD alone and not from modification of the antiepileptic drugs (AEDs)? To which degree was the beneficial effect of KD dependent on the choice of the AED? Previous reports have shown a beneficial effect of KD also on the frequency and intensity of migraine attacks.[4] Did migraine improve under KD in the proband? KD has been shown to reduce heteroplasmy rates in cell cultures.[5] Was heteroplasmy rate determined a second time and did it actually decrease after KD? The patient was put on a cocktail of CoQ, L-carnitine, folic acid, vitamin-D, and vitamin-B.[1] Did these agents enhance or diminish the effect of KD or were they ineffective? Since MELAS is associated with myopathy, it is essential for sustaining mobility that affected patients do not become obese. Did KD in the presented patient have an effect on the body weight? Was she told to limit KD by a certain maximum of calories? The proband’s affected sister presented with highly elevated lactate levels.[1] Did she receive any specific lactate-lowering treatment as that has not been mentioned and she was discharged with almost normal serum lactate? Was she also put on a KD? Did KD also reduce serum lactate? Overall, a number of concerns and questions remain after reading this interesting article. Results of one trial need to be interpreted with caution. Further clarification of the KD effect and its implementation in the treatment of MELAS could be achieved from cohort studies and continuing KD for longer.

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References 1 Steriade C, Andrade DM, Faghfoury H, Tarnopolsky MA, Tai P. Mitochondrial Encephalopathy With Lactic Acidosis and Stroke-like Episodes (MELAS) May Respond to Adjunctive Ketogenic Diet. Pediatr Neurol 2014;50:498-502. 2 Lee YM, Kang HC, Lee JS, Kim SH, Kim EY, Lee SK, Slama A, Kim HD. Mitochondrial respiratory chain defects: underlying etiology in various epileptic conditions. Epilepsia 2008;49:685-90. 3 Taub KS, Kessler SK, Bergqvist AG. Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet. Epilepsia 2014 Mar 27. doi: 10.1111/epi.12583. 4 Strahlman RS. Can ketosis help migraine sufferers? A case report. Headache 2006:46:182. 5 Santra S, Gilkerson RW, Davidson M, Schon EA. Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells. Ann Neurol 2004;56:662-9.