Abstract Background and purpose Primary mitochondrial diseases (PMDs) are common inborn
errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders
typically affect tissues with high energy requirements, including heart, muscle and
brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and
often represents a poor prognostic feature. The aim of this study was to develop guidelines
and consensus recommendations on safe medication use and seizure management in mitochondrial
epilepsy. Methods A panel of 24 experts in mitochondrial medicine, pharmacology and
epilepsy management of adults and/or children and two patient representatives from
seven countries was established. Experts were members of five different European Reference
Networks, known as the Mito InterERN Working Group. A Delphi technique was used to
allow the panellists to consider draft recommendations on safe medication use and
seizure management in mitochondrial epilepsy, using two rounds with predetermined
levels of agreement. Results A high level of consensus was reached regarding the safety
of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute
for Health and Care Excellence guidelines for seizure management, with some modifications.
Exceptions including valproic acid in POLG disease, vigabatrin in patients with ?-aminobutyric
acid transaminase deficiency and topiramate in patients at risk for renal tubular
acidosis were highlighted. Conclusions These consensus recommendations describe our
intent to improve seizure control and reduce the risk of drug-related adverse events
in individuals living with PMD-related epilepsy.
