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Do seizures in POLG1-related mitochondrial disorder become refractory due to mitochondrion-toxic anti-seizure drugs?

      With interest we read the article by Menon et al. about a 28 years old female, with a non-syndromic mitochondrial disorder (MID) due to the compound heterozygous variants c.2070+2T>C and c.2243G>C in POLG1, which manifested phenotypically with mild intellectual disability and epilepsy since age 10 years [
      • Menon D.
      • Marasakatla S.
      • Holla V.V.
      • Kamble N.
      • Netravathi N.
      • Pal P.K.
      Fever related super-refractory status epilepticus: an adulthood presentation of a novel POLG variant: a case report.
      ]. She was admitted for fever and serial focal tonic-clonic seizures, which did not respond to phenytoin (PHT), carbamazepine (CBZ), and clobazam (CLB), why levetirazetam (LEV), lacosamide (LCM), and topirmate (TPM) were given, but also without benefit [
      • Menon D.
      • Marasakatla S.
      • Holla V.V.
      • Kamble N.
      • Netravathi N.
      • Pal P.K.
      Fever related super-refractory status epilepticus: an adulthood presentation of a novel POLG variant: a case report.
      ]. After a short-term benefit from plasma exchange and glucocorticoids, the patient developed epilepsia partialis continua [
      • Menon D.
      • Marasakatla S.
      • Holla V.V.
      • Kamble N.
      • Netravathi N.
      • Pal P.K.
      Fever related super-refractory status epilepticus: an adulthood presentation of a novel POLG variant: a case report.
      ]. After two weeks non-convulsive status epilepticus (NCSE) was diagnosed and mechanical ventilation started [
      • Menon D.
      • Marasakatla S.
      • Holla V.V.
      • Kamble N.
      • Netravathi N.
      • Pal P.K.
      Fever related super-refractory status epilepticus: an adulthood presentation of a novel POLG variant: a case report.
      ]. Although she became seizure-free under midazolam, propofol, and ketamine, she deceased from sepsis [
      • Menon D.
      • Marasakatla S.
      • Holla V.V.
      • Kamble N.
      • Netravathi N.
      • Pal P.K.
      Fever related super-refractory status epilepticus: an adulthood presentation of a novel POLG variant: a case report.
      ]. The report is appealing but raises several comments and concerns.

      Keywords

      Abbreviations:

      CBZ (carbamazepine), CLB (clobazam), LCM (lacosamide), LEV (levetirazetam), MID (mitochondrial disorder), NCSE (non-convulsive status epilepticus), PB (phenobarbital), PHT (phenytoin), TPM (topiramate)
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      Linked Article

      • Fever related super-refractory status epilepticus: An adulthood presentation of a novel POLG variant: A case report
        Seizure - European Journal of EpilepsyVol. 99
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          Mitochondrial DNA depletion syndromes caused by POLG mutations clinically constitute a heterogeneous group and can involve any part of the neuraxis [1]. Non-syndromic presentations that do not conform with the recognised classical POLG mutation syndromes are infrequently encountered, and given their protean manifestations, require a high index of suspicion to delineate from other more common aetiologies. Here we expand the FIRES (febrile infection-related status epilepticus)- like presentation of a novel POLG mutation in a twenty-eight-year-old lady, who had a complex medical history that included intellectual disability, behavioural changes, and initially well-controlled seizures.
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      • POLG mutation setting off ‘FIRES’
        Seizure - European Journal of Epilepsy
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          We appreciate the interest shown by Joseph Finsterer, MD, PhD to our case report ‘Fever related super-refractory status epilepticus: An adulthood presentation of a novel POLG variant: A case report.’ [1]. We read with interest some of the insightful observations and comments and have the following response.
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