Table 2.
Summary of published studies of adjunctive KDT for refractory and super-refractory status epilepticus in children (age < 18 years)
| First author (year) |
Subjects, n |
Etiology | KDT | Time to diet start (days) |
Time to ketosis (days) |
Time to SE response (days) |
Response% | AE |
|---|---|---|---|---|---|---|---|---|
| François (2003)59 | 6 | Refractory SE | KD | 8–75 | Mean 2 | Mean 2 or NA | 50 | NR |
| Mikaeloff (2006)60 | 2 | Epileptic encephalopathy | KD | 53 or NR | NR | 2 or NA | 50 | NR |
| Chevret (2008)61 | 1 | Febrile refractory SE | KD | NR | NR | NA | 0 | NR |
| Schrader (2009)62 | 2 | 1 FCD, 1 Rasmussen’s syndrome and FCD | KD | NR | NR | NA | 0 | NR |
| Villeneuve (2009)63 | 4 | SWS, 1 encephalitis, cryptogenic | KD | 2–14 | NR | 1–10 | 75 | NR |
| Kumada (2010)64 | 2 | 1 heterotopia, 1 frontal lobe epilepsy | MAD | NR | 2–3 | 10–21 | 100 | NR |
| Nabbout (2010)65 | 9 | 9 FIRES | KD | 4–55 | 2–4 (mean 2.8) or NA | 4–6 (mean 4.8) or NA | 78 | NR |
| Ismail (2011)66 | 1 | FIRES | KD | 90 | NR | 10 | 100 | NR |
| Nam (2011)67 | 4 | 4 FIRES | KD | 30–420 (mean 30) | NR | 3–18 (median 8) | 50, 50a | 4 constipation, 2 GER, 1 ↑TG |
| Vaccarezza (2012)68 | 5 | 3 FIRES, 2 DRE | KD | Mean 32 | NR | NR | 80 | NR |
| Sort (2013)69 | 3 | 1 FIRES, 1 mitochondrial, 1 HHES | KD | 6–83 | 1–12 | 1–13 or NA | 66 | 1 ↑TG |
| Caraballo (2013)70 | 2 | 2 FIRES | KD | NR | NR | NR | 0, 50a | NR |
| Gedik (2014)71 | 1 | Meningoencephalitis | KD | 27 | NR | NA | 0 | NR |
| Barros (2014)72 | 1 | NMDA | KD | NR | NR | NA | 0 | NR |
| O’Connor (2014)73 | 5 | 1 POLG, 1 mitochondrial, 3 unknown | KD | 4–22 | 2–8 | 2–8 (mean 5) | 100 | 0 |
| Caraballo (2014)74 | 10 | 1 NMDA, 2 FCD, 1 hemimegalencephaly, 6 unknown | KD | NR | 2–4 (mean 3) | 5–7 (mean 5) or NA | 20, 50a | 2 pancreatitis, 1 vomiting and hypoglycemia |
| Cobo (2015)75 | 4 | 1 TSC, 3 cryptogenic epilepsy | KD | 19–67 | <10 | 2–8 or NA | 0, 75b | 1 nephrolithiasis, 1 constipation and GER, 1 hypoglycemia |
| Fung (2015)76 | 4 | 1 NORSE, 1 VGKC encephalitis, 1 FIRES, 1 limbic encephalitis | KD | 12–21 (median 17.5) | 4–5 | 5 or NA | 25 | 1 vomiting |
| Incecik (2015)77 | 1 | DRE | KD | NR | NR | NA | 0 | NR |
| Lin (2015)78 | 1 | Focal epilepsy | KD (IV → EN) | 2 | 1 | 6 | 100 | Weight loss, diarrhea |
| Caraballo (2015)79 | 2 | Refractory myoclonic SE | KD | 21–30 | 1 | 7 | 0, 100a | 0 |
| Chiusolo (2016)80 | 1 | DRE | KD (IV → EN) | NR | 2 | NA | 0 | |
| Appavu (2016)81 | 10 | 2 NMDA, 2 FIRES, 1 NORSE, 1 LGS, 1 Rasmussen, 1 mycoplasma, 1 DRE, 1 NKH | KD (9 EN, 1 TPN → EN) | 1–45 (median 18) | 0–13 (median 6) or NA | 1–19 (median 7) or NA | 90 | 1 acidosis, hypophosphatemia, and hypokalemia |
| Farias-Moeller (2017)82 | 9 | 7 FIRES, 1 epileptic encephalopathy, 1 HLH | KD (7 EN, 1 IV, 1 IV → EN) | 7–41 (median 13) | 2–13 (mean 4) | 7 or NA | 55, 11a | 2 ↑TG, 1 pancreatitis, hypoglycemia |
| Arya (2018)83 | 14 | 10 unknown, 1 TSC, 1 MCD, 1 FIRES | KD | 3–39 (median 13) | 0–10 (median 2) | 7 or NA | 71 | 2 ↑TG, 1 GI paresis |
| Peng (2019)84 | 7 | 7 FIRES | KD (2 IV → EN, 5 EN) | 7–31 | 1–11 | 0–10 | 100 | 4 HLD, 3 diarrhea |
| Park (2019)85 | 10c | 4 FIRES, 2 HIE, 2 Viral encephalitis, 1 hemimegalencephaly, 1 cryptogenic epilepsy | KD | 3–237 | 2–6 (median 3) | 7 | 60, 30a | 4 GER, 1 nephrolithiasis, 1 acidosis, 1 ↑TG, 1 ↑ liver enzymes |
Abbreviations: AE, adverse events deemed related to KDT use; DRE, drug-resistant epilepsy; EN, enteral; FCD, focal cortical dysplasia; FIRES, febrile infection related epilepsy syndrome; GER, gastroesophageal reflex; GI, gastrointestinal; HHES, hemiconvulsion-hemiplegia epilepsy syndrome; HIE, hypoxic ischemic encephalopathy; HLD, hyperlipidemia; HLH, hemophagocytic lymphohistiocytosis; IV, intravenous; KD, classic or modified ketogenic diet; KDT, ketogenic diet therapy; LGS, Lennox–Gastaut syndrome; MAD, modified Atkins diet; MCD, malformation of cortical development; NA, not achieved; NKH, nonketotic hyperglycinemia; NMDA, N-methyl D-aspartate receptor encephalitis; NORSE, new-onset refractory status epilepticus of unknown etiology; NR, not reported; POLG, mitochondrial polymerase γ related epilepsy; response %, proportion of patients who had resolution of SE; SE, status epilepticus; SWS, Sturge–Weber syndrome; TG, triglycerides; TPN, total parenteral nutrition; TSC, tuberous sclerosis complex; VGKC, voltage-gated potassium channel.
Proportion of patients with ≥50% reduction in seizures.
Proportion of patients successfully weaned off continuous infusions of anesthetic medications without recurrence of SE.
Excludes 4 patients previously reported in Nam et al (2011).67