Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus.
OBJECTIVE
To investigate the feasibility, safety, and efficacy of a ketogenic diet (KD) for superrefractory status epilepticus (SRSE) in adults.


METHODS
We performed a prospective multicenter study of patients 18 to 80 years of age with SRSE treated with a KD treatment algorithm. The primary outcome measure was significant urine and serum ketone body production as a biomarker of feasibility. Secondary measures included resolution of SRSE, disposition at discharge, KD-related side effects, and long-term outcomes.


RESULTS
Twenty-four adults were screened for participation at 5 medical centers, and 15 were enrolled and treated with a classic KD via gastrostomy tube for SRSE. Median age was 47 years (interquartile range [IQR] 30 years), and 5 (33%) were male. Median number of antiseizure drugs used before KD was 8 (IQR 7), and median duration of SRSE before KD initiation was 10 days (IQR 7 days). KD treatment delays resulted from intravenous propofol use, ileus, and initial care received at a nonparticipating center. All patients achieved ketosis in a median of 2 days (IQR 1 day) on KD. Fourteen patients completed KD treatment, and SRSE resolved in 11 (79%; 73% of all patients enrolled). Side effects included metabolic acidosis, hyperlipidemia, constipation, hypoglycemia, hyponatremia, and weight loss. Five patients (33%) ultimately died.


CONCLUSIONS
KD is feasible in adults with SRSE and may be safe and effective. Comparative safety and efficacy must be established with randomized placebo-controlled trials.


METHODS
This study provides Class IV evidence that in adults with SRSE, a KD is effective in inducing ketosis.
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD. mcerven1@jhmi.edu.
Mackenzie C
MC
Cervenka
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Sara
S
Hocker
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Matthew
M
Koenig
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Barak
B
Bar
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Bobbie
B
Henry-Barron
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Eric H
EH
Kossoff
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Adam L
AL
Hartman
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
John C
JC
Probasco
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
David R
DR
Benavides
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Arun
A
Venkatesan
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Eliza C
EC
Hagen
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Denise
D
Dittrich
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Tracy
T
Stern
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Batya
B
Radzik
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Marie
M
Depew
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Filissa M
FM
Caserta
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Paul
P
Nyquist
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Peter W
PW
Kaplan
From the Departments of Neurology (M.C.C., E.H.K., A.L.H., J.C.P., D.R.B., A.V., B.R., M.D., F.M.C., P.N.), Pediatrics (E.H.K., A.L.H.), and Anesthesiology-Critical Care Medicine (R.G.G.), Neurosurgery and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Neuroscience Institute (M.K., E.C.H., D.D., T.S.), Queen's Medical Center, Honolulu, HI; Department of Neurology (B.B.), Loyola University Health System, Maywood, IL; Institute for Clinical and Translational Research (B.H.-B.), Johns Hopkins University, Baltimore, MD; and Department of Neurology (P.W.K.), Johns Hopkins Bayview Medical Center, Baltimore, MD.
Romergryko G
RG
Geocadin
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055423:Diet, Ketogenic / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D013226:Status Epilepticus / Q000178:diet therapy*; D016896:Treatment Outcome; D055815:Young Adult