LETTERS TO THE EDITOR
|Year : 2021 | Volume
| Issue : 1 | Page : 111-115
Ketogenic diet for super-refractory status epilepticus: A case series and review of literature
Sucharita Anand, Amar S Vibhute, Ananya Das, Shilpi Pandey, Vimal Kumar Paliwal
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Submission||13-Mar-2020|
|Date of Acceptance||13-Apr-2020|
|Date of Web Publication||05-Feb-2021|
Dr. Vimal Kumar Paliwal
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow - 226 014, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Anand S, Vibhute AS, Das A, Pandey S, Paliwal VK. Ketogenic diet for super-refractory status epilepticus: A case series and review of literature. Ann Indian Acad Neurol 2021;24:111-5
|How to cite this URL:|
Anand S, Vibhute AS, Das A, Pandey S, Paliwal VK. Ketogenic diet for super-refractory status epilepticus: A case series and review of literature. Ann Indian Acad Neurol [serial online] 2021 [cited 2021 Mar 3];24:111-5. Available from: https://www.annalsofian.org/text.asp?2021/24/1/111/308707
Super-refractory status epilepticus (SRSE) is a life-threatening condition with high mortality (16–23%). There are no clear guidelines for its treatment. Failure of anesthetic agents has prompted the use of immunotherapy, intravenous magnesium, pyridoxine, hypothermia, resective surgery, and ketogenic diet (KD) in SRSE.
We share our experience and discuss the literature regarding use of KD in SRSE.
| Cases|| |
Our protocol for KD in SRSE is given in [Figure 1]. Details of MRI, EEG, and KD are given in [Table 1].
|Figure 1: Protocol for the use of ketogenic diet in superrefractory status epilepticus|
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|Table 1: Clinical details, diagnosis, and treatment details of patients treated with ketogenic diet|
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A 60-years-old lady presented with seizures leading to status epilepticus and left-hemiparesis for 3 days. She had left face/arm clonic seizures spreading to other side every few minutes. She had received lorazepam, loading dose of phenytoin sodium, levetiracetam, sodium valproate, and clobazam. In view of lower lobe pneumonia and sepsis, she was intubated and mechanically ventilated. She did not respond to midazolam (0.3 mg/kg/h). After 2 days of initiating classic KD, ketosis and seizure cessation were achieved. The KD was gradually weaned over 18 days. At 1 month, she was seizure free on phenytoin sodium and clobazam.
A 27-year-old man presented with headache, vomiting, and altered behavior for 5 days. On fifth day, he developed generalized tonic–clonic seizures that evolved to status epilepticus. He received diazepam, lorazepam, loading dose of phenytoin, levetiracetam, and lacosamide over next 5 days. He was referred to us on midazolam infusion (0.3 mg/kg/h). On examination, his consciousness was 8/16 (FOUR score), no focal weakness, and extensor planters. His seizure continued despite thiopentone sodium (5 mg/kg bolus followed by 5 mg/kg/h infusion). In view of new-onset refractory status epilepticus and white-mater hyperintensities on MRI, he was given methylprednisolone (1 g/day) for 3 days with no response. On day 14, he was initiated on KD that improved his seizures. Patient remained seizure free on levetiracetam and clobazam. He was successfully weaned from KD over 18 days. Autoantibody panel and repeat cranial MRI were normal.
A 24-year-old male, a known case of Lennox–Gastaut syndrome, developed generalized status epilepticus for 1 day after missing his antiepileptic drugs. Midazolam infusion (0.3 mg/kg/h) produced only transient seizure freedom. From day 2 of status epilepticus, patient was given KD (4:1). On day 5, patient had complete cessation of seizures. He is seizure free for 1 month on KD, sodium valproate, levetiracetam, and clobazam.
A 7-year-old boy, a known case of postencephalitis sequalae (minimal conscious state and epilepsy) for 6 months, presented with generalized tonic–clonic status epilepticus for 6 days. Before visiting us, he had received lorazepam, levetiracetam, phenytoin sodium, oxcarbazepine, and clobazam. The child was not arousable. The family refused the use of intravenous anesthetic agents. He was started on KD (4:1); ketosis achieved on day 5, seizure cessation from day 7. The child is seizure free on KD, oxcarbazepine, and clobazam for 10 months.
| Discussion|| |
The classic KD uses four-part fat to one-part protein and carbohydrate. The traditional way is to initiate KD after maintaining fasting for 1–3 days. Ketosis is measured by urinary ketones and serum beta-hydroxybutyrate levels. The other diet forms with similar efficacy are modified Atkins diet (allows 20 g of carbohydrate and fat: protein in 60–70%:40–30%), low glycemic index treatment (allows 60 g carbohydrates of < 50% glycemic index), and medium chain fatty acid (MCT) variant of classic KD (uses MCT as fat source). We preferred classic KD due to urgency of achieving ketosis. Contraindications to KD like persistent metabolic derangement, fatty acid oxidation disorders, pancreatitis, and severe dyslipidemia were excluded. Dextrose-free fluid was used and tablets replaced syrups [Figure 1]. We gave one-third of total required calories on first day, escalated to full KD dose by third day.
We compiled studies that used KD for SRSE in [Table 2].,,,,,,,,,,,,,,, Response rate with KD in SRSE is not known due to lack of controlled trials. KD is postulated to be more effective in children than adults probably due to high levels of ketone-metabolizing enzymes in their brain, resulting in higher uptake of ketone bodies. With cerebral maturation, the number of monocarboxylic acid transporters in brain decreases. However, the ketone-dependent monocarboxylic acid transporters increase in adults in situations like ischemia, trauma, and sepsis. A multicenter study did not find relationship between KD outcome and age, sex, seizure type, or EEG findings.
|Table 2: Review of studies reporting the effect of ketogenic diet on refractory/superrefractory and nonconvulsive status epilepticus|
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The optimal timing of initiating KD and its duration in SRSE have not been established. KD showed similar efficacy, whether used early or after the seizure became refractory.
A recent review found no significant difference between KD responders and KD nonresponders based on age of seizure-onset, etiology, seizure types, number of previously tried anti-epileptic drugs/anesthetic agents, duration of SRSE before initiating KD, time to ketosis, and KD duration. Specifically, good response to KD was seen in children with febrile infection-related epilepsy syndrome., KD has been successfully used in nonconvulsive status epilepticus.,, Most people used classic KD. Only few used modified Atkins diet and low glycemic index diet., The time to freedom from status epilepticus ranged from zero to 10th day after initiation of KD. Time to ketosis ranged from 1 to 16 days. Most authors used KD after failure to control status epilepticus with anesthetic agents. The common adverse effects of KD were gastrointestinal disturbances, hypoglycemia, hyponatremia, hypertriglyceridemia, hypoproteinemia, metabolic acidosis, nephrolithiasis, and weight loss.
|Figure 2: (a) Cranial MRI diffusion-weighted sequence showing acute right middle cerebral artery infarct, (b) T2 FLAIR-weighted MRI of brain showing bilateral cerebral white-mater hyperintensity, and (c) T2 FLAIR-weighted MRI of brain showing gyral hyperintensities on right cerebral hemisphere|
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KD can be used in diabetics by closely monitoring for hypoglycemia and ketoacidosis. It can be rapidly withdrawn in diabetics after the control of status to prevent hyperlipidemia and weight loss/gain.
Use of KD for SRSE is a team effort. A trained dietician should institute and monitor KD. ICU staff should avoid glucose-containing fluids and syrups. KD poses a theoretical risk of renal stones if combined with zonisamide and topiramate. Poor palatability is other concern that can be managed by using 2:1 formulation or other KDs.
We conclude that KD is effective in controlling the SRSE irrespective of the age of the patient, etiology, duration of status epilepticus, and prior use anesthetic agents/antiepileptic drugs.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]