Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 h or more after the onset of anaesthetic therapy, including those cases where status epilepticus recurs on the reduction or withdrawal of anaesthesia. It is an uncommon but important clinical problem with high mortality and morbidity rates. This article reviews the treatment approaches. There are no controlled or randomized studies, and so therapy has to be based on clinical reports and opinion. The published world literature on the following treatments was critically evaluated: anaesthetic agents, anti-epileptic drugs, magnesium infusion, pyridoxine, steroids and immunotherapy, ketogenic diet, hypothermia, emergency resective neurosurgery and multiple subpial transection, transcranial magnetic stimulation, vagal nerve stimulation, deep brain stimulation, electroconvulsive therapy, drainage of the cerebrospinal fluid and other older drug therapies. The importance of treating the identifying cause is stressed. A protocol and flowchart for managing super-refractory status epilepticus is suggested. In view of the small number of published reports, there is an urgent need for the establishment of a database of outcomes of individual therapies.

The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol

Summary Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed.

/pdf/management-of-refractory-status-epilepticus-in-adults-still-1s92ordi4e.pdf

Management of refractory status epilepticus in adults: still more questions than answers

Objective: To describe a case series of adult patients in the intensive care unit in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours or more despite appropriate anesthetic treatment) who received treatment with the ketogenic diet (KD). Methods: We performed a retrospective case review at 4 medical centers of adult patients with SRSE treated with the KD. Data collected included demographic features, clinical presentation, diagnosis, EEG data, anticonvulsant treatment, and timing and duration of the KD. Primary outcome measures were resolution of status epilepticus (SE) after initiation of KD and ability to wean from anesthetic agents. Results: Ten adult patients at 4 medical centers were started on the KD for SRSE. The median age was 33 years (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had encephalitis. The median duration of SE before initiation of KD was 21.5 days (IQR 28) and the median number of antiepileptic medications used before initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three patients had minor complications of the KD including transient acidosis and hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the KD. Conclusion: We describe treatment of critically ill adult patients with SRSE with the KD, with 90% of patients achieving resolution of SE. Prospective trials are warranted to examine the efficacy of the KD in adults with refractory SE. Classification of evidence: This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE.

Ketogenic diet for adults in super-refractory status epilepticus.

Super-refractory status epilepticus (SE) is a stage of refractory SE characterized by unresponsiveness to initial anesthetic therapy. It is a new concept that has been the focus of recent basic and therapeutic work, and is defined as "SE that continues or recurs 24 hours or more after the onset of anesthesia, including those cases in which SE recurs on the reduction or withdrawl of anesthesia." It is encountered typically, but not exclusively, in two quite distinctive clinical situations: (1) in patients with severe acute brain injury, and (2) in patients with no history of epilepsy in whom status epilepticus develops out of the blue with no overt cause. There are a variety of treatments used, almost entirely based on open observational studies or case reports. Therapy includes anesthesia, antiepileptic drug therapy, hypothermia and ICU therapy, other medical, immunological, and physical therapies. In this review, the range of possible therapies is outlined and an approach to therapy is discussed.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2011.03238.x

Super-refractory status epilepticus: An approach to therapy in this difficult clinical situation

The ketogenic diet (KD) and the modified Atkins diet are effective therapies for intractable epilepsy. We compared retrospectively the KD and modified Atkins diet in 27 children and also assessed serum long chain fatty acid profiles. After 3 months, using an intent-to-treat analysis, the KD was more successful, with >50% seizure reduction in 11/17 (65%) vs. 2/10 (20%) with the modified Atkins diet, p = 0.03. After 6 months, however, the difference was no longer significant: 7/17 (41%) vs. 2/10 (20%) (p = 0.24). We observed a preventive effect of both diets on the occurrence of status epilepticus. After 1 and 3 months of either diet, responders experienced a significant decrease in serum arachidonic acid concentration compared to non-responders. The KD and modified Atkins diet led to seizure reduction in this small pilot series, with slightly better results after 3 months with the KD, but not after 6 months. The decrease of serum arachidonic acid levels might be involved in the anticonvulsive effects of KD or modified Atkins diet.

Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet

Intérêt du régime cétogène dans le traitement d'un état de mal épileptique résistant de l'adulte

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Intérêt du régime cétogène dans le traitement d'un état de mal épileptique résistant de l'adulte