Conference Coverage

ECT breaks super-refractory status epilepticus



Electroconvulsive therapy is a safe and efficacious albeit off-label adjunctive therapy in adults with super-refractory status epilepticus of the NORSE subtype, Madeline Tuong-Vi Nguyen, MD, declared at the International Epilepsy Congress.

Dr. Madeline Tuong-Vi Nguyen, a neurologist at Oregon Health and Science University, Portland Bruce Jancin/MDedge News

Dr. Madeline Tuong-Vi Nguyen

“These were highly refractory patients and ECT did contribute to their status termination,” she reported at the congress, sponsored by the International League Against Epilepsy.

Dr. Nguyen, a neurologist at Oregon Health and Science University, Portland, presented a single-center retrospective case series composed of four ECT-treated patients with NORSE (new onset refractory status epilepticus), three of whom experienced marked improvement in their seizure activity, including cessation of their status epilepticus, after completing a course of eight or nine ECT sessions.

A four-patient series may not seem to be compelling evidence, but it’s a significant contribution to the sparse literature regarding this off-label usage of ECT. Indeed, the biggest case series to date consists of eight patients treated at Indiana University, five of whom displayed neurotelemetry or clinical evidence of improvement within 24 hours after completing a full course of ECT (J ECT. 2018 Mar;34[1]:e5-e9. doi: 10.1097/YCT.0000000000000450).

And realistically, these small case series are as good as the supporting evidence is likely to get.

“It would be incredibly difficult to perform a randomized trial, and even a case-control study in such refractory patients would be quite difficult,” she observed.

Super-refractory status epilepticus is the term for seizures persisting despite 24 hours of adequate treatment with benzodiazepines, loading doses of antiepileptic drugs, and anesthetic agents for medically-induced coma, or for seizures that resume after withdrawal of general anesthesia. NORSE is defined as refractory status epilepticus without a history of seizures or a readily identifiable etiology. It is often associated with an autoimmune or paraneoplastic encephalitis. Outcomes are generally poor.

The four ECT-treated patients in the Oregon series were aged 27-48 years. Two had a prodromal viral illness, and a third had a vague prodrome but a negative infectious disease workup. Three patients were on four antiepileptic drugs at the time they began ECT, one was on seven. Two patients had generalized seizures, while the other two had both generalized and focal seizures. Two had normal brain MRI scans and the other two had abnormal MRIs. The patients had CSF white blood cell counts of 2, 5, 10, and 58 per mm3. All patients were on immunotherapy with intravenous corticosteroids, and three of the four were on additional immunomodulatory drugs.

ECT was started on a compassionate-use basis 16-49 days after hospital admission. These were patients who had run out of options, according to Dr. Nguyen.

Three of the four patients returned to consciousness after completing their course of ECT and withdrawal of their general anesthesia, with attenuation of their seizure activity and cessation of their super-refractory status epilepticus. Two of the three were discharged to a rehabilitation facility, including one who eventually could ambulate with slight assistance. Another patient died after discharge, while the fourth patient died during the initial hospital stay due to septic shock unrelated to the ECT.

At discharge, one patient had a modified Rankin Scale score (mRS) of 4, and two had a score of 5. At follow-up, two patients had a score of 3 and one was a 6.

Dr. Nguyen’s presentation met with undisguised audience skepticism.

“What is the theoretical basis to treat very severe epileptic seizures with another epileptic seizure? I mean, what made you do this?” one neurologist asked.

Dr. Nguyen replied that the mechanism of benefit isn’t clear. One possibility is enhanced inhibition of gamma-aminobutyric acid.

“When I describe ECT to the family, the way I think of it is as a hard reset. We tried burst suppression. This is an alternative approach,” she explained.

Another audience member said the treatment strategy smacks of homeopathy.

“These patients have a terrible disorder,” said session co-chair Gregory Krauss, MD. “Three of your four patients ultimately did not do very well.

“The question is, what are you really accomplishing in terms of the underlying encephalopathy and irritability that’s causing this? And are the seizures really a primary factor in their outcome? Is this treatment warranted to try to improve their overall outcome?” asked Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.

Dr. Nguyen answered that she can’t say if the seizures are the cause or result of the encephalopathy.

“ECT was done well into the patients’ admission. Our difficulty is that while we were able to stop the seizures, unfortunately we weren’t able to go back in time and save the brain that was lost due to the convulsive and nonconvulsive activity,” she said. Dr. Nguyen added that she and her coinvestigators are interested in exploring the possibility that utilizing ECT earlier might abort the super-refractory status epilepticus sooner and thereby result in better outcomes.

Still, she noted, three of the four patients were able to leave the hospital, and the two survivors show improved cognitive abilities at 51 and 100 months of follow-up.

Dr. Nguyen reported having no financial conflicts.

SOURCE: Nguyen MTV et al. IEC 2019, Abstract P031.

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