New research shows that immunotherapy given up to 18 weeks after onset may help some patients who suddenly develop refractory continuous seizures, according to an abstract presented at the AAN Annual Meeting, held in Denver in April.
The researchers reviewed data on 135 patients with new onset refractory status epilepticus (NORSE) over nine years, 74 of whom had cryptogenic new onset refractory status epilepticus (C-NORSE). All patients received first-line immunotherapy, such as steroids, with 83.8 percent returning to “mental functionality" within a median duration of 30 days.
Seventy patients were followed up for one year, and 62 patients for two years. A year after the first treatment, 26 of the 70 patients (37.1 percent) achieved favorable outcomes (mRS 0, 1, and 2), increasing to 31 of the 62 patients (50 percent) after two years.
Some patients did not improve; an unfavorable prognosis was associated with hippocampal atrophy plus extra-limbic lesions observed on a three-month MRI (OR1.295, 95 percent CI 1.086 to 1.544, p=006) and prolonged unconsciousness longer than 60 days. Of the 60 patients who underwent sequential brain MRI imaging, 20 (33.3 percent) exhibited both the extra-medial temporal lobe (MTL) lesion and MTL atrophy, said Yoonhyuk Jang, MD, PhD, a neurologist at Seoul National University Hospital.
Study authors said they were drawn to the research topic because patients with C-NORSE often do not respond to treatment, and researchers were uncertain why some patients responded well to longer immunotherapy treatment and some developed hippocampal atrophy.
Investigators defined "continuous immunotherapy" as an intravenous infusion of steroid and immune globulin for five days, which counted as one session, followed by rituximab or tocilizumab for three months, six months, or a year. To account for the washout period of immunotherapy, Dr. Jang said, patients were considered to have received continuous immunotherapy if the time gap between one session of any immunotherapy and the next session was less than 90 days.
“The only thing we found was that cytokines such as IL-6, CXCL9, MIP-1alpha—those involving innate immunity—had some significant differences among the groups that had hippocampal atrophy or extra limbic lesions," said Dr. Jang.
Dr. Rani Sarkis, MD, MSc, an assistant professor of neurology at Brigham and Women's Hospital, who was not involved in the study, said that because C-NORSE is an uncommon disease, determining the best treatment has been challenging.
“The strength of this study is its prospective data, because you're trying to get outcomes at different time points and determine the longitudinal imaging changes, so those are definitely strengths," he said. “They're not commonly done for a disorder like this; you're usually doing retrospective analyses and struggling to find enough patients."
There was not a lot of information about the timing and the nature of immunotherapy, particularly how to optimize treatment to avoid the risks such as infection, Dr. Sarkis said, adding that he expected that to be provided in a separate abstract.
But Dr. Sarkis said it was helpful to have information doctors could use to counsel patients, like the three-month MRI features associated with an unfavorable prognosis.
Michael Sperling, MD, FAAN, professor of neurology at Thomas Jefferson University and director of the Jefferson Comprehensive Epilepsy Center, said the findings were consistent with past studies, and that the research needed to clearly define “continuous immunotherapy."
“Usually, after IV therapy in the acute phase, therapy that alters the immune system is prescribed over a period of time. These agents are usually given in pulse fashion if intravenous, though some oral agents might be taken on a daily basis (but the IV drugs are usually preferred when therapy is started, though there are no good, randomized trials that have compared any two therapies)," Dr. Sperling said. He added that even the pulse IV therapies have long-lasting effect —for example, rituximab is given in two doses separated by two weeks, and it then lasts for up to six months.
“The problem with the immune therapies is that no trials have been conducted to see if they really work in NORSE, or if the improvement is coincidental. We all would like to believe that they improve outcome, but the medical profession has a history of employing ineffective therapies because these treatments made sense, until they didn't."
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