Blood–brain barrier damage and new onset refractory status epilepticus: An exploratory study using dynamic contrast‐enhanced magnetic resonance imaging

Abstract

Objective: This study was undertaken to characterize the blood-brain barrier (BBB) dysfunction in patients with new onset refractory status epilepticus (NORSE) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Methods: This study included three groups of adult participants: patients with NORSE, encephalitis patients without status epilepticus (SE), and healthy subjects. These participants were retrospectively included from a prospective DCE-MRI database of neurocritically ill patients and healthy subjects. The BBB permeability (Ktrans) in the hippocampus, basal ganglia, thalamus, claustrum, periventricular white matter, and cerebellum were measured and compared between these three groups.Results: A total of seven patients with NORSE, 14 encephalitis patients without SE, and nine healthy subjects were included in this study. Among seven patients with NORSE, only one had a definite etiology (autoimmune encephalitis), and the rest were cryptogenic. Etiology of encephalitis patients without SE included viral (n = 2), bacterial (n = 8), tuberculous (n = 1), cryptococcal (n = 1), and cryptic (n = 2) encephalitis. Of these 14 encephalitis patients without SE, three patients had seizures. Compared to healthy controls, NORSE patients had significantly increased Ktrans values in the hippocampus (.73 vs. .02 × 10 −3 /min, p = .001) and basal ganglia (.61 vs. .003 × 10 −3 /min, p = .007) and a trend in the thalamus (.24 vs. .08 × 10 −3 /min, p = .017). Compared to encephalitis patients without SE, NORSE patients had significantly increased Ktrans values in the thalamus (.24 vs. .01 × 10 −3 /min, p = .002) and basal ganglia (.61 vs. .004 × 10 −3 /min, p = .013).Significance: This exploratory study demonstrates that BBBs of NORSE patients were impaired diffusely, and BBB dysfunction in the basal ganglia and thalamus plays an important role in the pathophysiology of NORSE.

Treatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs

“…Only descriptive statistics were used to analyze type of EEG use and treatment goals because a large proportion of studies had unclear/unknown or mixed monitoring and treatment goals, which precluded meaningful statistical analyses (Table 2). The rate of continuous EEG (CEEG) monitoring was higher in publications after 2010 (pre-2010: continuous: 76%, 244 of 321 patients; intermittent: 24%, 77 of 321 patients; and 2010 onward: continuous: 89%, 493 of 555 patients; intermittent: 11%, 62 of 555 patients). The type of EEG monitoring was unknown/unclear for 45% of patients.…”

“…A total of 3603 publications were identified by search of Embase, PubMed, Ovid MEDLINE, and Web of Science, of which 66 publications were included (eFigure 1 in the Supplement). Other than 4 randomized clinical trials that included 32 patients, 23 patients, 23 patients, and 10 patients, and a retrospective case-control study with 33 patients, all remaining eligible studies were case cohort or case series (Table 1).…”

“…Other than 4 randomized clinical trials that included 32 patients, 23 patients, 23 patients, and 10 patients, and a retrospective case-control study with 33 patients, all remaining eligible studies were case cohort or case series (Table 1). Furthermore, based on our inclusion criteria (5 or more patients and at least 1 patient older than 12 years with a diagnosis of RSE), only 2 patients in the study by Mahvelati et al and 3 in the study by Rosati et al were included because other patients in these studies were younger than 12 years.…”

“…Fourteen patients were counted twice as described previously because 2 CIVADs were initiated simultaneously on these patients (Table 1). Our study included 4 publications totaling 103 patients (midazolam: 35 of 838; propofol: 22 of 619; barbiturates: 46 of 170) since 1994 that were also included in the Claassen study . We excluded 1 patient who received continuous intravenous phenobarbital from analysis due to the paucity of data.…”

Second‐line immunotherapy in new onset refractory status epilepticus

“…Tocilizumab is a recombinant humanized monoclonal antibody against the IL‐6 receptor, mainly used in the treatment of rheumatoid arthritis, various forms of juvenile arthritis, giant cell arteritis, and cytokine release syndrome, and for select hospitalized patients with COVID‐19 50–52 . Although its penetration into the CSF was shown to be very poor when the blood–brain barrier is intact, 53 this treatment could help manage peripheral inflammation as well as brain‐related inflammation when the blood–brain barrier is disrupted 54 . The use of tocilizumab has been reported during the acute phase in 11 case reports or case series involving a total of 20 patients, including 14 adults and six children (median age = 22.5 years, range = 6–61; Table 2).…”