Predicting Brain Atrophy Severity in Super-Refractory Status Epilepticus

brain atrophy MRI
brain atrophy MRI
Surprisingly, the authors found that change in VBR did not correlate with functional outcomes.

The duration of super-refractory status epilepticus (SRSE) impacts the severity of cortical and subcortical atrophy, results from a small study indicate.

The findings were published in JAMA Neurology.

Despite prior investigations, the prevalence and severity of atrophy after SRSE is not well known, however,“In the hours, days, and weeks after prolonged seizures, long-term changes in gene expression and chronic microhemorrhages due to an altered blood-brain barrier result in seizure-induced neuronal death and neuronal reorganization,” the study authors, led by Sara Hocker, MD, of Mayo Clinic in Rochester, Minn., wrote.

In order to better understand how SRSE and anesthetic agents affect brain atrophy, Dr Hocker and colleagues conducted a retrospective review of medical records from patients admitted to Mayo Clinic Hospital with SRSE from January 1, 2001 to December 30, 2013. Patients 18 years or older with SRSE, an initial MRI within 2 weeks of SRSE onset, another MRI within 6 months of SRSE resolution, and a minimum of 1 week between scans were included in the analysis.

Ultimately, 19 patients were included (10 men, 9 women; median age 41). Anesthetic agents, including midazolam hydrochloride (n=17), propofol (n=9), pentobarbital sodium (n=8), ketamine hydrochloride (n=5), phenobarbital (n=2), and isoflurane (n=1) were used for a median of 13 days, with patients receiving a median of 2.4 different anesthetic agents over the course of treatment.

Median ventricular brain ratio (VBR) at the initial MRI (0.06; IQR, 0.04-0.07) was significantly different from the median VBR at follow-up MRI (0.08; IQR, 0.07-0.12) (z = −3.82; P < .001). The median change in VBR (ΔVBR) was 23.3%, with a higher value signifying greater parenchymal loss.  There were significant positive correlations between ΔVBR and duration of anesthetic treatment (ρ = 0.54; P = .02) and length of hospital stay (ρ = 0.64; P = .003). The researchers also found significant negative correlations between ΔVBR and age, with mean VBR on initial MRI greater in patients older than 50 years.

Notably, no significant correlation was found between ΔVBR and Modified Rankin Scale score at admission (ρ = 0.13; P = .59), discharge (ρ = 0.13; P = .61), and follow-up (ρ = 0.13; P = .66).

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“Our study is, to our knowledge, the first to document the development of diffuse brain atrophy despite control of SRSE using quantitative imaging,” the authors wrote. “This finding suggests that parenchymal loss is ongoing, even after control of seizures with anesthetic drugs. The correlation between duration of anesthetic drug requirement and degree of global brain atrophy further strengthens the validity of the association.”

It is important to note that this study was not statistically powered to qualify whether the noted parenchymal atophy was a result of complications secondary to status epilepticus, anticonvulsant effect, or a direct cause of epileptic complications. The authors suggest that future studies should focus on the association of atrophy with clinical variables and its impact on the long-term cognitive prognosis of SRSE survivors.

Dr Hocker disclosed serving as a consultant for a clinical trial investigating allopregnanolone use for SRSE sponsored by SAGE Therapeutics. Mr Hanson disclosed receiving personal fees from AnalyzeDirect. Dr Britton disclosed serving as a coinvestigator for clinical trials investigating the use of cannabidiol in Lennox-Gastaut and Dravet syndrome sponsored by GW Pharma.


Hocker S, Nagarajan E, Rabinstein AA, Hanson D, Britton JW. Progressive brain atrophy in super-refractory status epilepticus. JAMA Neurol. 2016 Aug 15. doi:10.1001/jamaneurol.2016.1572.