Thursday, May 12, 2016

Reduction in mortality after epilepsy surgery

Sperling MR, Barshow S, Nei M, Asadi-Pooya AA. A reappraisal of mortality after epilepsy surgery. Neurology. 2016 Apr 27. pii:10.1212/WNL.0000000000002700. [Epub ahead of print]

To assess whether epilepsy surgery is associated with a reduction in mortality rate and if postoperative seizure frequency and severity affect mortality.

A total of 1,110 patients were evaluated (1,006 surgically and 104 nonsurgically treated) for a total follow-up of 8,126.62 person-years from 1986 to 2013. Deaths were ascertained through database and Social Security Death Index query. Patients were grouped by surgery type and seizure status; standardized mortality ratio and deaths per 1,000 person-years were calculated. Survival analysis and Cox proportional hazard regression were performed.

Eighty-nine deaths were observed. Surgically treated patients had a lower mortality rate (8.6 per 1,000 person-years [95% confidence interval (CI) 6.58-11.15]) than nonsurgically treated patients (25.3 per 1,000 person-years [14.50-41.17]; p < 0.001). Seizure-free patients had a lower mortality rate (5.2 per 1,000 person-years [95% CI 2.67-9.02]) than non-seizure-free patients (10.4 per 1,000 person-years [95% CI 7.67-13.89] p = 0.03). More frequent postoperative tonic-clonic seizures (>2 per year) were associated with increased mortality (p = 0.006) whereas complex partial seizure frequency was not related to death rate. Mortality was similar in temporal and extratemporal epilepsy patients (p = 0.7).

Brain surgery is associated with a reduction in mortality rate in drug-resistant epilepsy, both when seizures are abolished and when it results in significant palliation of tonic-clonic seizure frequency. These observations provide further rationale for earlier consideration of epilepsy surgery.

“I see many patients in the office who have had uncontrolled seizures for many years, sometimes for decades, and you really have to wonder why they hadn't been referred sooner,” said Michael R. Sperling, MD, FAAN, professor of neurology and director of the Jefferson Comprehensive Epilepsy Center at the Thomas Jefferson University Hospital in Philadelphia. “We hope this will serve as a wake-up call to neurologists that there is a risk to not referring patients for surgery, said Dr. Sperling, who also serves as editor-in-chief of the journal Epilepsia. “The decision to persist in futile therapy is one with potentially fatal consequences. ”The results of the new study extend results Dr. Sperling reported in a smaller prospective cohort study he published in 2005….

“This paper is incredibly important,” said Steven Karceski, MD, assistant professor of neurology and director of clinical trials at the Weill Cornell Epilepsy Center. “It tells us that we can have a tremendous impact by getting these seizures under control. There has been too much complacency, and this study tells us that complacency has a very real cost.” An accompanying editorial coauthored by Nathalie Jette, MD, of the University of Calgary and Jerome Engel, MD, PhD, of the University of California, Los Angeles, noted that despite surgery's high efficacy and cost effectiveness, no improvement in delays to referral have been observed since the AAN published a practice parameter in 2003 declaring surgery to be the treatment of choice for drug-resistant temporal lobe epilepsy. The editorial noted, however, that despite its strengths, the study did have a few limitations. First, the cause of death was unknown in over half of the patients, precluding stratification into epilepsy-related versus non epilepsy-related causes. Second, the editorial continued, “the surgical and the non-surgical group were not matched, with the non-surgical group having more severe epilepsy and more comorbidity, thus resulting in selection bias. In addition, the surgical group is ten times larger than the non-surgical group. Finally, the lack of risk adjustment for comorbidity is an important limitation, as a number of comorbidities are associated with mortality. There even exists a validated epilepsy-specific comorbidity risk adjustment index for mortality that could have been applied as part of the analysis.” Lara Jehi, MD, research director and head of the outcomes research program at the Cleveland Clinic Epilepsy Center, said that while such limitations are valid, they do not call into question the study's conclusions or its importance to the field…

“Neurologists may feel, despite the publications, that surgery is not right for their patients, that it's too risky,” said Carl W. Bazil, MD, PhD, FAAN, professor of neurology and director of the division of epilepsy and sleep at Columbia University College of Physicians and Surgeons. “They may feel they can take care of it medically. But they owe it to their patients to tell them, ‘If you get your epilepsy cured by surgery, it decreases your chances of death.’ That's a really important message.”“You may be able to identify individuals with medically-refractory epilepsy after the initial two or three antiepileptic medication trials,” said Gregory D. Cascino, MD, FAAN, Whitney Macmillan, Jr., professor of neuroscience and enterprise director of epilepsy at the Mayo Clinic in Rochester, MN.

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