Diagnosis of psychogenic nonepileptic seizures has ‘implications for future mortality’

Patients with psychogenic nonepileptic seizures have a standardized mortality ratio 2.5 times greater than the general population and die at a rate similar to patients with drug-resistant epilepsy, according to findings published in Neurology.

“Mortality is increased in people with epilepsy, but less than half of deaths are related directly to seizures,” the researchers wrote. “Having a psychiatric comorbidity increases the risk of death in people with epilepsy and in the general population. Between 49% and 100% of patients with [psychogenic nonepileptic seizures] have an additional psychiatric comorbidity, which is higher than those with epilepsy. Patients with epilepsy and [psychogenic nonepileptic seizures] die of sudden unexpected death in epilepsy at younger ages than those with epilepsy alone.”

Russell Nightscales, BSc(Hons), of the department of neuroscience at the Central Clinical School of Monash University and the departments of medicine and neurology at the University of Melbourne, and colleagues examined mortality rates among patients with psychogenic nonepileptic seizures who were admitted for video-EEG monitoring, as events observed during this type of monitoring are considered “the gold standard for diagnosis.” Patients with psychogenic nonepileptic seizures comprise approximately one-fourth of all admissions for video-EEG monitoring, according to the researchers.

The retrospective cohort study evaluated patients admitted to video-EEG monitoring units at 3 hospitals in Melbourne between Jan. 1, 1995, and Dec. 31, 2015. Multidisciplinary teams composed of epileptologists, neuropsychiatrists, radiologists, neuropsychologists, neurophysiology scientists and nurses made diagnoses of psychogenic nonepileptic seizures, epilepsy or both conditions based on reviews of several different sources, including clinical data, video-EEG monitoring, neuropsychology data and investigational information, defined by the researchers as MRI, PET and single-photon emission CT. The researchers determined psychiatric diagnoses based on written formal assessments from consultant neuropsychiatrists and categorized them according to a previously published system, according to the study. They examined mortality by linking the cohort to the Australian National Death Index, a national database with information regarding all deaths after 1980.

Among 5,508 patients who underwent video-EEG monitoring, researchers made the following diagnoses: epilepsy (55.6%); psychogenic nonepileptic seizures (12.2%); or both conditions (3.2%). Nightscales and colleagues made other diagnoses — or no diagnosis — in more than a quarter of patients (29%).

Patients diagnosed with psychogenic nonepileptic seizures experienced a mortality rate 2.5 times higher than the general population (standardized mortality rate, 2.5; 95% CI, 2-3.3). In the psychogenic nonepileptic seizures plus epilepsy and epilepsy groups, the standardized mortality rate was 3.7 (95% CI, 2.2–6.3) and 3.3 (95% CI, 3.0–3.7), respectively. The standardized mortality rate in the psychogenic nonepileptic seizures or the psychogenic nonepileptic seizures plus epilepsy groups did not differ significantly compared with the rate in the epilepsy group. When researchers omitted all deaths in the psychogenic nonepileptic seizures group due to epilepsy (n = 13), the standardized mortality rate in the remaining psychogenic nonepileptic seizures group (n = 42) was 2.1 (95% CI, 1.5–2.8).

The RR for mortality in the psychogenic nonepileptic seizures group increased 8.6-fold (95% CI, 3.6-20.7) among patients aged 18 to 29 years and 7.2-fold (95% CI, 3.6–14.4) in patients aged 30 to 39 years. The RR remained significantly elevated until 59 years, but was still significantly elevated in patients older than 70 years (RR = 1.6; 95% CI, 1.01–2.62).

Multivariable regression analysis demonstrated no differences in death rates between the epilepsy groups and the psychogenic nonepileptic seizures group during the study period (HR = 0.84; 95% CI, 0.62–1.12), adjusting for age at video-EEG monitoring, sex and hospital site.

External causes contributed to 18% of deaths among patients with psychogenic nonepileptic seizures (n = 55), with 20% of deaths among patients aged less than 50 years attributed to suicide and epilepsy recorded as the cause of death in 24%.

Nightscales and colleagues also found that patients with psychogenic nonepileptic seizures were more likely to live in socioeconomically deprived areas compared with the epilepsy group, a finding that they note is consistent with previous reports.

“We suspect that social determinants such as low income, employment, and social support, and associated lifestyle factors such as higher rates of smoking, alcohol consumption and poor diet, are important contributors to medical comorbidity and excess mortality in [psychogenic nonepileptic seizures],” the investigators wrote.

They note that, as the causes of excess mortality in patients with psychogenic nonepileptic seizures were “largely preventable,” the results have ramifications.

“These important findings should inform neurologists, psychiatrists, and medical practitioners that a diagnosis of [psychogenic nonepileptic seizures] has significant implications for future mortality, which is comparable to that of drug-resistant epilepsy, and therefore deserves attention from the clinical and research community to identify how to better manage this patient group,” Nightscales and colleagues wrote.