Cognitive Impairments Observed in Patients With Functional Seizures

Patients with functional seizures had slightly better cognitive performance than those with epilepsy, but worse performance compared with a healthy cohort of patients, according to a systematic review and meta-analysis.

Across 84 studies with more than 8,600 patients, cognitive performance in those with functional seizures was better than in those with epilepsy (Hedges’ g=0.17, 95% CI 0.10-0.25, P<0.0001), with moderate-to-high heterogeneity, reported Ryan Van Patten, PhD, of Brown University in Providence, Rhode Island, and co-authors in Lancet Psychiatry.

This was driven by better performance in global cognition and intelligence quotient (Hedges’ g=0.15, P=0.022), as well as language (Hedges’ g=0.28, P=0.0001). However, patients with functional seizures underperformed on cognitive testing in all domains relative to healthy comparisons (Hedges’ g = -0.61, P<0.0001).

“The findings of widespread and moderately sized cognitive deficits in multiple domains in patients with functional seizures warrant consideration of neuropsychological assessment and cognitive rehabilitation, as clinically appropriate in individual patients,” Van Patten and colleagues wrote. “Given substantial overlap in cognitive profiles between functional seizures and epilepsy, the results suggest that cognitive testing cannot be used to differentially diagnose functional seizures from epilepsy.”

Functional seizures, formerly called psychogenic nonepileptic seizures, are seizure-like episodes without abnormal electroencephalography. They are diagnosed as a functional neurological disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and often treated with cognitive behavioral therapy.

“Previously a diagnosis of exclusion, functional neurological disorders should now only ever be diagnosed on the basis of positive diagnostic criteria,” noted Ingrid Hoeritzauer, PhD, of Royal Infirmary Hospital in Edinburgh, in an accompanying editorial. “For example, positive diagnosis of functional seizures can be made clinically on the basis of phenotyping, such as duration of convulsion of more than 3 minutes and eyelids actively held closed during seizures.”

Functional neurological disorders “transcend the artificial borders drawn between neurology and psychiatry,” Hoeritzauer wrote. “They exist in both brain and mind at biological, psychological, and network levels, cause physical and mental effects, and can be viewed as neurological, psychiatric, or even philosophical with the questions that they raise of whether we have agency over our own movements.”

The presence of cognitive dysfunction on testing is not surprising, Hoeritzauer added. “In clinical practice, no matter the type of functional neurological disorder with which patients present, from seizures to paralysis, cognitive symptoms will be one of the top issues. In fact, if at least one of cognitive difficulties, pain, and fatigue is not described by patients, then questions are raised about whether the diagnosis of functional neurological disorders is correct.”

For this systematic review and meta-analysis, a medical librarian searched Medline, Embase, PsycINFO, and Web of Science for reports documenting raw or standardized cognitive test data in adults with functional seizures compared with adults with epilepsy, prospectively recruited healthy comparisons, or published norms.

Van Patten and team included 84 studies with 8,654 participants — 4,193 with functional seizures, 3,638 with epilepsy, and 823 with healthy comparisons. Functional seizures could be “diagnosed at any level of diagnostic certainty” based on existing published criteria.

Mean age was 36 for patients with functional seizures, 36 for epilepsy patients, and 34 for healthy comparisons, and the proportion of women per group was 72% for functional seizures, 59% for epilepsy, and 69% for healthy comparisons.

Cognitive and neuropsychological tests included measures of intelligence, attention, processing speed, language, visuospatial skills, learning and memory, executive functioning, social cognition, motor abilities, and overall (composite) cognitive functioning.

There were no language or date restrictions, but studies that reported on mixed functional seizures and epilepsy were excluded.

Areas of bias included inconsistent reporting about medical background. There was also infrequent documentation of disability and legal issues, and some uncertainty over whether or not patients with epilepsy history were excluded from functional seizure groups.

“It is unclear whether a systematic review can answer the question of whether clinically meaningful cognitive deficits exist in patients with functional seizures,” Hoeritzauer observed. “Like all systematic reviews, this paper is limited by the data available to be compiled.”

The studies in this analysis had small sample sizes, with no reporting on racial or ethnic background, and little reporting on clinical features of the epilepsy cohorts, Van Patten and colleagues acknowledged. It was also unclear whether or not telehealth-based cognitive testing for this population was feasible and clinically useful. Only two longitudinal studies were included.

Many functional seizure patients were taking antiseizure medication at the time of cognitive testing, which may have cognitive side effects. More important was a lack of consistent reporting on background factors that affect functional seizures, like mental illness, traumatic brain injury, chronic pain, and attention deficit-hyperactivity disorder and autism, or exclusion of patients with these conditions, the researchers said.

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