Clinical MRI morphological analysis of functional seizures compared to seizure-naïve and psychiatric controls.

PURPOSE: Functional seizures (FS), also known as psychogenic nonepileptic seizures (PNES), are physical manifestations of acute or chronic psychological distress. Functional and structural neuroimaging have identified objective signs of this disorder. We evaluated whether magnetic resonance imaging (MRI) morphometry differed between patients with FS and clinically relevant comparison populations. METHODS: Quality-screened clinical-grade MRIs were acquired from 666 patients from 2006 to 2020. Morphometric features were quantified with FreeSurfer v6. Mixed-effects linear regression compared the volume, thickness, and surface area within 201 regions-of-interest for 90 patients with FS, compared to seizure-naïve patients with depression (n = 243), anxiety (n = 68), and obsessive-compulsive disorder (OCD, n = 41), respectively, and to other seizure-naïve controls with similar quality MRIs, accounting for the influence of multiple confounds including depression and anxiety based on chart review. These comparison populations were obtained through review of clinical records plus research studies obtained on similar scanners. RESULTS: After Bonferroni-Holm correction, patients with FS compared with seizure-naïve controls exhibited thinner bilateral superior temporal cortex (left 0.053 mm, p = 0.014; right 0.071 mm, p = 0.00006), thicker left lateral occipital cortex (0.052 mm, p = 0.0035), and greater left cerebellar white-matter volume (1085 mm3, p = 0.0065). These findings were not accounted for by lower MRI quality in patients with FS. CONCLUSIONS: These results reinforce prior indications of structural neuroimaging correlates of FS and, in particular, distinguish brain morphology in FS from that in depression, anxiety, and OCD. Future work may entail comparisons with other psychiatric disorders including bipolar and schizophrenia, as well as exploration of brain structural heterogeneity within FS.

Title: Functional seizures across the adult lifespan: female sex, delay to diagnosis and disability.

OBJECTIVE: The clinical characteristics of functional seizures may vary based on age-of-onset or age-of-presentation. Description of age-related differences has focused on three categories: pediatric, young-adult, and older-adult. We evaluated how factors continuously varied based on age-of-presentation across the adult lifespan. METHODS: Based on cross-sectional data from 365 adult (18 to 88 years old) patients with documented diagnoses of functional seizures, we evaluated how the quantity and prevalence of specific ictal behaviors, historical factors, and comorbidities varied based on patient age-of-presentation using sequential weighted averages. RESULTS: Four factors changed prominently with age-of-presentation: female predominance decreased at two inflection points - ages 35 and 62; the prevalence of work disability was higher until age-of-presentation 30 then plateaued at 80%; there was greater delay to diagnosis in older patients; and comorbidities was higher with age-of-presentation, starting from early adulthood. The proportion of patients who presented with functional seizures decreased after 50. Ictal behavior did not substantially vary with age-of-presentation. CONCLUSION: The time from onset to diagnosis increased with age-of-presentation, which may be related to increased comorbidities and the misconception that FS do not start in older age. The female predominance decreased nonlinearly with age. By age 30, most patients' seizures already had substantial association with unemployment. These findings emphasize that patients can develop functional seizures at any age. The rapid development of disability relatively early in life, which then stays at a high prevalence rate, demonstrates the need for prompt referral for definitive diagnosis and treatment.

A minority of patients with functional seizures have abnormalities on neuroimaging.

OBJECTIVE: Functional seizures often are managed incorrectly as a diagnosis of exclusion. However, a significant minority of patients with functional seizures may have abnormalities on neuroimaging that typically are associated with epilepsy, leading to diagnostic confusion. We evaluated the rate of epilepsy-associated findings on MRI, FDG-PET, and CT in patients with functional seizures. METHODS: We studied radiologists' reports from neuroimages at our comprehensive epilepsy center from a consecutive series of patients diagnosed with functional seizures without comorbid epilepsy from 2006 to 2019. We summarized the MRI, FDG-PET, and CT results as follows: within normal limits, incidental findings, unrelated findings, non-specific abnormalities, post-operative study, epilepsy risk factors (ERF), borderline epilepsy-associated findings (EAF), and definitive EAF. RESULTS: Of the 256 MRIs, 23% demonstrated ERF (5%), borderline EAF (8%), or definitive EAF (10%). The most common EAF was hippocampal sclerosis, with the majority of borderline EAF comprising hippocampal atrophy without T2 hyperintensity or vice versa. Of the 87 FDG-PETs, 26% demonstrated borderline EAF (17%) or definitive EAF (8%). Epilepsy-associated findings primarily included focal hypometabolism, especially of the temporal lobes, with borderline findings including subtle or questionable hypometabolism. Of the 51 CTs, only 2% had definitive EAF. SIGNIFICANCE: This large case series provides further evidence that, while uncommon, EAF are seen in patients with functional seizures. A significant portion of these abnormal findings are borderline. The moderately high rate of these abnormalities may represent framing bias from the indication of the study being "seizures," the relative subtlety of EAF, or effects of antiseizure medications.