Localizing value of disturbances of self-integration, depersonalization, and forced thinking: A systematic review

We performed a systematic review of the localizational value of disturbances of self-integration, depersonalization and forced thinking in focal epilepsy with the aim to summarize the state-of-the-art anatomo-clinical correlations in the field and help guide interpretation of ictal semiology within the framework of pre-surgical evaluation. The review was performed using a PRISMA- and QUADAS2-based approach. Three separate PubMed and EMBASE searches were undertaken using the keywords self-integration, depersonalization and forced thinking, along with synonyms, in combination with terms to identify epileptogenic zone as defined by surgical outcome, MRI-findings or intracranially recorded EEG. Studies published in peer-reviewed journals with an abstract available, limited to English, French, German, Spanish, or Italian were included for review. Abstracts from scientific meetings were included if precise data on semiology in addition to either localization or surgical outcome was presented. Cases were regarded as eligible if data informing on anatomo-clinical correlations were sufficient to allow determination of an epileptogenic zone and evaluate its level of confidence. For disturbances of self-integration, the search identified 18 publications containing 23 eligible cases, with 10 additional cases identified in the literature. For depersonalization, a single case from a two patient study fulfilled inclusion criteria. For forced thinking, the search identified two publications containing four eligible cases, with six additional cases identified through literature searches. The retrieved cases suggest that disturbances of self-integration often reflect an epileptogenic zone centered around the temporoparietal region, where neighboring areas in the parietal lobe, the posterior insula, and likely depending on the type of disturbance also the adjoining occipital lobe, the anterior and middle cingulum, premotor and supplementary motor in addition to medial temporal structures could be involved. When present, lateralized symptomatology reflects a contralateral focus. Depersonalization, as a localizing ictal phenomenon was quite elusive. Forced thinking either pointed to premotor frontal or temporal epileptogenic zones. Currently, outlined epileptogenic zones of ictal disturbances of self-integration and forced thinking are quite widespread and should be regarded with a low-to-moderate degree of reliability. A focus on such rarer ictal phenomena, in combination with improved imaging techniques and increased use of SEEG, will hopefully lead to an accumulation of cases with better defined epileptogenic zones.