Craniopharyngiomas Primarily Involving the Hypothalamus: A Model of Neurosurgical Lesions to Elucidate the Neurobiological Basis of Psychiatric Disorders

Objective: This study provides a systematic review and meta-analysis of psychiatric disorders caused by craniopharyngiomas and the hypothalamic alterations underlying these symptoms.

Methods: We investigated a collection of 210 craniopharyngiomas reported from 1823 to 2017 providing detailed clinical and pathologic information about psychiatric disturbances, including 10 of our own series, and compared the hypothalamic damage in this cohort with the present in a control cohort of 105 cases without psychiatric symptoms.

Results: Psychiatric disorders occurred predominantly in patients with craniopharyngiomas developing primarily at the infundibulotuberal region (45%) or entirely within the third ventricle (30%), mostly affecting adult patients (61%; P < 0.001). Most tumors without psychic symptoms developed beneath the third ventricle floor (53.5%; P < 0.001), in young patients (57%; P < 0.001). Psychiatric disturbances were classified in 6 major categories: 1) Korsakoff-like memory deficits, 66%; 2) behavior/personality changes, 48.5%; 3) impaired emotional expression/control, 42%; 4) cognitive impairments, 40%; 5) mood alterations, 32%; and 6) psychotic symptoms, 22%. None of these categories was associated with hydrocephalus. Severe memory deficits occurred with damage of the mammillary bodies (P < 0.001). Mood disorders occurred with compression/invasion of the third ventricle floor and/or walls (P < 0.012). Coexistence of other hypothalamic symptoms such as temperature/metabolic dysregulation or sleepiness favored the emergence of psychotic disorders (P < 0.008). Postoperative psychiatric outcome was better in strictly intraventricular craniopharyngiomas than in other topographies (P < 0.001). A multivariate model including the hypothalamic structures involved, age, hydrocephalus, and hypothalamic symptoms predicts the appearance of psychiatric disorders in 81% of patients.

Conclusions: Craniopharyngiomas primarily involving the hypothalamus represent a neurobiological model of psychiatric and behavioral disorders.