2026 Proffered Presentations
S085: TOPOGRAPHY OF HYPOTHALAMIC FIBER TRACTS: IMPLICATIONS FOR NEUROPSYCHIATRIC AND BEHAVIORAL CORRELATES IN CRANIOPHARYNGIOMA
Yuanzhi Xu, MD; Vera Vigo, MD; Ana Sofia Alvarez, MD; Jonathan Lamano, MD; Shilei Ni, MD; Yuhei Sangatsuda, MD; Byron Hontiveros, MD; Matei Banu, MD; Juan Fernandez-Miranda, MD; Department of Neurosurgery, Stanford Hospital, Stanford, California
Objectives: Precise characterization of hypothalamic fiber tract anatomy is critical for understanding the neuropsychiatric and behavioral sequelae of craniopharyngioma. While hypothalamic damage has been classically associated with endocrine and metabolic dysfunction, systematic analysis of directional fiber pathways in relation to postoperative behavioral and affective changes remains limited. We aimed to delineate a directional framework of hypothalamic tracts and investigate symptom correlates in a craniopharyngioma cohort.
Methods: Eighteen cadaveric specimens underwent white matter fiber dissection to establish the microsurgical anatomy of hypothalamic tracts. High-resolution diffusion spectrum imaging (DSI) tractography was performed using a hypothalamic atlas co-registered to a group-averaged MNI template to validate trajectories. Clinical correlates were analyzed in a retrospective review of 41 patients with craniopharyngioma (median follow-up 3.6 years), focusing on postoperative neuropsychiatric and behavioral outcomes.
Results: A five-directional framework of hypothalamic fibers was delineated: 1) Ventral group included the tuberoinfundibular tract, essential for pituitary–endocrine regulation, and preoptic-hypothalamic fibers, contributing to autonomic and thermoregulatory control. 2) Dorsal group encompassed the dorsal longitudinal fasciculus, mediating visceral autonomic functions, and the mammillotegmental tract, critical for arousal and sleep–wake regulation. 3) Rostral group included the fornix and mammillothalamic tract, both key to episodic memory and limbic relay, the stria medullaris linking hypothalamus and habenula in stress–affective processing, and the hypothalamo-thalamic fibers projecting to midline thalamic nuclei involved in arousal and motivation. 4) Caudal fibers comprised the medial forebrain bundle (medial path), supporting brainstem arousal and motivational drive. 5) The lateral group included the medial forebrain bundle—lateral path (reward, affect, motivation), the ventral amygdalofugal/ansa peduncularis pathway (emotional–autonomic integration), and the Diagonal Band of Broca (septohypothalamic cholinergic projections contributing to arousal, memory modulation, and autonomic integration, Fig.1). In the clinical cohort, postoperative complications were observed in multiple domains: blood pressure dysregulation in 6/41 (14.6%), often converting from preoperative hypertension to postoperative hypotension; abnormal sweating in 3/41 (7.3%); memory impairment in 10/41 (24.4%); sleep–wake disturbances in 5/41 (12.2%); motivational or affective changes such as apathy and anhedonia in 6/41 (14.6%); and social withdrawal in 4/41 (9.8%).
Conclusion: This study integrates cadaveric dissection, tractography, and clinical outcome analysis to establish a surgically oriented, direction-based framework of hypothalamic fiber tracts. Findings highlight that hypothalamic tract injury in craniopharyngioma extends beyond endocrine dysfunction to include profound neuropsychiatric and behavioral sequelae. The directional schema provides a structural basis for preoperative planning, risk prediction, and preservation of hypothalamic connectivity in skull base surgery.
