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Interpeduncular fossa

The interpeduncular fossa is a diamond-shaped depression located on the ventral (anterior) surface of the midbrain, bounded laterally by the cerebral peduncles and extending posteriorly from the optic chiasm toward the pons.^[1]^[2] This fossa forms a critical neuroanatomical landmark at the base of the brain, separating the descending fiber tracts of the cerebral peduncles and serving as a conduit for several vital neurovascular elements.^[2]^[3] From rostral to caudal, the interpeduncular fossa contains the tuber cinereum (including the infundibular stalk of the pituitary gland), the paired mammillary bodies, the posterior perforated substance, and the emerging rootlets of the oculomotor nerves (cranial nerve III).^[1] The oculomotor nerve rootlets exit the midbrain medial to the cerebral peduncles within this fossa, innervating the extraocular muscles (except the lateral rectus and superior oblique) and contributing to pupillary constriction and accommodation.^[2] The posterior perforated substance, occupying much of the anterior two-thirds of the fossa, is characterized by numerous small perforations through which paramedian thalamic and mesencephalic arteries penetrate to supply the midbrain, thalamus, and subthalamic regions.^[4] These perforating branches arise primarily from the terminal segment of the basilar artery (23%), the proximal superior cerebellar arteries (45%), and the P1 segment of the posterior cerebral arteries (32%), with diameters ranging from 0.20 mm to 0.57 mm and frequent anastomoses between them.^[4] The basilar artery itself courses along the floor of the fossa, accompanied by the posterior cerebral and superior cerebellar arteries, forming part of the circle of Willis.^[5] Clinically, the interpeduncular fossa holds significant surgical importance due to its deep location and dense neurovascular content, making it a target for approaches such as the subtemporal route to address midbrain lesions, basilar artery aneurysms, or tumors in the posterior fossa.^[5] Endoscopic assistance in these procedures can enhance visualization of structures like the contralateral oculomotor nerve and posterior perforated substance by up to 81.7% compared to standard microscopy.^[5] Damage to the perforating vessels here can lead to devastating infarcts in the midbrain or diencephalon, underscoring the need for precise microsurgical techniques.^[4]

Anatomy

Location and gross features

The interpeduncular fossa is a deep depression on the ventral surface of the midbrain, located between the two cerebral peduncles (crura cerebri).^[3] It lies at the base of the brain within the subarachnoid space, forming the posterior floor of the interpeduncular cistern, a widening of the ambient cistern that contains cerebrospinal fluid and key neurovascular structures.^[3] This positioning situates the fossa immediately superior to the pons and posterior to the optic chiasm, contributing to the overall contour of the midbrain's inferior aspect.^[1] Macroscopically, the interpeduncular fossa appears as a narrow, longitudinally oriented depression that narrows caudally as the cerebral peduncles converge toward the pons.^[3] A prominent gross feature is the paired oculomotor sulci, shallow grooves located along the medial aspects of each cerebral peduncle that border the fossa laterally; these sulci mark the emergence point for the rootlets of the oculomotor nerve (cranial nerve III), which exit the midbrain to enter the interpeduncular cistern.^[3] The floor of the fossa itself is relatively smooth, reflecting the underlying tegmental structures of the midbrain without prominent surface markings beyond these sulci.^[1]

Boundaries

The interpeduncular fossa constitutes a wedge-shaped depression on the anterior aspect of the midbrain, situated between the cerebral peduncles.^[6] Its anterior boundary is demarcated by the optic chiasm, which forms the rostral limit of this structure.^[7]^[8] Anterolaterally, the fossa is confined by the converging optic tracts, which cradle its sides as they extend from the optic chiasm toward the lateral geniculate bodies.^[7]^[8] The posterolateral boundaries are established by the diverging cerebral peduncles, which emerge caudally and laterally to enclose the fossa's margins.^[7]^[8] Posteriorly, the anterosuperior surface of the pons defines the caudal extent, where the peduncles transition into pontine structures.^[7] In depth, the ventral tegmental area occupies the region immediately dorsal to the fossa's floor, with the interpeduncular fossa serving as its ventral boundary in anatomical delineations.^[9]

The interpeduncular fossa serves as a key neuroanatomical depression housing several critical structures on its floor, which extends from posterior to anterior. Posteriorly, the floor features the posterior perforated substance, a triangular region of gray matter perforated by numerous small arteries that supply the midbrain and diencephalon.^[10] Moving anteriorly, the mammillary bodies appear as paired, rounded elevations of hypothalamic gray matter involved in memory processing and limbic circuitry.^[6] Further forward lies the tuber cinereum, a shallow depression of the hypothalamus from which the infundibulum, or pituitary stalk, arises to connect directly to the pituitary gland, facilitating neuroendocrine regulation.^[1] Emerging from the oculomotor sulcus along the lateral margins of the fossa are the rootlets of the oculomotor nerve (cranial nerve III), which originate in the midbrain tegmentum and course anteriorly to innervate extraocular muscles and contribute to pupillary control.^[2] The basal vein of Rosenthal passes alongside the fossa, receiving tributaries from its vicinity before draining into the great cerebral vein, thus contributing to deep cerebral venous drainage.^[11] Vascularly, the fossa is traversed by segments of the circle of Willis, including the bifurcation of the basilar artery at its posterior aspect into the posterior cerebral arteries and the posterior communicating arteries linking to the internal carotid arteries, forming an anastomotic ring essential for cerebral blood supply.^[12] Additionally, the interpeduncular cistern occupies the subarachnoid space overlying the fossa, containing cerebrospinal fluid (CSF) that circulates between the midbrain and surrounding structures to cushion and nourish the brain.^[13]

Embryology and development

Formation in embryonic development

The interpeduncular fossa forms during early human embryonic development as part of the differentiation of prosomere 1 (p1) from the neural tube, marking the ventral midline at the junction between the diencephalon and mesencephalon. At this stage, the prosencephalon has divided into telencephalon and diencephalon, and the mesencephalon emerges as a distinct primary brain vesicle, with p1 representing the rostral-most diencephalic segment whose floor plate contributes significantly to the fossa's depression. This regionalization follows the prosomeric model, where transverse neuromeric units segment the neural tube, establishing the foundational architecture for ventral brainstem structures.^[14]^[15] The ventral midline of the developing brainstem, including the interpeduncular fossa, is critically patterned by sonic hedgehog (SHH) signaling, which induces floor plate formation and ventralizes the neural epithelium. SHH, secreted from the notochord and prechordal plate during early somitogenesis (around week 4), diffuses dorsally to specify ventral identities in the midbrain and diencephalon, promoting the proliferation and differentiation of midline progenitors that line the future fossa. This signaling pathway ensures the precise dorsoventral polarity essential for the fossa's role as a conduit for midline nuclei and tracts.^[16]^[17] During neural tube closure (completed by week 4) and subsequent prosencephalon division (week 5), the interpeduncular fossa integrates with adjacent diencephalic structures, such as the hypothalamus and mammillary bodies, through shared signaling gradients and boundary formation. The mammillary bodies arise from the ventral diencephalon near p1, while hypothalamic progenitors emerge rostrally, with SHH maintaining midline integrity across these interfaces to prevent ectopic growth. By week 8, key milestones include the establishment of the oculomotor nucleus in the midbrain tegmentum, adjacent to the fossa, and the initial bundling of longitudinal fibers that outline the cerebral peduncles, deepening the fossa's contours.^[14]^[18]

Associated congenital anomalies

The interpeduncular fossa is prominently involved in Joubert syndrome, a ciliopathy characterized by midbrain-hindbrain malformations, where the fossa appears abnormally deepened on magnetic resonance imaging (MRI) due to cerebellar vermian hypoplasia and the pathognomonic "molar tooth sign."^[19]^[20] This sign arises from the combination of a deepened interpeduncular fossa, elongated and thickened superior cerebellar peduncles that appear horizontal, and vermian hypoplasia, reflecting disrupted isthmic organizer signaling during early brain development. Joubert syndrome results from biallelic mutations in over 40 genes associated with primary cilia dysfunction, with notable examples including AHI1 (encoding jouberin, involved in cerebellar development) and NPHP1 (encoding nephrocystin-1, linked to ciliopathy pathways); these mutations typically follow an autosomal recessive inheritance pattern.^[21] The condition is rare, with an estimated prevalence of 1 in 80,000 to 1 in 100,000 live births, though underdiagnosis may occur due to variable expressivity.^[22] Imaging in Joubert syndrome consistently reveals the deepened interpeduncular fossa as a core feature of the molar tooth sign, alongside superior cerebellar peduncle thickening and midbrain tectal beaking, which aid in early diagnosis via axial MRI sequences.^[23] Neurologically, involvement of the interpeduncular fossa and associated structures contributes to characteristic symptoms such as truncal ataxia from cerebellar dysfunction, neonatal hypotonia evolving into spasticity, and global developmental delays affecting motor, cognitive, and language milestones; these arise from impaired decussation of corticospinal and sensory tracts in the malformed midbrain-hindbrain junction.^[24]

Clinical significance

Pathological conditions

The interpeduncular fossa, as part of the basal cisterns, is susceptible to various acquired pathological processes that can lead to compression, inflammation, or vascular compromise of adjacent neural structures. These conditions often manifest through mass effect on the midbrain, cranial nerves, or cerebrospinal fluid (CSF) pathways, resulting in neurological deficits.^[25] Neurocutaneous melanosis (NCM), a rare phakomatosis arising from congenital melanocytic proliferation, frequently involves leptomeningeal melanocytic deposits along the ventral brainstem, including the interpeduncular fossa. These deposits can cause hydrocephalus due to CSF obstruction and leptomeningeal involvement, with malignant transformation to melanoma occurring in up to 40-50% of symptomatic cases. Primary intracranial melanomas, representing about 1% of all melanomas, may also localize to the interpeduncular fossa, leading to mass effect and neurological symptoms.^[26]^[27]^[28] Vascular pathologies, such as aneurysms of the basilar artery or circle of Willis, can compress the interpeduncular fossa, particularly giant or partially thrombosed basilar apex aneurysms that extend into the cistern and cause midbrain edema or cranial nerve dysfunction. Infarction risks arise from occlusion of peduncular perforators, which supply the midbrain; for instance, Weber syndrome involves ischemic damage to oculomotor nerve fascicles in the fossa, presenting as ipsilateral third nerve palsy with contralateral hemiparesis. Bilateral cerebral peduncular infarctions, though rare (occurring in approximately 0.26% of acute ischemic stroke cases), can result from vertebrobasilar occlusive disease affecting these perforators.^[29]^[30]^[31] Infectious and inflammatory conditions often affect the interpeduncular cistern, leading to CSF accumulation and basal meningeal involvement. Tuberculous meningitis commonly produces exudates in the interpeduncular cistern, compromising midbrain-supplying vessels and causing infarcts or hydrocephalus. Other infections, such as Epstein-Barr virus or cryptococcal meningitis, may show leptomeningeal enhancement in the basal cisterns, including the interpeduncular fossa, on MRI. Chronic meningitis can present with focal enhancement at the fossa, indicating localized inflammation.^[32]^[33]^[34] Rare tumors like craniopharyngiomas can invade the interpeduncular fossa floor, splaying the cerebral peduncles and compressing the midbrain, often without significant brainstem edema. These lesions typically arise from sellar/suprasellar regions and extend posteriorly. Multiple sclerosis may also present with demyelinating lesions in the fossa, causing ophthalmoplegia due to involvement of the third nerve.^[35]^[36] Common symptoms across these pathologies include oculomotor nerve palsy, leading to ptosis, mydriasis, and eye movement deficits, as well as pituitary dysfunction from suprasellar extension in tumors. Hydrocephalus may cause headache, nausea, and altered consciousness. Diagnosis relies on MRI or CT imaging, which reveals mass effect, signal hyperintensities in the cistern (e.g., on FLAIR for meningitis), or vascular abnormalities like aneurysm filling defects.^[37]^[38]^[39]

Surgical and diagnostic relevance

The interpeduncular fossa serves as a critical surgical target in neurosurgical interventions for vascular anomalies and neoplasms in the posterior fossa and midbrain region. Common approaches include the subtemporal craniotomy, pioneered by Drake in the 1970s, which offers a lateral trajectory to the fossa by retracting the temporal lobe superiorly, facilitating access to basilar artery aneurysms and adjacent tumors.^[40] The pterional craniotomy, refined by Yasargil in the mid-1970s as part of broader microsurgical advancements, provides anterolateral exposure and is often combined with pretemporal modifications to enhance visualization of the interpeduncular cistern for lesions such as basilar tip aneurysms.^[40] Endoscopic-assisted techniques, integrated with standard subtemporal approaches since the early 2000s, utilize 0° and 30° endoscopes to improve illumination and depth perception, increasing visibility of key structures like the basilar artery by up to 81.7% and reducing the need for extensive brain retraction during tumor resections or aneurysm clippings.^[5] In diagnostic imaging, the interpeduncular fossa acts as a reliable landmark for evaluating subarachnoid spaces and vascular pathology. Computed tomography (CT) angiography is the initial modality for detecting vascular anomalies, such as aneurysms arising from the circle of Willis, by delineating the posterior communicating and basilar arteries within the fossa.^[6] The "interpeduncular fossa sign"—hyperdensity in the fossa on non-contrast CT—indicates subarachnoid hemorrhage with high specificity, second only to Sylvian fissure involvement in diagnostic reliability.^[41] Magnetic resonance imaging (MRI), particularly T2-weighted sequences and cisternography, assesses cistern patency and brainstem displacement, with the interpeduncular angle serving as an objective marker for intracranial pressure changes; an angle below 40.5° signals hypotension affecting the cistern.^[42] These imaging techniques also aid preoperative planning for brainstem surgery by identifying the fossa as a ventral midbrain reference point.^[43] Surgical risks in the interpeduncular fossa stem from its proximity to the oculomotor nerve (cranial nerve III) and perforating branches of the circle of Willis, where manipulation can lead to nerve palsy or ischemia. Perforators from the posterior cerebral artery (averaging four per P1 segment) and posterior communicating artery (averaging seven) supply critical midbrain structures, and their injury during aneurysm clipping risks third nerve dysfunction, with recovery rates varying from 80% in partial palsies but poorer in complete cases preoperatively.^[44]^[45] Microsurgical evolution since the 1970s has mitigated some hazards through better illumination and navigation, yet venous infarction from temporal retraction remains a concern in subtemporal routes.^[5] Procedurally, the fossa's cistern is relevant in lumbar puncture, where cerebrospinal fluid removal alters interpeduncular cistern pressure, potentially widening the interpeduncular angle or inducing hypotension signs on follow-up MRI, guiding management in conditions like normal pressure hydrocephalus.^[42] In stereotactic navigation for deep midbrain lesions, the fossa provides a ventral reference for trajectory planning, enhancing precision in endoscopic or microsurgical entries to minimize parenchymal damage.^[43]

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