Acquired hypothalamic obesity: A clinical overview and update.

Hypothalamic obesity (HO) is a rare and complex disorder that confers substantial morbidity and excess mortality. HO is a unique subtype of obesity characterized by impairment in the key brain pathways that regulate energy intake and expenditure, autonomic nervous system function, and peripheral hormonal signalling. HO often occurs in the context of hypothalamic syndrome, a constellation of symptoms that follow from disruption of hypothalamic functions, for example, temperature regulation, sleep-wake circadian control, and energy balance. Genetic forms of HO, including the monogenic obesity syndromes, often impact central leptin-melanocortin pathways. Acquired forms of HO occur as a result of tumours impacting the hypothalamus, such as craniopharyngioma, surgery or radiation to treat those tumours, or other forms of hypothalamic damage, such as brain injury impacting the region. Risk for severe obesity following hypothalamic injury is increased with larger extent of hypothalamic damage or lesions that contain the medial and posterior hypothalamic nuclei that support melanocortin signalling pathways. Structural damage in these hypothalamic nuclei often leads to hyperphagia, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue, the collective effect of which is rapid weight gain. Individuals with hyperphagia are perpetually hungry. They do not experience fullness at the end of a meal, nor do they feel satiated after meals, leading them to consume larger and more frequent meals. To date, most efforts to treat HO have been disappointing and met with limited, if any, long-term success. However, new treatments based on the distinct pathophysiology of disturbed energy homeostasis in acquired HO may hold promise for the future.

Microsurgical Resection of a Parachiasmatic Craniopharyngioma via a Left-Sided Pterional Transsylvian Approach.

Craniopharyngiomas are histologically benign tumors that originate from squamous rests along the pituitary stalk. They make up approximately 1.2% to 4.6% of all intracranial tumors and do not show significant differences in occurrence based on sex. Adamantinomatous craniopharyngiomas have 2 peaks of incidence, commonly observed in patients from ages 5 to 15 years and again from 45 to 60 years. In contrast, papillary craniopharyngiomas mainly affect adults in their fifth and sixth decades of life.1 The "malignancy" of craniopharyngiomas is attributed to their location and the challenges associated with achieving complete removal because they can manifest in the sellar, parachiasmatic, and intraventricular regions or a combination of these.2,3 Various approaches have been used to resect these tumors.4,5 Radical resection offers the most promising option for disease control, potential cure, and the ability to transform the disease from lethal to survivable in children, allowing for a functional adult life.2,3 Meticulous evaluation is crucial to determine the appropriate approach and side, with particular emphasis on closely examining the relationship between the tumor and optic pathways (nerve, chiasm, tract), which are frequently involved. This assessment should also include the tumor's relationship with other crucial structures, such as the hypothalamus and adjacent arteries, to ensure that the strategy is adjusted accordingly to further minimize the risk of postoperative morbidity. Video 1 demonstrates a left-sided pterional transsylvian approach to remove a parachiasmatic craniopharyngioma involving the left optic chiasm and tract.

The Role of Tumor-Associated Hypothalamic Involvement in Surgical Treatment and Long-Term Outcome in Adult Patients with Craniopharyngioma.

INTRODUCTION: Hypothalamic invasion in pediatric patients with craniopharyngioma negatively influences clinical outcomes. It has been shown that radiologic classification of hypothalamic invasion can effectively predict surgical strategies to minimize postoperative comorbidities in pediatric patients. However, no comparative analysis has been performed in adult patients with craniopharyngioma. This study implements the previously established radiologic classification to characterize postoperative morbidity, surgical outcome, and distress in adult patients with craniopharyngioma. METHODS: Electronic medical records of 22 adult patients with craniopharyngioma were used to analyze patient demographics, surgical data, endocrinologic and ophthalmologic status, and histopathology in a retrospective single-center study. Questionnaires regarding postoperative distress (National Comprehensive Cancer Network Distress Thermometer and Problem List), comorbidities (Charlson Comorbidity Index), employment status, and need for supportive care were distributed. Magnetic resonance imaging scans were categorized according to Puget et al. RESULTS: Patients with hypothalamic involvement show significantly higher rates of postoperative diabetes insipidus and higher scores on the National Comprehensive Cancer Network Distress Thermometer. This significant difference was lost when considering postoperative Puget grades. Puget grades 1 and 2 were found to be associated with the use of a subfrontal surgical approach (hazard ratio, 4.080; confidence interval, 1.153-14.431; P = 0.029). CONCLUSIONS: Our results point toward a possible predictive role of preoperative hypothalamic invasion for postoperative diabetes insipidus as well as higher perceived levels of distress after surgery, which may be established in larger patient cohorts. Furthermore, a subfrontal surgical approach seems to be predicted by tumors with hypothalamic invasion. In this case, preoperative magnetic resonance imaging grading may help guide the planning of an optimal surgical strategy for adults with craniopharyngioma to reduce postoperative morbidity.

Pediatric craniopharyngiomas: magnetic resonance imaging assessment for hypothalamus-pituitary axis dysfunction and outcome prediction.

BACKGROUND: In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis. OBJECTIVE: To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas. MATERIALS AND METHODS: We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2min). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes. RESULTS: Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), and between peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34). CONCLUSION: Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2min intensity of the tumor cystic component are independent predictors of extent of adamantinomatous craniopharyngioma excision and recurrence.

Treatment of hypothalamic obesity in people with hypothalamic injury: new drugs are on the horizon.

Hypothalamic obesity (HO) is a complex and rare disorder affecting multiple regulatory pathways of energy intake and expenditure in the brain as well as the regulation of the autonomic nervous system and peripheral hormonal signaling. It can be related to monogenic obesity syndromes which often affect the central leptin-melanocortin pathways or due to injury of the hypothalamus from pituitary and hypothalamic tumors, such as craniopharyngioma, surgery, trauma, or radiation to the hypothalamus. Traditional treatments of obesity, such as lifestyle intervention and specific diets, are still a therapeutic cornerstone, but often fail to result in meaningful and sustained reduction of body mass index. This review will give an update on pharmacotherapies of HO related to hypothalamic injury. Recent obesity drug developments are promising for successful obesity intervention outcomes.

Tocilizumab for the fifth progression of cystic childhood craniopharyngioma-a case report.

We present the case of a 15-year-old girl, with a fifth cystic progression of an adamantinomatous craniopharyngioma after multiple surgeries and previous local radiotherapy. She had severe visual impairment, panhypopituitarism including diabetes insipidus, and several components of hypothalamic damage, including morbid obesity and severe fatigue. To prevent further late effects hampering her quality of survival, she was treated biweekly with intravenous tocilizumab, an anti-interleukin-6 agent, which stabilized the cyst for a prolonged time. Based on the biology of adamantinomatous craniopharyngioma, this immune-modulating treatment seems promising for the treatment of this cystic tumor in order to reduce surgery and delay or omit radiotherapy.

National UK guidelines for the management of paediatric craniopharyngioma.

Although rare, craniopharyngiomas constitute up to 80% of tumours in the hypothalamic-pituitary region in childhood. Despite being benign, the close proximity of these tumours to the visual pathways, hypothalamus, and pituitary gland means that both treatment of the tumour and the tumour itself can cause pronounced long-term neuroendocrine morbidity against a background of high overall survival. To date, the optimal management strategy for these tumours remains undefined, with practice varying between centres. In light of these discrepancies, as part of a national endeavour to create evidence-based and consensus-based guidance for the management of rare paediatric endocrine tumours in the UK, we aimed to develop guidelines, which are presented in this Review. These guidelines were developed under the auspices of the UK Children's Cancer and Leukaemia Group and the British Society for Paediatric Endocrinology and Diabetes, with the oversight and endorsement of the Royal College of Paediatrics and Child Health using Appraisal of Guidelines for Research & Evaluation II methodology to standardise care for children and young people with craniopharyngiomas.

Inhibition of integrated stress response protects against lipid-induced senescence in hypothalamic neural stem cells in adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a benign tumor with malignant clinical manifestations. ACP adjacent to the hypothalamus often presents with more severe symptoms and higher incidence of hypothalamic dysfunction. However, the mechanism underlying hypothalamic dysfunction remains unclear. METHODS: Immunostaining was performed to determine the nerve damage to the floor of the third ventricle (3VF) adjacent to ACP and to examine the recruitment and senescence of hypothalamic neural stem cells (htNSCs). The accumulation of lipid droplets (LDs) in htNSCs was evaluated via BODIPY staining, oil red O staining, and transmission electron microscopy. In vitro and in vivo assays were used to evaluate the effect of cystic fluid or oxidized low-density lipoprotein and that of oxytocin (OXT) on htNSC senescence and the hypothalamic function. The protein expression levels were analyzed using western blotting. RESULTS: htNSCs with massive LD accumulation were recruited to the damaged 3VF adjacent to ACP. The LDs in htNSCs induced senescence and reduced neuronal differentiation; however, htNSC senescence was effectively prevented by inhibiting either CD36 or integrated stress response (ISR) signaling. Furthermore, OXT pretreatment reduced lipotoxicity via the inhibition of ISR signaling and the repair of the blood-brain barrier. CONCLUSIONS: Reduced LD aggregation or ISR signaling inhibition prevented senescence in htNSCs and identified molecular pathways and potential therapeutic targets that may improve hypothalamic dysfunction in ACP patients.

Expanded endoscopic endonasal approach for the resection of midline craniopharyngiomas with hypothalamic involvement.

BACKGROUND: With relevant surrounding neurological structures and potential involvement of the hypothalamus, the surgical management of craniopharyngiomas is complex. Compared to the transcranial approach, the expanded endoscopic endonasal approach provides direct access to the supradiaphragmatic and retrochiasmatic areas without crossing nerves and arteries. METHOD: Based on our substantial experience of 68 patients operated on between 2008 and 2022 by endoscopic surgery, our strategy has evolved such that all of our midline infundibular craniopharyngiomas with hypothalamic involvement are currently treated with an expanded endonasal route, except for tumours isolated to the third ventricle. Vascularized mucosal nasoseptal flaps are required for closure. Fine details of the related anatomy and surgical technique are described. CONCLUSION: Expanded endoscopic endonasal approach is a safe and effective route for resection of midline suprasellar craniopharyngiomas with hypothalamic involvement in centres of expertise.

Exploring the pathological relationships between adamantinomatous craniopharyngioma and contiguous structures with tumor origin.

PURPOSE: Identifying relationships between craniopharyngiomas (CPs) and contiguous structures, and tumor origin are crucial for treatments. This study attempted to explore the relationships and tumor origin. METHODS: CPs that underwent endoscopic surgeries were enrolled. The interfacial specimens of CPs attaching the hypothalamus, pituitary stalk (PS), pituitary grand (PG), optic chiasma (OC) and brain tissue (BT) were pathologically examined. Boundaries between CPs and these structures were observed during operations. Expression of ß-catenin and stem cell markers were analyzed to explore the tumor origin. Outcomes of patients were assessed. RESULTS: A total of 34 CPs were categorized into two groups based on the locations of finger-like protrusions (FP). Group A comprised 18 CPs with FP only present in the specimens attaching to hypothalamus. The surface of these CPs was fused with hypothalamus under endoscopic videos. However, the specimens attaching to the PS, PG, OC, and BT showed no FP. Clear boundaries was observed between these CPs and these structures. Group B comprised 16 CPs with FP only present in the specimens attaching to PS. The tumor surface was fused with PS. Specimens attaching to the hypothalamus, PG, OC and BT showed no FP. Clear boundary was observed among these CPs with these structures. These results implied CPs only invaded a certain part of hypothalamic-pituitary axis. ß-catenin and stem cells markers mainly distributed in the FP tissues of both groups. Patients in group B achieved better outcomes than group A. CONCLUSIONS: CPs only invade the hypothalamic-pituitary axis with FP and the FP would be the tumor origin.

Postoperative hypothalamic damage predicts postoperative weight gain in patients with adult-onset craniopharyngioma.

OBJECTIVE: This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult-onset craniopharyngioma. METHODS: The data of 96 patients with surgically treated primary adult-onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression. RESULTS: Forty-seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow-up, respectively. Postoperative weight significantly increased during the first 6 months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p = 0.005 and p = 0.002) and with HO (p = 0.001 and p = 0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p = 0.008) could predict postoperative weight gain ≥5%. CONCLUSIONS: Significant postoperative weight gain is common in patients with adult-onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO.

Quality of Life in Craniopharyngioma: A Systematic Review.

BACKGROUND: Craniopharyngiomas are morbid tumors that significantly reduce patients' quality of life (QoL). The lifelong burden of endocrine, visual, hypothalamic, and limbic dysfunction can have disastrous consequences for the physical and psychosocial health of patients. Elucidating the factors that influence QoL could guide therapeutic interventions to improve patient well-being. METHODS: A systematic review was performed in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement using the PubMed and Medline databases. Studies that had reported patient QoL using validated metrics in both adult and pediatric populations were included. Bias and methodological rigor were assessed using the MINORS (methodological index for nonrandomized studies) criteria. RESULTS: A total of 25 studies, including 2025 patients, were available for review. Most studies were small, retrospective, cohort studies with a high risk of bias. The QoL of the patients with craniopharyngioma was lower than that of the general population. Hypothalamic involvement was consistently the strongest predictor of QoL. Endocrinopathy contributed to morbidity but could be ameliorated by hormone replacement therapy. Social and emotional dysregulation and a poor memory are common complaints after surgery, and iatrogenic damage to the infundibulum, hypothalamus, limbic system, and frontal lobes might underlie these concerns. Sleep-wake cycle dysfunction and hypothalamic obesity are serious consequences of hypothalamic damage. CONCLUSIONS: An experienced multidisciplinary team is necessary to optimally manage the complex cases of these patients. The poor QoL of patients with craniopharyngioma is multifactorial. However, the contribution of iatrogenesis is not insubstantial. Improved surgical techniques, focusing on hypothalamic preservation, and adjuvant treatment options are required to improve the well-being of these patients.

Adamantinomatous craniopharyngioma cyst fluid can trigger inflammatory activation of microglia to damage the hypothalamic neurons by inducing the production of ß-amyloid.

INTRODUCTION: The mechanism by which adamantinomatous craniopharyngioma (ACP) damages the hypothalamus is still unclear. Cyst fluid rich in lipids and inflammatory factors is a characteristic pathological manifestation of ACP and may play a very important role in hypothalamic injury caused by tumors. OBJECTIVE: The objective of this study was to construct a reliable animal model of ACP cyst fluid-induced hypothalamic injury and explore the specific mechanism of hypothalamic injury caused by cyst fluid. METHODS: An animal model was established by injecting human ACP cyst fluid into the bilateral hypothalamus of mice. ScRNA-seq was performed on the mice hypothalamus and on an ACP sample to obtain a complete gene expression profile for analysis. Data verification was performed through pathological means. RESULTS: ACP cystic fluid caused growth retardation and an increased obesity index in mice, affected the expression of the Npy, Fgfr2, Rnpc3, Sst, and Pcsk1n genes that regulate growth and energy metabolism in hypothalamic neurons, and enhanced the cellular interaction of Agrp-Mc3r. ACP cystic fluid significantly caused inflammatory activation of hypothalamic microglia. The cellular interaction of CD74-APP is significantly strengthened between inflammatory activated microglia and hypothalamic neurons. Beta-amyloid, a marker of neurodegenerative diseases, was deposited in the ACP tumor tissues and in the hypothalamus of mice injected with ACP cyst fluid. CONCLUSION: In this study, a novel animal model of ACP cystic fluid-hypothalamic injury was established. For the first time, it was found that ACP cystic fluid can trigger inflammatory activation of microglia to damage the hypothalamus, which may be related to the upregulation of the CD74-APP interaction and deposition of ß-amyloid, implying that there may be a similar mechanism between ACP cystic fluid damage to the hypothalamus and neurodegenerative diseases.

Hypothalamic syndrome.

Hypothalamic syndrome (HS) is a rare disorder caused by disease-related and/or treatment-related injury to the hypothalamus, most commonly associated with rare, non-cancerous parasellar masses, such as craniopharyngiomas, germ cell tumours, gliomas, cysts of Rathke's pouch and Langerhans cell histiocytosis, as well as with genetic neurodevelopmental syndromes, such as Prader-Willi syndrome and septo-optic dysplasia. HS is characterized by intractable weight gain associated with severe morbid obesity, multiple endocrine abnormalities and memory impairment, attention deficit and reduced impulse control as well as increased risk of cardiovascular and metabolic disorders. Currently, there is no cure for this condition but treatments for general obesity are often used in patients with HS, including surgery, medication and counselling. However, these are mostly ineffective and no medications that are specifically approved for the treatment of HS are available. Specific challenges in HS are because the syndrome represents an adverse effect of different diseases, and that diagnostic criteria, aetiology, pathogenesis and management of HS are not completely defined.

Papillary Craniopharyngioma: A Type of Tumor Primarily Impairing the Hypothalamus - A Comprehensive Anatomo-Clinical Characterization of 350 Well-Described Cases.

OBJECTIVE: Papillary craniopharyngiomas (PCPs) represent a rare histological type of craniopharyngiomas (CPs) usually involving the hypothalamus. This study systematically analyzes the clinical-anatomical correlation between tumor topography and symptoms related to hypothalamic dysfunction in the largest series of PCPs ever gathered. METHODS: From 5,346 CP reports published from 1856 to 2021, we selected 350 well-described cases of the squamous-papillary type. Clinical presentation, tumor topography, severity of hypothalamic adhesion, patient outcome, and tumor recurrence were thoroughly analyzed. RESULTS: PCPs predominantly occur in adult (96.3%), male (61.7%) patients presenting with headache (63.4%), visual alterations (56.2%), and psychiatric disturbances (50.4%). Most PCPs are solid (50%), round (72%) lesions that occupy the third ventricle (3V, 94.8%) and show low-risk severity adhesions to the hypothalamus (66.8%). Two major topographical categories can be found: strictly 3V (57.5%), growing above an intact 3V floor, and not-strictly or infundibulo-tuberal (32.9%), expanding at the infundibulum and/or tuber cinereum. The hypothalamic syndrome predominated among strictly 3V PCPs (p < 0.001). Psychiatric symptoms (p < 0.001) and high-risk hypothalamic attachments (p = 0.031) related to unfavorable postoperative outcomes among patients treated from 2006 onwards. The not-strictly 3V topography was identified as the major predictor of high-risk hypothalamic attachments (71.2% correctly predicted), which, along with incomplete tumor removal (p = 0.018), underlies the higher tumor recurrence of this topography (p = 0.001). CONCLUSIONS: This systematic review evidences that PCP topography is a major determinant of hypothalamic-related symptoms, type of hypothalamic attachments, and tumor recurrence rate. Accurate preoperative definition of PCP-hypothalamus relationships is essential for the judicious, safe management of these complex lesions.

Trans-lamina Terminalis Approach for Resection of Third Ventricular Tumor.

Granular cell tumors are rare vascular neoplastic lesions of the sellar and suprasellar region that usually arise from the pituitary stalk but can originate as low as the posterior pituitary or as high as the tuber cinereum.1 Complete resection, although ideal, can yield high rates of endocrine or visual morbidity.1,2 On headache workup, a 66-year-old woman was found to have a 1.2 × 1.1 × 1.3-cm contrast-enhancing lesion in the anterior-inferior third ventricle, posterior to the infundibulum. Endocrine testing was unremarkable, and a lumbar puncture was nondiagnostic. An open biopsy and possible resection were selected by the patient over short-interval imaging. A translamina terminalis approach was selected over a transsphenoidal approach to preserve the third ventricular floor (Video 1). A right frontotemporal craniotomy was performed, including flattening of the lesser sphenoid wing. The optic chiasm was exposed via subfrontal microsurgical dissection, and the lamina terminalis was opened sharply. A firm, vascular tumor was identified extending into the anterior-inferior aspect of the third ventricle. Frozen pathologic analysis was nondiagnostic. Given the proximity of the optic chiasm, a complete piecemeal microsurgical resection was performed, preserving the floor and lateral walls of the third ventricle and optic apparatus. Final pathology was a granular cell tumor. Postoperatively, the patient had transient diabetes insipidus, with preserved vision and normal endocrine function on follow-up. The trans-lamina terminalis approach can be used for safe resection of anterior third ventricular tumors. Preservation of the floor and walls of the third ventricle is critical to avoid morbidity.

Strictly third ventricle craniopharyngiomas: pathological verification, anatomo-clinical characterization and surgical results from a comprehensive overview of 245 cases.

The strictly third ventricle craniopharyngioma topography (strictly 3V CP) defines the subgroup of lesions developed above an anatomically intact third ventricle floor (3VF). The true existence of this exceedingly rare topographical category is highly controversial owing to the presumed embryological CP origin from Rathke's pouch, a structure developmentally situated outside the neural tube. This study thoroughly analyzes the largest series of strictly 3V CPs ever collected. From 5346 CP reports published between 1887 and 2021, we selected 245 cases with reliable pathological, surgical, and/or neuroradiological verification of an intact 3VF beneath the tumor. This specific topography occurs predominantly in adult (92.6%), male (64.4%) patients presenting with headache (69.2%), and psychiatric disturbances (59.2%). Neuroradiological features defining strictly 3V CPs are a tumor-free chiasmatic cistern (95.9%), an entirely visible pituitary stalk (86.4%), and the hypothalamus positioned around the tumor's lower pole (92.6%). Most are squamous papillary (82%), showing low-risk severity adhesions to the hypothalamus (74.2%). The adamantinomatous variant, however, associates a higher risk of severe hypothalamic adhesion (p < .001). High-risk attachments are also associated with psychiatric symptoms (p = .013), which represented the major predictor for unfavorable prognoses (83.3% correctly predicted) among cases operated from 2006 onwards. CP recurrence is associated with infundibulo-tuberal symptoms (p = .036) and incomplete surgical removal (p = .02). The exclusive demographic, clinico-pathological and neuroradiological characteristics of strictly 3V CPs make them a separate, unique topographical category. Accurately distinguishing strictly 3V CPs preoperatively from those tumors replacing the infundibulum and/or tuber cinereum (infundibulo-tuberal or not strictly 3V CPs) is critical for proper, judicious surgical planning.