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.

Feasibility of transsphenoidal approach for hypothalamic biopsy based on a radiological evaluation of subchiasmatic corridor dimension.

BACKGROUND: Surgical access to hypothalamic pathologies can be challenging. Recent case series demonstrate that the transsphenoidal approach to the hypothalamus can be safe and effective, however, may not be feasible in all patients. This study aims to investigate the feasibility of the endonasal transsphenoidal suprasellar subchiasmatic (ETSS) approach to the hypothalamus through a radiological evaluation of the subchiasmatic corridor dimension in an adult population. METHODS: A retrospective review of magnetic resonance imaging of the brain was performed on 164 consecutive adult patients at our institution, of which 100 patients were deemed eligible for inclusion. Measurements were obtained at the two narrowest points along the subchiasmatic corridor: the subchiamastic window, which is the face of the subchiasmatic corridor and the midpoint window, which is located in the middle of the subchiasmatic corridor. Based on defined parameters, including the subchasmiatic window width (SW), subchiasmatic window height (SH), midpoint window width (MW), and midpoint window height (MH), patients were dichotomised into groups: patients with subchiasmatic corridor measurements any dimension of less than 3 mm, or patients with dimensions greater than or equal to 3 mm. RESULTS: A total of 72 (72%) of the study population had dimensions of equal to or greater than 3 mm throughout the entirety of the subchiasmatic corridor, making hypothalamic biopsy feasible through the ETSS route for these patients. CONCLUSION: Based on a radiological evaluation of the subchiasmatic corridor dimension in an Australian adult population, the majority of the population are suitable to undergo an endonasal transsphenoidal suprasellar subchiasmatic biopsy of the hypothalamus.

Syndrome of inappropriate secretion of antidiuretic hormone as an initial sign of primary central nervous system lymphomas in the hypothalamus.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) rarely originates in the hypothalamus. Hypothalamic PCNSL can present with various symptoms specific to dysfunction of the hypothalamus, including consciousness disturbance, cognitive impairment, hypopituitarism, and diabetes insipidus (DI). However, it remains unclear whether syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can present as an initial sign of hypothalamic PCNSL. METHODS: Ninety-nine patients with PCNSL were diagnosed between January 2006 and December 2020 at our institutes. The initial symptoms and signs, hypothalamic-pituitary functions, serum sodium (Na) value, Karnofsky Performance Status (KPS) score on admission, and duration from onset to diagnosis were retrospectively investigated from the medical charts. RESULTS: Eight and 91 patients had hypothalamic PCNSL (hypothalamic group) and PCNSL located in other regions (control group), respectively. Patients' pathological diagnoses were diffuse large B-cell lymphoma (97 patients) and intravascular lymphoma (two patients). Six patients presented with hyponatremia derived from SIADH or suspected SIADH, and one presented with DI. Statistically significant differences between the hypothalamic and control groups were detected only in the preoperative serum Na values and KPS scores. CONCLUSION: SIADH can be an initial presentation of hypothalamic PCNSL. Early detection of hypothalamic PCNSL from SIADH may lead to proper management and improved prognosis.

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.

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.

Hypothalamic connectivities predict individual differences in ADT-elicited changes in working memory and quality of life in prostate cancer patients.

Androgen deprivation therapy (ADT) has been associated with adverse effects on cognition. However, we currently lack understanding of the neurobiology and prognostic markers of these effects. Given that ADT acts via the hypothalamus-pituitary-gonadal axis, we assessed whether baseline hypothalamic resting state functional connectivity (rsFC) could predict changes in working memory and quality of life in prostate cancer patients following androgen deprivation. In a prospective observational study, 28 men with non-metastatic prostate cancer receiving ADT and 38 patients not receiving ADT (controls), matched in age, years of education and Montreal Cognitive Assessment score, participated in brain imaging at baseline, and N-back task and quality-of-life (QoL) assessments at baseline and at 6 months follow-up. Imaging data were processed with published routines and evaluated at a corrected threshold. ADT and control groups did not differ in N-back performance or QoL across time points. In ADT, the changes in 0-back correct response rate (follow-up-baseline) were correlated with baseline hypothalamus-precentral gyrus rsFC; the changes in 1-back correct response rate and reaction time were each correlated with hypothalamus-middle frontal gyrus and superior parietal lobule rsFC. The changes in physical well-being subscore of QoL were correlated with baseline hypothalamus-anterior cingulate and cuneus rsFC. The hypothalamus rsFCs predicted N-back and QoL change with an area under the receiver operating characteristic curve of 0.93 and 0.73, respectively. Baseline hypothalamus-frontoparietal and salience network rsFC's predict inter-subject variations in the changes in working-memory and QoL following 6 months of ADT. Whether and how hypothalamic rsFCs may predict the cognitive and QoL effects with longer-term ADT remain to be investigated.

The effects of androgen deprivation on working memory and quality of life in prostate cancer patients: The roles of hypothalamic connectivity.

BACKGROUND: Androgen deprivation therapy (ADT) has been associated with adverse effects on the brain. ADT alters testosterone levels via its action on the hypothalamus-pituitary-gonadal axis and may influence hypothalamic functions. Given the wide regional connectivity of the hypothalamus and its role in regulating cognition and behavior, we assessed the effects of ADT on hypothalamic resting state functional connectivity (rsFC) and their cognitive and clinical correlates. METHODS: In a prospective observational study, 22 men with nonmetastatic prostate cancer receiving ADT and 28 patients not receiving ADT (controls), matched in age, years of education, and Montreal Cognitive Assessment score, participated in N-back task and quality of life (QoL) assessments and brain imaging at baseline and at 6 months. Imaging data were processed with published routines and the results of a group by time flexible factorial analysis were evaluated at a corrected threshold. RESULTS: ADT and control groups did not differ in N-back performance or QoL across time points. Relative to controls, patients receiving ADT showed significantly higher hypothalamus-right mid-cingulate cortex (MCC) and precentral gyrus (PCG) rsFC during follow-up versus baseline. Further, the changes in MCC and PCG rsFC were correlated positively with the change in QoL score and 0-back correct response rate, respectively, in patients with undergoing ADT. CONCLUSION: Six-month ADT affects hypothalamic functional connectivity with brain regions critical to cognitive motor and affective functions. Elevated hypothalamic MCC and PCG connectivity likely serve to functionally compensate for the effects of ADT and sustain attention and overall QoL. The longer-term effects of ADT remain to be investigated.

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.

The eagle sign: a new preoperative MRI-based tool for predicting topographic correlation between craniopharyngioma and hypothalamus.

PURPOSE: Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological-surgical-pathological-outcome analysis. MATERIALS AND METHODS: Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named "eagle sign" was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. RESULTS: A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of "eagle sign". Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical-pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of "eagle sign" were more than 90%. CONCLUSION: "Eagle sign" is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.

The Central Inflammatory Network: A Hypothalamic fMRI Study of Experimental Endotoxemia in Humans.

INTRODUCTION: Inflammation is a mechanism of the immune system that is part of the reaction to pathogens or injury. The central nervous system closely regulates inflammation via neuroendocrine or direct neuroimmune mechanisms, but our current knowledge of the underlying circuitry is limited. Therefore, we aimed to identify hypothalamic centres involved in sensing or modulating inflammation and to study their association with known large-scale brain networks. METHODS: Using high-resolution functional magnetic resonance imaging (fMRI), we recorded brain activity in healthy male subjects undergoing experimental inflammation from intravenous endotoxin. Four fMRI runs covered key phases of the developing inflammation: pre-inflammatory baseline, onset of endotoxemia, onset of pro-inflammatory cytokinemia, and peak of pro-inflammatory cytokinemia. Using masked independent component analysis, we identified functionally homogeneous subregions of the hypothalamus, which were further tested for changes in functional connectivity during inflammation and for temporal correlation with tumour necrosis factor and adrenocorticotropic hormone serum levels. We then studied the connection of these inflammation-associated hypothalamic subregions with known large-scale brain networks. RESULTS: Our results show that there are at least 6 hypothalamic subregions associated with inflammation in humans including the paraventricular nucleus, supraoptic nucleus, dorsomedial hypothalamus, bed nucleus of the stria terminalis, lateral hypothalamic area, and supramammillary nucleus. They are functionally embedded in at least 3 different large-scale brain networks, namely a medial frontoparietal network, an occipital-pericentral network, and a midcingulo-insular network. CONCLUSION: Measuring how the hypothalamus detects or modulates systemic inflammation is a first step to understand central nervous immunomodulation.

Successful Diagnoses and Remarkable Metabolic Disorders in Patients With Solitary Hypothalamic Mass: A Case Series Report.

Background: Solitary intracranial hypothalamic mass occurs rarely. The etiological diagnosis of solitary hypothalamus lesion is challenging and often unachievable. Although previous studies indicated that lesions affecting the hypothalamus often cause significant metabolic disorders, few reports about the metabolic disturbances of patients with solitary hypothalamic mass have been reported. Method: Twenty-five patients with solitary hypothalamus lesions who had been evaluated and treated in Huashan Hospital from January 2010 to December 2020 were retrospectively enrolled. The clinical manifestations, radiological features, endocrine and metabolic disorders, and pathology were analyzed. Results: The male to female ratio was 5/20. The median age of onset was 22 (19, 35) years old. The most common initial symptom was polydipsia/polyuria (19/25, 76.0%) and amenorrhea (9/20, 45.0%). A high prevalence of hypopituitarism of different axes was found, with almost all no less than 80%. Central hypogonadism (21/22, 95.5%) and central diabetes insipidus (19/21, 90.5%) were the top two pituitary dysfunctions. Conclusive diagnoses were achieved by intracranial surgical biopsy/resection or stereotactic biopsy in 16 cases and by examining extracranial lesions in 3 cases. The pathological results were various, and the most common diagnoses were Langerhans cell histiocytosis (7/19) and hypothalamitis (5/19). The mean timespan from onset to diagnosis in the 19 cases was 34 ± 26 months. Metabolic evaluations revealed remarkable metabolic disorders, including hyperlipidemia (13/16, 81.3%), hyperglycemia (10/16, 62.5%), hyperuricemia (12/20, 60%), overweight/obesity (13/20, 65.0%), and hepatic adipose infiltration (10/13, 76.6%). Conclusion: Either surgical or stereotactic biopsy will be a reliable and relatively safe procedure to help to confirm the pathological diagnosis of solitary hypothalamic mass. Metabolic disorders were severe in patients with solitary hypothalamic mass. The management of such cases should cover both the treatment of the primary disease, as well as the endocrine and metabolic disorders.

Disruption of orbitofrontal-hypothalamic projections in a murine ALS model and in human patients.

BACKGROUND: Increased catabolism has recently been recognized as a clinical manifestation of amyotrophic lateral sclerosis (ALS). The hypothalamic systems have been shown to be involved in the metabolic dysfunction in ALS, but the exact extent of hypothalamic circuit alterations in ALS is yet to be determined. Here we explored the integrity of large-scale cortico-hypothalamic circuits involved in energy homeostasis in murine models and in ALS patients. METHODS: The rAAV2-based large-scale projection mapping and image analysis pipeline based on Wholebrain and Ilastik software suites were used to identify and quantify projections from the forebrain to the lateral hypothalamus in the SOD1(G93A) ALS mouse model (hypermetabolic) and the FusΔNLS ALS mouse model (normo-metabolic). 3 T diffusion tensor imaging (DTI)-magnetic resonance imaging (MRI) was performed on 83 ALS and 65 control cases to investigate cortical projections to the lateral hypothalamus (LHA) in ALS. RESULTS: Symptomatic SOD1(G93A) mice displayed an expansion of projections from agranular insula, ventrolateral orbitofrontal and secondary motor cortex to the LHA. These findings were reproduced in an independent cohort by using a different analytic approach. In contrast, in the FusΔNLS ALS mouse model hypothalamic inputs from insula and orbitofrontal cortex were maintained while the projections from motor cortex were lost. The DTI-MRI data confirmed the disruption of the orbitofrontal-hypothalamic tract in ALS patients. CONCLUSION: This study provides converging murine and human data demonstrating the selective structural disruption of hypothalamic inputs in ALS as a promising factor contributing to the origin of the hypermetabolic phenotype.

Biochemical predictors of structural hypothalamus-pituitary abnormalities detected by magnetic resonance imaging in men with secondary hypogonadism.

PURPOSE: Organic conditions underlying secondary hypogonadism (SH) may be ascertained by magnetic resonance imaging (MRI) of the hypothalamic-pituitary region that could not be systematically proposed to each patient. Based upon limited evidence, the Endocrine Society (ES) guidelines suggest total testosterone (T) < 5.2 nmol/L to identify patients eligible for MRI. The study aims to identify markers and their best threshold value predicting pathological MRI findings in men with SH. METHODS: A consecutive series of 609 men seeking medical care for sexual dysfunction and with SH (total T < 10.5 nmol/L and LH ≤ 9.4 U/L) was retrospectively evaluated. An independent cohort of 50 men with SH was used as validation sample. 126 men in the exploratory sample and the whole validation sample underwent MRI. RESULTS: In the exploratory sample, patients with pathological MRI findings (n = 46) had significantly lower total T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate specific antigen (PSA) than men with normal MRI (n = 80). Receiver Operating Characteristics analysis showed that total T, LH, FSH and PSA are accurate in identifying men with pathologic MRI (accuracy: 0.62-0.68, all p < 0.05). The Youden index was used to detect the value with the best performance, corresponding to total T 6.1 nmol/L, LH 1.9 U/L, FSH 4.2 U/L and PSA 0.58 ng/mL. In the validation cohort, only total T ≤ 6.1 nmol/L and LH ≤ 1.9 U/L were confirmed as significant predictors of pathologic MRI. CONCLUSION: In men with SH, total T ≤ 6.1 nmol/L or LH ≤ 1.9 U/L should arise the suspect of hypothalamus/pituitary structural abnormalities, deserving MRI evaluation.

Optimization of whole-brain rabies virus tracing technology for small cell populations.

The lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressing LH neurons remain unknown. We used rabies virus tracing technology to map these inputs, but encountered non-specific tracing. To optimize this technology for a minor cell population (LepRb is not ubiquitously expressed in LH), we used LepRb-Cre mice and assessed how different titers of the avian tumor virus receptor A (TVA) helper virus affected rabies tracing efficiency and specificity. We found that rabies expression is dependent on TVA receptor expression, and that leakiness of TVA receptors is dependent on the titer of TVA virus used. We concluded that a titer of 1.0-3.0 × 107 genomic copies per µl of the TVA virus is optimal for rabies tracing. Next, we successfully applied modified rabies virus tracing technology to map inputs to LepRb-expressing LH neurons. We discovered that other neurons in the LH itself, the periventricular hypothalamic nucleus (Pe), the posterior hypothalamic nucleus (PH), the bed nucleus of the stria terminalis (BNST), and the paraventricular hypothalamic nucleus (PVN) are the most prominent input areas to LepRb-expressing LH neurons.

Genetic underpinnings of risky behaviour relate to altered neuroanatomy.

Previous research points to the heritability of risk-taking behaviour. However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving and sexual behaviour in a European sample from the UK Biobank (N = 12,675). We find negative associations between risky behaviour and grey-matter volume in distinct brain regions, including amygdala, ventral striatum, hypothalamus and dorsolateral prefrontal cortex (dlPFC). These effects are replicated in an independent sample recruited from the same population (N = 13,004). Polygenic risk scores for risky behaviour, derived from a genome-wide association study in an independent sample (N = 297,025), are inversely associated with grey-matter volume in dlPFC, putamen and hypothalamus. This relation mediates roughly 2.2% of the association between genes and behaviour. Our results highlight distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking.

Clinical Implication of Individually Tailored Segmentation Method for Distorted Hypothalamus in Craniopharyngioma.

Objective: Several attempts have been done to capture damaged hypothalamus (HT) using volumetric measurements to predict the development of hypothalamic obesity in patients with craniopharyngioma (CP). This study was to develop a novel method of HT volume measurement and examine the associations between postoperative HT volume and clinical parameters in patients with CP. Methods: We included 78 patients with adult-onset CP who underwent surgical resection. Postoperative HT volume was measured using T1- and T2-weighted magnetic resonance imaging (MRI) with a slice thickness of 3 mm, and corrected for temporal lobe volume. We collected data on pre- and postoperative body weights, which were measured at the time of HT volume measurements. Results: The corrected postoperative HT volume measured using T1- and T2-weighted images was significantly correlated (r=0.51 [95% confidence interval (CI) 0.32 to 0.67], P<0.01). However, HT volume was overestimated using T1-weighted images owing to obscured MR signal of the thalamus in patients with severe HT damage. Therefore, we used T2-weighted images to evaluate its clinical implications in 72 patients with available medical data. Postoperative HT volume was negatively associated with preoperative body weight and preoperative tumor volume (r=-0.25 [95% CI -0.45 to -0.04], P=0.04 and r=-0.26 [95% CI -0.40 to -0.15], P=0.03, respectively). In the subgroup analysis of CP patients who underwent primary surgery (n=56), pre- and postoperative body weights were negatively associated with HT volume (r=-0.30 [95% CI -0.53 to -0.03], P=0.03 and r=-0.29 [95% CI -0.53 to -0.02], P=0.03, respectively). Conclusions: Adult-onset CP patients showed negative associations between postoperative HT volume and preoperative/postoperative body weight using a new method of HT volume measurement based on T2-weighted images.

Optic pathway tumor in children: Toward a new classification for neurosurgical use.

OBJECT: Optic pathway tumors (OPT) represent a challenge for pediatric neurosurgeons. Role of surgery is debated due to the high risk of iatrogenic damage, and in lasts decades it lost its importance in favor of chemotherapy. However, in some cases surgery is necessary to make biomolecular and histological diagnosis, to manage intracranial hypertension (IH) and to cooperate with medical therapies in controlling tumor relapse. With the aim to standardize selection of surgical OPT cases, we propose a simple, practical and reproducible classification. METHODS: We retrospectively analyzed data of 38 patients with OPT treated at our institution (1990-2018). After careful analysis of MRI images, we describe a new classification system. Group 1: lesion limited to one or both optic nerve(s). Group 2: chiasmatic lesions extending minimally to hypothalamus. Group 3: hypothalamo-chiasmatic exophitic lesions invading the third ventricle; they can be further divided on the base of concomitant hydrocephalus. Group 4: hypothalamo-chiasmatic lesions extending widely in lateral direction, toward the temporal or the frontal lobes. Patients' data and adopted treatment are reported and analyzed, also depending on this classification. RESULTS: Twenty children were operated on for treatment of OPT during the study period. Permanent clinical impairment was noted in 5 (25%) of operated patients, while visual improvement was noted in 1 patient. OS rate was 100% at 5 years, with a median follow up of 9 years (ranging from 2 to 23). Prevalence of intracranial hypertension and proportion of first-line surgical treatment decision were significantly higher in groups 3-4 compared to groups 1-2 (P<0.001 for both tests). CONCLUSION: Surgery can offer a valuable therapeutic complement for OPT without major risk of iatrogenic damage. Surgery is indispensable in cases presenting with IH, as in groups 3 and 4 lesions. Eligibility of patients to surgery can be based on this new classification system.

Hypothalamic injury patterns after resection of craniopharyngiomas and correlation to tumor origin: A study based on endoscopic observation.

The precise understanding of hypothalamic injury (HI) patterns and their relationship with different craniopharyngioma (CP) classifications remains poorly addressed. Here, four HI patterns after CP resection based on endoscopic observation were introduced. A total of 131 CP cases treated with endoscopic endonasal approach (EEA) were reviewed retrospectively and divided into four HI patterns: no-HI, mild-HI, unilateral-HI and bilateral-HI, according to intraoperative findings. The outcomes were evaluated and compared between groups in terms of weight gain, endocrine status, electrolyte disturbance and neuropsychological function before and after surgery. A systematic correlation was found between CP origin and subsequent HI patterns. The majority of intrasellar and suprasellar stalk origins lead to a no-HI pattern, the central-type CP mainly develops a mild or bilateral HI pattern, and the majority of tumors with hypothalamic stalk origins result in unilateral HI and sometimes bilateral HI patterns. The proportion of tumors with a maximum diameter >3 cm in the no-HI group was higher than that in the mild-HI group, BMI and quality of life in the no-HI group showed better results than those in the other groups. The incidence of new-onset diabetes insipidus in the bilateral-HI group was significantly higher than that in the other groups. Memory difficulty was observed mainly in the unilateral-HI and bilateral-HI groups. However, the outcomes of electrolyte disturbance, sleep, and cognitive disorder in the unilateral-HI group were significantly better than those in the bilateral-HI group. This study suggests the possibility of using pre- and intraoperative observation of CP origin to predict four HI patterns and even subsequent outcomes after tumor removal.