Impact of sleep, neuroendocrine, and executive function on health-related quality of life in young people with craniopharyngioma.

AIM: To examine the impact of clinical factors, cognitive deficits, and sleepiness on health-related quality of life (HRQoL) among young people with craniopharyngioma. METHOD: Seventy-eight patients (67% White; 41 males, 37 females; mean age 10y 8mo, SD 3y 11mo, range 6-20y) with craniopharyngioma were assessed for tumor extent and diabetes insipidus. All patients underwent overnight polysomnography and multiple sleep latency tests after surgical resection. Executive functioning was assessed using parent-reported measures. Patients and their parents completed measures of HRQoL. None had a history of previous radiation therapy. RESULTS: Path analysis was used to test hypothesized relations while controlling for demographic and disease characteristics. Analyses revealed poorer parent-reported HRQoL among young people with greater executive functioning symptoms (estimate -0.83; p<0.001). Direct and indirect effects were found among diabetes insipidus, executive functioning, and parent-reported HRQoL. Diabetes insipidus directly predicted greater global executive functioning impairment (estimate 5.15; p=0.04) and indirectly predicted lower HRQoL through executive functioning impairment (estimate -4.25; p=0.049). No significant effects were found between excessive daytime sleepiness, tumor hypothalamic involvement, diabetes insipidus, executive functioning, and patient-reported HRQoL. INTERPRETATION: These findings suggest that young people with craniopharyngioma presenting with diabetes insipidus may benefit from targeted neurocognitive and psychosocial screening to inform interventions. What this paper adds Children with craniopharyngioma and executive functioning impairment are more likely to have poorer health-related quality of life (HRQoL). Diabetes insipidus, a complication associated with surgery, predicted greater executive functioning impairment. Diabetes insipidus indirectly predicted lower parent-reported HRQoL through executive functioning impairment.

MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma.

Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and disease of numerous organs, its role during pituitary development and tumourigenesis remains largely unknown. Here, we show that the over-activation of the MAPK pathway, through conditional expression of the gain-of-function alleles BrafV600E and KrasG12D in the developing mouse pituitary, results in severe hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell-lineage commitment and terminal differentiation are disrupted, leading to a significant reduction in numbers of most of the hormone-producing cells before birth, with the exception of corticotrophs. Of note, Sox2+ stem cells and clonogenic potential are drastically increased in the mutant pituitaries. Finally, we reveal that papillary craniopharyngioma (PCP), a benign human pituitary tumour harbouring BRAF p.V600E also contains Sox2+ cells with sustained proliferative capacity and disrupted pituitary differentiation. Together, our data demonstrate a crucial function of the MAPK pathway in controlling the balance between proliferation and differentiation of Sox2+ cells and suggest that persistent proliferative capacity of Sox2+ cells may underlie the pathogenesis of PCP.

The endoscopic endonasal approach for pediatric craniopharyngiomas: the key lessons learned.

PURPOSE: The aim of this study is to highlight the role of the endoscopic endonasal approach (EEA) in pediatric craniopharyngiomas by reviewing our experience and the key lessons learned from the application of this approach in children. METHODS: Between 1998 and 2017, 12 pediatric craniopharyngiomas were treated via EEA at our institution. Demographic data, preoperative assessment, tumor features, surgical results, complications, and recurrences were analyzed. RESULTS: Visual defects were the most frequent presenting sign. Seven craniopharyngiomas were infradiaphragmatic, and five were supradiaphragmatic. The EEA was successfully performed in all cases with no complication related to children's sinonasal anatomy. Gross total resection (GTR) rate was of 75%. Endocrinological disturbances improved in one case (20%) and worsened in three (60%). New onset of diabetes insipidus was observed in four (36%) children. Visual defect improved in 91% of cases, with no new postoperative deficit. Postoperative cerebrospinal fluid (CSF) leak occurred in one patient (8%). Three patients (27%) experienced tumor regrowth, and one craniopharyngioma recurred (mean follow-up, 78 months). CONCLUSIONS: The EEA offers a straight route to the sellar-suprasellar, making it the ideal approach for pediatric infradiaphragmatic craniopharyngiomas. In supradiaphragmatic craniopharyngiomas, the extended EEA provides a clearer and close-up visualization of the tumor-hypothalamus interface, which can grant better results in terms of quality of life. The pediatric skull base anatomy should not represent a contraindication for the endoscopic technique. Larger series encompassing a wider spectrum of pediatric craniopharyngiomas are needed to further support the benefits of this surgical approach.

Outcomes following endoscopic endonasal resection of sellar and supresellar lesions in pediatric patients.

PURPOSE: The endoscopic endonasal approach (EEA) is a credible surgical alternative for the resection of sellar and suprasellar lesions such as pituitary adenomas, craniopharyngiomas, and Rathke cleft cysts. However, its application to pediatric patients poses several unique challenges that have not yet been well evaluated. The authors evaluate the safety, efficacy, and outcomes associated with the use of the EEA for treatment of these pathologic entities in pediatric patients. METHODS: Retrospective review of 30 patients between the ages of two and 24 who underwent endoscopic endonasal resection of sellar or suprasellar lesions between January 2010 and December 2015. Endocrinological and ophthalmological outcomes, as well as extent of resection and complications were all evaluated. RESULTS: Gross total resection was achieved in eight of the nine pituitary adenomas, nine of the 12 craniopharyngiomas, and six of the nine Rathke cleft cysts. Of the 30 patients, 22 remained disease free at last follow-up. A total of six patients developed hypopituitarism and five developed diabetes insipidus. Eleven patients experienced improved vision, sixteen experienced no change, and one patient experienced visual worsening. Postoperative cerebrospinal fluid leak was seen in a single case and later resolved, vasospasm/stroke was experienced by 10% of patients, and new obesity was recorded in 10% of patients. There were no perioperative deaths. CONCLUSIONS: Endoscopic endonasal resection is a safe and effective surgical alternative for the management of sellar and suprasellar pathologies in pediatric populations with excellent outcomes, minimal complications, and a low risk of morbidity.

Pediatric craniopharyngioma.

BACKGROUND: Craniopharyngioma has historically been recognized to be a formidable pathology primarily due to its proximity to critical neurovascular structures and the challenging surgical corridors that surgeons have tried to reach this lesion. FOCUS OF REVIEW: In this work, we review the medical and surgical management of these tumors with a focus on clinical presentation, diagnostic identification, surgical approach, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to craniopharyngiomas. The management of craniopharyngiomas requires a multidisciplinary team of surgeons, endocrinologists, and neuroanesthesiologists as well as neurocritical care specialists to deliver the most comprehensive and safest surgical resection with minimal postoperative morbidity.

Endoscopic endonasal skull base surgery for pediatric brain tumors.

PURPOSE: The utility of endoscopic endonasal skull base surgery (EES) in various pathologic entities in adults has been published in the literature. However, the role of EES in children has not been clearly elucidated. We evaluated the feasibility of EES in children with brain tumors. METHODS: We retrospectively reviewed clinical features, surgical outcomes, and complications in children who underwent EES for intracranial and skull base tumors at a single institution from July 2010 to October 2018. RESULTS: A total of 82 patients underwent EESs for 77 intracranial and 5 skull base bony tumors. The mean age at diagnosis was 11.4 years (range 4-18 years), and the mean follow-up period was 46.8 months. The most common tumors were craniopharyngioma in the intracranial tumor and chordoma in the skull base. Gross total resection was the goal of surgery in 55 patients and achieved in 90.9%. The vision was improved in 76.1% of patients with visual impairments. Preoperatively, various endocrinological deficiencies were revealed in 73.7% of 76 patients with hypothalamus-pituitary lesions, and the hyposomatotropism was most common. Endocrinological status was improved only in 10. Aseptic or bacterial meningitis (7.3%) was the most common surgical complication, and the cerebrospinal fluid leakage rate was 2.4%. CONCLUSIONS: EES provides favorable neurological outcomes with acceptable risk for children with brain tumors. The high incidence of endocrinological deficits in cases with hypothalamus-pituitary lesions emphasizes the importance of judicious pre- and postoperative evaluation.

Childhood Craniopharyngioma: A 22-Year Challenging Follow-Up in a Single Center.

Craniopharyngioma is a sellar/suprasellar benign tumor whose aggressiveness may imply in endocrine disturbances (hypothalamic obesity and hormone deficiencies). Fifty-seven patients were evaluated according to clinical characteristics, hypothalamic involvement, type of treatment, anthropometric variables, adiposity indexes (body mass index Z score category at diagnosis and post-treatment, total body fat, visceral adipose tissue, and metabolic syndrome components) and analyzed through multiple regression and logistic models. Patients were stratified according to growth hormone deficiency and recombinant human growth hormone use. Mean ages at diagnosis and at study evaluation were 9.6 and 16.6 years old, respectively. A set of 43/57 (75.4%) patients presented with important hypothalamic involvement, 24/57 (42.1%) received surgical treatment and cranial radiotherapy, and 8/57 (14%) interferon-α exclusively. Fifty-five patients (96.5%) were considered growth hormone deficient, and 26/57 (45.6%) grew despite no recombinant human growth hormone replacement therapy. At diagnosis, 12/57 (21%) patients were obese, and 33/57 (57.9%) at study evaluation, and after 3.2 years (median) post first therapy. There was no influence of height Z score on body mass index Z score. Body mass index Z score at diagnosis positively influenced body mass index Z score, total body fat, waist circumference and the presence of the metabolic syndrome post-treatment. Replacement of recombinant human growth hormone decreased total body fat and visceral adipose tissue. Craniopharyngioma patients worsened body mass index Z score category 3.2 years (median) after first treatment. Body mass index Z score increased due to real weight gain, without height decrease. Replacement of recombinant human growth hormone had beneficial effect on adiposity.

Long-term visual outcomes of craniopharyngioma in children.

Visual function is a critical factor in the diagnosis, monitoring, and prognosis of craniopharyngiomas in children. The aim of this study was to report the long-term visual outcomes in a cohort of pediatric patients with craniopharyngioma. The study design is a retrospective chart review of craniopharyngioma patients from a single tertiary-care pediatric hospital. 59 patients were included in the study. Mean age at presentation was 9.4 years old (range 0.7-18.0 years old). The most common presenting features were headache (76%), nausea/vomiting (32%), and vision loss (31%). Median follow-up was 5.2 years (range 1.0-17.2 years). During follow-up, visual decline occurred in 17 patients (29%). On Kaplan Meier survival analysis, 47% of the cases of visual decline occurred within 4 months of diagnosis, with the remaining cases occurring sporadically during follow-up (up to 8 years after diagnosis). In terms of risk factors, younger age at diagnosis, optic nerve edema at presentation, and tumor recurrence were found to have statistically significant associations with visual decline. At final follow-up, 58% of the patients had visual impairment in at least one eye but only 10% were legally blind in both eyes (visual acuity 20/200 or worse or < 20° of visual field). Vision loss is a common presenting symptom of craniopharyngiomas in children. After diagnosis, monitoring vision is important as about 30% of patients will experience significant visual decline. Long-term vision loss occurs in the majority of patients, but severe binocular visual impairment is uncommon.

Clinical and prognostic role of annexin A2 in adamantinomatous craniopharyngioma.

Annexin A2 (AnxA2) is a highly conserved Ca2+-regulated membrane binding protein, which affects cell mobility and tumor progression. Adamantinomatous craniopharyngioma (AdaCP) are a kind of epithelial tumors of the sellar region with high tendency to recur. Robust biomarkers are required to predict tumor behavior and to establish follow-up individualized treatment approaches. In this study, we firstly compared four surgical AdaCP samples with normal brain by two-dimensional gel electrophoresis (2DE) proteomic analysis. Potential prognostic biomarkers were further validated in a large cohort of 65 AdaCPs by immunohistochemistry. The effects of AnxA2 on AdaCP cells proliferation and migration were analyzed in vitro with isolated primary AdaCP cells as well as SV40T-immortalized cells. Finally, the gefitinib sensitivity of AdaCPs with differentially expressed AnxA2 and the potential molecular mechanisms were examined by flow cytometric analysis, Real-time PCR and immunoblot assays. Proteomic analysis indicated that AnxA2 was the protein spot with the most elevated expression in AdaCP samples. Immunohistochemistry assays indicated the expression level of AnxA2 was significantly higher in recurrent AdaCPs compared with primary ones. Moreover, AnxA2+ AdaCP cells exhibited enhanced proliferation and migration ability compared with AnxA2- AdaCP cells in vitro. Further, we show that AnxA2+ AdaCP cells exhibited elevated expression of EGFR and downstream p-AKT (S308) and p-AKT (S473), and were more sensitive to tyrosine kinase inhibitor gefitinib. Our data suggest that AnxA2 may serve as a promising biomarker for AdaCP progression, recurrence and drug susceptibility. Our data support potential clinical implications for the follow-up treatment of AdaCP patients with high AnxA2 expression.

Polysomnographic findings in craniopharyngioma patients.

PURPOSE: The purpose of this study is to evaluate whether damage to the hypothalamus due to craniopharyngioma or consequent surgery may involve the sleep-wake regulatory system, resulting in sleep disturbances and sleepiness. METHODS: Seven craniopharyngioma patients and 10 healthy controls were evaluated with sleep questionnaires including the Epworth Sleepiness Scale, polysomnography, and a multiple sleep latency test (MSLT). Five patients and eight controls had lumbar puncture performed to determine hypocretin-1 levels. RESULTS: Patients tended to feel sleepier than control individuals of the same age (p = 0.09). No subjects had symptoms of hypnagogic hallucinations, sleep paralyses, or cataplexies. Four patients and one control had periodic leg movements (PLMs). One patient had fragmented sleep pattern, rapid eye movement (REM) sleep without atonia, and PLMs. One patient had short sleep periods during the daytime. Four patients had fragmented sleep pattern. With the MSLT, four patients and two controls had mean sleep latency of < 8 min. One patient and three controls had sudden onset of REM sleep in 2/5 and 3/5 sleep periods, respectively. All subjects showed normal hypocretin-1 levels. Four patients had electrophysiological findings indicative of central hypersomnia including one patient meeting the criteria of narcolepsy. CONCLUSION: The sleep-wake regulatory system may be involved in craniopharyngioma patients.

[Effect of recombinant human growth hormone therapy on metabolic parameters in patients with craniopharyngioma].

Objective: To investigate the effects of recombinant human growth hormone (rhGH) on metabolic parameters in patients with craniopharyngioma surgeries. Methods: Totallys 30 patients with craniopharyngioma were included in this retrospective study. They were divided into growth hormone (GH) group and control group according to whether they received rhGH therapy or not. The following parameters, including body mass index (BMI), weight, waist circumstance, transaminase, fasting blood glucose, lipid profile and high-sensitivity C-reactive protein (hsCRP) were compared after rhGH therapy for 4-6 months. Results: In GH group, patients were 18-46 (30.0±8.8) years old. The duration after craniopharyngioma surgery was (12.9±5.4) years. Before rhGH therapy, they had got sufficient thyroid and glucocorticoid hormone replacement. After rhGH therapy, the body weight decreased from (92.3±20.1) to (87.6 ±14.6) kg (P=0.190), with a reduction of BMI from (30.1±5.9) to (28.2±3.7) kg/m(2) (P=0.120). The waist circumference decreased from (104.4±9.4) cm to (98.8±10.6) cm (P=0.002). Alanine aminotransferase (ALT) decreased from (52±34) to (28±19) U/L (P=0.029), with a reduction of aspartate transaminase (AST) from (46±21) to (33±18) U/L (P=0.035) and γ-glutamyl transpeptadase (GGT) from (59±42) to (29±15) U/L (P=0.02). hsCRP decreased from (5.3±4.9) to (2.3±2.8) mg/L (P=0.006) and triglyceride (TG) decreased from (1.8±0.7) to (1.5±0.6) mmol/L (P=0.028). Fasting blood glucose, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and free fat acid (FFA) were not significantly changed(all P>0.05). In the control group, the above mentioned parameters did not changed significantly during 4-6 months of observational period(all P>0.05). Conclusion: rhGH therapy improves metabolic parameters in patients after craniopharyngioma surgery by decreasing body weight, waist circumstance and fat deposit in liver, as well as lowering TG and hsCRP levels.

[Transient enlargement of craniopharyngioma cysts after stereotactic radiotherapy and radiosurgery]. / Tranzitornoe uvelichenie ob''ema kist kraniofaringiom posle stereotaksicheskoi luchevoi terapii i radiokhirurgii.

Stereotactic radiotherapy/radiosurgery (RT/ES) is an effective technique for treating craniopharyngiomas (CPs). However, enlargement of the cystic part of the tumor occurs in some cases after irradiation. The enlargement may be transient and not require treatment or be a true relapse requiring treatment. MATERIAL AND METHODS: In this study, we performed a retrospective analysis of 79 pediatric patients who underwent stereotactic RT or RS after resection of craniopharyngioma. RESULTS: Five-year relapse-free survival after complex treatment of CP was 86%. In the early period after irradiation, 3.5 months (2.7-9.4) on average, enlargement of the cystic component of the tumor was detected in 10 (12.7%) patients; in 9 (11.4%) of them, the enlargement was transient and did not require treatment; in one case, the patient underwent surgery due to reduced visual acuity. In 8 (10.1%) patients, an increase in the residual tumor (a solid component of the tumor in 2 cases and a cystic component of the tumor in 6 cases) occurred in the long-term period after irradiation - after 26.3 months (16.6-48.9) and did not decrease during follow-up in none of the cases, i.e. continued growth of the tumor was diagnosed. A statistical analysis revealed that differences in the terms of transient enlargement and true continued growth were statistically significant (p<0.01). CONCLUSION: Enlargement of a craniopharyngioma cyst in the early period (up to 1 year) after RT/RS is usually transient and does not require surgical treatment (except cases where worsening of neurological symptoms occurs, or occlusive hydrocephalus develops).

[A rare case of diencephalic cachexia in an adult female with cranio-pharyngioma]. / Redkii sluchai razvitiia diéntsefal'noi kakheksii u vzrosloi zhenshchiny s kraniofaringiomoi.

Diencephalic cachexia (DС) is progressive weight loss despite a normal caloric intake and a satisfactory state of health, which is caused by hypothalamic lesions. This is a rare (about 100 cases were reported) and potentially fatal disorder of unknown pathogenesis. At present, there is no effective pharmacological therapy for the disorder. Cachexia may regress only if the tumor reduces in size, therefore the timely diagnosis and treatment are of vital importance for the patient. DС is typical of early childhood, and only a few cases have been reported in adults. We present a rare case of DС in a 24-year-old female with papillary craniopharyngioma.

The infundibulo-tuberal syndrome caused by craniopharyngiomas: clinicopathological evidence from an historical French cohort (1705-1973).

PURPOSE: Infundibulo-tuberal syndrome groups endocrine, metabolic and behavioral disturbances caused by lesions involving the upper neurohypophysis (median eminence) and adjacent basal hypothalamus (tuber cinereum). It was originally described by Henri Claude and Jean Lhermitte in 1917, in a patient with a craniopharyngioma. This study investigates the clinical, pathological and surgical evidence verifying the infundibulo-tuberal syndrome caused by craniopharyngiomas (CPs). METHODS: A systematic retrospective review of craniopharyngiomas reported in French literature between 1705 and 1973 was conducted. A total of 128 well described reports providing a comprehensive clinical and pathological description of the tumors were selected. This series represents the historical French cohort of CPs reported in the pre-CT/MRI era. RESULTS: Three major syndromes caused by CPs were categorized: pituitary syndrome (35%), infundibulo-tuberal syndrome (52%) and hypothalamic syndrome (49%). CP topography was significantly related to the type of syndrome described (p < 0.001). Infundibulo-tuberal syndrome occurred in CPs which replaced or invaded the third ventricle floor. In contrast, the majority of sellar/suprasellar CPs growing below the third ventricle showed a pituitary syndrome (82%). Cases with hypothalamic syndrome were characterized by anatomical integrity of the pituitary gland and stalk (p = 0.033) and occurred predominantly in adults older than 41 years old (p < 0.005). Among infundibulo-tuberal symptoms, abnormal somnolence was not related with the presence of hydrocephalus. All squamous-papillary CPs presented psychiatric disturbances (p < 0.001). CONCLUSION: This historical CP cohort evidences a clinical-topographical correlation between the patient's type of syndrome and the anatomical structures involved by the tumor along the hypophysial-hypothalamic axis.

[A significant increase in intraoperative flash visual evoked potential amplitude during craniopharyngioma surgery-case report].

The flash visual evoked potential (VEP) is a useful diagnostic modality for visual preservation during surgery. Decreased VEP amplitude is recognized to indicate visual deterioration;however, whether intraoperative VEP can detect visual improvement remains unclear. We describe a craniopharyngioma case with a significant increase in VEP amplitude during surgery. A 67-year-old woman presented with progressive gait disturbance and impaired consciousness. Head magnetic resonance imaging demonstrated a sellar-suprasellar tumor compressing the optic chiasm upward with significant ventricular dilation. Her Glasgow Coma Scale was E3V3M5. Visual fields and acuity could not be examined because of impaired consciousness, and she could not see/recognize objects on a table. Preoperative VEP showed reproducible waveforms. Tumor removal by the extended transsphenoidal approach was performed with VEP monitoring. Increased VEP amplitude was observed after dural incision and persisted until the surgery ended. Postoperative VEP waveforms were also reproducible, but visual fields/acuity could not be examined because of cognitive dysfunction. Useful visual function was restored, and she became independent in daily life. The histological diagnosis was craniopharyngioma. The patient underwent ventriculo-peritoneal shunting for hydrocephalus 16 days after tumor removal. The postoperative course was uneventful and she was transferred to another hospital for rehabilitation. Intraoperative VEP may indicate visual improvement during surgery, which is a useful objective assessment for visual function in patients with impaired consciousness and cognitive dysfunction.

Neuropsychological outcome in patients with childhood craniopharyngioma and hypothalamic involvement.

OBJECTIVE: To test memory performance and executive functions in patients with childhood craniopharyngioma and hypothalamic involvement. STUDY DESIGN: Using standardized neuropsychological tests, we compared cognitive performance in a group of 15 patients with childhood craniopharyngioma and known hypothalamic involvement and a group of 24 age- and intelligence-matched control subjects. In addition, we compared individual patients' results with normative data to detect abnormal performance in the clinically relevant range. Within the patient group, we further tested whether the grade of hypothalamic involvement had an impact on cognitive performance and quality of life. RESULTS: Relative to healthy controls, the patients demonstrated significantly lower performance scores in tests of memory and executive functioning. On the individual performance level, delayed recall performance was severely impaired in one-third of the patients. Compared with patients with low-grade hypothalamic involvement, those with high-grade hypothalamic involvement showed worse performance in executive functions and reduced functional capabilities for daily life actions, indicating lower quality of life. CONCLUSION: Our findings demonstrate that hypothalamic involvement is related to impairments in memory and executive functioning in patients with childhood craniopharyngioma and indicate that a high grade of hypothalamic involvement is related to worse outcomes.

Remote effects of hypothalamic lesions in the prefrontal cortex of craniopharygioma patients.

Albeit histologically low grade (WHO I(o)) brain tumors, craniopharyngiomas and/or their surgical removal frequently affect the hypothalamus, amongst other brain regions at risk. Due to rich hypothalamic connections with prefrontal and limbic regions, hypothalamic injury may adversely affect neural substrates of emotion processing and higher cognitive control, including memory and executive functions. The current study is the first to investigate the consequences of hypothalamic involvement on neural substrates of emotional and cognitive functioning. Ten patients with childhood craniopharyngioma and known hypothalamic involvement and fifteen age- and intelligence matched control subjects (median age: 17.8 and 17.3 yrs.) were studied with functional magnetic resonance imaging and an emotional face recognition task. During encoding, participants were asked to classify neutral and emotional faces. In a subsequent recognition phase, participants had to recognize these old faces within a set of new faces. Behavioral performance was comparable between patients and controls. Neural activity revealed, however, differential recruitment of fronto-limbic brain regions during recognition. Patients exhibited an abnormal pattern of task-induced activation and deactivation in the anterior and posterior rostral medial prefrontal cortex and a higher functional coupling between anterior rostral medial prefrontal cortex and the thalamus. Additionally, we found a higher reactivity in the patients' amygdala to emotional relative to neutral faces when compared to healthy controls. Our data provide first evidence that hypothalamic damage impacts neural correlates of memory retrieval in medial prefrontal cortex, indicating a less efficient use of an area involved in executive control processes. We propose that the deactivation failure in the patients' anterior rostral medial prefrontal cortex is related to an increased coupling with the thalamus and reflects a reduced efficiency to flexibly adapt to task demands.

The ophthalmic natural history of paediatric craniopharyngioma: a long-term review.

We present our experience over the long-term of monitoring of visual function in children with craniopharyngioma. Our study involves an analysis of all paediatric patients with craniopharyngioma younger than 16 at the time of diagnosis and represents a series of predominantly sub-totally resected tumours. Visual data, of multiple modality, of the paediatric patients was collected. Twenty patients were surveyed. Poor prognostic indicators of the visual outcome and rate of recurrence were assessed. Severe visual loss and papilledema at the time of diagnosis were more common in children under the age of 6. In our study visual signs, tumour calcification and optic disc atrophy at presentation are predictors of poor visual outcome with the first two applying only in children younger than 6. In contrast with previous reports, preoperative visual field (VF) defects and type of surgery were not documented as prognostic indicators of poor postoperative visual acuity (VA) and VF. Contrary to previous reports calcification at diagnosis, type of surgery and preoperative VF defects were not found to be associated with tumour recurrence. Local recurrence is common. Younger age at presentation is associated with a tendency to recur. Magnetic resonance imaging (MRI) remains the recommended means of follow-up in patients with craniopharyngioma.

Abnormal hypothalamic functional connectivity associated with cognitive impairment in craniopharyngiomas.

OBJECTIVE: This study sought to characterize resting-state functional connectivity (rsFC) patterns of the hypothalamic and extrahypothalamic nuclei in craniopharyngioma (CP) patients, and to investigate potential correlations between hypothalamic and extrahypothalamic rsFC maps and neurocognitive performance. METHODS: Ninety-two CP patients and 40 demographically-matched healthy controls were included. Whole-brain seed-to-voxel analyses were used to test for between-group rsFC differences, and regression analyses were used to correlate neurocognitive performance with voxel-wise hypothalamic and extrahypothalamic rsFC maps for CP patients. Finally, spectral DCM analysis was used to explore the hypothalamus circuit associated with neurocognitive performance. RESULTS: The seed-to-voxel analyses demonstrated that the hypothalamic nuclei showed mainly significant rsFC reduction in brain areas overlayed with the cortical regions of default mode network (DMN), notably in the bilateral anterior cingulate cortices and posterior cingulate cortices. The extrahypothalamic nuclei showed significant rsFC reduction in the limbic system of bilateral caudate nuclei, corpus callosum, fornix, and thalamus. Regression analyses revealed that worse cognitive performance was correlated with abnormal hypothalamic rsFC with brain areas in DMN, and DCM analysis revealed a hypothalamus-DMN circuit responsible for functional modulation of cognitive impairment in CP patients. CONCLUSIONS: Our study demonstrated that CPs invading into hypothalamus impacted hypothalamic and extrahypothalamic rsFC with brain areas of DMN and limbic system, the severity of which was parallel with the grading system of hypothalamus involvement. In addition to the CP-induced structural damage to the hypothalamus alone, abnormal functional connectivity within the hypothalamus-DMN circuit might be a functional mechanism leading to the cognitive impairment in CP patients.

The risk of osteopenia in premenopausal women with various sellar tumors.

OBJECTIVE: Patients with prolactinoma seem to be at high risk for osteopenia. However, whether patients with various pathological sellar tumors have risk for osteopenia remains unclear. The aim of the present study is to assess the bone mass alteration in patients with various sellar tumors and further to investigate the risk factors of bone mass alteration. MATERIALS AND METHODS: 65 premenopausal female patients with diverse sellar tumors and 325 normal controls were enrolled in this study. Bone mineral density (BMD) of lumbar spine and comprehensive endocrinological evaluations were undergone. RESULTS: Compared to the matched controls, BMD of patients with prolactinoma or craniopharyngioma significantly decreased. Patients with sellar meningioma and nonfunctioning adenoma are with a decreasing tendency and patients with growth hormone-secreting adenoma are with an increasing tendency compared to controls. Univariate and multivariate regression analysis indicated that the bone loss in prolactinomas was significantly correlated to disease duration and hypogonadism. CONCLUSION: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma. Continuous surveillance of BMD is recommended in patients with meningioma or nonfunctioning adenoma.