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The hypothalamic region is susceptible to involvement of several processes. 1 Lesions in this region remain challenging for surgical access and treatment. Strategies include both endoscopic and microsurgical approaches. 2 A cranio-orbital approach with extradural clinoidectomy and optic canal unroofing provides the necessary corridor to visualize and decompress the optic nerve/chiasm and remains an important tool in achieving complete tumor resection with favorable functional and visual outcomes. 3-12 Endoscope assistance in transcranial surgery is well established, used to provide direct visualization of hidden adjacent tissues. 13 A 25-year-old woman presented with headache and progressive visual loss to blindness (hand waving and light perception) on admission. Magnetic resonance imaging demonstrated a 28-mm-diameter tumor in the hypothalamic region with no significant postcontrast enhancement. She underwent right cranio-orbital craniotomy, extradural anterior clinoidectomy, and optic canal unroofing with a 2-mm high-speed diamond drill and copious irrigation. After ipsilateral falciform ligament release, the tumor capsule was coagulated, sharply opened, and resected in a piecemeal fashion. Endoscopic assistance warranted the removal of hidden parts and confirmed tumor removal. Histopathology and next-generation sequencing confirmed the diagnosis of rosette-forming glioneural tumor. Follow-up revealed gross total tumor removal on magnetic resonance imaging and complete recovery of visual function as per ophthalmologist examination. Rosette-forming glioneural tumors are considered rare and classified as World Health Organization grade I tumors usually found in the fourth ventricle. 14 To our knowledge, we present the first operative video (Video 1) demonstrating the removal of rosette-forming glioneural tumor in the hypothalamic region with endoscopic assistance., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key role in the management of OPHG especially when the tumor exhibits mass effect and causes symptoms. However, data regarding outcomes and complications of surgical resection for OPHG remains heterogenous. The authors performed a systematic review on pediatric OPHG in four databases: PubMed, EMBASE, Cochrane Library, and Google Scholar. We included studies that reported on the visual outcomes and complications of OPHG resection. A meta-analysis was performed and reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 26 retrospective studies were included. Seven hundred ninety-seven pediatric patients with OPHG undergoing surgical resection were examined. A diagnosis of NF1 was confirmed in 9.7%. Gross total resection was achieved in 36.7%. Intraorbital optic pathway gliomas showed a significantly higher gross total resection rate compared to those located in the chiasmatic/hypothalamic region (75.8% vs. 9.6%). Postoperatively, visual acuity improved in 24.6%, remained unchanged in 68.2%, and worsened in 18.2%. Complications included hydrocephalus (35.4%), anterior pituitary dysfunction (19.6%), and transient diabetes insipidus (29%). Tumor progression post-resection occurred in 12.8%, through a mean follow-up of 53.5 months. Surgical resection remains an essential strategy for treating symptomatic and large pediatric OPHG and can result in favorable vision outcomes in most patients. Careful patient selection is critical. Patients should be monitored for hydrocephalus development postoperatively and followed up to assess for tumor progression and adjuvant treatment necessity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypothalamic hamartomas are uncommon congenital malformations that present as precocious puberty, gelastic seizures and/or psychiatric disorders. Characteristic changes in MRI scans lead to a diagnosis. Treatment may include surgery or gonadotropin-releasing hormone agonists (GnRHa) depending on clinical manifestations.Here, we describe a case of hypothalamic hamartoma diagnosed in a girl in middle childhood, who presented with early development of secondary sexual characteristics. Physical examination, hormonal study, bone age and pelvic ultrasound findings were consistent with those of precocious puberty. The investigation also included a brain MRI scan, which revealed a small nodule with regular limits in the left hypothalamic region/tuber cinereum. GnRHa treatment and neurosurgical follow-ups were initiated promptly. The patient showed a reversal of secondary sexual characteristics and stable hamartoma size. This case illustrates the importance of brain MRI scans as part of the assessment of suspected precocious puberty because clinical features do not identify patients with an underlying pathology., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A standardized approach for identifying and treating hypothalamic obesity (HO) in children with hypothalamic tumours is lacking., Objectives: To describe children with hypothalamic tumours at risk for obesity, assess outcomes of a novel HO clinical algorithm, and identify factors associated with weight gain., Methods: Retrospective analysis of youth with hypothalamic and suprasellar tumours, seen at a paediatric tertiary care centre from 2010 to 2020., Results: The study cohort (n = 130, 50% female, median age at diagnosis 5 [range 0-17]y) had a median duration of follow up of 5 (0.03-17)y. At last recorded body mass index (BMI) measurement, 34% had obesity, including 17% with severe obesity. Median onset of overweight and obesity after diagnosis was 6.2 (0.3-134) and 8.9 (0.7-65) months, respectively. After algorithm implementation (n = 13), the proportion that had an early dietitian visit (within 6 months) increased from 36% to 54%, (p = 0.498) and weight management referrals increased from 51% to 83% (p = 0.286). Higher BMI z-score at diagnosis was associated with overweight and obesity development (p < 0.001)., Conclusion: Patients with hypothalamic tumours commonly develop obesity. Use of a clinical algorithm may expedite recognition of HO. Further research is needed to identify predictors of weight gain and to develop effective treatment., (© 2022 World Obesity Federation.)

Objective: Youth with craniopharyngioma experience weight gain, fragmented sleep, excessive daytime sleepiness (EDS), fatigue, and psychosocial problems that negatively impact their overall health-related quality of life (HRQoL). Greater hypothalamic tumor involvement (HI) may be associated with higher rates or severity of these impairments; however, the direct and indirect impact of HI on the physical and psychosocial consequences associated with pediatric craniopharyngioma remain unclear. The purpose of the current study was to examine relations between HI, body mass index (BMI), fragmented sleep, EDS, fatigue, psychosocial problems, and HRQoL among youth with craniopharyngioma., Methods: Eighty-four youth with craniopharyngioma (M age  = 10.27 ± 4.3 years, 53.6% female, 64.3% White) were assessed with actigraphy, nocturnal polysomnography, and multiple sleep latency tests prior to proton therapy, when indicated. Caregivers completed measures of fatigue, psychosocial functioning, and HRQoL., Results: Hypothalamic tumor involvement was associated with greater BMI (Est. = 2.97, p = 0.003) and daytime sleepiness (Est. = 2.53, p = 0.01). Greater fatigue predicted more psychosocial problems (Est. = 0.29, p < 0.001) and lower HRQoL (Est. = 0.23, p = 0.001). Psychosocial problems also predicted lower HRQoL (Est. = -0.34, p = 0.004). Fragmented sleep (Est. = 0.03, p = 0.04) and fatigue (Est. = 0.10, p = 0.02) indirectly predicted lower HRQoL through psychosocial problems., Conclusions: Youth with craniopharyngioma with greater HI may benefit from weight reduction interventions and management of excessive sleepiness. Patients should be prospectively monitored for sleep problems, fatigue, and psychosocial problems, as these patients may benefit from interventions targeting fatigue and psychosocial health to improve HRQoL., (© 2021 John Wiley & Sons Ltd.)

Background: Cavernous malformations (cavernomas) are angiographically occult vascular lesions that can present symptomatically or be discovered incidentally. Rarely, they present in the hypothalamus or in children., Case Description: We describe the case of a 14-year-old male patient who presented with headaches and fever and was found to have a hypothalamic cavernoma that hemorrhaged. It was managed expectantly, with 1 rehemorrhage 21 months later, and the patient remains asymptomatic to this day aside from headaches., Conclusions: This is to our knowledge the youngest case of a hypothalamic cavernoma to be reported and includes 8.5 years of follow-up and imaging. In addition, a literature review is performed that summarizes the 11 previously reported cases of hypothalamic cavernomas, including associated symptoms, management options, and outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patients with childhood-onset craniopharyngioma (CP) often suffer from tumour or treatment-related hypothalamic lesions (HL). These lesions may alter production of oxytocin, which plays a major role in the regulation of eating behaviour and body composition., Objective: In CP with different degrees of HL, we investigated associations between HL, eating behaviour/eating attitudes, and oxytocin saliva concentrations (OSC)., Methods: In a cross-sectional case-control study on 34 CP and 73 healthy controls, OSC were measured before, and 60 minutes after breakfast by immunoassay. Eating behaviour, attitudes, and habits were assessed by standardized questionnaires., Results: CP with anterior + posterior HL presented with more adverse eating behaviours/symptoms of eating disorders than CP without HL, CP with anterior HL, and controls. Eating behaviour in CP with anterior HL was similar to controls, except for their tendency towards high dietary restraints. Decreases in postprandial compared with fasting OSC were associated with adverse eating behaviour in CP and controls and with higher BMI in CP., Conclusions: CP with anterior HL and CP with anterior + posterior HL present with distinct patterns of eating behaviour. Reduced postprandial compared with fasting OSC is associated with weight problems in CP and with adverse eating behaviour and symptoms of eating disorders in both CP and controls., (© 2019 World Obesity Federation.)

Purpose: Hydrocephalus is a common condition in pediatric neurosurgeon's clinical practice. Peritoneal and atrial shunting is the treatment of choice in the immense majority of patients. Sometimes, there are complex cases that may need innovative solutions in order to implant the distal catheter of the shunt: in these situations, the gallbladder is a well-described option and it can be safely used., Methods: We report the case of a 4-month-old baby with a wide optic-chiasmal hypothalamic glioma generating hydrocephalus with high protein values in CSF. Ventriculobiliary shunting was decided, and the distal catheter was directed by the assistance of laparoscopic surgery., Results: The outcome was satisfactory., Conclusions: As far as we know, laparoscopic placement of a distal catheter in the gallbladder has not been described in the literature; herein, we describe the tenets and the technical tips of this approach.

Background: Diffuse midline glioma H3 K27M mutant is a new tumor entity described in the revised 2016 World Health Organization classification. It is most frequently observed in children and develops in midline structures, including the brainstem, thalamus, and spine. We describe a rare diffuse midline glioma with an H3 K27M mutation arising in the hypothalamus of an adult., Case Description: A 27-year-old woman was admitted to our department complaining of amenorrhea, polydipsia, and diuresis for the previous 3 months, and headache and lethargy for approximately 10 days. Computed tomography scan showed an oval isodense solid mass extending from the pituitary toward the suprasellar cistern. A gadolinium-enhanced magnetic resonance imaging (MRI) showed a strongly heterogeneous enhanced solid lesion and nonenhanced cystic lesion. The patient underwent surgery and chemoradiotherapy with temozolomide. Histologic and immunohistochemical analyses revealed H3 K27M-mutant diffuse midline glioma. The patient underwent another resection for a recurrent tumor 5 months after the first surgery. Three months after the second operation, the patient relapsed, with MRI revealing spinal cord and meningeal metastases; she died shortly afterward., Conclusions: Diffuse midline glioma with an H3 K27M mutation occurring in the hypothalamus of an adult is rare but should be considered in differential diagnoses. Because histone H3 K27M mutations are associated with aggressive clinical behavior and poor prognosis, molecular analyses should be used to determine the clinical and histopathologic features of such tumors. This will contribute to developing targeted drugs and gene therapy going forward., (Copyright © 2019. Published by Elsevier Inc.)

Tumors of hypothalamic neurons that produce vasopressin are rare. We retrieved all cases of vasopressin-positive tumors in the sellar region from the database of the Department of Pathology. Five cases fulfilled the selection criteria, representing the first series of such tumors. Clinical, radiologic, and pathologic features were reviewed. Four tumors classified as neurocytomas were identified in 3 females and 1 male patient; the ages at onset of symptoms ranged from 17 to 40 years. All were large sellar masses with suprasellar extension and/or invasion of the parasellar sinuses. Three patients had the syndrome of inappropriate antidiuresis; in one of these, a 6-year history was initially considered to be idiopathic. One patient died of progressive disease; 3 had incomplete resections and are being followed. In contrast to these patients with neurocytoma, a 65-year-old woman had Cushing disease and a 0.8 cm mass that was completely resected at transsphenoidal surgery; this tumor was a gangliocytoma producing vasopressin associated with corticotroph hyperplasia. We postulate that the small amount of vasopressin secreted by this mature gangliocytic tumor was locally bound to corticotrophs, resulting in hyperplasia and Cushing disease, without sufficient overproduction to cause systemic effects of vasopressin excess. Hypothalamic neurocytoma is a tumor that can mimic pituitary neuroendocrine tumors and olfactory neuroblastoma but is distinguished by positivity for neurofilaments, NeuN, and TTF-1 and negative staining for adenohypophysial biomarkers. Our cases illustrate that neurocytoma and gangliocytoma are 2 variants of tumors of hypothalamic neurons that can produce vasopressin. The morphologic and proliferative features of these 2 tumor types represent 2 ends of a spectrum; their function also can result in divergent clinical manifestations, one characterized by reduced urine output and the other by the more insidious features of glucocorticoid excess.

Objective: The purpose of this study is to investigate the outcomes of epilepsy surgery targeting the subcentimeter-sized resting state functional magnetic resonance imaging (rs-fMRI) epileptogenic onset zone (EZ) in hypothalamic hamartoma (HH)., Methods: Fifty-one children with HH-related intractable epilepsy received anatomical MRI-guided stereotactic laser ablation (SLA) procedures. Fifteen of these children were control subjects (CS) not guided by rs-fMRI. Thirty-six had been preoperatively guided by rs-fMRI (RS) to determine EZs, which were subsequently targeted by SLA. The primary outcome measure for the study was a predetermined goal of 30% reduction in seizure frequency and improvement in class I Engel outcomes 1 year postoperatively. Quantitative and qualitative volumetric analyses of total HH and ablated tissue were also assessed., Results: In the RS group, the EZ target within the HH was ablated with high accuracy (>87.5% of target ablated in 83% of subjects). There was no difference between the groups in percentage of ablated hamartoma volume (P = 0.137). Overall seizure reduction was higher in the rs-fMRI group: 85% RS versus 49% CS (P = 0.0006, adjusted). The Engel Epilepsy Surgery Outcome Scale demonstrated significant differences in those with freedom from disabling seizures (class I), 92% RS versus 47% CS, a 45% improvement (P = 0.001). Compared to prior studies, there was improvement in class I outcomes (92% vs 76%-81%). No postoperative morbidity or mortality occurred., Significance: For the first time, surgical SLA targeting of subcentimeter-sized EZs, located by rs-fMRI, guided surgery for intractable epilepsy. Our outcomes demonstrated the highest seizure freedom rate without surgical complications and are a significant improvement over prior reports. The approach improved freedom from seizures by 45% compared to conventional ablation, regardless of hamartoma size or anatomical classification. This technique showed the same or reduced morbidity (0%) compared to recent non-rs-fMRI-guided SLA studies with as high as 20% permanent significant morbidity., (© 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

Objective: A rare, low-grade tumor found in the hypothalamus and anterior third ventricle, a chordoid glioma presents a challenge to neurosurgeons: Its successful resection is complicated by its inconvenient location., Case Description: A 42-year-old male patient presented with a 1-year history of major depressive disorder, with psychotic features associated with generalized tonic-clonic seizures. Brain magnetic resonance imaging (MRI) with contrast revealed a suprasellar mass extending into the third ventricle To resect the lesion, an interhemispheric transcallosal transventricular subfornical approach was used. Pathology revealed a chordoid glioma. The patient had a complicated post-operative period that included the development of neurogenic diabetes insipidus, followed by intractable hyponatremia and death (caused by malignant brain edema)., Conclusion: A chordoid glioma is a rare neoplasm that, in 2000, was incorporated into the World Health Organization (WHO) classification of central nervous system tumors. Due to its rarity, it is seldom considered in the differential diagnosis of suprasellar masses. Moreover, its unusual presentation and difficult location present a challenge for surgical and medical management.

Hypothalamic dysfunction leading to severe obesity is a serious long-term consequence of paediatric craniopharyngioma. It compromises quality of life, leads to long-term metabolic hazards, and may shorten life expectancy. Therefore, a proactive approach is required. Conventional treatment of hypothalamic obesity is difficult and hardly successful. Experience with bariatric surgery is limited, especially in younger patients. Two retrospective studies recently reported on classic bariatric surgery in a small series of individuals after craniopharyngioma. Of these, one included nine paediatric patients who underwent laparoscopic adjustable gastric banding (LAGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) or biliopancreatic diversion (BPD). The immediate effects were promising: The mean weight loss was 20.9 kilograms at 6 months and 15.1 kilograms at 12 months. A duodenal-jejunal bypass sleeve (DBJS; EndoBarrier) is a mini-invasive, endoscopically placed and fully reversible bariatric procedure. We reported a boy diagnosed with craniopharyngioma at 10 years old who underwent surgery and radiotherapy. His body weight increased to 139 kilograms and body mass index (BMI) to 46.1 kg/m2 (+4.0 SD) within the subsequent 4.5 years. Fifteen months after DJBS placement, he lost 32.8 kilograms, and his BMI dropped to 32.7 kg/m2 (+2.9 SD). Thus, DJBS proved to be a promising procedure in the treatment of hypothalamic obesity. We suggest performing it in children and adolescents with hypothalamic obesity to prevent or attenuate its devastating long-term sequelae., (Copyright© of YS Medical Media ltd.)

Severe obesity is a common consequence of hypothalamic region diseases and their treatment. Only two previous case reports have described hypothalamic lipomas in children with obesity. We described a case of an adult with severe obesity associated with hypothalamic lipoma attached to the third ventricle floor who underwent Roux-en-Y gastric bypass. He lost 38 and 59 kg at 6 and 12 months after surgery, respectively. Weight loss after bariatric surgery was as expected in this patient with severe obesity. At 6 and 12 months, brain magnetic resonance imaging (MRI) showed stability in lipoma's size.

Pilomyxoid astrocytoma (PMA) is a rare, low-grade glioma that is recognised as a variant of pilocytic astrocytoma. There have been few reports on this pathologic entity presenting with spontaneous haemorrhage. In this study, we report a rare case of PMA in the hypothalamic/chiasmatic region presenting with intratumoural and intraventricular haemorrhage. An external ventricular drain was urgently inserted. A ventriculo-peritoneal shunt (VP) was undergone 4weeks thereafter. The patient received fractionated Gamma Knife radiosurgery in another hospital 3weeks after the VP shunt. Three months later, subtotal resection of the tumour was performed in our hospital via a pterional approach. The pathological diagnosis was PMA. Postoperatively, no adjuvant therapy was given, and the neurologic deficits were improved. However, the presentation of endocrine deficits remained. Notably, PMAs in the hypothalamic/chiasmatic region presenting with massive intratumoural and intraventricular haemorrhage may result in a severe condition and long-term impairment of endocrine function. Long-term follow-up is required to monitor the recurrence of the tumour and endocrinopathy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The authors report a case of a child with hypothalamic-origin pilocytic astrocytoma and hydrocephalus, which was refractory to treatment with a ventriculoperitoneal shunt due to high CSF protein content. With parental education, the child's hydrocephalus was managed long-term in the community with a long-tunnelled external ventricular drain, which was maintained by his parents. To the authors' knowledge this is the first report of this management option as a long-term measure. No harm has come to the patient. The authors propose long-term, long-tunnelled external ventricular drain as a viable treatment option for such patients.

Background: Hypothalamic obesity (HyOb) is a common complication of childhood hypothalamic tumours. Patients with HyOb probably have a higher mortality rate than those with other types of obesity due in many cases to obstructive sleep apnoea/hypoventilation., Objectives: To identify predictive factors for mortality caused by HyOb in children., Methods: Twenty children with HyOb secondary to hypothalamic tumours that were followed-up for ≥3 years and aged <15 years at diagnosis, and received supraphysiological glucocorticoid treatment for ≤1 month., Results: Mean age at diagnosis was 6.36 ± 3.60 years. Mean body mass index (BMI) Standard deviation of the samples (SDS) increased from 0.77 ± 1.26 to 2.66 ± 1.45 during the first 6 months, but slowed from month 6-12 (2.73 ± 1.35). ΔBMI SDS at 0-6 months was significantly higher in patients aged <6 years at diagnosis than in those aged >6 years at diagnosis (3.71 ± 1.96 vs. 0.83 ± 0.73, P < 0.001). Maximum BMI SDS was also significantly higher in the younger group (3.88 ± 1.39 vs. 2.79 ± 0.64, P < 0.05). In all, four patients died and the mortality rate was significantly higher in the patients with a further increase in BMI SDS > 1 SDS after 6 months of therapy (RR: 8.4, P < 0.05). Both overall mortality and obesity-related mortality rates were higher in the patients aged <6 years at diagnosis (4.5-fold, 7.2-fold higher, respectively, P > 0.05). The mortality rate was also 3.7-fold higher in the patients with a maximum BMI SDS ≥ 3 at any time during the first 3 years after therapy(P > 0.05)., Conclusions: An increase in BMI SDS after 6 months of therapy was observed to be a risk factor for mortality caused by HyOb. In addition, age <6 years at diagnosis and a maximum BMI SDS ≥ 3 were associated with a higher mortality rate, indicating that earlier and more aggressive treatment of obesity is required., (© 2015 World Obesity.)

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by vascular malformations involving brain, skin, and occasionally eyes. There is no recognized tumor predisposition in patients with SWS as there is with some other phakomatoses. We present a patient with SWS who developed a low-grade glioma (LGG). We hypothesize that there could be an association between SWS and LGG formation, noting that GNAQ mutations have been implicated in the underlying biology of both SWS and a subset of pediatric LGG. It is suggested that SWS may be a cancer predisposition syndrome.

Rosette-forming glioneuronal tumors (RGNT) of the fourth ventricle are slow-growing tumors that primarily involve the fourth ventricular region. We here report the first patient, an 8-year-old girl, with an RGNT originating in the hypothalamus and manifesting with precocious puberty. After partial removal, the remaining tumor showed rapid enlargement, and the pathologic diagnosis at the second surgery revealed histopathologic features similar to those found in the initial samples, including biphasic patterns of neurocytic rosettes and GFAP-stained astrocytic components. These tumor cells had mildly atypical nuclei; however, mitotic figures and necrosis were absent. Eosinophilic granular bodies and a glomeruloid vasculature were found, but Rosenthal fibers were absent. The Ki-67 proliferative index was 3.5 % (vs 1.1 % at the initial surgery). No recurrence was recorded during the 3-year period after the proton radiotherapy.

Background: Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas., Case Presentation: We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy., Conclusions: Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

Objective: Hypothalamic obesity in childhood craniopharyngioma (CP) patients carries a high risk for development of metabolic syndrome. In metabolic syndrome, the development of nonalcoholic fatty liver disease (NAFLD) is known. The aim of this study is to detect the risk for NAFLD in childhood-onset CP., Design: This cross-sectional study included liver computed tomography (CT); ultrasound analysis of abdomen; measurements of serum parameters, height, weight and body composition; and daily medication of patients with childhood-onset CP., Methods: A total of 384 patients recruited in trials HIT Endo and KRANIOPHARYNGEOM 2000 were analyzed. Ninety-four survivors were included by fulfilling the criteria of proven hypothalamic involvement (HI), a minimum time interval of 5 years between diagnosis and study, and a minimum age of 18 years at the time of evaluation. A total of 19 patients agreed to participate. To quantify the degree of steatosis hepatis, analyses of liver density were performed once by non-contrasted CT of liver sections., Results: NAFLD occurs in about 50% of CP patients with HI and is associated with elevated liver enzymes and homeostasis model assessment index. BMI is not an effective predictive factor but body fat mass measured by near-infrared spectroscopy (NIRS) is. Over half of CP patients (60%) with NAFLD are treated with stimulating agents, with risk of hepatic side effects., Conclusions: NAFLD is a major adverse late effect in childhood-onset CP. NIRS rather than BMI should be used to measure body composition and predict NAFLD. Stimulating agents for treatment of fatigue and daytime sleepiness in CP should be prescribed judiciously., (© 2015 European Society of Endocrinology.)

Background: Quality of life (QoL) and long-term prognosis are frequently, and often severely, impaired in craniopharyngioma (CP) patients. Knowledge of risk factors for long-term outcome is important for optimization of treatment., Methods: Overall survival (OS) and progression-free survival (PFS), body mass index (BMI), neuropsychological status (EORTCQLQ-C30, MFI-20), and psychosocial status were analyzed in 261 patients with childhood-onset CP diagnosed before 2000 and longitudinally observed in HIT-Endo., Results: Twenty-year OS was lower (P = .006) in CP with hypothalamic involvement (HI) (n = 132; 0.84 ± 0.04) when compared with CP without HI (n = 82; 0.95 ± 0.04). OS was not related to degree of resection, sex, age at diagnosis, or year of diagnosis (before/after 1990). PFS (n = 168; 0.58 ± 0.05) was lower in younger patients (<5 y at diagnosis) (n = 30; 0.39 ± 0.10) compared with patients aged 5-10 years (n = 66; 0.52 ± 0.08) and older than 10 years (n = 72; 0.77 ± 0.06) at diagnosis. PFS was not associated with HI, degree of resection, or sex. HI led to severe weight gain during the first 8-12 years of follow-up (median BMI increase: +4.59SD) compared with no HI (median increase: +1.20SD) (P = .00). During >12 years of follow-up, patients with HI presented no further increase in BMI. QoL in CP patients with HI was impaired by obesity, physical fatigue, reduced motivation, dyspnea, diarrhea, and nonoptimal psychosocial development., Conclusions: OS and QoL are impaired by HI in long-term survivors of CP. HI is associated with severe obesity, which plateaus after 12 years. OS/PFS are not related to degree of resection, but gross-total resection should be avoided in cases of HI to prevent further hypothalamic damage, which exacerbates sequelae., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Tumors in eloquent areas of the brain like Broca or Wernicke might have disastrous consequences for patients. We intended to visualize the arcuate fasciculus (AF) and to demonstrate his relation with the corticospinal tract and the visual pathway using diffusion tensor imaging (DTI)., Methods: We depicted between 2012 and 2014 the AF in 71 patients. Men and women of all ages were included. Eleven patients had postoperative controls also. We used a 3DT1-sequence for the navigation. Furthermore T2- and DTI-sequences were performed. The FOV was 200 × 200 mm(2), slice thickness 2mm, and an acquisition matrix of 96 × 96 yielding nearly isotropic voxels of 2 × 2 × 2 mm. 3-Tesla-MRI was carried out strictly axial using 32 gradient directions and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2. b-Value was 800 s/mm(2). Additional scanning time was less than 9 min., Results: AF was portrayed in 63 patients bilaterally. In one glioblastoma patient it was impossible to visualize the left AF and in seven other patients we could not portray the right one. The lesions affected AF by disrupting or displacing the fibers., Conclusions: DTI might be a useful tool to portray AF. It is time-saving and can be used to preserve morbidity in patients with lesions in eloquent brain areas. It might give deeper insights of the white matter and the reorganization of AF-fibers postoperatively., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Pilomyxoid astrocytomas are a more aggressive variant of pilocytic astrocytoma. Over the last 14 years, there has been increasing evidence to suggest that these tumours are distinct pathological entities to pilocytic astrocytomas. Radiological features of these tumours are slowly emerging in the neuroradiological literature. We report a unique radiological appearance of a multicystic, disseminated astrocytoma with pilomyxoid characteristics presenting in a 4-year-old boy and highlight the importance of considering this diagnosis with similar imaging.

Klinefelter Syndrome is the most frequent cause of hypergonadotropic hypogonadism in men. A flat response at luteinizing hormone releasing hormone stimulation test could be the first sign of hypothalamic tumor in these patients. We report the case of a patient diagnosed by neonatal screening with Klinefelter Syndrome, 47 XXY, that at 17 years follow-up presents analytical modification of the response to luteinizing hormone releasing hormone stimulation test with suppressed luteinizing hormone and follicle-stimulating hormone values; lately he presents with headache and loss of left eye vision. A magnetic resonance imaging of the brain showed a mixed germ cell hypothalamus tumor, requiring surgery, chemotherapy and radiotherapy with optimal response.

Background: Severe obesity due to hypothalamic involvement has major impact on prognosis in long-term survivors of childhood craniopharyngioma. The long-term effects of rehabilitation efforts on weight development and obesity in these patients are not analyzed up to now., Patients and Methods: 108 patients with childhood craniopharyngioma recruited in HIT Endo before 2001 were included in the study. Long-term weight development (BMI SDS after >10 yrs follow-up) was analyzed in regard to rehabilitation, which was performed in 31 of 108 (29%) patients (one rehabilitation in 4 patients (13%), more than one in 21 patients (68%), 6 patients unknown) in 13 German rehabilitation -clinics., Results: 84% of patients underwent rehabilitation in order to reduce hypothalamic obesity (BMI>+ 2 SD), whereas 12% of patients were normal weight. Childhood craniopharyngioma pa-tients with rehabilitation presented with higher BMI at diagnosis (median BMI: +1.32 SD; range: -1.08 to + 7.00 SD) and at last evaluation (median BMI: +4.93 SD; range: -0.20 to + 13.13 SD) when compared with patients without rehabilitation (median BMI at diagnosis: +0.24 SD; range: -2.67 to + 6.98 SD; BMI at evaluation: +2.09 SD; range: -1.48 to + 10.23 SD). A long-term weight reducing effect of rehabilitation was no detectable regardless of degree of obesity, frequency of rehabilitation, and hospital of rehabilitation., Conclusion: Treatment options for hypothalamic obesity in terms of rehabilitation are limited. Accordingly, strategies for prevention of hypothalamic lesions and psychosocial effects of rehabilitation are currently in focus for improvement of prognosis in childhood craniopharyngioma patients., (© Georg Thieme Verlag KG Stuttgart · New York.)

We report the case of a child who presented with diencephalic syndrome. During diagnostic work- up, he was found to have a supra-sellar hypothalamic tumour. Histopathological examination of the tumour revealed it to be pilomyxoid astrocytoma, which is a WHO grade-II tumour, previously considered to be part of the spectrum of WHO grade-I pilocytic astrocytomas. However, because of its characteristic histopathology and behaviour, it was later segregated from pilocytic astrocytomas. In this case report, we discuss the cytological and histopathological features of this tumor with the aim of increasing awareness of this tumour amongst general histopathologists, to highlight the importance of its differentiation from pilocytic astrocytomas in view of its different behaviour, treatment and prognosis and that it should be included in the differential diagnosis of diencephalic syndrome.

Object: Optic pathway/hypothalamic gliomas (OPHGs) are generally benign tumors situated in an exquisitely sensitive brain region. The location and natural history of OPHGs has led to much debate about optimal treatment. This paper revisits the role of and optimal timing of debulking surgery in OPHG., Methods: This paper presents a series of cases managed by the neuro-oncology team at Alder Hey Children's Hospital and a single surgeon. Data were collected retrospectively for periods prior to 2009 and prospectively thereafter. Tailored treatment strategies were used, including observation and combinations of surgery, chemotherapy, and radiotherapy. Tumor control rates and outcomes are reviewed., Results: Forty-two patients were treated between 1998 and 2011. Their median age at diagnosis was 5 years 7 months. Nineteen patients were positive for neurofibromatosis Type 1 (NF1) and 23 patients were negative for NF1. The median duration of follow-up was 77 months (range 21.8-142.3 months). Presenting symptoms included visual impairment (in 50% of cases), headache (in 24%), and hypothalamic/pituitary dysfunction (in 29%). Twenty-two debulking procedures were performed in 21 patients. Four biopsies (3 open, 1 endoscopic) were also performed. The histological diagnosis was pilocytic astrocytoma in 21 patients and pilomyxoid astrocytoma in 2 patients. Ten patients (Group 1) had primary surgical debulking alone and were then observed. Four patients (Group 2) had surgical debulking, plus planned chemotherapy within 3 months. Seven patients (Group 3) required surgical debulking for progressive disease following a variety of treatments. Patient age had the greatest impact on subsequent tumor progression. In total, 13 patients received chemotherapy, 4 on initial presentation, 4 in combination with surgery, and 5 for further tumor progression. Five patients were treated with radiotherapy, 3 prior to referral to Alder Hey. Eleven patients required shunt insertion for hydrocephalus. Vision was stabilized for 74% of patients. The number of patients with hypothalamic/pituitary dysfunction increased from 12 at presentation to 16 by the end of treatment. The overall survival rate was 93%. Three patients died-1 from tumor progression, 1 from infective complications from tumor biopsy, and 1 from a spontaneous posterior fossa hemorrhage. NF1 was associated with improved outcome-fewer patients required active intervention and rates of visual impairment and/or or hypothalamic/pituitary dysfunction were lower., Conclusions: Good long-term survival and functional outcomes can be achieved in children with OPHG. Tumor control was achieved through an individualized approach using surgery, chemotherapy, or radiotherapy in varied combinations. The authors aim to limit radiotherapy to cases involving older children in whom other therapies have failed, due to the well-described and often devastating late effects associated with midline cranial irradiation. Surgery has a clear role for diagnosis, tumor control, and relief of mass effect. In particular, primary surgical debulking of tumor (without adjuvant therapy) is safe and effective. Recent advances in intraoperative MRI may add value and need further assessment.

Psychosis is more common in people with temporal lobe epilepsy than it is in the general population. Treatment can be difficult in these patients because of the complex interactions between antipsychotic and antiepileptic drugs. Some antipsychotic drugs also decrease the seizure threshold. We report the case of a 49-year-old man with a hypothalamic hamartoma, with a history of both gelastic and temporal lobe seizures. The patient was rendered seizure-free after three neurosurgical procedures but developed a drug-resistant paranoid psychosis. He was treated with electroconvulsive therapy (ECT). After two weeks with six stimulations that resulted in seizures, the psychiatric phenomena disappeared completely. There was no relapse of either the psychiatric symptoms or the seizures during the 42 months of follow-up. This case report suggests that ECT might be safe for psychosis in patients with a history of seizures that have previously been successfully treated with neurosurgery, although caution should be exercised in drawing general conclusions from a single case report.

Severe obesity is a major problem in pediatric craniopharyngioma. We investigated whether tumor origin, growth pattern, and surgical damage predict obesity in pediatric craniopharyngioma. Subjects were 58 patients (30 males) with no tumor recurrence during the first postoperative 18 months. Preoperative hypothalamic involvement was classified into no (pre&#95;G0, n = 19), little (pre&#95;G1, n = 21), and severe (pre&#95;G2, n = 18) involvement groups based on sub- or supradiaphragmatic tumor origin and growth patterns. Postoperative hypothalamic involvement was classified into no (post&#95;G0, n = 4), minimal (post&#95;G1, n = 19), and significant (post&#95;G2, n = 35) involvement groups according to follow-up imaging. The prevalence of obesity increased from 13.2 % at diagnosis (mean age = 8.1 years) to 37.9 % at last follow-up (mean duration = 9.1 years). Only the body mass index (BMI) Z-score increment of the first postoperative year (first-year ΔBMI&#95;Z) was significant (P = 0.007). Both the preoperative BMI&#95;Z (P = 0.001) and the first-year ΔBMI&#95;Z (P = 0.017) showed an increasing trend from the pre&#95;G0 to pre&#95;G1 to pre&#95;G2 group. For the 40 patients with pre&#95;G0 or pre&#95;G1, the first-year ΔBMI&#95;Z was higher in the post&#95;G2 group than the post&#95;G1 group (0.02 ± 0.91 vs. 0.89 ± 0.72, P = 0.003). Tumor origin and growth pattern affect preoperative BMI&#95;Z and postoperative weight gain. Despite little or no hypothalamic involvement at diagnosis, surgical damage contributes to postoperative weight gain in patients with craniopharyngioma.

Context: Hypernatremia is encountered after pituitary or hypothalamic surgery and typically is secondary to vasopressin deficiency resulting in increased free water clearance with inadequate water replacement., Objective: We report a type 2 diabetic patient with severe hypernatremia (Na⁺ = 161 mEq/L) after hypothalamic surgery. Unexpectedly, this was accompanied by persistent urinary hypertonicity and negative total but positive electrolyte free water clearance., Main Outcome Measure: Measurement of urinary electrolytes and urea revealed that an osmotic diuresis induced by urea derived principally by breakdown of endogenous protein was causative. Body protein losses over 48 hours were estimated to exceed 2 kg of lean mass. High-dose glucocorticoid, insulin resistance, and a postsurgical catabolic stress likely contributed., Conclusion: In surgically severely stressed individuals, proteolysis of endogenous protein can strongly impact body water metabolism and contribute to severe hypernatremia.

Diencephalic syndrome (DS) related to hypothalamic/chiasmatic region tumor has mainly been reported with low-grade glioma. We described 2 young children with DS related to pilomyxoid astrocytoma. Despite the recognized more agressive clinical behavior of this histologic subtype, we report successful resolution of DS and sustained tumor response with prolonged use of single-agent vinblastine.

Objective: To evaluate whether analyses of clinical and endocrine presenting symptoms could help to shorten the time to diagnosis of hypothalamic-pituitary lesions in children., Study Design: A retrospective, single-center, cohort study of 176 patients (93 boys), aged 6 years (range, 0.2-18 years), with hypothalamic-pituitary lesions was performed., Results: The lesions were craniopharyngioma (n = 56), optic pathway glioma (n = 54), suprasellar arachnoid cyst (n = 25), hamartoma (n = 22), germ cell tumor (n = 12), and hypothalamic-pituitary astrocytoma (n = 7). The most common presenting symptoms were neurologic (50%) and/or visual complaints (38%), followed by solitary endocrine symptoms (28%). Precocious puberty led to diagnosis in 19% of prepubertal patients (n = 131), occurring earlier in patients with hamartoma than in patients with optic-pathway glioma (P < .02). Isolated diabetes insipidus led to diagnosis for all germ-cell tumors. For 122 patients with neuro-ophthalmic presenting symptoms, the mean symptom interval was 0.5 year (95% CI, 0.4-0.6 year), although 66% of patients had abnormal body mass index or growth velocity, which preceded the presenting symptom interval onset by 1.9 years (95% CI, 1.5-2.4 years) (P < .0001) and 1.4 years (95% CI, 1-1.8 years) (P < .0001), respectively. Among them, 41 patients were obese before diagnosis (median 2.2 years [IQR, 1-3 years] prior to diagnosis) and 35 of them had normal growth velocity at the onset of obesity. The sensitivity of current guidelines for management of childhood obesity failed to identify 61%-85% of obese children with an underlying hypothalamic-pituitary lesion in our series., Conclusions: Endocrine disorders occurred in two-thirds of patients prior to the onset of the neuro-ophthalmic presenting symptom but were missed. Identifying them may help to diagnose hypothalamic-pituitary lesions earlier., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Hypothalamic obesity is an intractable form of obesity syndrome that was initially described in patients with hypothalamic tumours and surgical damage. However, this definition is now expanded to include obesity developing after a variety of insults, including intracranial infections, infiltrations, trauma, vascular problems and hydrocephalus, in addition to acquired or congenital functional defects in central energy homeostasis in children with the so-called common obesity. The pathogenetic mechanisms underlying hypothalamic obesity are complex and multifactorial. Weight gain results from damage to the ventromedial hypothalamus, which leads, variously, to hyperphagia, a low-resting metabolic rate; autonomic imbalance; growth hormone-, gonadotropins and thyroid-stimulating hormone deficiency; hypomobility; and insomnia. Hypothalamic obesity did not receive enough attention, as evidenced by rarity of studies in this group of patients. A satellite symposium was held during the European Congress of Obesity in May 2011, in Istanbul, Turkey, to discuss recent developments and concepts regarding pathophysiology and management of hypothalamic obesity in children. An international group of leading researchers presented certain aspects of the problem. This paper summarizes the highlights of this symposium. Understanding the central role of the hypothalamus in the regulation of feeding and energy metabolism will help us gain insights into the pathogenesis and management of common obesity., (© 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.)

Background/aims: Patients with hypothalamic tumors frequently experience severe obesity, and its treatment with diet, exercise, and/or pharmacologic treatment has had limited effect. Glucagon-like peptide-1 agonist exenatide (exendin-4), used for treatment of type 2 diabetes, causes persistent weight loss via signaling in the brainstem., Methods: We report the case of a 17-year-old patient with obesity resulting from a hypothalamic germ cell tumor. He was treated by chemoradiotherapy and exenatide at a dose of 5 µg subcutaneously twice daily., Results: Exenatide resulted in a 29-kg weight loss (BMI reduction from 37.1 to 29.1) after 2.5 years of treatment; significant weight gain occurred shortly after exenatide was discontinued., Conclusion: Exenatide resulted in considerable reduction of body weight in a patient with severe hypothalamic obesity. This novel observation requires follow-up clinical studies for establishing the effects of exenatide in patients with disrupted hypothalamic energy regulatory pathways., (Copyright © 2012 S. Karger AG, Basel.)

Central precocious puberty (CPP) is fairly common in girls. In most girls, the etiology for the CPP is unknown. Among the more rare causes of CPP in girls are central nervous system tumors and hamartomas. Osteolipoma of the tuber cinereum, which is the most commonly diagnosed at autopsy, has been reported as a cause of CPP. We describe an 8-year-old girl with central precocious puberty in whom MRI demonstrated a lesion compatible with osteolipoma. Her symptom was breast development that begun at age 7 years and 9 months. Her case history, laboratory studies and imaging are presented. Her puberty was rapidly progressive. She was treated successfully with a GnRHa (Triptorelin 3.75 mg IM q 4 weeks). Her case brings to the forefront the need to perform an MRI in children with rapidly progressing puberty.

A Fabry patient with poikilothermia is described. Laboratory investigations, neuro-imaging and autonomic function tests did not disclose a cause. Assessment of intra-epidermal nerve fibre density and quantitative sensory testing revealed small fibre neuropathy with a highly impaired cold sensation. We speculate that the poikilothermia is either caused by a vascular lesion in the hypothalamus not visible on MRI or by small fibre neuropathy leading to disturbed body temperature perception and therefore impaired thermoregulation.

We present an unusual case of primary central nervous system (CNS) lymphoma presenting with bilateral symmetric hypothalamic lesions causing diabetes insipidus and hypopituitarism. A 50-year-old male presented initially with mental status changes, polyuria and polydipsia. The patient was determined to have diabetes insipidus (DI) and significant anterior pituitary deficiencies resulting in symptomatic pleural and pericardial effusions. Brain MRI with contrast demonstrated bilateral enhancement of his hypothalamus extending to the optic tract. The extensive diagnostic workup that ensued on his initial presentation was non-diagnostic as he had no obvious site of involvement that was easily accessible to biopsy. With close follow-up, the patient had rapid radiographic progression of his disease to his cerebral hemispheres. He therefore underwent brain biopsy and was diagnosed with primary CNS large B cell lymphoma. Chemotherapy has resulted in disease remission with resolution of MRI findings, but the patient has not had resolution of the hypopituitarism or DI. This case highlights the unique diagnostic challenge of patients with isolated hypothalamic lesions., (© Springer Science+Business Media, LLC 2009)

Patients with craniopharyngioma (CP), a tumor located in the pituitary and/or hypothalamus, are susceptible to developing obesity and many metabolic complications. The study aim was to create a rodent model that mimics the complex neuroanatomical and metabolic disturbances commonly seen in obese CP patients. We compared the metabolic phenotype of animals with three distinct types of hypothalamic lesions: 1) destruction of the arcuate nucleus (ARC) induced by monosodium glutamate (MSG), 2) electrolytic lesion of the adjacent ventromedial nucleus (VMN) alone, 3) both the VMN and dorsomedial nucleus (DMN), or a 4) combined medial hypothalamic lesion (CMHL) affecting the VMN, DMN, and the ARC. Only the CMHL model exhibited all key features observed in patients with hypothalamic obesity induced by CP. These features included excessive weight gain due to increased adiposity, increased food intake, and pronounced hyperinsulinemia and hyperleptinemia. Similar to characteristics of patients with CP, CMHL animals exhibited reduced plasma levels of alpha-melanocyte stimulating hormone and reduced ambulatory activity compared with weight-matched controls. Therefore, the CMHL model best mimics the complex metabolic abnormalities observed in obese CP patients compared with lesions to other hypothalamic areas and provides a foundation for future pharmacological approaches to treat obesity in children with hypothalamic damage.

Many patients with hypothalamic hamartomas present in infancy with gelastic seizures of subcortical origin, but later develop additional seizure types, including complex partial, tonic, and generalized tonic-clonic seizures. The basic cellular mechanisms responsible for this evolution in seizure types are unknown. Using voxel-based morphometry of T1 weighted MRI scans we compared eight patients with only gelastic seizures with 16 age-matched patients with multiple seizure types and found significantly greater white matter density in the temporal lobes and cerebellum in those with multiple seizure types. This suggests that increased white matter density, perhaps resulting from maturational changes and resulting in increased brain connectivity, is associated with a higher likelihood of cortical involvement in epilepsy resulting from hypothalamic hamartoma., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Optic chiasmatic-hypothalamic gliomas are sellar-suprasellar lesions with variable radiological features. The advocated treatment is mainly primary radiotherapy without a histological diagnosis. However, in developing countries, like India infective granulomas (tuberculomas) in the suprasellar region radiologically can mimic optic chiasmatic-hypothalamic gliomas. Hence primary radiotherapy without histological confirmation may have deleterious consequences., Aim: The aim of the paper was to analyze the sensitivity and specificity of magnetic resonance imaging (MRI) in these lesions and to analyze the feasibility of primary radiotherapy., Patients and Methods: The magnetic resonance imaging (MRI) characteristics of 24 patients with either histologically proven optic chiasmatic "pilocytic astrocytoma" or radiologically suspected optic chiasmatic-hypothalamic gliomas were analyzed. They were grouped into three groups on the basis of radiological features and treated with a suspected diagnosis. The final diagnosis was correlated with preoperative diagnosis, and the feasibility of managing these lesions without a histopathological confirmation is discussed., Results: The three radiological groups were: Group-1 solid tumors with or without microcysts in 9 patients (histology: 8 pilocystic astrocytomas and 1 tuberculoma); Group-2 mixed tumors with solid and cystic components in 9 patients (histology: 7 pilocytic astrocytomas and 2 craniopharyngiomas); Group-3 ring enhancing lesions in 6 patients (all the 6 patients initially received antituberculous treatment, in 3 patients the lesion resolved and in the remaining 3 patients the lesion was subjected to biopsy as it did not resolve, the biopsy was suggestive of pilocytic astrocytoma). Thus, MRI was shown to have a sensitivity of 83.33% and a specificity of 50% for diagnosing optic chiasmatic-hypothalamic gliomas., Conclusions: Various lesions like craniopharyngiomas, tuberculomas can mimic optic chiasmatic-hypothalamic gliomas radiologically, and it is not possible to diagnose them with certainty on the basis of radiological findings alone. Biopsy and tissue diagnosis should always be sought before instituting radiotherapy or chemotherapy for optic chiasmatic-hypothalamic gliomas.