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.

Our experience in prolactinomas larger than 60mm / Nuestra experiencia en prolactinomas mayores de 60mm

INTRODUCTION: Giant prolactinomas (tumor size larger than 40mm) are a rare entity of benign nature. Prolactinomas larger than 60mm are usually underrepresented in published studies and their clinical presentation, outcomes and management might be different from smaller giant prolactinomas. PATIENTS AND METHODS: We retrospective collected data from patients with prolactinomas larger than 60mm in maximum diameter and prolactin (PRL) serum levels higher than 21,200μIU/mL in our series of prolactinomas (283). Data were collected from January 2012 to December 2017. We included three patients with prolactinomas larger than 60mm. RESULTS: At diagnosis, two patients presented neurological symptoms and one nasal protrusion. All patients received medical treatment with dopamine agonists. No surgical procedure was performed. Median prolactin levels at diagnosis was 108,180 [52,594-514,984]μIU/mL. Medical treatment achieved a marked reduction (>99%) in prolactin levels in all cases. Tumor size reduction (higher than 33%) was observed in all cases. In one patient cerebrospinal fluid (CSF) leak was observed after tumor shrinkage. CONCLUSIONS: Dopamine agonists appear to be an effective and safe first-line treatment in prolactinomas larger than 60mm even in life-threatening situations. More studies with a higher number of patients are necessary to obtain enough data to make major recommendations

INTRODUCCIÓN: Los prolactinomas gigantes (de tamaño superior a 40mm) son una entidad rara de naturaleza benigna. Los prolactinomas mayores de 60mm suelen estar infrarrepresentados en los estudios publicados, y su presentación clínica, resultados y tratamiento podrían ser diferentes de los de prolactinomas gigantes más pequeños. PACIENTES Y MÉTODOS: Recogimos retrospectivamente datos de pacientes con prolactinomas de más de 60mm de diámetro máximo y con concentraciones séricas de prolactina (PRL) superiores a 21.200μIU/ml de nuestra serie de prolactinomas (283). Los datos se recogieron entre enero de 2012 y diciembre de 2017. Se incluyeron 3 pacientes con prolactinomas mayores de 60mm. RESULTADOS: En el momento del diagnóstico, 2 pacientes presentaban síntomas neurológicos, y uno protrusión nasal. Todos los pacientes recibieron tratamiento médico con agonistas dopaminérgicos. No se realizó ninguna intervención quirúrgica. La mediana de las concentraciones de PRL al diagnóstico fue de 108.180 (52.594-514.984)μIU/ml. El tratamiento médico logró una reducción notable (>99%) de los valores de prolactina en todos los casos. En todos los casos se observó una reducción del tamaño del tumor (superior al 33%). En un paciente se observó una fuga de líquido cefalorraquídeo (LCR) tras la reducción del tumor. CONCLUSIÓN: Los agonistas dopaminérgicos parecen ser un tratamiento de primera línea eficaz y seguro en los prolactinomas mayores de 60mm incluso en situaciones peligrosas para la vida. Se necesitan más estudios con un mayor número de pacientes para obtener datos suficientes para hacer recomendaciones importantes

Hypothalamic Cavernomas: Pediatric Case Report with 8.5-Year Follow-up and Review of the Literature.

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.

Generalizability of "GWAS Hits" in Clinical Populations: Lessons from Childhood Cancer Survivors.

With mounting interest in translating genome-wide association study (GWAS) hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here, we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study, and we show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (n = 2,231; observed-to-expected replication ratio = 0.70, p = 6.2 × 10-8). An examination of five comparable phenotypes in a second independent cohort of survivors from the Childhood Cancer Survivor Study corroborated the overall limited generalizability of meta-GWAS hits to survivors (n = 4,212; observed-to-expected replication ratio = 0.55, p = 5.6 × 10-15). Finally, in direct comparisons of survivor samples against independent equivalently powered general population samples from the UK Biobank, we consistently observed lower meta-GWAS hit replication rates and poorer polygenic risk score predictive performance in survivor samples for multiple phenotypes. As a possible explanation, we found that meta-GWAS hits were less likely to be replicated in survivors who had been exposed to cancer therapies that are associated with phenotype risk. Examination of complementary DNA methylation data in a subset of survivors revealed that treatment-related methylation patterns at genomic sites linked to meta-GWAS hits may disrupt established genetic signals in survivors.

Frequent Clinical and Radiological Progression of Optic Pathway/Hypothalamic Pilocytic Astrocytoma in Adolescents and Young Adults.

Most cases of optic hypothalamic pilocytic astrocytoma (OHPA) develop during childhood, so few cases of histologically verified OHPA have been described in adolescents and young adults (AYA). To elucidate the clinical features of OHPA with histological verification in AYA, we reviewed the clinical and radiological finding of OHPA treated at our institute from January 1997 and July 2017. AYA are aged between 15 and 39 years. The clinical courses of 11 AYA patients with optic hypothalamic glioma (OHG) without neurofibromatosis type 1 were retrospectively reviewed. About six patients were diagnosed in childhood and followed up after 15 years of age, and five patients developed OHPA during AYA. Histological diagnosis, verified at initial presentation or recurrence, was pilocytic astrocytoma in 10 and pilomyxoid astrocytoma in one. After initial treatment including debulking surgery and/or chemotherapy, tumor progression occurred 16 times in seven patients as cyst formation, tumor growth, and intratumoral hemorrhage. Five of 10 patients suffered deterioration of visual function during AYA. One of 10 cases had endocrinopathies requiring hormone replacement at last follow-up examination. In conclusion, histological diagnoses of OHG before and in AYA were pilocytic astrocytoma or pilomyxoid astrocytoma. Both pediatric and AYA-onset OHPA demonstrate high incidences of tumor progression and visual dysfunctions in AYA, so that long-term follow up is essential after the completion of treatment for pediatric and AYA-onset OHPA. The optimal timing of debulking surgery and radiation therapy should be established to achieve the long-term tumor control and to preserve the visual function.

Hypothalamic Vasopressin-Producing Tumors: Often Inappropriate Diuresis But Occasionally Cushing Disease.

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.

Progression of pituitary tumours: impact of GH secretory status and long-term GH replacement therapy.

BACKGROUND: Most patients treated for hypothalamic-pituitary tumours develop GH deficiency. Long-term GH replacement treatment in adults with a previous history of hypothalamic-pituitary tumour could represent a concern about increasing the risk of tumour enlargement or recurrence. PURPOSE: To assess the progression risk of hypothalamic-pituitary tumours according to the GH secretory status (normal GH secretion, non-treated and treated GH deficiency). and determine the predictors of neoplasm recurrence. METHODS: We retrospectively reviewed 309 patients with tumours of the hypothalamic-pituitary region (294 subjects underwent neurosurgery while 81 radiotherapy) who were followed for 9.9 ± 8.3 years. RESULTS: Out of 309 patients, 200 were affected by severe GH deficiency; 90 of these underwent GH therapy. The tumour progression rate did not differ among GH-sufficient, not-treated and treated GH-deficient patients (16.5%, 16.4%. and 10.0%, respectively). In a multivariate analysis, previous radiotherapy (HR 0.12, CI 0.03-0.52, p < 0.005) and residual tumour (HR 8.20, CI 2.38-28.29, p < 0.001) were independent predictors of recurrence. After controlling for multiple covariates, the tumour recurrence risk in GH-sufficient and GH-treated patients was similar to that observed in not-treated GH-deficient patients. CONCLUSIONS: With limitations of retrospective analysis, GH therapy is not associated with an increased progression rate of tumours of the hypotalamic-pituitary region during long follow-up, thus supporting the long-term safety of GH treatment. The only predictors of tumour recurrence appear to be the presence of residual disease and the lack of radiotherapy.

Endoscopic Transsphenoidal Surgery for an Adult Patient With Giant Exophytic Chiasmatic/Hypothalamic Glioma.

Optic pathway hypothalamic gliomas are intrinsic low-grade gliomas involving the optic nerve, chiasm, optic tract, and hypothalamus. The rarity of these tumors and their unpredictable course make assessment and standardization of treatment modalities difficult. Tumor debulking via various transcranial approaches was considered to be effective at controlling tumor growth, but with high rates of severe surgery-related complications. In the present case, endoscopic transsphenoidal surgery was initiated to debulk the exophytic chiasmatic/hypothalamic glioma with good preservation of hypothalamic and endocrine functions. The authors suggest transsphenoidal surgery with tumor debulking could be an effective and safe treatment for patients with chiasmatic/hypothalamic gliomas.

Neurofibromatosis type 1: A neuro-psycho-cutaneous syndrome?

Neurofibromatosis type 1 (NF1) is an inherited disorder often associated with optic nerve gliomas, low-grade brain tumors, and readily visible signs. Though these features are frequently emphasized, the psychosocial and emotional morbidities are often overlooked. We present a patient with depressive disorder resulting in suicide in a patient with NF1.

Radiation Therapy for Optic Pathway and Hypothalamic Low-Grade Gliomas in Children.

PURPOSE: The long-term survival of pediatric patients with optic pathway or hypothalamic low-grade glioma (LGG) who receive radiation therapy (RT) has not been previously assessed. METHODS AND MATERIALS: A retrospective study was performed of all patients with optic-hypothalamic pediatric LGG treated with RT at a single institution. Eligible patients were aged ≤21 years at the time of RT and had localized LGG diagnosed by neuroimaging or histology. The median RT dose was 54 Gy, delivered in 30 fractions. Event-free survival (EFS) was defined as survival without progression or secondary high-grade glioma. Days were counted from the first day of RT. RESULTS: Eighty-nine patients were included in the study, with a median follow-up period of 12.5 years. Of the patients, 14 had neurofibromatosis type 1 (NF-1). The 10-year EFS rate was 61.9% (95% confidence interval [CI], 31.2%-82.1%) for patients with NF-1 and 67.5% (95% CI, 54.8%-77.3%) for those without NF-1. The 10-year overall survival rate was 92.3% (95% CI, 56.6%-98.9%) for patients with NF-1 and 98.4% (95% CI, 89.1%-99.8%) for those without NF-1. Pre-RT chemotherapy (which was more commonly given to younger patients) was associated with reduced EFS, whereas younger age was associated with reduced overall survival. Possible RT-induced neoplasms developed in 8 patients, including 4 with NF-1. The 10-year cumulative incidence of clinically significant vasculopathy was 7.1% (95% CI, 2.9%-13.9%); vasculopathy did not develop in any child aged >10 years at the commencement of RT. CONCLUSIONS: RT is an effective treatment for optic-hypothalamic LGG. Older children without NF-1 have a low risk of late toxicity. RT can be considered for selected younger patients or individuals with NF-1 as a salvage treatment after progression.

Hypothalamic tumors impact gray and white matter volumes in fronto-limbic brain areas.

Patients with hypothalamic involvement of a sellar/parasellar tumor often suffer from cognitive and social-emotional deficits that a lesion in the hypothalamus cannot fully explain. It is conceivable that these deficits are partly due to distal changes in hypothalamic networks, evolving secondary to a focal lesion. Focusing on childhood-onset craniopharyngioma patients, we aimed at investigating the impact of hypothalamic lesions on gray and white matter areas densely connected to the hypothalamus, and to relate structural changes to neuropsychological deficits frequently observed in patients. We performed a voxel-based morphometric analysis based on data of 11 childhood-onset craniopharyngioma patients with hypothalamic tumor involvement, and 18 healthy controls (median age: 17.2 and 17.4 yrs.). Whole-brain analyses were used to test for volumetric differences between the groups (T-tests) and subsequent regression analyses were used to correlate neuropsychological performance with gray and white matter volumes within the patient group. Patients compared to controls had significantly reduced gray matter volumes in areas of the anterior and posterior limbic subsystems which are densely connected with the hypothalamus. In addition, a reduction in white matter volumes was observed in tracts connecting the hypothalamus to other limbic areas. Worse long-term memory retrieval was correlated with smaller gray matter volumes in the posterior cingulate cortex. Our data provide the first evidence that hypothalamic tumor involvement impacts gray and white matter volumes in limbic areas, outside the area of tumor growth. Notably, the functional range of the two limbic subsystems affected, strikingly parallels the two major domains of psychological complaints in patients i.e., deficits in episodic memory and in socio-emotional functioning. We suggest that focal hypothalamic lesions may trigger distal changes in connected brain areas, which then contribute to the impairments in cognitive, social and emotional performance often observable in patients, and not explicable by a hypothalamic lesion alone.

Long-tunnelled external ventricular drain as a long-term treatment option for hydrocephalus in a child with an unresectable low-grade supratentorial tumor: case report.

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.

Neuroendoscopic Intraventricular Biopsy in Children with Small Ventricles Using Frameless VarioGuide System.

Endoscopic biopsy for intraventricular tumors in pediatric patients with small ventricles is a challenging procedure because of the risk of morbidity during the intraventricular approach. We describe the use of the VarioGuide system for intraventricular endoscopic biopsy in 9 consecutive pediatric patients with intraventricular lesions and small ventricular size. All patients had lesions in the anterior part of the third ventricle with a median frontal and occipital horn ratio of 0.33. Patients presented with growth failure (n = 4), visual disturbances (n = 4), and seizures (n = 1). The VarioGuide system consists of an ergonomic arm with 3 joints for gross adjustment. The 3 rotational joints on the distal side of the system are adjusted according to the angles of the planned trajectory. The endoscope is adjusted to the distal side of the VarioGuide and inserted through the ring, previously set for the diameter of the endoscope and for the planned trajectory. The accuracy of the trajectory and correct ventricular cannulation are confirmed under endoscopic guidance. The biopsy is carried out according to the standard technique. In all cases, the biopsy sample provided the definitive diagnosis. Diagnoses included germinomas in 4 patients, hamartoma in 1 patient, hypothalamic astrocytoma in 2 patients, and craniopharyngioma in 2 patients. The use of the VarioGuide system for intraventricular endoscopic biopsy is highly recommended for pediatric patients with small ventricle size. This technique may help minimize the risk of unnecessary brain damage during the entrance to small ventricles.

[SCT perfusion in the diagnosis of sellar and parasellar tumors].

UNLABELLED: The study is devoted to the use of a minimally invasive method of SCT perfusion for the differential diagnosis of sellar and pаrаsellar tumors. Given a wide differential diagnostic range of tumors occurring in this area, the tumor perfusion indicators were used as an auxiliary diagnostic criterion. MATERIAL AND METHODS: The study analyzed outcomes in 115 patients with various tumors of the sellar area who underwent surgery or biopsy for histological verification of the diagnosis. RESULTS: The statistically significant differences were obtained for certain groups of tumors based on the values of hemodynamic parameters (p<0.05) that enable, with a high confidence, making a conclusion on the histologic type of most tumors. CONCLUSION: These findings demonstrated that SCT perfusion is a highly informative method of the preoperative differential diagnosis of these tumors. The sensitivity and specificity of SCT perfusion in the study were 100% and 81.2%, respectively.

Rosette-forming glioneuronal tumor originating in the hypothalamus.

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.

Symptomatic osteolipoma of the tuber cinereum masquerading as calcified retroclival mass.

We present a case of symptomatic osteolipoma of the tuber cinereum in a 51 year old male with rapid visual deterioration over several months leading to bilateral visual loss. Preoperatively the lesion masqueraded as a calcified retroclival mass. Intracranial osteolipomas are rare benign lesions that are usually asymptomatic and have an indolent course. Additionally, we discuss our intraoperative findings highlighting the technical challenges encountered along with a review of the English language literature on histologically proven intracranial osteolipomas.

Diffusion tensor imaging--arcuate fasciculus and the importance for the neurosurgeon.

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.