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Spontaneous regression of low-grade astrocytomas in childhood.

An 8-year-old boy with neurofibromatosis type 1 (NF1) and a biopsy-proven juvenile pilocytic astrocytoma of the hypothalamic/chiasmatic region was followed with serial MRIs over 4 years. Spontaneous tumor regression was followed by progression and biopsy; 6 months later, the tumor regressed again. This bimodal regression is rare, but highlights the variable natural history of low-grade gliomas in children with NF1 and the difficulty in evaluating response of such tumors to therapy.

Astrocytoma↗

Chemotherapy: low-grade gliomas of the hypothalamus and thalamus.

Chemotherapy is an increasing component of the management of diencephalic gliomas. It can result in tumor shrinkage and significant disease control in some patients. However, decisions concerning the institution of treatment should be based on the goals of treatment. Factors include: (1) age of the patient; (2) whether the child has neurofibromatosis type 1; (3) tumor size and location; (4) the potential sequelae of radiotherapy, and (5) the acute and long-term toxicity of the chemotherapeutic approach utilized. The erratic natural history of diencephalic tumors confounds evaluation of efficacy of the regimen chosen.

Adult↗

Thalamic and hypothalamic tumors of childhood: endocrine late effects.

Children who have received chemotherapy and radiation therapy for treatment of thalamic/hypothalamic tumors are at risk for late effects, specifically endocrine dysfunction. Evaluation of growth and pubertal development, thyroid function and integrity of the hypothalamic-pituitary-adrenal axis should be undertaken in a prospective manner. Issues of metabolic disturbances such as obesity, altered body composition/bone density as well as ultimate fertility also need to be addressed by ongoing prospective evaluations.

Adolescent↗

Optic pathway hypothalamic gliomas in children under three years of age: the role of chemotherapy.

OBJECTIVES: Optic pathway/hypothalamic gliomas (OPHGs) tend to occur in young children. Treatment options consist of surgical resection, radiation therapy (RT) and chemotherapy. Due to complications induced by surgery and RT, chemotherapy has gained significant recognition for the treatment of OPHG in young children. Chemosensitivity of OPHG in very young children under 3 years of age has not been well documented. We analyzed 14 patients who were treated with chemotherapy with or without surgery. MATERIALS AND METHODS: Fourteen children younger than 3 years (median age of 10 months) with OPHG were treated between 1988 and 1998. Magnetic resonance imaging was obtained in all cases. Hydrocephalus was present in 8 patients and diencephalic syndrome was noted in 6. Only 3 of these had evidence of neurofibromatosis-1. Five patients had partial tumor resection and 4 had endoscopic biopsy at the time of ventriculoperitoneal shunt placement. Pathological examination revealed low-grade astrocytoma in 5 and juvenile pilocytic astrocytoma in 4. All patients received chemotherapy: carboplatin in 8, a combination of carboplatin and vincristine in 4 and a combination of other agents in 2. RESULTS: Eight (57%) of 14 patients had a sustained reduction of tumor during the follow-up time between 15 months and 8 years. The 5-year progression-free survival was 63%. These tumor reductions were often accompanied by clinical improvements. Diencephalic syndrome responded to chemotherapy alone in 4 of 6 patients. However, 5 others had progressive disease; 3 during the treatment and 2 following the treatment (9 months and 2 years, respectively). All these 5 patients had a partial tumor resection prior to chemotherapy. CONCLUSION: A majority of OPHGs responds to chemotherapy. Due to slow progression of these tumors and adverse effects of other therapeutic modalities, we recommend chemotherapy as a primary treatment for OPHGs. Our present data indicates that partial surgical resection does not enhance chemotherapy effectiveness for OPHGs in infants or children younger than 3 years.

Antineoplastic Combined Chemotherapy Protocols↗

Neuroendocrinology of aging: the potential of gene therapy as an interventive strategy.

OBJECTIVE: This paper reviews the current status of gene therapy in the neuroendocrine system and discusses the interventive potential of this methodology for neuroendocrine pathologies associated with aging. BACKGROUND AND RESULTS: A brief description is first presented of the viral-vector-based gene delivery systems being currently used in the neuroendocrine system, namely the adenoviral and herpetic (HSV1) vector systems. Next, an account of the neuroendocrine pathologies for which gene therapy approaches in animal models are being implemented is provided. This includes the treatment of experimental pituitary tumors by adenoviral-vector-mediated transfer of the suicide gene for the HSV-1 thymidine kinase. At the hypothalamic level, an adenovirus harboring the cDNA for arginine vasopressin has been used in Brattleboro rats to correct their diabetes insipidus. Next, the interventive potential of gene therapy for correcting age-associated neurodegenerative processes at neuroendocrine level is outlined. Finally, the role that emerging technologies may play in the development of future genetic therapies for aging is considered. CONCLUSION: Although effective implementation of gene therapy strategies still faces significant technical obstacles, these are likely to be progressively overcome as gene delivery systems are refined.

Aged↗

Peripheral venous thrombosis in children and adolescents with adipsic hypernatremia secondary to hypothalamic tumors.

OBJECTIVE: To determine the clinical presentation and laboratory follow-up in patients with the syndrome of adipsic hypernatremia complicated with a peripheral thrombosis event. METHODS: Report of 3 patients (6-19 years old) with chronic hypernatremia with sustained difficulties to normalize their serum osmolality levels. RESULTS: During post-surgical management the 3 patients developed a peripheral venous thrombotic event as a complication of their chronic hyperosmolality. CONCLUSIONS: Chronic hypernatremia in patients with prolonged immobilization is associated with an increased risk for development of deep venous thrombosis.

Adult↗

A note on gelastic epilepsy.

Laughter epilepsy or gelastic seizures have been described in various epilepsies arising from the temporal or frontal lobes, but most commonly from hypothalamic hamartomata. Gelastic seizures also arise from temporal and frontal lobe tumours and atrophic lesions. The essential clinical features are: stereotyped recurrence; absence of external precipitants; concomitance of other manifestations generally accepted as epileptic; presence of interictal or interictal EEG epileptiform discharges, and absence of conditions in which pathological laughter might occur. The history and clinical significance are discussed.

Epilepsies, Partial↗

The craniopharyngioma.

The craniopharyngioma is one of the most common destructive lesions of the hypothalamus and pituitary gland. It still remains one of the most difficult tumors to treat effectively since complete resection is often impossible and is associated with frequent recurrence. Current therapy is multimodal and focuses on a combination of surgical decompression, medical treatment, as well as stereotactic radiosurgery. This chapter reviews the embryology, neuroanatomy, current treatment strategies, clinical features and the several surgical approaches to its treatment.

Central Nervous System Cysts↗

intraoperative neuronavigation using diffusion tensor MR tractography for the resection of a deep tumor adjacent to the corticospinal tract.

OBJECTIVE AND IMPORTANCE: Delineation of cerebral white matter tracts using MR tractography adds essential information for planning intracranial surgery. Integrating tractography with intraoperative neuronavigation may reduce the likelihood of new neurological deficits after surgery done to remove tumors adjacent to the projection fibers of eloquent cortex. We report the utility of such integration for the resection of deep (paraventricular) tumors. CLINICAL PRESENTATION: A 67-year-old male with malignant melanoma underwent stereotactic radiosurgery for a single metastasis within the paraventricular white matter of the right frontal lobe near the corticospinal tract. The lesion doubled in size within 12 months of radiotherapy. Surgical extirpation was performed aided by intraoperative neuronavigation. TECHNIQUE: MR images of the brain including MR tractography and post-contrast T1-weighted sequences were acquired and imported into a neuronavigational workstation. Asymmetric fusion of contrast-enhanced images and tractography was employed to assist in preservation of the integrity of critical white matter tracts during the surgical procedure. CONCLUSION: Inclusion of tractography in standard imaging protocols for neuronavigational systems may increase the safety of neurosurgical intervention near white matter tracts, including deep areas adjacent to the ventricles.

Aged↗

Hypothalamic glioma presenting with seizures. a case report and review of the literature.

A rare case of hypothalamic glioma in a 7-year-old boy presenting with seizures and diabetes insipidus is reported. Near total decompression of the hypothalamic glioma was done successfully using subfrontal approach. The patient had a stormy postoperative course due to status epilepticus but went on to make a complete recovery. Postoperative radiotherapy/chemotherapy was not given in view of tumor histology (low grade glioma), patient's age and tumor location. Patient remains symptom and seizure free on antiepileptics at 3-year follow-up. The case is presented in the light of its rarity and the literature is reviewed.

Child↗

Gamma knife radiosurgery for refractory epilepsy caused by hypothalamic hamartomas.

BACKGROUND: Hypothalamic hamartomas are associated with precocious puberty and chronic epilepsy characterized by gelastic seizures. The seizure disorder is usually refractory to most antiepileptic drugs. Gamma knife surgery has emerged as an alternative to microsurgical removal or radiofrequency ablation to improve seizure control. We present our experience with radiosurgery in 4 patients afflicted by this disorder. METHODS: Using gamma knife radiosurgery, 4 patients with intractable gelastic seizures and complex epilepsy were managed. Patient age varied from 5 to 29 years. The duration of symptoms was 4-28 years. A conformal radiosurgery plan was designed with a mean of 4.25 isocenters to cover the hamartoma at the 50% isodose line. A mean margin dose of 17.5 Gy was used. The clinical outcome was evaluated with the Engel scale. RESULTS: No complication occurred. After a median follow-up of 22 months, 3 patients had shown some improvement, with 2 attaining Engel class II status. CONCLUSION: Gamma knife surgery is a promising alternative to microsurgical removal for patients with refractory epilepsy caused by hypothalamic hamartomas.

Adolescent↗

Hyponatremia after transsphenoidal surgery for hypothalamo-pituitary tumors.

Transient diabetes insipidus is a well-known complication after transsphenoidal surgery (TSS). On the other hand, transient hyponatremia has been reported as being a delayed complication of TSS. Transient hyponatremia has been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but the details of hyponatremia have not been clarified. In the present study, we retrospectively reviewed 110 consecutive patients (39 males and 71 females, age 9-80 years) operated on transsphenoidally for pituitary and hypothalamic tumors. We investigated the frequency, time of onset, duration of hyponatremia after TSS, and analyzed possible factors associated with it. A postoperative sodium concentration <135 mEq/l was observed in 29 (26%) patients. Five patients were excluded from this study because their hyponatremia could be due to either overdose of desmopressin or SIADH for meningitis. Therefore, we investigated 24 (22%) patients with hyponatremia in this study. The sodium levels in the patients with hyponatremia ranged from 110 to 134, with a mean of 126.2 +/- 5.3 mEq/l. Hyponatremia was observed on average on postoperative day 9.5 +/- 2.4, the serum sodium levels normalized within 3.8 +/- 1.7 days. Hyponatremia occurred in patients with non-functioning pituitary adenoma (26%, 11/42), Rathke's cleft cyst (29%, 5/17), prolactinoma (31%, 4/13) and acromegaly (15%, 4/27). 18 patients (75%, 6/24) who developed hyponatremia had macrotumor (>10 mm), and 6 patients (25%, 6/24) had microtumor. The plasma arginine vasopressin (AVP) levels in the patients with hyponatremia ranged from 0.21 to 2.1, with a mean of 0.79 +/- 0.46 pg/ml, and the levels were inversely correlated with plasma osmolality (r = -0.80, p = 0.002). The urine to plasma osmolality ratios were >1. All the patients received appropriate hormonal replacement, including hydrocortisone. These data showed that postoperative hyponatremia after TSS was not rare, and the hyponatremia was mainly associated with SIADH. As the hyponatremia could be a life-threatening complication, all patients should be screened for serum electrolytes after TSS.

Adolescent↗

Clinical and surgical aspects of hypothalamic hamartoma associated with precocious puberty in a 15-month-old boy.

A case is reviewed of precocious puberty associated with hypothalamic hamartoma in a 15-month-old boy. The authors believe this to be the first documented case in which significant reductions occurred in the level of serum testosterone and in the result of the luteinizing hormone-releasing hormone (LHRH) infusion test following surgical removal of the tumor. Such surgery appears to be safe when a planned microsurgical course is employed.

Follicle Stimulating Hormone↗

Hypothalamic hamartoma: a report of 2 cases.

Two patients with hypothalamic hamartoma presented with isosexual precocious puberty. LHRH challenge showed a pubertal LH response in both cases. Serum FSH responses to LHRH were pubertal in case 1, but prepubertal for case 2. Computed tomography revealed isodense noncontrast-enhancing retrosellar mass lesions in both cases. The tumors were composed of mature neurons and neuroglial tissue. Electron microscopy of the lesions failed to demonstrate dense core (neurosecretory) granules in either case. Subtotal removal of the harmartomas resulted in decreased LH responsiveness to LHRH in both cases. Serum FSH responsiveness to LHRH was not significantly suppressed postoperatively in case 1, and FSH responsiveness to LHRH in case 2 showed exaggerated levels, more typical of very young prepubertal girls. Postoperative magnetic resonance imaging (MRI) scans of both patients are also presented.

Child, Preschool↗