Hypothalamic-pituitary lesions in pediatric patients: endocrine symptoms often precede neuro-ophthalmic presenting symptoms.

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.

[A successful surgical case of a hypothalamic hamartoma with gelastic seizure: a case report].

Gelastic seizure is a rare form of epilepsy defined as automatic bouts of laughter without mirth commonly associated with a hypothalamic hamartoma. Surgical treatment of hypothalamic hamartomas is associated with a high risk of complications because of the close vicinity of adjacent structures such as the optic tracts and mammillary bodies. This case was an 11-year-old girl who presented with gelastic seizure and complicated partial seizure. She developed gelastic seizure at a frequency of 10 bouts per day. She was found to have an elliptical mass close to the left hypothalamus. The signal intensity on magnetic resonance imaging (MRI) was consistent with hypothalamic hamartoma. The patient underwent surgical resection by a subtemporal approach. Pathological findings confirmed the diagnosis of hypothalamic hamartoma. Postoperative MRI demonstrated that the hypothalamic hamartoma was successfully resected. Twenty four months after surgery, complicated partial seizure in this patient has improved to Engel's class 1a and gelastic seizure has improved to Engel's class IIIa.

[Childhood diencephalic pilocytic astrocytoma. A review of seven observations]. / Les astrocytomes pilocytiques du diencephale de l'enfant. à propos de sept observations.

BACKGROUND AND PURPOSE: Pilocytic astrocytoma (PA) is a WHO grade I tumor of the central nervous system mostly arising in children and young adults. Management of diencephalic PA is a difficult challenge. Surgical treatment has to cope with both the difficulties of deep location and eloquent area tumors. MATERIALS AND METHODS: We retrospectively reviewed seven pediatric cases (female: 4, male: 3) of diencephalic PA. Opto-chiasmatic tumors were excluded from the series. Mean age at diagnosis was 108 months (9 years) (range: 4 month-18 years), median age was 111 months. Median follow-up for the series was 125 months. Tumor locations were as followed: right thalamus: 2, both thalami: 1, hypothalamus: 3, and right basal ganglia: 1. At the onset, the first symptom was mostly raised intracranial pressure. The delay in diagnosis ranged from 48 hours up to 6 years. TREATMENT: a shunting procedure was performed in 3 patients, a direct surgical approach in 5 patients (gross total removal: 2; partial removal: 3) and one patient had only a biopsy. Three children were re-operated. Three patients were treated by radiationtherapy (RT) after surgery. Chemotherapy was delivered for 4 children. RESULTS: The overall survival rate was 71.4 months (almost 6 years) (range: 3-184 months). Median survival rate was 42 months (3.5 years). Three children died, two by tumor progression and one death related to late side-effects of RT. Four patients have a good quality of life with GOS I (n = 3) or II (n = 1). We observed tumor regression in two patients at 1 and 17 years after the beginning of treatment. Correct diagnosis was only made for two cases at the initial pathological examination. CONCLUSION: The course of diencephalic PA is still unpredictable. The tumor can be controlled by a partial surgical removal, and a residual tumor can sometimes decrease in size after surgery. Gross total removal of these tumors, although difficult, may be performed. With cranial navigation systems, the risk is low. Pathological diagnosis is sometimes difficult to assess.

Primary hypothalamic lymphoma with panhypopituitarism presenting as stiff-man syndrome.

We report an unusual case of primary hypothalamic lymphoma with hypopituitarism presenting as Stiff-man syndrome (SMS). A 64-year-old man was hospitalized due to a 3-week history of general weakness, anorexia, vomiting, weight loss, and muscle pain and spasms precipitated by motion and tactile stimuli resulting in muscle stiffness and difficulty in mobility. Physical examination revealed normal sensorimotor function and reflexes, except for bitemporal visual field defect. Routine laboratory and gastrointestinal examinations provided no remarkable clues. Endocrine assessment revealed low levels of morning cortisol, thyroxine, and anterior pituitary hormones but an increase in prolactin level. The patient's muscle pain and stiffness improved dramatically within 2 days after hydrocortisone therapy and thyroxine replacement. Magnetic resonance imaging (MRI) of the brain confirmed an 18-mm enhancing hypothalamic tumor with optic chiasm involvement, which proved to be a B-cell lymphoma. The results of the extensive studies for systemic lymphoma were negative, suggesting a primary hypothalamic lymphoma. The tumor regressed completely and was invisible on MRI scan after adjuvant radiotherapy. The patient's condition was satisfactory and there was no recurrence of SMS during the 2-year follow-up period. This case demonstrated that primary hypothalamic lymphoma complicated with adrenal insufficiency may manifest as SMS. Early diagnosis and prompt intervention can lead to a favorable outcome and reduce morbidity.

Hypothalamic ganglioglioma treated by temporal lobectomy. Case report and review of the literature.

The authors report the case of a hypothalamic ganglioglioma with left-sided temporal lobe extension in an 8-year-old girl who presented with seizures. Other cases of ganglioglioma involving the hypothalamus have been reported in the literature; however, this site of origin is exceedingly rare and worthy of report. Treatment involved medial temporal lobectomy with the hypothalamic component of the tumor remaining untouched. The patient recovered postoperatively with no neurological deficits and was seizure free at 12 months. Neither radio- nor chemotherapy was recommended because of the tumor histology, location, and the patient's age. The authors recommend follow up and surgical treatment for possible tumor recurrence. The prognosis for hypothalamic ganglioglioma is unknown.

Heavily T2-weighted MR imaging of white matter tracts in the hypothalamus: normal and pathologic demonstrations.

BACKGROUND AND PURPOSE: The MR appearance of white matter tracts in the hypothalamus and the role of the hypothalamus as a memory mechanism have not been sufficiently described in clinical settings. Heavily T2-weighted black-and-white reversed (T2R) images were assessed to reveal their visualization and clinical significance. METHODS: One hundred healthy subjects and three patients with hypothalamic lesions underwent fast spin-echo MR imaging to reveal the postcommissural fornix (PF) and mammillothalamic tract (MT). RESULTS: The PF was identifiable in axial and/or coronal sections in all healthy subjects. No remarkable asymmetry of its size or course was evident. Both anteroposterior and vertical dimensions ranged from 10.5 to 14 mm. The MT was visible in one or two axial sections above the mammillary body in 64% of healthy subjects and in a coronal section in 36%. Two patients with glioblastoma multiforme and lacunar infarct at the hypothalamus presented with anterograde amnesia; T2R imaging revealed involvement of both the PF and MT. The third patient had a suprasellar craniopharyngioma with PF injury sparing the MT resulting from surgical manipulation and was free of memory deficit. Anterograde amnesia was evident only when both the PF and MT were injured. CONCLUSION: T2R images have made a high rate of detection of the PF and MT possible and could provide a more detailed correlation of hypothalamic neuroanatomy and memory mechanism in clinical settings.

Radiologic features of pediatric thalamic and hypothalamic tumors.

A variety of histologic subtypes of tumor may affect the thalamus and the hypothalamus in the pediatric population. These tumors have radiologic features that are useful in predicting pathology. We discuss the radiologic findings of childhood thalamic and hypothalamic tumors and provide imaging examples.

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.

Initial management of children with hypothalamic and thalamic tumors and the modifying role of neurofibromatosis-1.

Diencephalic gliomas may be grouped into 2 clinical categories. Optic pathway/hypothalamus gliomas (OPG) arise primarily from a slower-growing juvenile pilocytic astrocytoma, and thalamic gliomas arise primarily from a fibrillary astrocytoma which can become clinically and histologically more aggressive. Children with OPG have an excellent long-term prognosis with a 10-year survival of over 85%. The major therapeutic challenge for these patients is to maximize their quality of life by preserving visual and endocrine function while minimizing treatment-related morbidity. Treatment is often initiated at diagnosis in infants and toddlers who have a major visual impairment or the diencephalic syndrome. The judicious application of chemotherapy may serve to forestall the need for radiotherapy or surgery. Children with neurofibromatosis-1 (NF-1) usually have a more indolent course. Tumors may grow more slowly or occasionally regress spontaneously. However, over 90% of children with OPG without NF-1 will require some form of therapy. Patients with thalamic gliomas present with a shorter history, often with hydrocephalus. Surgical intervention is often required to relieve intracranial pressure and establish the histologic identity of the tumor. Over 75% of these tumors will become locally aggressive. Current multimodality therapy is relatively ineffective. The bithalamic variant behaves similarly to a pontine glioma.

Infundibuloneurohypophysitis in children. A report of 2 cases.

Two children with diabetes insipidus secondary to a chronic inflammatory infiltrate of the infundibulum - infundibuloneurohypophysitis - are presented. Features unique to these cases are contrasted with prior case reports. The differential diagnoses of diabetes insipidus and inflammatory pituitary disorders are discussed. Recommendations for diagnosis and treatment are proposed.

Gelastic epilepsy: symptomatic and cryptogenic cases.

PURPOSE: To describe the etiology, characteristics, and clinical evolution of epilepsy in patients with gelastic seizures (GSs). METHODS: Nine patients whose seizures were characterized by typical laughing attacks were observed between 1986 and 1997. Patients were selected based on electroencephalogram (EEG) or video-EEG recordings of at least one GS and on magnetic resonance imaging (MRI) study. RESULTS: Five patients were affected by symptomatic localization-related epilepsy (LRE), with four of the patients' disorders related to a hypothalamic hamartoma (HH) and one to tuberous sclerosis (TS) without evident hypothalamic lesions. In four patients (the cryptogenic cases) MRI was negative also in these cases, clinical and EEG data suggested a focal origin of the seizures. The epileptic syndrome in the HH cases was usually drug-resistant, and was surgically treated in two of the patients. The patient with TS became seizure free with vigabatrin. In the cryptogenic cases, the ictal, clinical, and EEG semiology were similar to the symptomatic cases: the clinical evolution was variable, with patients having transient drug resistance or partial response to treatment. No cognitive defects were observed in the cryptogenic patients. None of the nine patients had precocious puberty. CONCLUSIONS: We confirm the frequent finding of HHs in GSs and further underline how GSs may also be observed in patients without MRI lesions and with normal neurologic status. In these patients, clinical and EEG seizure semiology is similar to symptomatic cases, but the clinical evolution is usually more benign.

[Gelastic seizures treated by partial resection of a hypothalamic hamartoma].

A 13-year-old girl developed atonic seizure at 2 years of age. At the age of 10 years, gelastic seizures were noted. Magnetic resonance imaging (MRI) revealed a hypothalamic mass protruding down into the basal cistern and up into the third ventricle. An interictal electroencephalogram (EEG) showed paroxysmal spike and wave complex discharges. Since the seizures failed to respond to medical therapy, it was decided to try to control them by removing the mass. The operation was carried out through an interhemispheric trans-lamina terminalis approach. The lesion was so similar to normal brain tissue that the resection had to be limited enough to avoid complications. Histological examination of the mass showed a hamartoma. Postoperative MRI showed residual mass, but no seizure has been noted since the operation. The EEG recorded one year after the operation showed no spike and wave complex discharge, although she was still on anticonvulsant drugs. The authors propose that surgical therapy should be considered as a treatment for intractable gelastic epilepsy with hypothalamic hamartoma and that the first operation should be conservative enough to avoid complications, because it can bring about good results even if it is only a partial resection.

Proton spectroscopy of suprasellar tumors in pediatric patients.

OBJECTIVE: Magnetic resonance imaging and computed tomography provide good anatomic detail of suprasellar tumors in pediatric patients but are not able to predict histology in many cases. Proton magnetic resonance spectroscopy provides metabolic data that may add to diagnostic specificity. We preoperatively performed localized proton magnetic resonance spectroscopy on pediatric patients with suprasellar tumors and correlated the results with the histological findings. Cyst fluid obtained from patients with craniopharyngiomas was studied with high-resolution magnetic resonance spectroscopy to better understand the in vivo data. METHODS: Nineteen patients aged 1 to 21 years underwent spectroscopy. Surgical pathological samples were obtained from 14 patients. In each of five patients, the presence of a solid chiasmatic mass in addition to clinical evidence of neurofibromatosis Type I allowed the presumptive diagnosis of chiasmatic astrocytoma. Thus, the study population included 6 patients with craniopharyngiomas, 10 with chiasmatic/hypothalamic astrocytomas, and 3 with pituitary adenomas. The data obtained were compared with those of healthy brain from age-matched participants. RESULTS: Spectroscopy was specific for the diagnosis. All craniopharyngiomas showed a dominant peak at 1 to 2 ppm, consistent with lactate or lipids, with trace amounts of other metabolites. This was confirmed using high-resolution spectroscopy. Chiasmatic gliomas showed a profile of choline, N-acetylaspartate, and creatine, and the choline:N-acetylaspartate ratio was 2.6 +/- 1.3, compared with 0.7 +/- 0.3 for samples of healthy brain (t test, P = 0.0003). Pituitary adenomas showed only a choline peak or no metabolites at all. CONCLUSION: Proton spectroscopy may be helpful in supplementing standard imaging for the preoperative diagnosis of three types of suprasellar tumors that are common in pediatric patients.

[The electroencephalographic correlates of a disorder in higher cortical functions in local lesions of the hypothalamic area]. / Elektroéntsefalograficheskie korreliaty narusheniia vysshikh korkovykh funktsii pri lokal'nykh porazheniiakh gipotalamicheskoi oblasti.

In order to reveal correlations between disturbances in higher cortical functions and characteristics of electrical activity 70 patients with pathological foci in the hypothalamic regions were examined using computer data processing. Destruction of the normal intercentral relations between EEG rhythms develops under the influence of the hypothalamic focus. The process builds up with the aggravation of cortical disorders (mnestic, emotional-affective, consciousness oppression with sleep inversion). General decrease of EEG coherence is observed with the highest destruction of correlations in the frontal cortical areas. The structure of high-frequency alpha-rhythm becomes deranged even in slight cortical disorders, its coherence decreases predominantly in the frontal cortical areas. With intensification of the pathological process in the focus, the stage of delta-rhythm coherence increase is observed and at the background of general destruction of correlations new, pathological intercentral relations develop. Using a BRAINLOC computer technique "sources" of the delta- and theta-activity have been localized in the medio-basal brain regions. The area of localization is specific for hypothalamic lesions. The "source" is mostly expressed in the slightest pathology of higher cortical functions. With aggravation of the process in the hypothalamic pathological focus and further derangement in the cortical functions expression of the "sources" reduces up to their complete disintegration in coma.