Assessment of hemorrhage in pituitary macroadenoma by T2*-weighted gradient-echo MR imaging.

BACKGROUND AND PURPOSE: Intratumoral hemorrhage occurs frequently in pituitary macroadenoma and manifests as pituitary apoplexy and recent or old silent hemorrhage. T2*-weighted gradient-echo (GE) MR imaging is the most sensitive sequence for the detection of acute and old intracranial hemorrhage. T2*-weighted GE MR imaging was used to investigate intratumoral hemorrhage in pituitary macroadenomas. MATERIALS AND METHODS: Twenty-five consecutive patients who underwent total or subtotal resection of pituitary macroadenoma with heights from 17 to 53 mm, including 1 patient with classic pituitary apoplexy, underwent MR imaging before surgery, including T2*-weighted GE MR imaging. For histologic assessment of the hemorrhage in whole surgical specimens, we used hematoxylin-eosin staining. RESULTS: T2*-weighted GE MR imaging detected various types of dark lesions, such as "rim," "mass," "spot," and "diffuse" and combinations, indicating clinical and subclinical intratumoral hemorrhage in 12 of the 25 patients. The presence of intratumoral dark lesions on T2*-weighted GE MR imaging correlated significantly with the hemorrhagic findings on T1- and T2-weighted MR imaging (P < .02 and <.01, respectively), and the surgical and histologic hemorrhagic findings (P < .001 and <.001, respectively). CONCLUSION: T2*-weighted GE MR imaging could detect intratumoral hemorrhage in pituitary adenomas as various dark appearances. Therefore, this technique might be useful for the assessment of recent and old intratumoral hemorrhagic events in patients with pituitary macroadenomas.

A novel transcript for the thyrotropin-releasing hormone receptor in human pituitary and pituitary tumors.

We measured the amounts of TRH receptor (TRHR) messenger ribonucleic acid (mRNA) in human normal pituitary and pituitary tumors and found a novel transcript of the TRHR gene. Competitive PCR revealed expression of the TRHR mRNA in all pituitary adenomas examined, and its level was variable and similar to that in the normal pituitary. When the C-terminal region was amplified by PCR, an additional short product was observed. Cloning and sequence analysis of this short fragment revealed that the deleted sequence corresponded exactly to the 5'-sequence of exon 3, indicating alternative splicing of the TRHR mRNA. This alternative splicing resulted in a frame shift, yielding a C-terminal truncated protein (HTRHR2) on translation. Expression analysis of HTRHR2 in Chinese hamster ovary cells showed no significant binding to [3HIMeTRH or response of intracellular calcium to TRH administration. However, the mRNA ratio of HTRHR2 vs. the wild type (HTRHR1) was significantly different among pituitary tumors. The highest ratio was observed in prolactinomas (30%), and almost no detectable expression was found in GH-producing tumors. These findings indicate that this novel transcript of the human TRH receptor gene is produced in a tumor-specific manner and may be a useful parameter for evaluation of individual pituitary tumors.

Retinoic acid-induced neural tube defects with multiple canals in the chick: immunohistochemistry with monoclonal antibodies.

When retinoic acid was injected into chicken yolks before incubation, various types of neural tube defect (NTD) were induced in 38-46% of the embryos after 48-96 h of incubation. The cranial NTD consisted of a delay in closing of the neural plate in 48-h embryos and some remained as disorganized, hyperplastic masses in older embryos. In spinal NTD of 48-h embryos the posterior neuropore remained widely open. In older embryos with a closed posterior neuropore, the neural tube appeared dissociated or disorganized locally at the trunk level. The tissue consisted of a dorsally-situated, neural-plate-like structure and a ventrally-located cell mass containing multiple canals. Although the location was different, this arrangement was similar to the overlap zone which appears between primary and secondary neurulation in normal development. Immunohistochemistry was performed using monoclonal antibodies which selectively stained various components of chick tissue. Considering the similarity in neural tube formation between chick and human, this experimental NTD may provide clues to understanding the etiology of human myelomeningocele.

Extrapontine myelinolysis and behavioral change after transsphenoidal pituitary surgery: case report.

OBJECTIVE AND IMPORTANCE: Rapid correction of hyponatremia is considered the usual cause of central pontine myelinolysis and extrapontine myelinolysis. Little has been reported about mental changes associated with this disorder or its occurrence after transsphenoidal surgery. CLINICAL PRESENTATION: A 24-year-old woman suddenly developed markedly abnormal behavior associated with rapid correction of hyponatremia 11 days after undergoing transsphenoidal surgery for a prolactin-secreting pituitary adenoma. INTERVENTION: Magnetic resonance imaging and positron emission tomography with 18F-fluorodeoxyglucose showed bilateral caudate nuclei and putaminal lesions. Gradual, complete clinical resolution preceded the resolution that was revealed by magnetic resonance imaging. CONCLUSION: We emphasize the importance of cautious correction with frequent electrolyte determinations and attention to behavioral changes in the management of delayed hyponatremia after pituitary tumor surgery.

Treatment and prevention of tethered and retethered spinal cord using a Gore-Tex surgical membrane.

The incidence of the tethered cord syndrome after repair of spinal dysraphism is not insignificant. A retethered spinal cord may also develop after an untethering operation. In order to treat and/or prevent the tethered and retethered spinal cord, the authors developed and successfully used a new method in 12 cases. After complete release and reconstruction of the spinal cord, a Gore-Tex surgical membrane was placed over the cord and fixed to the lateral dural surface with stay sutures. During a postoperative follow-up period ranging from 23 months to 7 years, no further neurological deterioration was observed in the 12 patients and magnetic resonance imaging studies showed no adhesion of the spinal cord to the operative site. It is concluded that this simple new method is effective for the treatment and prevention of tethering and/or retethering of the spinal cord, although a longer follow-up study is required.

Cerebrospinal fluid immunocytochemical analysis and neuroimaging in the diagnosis of primary leptomeningeal melanoma. Case report.

A 20-year-old man presented with slowly progressing symptoms indicative of increased intracranial pressure. Two weeks later he underwent surgery for placement of a ventriculoperitoneal shunt. Cytological examination of the patient's cerebrospinal fluid (CSF) revealed atypical cells that contained no detectable melanin deposits, but proved to be immunocytochemically positive for monoclonal antibodies to melanocytic cells (HMB-45) and S-100 protein. Dermatological and ophthalmological examinations failed to demonstrate any abnormalities. On the basis of these findings, a diagnosis of primary leptomeningeal melanoma was made. Gadolinium-enhanced magnetic resonance (MR) images of the brain and spinal regions obtained 2 months after admission demonstrated typical widespread leptomeningeal enhancement. Results of technetium-99m-hexakis (2-methoxyisobutyl isonitrile) single-photon emission computerized tomography (99mTc-MIBI SPECT) scanning revealed intense uptake of the isotope in the leptomeningeal regions and some cisterns. The patient's condition progressively worsened and he died 5 months after admission. The diagnosis was confirmed at autopsy. Immunocytochemical analysis of CSF performed using HMB-45 and S-100 protein antibodies is important for the diagnosis of leptomeningeal melanoma because of the test's simplicity, high specificity, and sensitivity. Gadolinium-enhanced MR imaging is used to demonstrate the extent of the leptomeningeal melanoma. An additional and supplemental neuroimaging modality, 99mTc-MIBI SPECT scanning has good potential for the detection and diagnosis of leptomeningeal melanoma.

A comparison of children with suprasellar germ cell tumors and craniopharyngiomas: final height, weight, endocrine, and visual sequelae after treatment.

BACKGROUND: Although treatment results of craniopharyngiomas and germ cell tumors in children have been reported extensively, the relationship between various posttreatment sequelae and the nature of the tumor is not well understood. METHODS: From 1968-94, 47 children with 23 suprasellar germ cell tumors and 24 craniopharyngiomas were treated at Gunma University Hospital, Japan. Forty survivors were assessed with regard to Karnofsky scores, visual scores, final height, final weight, and other endocrine sequelae as long-term functional prognostic indicators. RESULTS: Kaplan-Meier life-table estimates and Karnofsky scores were not significantly different between the two histologic groups. The visual function of survivors did not differ significantly at diagnosis. However, the final visual function following treatment in the germ cell tumor group was better than in the craniopharyngioma group (p < 0.05). Antidiuretic hormone secretion was significantly impaired at diagnosis in the germ cell tumor group (p < 0.0001). However, there was only a marginally significant difference in posttreatment persistent diabetes insipidus. Craniopharyngioma children were shorter and more obese at diagnosis (p < 0.02), and became much more obese than germinoma children with the same hormone therapy (p < 0.003), although the height difference became insignificant following growth hormone treatment. CONCLUSIONS: Children with craniopharyngiomas tended to have more visual disturbances, increased dwarfism and obesity, and less diabetes insipidus than patients with germ cell tumors despite adequate therapy. The method of quantifying visual function may in itself be useful.

Radiosensitive craniopharyngiomas: the role of radiosurgery.

Clinical characteristics of radiosensitive craniopharyngiomas and histologically identical tumours were re-evaluated from among 53 patients. There were 9 squamous cell type and 3 mixed type tumours. Early effects of radiosurgery for two recent cases are reported. Radiosurgery may have an important role to play in the treatment of craniopharyngiomas, especially of the squamous cell type.

Long-term follow-up study of conventional irradiation for brain tumours in children: a role for radiosurgery.

21 younger patients (less than 10 years of age) with brain tumours, treated by conventional irradiation, were followed 5 to 20 years (mean 12), using CT scan and/or MR imaging, in order to evaluate adverse effects on the developing brain. Pathological changes such as brain atrophy, lesions in the white matter, calcifications in the brain, and angiopathy were observed in 13 (62%) out of 21 cases. The incidence of abnormalities was related to the age at treatment and the follow-up period. All six cases treated at or under 5 years old and followed more than 10 years showed pathological changes in the brain. In order to minimize the radiation damage, 5 patients with brain tumours less than 5 years old were treated by gamma knife surgery. The early results encourage further trials. Radiosurgery may play a role as an alternative treatment or as a component of future multidisciplinary treatment for brain tumours is children.

Peripheral nerve regeneration in a silicone tube: effect of collagen sponge prosthesis, laminin, and pyrimidine compound administration.

Regeneration of transected peripheral nerve with a 10-mm gap encased in a silicone tube was evaluated in the presence of collagen sponge with or without laminin, or with systemic administration of a pyrimidine compound, MS-818. The sciatic nerve of 20 adult rats was transected and the proximal and distal nerve stumps were fixed in a silicone tube. The lumen of the silicone tube was empty, or filled with a collagen sponge alone or with a laminin-soaked collagen sponge. Also, a pyrimidine compound was injected intraperitoneally after implantation of the empty silicone tube. Three weeks later, the contents of the silicone tubes were processed for histological examination of regenerated nerve fibers. Other animals were observed 6, 12, and 18 months after surgery to examine the long-term effects of the collagen sponge on nerve regeneration. All animals had regenerated tissue within the tube 3 weeks after nerve transection. The diameter of the tissue decreased toward the distal stump in the empty tube, but was the same throughout the full length in the collagen sponge-containing tube. Immunohistochemical studies revealed that the nerve fibers extended beyond the midline of the regenerated tissue in animals treated with a laminin-containing collagen sponge or receiving a pyrimidine compound. Long-term observation showed the regenerated nerve was thick as the proximal stump and many neurofilament- and peripheral myelin-positive fibers were observed around the collagen sponge. Collagen sponge assists the progress of regenerated tissues in silicone tubes, and laminin-containing prostheses and administration of a pyrimidine compound enhance peripheral nerve regeneration.

A lung cancer case with numerous calcified metastatic nodules of the brain.

A case of pulmonary adenocarcinoma with numerous calcified metastatic nodules of the brain is reported. Autopsy revealed about 400 metastatic nodules in the central nervous system, most of which were calcified.

Basal interhemispheric supra- and/or infrachiasmal approaches via superomedial orbitotomy for hypothalamic lesions: preservation of hypothalamo-pituitary functions in combination treatment with radiosurgery.

Although several approaches to the hypothalamus have been used, none is able to give full views of the hypothalamus. The risk of permanent morbidity for hypothalamo-pituitary functions is still high, especially in patients with craniopharyngioma. Basal interhemispheric supra-chiasmal or infra-chiasmal approaches via superomedial orbitotomy were developed for better visualization of the hypothalamus. Operative techniques and results, including combination treatment with radiosurgery, are reported. Twelve patients with tumors compressing the hypothalamus upward or extending into the III ventricle, or both, were operated on: 3 tumors were removed totally, 6 tumors subtotally and 3 tumors partially. Six patients received radiosurgery for residual tumor. Four patients with hypopituitarism preoperatively required oral corticosteroids and thyroid hormones postoperatively. The basal interhemispheric approach via superomedial orbitotomy is useful for better visualization of the hypothalamus and preservation of hypothalamo-pituitary functions.

Neurobiologic effects of radiosurgery: histologic, immunohistochemical and electron-microscopic studies of a rat model.

Spinal cords of rats were irradiated with a single fraction of 14-36 Gy (group A) or 55 Gy (group B) and examined by light and electron microscopy. Degeneration and reduced numbers of motor neurons were found even at an early stage in group B animals. Necrosis in the spinal cord was found at a later stage. The ultrastructure of vessels around areas of necrosis showed degeneration of pericytes and vacuolar changes of vascular walls. This study indicates that single, high-dose irradiation causes direct effects on neurons at early stages and degeneration of vascular walls followed by necrosis at a later stage.

Pathobiology of cerebral gliomas in children and the role of radiosurgery.

Twenty-five gliomas of the cerebral hemisphere in children were examined. Most hemispheric gliomas in children have relatively clear margins and less infiltrative potential. Radiosurgery has a role in the treatment of these tumors in addition to reducing the risk of radiation injuries developing later. Fifteen patients were alive 1-27 years (mean 8.4) following treatment and 10 patients died. Histologic examination demonstrated 10 differentiated gliomas, 10 poorly differentiated gliomas and 5 other gliomas. Most tumors had relatively clear margins on computed tomography and/or magnetic resonance images, and peritumoral edema was slight. In 9 autopsy cases, tumor dissemination and/or metastasis were seen in 7. However, tumor infiltration was not extensive, and clear tumor margins were found in some cases. Thus, cerebral gliomas in children have relatively clear margins and low infiltrative potential. Radiosurgery has a role in the treatment of these tumors.

Calcified astrocytoma of the amygdalo-hippocampal region in children.

Three pediatric cases of temporal lobe seizure due to calcified glioma of amygdalo-hippocampal region are described. Computed tomography and magnetic resonance imaging showed dense calcification with no postcontrast enhancement in the amygdalo-hippocampal region. Positron emission tomography showed low oxygen metabolism, low glucose metabolism, hypermetabolism of amino acids, and low regional cerebral blood flow in the tumors. Single photon emission computed tomography showed a high accumulation of 201Tl chloride and 123I-isopropyl iodoamphetamine in one tumor, but otherwise low radioisotope uptake. These studies indicated low-grade malignancies. The patients were treated by partial tumor removal and radiotherapy. Histological examination of the tumor specimens showed astrocytoma with interstitial calcification. One patient died due to tumor recurrence, while the others are doing well with minimal seizure. We recommended temporal lobectomy in similar cases to achieve complete remission.

Hypothalamic hamartoma: anatomic, immunohistochemical and ultrastructural features.

Four patients with hypothalamic hamartoma were examined by CT and/or MR imaging, immunohistochemistry and electron microscopy. The hamartomas arose from the hypothalamus and extended inferiorly. LH-RH neurons were detected in three cases by immunohistochemistry. Electron microscopy revealed large myelinated axons, axon terminals containing dense-core vesicles and axon terminals with clear vesicles forming asymmetrical synapses. The development of hypothalamic hamartoma and its functional manifestations (precocious puberty and laugh attacks) are discussed in reference to the migration of LH-RH neurons from the olfactory placode.

Classification of arteriovenous malformations for radiosurgery. Neuroimaging, histopathology and radiobiologic effects.

Arteriovenous malformations (AVMs) were classified based on morphologic and hemodynamic factors. They were categorized as Moya type, shunt type or mixed type on the basis of hemodynamic factors, and as homogeneous or heterogeneous types on the basis of morphology. Histopathologic and radiobiologic characteristics were evaluated with respect to these AVM types. Classification depending on the type as well as the size of an AVM is important for modern treatment modalities, especially radiosurgery.

Genomic organization and promoter function of the human thyrotropin-releasing hormone receptor gene.

We isolated and characterized the gene for the human thyrotropin-releasing hormone receptor. The gene spanned more than 30 kilobases and contained three exons and two introns. Intron 1 exists in the 5'-untranslated region, and intron 2 is more than 25 kilobases in length which interrupts the coding region before the beginning of the putative sixth transmembrane domain. Exon 3 encodes the rest of the coding region and the entire 3'-untranslated region. The 3'-flanking region contains four potential polyadenylation signals, and 3'-rapid amplification of cDNA ends studies showed that only a signal at 2076 base pairs downstream of the stop codon was functional in the anterior pituitary. Primer extension and anchor-polymerase chain reaction studies indicated a transcriptional start site at 344 base pairs upstream of the translational start site. The promoter region does not contain either a TATA box or a CAAT box in the appropriate location. Transient transfection study revealed significant activity of the promoter in GH4C1 cells, and the region between -338 and -933 bp from the transcriptional start site worked as a negative regulator. Knowledge of the genomic organization and the promoter region of thyrotropin-releasing hormone (TRH) receptor gene will allow further studies of possible disorders of the TRH receptor, as well as facilitate elucidation of transcriptional control of the human TRH receptor gene.

Radiosensitive squamous cell craniopharyngioma: clinical and pathological comparison with the adamantinomatous type.

Five patients with the squamous cell type of craniopharyngioma were examined clinically and pathologically, and comparisons were made with the adamantinomatous type of craniopharyngioma. In three patients, the tumor remaining after partial or subtotal resection was treated with conventional radiation therapy, and all three lesions disappeared completely. The squamous cell tumors consisted of basal cubodial cells and polygonal superficial cells with areas of cellular detachment and degeneration. Our findings suggest that these tumors are more radiosensitive than adamantinomatous craniopharyngiomas and represent a distinct clinical entity.