Tentorial enhancement on MR images is a sign of cavernous sinus involvement in patients with sellar tumors.

BACKGROUND AND PURPOSE: This study was undertaken to analyze enhancement patterns of the dura around sellar tumors and to compare the results with tumor invasion or compression of the cavernous sinuses. Postoperative enhancement patterns on MR images were compared with preoperative findings. METHODS: Contrast-enhanced coronal and sagittal MR images were examined prospectively in 96 patients with sellar tumors (65 macroadenomas, 15 microadenomas, 14 Rathke cleft cysts, and two chordomas at the sella). All patients underwent surgical treatment, and pre- and postsurgical features on MR images were compared. RESULTS: Presurgical MR images showed dural enhancement in 36.5% of the patients: asymmetric tentorial enhancement in 24 patients, symmetric tentorial enhancement in seven, and sphenoidal ridge or clivus enhancement in four. Asymmetric tentorial enhancement disappeared after surgical decompression in seven patients. For evaluation of cavernous sinus invasion ipsilateral to the enhancement, sensitivity and specificity of the asymmetric tentorial enhancement sign were 81.3% and 86.3%, respectively. Sensitivity and specificity of the sign were 42.9% and 93.6% for cavernous sinus involvement, including compression and invasion. CONCLUSION: Asymmetric tentorial enhancement is a useful sign in the diagnosis of invasion or severe compression of the cavernous sinus by sellar tumor. The sign may represent venous congestion or collateral flow in the tentorium due to obstructed flow in the medial portion of the cavernous sinus.

Effects of blood sugar level on rat transient focal brain ischemia consecutively observed by diffusion-weighted EPI and (1)H echo planar spectroscopic imaging.

The effects of blood sugar level on transient focal brain ischemia were examined by consecutive diffusion-weighted EPI and (1)H echo planar spectroscopic imaging. A remote-controlled rat intraluminal suture middle cerebral artery occlusion (MCAO) model was prepared. Animals were divided into three experimental groups: control, 1 g/kg, and 2 g/kg glucose groups (n = 6 for each). Saline or glucose was infused intraperitoneally 30 min prior to MCAO. The glucose-loaded groups showed increased lactate accumulation and marked decreases in average diffusion coefficient in the ischemic region during 40-min MCAO. These changes were correlated with blood sugar levels at the onset of MCAO. After reperfusion, all rats in the control and 1 g/kg groups recovered from the ischemic changes, but three rats with marked hyperglycemia in the 2 g/kg group showed irreversible changes. The adverse effects of hyperglycemia on transient focal brain ischemia were clearly demonstrated by sequential 2D images. Magn Reson Med 42:895-902, 1999.

Atypical Rathke's cleft cyst associated with ossification.

We report a case of symptomatic Rathke's cleft cyst with ossification. CT scans showed curvilinear calcification on the wall of the cyst. MR images revealed a cystic sellar lesion with a nodular solid mass extending to the floor of the third ventricle. This case shows that calcification of the suprasellar cyst does not always suggest craniopharyngioma. Rathke's cysts should be histologically differentiated from craniopharyngiomas because their treatments are different.

Preoperative identification of meningiomas that are highly likely to recur.

OBJECT: Although generally they are well-circumscribed benign tumors, meningiomas recur even after complete removal. The aims of this study are to identify preoperatively groups of patients who have a high risk of meningioma recurrence by reviewing their clinicoradiological features and to plan appropriate treatments. METHODS: One hundred one patients who underwent macroscopically complete removal of meningiomas were observed postoperatively for at least 5 years or until tumor recurrence. Preoperative radiological findings and clinical characteristics were assessed. Fifteen meningiomas recurred during the follow-up period, which extended to a maximum duration of 18 years. On univariate analysis, tumor size and shape, relation to the major sinuses, calcification, bone changes, and characteristics of the tumor-brain interface were significant predictive factors for recurrence. Patient age and gender were not deemed significant. Multivariate analysis revealed that only the shape of the tumor was significant; both "mushrooming" and lobulated meningiomas were more likely to recur than round ones. Recurrences most frequently occurred at the edge of the dural resection after a Simpson Grade I removal, whereas local recurrences were predominant after a Simpson Grade II or III removal. CONCLUSIONS: Meningiomas with mushrooming or lobulated shapes should be treated more aggressively with a wider dural excision. This is not usually necessary for round tumors, although it may be beneficial in younger patients.

Shock syndrome induced by bromocriptine test in a patient with prolactinoma--case report.

A 72-year-old male developed shock syndrome after a single dose of bromocriptine. He had undergone uncomplicated subtotal removal of an invasive prolactinoma in our department. The patient had normal ranges of pituitary hormones apart from hyperprolactinemia (167.7 ng/ml) after surgery. An acute suppression test with bromocriptine (2.5 mg per os) was done in the supine position 6 days following surgery. Three and a half hours after bromocriptine administration, he suddenly complained of anterior chest discomfort in bed. Cyanosis and profuse diaphoresis were noted. His blood pressure was 80/60 mmHg. Electrocardiography revealed sporadic premature contractions and slight depression in the ST segments. He recovered in about 10 hours after a rapid infusion of corticosteroid and lactic Ringer solution, and was discharged without sequelae. This is a very rare complication of bromocriptine, but the cardiovascular function of patients taking bromocriptine for therapeutic and diagnostic purpose should be monitored carefully.

Postoperative sella: evaluation with fast spin echo T2-weighted high-resolution imaging.

OBJECTIVE: The purpose of this study was to investigate the magnetic resonance features of the postoperative sella with fast spin echo (FSE) T2-weighted high-resolution imaging and to evaluate the benefits of the sequence using a follow-up magnetic resonance imaging protocol after transsphenoidal surgery. METHODS: Coronal spin echo (SE) T1-weighted and FSE T2-weighted images were prospectively obtained in 24 patients after surgery for pituitary adenomas. We observed the signals and the contour of normal structures, fluid collection, implanted materials, and mass lesions, including granulation tissue and adenoma. RESULTS: The pituitary gland was delineated in 51 of 59 FSE T2-weighted images, 90.2% of which presented clear boundaries. Whereas the gland was detected in 49 of 58 SE T1-weighted images, only 20.4% showed the boundaries. A mass lesion was identified in each of 12 patients with good resolution on FSE T2-weighted images. SE T1-weighted images detected mass lesions in 7 of 12 patients without distinctive boundaries. Contrast enhancement had little advantage in clarifying the boundaries between normal and abnormal structures. For the detection of mass lesions in the sella, the kappa values for interobserver agreement were 0.8 for FSE T2-weighted images and 0.25 for SE T1-weighted images. CONCLUSION: FSE T2-weighted imaging is a reliable method with which to assess the sella with sufficient resolution after transsphenoidal surgery. The combination of unenhanced SE T1-weighted and FSE T2-weighted images may reduce the use of contrast material after pituitary surgery.

Alteration of bcl-2 and bax expression in embolized meningiomas.

We examined the expression of the p53 and bcl-2 family in embolized meningiomas and investigated the interaction between them. p53 and its downstream effector p21 accumulated mainly in perinecrotic areas, where apoptosis was also observed. bcl-2 was often expressed in the areas distant from necrosis, whereas Bax was immunostained more intensely in the perinecrotic areas. Double staining for both p53 and Bcl-2 showed a reciprocal pattern. This appeared to be due to the down-regulation of Bcl-2 by p53. However, regulation of Bax by p53 was not distinct. The expression of p21 was not apparent 13 days after embolization, and apoptosis was observed until 6 days after embolization. The effect of embolization was most likely temporary, although growth arrest has been reported to persist for a long time in a limited number of embolized cases.

Inhibition by nitric oxide of the uptake of [3H]serotonin into rat brain synaptosomes.

[3H]Serotonin (5-HT) uptake by synaptosomes of rat brain was dose-dependently inhibited by nitric oxide (NO) donors such as sodium nitroprusside (SNP), 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin e, 3-morpholinosydnonimine and S-nitroso-L-cysteine (NO-CYS). The inhibitory effect was blocked by reduced hemoglobin. The effect was not mimicked by ferrocyanide and ferricyanide. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-bromo cGMP) did not affect [3H]5-HT uptake into rat cortical synaptosomes. The reduced activity of [3H]5-HT uptake into the cortical synaptosomes pretreated with NO-CYS was partially reversed by washing the preparation after the treatment. Kinetic analysis showed that NO-CYS (100 microM) decreased the Vmax value without any change in the Km value. NO-CYS did not affect the specific binding of [3H]paroxetine, a ligand that binds to the 5-HT transporter, in membranes. NO-CYS and SNP, like iodoacetic acid and sodium cyanide, decreased the ATP content in cortical synaptosomes, but the effect on ATP content was not related to that on [3H]5-HT uptake. These findings suggest that NO inhibits reversibly [3H]5-HT uptake into rat brain synaptosomes without affecting the recognition site of the 5-HT transporter in a cGMP-independent manner, and the observed effect is not due to its metabolic effect.

p53 accumulation and apoptosis in embolized meningiomas.

Preoperative embolization of meningiomas is performed to decrease blood loss at surgery. While it is also expected to reduce tumor recurrence by producing necrosis at the site of dural attachment, very little has been described about what happens to the non-necrotic tumor cells. We investigated how the proliferative activities of meningiomas were modified after embolization. In nine meningiomas which were embolized preoperatively, proliferative potentials and expression of cell cycle inhibitors were assessed immunohistochemically using MIB-1, anti-53 (DO-1 and DO-7), and anti-p21 (WAF1/CIP1) monoclonal antibodies. To determine whether a cell underwent apoptotic death besides necrosis, we applied the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling method. Results were compared with control meningiomas without embolization. MIB-1 positive cells often gathered in perinecrotic areas, although the mean MIB-1 staining index of the embolized meningiomas was not significantly different from the control. p53 and its downstream effector p21 accumulated mainly in the perinecrotic areas in eight of the nine embolized meningiomas. Apoptosis was also observed in the concomitant areas. Double staining for both MIB-1 and p21 frequently showed positive cells for both antibodies. The accumulation of MIB-1 positive cells in the embolized meningiomas may not be a sign of fast growth or malignancy, but it may implicate arrest of cell cycle by the p21. This study indicates that embolized meningiomas exhibit not only necrosis but also apoptosis and cell cycle arrest. The latter effects appear to be at least partly p53 dependent.

Serial magnetic resonance imaging findings of Rasmussen's encephalitis--case report.

A 12-year-old boy presented with Rasmussen's encephalitis. Serial magnetic resonance (MR) imaging one year after the onset of seizure showed no abnormality. T2-weighted imaging detected a high intensity lesion in the left frontal cortex when the frequency of seizures increased 11 months later. MR imaging showed the lesion rapidly spread into the white matter, then gradually regressed after biopsy and immunoglobulin therapy, and mild focal atrophy of the left frontal lobe in spite of recurrence of seizures 3 months after the therapy. Histological examination of the biopsy sample showed the characteristic findings of Rasmussen's encephalitis. Five months after the biopsy, another new high intensity lesion was detected next to the previous one, although his seizures were well controlled at that time. Although the extent of the high intensity lesion did not correlate with the frequency of seizures, such sequential changes in MR imaging appearance seemed to reflect the course of this disease.

Potential doubling time and tumour doubling time in meningiomas and neurinomas.

Cell kinetic study plays an important role in treatment planning of brain tumour patients. MIB-1 antibody has recently become available, which detects Ki-67 antigen even in the formalin-fixed paraffin-embedded specimens. We performed MIB-1 immunostaining in 50 meningiomas and 50 neurinomas, and estimated the cell cycle time (tc) and potential doubling time (Tpot) from MIB-1 staining index (MIB-1 SI) and mitotic index (MI). MIB-1 SI logarithmically correlated with MI in both meningiomas and neurinomas. The tc and the Tpot were expressed as a function of the mitosis time (tm), while the tm is known to be around one hour and not exceeding two hours. When the tm was assumed to be one hour, the average tcs of meningiomas and neurinomas were 6.53 +/- 3.56 days and 7.67 +/- 3.27 days, respectively. The Tpots were 447 X (MIB-1 SI)-1.29 X tm in meningiomas, and 490 X (MIB-1 SI)-0.98 X tm in neurinomas. The tumour doubling times (Tds) were calculated from serial imaging studies in 22 neurinomas and 15 meningiomas. The Tds were formulated as 794 X (MIB-1 SI)-0.83 in meningiomas and 1380 X (MIB-1 SI)-0.97 in neurinomas. Most of the Tds correlated well with the Tpots in meningiomas and neurinomas, and exceeded values of the Tpot when the tm is assumed to be one hour, although a few tumours showed unexpectedly longer Tds. The Tpot and the to estimated from MIB-1 SI and MI are clinically useful parameters for predicting the growth potential of meningiomas and neurinomas where no other simple methods are available.

Basic FGF partially prevents degeneration of paraventricular vasopressin neurons after hypophysectomy.

This experiment was designed to determine if basic fibroblast growth factor (bFGF) had neurotrophic effects on vasopressin neurons after hypophysectomy. Adult male Sprague-Dawley rats received 1 µg bFGF (bFGF group) or 0.1% bovine serum albumin (BSA group) to the sellar cavity immediately after hypophysectomy via parapharyngeal approach. Seven sham-operated non-hypophysectomized rats were used as control. Later (7 weeks) the number of arginine vasopressin (AVP) neurons was quantitatively examined in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) by immunohistochemistry. AVP neurons in both the PVN and SON of the hypophysectomy groups exhibited a significant reduction in number, compared with the control group. In the PVN, the number of AVP neurons was significantly greater in the FGF group than in the BSA group. Particularly, the difference was confirmed in the posterior magnocellular division, that consists of AVP neurons mainly projecting their axons to the posterior pituitary. In the SON, however, there was no difference in the number of AVP neurons between the bFGF group and BSA group. These results suggest that bFGF has a preserving effect on AVP neurons in the PVN following hypophysectomy.

Meningioma: proliferating potential and clinicoradiological features.

We examined the proliferative potentials of meningiomas in 120 patients using the MIB-1 antibody against the Ki-67 antigen and compared them with the clinicoradiological features. The Ki-67 staining index (SI) did not relate to the age and sex of the patients or the location of the tumors. Asymptomatic meningiomas showed significantly lower SIs (mean +/- standard deviation [SD], 0.87 +/- 0.56%) than symptomatic meningiomas (mean +/- SD, 1.63 +/- 2.17%). We found no relation between SIs and clinical symptoms and signs in the symptomatic meningiomas. A weak correlation was found between the size of tumors and Ki-67 SIs (r = 0.21; P = 0.024). There were significant differences in SIs between calcified (mean +/- SD, 0.77 +/- 0.41%) and noncalcified tumor (mean +/- SD, 1.75 +/- 2.25%). Diffusely calcified tumors (mean +/- SD, 0.57 +/- 0.34%) showed lower SIs than focally calcified tumors (mean +/- SD, 0.92 +/- 0.41%). Lobulated tumors showed higher SIs (mean +/- SD, 2.85 +/- 3.68%) than round tumors (mean +/- SD, 1.06 +/- 0.67%). Tumors with perifocal edema or unclear borders had higher SIs than did those without such features. Signal intensities on T1-weighted magnetic resonance images had no relation to SIs, whereas low-intensity tumors on T2-weighted images, most of which presented diffuse calcification on computed tomographic scans, showed lower SIs. This study indicates that several clinicoradiological features relate to the proliferative potential of meningiomas and that they may contribute to the management of patients.

Novel benzodioxan derivative, 5-(3-[((2S)-1,4-benzodioxan-2- ylmethyl)amino]propoxy)-1,3-benzodioxole HCl (MKC-242), with a highly potent and selective agonist activity at rat central serotonin1A receptors.

The present study characterizes the neurochemical profile of the newly synthesized compound 5-(3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy)-1,3-be nzodioxole HCl (MKC-242). In in vitro experiments, MKC-242 had high affinity for serotonin1A (5-HT1A) receptors (Ki: 0.35 nM) and moderate affinity for alpha 1-adrenoceptors (Ki: 21 nM), whereas it had no appreciable affinity for any other neurotransmitter recognition sites studied and 5-HT transporter. MKC-242 (0.3-3.0 mg/kg, s.c.; 1-10 mg/kg, p.o.) caused presynaptic 5-HT1A-receptor-mediated responses (decreases in 5-HT turnover and 5-HT release) and postsynaptic 5-HT1A-receptor-mediated responses (hypothermia, an increase in serum corticosterone level and 5-HT1A behavioral syndrome). The effects of MKC-242 on decarboxylase inhibitor-induced 5-hydroxytryptophan accumulation and rectal temperature were blocked by the 5-HT1A-receptor antagonist N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropana mide. The comparative studies on the in vivo responses induced by MKC-242 and the 5-HT1A-receptor full agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) showed that MKC-242 and 8-OH-DPAT had similar efficacy at presynaptic 5-HT1A receptors, whereas the former had less efficacy than the latter at postsynaptic 5-HT1A receptors. Furthermore, MKC-242 partially inhibited forskolin-stimulated adenylate cyclase activity in hippocampal membranes. These findings suggest that MKC-242 acts as a full and partial agonist at pre- and postsynaptic 5-HT1A receptors, respectively, in the central nervous system.

Diffusion-weighted MR in experimental sustained seizures elicited with kainic acid.

PURPOSE: To investigate the early changes in diffusion-weighted MR images in the sustained limbic seizures. METHOD: Intraperitoneal injection of kainic acid was used to induce sustained limbic seizures in seven rats. The animals were investigated with serial 2.0-T MR imaging beginning immediately after kainic acid-induced seizures, and at 24 hours, 3 days, and 7 days after the kainic acid injection. Diffusion-weighted spin-echo and T2-weighted images and apparent diffusion coefficients were sequentially assessed and compared with histologic changes. The results were compared with eight control animals given buffered saline intraperitoneally. RESULTS: Diffusion-weighted MR images revealed an increase in signal intensity bilaterally in the amygdala and the piriform cortices immediately after the sustained seizures, whereas T2-weighted images did not show changes in signal intensity at this time. Both diffusion-weighted and T2-weighted images showed marked increase in signal intensities in these same areas 24 hours after kainic acid injection. The apparent diffusion coefficient values were significantly lower in the area of the amygdala and the piriform cortex immediately after and lower again 24 hours after the sustained seizures. The area of hyperintensity in diffusion-weighted images was concordant with the histologic distribution of neuronal pyknosis and neuropile vacuolation. CONCLUSION: Diffusion-weighted MR revealed focal abnormalities in the limbic system after 1 hour of sustained seizures induced with kainic acid, before changes on T2-weighted imaging. Diffusion-weighted MR is a potential method for studying the mechanisms of brain damage caused by sustained seizures.

bcl-2 protein expression in tumors of the central nervous system.

bcl-2 protein (BCL-2) expression was immunohistochemically studied in 140 varied central nervous system tumors. The protein was most frequently expressed in neurinomas and ependymomas, and in normal ependymal cells and Schwann cells. Most pituitary adenomas could be classified into one of two subgroups, diffusely positive or diffusely negative tumors, while BCL-2 localized heterogeneously in normal pituitary glands. Although the protein was not detected in normal astrocytes, it was positive in reactive hypertrophic astrocytes observed in various pathological conditions. Similarly, astrocytic tumor cells often expressed BCL-2. Since low-grade astrocytomas more often exhibited the protein than malignant gliomas, the degree of BCL-2 expression appeared to be related to the degree of malignancy of the gliomas. On the other hand, 7 out of 17 recurrent gliomas and medulloblastomas showed an increase in the frequency of protein expression compared with specimens from initial treatments. One recurrent astrocytic tumor which demonstrated anaplastic change showed a decrease in the frequency of BCL-2-positive cells. It is concluded that the frequency of BCL-2 expression in CNS tumors is increased when the non-neoplastic counterparts of the tumors exhibit the protein. Although it has been reported that overexpression of BCL-2 protects cells from damage by radiation and/or chemotherapy, we could not find any significant relationship between the degree of BCL-2 expression and the length of survival of patients with glioblastomas or medulloblastomas.

[Ossification and calcification of the cervical ligamentum flavum--case reports].

Ossification of ligamentum flavum was reported usually lower thoracic and lumbar region, and rarely seen in the cervical region. Calcification of cervical ligamentum flavum is also relatively rare. We report a case of ossification and another of calcification of cervical ligamentum flavum, and discussed the difference of the clinical and radiological features in these conditions. Case 1: A 55-year-old man presented with numbness of the left shoulder and urinary dysfunction. Neurological examination revealed weakness, muscle atrophy and elevated deep tendon reflexes of the left extremities. CT showed ossified mass protruding into the right side of the canal and compressing the spinal cord at C 3/4 and C 4/5. MRI showed low intensity mass both on T1- and T2-weighted images and severe compression of the spinal cord. Left side partial hemilaminectomy with foraminotomy, so called "key hole" foraminotomy, satisfactorily decompressed the cord with clinical improvement. Case 2: A 70-year-old woman complained numbness of both hands for two years. She had sensory disturbance of both hands and spastic gait disturbance. Cervical X-ray films showed calcified nodules on the inner surface of lamina at C4/5. Axial CT demonstrated calcification in the ligamentum flavum at the C4/5 and C5/6 levels. MRI showed posterior spinal cord compression at the C4/5 and C5/6 levels. Osteoplastic laminotomy and removal of the affected ligamentum flavum were performed with successful result. Only 8 cases ossification of cervical ligamentum flavum above C6/7 have been so far reported. All are Japanese; four male and four female cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential MRI findings in a patient with a germ cell tumor in the basal ganglia.

Serial changes of MRI scanning of an 11-year-old boy with hemiparesis due to a germ cell tumor in the basal ganglia are presented. Initial brain MRI T1-weighted images revealed a subtle mixed signal intensity lesion at left anterior and posterior limbs of the internal capsule. This lesion was not enhanced with Gd-DTPA, however, T2-weighted images showed a misty high signal intensity lesion in the same region. The MR images also showed hemiatrophy of the left basal ganglia. Histologic examination of biopsy specimens of the tumor revealed an embryonal carcinoma. The patient was treated with chemotherapy with subsequent improvement in the hemiparesis. Our case suggests that germ cell tumors must be considered in the differential disorders of lesions in the ipsilateral hemiatrophic basal ganglia in pediatric patients with hemiparesis.