Comparison of multiple parameters obtained on 3T pulsed arterial spin-labeling, diffusion tensor imaging, and MRS and the Ki-67 labeling index in evaluating glioma grading.

BACKGROUND AND PURPOSE: Pulsed arterial spin-labeling, DTI, and MR spectroscopy provide useful data for tumor evaluation. We evaluated multiple parameters by using these pulse sequences and the Ki-67 labeling index in newly diagnosed supratentorial gliomas. MATERIALS AND METHODS: All 32 patients, with grade II (3 each of diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma), grade III (3 anaplastic astrocytomas, 4 anaplastic oligodendrogliomas, and 1 anaplastic oligoastrocytoma), and grade IV (14 glioblastomas and 1 glioblastoma with an oligodendroglioma component) cases underwent pulsed arterial spin-labeling, DTI, and MR spectroscopy studies by using 3T MR imaging. The following variables were used to compare the tumors: relative cerebral blood flow, fractional anisotropy; ADC tumor/normal ratios; and the Cho/Cr, NAA/Cho, NAA/Cr, and lactate/Cr ratios. A logistic regression and receiver operating characteristic analysis were used to assess parameters with a high sensitivity and specificity to identify the threshold values for separate grading. We compared the Ki-67 index with various MR imaging parameters in tumor specimens. RESULTS: Significant correlations were observed between the Ki-67 index and the mean, maximum, and minimum ADC, Cho/Cr, and lactate/Cr ratios. The receiver operating characteristic analysis showed that the combination of the minimum ADC and Cho/Cr ratios could differentiate low-grade and high-grade gliomas, with a sensitivity and specificity of 87.0% and 88.9%, respectively. The mean and maximum relative cerebral blood flow ratios were used to classify glioblastomas from other-grade astrocytomas, with a sensitivity and specificity of 92.9% and 83.3%, respectively. CONCLUSIONS: Our findings indicate that pulsed arterial spin-labeling, DTI, and MR spectroscopy are useful for predicting glioma grade. Additionally, the parameters obtained on DTI and MR spectroscopy closely correlated with the proliferative potential of gliomas.

The clinical and pathological significance of nitric oxide synthase in human pituitary adenomas: a comparison with MIB-1.

The purpose of the present study was to define the clinical and pathological significance of nitric oxide synthase (NOS) in human pituitary adenomas, and to compare these values with those of the MIB-1 labeling index (LI) using an immunohistochemical method. Tissue specimens from 82 cases of surgically-treated pituitary adenomas were immunostained for hormone production for the MIB-1 LI and for the three NOS isoenzymes and five normal pituitary glands were immunostained for the three NOS isoenzymes as a control. The correlation between the clinical variables (age, functional status, tumor size, Hardy's grading, cavernous and/or sphenoid invasiveness, and progression) and mean MIB-1 LI, or between the same clinical variables and NOS immunoreactivity (IR) were analyzed. There was a statistically significant difference in the MIB-1 LI between macroadenomas and microadenomas, and between invasive adenomas and noninvasive adenomas. On the other hand, there was a statistically significant difference in the inducible NOS (iNOS) IR between invasive adenomas and noninvasive adenomas. Furthermore, the iNOS IR had a significant correlation with the MIB-1 LI. Invasive adenomas have a higher iNOS IR, and this correlated with the MIB-1 LI. These findings may be due to the function of iNOS, which plays an important role in tissue injury and repair.

The association between high VEGF levels and multiple probable punctuate cavernous malformations.

Cerebral cavernous malformations (CCMs) are congenital abnormalities of the cerebral vessels. The de novo development of new lesions in this disease has been reported. However, the underlying mechanism of progressive CCMs in such patients remains unclear. This report documents two cases of multiple probable CCMs that showed a progressive behaviour. The plasma levels of vascular endothelial growth factor (VEGF), and transforming growth factor-beta1 (TGF-beta1) were measured using an enzyme-linked immunosorbent assay (ELISA). The concentration of both VEGF and TGF-beta1 in plasma was increased in these patients. A relationship was observed between high concentrations of growth factors and progressive CCMs. Even though a causal linkage between these conditions cannot be confirmed, a continuous high VEGF level in plasma could be a possible clinical indicator for subsequent intracerebral haemorrhages in the CCM patients.

Neuroprotective effects of edaravone, a free radical scavenger, on the rat hippocampus after pilocarpine-induced status epilepticus.

PURPOSE: Edaravone (MCI-186) is a newly developed antioxidative radical scavenger for the treatment of acute cerebral infarction, exerting neuroprotective effects against ischemic insult. The neuroprotective effects of edaravone on pilocarpine-induced seizures in rats were investigated. METHODS: Rats were treated intraperitoneally with saline or edaravone (1-30 mg/kg), applied 30 min before pilocarpine hydrochloride (330 mg/kg). The onset of status epilepticus (SE) and mortality were recorded for a period of at least 3 days. The cell loss and immunoreactivities of nitric oxide synthase (NOS) in the hippocampus from control and the day 3 rats after SE, treated with saline or edaravone, were evaluated. RESULTS: Edaravone (1mg/kg) significantly prevented cell loss in the hippocampus after SE while easier inducing SE. The higher dose of drug could not induce SE significantly but tended to increase the rate of mortality. Inducible NOS (iNOS) expression was significantly decreased in the hippocampus from day 3 rats treated with 1mg/kg edaravone, compared with saline group, while neuronal NOS (nNOS) and iNOS significantly increased in the hippocampus treated with saline, compared with control group. Significant alteration of endothelial NOS (eNOS) expression in the hippocampus among control group, saline group, and edaravone group was not shown. CONCLUSIONS: Edaravone may act as a neuroprotector for the hippocampus after SE by reducing at least iNOS although the low dose of drug easier induces SE because of preventing an endogenous antiepileptic effect of NO.

Nitric oxide synthase and NMDA receptor expressions in cavernoma tissues with epileptogenesis.

OBJECTIVES: To investigate the contribution of nitric oxide (NO) and the glutamate systems to epileptogenicity of cavernoma (CA). METHODS: Using immunohistochemistry we examined NO synthases (NOS; neuronal, inducible and endothelial) and N-methyl-D-aspartate (NMDA) receptor subunits 1(NR1) and 2A/B (NR2A/B) in tissues, with and without hemosiderin deposits, adjacent to CA resected from temporal (seven patients) and frontal (one patient) lobes. RESULTS: All isoforms of NOS, especially iNOS expression, was significantly upregulated in company with NR2A/B expression, not only in declining neuronal cells but also in reactive astrocytes in the tissue, with hemosiderin deposits, adjacent to CA and moreover the degree of iNOS expression was significantly correlated with seizure frequency. CONCLUSIONS: These preliminary results sustain a speculation that excessive NO may generate in the tissue surrounding CA with repeated microhaemorrhaging and seizures. The neuronal loss and reactive glial proliferation induced by iron or NO may play a role in epileptogenesis.

Overlapping free bone graft with galea-pericranium in reconstruction of the anterior skull base to prevent CSF leak and sequestrum formation.

Background. Reconstruction of the skull base after resection of a tumour is important to prevent postoperative complications such as infectionsand cerebrospinal fluid (CSF) leakage. Several reconstructive methods of the anterior skull base have been reported but, their long-term results are not clear. Methods. We describe a technique used after removal of an olfactory neuroblastoma with infiltration of the skull base. The reconstructed dura was covered with a galeal patch, a replicated galeal-pericranial flap, a graft from the inner table of skull, and a vascularised galeal-pericranial flap placed on the skull base defect. All layers were fixed with fibrin glue. Conclusion. Three dimensional computed tomography (3D-CT) at bone window settings demonstrated the bone graft covered the bone defect and was not absorbed and after 11 years there have been no signs of tumour regrowth or complications.

The relationship between paired pulse magnetic MEP and surgical prognosis in patients with intractable epilepsy.

PURPOSE: To assess whether paired pulse magnetic motor evoked potential (MEP) can predict surgical prognosis in patients with intractable epilepsy. METHODS: MEP of the unilateral hand muscles were recorded following paired pulse transcranial magnetic stimulation (TMS) of the motor cortex. The interstimulus intervals of paired stimulation were 1-16 ms with a conditioning stimulus that was 90% active motor threshold. Subjects were six patients with temporal lobe epilepsy (TLE) scheduled for anterior temporal lobectomy and three patients with myoclonic or head-drop seizures scheduled for anterior corpus callosotomy, resulting in the unilateralization of epileptic discharges. The hemisphere showing unilateral discharges was defined as the affected hemisphere. The intracortical inhibition and facilitation curve was drawn based on MEP before and after surgery and the relationship between MEP and surgical prognosis was investigated. RESULTS: In five patients with TLE showing class I surgical results (Engel's classification), the affected hemisphere showing cortical hyperexcitability preoperatively was almost normalized after surgery. However, in a patient with class III, the unaffected hemisphere showed cortical hyperexcitability before and after surgery. In the callosotomy group, two patients with excellent outcomes showed the same results as TLE group with class I. CONCLUSIONS: Paired pulse magnetic MEP may provide predictive value in terms of surgical outcome in those patients with intractable epilepsy.

Total callosotomy for a case of lissencephaly presenting with West syndrome and generalized seizures.

CASE REPORT: An 11-month-old girl had an onset of oculogyric crisis at 2 months and she presented with epileptic spasms and generalized tonic seizures with series formation at 3 months. Her seizures were medically intractable and her development had gradually regressed after that. MRI showed severe lissencephaly in bilateral hemispheres. Interictal EEG showed hypsarrhythmia periodically and sporadic spike waves in the right hemisphere. The generalized tonic seizures began with bi-frontal polyspikes on EEG. Our diagnosis was lissencephaly presenting with West syndrome and generalized tonic seizures. A total callosotomy was performed at 11 months. OUTCOME: Postoperative frequency of seizures decreased prominently and developmental progression was resumed. CONCLUSIONS: This case showed that the corpus callosum may play an important role in some types of symptomatic West syndrome. Corpus callosotomy for treating symptomatic West syndrome should be considered as an option after careful selection and consideration of the timing of surgery.

[Ictal semiology in patients with medial temporal lobe epilepsy: value in lateralizing the seizure focus].

We have evaluated useful lateralizing signs in 28 patients with medial temporal lobe epilepsy who were seizure-free after anterior temporal lobectomy by reviewing videotapes during video-EEG monitoring. The most frequent types of aura were epigastric sensation and psychic symptom in 8, respectively, both of which did not predict lateralization of the focus. Of the motor signs, early head deviation and unilateral upper extremity automatism predicted an ipsilateral focus in 72 and 80%, respectively. On the other hand, late head deviation(< 15 seconds before secondarily generalized seizure) and unilateral upper extremity dystonic posturing predicted a contralateral focus in 80 and 100%, respectively. Twelve of the patients displayed oroalimentary automatism which did not predict focus lateralization. Three patients with ictal speech demonstrated a seizure focus contralateral to their language-dominant hemisphere. In medial temporal lobe epilepsy, several clinical seizure manifestations such as: early and late head deviation, unilateral upper extremity automatism and dystonic posturing were not a little noted and provided additional information as to the side of seizure origin.

Clinical features of symptomatic Rathke's cleft cyst.

To investigate the clinical features of Rathke's cleft cysts (RCCs), we retrospectively analyzed 15 cases with histologically confirmed RCCs. All patients underwent formal testing of visual field, endocrinological evaluation and magnetic resonance imagings. As overall presenting symptoms, endocrine disturbance was the most common symptoms, followed by visual disturbance and headache. Among the endocrine disturbances based on adenohypophysial dysfunction, hyperprolactinemia was most common. Considering the size of RCCs, RCCs could induce hyperprolactinemia only when the cysts became large enough to compress the infundibular system. Our series showed relative high incidence of pituitary dwarfism and diabetes insipidus (DI). These facts indicated that RCCs could evoke hyposecretion of growth hormone in young patients and DI in aged patients by direct compression of the pituitary gland in the early stage of progression. All cases who had headache had no other symptoms. We could not prove the evidence that RCCs could induce headaches in these cases. This might be suggested that headache could not be a sole symptom in cases of RCCs.

Retro-odontoid soft tissue mass associated with atlantoaxial subluxation in an elderly patient: a case report.

BACKGROUND: We present the case of an elderly patient with a retro-odontoid soft tissue mass associated with atlanto-axial subluxation. CASE DESCRIPTION: A 74-year-old man was admitted to our hospital with progressive motor weakness in his right arm and neck pain. Radiological examinations revealed atlantoaxial subluxation and diffuse degenerative changes. Cervical MRI revealed a syrinx at the C1 level and a retro-odontoid soft tissue mass that severely compressed the spinal cord. The mass was of low signal intensity on both T1- and T2-weighted images. Conservative therapy could not stop the progression of his symptoms, so posterior decompression via a laminectomy of C1 and occipitocervical fixation was performed. These procedures resulted in an improvement of his neurological condition and in reduction of the mass and the compression of the spinal cord. CONCLUSION: The patient lacked any specific conditions that might have caused chronic atlantoaxial subluxation. The degenerative changes alone might have provoked chronic atlantoaxial subluxation and a subsequent retro-odontoid soft tissue mass. In patients with this condition, posterior fixation without direct removal of the mass should be the first choice for surgical intervention.

[Staged total callosotomy for medically intractable seizures].

For the treatment of intractable generalized epilepsies, two-staged total callosotomy was performed in five patients. In all patients, preceded anterior callosotomy failed to obtain satisfactory seizure control. All patients showed mental retardation with various degrees. Mean age at the first operation was 10.2 years and 4 patients were operated in their childhood. All patients showed various types of seizures; drop attack (DA) in 3 patients, tonic seizure (TS) in 2, myoclonus (MY) in 2, complex partial seizure (CPS) in 2, atypical absence (AA) in 1, and head drop (HD) in 2. After anterior callosotomy, complete cessation of CPS and 50-80% reduction of DA was obtained in one, respectively. However, only less than 50% reduction of seizures was obtained in other types of seizures. Two years after anterior callosotomy, posterior portion of the corpus callosum was divided. After staged total callosotomy, complete cessation of DA was obtained in all patients and 80-100% reduction of AA was obtained in one patient. One adult patient showed the disconnection syndrome which did not affect activities of his daily life. Our study revealed the efficacy of posterior callosotomy in DA patients with unsatisfactory results after anterior callosotomy. This strategy should be considered especially in childhood cases, since obvious complication was not observed in such cases.

Conduction pathways of motor evoked potentials following transcranial magnetic stimulation: a rodent study using a "figure-8" coil.

We have examined the conduction pathways of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation, and their correlation with locomotor function in rats. MEPs were concomitantly recorded from the spinal cord (sMEPs) and the limb muscles (mMEPs) before and after various spinal tract ablations. Motor function was also examined using an inclined plane test. sMEPs were composed of four negative peaks (N1-N4) and mMEPs of high-voltage, biphasic waves. Ventral funiculus transection reduced the N1-N3 peaks and abolished mMEPs. Contrarily, dorsal funiculus transection including the pyramidal tract did not alter these MEPs. Motor performance on an inclined plane was worse after ventral funiculus transection than after other transections. These findings indicate that, in rats, the N1-N3 peaks of magnetic sMEPs conduct ventral funiculus activity, and that magnetic mMEPs mainly reflect extrapyramidal activities and are correlated with locomotor function.

[Neovascularization after encephalo-duro-arterio-synangiosis in elderly quasi-moyamoya disease: a case report].

A 65-year-old man who had a history of diabetes mellitus visited a hospital for recent memory disturbance. MR angiography showed stenoses of the main trunks of the intracranial arteries. He was admitted to our hospital, and angiography revealed occlusion of the left cervical internal carotid and right middle cerebral arteries, and stenoses of the right internal carotid, right anterior cerebral, left vertebral, and right posterior cerebral arteries. There was collateral circulation formed from the left external carotid and left posterior cerebral arteries. Basal moyamoya vessels were also observed. 123I-IMP SPECT showed low perfusion of the right cerebral hemisphere, and response to acetazolamide was poor. Based on the angiographical findings and the presence of diabetes mellitus, the patient was diagnosed as having quasi-moyamoya disease. Vascular reconstructive surgery was indicated. Since there was no recipient artery adequate for STA-MCA anastomosis, encephalo-duro-arterio-synangiosis was performed on the right side. Postoperatively, the patient's recent memory improved gradually, and angiography performed 7 months after the operation revealed neovascularization from the superficial and deep temporal arteries. Although indirect bypass surgery has been applied mainly to child moyamoya disease, its effectiveness for cerebral ischemia in adult patients has also been reported, particularly in cases with misery perfusion. Neovascularization with indirect bypass surgery can be expected if the patient is under misery perfusion, even in elderly patients.