Formation and Rupture of the Internal Carotid Artery Aneurysm after Multiple Courses of Intensity-Modulated Radiation Therapy for Management of the Skull Base Ewing Sarcoma/PNET: Case Report.

Background Aneurysm formation after stereotactic irradiation of skull base tumors is rare. The formation and rupture of an internal carotid artery (ICA) aneurysm in a patient with skull base Ewing sarcoma/primitive neuroectodermal tumor (PNET), who underwent surgery followed by multiple courses of intensity-modulated radiation therapy (IMRT) and chemotherapy, is described. Case Description A 25-year-old man presented with a sinonasal tumor with intraorbital and intracranial growth. At that time cerebral angiography did not reveal any vascular abnormalities. The lesion was resected subtotally. Histopathologic diagnosis was Ewing sarcoma/PNET. The patient underwent multiple courses of chemotherapy and three courses of IMRT at 3, 28, and 42 months after initial surgery. The total biologically effective dose delivered to the right ICA was 220.2 Gy. Seven months after the third IMRT, the patient experienced profound nasal bleeding that resulted in hypovolemic shock. Angiography revealed a ruptured right C4-C5 aneurysm and irregular stenotic changes of the ICA. Lifesaving endovascular trapping of the right ICA was done. The patient recovered well after surgery but died due to tumor recurrence 6 months later. Conclusion Excessive irradiation of the ICA may occasionally result in aneurysm formation, which should be borne in mind during stereotactic irradiation of malignant skull base tumors.

Usefulness of Leksell GammaPlan for preoperative planning of brain tumor resection: delineation of the cranial nerves and fusion of the neuroimaging data, including diffusion tensor imaging.

Leksell GammaPlan (LGP) software was initially designed for Gamma Knife radiosurgery, but it can be successfully applied to planning of the open neurosurgical procedures as well. We present our initial experience of delineating the cranial nerves in the vicinity of skull base tumors, combined visualization of the implanted subdural electrodes and cortical anatomy to facilitate brain mapping, and fusion of structural magnetic resonance imaging and diffusion tensor imaging performed with the use of LGP before removal of intracranial neoplasms. Such preoperative information facilitated choosing the optimal approach and general surgical strategy, and corresponded well to the intraoperative findings. Therefore, LGP may be helpful for planning open neurosurgical procedures in cases of both extraaxial and intraaxial intracranial tumors.

Management of non-benign meningiomas with Gamma Knife radiosurgery.

OBJECTIVE: Results of Gamma Knife radiosurgery (GKS) were retrospectively evaluated in 16 patients with histologically confirmed atypical and anaplastic intracranial meningiomas. MATERIALS AND METHODS: There were nine men and seven women (mean age 61.0 years). Atypical meningiomas were diagnosed in nine cases and anaplastic meningiomas in seven. In nine patients there was malignant transformation of a tumor that had initially proved to be benign. In total, 21 radiosurgical procedures were performed. The mean tumor volume at the time of GKS was 7.1 cm3. The mean marginal and maximum irradiation doses were 18.8 and 37.0 Gy, respectively. The mean length of follow-up after treatment was 37.1 months. FINDINGS: Of 21 radiosurgical procedures, 6 (29 %) led to stabilization of tumor growth during the mean follow-up of 40.5 months. It was significantly associated with small lesion volume (P = 0.02), and greater marginal (P = 0.04) and maximum (P = 0.02) irradiation doses. Seven patients underwent eight surgical resections of a progressing tumor during the mean period of 26.1 months after irradiation. Five patients (31 %) died because of tumor progression within the average time period of 16.8 months after GKS. Overall, at the time of the last follow-up just two patients (13 %) had no evidence of tumor regrowth, and only three patients (19 %) maintained good activities of daily living during 12, 59, and 69 months, respectively, after radiosurgery. CONCLUSION: GKS has limited efficacy in cases of non-benign meningioma. Better tumor control rates can be attained for small neoplasms treated with greater marginal and maximum irradiation doses.

Reduced pallidal output causes dystonia.

Dystonia is a neurological disorder characterized by sustained or repetitive involuntary muscle contractions and abnormal postures. In the present article, we will introduce our recent electrophysiological studies in hyperkinetic transgenic mice generated as a model of DYT1 dystonia and in a human cervical dystonia patient, and discuss the pathophysiology of dystonia on the basis of these electrophysiological findings. Recording of neuronal activity in the awake state of DYT1 dystonia model mice revealed reduced spontaneous activity with bursts and pauses in both internal (GPi) and external (GPe) segments of the globus pallidus. Electrical stimulation of the primary motor cortex evoked responses composed of excitation and subsequent long-lasting inhibition, the latter of which was never observed in normal mice. In addition, somatotopic arrangements were disorganized in the GPi and GPe of dystonia model mice. In a human cervical dystonia patient, electrical stimulation of the primary motor cortex evoked similar long-lasting inhibition in the GPi and GPe. Thus, reduced GPi output may cause increased thalamic and cortical activity, resulting in the involuntary movements observed in dystonia.

Cilostazol activates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model.

BACKGROUND: Cilostazol(CLZ) has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM)-derived endothelial progenitor cell (EPC) contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. METHODOLOGY/PRINCIPAL FINDINGS: Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2 weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvß3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CONCLUSIONS/SIGNIFICANCE: CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for endothelial regeneration, which is a key event for preventing atherosclerosis or restenosis after vascular intervention.

Analysis of factors affecting the long-term functional outcome of patients with skull base meningioma.

We analyzed the factors that affect the long-term clinical outcome of a series of patients with skull base meningiomas. Clinical records of 73 patients with cranial base meningiomas were reviewed retrospectively, of whom 13 patients experienced a recurrence at various times following the initial surgery. The mean follow-up time was 90.4 ± 21.2 months (range=60-124 months). Based on the location of the recurrence, patients with recurrence were divided into peripheral (n=6) and central (n=7) skull base groups. Of several variables analyzed using a multivariate logistic regression model, "high MIB-1 (Ki-67 proliferation antigen) labeling index" was an independent variable predicting poor long-term functional outcomes. Recurrence of the tumor at the central skull base was also a strong predictor of poor long-term outcomes. An increased proliferative potential, as indicated by a high MIB-1 labeling index, may induce repeated recurrences, eventually leading to worse functional outcomes, particularly for patients with central skull base meningiomas.

Surgical outcome of the endoscopic endonasal approach for non-functioning giant pituitary adenoma.

Pituitary adenomas with extensive suprasellar extension are a therapeutic challenge. The efficacy and safety of the endoscopic endonasal approach for non-functioning giant pituitary adenoma was evaluated retrospectively. A total of 43 consecutive patients with pituitary adenomas with a suprasellar extension of >20mm underwent tumor resection with a purely endoscopic endonasal approach, and their surgical outcomes were analyzed. At surgery, irrespective of the size and shape of the adenoma, every effort was made to perform intracapsular resection under direct visual control using an angled-lens endoscope. Gross total removal was achieved in 20 out of 43 patients. Postoperatively, 42 patients showed varying improvement of both visual field defects and impaired visual acuity. In two patients who presented with gait disturbance and cognitive dysfunction due to obstructive hydrocephalus, these symptoms were completely resolved. There were no serious operative complications. The results indicate that intracapsular resection via the endoscopic approach can be a safe and effective treatment for giant pituitary adenomas.

Ictal asomatognosia due to dominant superior parietal cortical dysplasia.

We report a 23-year-old man with left dominant parietal cortical dysplasia manifesting as ictal asomatognosia. The man had experienced seizures, during which he underwent ictal asomatognosia as a feeling of loss of his right extremities. Scalp electroencephalography (EEG) showed interictal discharges in the left parietal region of his brain. Magnetic resonance fluid-attenuated inversion recovery (FLAIR) imaging revealed a hyperintense lesion in the left superior parietal lobule. A [(123)I]-iomazenil (IMZ) single-photon-emission CT scan demonstrated an area of low IMZ binding coincident with the lesion observed in the MRI scan. Invasive EEG monitoring showed ictal discharges in the cortex posterior to the postcentral sulcus. High-frequency electrical stimulation of the same area of the cortex also induced asomatognosia of the patient's right forearm. We performed a corticectomy of the anterior part of the superior parietal lobule, which resulted in no new neurological deficits. The seizures disappeared after surgery with the maintenance of preoperative medication. Therefore, the anterior part of the superior parietal lobule may be a symptomatogenic zone for ictal asomatognosia.

Intra-axial pseudotumors in the central nervous system: clinicopathological analysis.

Intra-axial pseudotumors in the central nervous system often mimic malignant brain tumors and cause difficulty in diagnosis and treatment. The present study investigates their radiologic and histological features to elucidate diagnostic clues. Six cases were included in the study, one man and five women, ranging in age from 44 to 87 years (mean age, 61 years). Histologically, three cases had demyelination, and one case each had abscess, angiitis, and non-Langerhans cell histiocytosis. All cases were evaluated radiologically on MRI, most of them by thallim-201 single photon emission tomography ((201)Tl-SPECT). These cases were examined using H&E, special stains, and immunohistochemical studies with a variety of antibodies. MRI demonstrated perifocal edema and ring-like or solid enhancement, mimicking the malignant tumors. Diffusion-weighted MRI showed a hypo-iso-intensity with a hyperintensity on the apparent diffusion coefficient. A (201)Tl-SPECT study revealed no uptake. Although there were various kinds of pathology, inflammatory cells were observed, associated with vascular proliferation and reactive astrocytosis. In addition, some cases showed demyelinating or destructive changes. These results suggested that intra-axial pseudotumors in the central nervous system contain various kinds of pathology, and detailed clinicopathological analysis is important from the point of view of differential diagnosis.

Immunoglobulin D multiple myeloma involving the sella manifesting as oculomotor palsy: case report.

OBJECTIVE: Immunoglobulin D multiple myeloma (IgD MM) is an uncommon type of MM characterized by an aggressive clinical behavior and a short survival time. We report a rare case in which oculomotor palsy caused by a sellar lesion was the initial manifestation of IgD MM; systemic treatments were beneficial in this case. CLINICAL PRESENTATION: A 61-year-old man presented with diplopia, left-sided ptosis, and retro-orbital pain. An examination revealed left cranial nerve (CN) III and IV palsies. CT scanning demonstrated a mass in the sellar and parasellar regions and partial destruction of the left side of the dorsum sellae. MRI revealed that the mass extended into the left cavernous sinus with minimal suprasellar extension. An endocrinologic evaluation did not reveal any abnormality. At the time of admission, the patient had no symptoms of MM. INTERVENTION: A transsphenoidal resection was performed. Histopathologic examination revealed a tumor consisting of plasma cells. Appropriate laboratory studies, a bone scan, and a bone marrow biopsy led to a diagnosis of IgD lambda-type MM. High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation was therapeutically beneficial. The patient's symptoms were gradually relieved. CONCLUSION: This case demonstrates that an unusual sellar tumor might be the first manifestation of IgD MM. Careful observation can suggest a possible non-pituitary etiology for a tumor, leading to appropriate diagnostic and therapeutic procedures.

[Unruptured aneurysm arising from fenestration of the horizontal (A1) segment in the anterior cerebral artery: a case report and review of the literature].

Cerebral aneurysms arising from fenestration of the horizontal (A(1)) segment in the anterior cerebral artery (ACA) are very rare. In this paper, we report our case, discuss radiological features, and review previous cases. A 70-year-old male was referred to our hospital presenting with memory disturbance. His unruptured cerebral aneurysm in the A(1) segment was incidentally found by magnetic resonance angiography (MRA). Three dimensional computed tomographic angiography (3D-CTA) demonstrated this aneurysm arising from fenestration of the A(1) segment. Surgical neck clipping was performed via the pterional approach, while sacrificing one pair of the A(1) segment. The patient's post operative course was uneventful. Only 14 cases with an aneurysm arising from fenestration of the A(1) segment have been reported previously. In the present case, 3D-CTA was very useful for finding out where the aneurysm arose from, and we also had to be careful about perforating arteries from the A(1) segment during the surgery.

Temporal lobe encephalocele in the lateral recess of the sphenoid sinus presenting with intraventricular tension pneumocephalus.

A basal encephalocele often shows an insidious clinical course. Only two cases of temporal lobe encephalocele accompanied with tension pneumocephalus have previously been reported. In this paper, we describe a case of lateral sphenoid sinus encephalocele presenting with intraventricular tension pneumocephalus. A 54-year-old man was referred to our institution presenting with intraventricular tension pneumocephalus. He had undergone ventriculoperitoneal shunt placement for postmeningitis hydrocephalus 3 months before this admission. Precise imaging examinations detected evidence suggestive of a lateral sphenoidal sinus recess encephalocele. Endoscopic transnasal approach was performed for surgical repair of the encephalocele. The encephalocele was removed with subsequent repair of the bony defect. Histological examination showed that the encephalocele includes a part of the ventricular system. This indicates that air might enter directly into the ventricular system after rupture of the temporal lobe encephalocele. A lateral sphenoid sinus encephalocele would potentially cause intraventricular tension pneumocephalus, although pneumocephalus is an extremely unusual complication of this type of basal encephaloceles.

Surgical treatment and outcome of skull base meningiomas with extracranial extensions.

OBJECTIVE: Recurrent cranial base meningiomas occasionally extend into craniofacial structures, and are one of the most difficult tumors to surgically manage. We reviewed our experience of surgical treatment in a series of patients with meningiomas showing extensive extracranial extensions. METHODS: We surgically treated a total of 10 patients with recurrent cranial base meningiomas with large extension to multiple craniofacial structures. All patients underwent orbitozygomatic or zygomatic frontotemporal craniotomy for surgical resection of the tumor. An endoscopic endonasal technique was also employed, if necessary, as an adjunct to the transcranial approach. RESULTS: Eight patients were treated solely with a frontotemporal approach associated with an extended resection of the floor of the middle fossa. In 2 patients, an endoscopic endonasal approach was additionally required for resection of tumors located in the nasal cavity and ethmoid sinus. A gross total resection was achieved without serious surgical complications in 9 out of the 10 patients. In all patients, the tumors were found to invade the surrounding tissue such as the bone and skeletal muscle to varying degrees. CONCLUSION: Our data indicate that recurrent craniofacial meningiomas can usually be managed by using a lateral cranial base approach. Whereas it would be expected that a radical resection may prevent further recurrence with an acceptable quality of life, a long-term follow-up would be required for confirming the benefit of this treatment strategy.

Endovascular recanalization of the completely occluded internal carotid artery using a flow reversal system at the subacute to chronic stage.

OBJECT: The efficacy and pitfalls of endovascular recanalization were evaluated in cases of internal carotid artery (ICA) occlusion in the subacute to chronic stage. METHODS: Fourteen cases (15 lesions) of symptomatic ICA occlusion with hemodynamic compromise or recurrent symptoms were treated at the subacute to chronic stage using an endovascular technique. The Parodi embolic protection system was used during the recanalization procedure to prevent embolic stroke by reversing the flow from the distal ICA to the common carotid artery. RESULTS: Recanalization of the occluded ICA was possible in 14 of 15 lesions. The occlusion points were 10 cervical ICAs and 4 petrous/cavernous ICAs in successfully recanalized cases. Ischemic symptoms disappeared completely after the treatment, and new ischemic symptoms did not appear related to the treated lesion. Single photon emission computed tomography findings demonstrated the improvement of hemodynamic compromise in all cases. One case showed right middle cerebral artery branch occlusion during the procedure, but this patient's neurological symptoms were stable due to preexisting hemiparesis. Endovascular recanalization was possible and effective in improving hemodynamic compromise. However, there are still several problems with this technique, such as hyperperfusion syndrome after recanalization, cerebral embolism during treatment, durability after treatment, and identification of the occlusion point before treatment. CONCLUSIONS: Endovascular recanalization using an embolic protection device can be considered as an alternative treatment for symptomatic ICA occlusion with hemodynamic compromise or refractoriness to antiplatelet therapy, even in the subacute to chronic stage of the illness.

Percutaneous vertebroplasty using hydroxyapatite blocks for the treatment of vertebral body fracture.

Vertebroplasty with hydroxyapatite blocks through a modified percutaneous approach was used to treat 30 patients with vertebral body fractures in 32 vertebral bodies between February 2003 and March 2007. The mean follow-up period was 16.6 months. The pain associated with this procedure, effects on adjacent vertebral bodies, and other complications were evaluated. The rate of recollapse after vertebroplasty was examined in 26 patients with 26 vertebral bodies treated and followed up for more than 3 months. Mean time of operation was 57 minutes and mean number of blocks used per vertebral body was 104. The mean visual analogue scale score was 7.0 preoperatively and 1.6 postoperatively. The mean decline in postoperative vertebral body height was 13%. New vertebral body fractures occurred postoperatively in 3 vertebral bodies in 2 patients. Leakage of blocks outside the vertebral body occurred in 2 patients during the operation, and after the operation in one patient, and the hydroxyapatite plug broke postoperatively in one patient. Hydroxyapatite blocks yielded good pain relief comparable to bone cement, with no serious complications such as a pulmonary embolism or leakage into the spinal canal, and are effective for percutaneous vertebroplasty.

Nondominant parietotemporal cortical dysplasia manifesting as hypermotor seizures.

We describe the case of a 33-year-old man with nondominant right parietotemporal cortical dysplasia. Habitual seizures were violent, ballistic movements of the extremities with pelvic thrusting, resembling complex gestural automatisms or "hypermotor seizures." Scalp electroencephalography (EEG) and interictal [(123)I]iomazenil single-photon-emission computed tomography revealed an epileptogenic zone including a lesion observed on magnetic resonance imaging. Corticectomy of the inferior parietal lobule was performed via invasive EEG monitoring, but resulted in failed seizure control. The middle and posterior temporal cortices were additionally resected in the second surgery. The patient experienced contralateral hemianopsia postoperatively, but no hemispatial neglect. Hypermotor seizures have not been seen for 1.5years since surgery. This is the first description of a patient with a parietal lobe lesion experiencing hypermotor seizures. The middle and posterior temporal cortices were considered epileptogenic together with the inferior parietal lobule in the present case.

Timing of craniotomy in a patient with multiple trauma including head injury.

A 7-year-old boy suffered blunt multiple injuries to the head, face, chest, and abdomen in a motor vehicle accident. On admission he had impaired consciousness and dyspnea. Radiographic studies revealed facial fracture and pulmonary contusion. Shortly after admission, he fell into shock due to intraabdominal bleeding. Laparotomy revealed spleen rupture. His vital signs remained unstable and bloody drainage from the abdominal cavity continued after surgery. Computed tomography showed traumatic intracerebral hematoma in the right temporal lobe, enlarging and compressing the brainstem. Abdominal reoperation was performed first to control the bleeding and stabilize the hemodynamics, disclosing renal laceration. Then evacuation of the intracerebral hematoma and decompressive craniectomy was performed. Postoperatively, his hemodynamics were stabilized. Clinical course was uneventful and neurological deficits gradually improved. Three months after the trauma, the patient was discharged on foot. This case emphasizes the importance of hemodynamic stability in decisions of neurosurgical indication and timing in patients with multiple trauma including head injury.

Antitumor activity of cetuximab against malignant glioma cells overexpressing EGFR deletion mutant variant III.

Anti-epidermal growth factor receptor (EGFR) monoclonal antibody, cetuximab, is a promising targeted drug for EGFR-expressing tumors. Glioblastomas frequently overexpress EGFR including not only the wild type but also a deletion mutant form called 'variant III (vIII)', which lacks exon 2-7, does not bind to ligands, and is constitutively activated. In this study, we investigated the antitumor activity of cetuximab against malignant glioma cells overexpressing EGFRvIII. For this purpose, we transfected human malignant glioma cell lines with the retroviral vector containing cDNA for EGFRvIII, and analyzed the mode of cetuximab-induced action on the EGFRvIII in the cells. Immunoprecipitation and immunofluorescence revealed binding of cetuximab to EGFRvIII. Notably, immunoblotting analyses showed that cetuximab treatment resulted in reduced expression levels of the EGFRvIII. However, cetuximab alone did not exhibit a growth-inhibitory effect against the EGFRvIII-expressing cells. On the other hand, an assay for antibody-dependent cell-mediated cytotoxicity (ADCC) demonstrated cetuximab-induced cytolysis in the presence of human peripheral blood mononuclear cells in a dose-dependent manner. These results suggest that deletion mutant EGFRvIII can be a target of cetuximab and that ADCC activity substantially contributes to the antitumor efficacy of cetuximab against the EGFRvIII-expressing glioma cells. Thus, cetuximab could be a promising therapy in malignant gliomas that express EGFRvIII.

Late-onset tumefactive multiple sclerosis.

A patient with tumefactive multiple sclerosis (MS) initially presented at the age of 87 years; the revised diagnostic criteria from the International Panel on MS (2001) were fulfilled. Late-onset MS and tumefactive demyelinating lesions are discussed. This case suggests that MS can occur at any age. MS should be borne in mind for differential diagnosis if a brain tumor-like lesion with little mass effect and edema is found in an elderly patient.