Intracerebral microinjection of interleukin-4/interleukin-13 reduces ß-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice.

We previously reported that the anti-inflammatory cytokine interleukin (IL)-4 induced selective clearance of oligomeric ß-amyloid (Aß(1-42)) in rat primary type 2 microglial cells. For the present study, we investigated whether IL-4 and IL-13 could activate microglial cells to induce Aß clearance in vivo and improve cognitive deficits in APP23 mice, which are amyloid precursor protein transgenic mice. We administered an intracerebral microinjection of a mixture of IL-4 and IL-13 or of saline vehicle into one hemisphere of APP23 mice and their wild-type littermates, 4.5 and 9 months old, after which we evaluated the effects of these treatments on spatial learning and memory by Morris Water Maze test and on accumulated amounts of Aß. The cytokine injection significantly improved memory deficits of 4.5-month-old APP23 mice, but did not do so in 9-month-old APP23 mice, even though similar Aß reductions were observed in both age groups of APP23 mice in the ipsilateral neocortex. The cytokine injection improved memory impairment of 9-month-old wild-type (WT) mice in the probe trial. Immunohistochemical analysis of the 4.5-month-old APP23 mice revealed the presence of increased numbers of microglial cells at 2 days after the cytokine injection. In addition to induced CD36 expression in the activated microglia, increased expression of neprilysin, mainly in neurons, suggested that the cytokines improved the cognitive deficits via degradation and clearance of intra- and extraneuronal Aß peptides, of buffer-extractable nonplaque form. Double immunostaining also revealed that most of the activated microglia had the M2-like phenotype. This unique mechanism of IL-4/IL-13-induced clearance of Aß may provide an additional strategy to prevent and/or cure Alzheimer's disease at early stage.

Retrieving microcatheters from Onyx casts in a series of brain arteriovenous malformations: a technical report.

INTRODUCTION: To date, the "monorail snare technique" for the retrieval of entombed microcatheter tips during Onyx(TM) (ev3, Irvine, CA) embolisation of brain arteriovenous malformations (BAVM) has not been described. We report our experiences and some technical aspects in using this technique for the retrieval of entombed Marathon(TM) microcatheter (ev3, Plymouth, MN) tips during Onyx embolisation of BAVM treatment. METHODS: Onyx was used in the embolisation of 11 patients using 25 feeders over 14 sessions. The 'monorail snare technique' was employed for 14 feeders. Each time, an Amplatz 4 mm Gooseneck Microsnare(TM) (ev3, Plymouth, MN) was loaded into an Excelsior 1018(TM) microcatheter (Boston Scientific, Natick, MA). The Marathon microcatheter was cut just distal to the hub, and the Amplatz/Excelsior combination was introduced along the length of the Marathon microcatheter towards its distal end, as far as possible. The embedded catheter was ensnared and both catheters were pulled free. RESULTS: Microcatheter tip removal was successful in all cases, except for one microcatheter tip becoming detached and needing no further intervention. There were no complications as a direct result of the snare technique. CONCLUSIONS: The monorail snare technique is a safe and easy technique for retrieving Onyx-encased microcatheter tips in the treatment of BAVM.

Phase II trial of radiotherapy after hyperbaric oxygenation with chemotherapy for high-grade gliomas.

We conducted a phase II trial to evaluate the efficacy and toxicity of radiotherapy immediately after hyperbaric oxygenation (HBO) with chemotherapy in adults with high-grade gliomas. Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO with the period of time from completion of decompression to irradiation being less than 15 min. Chemotherapy consisted of procarbazine, nimustine (ACNU) and vincristine and was administered during and after radiotherapy. A total of 41 patients (31 patients with glioblastoma and 10 patients with grade 3 gliomas) were enrolled. All 41 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. Of 30 assessable patients, 17 (57%) had an objective response including four CR and 13 PR. The median time to progression and the median survival time in glioblastoma patients were 12.3 months and 17.3 months, respectively. On univariate analysis, histologic grade (P=0.0001) and Karnofsky performance status (P=0.036) had a significant impact on survival, and on multivariate analysis, histologic grade alone was a significant prognostic factor for survival (P=0.001). Although grade 4 leukopenia and grade 4 thrombocytopenia occurred in 10 and 7% of all patients, respectively, these were transient with no patients developing neutropenic fever or intracranial haemorrhage. No serious nonhaematological or late toxicities were seen. These results indicated that radiotherapy delivered immediately after HBO with chemotherapy was safe with virtually no late toxicity in patients with high-grade gliomas. Further studies are required to strictly evaluate the effectiveness of radiotherapy after HBO for these tumours.

Thromboembolic Events Associated with Coil Protrusion into Parent Arteries after GDC Treatment.

SUMMARY: Aneurysm embolization using Guglielmi detachable coils(GDC) is gaining acceptance as a viable alternative to surgery in the treatment of cerebral aneurysms. During GDC treatment of cerebral aneurysms, thromboembolic events are the most frequent complications. As risk factors of thromboembolic events, large aneurysms, wide-necked aneurysms, use of the balloon-assisted technique and protruding coils into the parent arteries are previously reported. From March, 1997 till August, 2004, 270 consecutive patients were treated with GDC embolization at our institute. Fourteen (5.2%) patients with 14 aneurysms of these 270 patients presented with protruding coils into the parent vessels. Twelve aneurysms of these 14 aneurysms were small (diameter < 10 mm), and two were large (diameter 15 mm). Nine aneurysms had small necks (neck diameter < 4 mm), and five had wide necks(neck diameter > 4 mm). The fundus-toneck ratio ranged from 1.04 to 2.78, with an average of 1.53. In this series, ten patients (71%) were treated with balloon-remodelling technique because every patient had either a wide-necked aneurysm or complicated morphologic factors. These 14 aneurysms were divided into two groups according to the mode of coil protrusion, loop type and tail type protrusion. The first coil was protruded in five (36%) cases of 14 patients, four of these five cases presented with the loop type protrusion. The last coil was protruded in seven cases (50%), Five of these seven cases presented with the tail type protrusion. Diffusion-weighted imaging abnormalities were found for seven (50%) of 14 patients within 24 hours of the coiling procedures. Three (21%) of 14 patients showed small lesions (< 5 mm) in the subcortical white matter at the border zone or perforating regions. In four (29%) patients, large territorial infarctions (> 5 mm) were detected. Symptomatic complications occurred in four (29%) patients, and all of these four patients presented the loop type protrusion. One patient who had small infarctions experienced minimal deficits (slight motor weakness, quadrantic hemianopsia) after six days postprocedure and fully recovered by discharge after stronger systemic heparinization (24000U, for three days), aspirin (100 mg/day) and Ticlopidine (100 mg/day). Three patients who had large territorial infarctions experienced moderate deficits. Two patients were treated with stronger systemic heparinization and one with Argatroban (60 mg/day, for two days), and following aspirin (100 mg/day) and Ticlopidine (100 mg/day). Finally, two patiens were discharged with permanent minimal deficits (hypoesthesia only) and one with moderate hemiparesis. The infarctions related to the GDC procedures were more common sequelae in wide-necked aneurysms and coil protrusions, especially loop type protrusion. Although permanent neurological deficits were rare, the high rate of thromboembolic events associated with coil protrusion suggest that more aggressive medical treatment should be considered.

Percutaneous transluminal angioplasty for atherosclerotic stenoses of intracranial vessels.

SUMMARY: To study the efficacy and long-term outcome of percutaneous transluminal angioplasty (PTA) with/without stent placement for intracranial atherosclerotic stenoses, we reviewed our treated cases retrospectively. Between May 1992 and October 2003, PTA with/without stents was performed in 64 intracranial and skull base vessels in 62 patients, including 24 middle cerebral arteries, 16 internal carotid arteries, 13 vertebral arteries, and 11 basilar arteries. PTA was technically successful in 55 vessels (86%). However, four vessels (6%) failed to achieve satisfactory dilatation. We encountered five periprocedural strokes as symptomatic complications, for a mortality rate of 4.7% and a morbidity rate of 3.1%. All the patients with stent placements survived angioplasty without any complication. In the clinical follow-up available for one week to 11.5 years (mean, 4.7 years), there were three strokes related to the treated vessels. The annual stroke rate in the affected territory was estimated at 1.2% per year. According to these results, PTA for intracranial atherosclerotic stenoses seems to be a beneficial therapy for immediate anatomical results and long-term stroke prevention. Stent-assisted PTA could help patients achieve successful dilatation and avoid complications.

Stenting for atherosclerotic stenosis of the intracranial or skull base cerebral arteries. Effectiveness and problems.

SUMMARY: Since May 1992, we have performed percutaneous transluminal angioplasty (PTA) or stenting 70 times for 65 lesions in 62 patients with atherosclerotic stenosis of the intracranial or skull base cerebral arteries. Stenting was carried out nine times for nine lesions in nine cases. Stenting was performed on patients with an average age of 62. The patients were eight men and one woman. The stenotic lesions involved the internal carotid artery (petrous portion) in four cases, the internal carotid artery (cavernous portion) in two cases, the internal carotid artery (supraclinoid portion) in one case, the middle cerebral artery (M1) in one case, and the vertebral artery (V4) in one case. The degree of stenosis ranged from 70% to 99%, with a mean of 80%. A stent for coronary arteries was used in all cases. After PTA was carried out in four cases, their initial extension was inadequate, and dissection was performed in five cases after PTA. As for the results of the treatment, subarachnoid haemorrhage occurred in one case due to perforation by the guidewire, and a major deficit was accepted. During the operation, asymptomatic cerebral infarction by distal embolism occurred in one case. Although obstruction of the lesion occurred three months after treatment in one case, symptoms did not appear. Stents used for atherosclerotic stenosis of the intracranial or skull base cerebral arteries still do not have sufficient performance. Although the stenting had problems, such as a prolonged patent, in the present condition, it was effective in terms of recovery from complications due to PTA.

Education and propagation of intravascular surgery in okinawa.

SUMMARY: Okinawa is an island located on the southwest edge of the Japanese Islands in which about 1,300,000 people live, and is an area where selfconclusion type medical treatment is desired. In this area, intravascular surgery was only performed for several cases per year until 1998. From May 1999, intravascular surgery started being performed in earnest, and 140 or more cases of intravascular surgery per year were performed in 2002. In the meantime, various measures for the propagation and development of intravascular surgery that we undertook led to the increase in the number of cases. As a result, the choice of medical treatment has increased by propagating these medical treatments, and it seems that this has contributed to the welfare of the people of Okinawa.

Longitudinal study of functional spinal alpha motor neuron loss in amyotrophic lateral sclerosis.

Using a microstimulation technique for obtaining motor unit number estimates (MUNEs) of the hypothenar and extensor digitorum brevis (EDB) muscles, we performed a longitudinal study on the natural course of change in the clinical rating scale (Appel score) and of loss of functional spinal alpha motor neurons in amyotrophic lateral sclerosis. The Appel score increased to about 150% of normal at 12 months after onset, about 225% at 18 months after onset, and about 370% at 24 months after onset. By contrast, MUNEs decreased to about 27% of normal at 12 months after onset, about 12% at 18 months after onset, and about 5% at 24 months after onset. The relative merits of these different approaches in detecting changes in the disease process in its early phase are discussed.

Venous malformation serving as the draining vein of an adjoining arteriovenous malformation. Case report and review of the literature.

BACKGROUND: Widely accepted pathologic classification of venous malformations includes discrete venous, arteriovenous, capillary, and cavernous malformations, each with distinct pathological criteria for definition. Several authors have described mixed or transitional vascular malformations with pathological features of more than one type of malformation within the same lesion. We present a rare case of a venous malformation associated with an arteriovenous malformation (AVM). CASE DESCRIPTION: A 37-year-old woman presented with a loss of consciousness. Computed tomography showed an enlarged vein running along the lateral wall of the right lateral ventricle. A cerebral angiogram demonstrated an AVM and a venous malformation in the right hemisphere; the AVM and the venous malformation were located in proximity to each other with the AVM using the venous malformation as its draining vein. In this case, where an AVM used the venous malformation as the draining vein, only the AVM was treated by proton-beam radiosurgery. Follow-up magnetic resonance angiography demonstrated complete obliteration of the AVM with the venous malformation remaining unchanged. CONCLUSION: Arteriovenous shunting would have disturbed venous drainage resulting in the development of the venous malformation. Thus, in addition to demonstrating a rare coexistence of AVM and venous malformation, this case also offers a new insight into the pathogenesis of these vascular malformations.

Suppression of head formation by Xmsx-1 through the inhibition of intracellular nodal signaling.

It is well established that in Xenopus, bone morphogenetic protein (BMP) ventralizes the early embryo through the activation of several target genes encoding homeobox proteins, some of which are known to be necessary and sufficient for ventralization. Here, we used an inhibitory form of Xmsx-1, one of BMP's targets, to examine its role in head formation. Interestingly, ventral overexpression of a dominant Xmsx-1 inhibitor induced an ectopic head with eyes and a cement gland in the ventral side of the embryo, suggesting that Xmsx-1 is normally required to suppress head formation in the ventral side. Supporting this observation, we also found that wild-type Xmsx-1 suppresses head formation through the inhibition of nodal signaling, which is known to induce head organizer genes such as cerberus, Xhex and Xdkk-1. We propose that negative regulation of the BMP/Xmsx-1 signal is involved not only in neural induction but also in head induction and formation. We further suggest that the inhibition of nodal signaling by Xmsx-1 may occur intracellularly, through interaction with Smads, at the level of the transcriptional complex, which activates the activin responsive element.

[Schwannoma of the cervical spinal cord with cervical angina: a case report].

A case of schwannoma of the cervical spinal cord presenting with cervical angina is reported. A 49-year-old man was admitted to our hospital with severe chest pain, cold sweats, and unconsciousness. Extensive cardiac examination showed no abnormal findings. Neurological deficits were muscular weakness and atrophy of the left arm, bilateral hypersthesia of the arms, and hyporeflexia of the left biceps. MRI revealed a tumor in the left side of the spinal canal between C4 and C5. The diagnosis was neurinoma of the left nerve root in C5. The tumor was completely removed surgically by laminectomy. Surgery confirmed that the tumor had originated from the left posterior root of C5 and that, histologically, it was schwannoma. The severe chest pain immediately disappeared after removal of the tumor with only dull post-operative chest pain remaining. We hypothesized that the severe chest pain was protopathic pain caused by compression of the anterior C5 root by the tumor and/or disturbance of the inhibitory pain mechanisms of the sympathetic nerve located in the posterior horn of the spinal cord. It must be kept in mind that cervical angina caused by spinal schwannoma is one of the differential diagnoses of chest pain.

Expression of enzymes and oncogene induced after radiotherapy and/or chemotherapy in patients with brain tumors.

The relationship between the degree of the expression of Cu/Zn SOD, GST-pi and bcl-2 in the initial and recurrent tumor tissue after radiotherapy and/or chemotherapy and the cellular heterogeneity obtained from DNA content by image cytometry was investigated. Subjects were 7 patients who had glial tumors which were surgically removed at onset and removed a second time at recurrence. Radiotherapy and chemotherapy were also administered after initial resection. Immunoreactivity for copper/zinc super oxide dismutase (Cu/Zn SOD), GST (glutathione-S-transferase)-pi, and bcl-2 were evaluated from routinely prepared tissue blocks. Tumors were classified into two groups by cytometric analysis of DNA ploidy in the G2M cell cycle phase. One tumor group consisted of single clonal cells in both the initial and recurrent tumors and the other group consisted of tumors with polyclonal cells in the initial and recurrent tumor. In this study, one patient (case 3) with single clonal cell glioblastoma at recurrence did not show high Cu/Zn SOD activity after radiotherapy and chemotherapy but showed a short survival time after recurrence. In three patients (cases 1, 2, 3) with single clonal-cell glioblastoma, the recurrent tumor cells showed high GST-pi immunoreactivity and survival time was short after recurrence. Tumor cells in two patients (cases 5, 7) with single clonal cell anaplastic glioma at recurrence, showed high GST-pi immunoreactivity and had a short survival time after recurrence. In three single clonal glioblastomas (cases 1, 2, 3), the recurrent tumor showed the increased bcl-2 immunoreactivity and showed a short survival time after recurrence. In two patients (case 5, 7) with single clonal cell anaplastic glioma at recurrence, tumor cells showed a high bcl-2 immunoreactivity and these patients showed a short survival time after recurrence. Although the number of subjects is very small, our study shows that the immunoreactivity of bcl-2 and GST-pi in malignant gliomas may be very important factors in radio- and chemosensitivity, and shows that GST-pi is induced by radiation and anti-cancer drugs.

Anaplastic meningioma with papillary, rhabdoid, and epithelial features: a case report.

A 74-year-old man manifested disturbed consciousness and right hemiparesis. Computed tomography revealed a left frontal parasagittal meningeal tumor with extensive peritumoral brain edema and skull invasion. Subtotal removal was performed. Five years later, he underwent two more operations of massive recurrences. Pathological studies revealed anaplastic meningioma with two different histological areas. One was an epithelial and meningothelial area, and the other was a papillary and rhabdoid area. In the papillary and rhabdoid area, small tumor cells with a high nucleus/cytoplasm ratio proliferated densely around the dilated central capillaries with a pseudopapillary pattern. Many rhabdoid cells (vimentin ++, cytokeratin AE1/AE3 +, epithelial membrane antigen [EMA] + +) tended to be distributed far from the central capillaries. There were many mitotic figures near the central vessels. Dense MIB1-positive nuclei were also observed near the central vessels. The trabecular pattern of the tumor cells in the epithelial area was quite different from the histological features of chordoid meningioma.

Intramedullary clear cell ependymoma in the cervical spinal cord: case report.

OBJECTIVE AND IMPORTANCE: Clear cell ependymoma of the spinal cord has not been reported in the literature, although ependymoma in the cerebral and cerebellar hemispheres has been described. We present the first case report of this rare histological type of ependymoma arising in the cervical spinal cord and emphasize the importance of recognizing this histological entity. CLINICAL PRESENTATION: A 42-year-old woman presented with numbness in both upper limbs and spastic gait. Magnetic resonance imaging revealed an intramedullary tumor at the C6-T1 level with syringomyelia. INTERVENTION: The tumor was totally removed. Histological analysis revealed that the tumor was composed of round cells with perinuclear halos similar to those observed in oligodendroglioma. However, we diagnosed clear cell ependymoma because these tumor cells exhibited epithelial features and ependymal rosettes under light microscopic examination. CONCLUSION: Histological diagnosis was crucial to our determining whether to perform postoperative adjuvant therapy in this patient. Neurosurgeons should be aware of the possibility of this histological entity among intramedullary spinal cord tumors.

Infratentorial arteriovenous malformation associated with persistent primitive trigeminal artery--case report.

A 58-year-old male presented with a rare association of an infratentorial arteriovenous malformation (AVM) and ipsilateral persistent primitive trigeminal artery (PPTA) manifesting as sudden onset of headache and vomiting. Computed tomography revealed subarachnoid hemorrhage, and digital subtraction angiography demonstrated an infratentorial AVM mainly fed by the left superior cerebellar artery via the left PPTA. The patient refused radical treatment for the AVM, and was conservatively treated. The adjacent AVM may have been important in the preservation of the PPTA, as blood flow into the infratentorial AVM via the PPTA and the hemodynamic stress to the PPTA could have disturbed the spontaneous closure of the PPTA.

Brain metastasis of epithelioid sarcoma--case report.

A 20-year-old-female first presented with an epithelioid sarcoma of the right thumb, and the right thumb was amputated. Five years later, a metastasis was found in the right lower lung and a partial lobectomy was performed. Three years later, computed tomography showed a metastatic brain tumor in the left frontal lobe, which was removed surgically. Adjuvant radiotherapy and chemotherapy were given after all operations. Histological examination showed all resected tumors were epithelioid sarcoma. She has maintained a good activity of daily living level as an outpatient for 2 years, although subcutaneous metastases and bronchial lymph node metastases have been observed. Such intensive treatment of slowly growing tumors often prolongs survival time, even in patients with multiple metastases.

Distal superior cerebellar artery aneurysm in a patient with systemic lupus erythematosus: case report.

BACKGROUND: The authors describe a case of ruptured distal superior cerebellar artery (SCA) aneurysm in a patient with systemic lupus erythematosus (SLE). CASE DESCRIPTION: A 31-year-old female who had been treated for SLE for 13 years presented with a subarachnoid hemorrhage. Cerebral angiography demonstrated an aneurysm arising from the cisternal portion of the left superior cerebellar artery. The patient underwent early endovascular coil embolization and was discharged from our hospital without neurological deficit. CONCLUSION: Aneurysms arising from peripheral segments of cerebellar arteries are rare, and delayed surgical clipping has been recommended for these lesions. In addition, the outcomes of SLE patients with ruptured cerebral aneurysms are reported to be very poor due to the systemic complications of SLE. However, our patient had a favorable outcome with early endovascular treatment for the ruptured aneurysm and with appropriate medical treatment for the accompanying SLE. Therefore, early endovascular coil embolization is worthy of consideration among the options for therapeutic intervention in these conditions.

Symptomatic arachnoid cyst of the left frontal convexity presenting with memory disturbance--case report.

A 48-year-old female presented with vertiginous feeling and behavior disturbance. Computed tomography showed an arachnoid cyst on the left cerebral convexity. Single photon emission computed tomography revealed decreased cerebral blood flow (CBF) in the left frontal lobe. The Wechsler Memory Scale-Revised test demonstrated memory dysfunction. The arachnoid cyst was partially removed. Disturbances in CBF and behavior disappeared postoperatively. Local ischemia induced by compression due to arachnoid cyst may cause memory dysfunction and behavior disturbance. Neuropsychometric examination is useful for the evaluation of such symptoms.