Naoyuki Uchiyama

Prediction of high-grade meningioma by preoperative MRI assessment

High-grade (World Health Organization grades II and III) meningiomas grow aggressively and recur frequently, resulting in a poor prognosis. Assessment of tumor malignancy before treatment initiation is important. We attempted to determine predictive factors for high-grade meningioma on magnetic resonance (MR) imaging before surgery. We reviewed 65 meningiomas (39 cases, benign; 26 cases, high-grade) and assessed four factors: (1) tumor–brain interface (TBI) on T1-weighted imaging (T1WI), (2) capsular enhancement (CapE), i.e., the layer of the tumor–brain interface on gadolinium-enhanced T1WI (T1Gd), (3) heterogeneity on T1Gd, and (4) tumoral margin on T1Gd. All four factors were useful in distinguishing high-grade from benign meningiomas, according to univariate analysis. On multivariate regression analysis, unclear TBI and heterogeneous enhancement were independent predictive factors for high-grade meningioma. In meningiomas with an unclear TBI and heterogeneous enhancement, the probability of high-grade meningioma was 98%. Our data suggest that this combination of factors obtained from conventional sequences on MR imaging may be useful to predict high-grade meningioma.

Sphingosine-1-phosphate receptor type 1 regulates glioma cell proliferation and correlates with patient survival

Sphingosine‐1‐phosphate (S1P) is a bioactive lipid that signals through a family of G protein‐coupled receptors consisting of 5 members termed S1P1–5, and it regulates cellular proliferation, migration and survival. We investigated the expression and role of S1P receptors in glioma. Human glioma expressed S1P1, S1P2, S1P3, and S1P5 by quantitative real‐time PCR analysis. Expression of the S1P1 was significantly lower in glioblastoma than in the normal brain (p < 0.01) and diffuse astrocytoma (p < 0.05). Immunoblotting showed that normal brain expressed more S1P1 protein than did glioblastoma. Immunohistochemistry showed that S1P1 was localized predominantly in the astrocytes in the normal brain, but no staining was observed in glioblastoma. Downregulation of S1P1 expression correlated with poor survival of patients with glioblastoma (p < 0.05). S1P1 small interfering RNA promoted cell proliferation in high‐expressor glioma cell lines (T98G, G112). Cell proliferation was promoted by the pertussis toxin, which deactivates Gi/o type of G proteins; the S1P1 is exclusively coupled to these proteins. Forced expression of the S1P1 in low‐expressor cell lines (U87, U251) resulted in decreased cell growth and led to suppressed tumor growth in transplanted gliomas in vivo. Furthermore, we found a significant association between the S1P1 expression and early growth response‐1, a transcriptional factor that exhibits tumor suppression in glioblastoma cells (p < 0.05). These data indicate that the downregulation of S1P1 expression enhances the malignancy of glioblastoma by increasing cell proliferation and correlates with the shorter survival of patients with glioblastoma.

A reevaluation of the primary diagnosis of hemangiopericytoma and the clinical importance of differential diagnosis from solitary fibrous tumor of the central nervous system.

OBJECTIVES Hemangiopericytomas (HPCs) are rare neoplasms with relatively high rates of recurrence and extracranial metastasis. Though the differential diagnoses from angiomatous meningiomas and from solitary fibrous tumors (SFTs) are both important, the latter diagnosis is somewhat more important in light of the benign prognosis of SFTs and the difficulties in distinguishing SFTs from HPCs. Newly developed immunohistochemical methods reveal differences in the specific immunohistochemical features of HPCs and SFTs. To elucidate whether SFTs have been misdiagnosed as HPCs in the past, our group used recent immunohistochemical methods to re-evaluate tissues that had been originally diagnosed as HPCs. We also compared the clinical features of these cases. PATIENTS AND METHODS Thirteen sequential cases of HPC diagnosed in Kanazawa University Hospital and Kumamoto University Hospital between 1970 and 2006 were retrospectively analyzed by immunohistochemical staining for CD34, Bcl-2, epithelial membrane antigen (EMA), vimentin, and S100 protein, and by measurement of the MIB-1 labeling index (LI). The cases were then re-evaluated and newly diagnosed based on the results of the immunohistochemical stainings. The clinical course of each case was also evaluated. RESULTS Four of the 13 cases were newly diagnosed as SFTs and eight were reconfirmed as HPCs, based on the immunohistochemical studies for CD34, Bcl-2, and reticulin staining. One case was newly diagnosed as meningioma on the basis of a strong EMA positivity. The MIB-1 LI was less than 1% in 12 of the cases. In two cases, one case of HPC and the other of meningioma, the MIB-1 LI was relatively high, 8% and 4% respectively. All eight of the HPCs recurred, and 5 of the HPC patients died of the disease. Only one case of the SFTs recurred. CONCLUSION Our study suggests that a relatively high percentage of the tumors diagnosed as HPCs in the past may have in fact been intracranial SFTs. Immunohistochemical examinations of CD34, Bcl-2, and reticulin stains are keys for the differential diagnosis. Given that SFTs have a considerably better prognosis than HPCs, it is important to carry out meticulous immunohistochemical examinations for the primary diagnosis.

Significance of Volume Embolization Ratio as a Predictor of Recanalization on Endovascular Treatment of Cerebral Aneurysms with Guglielmi Detachable Coils

The purposes of this study are, firstly, to define the relationship between volume embolization ratio (VER) and degree of angiographical occlusion in endovascular treatment with Guglielmi detachable coils, and secondly, to examine influences of neck and dome sizes of aneurysms on the VER and the angiographical treatment result, and thirdly, to determine the relationship between the VER and the recanalization of coiled aneurysms. Fifty-two aneurysms in 46 patients were examined. VER ranged 8.1–31.9% (mean 18.5%). The mean VERs of each categories based on angiographical treatment results were 23.1% in complete occlusion, 16.1% in neck remnant and 12.2% in incomplete occlusion, respectively. The VER correlated significantly with both neck and dome size, while the angiographical treatment result was only affected by neck size. Five aneurysms showed aneurysmal recanalization among followed-up 41 aneurysms. All recanalized aneurysms were large, and their VERs were in range of 10.4–17.6%. Measurement of VER is useful to estimate the degree of occlusion objectively and to predict the aneurysmal recanalization. A small aneurysms with a small neck is relatively easy to achieve high VER and angiographical complete occlusion, with the consequence of less recanalization. On the other hand, a large aneurysm is liable to recanalize due to low VER, even if there was little filling of contrast medium in the aneurysmal cavity.

Localization of E-cadherin in peripheral glia after nerve injury and repair

Peripheral nerve injury results in histological and histochemical changes in neurons and glia. We have recently found that Ca2+-dependent cell adhesion molecule E-cadherin plays an important role in the selective fasciculation of a particular subset of unmyelinated sensory fibers. In the present immunohistochemical and immunoblot analyses, the temporal profile of the subcellular expression of this molecule in spinal nerves was examined after crushing, transecting, or ligaturing the sciatic nerve in mice with special attention paid to E-cadherin expression in glial cells. After axotomy of the sciatic nerve, distal axons of the proximal stump and the fibers of the distal stump degenerated, but E-cadherin was still detectable at the outer mesaxons of the myelinated axons as long as they remained morphologically intact. Subsequently, Schwann cells proliferated and migrated to form Schwann cell columns (Büngners bands) as initial responses to denervation, and expressed E-cadherin at their site of contact with each other and later with sprouting axons. At the initial stage of myelin formation, slender processes of a single Schwann cell interdigitated with and enveloped axons, and expressed E-cadherin at the contact site elaborated by a single Schwann cell. Immunoblot analysis on day 7 revealed that E-cadherin was detected in both the proximal nerve segments and the regenerative distal segments, but was negative in the degenerative distal segments. On the basis of present data, it is suggested that E-cadherin might be involved in the stabilization of the peripheral glial network which provides the guidance of sprouting axons and myelination

Paramedian supracerebellar transtentorial approach for a medial tentorial meningioma with supratentorial extension: technical case report.

OBJECTIVE AND IMPORTANCE The choice of surgical approach to treat medial tentorial meningiomas is crucial and sometimes difficult to make. Although the subtemporal approach is most commonly used for lesions that extend mostly supratentorially, it risks injury to the vein of Labbé or the veins coursing along the subtemporal surface. To avoid venous injury, a medial tentorial meningioma was removed transtentorially through the infratentorial space via the paramedian supracerebellar transtentorial (PSCTT) approach. CLINICAL PRESENTATION A 35-year-old right-handed woman presented with a generalized convulsion. Magnetic resonance imaging scans revealed a left medial tentorial meningioma with supratentorial extension at the dominant hemisphere. The main venous drainage route from the ipsilateral temporal lobe was a sphenopetrosal vein. INTERVENTION An operation was performed with the patient in a sitting position, and the tumor was resected totally via the paramedian supracerebellar transtentorial approach without perioperative complications. CONCLUSION The paramedian supracerebellar transtentorial approach is useful for supratentorially located medial tentorial meningiomas without retraction of the temporal lobe and without damage to the vein of Labbé or the sphenopetrosal vein.

Improved cerebral perfusion and metabolism after stenting for basilar artery stenosis: technical case report.

OBJECTIVERecent advances in stent technology have allowed the introduction of more flexible stents that may be tracked more easily in the intracranial vessels. We present a patient with improved cerebral blood flow and metabolism as assessed by positron emission tomography after stent-assisted angioplasty for symptomatic basilar artery stenosis. CLINICAL PRESENTATION A 62-year-old man, who had undergone left superficial temporal artery to middle cerebral artery bypass surgery for left internal carotid artery occlusion 10 years previously, presented with dizziness, blurred vision, and memory disturbance. Angiography revealed severe stenosis of the proximal basilar artery. Positron emission tomographic scans revealed decreased cerebral blood flow associated with increased oxygen extraction fraction in the entire brain, particularly in the posterior circulation and the left middle cerebral artery territory. Despite medical treatment, the patient experienced worsening visual disturbance and right-sided motor weakness. INTERVENTIONTiclopidine and aspirin were used as antiplatelet agents. In addition, we used argatroban, which is a direct thrombin inhibitor, as an anticoagulant during the procedure. Predilation with a coronary artery balloon was performed, followed by placement of a GFX 3- by 8-mm stent (Arterial Vascular Engineering, Santa Rosa, CA), with excellent angiographic results. The patient made a good neurological recovery, and the postoperative positron emission tomographic scan demonstrated increases in both cerebral blood flow and cerebral metabolic rate of oxygen with a normalization of oxygen extraction fraction. CONCLUSIONStent-assisted angioplasty can provide a favorable clinical course as well as improved cerebral perfusion and metabolism for a patient with basilar artery stenosis. Long-term follow-up data and additional clinical experience are required to assess the durability of this approach.

Immunoelectron microscopic localization of E-cadherin in dorsal root ganglia, dorsal root and dorsal horn of postnatal mice.

SummarySensory neurons and associated glial cells are known to express the cell-cell adhesion molecule E-cadherin. The cellular and subcellular localization of this molecule in the dorsal root ganglion, dorsal root, and spinal cord of postnatal mice was studied by the pre-embedding immunoelectron microscopic labelling technique. In the dorsal root and the superficial layer of the dorsal horn, a subset of fasciculating unmyelinated axons expressed E-cadherin at their axon-axon contacts at all ages studied, and these axons were clustered together and segregated from E-cadherin-negative axons. In contrast, pre-myelinating large-diameter axons in P2 mice as well as myelinated axons in mice from P14 to adulthood were E-cadherin-negative. Glial cells also expressed E-cadherin: In the dorsal root ganglia, all of the satellite cells expressed E-cadherin at contact sites with neurons, other satellite cells, and basal lamina, at all ages studied. In dorsal roots from P14 to adulthood, myelin-forming Schwann cells expressed E-cadherin at the outer mesaxons and the contact sites with basal lamina. Non-myelin-forming Schwann cells occasionally stained for this molecule at contact sites with the plasma membrane of E-cadherin-positive axons and at other sites. These results strongly suggest that E-cadherin plays an important role in the selective fasciculation of a particular subset of unmyelinated sensory fibres, and also in glial cell contacts.

Retro-odontoid pseudotumor without atlantoaxial subluxation

A retro-odontoid pseudotumor (ROP) is commonly associated with atlantoaxial subluxation (AAS). Here, we report a patient with ROP but without AAS. The patient was a 72-year-old man who did not have a history of rheumatoid arthritis or trauma to the head and neck. The patient was admitted to our hospital with gait disturbance, progressive motor weakness in both upper extremities and sensory disturbance in all four extremities. MRI showed a retro-odontoid mass with severe compression of the cervical spinal cord. A CT scan showed spondylotic changes in C5, C6, and C7 and bilateral facet fusion between C3 and C4. Dynamic radiography showed no evidence of AAS; there was loss of mobility at C2-C7 and excessive mobility at C1. Intraoperative pathological examination revealed that the lesion was a pseudotumor; therefore, posterior C1-C2 fixation was performed. MRI performed 6 months after the operation revealed that the pseudotumor was markedly reduced. To the best of our knowledge, patients with ROP without AAS are uncommon.

Alteration of E-cadherin and Alpha N-catenin Immunoreactivity in the Mouse Spinal Cord following Peripheral Axotomy

We examined the effects of peripheral axotomy on the immunoreactivity of E-cadherin and cadherin-associated protein alpha N-catenin in the spinal cord. E-cadherin is known to be exclusively expressed in lamina II of Rexed in the spinal cord dorsal horn. This expression disappeared by day 7 after axotomy and reappeared following nerve ligature (partial axonal regeneration model) on day 63. In contrast, it remained undetectable following nerve clipping (complete degeneration model). Alpha N-catenin was diffusely stained in the gray matter, and the immunoreactivity was specifically intense in the central canal and superficial dorsal horn. The expression of alpha N-catenin in the superficial dorsal horn was similarly reduced by day 7 after axotomy, but recovered by day 63 after nerve ligature. In contrast, it remained at the reduced level after nerve clipping. The alteration of alpha N-catenin immunoreactivity showed a similar pattern consistent with that of E-cadherin. Administration of nerve growth factor (NGF) rescued the immunoreactivity of substance P, which is known to disappear after peripheral axotomy, but not influence that of both E-cadherin or alpha N-catenin. These results clearly showed that peripheral axotomy simultaneously alters the immunoreactivity of E-cadherin and alpha N-catenin in the spinal cord, suggesting a correlation in the expression of both E-cadherin and alpha N-catenin in vivo. E-cadherin-alpha N-catenin complex might be crucial for plasticity of the spinal cord dorsal horn after peripheral axotomy.