Photodynamic Therapy of Malignant Gliomas.

Recently, the clinical applications of photodynamic therapy (PDT) in the management of malignant brain tumors have attracted significant attention. Meta-analysis of the observational studies on this treatment in high-grade gliomas (Eljamel, 2010) included more than 1,000 patients and reported median survival in cases of newly diagnosed and recurrent glioblastoma multiforme (GBM) of 16.1 and 10.3 months, respectively. In some series, increase in the long-term survival rates was also observed. Few controlled trials demonstrated statistically significant impact of PDT on prolongation of survival in patients with GBM in comparison to conventional management. The main treatment-related adverse event is short-lasting excessive photosensitivity of the skin and retina after photosensitizer administration, but its negative consequences can be easily avoided with appropriate protective measures. Overall, PDT may be considered to be a safe and effective adjuvant therapeutic option for patients with newly diagnosed and recurrent malignant gliomas. Aggressive tumor resection seems to be an important prerequisite to maximize treatment efficacy.

Rebamipide suppresses 5-fluorouracil-induced cell death via the activation of Akt/mTOR pathway and regulates the expression of Bcl-2 family proteins.

Oral mucositis is a common adverse effect of chemotherapy that limits the required dose of chemotherapeutic agents. Numerous attempts to mitigate chemotherapy-induced oral mucositis have failed to identify an appropriate treatment. Recently, it has been indicated that rebamipide prevents chemoradiotherapy-induced oral mucositis in patients. However, the details of the underlying mechanism involved in the cytoprotective effect of rebamipide remain obscure. In the present study, we investigated the mechanism behind rebamipide cytoprotective effect in the oral mucosa using primary normal human oral keratinocytes (NHOK cells). We found that rebamipide prevented 5-fluorouracil (5-FU)-induced cell death in NHOK cells. In addition, rebamipide increased the levels of phosphorylated Akt and mTOR, enhanced the Bcl-2 and Bcl-xL expressions, and suppressed the expression of Bax and Bim. This is in contrast to 5-FU-induced suppression of Akt and mTOR activation, Bcl-2 and Bcl-xL expressions, and the enhanced expression of Bax and Bim. These findings suggest that rebamipide can potentially be used for the protection of oral mucosa from chemotherapy-induced mucositis. This is the first study that elucidates the specific molecular pathway for the cytoprotective effect of rebamipide.

Sonographic Detection of Abnormal Plaque Motion of the Carotid Artery: Its Usefulness in Diagnosing High-Risk Lesions Ranging from Plaque Rupture to Ulcer Formation.

We investigated the feasibility of using sonography of abnormal plaque motion to diagnose high-risk carotid lesions ranging from plaque rupture to ulcer formation. Fifty consecutive carotid arteries of 49 patients (71 ± 7 y, 37 males) who underwent carotid endarterectomy were investigated by carotid sonography to find a plaque concavity (sonographic ulcer [SU]), fine trembling motion inside the plaque (FTMI) and systolic retractive motion of the plaque surface (SRMS). Plaque rupture or ulcer, necrotic core and intra-plaque hemorrhage were determined at carotid endarterectomy. Twenty-two SUs, 41 cases of FTMI and 20 cases of SRMS were detected by carotid sonography. The sensitivity and specificity of SU in diagnosing plaque rupture or ulcer at carotid endarterectomy were 48% and 90%, and those of FTMI were 93% and 60%. Plaques with SRMS more frequently had both a necrotic core and intra-plaque hemorrhage than those without SRMS (80% vs. 30%, p = 0.0005). Abnormal plaque motion detected by carotid sonography is useful in detecting a ruptured or ulcerated plaque with a necrotic core and/or hemorrhage.

Immunohistochemical evaluation of O6 -methylguanine DNA methyltransferase (MGMT) expression in 117 cases of glioblastoma.

Temozolomide (TMZ) is an oral alkylating agent which is widely used in the treatment of glioblastoma (GBM) and is composed of astrocytic and/or oligodendroglial tumors, and the evaluation of O(6) -methylguanine DNA methyltransferase (MGMT) expression is important to predict the response to TMZ therapy. In this study, we conducted immunohistochemical analysis of 117 cases of Japanese GBM including 19 cases of GBM with oligodendroglioma component (GBMO), using a scoring system for quantitative evaluation of staining intensity and proportion of MGMT, and performed survival analysis of these patients. Immunohistochemically, 55 cases (47%) were positive for MGMT with various intensities and proportions (total score (TS) ≥ 2), while 62 cases (53%) were negative (TS = 0). The distribution of MGMT expression pattern was not affected by any clinicopathological parameters such as the histological subtype (GBM vs. GBMO), age and gender. The survival analysis of these patients revealed that the minimal expression of MGMT (TS ≥ 2) was a significant unfavorable prognostic factor (P < 0.001) as well as resectability (P = 0.004). Moreover, multivariate analysis showed that minimal MGMT expression in GBM was the most potent independent predictor for progression free survival (P < 0.001) and also overall patient survival (P < 0.001). This is the first report employing the scoring system for both staining intensity and proportion to evaluate immunohistochemical MGMT expression in GBM. In addition, our results emphases the clinicopathological values of the immunohistochemical approach for MGMT expression in glioma patients as a routine laboratory examination.

Activation of NF-κB by the RANKL/RANK system up-regulates snail and twist expressions and induces epithelial-to-mesenchymal transition in mammary tumor cell lines.

BACKGROUND: Increased motility and invasiveness of cancer cells are reminiscent of the epithelial-mesenchymal transition (EMT), which occurs during cancer progression and metastasis. Recent studies have indicated the expression of receptor activator of nuclear factor-κB (RANK) in various solid tumors, including breast cancer. Although activation of the RANK ligand (RANKL)/RANK system promotes cell migration, metastasis, and anchorage-independent growth of tumor-initiating cells, it remains to be investigated if RANKL induces EMT in breast cancer cells. In this study, we investigated whether RANKL induces EMT in normal breast mammary epithelial cells and breast cancer cells, and the mechanism underlying such induction. METHODS: Expression levels of vimentin, N-cadherin, E-cadherin, Snail, Slug, and Twist were examined by real-time polymerase chain reaction. Cell migration and invasion were assessed using Boyden chamber and invasion assays, respectively. The effects of RANKL on signal transduction molecules were determined by western blot analyses. RESULTS: We found that stimulation by RANKL altered the cell morphology to the mesenchymal phenotype in normal breast epithelial and breast cancer cells. In addition, RANKL increased the expression levels of vimentin, N-cadherin, Snail, and Twist and decreased the expression of E-cadherin. We also found that RANKL activated nuclear factor-κB (NF-κB), but not extracellular signal-regulated kinase 1/2, Akt, mammalian target of rapamycin, c-Jun N-terminal kinase, and signal transducer and activator of transcription 3. Moreover, dimethyl fumarate, a NF-κB inhibitor, inhibited RANKL-induced EMT, cell migration, and invasion, and upregulated the expressions of Snail, Twist, vimentin, and N-cadherin. CONCLUSIONS: The results indicate that RANKL induces EMT by activating the NF-κB pathway and enhancing Snail and Twist expression. These findings suggest that the RANKL/RANK system promotes tumor cell migration, invasion, and metastasis via the induction of EMT.

Diagnostic impact of baseline cerebral blood flow in patients with acute ischemic stroke prior to intravenous recombinant tissue plasminogen activator therapy.

OBJECTIVE: To determine whether severe cerebral perfusion defects measured by SPECT prior to rt-PA therapy attribute to severe intracerebral hemorrhage (SICH). METHODS: We measured baseline cerebral blood flow (CBF) using technetium-99m-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT qualitatively prior to rt-PA therapy, in 52 consecutive patients (range 38-93 years). The degree and extent of the asymmetry of local CBF were analyzed semi-quantitatively. We did not administrate rt-PA in patients with severe perfusion defects. Clinical outcome and the incidence of SICH were studied. RESULTS: Three (5.8%) patients had severe perfusion defects that were undetected by CT and/or DWI. The other 49 (94.2%) patients had mild perfusion defects. The asymmetry of local CBF was 0.08±0.08 (n=3) and 0.3±0.15 (n=49) in the two groups, respectively. The percentages of the ipsilateral hemisphere in which perfusion was impaired severely were 17.5±9.5% (n=3) and 0.43±0.87% (n=49). Two patients were found petechial hemorrhage, but there was no patient who developed SICH in the former group following conventional antithrombotic therapy. In the latter group, SICH occurred in 1/49 (2.0%) patient following rt-PA therapy. CONCLUSION: These results suggest that rt-PA therapy for patients with severe cerebral perfusion defects may cause SICH and baseline CBF may contribute to identify patients at high risk for SICH after intravenous rt-PA therapy.

Spontaneous echo contrast and thrombus formation at the carotid bifurcation after carotid endarterectomy.

Spontaneous echo contrast (SEC) consists of numerous microechoes swirling in the cardiovascular lumen and is usually seen during blood stasis in dysfunctional left atrium. However, SEC and consecutive local thrombus formation at the carotid artery early after carotid endarterectomy (CEA) have not been reported. This study retrospectively investigated the clinical importance and therapeutic strategy of postoperative SEC and thrombus formation in 113 consecutive patients who underwent CEA between 2001 and 2009. Ultrasonography was routinely performed preoperatively, intraoperatively, and 1 day and 1 week after the operation. If SEC and/or thrombus was detected at any time after the operation, follow-up ultrasonography was performed at short intervals, once a week for inpatients and once every 1-2 months for outpatients. Eight of the 113 patients (7%) had SEC after the operation from Day 1 to 12 (mean 7.2 days), and 6 of these 8 patients developed local de novo thrombus formation at the site of SEC from Day 6 to 33 (mean 14.7 days). The maximum luminal narrowing by the thrombi were 26-62% (mean 37%). After administering anticoagulant therapy, all thrombi disappeared from Day 13 to 190 (mean 57 days) from CEA. SEC seen after CEA is highly associated with consecutive local thrombus formation. Postoperative geometric blood stasis with the absence of intima may be the causative factor for its development.

Identification of high-risk carotid artery stenosis: motion of intraplaque contents detected using B-mode ultrasonography.

OBJECT: Identification of the risk of rupture and vulnerability of arterial plaque is not yet clearly understood. The aim of this study was to assess the clinical features of the motion of intraplaque contents (MIC) detected by B-mode ultrasonography. The MIC is characterized by the peculiar movement of the intraplaque contents that is not synchronized with the heartbeat; however, the movement of the carotid artery (CA) wall depends on the heartbeat. METHODS: From January 2008 to November 2010, 1798 consecutive patients with transient ischemic attacks (TIAs) or acute ischemic stroke underwent CA ultrasonography for the examination of the MIC. Patients with CA stenosis greater than 50% were followed up until they underwent carotid endarterectomy or CA angioplasty and stent placement. If neither of these procedures were used, the patients were followed up at 90 days. Chi-square and Mann-Whitney tests were performed to compare the categorical and continuous demographic data and risk factors. The effect of the MIC on the rate of recurrent cerebral ischemia was examined using Kaplan-Meier and univariate Cox regression analyses. RESULTS: One hundred and fifteen patients had CA stenosis greater than 50%. Among these 115 patients, 58 with a total of 59 CA stenoses had MIC. Twenty-four recurrent ischemic events were associated with MIC, whereas only 6 such events occurred in the absence of MIC. The MIC decreased event-free survival (log-rank test = 15.8, p < 0.001); univariate Cox analysis confirmed that MIC increased the risk of a recurrent ischemic event (HR 5.12, 95% CI 2.08-12.58; p < 0.001). CONCLUSIONS: The MIC is one of the findings of vulnerable plaques. The MIC is more useful in predicting the recurrence of TIAs or ischemic events in patients with symptomatic CA stenosis.

New criteria for the sonographic diagnosis of a plaque ulcer in the extracranial carotid artery.

OBJECTIVE: The diagnostic power of carotid sonography in detecting plaque ulcers may be inadequate when using the conventional criteria. We aimed to evaluate the usefulness of new criteria that we devised through a preliminary analysis of 50 endarterectomy cases before the present series. SUBJECTS AND METHODS: Thirty carotid arteries of 30 consecutive patients who underwent endarterectomy (28 men; age range, 46-83 years) were studied. In the long- and short-axis B-mode images of carotid arteries, the concavity of the plaque surface and the surface echo intensity were carefully investigated. The conventional criteria stipulate a concavity larger than 2 × 2 mm with a well-defined back wall and flow reversal within the recess. Our new criteria specify a concavity in the plaque with the basal border echo weaker than that of the adjacent plaque surface, regardless of size. The final diagnosis was based on surgical and histologic findings. RESULTS: Among the 30 carotid arteries, 14 arteries had 14 ulcers at surgery. Seventeen concavities were detected by sonography, and 12 of them, including six smaller than 2 × 2 mm, were truly ulcers. Two concavities with an echo intensity of the basal border equal to or greater than that of the adjacent surface were not true ulcers. Only two of 14 ulcers were not detected by sonography. The sensitivity and specificity of the conventional criteria were 35.7% and 75.0%, respectively, and those of our new criteria were 85.7% and 81.3%, respectively. CONCLUSION: Our new criteria for the sonographic diagnosis of plaque ulcer are more useful than the conventional ones.

Cilostazol may suppress restenosis and new contralateral carotid artery stenosis after carotid endarterectomy.

Carotid artery restenosis is a serious complication following carotid endarterectomy (CEA), so preventative management of the risk factors is important. The present study investigated the potential of cilostazol, a mediator of vascular stabilization as well as inhibitor of platelet aggregation, to suppress restenosis on the ipsilateral carotid artery and new plaque development on the contralateral carotid artery. Eighty-two patients treated by CEA were divided into two groups according to the postoperative antiplatelet aggregation drugs into the cilostazol and other groups. Patients were periodically examined for recurrence of the plaque on the ipsilateral side, development of plaque on the contralateral side, and the bilateral intermedia thicknesses measured by ultrasonographic examination for up to 6 years. Restenosis and development of the contralateral plaque were not detected in any patients in the cilostazol group, whereas such changes were found in seven patients in the other group. Cilostazol might be effective to inhibit the growth mechanism of plaque.

Cilostazol may prevent cerebral vasospasm following subarachnoid hemorrhage.

Cilostazol is an antiplatelet aggregation inhibitor drug associated with increased cerebral blood flow and inflammation suppression. This study evaluated administration of cilostazol to prevent cerebral vasospasm following subarachnoid hemorrhage (SAH) in 50 patients treated surgically from December 2004 to November 2006. All patients, excluding those with Hunt and Kosnik grade 5 or who had undergone late surgery, were classified into two groups: 26 patients who received 200 mg/day cilostazol from postoperative day 1 to day 14 and 24 control patients. The frequency and the degree of cerebral vasospasm, occurrence of ischemic lesion, and clinical symptoms due to vasospasm were compared between the two groups. The appearance of severe vasospasm on angiography, persistent symptomatic spasm, and new cerebral infarction due to vasospasm demonstrated by neuroimaging were apparently lower in the cilostazol group than in the control group, suggesting that cilostazol may significantly suppress cerebral vasospasm following SAH.

Careful exclusion of non-neoplastic brain components is required for an appropriate evaluation of O6-methylguanine-DNA methyltransferase status in glioma: relationship between immunohistochemistry and methylation analysis.

Evaluation of O6-methylguanine-DNA methyltransferase (MGMT) expression is important for antiglioma therapy as many clinical trials have demonstrated that promoter hypermethylation and low level expression of MGMT are associated with an enhanced response to alkylating agents. However, here we report that the current strategies used to evaluate MGMT status in gliomas are unreliable. We observed discordance in the MGMT expression status when immunohistochemical evaluation and polymerase chain reaction-based methylation assessments were used: 73% of gliomas with methylated MGMT promoter had substantial numbers of MGMT-immunopositive tumor cells. Furthermore, when MGMT expression was tested in tumor homogenates using reverse transcription-polymerase chain reaction, 43% of tumors were found positive, in comparison to only 24%, when histologic samples were assayed immunohistochemically. To explain these inconsistencies we undertook a detailed immunohistochemical evaluation of tumor samples and found that some gliomas demonstrated remarkably high expression of MGMT in the entire tumor whereas others contained only a small immunopositive area. Additionally, we found that gliomas contained various types of non-neoplastic cells expressing MGMT, including lymphocytes, vascular endothelial cells, and macrophages/microglias, which contribute to overall MGMT expression detected in tumor homogenates, and thus result in overestimation of tumor MGMT expression. Therefore, to correctly establish MGMT expression in the tumor, which could be informative of glioma sensitivity to alkylating agents, exclusion of non-neoplastic brain components from analysis is required.

Stepwise revascularization for prevention of postoperative hyperperfusion.

Abrupt normalization of cerebral blood flow (CBF) after surgical procedures to improve excessive cerebral hypoperfusion can cause irreversible brain parenchymal damage. Such hyperperfusion, which is caused by inflow at normal blood pressure into maximally dilated fine vessels, is an important complication following carotid endarterectomy (CEA). Strict control of blood pressure in the perioperative period can prevent this complication except in a few patients, who have severe cerebral hypoperfusion and poor cerebrovascular reserve due to extremely severe stenosis of the ipsilateral or the bilateral carotid arteries, for which CEA is indicated. The requirement for improved CBF and the risk of postoperative hyperperfusion conflict in the pathogenesis of these patients. We tried to prevent abrupt improvement in perfusion by attempting gradual restoration of CBF. Superficial temporal artery-middle cerebral artery anastomosis was first performed to improve the poor cerebrovascular reserve by allowing insufficient blood flow. A few weeks later, CEA was performed to completely restore CBF. This surgical approach obtained good results without postoperative problems in four patients. The indications of this surgical management and efficacy of stepwise restoration of CBF to prevent postoperative hyperperfusion depend on careful preoperative evaluation of perfusion studies.

Progressive multifocal leukoencephalopathy in an HTLV-I carrier.

This report describes a previously 28-year-old healthy woman, identified as an asymptomatic human T-lymphotropic virus type I (HTLV-I) carrier, who developed both progressive multifocal leukoencephalopathy (PML) and Pneumocystis jiroveci pneumonia. For diagnostic confirmation of PML, stereotactic brain biopsy demonstrated multiple demyelinating lesions with the presence of JC viral antigen. Intramuscular alpha-interferon therapy for 2 weeks brought considerable neurologic improvement. Three years later, the patient developed lymphoma-type of adult T-cell leukemia, suggesting that HTLV-I carrier might be one of the underlying diseases of PML.

Quercetin and NPPB-induced diminution of aldosterone action on Na+ absorption and ENaC expression in renal epithelium.

In renal epithelial A6 cells, aldosterone applied for 24 h increased the transepithelial Cl- secretion over 30-fold due to activation of the Na+/K+/2Cl- cotransporter and stimulated the transepithelial Na+ absorption, activity of epithelial Na+ channel (ENaC), and alpha-ENaC mRNA expression. The stimulatory action of aldosterone on the transepithelial Na+ absorption, ENaC activity, and alpha-ENaC mRNA expression was diminished by 24h-pretreatment with quercetin (an activator of Na+/K+/2Cl- cotransporter participating in Cl- entry into the cytosolic space) or 5-nitro 2-(3-phenylpropylamino)benzoate (NPPB) (a blocker of Cl- channel participating in Cl- release from the cytosolic space), while 24h-pretreatment with bumetanide (a blocker of Na+/K+/2Cl- cotransporter) enhanced the stimulatory action of aldosterone on transepithelial Na+ absorption. On the other hand, under the basal (aldosterone-unstimulated) condition, quercetin, NPPB or bumetanide had no effect on transepithelial Na+ absorption, activity of ENaC or alpha-ENaC mRNA expression. These observations suggest that although aldosterone shows overall its stimulatory action on ENaC (transepithelial Na+ transport), aldosterone has an inhibitory action on ENaC (transepithelial Na+ transport) via activation of the Na+/K+/2Cl- cotransporter, and that modification of activity of Cl- transporter/channel participating in the transepithelial Cl- secretion influences the aldosterone-stimulated ENaC (transepithelial Na+ transport).

Evaluation of carotid distal pressure for prevention of hyperperfusion after carotid endarterectomy.

BACKGROUND: Sometimes preoperative cerebral misery perfusion induces an occurrence of hyperperfusion after carotid endarterectomy (CEA). We intraoperatively measured carotid proximal and distal pressures and evaluated their role in predicting hyperperfusion. METHODS: Twenty-one sites with an indication of CEA were preoperatively assessed based on the bilateral perfusional state of the cerebral blood flow (CBF) and delta CBF by single photon emission computed tomography (SPECT). Postoperative SPECT was performed immediately and on the fifth day after surgery. The distal and proximal pressures were intraoperatively measured through an internal shunt tube, and the evaluated relationship against hyperperfusion was shown on postoperative SPECT. RESULTS: Despite strict control of blood pressure, 7 patients postoperatively showed hyperperfusion on SPECT and 2 of them had transient neurological symptoms. The distal pressure was significantly different between the postoperative hyperperfusion group and the normal one; however, proximal pressure and the difference between proximal and distal pressures were not significantly different. In the hyperperfusion group, delta pressure was apparently higher, and delta CBF and distal pressure were significantly lower than those of the normal group. CONCLUSION: Intraoperative measurement of distal pressure as well as preoperative estimation of the cerebrovascular perfusion and the reserve is of importance in predicting postoperative hyperperfusion.

Adoptive transfer of macrophages ameliorates renal fibrosis in mice.

We performed adoptive transfer of bone marrow-derived (BM) macrophages following pharmacological depletion of leukocytes in a mouse model of unilateral ureteral obstruction (UUO). Treatment with cyclophosphamide (CPM) caused marked decrease in the numbers of F4/80-positive interstitial macrophages as well as in peripheral blood leukocyte counts, and adoptive transfer of BM macrophages to CPM-treated mice resulted in significant increase in the numbers of interstitial macrophages both at day 5 and at day 14 after UUO. At day 5 after UUO, no significant change was observed in the degree of renal interstitial fibrosis either by treatment with CPM or with CPM+macrophage. However, at day 14 after UUO, treatment with CPM caused significant increase in the degree of interstitial fibrosis, and adoptive macrophage transfer to these mice attenuated this enhancement in renal fibrosis. Our result suggests the role of infiltrating macrophages on facilitating tissue repair at late stage of UUO.

[A case of steroid-responsive encephalopathy with positive 14-3-3 protein of the cerebrospinal fluid clinically resembling Creutzfelt-Jakob disease].

A 69-year old man developed subacutely progressive dementia, inactivity, and gait disturbance. On admission, he showed flutter-like oscillation of the bilateral eyes and myoclonus with upper extremities. Cerebrospinal fluid (CSF) analysis revealed elevation of protein (73.2mg/dl) and the positive 14-3-3 protein. An electroencephalogram (EEG) revealed diffuse slowing (2-3Hz, 80microV). Brain MRI showed high intensity lesions in the white matter and left thalamus on FLAIR and diffusion imaging. We first suspected Creutzfelt-Jakob disease (CJD), but his symptoms didn't progress and showed no PSD on EEG. Oral corticosteroid therapy (prednisolone 60mg/day) brought him remarkable recovery corresponding with improvement of CSF and EEG findings. Despite of etiology unknown, we made a diagnosis of steroid-responsive encephalopathy.

Effect of hematopoietic cytokines on renal function in cisplatin-induced ARF in mice.

In this study, the effect of hematopoietic cytokines, i.e., granulocyte-colony stimulating factor (G-CSF), stem cell factor (SCF), and granulocyte-macrophage-colony stimulating factor (GM-CSF), on renal function was studied in cisplatin-induced acute renal failure in mice. Treatment with G-CSF significantly ameliorated both BUN and serum creatinine increase induced by cisplatin administration with concomitant alleviation in the degree of necrotic change, enhancement in DNA synthesis, and decrease in apoptosis of renal tubular cells. There was no significant change observed among these parameters following treatment with SCF or with GM-CSF. Serum hepatocyte growth factor level was significantly lower in mice treated with cisplatin and G-CSF compared with that in those treated with cisplatin only. In conclusion, G-CSF, but not SCF or GM-CSF, acts to accelerate regeneration and prevent apoptosis of renal tubular epithelial cells and leads to reduced renal injury in cisplatin-induced acute renal failure in mice.

Spinal canal size in ossification of the posterior longitudinal ligament of the cervical spine.

BACKGROUND: The size of the spinal canal is a factor that contributes to the neurologic deficits associated with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: Bone-window computed tomography (CT) examinations of the cervical spine in 64 patients with cervical OPLL were reviewed. Forty-two patients underwent surgical treatment (anterior decompression: 16 patients, posterior decompression: 26 patients). The remaining 22 patients were managed conservatively. Selection of the surgical approach, anterior or posterior, was based on the longitudinal extent of cord compression. RESULTS: The mean developmental size of the spinal canal in the posterior decompression group (10.7 mm at C4) was significantly smaller than the other 2 groups. The spinal canal was narrowed by OPLL to 2.9 to 10.0 mm. The proportion of the patients showing motor deficits of the lower extremities significantly increased when the sagittal canal diameter was narrowed to less than 8 mm. CONCLUSIONS: This study demonstrates critical values of CT-determined spinal canal stenosis. Developmental size of the spinal canal and the residual anterior-posterior canal diameters resulting from OPLL spinal cord compression are important factors influencing clinical management and the neurologic state.