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Guidelines devised to ensure that multiple and highly functional in-vehicle information systems (IVISs) are designed to present a distraction-free interface at the same time, need to consider the safety, functionality, and usability of image displays. However, no guidelines exist for quantitatively assessing drivers' cognitive workloads, and this includes usability and memorability. In this paper, we propose a method to measure drivers' visuospatial workload quantitatively. The method is incorporated in various interface tests including driving and human machine interface evaluations. The results indicated that the success rates of visuospatial working memory tasks can be used to rank the relative difficulties of the tasks, and the ranking order of these rates tended to be similar to that of the subjective difficulties.

Introduction: Details of surgical and general complications for patients with cervical spondylotic myelopathy (CSM) are still uncertain. The purpose of this study was to describe surgeries and their complications among Japanese patients with CSM. Methods: The Japanese Society for Spine Surgery and Related Research performed a nationwide survey on spine surgery and complications in 2011. Data of patients with 2,961 CSM >40 years old were included. The clinicopathological variables were basic demographic and clinical information, surgical information, and surgical and general complications. To examine the influence of age, variables were compared among three age groups: patients 40-64 (n=1,123), 65-74 (n=966), and ≥75 (n=872) years of age. Results: The study included 1,970 males and 991 females and the mean age was 64.3 years old. There were 168 anterior (5.7%) and 2,770 posterior (94.2%) approach surgeries. The vast majority of patients with CSM were treated using the posterior approach, 89.4% of whom had decompression surgery only. Anterior surgeries were more common in the younger age group, but posterior surgeries were equally distributed. The incidence of total complications including surgical/general complications was similar for the anterior (16/168; 9.5%) and posterior (295/2,770; 10.6%) approaches. No patient died on the operating table, but four patients (0.1%) died within one month after surgery. No association was detected between complications and age, comorbidity, and other surgical factors. The incidence of complications was similar for the different age groups. However general complications were predominantly observed in the older group and those who had instrumented surgery. Conclusions: The results indicate that the indication and surgical performance for patients with CSM is favorable in Japan, despite the super-aging population. Few serious complications were reported in this study. However, more detailed informed consent about surgical and, in particular, general complications is necessary for the older patients with CSM.

Background Context Previous studies have shown that axial loading during magnetic resonance imaging (MRI) significantly reduces the size of the dural sac compared with conventional MRI in patients with degenerative lumbar disease. In our previous study, axial-loaded MRI showed a significantly larger degree of olisthesis than conventional MRI in patients with degenerative spondylolisthesis (DS). Furthermore, the degree of olisthesis on axial-loaded MRI correlated more strongly with that observed on X-ray in the upright position. However, no study has investigated whether or not the increase in the degree of olisthesis during axial loading correlates with the reduction in the dural sac size and affects the severity of clinical symptoms in patients with DS. Purpose The objective of this study was to determine whether or not the increase in the degree of olisthesis correlates with the reduction of the dural sac cross-sectional area (DCSA) detected on axial-loaded MRI and worsens the severity of clinical symptoms in patients with DS. Study Design/Setting This is an imaging cohort study. Patient Sample A total of 41 consecutive patients with DS were prospectively evaluated in this study. Outcome Measures The outcome measures include the degree of olisthesis, the DCSA, the Pearson correlation coefficient, and the severity of clinical symptoms. Materials and Methods The differences in the degree of olisthesis and the DCSA between conventional and axial-loaded MRIs were determined. The Pearson correlation coefficient of the increase in the degree of olisthesis with the reduction in the DCSA during axial loading was calculated. The reduction in the DCSA and the severity of clinical symptoms in patients exhibiting a ≥2-mm increase in the degree of olisthesis were compared with those in patients exhibiting a Results The increase in the degree of olisthesis was significantly correlated with the reduction in the DCSA during axial loading (Pearson correlation coefficient=0.63, p Conclusions The present study demonstrated that the increase in the degree of olisthesis was significantly correlated with the reduction in the dural sac size detected on axial-loaded MRI and worsened the severity of clinical symptoms in patients with DS. These results suggest that axial-loaded MRI may be a useful imaging study for detecting dynamic changes in the degree of olisthesis during axial loading to the lumbar spine related to the narrowing of the spinal canal and the severity of clinical symptoms in the assessment of patients with DS.

BACKGROUND AND PURPOSE: Axial-loaded MR imaging, which simulates the spinal canal in a standing position, demonstrates reductions of the dural sac cross-sectional area in patients with lumbar spinal canal stenosis. However, there has been no useful conventional MR imaging finding for predicting a reduction in the dural sac cross-sectional area on axial-loaded MR imaging. Previous studies have shown that increased facet fluid is associated with the spinal instability detected during positional changes. The purpose of this study was to analyze the correlations between facet fluid and dynamic changes in the dural sac cross-sectional area on axial-loaded MR imaging. MATERIALS AND METHODS: In 93 patients with lumbar spinal canal stenosis, the dural sac cross-sectional area was measured by using axial images of conventional and axial-loaded MR imaging. Changes in the dural sac cross-sectional area induced by axial loading were calculated. The correlation between the facet fluid width measured on conventional MR imaging and the change in dural sac cross-sectional area was analyzed. The change in the dural sac cross-sectional area was compared between the intervertebral levels with and without the facet fluid width that was over the cutoff value determined in this study. RESULTS: The dural sac cross-sectional area was significantly smaller on axial-loaded MR imaging than on conventional MR imaging. The facet fluid width significantly correlated with the change in the dural sac cross-sectional area (r = 0.73, P < .001). The change in the dural sac cross-sectional area at the intervertebral level with the facet fluid width over the cutoff value was significantly greater than that at the other level. CONCLUSIONS: The increased facet fluid on conventional MR imaging is highly predictive of the dynamic reduction of dural sac cross-sectional area detected on axial-loaded MR imaging in the clinical assessment of lumbar spinal canal stenosis.

Ossification of the posterior longitudinal ligament (OPLL) can cause severe and irreversible paralysis in not only the cervical spine but also the thoracolumbar spine. To date, however, the prevalence and distribution of OPLL in the whole spine has not been precisely evaluated in patients with cervical OPLL. Therefore, we conducted a multi-center study to comprehensively evaluate the prevalence and distribution of OPLL using multi-detector computed tomography (CT) images in the whole spine and to analyze what factors predict the presence of ossified lesions in the thoracolumbar spine in patients who were diagnosed with cervical OPLL by plain X-ray. Three hundred and twenty-two patients with a diagnosis of cervical OPLL underwent CT imaging of the whole spine. The sum of the levels in which OPLL was present in the whole spine was defined as the OP-index and used to evaluate the extent of ossification. The distribution of OPLL in the whole spine was compared between male and female subjects. In addition, a multiple regression model was used to ascertain related factors that affected the OP-index. Among patients with cervical OPLL, women tended to have more ossified lesions in the thoracolumbar spine than did men. A multiple regression model revealed that the OP-index was significantly correlated with the cervical OP-index, sex (female), and body mass index. Furthermore, the prevalence of thoracolumbar OPLL in patients with a cervical OP-index ≥ 10 was 7.8 times greater than that in patients with a cervical OP-index ≤ 5. The results of this study reveal that the extent of OPLL in the whole spine is significantly associated with the extent of cervical OPLL, female sex, and obesity.

Spinal disorders affect mainly older people and cause pain, paralysis and/or deformities of the trunk and/or extremities, which could eventually disturb locomotive functions. For ensuring safe and high-quality treatment of spinal disorders, in 1987, the Tohoku University Spine Society (TUSS) was established by orthopedic departments in Tohoku University School of Medicine and its affiliated hospitals in and around Miyagi Prefecture. All spine surgeries have been enrolled in the TUSS Spine Registry since 1988. Using the data from this registration system between 1988 and 2012, we demonstrate here the longitudinal changes in surgical trends for spinal disorders in Japan that has rushed into the most advanced "aging society" in the world. In total, data on 56,744 surgeries were retrieved. The number of spinal surgeries has annually increased approximately 4-fold. There was a particular increase among patients aged ≥ 70 years and those aged ≥ 80 years, with a 20- to 90-fold increase. Nearly 90% of the spinal operations were performed for degenerative disorders, with their number increasing approximately 5-fold from 705 to 3,448. The most common disease for surgery was lumbar spinal stenosis (LSS) (35.9%), followed by lumbar disc herniation (27.7%) and cervical myelopathy (19.8%). In 2012, approximately half of the patients with LSS and cervical myelopathy were ≥ 70 years of age. In conclusion, the number of spinal operations markedly increased during the 25-year period, particularly among older patients. As Japan has a notably aged population, the present study could provide a near-future model for countries with aging population.

Rapamycin is an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, plays an important role in multiple cellular functions. Our previous study showed rapamycin treatment in acute phase reduced the neural tissue damage and locomotor impairment after spinal cord injury (SCI). However, there has been no study to investigate the therapeutic effect of rapamycin on neuropathic pain after SCI. In this study, we examined whether rapamycin reduces neuropathic pain following SCI in mice. We used a mouse model of thoracic spinal cord contusion injury, and divided the mice into the rapamycin-treated and the vehicle-treated groups. The rapamycin-treated mice were intraperitoneally injected with rapamycin (1 mg/kg) 4 h after SCI. The rapamycin treatment suppressed phosphorylated-p70S6K in the injured spinal cord that indicated inhibition of mTOR. The rapamycin treatment significantly improved not only locomotor function, but also mechanical and thermal hypersensitivity in the hindpaws after SCI. In an immunohistochemical analysis, Iba-1-stained microglia in the lumbar spinal cord was significantly decreased in the rapamycin-treated mice. In addition, the activity of p38 MAPK in the lumbar spinal cord was significantly attenuated by rapamycin treatment. Furthermore, phosphorylated-p38 MAPK-positive microglia was relatively decreased in the rapamycin-treated mice. These results indicated rapamycin administration in acute phase to reduce secondary neural tissue damage can contribute to the suppression of the microglial activation in the lumbar spinal cord and attenuate the development of neuropathic pain after SCI. The present study first demonstrated that rapamycin has significant therapeutic potential to reduce the development of neuropathic pain following SCI. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:93-103, 2017.

The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in multiple cellular functions, such as cell metabolism, proliferation and survival. Many previous studies have shown that mTOR regulates both neuroprotective and neuroregenerative functions in trauma and various diseases in the central nervous system (CNS). Recently, we reported that inhibition of mTOR using rapamycin reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. Our results demonstrated that the administration of rapamycin at four hours after injury significantly increases the activity of autophagy and reduces neuronal loss and cell death in the injured spinal cord. Furthermore, rapamycin-treated mice show significantly better locomotor function in the hindlimbs following SCI than vehicle-treated mice. These findings indicate that the inhibition of mTOR signaling using rapamycin during the acute phase of SCI produces neuroprotective effects and reduces secondary damage at lesion sites. However, the role of mTOR signaling in injured spinal cords has not yet been fully elucidated. Various functions are regulated by mTOR signaling in the CNS, and multiple pathophysiological processes occur following SCI. Here, we discuss several unresolved issues and review the evidence from related articles regarding the role and mechanisms of the mTOR signaling pathway in neuroprotection and neuroregeneration after SCI.

STUDY DESIGN: We compared the sizes of the dural sac among conventional magnetic resonance imaging (MRI), axial loaded MRI, and upright myelography in patients with lumbar spinal canal stenosis (LSCS). OBJECTIVE: To determine whether axial loaded MRI can demonstrate similar positional changes of the dural sac size as were detected by upright myelography in LSCS. SUMMARY OF BACKGROUND DATA: In patients with LSCS, constriction of the dural sac is worsened and symptoms are aggravated during standing or walking. To disclose such positional changes, upright myelography has been widely used. Recently, axial loaded MRI, which can simulate a standing position, has been developed. However, there has been no study to compare the dural sac size between axial loaded MRI and upright myelography. METHODS: Forty-four patients underwent conventional MRI, axial loaded MRI, and myelography. Transverse and anteroposterior diameters and the cross-sectional areas of the dural sac from L2-L3 to L5-S1 were compared. Pearson correlations of the diameters between the MRIs and the myelograms were analyzed. On the basis of the myelograms, all disc levels were divided into severe and nonsevere constriction groups. In each group, the diameters and the cross-sectional areas were compared. Sensitivity and specificity to detect severe constriction were calculated for the conventional and axial loaded MRI. RESULTS: Transverse and anteroposterior diameters at L4-L5 in the axial loaded MRI and myelogram were significantly smaller than those observed in the conventional MRI (P < 0.001). Cross-sectional areas in the axial loaded MRI were significantly smaller than those in the conventional MRI at L2-L3, L3-L4, and L4-L5 (P < 0.001). Between the axial loaded MRI and the myelography, Pearson correlation coefficients of the transverse and anteroposterior diameters were 0.85 and 0.87, respectively (P < 0.001), which were higher than those for conventional MRI. Reductions of the dural sac sizes in the axial loaded MRI were more evident in the severe constriction group. The axial loaded MRI detected severe constriction with a higher sensitivity (96.4%) and specificity (98.2%) than the conventional MRI. CONCLUSION: The axial loaded MRI demonstrated a significant reduction in the dural sac size and significant correlations of the dural sac diameters with the upright myelogram. Furthermore, the axial loaded MRI had higher sensitivity and specificity than the conventional MRI for detecting the severe constriction observed in the myelogram. Therefore, the axial loaded MRI can be used to represent positional changes of the dural sac size detected by the upright myelography in patients with LSCS.

The objective of the present study was to investigate the natural history of intradural-extramedullary spinal cord tumors. Nine cases of intradural-extramedullary tumors were observed over the 2 years. The physical and magnetic resonance imaging (MRI) examination were performed in the first examination and every other year. Tumors were classified as the schwannoma type and the meningioma type based on the MRI findings. The tumor volume was calculated by the craniocaudal length on a sagittal image and maximum transverse diameter on an axial image of MRI, every year. The annual growth rate, which was defined as the change in the volume each year compared to the volume of the previous year, was examined. There were six cases in the schwannoma type and three cases in the meningioma type. The schwannoma type tumors presented several growth patterns: unchanging, continuous slight growth, and initial slight growth followed by rapid growth during the observation period (6.7 ± 2.7 years), while the meningioma type tumors presented the continuous growth pattern during the observation period (4.3 ± 2.5 years). The average annual growth rate was 2.3 ± 5.5% in the schwannoma type and 7.0 ± 8.5% in the meningioma type. Schwannoma type tumors showed relatively less change in their size and would be observed for a longer time.

Cross-sectional registry and imaging cohort study. OBJECTIVE.: To examine whether the dural sac cross-sectional area (DCSA) in axial loaded magnetic resonance imaging (MRI) correlates with the severity of clinical symptoms in patients with lumbar spinal canal stenosis (LSCS).Many studies have analyzed the relationship between DCSA on conventional MRI and the severity of symptoms in LSCS, but the link is still uncertain. Recently, axial loaded MRI, which can stimulate the spinal canal of patients in the upright position, has been developed. Axial loaded MRI demonstrates significant reduction of DCSA and provides valuable radiologic findings in the assessment of LSCS. However, there has been no study of the correlation between DCSA in axial loaded MRI and the severity of symptoms in LSCS.In 88 patients with LSCS, DCSA in conventional MRI, axial loaded MRI, and changes in the DCSA were determined at the single most constricted intervertebral level. The severity of symptoms was evaluated on the basis of the duration of symptoms, walking distance, visual analogue scale of leg pain/numbness, and Japanese Orthopaedic Association score. Spearman correlations of the DCSA in conventional MRI, axial loaded MRI, and changes in the DCSA with the severity of symptoms were analyzed. In addition, the severity of symptoms and DCSA in conventional and axial loaded MRI were compared, respectively, between patients with and without significant (15 mm) changes in the DCSA.The DCSA in axial loaded MRI had good correlations with walking distance and Japanese Orthopaedic Association score (rs = 0.46 and 0.45, respectively; P0.001). In addition, the change in the DCSA significantly correlated to walking distance, visual analogue scale of leg numbness, and Japanese Orthopaedic Association score (rs = 0.59, 0.44, and 0.54, respectively; P0.001). Furthermore, the symptoms were significantly worse in patients with more than 15 mm change in the DCSA (P0.001). Axial loaded MRI, but not conventional MRI, showed a significantly smaller DCSA in patients with more than 15 mm change in the DCSA (P0.05).DCSA in axial loaded MRI significantly correlated with the severity of symptoms. Axial loaded MRI demonstrated that changes in the DCSA significantly correlated with the severity of symptoms, which conventional MRI could not detect. Thus, MRI with axial loading provides more valuable information than the conventional MRI for assessing patients with LSCS.

The current study examined the hemodynamic response during the Go/NoGo task in children with/without attention deficit/hyperactivity disorder (ADHD). Using near-infrared spectroscopy, oxy-Hb and deoxy-Hb concentration changes in the frontal areas were compared during the conditions with/without inhibitory demand. Compared with typically developing children, children with ADHD showed significantly reduced activation during the conditions with inhibitory demand (NoGo-condition) in the frontal areas. However, no significant differences in activation during the conditions without inhibitory demand (Go-condition) were found between the two groups. The current findings revealed that children with ADHD exhibit an altered hemodynamic response specifically during response inhibition, but not during response execution, and suggested the clinical usefulness of near-infrared spectroscopy for the evaluation of response inhibition deficits in children with ADHD.

Congenital cytomegalovirus (CMV) infection can cause severe permanent disabilities. A mother who is seronegative before conception but acquires infection during pregnancy is a risk factor for congenital infection. We describe a neonate in whom congenital CMV infection was diagnosed at birth and confirmed with DNA quantitation by means of the polymerase chain reaction, was accompanied by cerebral ventriculomegaly and severe hearing loss, and was treated with ganciclovir/valganciclovir for 6 weeks. Initially, cerebral ventriculomegaly and calcification were also found with computed tomography, and severe hearing loss was detected with auditory brainstem response testing. After treatment, CMV DNA decreased in copy number and became undetectable. No marked side effects occurred after treatment. Surprisingly, 1 year after treatment, neurological and motor development was equivalent to that in a healthy infant. Audiometry indicated that auditory ability would improve with rehabilitation, speech and language therapy, and cochlear implantation. Single-photon emission computed tomography showed marked improvement 6 months after treatment. This case provides compelling evidence that a reliable diagnosis of congenital CMV infections coupled with a prompt and appropriate treatment program can prevent permanent disability. It is, therefore, important to establish a more effective strategy for the management of congenital CMV infection.

Many studies have been reported on recurrent lumbar disc herniations covering several pathological conditions. In those studies, reoperation rate of revised disc excisions was calculated by simple division between the number of reoperations and that of the total primary disc excisions. To determine the real reoperation rate, strict definition of pathologies, a large number of patients, a long observation period, and survival function method are necessary.Between 1988 and 2007, 5,626 patients with disc excision were enrolled by the spine registration system of the Department of Orthopaedic Surgery, Tohoku University, Japan. Among them, 192 had revised disc surgery, and we obtained data of 186 patients whose clinical features were assessed and reoperation rates analyzed using the Kaplan-Meier method.In total, 205 disc herniations were excised in the revision surgery (including contralateral herniation at the same level and new herniation at a different level), and 101 were real recurrent herniations (recurrence at the same level and side as the primary herniation). The kappa coefficient of the spinal level and side between the primary and revision surgeries was 0.41, indicting moderate correlations. Real recurrent herniations showed shorter intervals between primary and revision surgeries. Male patients with surgery at a younger age carried a higher risk of reoperation. In the revision surgery, transligamentous extrusion was significantly more common than other types of herniation. On Kaplan-Meier analysis, the reoperation rate of overall revised excisions was 0.62% at 1 year, 2.4% at 5 years, 4.4% at 10 years, and 5.9% after 17 years. That of real recurrent herniations was 0.5%, 1.4%, and 2.1%, respectively, and 2.8% after 15.7 years.Reoperation rate of real recurrent herniations calculated using survival function method gradually increased year by year, from 0.5% at 1 year after primary surgery to 2.8% at 15.7 years.

Object Tethered cord syndrome (TCS) is a disorder involving an abnormal stretching of the tethered spinal cord caused by several pathological conditions and presents with a variety of neurological symptoms. Untethering (tethered cord release) is the gold standard treatment for TCS. However, untethering carries risks of spinal cord injury and postoperative retethering. To avoid these potential risks, the authors applied spine-shortening osteotomy to adult patients with TCS, and report on the surgical procedure and treatment outcomes. Methods Eight patients with TCS caused by a lipomyelomeningocele were surgically treated by the authors' original procedure of spine-shortening osteotomy. Six patients were male and 2 were females; average age at the time of surgery was 31 years old. Spine-shortening osteotomy was performed at the level of L-1 in all but 2 patients, in whom it was performed at T-12, with spinal fusion between T-12 and L-2 or T-11 and L-1 using a pedicle screw–rod system. The average follow-up period was 6.2 years and the patients' pre- and postoperative conditions were evaluated clinically and radiologically. Results Preoperatively, all patients displayed severe neurological deficits such as motor disturbance, muscle atrophy, and bladder dysfunction. Several months before surgery, all showed progressive symptoms. Those symptoms showed initial improvement in 6 patients and stabilized in 2 postoperatively, but the improved symptoms worsened again in 4 of the 6 patients. The osteotomized vertebrae were shortened by 21 mm on average, and all spines showed complete bone union without loss of correction. At the final follow-up evaluations, 6 patients showed stabilization as per the modified Japanese Orthopaedic Association score for thoracic myelopathy. Conclusions Spine-shortening osteotomy successfully helps reduce the spinal cord tension without causing direct neural damage. At minimum, it stabilized the patients' symptoms and/or helped delay neurological deterioration for a period of time. Spine-shortening osteotomy might be a feasible mode of treatment for adult TCS caused by a spinal lipoma.

The interaction between laminar boundary layer reattachment and a rectangular cavity in a hypersonic compression ramp was investigated numerically and experimentally. It was found from the present results that the separation bubble becomes larger than that of the baseline flat ramp case. This is caused by higher adverse pressure gradient due to the cavity end wall. In the flowfield a high temperature separated shear layer collides with the endwall of cavity, where a hot stagnation point is formed. The endwall heat flux becomes about 10 times as large as the maximum heat flux in the baseline flat ramp case.

1–14 Several terms have been used based on the histology and location of the cyst: synovial cyst at the craniovertebral or C1/2 junction, retrodental or periodontoid synovial cyst, and more generally atlantoaxial degenerative articular cyst. Different terms might indicate the same disorders, and confusion in the terminology makes it diffi cult to understand this entity. As we indicated in our large case series of juxtafacet cysts in the lumbar spine, 15 it is more important to prove a communication channel between the cyst and neighboring facet joint radiologically or histologically to clarify the pathogenesis of the cyst. Once the communication channel is revealed, the cyst formation should be closely related to degeneration of the facet joint with or without synovial cells in the cyst histologically. 15,16

A small crack on body surface led to a tragic accident in 2003, which is the Columbia accident. During the shuttle's re-entry, high temperature gas penetrated crack on leading-edge of the left wing and melted the aluminum structure, finally the Columbia blew up. Since early times, there are many fundamental studies about simple cavity-flow formed on body surface in hypersonic speeds. However, an investigation of Shock/Boundary-Layer Interaction (SBLI) on crack has not been researched. For multistage space transportation vehicle such as TSTO, SBLI is an inevitable problem, and then SBLI on crack becomes a critical issue for TSTO development. In this study, the effects of crack, where SBLI occurs, were investigated for TSTO hypersonic speed (M∞ = 8.1). A square crack locates at SBLI point on the TSTO booster. Results show that a crack and its depth strongly effect on peak heat flux and aerodynamic interaction flow-field. In the cases of shallow crack (d/C ≤ 0.10), there exist two high heat flux regions on crack floor, which locates at a flow reattachment region and a back end wall of crack. In this case, a peak heat flux at flow reattachment region becomes about 2 times as large as the stagnation point heat flux, which value becomes larger compared with a peak heat flux in the case of No-Crack TSTO. While in the case of deep crack (d/C = 0.20), overall heat flux on crack floor decreases to below the stagnation point heat flux. These results provide useful data for a development of TSTO thermal protection system (TPS) such as thermal protection tile.

Middle distillates obtained by pyrolysis of oil shale and oil sands bitumen were denitrogenated by complex formation with CuCl2·2H2O, which reduced the nitrogen contents from 9900 to 2700 wtppm and from 1300 to 700 wtppm, respectively, without any change in the sulfur contents. The original and denitrogenated oils were hydrotreated over a conventional NiMo catalyst in a fixed-bed continuous flow reactor. The pre-removal of nitrogen compounds greatly enhanced hydrodenitrogenation (HDN) and hydrodesulfurization (HDS), and the rate constants were increased by 4.9-27 for HDN and 2.8-5.4 for HDS. As a result, the nitrogen and sulfur contents of the denitrogenated oils were reduced to < 1 and < 10 wtppm, respectively, under the conditions of H2 8 MPa, LHSV 1 h−1 and 350°C.

This paper presents experimental results of unsteady aerodynamic interactions including Shock/Shock Interaction (SSI) and Shock/Boundary Layer Interaction (SBLI) between two bodies at hypersonic speed. These interactions can be seen in space vehicles consisting of multi-bodies, such as a TSTO, or at a scramjet engine inlet. The present study considers the effect of a flat plate below the SSI where a boundary-layer is developed on the plate surface. More specifically, the interacted flow for a combination of a flat plate (FP) and a hemi-circular cylinder (HCC) is examined at a hypersonic speed (M∞=8.1); the distributions of surface pressure and heat transfer rate are measured. To obtain various SSI patterns, the clearance between two bodies (FP and HCC) is changed. Results show that unsteadiness at the SSI point causes a feedback loop between the two bodies; a jet flow impinges on the FP, the effect of which propagates upstream where the jet impinges on the FP, and the aerodynamic and aerothermodynamic loads reach their maxima. Finally, we found that the feedback loop can be destroyed by installing a fence on the FP to reduce unsteadiness of flow field.

Sacral and presacral schwannomas are often found incidentally, because they present with vague symptoms or symptomless. Schwannoma occurring in this area occasionally presents with enormous dimensions, known as a giant schwannoma. The tumor removal is a surgical challenge due to the difficult approach and abundant vascularity. The aim of this study is to review cases of giant sacral schwannomas focusing the surgical management and outcome. Six patients with sacral and presacral schwannoma were treated surgically. The patients included two males and four females, and the mean age was 47.8 years. All patients experienced pain at the time of presentation. The tumors were classified as intraosseous type in one case, dumb-bell type in four cases, and retroperitoneal type in one case. The tumors were removed with a piecemeal subtotal excision in three patients, a partial excision in two patients, and enucleation in one patient. The surgeries were performed by the combination of an anterior and posterior approach in three patients, a posterior approach in two patients, and an anterior approach in one patient. The mean surgical time was 7.8 hrs, and the mean blood loss was 2572 g. The tumor recurred in one patient after the partial excision and was removed completely in a second surgery. No patient, including the patient who underwent the second surgery, presented with pain and obvious neurological deficit at the final follow-up. The surgical treatment of the giant sacral schwannoma with a piecemeal subtotal excision can achieve a good outcome, avoiding unnecessary neurological deficit.

Prospective multicenter study.To clarify the significance of intramedullary Gd-DTPA enhancement in cervical myelopathy, the prevalence, morphologic features, clinical relevance and postoperative change were investigated.Four hospitals in Japan.A total of 683 patients with cervical myelopathy who underwent decompressive surgery were consecutively examined. T1, 2 and Gd-DTPA-enhanced MRI were taken before surgery. Fifty consecutive cases without intramedullary enhancement were allocated in the non-enhancement group. The following variables were investigated: prevalence of the enhancement, the morphologic feature, the relationship between the enhancement and T2 high-intensity areas, the change of the Japanese Orthopedic Association (JOA) score for cervical myelopathy and the change of the enhancement after surgery.Intramedullary enhancement was observed in 50 cases (7.3%). The enhancements were observed between the most severely compressed disc and the cranial half of the lower vertebral body. On axial images, they were observed at the posterior or posterolateral periphery of the spinal cord. Enhancement areas were observed within T2 high-intensity areas and smaller than them. The preoperative JOA score was 9.8+/-2.8 points in the enhancement group and 9.8+/-3.3 points in the non-enhancement group (NS). The postoperative JOA score was 12.7+/-2.9 points in the enhancement group and 14.2+/-2.4 in the non-enhancement group (P=0.006). Intramedullary enhancement disappeared in 60% of the patients 1 year after surgery.Intramedullary enhancement indicated not the severity of preoperative symptoms, but a sign of a worse prognosis.

The space transportation system using capsule/rocket configurations such as Apollo and Soyuz are simple compared with Space Shuttle, and have several merits from the viewpoint of reliability. The capsule/rocket system will take over the Space Shuttle, after it retires in 2010. As the Space Shuttle accidents had been caused by several factors, e.g., aerodynamic interaction of shock waves ahead of its wing, advanced abort systems such as LAS (Launch Abort System) are required for the capsule/rocket system. In the present study, as a baseline configuration, a combination of a cone and a cylinder is employed as a CEV (Crew Exploration Vehicle), which consists of a capsule (LAV: Launch Abort Vehicle) and a rocket (SM: Service Module). By changing the relative position of the two components as well as the profile area of the rocket, their effects on the capsule/rocket aerodynamic interaction and characteristics (drag and pitching moment) are experimentally and numerically investigated at a supersonic speed (M∞ = 3.0). It is found from the results that the clearance have little effects on the flow field for the case of the baseline configuration. The capsule always showed a positive drag (CD = 0.34), which means that thrust is required to overcome the drag. Otherwise the capsule will recontact the rocket. However in the case where the rocket contact area is 2.2 times as large as the capsule profile, more favorable effects were obtained. Especially in the case of a certain clearance (h/D = 0.40), the drag coefficient of the capsule is CD = −0.35, which means that the capsule suffers a thrust force from the aerodynamic interaction. Under this condition, if capsule has a pitch angle with 5 degrees instantaneously, then pitching moment coefficient becomes CMp = −0.41 therefore capsule stabilize. However, in the case of a very small clearance (h/D ∝ 0.00), the flow becomes unsteady involving pulsating shock wave, leading to a potentially risky separation of the capsule.

Just as with cervical radiculopathy, T1 radiculopathy can be caused by degenerative processes of the spine, such as intervertebral disc herniation. Since it was fi rst described by Svien and Karavitis in 1954, to our knowledge, only 33 cases have been reported excluding 1 case of a tumorous lesion. Patients suffering from T1 radiculopathy are rare, so the comprehensive clinical features may not be familiar to orthopedists or even spinal surgeons. The symptomatic characteristics of T1 radiculopathy mimic those of C8 radiculopathy involving the upper limbs. It is occasionally diffi cult to distinguish between these two radiculopathies symptomatologically. Therefore, a summary of the neurological fi ndings of T1 radiculopathy in comparison to those of C8 radiculopathy should be helpful in making a correct clinical diagnosis. Morgan and Abood described the symptomatic and neurological features of T1 radiculopathy in 23 patients, but their description might be inadequate. This article reports one case of T1 radiculopathy caused by intervertebral disc herniation that was treated surgically. In addition, 33 patients with this radiculopathy were analyzed in more detail than the summarized description by Morgan and Abood, including the rate of characteristic neurological fi ndings. The patient described here was informed that his data would be submitted for publication and gave his consent.

The authors report a rare case of tethered cord syndrome with low-placed conus medullaris complicated by a vertebral fracture that was successfully treated by a spine-shortening vertebral osteotomy. The patient was a 57-year-old woman whose neurological condition worsened after a T-12 vertebral fracture because a fracture fragment and the associated local kyphotic deformity directly compressed the tethered spinal cord. An osteotomy of the T-12 vertebra was performed in order to correct the kyphosis, remove the fracture fragment, and reduce the tension on the spinal cord. Postoperative radiographs showed the spine to be shortened by 22 mm, and the kyphosis between T-11 and L-1 improved from 23° to 0°. Two years after the surgery, the patient's neurological symptoms were resolved. The bone union was complete with no loss of correction.

ObjectThe increased kyphosis after thoracic laminectomy in adult patients was retrospectively evaluated and various factors affecting this spinal deformity were analyzed.MethodsThe authors conducted a retrospective study of 58 cases in which laminectomy was performed and more than half of the facet joints were left intact. The study group included 44 men (mean age 59 years) and 14 women (mean age 61 years) with thoracic myelopathy due to ossifications of the ligamentum flavum and/or the posterior longitudinal ligament or due to posterior bone spurs. Patients were followed up for a minimum of 2 years. Their neurological condition was evaluated using the Japanese Orthopaedic Association (JOA) scale (a full score is 11), and the magnitude of local kyphosis in the laminectomized area was determined using the Cobb angle method.ResultsThe mean preoperative JOA score was 5.4; the mean postoperative score was 8.3. No relationship was found between postoperative JOA score and increased kyphotic angle. The mean preoperative kyphotic angle was 7.0°. The mean postoperative kyphotic angle was 10.8°. Thus local kyphosis in the treated area increased by only 3.8°. The mean increase in kyphosis per spinal segment, calculated by dividing the kyphotic angle of the surgically decompressed area by the number of resected laminae, was 1.9°. Female patients with ≥ 3-level laminectomies showed a significant increase of kyphosis in both the laminectomized area and each spinal segment.ConclusionsThe increase in kyphosis after thoracic laminectomy is not large and thus spinal fusion is usually not necessary. In cases involving female patients who undergo long-segment laminectomies, however, careful radiographic follow-up is recommended.

To make space activities more brisk, TSTO (Two Stage To Orbit) has been investigated worldwide as an advanced space transportation system. TSTO vehicles, which have a booster and an orbiter, have to make flight in a wide range of flight speed from subsonic to hypersonic, where they undergo aerodynamic interactions due to their combined bodies. In hypersonic flow regime, aerodynamic heating is critical, which depends on aerodynamic interaction pattern. In the present study, a delta-wing is employed as a booster and a diagonally-cut circular cylinder as an orbiter to reduce the aerodynamic interaction between these two bodies. It was found as a result of experiment that the heat flux on the head part of the diagonally-cut circular cylinder becomes about 2.4 times as large as the stagnation heat flux, while that on the delta-wing becomes about 0.5 times as large. These two values are roughly half of those in the case of a baseline combination: hemisphere-cylinder and delta-wing, which suggests that the diagonally-cut circular cylinder is promising as an orbiter head shape.

To explore future RLVs, a hypersonic flowfield around a Two-Stage-To-Orbit (TSTO) configuration is analyzed in this paper. This study also demonstrates how CFD, as a powerful tool, can be applied to investigate such a complex flowfield involving a shock/shock interaction and a boundary-layer separation. First, the hypersonic flow around two bodies of the TSTO model has been numerically simulated, and then, the results are validated by comparing with experimental data taken at the UT-Kashiwa Hypersonic Tunnel. Finally, the detailed, computed flowfield is shown to have pairs of streamwise vortices (including horseshoe vortices) with alternating signs of rotation around the TSTO body surfaces.

The vertebral spine is frequently affected by the SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. We report the collective imaging findings of hybrid F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT), as well as bone scans and magnetic resonance imaging, in a patient who had suspected metastatic vertebral bone tumors. 18FDG-PET/CT can be utilized to exclude metastatic vertebral tumors, as well as identifying stable lesions, by demonstrating active inflammatory lesions with accurate anatomic localization through the convergence of the functional information from 18FDG uptake with the anatomic information of CT.

We present the first reported case of Menkes disease caused by an Alu element insertion mutation that interfered with splicing regulatory elements. A whole young AluYa5a2 element, which was 382-bp long, was identified within exon 9 of the ATP7A gene, and all of exon 9 was aberrantly skipped in the cDNA, resulting in severely truncated proteins. To confirm whether the aberrant skipping resulted in Alu insertion, an exonic splicing enhancer finder was used. The Alu element created two new high-score exonic splicing enhancer sequences in the mutation located near the site of the insertion. Exon 9, which encodes the first and second transmembrane domains, is necessary for the normal function of the ATP7A protein.

Supersonic flow fields around Two-Stage-To-Orbit (TSTO) models with different configurations have been experimentally examined in this paper. Four configurations for the orbiter have been considered: A) a hemisphere-cylinder, B) a hemisphere-cylinder with a flat bottom, C) an obliquely truncated circular cylinder, and D) a cone-cylinder. All the flow fields around these models showed complicated shock/shock and shock/boundary-layer interactions, which can be categorized into three patterns, depending on the extent to which the separation shock wave contributes to these interactions. The models B, C and D were proposed to suppress the pressure rise due to the interactions observed in the model A. As a result, the model B showed almost the same interactions as the model A, while in the model C they did not present. In the model D, a large pressure rise was seen in the case with no clearance, whereas the model undergoes the least aerodynamic interaction at a rather large clearance. It is concluded from these results that the model C is less affected by aerodynamic interactions due to the clearance than the other models.

To evaluate the psychological development of patients with congenital central hypoventilation syndrome (CCHS).We performed a questionnaire-based survey of 17 patients with CCHS aged over 7 years and assessed their clinical course, respiratory management, and psychological development.CCHS was present at birth in 15 patients, of which eight presented with respiratory failure with a low Apgar score. Twelve patients required mechanical ventilation with intubation, and five received mask ventilation. All patients with intubation underwent tracheostomy between 1 and 12 months of age (median 5.5 months), and most of them had associated conditions such as Hirschsprung disease. Four of 12 patients with intubation were eventually switched to mask ventilation and one to diaphragm pacing and mask ventilation. The patients undergoing mask ventilation had relatively milder disease severity and had fewer complications than did the patients with intubation. The psychological development of patients who received tracheostomy ranged from normal to severe retardation. Retardation was more likely to be severe in patients who received tracheostomy in late infancy. All patients who received mask ventilation experienced borderline to moderate psychological retardation. This effect could be attributed to poor compliance with mask fitting.Our findings suggest that the psychological development of CCHS patients was influenced by hypoxia; tracheostomy and strict respiratory management since the neonatal period were needed for neurological protection.

Background Necroptosis is a newly identified type of programmed cell death that differs from apoptosis. Recent studies have demonstrated that necroptosis is involved in multiple pathologies of various human diseases. Receptor-interacting protein 3 (RIP3) is known to be a critical regulator of necroptosis. This study investigated alterations in the RIP3 expression and the involvement in neural tissue damage after spinal cord injury (SCI) in mice. Results Immunohistochemical analysis demonstrated that the RIP3 expression was significantly increased in the lesion site after spinal cord hemisection. The increased expression of RIP3 started at 24 h, peaked at 3 days and lasted for at least 21 days after hemisection. The RIP3 expression was observed in neurons, astrocytes and oligodendrocytes. Western blot analysis also demonstrated the RIP3 protein expression significantly upregulated in the injured spinal cord. RIP3 staining using propidium iodide (PI)-labeled sections showed most of the PI-labeled cells were observed as RIP3-positive. Double staining of TUNEL and RIP3 demonstrated that TUNEL-positive cells exhibiting shrunken or fragmented nuclei, as generally observed in apoptotic cells, rarely expressed RIP3. Conclusions The present study first demonstrated that the expression of RIP3 is dramatically upregulated in various neural cells in the injured spinal cord and peaked at 3 days after injury. Additionally, most of the PI-labeled cells expressed RIP3 in response to neural tissue damage after SCI. The present study suggested that the upregulation of the RIP3 expression may play a role as a novel molecular mechanism in secondary neural tissue damage following SCI. However, further study is needed to clarify the specific molecular mechanism underlying the relationship between the RIP3 expression and cell death in the injured spinal cord.

BACKGROUND Failure of inserted anchors has been recognized as one of the major pathomechanisms of re-tearing after rotator cuff repair. OBJECTIVE To predict the inserted anchor failure using CT-based 3-dimensional finite element method (CT/3D-FEM). METHODS Among twenty patients who underwent rotator cuff repair, 5 had anchor failure (failed anchor group) and 15 had no anchor failure (stable anchor group). A 3D model of proximal humerus was developed for each patient based on the CT data. A virtual pullout testing of TWINFIX™ anchors inserted into bone at 6 different sites was performed using FEM. Then, mean failure load of 6 anchors for each patient was compared between two groups. Moreover, an optimal cut-off value of the mean failure load was determined for predicting anchor failure. RESULTS The mean failure load in the failed anchor group (70.3 N) was significantly lower than that in the stable anchor group (119.0 N; p

Purpose. To evaluate the safety and effectiveness of one-stage lateral rhachotomy and posterior fusion with compression hooks, for the treatment of Pott's paralysis in the elderly. Methods. 11 elderly patients underwent lateral rhachotomy (costotransversectomy and pediculectomy) to debride the tuberculosis focus extending into the epidural space and to decompress the spinal cord. After debridement, the interbody cavity was packed with autologous iliac bone chips. For stabilisation, posterior fusion was performed using a compression lamina hook system. Patients were followed up for at least 2 years for complications. Neurological status was assessed using the Frankel score. The kyphotic deformity was measured on lateral radiographs taken before surgery and at follow-up. Results. During separation of the adhesion around the abscess, a dural tear occurred in one patient and a pleural tear in another. Both tears were successfully repaired. One patient had mild pneumonia after surgery. The Frankel scores of the 11 patients improved from C or D before surgery to D or E after surgery. No relapse of spinal tuberculosis was encountered. The mean deformity angle was 25.5 degrees before surgery and 23.2 degrees at the final follow-up. Spinal fusion was achieved in all patients. Conclusion. Without the need of thoracotomy, one-stage lateral rhachotomy with posterior spinal fusion using compression hooks was an effective option for treating Pott's paralysis in the elderly.

Background: Patients with encephalopathy heralded by a prolonged seizure as the initial symptom often have abnormal subcortical white matter on diffusion-weighted MRI (DWI). Objective: To determine if these patients share other common features. Methods: Patients with encephalopathy heralded by a prolonged seizure and followed by the identification of abnormal subcortical white matter on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. Results: Seventeen patients were identified, ages 10 months to 4 years. All had a prolonged febrile seizure (longer than 1 hour in 12 patients) as their initial symptom. Subsequent seizures, most often in clusters of complex partial seizures, were seen 4 to 6 days after the initial seizure in 16 patients. Outcome ranged from almost normal to severe mental retardation. MRI performed within 2 days of presentation showed no abnormality. Subcortical white matter lesions were observed on DWI between 3 and 9 days in all 17 patients. T2-weighted images showed linear high intensity of subcortical U fibers in 13 patients. The lesions were predominantly frontal or frontoparietal in location with sparing of the perirolandic region. The diffusion abnormality disappeared between days 9 and 25, and cerebral atrophy was detected later than 2 weeks. Three patients having only frontal lesions had relatively good clinical outcome. Conclusions: Although the pathophysiologic mechanism remains unknown, these patients seem to have a distinctive encephalopathy syndrome. MRI is helpful in establishing the diagnosis of this encephalopathy.

Thoracic myelopathy is defined as spinal cord compression in the thoracic region, leading to sensory and motor dysfunctions in the trunk and lower extremities, and can be caused by various degenerative processes of the spine. Thoracic myelopathy is rare, and there are many unsolved problems including its epidemiological and clinical features. We have established a registration system of spinal surgeries, which covered almost all surgeries in Miyagi Prefecture, and enrolled the data of 265 patients with thoracic myelopathy from 1988 to 2002. The annual rate of surgery gradually increased and averaged 0.9 per 100,000 inhabitants, which was less than 1/10 of that for cervical myelopathy. About 20 patients with thoracic myelopathy are operated on in Miyagi Prefecture each year. It frequently develops in middle-aged males. About half of the cases were caused by ossification of the ligamentum flavum, followed by ossification of the posterior longitudinal ligament, intervertebral disc herniation and posterior spur. Patients usually noticed numbness or pain in the legs and the preoperative duration was long, averaging 2 years. Its symptomatic similarities to lumbar disorders might cause difficulty in making a correct diagnosis. Since thoracic myelopathy can markedly restrict the activities of daily life, even general physicians should recognize this entity.

There have been several pathologic descriptions of the spinal cord compressed chronically. Microglial changes, however, have been described scarcely. In the present study, microglial responses to the anterior unilateral compression were investigated by immunohistochemistry in the rabbit model. The cervical spinal cord was unilaterally compressed with a small screw at C5. The microglial response in the compressed and the contralateral halves of the spinal cord were investigated after 48 hours with the lectin RCA-1 immunostaining. Microglia were classified morphologically into resting and reactive microglia. Under mild compression, the mild proliferation of reactive microglia was observed in the anterior horn of the compressed half. A few reactive microglia were observed in the anterior horn of the contralateral half. The total number of resting and reactive microglia in each area of the gray and white matters did not differ between the sham and mild compression groups. Under severe compression, marked proliferation of reactive microglia was observed around the cavity in the gray matter of the compressed half. Moderate proliferation of reactive microglia was observed in gray matter of the contralateral half. These findings suggested that the resting microglia transformed into the reactive microglia, but not proliferated in the early stage of compression myelopathy.

We report a mild form of lissencephaly or a pachygyric brain in a girl with microcephalic osteodysplastic primordial 'dwarfism' (MOPD) type II. She was born with severe intrauterine growth failure. A diagnosis of MOPD type II was warranted by persistent postnatal growth failure, microcephaly with a Seckel-like facial appearance, and distinctive radiological findings, including overtubulation of the long bones, metaphyseal cupping of the distal femora, and brachyphalangy with ivory epiphyses. Brain MRI showed thickened cerebral cortices with few and large gyri, most prominently in the frontal and posterior temporal regions. The Sylvian fissures developed incompletely, and the posterior horns of the lateral ventricle were dilated (colpocephaly). Despite the severe imaging findings, she showed only mild retardation of psychomotor development. To date, only minor brain malformations have attracted attention in MOPD type II. Our experience may suggest a wider spectrum of brain anomalies in this entity.

West症候群に対するACTH療法中の副反応予防対策の現状についてアンケート調査を行った。日本小児神経学会評議員の所属する113施設に対し、アンケート調査を質問紙により行った。今回は、ACTHの減量中止の要否とその理由、感染予防・低K血症・脳退縮に対する対応について検討した。51施設から有効回答を得た。ACTHの漸減中止は、42施設で実施されており、35施設で必要と考えていた。必要と考える理由は、視床下部・下垂体・副腎系の機能不全などの内分泌的理由が最多であった。感染予防の配慮を行っているのは34施設であった。モニタリング以外の低K血症に対する介入は19施設で実施されていた。脳退縮への対応は46施設で行われていた。ACTH療法の副反応に対する予防対策は施設間で大きく異なっていた。ACTH療法を適切に施行するためには、副反応予防対策の標準化が必要であると思われた。

To study the pathophysiologic mechanism of astatic seizures in a patient with myoclonic astatic epilepsy of early childhood, ictal magnetoencephalography was recorded and the neuronal pathway involved was analyzed. The patient was a 12-year-old female who developed myoclonic and astatic seizures including nodding and sudden falling at the age of 4. The current source of spikes during nodding attacks was located in the bilateral frontal area with left predominance, possibly in the premotor cortex. Although we could not claim, on the basis of our findings, that myoclonic astatic epilepsy of early childhood is a type of focal epilepsy, it seems likely that the premotor cortex might be more excitable than other areas. Thus we speculate that the functionally altered premotor-reticulospinal tract which normally controls postural adjustment might play an important role in the generation of myoclonic astatic seizures. Furthermore, the underlying mechanism in the brainstem seems to be common, at least in part, for infantile spasms when considering the efficacy of synthetic adrenocorticotropic hormone for nodding seizures.

In myelopathy, unilateral compression of the spinal cord in cases of disc herniation would be expected to produce Brown-Séquard syndrome. However, a transverse lesion syndrome occurs in most clinical cases. In order to reveal the mechanism by which unilateral compression induces transverse damage to the spinal cord, damage of the gray and white matter in each half of the spinal cord were evaluated quantitatively to determine the density of GFAP-positive astrocytes. The cervical spinal cord in rabbits was unilaterally compressed with a small screw. The area of each half of the damaged cord and the density of GFAP-positive astrocytes of the compressed and contralateral halves were investigated one week after the surgery. No apparent paralysis was observed during the period of observation. As the compression increased, the area of the compressed half of the spinal cord decreased significantly compared to the contralateral half. The densities of GFAP-positive astrocytes in the gray matter and the anterior funiculus increased significantly in the compressed half. There were no significant differences in the densities at the lateral and dorsal funiculi between the compressed and contralateral halves. The tissue damage in the gray matter of the compressed half was markedly higher. No significant difference between the two halves in damage was seen in the lateral funiculus, where in the lateral pyramidal and the dorsal spinocerebellar tracts are found. These findings provide evidence of the mechanistic basis for the spinal cord damage that leads to transverse lesion syndrome in unilateral compression myelopathy.

This female patient was the second-born child to nonconsanguinous, healthy parents. The first child, her elder brother, had respiratory distress and metabolic acidosis at 3 days of age, and died at 5 days. After an uneventful gestation for 39 weeks, this patient was born by normal delivery. Immediately after birth, she weighed 2608 g and looked well. Twenty-one hours later, however, she became dyspneic and underwent mechanical ventilation until 8 days of age. Blood examination revealed severe lactic acidosis (pH 6.97, PaCO 2 23 mmHg, base excess 26 mEq/ l, lactate 135 mg/dL), which was treated with sodium bicarbonate and thiamine. Despite improvement of her general condition, metabolic acidosis persisted. At the age of 1 month, lactate and pyruvate levels were 36.8 and 1.80 mg/dL in the blood (normal values, 7.0–25.0 and 0.6– 1.35 mg/dL), and 51.1 and 2.77 mg/dL in the cerebrospinal fluid (normal values, 11.1–16.3 and 0.75–1.29 mg/dL), respectively. An analysis of mitochondrial DNA (mtDNA) of the peripheral blood cells disclosed a T-to-G mutation at nucleotide position 8993. When she was discharged at 2 months of age, she was unresponsive to environmental stimuli, and had spastic paraplegia. She began to follow objects with her eyes at 2 months, to show social smile at 3 months, to control her head at 5 months, to roll over at 7 months, and to sit unsupported at 7 months. Cranial MRI at 4 months of age showed no abnormal signals in the brain. After 8 months of age, she showed no further development. She smiled less frequently than previously. Dysphagia and stridor became more prominent. Ubidecarenone and levocarnitine were prescribed. MRI at 10 months of age showed T 1 and T 2 prolongation of the bilateral putamina, caudate nuclei, periaqueductal gray matter, and substantia nigra (Fig. 1). Spastic tetraparesis worsened. At 10.5 months, sudden appearance of nystagmus was followed by difficulty in sucking milk, loss of smile and other responses, and irregular respiration. When she was admitted again, she showed deep coma, no spontaneous movements, and minimal response to painful stimuli. The pupils were meiotic and unresponsive to light. There were marked muscle hypotonia and positive pathological reflexes. Blood examination showed lactic acidosis (pH 7.44, PaCO 2 21 mmHg, base excess 8 mEq/l, lactate 72.3 mg/dL, pyruvate 2.05 mg/dL). Despite mechanical ventilation, and administration of sodium dichloroacetate and cytochrome C, her condition deteriorated further with intercurrent pneumonia, appearance of mydriasis, and loss of spontaneous respiration. Cranial computed tomography showed hypodensity of the entire brain. Electroencephalogram and auditory evoked response showed a total loss of electrical activity. Two weeks later, she died at the age of 11 months.