Faculty Profiles - NAKASHIMA Hiroaki

Papers - NAKASHIMA Hiroaki

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Lumbar Thecal Sac Dimensions and Axial Spinal Cord Areas on Magnetic Resosnace Imaging in 626 Healthy Subjects

Nakashima, H; Ito, K; Katayama, Y; Matsumoto, T; Tsushima, M; Ando, K; Kobayashi, K; Machino, M; Imagama, S

SPINE Vol. 46 ( 24 ) page： E1327 - E1333 2021.12

Language：English Publisher：Spine

Study Design. A cross-sectional study. Objective. The aim of this study was to investigate the lumbar thecal sac dimensions and spinal cord area on magnetic resonance (MR) imaging in healthy volunteers. Summary of Background Data. There are few reports regarding lumbar spine MRI in healthy subjects, and the difference in spinal canal dimensions by age remains unclear. Methods. A total of 629 healthy volunteers were enrolled, including ≥50 males, females, and subjects in each of the 20s to 70s age decades. The anteroposterior and transverse diameters of the thecal sac and axial areas of the thecal sac and spinal cord were measured at the disc levels on T2-weighted axial MR images. The anteroposterior-to-transverse ratio of the thecal sac (APTR) was calculated. Results. The thecal sac area from T12/L1 to L4/5 was reduced in older age group, but there was no significant difference in L5/ S1. The thecal sac area was significantly reduced in older age group: 89.9%, 86.0%, 84.6%, 80.3% at T12/L1, L1/2, L2/3, and L3/4, respectively, and 79.9% at L4/5 in subjects in their 70 s relative to that in subjects in their 20 s. The APTR was significantly reduced in older age group from T11/12 to L2/L3 in males and at T10/11, L3/4 and from T11/12 to L2/3 in females. Narrow thecal sac areas <80mm<sup>2</sup> were found in 10 subjects. The spinal cord area was significantly reduced in older age group at T10/11 in males and at T9/10, T10/11, and T11/12 in females. The area was 92.0% at T10/11 in subjects in their 70s relative to the area of subjects in their 20s. Conclusion. The thecal sac area was reduced in older age group from T12/L1 to L4/5, and the thecal sac area was reduced in the anteroposterior and all directions in the upper and lower lumbar area in age group, respectively. Approximately, 3.0% of healthy population in their 50s or older will have severe asymptomatic stenosis.

DOI： 10.1097/BRS.0000000000004143

Comparison of Surgical Outcomes After Open- and Double-Door Laminoplasties for Patients with Cervical Ossification of the Posterior Longitudinal Ligament <i>A Prospective Multicenter Study</i> Reviewed

Nagoshi, N; Yoshii, T; Egawa, S; Sakai, K; Kusano, K; Nakagawa, Y; Hirai, T; Wada, K; Katsumi, K; Fujii, K; Kimura, A; Furuya, T; Kanchiku, T; Nagamoto, Y; Oshima, Y; Nakashima, H; Ando, K; Takahata, M; Mori, K; Nakajima, H; Murata, K; Matsunaga, S; Kaito, T; Yamada, K; Kobayashi, S; Kato, S; Ohba, T; Inami, S; Fujibayashi, S; Katoh, H; Kanno, H; Watanabe, K; Imagama, S; Koda, M; Kawaguchi, Y; Takeshita, K; Nakamura, M; Matsumoto, M; Yamazaki, M; Okawa, A

SPINE Vol. 46 ( 23 ) page： E1238 - E1245 2021.12

Language：English Publisher：Spine

Study Design.A prospective multicenter study.Objective.To evaluate and compare the surgical outcomes after open-door (OD) and double-door (DD) laminoplasties in subjects with cervical ossification of the posterior longitudinal ligament (OPLL).Summary of Background Data.Although previous studies compared clinical results after OD and DD laminoplasties, they were performed at a single institution with a relatively small sample size targeting mixed pathologies, including cervical spondylotic myelopathy.Methods.This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of these, 41 and 164 patients received OD and DD laminoplasties, respectively. Demographic information, medical history, and imaging findings were collected. Clinical outcomes were assessed using the cervical Japanese Orthopaedic Association, Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, and visual analog scale scores.Results.Age, sex, symptom duration, and comorbidities were not significantly different between the groups. Segmental ossification was the most frequent in both the groups. No significant differences in K-line type, canal occupying ratio, C2 to C7 angles, and range of motion were found. Both the procedures reduced the cervical range of motion postoperatively. A comparable frequency of perioperative complications was observed between the groups. The cervical Japanese Orthopaedic Association scores showed a similar improvement at 2 years postopera- tively. The reduction in visual analog scale score for neck pain was favorable in the OD group (P = 0.02), while other pain assessments did not show any significant differences between the groups. The functional outcomes assessed using the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire presented equivalent effective rates.Conclusion.The results demonstrated almost comparable surgical outcomes between OD and DD laminoplasties. Lamino- plasty is a valuable technique as a therapeutic option for cervical OPLL.Level of Evidence: 2.

DOI： 10.1097/BRS.0000000000004094

Comparison of Outcomes between Minimally Invasive Lateral Approach Vertebral Reconstruction Using a Rectangular Footplate Cage and Conventional Procedure Using a Cylindrical Footplate Cage for Osteoporotic Vertebral Fracture Open Access

Segi, N; Nakashima, H; Kanemura, T; Satake, K; Ito, K; Tsushima, M; Tanaka, S; Ando, K; Machino, M; Ito, S; Yamaguchi, H; Koshimizu, H; Tomita, H; Ouchida, J; Morita, Y; Imagama, S

JOURNAL OF CLINICAL MEDICINE Vol. 10 ( 23 ) 2021.12

Language：English Publisher：Journal of Clinical Medicine

The aim of the current study was to compare outcomes between lateral access vertebral reconstruction (LAVR) using a rectangular footplate cage and the conventional procedure using a cylindrical footplate cage in patients with osteoporotic vertebral fracture (OVF). We included 46 patients who underwent anterior–posterior combined surgery for OVF: 24 patients underwent LAVR (Group L) and 22 underwent the conventional procedure (Group C). Preoperative, postoperative, and 1‐ and 2‐year follow‐up X‐ray images were used to measure local lordotic angle, correction loss, and cage subsidence (>2 mm in vertebral endplate depression). In anterior surgery, the operation time was significantly shorter (183 vs. 248 min, p < 0.001) and the blood loss was significantly less (148 vs. 406 mL, p = 0.01) in Group L than in Group C. In Group C, two patients had anterior instrumentation failure. Correction loss was significantly smaller in Group L than in Group C (1.9° vs. 4.9° at 1 year, p = 0.02; 2.5° vs. 6.5° at 2 years, p = 0.04, respectively). Cage subsidence was significantly less in Group L than in Group C (29% vs. 80%, p < 0.001). LAVR using a rectangular footplate cage is an effective treatment for OVF to minimize surgical invasiveness and postoperative correction loss.

DOI： 10.3390/jcm10235664

Does pulmonary function improve after surgical correction of adult idiopathic scoliosis? Reviewed

Nakashima, H; Kawakami, N; Ohara, T; Saito, T; Tauchi, R; Imagama, S; Redding, GJ

SPINE DEFORMITY Vol. 9 ( 6 ) page： 1609 - 1616 2021.11

Language：English Publisher：Spine Deformity

Purpose: The aim was to investigate pulmonary function after surgical correction of adult idiopathic scoliosis. Methods: This study included 146 adult scoliosis patients aged 20–50 years (main curve in thoracic spine). Respiratory function was assessed as predicted forced vital capacity (%FVC) and the ratio of forced expiratory volume in 1 s / FVC (%FEV<inf>1</inf>) preoperatively and 2 years postoperatively and classified as a normal function (≥ 80%), mild impairment (≥ 65% and < 80%), and moderate impairment (< 65%). Results: Preoperative %FVC and %FEV<inf>1</inf> were 85.3% and 85.4%, which were 81.5% and 87.5% at 2 years post-surgery. The preoperative %FVC was mild and moderate in 39 (26.7%) and 12 patients (11.6%), respectively. The %FVC significantly improved (+ 6.2% ± 11.4%, P < 0.001) postoperatively for moderate severity but significantly decreased postoperatively (− 6.4% ± 9.4%, P < 0.001) for normal function. The preoperative %FEV<inf>1</inf> was mild and moderate in 27 (18.5%) and 0 patients, respectively. The %FEV1 significantly improved postoperatively (6.3% ± 5.3%, P < 0.001) for mild severity but did not significantly change for normal severity. Twenty-three (15.8%) and 41 (28.1%) patients showed improved ⊿%FVC and ⊿% FEV<inf>1</inf> > 5%. Logistic regression analysis showed that preoperative %FVC and %FEV<inf>1</inf> severities were independent factors affecting postoperative recovery of %FVC (OR 0.95) and %FEV<inf>1</inf> (OR 0.85). Conclusion: Pulmonary function improved in patients with preoperative pulmonary impairment of < 65% in %FVC and < 80% in %FEV<inf>1</inf>, and the real improvement was limited to patients with severe preoperative impairment.

DOI： 10.1007/s43390-021-00379-3

Factors Significantly Associated with Postoperative Neck Pain Deterioration after Surgery for Cervical Ossification of the Posterior Longitudinal Ligament: Study of a Cohort Using a Prospective Registry Open Access

Koda, M; Yoshii, T; Egawa, S; Sakai, K; Kusano, K; Nakagawa, Y; Hirai, T; Wada, K; Katsumi, K; Kimura, A; Furuya, T; Maki, S; Nagoshi, N; Watanabe, K; Kanchiku, T; Nagamoto, Y; Oshima, Y; Ando, K; Nakashima, H; Takahata, M; Mori, K; Nakajima, H; Murata, K; Matsunaga, S; Kaito, T; Yamada, K; Kobayashi, S; Kato, S; Ohba, T; Inami, S; Fujibayashi, S; Katoh, H; Kanno, H; Takahashi, H; Fujii, K; Miyagi, M; Inoue, G; Takaso, M; Imagama, S; Kawaguchi, Y; Takeshita, K; Nakamura, M; Matsumoto, M; Okawa, A; Yamazaki, M

JOURNAL OF CLINICAL MEDICINE Vol. 10 ( 21 ) 2021.11

Language：English Publisher：Journal of Clinical Medicine

Postoperative neck pain has been reported as an unsolved postoperative complication of surgery for cervical ossification of the posterior longitudinal ligament (OPLL). The aim of the present study was to elucidate factors having a significant association with postoperative deterioration of neck pain in cervical OPLL patients. We studied a cohort of patients in a prospective registry of 478 patients who had undergone cervical spine surgery for cervical OPLL. We excluded those without evaluation of preoperative neck pain. Therefore, 438 patients were included in the present study. Neck pain was evaluated with the visual analogue scale (VAS, 0–100 mm). Postoperative neck pain deterioration was defined as a ≥20 mm increase of VAS neck pain. Patient factors, neurological status, imaging factors and surgical factors were assessed. Univariate analyses followed by multivariate analysis using stepwise logistic regression was performed. Six months after surgery, 50 (11.6%) patients showed postoperative neck pain deterioration and 76 (17.4%) patients showed postoperative neck pain deterioration 2 years after surgery. Six months after surgery, the rate of neck pain deterioration was significantly higher in patients who had undergone posterior surgery. Two years after surgery, the number of levels fused was significantly correlated with neck pain deterioration.

DOI： 10.3390/jcm10215026

Relationship between use of sleep medication and accidental falls during hospitalization Open Access

Kobayashi, K; Ando, K; Nakashima, H; Suzuki, Y; Nagao, Y; Imagama, S

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 83 ( 4 ) page： 851 - 860 2021.11

Language：English Publisher：Nagoya Journal of Medical Science

Falls are common in elderly patients, and prevention of fall is important for safety and for reduction of health care costs. Sleep medications are among many potential causes of fall. In this study, we examined relationship of sleep medication with fall from January 2017 to December 2017. 726 falls occurred in 442 patients, and the average age at the time of fall was 60.7 ± 23.8 years. Fall was most common in patients with neurological disease, followed by gastroenterological, ophthalmological, respiratory, and orthopedic conditions. Sleep medication was used in 223 falls (31%). Fall occurred at all times of day, but with a different distribution in patients with and without use of sleep medication. Thus, the rate of falls from 22:00 to 6:00 was significantly higher in patients using sleep medication (62% vs. 18%, p<0.01). There was also a significantly higher rate of multiple falls in patient using sleep medication (p<0.01). Zolpidem (25%, n=63), a non-benzodiazepine, was the most frequently used sleep medication, followed by brotizolam (16%, n=41) and etizolam (13%, n=32), which are both benzodiazepines. Multiple falls from 22:00 to 6:00 occurred significantly more frequently in patients using ≥2 types of sleep medications compared to one (53% vs. 17%, p<0.01). Taking multiple sleeping pills makes it easier to fall, and even drugs with a short half-life, which are considered to be safe, can cause falls at night in elderly patients. The results of this study show that careful selection of sleep medications is required to prevent fall in elderly patients.

DOI： 10.18999/nagjms.83.4.851

Relationship of frequency of participation in a physical checkup and physical fitness in middle-aged and elderly people: the Yakumo study Open Access

Kobayashi, K; Ando, K; Nakashima, H; Machino, M; Kanbara, S; Ito, S; Inoue, T; Yamaguchi, H; Koshimizu, H; Segi, N; Hasegawa, Y; Imagama, S

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 83 ( 4 ) page： 841 - 850 2021.11

Language：English Publisher：Nagoya Journal of Medical Science

An annual physical checkup is provided as part of the long-term Yakumo study. The checkup is voluntary and there is variation in the frequency of participation. The aim of this study was to examine relationship of physical fitness with frequency of participation in this checkup. The subjects had all attended at least one annual physical checkup from 2006 to 2018. Data from 1,804 initial checkups were used for analysis. At the checkups, age, gender, height, weight, body mass index (BMI), and bone mineral density (BMD) were recorded, and physical activity was measured. The average number of physical checkups per participant for 13 years was 2.4 (1–13). Daily exercise habits were found to be significantly associated with higher participation in physical checkups. Furthermore, between groups with low (1–5 times; <90th percentile of participants) and high (≥6 times) participation, weight and BMI were significantly higher, and BMD, grip strength, 10-m gait time, back muscle strength, and two-step test were all significantly lower in the group with lower frequency of participation in the checkup. In conclusions, our results show that frequency of participation in a voluntary annual physical checkup is significantly associated with physical fitness in middle-aged and elderly people.

DOI： 10.18999/nagjms.83.4.841

Evaluation of the Association between Neck Pain and the Trapezius Muscles in Patients with Cervical Myelopathy Using Motor Evoked Potential: A Retrospective Study Open Access

Ito, S; Sakai, Y; Harada, A; Ando, K; Kobayashi, K; Nakashima, H; Machino, M; Kambara, S; Inoue, T; Hida, T; Ito, K; Ishiguro, N; Imagama, S

ASIAN SPINE JOURNAL Vol. 15 ( 5 ) page： 604 - 610 2021.10

Language：English Publisher：Asian Spine Journal

Study Design: Retrospective study.Purpose: We aimed to use motor evoked potentials (MEPs) to examine the association of electrophysiological assessment of thetrapezius muscle with neck pain.Overview of Literature: Previous reports on the association of neck pain with the trapezius muscle have focused on surface electromyogramsand muscle oxygenation; however, to our knowledge, none of these studies included detailed data on MEPs.Methods: The study included 100 patients with cervical myelopathy who underwent surgery at the National Center for Geriatrics andGerontology in Obu, Japan from June 2010 to March 2013. Before the surgery, neck pain was evaluated using a Visual Analog Scale(a score ≥50 indicated neck pain and a score <50 indicated no neck pain). The preoperative cross-sectional areas of the trapeziusmuscles were measured with cervical magnetic resonance imaging sagittal T2-weighted images. Cranial stimulation under generalanesthesia was used to derive the MEPs, enabling the measurement of latency and amplitude, using preoperative MEPs of the trapeziusmuscles.Results: The MEP of the trapezius muscle in patients with neck pain had significantly shorter latencies than those in patients whodid not have neck pain. However, there was no significant difference in the amplitude between patients with and without neck pain.However, this tended to be greater in patients with neck pain as compared to that in those without neck pain. The cross-sectionalarea of the trapezius muscle in patients with neck pain was significantly smaller than that in those who did not have neck pain.Conclusions: MEPs revealed electrophysiological abnormalities of the trapezius muscles in patients with neck pain, supporting arelationship of neck pain with the trapezius muscles

DOI： 10.31616/asj.2020.0186

Association between Severity of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of Other Spinal Ligaments in Patients with Ossification of the Posterior Longitudinal Ligament Open Access

Nishimura, S; Hirai, T; Nagoshi, N; Yoshii, T; Hashimoto, J; Mori, K; Maki, S; Katsumi, K; Takeuchi, K; Ushio, S; Furuya, T; Watanabe, K; Nishida, N; Kaito, T; Kato, S; Nagashima, K; Koda, M; Nakashima, H; Imagama, S; Murata, K; Matsuoka, Y; Wada, K; Kimura, A; Ohba, T; Katoh, H; Watanabe, M; Matsuyama, Y; Ozawa, H; Haro, H; Takeshita, K; Matsukura, Y; Inose, H; Yamazaki, M; Watanabe, K; Matsumoto, M; Nakamura, M; Okawa, A; Kawaguchi, Y

JOURNAL OF CLINICAL MEDICINE Vol. 10 ( 20 ) 2021.10

Language：English Publisher：Journal of Clinical Medicine

Background: Although diffuse idiopathic skeletal hyperostosis (DISH) is known to coexist with the ossification of spinal ligaments (OSLs), details of the radiographic relationship remain unclear. Methods: We prospectively collected data of 239 patients with symptomatic cervical ossification of the posterior longitudinal ligament (OPLL) and analyzed the DISH severity on whole-spine computed tomography images, using the following grades: grade 0, no DISH; grade 1, DISH at T3–T10; grade 2, DISH at both T3–T10 and C6–T2 and/or T11–L2; and grade 3, DISH beyond C5 and/or L3. Ossification indices were calculated as the sum of vertebral and intervertebral levels with OSL for each patient. Results: DISH was found in 107 patients (44.8%), 65 (60.7%) of whom had grade 2 DISH. We found significant associations of DISH grade with the indices for cervical OPLL (r = 0.45, p < 0.0001), thoracic ossification of the ligamentum flavum (OLF; r = 0.41, p < 0.0001) and thoracic ossification of the supra/interspinous ligaments (OSIL; r = 0.53, p < 0.0001). DISH grade was also correlated with the index for each OSL in the whole spine (OPLL: r = 0.29, p < 0.0001; OLF: r = 0.40, p < 0.0001; OSIL: r = 0.50, p < 0.0001). Conclusion: The DISH grade correlated with the indices of OSL at each high-prevalence level as well as the whole spine.

DOI： 10.3390/jcm10204690

Zonisamide upregulates neuregulin-1 expression and enhances acetylcholine receptor clustering at the in vitro neuromuscular junction Reviewed

Inoue, T; Ohkawara, B; Bushra, S; Kanbara, S; Nakashima, H; Koshimizu, H; Tomita, H; Ito, M; Masuda, A; Ishiguro, N; Imagama, S; Ohno, K

NEUROPHARMACOLOGY Vol. 195 page： 108637 2021.9

Language：English Publisher：Neuropharmacology

Decreased acetylcholine receptor (AChR) clustering compromises signal transmission at the neuromuscular junction (NMJ) in myasthenia gravis, congenital myasthenic syndromes, and motor neuron diseases. Although the enhancement of AChR clustering at the NMJ is a promising therapeutic strategy for these maladies, no drug is currently available for this enhancement. We previously reported that zonisamide (ZNS), an anti-epileptic and anti-Parkinson's disease drug, enhances neurite elongation of the primary spinal motor neurons (SMNs). As nerve sprouting occurs to compensate for the loss of AChR clusters in human diseases, we examined the effects of ZNS on AChR clustering at the NMJ. To this end, we established a simple and quick co-culture system to reproducibly make in vitro NMJs using C2C12 myotubes and NSC34 motor neurons. ZNS at 1–20 μM enhanced the formation of AChR clusters dose-dependently in co-cultured C2C12 myotubes but not in agrin-treated single cultured C2C12 myotubes. We observed that molecules that conferred responsiveness to ZNS were not secreted into the co-culture medium. We found that 10 μM ZNS upregulated the expression of neuregulin-1 (Nrg1) in co-cultured cells but not in single cultured C2C12 myotubes or single cultured NSC34 motor neurons. In accordance with this observation, inhibition of the Nrg1/ErbB signaling pathways nullified the effect of 10 μM ZNS on the enhancement of AChR clustering in in vitro NMJs. Although agrin was not induced by 10 μM ZNS in co-cultured cells, anti-agrin antibody attenuated ZNS-mediated enhancement of AChR clustering. We conclude that ZNS enhances agrin-dependent AChR-clustering by upregulating the Nrg1/ErbB signaling pathways in the presence of NMJs.

DOI： 10.1016/j.neuropharm.2021.108637

Associations between Clinical Findings and Severity of Diffuse Idiopathic Skeletal Hyperostosis in Patients with Ossification of the Posterior Longitudinal Ligament Open Access

Hirai, T; Nishimura, S; Yoshii, T; Nagoshi, N; Hashimoto, J; Mori, K; Maki, S; Katsumi, K; Takeuchi, K; Ushio, S; Furuya, T; Watanabe, K; Nishida, N; Watanabe, K; Kaito, T; Kato, S; Nagashima, K; Koda, M; Nakashima, H; Imagama, S; Murata, K; Matsuoka, Y; Wada, K; Kimura, A; Ohba, T; Katoh, H; Watanabe, M; Matsuyama, Y; Ozawa, H; Haro, H; Takeshita, K; Matsumoto, M; Nakamura, M; Yamazaki, M; Matsukura, Y; Inose, H; Okawa, A; Kawaguchi, Y

JOURNAL OF CLINICAL MEDICINE Vol. 10 ( 18 ) 2021.9

Language：English Publisher：Journal of Clinical Medicine

Background: This study investigated how diffuse idiopathic skeletal hyperostosis (DISH) influences clinical characteristics in patients with cervical ossification of the posterior longitudinal ligament (OPLL). Although DISH is considered unlikely to promote neurologic dysfunction, this relationship remains unclear. Methods: Patient data were prospectively collected from 16 Japanese institutions. In total, 239 patients with cervical OPLL were enrolled who had whole-spine computed tomography images available. The primary outcomes were visual analog scale pain scores and the results of other self-reported clinical questionnaires. Correlations were sought between clinical symptoms and DISH using the following grading system: 1, DISH at T3-T10; 2, DISH at both T3–10 and C6–T2 and/or T11–L2; and 3, DISH beyond the C5 and/or L3 levels. Results: DISH was absent in 132 cases, grade 1 in 23, grade 2 in 65, and grade 3 in 19. There were no significant correlations between DISH grade and clinical scores. However, there was a significant difference in the prevalence of neck pain (but not in back pain or low back pain) among the three grades. Interestingly, DISH localized in the thoracic spine (grade 1) may create overload at the cervical spine and lead to neck pain in patients with cervical OPLL. Conclusion: This study is the first prospective multicenter cross-sectional comparison of subjective outcomes in patients with cervical OPLL according to the presence or absence of DISH. The severity of DISH was partially associated with the prevalence of neck pain.

DOI： 10.3390/jcm10184137

Normative Magnetic Resonance Imaging Data of Age-Related Degenerative Changes in Cervical Disc Morphology

Machino, M; Ito, K; Ando, K; Kobayashi, K; Nakashima, H; Kato, F; Imagama, S

WORLD NEUROSURGERY Vol. 152 page： E502 - E511 2021.8

Language：English Publisher：World Neurosurgery

Objective: Few studies have examined a possible correlation between cervical disc degeneration and disc height. The aim of this study was to establish age-related changes and sex-specific differences of cervical disc height using magnetic resonance imaging (MRI) and to evaluate the relationship between degree of cervical disc degeneration and disc height in asymptomatic subjects. Methods: We measured the intervertebral disc anteroposterior diameter and disc height in each disc level using MRI in 1211 relatively healthy volunteers (606 men and 605 women, mean age 49.5 years). We included at least 100 males and 100 females in each decade of life between the 20s and the 70s. Cervical disc degeneration was defined according to the modified Pfirrmann classification system, and disc index and intervertebral disc height narrowing ratio were evaluated on sagittal plane MRI. Results: Intervertebral disc height decreased gradually with increasing age in both sexes. The grade of disc degeneration significantly increased with age in both sexes at every level. Mild disc degeneration was observed even in subjects their 20s. Disc degeneration occurred around the C5-C6 level. The average disc height decreased with aging after the 40s. Disc index and intervertebral disc height narrowing ratio decreased with a progression in the disc degeneration grade in both sexes. Conclusions: This large-scale cross-sectional analysis of cervical spine MRI data in healthy subjects demonstrated that cervical disc height narrowing progresses with age. Cervical disc height narrowing is highly correlated with the progression of disc degeneration.

DOI： 10.1016/j.wneu.2021.05.123

Age-related degenerative changes and sex-specific differences in osseous anatomy and intervertebral disc height of the thoracolumbar spine Open Access

Machino, M; Nakashima, H; Ito, K; Katayama, Y; Matsumoto, T; Tsushima, M; Ando, K; Kobayashi, K; Imagama, S

JOURNAL OF CLINICAL NEUROSCIENCE Vol. 90 page： 317 - 324 2021.8

Language：English Publisher：Journal of Clinical Neuroscience

The aim of this study was to determine age-related changes and sex-specific differences in sagittal alignment, range of motion (ROM), and intervertebral disc height of the thoracolumbar spine in healthy subjects. Lateral neutral and flexion–extension radiographs of the thoracolumbar spine of 627 asymptomatic subjects (307 males and 320 females; average age, 49.6 ± 16.5 years) were evaluated. We included at least 50 males and 50 females in each decade of life between the 20s and the 70s. Intervertebral disc height from T10/T11 to L5/S1, local lordotic alignment, and ROM from T10–T11 to L5–S1 were measured. T10–L2 kyphosis and T12–S1 lordosis as well as flexion, extension, and total ROM were measured. T10–L2 kyphosis did not markedly change with age in subjects of either sex but a sudden increase was noted in the 70s females. T12–S1 lordosis increased with age in both sexes, except the 70s. Flexion, extension, and total ROM at T10–L2 and T12–S1 decreased with age in most subjects. The levels from L3–L4 to L5–S1 were conspicuous as mobile segments. Intervertebral disc height gradually increased from T10/T11 to L4/L5; the shortest was at T10/T11 and the longest at L3/L4 or L4/L5 in all subjects. Age-related decreases in intervertebral disc height were most prominent at L4/L5 in middle-aged and elderly individuals of both sexes. Normative values of sagittal alignment, ROM, and intervertebral disc height at each segmental level were established in both sexes and all age groups in healthy subjects.

DOI： 10.1016/j.jocn.2021.06.020

Current Advances in Spinal Diseases of the Elderly: Introduction to the Special Issue Open Access

Hirai, T; Uehara, M; Miyagi, M; Takahashi, S; Nakashima, H

JOURNAL OF CLINICAL MEDICINE Vol. 10 ( 15 ) 2021.8

Impact of Diabetes Mellitus on Cervical Spine Surgery for Ossification of the Posterior Longitudinal Ligament Open Access

Kimura, A; Takeshita, K; Yoshii, T; Egawa, S; Hirai, T; Sakai, K; Kusano, K; Nakagawa, Y; Wada, K; Katsumi, K; Fujii, K; Furuya, T; Nagoshi, N; Kanchiku, T; Nagamoto, Y; Oshima, Y; Nakashima, H; Ando, K; Takahata, M; Mori, K; Nakajima, H; Murata, K; Matsunaga, S; Kaito, T; Yamada, K; Kobayashi, S; Kato, S; Ohba, T; Inami, S; Fujibayashi, S; Katoh, H; Kanno, H; Watanabe, K; Imagama, S; Koda, M; Kawaguchi, Y; Nakamura, M; Matsumoto, M; Yamazaki, M; Okawa, A

JOURNAL OF CLINICAL MEDICINE Vol. 10 ( 15 ) 2021.8

Language：English Publisher：Journal of Clinical Medicine

Ossification of the posterior longitudinal ligament (OPLL) is commonly associated with diabetes mellitus (DM); however, the impact of DM on cervical spine surgery for OPLL remains unclear. This study was performed to evaluate the influence of diabetes DM on the outcomes following cervical spine surgery for OPLL. In total, 478 patients with cervical OPLL who underwent surgical treatment were prospectively recruited from April 2015 to July 2017. Functional measurements were conducted at baseline and at 6 months, 1 year, and 2 years after surgery using JOA and JOACMEQ scores. The incidence of postoperative complications was categorized into early (_30 days) and late (>30 days), depending on the time from surgery. From the initial group of 478 patients, 402 completed the 2-year follow-up and were included in the analysis. Of the 402 patients, 127 (32%) had DM as a comorbid disease. The overall incidence of postoperative complications was significantly higher in patients with DM than in patients without DM in both the early and late postoperative periods. The patients with DM had a significantly lower JOA score and JOACMEQ scores in the domains of lower extremity function and quality of life than those without DM at the 2-year follow-up.

DOI： 10.3390/jcm10153375

Characteristics of cases with and without calcification in spinal meningiomas Reviewed

Kobayashi, K; Ando, K; Nakashima, H; Machino, M; Kanbara, S; Ito, S; Inoue, T; Yamaguchi, H; Koshimizu, H; Segi, N; Imagama, S

JOURNAL OF CLINICAL NEUROSCIENCE Vol. 89 page： 20 - 25 2021.7

Language：English Publisher：Journal of Clinical Neuroscience

Purpose: To quantify calcification in spinal meningiomas using Hounsfield unit (HU) values on CT, and to analyze the characteristics of cases with and without calcification and with different histologic subtypes. Methods: The subjects were 53 patients who underwent surgical resection of spinal meningioma between January 1999 and December 2019. Clinical and surgical data were collected, and all patients were examined neurologically preoperatively and at final follow-up using the modified McCormick scale and the American Spinal Injury Association scale. Calcification was quantified on CT of the spine prior to surgery. A HU value >60 was considered to indicate calcification. Results: The 53 patients (11 males, 42 females) were aged 62.4 ± 14.3 (range 19 to 91) years at surgery, and had a symptom duration of 10.8 ± 9.0 (1–36) months. The histological type was meningothelial in 35 cases, psammomatous in 13, and others in 5. The mean tumor volume was 1166 ± 350 (593–2176) mm<sup>3</sup>, and the mean HU value was 212.2 ± 192.8 (43–648). Forty cases (75%) had calcification (HU value > 60). HU values were significantly related to duration of symptoms (R = 0.590, p < 0.05) and significantly higher in psammomatous cases (p < 0.05). Cases with calcification had longer operative times and greater blood loss, and a significantly lower rate of neurological improvement. Conclusion: CT was effective for detecting calcification based on HU values. Detection of a HU value > 60 in spinal meningioma may be useful to narrow the differential diagnosis, evaluate the difficulty of resection, and improve intraoperative management, all of which may improve outcomes.

DOI： 10.1016/j.jocn.2021.04.019

The Level of Conus Medullaris in 629 Healthy Japanese Individuals Reviewed Open Access

Nakashima, H; Ito, K; Katayama, Y; Tsushima, M; Ando, K; Kobayashi, K; Machino, M; Ito, S; Koshimizu, H; Segi, N; Tomita, H; Imagama, S

JOURNAL OF CLINICAL MEDICINE Vol. 10 ( 14 ) 2021.7

Language：English Publisher：Journal of Clinical Medicine

The conus medullaris typically terminates at the L1 level; however, variations in its level and the factors associated with the conus medullaris level are unclear. We investigated the level of conus medullaris on magnetic resonance imaging in healthy volunteers. In total, 629 healthy adult volunteers (≥50 individuals of each sex and in each decade of age from 20 to 70 ) were enrolled. The level of the conus medullaris was assessed based on the T2-weighted sagittal magnetic resonance images, and factors affecting its level were investigated employing multivariate regression analysis including the participants’ background and radiographical parameters. L1 was the most common conus medullaris level. Participant height was significantly shorter in the caudally placed conus medullaris (p = 0.013). With respect to the radiographical parameters, pelvic incidence (p = 0.003), and pelvic tilt (p = 0.03) were significantly smaller in participants with a caudally placed conus medullaris. Multiple regression analysis showed that the pelvic incidence (p < 0.0001) and height (p < 0.0001) were significant factors affecting the conus medullaris level. These results indicated that the length of the spinal cord varies little among individuals and that skeletal differences affect the level of the conus medullaris.

DOI： 10.3390/jcm10143182

Impact of Neck and Shoulder Pain on Health-Related Quality of Life in a Middle-Aged Community-Living Population Open Access

Machino, M; Ando, K; Kobayashi, K; Nakashima, H; Morozumi, M; Kanbara, S; Ito, S; Inoue, T; Koshimizu, H; Seki, T; Ishizuka, S; Takegami, Y; Hasegawa, Y; Imagama, S

BIOMED RESEARCH INTERNATIONAL Vol. 2021 page： 6674264 2021.6

Language：English Publisher：Biomed Research International

Purpose. Neck and shoulder pain (NSP) is very common in the general population. However, scarce information exists on the relationship between NSP and health-related quality of life (HRQOL) outcomes in this population. The present study described NSP prevalence and its impact on the HRQOL of middle-aged and older persons undergoing a routine medical checkup. Methods. This study recruited 318 subjects (125 males and 193 females; average age, 63.4 years) in good health, collected underwent anthropometric measurements, physical function examinations, and blood testing. This study defined NSP as the presence of muscle tension, stiffness, pressure, or dull pain in areas between the neck and the arch of the scapular. Study subjects were divided into two groups (NSP (+) and NSP (-) groups). The subjects completed questions on the Medical Outcomes Study 36-item short-form health survey (SF-36) and the EuroQol 5-dimension, 5-level version (EQ-5D-5L) tool. Results. Of the patients, 150 and 168 were NSP (+) and NSP (-), respectively. The NSP complaint rate was 47.2%. The NSP (+) group had younger and more female participants than the NSP (-) group. In the multivariate regression analysis, the NSP (+) group had lower physical QOL based on the SF-36 physical component summary (odds ratio (OR), 2.45) and lower mental QOL based on the SF-36 mental component summary (OR, 2.05). Overall, the NSP (+) group had a higher risk of having low QOL scores (EQ-5D-5L index; OR, 1.76). Conclusions. The NSP (+) rate in healthy middle-aged and older persons was 47.2%. Furthermore, NSP (+) status was directly related poor HRQOL. NSP is a predictor of suboptimal physical and mental QOL. Therefore, NSP prevention or intervention for NSP may improve middle-aged and older adults' QOL.

DOI： 10.1155/2021/6674264

Neurological improvement is associated with neck pain attenuation after surgery for cervical ossification of the posterior longitudinal ligament Open Access

Koda, M; Yoshii, T; Egawa, S; Sakai, K; Kusano, K; Nakagawa, Y; Hirai, T; Wada, K; Katsumi, K; Kimura, A; Furuya, T; Maki, S; Nagoshi, N; Watanabe, K; Kanchiku, T; Nagamoto, Y; Oshima, Y; Ando, K; Nakashima, H; Takahata, M; Mori, K; Nakajima, H; Murata, K; Matsunaga, S; Kaito, T; Yamada, K; Kobayashi, S; Kato, S; Ohba, T; Inami, S; Fujibayashi, S; Katoh, H; Kanno, H; Takahashi, H; Fujii, K; Miyagi, M; Inoue, G; Takaso, M; Imagama, S; Kawaguchi, Y; Takeshita, K; Nakamura, M; Matsumoto, M; Okawa, A; Yamazaki, M

SCIENTIFIC REPORTS Vol. 11 ( 1 ) page： 11910 2021.6

Language：English Publisher：Scientific Reports

Although favourable surgical outcomes for myelopathy caused by cervical ossification of the posterior longitudinal ligament (OPLL) have been reported, factors significantly associated with post-operative neck pain attenuation still remain unclear. The primary aim of the present study was to determine factors significantly associated with post-operative neck pain attenuation in patients with cervical OPLL using a prospective multi-centre registry of surgically treated cervical OPLL. Significant postoperative neck pain reduction (50% reduction of neck pain) was achieved in 31.3% of patients. There was no significant difference in neck pain attenuation between surgical procedures. Statistical analyses with univariate analyses followed by stepwise logistic regression revealed neurological recovery as a factor having a significant positive association with post-operative neck pain attenuation (p = 0.04, odds ratio 5.68 (95% confidence interval: 1.27–22.2)). In conclusion, neurological recovery was an independent factor having a significant positive association with post-operative neck pain attenuation in patients with cervical myelopathy caused by OPLL who underwent cervical spine surgery.

DOI： 10.1038/s41598-021-91268-2

Clinical features and prognostic factors in spinal meningioma surgery from a multicenter study Open Access

Kobayashi, K; Ando, K; Matsumoto, T; Sato, K; Kato, F; Kanemura, T; Yoshihara, H; Sakai, Y; Hirasawa, A; Nakashima, H; Imagama, S

SCIENTIFIC REPORTS Vol. 11 ( 1 ) page： 11630 2021.6

Language：English Publisher：Scientific Reports

Meningiomas are benign tumors that are treated surgically. Local recurrence is likely if the dura is preserved, and en bloc tumor and dura resection (Simpson grade I) is recommended. In some cases the dura is cauterized and preserved after tumor resection (Simpson grade II). The purpose of this study was performed to analyze clinical features and prognostic factors associated with spinal meningioma, and to identify the most effective surgical treatment. The subjects were 116 patients (22 males, 94 females) with spinal meningioma who underwent surgery at seven NSG centers between 1998 and 2018. Clinical data were collected from the NSG database. Pre- and postoperative neurological status was defined using the modified McCormick scale. The patients had a mean age of 61.2 ± 14.8 years (range 19–91 years) and mean symptom duration of 11.3 ± 14.7 months (range 1–93 months). Complete resection was achieved in 108 cases (94%), including 29 Simpson grade I and 79 Simpson grade II resections. The mean follow-up period was 84.8 ± 52.7 months. At the last follow-up, neurological function had improved in 73 patients (63%), was stable in 34 (29%), and had worsened in 9 (8%). Eight patients had recurrence, and recurrence rates did not differ significantly between Simpson grades I and II in initial surgery. Kaplan–Meier analysis of recurrence-free survival showed that Simpson grade III or IV, male, and dural tail sign were significant factors associated with recurrence (P < 0.05). In conclusion, Simpson I resection is anatomically favorable for spinal meningiomas. Younger male patients with a dural tail and a high-grade tumor require close follow-up. The tumor location and feasibility of surgery can affect the surgical morbidity in Simpson I or II resection. All patients should be carefully monitored for long-term outcomes, and we recommend lifelong surveillance after surgery.

DOI： 10.1038/s41598-021-91225-z

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