A case of coexistence of multiple vascular anomalies including the absence of a left internal carotid artery, a left vertebral artery arising from the subclavian artery in a high cervical location, and a bovine arch associated with vertebral fusion.

We report a rare 16-year-old male case of Klippel-Feil anomaly associated with fetal alcohol syndrome exhibiting complex congenital vascular anomalies. The congenital vascular anomalies observed were the absence of a left internal carotid artery, a left vertebral artery arising from the subclavian artery in a very high cervical location and a bovine arch. The vascular and vertebral anomalies were evaluated using CT and MRI before cervical surgery.

Gravitational instability in a planet-forming disk.

The canonical theory for planet formation in circumstellar disks proposes that planets are grown from initially much smaller seeds1-5. The long-considered alternative theory proposes that giant protoplanets can be formed directly from collapsing fragments of vast spiral arms6-11 induced by gravitational instability12-14-if the disk is gravitationally unstable. For this to be possible, the disk must be massive compared with the central star: a disk-to-star mass ratio of 1:10 is widely held as the rough threshold for triggering gravitational instability, inciting substantial non-Keplerian dynamics and generating prominent spiral arms15-18. Although estimating disk masses has historically been challenging19-21, the motion of the gas can reveal the presence of gravitational instability through its effect on the disk-velocity structure22-24. Here we present kinematic evidence of gravitational instability in the disk around AB Aurigae, using deep observations of 13CO and C18O line emission with the Atacama Large Millimeter/submillimeter Array (ALMA). The observed kinematic signals strongly resemble predictions from simulations and analytic modelling. From quantitative comparisons, we infer a disk mass of up to a third of the stellar mass enclosed within 1″ to 5″ on the sky.

Flatfoot Surgery for Flexible Progressive Collapsing Foot Deformity With Inflammatory Joint Diseases: A Report of 3 Cases.

CASE: Three cases of inflammatory joint diseases (systemic lupus erythematosus and ongoing juvenile idiopathic arthritis) with painful flexible progressive collapsing foot deformity (PCFD) underwent flatfoot surgery. All cases maintained sufficient radiological correction and achieved good clinical condition at final follow-up. CONCLUSION: Although the prospect for recurrence of the deformity is not clear, even in inflammatory joint diseases, flat foot surgery such as flexor digitorum longs transfer, spring ligament reconstruction, and lateral column lengthening could have a possibility to be indicated against PCFD, as long as disease activity could be well suppressed by drug therapy, subsequently subtalar and talonavicular joints could be preserved.

Arthroscopic treatment of septic arthritis of the ankle joint caused by streptococcus in patients with chronic inflammatory diseases: two case reports.

This report describes the arthroscopic treatment of septic arthritis of the ankle joint in two patients with inflammatory diseases, including rheumatoid arthritis (RA) and nail psoriasis. We treated both the ankle joints with antibiotic administration and urgent arthroscopic synovectomy and irrigation, although the procedure was performed several days (4 and 6 days) after the time at which the infection would have occurred. Fortunately, no recurrence has been seen for more than 18 and 20 months, respectively, after surgery, without antibiotic administration. Although septic arthritis of the ankle joint accounts for a small proportion of joint arthritis cases, diagnosis as early as possible is important. Our experience suggests that arthroscopic synovectomy and irrigation are effective for septic ankle arthritis even in chronic inflammatory disease cases.

Full-endoscopic discectomy utilizing an interlaminar approach for gas-containing herniation at L5-S1.

Background: Intradiscal gas is frequently observed in older patients with disc degeneration and can occasionally result in nerve root compression. Case Description: A 79-year-old male patient presented with increasing left lower extremity sciatica. Lumbar computed tomography (CT) and magnetic resonance (MR) images revealed a left paramedian L5-S1 gas-containing disc herniation. Utilizing an interlaminar approach, a full-endoscopic discectomy (FED) was performed at L5-S1. During disc removal, we countered intradiscal gas bubbles. Postoperatively, the patient's symptoms/signs fully resolved, and follow-up MR and CT images revealed total resection of the disc herniation, and no further gas. Conclusion: Through an interlaminar FED, we effectively removed an L5-S1 MR/CT-documented gas-containing disc herniation.

Perioperative complications and cost of posterior decompression with fusion in thoracic spine for ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum -a comparative study using a national inpatient database.

BACKGROUND: Although posterior decompression with fusion (PDF) are effective for treating thoracic myelopathy, surgical treatment has a high risk of various complications. There is currently no information available on the perioperative complications in thoracic ossification of the longitudinal ligament (T-OPLL) and thoracic ossification of the ligamentum flavum (T-OLF). We evaluate the perioperative complication rate and cost between T-OPLL and T-OLF for patients underwent PDF. METHODS: Patients undergoing PDF for T-OPLL and T-OLF from 2012 to 2018 were detected in Japanese nationwide inpatient database. One-to-one propensity score matching between T-OPLL and T-OLF was performed based on patient characteristics and preoperative comorbidities. We examined systemic and local complication rate, reoperation rate, length of hospital stays, costs, discharge destination, and mortality after matching. RESULTS: In a total of 2,660 patients, 828 pairs of T-OPLL and T-OLF patients were included after matching. The incidence of systemic complications did not differ significantly between the T-OPLL and OLF groups. However, local complications were more frequently occurred in T-OPLL than in T-OLF groups (11.4% vs. 7.7% P = 0.012). Transfusion rates was also significantly higher in the T-OPLL group (14.1% vs. 9.4%, P = 0.003). T-OPLL group had longer hospital stay (42.2 days vs. 36.2 days, P = 0.004) and higher medical costs (USD 32,805 vs. USD 25,134, P < 0.001). In both T-OPLL and T-OLF, the occurrence of perioperative complications led to longer hospital stay and higher medical costs. While fewer patients in T-OPLL were discharged home (51.6% vs. 65.1%, P < 0.001), patients were transferred to other hospitals more frequently (47.5% vs. 33.5%, P = 0.001). CONCLUSION: This research identified the perioperative complications of T-OPLL and T-OLF in PDF using a large national database, which revealed that the incidence of local complications was higher in the T-OPLL patients. Perioperative complications resulted in longer hospital stays and higher medical costs.

Utility of Echo-planar Imaging with Compressed Sensitivity Encoding (EPICS) in the Evaluation of Small Breast Cancers Using Diffusion-weighted Imaging with Background Suppression (DWIBS).

PURPOSE: High b-value acquisition and diffusion-weighted imaging with background suppression (DWIBS) are desirable in high-specificity breast cancer diagnosis on non-contrast-enhanced magnetic resonance imaging; however, this inherently results in a lower signal-to-noise ratio (SNR). Compressed sensitivity encoding (C-SENSE), which combines SENSE with compressed sensing, improves the SNR by reducing noise. Recent technological improvements allow us to incorporate this acceleration technique into echo-planar imaging, called echo-planar imaging with C-SENSE (EPICS). This study aimed to compare image quality and reliability of the apparent diffusion coefficient (ADC) between DWIBS obtained using SENSE and EPICS in patients with small breast cancers. METHODS: Thirty-seven patients with pathologically confirmed breast cancer underwent DWIBS, and images were reconstructed using both conventional SENSE (SENSE-DWIBS) and EPICS (EPICS-DWIBS). Two board-certified radiologists independently evaluated lesion conspicuity (LC) and noise using a 5-point grading scale. The same 2 radiologists independently measured SNR, contrast-to-noise ratio (CNR), and the mean cancer ADC. The Pearson coefficient and Bland-Altman plot were applied to assess the accuracy of ADCs. RESULTS: LC scores were higher with EPICS than with SENSE, reaching significance for one reviewer but not the other reviewer. Noise ratings on visual evaluation were significantly lower with EPICS than with SENSE (P < 0.001 for both reviewers). SNR was significantly higher with EPICS than with SENSE (P < 0.005 for both reviewers). CNR was significantly higher with EPICS than with SENSE (P < 0.001 for both reviewers). Bland-Altman plots of cancer ADCs using EPICS-DWIBS and SENSE-DWIBS showed excellent concordance, with a bias of 0.026 × 10-3 mm2/s and limits of agreement ranging 0.054 × 10-3 mm2/s; the Pearson's correlation coefficient was 0.997 (P < 0.0001). CONCLUSION: EPICS enhances breast DWIBS image quality, with improved SNR and CNR and reduced noise levels. The ADCs of breast cancers obtained using EPICS were almost perfectly correlated with those obtained using conventional SENSE.

Case of Isolated Absence of the Azygos Vein: Evaluation Using Photon-counting Detector CT.

The isolated absence of the azygos vein was incidentally found on computed tomography (CT) examination in a 60-year-old female. The exact anomaly can be evaluated on high-resolution images of 0.4-mm slice thickness with low keV using photon-counting detector CT. The azygos vein, including the azygos arch, was absent, and a mildly dilated hemiazygos vein flowed to the left brachiocephalic vein through the left superior intercostal vein. A hemiazygos vein connected the left renal vein at the level of the first lumbar vertebra. This patient was the second patient to undergo evaluation using volume rendering images. High-resolution maximum-intensity projection images were useful for assessing the anatomy. Radiation dose was decreased compared with that in conventional CT.

Evaluation of Incidental Findings on Abdominopelvic CT: Potential Benefit of Photon-counting Detector CT Over Conventional Single-energy CT.

PURPOSE: To assese of potential benefint of photon-counting detector CT (PCD-CT) over conventional single-energy CT (CSE-CT) on accurate diagnosis of incidental findings with high clinical significance (IFHCS). MATERIALS AND METHODS: This retrospective study included 365 patients who initially underwent abdominopelvic contrast-enhanced CT (AP-CECT) without non-enhancement (PCD-CT: 187 and CSE-CT: 178). We selected IFHCS and evaluated their diagnosability using CE-CT alone. IFHCSs that could not be diagnosed with only CE-CT were evaluated using additional PCD-CT postprocessing techniques, including virtual non-contrast image, low keV image, and iodine map. A PCD-CT scanner (NAEOTOM Alpha, Siemens Healthineer, Erlangen, Germany) was used. RESULTS: Thirty-nine IFHCSs (PCD-CT: 22 and CSE-CT: 17) were determined in this study. Seven IFHCSs in each group were able to diagnose with only CE-CT. Fifteen IFHCSs were able to diagnose using the additional PCD-CT postprocessing technique, which was useful for detecting and accurately diagnosing 68.2% (15/22) of lesions and 65% (13/20) of patients. All IFHCSs were accurately diagonosed with PCD-CT. CONCLUSION: PCD-CT was useful for characterizing IFHCSs that are indeterminate at CSE-CT. PCD-CT offered potential benefit of PCD-CT over conventional single-energy CT on evaluation of IFHCS on only abdominopelvic CT.

Detection of Dural Defect Localization Using 4-Dimensional Dynamic Computed Tomography Myelography for Patients with Superficial Siderosis.

BACKGROUND: There are cases of superficial siderosis (SS) with spinal ventral fluid-filled collection in the spinal canal. In our previous study, the balanced steady-state free precession sequence magnetic resonance imaging is useful in identifying the location of dural defects. However, because of its narrow scan area and long scan time, it cannot easily detect the defect location in some patients with small dural defect. In this study, we applied 4-dimensional (4D) dynamic computed tomography (CT) imaging, including time-axis imaging, to myelography using the latest CT imaging equipment, which can perform short-time continuous imaging, to identify the dural defect site. METHODS: Twenty SS patients with ventral fluid-filled collection in the spinal canal (9 males, 11 females; mean age 61.6 years) underwent 4D dynamic CT myelography. A 192-row helical CT (SOMATOM Force, SIEMENS, Munich, Germany) with high-speed scanning capability was used to obtain 9-11 scans per minute at low dose while passing contrast medium into the subarachnoid space. Then, contrast leakage sites were identified. RESULTS: The contrast leakage sites could be identified in all 20 cases: C7/Th1, 2 cases; Th1/2, 5 cases; Th2/3, 9 cases; Th3/4, 1 case; Th5/6, 1 case; Th7/8, 1 case; and Th8/9, 1 case. Eighteen cases underwent surgical operation, and actual dural defects were confirmed at the contrast leakage sites. The mean ± standard deviation of leakage time from contrast agent injection was 19.0 ± 9.2 s. CONCLUSIONS: The 4D dynamic CT myelography can be used to reliably identify the location of spinal fluid leakage. In SS cases, dural defects could be visualized in an average of 19 seconds.

Nonunion after medial malleolar osteotomy in total ankle arthroplasties for severe varus deformity: a report of 3 cases.

Of the three ankles after total ankle arthroplasty (TAA) with medial malleolar osteotomy for severe varus deformity (talar varus tilt >10°), two failed in varus migration of the tibial component. In these two cases, tibial osteotomy was performed with varus alignment of 5°and 2°, and with medially shifted placement of tibial component, while one ankle showed no migratoin of prostheses after 5 years, even with nonunion. In this case, tibial osteotomy was performed with a valgus alignment of 4°. Internal fixation after medial malleolar osteotomy should be done for severe varus cases. Medially shifted placement of tibial component should be avoided. Fortunately, the failure did not occur in a case of valgus of the distal tibia. Valgus tibial osteotomy might help to reduce the collision of the talus against the medial malleolus.

Midterm Outcomes After Total Knee Arthroplasty With Lateral Approach for Valgus Knee Deformity in Patients With Rheumatoid Arthritis.

Background Valgus knee deformity is often seen in rheumatoid arthritis (RA) cases. Usually, the medial approach has been often utilized for total knee arthroplasty (TKA), even in valgus deformity cases; however, the medial approach is feared to induce further instability in the medial side because it could further break the soft tissue structure, including medial collateral ligament (MCL) and medial patellofemoral ligament (MPFL). Consequently, loosening of the implant, recurrence of valgus knee deformity, and pain due to instability might be induced in the early period after surgery. In this study, a lateral approach for TKA against valgus deformity in RA cases was utilized to avoid further damage on the medial side. Methods Eleven valgus knees in 10 patients with RA (mean age, 61.1 years; mean follow-up, 33.1 months) underwent primary TKA with the lateral approach. Iliotibial band (ITB) dissection and/or peroneal nerve release were performed if necessary. Radiological and clinical investigations were evaluated pre- and postoperatively. Results The average operating time was 106 minutes, which was no longer compared with the time after the medial approach described previously. The extension angle was significantly improved from -15.0 ± 10.2 to -5.5 ± 4.2 degrees (P = 0.03), while the flexion angle showed no significant change (from 111.8 ± 15.9 to 115.0 ± 13.2 degrees). The hip-knee-ankle angle (HKA) was also significantly corrected from -9 ± 4.9 to 0.4 ± 1.7 degrees (P < 0.001). The 2011 Knee Score System (KSS) scores were significantly improved from 6.9 ± 3.4 to 21.5 ± 2.9 (P < 0.001) in symptoms, from 15.6 ± 2.7 to 31.1 ± 4.1 (P < 0.001) in satisfaction, and from 31.5 to 59.5 (P < 0.01) in activity. Conclusion Midterm outcomes after lateral approach TKA were good, and knee alignment was significantly improved. The lateral approach TKA for valgus deformity in patients with RA was not complicated and difficult because it required no additional operating time compared with the medial approach. From the perspective of preventing further damage to the soft tissue structure on the medial side, the lateral approach was meaningful for valgus deformity in patients with RA.

Comparison of Postoperative Complications and Outcomes in Anterior Cervical Spine Surgery: Ossification of the Posterior Longitudinal Ligament Versus Cervical Spondylotic Myelopathy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare the frequency of complications and outcomes between patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine and those with cervical spondylotic myelopathy (CSM) who underwent anterior surgery. SUMMARY OF BACKGROUND DATA: Anterior cervical spine surgery for OPLL is an effective surgical procedure; however, it is complex and technically demanding compared with the procedure for CSM. Few reports have compared postoperative complications and clinical outcomes after anterior surgeries between the 2 pathologies. METHODS: Among 1434 patients who underwent anterior cervical spine surgery at 3 spine centers within the same spine research group from January 2011 to March 2021, 333 patients with OPLL and 488 patients with CSM were retrospectively evaluated. Demographics, postoperative complications, and outcomes were reviewed by analyzing medical records. In-hospital and postdischarge postoperative complications were investigated. Postoperative outcomes were evaluated 1 year after the surgery using the Japanese Orthopaedic Association score. RESULTS: Patients with OPLL had more comorbid diabetes mellitus preoperatively than patients with CSM ( P <0.001). Anterior cervical corpectomies were more often performed in patients with OPLL than in those with CSM (73.3% and 14.5%). In-hospital complications, such as reoperation, cerebrospinal fluid leak, C5 palsy, graft complications, hoarseness, and upper airway complications, occurred significantly more often in patients with OPLL. Complications after discharge, such as complications of the graft bone/cage and hoarseness, were significantly more common in patients with OPLL. The recovery rate of the Japanese Orthopaedic Association score 1 year postoperatively was similar between patients with OPLL and those with CSM. CONCLUSION: The present study demonstrated that complications, both in-hospital and after discharge following anterior spine surgery, occurred more frequently in patients with OPLL than in those with CSM.

Assessing ulnar neuropathy at the elbow using magnetoneurography.

OBJECTIVE: To measure neuromagnetic fields of ulnar neuropathy patients at the elbow after electrical stimulation and evaluate ulnar nerve function at the elbow with high spatial resolution. METHODS: A superconducting quantum interference device magnetometer system recorded neuromagnetic fields of the ulnar nerve at the elbow after electrical stimulation at the wrist in 16 limbs of 16 healthy volunteers and 21 limbs of 20 patients with ulnar neuropathy at the elbow. After artifact removal, neuromagnetic field signals were processed into current distributions, which were superimposed onto X-ray images for visualization. RESULTS: Based on the results in healthy volunteers, conduction velocity of 30 m/s or 50% attenuation in current amplitude was set as the reference value for conduction disturbance. Of the 21 patient limbs, 15 were measurable and lesion sites were detected, whereas 6 limbs were unmeasurable due to weak neuromagnetic field signals. Seven limbs were deemed normal by nerve conduction study, but 5 showed conduction disturbances on magnetoneurography. CONCLUSIONS: Measuring the magnetic field after nerve stimulation enabled visualization of neurophysiological activity in patients with ulnar neuropathy at the elbow and evaluation of conduction disturbances. SIGNIFICANCE: Magnetoneurography may be useful for assessing lesion sites in patients with ulnar neuropathy at the elbow.

Early full weight-bearing and gait exercise after cemented total ankle arthroplasty with modified antero-lateral approach.

BACKGROUND: According to the conventional postoperative procedure after total ankle arthroplasty (TAA) against end-stage osteoarthritis (OA) and rheumatoid arthritis (RA), mobilization and weight-bearing is currently started after completion of wound healing. Recently, early mobilization for dorsiflexion after TAA with modified antero-lateral approach was reported to be feasible and safe. To investigate the further possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early full weight-bearing and gait exercise after cemented TAA utilizing a modified antero-lateral approach. MATERIALS AND METHODS: This retrospective, observational study investigated 23 consecutive ankles (OA: 14 ankles, RA: 9 ankles) that had received cemented TAA with a modified antero-lateral approach. These ankles were divided into three groups [1. conventional postoperative protocol: 8 ankles, 2. early dorsiflexion protocol: 7 ankles, 3. early dorsiflexion+full weight-bearing protocol: 8 ankles]. In group 3, after early dorsiflexion mobilization (day 3), full weight-bearing/gait exercise was started from 7 days after surgery (10 days after if malleolar osteotomy was added). Postoperative wound complications were observed and recorded. Number of days for hospitalization was also evaluated. Range of motion (ROM) of dorsiflexion/plantar flexion was measured. Patients also completed a self-administered foot evaluation questionnaire (SAFE-Q) and the scale of Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot score preoperatively and at final follow-up. RESULTS: No postoperative complications related to wound healing were observed even after early full weight-bearing and gait exercise. Days for hospitalization was significantly shortened in early full weight-bearing and gait exercise group (group 3) from 35-38 days to 24 days. ROM for both dorsiflexion and plantar flexion significantly increased in group 3, furthermore all indices of SAFE-Q score also showed stronger significant improvement in group 3. JSSF score improved significantly after TAA in all groups. CONCLUSION: Within this small number of cases, early full weight-bearing and gait exercise from 7 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Combination of early dorsiflexion mobilization and weight-bearing/gait exercise contributed to shortening the hospitalization day, and improving ROM for both dorsiflexion and plantar flexion after surgery. Innovations in postoperative procedures for rehabilitation after TAA can be expected.

Safety and effectiveness of risedronate in Paget's disease of bone: postmarketing surveillance study in Japan.

INTRODUCTION: We conducted an all-case postmarketing surveillance study between 2008 and 2017 to evaluate the safety and effectiveness of risedronate for Paget's disease of bone (PDB) in Japan. MATERIAL AND METHODS: This study registered all patients who received once-daily risedronate 17.5 mg for the treatment of PDB and collected data over a 48-week follow-up period per treatment cycle for each patient. RESULTS: The safety analysis set included 184 patients (mean age, 63.7 years), 81 (44.0%) of whom previously received a bisphosphonate. Of them, 41 (22.3%) experienced 72 adverse drug reactions (ADRs), and 8 (4.3%) experienced 14 serious ADRs. Common ADRs included gastrointestinal disorders (20 patients, 10.9%) and hypocalcemia (6 patients, 3.3%). The effectiveness analysis set included 182 patients, 124 of whom completed only one treatment cycle and 58 of whom completed multiple treatment cycles. The proportions of patients who normalized serum alkaline phosphatase (ALP) concentration were 71.1% (113/159 patients) and 67.3% (33/49 patients) for the first and second treatment cycles, respectively. The relapse rate according to ALP levels after the end of treatment for the first cycle was 5.0% (95% confidence interval [CI] = 2.1-11.5) at 24 weeks and 12.9% (95% CI = 7.5-21.7) at 40 weeks. Regarding pain relief, the achievement rates were 70.0% (49/70 patients) and 30.8% (4/13 patients) for the first and second treatment cycles, respectively. CONCLUSION: To conclude, risedronate 17.5 mg/day is safe and effective for treating patients with PDB in daily practice.

Reverse V-shaped osteotomy for ankylosing rocker-bottom foot deformity in patients with rheumatoid arthritis: A report of three cases.

This study evaluated a reverse V-shaped osteotomy for ankylosing rocker-bottom foot deformity in patients with rheumatoid arthritis. Three feet were presented in this study: rheumatoid rocker-bottom deformities with painful and/or infectious bony prominence towards the bottom of the foot, treated with a reverse V-shaped osteotomy in the mid-hindfoot. In all three cases, significant correction was achieved with restoration of the medial longitudinal arch, and improvement in clinical scores was confirmed. Reverse V-shaped osteotomy has the potential to be a useful and definitive procedure for ankylosing rocker-bottom deformity in patients with rheumatoid arthritis.

Factors associated with the time required for CRP normalization in pyogenic spondylitis: A retrospective observational study.

Background: Treatment for pyogenic spondylitis tends to be prolonged; however, few studies have examined the factors associated with the time required for infection control. Therefore, we analyzed a consecutive cohort of patients to identify factors associated with the time required to control infection in pyogenic spondylitis. This study aimed to clarify the factors linked to the duration necessary for achieving infection control in cases of pyogenic spondylitis, using C-reactive protein (CRP) normalization as an indicator. Methods: In this retrospective observational study, we investigated 108 patients diagnosed with pyogenic spondylitis. We evaluated the number of days from the first visit to CRP normalization; for cases wherein CRP did not normalize, the number of days to the date of final blood sampling was evaluated. In the present study, infection control in pyogenic spondylitis was defined as a CRP falling within the normal range (≤0.14 mg/dL). We performed univariate and multivariate Cox regression analyses to identify various factors associated with the time required for CRP normalization in pyogenic spondylitis. Results: The mean time required for CRP normalization was 148 days. Univariate Cox regression analysis showed that the serum creatinine level, estimated glomerular filtration rate (eGFR), lymphocyte percentage, neutrophil percentage, CRP level, CRP-albumin ratio, and neutrophil-to-lymphocyte ratio were significantly associated with the time required to control infection. Multivariate Cox regression analysis showed that a higher neutrophil percentage, diabetes mellitus, and a lower eGFR were the independent factors associated with a longer infection control time. Conclusions: We found that a higher neutrophil percentage, diabetes mellitus, and a lower eGFR were significantly associated with a longer time for CRP normalization in pyogenic spondylitis. These findings may help identify patients with pyogenic spondylitis who are at a high risk for an extended infection control period.

Nationwide survey of patients with multisystem proteinopathy in Japan.

OBJECTIVE: Multisystem proteinopathy (MSP) is an inherited disorder in which protein aggregates with TAR DNA-binding protein of 43 kDa form in multiple organs. Mutations in VCP, HNRNPA2B1, HNRNPA1, SQSTM1, MATR3, and ANXA11 are causative for MSP. This study aimed to conduct a nationwide epidemiological survey based on the diagnostic criteria established by the Japan MSP study group. METHODS: We conducted a nationwide epidemiological survey by administering primary and secondary questionnaires among 6235 specialists of the Japanese Society of Neurology. RESULTS: In the primary survey, 47 patients with MSP were identified. In the secondary survey of 27 patients, inclusion body myopathy was the most common initial symptom (74.1%), followed by motor neuron disease (11.1%), frontotemporal dementia (FTD, 7.4%), and Paget's disease of bone (PDB, 7.4%), with no cases of parkinsonism. Inclusion body myopathy occurred most frequently during the entire course of the disease (81.5%), followed by motor neuron disease (25.9%), PDB (18.5%), FTD (14.8%), and parkinsonism (3.7%). Laboratory findings showed a high frequency of elevated serum creatine kinase levels and abnormalities on needle electromyography, muscle histology, brain magnetic resonance imaging, and perfusion single-photon emission computed tomography. INTERPRETATION: The low frequency of FTD and PDB may suggest that FTD and PDB may be widely underdiagnosed and undertreated in clinical practice.