Multiple system atrophy (MSA) is an adult-onset, progressive neurodegenerative disorder. Patients with MSA show various phenotypes during the course of their illness, including parkinsonism, cerebellar ataxia, autonomic failure, and pyramidal signs. Patients with MSA sometimes present with isolated autonomic failure or motor symptoms/signs. The median duration from onset to the concomitant appearance of motor and autonomic symptoms is approximately 2 years but can range up to 14 years. As the presence of both motor and autonomic symptoms is essential for the current diagnostic criteria, early diagnosis is difficult when patients present with isolated autonomic failure or motor symptoms/signs. In contrast, patients with MSA may show severe autonomic failure and die before the presentation of motor symptoms/signs, which are currently required for the diagnosis of MSA. Recent studies have also revealed that patients with MSA may show nonsupporting features of MSA such as dementia, hallucinations, and vertical gaze palsy. To establish early diagnostic criteria and clinically definitive categorization for the successful development of disease-modifying therapy or symptomatic interventions for MSA, research should focus on the isolated phase and atypical symptoms to develop specific clinical, imaging, and fluid biomarkers that satisfy the requirements for objectivity, for semi- or quantitative measurements, and for uncomplicated, worldwide availability. Several novel techniques, such as automated compartmentalization of the brain into multiple parcels for the quantification of gray and white matter volumes on an individual basis and the visualization of α-synuclein and other candidate serum and cerebrospinal fluid biomarkers, may be promising for the early and clinically definitive diagnosis of MSA.
Biomarkers ; Brain ; Cerebellar Ataxia ; Cerebrospinal Fluid ; Dementia ; Diagnosis ; Early Diagnosis ; Hallucinations ; Humans ; Multiple System Atrophy ; Neurodegenerative Diseases ; Paralysis ; Parkinsonian Disorders ; Phenotype ; White Matter

Methods: This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. Results: Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. Conclusions Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.

Methods: A total of 14 patients with unilateral radicular symptoms and five healthy subjects were subjected to simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement signaling (SHINKEI-Quant) using a 3-Tesla magnetic resonance imaging. The Visual Analog Scale (VAS) score for neck pain and upper arm pain was used to evaluate clinical symptoms. T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus were measured bilaterally from C4 to C8 in patients with radicular symptoms and from C5 to C8 in healthy controls. The T2 ratio was calculated as the affected side to unaffected side. Results: When comparing nerve roots bilaterally at each spinal level, no significant differences in T2 relaxation times were found between patients and healthy subjects. However, T2 relaxation times of nerve roots in the patients with unilateral radicular symptoms were significantly prolonged on the involved side compared with the uninvolved side (p<0.05). The VAS score for upper arm pain was not significantly correlated with the T2 relaxation times, but was positively correlated with the T2 ratio. Conclusions In patients with cervical radiculopathy, the SHINKEI-Quant technique can be used to quantitatively evaluate the compressed cervical nerve roots. The VAS score for upper arm pain was positively correlated with the T2 ratio. This suggests that the SHINKEI-Quant is a potential tool for the diagnosis of cervical nerve entrapment.

Endurance exercises, such as cycling or running, are useful for reducing arterial stiffness. However, individuals with a low physical fitness level, or patients suffering from leg diseases with pain, are unable to perform such moderate-intensity lower-limb exercises for long periods of time. The aim of this study was to evaluate the effects of acute cycling with Electrical muscle stimulation (EMS) on the brachial to ankle pulse wave velocity (ba-PWV). Ten healthy adult men performed 3 sessions, as follows of 20 min: cycling at 50% VO2max (C), cycling at an intensity of 50%VO2max subtracted from VO2 during EMS (LC), and cycling at the intensity of the LC trial while also being combined with EMS (LC+E). The ba-PWV was measured before and after each exercise. In addition, the femoral artery blood flow (BF) was measured in eight healthy adult men before and after exercise using an ultrasound imaging system. In the C and LC+E trials, the ba-PWV significantly decreased immediately after the exercise session, whereas the ba-PWV did not significantly change following the LC trial in any session. Compared with the baseline, the femoral artery BF values significantly increased after all trials. In the C and LC+E trials, the femoral artery BF was significantly greater than that in the LC trial. Acute endurance low-intensity cycling with EMS results in a reduction in the arterial stiffness which is similar to that with moderate-intensity exercise.

Purpose: In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects. Materials and Methods: Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1–2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5–7 months after the administration of romosozumab. Results: A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1–2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5–7 months after romosozumab administration;and a significant increase only observed in the lumbar spine. Conclusion Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.

Purpose: In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects. Materials and Methods: Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1–2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5–7 months after the administration of romosozumab. Results: A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1–2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5–7 months after romosozumab administration;and a significant increase only observed in the lumbar spine. Conclusion Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.

This study sought to demonstrate the benefits of conducting cervical cytology and human papillomavirus (HPV) testing in our cervical cancer screening program and was conducted between April 2012 and March 2017 in the Yuri-Honjo district of Akita Prefecture. A total of 3581 women aged 20-49 years underwent this combined screening for 5 years. Of these, 10.3% (369/3581) tested positive for HPV, and 433 women were initially diagnosed as positive for atypical squamous cells of undetermined significance and/or positive for HPV. Of those, 342 women (79.0%) underwent cervical biopsy, among whom 62 (18.1%) were diagnosed as positive for cervical intraepithelial neoplasia (CIN)2+. Of 204 women who were positive for HPV but showed no abnormalities in cytology, 24 women (11.8%) were positive for CIN2+ and 6 women were positive for CIN3+. Conventional cytology (Pap test) detected only 0.58% of the examinees positive for CIN2+ in Akita Prefecture, whereas our combined screening involving a Pap test and HPV testing detected 1.73% of the examinees (P<0.0001). We recommend HPV testing be used in combination with the Pap test to improve cervical cancer screening and accurately identify CIN2/3 disease.