Fumiaki Terajima

Identification of clinical parameters associated with serum oxidative stress in patients with rheumatoid arthritis

Abstract Objectives. Reactive oxygen species (ROS) are considered to be involved in the pathobiology of rheumatoid arthritis (RA); however, their association with disease activity has not been elucidated. In this study, we measured reactive oxygen metabolites (ROM) in patients with RA using a new Free Radical Analytical System and determined clinical parameters associated with ROM. Methods. One hundred and fifty-two patients with RA and 80 patients with diabetes mellitus (DM) were included in this observational study. To measure ROM, the d-ROM test was performed on blood samples drawn from all subjects. The correlation between ROM and biomarkers, disease activity, doses of methotrexate (MTX), and prednisolone (PSL) were investigated. Results. There were significant, positive correlations between ROM and CRP, matrix metalloproteinase 3 (MMP3), Disease Activity Score 28–erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). Multiple regression analysis revealed that CRP and DAS28-ESR were correlated with ROM. Conclusions. The serum level of ROM was associated with CRP and DAS28-ESR, suggesting that ROM, in conjunction with CRP and MMP3, may be able to be used as a new biological disease marker to evaluate the disease activity of RA.

Phosphorylated neurofilament subunit NF-H becomes elevated in the cerebrospinal fluid of patients with acutely worsening symptoms of compression myelopathy

It is known that the severity of compression myelopathy sometimes worsens rapidly and results in poor functional recovery because of limited axonal regeneration. Levels of phosphorylated neurofilament subunit NF-H (pNF-H), which indicate axonal degeneration, are elevated in other neurological disorders. To our knowledge, there has been no examination of pNF-H levels in compression myelopathy. Therefore, we conducted a pilot cross-sectional study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) of patients with worsening symptoms of cervical compression myelopathy. From January 2011 to March 2013, 51 samples of CSF were collected from patients at the time of myelography before spinal surgery. The indications for surgery were acutely worsening compression myelopathy (AM) in eight, chronic compression myelopathy (CM) in six, and lumbar canal stenosis (LCS) in 37 patients. The pNF-H levels were measured using a standard enzyme-linked immunosorbent assay. The mean ± standard deviation pNF-H value was 2127.1 ± 556.8 pg/ml in AM patients, 175.8 ± 67.38 pg/ml in CM patients and 518.7 ± 665.7 pg/ml in LCS patients. A significant increase in pNF-H levels was detected in the CSF of patients with AM compared with those with either CM or LCS. The clinical outcome of surgical treatment for patients with cervical myelopathy was satisfactory in both AM and CM patients. Despite the limitations of small sample size and lack of healthy CSF control data due to ethical considerations, our results suggest that pNF-H in CSF can act as a biomarker that reflects the severity of AM.

Isolated neck extensor myopathy causing a dropped head: a case report

This report is of a 71-year-old woman who presented with a dropped head and difficulty in extending her neck. She was diagnosed with isolated neck extensor myopathy. Conservative treatment (use of a cervical collar and muscular strength training) temporarily improved her symptoms. However, destruction of cervical vertebrae and myelopathy progressed secondary to repeated microfractures from mechanical stress. The patient underwent 2-stage combined anterior and posterior decompression and fusion using autografts. At one-year follow-up, numbness of the bilateral upper limbs had resolved, and bone union was achieved. The patient was able to look straight ahead and was very satisfied with the outcome.

Axonal damage is remarkable in patients with acutely worsening symptoms of compression myelopathy: biomarkers in cerebrospinal fluid samples

PurposeTo determine levels of biomarkers reflecting damage to axon, myelin, astrocytes, and neuron in cerebrospinal fluid (CSF) of patients with cervical compression myelopathy.MethodsWe collected 69 CSF samples from patients before spinal surgery for acutely worsening compression myelopathy (AM, 20), chronic compression myelopathy (CM, 20), and lumbar canal stenosis (LCS 29; control). We measured levels of phosphorylated neurofilament subunit H (pNF-H), tau (reflecting axonal damage), myelin basic protein (MBP) (reflecting demyelination), S100b (reflecting astrocyte damage), and neuron-specific enolase (NSE) (reflecting neuronal damage). Change of neurological function by surgery was determined using a Japanese Orthopaedic Association (JOA) score for cervical myelopathy.ResultsSignificantly higher levels of pNF-H were detected in AM compared with those in either CM or LCS (P < 0.01). Significantly higher levels of tau were detected in AM compared with those in CM (P < 0.05). Levels of MBP were undetectable in almost all the patients. Levels of S100b were equivalent in the three groups. Levels of NSE in AM and CM were significantly lower than those in LCS (P < 0.01). The recovery rate of JOA score was significantly greater for patients with AM than CM. We found a positive correlation between pNF-H and recovery of JOA score (r = 0.381, P = 0.018).ConclusionThe present results suggest that axonal damage is remarkable compared with demyelination, astrocytic, and neuronal damage in AM. Better clinical outcome in AM with high CSF levels of pNF-H indicates that axonal compensatory plasticity in spinal cord is preserved, and pNF-H can be predictive of good surgical outcome for AM.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

Response to ‘Increase of nerve growth factor levels in the human herniated intervertebral disc: can annular rupture trigger discogenic back pain?’ – authors’ reply

We appreciate the interest and attention paid by Agilli and Ekinci, and we agree with their point that nerve growth factor (NGF) levels could be affected by multiple factors [1]. As pointed out, the paper would be improved by considering the effects of these factors; thus the data were re-examined. This analysis found that the number of patients who had neuropsychiatric diseases and use medications (one patient in the herniated group and two patients in the nonherniated group) and had diabetes mellitus (two patients in each group) were similar between the two groups. As Bullo and colleagues described, obesity is one of the important factors affecting NGF levels in blood samples [2]. These authors also indicated the influence of body mass index (BMI) on NGF levels; thus, the BMI of our patients was analyzed and included in the multivariate analysis. The BMI of the two groups showed no significant difference (24.0 ± 4.0 in the herniated group and 25.3 ± 3.2 in the nonherniated group, P = 0.20), and Pearson’s correlation analysis showed no significant correlation between the level of NGF and BMI (P = 0.91). The multivariate analysis adjusted for age, sex, disc degeneration and BMI still showed a significant correlation between disc herniation and NGF levels (P = 0.018). A previous report of a rat study described that disc injury induced an inflammatory response and NGF upregulation in the disc [3]. It has also been reported that inflammatory mediators including NGF were increased in human symptomatic discs [4,5]. The intervertebral disc is avascular, and metabolic transport depends on diffusion through the vertebral endplates [6]. This limited molecular transport may explain why NGF did not increase in discs from our obese patients. These observations suggest that the significant increase of NGF in herniated discs was due to local tissue reaction following annular rupture. Because there may be many factors affecting NGF levels in the disc, it would be difficult to include them all in a multivariate analysis. However, as Agilli and Ekinci indicated, several important factors should be taken into account when studying NGF levels in the disc.

A Case of Delayed Myelopathy Caused by Atlantoaxial Subluxation without Fracture

We report a case of delayed myelopathy caused by atlantoaxial subluxation without fracture. The patient was a 38-year-old male who became aware of weakness in extremities. The patient had a history of hitting his head severely while diving into a swimming pool at the age of 14 years old. At that time, cervical spine plain X-ray images showed no fracture, and the cervical pain disappeared after use of a collar for several weeks. At his first visit to our department, X-ray images showed an unstable atlantoaxial joint. After surgery, weakness of the extremities gradually improved. At 6 months after surgery, bone union was completed and the symptoms disappeared. This case shows that atlantoaxial ligament injuries are difficult to diagnose and may easily be missed. A high level of suspicion is important in such cases, since neurological compromise or deterioration may occur many years after the injury.