Relevance of callosal and periventricular MRI lesions to oligoclonal bands in multiple sclerosis.

OBJECTIVES: To evaluate the association between callosal or periventricular lesions, and the presence of oligoclonal IgG bands (OB) or the IgG index in Japanese patients with multiple sclerosis (MS). MATERIALS AND METHODS: Brain magnetic resonance imaging (MRI) was studied in 34 Japanese clinically definite MS cases. Sagittal 2-mm fast fluid-attenuated inversion-recovery (FLAIR) imaging was added to the routine MRI studies. RESULTS: Among the 34 patients, 20 (59%) were OB positive. Among the 20 patients with OB-positive MS, 17 (85%) had callosal lesions, although only two (14%) of 14 OB-negative MS patients had callosal lesions. The periventricular lesion area was significantly larger in the OB-positive patients compared with the OB-negative patients. CONCLUSIONS: The present study clearly demonstrated a strong association between the periventricular lesions and OB in Japanese MS. Certain OB-related immune mechanisms may contribute to the development of callosal and periventricular lesions in MS. OB may be an important factor to understand the pathomechanisms of MS lesions.

Epitope analysis of the cerebrospinal fluid IgG in HTLV-I associated myelopathy patients using phage display method.

We, for the first time, analyzed the binding motifs of immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with a phage library displaying 12-mer random peptides. As a result, the sequences highly homologous to HTLV-I gp46 192-199, 237-243 and 255-261 were the common linear epitopes of high affinity- IgG exclusively detected in both CSF and sera of the patients. These IgG responses were confirmed with corresponding HTLV-I peptides and serum antibody titers significantly correlated with disease severity or duration. Gp46 237-243 has not been detected in previous enzyme-linked immunosorbent assay (ELISA) studies using bound longer peptides, suggesting the usefulness of the phage display method.

MRI characteristics of sporadic CJD with valine homozygosity at codon 129 of the prion protein gene and PrPSc type 2 in Japan.

Two Japanese sporadic Creutzfeld-Jakob disease (sCJD) patients with valine homozygosity at codon 129 of the prion protein gene and protease-resistant prion protein (PrP(Sc)) type 2 (VV2) are described. In contrast with Western countries, this type of sCJD is very rare in Japan. In 123 sCJD cases, only two were recognised as VV2 by the Japanese CJD surveillance committee. The clinical symptoms and pathological findings of the patients were similar to those of European and US patients. The noteworthy finding of diffusion weighted MRI (DWI) was that an abnormal high intensity covered a wide range of the thalamus including the dorsomedial nucleus, the pulvinar, and the ventral anterior, lateral, and posterolateral nuclei. This thalamic pattern has not been recognised in sCJD with methionine homozygosity and PrP(Sc) type 1 (MM1) or methionine/valine heterozygosity and PrP(Sc) type 1 (MV1) which comprises the vast majority of sCJD. This finding may be characteristic to VV2 and may distinguish it from MM1, MV1, and variant CJD. DWI can provide a very important clue for the antemortem diagnosis of VV2 subjects.

Absence of IgG1 response in the cerebrospinal fluid of relapsing neuromyelitis optica.

The authors studied immunoglobulin (Ig) G subclasses in the CSF and sera of patients with relapsing neuromyelitis optica (RNMO) and typical multiple sclerosis (MS). Although the total IgG concentrations were elevated in the CSF of patients with RNMO and MS, IgG1% and IgG1 index were significantly elevated only in patients with MS. The absence of the CSF IgG1 responses in the patients with RNMO may suggest less Th1 immunity and may also explain the rarity of oligoclonal IgG bands in patients with this disease.

A comparative study of Japanese multiple sclerosis patients with and without oligoclonal IgG bands.

The cerebrospinal fluid oligodonal IgG bands (OB) are less frequently observed in Japanese multiple sclerosis (MS) patients compared with Caucasian patients. We studied 40 consecutive Japanese MS patients to investigate the differences in the clinical and magnetic resonance imaging (MRI) features of MS between OB-positive patients and OB-negative ones. Among the 40 patients, 22 (55%) patients were OB-positive by either agarose gel electrophoresis (AGE) or isoelectric focusing (IEF), and 18 (45%) patients were OB-negative by both AGE and IEF. There were differences between the two groups only in the clincal forms of MS, but not in terms of gender, onset age, disease duration, or disease severity. In the OB-negative group, nine (50%) of the patients had the optic-spinal form of MS (OS-MS), but only one patient (4.5%) in the OB-positive group had OS-MS. Although most OB-positive patients showed brain MRI lesions typical of MS, 13 (72%) of the OB-negative patients showed no or few brain MRI lesions and the rest of the OB-negative patients showed atypical MS lesions, such as diffuse white matter lesions or large ring-enhanced lesions. Our results suggest that the majority of OB-negative Japanese MS patents show either no or few brain MRI lesions or atypical brain MRI lesions.

[A case of potassium-sensitive periodic paralysis with cardiac dysrhythmia controlled with imipramine and acetazolamide].

We report a patient with potassium-sensitive periodic paralysis with cardiac dysrhythmia. The patient was a 16-year-old man. He presented with asymptomatic ventricular dysrhythmia and periodic paralysis when he was 6 and 12 years old, respectively. Physical examination revealed slight dysmorphic features such as hypoplastic mandible, low-set ears and clinodactyly. Through an exercise test, a potassium tolerance test and a muscle biopsy, his illness was diagnosed as potassium-sensitive periodic paralysis with cardiac dysrhythmia. For the treatment of his episodic paralysis, we started acetazolamide, which improved both the incidence and the severity of paralysis. However, the incidence of cardiac dysrhythmia was increased after the use of acetazolamide. Routine anti-arrhythmic drugs such as lidocaine failed to control his ventricular dysrhythmia. Only imipramine showed its efficacy by improving the degree and the incidence of cardiac dysrhythmia without aggravating periodic paralysis. This syndrome is relatively rare and there have been no standard protocols for the treatment. We propose the combination of acetazolamide and imipramine as the first choice for this clinical entity. We also discussed the efficacy of the exercise test. It enabled us to confirm the diagnosis of periodic paralysis safely and easily by recording the change of compound muscle action potential amplitudes.

[A multicenter cross-sectional study on the Health Related Quality of Life of patients with rheumatoid arthritis using a revised Japanese version of the Arthritis Impact Measurement Scales Version 2 (AIMS 2), focusing on physical disability and its associative factors].

OBJECTIVE: A multicenter cross-sectional survey was conducted to study the current status of Health Related Quality of Life (HRQL) of Japanese patients with rheumatoid arthritis using a revised Japanese version of the AIMS 2, to investigate the association among the self-report physical disability scores and demographic, socioeconomic, and clinical variables in these patients. METHODS: A Japanese version of the AIMS 2 was administered to the randomly chosen 1614 patients with classical and definite rheumatoid arthritis attending arthritis clinics at eleven hospitals across the country. Self-report functional disability scores (FDSs) were calculated, by which patients were classified into five groups with graded levels of disability. Univariate correlations were examined between FDSs and the scores of the other four components of AIMS-HRQL, disease duration, age, medical costs, and physical and laboratory measures. Analysis of variance was performed to test for among level differences of these variables in each group of patients. Mean values and standard deviations of FDSs were calculated and analysis of variance was used to test for among level differences of the following factors: demographic, socio-economic, clinical measures, and treatment status. RESULTS: Among four scales composing the AIMS 2-HRQL, work disability scores were most strongly correlated with FDSs, followed by the scores of pain, affection and social interaction. The more severely disabled group proved to have weaker grip strength, higher joint count, longer disease duration, higher ESR and blood level of CRP, and lower level of Hb. Patients with more disabilities proved to be older, pay more medical costs, have longer duration of morning stiffness, and higher level of RF. Patients with more advanced Steinbrocker's functional class, doctor's global assessment, Steinbrocker's anatomical stage, higher daily dose of prednisolone intake, lower level of annual income and formal education, and patients taking more kinds of NSAIDs proved to be more severely disabled. Separate, single (never married, widowed), and divorced patients proved to be more severely disabled compared with married ones. Overall, females were more disabled than males. CONCLUSION: Physical disability is associated with the other important aspects of QOL, clinical signs and symptoms, and socio-economic conditions in RA patients. Prevention and management of physical disability should be seriously planned in consideration of the changes in these conditions in RA patients.

Validity and reliability of a revised Japanese version of the Arthritis Impact Measurement Scales version 2 (AIMS2).

Abstract This study aims to evaluate the validity and reliability of a Japanese version of the Arthritis Impact Measurement Scales, version 2 (AIMS2) for patients with rheumatoid arthritis (RA). The Japanese version of the AIMS2 questionnaire was administered to 1643 patients with classical or definite RA at 11 hospitals nationwide in Japan. Reliability was assessed by a test-retest procedure, 4 weeks apart, using 75 randomly selected patients. Internal consistency was measured by Cronbach's α, and factor analysis was used to obtain the proportion of variance explained by the first factor in principal component analysis. The validity of the AIMS2 scales was assessed by internal standards. Internal consistency (α coefficients, 0.84-0.94), test-retest reliability (intraclass correlation coefficients, 0.75-0.93), and factor analysis (0.62-0.85) of the AIMS2 health status scales proved that they are highly reliable in the Japanese version. Validity, as measured by the relationships among the scores on the questionnaire items, was also sufficiently secured. The validity and reliability of the Japanese version of the AIMS2 are sufficient for all practical purposes when compared with the original and with other translated versions of the questionnaire.

[A case of various neurological deficits caused by multi-vitamin deficiency associated with malabsorption syndrome after pancreatomy and small bowel resection].

A 34-year-old woman presented with walking difficulty and pain in the legs 3 years after several abdominal operations for pancreatic cancer and intestinal obstruction thereafter. Corneal erosion, loss of deep sensation in the legs, polyneuropathy, myopathy, and memory disturbance were recognized. Deficiency of multiple vitamins (A, B1, B6, D, E, K) was found. The diagnoses were vitamin A-deficient corneal erosion, vitamin K-deficient bleeding abnormality (asymptomatic), and the neurological deficits caused by vitamin E, B1, B6 and D deficiency. Although the vitamin supplement started 2 years after the onset of the neurological disease, both clinical and electrophysiological recovery was seen. She was unable to walk on admission, but became able to walk after vitamin E supplement. To our knowledge, this is the first report showing multi-vitamin deficiency causing extensive neurological, ophthalmological, and hematological deficits. Recognition of this condition would prevent the progression of potentially irreversible neurological disorders in patients with malabsorption syndrome after extensive abdominal surgery.

Ankle arthrodesis in rheumatoid arthritis using an intramedullary nail with fins.

We describe an intramedullary nail with fin-like longitudinal ridges that we have developed for arthrodesis of the ankle in rheumatoid arthritis. Four fins with sharp tips were attached to the distal part of a cylindrical nail to stabilize the tibiotalar and subtalar joints. We used this nail in 15 feet of 15 patients with rheumatoid arthritis who were followed for an average of 34.9 months. Postsurgery, 13 patients were allowed to bear weight immediately, as tolerated, without immobilization. By 3 weeks, these patients were able to bear weight fully. Solid fusion of the ankle joint in an acceptable position and good clinical results were obtained in all patients. The only complications were two cases of delayed wound-healing.

Outcome of radical multiple synovectomy as a novel surgical treatment for refractory rheumatoid arthritis: implication of HLA-DRB1*0405 in post-operative results.

OBJECTIVE: The authors developed a technique for radical multiple synovectomy (RaMS), a novel surgical treatment for refractory rheumatoid arthritis (RA) intended to control RA activity as much as possible. The purpose of this article is to describe the technique and its short-term results. METHODS: Eighteen RA patients were followed up for at least 3 years after RaMS. Post-operative results were determined and the significance of the HLA-DRB1 alleles was studied. RESULTS: Six patients met the ARA criteria for clinical remission persistently and were classified as "remission" cases. Thirteen patients in whom the limited Lansbury index remained improved were rated as "improvement". The cumulative success rates for "remission" and "improvement" were 33.3% and 57.8%, respectively, at the time point of the latest observation. Remission was not achieved in any of the DRB1*0405-positive patients. Nine out of 10 DRB1*0405-negative patients showed persistent improvement. CONCLUSION: RaMs provided good results in one-third of patients with refractory RA at a minimum of 3 years. HLA-DRB1*0405 may be a good marker to follow the effects of RaMS in RA patients.

Improvement in rheumatoid arthritis following application of an extracorporeal granulotrap column, G-1.

Patients with rheumatoid arthritis (RA) showed significantly (P < 0.01) increased numbers of granulocytes in their peripheral blood compared with normal donors and patients with osteoarthritis, and this finding correlated with interleukin-6 and C-reactive protein levels and active joint score. Then, 17 patients with RA were treated eight times in 4 weeks with a newly developed extracorporeal granulotrap column containing cellulose acetate beads (G-1 column). This column reduced granulocytes in the outflow blood by 50.2% compared with inflow counts. To evaluate the efficacy of G-1 therapy, 17 patients were followed for 12 weeks from the beginning of this therapy. The modified Lansbury index (LI) for monitoring RA activity significantly improved from a pretreatment mean score of 60.8% to a posttreatment score of 51.3%. The lowered scores were maintained up to 12 weeks after the initiation of therapy. Of the four LI items, tender and swollen joint scores showed the most significant improvement, with the tender joint score showing a particularly significant decrease throughout the study period. No serious side-effects were observed. These findings suggested that G-1 therapy was effective for RA.

[Prognosis and outcome of rheumatoid arthritis--10 to 16 years of anti-rheumatic therapy].

One hundred twenty-eight rheumatoid arthritis (RA) patients were followed up over a long period of time (mean, 13.3 years; range, 10-16 years) in order to determine the role of pharmacotherapy in RA. Patients were aged 48.2 years on the average (23-79 years) and the mean RA duration was 7.8 years (0-58 years) upon initial visit to this unit. Although pharmacotherapy was effective in improving Lansbury's activity index and ESR, articular bone and cartilage destruction and functional impairment progressed gradually, resulting in the need for total hip, knee or ankle arthroplasty in 46 (96 joints) of the 128 patients. This finding indicates that current pharmacotherapy for RA has limitations in that it cannot completely prevent joint destruction and resulting functional impairment. This suggests that new therapeutic modalities, including new drugs, are necessary. Efforts were also made to determine factors which affect the prognosis of RA. The prognosis seemed pessimistic in RA patients with high activity and rheumatoid factor (RAPA) levels, long duration of illness, high Larsen scores and advanced functional impairment at the time of initial active therapy. It appeared necessary to maintain Lansbury's activity index at 30% or below in order to obtain a good prognosis.

Total knee arthroplasty in Charcot's joint.

The authors report three cases with neuropathic (Charcot) knee joint due to tabes dorsalis in which total knee arthroplasty (TKA) was performed. Three cases (5 joints) were observed for more than 8 years after TKA. No ataxia was seen before or after surgery. The postoperative clinical course had been satisfactory in two cases (3 joints) for 9-10 years after TKA with no evidence of loosening. Although the other case had medial condylar fracture of the right upper tibia during postoperative treatment, the clinical course of the right knee had been satisfactory over the 7 years since revision arthroplasty using a tibial component with a long stem. This case also had loosening of the left tibial component 8 years after TKA. Total knee arthroplasty appears to be useful for the treatment of Charcot's joint with no ataxia at Eichenholtz' stage of coalescence and reconstruction if (1) proper surgical techniques to establish good ligamentous balancing and bony alignment by releasing ligaments are employed; (2) an adequate amount of bone is resected and remaining bony defects are reinforced with bone graft; (3) long-stem components are used on both the femoral and tibial sides.

[A case report of rheumatoid arthritis patient with thoracic myelopathy].

The authors report a 39-year-old woman with rheumatoid arthritis associated with myelopathy at the thoracic level. X-ray films of thoracic spine showed scoliosis which had its apex at T6. Myelography demonstrated incomplete block at the level of T6. Computerized tomogram revealed destruction of left pedicle of the sixth thoracic vertebra and dislocation of the sixth rib into the spinal canal which compressed cord at T6 level. Hemi-laminectomy at T5-T7 level and decompression were performed. Pathological investigations of soft tissue around the cord and dura mater showed infiltration of small round cells. We concluded that the synovitis of costo-transverse joint or costovertebral joint led to the destruction of the pedicle. As a result, dislocation of the rib, scoliotic deformity and thoracic myelopathy occurred.

[Psychosomatic medicine in rheumatoid arthritis].

Recent studies have shown that neuropeptides, such as substance P, are responsible for arthritis. We therefore studied opioid peptides (beta-endorphin, Methionine-enkephalin, Leucine-enkephalin) in order to confirm our belief that mental status may have some influence on the activity of rheumatoid arthritis (RA). We examined opioid peptides, lymphocyte subsets, psycologic test (Cornell Medical Index-Health questionnaire (CMI), the Face scale) and clinical data in patients with RA. Plasma Leu-enk, % Leu2a+ Leu15- cells,% Leu3a+ Leu8- cells and % Leu11+ Leu7- cells were higher in patients with a larger number of psycologic complaints in CMI. Plasma Leu-enk concentration was higher while % Leu11+ Leu7- cells was lower in proportion to the degree of neurosis, as indicated by the descrimitive chart of CMI. Plasma Met-enk concentration, % Leu2a+ Leu15- cells, and Lansbury's index were significantly higher in the group of patients whose facial expression was more severe. These findings suggest that mentala status have some relationship with the plasma level of opioid peptides (enkephalins) and immunologic functions, and that it may exert indirect effects on RA.

[Clinical studies on 9 patients with Heberden's nodes of premenopausal onset].

Nine patients with Heberden's nodes of premenopausal onset were studied for complications in the form of thyroid disorders as well as from the hereditary, roentgenological and immunological aspects. In addition, rheumatoid arthritis, psoriatic arthritis, traumatic arthritis, erosive osteoarthritis or adult Still's disease was excluded in these patients. All patients had thyroid disorder (Basedow's disease in 6 patients, Hashimoto's thyroiditis in 2 patients and granular thyroiditis in one patient). Immunological examinations were positive for anti-thyroglobulin antibody in 5 patients and anti-microsome antibody in 3 patients and anti-nuclear antibody in 2 patients. Roentgenological findings revealed no typical signs of primary generalized osteoarthritis.