Antibodies against the main immunogenic region of the acetylcholine receptor correlate with disease severity in myasthenia gravis.

OBJECTIVE: We developed an assay that detects autoantibodies against the main immunogenic region (MIR) located at the extracellular end of the nicotinic acetylcholine receptor (AChR) α subunit, and investigated its clinical relevance in myasthenia gravis (MG). METHODS: In this retrospective cohort study, we measured MIR antibody (Ab) titres in sera obtained before treatment and analysed their associations with clinical parameters in 102 MG patients from two neurological centres. MIR Ab titres were determined using a modified competition immunoprecipitation assay in the presence or absence of monoclonal antibody 35. RESULTS: 11 of 23 (47.8%) ocular type and 66 of 72 (91.7%) generalised type MG patients were positive for the presence of MIR Abs, defined as a titre >16.8% (3 SDs above the mean for 70 healthy controls). A significantly higher MIR Ab titre (p<0.001) was shown in generalised type (47.9±19.2%) rather than in ocular type MG patients (16.4±8.4%). Bivariate regression analysis using both titre levels of MIR Ab and routine AChR binding Ab as variables revealed MIR Abs to be an exclusive indicator positively associated with disease severity (Myasthenia Gravis Foundation of America classification, p<0.0001; Quantitative MG score, p=0.008), the presence of bulbar symptoms (p<0.0001) and thymoma (p=0.016), and negatively associated with ocular MG (p<0.0001). CONCLUSIONS: MIR Ab titre levels show much better correlations with factors related to disease severity compared with AChR binding Ab titres. The MIR Ab assay may be useful for predicting MG symptom severity, especially for discriminating between ocular and generalised types of MG.

[Differences in the bone mineral density in patients with Kanemi Yusho treated before and after the age of 18 years].

This study examined patients with Kanemi Yusho. The patients' height, weight, and bone mineral density were measured. The density of the distal end of the radius was measured using dual energy X-ray absorptiometry and the calcaneum was measured with ultrasound. We also measured urine levels of cross-linked N-telopeptides of type I collagen, serum tartrate-resistant acid phosphatase 5b, serum bone-specific alkaline phosphatase, serum Ca, serum P and blood PCB level. The patient group that took PCBs when they were 0 to 18 years old (such patients were 42 to 60 years old at the time of the study) showed no correlation between the bone density of the radius and calcaneum in spite of treatment received when they were over 18 years of age (> 60 years of age at the time of the study). The bone mineral density in Kanemi Yusho was not different from the control group. The levels of only serum bone-specific alkaline phosphatase were correlated with the bone mineral density of the radius and calcaneum in patients treated when they were over 18 years of age (currently over 60 years old). PCBs might have had an effect on bone density and bone metabolism.

Macrophagic myofascitis associated with rheumatoid arthritis.

Macrophagic myofascitis (MMF) is an unusual inflammatory myopathy characterized by muscle infiltration by macrophages and lymphocytes. Here, we describe a case of MMF which is associated with rheumatoid arthritis. A 53-year-old Japanese rheumatoid arthritis (RA) patient presented with focal tenderness of lower extremities. Magnetic resonance imaging showed evidence of myofascitis involving fascias of anterior tibialis muscle. Muscle biopsy showed a unique pathological pattern of MMF. MMF is known to be associated with vaccination containing aluminum. However, our case was not related to aluminum containing vaccinations and etiologies are unknown. The possible link needs to be discussed.

IgG4-related disease with cavernous sinus and intra-orbital lesions diagnosed by nasal mucosa biopsy.

IgG4-related disease is a systemic disease characterized by lesions with IgG4 positive plasma cell infiltration in the involved organs and a raised serum IgG4 level. We report a patient of 70-year-old male presented orbital inflammation of IgG4-related disease. The patient developed right eye pain, double vision, and reduced eye sight. MRI image revealed mild right ocular proptosis and swelling of right carvenous sinus, bilateral intraorbital extraocular muscles and right optic nerve. Right optic nerve showed ring-like enhancement. IgG4-related disease was suspected with increased serum IgG4 level of 355 mg/dl, mediastinal lymphadenopathy and prostate enlargement. Transbronchial lung biopsy and prostate needle biopsy were administered with negative results. The eye related symptoms resolved with time, but serum IgG4 continuously increased. IgG4-related disease was diagnosed by nasal mucosa biopsy, which showed IgG4 positive plasma cells within the inflammatory infiltrate. This report emphasizes the usefulness of nasal mucosa biopsy for the diagnosis of IgG4 related disease with lesions difficult to approach.

Antibodies to myelin oligodendrocyte glycoprotein in idiopathic optic neuritis.

OBJECTIVES: To investigate the differences of clinical features, cerebrospinal fluid (CSF), MRI findings and response to steroid therapies between patients with optic neuritis (ON) who have myelin oligodendrocyte glycoprotein (MOG) antibodies and those who have seronegative ON. SETTING: We recruited participants in the department of neurology and ophthalmology in our hospital in Japan. METHODS: We retrospectively evaluated the clinical features and response to steroid therapies of patients with ON. Sera from patients were tested for antibodies to MOG and aquaporin-4 (AQP4) with a cell-based assay. PARTICIPANTS: Between April 2009 and March 2014, we enrolled serial 57 patients with ON (27 males, 30 females; age range 16-84 years) who ophthalmologists had diagnosed as having or suspected to have ON with acute visual impairment and declined critical flicker frequency, abnormal findings of brain MRI, optical coherence tomography and fluorescein fundus angiography at their onset or recurrence. We excluded those patients who fulfilled the diagnostic criteria of neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD), MS McDonald's criteria, and so on. Finally we defined 29 patients with idiopathic ON (14 males, 15 females, age range 16-84 years). RESULTS: 27.6% (8/29) were positive for MOG antibodies and 3.4% (1/29) were positive for AQP4. Among the eight patients with MOG antibodies, five had optic pain (p=0.001) and three had prodromal infection (p=0.179). Three of the eight MOG-positive patients showed significantly high CSF levels of myelin basic protein (p=0.021) and none were positive for oligoclonal band in CSF. On MRIs, seven MOG-positive patients showed high signal intensity on optic nerve, three had a cerebral lesion and one had a spinal cord lesion. Seven of the eight MOG-positive patients had a good response to steroid therapy. CONCLUSIONS: Although not proving primary pathogenicity of anti-MOG antibodies, the present results indicate that the measurement of MOG antibodies is useful in diagnosing and treating ON.

[A case of meningeal disseminated sarcoidosis with marked hypoglycorrhachia in the CSF].

A 29-year-old man diagnosed as having pulmonary sarcoidosis in 2008, and hypothyroidism secondary to thyroidectomy for Basedow's disease was admitted to our hospital with pustular psoriasis in November 2010. He experienced high fever (38°C) and headache in late October 2010. Gadolinium-enhanced T1-weighted image showed multiple micronodular lesions with leptomeningeal enhancement, mainly in the brainstem. Cerebrospinal fluid (CSF) analysis revealed pleocytosis, raised protein level and hypoglycorrhachia (7 mg/dl). The patient was also found to have osteonecrosis of the left femoral head. Antituberculous treatment and steroid pulse therapy were started, but produced no improvement of either the symptoms or the laboratory data. Finally, the patient was diagnosed as having meningeal disseminated sarcoidosis by meningeal biopsy in late March 2011. He was started on treatment with 60 mg prednisolone per day, which resulted in marked clinical improvement. It should be borne in mind that marked hypoglycorrhachia in the CSF can also be seen in meningeal disseminated sarcoidosis.

A case of Japanese spotted fever complicated with central nervous system involvement and multiple organ failure.

Japanese spotted fever (JSF), first reported in 1984, is a rickettsial disease characterized by high fever, rash, and eschar formation. A 61-year-old man was admitted to a local hospital in Nagasaki City, Japan, after several days of high fever and generalized skin erythema. His condition deteriorated and laboratory findings indicated disseminated intravascular coagulation (DIC). The patient was transferred to our hospital with mental disturbance and status epilepticus. Treatment included minocycline, and new quinolone. Definitive diagnosis was made with a serological test showing increased antibody levels against Rickettsia japonica. Rickettsial infections are rare, but should be seriously considered for the differential diagnosis of aseptic meningitis and encephalitis, as they show no response to conventional antibiotic treatment.