Antineutrophil cytoplasmic antibodies in patients with idiopathic inflammatory-demyelinating diseases.

OBJECTIVE: We assessed the clinical significance of antineutrophil cytoplasm antibodies (ANCA) in patients with idiopathic inflammatory-demyelinating disease (IIDD). METHODS: A consecutive cohort of 269 subjects with IIDD and 595 controls was analyzed retrospectively. RESULTS: Among all subjects, ANCA positivity rates were low [9.5% in a perinuclear pattern (pANCA) and 2.3% in a cytoplasmic pattern (cANCA)]. One of the 117 patients with multiple sclerosis (MS) had cANCA and 2 had pANCA. Ten patients with neuromyelitis optica (NMO; 13.9%) had pANCA and 3 (4.2%) had cANCA. Four patients with recurrent longitudinal extensive transverse myelitis (RLETM; 19.0%) had pANCA and 1 (4.8%) had cANCA. In monophasic TM, 22.9% were pANCA seropositive. Among patients with brainstem syndromes, 14.3% were pANCA seropositive. Patients with NMO, RLETM or monophasic TM had higher pANCA levels than patients with MS. There was a positive association between spinal cord (SC) lesions and ANCA, and especially between longitudinal extensive transverse myelitis and ANCA. Among anti-aquaporin 4 antibody-positive patients, ANCA-positive patients (n = 16) were older and had higher Expanded Disability Status Scale scores, more antinuclear antibodies, longer SC lesions and fewer brain abnormalities than the ANCA-negative patients (n = 68). In the NMO subgroup, ANCA-positive patients were older and had more antinuclear antibodies and longer SC lesions than ANCA-negative patients. CONCLUSION: Among the IIDDs, we found a higher occurrence of ANCA in patients with NMO spectrum disorders than in patients with MS. Therefore, ANCA is another interesting marker of autoimmunity in IIDD patients, especially those with anti-aquaporin 4 antibody.

Cerebral venous sinus thrombosis may be associated with hepatitis B virus infection: a preliminary finding.

OBJECTIVE: To assess the clinical significance of hepatitis B virus (HBV) infection in patients with cerebral venous sinus thrombosis (CVST). METHODS: Twenty-two patients with CVST confirmed by magnetic resonance venography (MRV) or digital subtraction angiography (DSA) and 743 controls with ischemic stroke confirmed by magnetic resonance imaging (MRI) were analyzed retrospectively. RESULTS: Among all researches, HBV surface antigen (HBsAg)-positive rate was high. Six of the 22 (27.3%) confirmed cases had HBsAg. However, HBsAg-positive rate in patients with ischemic stroke was only 45 of the 743 cases (6.1%), closed to the average prevalence in China (∼ 8.6%), but much lower than the positive rate in CVST patients (27.3 vs 6.1%, P  =  0.002). Odd ratio (OR) value between HBsAg-positive CVST patients (27.3%) and HBsAg-positive ischemic stroke patients (6.1%) was 5.78. The OR value between HBsAg-positive CVST patients (27.3%) and average prevalence of HBV infection in China (8.6%) was nearly 3.99. It meant that HBV infection might be a risk factor for CVST. However, there existed no statistically significant difference in HBV surface antibody (HBsAb), HBV e antigen (HBeAg), HBV e antibody (HBeAb), and HBV central antibody (HBcAb)-positive rate. The HBV surface antigen (HBsAg)-positive CVST patients did not show worse liver function. Most of them were inactive HBV carriers. CONCLUSION: Hepatitis B virus infection may be a risk factor for CVST.

Serum thyroid-stimulating hormone and anti-thyroglobulin antibody are independently associated with lesions in spinal cord in central nervous system demyelinating diseases.

Transverse myelitis (TM) is associated with neuromyelitis optica (NMO) and multiple sclerosis (MS). Early recognition of useful parameters may be helpful to distinguish their difference. This retrospective study analyzed thyroid parameters from 243 serum samples (relapse = 128; remission = 115) of 178 patients with demyelinating diseases (NMO, n = 25; TM, n = 48; MS, n = 105). The relationship between thyroid and clinical parameters was analyzed. Patients with NMO and TM had a higher frequency of abnormal thyroid-stimulating hormone (TSH), anti-thyroglobulin antibodies (TG-Ab), and antithyroid peroxidase antibody (TPO-Ab) than MS patients (p<0.05). The level of TSH and TG-Ab returned to normal levels after administration of high-dose intravenous methylprednisolone (p<0.05). In 96 patients (NMO, n = 19; TM, n = 25; MS, n = 52) without treatment, serum levels of TSH, TG-Ab and TPO-Ab were significantly different between patients with and without myelitis (p<0.01). Patients positive for aquaporin-4 (AQP4) antibodies showed higher abnormalities of TSH (p = 0.001), TG-Ab (p = 0.004) and TPO-Ab (p<0.0001) levels than AQP4 antibodies negative patients. Logistic regression analyses revealed independent relationships between TSH (odds ratio [OR]  = 33.994; p<0.0001), TG-Ab (OR = 7.703; p = 0.017) and myelitis occurrence in 96 patients at the active stage. In 52 MS patients experiencing their first attack, MS patients with myelitis were associated with TSH abnormalities (OR = 42.778; p<0.0001). This study showed increased abnormalities of thyroid parameters in patients with NMO and TM than in MS patients. MS patients with myelitis also had greater TSH abnormality than in MS patients without myelitis. Abnormal TSH and TG-Ab were independently associated with myelitis occurrence in central nervous system demyelinating disorders.

Brain gadolinium enhancement along the ventricular and leptomeningeal regions in patients with aquaporin-4 antibodies in cerebral spinal fluid.

BACKGROUND: Aquaporin-4 (AQP4) is densely expressed in the ependymal region and leptomeninges, and it is susceptible to pathological responses triggered by antibodies from blood and cerebral spinal fluid (CSF). Therefore, enhancement of these regions may be related to neuromyelitis optica spectrum disorder (NMOSD). METHODS: MRI from a consecutive cohort of 84 subjects (NMOSD=47, multiple sclerosis [MS]=37) with AQP4 antibodies in serum and CSF were analyzed retrospectively. RESULTS: The brain was normal in five of the 47 patients with NMOSD and none of the MS patients showed a normal brain. Twelve patients in each group had parenchymal enhancing lesions. Of these, white matter enhancement was more frequently found in MS patients than in NMOSD patients (12/12 vs 4/12, p=0.001). "Cloud-like" enhancement was found in three NMOSD patients (3/12) and in one MS patient. Nine of the 12 NMOSD patients showed "pencil-thin" ependymal enhancement, whereas one of the 12 MS patients showed ependymal enhancement (p=0.003). Enhancement along the lateral ventricle was more frequently found in NMOSD patients than in MS patients (p=0.027), whereas enhancing lesions around the fourth ventricle tended to be more frequent in NMOSD patients than MS patients (p=0.097). Leptomeningeal enhancement around the brainstem was found in six (12.8%) NMOSD patients and in no MS patients (p=0.032). CONCLUSION: Enhancement of the leptomeninges and ventricular ependymal region more frequently occurs in NMOSD patients than in MS patients. This may be considered as characteristic clue in the diagnosis of NMOSD.

Development of a cell-based assay for the detection of anti-aquaporin 1 antibodies in neuromyelitis optica spectrum disorders.

OBJECTIVE: To develop a cell-based assay (CBA) to detect aquaporin 1 (AQP1) antibodies and determine sensitivity/specificity in patients with neuromyelitis optica (NMO) spectrum disorders. METHODS: A HEK-293T transfected cell model expressing AQP1 was established and detected to be serum AQP1 antibodies. RESULTS: AQP1 antibodies were present in 73/98 (74.5%) AQP4 antibody-positive patients. Some AQP4 antibody-negative patients were also AQP1 antibody-positive. Test sensitivity was 74.5% in 98 AQP4 antibody-positive patients. Test specificity was 79.6% in 67 multiple sclerosis (MS) patients and 31 controls. CONCLUSION: A sensitive and simple CBA was developed to detect serum AQP1 antibodies. AQP1 antibodies were mainly present in NMO and its high-risk syndrome, but also in some MS patients.

Serum anticardiolipin antibodies in patients with neuromyelitis optica spectrum disorder.

The presence of anticardiolipin antibodies (ACLA) in multiple sclerosis (MS) patients has been reported, but there are some debates on the relationship between ACLA and MS. We assessed the clinical features of neuromyelitis optica spectrum disorders (NMOSD) patients with ACLA. A consecutive cohort of 480 subjects with NMOSD (n = 70), MS (n = 90) and control (n = 220) were analysed retrospectively. Patients' serum was tested by a dot-immunogold filtration assay for the presence of ACLA-IgG, IgM and IgA antibodies. In MS patients, 5 (5.6 %) of the 90 patients showed ACLA-IgG reactivity in the serum. In NMOSD patients, 32 (45.7 %) of the 70 patients showed ACLA reactivity in the serum, among which ACLA-IgG seropositivity was 45.7 % (32/70), ACLA-IgG + IgM seropositivity was 8.6 % (6/70), and ACLA-IgG + IgA seropositivity was 4.3 % (3/70). NMOSD patients were higher in ACLA-IgG (p < 0.0001) and ACLA-IgG + IgM (p = 0.006) than the MS patients. NMOSD patients had higher ACLA-IgG than the control patients (p < 0.0001). In comparison with the controls, the MS patients were lower in ACLA for IgG (p = 0.014) and IgM (p = 0.004). Seropositive ACLA patients increased in age (p = 0.013) and had higher D-dimer levels (DD) (p = 0.002) than the seronegative NMOSD patients. Furthermore, positive ACLA-IgG + IgM patients were increased in age (p = 0.001), had higher baseline EDSS (p = 0.001), antithrombin III activity (p = 0.04), and DD levels (p = 0.005) than the pure positive ACLA-IgG NMOSD patients. Patients with NMOSD had more occurrences of ACLA than patients with MS. NMOSD patients with positive ACLA-IgG + IgM had a worse outcome that may be associated with elder age and abnormal coagulation parameters in blood.