Yoshimitsu Doi

Expression of Th1/Th2-Related Chemokine Receptors on Peripheral T Cells and Correlation with Clinical Disease Activity in Patients with Multiple Sclerosis

Th1 cells play an important role in the pathogenesis of multiple sclerosis (MS), a disease likely linked to an autoimmune process. We measured the levels of chemokines in serum or cerebrospinal fluid (CSF) samples by ELISA, and also studied the expression of Th1-related CXCR3/CCR5 chemokine receptors and Th2-related CCR4/CCR3 chemokine receptors on blood cells from MS patients using three-color flow cytometry. The Bonferroni correction was used for the statistical analysis. The levels of CXCL10, CCL3, and CCL5 in the CSF samples for the MS groups were significantly higher than those for the control group. However, the levels of CCL2 in both the CSF and serum samples for the remission group were significantly higher than those for the active group. The percentage of CXCR3-expressing CD4+ T cells in patients with MS was significantly elevated compared with the healthy controls. Moreover, MS patients in an active phase showed a more increased CD4+CXCR3+/CD4+CCR4+ ratio than patients in a remission phase. The increased percentage of CD4+CXCR3+ cells in the blood was associated with relapses in MS. This study suggested that the CD4+CXCR3+/CD4+CCR4+ ratio could be a sensitive maker of immune dysfunction in MS.

Increased serum matrix metalloproteinase-9 in neuromyelitis optica: implication of disruption of blood-brain barrier.

Matrix metalloproteinase-9 (MMP-9) plays an important role in some neuroinflammatory diseases through the blood-brain barrier (BBB) disruption. To investigate the pathogenicity of MMP-9 in neuromyelitis optica (NMO), serum and CSF MMP-9 concentrations were measured in 13 NMO and 15 multiple sclerosis (MS) patients and 14 healthy controls, and correlated with clinical and laboratorial parameters. Serum MMP-9 concentrations were significantly higher in NMO than MS and controls, and correlated with EDSS score, CSF/serum albumin ratio, and CSF IL-8 concentrations. Our results indicate that MMP-9, promoted by elevated IL-8 activation, plays a crucial role in the pathogenesis of NMO through the BBB disruption.

Eicosapentaenoic acid (EPA) induces peroxisome proliferator-activated receptors and ameliorates experimental autoimmune encephalomyelitis

Eicosapentaenoic acid (EPA), one of the n-3 polyunsaturated fatty acids, is a neuroprotective lipid with anti-inflammatory properties. We investigated the possible therapeutic effect of EPA on experimental autoimmune encephalomyelitis (EAE). EAE mice were fed a diet with or without EPA. The clinical EAE scores of the EPA-fed mice were significantly lower than those of the non-EPA mice. In the EPA-treated mice, IFN-γ and IL-17 productions were remarkably inhibited and the expression levels of peroxisome proliferator-activated receptors were significantly enhanced in the CNS-infiltrating CD4T cells. Thus EPA shows promise as a potential new therapeutic agent against multiple sclerosis.

Postural Abnormality as a Risk Marker for Leg Deep Venous Thrombosis in Parkinson’s Disease

Background Pulmonary thromboembolism is a common cause of death in patients with autopsy-confirmed Parkinsonism. This study investigated the incidence of leg deep vein thrombosis in Parkinson’s disease and relationships between deep vein thrombosis and clinical/laboratory findings, including postural abnormalities as assessed by photographic measurements. Methods This cross-sectional study assessed the presence of deep vein thrombosis using bilateral leg Doppler ultrasonography in 114 asymptomatic outpatients with Parkinson’s disease. Results Deep vein thrombosis was detected in 23 patients (20%) with Parkinson’s disease. Deep vein thrombosis was located in the distal portion in 18 patients and in the proximal portion in 5 patients. No significant differences in age, sex, body mass index, disease duration, Hoehn-Yahr stage, anti-Parkinson’s drugs, or daily levodopa-equivalent dose were seen between deep vein thrombosis-positive and -negative groups. Univariate analysis for developing deep vein thrombosis in patients with Parkinson’s disease identified the following markers: long-term wheelchair use, bent knee, bent spine, and D-dimer elevation. Bending angles were significantly greater in the deep vein thrombosis-positive group at the knee and spine than in the deep vein thrombosis-negative group. Half of Parkinson’s disease patients with camptocormia had deep vein thrombosis. Among diabetes mellitus cases, long-term wheelchair use, bent knee over 15°, camptocormia, D-dimer elevation, the more risk markers were associated with a higher incidence of DVT. The presence of risk markers contributed to the development of deep vein thrombosis. On multivariate logistic regression analysis, a bent knee posture was strongly associated with an increased risk of deep vein thrombosis. Conclusion Presence of leg deep vein thrombosis correlated with postural abnormalities in Parkinson’s disease. We recommend non-invasive ultrasonographic screening for leg deep vein thrombosis in these high-risk patients with Parkinson’s disease.

Clinical manifestations of chronic inflammatory demyelinating polyneuropathy with anti-cardiolipin antibodies

Objective – Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune syndrome where certain autoantibodies define clinicopathologic subgroups. In the present study, serum anti‐cardiolipin antibodies (aCL) were evaluated.

Recurrent cerebral embolism in a young adult with Down's syndrome. A case report.

Sirs: Patients with Down’s syndrome, the most common human chromosomal malformation, often suffer from a variety of concomitant disorders, such as congenital heart disease, leukemia, or malignancy [5]. Several cases of Down’s syndrome (DS) with stroke disorders and moyamoya-like vessels have been reported in the literature [2, 3, 10, 11]. We report here a case of recurrent embolic stroke in a young adult with DS. A 31-year-old right-handed female with DS developed a sudden onset of nuchal pain and vertigo. She could not stand because of weakness in her lower extremities. She was admitted to Osaka Medical College on September 6, 2003. A karyotype of trisomy 21 had been confirmed when the patient was 1 month old. Upon her admission now, the stigmata of DS were present: ocular hypertelorism; broad, flat facies; wide neck; low-set, posteriorly rotated ears; and short hands with clinodactylism. The rest of the physical examination, including her cardiovascular system, was unremarkable. She had entered into a confused state and her speech had become slow and slurred. A neurological examination showed hemiparesis with hyperreflexia and Babinski’s sign on the right side. Both eyes rested in an inward position, and there was paralysis of upward and downward gaze. Striking dysmetria was noted in the left upper and lower extremities. Her gait was very broad-based and she could not walk without support. Cranial MRI showed hypersignal intensity in the left cerebellar hemisphere on T2 and diffusionweighted images, and in the medial part of the left thalamus on diffusion-weighted images (Fig. 1a, b). MR angiography of the brain was normal. There were normal findings in several studies: complete blood count, sedimentation rate, prothrombin time, partial thromboplastin time, thrombin anti-thrombin III complex, fibrinogen, fasting plasma glucose, serum cholesterol, triglyceride, C-reactive protein, antinuclear antibody, rheumatoid factors, serology of syphilis, antiphospholipid antibodies, protein C, and urine homocystine levels. There were normal results in a cardiac evaluation that included electrocardiogram, echocardiogram, and 24-hour rhythm monitor. A spine roentgenogram revealed a dislocation of the C1 and C2 vertebrae (Fig. 2a). Color-coded Doppler ultrasonography showed anterograde and severely reduced flow in the left vertebral artery. She was treated with aspirin. On 13th day after admission, she suddenly developed memory disturbance. Neurologically, her hemiparesis and motor ataxia were not aggravated, and there was no evidence of other abnormalities. A follow-up MRI of the brain showed high signals in the pons as well as in the bilateral hippocampal and occipital regions on T2 and diffusion-weighted images (Fig. 1c, d). Three-dimensional helical CT (3D-CT) demonstrated hypoplasia of the left vertebral artery and local occlusion at the C2 level; this was the same portion where there was the atlantoaxial dislocation (Fig. 2b). After a relapse of the disease, she was treated with aspirin and ticlopidine hydrochloride. Her neurological signs, except for amnesia, then improved. The occurrence of stroke in DS has been rarely reported; and some of the cases that have been reported were secondary to cyanotic heart disease with paradoxical emboli or to meningitis [11]. Epidemiologic studies have found a higher incidence of moyamoya syndrome in patients with DS [6]. Patients with DS associated with cerebral amyloid angiopathy have been represented in few previous reports [4]. Our patient manifested a top-ofthe-basilar-artery syndrome without evidence of any congenital cardiac lesion, right-to-left shunts, or valvular endocarditis. These emboli usually present as cerebral infarcts in the carotid distribution. Moreover, there were no stenosed or occluded lesions of major arteries on cranial MR angiography. The findings of 3D-CT and Doppler ultrasonography suggested that posterior circulation stroke in our patient might result from kinking and occlusion of the vertebral artery at the level of an atlantoaxial dislocation. To our knowledge, there have been no previous reports of patients with DS associated with infarction caused by atlantoaxial dislocation. Stroke due to atlantoaxial dislocation has been observed in a few cases, most of which were caused by cervical spine trauma [8, 9] and rarely by ankylosing spondylitis [14] or cranio-cervical anomalies [1]. In a retrospective review of cineangiography of patients with DS, 40 % of LETTER TO THE EDITORS