Shimon Ishida

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.

Anhedonia in Japanese patients with Parkinson's disease

Aim:  Anhedonia has been proposed as a specific mood disorder related to the dopaminergic nerve dysfunction seen in Parkinsons disease (PD). This study examined hedonic tone in patients with PD using the Snaith–Hamilton Pleasure Scale (SHAPS) and investigated the associations with depressive mood by the Self‐Rating Questionnaire for Depression (SRQ‐D).

Expression of vascular endothelial growth factor by plasma cells in the sclerotic bone lesion of a patient with POEMS syndrome

Sirs: Bone lesions are frequently present in patients with POEMS syndrome [1, 2]. Since solitary bone lesions are often plasmacytomas, they must be aggressively treated with surgery or radiotherapy. We report a case of POEMS syndrome with a solitary bone lesion. In this patient, plasma cells in the osteosclerotic lesion were the source of vascular endothelial growth factor (VEGF). A 42–year-old man developed distal dominant polyneuropathy two months after myocardial infarction. Following the onset of neurological symptoms, he exhibited edema, bristly skin, and swelling of the liver in the abdominal CT. Platelet counts were 822,000/mm, and immunoelectrophoresis demonstrated Mprotein of IgA k. Serum IL-6 and VEGF were measured using standardized ELISA (SRL, Inc., Tokyo, Japan). Although the IL-6 level was normal (2.1 pg/ml. Normal value; <4.0 pg/ml), the serum VEGF level was significantly elevated (18,500 pg/ml). He was diagnosed with POEMS syndrome. However, bone marrow aspiration from the ileum exhibited a normal appearance, and CT of the chest and the abdomen revealed no abnormal lesions, suggesting solitary or extramedullary plasmacytoma. Following steroid pulse therapy, treatment with prednisolone reduced the serum VEGF to 860 pg/ ml with marked improvement of muscle weakness and skin lesions. Although the neuropathy remained clinically stable, he again exhibited edema and bristly skin 9 months after the pulse therapy, and the serum VEGF was increased to 5,120 pg/ml. Bone scintigraphy demonstrated a spot

Fine mapping of 16q-linked autosomal dominant cerebellar ataxia type III in Japanese families

Abstract.The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. To date, at least 11 genes and 13 additional loci have been identified in ADCAs. Despite phenotypic differences, spinocerebellar ataxia 4 (SCA4) and Japanese 16q-linked ADCA type III map to the same region of 16q22.1. We report four Japanese families with pure cerebellar ataxia and a disease locus at 16q22.1. Our families yielded a peak lod score of 6.01 at marker D16S3141. To refine the candidate region, we carried out genetic linkage studies in four pedigrees with a high density set of DNA markers from chromosome 16q22.1. Our linkage data suggest that the disease locus for 16q-ADCA type III is within the 1.25-Mb interval delineated by markers 17msm and CTTT01. We screened for mutations in 36 genes within the critical region. Our critical region lies within the linkage interval reported for SCA4 and for Japanese 16q-ADCA type III. These data suggest that the ADCA that we have characterized is allelic with SCA4 and Japanese 16q-linked ADCA type III.

Clinical and genetic characterization of 16q-linked autosomal dominant spinocerebellar ataxia in South Kyushu, Japan

16q-ADCA (OMIM no. 117210) is an autosomal dominant spinocerebellar ataxia (AD-SCA) characterized by late-onset pure cerebellar ataxia and −16C>T substitution of the puratrophin-1 gene. Recently, a series of single-nucleotide polymorphisms (haplotype block) were found to be specific to 16q-ADCA. We screened patients with ataxia and found 62 patients, including four homozygotes who carry the C–T substitution of the puratrophin-1 gene. By further analysis of the patients with the haplotype block, we observed a single-founder effect for 16q-ADCA, even in patients who are supposed to be sporadic late cortical cerebellar atrophy (LCCA). We also observed slippage mutations of microsatellite markers, GATA01 and 17msm, in the pedigrees. We compared the clinical course of 16q-ADCA in heterozygotes and homozygotes with the haplotype block and observed no apparent gene dosage effect. 16q-ADCA accounts for 27% of AD-SCAs and is the most frequent AD-SCA in South Kyushu, Japan.

Serial MRI findings in a relapsing-remitting form of neuro-Behcet's disease A case report

We describe a case of neuro-Behcets disease (NBD) characterized by recurrent attacks of neurologic deficit. T2-weighted images showed a high signal intensity lesion with extensive edema in the right thalamolenticular region, midbrain, and pons as well as the cerebral white matter. After a relapse of the disease, MRI demonstrated a high signal intensity in the left thalamus, internal capsule, and midbrain. These MRI abnormalities showed marked resolution with steroid treatment. We observed sequential MRI findings in a patient with a relapsing-remitting form of NBD who had parenchymal CNS involvement, and we examined the correlation among the MRI findings and clinical features during the clinical course.

Multiple organ injury associated with neuromyelitis optica spectrum disorder in a low-grade B-cell lymphoma suspected of being follicular lymphoma

A 57-year-old woman was admitted to our hospital because she developed progressive paresthesia in the chest, lower limb weakness, and pain and swelling of the femoral region. Magnetic resonance imaging (MRI) of the spinal cord showed longitudinally extended transverse myelitis and a T2-hyperintense lesion extending from C5 to T4 (Fig. 1a). Brain MRI showed T2-hyperintense lesions predominantly in periventricular white matter, and corona radiata (Fig. 1b). MRI of the thighs showed T2-hyperintense lesions with hematomas in the rectus femoris muscles bilaterally associated with severe edema (Fig. 1c). Computed tomography showed no lymphadenopathy. The results of blood analysis were as follows: white blood cell count, 15.25 9 10/l (38.5% abnormal small cleaved lymphoid cells with inconspicuous nucleoli); creatine kinase, 2156 U/l; and C-reactive protein, 2.10 mg/dl. Serum NMO immunoglobulin G (NMO-IgG) (often called anti-aquaporin-4 [AQP4] antibody [AQP4-Ab]) was 3.8 U/ ml (normal \1.0 U/ml). A bone marrow aspirate showed an abnormal lymphoid infiltration of 32.6%. Immunohistochemical analysis showed that the cells were positive for CD10, CD20, and bcl-2. Southern-blot analysis showed clonal rearrangement of the immunoglobulin heavy-chain gene. We diagnosed her as a case of neuromyelitis optica (NMO) spectrum disorder [1] and AQP4-Ab–associated hematoma in rectus femoris bilaterally. We suspected follicular lymphoma but could not locate the primary site. Therefore, we also diagnosed low-grade B-cell lymphoma that was highly suspected of being follicular lymphoma. Methylprednisolone (1,000 mg/day) was administered intravenously, and was followed by a reduced dose of betamethasone (2 mg/day). However, a few days later, progressive paresthesia and leg weakness reappeared and she was diagnosed as a case of NMO spectrum disorder. Moreover, the patient’s serum sodium level had decreased to 127 mEq/l (normal 135–148 mEq/l), plasma osmolarity was 265 mOsm/kg/H2O (normal 285–295 mOsm/kg/H2O), while the urine osmolarity was 906 mOsm/kg/H2O. Plasma antidiuretic hormone (ADH) concentration was 8.3 pg/ml (normal 1.3–4.1 pg/ml). The patient was diagnosed with AQP4-Ab–associated syndrome of inappropriate secretion of ADH (SIADH). The NMO spectrum disorder was controlled by increasing the methylprednisolone dose to 125 mg/day followed by reducing the dose to 60 mg/day. Two weeks later, cough and dyspnea developed and the blood gas values showed a deteriorated condition. Chest radiograph revealed marked infiltrative shadows in bilateral lung fields (Fig. 1d). The clinical course and findings led to the diagnosis of AQP4-Ab-associated adult respiratory distress syndrome (ARDS). Methylprednisolone (1,000 mg/day) was administered, after which methylprednisolone was tapered off. Four days later, improvement of infiltrative shadows was observed on chest radiographs S. Nakayama-Ichiyama (&) T. Yokote N. Hiraoka K. Iwaki A. Takayama K. Kobayashi T. Akioka S. Oka T. Miyoshi S. Ishida T. Hanafusa Department of Internal Medicine (I), Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-0801, Japan e-mail: 1304@poh.osaka-med.ac.jp

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

Interferon-β1b Increases Th2 Response in Neuromyelitis Optica

A Japanese randomized controlled study showed that Interferon â (IFN-â1b) therapy is clinically effective in decreasing the frequency of attacks in multiple sclerosis (MS), even in optico-spinal MS (OSMS). However, recent studies have shown that IFN-â (IFN-â1a/IFN-â1b) treatment was not effective in neuromyelitis optica (NMO) patients and that the diminished benefit of IFN-â treatment in NMO may be due to different immune responses to IFN-â. We determined longitudinally the expression of CCR5, CXCR3 and CCR4 on CD4+ T and CD8+ T cells in the blood from patients with NMO and MS treated with IFN-â1b. During a 12-month period of IFN-â1b therapy, the annualized relapse rate decreased in MS patients but not in NMO patients. There was no significant difference in the expression of the chemokine receptors between NMO and MS at baseline. The percentages of CD4+CCR5+ and CD4+CXCR3+ T cells, representative of the Th1 response, were decreased in both NMO and MS after treatment. The percentage of CD4+CCR4+ T cells, representative of the Th2 response, was decreased in MS, but those for NMO was significantly increased compared with the pretreatment levels. Our results indicate that IFN-â1b-induced up-modulation of the Th2 response in NMO patients may be the source of differences in the therapeutic response to IFN-â1b therapy. In the present study, Th2 predominance is involved in the pathogenesis of NMO.

Acute Cerebellar Ataxia with an MRI Abnormality: A Sequential Imaging Study

Introduction Acute cerebellar ataxia (ACA), or acute cerebellitis, is a benign disease occurring with or after a nonspecific viral infection and generally has a good prognosis [1, 2]. ACA occurs most commonly in young children, and in the majority of cases, cerebrospinal fluid (CSF) and neuroimaging analysis are normal. Serial MRI findings have been reported in single-case studies in children [3, 4]. We report a sequential study of MRI in adult with ACA.