Shu-ichi Ikeda

Shinshu University, Shonai, Nagano, Japan

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Publications (344)847 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A 57-year-old woman with familial amyloid polyneuropathy (FAP) was scheduled to undergo living-donor liver transplantation (LDLT), but the operation was cancelled because the only potential donor had chronic alcohol-related liver disease (ALD). One year later, FAP-related neurological symptoms progressed rapidly, and emergency LDLT was planned. The donor's hepatic function had returned to normal range after 1 year of abstinence. The left liver graft volume was equivalent to 37.7% of the standard liver volume (SLV) of the recipient. However, a liver biopsy revealed mild fibrosis (score: F1). LDLT was successfully performed without any complications. The recipients' neurological findings returned to normal. One year after LDLT, the liver graft volume was equivalent to about 90% of the SLV, and the fibrosis had improved. LDLT using a graft with a fibrosis score of up to F1 might be an acceptable alternative for recipients with normal hepatic function. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Hepatology Research 01/2015; · 2.07 Impact Factor
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    ABSTRACT: SLC25A13 (citrin or aspartate-glutamate carrier 2) is located in the mitochondrial membrane in the liver and its genetic deficiency causes adult-onset type II citrullinemia (CTLN2). CTLN2 is one of the urea cycle disorders characterized by sudden-onset hyperammonemia due to reduced argininosuccinate synthase activity. This disorder is frequently accompanied with hepatosteatosis in the absence of obesity and ethanol consumption. However, the precise mechanism of steatogenesis remains unclear. The expression of genes associated with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from 16 CTLN2 patients and compared with 7 healthy individuals. Although expression of hepatic genes associated with lipogenesis and TG hydrolysis was not changed, the mRNAs encoding enzymes/proteins involved in FA oxidation (carnitine palmitoyl-CoA transferase 1α, medium- and very-long-chain acyl-CoA dehydrogenases, and acyl-CoA oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1), were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial β-oxidation activity. Consistent with these findings, the expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of hepatic lipid metabolism, was significantly down-regulated. Hepatic PPARα expression was inversely correlated with severity of steatosis and circulating ammonia and citrulline levels. Additionally, phosphorylation of c-Jun-N-terminal kinase was enhanced in CTLN2 livers, which was likely associated with lower hepatic PPARα. Collectively, down-regulation of PPARα is associated with steatogenesis in CTLN2 patients. These findings provide a novel link between urea cycle disorder, lipid metabolism, and PPARα. (248 words). Copyright © 2014. Published by Elsevier B.V.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 12/2014; · 5.09 Impact Factor
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    ABSTRACT: Autosomal recessive cerebellar ataxias and autosomal recessive hereditary spastic paraplegias (ARHSPs) are clinically and genetically heterogeneous neurological disorders. Herein we describe Japanese siblings with a midlife-onset, slowly progressive type of cerebellar ataxia and spastic paraplegia, without intellectual disability. Using whole exome sequencing, we identified a homozygous missense mutation in DDHD2, whose mutations were recently identified as the cause of early-onset ARHSP with intellectual disability. Brain MRI of the patient showed a thin corpus callosum. Cerebral proton magnetic resonance spectroscopy revealed an abnormal lipid peak in the basal ganglia, which has been reported as the hallmark of DDHD2-related ARHSP (SPG 54). The mutation caused a marked reduction of phospholipase A1 activity, supporting that this mutation is the cause of SPG54. Our cases indicate that the possibility of SPG54 should also be considered when patients show a combination of adult-onset spastic ataxia and a thin corpus callosum. Magnetic resonance spectroscopy may be helpful in the differential diagnosis of patients with spastic ataxia phenotype.
    Scientific Reports 11/2014; 4:7132. · 5.08 Impact Factor
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    Amyloid 09/2014; · 2.51 Impact Factor
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    ABSTRACT: IntroductionFamilial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent self-limiting fever and serositis that mainly affects Mediterranean populations. Many patients with FMF have been reported in Japan due to increasing recognition of this condition and the availability of genetic analysis for the gene responsible, MEFV. The present study was performed to elucidate the clinical characteristics of Japanese FMF patients and to examine the precise genotype-phenotype correlation in a large cohort of Japanese FMF patients.Methods We analyzed the MEFV genotypes and clinical manifestations in 116 patients clinically diagnosed as having FMF and with at least one mutation.ResultsThe most frequent mutation in Japanese patients was E148Q (40.2%), followed by M694I (21.0%), L110P (18.8%), P369S (5.4%), and R408Q (5.4%). In contrast, common mutations seen in Mediterranean patients, such as M694V, V726A, and M680I, were not detected in this population. The clinical features with M694I were associated with more severe clinical course compared to those seen with E148Q. P369S/R408Q showed variable phenotypes with regard to both clinical manifestations and severity. Patients with M694I showed a very favorable response to colchicine therapy, while those with P369S and R408Q did not.Conclusions Clinical features and efficacy of treatment in Japanese FMF patients vary widely according to the specific MEFV gene mutation, and therefore genetic analysis should be performed for diagnosis in cases of Japanese FMF.
    Arthritis Research & Therapy 09/2014; 16(5):439. · 4.12 Impact Factor
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    ABSTRACT: The clinical characteristics of wild-type transthyretin amyloid deposition among patients with carpal tunnel syndrome (CTS) have not been well investigated.
    Journal of Orthopaedic Science 08/2014; · 1.01 Impact Factor
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  • Masahide Yazaki, Shu-Ichi Ikeda
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    ABSTRACT: Abstract Amyloidosis refers to disorders that cause organ failure due to amyloid deposition. Deposited amyloid is clearly stained by Congo red and is detected by apple-green birefringence under polarized light. Amyloid fibril proteins are very stable, but several recent studies have revealed that amyloid deposition and the clearance of fibrils cause the steady turnover of deposited amyloid proteins. Therefore, in several amyloidosis disorders, especially primary AL, reactive AA, and transthyretin-related amyloidosis, effective therapies are expected to cause the regression of tissue-deposited amyloid.
    07/2014; 66(7):723-30.
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    Amyloid. 06/2014;
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    ABSTRACT: Histological evaluation of a peripheral nerve is often the final diagnostic work-up for a neuropathy of unknown origin, and a distal sensory nerve is usually biopsied. Here, we report the case of a female patient with painful unilateral neuropathy in the upper arm. According to the histological evaluation of the pronator teres motor branch, vasculitis seemed to be the most probable cause of the condition, and steroid therapy improved the patients' symptoms. A biopsy of the motor branch of the pronator teres muscle nerve may be considered a valuable diagnostic option in selected cases with neuropathy affecting the upper limb, when performed in cooperation with neurologists and orthopedic surgeons.
    Case Reports in Neurology 05/2014; 6(2):202-6.
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    ABSTRACT: Familial amyotrophic lateral sclerosis accounts for about 5% of all cases of the neurodegenerative disorder amyotrophic lateral sclerosis. Genetic mutations in Cu/Zn superoxide dismutase (SOD1) have been associated with one kind of familial amyotrophic lateral sclerosis (ALS1). We identified a novel duplication mutation in exon 1 of the SOD1 gene in a Japanese family whose members had lower motor neuron diseases. The patients showed slow disease progression, with the onset of lower limb muscle weakness and exertional dyspnea. Some patients had mild motor and sensory neuropathy and/or bladder dysfunction, which is further evidence that SOD1 mutation results in a predominantly lower motor neuron phenotype.
    Neurobiology of Aging 04/2014; 35(10):2420.e7-e12. · 4.85 Impact Factor
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    ABSTRACT: A 63-year-old woman with a past history of right subdural hematoma (SDH) at the age of 61 years was referred to our hospital under a suspicion of aceruloplasminemia (ACP). A neurological examination revealed very mild cognitive impairment and cerebellar ataxia. Blood chemistry data showed deficient ceruloplasmin (Cp), decreased copper, and increased ferritin. A nonsense mutation (c.2630G > A, p.Trp877Ter) was detected in the Cp gene. Brain magnetic resonance imaging (MRI) showed marked hypointensity at the surface of the cerebrum, cerebellum, and brainstem bilaterally, in addition to the bilateral basal ganglia, thalamus, and dentate nucleus, suggesting the coexistence of ACP and superficial siderosis (SS). The characteristics of SS in ACP have not been examined neuroradiologically or neuropathologically in great detail, while SDH and its curative surgery are known to cause SS. The distribution of the hypointensity areas on MRI was expanded bilaterally to the subtentorial areas of this patient, which was much more widespread than observed in typical SS after SDH. We speculate that the underlying ACP may expand the SS induced by SDH. Cp would accelerate iron export from the brain via the blood-cerebrospinal fluid (CSF) barrier, or CSF-brain barrier when excessive iron is loaded into the subarachnoid space.
    Journal of the neurological sciences 04/2014; · 2.32 Impact Factor
  • Hiroshi Morita, Minori Kodaira, Shu-Ichi Ikeda
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    ABSTRACT: Freezing phenomenon at onset of movement causes gait disturbance in Parkinson's disease (PD), but the pathophysiology is unclear. We studied motor property at onset of dorsiflexion in PD. In 9 patients with PD and 8 normal subjects, motor evoked potential was recorded from the tibialis anterior muscle under 3 conditions: at rest, during tonic contraction, and at onset of contraction. Motor threshold, size of motor evoked potential and the relationship between the intensity of transcranial magnetic stimulation, and the size of motor evoked potentials (recruitment gain) were examined. Motor threshold decreased with voluntary contraction in both PD and normal subjects, but the threshold at rest and during tonic contraction was lower in Parkinson's disease. The size of motor evoked potential with maximal stimulus intensity increased with voluntary contraction in both groups; this tendency was more pronounced in normal subjects. The recruitment gain during contraction was steeper than at rest in normal subjects. However, there was no such increase in PD. There was no increase in recruitment gain with voluntary contraction in PD, which was obvious in normal subjects, especially at onset of voluntary contraction. Modulation of motor excitability at onset of voluntary contraction was impaired in PD.
    Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 04/2014; 31(2):175-9. · 1.47 Impact Factor
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    ABSTRACT: Autosomal-recessive hereditary spastic paraplegias (AR-HSP) consist of a genetically diverse group of neurodegenerative diseases characterised by pyramidal tracts dysfunction. The causative genes for many types of AR-HSP remain elusive. We tried to identify the gene mutation for AR-HSP with cerebellar ataxia and neuropathy. This study included two patients in a Japanese family with their parents who are first cousins. Neurological examination and gene analysis were conducted in the two patients and two normal family members. We undertook genome-wide linkage analysis employing single nucleotide polymorphism arrays using the two patients' DNAs and exome sequencing using one patient's sample. We detected a homozygous missense mutation (c.4189T>G, p.F1397V) in the lysosomal trafficking regulator (LYST) gene, which is described as the causative gene for Chédiak-Higashi syndrome (CHS). CHS is a rare autosomal-recessive syndrome characterised by hypopigmentation, severe immune deficiency, a bleeding tendency and progressive neurological dysfunction. This mutation was co-segregated with the disease in the family and was located at well-conserved amino acid. This LYST mutation was not found in 200 Japanese control DNAs. Microscopic observation of peripheral blood in the two patients disclosed large peroxidase-positive granules in both patients' granulocytes, although they had no symptoms of immune deficiency or bleeding tendency. We diagnosed these patients as having adult CHS presenting spastic paraplegia with cerebellar ataxia and neuropathy. The clinical spectrum of CHS is broader than previously recognised. Adult CHS must be considered in the differential diagnosis of AR-HSP.
    Journal of neurology, neurosurgery, and psychiatry 02/2014; · 4.87 Impact Factor
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    ABSTRACT: Objective Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is an adult-onset white matter disease that presents clinically with cognitive, mental and motor dysfunction. Several autopsy reports have indicated that the corpus callosum (CC), the largest bundle of white matter, is severely affected in patients with HDLS. The aim of this study was to evaluate corpus callosum atrophy (CCA) quantitatively in HDLS patients. Methods We assessed CCA in six genetically-proven HDLS patients (HDLS group), in comparison with that observed in 20 patients with vascular dementia (VaD group) and 24 age-matched patients without organic central nervous system (CNS) disease (non-CNS group). Using midsagittal MR images, five measurements of the CC were obtained: the width of the rostrum (aa'), body (bb') and splenium (cc'), the anterior to posterior length (ab) and the maximum height (cd). Next, the corpus callosum index (CCI) was calculated as (aa' + bb' + cc')/ab. Results All HDLS patients had white matter lesions in the CC and frontoparietal lobes on the initial MRI scans. Compared with that observed in the VaD and age-matched non-CNS groups, the CCI was significantly decreased in the HDLS group (with VaD group, p<0.01; with non-CNS group, p<0.01). Conclusion This study showed significant atrophy of the CC in all HDLS patients on the initial MRI scans obtained 6-36 months after onset. We propose that the early appearance of CCA, frequently accompanied by high-intensity in the genu and/or splenium, on T2 images is an important diagnostic clue to HDLS.
    Internal Medicine 01/2014; 53(1):21-7. · 0.97 Impact Factor
  • Masayuki Matsuda, Nagaaki Katoh, Shu-Ichi Ikeda
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    ABSTRACT: Objective To retrospectively investigate the clinical manifestations at diagnosis in Japanese patients with systemic AL amyloidosis. Methods We reviewed the medical records of 230 Japanese patients who had visited our hospital and been diagnosed with AL amyloidosis, and abstracted those with the systemic type. The clinical data at diagnosis of systemic AL amyloidosis, including laboratory and imaging findings, were analyzed. Results Two hundred and two patients (mean, 58.7±9.5 years) were enrolled in this study. Immunofixation or immunoelectrophoresis was performed in 173 patients, 144 of whom were positive for M-protein in the serum and/or urine (κ:λ=30:114). The primary clinical manifestations at diagnosis were proteinuria and/or renal dysfunction (54.0%), congestive heart failure (24.8%), peripheral neuropathy (10.4%), hepatomegaly (7.9%) and arrhythmia (5.0%). The remaining patients developed unusual manifestations, such as solitary tumor, lymphadenopathy, gastrointestinal bleeding, intestinal pseudoobstruction, hemorrhagic tendencies and polyarthralgia. Dilatation of the intestine with marked thickening of the gastrointestinal wall on computed tomography and multiple nodular lesions with associated mucosal friability on endoscopy are characteristic findings of systemic AL amyloidosis. Conclusion The clinical pictures of Japanese patients with systemic AL amyloidosis are similar to those previously reported from the US and European nations; however, some patients with this disease develop uncommon symptoms. Conducting laboratory and histological examinations for systemic AL amyloidosis is necessary when making a differential diagnosis of these symptoms.
    Internal Medicine 01/2014; 53(5):403-12. · 0.97 Impact Factor
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    ABSTRACT: Objective To investigate the causes of neurological manifestations in girls immunized with the human papillomavirus (HPV) vaccine. Methods During the past nine months, 44 girls visited us complaining of several symptoms after HPV vaccination. Four patients with other proven disorders were excluded, and the remaining forty subjects were enrolled in this study. Results The age at initial vaccination ranged from 11 to 17 years, and the average incubation period after the first dose of the vaccine was 5.47±5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the legs, limb pain and weakness. The skin temperature examined in 28 girls with limb symptoms exhibited a slight decrease in the fingers (30.4±2.6°C) and a moderate decrease in the toes (27.1±3.7°C). Digital plethysmograms revealed a reduced height of the waves, especially in the toes. The limb symptoms of four girls were compatible with the Japanese clinical diagnostic criteria for complex regional pain syndrome (CRPS), while those in the other 14 girls were consistent with foreign diagnostic criteria for CRPS. The Schellong test identified eight patients with orthostatic hypotension and four patients with postural orthostatic tachycardia syndrome. The girls with orthostatic intolerance and CRPS commonly experienced transient violent tremors and persistent asthenia. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined. Conclusion The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the studied girls was psychosomatic disease. The social problems of the study participants remained unresolved in that the severely disabled girls stopped going to school.
    Internal Medicine 01/2014; 53(19):2185-200. · 0.97 Impact Factor
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    ABSTRACT: We herein describe the case of a Japanese cerebrotendinous xanthomatosis (CTX) patient with a novel CYP27A1 gene mutation. The patient had been diagnosed with cataracts at 25 years of age and subsequently developed neurological symptoms in his forties, being referred to our hospital at 47 years of age. Upon admission, Achilles tendon xanthomas, cognitive impairment, dysphagia, dysarthria, dystonia, spasticity, muscle weakness and ataxia were observed. Brain MRI revealed abnormal signals in the dentate nuclei, periventricular white matter and pyramidal tract, and the serum cholestanol level was elevated. A CYP27A1 gene analysis identified compound heterozygosity for p.A335V, a novel mutation, and p.R405Q, a previously reported mutation. Making an early diagnosis of CTX is crucial, as the administration of chenodeoxycholic acid reverses metabolic derangement.
    Internal Medicine 01/2014; 53(23):2725-9. · 0.97 Impact Factor

Publication Stats

3k Citations
847.00 Total Impact Points


  • 1986–2014
    • Shinshu University
      • • Division of Neurology and Rheumatology
      • • Department of Neurosurgery
      • • Department of Surgery
      • • Department of Medicine
      Shonai, Nagano, Japan
  • 2013
    • Tokyo Metropolitan Institute of Medical Science
      Edo, Tōkyō, Japan
  • 2005–2013
    • Uppsala University
      • Department of Immunology, Genetics and Pathology
      Uppsala, Uppsala, Sweden
  • 2009–2012
    • Kumamoto University
      • Department of Diagnostic Medicine
      Kumamoto, Kumamoto Prefecture, Japan
  • 2011
    • Yokohama City University
      Yokohama, Kanagawa, Japan
  • 2010
    • Okaya Municipal Hospital
      Hirano, Nagano, Japan
  • 2006–2009
    • Aizawa Hospital
      Honjō, Saitama, Japan
  • 2007
    • Dohgo Spa Hospital
      Matuyama, Ehime, Japan
  • 2004–2007
    • National Center of Neurology and Psychiatry
      • Department of Molecular Therapy
      Кодаиры, Tōkyō, Japan
    • Ishikawa Prefectural Central Hospital
      Ishiza, Okinawa, Japan
    • Otsu Red Cross Hospital
      Ōtu, Shiga, Japan
  • 2001–2003
    • Saku Central Hospital
      Сакура, Chiba, Japan
    • National Defense Medical College
      • Department of Internal Medicine
      Tokorozawa, Saitama-ken, Japan
  • 2002
    • Shimane University
      • Department of Internal Medicine
      Matsu, Shimane Prefecture, Japan
  • 1988
    • Kyushu University
      • Research Center for Genetic Information
      Fukuoka-shi, Fukuoka-ken, Japan