Tetsuro Konishi

National Hospital Organization Minami Kyoto Hospital, Kioto, Kyōto, Japan

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Publications (8)13.59 Total impact

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    ABSTRACT: Purpose To examine the incidence and clinical features of epileptic seizures in Japanese patients with multiple sclerosis (MS) and neuromyelitis optica (NMO). Methods We reviewed medical records of all patients who visited the Neurology Clinic in Utano National Hospital between January and December, 2009, and enrolled 63 MS patients who fulfilled the McDonald criteria (2005) (mean age, 41.1 years) and 31 NMO patients who fulfilled the Wingerchuk criteria (2006) (mean age, 44.6 years). Patients with a history of epileptic seizures were selected and their clinical features were obtained. Results Four MS patients (6.3%; 2 men and 2 women; mean age, 32.5 years) and 4 NMO patients (12.9%; 4 women; mean age, 36.0 years) had epileptic seizures. Disease onset age of MS patients with seizures was significantly younger than those without seizures by 13.1 years, and Expanded Disability Status Scale of NMO patient with seizures was significantly higher than those without seizures by 2.2. All 8 patients showed brain lesions on magnetic resonance imaging and 2 MS patients had tumefactive demyelinating lesions. Electroencephalography showed interictal epileptiform discharges in 5 patients. Seizure types of 6 patients were recognized as partial seizures based on clinical semiology. All patients responded to antiepileptic therapy well. In both MS and NMO, there were both seizures with and without concurrent relapse. Conclusions Similar to MS, NMO patients possibly have higher risk to develop epileptic seizures than general population.
    Epilepsy research 03/2013; 104(s 1–2):175–180. · 2.48 Impact Factor
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    ABSTRACT: This study investigated the effect of 3,4-diaminopyridine (3,4-DAP), a potent potentiator of transmitter release, on neuromuscular transmission in vivo in a mouse model of myasthenia gravis (MG) caused by antibodies against muscle-specific kinase (MuSK; MuSK-MG) and ex vivo in diaphragm muscle from these mice. 3,4-DAP significantly improved neuromuscular transmission, predominantly by increasing acetylcholine (ACh) release, supporting presynaptic potentiation as an effective treatment strategy for MuSK-MG patients who have defective transmitter release. In MuSK-MG, we suggest that only low-dose acetylcholinesterase (AChE) inhibitors be used to avoid side effects, and we propose that 3,4-DAP may be effective as a symptomatic therapy.
    Journal of neuroimmunology 03/2012; 245(1-2):75-8. · 2.84 Impact Factor
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    ABSTRACT: Antibodies against acetylcholine receptors (AChRs) cause pathogenicity in myasthenia gravis (MG) patients through complement pathway-mediated destruction of postsynaptic membranes at neuromuscular junctions (NMJs). However, antibodies against muscle-specific kinase (MuSK), which constitute a major subclass of antibodies found in MG patients, do not activate the complement pathway. To investigate the pathophysiology of MuSK-MG and establish an experimental autoimmune MG (EAMG) model, we injected MuSK protein into mice deficient in complement component five (C5). MuSK-injected mice simultaneously developed severe muscle weakness, accompanied by an electromyographic pattern such as is typically observed in MG patients. In addition, we observed morphological and functional defects in the NMJs of EAMG mice, demonstrating that complement activation is not necessary for the onset of MuSK-MG. Furthermore, MuSK-injected mice exhibited acetylcholinesterase (AChE) inhibitor-evoked cholinergic hypersensitivity, as is observed in MuSK-MG patients, and a decrease in both AChE and the AChE-anchoring protein collagen Q at postsynaptic membranes. These findings suggest that MuSK is indispensable for the maintenance of NMJ structure and function, and that disruption of MuSK activity by autoantibodies causes MG. This mouse model of EAMG could be used to develop appropriate medications for the treatment of MuSK-MG in humans.
    American Journal Of Pathology 12/2011; 180(2):798-810. · 4.60 Impact Factor
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    ABSTRACT: In order to clarify the immunological characteristics of multiple sclerosis (MS) and neuromyelitis optica (NMO), we analyzed CD3, CD4, CD8, CD20, CD4(+)CD25(+), CD4(+)CD29(+), and CD8(+)CD11a(high) cells in peripheral blood from patients with MS (16 stable, 6 active) and NMO (15 stable, 7 active), as well as 9 with NMO spectrum, 6 with clinically isolated syndrome (CIS), and 13 with other neurological diseases using flow cytometry. Significant decreases in the numbers of CD8(+) CD11a(high) cells were observed in stable and active MS and CIS. Our findings indicate that CD8(+)CD11a(high) cells play different roles in MS and NMO, and their presence may be related to the pathogenesis of MS from the early stage.
    European Neurology 01/2010; 63(3):159-163. · 1.50 Impact Factor
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    ABSTRACT: In order to clarify the clinical characteristics and effects of acetylcholinesterase inhibitors of patients with generalized myasthenia gravis with antibodies to muscle specific kinase (MuSK), we investigated seven patients with MuSK antibodies and eleven patients without both antibodies of acetylcholine receptor and MuSK. All patients with MuSK antibodies showed bulbar symptoms, which frequency was significantly higher compared to those in patients without double antibodies. The frequency of positive result of Tensilon test was significantly lower in patients with MuSK antibodies than in those without double antibodies. In response to intravenous edrophonium chloride, MuSK positive patients showed adverse reactions in a small dosage of edrophonium chloride, less than 5 mg, such as fasciculation on facial muscles and stuffy sensation of throat. The adverse responses to a small dosage of intravenous edrophonium chloride injection is useful information to distinguish patients with seronegative generalized MG, whether they have MuSK antibodies or not. When acetylcholinesterase inhibitors medication is tried to patients with MuSK antibodies, if necessary, a small dosage of inhibitors should be used to avoid cholinergic hypersensitivity.
    Rinsho shinkeigaku = Clinical neurology 10/2009; 49(10):660-3.
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    ABSTRACT: Patients with relapsing neuromyelitis optica (NMO) showing contiguous long spinal cord lesions extending over three vertebral segments on the MRI and with positive anti-aquaporin 4 antibodies in sera are usually treated with glucocorticoids or azathioprine. However, some NMO patients even after adequate treatments show relapses. Rituximab (anti-CD 20) therapy has recently been reported to inhibit relapses. We used rituximab to treat three NMO patients defined by the revised NMO criteria of Wingerchuk et al, with rituximab for 2 years and 3 months (mean) at an intervals of about nine months. The annualized relapse rate for the 3 patients during the year before rituximab therapy was 4, 5, and 6, respectively, and this decreased to 3, 1, and 0 in the year after therapy. Case 1 showed three relapses after therapy: however, the symptoms and signs of each of the relapses were milder and the patient showed good responses to steroid pulse therapy. One year after therapy, relapses had disappeared in all cases (observation periods; 18, 18, and 9 months, respectively). After rituximab therapy, these NMO patients showed a decreased mean annualized relapse rate (from 5.0 to 0.6) and EDSS score (from 8.7 to 8.0) after rituximab therapy. No adverse effects were seen. We recommend rituximab therapy for NMO patients resistant to other immunosuppressive therapies such as oral glucocorticoid administration introduced after a severe relapse. However, during long term rituximab treatment, attention needs to be given to infections such as progressive multifocal leucoencephalopathy.
    Rinsho shinkeigaku = Clinical neurology 08/2009; 49(8):457-62.
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    ABSTRACT: Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by autoantibodies. That is, the binding of autoantibodies to postsynaptic membranes in neuromuscular junctions (NMJ) results in weakening of the ocular, bulbar and limb muscles and produces the characteristic syndrome of MG. About 80 to 85% of patients witth MG have autoantibodies against acetylcholine receptors (AChR). Antibodies against muscle-specific kinase (MuSK) have been found in 30% of MG patients without AChR antibodies. Here we describe recent progress toward understanding the pathogenic role of MuSK antibodies in the decline of muscle strength that typifies MG.
    Nippon rinsho. Japanese journal of clinical medicine 07/2008; 66(6):1149-54.
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    ABSTRACT: Anti-alkaline phosphatase antibody (AP Ab) was specific in 9% of 249 anti-acetylcholine receptor (AChR) Ab-positive myasthenia gravis (MG) (SPMG) patients but not in patients with AChR Ab-negative MG (SNMG), other neurological and immunological diseases, or healthy volunteers. No cross-reactivity and no significant titer correlation were found between AP Ab and AChR Ab. We confirmed immunologically by radioimmunoassay and western blot analysis the presence of antibodies directed against AP. AP Ab-positive SPMG patients were characterized clinically as having female predominance and a more severe form of generalized MG than AP Ab-negative SPMG patients, and about half required artificial ventilation at maximum severity. AP Ab's pathogenic role in MG is yet unclarified, but our findings show AP to be a novel antigen among the various autoantigens present in MG patients and in whom AP Ab may modify clinical symptoms.
    Journal of the Neurological Sciences 01/2008; 263(1-2):89-93. · 2.24 Impact Factor