Keiichi Shinoda

Herpes simplex Virus Myelitis: Clinical Manifestations and Diagnosis by the Polymerase Chain Reaction Method

Herpes simplex virus (HSV) myelitis has previously been reported to be a form of acute ascending necrotizing myelitis caused by HSV type 2 (HSV-2). We studied neurological symptoms, clinical course, magnetic resonance imaging (MRI) findings, and diagnosis by polymerase chain reaction (PCR) methods in 9 patients with HSV myelitis. In 6 cases, disease onset was marked by sensorimotor disturbances of lower extremities and urinary disturbances, with the transverse myelopathy gradually ascending to the cervicothoracic spinal cord level. The other 3 cases showed transverse myelopathy without an ascending pattern. Six cases showed acute progression, while 3 cases showed a subacute course. There were 2 cases with recurrent episodes. Three patients recovered, however, in the remaining 6 patients severe sequelae such as paraplegia persisted despite antiviral therapy. MRI showed a hyperintense lesion on T2-weighted images. Gadolinium enhancement was observed in 2 cases, and 1 case showed a hyperintense lesion both on T1- and on T2-weighted images, suggesting hemorrhagic necrosis. HSV-2 was detected by PCR techniques in all 6 cases with an ascending pattern. HSV-1 DNA was detected in 2 and HSV-2 DNA in 1 of the 3 cases with a nonascending pattern. Our findings demonstrate diverse clinical manifestations of HSV myelitis.

Transcriptional activation by the androgen receptor in X-linked spinal and bulbar muscular atrophy

Polyglutamine tracts encoded by trinucleotide CAG repeats have been found in some transcription factors. Expansion of the polyglutamine tracts in the androgen receptor (AR) has been recognized as a cause of X-linked spinal and bulbar muscular atrophy (SBMA). To study the role of AR as a transcription factor in SBMA, we constructed AR genes encoding expanded polyglutamine tracts (repeat numbers = 52, 92, 132, and 212), and analyzed AR-induced transcriptional activation in NG108-15 cells. We found that AR-induced transcriptional activation gradually decreased with increasing glutamine repeat numbers, and polyglutamine expansion caused a specific reduction in transcription activity in motor neurons. However, the degree of reduction was slight in comparison with the normal AR gene and that of SBMA. Thus, subtle disorders of transcriptional control may occur in SBMA.

Effects of androgen receptor polyglutamine tract expansion on proliferation of NG108–15 cells

Expansion of the polyglutamine tracts in the androgen receptor (AR) has been recognized as a cause of X-linked spinal and bulbar muscular atrophy (SBMA). In the present study, NG108-15 cells were stably transfected with expression vectors coding for either the wild type (WT) AR gene (CAG repeat number = 22) or a mutated (MT) AR gene (CAG repeat number = 52). Cells proliferation and cell cycle parameters were evaluated for NG108-15-WT and NG108-15-MT cells in the presence or absence of androgen. NG108-15-WT cells demonstrated an androgen-dependent increase in cell number, while NG108-15-MT cells did not. Our results demonstrate that expansion of polyglutamine tracts in the AR may affect the proliferation and differentiation of nerve cells.

A Chronic Progressive Case of Enteroviral Limbic Encephalitis Associated with Autoantibody to Glutamate Receptor 2

(mononuclear), pro-tein concentration 54 mg/dl and glucose 63 mg/dl. PCR for herpes simplex virus (HSV) DNA was negative. He was treated with acyclovir (30 mg/kg/day for 14 days) and betamethasone (16 mg/day for 7 days) based on the diagnosis of limbic encepha-litis. His symptoms and MRI abnormali-ties gradually disappeared by the second hospital month, and he was discharged without any sequelae. In November 1995, the patient again experienced a week of fever, headache and disorientation. At second admission, the patient was disoriented with memory im-pairment, including anterograde and ret-rograde amnesia. His Mini-Mental State Examination score was 17/30. FLAIR MRI again revealed hyperintense lesions in the bilateral hippocampal structures (f ig. 1B ). CSF examination showed 6 cells/mm

Lymphocytapheresis in Combination with Immunosuppressive Drugs for Refractory Myasthenia gravis: Two-Color Flow Cytometric Analysis of Changes in Peripheral Blood Lymphocyte Subsets

We carried out lymphocytapheresis (LCP) in combination with the administration of immunosuppressive drugs in patients with myasthenia gravis (MG), who were resistant to conventional immunosuppressive therapy, and examined its efficacy and effects on peripheral blood lymphocyte subsets. LCP was carried out once a week for 1 month (one course, 4 times) using a continuous-flow blood cell separator. Immunosuppressive medication (prednisolone or prednisolone and azathioprine) was continued during the course of treatment. After LCP, clinical improvement was noted in 5 of 6 patients. Anti-AChR antibody titers and the number of lymphocytes were significantly reduced in all patients. A significant decrease in CD4+CD45RA- (memory) T cell level and significant increase in CD4+CD45RA+ (naive) T cell level were also observed. In the patients having good response to LCP, follow-up evaluation showed long-term clinical improvements, as well as the memory T cell level staying at the decreased level. Our study suggests that LCP in combination with the administration of immunosuppressive drugs can suppress the disease activity of MG.

Recurrent high-dose intravenous methylprednisolone succinate pulse therapy-induced hepatopathy in a patient with multiple sclerosis.

Objective: We describe recurrent and reversible hepatopathy in a girl with multiple sclerosis (MS) after glucocorticoid pulse therapy, to point out the possibility that glucocorticoid may harm the liver. Clinical Presentation and Intervention: An 11-year-old girl with MS, who was treated with high-dose methylprednisolone succinate pulse therapy, developed elevation of liver enzymes. The episodes of hepatopathy occurred 1–5 weeks after the therapy and disappeared within several weeks. The examination for antinuclear antibody and viruses which can cause hepatitis produced negative results. Conclusion: The present case emphasizes the possible effects of high-dose glucocorticoids in the induction of liver enzymes and the importance of follow-up liver tests after pulse therapy.