[Anti-MuSK antibody-positive myasthenia gravis with nephrotic syndrome: a case report].

A 40-year-old man was admitted to our hospital because of dysarthria, difficulty swallowing, double vision and weakness of both upper extremities. There were no detectable anti-AChR antibodies. He was diagnosed with seronegative myasthenia gravis (SNMG) based on a positive edrophonium test and positive waning on repetitive stimulation. Thereafter serological examination detected anti-muscle-specific kinase (MuSK) antibodies and he was diagnosed with anti-MuSK antibody-positive MG. Three years after the onset, the patient developed rapidly progressing respiratory failure and fever. He was diagnosed with aspiration pneumonia caused by swallowing difficulty. He was treated with mechanical ventilation, plasma exchange and antibiotics. Laboratory tests on admission also demonstrated nephrotic syndrome. Renal biopsy specimens showed diffuse thickening of the basement membrane by PAS and PAM stain, and granular immunofluorescent deposits of IgG4 along the glomerular capillary walls. Therefore, he was also diagnosed with membranous nephropathy in addition to anti-MuSK antibody-positive MG. MG is sometimes complicated with nephrotic syndrome, however there has been no report of anti-MuSK-antibody positive MG complicated with nephrotic syndrome. It has been reported that anti-MuSK-antibodies are IgG4 and that membranous nephropathy is suggested to be an IgG4 mediated disease. Our findings suggest that IgG4 may play an important role in the pathogenesis of our patient.

A severe case of chronic infantile neurologic, cutaneous, articular syndrome treated with biologic agents.

In this report we describe a case of severe chronic infantile neurologic, cutaneous, articular (CINCA) syndrome with a novel G307V cryopyrin mutation and all of the characteristic clinical and laboratory features of this autoinflammatory disease. There was no clear response to standard therapies, including human interleukin-1 (IL-1) receptor antagonist (anakinra) and soluble tumor necrosis factor receptor (etanercept). The patient finally had a partial clinical response (reduction in fever and irritability) and complete laboratory response (improved C-reactive protein and serum amyloid A levels) to humanized anti-IL-6 receptor antibody (MRA), but died from congestive heart failure and interstitial pneumonia 2 months after initiation of therapy. We serially measured the serum cytokine levels and expression of NF-kappaB activation in the patient's peripheral blood mononuclear cells before and during consecutive therapies. Pathologic examination of autopsy specimens was also performed. This case illustrates the continued difficulty in management of patients with CINCA syndrome and the complexity of the inflammatory pathways in this disorder.

[Bacterial meningitis with Campylobacter fetus manifesting chronic clinical course].

A 43-year-old man with no past history of underlying disease was admitted to an affiliated hospital, complaining of high fever and severe headache. Polynuclear dominant pleocytosis in the cerebrospinal fluid (CSF) suggested bacterial meningitis. He was immediately treated with several antibiotics, then his clinical symptoms improved, although intractable headache relapsed after withdrawal of the initial therapy. Thereafter he consulted our hospital for a second opinion. CSF examination in our hospital demonstrated mononuclear dominant pleocytosis with normal sugar value. However, bacterial culture of the CSF specimen yielded a gram-negative bacillus that was finally identified as a Campylobacter fetus on Skirrow's culture. Treatment with meropenem and other antibiotics improved both the clinical symptoms and CSF findings. Thus, meningitis with a Campylobacter fetus could manifest a chronic and atypical clinical course, careful attention should be paid to establish an early diagnosis.

[Vasospastic cerebral infarction induced by smoking: a case report].

A 31-year-old man was admitted to our hospital because of frequent transient ischemic attacks (TIAs). The first episode involved right amaurosis fugax and left hemiparesis at the age of 26. Treatment with aspirin did not reduce frequency of TIA. Cerebral angiography at the age of 29 showed a significant stenosis in the right internal carotid artery with a string-of-beads-like appearance. This pattern suggested fibromuscular dysplasia. TIAs persisted despite of prophylactic medication with ticlopidine. When cerebral angiography was repeated at age of 28, stenosis in the right internal carotid artery had almost disappeared. At the present admission, MR angiography showed stenoses of bilateral internal carotid arteries and middle cerebral arteries, which had disappeared when the study was repeated after 5 days. Vasospasm was suspected based on reversibility of changes in both conventional and MR angiographies. The patient was treated with a calcium antagonist to prevent vasospasm as well as cessations of smoking. The patient had a history of 20 cigarettes a day for 12 years and neurologic deficits often occurred after smoking. Therefore, smoking is considered to be a main trigger for TIAs in this patient.

[Diffusion-weighted magnetic resonance imaging findings at early stage of acute Wernicke encephalopathy].

We describe a patient with acute Wernicke encephalopathy (WE) in whom diffusion-weighted magnetic resonance imaging (DWI) were helpful for early diagnosis. A 66-year-old alcoholic man was admitted to our department because of recurrent mild drowsiness. Thiamine concentrations in blood were at the lower limit of normal. DWI demonstrated an abnormal signal intensity in the dorsal part of the midbrain, and high-dose thiamine therapy was started. These lesions disappeared on DWI after one month of follow-up, in association with clinical improvement. These findings suggest that DWI is useful for detecting WE at the early stage when high-dose thiamine treatment can improve the prognosis of WE.

Myelodysplastic syndrome following therapy for brain tumor--two case reports.

A 3-month-old boy and a 29-year-old woman presented with myelodysplastic syndrome (MDS) following therapy for primary malignant brain tumor. Both received intensive alkylating agent doses for induction and maintenance chemotherapy combined with craniospinal or cranial radiation for medulloblastoma and anaplastic astrocytoma, respectively. They developed refractory anemia and pancytopenia. Approximately 9 years after the completion of induction chemoradiotherapy, chromosomal analysis of bone marrow cells resulted in the diagnosis of MDS. The boy died of leukemic evolution 15 months later, the woman died of hematopoietic failure 3 months later. The most common symptom of MDS is refractory anemia, either alone or as part of bi- or pancytopenia. Clonal proliferation with chromosomal analysis of bone marrow cells establishes the diagnosis of MDS. Patients with malignant brain tumors are at risk of the development of MDS as a late complication of chemotherapy based on high cumulative doses of alkylating agents.