[Juvenile-onset anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis with joint contractures before manifestation of myositis: a case report].

A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy. The serum creatine kinase level was 272 |IU/l and muscle biopsy showed typical perifascicular atrophy but little lymphocyte invasion. There was no interstitial pneumonia or malignancy, but muscle tendons showed elevated CT values suggesting calcification or fibrosis. Anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis was diagnosed on the basis of the serum antibody level. Methylprednisolone pulse therapy ameliorated the skin rash and bulbar palsy, but muscle weakness, atrophy and joint contractures were resistant to the treatment. There have been no previous reports of young adults with anti-NXP-2 antibody-positive dermatomyositis in whom joint contracture became evident as early as 4 years beforehand, which is a important feature for differential diagnosis of dermatomyositis.

[Cryopyrin-associated periodic fever syndrome (CAPS) presenting as early-onset dementia, lacking typical recurrent fever or skin rash: a case report].

A 54-year-old man with a university degree was admitted to our hospital because of a two-year history of progressive dementia. He had familial sensorineural hearing loss and had been treated for epilepsy since his 30s. On admission, he showed severe dementia and parkinsonism without fever or skin rash. Systemic inflammation was evident, and the CSF cell count and IL-6 level were elevated to 53/µl and 307 |pg/ml, respectively. Brain MRI demonstrated diffuse brain atrophy. More detailed anamnesis revealed a history of rheumatoid arthritis in childhood and aseptic meningitis in his 20s. Genetic examination for autoinflammatory diseases demonstrated compound heterozygotic mutations in the NLRP3 gene, causing cryopyrin-associated periodic fever syndrome (CAPS). This case was atypical CAPS presenting as early-onset progressive dementia, without recurrent fever or urticaria-like eruption which are usually seen in this disease.

[Posterior reversible encephalopathy syndrome caused by long-term administration of Azathioprine: a case report].

A 57-year-old woman, who had been taking azathioprine (AZP) for systemic sclerosis and interstitial pneumonia over 16 years, presented with right hemiparesis and paresthesia. On admission, brain MRI diffusion-weighted imaging (DWI) demonstrated high-signal-intensity lesions in the right frontal lobe. Although the symptoms had disappeared quickly, brain MRI on the 7th day revealed that these lesions had spread to the left cerebellar hemisphere and the right fronto-parietal lobes, appearing as high signal intensity lesions on ADC map. On the basis of the MRI imaging and clinical courses, posterior reversible encephalopathy syndrome (PRES) caused by AZP was suspected, and brain MRI revealed the immediate improvement of the lesions after the AZP discontinuation. There have been a few reports of PRES caused by AZP, all of which occurred within one month after administration. It is noteworthy in considering differential diagnosis that PRES can also occur during long-term administration of AZP.

[A case of intravascular large B-cell lymphoma manifested as lacunar infarction].

A 79-year-old man was admitted to our hospital because of sudden onset of left ataxic hemiparesis. Brain MRI diffusion weighted images showed typical lacunar infarction on the right internal capsule. He had no risk factors of cerebrovascular disorder such as hypertension, diabetes mellitus, hyperlipidemia and arrhythmia. On admission, he had a slight fever and his laboratory data showed anemia, thrombocytopenia and elevation of CRP and LDH. Intravascular large B-cell lymphoma (IVLBCL) was suspected because the serum level of soluble IL-2 receptor was also elevated. Pathological diagnosis of IVLBCL was underwent by the skin biopsy from his senile hemangiomas. Although IVLBCL was known to demonstrate various CNS lesions, it is extremely rare to be manifested as a single lacunar infarction, and this case must be important for the differential diagnosis.

[A case of neuromyelitis optica associated with pulmonary Mycobacterium avium complex disease].

A 62-year-old woman suffering from pulmonary Mycobacterium avium complex (MAC) disease was admitted to our hospital with fever, visual impairment, and lower limb weakness. MRI detected lesions in the optic chiasm and spinal cord extending the length of 6 vertebrae. The anti-aquaporin 4 (AQP4) antibody titer determined by ELISA was elevated to 8.3 IU/l. On the basis of these findings, the patient was diagnosed as having neuromyelitis optica (NMO), when chest CT also demonstrated exacerbation of pulmonary lesions. Methylprednisolone pulse therapy and double-filtered plasma exchange ameliorated the symptoms, and the EDSS score improved from 8.5 to 6.5. Six months later, visual impairment recurred, although ELISA showed that the anti-AQP4 antibody titer had become undetectable. Also, the CSF interleukin-6 (IL-6) level was elevated to 34.8 pg/ml. There have been few reports of NMO associated with pulmonary MAC disease. An increase of IL-6 is considered to exacerbate the clinical picture of NMO, whereas it may suppress progression of the pulmonary MAC disease. Exacerbation of the pulmonary MAC disease and the following internal counteraction with IL-6 may have resulted in a NMO relapse. The present patient was therefore administered eculizumab but not satralizumab, a humanized anti-IL-6 receptor antibody, for prevention of NMO recurrence.

[Observing the time course of early long pyramidal tract Wallerian degeneration after acute ischemic stroke: a case report].

A 75-year-old man was found lying prostrate in a hot room in the middle of summer. On admission, he had high fever, dehydration, and multiple decubitus, in addition to right hemiparesis and total aphasia. Brain CT showed subacute ischemic stroke in the territory of left middle cerebral artery. Brain MRI diffusion-weighted imaging (DWI) 4 days after admission detected high signal intensity lesions in the left pyramidal tract from the midbrain cerebral peduncle to the lower pons, indicating early Wallerian degeneration. The lesions were found to extend to the contralateral pyramidal decussation by MRI DWI day 12, but they had disappeared on day 28. On the other hand, brain MRI FLAIR images detected the lesions clearly day 44. Also, diffusion tensor tractography detects fewer left cerebral pyramidal tracts. No previous reports have documented the time course of such long Wallerian degeneration. This case suggests that dehydration may promote the onset of early and long Wallerian degeneration.

[Selenoprotein-related myopathy in a patient with old-age-onset type 2 respiratory failure: a case report].

A 71-year-old woman was admitted to our hospital with type2 respiratory failure. Her daily life activities had been normal, although she had noticed mild truncal weakness in her sixties. Her parents were consanguineous, and her sister had suffered similar symptoms. Although Pompe disease was suspected on the basis of the clinical course and CT findings of selective muscular atrophy in the paraspinal, thigh flexor and sartorius muscle, acid alpha-glucosidase activity was normal. The serum creatine kinase level was not elevated, and muscle biopsy showed no specific change. Genetic analysis revealed a novel homozygous variant c.227T>C (p.Phe76Ser) in the SELENON gene, and she was suspected to have selenoprotein-related myopathy, which is reported to develop in childhood. Selenoprotein-related myopathy should be considered as a differential diagnosis in aged patients presenting with respiratory failure of unknown origin.

[A case of meningeal melanomatosis diagnosed by immunostaining of cerebrospinal fluid].

A 49-year-old woman was admitted to our hospital with suspected hypertensive encephalopathy. On the basis of MRI showing leptomeningeal enhancement and Class V cytology of the CSF, she was diagnosed as having leptomeningeal carcinomatosis. Although no primary site was detected, a few melanin granules were observed at the third CSF examination. The atypical cells in the CSF demonstrated immunoreactivity for HMB-45 and S-100, which are specific markers of malignant melanoma. There have been few reports of meningeal melanomatosis in Japan. This case illustrates that immunostaining is diagnostically useful in patients with leptomeningeal carcinomatosis from neoplasms with unknown primary sites.

[A case of chordoma presenting as recurrent bacterial meningitis with cerebrospinal fluid leakage].

A 52-year-old man was admitted to our hospital because of two episodes of bacterial meningitis within a 6-month period. CSF examination showed neutrophilic pleocytosis with marked elevation of protein and hypoglycorrhachia, but the inflammatory reaction was mild and blood and CSF cultures were negative. At the time of the second admission, intermittent watery nasal discharge caused by CSF rhinorrhea was evident. CT and MR imaging revealed a tiny clival bone defect, and transnasal endoscopic repair was performed successfully. The pathological diagnosis was chordoma based on immunohistochemical staining for brachyury. Although chordoma presenting as recurrent bacterial meningitis occurs extremely rare, asking patients detailed questions about the CSF rhinorrhea must be essential for disclosing unclear infection sources.

[A case of multiple cerebral hemorrhage caused by sudden increase of eosinophil in a patient with eosinophilic granulomatosis with polyangiitis].

A 42-year-old woman with bronchial asthma was admitted to our hospital due to sensory dominant mononeuritis multiplex lasting for more than 6 months. At that time, her eosinophil count was 761/µl and her sural nerve biopsy showed no findings suggestive of vasculitis. Four months later, she experienced sudden convulsions and right hemiparesis due to left lobular parietal subcortical hemorrhage, when her eosinophil count was elevated to 3,257/µl. Numerous microbleeds and small infarctions were also detected in the intracerebral areas of different regions with MRI. Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis of the small vessels, commonly affecting the peripheral nerves. Subarachnoid hemorrhage in patients with EGPA is extremely rare. Steep elevation of the eosinophil count may release certain cytokines, causing cerebral hemorrhage.

Herpes simplex encephalitis presenting as stroke-like symptoms with atypical MRI findings and lacking cerebrospinal fluid pleocytosis.

A 73-year-old woman presented with sudden onset of right hemiparesis and was diagnosed as having cerebral infarction on the basis of diffusion-weighted brain MRI, which demonstrated lesions in the left parietal cortex. On the 3rd day, the patient developed right upper limb myoclonus, aphasia, and disturbance of consciousness with high fever. On the 6th day, she was transferred to our hospital with suspected viral encephalitis, and treatment with acyclovir was started. By the 6th day, the lesions detected by MRI had expanded to the gyrus cinguli, insula and thalamus, but not to the temporal lobe. At that time, the CSF cell count was 8/µl, and this later increased to 17/µl by the 13th day. Although herpes simplex virus DNA was detected in the CSF on the 6th day, there was no evidence of CSF pleocytosis or temporal lobe abnormalities demonstrable by brain MRI throughout the whole follow-up period. This was very atypical case of herpes simplex encephalitis characterized by a stroke-like episode, atypical MRI findings, and absence of cerebrospinal fluid pleocytosis. It is important to be mindful that herpes simplex encephalitis (HSE) can have an atypical presentation, and that sufficient acyclovir treatment should be initiated until HSE can be ruled out.

[A case of Behçet disease developing recurrent ischemic stroke with fever and scrotal ulcers].

A 30-year-old man, who was diagnosed with Behçet disease at 10 years of age, was hospitalized because of transient right hemiparesis after presenting with high fever and scrotal ulcers. Brain MRI revealed ischemic lesions in the area supplied by the anterior cerebral arteries. Analysis of cerebrospinal fluid (CSF) showed pleocytosis and a high interleukin-6 (IL-6) concentration (668 pg/ml). The patient was diagnosed with acute ischemic stroke associated with exacerbation of Behçet disease. After initiation of corticosteroid therapy, his clinical symptoms improved, and the CSF IL-6 concentration decreased. One year later, the patient developed high fever and scrotal ulcers after the onset of transient left upper limb plegia. Brain MRI showed an acute ischemic lesion in the right putamen, and CSF analysis showed an elevated IL-6 concentration (287 pg/ml). Brain CT angiography revealed stenosis of the left anterior cerebral artery and occlusion of the right anterior cerebral artery, which had been well visualized one year previously. Involvement of the intracranial cerebral arteries in Behçet disease is extremely rare. To the best of our knowledge, this is the first case report of a patient with recurrent symptomatic ischemic stroke associated with high fever and scrotal ulcers, which suggests exacerbation of Behçet disease.

[Neurolymphomatosis presenting as bilateral tongue atrophy: a case report].

A 62-year-old woman had progressive dysarthria for 2 months and was suspected of having amyotrophic lateral sclerosis because of the presentation of bilateral tongue atrophy and fasciculation. Brain magnetic resonance imaging (MRI) showed enlargement of the left hypoglossal nerve, and whole-body gallium scintigraphy showed abnormal uptake in the left pelvic cavity and left thigh. On the basis of the findings of biopsy of the mass lesion in the left thigh, she was diagnosed with diffuse large B-cell lymphoma. After chemotherapy for diffuse large B-cell lymphoma, the tongue atrophy improved. The patient subsequently developed left oculomotor nerve palsy, weakness of the right arm, and weakness of the right leg. The cause of these symptoms was thought to be neurolymphomatosis on the basis of the typical MRI findings observed. We report a rare case of neurolymphomatosis presenting as bilateral tongue atrophy, mimicking amyotrophic lateral sclerosis.

[A case of CADASIL without characteristic anterior temporal pole lesion diagnosed by skin biopsy].

A 40 year-old man with migraine presented cerebral ischemic attacks several times in one year. He had no risk factors for cerebrovascular disease including hypertension, but had strong family history suggesting autosomal dominant inheritance. A brain MRI on T(2) weighted and FLAIR images revealed patchy and confluent hyper intensity areas in the subcortical white matters and bilateral external capsules, while no anterior temporal pole lesions characteristic of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) were detected. His skin biopsy demonstrated granular osmiophilic materials (GOM) on the basement membrane of the vascular smooth muscle cells in dermis as shown by an electron microscope. The following mutational analysis of the Notch3 gene disclosed a missense mutation of p.Arg133Cys in exon 3. Molecular diagnosis of CADASIL may be time consuming because Notch3 is a huge gene and mutations may occur at multiple sites. GOM on skin biopsy is diagnostic especially in cases where anterior temporal pole involvement on MRI is negative.

[A case of inflammatory myopathy with widely skin rash following use of supplements containing Spirulina].

A 49-year old woman noticed her skin rash several days after taking supplements containing Spirulina, a planktonic blue-green alga. Her skin rash was spreading over large parts of her body, even after stop ingestion two months later. Five months later, she developed muscle weakness of neck flexor and left proximal upper extremity. On admission, creatine kinase (CK) was elevated to 1,268 IU/ml in the serum. A muscle specimen revealed many necrotizing muscle fibers and the infiltration of mononuclear cells in the peri- and endomysium including a lot of eosinophils. Immunohistochemical staining showed the infiltration of CD4 positive cells in the peri- and endomysium and that of CD20 positive B cells in the perivascular regions. She was diagnosed as having inflammatory myopathy with widely skin rash. Therapy with administration of prednisolone and cyclophosphamide followed by methyl-prednisolone pulse improved her clinical symptoms. There is a similar report describing a case of dermatomyositis after ingestion of Spirulina, which is known to have immune-stimulating property such as accelerating tumor necrosis factor (TNF)-alpha production. Also, TNF-alpha single nucleotide polymorphisms (TNF-308A) was demonstrated to have strong association with onset of myositis in Caucasians. The use of Spirulina could result in inflammatory myopathy under some specific conditions.

[Case of orbital apex syndrome caused by invasive aspergillosis successfully treated during the diagnostic procedure by the use of voriconazole].

A 75-year-old woman developed loss of vision and decreased ocular motility in all directions. She exhibited a left orbital apex syndrome, accompanied by sphenoiditis and hypertrophic pachymeningitis. Voriconazole treatment was initiated on the basis of clinical suspicion, although use of the serum beta-D glucan had negative results and a biopsy was not performed. Five days later, the left eye movements started to improve, and at that time the use of the serum aspergillus galactomannan antigen proved to have positive results. Six months later, the patient was neurologically intact and stable, except for a lack of visual acuity in counting fingers. Earlier prognoses of invasive sino-orbital aspergillosis were dismal, especially when corticosteroid therapy was done before diagnosis. This case suggests the usefulness of antifungal agents during the diagnostic procedure even when localized invasive aspergillosis is not ruled out.

[Case of cerebral venous thrombosis due to graves' disease with increased factor VIII activity].

A 39 year-old man was admitted to our hospital because of severe headache with fever continuing over two weeks. Three days after admission he developed aphasia and right hemiparesis, when his CT revealed subarachnoid hemorrhage at the left sylvian fissure. He was diagnosed as suffering from cerebral venous thrombosis because empty delta sign was positive on the enhanced brain CT. Suprasagittal sinus and bilateral transverse sinuses were not detected on the cerebral angiography. He was also diagnosed as having Graves' disease for the first time on the basis of free T3 13.56 pg/ml, free T4 4.65 ng/dl, TSH < 0.01 IU/ml, anti-TSH receptor antibody 4.3 IU/l, and thyroid stimulating antibody 224%. On the examination, homocystine and activities of antithrombin III, protein C, and protein S were normal. Antinculear, anti-DNA, anti-Sm, anticardiolipin beta2GP-I antibodies, and PR3ANCA were negative. Factor VIII activity, however, markedly increased over 300%, which has been known to increase in the cases of hyperthyroidism. He recovered well after the treatment with thiamazole in addition to warfarin followed by intravenous heparin. There are only six cases of cerebral venous thrombosis due to hyperthyroidism with increased factor VIII level. All of those cases were female, and 5 of them were taking oral contraceptives. This is a first Japanese male case.

[A case of dermatomyositis associated with chronic idiopathic myelofibrosis].

A 74-year old woman had been suffering from chronic idiopathic myelofibrosis (CIMF) for three years before noticing skin rash and subsequent muscle weakness. On admission, purplish and erythematous skin rash was seen spreading over large parts of her body, including the face, chest, back and extremities. She could not stand up without assistance due to weakness. On laboratory examination, her hemoglobin was found to be 11.8g/dl, platelet 17,000/microl, WBC 22,500/microl (with blast cells), and CK 1,757 IU/I. Auto-antibodies including antinuclear antibody, Jo-I antibody and rheumatoid factors were negative. Abdominal CT revealed giant splenomegaly. She was diagnosed as having dermatomyositis (DM) associated with CIMF. Although administration of prednisolone followed by methyl-prednisolone pulse therapy ameliorated the weakness and skin rash, WBC increased to 35,000/ microl. In case of worsening of CIMF, azathioprine (AZP) administered. This decreased the WBC count to 13,700/microl and the CK to 49 IU/I 40 days after the administration. Patients with CIMF have an increased incidence of complications of other autoimmune diseases, indicating that the immunological mechanism plays some roles in the progression of the disease. There has been only one other reported case of DM complication. This case suggests usefulness of AZP treatment combined with prednisolone in these patients.

[Reevaluation of validity of percent creatinuria for diagnosing steroid myopathy].

Steroid myopathy is usually a slowly progressive disease, which causes weakness primarily to the proximal muscles of the upper and lower extremities. The monitoring of this problem is difficult in situations in which the primary disease itself produces muscle weakness. The distinguishing feature in steroid myopathy is the occurrence of creatinuria in the presence of normal muscle enzymes including creatine kinase and aldolase. To evaluate the usefulness of percent creatinuria {urinary excretion of creatine/(urinary excretion of creatine + urinary excretion of creatinine)} in the diagnosis of steroid myopathy, we measured percent creatinuria in 26 patients (14 male and 12 female) without muscle diseases before the initiation of steroid treatment We found that the median values of percent creatinuria of the male and female patients were 2.5% and 17.1%, and that the ratios of the male and female patients presenting with an elevated percent creatinuria (more than 10%) were 3 out of 14 patients (21.4%) and 8 out of 12 patients (66.7%), respectively. We also found one patient with mild renal dysfunction presenting with an elevated percent creatinuria but without muscle weakness or myalgia. These findings suggest that the measurement of percent creatinuria is of little value in the diagnosis of steroid myopathy with a cutoff value of 10%. Furthermore, it is important to measure percent creatinuria before the steroid treatment, while paying close attention to the measurement method, sex, renal function and protein level of the diet.

[Gadolinium enhancement of the anterior portion of the lumbosacral roots in a case of post-irradiation lumbosacral radiculopathy].

A 35-year-old woman, who underwent the removal of her uterus as a result of treatment for cancer of the cervix, developed weakness in the distal lower limbs after 8 months of subsequent radiation therapy. Although she could not walk because of distal dominant weakness and atrophy in the legs, no sensory disturbances were observed. An MRI scan showed gadolinium enhancement of the anterior portion of the lumbosacral roots in the cauda equina, which corresponded to her neurological symptoms. The administration of corticosteroid and warfarin dramatically alleviated her neurological symptoms, and a follow-up MRI scan one month later demonstrated a marked diminution of the gadolinium enhancement. There were only seven reports describing the abnormalities of the MRI findings, all of which noted the gadolinium enhancement of the anterior portion of the lumbosacral roots. Together with the findings in other reports, the enhancement abnormalities seem to be characteristic of post-irradiation lumbosacral radiculopathy.