[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.

[Isolated ACTH deficiency clinically presented as stiff-person syndrome, successfully treated by hormonal replacement: a case report].

A 65-year-old man was admitted to our hospital with a 6-year history of painful muscle stiffness in his trunk and lower limbs, preventing him from walking. Stiff-person syndrome (SPS) was diagnosed because the patient had symptoms of painful muscle spasms elicited by tactile stimulation without joint contracture. Although SPS- related autoantibodies in the serum, including anti-glycine R, anti-amphiphysin, anti-glutamic acid decarboxylase (GAD), anti-dipeptidyl peptidase-like protein (DPPX) and anti-γ-aminobutyric acid-A (GABAA) R, were negative, the ACTH and cortisol levels were low. On the basis of additional loading tests for anterior pituitary function and ACTH, isolated ACTH deficiency (IAD) was diagnosed. Hormonal replacement therapy with hydrocortisone at 15 mg/day ameliorated the condition quickly, and the patient became asymptomatic after three months. Flexion contractures have been reported as musculoskeletal symptoms of IAD, but are not usually evident in patients with SPS. The present case illustrates that the painful muscle spasms elicited by tactile stimulation without joint contracture characteristic of SPS can also be symptoms of IAD.

[Recurrent autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy with long cervical cord lesions: a case report].

A 61-year-old man who had suffered two episodes of generalized convulsion in a two-year period was admitted to our hospital because of progressive gait disturbance during the previous five months. Neurological examination revealed cognitive impairment, spasticity of the lower limbs, truncal ataxia, and dysautonomia including orthostatic hypotension, dysuria and hypohydrosis. Brain fluid-attenuated inversion recovery (FLAIR) MRI detected high-signal-intensity lesions in the periventricular white matter and centrum semiovale, with punctate gadolinium (Gd) enhancement. Spinal MRI detected swollen cervical long cord lesions extending from C2 to C6. Although methylprednisolone pulse treatment initially ameliorated the symptoms and MRI abnormal findings, clinical symptoms and MRI abnormalities including new cervical lateral column lesions reminiscent of those in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) relapsed two months later. At this point, anti-GFAPα antibody was detected in the cerebrospinal fluid. Although the clinical course of GFAP-A has been well reported, the present case showed a chronic refractory course.

[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.

[Paraneoplastic anti-gamma aminobutyric acid (GABA)B receptor antibody limbic encephalitis associated with small cell lung cancer presenting as new-onset status epilepticus: a case report].

An 84-year-old man was admitted to our hospital with new-onset refractory status epilepticus of unclear etiology. On the third day, diffusion-weighted brain MRI demonstrated lesions in the right medial temporal and parietal lobes. As a CSF sample showed pleocytosis, paraneoplastic limbic encephalitis (PLE) associated with small cell lung cancer (SCLC) was suspected. The patient was also positive for anti-gamma aminobutyric acid (GABA)B receptor antibody in the CSF, which has recently been reported in elderly patients with SCLC-related PLE. Methylprednisolone pulse therapy ameliorated the symptoms. It is noteworthy that immune therapy often improves the symptoms of PLE with anti-GABAB receptor antibody, even though radical therapy for the lung cancer may be difficult.

[A case of thyrotoxic myopathy with generalized body muscular atrophy including the tongue muscle, lacking physical manifestations of Basedow disease].

We report a 74-year-old man with a 2-year history of proximal limb pain, body weight loss of 15 kg, and muscle weakness. Muscle atrophy was evident in the limbs and trunk, as well as the tongue. He was admitted to our hospital with suspected amyotrophic lateral sclerosis (ALS). Although he had no physical manifestations of Basedow disease such as palpitations, hyperhidrosis, hand tremor, exophthalmos, and an enlarged thyroid, he was diagnosed as having thyrotoxic myopathy as laboratory examinations indicated hyperthyroidism and positivity for TSH receptor antibody. The serum level of soluble IL-2 receptor was also elevated. Despite the severe muscle atrophy, the serum CK level was normal. A biopsy from the left quadriceps muscle revealed Type 1 fibers atrophy. Administration of anti-thyroid drugs normalized his thyroid function and the level of soluble IL-2 receptor, leading to improvement of the generalized muscle atrophy.

[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 conus medullaris infarction expanding to the vertebral bodies, major psoas and erector spinae muscles].

A 77-year-old woman presented with conus medullaris and cauda equina syndrome following a sudden pain in the bilateral lower abdomen and right buttock. Lumbar magnetic resonance imaging (MRI) showed not only a conus medullaris lesion, but also several lesions in the vertebral bodies (L1, L2), right major psoas muscle, right multifidus muscle and bilateral erector spinae muscles. As these areas receive blood supply from each branch of the same segmental artery, we considered all of the lesions as infarctions that were a result of a single parent vessel occlusion. It is known that a vertebral body lesion can be accompanied by a spinal cord infarction, but in combination with infarction of a muscle has not been reported. This is the first report of a concomitant spinal cord and muscle infarction revealed by MRI. It is noteworthy that a spinal cord infarction could expand not only to neighboring vertebral bodies, but also to muscles.

[Transformation from chronic subdural hematoma into subdural empyema following cat bites: a case report].

A 69-year-old man developed motor aphasia and right hemiparesis with severe headache, during the treatment of cellulitis and sepsis due to cat bites. Brain CT showed a low density, crescent-shaped lesion in the left subdural space, which was hypointense on brain diffusion-weighted imaging (DWI). One week later, when his neurological symptoms had worsened, the signal of the subdural lesion had changed to hyperintense on DWI. The lesion was capsule-shaped when enhanced by Gadolinium. The signal changes on DWI of the lesion indicated the existing hematoma had changed to an empyema, or so-called infected subdural hematoma, due to a hematogenous bacterial infection. Pasteurella multocida, a resident microbe in the oral cavity of cats, could be the responsible pathogen in this case. The patient recovered completely after treatment with intravenous high dose antibiotics. This is an important case report describing the transformation from a chronic subdural hematoma into a subdural empyema by DWI.

[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.

[A case of progressive encephalomyelitis with rigidity and myoclonus associated with anti-GAD, anti-glycine receptor and anti-GM1 antibodies].

A 62-year-old woman with one-year history of type 1 diabetes mellitus was admitted to our hospital with progressive weakness in the lower extremities and urinary dysfunction following high fever. On admission, she had rigidity and myoclonus in the upper extremities with sensory ataxia. Cerebrospinal fluid examination revealed mild pleocytosis and oligoclonal band. Glutamic acid decarboxylase (GAD) antibodies were detected at high titer in serum, but antibodies to glycine receptor (GlyR), thyroid peroxidase, mitochondrial M2, and GM1 were also detected. She was diagnosed with progressive encephalomyelitis with rigidity and myoclonus (PERM), which probably developed on the basis of polyglandular autoimmune syndromes. The clinical symptoms began to improve after initiation of intravenous high-dose methylprednisolone. Muscle weakness might be related to GM1 antibodies. This is the first report of PERM, in which GM1 antibodies were detected with GAD and GlyR antibodies.

Pathology and sensitivity of current clinical criteria in corticobasal syndrome.

The aim of this study was to investigate corticobasal syndrome with respect to underlying pathologies, the ability of current clinical criteria to detect early stages of disease, and symptoms and signs predicting background pathologies. We retrospectively analyzed the clinicopathological findings from patients with corticobasal syndrome. We also analyzed whether those findings fulfilled the diagnostic criteria for corticobasal degeneration (CBD). Finally, we investigated characteristic clinical features that are specific to each background pathology. Of 10 consecutive autopsied patients who had corticobasal syndrome (mean age ± standard deviation, 67.9 ± 9.3 years; male:female ratio, 6:4), three had corticobasal degeneration pathology, three had progressive supranuclear palsy, three had Alzheimer's disease, and one had atypical four-repeat tauopathy. Nine patients fulfilled Mayo criteria, and all 10 patients fulfilled modified Cambridge criteria at the later stage, but only two patients fulfilled either clinical criteria within 2 years of disease onset. Five patients fulfilled the clinical criteria for possible CBD (p-CBD), and one patient fulfilled the clinical research criteria for probable sporadic CBD (cr-CBD) at the later stage. Only two patients fulfilled the criteria for either p-CBD or cr-CBD within 2 years of disease onset. Although we could not find any predictive characteristic clinical features that were specific to CBD pathology, only patients with progressive supranuclear palsy developed apraxia of eyelid opening and cerebellar ataxia. Myoclonus and memory impairment, especially if they appear at an early stage of the disease, may predict Alzheimer's disease pathology. Sensitivity of the available clinical criteria for corticobasal syndrome was poor within 2 years of disease onset.

[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.

DRPLA transgenic mouse substrains carrying single copy of full-length mutant human DRPLA gene with variable sizes of expanded CAG repeats exhibit CAG repeat length- and age-dependent changes in behavioral abnormalities and gene expression profiles.

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant progressive neurodegenerative disorder with intellectual deterioration and various motor deficits including ataxia, choreoathetosis, and myoclonus, caused by an abnormal expansion of CAG repeats in the DRPLA gene. Longer expanded CAG repeats contribute to an earlier age of onset, faster progression, and more severe neurological symptoms in DRPLA patients. In this study, we have established DRPLA transgenic mouse lines (sublines) harboring a single copy of the full-length mutant human DRPLA gene carrying various lengths of expanded CAG repeats (Q76, Q96, Q113, and Q129), which have clearly shown motor deficits and memory disturbance whose severity increases with the length of expanded CAG repeats and age, and successfully replicated the CAG repeat length- and age-dependent features of DRPLA patients. Neuronal intranuclear accumulation of the mutant DRPLA protein has been suggested to cause transcriptional dysregulation, leading to alteration in gene expression and neuronal dysfunction. In this study, we have conducted a comprehensive analysis of gene expression profiles in the cerebrum and cerebellum of transgenic mouse lines at 4, 8, and 12 weeks using multiple microarray platforms, and demonstrated that both the number and expression levels of the altered genes are highly dependent on CAG repeat length and age in both brain regions. Specific groups of genes and their function categories were identified by further agglomerative cluster analysis and gene functional annotation analysis. Calcium signaling and neuropeptide signaling, among others, were implicated in the pathophysiology of DRPLA. Our study provides unprecedented CAG-repeat-length-dependent mouse models of DRPLA, which are highly valuable not only for elucidating the CAG-repeat-length-dependent pathophysiology of DRPLA but also for developing therapeutic strategies for DRPLA.

[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.