Detection of APP gene recombinant in human blood plasma.

The pathogenesis of Alzheimer's disease (AD) is believed to involve the accumulation of amyloid-ß in the brain, which is produced by the sequential cleavage of amyloid precursor protein (APP) by ß-secretase and γ-secretase. Recently, analysis of genomic DNA and mRNA from postmortem brain neurons has revealed intra-exonic recombinants of APP (gencDNA), which have been implicated in the accumulation of amyloid-ß. In this study, we computationally analyzed publicly available sequence data (SRA) using probe sequences we constructed to screen APP gencDNAs. APP gencDNAs were detected in SRAs constructed from both genomic DNA and RNA obtained from the postmortem brain and in the SRA constructed from plasma cell-free mRNA (cf-mRNA). The SRA constructed from plasma cf-mRNA showed a significant difference in the number of APP gencDNA reads between SAD and NCI: the p-value from the Mann-Whitney U test was 5.14 × 10-6. The transcripts were also found in circulating nucleic acids (CNA) from our plasma samples with NGS analysis. These data indicate that transcripts of APP gencDNA can be detected in blood plasma and suggest the possibility of using them as blood biomarkers for Alzheimer's disease.

Author Correction: Insufficient production of IL-10 from M2 macrophages impairs in vitro endothelial progenitor cell differentiation in patients with Moyamoya disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Insufficient production of IL-10 from M2 macrophages impairs in vitro endothelial progenitor cell differentiation in patients with Moyamoya disease.

Moyamoya disease (MMD) is well known to be caused by insufficient cerebral vascular formation. However, the essential pathogenesis has not yet been identified. Using our recently developed technique of generating vasculogenic and anti-inflammatory cultures, we investigated endothelial progenitor cell (EPC) expansion and differentiation under the cytokine milieu generated by the peripheral blood mononuclear cells (PBMNCs) of the operated and non-operated MMD patients. EPC colony forming assay of the cultured PBMNCs disclosed the decline of the definitive EPC colony numbers in the both MMD patients. The level of interleukin-10 (IL-10) was lower in secretory cytokines from the cultured PBMNCs of MMD patients than that in that of controls using a cytometric bead array. The addition of human recombinant IL-10 to PBMNCs cultured from MMD patients restored the EPC colony forming potential of MMD PBMNCs. Following phorbol myristate acetate stimulation of the cultured PBMNCs, flow cytometry revealed a decrease in intracellular IL-10 storage in the main cell populations of the PBMNCs cultured from MMD patients relative to those cultured from controls. The present data provide the expected mechanism of vascular malformation in MMD pathogenesis originated from the insufficient production of IL-10 secreting cells from PBMNCs fostering EPC expansion and differentiation.

Common and specific risk factors for ischemic stroke in elderly: Differences based on type of ischemic stroke and aging.

BACKGROUND: The risk factors among the types of ischemic stroke (atherothrombotic cerebral infarction: ATI, cardio-embolic infarction: CEI, lacunar infarction: LI) in aged stroke patients have rarely been compared to each other. METHODS: We compared the clinical parameters of 300 elderly patients with ischemic stroke, age 65-98years, to 100 age-matched control patients. RESULTS: Comparison by parametric test and logistic regression analysis between all 300 and 100 control patients showed higher systolic and diastolic blood pressures (p<0.001, p=0.03), lower estimated glomerular filtration rate (eGFR) (p=0.01), larger cardiothoracic ratio (CTR) (p<0.001), smoking (p<0.01) and possibly poor adherence to anti-hypertensive agents in the ischemic stroke patients (p<0.001). Comparisons among three types (n=100 for each) showed the highest atheromatous risk factors for ATI to be hemoglobin A1c (p=0.01) and low-density lipoprotein (p<0.001) and for CEI to be largest cardiac load, indicated by largest left atrial dimension (p<0.001), and CTR (p<0.001). Triglyceride level was found to be a borderline risk factor for LI (p=0.054). Comparison between those aged <74 versus ≥75years (n=150 for each) showed a lower eGFR (p=0.02) and larger right atrial dimension (p<0.001) in patients ≥75. CONCLUSION: The risk factors were quite different among the subtypes and aging.

The vital prognosis of elderly adults living in a group home in their mid-eighties.

The purpose of the present study is to evaluate the vital prognoses of elderly people in their mid-eighties living in a group home (GH) compared to age- and sex-matched outpatient clinic (OPC) in an observational study conducted over 6 years. We investigated the association between mortality and general, cardiac, and nutritional parameters, including eicosapentaenoic acid (EPA) in 54 GH residents (83 ± 8 years old) and 57 OPC attendees (83 ± 5 years old). Kaplan-Meier curves and Cox proportional hazard ratio analyses were used to assess the association between EPA drug administration and mortality in the GH residents and OPC attendees, respectively. The 54 GH residents had higher mortality and poorer nutritional states, as indicated by lower EPA/arachidonic acid values (median 0.20 vs 0.55, p < 0.001), and BMI under the condition without EPA drug administration (1800 mg daily) than did the OPC group. The significant factors that differed between survivors and deceased in the GH residents and OPC attendees were nutritional and cardiac factors. Cox proportional hazard ratio analysis confirmed that a possible determinant of the prognosis was a lower incidence of EPA drug administration and lower hemoglobin in GH. Kaplan-Meier curves and Cox proportional hazard ratio analyses revealed that EPA drug administration significantly reduced the relative mortality by 82 % in the GH residents (p < 0.001) but not in the OPC attendees. The vital prognosis in individuals from GHs was potentially improved by EPA drug administration, which was not the case in the OPC group; however, further prospective studies are needed.

[A case of sensory ataxic axonal polyneuropathy with IgGλ monoclonal gammopathy successfully treated with intravenous immunoglobulin therapy].

We report the case of an 84-year-old man with sensory ataxic polyneuropathy and IgGλ monoclonal gammopathy of undetermined significance (MGUS), which was successfully treated with intravenous immunoglobulin (IVIG) therapy. He had developed progressive ataxic gait over the span of 2 years before he was admitted to our hospital. On admission, he was unable to walk without assistance because of severe sensory ataxia. He performed poorly on the finger-nose-finger and heel-knee tests, and his vibration and position sense in the feet was remarkably diminished. However, motor involvement was not remarkable. Serum immunoelectrophoresis revealed IgGλ monoclonal gammopathy, and MGUS was diagnosed. Nerve conduction studies revealed sensory-dominant axonal polyneuropathy. The patient was successfully treated with IVIG (400 mg/kg/day, for 5 days). He regained his capacity to walk independently after treatment, but his nerve conduction results remained unchanged. This sensory ataxia might be partially due to underlying cervical spondylotic myelopathy. To our knowledge, this is the first report in our country of the successful use of IVIG therapy to treat a patient with IgGλ monoclonal gammopathy and related sensory ataxic axonal polyneuropathy.

Gaze palsy and exotropia in internuclear ophthalmoplegia.

BACKGROUND AND PURPOSE: Unilateral gaze palsy associated with internuclear ophthalmoplegia (INO), i.e., one-and-a-half syndrome, is well known. Exotropia can also be associated with INO, but it has been reported only rarely. We sought to determine the frequencies and courses of gaze palsy and exotropia in INO. METHODS: Patients hospitalized with acute-onset INO during the period January 2009 through December 2013 were identified from our clinical registry. Associated gaze palsy and exotropia were evaluated in the identified patients. RESULTS: Twenty-five patients with unilateral INO and 7 patients with bilateral INO were included in this study. Of the 25 patients with unilateral INO, 4 (16.0.0%) had ipsilateral gaze palsy (one-and-a-half syndrome), 8 (32.0%) had exotropia (non-paralytic pontine exotropia), and 6 (24.0%) had both ipsilateral gaze palsy and exotropia (paralytic pontine exotropia). Six (85.7%) of the 7 patients with bilateral INO had exotropia. The gaze palsy persisted more than 1 week in 40.0% of patients, whereas the exotropia disappeared within 1 week in 92.9% of patients when the INO was unilateral. CONCLUSION: Exotropia is not uncommon in the acute stage of INO. However, it is often overlooked because of its short duration.

Rapidly progressive dementia caused by a superior sagittal sinus dural arteriovenous fistula: a case report.

We describe the case of a 72-year-old man who presented with dementia that had progressed rapidly over a few months. Laboratory analysis of blood and cerebrospinal fluid (CSF) showed no abnormalities, with the exception of a slightly increased CSF protein level. Results of routine magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) were unremarkable. However, detailed neuroimaging studies including contrast-enhanced T1-weighted MRI and conventional angiography revealed a superior sagittal sinus (SSS) dural arteriovenous fistula (DAVF). After endovascular embolization and surgical interruption of all arteries feeding the DAVF, the dementia reversed. We should be aware of the possibility of DAVF as the cause of rapidly progressive dementia even if routine MRI reveals no or only minimal abnormality.

Isolated unilateral oculomotor paresis in pure midbrain stroke.

BACKGROUND AND PURPOSE: Pure midbrain stroke can cause isolated unilateral oculomotor paresis. We attempted to determine whether there is a difference in the oculomotor paresis pattern between pure midbrain infarction and midbrain hemorrhage. METHODS: Pure midbrain stroke patients who presented with isolated unilateral oculomotor paresis were identified from a group of 2447 consecutive patients hospitalized for acute cerebral infarction or hemorrhage during the period May 2008 through April 2014. Detailed oculomotor findings were evaluated in the identified patients per the cause of the stroke. RESULTS: Five patients with infarct and 1 with hemorrhage became our study subjects. Lesions were located in the paramedian area of the midbrain involving the oculomotor fascicles. The pupillary sphincter and inferior rectus muscles were selectively spared in the infarct patients, whereas these muscles were selectively affected in the hemorrhage patient. CONCLUSION: Fibers in the oculomotor fascicle that innervate the levator palpebrae, superior rectus, and inferior oblique muscles appear to be more susceptible to ischemic damage than those that innervate the pupillary sphincter and inferior rectus muscles. Isolated impairment of the pupillary sphincter and inferior rectus muscles may be suggestive of a non-ischemic process.

An adult case of hand, foot, and mouth disease caused by enterovirus 71 accompanied by opsoclonus myoclonica.

We reported a 23-year-old female who was treated for rash due to hand, foot, and mouth disease (HFMD). On day 4 of hospitalization, the patient showed opsoclonus (jerky eye movements in all directions), myoclonus of the neck, trunk, and extremities, and cerebellar ataxia. Based on the changes in serum viral antibody titer, the patient was diagnosed as enterovirus 71 infection. No obvious abnormal findings were noted in head MRI. Immunoglobulin 5 g/day was administered for 3 days in the early stages of infection, and administration of methylprednisolone 500 mg/day for 3 days was repeated twice. Afterwards, oral corticosteroids were given, resulting in neurological improvements a month. Including our case, there are only 2 cases within opsoclonus myoclonica associated with enterovirus 71 infection. Our case suggests, based on the course of treatment, possible involvement of direct viral action or autoimmune response in opsoclonus myoclonica.