Convulsive Movements in Bilateral Paramedian Thalamic and Midbrain Infarction

Although some previous reports have described convulsive movements in bilateral paramedian thalamic and midbrain infarction, little is known about their nature. A 71-year-old man presented with impaired consciousness and clonic movements of both arms. Each series of movements lasted 10 to 20 s and occurred at 2-to 3-min intervals, which disappeared after intravenous administration of diazepam and phenytoin. Magnetic resonance imaging showed acute bilateral paramedian thalamic and midbrain infarction. A review of the literature revealed that convulsive movements were observed mostly at the onset of infarction. Clonic movements appeared frequently in the limbs, particularly in both arms. Clinical observations and results of animal experiments suggest that these seizures might originate from the mesencephalic reticular formation. Physicians should recognize this condition, because not only seizure control but also early management of ischemic stroke is required

Light- and Electron- microscopic and Immunohistochemical Studies of Human Rhabdomyosarcomas. Comparisons Among Primary Tumors, Heterotransplants in Nude Mice, and Cultured Cells from 13 Patients

Eighteen human rhabdomyosarcomas (RMS) were transplanted into the sub-cutaneous space on the back of nude mice. Thirteen of the tumors gave rise to transplantable tumors that were further examined morphologically and immuno-histochemically. The morphology of the transplanted tumors was similar to that of the primary tumors. Immunohistochemically, five primary tumors and six transplanted tumors were reacted with both desmin and myoglobin. However, in eleven cases cultured cells derived from the transplanted tumors, which showed elongated to strap-spindle-shaped cytoplasm resembling myotubules, reacted more intensely with both myoglobin and desmin. On ultrastructural examination, six primary tumors and seven transplanted tumors were found to have myofilaments or Z-bands. However, cultured cells showed myofilaments or Z-bands in their cytoplasm in all cases examined. We concluded that, on xeno-grafting, the histologic characteristics of the primary tumor are essentially con-served, and that tumor cells under culture conditions undergo an increased differentiation of skeletal muscle. These human RMS strains in nude mice and in cell lines will provide an excellent model system for investigating the biology of RMS and for further study of the molecular events underlying the genesis of this tumor

Percutaneous sclerotherapy using a 4 F pigtail catheter and 40 milliliters of 5% ethanolamine oleate for symptomatic large hepatic cysts

PURPOSEWe retrospectively evaluated the efficacy of percutaneous sclerotherapy using a 4 F catheter and 40 mL of 5% ethanolamine oleate (EO) for symptomatic large hepatic cysts.METHODSTwenty-four patients, including 10 with polycystic liver disease (PLD), were eligible. The mean long- and short-axis diameters of the cyst on computed tomography (CT) were 145.0 ± 35.5 mm (range, 72-216 mm) and 110.5 ± 21.4 mm (range, 63-150 mm), respectively. After aspiration of the fluid contents using a 4 F pigtail catheter, 40 mL of 5% EO was injected into the cyst for 30 min. Then, the catheter was withdrawn after EO removal. Symptomatic relief and complications were evaluated. The percentage reductions at the early (1-3 months later) and late (at the final follow-up) responses were evaluated using an estimated cyst volume calculated by using the following formula: volume = π/6 × long-axis diameter × (short-axis diameter)2 on the maximum cross-section image on CT. Spearman’s rank correlation coefficient (ρ) was used to evaluate the correlation between the pretreatment estimated cyst volume and percentage reduction of early and late responses and between the percentage reduction of the late response and length of the follow-up period after sclerotherapy.RESULTSThe symptoms disappeared in 23 patients and improved in 1 patient with PLD. The mean aspirated fluid volume was 1337.8 ± 845.4 mL (range, 140-3200 mL). In 1 patient, EO injection was postponed until the second procedure was performed 40 days later due to intraperitoneal leakage of contrast material. In another patient, the EO volume was reduced to 20 mL because of a small cyst size. The mean early and late percentage reductions of the treated cyst were 52.3% ± 23.8% and 87.5% ± 20.4% (mean follow-up period: 48.0 ± 42.4 months), respectively. The symptom recurred in 2 patients with PLD and 1 underwent additional sclerotherapy 14 months later due to re-enlargement of the treated cyst. Another patient underwent transarterial embolization 5 years and 4 months later for other enlarged cysts, although the treated cyst markedly shrank. There were significant negative correlations between the pretreatment estimated cyst volume and percentage reduction of early (P = .027, ρ = − 0.46) and late (P= .007, ρ = − 0.52) responses. However, there were no significant correlations between the percentage reduction and length of the follow-up period (P = .19, ρ = 0.31). Transient pain developed in 1 patient and low-grade fever in 3.CONCLUSIONSclerotherapy using a 4 F catheter and 40 mL of 5% EO is safe and effective for symptomatic large hepatic cysts

A Genome-Wide Association Analysis Identified a Novel Susceptible Locus for Pathological Myopia at 11q24.1

Myopia is one of the most common ocular disorders worldwide. Pathological myopia, also called high myopia, comprises 1% to 5% of the general population and is one of the leading causes of legal blindness in developed countries. To identify genetic determinants associated with pathological myopia in Japanese, we conducted a genome-wide association study, analyzing 411,777 SNPs with 830 cases and 1,911 general population controls in a two-stage design (297 cases and 934 controls in the first stage and 533 cases and 977 controls in the second stage). We selected 22 SNPs that showed P-values smaller than 10−4 in the first stage and tested them for association in the second stage. The meta-analysis combining the first and second stages identified an SNP, rs577948, at chromosome 11q24.1, which was associated with the disease (P = 2.22×10−7 and OR of 1.37 with 95% confidence interval: 1.21–1.54). Two genes, BLID and LOC399959, were identified within a 200-kb DNA encompassing rs577948. RT–PCR analysis demonstrated that both genes were expressed in human retinal tissue. Our results strongly suggest that the region at 11q24.1 is a novel susceptibility locus for pathological myopia in Japanese

Association between the SERPING1 Gene and Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Japanese

PURPOSE: Recently, a complement component 1 inhibitor (SERPING1) gene polymorphism was identified as a novel risk factor for age-related macular degeneration (AMD) in Caucasians. We aimed to investigate whether variations in SERPING1 are associated with typical AMD or with polypoidal choroidal vasculopathy (PCV) in a Japanese population. METHODS: We performed a case-control study in a group of Japanese patients with typical AMD (n = 401) or PCV (n = 510) and in 2 independent control groups--336 cataract patients without age-related maculopathy and 1,194 healthy Japanese individuals. Differences in the observed genotypic distribution between the case and control groups were tested using chi-square test for trend. Age and gender were adjusted using logistic regression analysis. RESULTS: We targeted rs2511989 as the haplotype-tagging single nucleotide polymorphism (SNP) for the SERPING1 gene, which was reported to be associated with the risk of AMD in Caucasians. Although we compared the genotypic distributions of rs2511989 in typical AMD and PCV patients against 2 independent control groups (cataract patients and healthy Japanese individuals), SERPING1 rs2511989 was not significantly associated with typical AMD (P = 0.932 and 0.513, respectively) or PCV (P = 0.505 and 0.141, respectively). After correction for age and gender differences based on a logistic regression model, the difference in genotypic distributions remained insignificant (P>0.05). Our sample size had a statistical power of more than 90% to detect an association of a risk allele with an odds ratio reported in the original studies for rs2511989 for developing AMD. CONCLUSIONS: In the present study, we could not replicate the reported association between SERPING1 and either neovascular AMD or PCV in a Japanese population; thus, the results suggest that SERPING1 does not play a significant role in the risk of developing AMD or PCV in Japanese

Correction: Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke.

[This corrects the article DOI: 10.1371/journal.pone.0171521.]

Cerebral microbleeds and blood pressure abnormalities in Parkinson's disease

Blood pressure abnormalities are frequently observed in patients with Parkinson's disease (PD), and are associated with cerebrovascular diseases such as white matter hyperintensities and carotid atherosclerosis. We assessed the relationship between blood pressure abnormalities and cerebral microbleeds (CMBs), a marker of cerebral small vessel disease, in 128 patients with PD. We examined supine and orthostatic blood pressures and used 24-hour ambulatory blood pressure monitoring to assess the presence or absence of orthostatic hypotension (OH), supine hypertension (SH), nocturnal hypertension (NH), and loss of nocturnal blood pressure dips (non-dipping). CMBs were found in 13 (10.2%) patients, and the median number of CMBs was 1 (range: 1 to 10). Six of these patients had deep or infratentorial CMBs, six had strictly lobar CMBs, and one had mixed CMBs. Linear regression analysis indicated that presence of both OH and SH was independently associated with greater numbers of CMBs in deep or infratentorial regions, independent of age, sex, cardiovascular risk factors, and white matter hyperintensities. NH and non-dipping were not associated with CMBs in deep or infratentorial regions, and there was no association between blood pressure and CMBs in lobar regions. Our results suggest that the presence of both OH and SH may be related to deep or infratentorial CMBs in patients with PD. Keywords: Autonomic dysfunction, Cerebral microbleeds, Orthostatic hypotension, Parkinson's disease, Supine hypertensio

Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator.

Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections