Improvements in both psychosis and motor signs in Parkinson's disease, and changes in regional cerebral blood flow after electroconvulsive therapy

Purpose

Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. The use of anti-PD medications has been the most widely identified risk factor for PD psychosis (PDP). However, the pathophysiology of PDP remains unclear. Although the efficacy of electroconvulsive therapy (ECT) for PD had been pointed out, only one study has demonstrated the effectiveness of ECT on both psychotic symptoms and motor symptoms. The aim of this study was to examine the acute effectiveness of ECT on PD and to identify the brain areas associated with PDP.

Methods

The study was conducted at Juntendo University Hospital in Tokyo. Eight patients with L-DOPA- or dopamine (DA) agonist-induced PDP, who were resistant to quetiapine treatment, were enrolled. Severity of PD was evaluated using the Hoehn and Yahr stage. Psychotic symptoms were evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS). Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (99mTc ECD SPECT) was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. A voxel-by-voxel group analysis was performed using Statistical Parametric Mapping (SPM5).

Results

Our study clearly demonstrated that PDP was significantly less severe after ECT than before ECT, as indicated by change in mean SAPS total domain score (t = 7.2, P = 0.0002). Furthermore, the patients showed significant improvement in Hoehn and Yahr stage after ECT (t = 11.7, P < 0.0001). A further notable observation was significant increase in rCBF in the right middle frontal gyrus after ECT.

Conclusion

We conclude that a course of ECT produced notable improvements not only in PDP but also in the severity of PD. The findings of change in rCBF suggest implications for dysfunction in the middle frontal region for patients with PDP.     

Effect of subthalamic nucleus deep brain stimulation on visual scanning

Objective

Deep brain stimulation (DBS) can provide insights into the workings of the basal ganglia (BG) by interfering with their function. In patients with Parkinson's disease (PD) treated with DBS of the subthalamic nucleus, we studied the effect of DBS on scanning eye movements.

Early salvage radiotherapy for patients with PSA relapse after radical prostatectomy

Purpose  

To assess the effectiveness of early salvage radiotherapy (RT) for patients with prostate-specific antigen (PSA) relapse after radical prostatectomy (RP) retrospectively.     

Development of plasmacytoid dendritic cells in bone marrow stromal cell niches requires CXCL12-CXCR4 chemokine signaling

Plasmacytoid dendritic cells (pDCs), also known as type I interferon (IFN)-producingcells, are thought to play central roles in antiviral immunity and the pathogenesis of some autoimmune diseases. pDCs are produced from hematopoietic stem cells in bone marrow. However, the environmental regulation of the development of pDCs is not fully understood. Here, we show that the numbers of pDCs and their earliest progenitors are severely reduced in the absence of CXCR4, the primary physiologic receptor for CXC chemokine ligand 12 (CXCL12), also known as stromal cell-derived factor-1 (SDF-1) in vivo. In vitro, CXCL12 induces a significant increase in pDC numbers generated from primitive hematopoietic cells, and pDCs and their progenitors migrate to CXCL12. In addition, most pDCs are in contact with CXCL12-abundant reticular (CAR) cells in the intersinal space of bone marrow, although many primitive hematopoietic cells adjoin CAR cells surrounding sinusoidal endothelial cells or residing near the bone surface. Thus we identified CXCL12 as a key regulator of pDC development produced by cellular niches, providing new targets for pDC therapeutic control.     

Phosphodiesterase III inhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain

Vascular dementia is caused by blockage of blood supply to the brain, which causes ischemia and subsequent lesions primarily in the white matter, a key characteristic of the disease. In this study, we used a chronic cerebral hypoperfusion rat model to show that the regeneration of white matter damaged by hypoperfusion is enhanced by inhibiting phosphodiesterase III. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. Performance at the Morris water-maze task, immunohistochemistry for bromodeoxyuridine, as well as serial neuronal and glial markers were analyzed until 28 days after hypoperfusion. There was a significant increase in the number of oligodendrocyte progenitor cells in the brains of patients with vascular dementia as well as in rats with cerebral hypoperfusion. The oligodendrocyte progenitor cells subsequently underwent cell death and the number of oligodendrocytes decreased. In the rat model, treatment with a phosphodiesterase III inhibitor prevented cell death, markedly increased the mature oligodendrocytes, and promoted restoration of white matter and recovery of cognitive decline. These effects were cancelled by using protein kinase A/C inhibitor in the phosphodiesterase III inhibitor group. The results of our study indicate that the mammalian brain white matter tissue has the capacity to regenerate after ischemic injury.     

An epidemiological survey of moyamoya disease,unilateral moyamoya disease and quasi-moyamoya disease in Japan

Objectives

Moyamoya disease (MMD) is a unique occlusive disease of the bilateral internal carotid arteries in which, compensation for occlusion results in an enrichment of collateral arteries at the base of the brain. However, the epidemiology of unilateral MMD (typical angiographic evidence of MMD unilaterally with equivocal contralateral findings), and quasi-MMD (MMD present with inherited or acquired disorders) is poorly known. Here, a nationwide epidemiological survey was conducted to estimate the total numbers of patients, the annual incidence rates and prevalences of MMD, unilateral MMD and quasi-MMD in Japan.

Patients and methods

The neurosurgery, neurology and pediatrics departments that were listed in Japanese resident training programs were recruited to participate in this survey. Questionnaires were directly mailed to 2998 departments in February 2006.

Results

A total of 1183 departments replied to the questionnaire (39.5% response rate). It was estimated that there were 6670.9 MMD patients, 840.5 unilateral MMD patients and 430.4 quasi-MMD patients in Japan. The annual incidence rates of MMD, unilateral MMD and quasi-MMD are 1.13, 0.23 and 0.11/100,000, respectively, and the prevalences are 5.22, 0.66 and 0.34/100,000, respectively. These patients were mainly treated by neurosurgeons. An estimated total of 929.1 surgical interventions are performed in Japan annually.

Conclusion

This nationwide study reports the current epidemiologic status of MMD, unilateral MMD and quasi-MMD in Japan.     

Morphology of the olivocerebellar projection of the chick: An axonal reconstruction study

The projection pattern of the olivocerebellar (OC) axons, which terminate mainly as climbing fibers (CFs) in the cerebellar cortex, tightly reflects the compartmental and developmental organization of the cerebellum as revealed by mapping and reconstruction studies in the rat. The avian cerebellum is well lobulated and longitudinally compartmentalized like the mammalian cerebellum. However, the projection pattern of the OC axons has not been studied in detail for most areas of the avian cerebellum. In the present study, we reconstructed labeled chick OC axons resulting from a small focal injection of biotinylated dextran amine into the inferior olive to investigate their morphological characteristics, and to determine their relationship to the general morphology of the chick cerebellum. Labeled CFs were distributed basically in a single longitudinally elongated narrow band‐shaped area in lobules I–VIII, but in multiple, transversely widened, band‐shaped areas in lobules IX–X. Three of the four reconstructed OC axons terminated in a single longitudinally band‐shaped area in lobules IXa–c, whereas the other one terminated in multiple mediolaterally separated areas in lobule IXc, which is part of the flocculus. Single OC axons branched into 14 CFs on average. Two CFs occasionally merged to form a single terminal arbor. Axons also had thin, non‐CF collaterals that projected either to a cerebellar nucleus or to the cortex. The results indicate that the morphological characteristics of OC axons, including branching and termination, are basically conserved between the chick and the rat. J. Comp. Neurol. 521:3321–3339, 2013. © 2013 Wiley Periodicals, Inc.     

Results of surgical treatments of primary hepatocellular carcinoma: Some aspects to improve long-term survival

From 1973 through 1982 we have treated 226 patients with primary hepatocellular carcinoma, including 103 by hepatectomy and 93 by hepatic artery ligation. Most were associated with cirrhosis or related liver diseases and one-third with esophageal varices. As in other Japanese and Asian series, our long-term overall results for the 90 patients who survived hepatectomy were poor in comparison with Western series dealing with non-cirrhotic patients. However, the actuarial survival rate at 3 years was 90% in patients with carcinomas smaller than 3 cm in diameter (n = 18). The 5-year survival rate was 70.8% in the 25 patients whose carcinoma had a curative resection, and 100% at 3 years in the 16 patients in whom a tumor smaller than 5 cm had been resected. Eighty-four patients survived hepatic artery ligation; in 50 of them the area of ischemia was thought to include all the neoplastic lesions within the liver. The survival rate of these 50 patients was superior to that of the patients who had undergone noncurative hepatic resection. We conclude that early detection and curative resection is the best way to improve the long-term results in cirrhotic patients with hepatocellular carcinoma and that hepatic artery ligation is better than incomplete (noncurative) resection.

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Resumen Hemos tratado 226 pacientes con carcinoma hepatocelular primario entre 1973 y 1982, incluyendo 103 con hepatectomía y 93 con ligadura de la arteria hepática. La mayoría apareció asociada con cirrosis o enfermedades hepáticas relacionadas y un tercio con varices esofágicas. Al igual que en otras series japonesas y asiáticas, nuestros resultados globales a largo término para los 90 pacientes que sobrevivieron la hepatectomía fueron pobres en comparación con las series occidentales que incluyen pacientes no cirróticos. Sin embargo, la tasa de supervivencia actuarial a 3 años fue del 90% en pacientes con carcinomas menores de 3 cm de diámetro (n= 18). La tasa de supervivencia en 5 años fue de 70,8% en los 25 pacientes cuyos carcinomas fueron sometidos a resección curativa, y del 100% en 3 años en los 16 pacientes en quienes se resecó un tumor de menos de 5 cm de diámetro. Ochenta y cuatro pacientes sobrevivieron la ligadura de la arteria hepática; en 50 de éstos se consideró que el área de isquemia incluía las lesiones neoplásicas contenidas en el hígado. La tasa de supervivencia de estos 50 pacientes fue superior a la de los pacientes que fueron sometidos a resección hepática no curativa.Nuestra conclusión es que la detección precoz y la resección curativa son la mejor manera de superar los resultados a largo plazo en pacientes cirróticos con carcinoma hepatocelular y que la ligadura de la arteria hepática es superior a la resección incompleta (no curativa).

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Résumé De 1973 à 1982 les auteurs ont opéré 226 malades qui présentaient un cancer hépatocellulaire, 103 par hépatectomie et 93 par ligature de l'artère hépatique. La majorité des patients présentaient une cirrhose ou des lésions hépatiques, un tiers étaient porteurs de varices oesophagiennes. Comme dans les autres séries japonaises ou asiatiques, les résultats à long terme chez les 90 malades qui avaient subi une hépatectomie furent décevants par comparaison avec les séries occidentales concernant les sujets indemnes de cirrhose. Cependant la survie actuarielle à 3 ans fut de 90% chez les opérés qui présentaient un cancer d'un diamètre inférieur à 3 cm (n=18). Le taux de survie à 5 ans fut de 70,8% chez 25 malades qui avaient subi une résection à but curatif, et le taux de survie à 3 ans fut de 100% chez 16 opérés qui avaient subi une résection pour une tumeur d'un diamètre inférieur à 5 cm. Quatrevingt-quatre malades ont survécu à la ligature de l'artère hépatique; chez 50 d'entre eux la zone ischémique provoquée par la ligature intéressait la totalité de la région hépatique occupée par les lésions néoplasiques. Le taux de survie de ces 50 malades fut toujours supérieur à celui de ceux qui n'avaient pu être l'objet d'une résection hépatique.De cette étude, on peut retenir les conclusions suivantes: le diagnostic précoce et la résection à but curatif du cancer hépatocellulaire chez les cirrhotiques représentent des conditions favorables à l'obtention de résultats à long terme satisfaisants; les résultats de la ligature de l'artère hépatique sont supérieurs à ceux de la résection incomplète (résection à but non curatif).

     

Compartmentalization of the chick cerebellar cortex based on the link between the striped expression pattern of aldolase C and the topographic olivocerebellar projection

The avian cerebellum is organized into multiple longitudinal stripes defined by expression profiles of aldolase C (zebrin II) in Purkinje cells. The relationship between the aldolase C striped pattern and the olivocerebellar projection pattern is crucial in understanding cerebellar functional compartmentalization. We identified all aldolase C stripes across all lobules with the serial section alignment analysis method and then looked at this relationship by anterograde and retrograde labeling of olivocerebellar axons in the chick cerebellum. Aldolase C stripes were generally consistent and continuous from lobule I through VII and to the medial part of lobules VIII–IXb. The dorsal and ventral lamellas (DL, VL) of the inferior olive projected to the stripes in these areas with a simple mediolateral topographic relation. A few aldolase C stripes appeared at the lateral edge of lobules VI–VIII. Several more stripes were added in the lateral parts of lobules IXa–IXb and IXc–X. The medial column (MC) of the inferior olive projected to the stripes in lobules VIII–X, including the added lateral stripes, with a complex topographic relation. Sharp boundaries between aldolase C‐positive and ‐negative stripes often accompanied a gap in the Purkinje cell layer and bordered topographically distinct groups of axons. Although the compartmental organization of the chick cerebellum is comparable to that of the mammalian cerebellum, several significant differences in the organization suggest partly separate evolutionary lineages of the mammalian and avian cerebella. We propose that rostral lobules may be evolved by rostral extension of medial stripes from caudal lobules in the avian cerebellum. J. Comp. Neurol. 523:1886–1912, 2015 © 2015 Wiley Periodicals, Inc.     

Five‐year efficacy of finasteride in 801 Japanese men with androgenetic alopecia

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.