The rare inherited form of Parkinson's disease (PD), PARK5, is caused by a missense mutation in ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) gene, resulting in Ile93Met substitution in its gene product (UCH-L1 Ile93Met ). PARK5 is inherited in an autosomal-dominant mode, but whether the Ile93Met mutation gives rise to a gain-of-toxic-function or lossof-function of UCH-L1 protein remains controversial. Here, we investigated the selective vulnerabilities of dopaminergic (DA) neurons in UCH-L1-transgenic (Tg) and spontaneous UCH-L1-null gracile axonal dystrophy mice to an important PDcausing insult, abnormal accumulation of a-synuclein (aSyn).Immunohistochemistry of midbrain sections of a patient with sporadic PD showed aSyn-and UCH-L1-double-positive Lewy bodies in nigral DA neurons, suggesting physical and/or functional interaction between the two proteins in human PD brain. Recombinant adeno-associated viral vector-mediated over-expression of aSyn for 4 weeks significantly enhanced the loss of nigral DA cell bodies in UCH-L1 Ile93Met-Tg mice, but had weak effects in age-matched UCH-L1wild-type -Tg mice and non-Tg littermates. In contrast, the extent of aSyn-induced DA cell loss in gracile axonal dystrophy mice was not significantly different from wild-type littermates at 13-weeks post-injection. Our results support the hypothesis that PARK5 is caused by a gain-of-toxic-function of UCH-L1 Ile93Met mutant, and suggest that regulation of UCH-L1 in nigral DA cells could be a future target for treatment of PD. Keywords: a-synuclein, adeno-associated virus, dopaminergic neurons, Parkinson's disease, ubiquitin carboxyterminal hydrolase-L1. missense mutations resulting in amino acid substitutions in aSyn protein (Ala53Thr, Ala30Pro, or Glu46Lys) (Polymeropoulos et al. 1997;Kruger et al. 1998;Zarranz et al. 2004). Furthermore, PARK4 is caused by duplication or triplication of aSyn gene (SNCA) locus (Singleton et al. 2003;Nishioka et al. 2006). In sporadic cases of PD, aSyn protein is the major component of Lewy bodies (Spillantini et al. 1997;Baba et al. 1998). These findings suggest an important role for aSyn protein accumulation in DA cells in the pathogenesis of PD. Previous studies also reported that overexpression of aSyn protein by using a recombinant adeno-associated viral (rAAV) or lentiviral vector caused DA neurodegeneration in rats and monkeys (Kirik et al. 2002(Kirik et al. , 2003Lo Bianco et al. 2002;Yamada et al. 2004;Yasuda et al. 2007). Ubiquitin carboxy-terminal hydrolase-L1 constitutes 1-2% of brain proteins and functions in the ubiquitin-proteasome system (Wilkinson et al. 1989;Larsen et al. 1996Larsen et al. , 1998. The ubiquitin hydrolase activity of UCH-L1 is important to free reusable ubiquitin monomers. UCH-L1 protein is also known to bind to and stabilize monomeric ubiquitin molecule (Osaka et al. 2003). PARK5 is caused by a missense mutation in UCH-L1 gene resulting in Ile93Met substitution in UCH-L1 protein (UCH-L1 Ile93Met ), and inherited in an autosomal-dominant mode (Leroy et al...

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Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome characterized by headache, confusion, seizures, and cortical visual loss, as well as subcortical edema without infarction on neuroimaging. We report a 56-year-old woman who developed typical manifestations of PRES, 6 days after blood transfusion for severe anemia. Acute volume overloads by transfusion may exceed the capacity of autoregulation of perfusion pressure, possibly resulting in vasogenic edema. We propose that it is clinically important to recognize that rapid correction of anemia by blood transfusion may carry the risk of inducing PRES.

The interstitial nucleus of Cajal (INC) is thought to play an important role in torsional/vertical eye position and head posture, and disorders of the INC induce abnormal ocular movements and head tilt. Our patients with ocular tilt reactions simultaneously also had disturbances in ambulatory balance, yet no reports address the loss of balance control induced by disorders of the INC. We examined the ambulatory disturbances induced by INC lesion. We experienced three patients with ocular movement disorders and abnormal head tilt due to thalamic infarction. We performed ophthalmic examinations on and checked the balance of them. With funduscopy, abnormal cycloduction was seen in the unaffected side and normal cycloduction was observed in the affected side. Nevertheless, Hess charts showed distortions in the visual image of both eyes. They all had disorders of balance control. We tried to treat them using the Bobath approach for improving their ambulatory balance. With subsequent improvements in balance control it was possible for them to take short walks, but it was difficult to make any improvements in their ocular movement. The INC is related to balance control of ambulation and disorders of the INC induce ambulatory disturbances. Cycloduction was only observed in the unaffected side, but Hess charts showed distortions of the visual image in both eyes. Ambulation was briefly improved, but diplopia persisted in these patients.

BackgroundIt is extremely rare to see cerebrospinal fluid dissemination of intraventricular meningioma, particularly with the development of acute, progressive brainstem/cerebellar dysfunction with an absence of mass formation in the corresponding anatomical sites.Case presentationAn 81-year-old man was admitted because of double vision, right facial nerve palsy and truncal ataxia. Brain magnetic resonance imaging showed normal findings except for a tumor mass in the left lateral ventricle, which had been noted over 6 months previously. The patient developed hiccups, hyperventilation, and drowsiness, which worsened progressively, and did not respond to corticosteroid or intraventricular immunoglobulin therapy. Cerebrospinal fluid study revealed a mild elevation of protein, and cytology was negative. The patient died and an autopsy was performed. Postmortem investigation disclosed a malignant transformation of benign fibroid meningioma with cerebrospinal fluid dissemination of the malignant cells, diversely involving the surface of brainstem, cerebellum, and spinal cords, secondarily resulting in extensive ischemia in the brain parenchyma by vessel occlusion.ConclusionIf a patient with an intraventricular tumor develops acute, progressive neurological symptoms, the possibility that it is be caused by cerebrospinal fluid dissemination of tumor cells, after malignant transformation, should be considered.