Cerebrospinal fluid dissemination of anaplastic intraventricular meningioma: report of a case presenting with progressive brainstem dysfunction and multiple cranial nerve palsies.

BACKGROUND: It 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 PRESENTATION: An 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. CONCLUSION: If 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.

Effects of UCH-L1 on alpha-synuclein over-expression mouse model of Parkinson's disease.

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 loss-of-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 PD-causing insult, abnormal accumulation of alpha-synuclein (alphaSyn). Immunohistochemistry of midbrain sections of a patient with sporadic PD showed alphaSyn- 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 alphaSyn 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-L1(wild-type)-Tg mice and non-Tg littermates. In contrast, the extent of alphaSyn-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.

Correlation between levels of pigment epithelium-derived factor and vascular endothelial growth factor in the striatum of patients with Parkinson's disease.

Parkinson's disease (PD) is caused by progressive degeneration of nigrostriatal dopaminergic neurons and can potentially be treated by intrastriatal delivery of neurotrophic factors. Pigment epithelium-derived factor (PEDF), which exhibits protective effects on various neuronal populations, is up-/down-regulated in the cerebrospinal fluid in some neurodegenerative conditions. Here we investigated the level of PEDF protein in the striatum and immunoreactivity for PEDF in the substantia nigra (SN) of patients with PD to assess its role in the pathophysiology of PD. We also studied changes in PEDF expression in the striatum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We found a transient and rapid up-regulation of PEDF transcripts and a marked increase in immunoreactivity for PEDF protein in response to MPTP administration in mice. However, there were no significant changes in striatal levels of PEDF and immunoreactivity for PEDF in the SN of PD patients compared with age-matched non-PD patients. Intriguingly, the striatal levels of PEDF and vascular endothelial growth factor (VEGF), which has opposite functions to PEDF in terms of angiogenesis and vascular permeability, correlated positively in PD patients. Our results suggest up-regulation of PEDF in response to acute insult to the dopaminergic pathway, but such response might be disturbed in patients with advanced PD. The correlation between PEDF and VEGF striatal levels in PD patients suggests that concerted neurotrophic functions of these factors or structural changes in blood vessel walls play an important role in the pathophysiology of PD.

[An 81-year-old man with personality change, dementia, and gait disturbance with diffuse leukoaraiosis of the cerebral white matter].

We report an 81-year-old patient with progressive dementia, disinhibition, and gait disturbance. He showed visuospacial disorientation, apathy, and gait disturbance at 76 years of age. When he was 77 years old, he was diagnosed Parkinson's disease and treated with the 1-dopa, the dopamine agonist, the amantadin, and the anti-cholinergic drug. These treatments didn't improve his motor disturbances. His motor disturbances, apathy, and abnormal behavior progressed gradually. He was admitted to the hospital at the age of 77. He was severely demented and akinetic. Sometime, violent behavior and hallucination were seen. The brain MRI showed frontotemporal lobe atrophy and severe leukoaraiosis of the frontal white matter. At 79 years of age, he became mute and bedridden. When he was 80 years old, large infarction occurred in his occipital lobe. He died due to renal failure and respiratory suppression at 81 years of age. His brain was examined pathologically. At the neurological CPC, the chief discussant arrived at the conclusion that his diagnosis was Binswanger's disease. Other possibilities discussed were FTD, CBD, and progressive subcortical gliosis. The post-mortem examination revealed diffuse white matter degeneration due to atherosclerotic change of the small artery, many lacunar infarctions, and severe infarction of the occipital lobe. These findings led the diagnosis of Binswanger's disease and cerebral infarction.