Posterior Reversible Encephalopathy Syndrome after a Variety of Combined Chemotherapies Containing Bevacizumab for Metastatic Colon Cancer.

A 44-year-old woman with advanced metastatic colon cancer received chemotherapies comprising oxaliplatin and capecitabine (XELOX), irinotecan hydrochloride, leucovorin calcium and fluorouracil irinotecan (FOLFIRI)/panitumumab and mFOLFOX6/bevacizumab. Fifteen months later, she presented with the acute onset of a headache, drowsiness and seizure with a fever and hypertension. Brain magnetic resonance imaging (MRI) indicated bilateral regions of signal hyperintensity in the white matter with spasms of bilateral cerebral arteries apparent on magnetic resonance angiography. Posterior reversible encephalopathy syndrome (PRES) was diagnosed, and treatments resulted in improvement of the MRI findings, but the patient experienced cerebral infarction and ultimately died of deterioration of cancer on day 26 after the onset of PRES.

Comparison of effects of valsartan and amlodipine on cognitive functions and auditory p300 event-related potentials in elderly hypertensive patients.

OBJECTIVE: We compared the antihypertensive effect of valsartan (VAL) and amlodipine (AML) treatments in elderly hypertensive patients by examining the long-term changes in cognitive function and auditory P300 event-related potentials. METHODS: We enrolled 20 outpatients, including 12 men and 8 women in the age group of 56 to 81 years who had mild to moderate essential hypertension. The subjects were randomly allocated to receive either 80 mg VAL once a day (10 patients) or 5 mg AML once a day (10 patients). Neuropsychological assessment and auditory P300 event-related potentials were obtained before initiation of VAL or AML treatment and after 6 months of the treatment with VAL or AML. Neuropsychological assessment was evaluated by conducting the Mini-Mental State Examination, the verbal fluency, word-list memory, word-list recall test, word-list recognition, and Trails B tests. RESULTS: Both the groups showed significantly reduced-blood pressure after 6 months of treatment, and the intergroup difference was not significant. The mean baseline Mini-Mental State Examination scores of the VAL and AML groups were not significantly different. Amlodipine treatment did not significantly affect any test score, but VAL treatment significantly increased the word-list memory and word-list recall test scores. Valsartan, and not AML, significantly reduced the mean P300 latency after 6 months. CONCLUSIONS: These results suggest that VAL exerts a positive effect on cognitive functions, independent of its antihypertensive effect.

Suppression of astrocyte lineage in adult hippocampal progenitor cells expressing hippocampal cholinergic neurostimulating Peptide precursor in an in vivo ischemic model.

Hippocampal cholinergic neurostimulating peptide (HCNP) is known to promote differentiation of septohippocampal cholinergic neurons. The HCNP precursor protein (HCNP-pp) may play several roles, for example, as an ATP-binding protein, a Raf kinase inhibitor protein, and a phosphatidylethanolamine-binding protein, as well as a precursor for HCNP. This study therefore aimed to elucidate the involvement of HCNP-pp in specific neural lineages after stroke using a hypoxic-ischemic (HI) rat model of brain ischemia. The specific neural lineages in the hippocampus were investigated 14 days after ischemia. Some bromodeoxyuridine (BrdU)(+) neural progenitor cells in the hippocampus of hypoxic, HI, or sham-operated rats expressed HCNP-pp. Almost half of the BrdU(+)/HCNP-pp(+) cells also expressed the oligodendrocyte lineage marker 2',3'-cyclic nucleotide 3'-phosphodiesterase, whereas only a few BrdU(+)/HCNP-pp(+) cells in the hippocampus in HI brains expressed the neuronal lineage marker, doublecortin (DCX). Interestingly, no BrdU(+)/HCNP-pp(+) progenitor cells in hypoxic, HI, or sham-operated brains expressed the astrocyte lineage marker, glial fibrillary acidic protein. Together with previous in vitro data, the results of this study suggest that the expression level of HCNP-pp regulates the differentiation of neural progenitor cells into specific neural lineages in the HI hippocampus, indicating that neural stem cell fate can be controlled via the HCNP-pp mediating pathway.

Suppressed phosphorylation of collapsin response mediator protein-2 in the hippocampus of HCNP precursor transgenic mice.

We previously reported a novel peptide, Hippocampal Cholinergic Neurostimulating Peptide (HCNP), which induces acetylcholine synthesis by increasing the amount of choline acetyltransferase (ChAT) in medial septal nuclei. The HCNP precursor protein (HCNP-pp), composed of 186 amino acids, is an inhibitory factor of the c-Raf/MEK cascade and may be involved in fetal rat brain development via the inhibition of phosphorylation of Erk. To clarify the involvement of HCNP in hippocampal cholinergic circuitry, we previously generated HCNP-pp transgenic (HCNP-pp Tg) mice using the promoter of the α subunit of Ca(2+) calmodulin-dependent protein kinase II (CaMKIIα). These mice showed increased levels of ChAT in medial septal nuclei at 12 weeks of age, and the phenotype of depressive mood at 30 weeks of age. Here, through proteomic analysis we investigated the alteration of protein expression in the hippocampus of HCNP-pp Tg mice compared with wild-type littermate mice. We demonstrate that the activation of collapsin response mediator protein-2 (CRMP-2) is increased in the transgenic mice at 12 weeks of age when compared with wild-type littermate mice.

Directed neural lineage differentiation of adult hippocampal progenitor cells via modulation of hippocampal cholinergic neurostimulating peptide precursor expression.

Hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from young rat hippocampus, has been known to promote the differentiation of septo-hippocampal cholinergic neurons. Recently, the precursor protein of HCNP (HCNP-pp) has also received attention as a multifunctional protein with roles, in addition to serving as the HCNP precursor, such as acting as an ATP-binding protein, a Raf kinase inhibitor protein (RKIP), and phosphatidylethanolamine-binding protein (PEBP). In particular, the function of RKIP has attracted attention over several years for its role in controlling cellular proliferation and metastasis in cancer cells. HCNP-pp is also thought to be important in regulating the proliferation and differentiation of neuronal cells in vitro and in vivo by modification of the MAPK cascade. In the present study, we used cultured adult rat hippocampal progenitor cells (AHPs), which are thought to be important for memory formation, and focused on the role of HCNP-pp in adult neurogenesis, namely, the production of new neurons from neural stem/progenitor cells. We found that HCNP-pp expression in AHPs was closely associated with differentiation into MAP2ab-positive neurons and RIP-positive oligodendrocytes, but not into GFAP-positive astrocytes. By contrast, a down-regulated HCNP-pp expression in AHPs accompanied differentiation into GFAP-positive astrocytes. Direct manipulations of HCNP-pp via viral over-expression or siRNA downregulation further confirmed the HCNP-pp contribution to specific neural lineage commitment of AHPs. Our results show that the expression level of HCNP-pp acts as a key regulator for differentiation of cultured AHPs into specific neural lineages, indicating that the control of neural stem cell fate can be achieved via the HCNP-pp pathway.

Overexpression of hippocampal cholinergic neurostimulating peptide in heterozygous transgenic mice increases the amount of ChAT in the medial septal nucleus.

Acetylcholine modulates neural activity in the hippocampal glutamatergic pathway via the induction of phosphorylated Erk and may act as a novel transmitter in septohippocampal memory formation. However, how acetylcholine synthesis in the septal nucleus is regulated is unknown. We have purified a peptide from the hippocampus of the young adult rat, named hippocampal cholinergic neurostimulating peptide (HCNP) that induces acetylcholine synthesis in vitro in the septal nucleus. Previously, levels of this peptide and/or precursor protein were reported to be decreased, and the protein to be nitrated in the brains of patients with Alzheimer's disease. Here, to clarify the involvement in the regulation of acetylcholine synthesis in vivo in the medial septal nucleus, we generated HCNP precursor transgenic mice, using a Ca2+ calmodulin-dependent protein kinase II genomic promoter. The amount of cholineacetyltransferase (ChAT) in the medial septal nucleus was increased in heterozygous HCNP transgenic mice, compared with non-transgenic littermates. This result suggests that HCNP is involved in regulating acetylcholine synthesis in vivo in the medial septal nucleus and, as such, is important for memory function.

[A case of neurolymphomatosis diagnosed with FDG-PET].

A 38-year-old man with non-Hodgkin's lymphoma presented with hypesthesia and muscle weakness in the left upper limb. A lack of F-waves in left median and ulnar nerve conduction studies suggested a lesion at the proximal segments of the peripheral nerves, such as the left brachial plexus or nerve roots. Cervical magnetic resonance imaging revealed no lesions compressing nerve roots or peripheral nerves. Small and obscure uptake on the left side of the cervical nerve roots on 67Ga-scintigraphy was indistinguishable from artifact. Positron emission tomography-computed tomography (PET/CT) revealed a region of high glucose uptake in a left cervical intervertebral foramen, leading to a diagnosis of neurolymphomatosis. Neurological symptoms improved following additional chemotherapy, and the high glucose-uptake lesion disappeared. FDG-PET/CT is useful for rapid and non-invasive evaluation of neurolymphomatosis.

[An adult case of cyclic vomiting syndrome in which tricyclic antidepressant was effective].

A 30-year-old man presented with a 10-year history of recurrent, stereotypic episodes of incapacitating nausea and vomiting. Initially, he had been diagnosed as having superior mesenteric artery syndrome, and had undergone abdominal surgery at age 20. The patient was in good health between episodes. During each episode, oral intake was impossible and total parenteral nutrition and sedation were necessary. Conventional antiemetics such as metoclopramide were not effective, and the 5-HT3 antagonist ondansetron hydrochloride was only partially effective. Investigations into gastrointestinal, hormonal, and metabolic function were unremarkable, as was psychiatric evaluation. Diagnosing this to be an adult case of cyclic vomiting syndrome, we administered amitriptyline hydrochloride; a prophylactic agent for migraine. This resulted in rapid resolution of the episodes, which have not recurred over several years' follow up. Recently, cyclic vomiting syndrome has been considered a subtype of migraine. In the present case, effectiveness of the tricyclic antidepressant amitriptyline hydrochloride indicated that migraine and cyclic vomiting syndrome have a common pathology. Clinicians should be aware that cyclic vomiting syndrome can affect adults as well as children, and that treatment for migraine may be effective.

[An autopsy case of purulent meningitis, presenting high signals in subarachnoid space and ventricles in diffusion weighted images (DWIs)].

A 79-year-old, bedridden woman with an untreated colon cancer, developed abrupt disturbance of consciousness and high fever. Brain MRI showed significant high signals in the subarachnoid space and ventricles in diffusion-weighted images (DWIs), and she died on the same day. At autopsy, much exudate was found over the base of the brain, leading to a diagnosis of purulent meningitis. On histological findings, inflammatory cell infiltration was significantly restricted within the subarachnoid space, but not into the brain parenchyma. This case report demonstrated that high signals in subarachnoid space and ventricles in DWIs may be very useful for diagnosis of purulent meningitis.