Kohei Ohta

Treatment of tuberculum sellae meningiomas:a long-term follow-up study

Surgical techniques and their results for tuberculum sellae meningiomas were studied. Thirty-three cases, the first of which was operated in 1980, were analysed. There were 4 men and 29 women with an average age of 46.7 years. Eight cases underwent reoperations. The mean follow-up was 10.7 years. Approaches were pterional for 15 patients, FOZ/FO for 10, bilateral subfrontal for 6, and others for 2. Simpsons grade (I, II, III, IV) were 12, 9, 0, and 12 cases respectively. Recurrence rate was 0% for grade I and 58.3% for grade IV. The FOZ/FO approach resulted in a lower Simpsons grade (P=0.05), but other factors were not related to Simpsons grade (P=0.05). The postoperative visual outcome did not depend on total (grade I and II) or subtotal (grade III and IV) removal (P=0.01). We conclude that radical removal of the tumours may result in lower recurrence rate without increasing surgical complications. Furthermore, skull base approaches can improve the rate of radical removal of tuberculum sellae meningiomas.

Post-licensed 1-year experience of systemic thrombolysis with tissue plasminogen activator for ischemic stroke in a Japanese neuro-unit

OBJECTIVEnIn Japan, intravenous thrombolysis with tissue plasminogen activator (tPA) for ischemic stroke within 3h of onset was officially approved in October 2005.nnnMETHODSnWe report initial 1-year clinical experience of intravenous alteplase at 0.6mg/kg in a Japanese neuro-unit.nnnRESULTSnTwenty patients received intravenous tPA, corresponding to 12% of all ischemic strokes (n=166) and 38% of ischemic strokes within 3h of onset (n=52). The mean age was 68 years old and 15% had pre-morbid dependency with modified Rankin Scale (mRS) of 3 or 4. The median baseline National Institute of Health Stroke Scale score was 19 points (range; 5-37). Average time from stroke onset to tPA delivery was 136 min (range; 87-180). Of 18 (90%) patients receiving pretreatment vascular imaging, 16 (80%) patients had a large arterial occlusion. At 3 months, excellent outcome with mRS of 0 or 1 was 25%, and good outcome with mRS of 0-2 was 35%. One patient (5%) developed symptomatic intracranial hemorrhage within 36 h. Mortality rate was 15%.nnnCONCLUSIONSnIntravenous tPA within 3h was safe and feasible, and possibly effective in clinical practice. The higher stroke severity in our cohort precluded to compare the sufficient effectiveness with clinical trials. In Japan, a post-licensed national surveillance is currently under way.

2-Pyrrolidinone induces a long-lasting facilitation of hippocampal synaptic transmission by enhancing α7 ACh receptor responses via a PKC pathway

2-Pyrrolidinone, a metabolite of aniracetam, potentiated currents through alpha7 receptors expressed in Xenopus oocytes, in a bell-shaped dose-dependent manner at concentrations ranged from 1 nM to 10 microM, with a maximum at 100 nM (189% of original levels 60 min after 20-min treatment). The potentiation was inhibited by GF109203X, a selective inhibitor of protein kinase C (PKC), but not by KN-93, a selective inhibitor of CaMKII, or H-89, a selective inhibitor of protein kinase A (PKA). In the PKC assay using reversed-phase high-performance liquid chromatography, 2-pyrrolidinone enhanced activity of PKC-epsilon activated by linoleic acid to about 1.8-times greater than that in the absence of 2-pyrrolidinone, although it did not directly activate PKC-epsilon. In the Western immunoblot analysis, rat hippocampal slices treated with 2-pyrrolidinone (100 nM) was more reactive to an antibody against phosphorylated myristoylated alanine-rich C kinase substrate (MARCKS) than untreated slices. 2-Pyrrolidinone (100 nM) induced a long-lasting facilitation of hippocampal synaptic transmission in the CA1 region of rat hippocampal slices, and the facilitation was inhibited by GF109203X or alpha-bungarotoxin, an inhibitor of alpha7 receptors. The results of the present study suggest that 2-pyrrolidinone enhances activity of activated PKC, thereby potentiating alpha7 receptor responses, and then leading to a facilitation of hippocampal synaptic transmission.

L-trans-PDC enhances hippocampal neuronal activity by stimulating glial glutamate release independently of blocking transporters.

The glutamate transporter inhibitor, L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) reversibly enhanced hippocampal neuronal activity in the rat and mouse dentate gyrus. The PDC action was still found in mice lacking the glial glutamate transporter GLT-1. PDC did not influence the rate of spontaneous miniature excitatory postsynaptic currents and spontaneous inhibitory postsynaptic currents, ionotropic glutamate receptor currents, or GABA-evoked currents in cultured rat hippocampal neurons. PDC increased glutamate released from cultured hippocampal astrocytes from normal rats, normal mice, and GLT-1 knock-out mice, that is not inhibited by deleting extracellular Na(+), while the drug had no effect on the release from cultured rat hippocampal neurons. The results of the present study thus suggest that PDC stimulates glial glutamate release by a mechanism independent of inhibiting glutamate transporters, which perhaps causes an increase in synaptic glutamate concentrations, in part responsible for the enhancement in hippocampal neuronal activity.

Primary granulocytic sarcoma in the sphenoidal bone and orbit

Case reportWe report a case of a primary cranial chloroma in boy aged 2xa0years and 8xa0months. The symptoms were progressive bilateral exophthalmos, right abducens palsy, and bilateral papilledema. The tumor was partially calcified and was a round mass located in the bilateral sphenoidal bone extending into the orbit. Laboratory study did not show hematological abnormality. The tumor was partially removed by bilateral frontotemporal craniotomy and a diagnosis of primary granulocytic sarcoma was made from the surgical specimen. Progressive deterioration of visual acuity was seen and chemotherapy started on the 11th postoperative day followed by local cranium irradiation (24xa0Gy). The patient has been in complete remission for 37xa0months. The visual acuity recovered partially and follow-up magnetic resonance imaging showed a significant decrease in the size of the tumor.DiscussionRadiological diagnosis of primary intracranial granulocytic sarcoma is difficult. Surgical removal may be an option for progressive neurological deterioration but chemotherapy is more important for both neurological stabilization and induction of remission.

The protective action of nefiracetam against electrophysiological and metabolic damage in the hippocampus after deprivation of glucose and oxygen.

The present study examined the effect of nefiracetam on ischemic brain damage by monitoring population spikes (PSs) in the dentate gyrus of guinea pig hippocampal slices; assaying high-energy phosphates (ATP and CrP) in guinea pig hippocampal slices; and monitoring whole-cell membrane-currents and intracellular Ca(2+) levels in cultured hippocampal neurons. Twenty-minute ischemic insult to slices, i.e., deprivation of glucose and oxygen from artificial cerebrospinal fluid, abolished PSs. As compared with only 35% recovery of the PS amplitude for control, PS amplitude reversed to 65% of basal levels 40 min after returning normal conditions by treatment with nefiracetam (0.01 microM). Ischemic insult reduced the levels of adenosine triphosphate (ATP) and creatine phosphate (CrP) in slices, and when returned to normal conditions, recovering to 70 and 85% of basal values, respectively, 30 min after returning normal conditions. Nefiracetam (0.01 microM) facilitated the recovery of ATP and CrP, reaching 110 and 140% of basal values, respectively. Nefiracetam inhibited N-methyl-D-aspartate (NMDA)-evoked currents to 35% of basal amplitudes. Likewise, nefiracetam (0.01 microM) inhibited intracellular Ca(2+) rise through NMDA receptor channels to 30% of basal levels. The results of the present study, thus, suggest that nefiracetam has the potential to protect against ischemic brain damage, possibly in part by preventing from accumulation of intracellular calcium through NMDA receptor channels.

Subarachnoid Hemorrhage Due to Rupture of an Intracavernous Carotid Artery Aneurysm Coexisting with a Prolactinoma under Cabergoline Treatment

We report an unusual case of subarachnoid hemorrhage caused by intraoperative rupture of an intracavernous carotid artery aneurysm coexisting with a prolactinoma. A 58-year-old man presenting with diplopia was found to have a left intracavernous carotid artery aneurysm encased by a suprasellar tumor on magnetic resonance imaging. His serum prolactin level was 5036 ng/mL. Proximal ligation of the left internal carotid artery with a superficial temporal artery to middle cerebral artery anastomosis was scheduled. Because the patients diplopia had deteriorated, we started him on cabergoline at a dose of 0.25u2009mg once a week. One month after administration of cabergoline, the diplopia was improved to some extent and serum prolactin was decreased to 290 ng/ml. Six weeks after starting the cabergoline, the patient underwent a left frontotemporal craniotomy to treat the aneurysm. When the dura mater was opened, abnormal brain swelling and obvious subarachnoid hemorrhage were observed. Postoperative computed tomography demonstrated a thick subarachnoid hemorrhage. This case suggests that medical therapy for a pituitary adenoma should be started after treatment for a coexisting intracavernous aneurysm is completed.

Role of glial glutamate transporters in the facilitatory action of FK960 on hippocampal neurotransmission.

We found previously that N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960) facilitated hippocampal neurotransmission in the dentate gyrus of rat hippocampal slices. The present study was conducted to understand the mechanism underlying the facilitatory action of FK960. The facilitation was inhibited by H-89, an inhibitor of cAMP-dependent protein kinase (PKA), but it was not affected by cycloheximide, a protein synthesis blocker. In cultured rat hippocampal neurons, the drug had no effect on either spontaneous miniature excitatory postsynaptic currents or whole-cell membrane currents evoked by glutamate, kainate, or NMDA, suggesting that the facilitatory action of FK960 is not caused by increasing presynaptic transmitter release or excitatory postsynaptic conductances. FK960 inhibited responses of the glial glutamate transporter, GLT-1, expressed in Xenopus oocytes, and a similar effect was found with cultured rat astrocytes. The FK960 action was inhibited in the presence of H-89. The results of the present study thus suggest that FK960 facilitates hippocampal neurotransmission by inhibiting GLT-1 glial glutamate reuptake via a PKA pathway, thereby increasing synaptic glutamate concentrations.