Huge facial schwannoma extending into the middle cranial fossa and cerebellopontine angle without facial nerve palsy--case report.

A 46-year-old male presented with a huge facial schwannoma extending into both the middle cranial fossa and the cerebellopontine angle but without manifesting facial nerve palsy. Neurological examination on admission revealed no deficits except for speech disturbance. Computed tomography showed a multicystic tumor extending into the middle cranial fossa and the cerebellopontine angle, with destruction of the petrous bone. The tumor was totally grossly removed. Histological examination identified schwannoma. Total facial nerve palsy appeared postoperatively, but hearing acuity was preserved at a useful level. Facial nerve palsy is one of the most typical symptoms in patients with facial schwannoma, but is not always manifested even if the tumor extends into both the middle cranial fossa and the cerebellopontine angle.

[Surgical management for preserving motor function in patients with gliomas near the primary motor cortex: usefulness of preoperative identification of motor cortex and intraoperative monitoring of motor evoked potentials].

Preoperative identification of precentral gyrus and intraoperative monitoring of motor evoked potentials (MEPs) were performed to preserve postoperative motor function in seven patients with gliomas near the primary motor cortex. Tumors were astrocytomas in 3 patients, glioblastomas in 2 patients, anaplastic astrocytoma and mixed glioma in one patient each. Preoperative identification of the primary motor cortex was performed by three-dimensional (3D) display of magnetic resonance (MR) images and by functional images using MR imaging and single-photon emission tomography. The primary motor cortex identified by 3D display of MR images coincided well with that identified by functional images. 3D display of MR images was also useful for detecting the relationship between the tumor and the primary motor cortex. Intraoperatively, the central sulcus was confirmed by the finding of phase reversal of cortical somatosensory evoked potential, and this corresponded with the preoperative identifications by 3D display and by functional mapping. The primary motor cortex was stimulated electrically, and MEP (corticospinal evoked potential) was continuously monitored during surgery using electrodes inserted in the cervical epidural space. The amplitude of direct waves of MEPs during surgery was maintained above half of that recorded at the beginning of tumor removal, and all patients showed preservation of preoperative motor function. These results suggest that preoperative identification of precentral gyrus and intraoperative MEP monitoring provide useful information for preserving motor function in patients with gliomas near the primary motor cortex.

E2011 a novel, selective and reversible inhibitor of monoamine oxidase type A.

E2011, (5R)-3-[2-((1S)-3-cyano-1hydroxypropyl)benzothiazol- 6-yl]-5-methoxymethyl-2-oxazolidine, is a novel inhibitor of monoamine oxidase type A (MAO-A). We have characterized the neurochemical and pharmacological profiles of E2011 and compared them with those of known inhibitors of MAO-A. E2011 potently inhibited MAO-A with more than 30,000 times higher selectivity for MAO-A relative to MAO-B in rat brain homogenate. E2011 did not affect putative neural receptors or reuptake of biogenic amines into synaptosomes of rat brain, which suggests that it is specific to monoaminergic systems. In vivo, E2011 at a dose of 0.3 mg/kg p.o. exhibited potent MAO-A inhibitory activity, whereas MAO-B inhibition was not observed even at 100 mg/kg p.o. E2011 inhibited monoamine metabolism in the rat brain, but the effect disappeared 24 h after administration. Like other reversible MAO-A inhibitors, E2011 did not show a cumulative inhibitory effect during repeated administration for 7 days. However, inhibition of MAO-A by E2011 in ex vivo experiments appeared to be less potent than that by moclobemide. The MAO-A inhibition by E2011 was partially but significantly reversed by dialysis at 4 degrees C for 24 h, which indicates that E2011 could be dissociated from the enzyme. These findings suggest that E2011 is a reversible and highly selective inhibitor of MAO-A. The potency of inhibition by highly reversible MAO-A inhibitors such as E2011 is likely to be underestimated in ex vivo studies because of dilution of the homogenate in the assay system.

Application of pharmacokinetic studies to a novel antidepressant, E2011.

1. The original drug tested here, (5R)-3-[2-(3-cyanopropyl)benzothiazol-6-yl]-5-methoxymethyl-2-oxaz olidinone (ER-4539), exhibited strong MAO-A inhibitory activity in vitro, but its bioavailability in rat was very low. After ER-4539 was administered orally to dog, a metabolite was found in plasma. 2. The metabolite was isolated by hplc after incubation with dog liver microsomal preparations. Its structure, determined by ms and nmr analysis, was alpha-hydroxy-ER-4539. The configuration of the alpha-hydroxy metabolite was (S), determined in comparison with the authentic sample of (R) and (S) by hplc. The isolated metabolite had potent MAO-A inhibitory action in vitro, indicating that it would have antidepressant action. 3. (5R)-3-[2-((1S)-3-Cyano-1-hydroxypropyl)benzothiazol-6-yl]-5- methoxymethyl-2-oxazolidinone (E2011), the synthesized metabolite, has been improved in regard to biopharmaceutical characteristics in rat and dog.