Toru Hatayama

An in Vivo Quantifiable Model of Cochlear Neuronal Degeneration Induced by Central Process Injury

In the available in vivo experimental models for cochlear neuronal degeneration, the peripheral (hair cell side) process of the cochlear nerve has been injured in order to induce neuronal degeneration. However, there has been no dependable experimental model in which cochlear neuronal degeneration begins from the central (brain stem side) process. This lack of a central process injury model has probably been due to the experimental difficulties that had to be overcome in order to reproducibly and selectively injure the central process of the cochlear neurons while maintaining the patency of the internal auditory artery in small experimental animals such as rats. Using rats, we first developed a central process injury model in which the reduction of the spiral ganglion cells due to retrograde degeneration of cochlear neurons can be quantitatively evaluated. In our experimental model, the cochlear nerve was compressed and injured by a compression-recording (CR) electrode placed at the internal auditory meatus. First, the cochlear nerve was compressed until the compound action potentials of the cochlear nerve became flat, and then the CR electrode was advanced by various compression speeds (5, 10, or 200 micrometer/s) to reach the same depth (400 micrometer). In our model, therefore, the reduction of the spiral ganglion cells was caused compression speed dependently. This method made it possible to produce compression injury to the cochlear nerve without evidence of damage to the blood supply to the cochlea via the internal auditory artery. This model gives us the means to obtain knowledge that was previously impossible to derive from the peripheral process injury models.

Methylprednisolone ameliorates cochlear nerve degeneration following mechanical injury

We investigated whether methylprednisolone sodium succinate can ameliorate cochlear nerve degeneration following compression injury on the cerebellopontine angle portion of the cochlear nerve, using a quantitative animal experimental model that we have developed recently. In this model, cochlear nerve degeneration after compression could be quantitatively evaluated, while cochlear ischemia induced by the compression carefully maintained below the critical limit that causes irreversible damage to the cochlea. Eleven rats were treated with methylprednisolone during the pre- and post-compression period. Two weeks after compression, the numbers of SGC were compared between the rats that received the compression without and with methylprednisolone treatment. Methylprednisolone treatment improved the survival of SGC following cochlear nerve injury statistically highly significantly in the basal turn where the traumatic stress had been less than in the other cochlear turns in our experimental setting. Although it was not statistically significant, greater survival was also observed in the other cochlear turns. The results of this experimental study indicated that at least a portion of injured cochlear nerve had been potentially treatable, and that methylprednisolone might prevent such cochlear neurons from entering into the vicious process of irreversible damaging process.

Coil embolisation for ruptured vertebral artery dissection distal to the origin of the posterior inferior cerebellar artery.

Abstract Although many surgical or endovascular treatments for ruptured vertebral artery dissection have been reported, the best treatment is controversial. We treated five cases of ruptured vertebral artery dissection distal to the origin of the posterior inferior cerebellar artery (PICA), using retrievable platinum coils packed in the dissection site and the immediately proximal vertebral artery. All patients had a contralateral vertebral artery of the same calibre or larger. All dissections were occluded completely, together with the portion of the vertebral artery distal to the PICA origin. No complications related to the procedure were seen. The purpose of the treatment is to isolate the dissection from the cerebral circulation. Occlusion of the rupture site, preserving perforating arteries arising from the vertebral artery, would be ideal. Short-segment occlusion by retrievable platinum coils is close to the ideal.

Effect of compression on the cochlear nerve: a short- and long-term electrophysiological and histological study.

The short- and long-term effects of static compression of the cochlear nerve were studied in dogs. The nerve was exposed in the cerebellopontine angle and a modified aneurysm clip was applied to reduce the diameter of the nerve trunk to 50%, 40%, 30% or 20% of normal (designated respectively as 50%, 60%, 70%, and 80% compression). Brainstem auditory evoked potentials (BAEPs) were monitored intraoperatively and post-operatively. The animals were sacrificed between 5 and 119 days after nerve compression and temporal bones were examined histologically. In the 50% compression group, all peaks except peak I disappeared immediately after nerve compression. After release of the clip, however, peak II and subsequent components recovered and prolonged interpeak latency (IPL) between peaks I and IV normalized within 7 days. In the 60% compression group, recovery was incomplete for as long as 49 days after compression. Significant histological changes were not always reflected in the electrophysiological recordings, as shown by the finding of multiple cavitations at the compressed portion of the cochlear nerve in cases in which conduction block of cochlear nerve impulses was reversible. In the 70% compression group, peak IV did not reappear for more than 1 week, and histological examination revealed severe damage to all cochlear nerve fibers except those from the apical turn, which lie in the center of the cochlear nerve trunk. Severe injury occurred to the cochlear nerve fibers that are situated more superficially in the nerve, which are tonotopically responsible for the perception of high-frequency sound and the generation of BAEPs. This means that the BAEP changes due to cochlear nerve compression would be detectable by BAEP monitoring, although changes in the apical region of the cochlea are not fully detectable by BAEP monitoring. In the 80% compression group, all peaks except peak I were lost permanently and the amplitude of peak I, which had been preserved in the acute phase, gradually decreased. Reversibility of impaired cochlear nerve impulse conduction was related to the severity of compression, and at some level of compression between 70% and 80% the nerve fibers generating BAEPs permanently lost the ability to conduct electrical impulses proximal to the site of compression. In the 70% and 80% compression groups, the amplitude of peak I gradually decreased over the first 30 days after compression and did not change significantly thereafter. Histologically, the branches of the internal auditory artery were resilient to compression, although they are easily avulsed due to stretch force. Furthermore, retrograde degeneration of cochlear neurons triggered by compression at the cisternal portion of the cochlear nerve was apparent. Such slowly progressive degeneration of nerve fibers may play a part in development of the delayed postoperative hearing disturbance.

Enhanced phospholipase C activity in the cultured skin fibroblast obtained from patients with coronary spastic angina: possible role for enhanced vasoconstrictor response.

OBJECTIVES We measured phospholipase C (PLC) activity in the cultured skin fibroblasts obtained from patients with and without coronary spasm and examined its correlation with coronary artery vasomotility. BACKGROUND Coronary artery vasomotility is enhanced in coronary spastic angina (CSA), but no information is available for the intracellular signaling. In spontaneously hypertensive rats, PLC activity in the skin fibroblasts has been shown to be enhanced. METHODS Skin fibroblasts obtained from 24 patients with CSA-14 with organic coronary artery disease (CAD) and 12 control subjects--were cultured by the explant method. Activity of PLC was determined by incubating the membrane fraction with 3H-phosphatidyl inositol bisphosphate and by quantifying 3H-inositol trisphosphate. In patients with CSA and control subjects, the relations between PLC activity and coronary artery basal tone and constrictor response to intracoronary acetylcholine (ACh) were examined. RESULTS Activity of PLC (pmol/protein [mg] per min) was 1.74+/-0.19 in patients with CSA; 0.90+/-0.12 in patients with CAD; and 0.65+/-0.07 in control subjects (p<0.001, patients with CSA vs. patients with CAD and control subjects; p = NS, patients with CAD vs. control subjects). According to the Lineweaver-Burk plot, Michaelis constant (micromol/liter) of PLC was 28+/-4 in patients with CSA; 49+/-14 in patients with CAD; and 56+/-10 in control subjects (p<0.05, patients with CSA vs. control subjects), whereas the maximal velocity was not different between the three groups. There were significant positive correlations between PLC activity and both basal tone (p = 0.0108) and response to ACh (p = 0.0053). Western blot analysis using membrane fraction demonstrated that 89% of PLC isoenzymes detected was of the delta1 isoform. CONCLUSIONS Because the PLC activity measured was genetically defined and was positively correlated with coronary artery vasomotility, enhanced PLC activity may be involved in the pathogenesis of coronary spasm.

Relation between the Persistence of an Abnormal Muscle Response and the Long-Term Clinical Course after Microvascular Decompression for Hemifacial Spasm

Mentalis muscle responses to electrical stimulation of the zygomatic branch of the facial nerve are considered abnormal muscle responses (AMRs) and can be used to monitor the success of decompression in microvascular decompression (MVD) surgery. The aim of this study was to compare the long-term outcome of MVD surgery in which the AMR disappeared to the outcome of surgery in which the AMR persisted. From 2005 to 2009, 131 patients with hemifacial spasm received MVD surgery with intraoperative monitoring of AMR. At 1 week postsurgery, spasms had resolved in 82% of cases in the AMR-disappearance group and 46% of cases in the persistent-AMR group, mild spasms were present in 10% of cases in the AMR-disappearance group and 31% of cases in the persistent-AMR group, and moderate were present spasms in 8% of cases in the AMR-disappearance group and 23% of cases in the persistent-AMR group (P < 0.05). At 1 year postsurgery, spasms had resolved in 92% of cases in the AMR-disappearance group and 84% of cases in the persistent-AMR group, mild spasms were present in 6% of cases in the AMR-disappearance group and 8% of cases in the persistent-AMR group, and moderate spasms were present in 3% of cases in the AMR-disappearance group and 8% of the cases in the persistent-AMR group (P = 0.56). These results indicate that the long-term outcome of MVD surgery in which the AMR persisted was no different to that of MVD surgery in which the AMR disappeared.

Vestibular nerve injury as a complication of microvascular decompression.

We report a case of hemifacial spasm in which hearing was well preserved after microvascular decompression, but the vestibular nerve was injured selectively. We review the pathophysiological mechanisms relevant to this complication in the light of results of animal experimental studies we have conducted. In addition, we discuss the clinical significance of this particular type of cranial nerve injury.

A comprehensive classification system of vestibular schwannomas.

Because traditional classifications of vestibular schwannomas (according to relative size) cannot comprehensively describe lesions that grow in different patterns after arising in regions as diverse as the cerebellopontine (CP) angle, the internal auditory canal, and the region lateral to the fundus of the internal auditory canal (labyrinth), we developed a new system to classify vestibular schwannomas, a system that describes the anatomical structures involved by the tumour, rather than size alone. The vestibular schwannoma is classified first by location and then by extent. Our system provides surgeons information helpful in choosing the surgical approach, in estimating the difficulty of tumour excision, and in determining whether hearing might be preserved. Our system also avoids confusion and misunderstanding in discussions of treatment results because it reflects the diverse biological characteristics of vestibular schwannomas.

A case of endolymphatic sac tumor with long-term survival.

A 72-year-old man developed left facial palsy at age 14 and left-sided hearing loss at age 20. At the age of 59, he presented with gait disturbance, and a large left cerebellopontine angle tumor was detected, which had markedly destroyed the pyramidal bone. The tumor was subtotally resected, but he required two more operations at the ages of 64 and 69 because of tumor regrowth. At the present time, recurrent tumor has destroyed the occipital bone and is invading the scalp. However, eventhough he has several cranial nerve palsies and cerebellar ataxia, he remains in stable condition and demonstrates long-term survival. The patients surgical specimens revealed a papillary adenoma, which was recently thought to be of endolymphatic sac origin, although the origin of this kind of tumor, whether arising from the middle ear or from the endolymphatic sac, has not been established with certainty so far. In this paper, we provide further evidence that this tumor originates from the endolymphatic sac, based on anatomical, histopathological, and embryological evidence.

Indications and Timings of Re-operation for Residual or Recurrent Hemifacial Spasm after Microvascular Decompression: Personal Experience and Literature Review.

We reviewed reports about the postoperative course of hemifacial spasm (HFS) after microvascular decompression (MVD), including in our own patients, and investigated treatment for delayed resolution or recurrence of HFS. Symptoms of HFS disappear after surgery in many patients, but spasm persists postoperatively in about 10–40%. Residual spasm also gradually decreases, with rates of 1–13% at 1 year postoperatively. However, because delayed resolution is uncommon after 1 year postoperatively, the following is advised: (1) In patients with residual spasms after 1 year postoperatively (incomplete cure) or who again experience spasm ≥ 1 year postoperatively (recurrence), re-operation is recommended if the spasms are worse than before MVD. (2) When re-operation is considered, preoperative magnetic resonance imaging (MRI) findings and intraoperative videos should be reviewed to ensure that no compression due to a small artery or vein was missed, and to confirm that adhesions with the prosthesis are not causing compression. If any suspicious findings are identified, the cause must be eliminated. Moreover, because of the risk of nerve injury, decompression of the distal portion of the facial nerve should be performed only in patients in whom distal compression is strongly suspected to be the cause of symptoms. (3) Cure rates after re-operation are high, but complications such as hearing impairment and facial weakness have been reported in 10–20% of cases, so surgery must be performed with great care.