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Background Microvascular decompression (MVD) is the most effective procedure for hemifacial spasm (HFS). MVD results from nonspecialized or low-volume institutes are not always reliable. Most studies on MVD for HFS are retrospective and single centered; to the best of our knowledge, no prospective, multicenter studies exist. Objective To evaluate short- and long-term outcomes and complications in patients who underwent MVD for HFS in specialized Japanese institutions, in this multicenter, prospective, cohort study. Methods Included patients had undergone MVD for HFS in study centers between April 2012 and March 2015. Patients' postoperative grade of involuntary movements and complications were recorded postoperatively at 7 d (short-term) and at 1 (mid-term) and 3 (long-term) yr. Results A total of 486 patients (150 men, 336 women; mean age 53.9 yr with 181 patients over 60 yr) were enrolled during the study period. Neuromonitoring was used in 96.3% of the cases. The complete cure rate of symptom relief, mortality rate, and complication rate at short-term follow-up were 70.6%, 0%, and 15%, respectively. The long-term follow-up was completed by 463 patients (95.3%); the complete cure rate of symptom relief and complication rate were 87.1% and 3.0%, respectively. Conclusion Our study revealed that under expert guidance and intraoperative neuromonitoring, the long-term curative effect rate of MVD for HFS is high, while complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with HFS, including elderly patients.

Background Microvascular decompression (MVD) is the most effective procedure for the long-term management of trigeminal neuralgia (TGN). However, retrospective and single-center studies are inherently biased, and there are currently no prospective, multicenter studies. Objective To evaluate the short- and long-term outcomes and complications in patients with TGN who underwent MVD at specialized Japanese institutions. Methods We enrolled patients with TGN who underwent MVD between April 2012 and March 2015. We recorded their facial pain grade and complications at 7 d (short term), 1 yr (mid-term), and 3 yr (long term) postoperatively. Results There were 166 patients, comprising 60 men and 106 women (mean age 62.7 yr). Furthermore, 105 patients were aged over 60 yr. We conducted neuromonitoring in 84.3% of the cases. The complete pain relief, mortality, and complication rates at the short-term follow-up were 78.9%, 0%, and 16.3%, respectively. Overall, 155 patients (93.4%) completed the long-term follow-up, with the complete pain relief and complication rates of 80.0% and 5.2%, respectively. Conclusion In the hands of experienced neurosurgeons, MVD for TGN can achieve high long-term curative effects. In addition, complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with TGN, including elderly patients.

The purpose of this study was to evaluate and analyze overall postoperative results from microvascular decompression (MVD) by combining the cure rate of symptoms with the complication rate. A new scoring system for obtaining objective surgical results from MVD for trigeminal neuralgia (TN) and hemifacial spasm (HFS) is proposed to document treatment results using consistent criteria in a standardized manner. Surgical results combining complications , if any, were obtained from a questionnaire sent to patients who had undergone surgery for TN or HFS in recent years and had been followed-up for more than 1 year after surgery (TN patients, n = 54; HFS patients, n = 81) When surgical outcome is complete resolution of symptoms, the efficacy of surgery (E) is designated E-0, but when moderate symptoms are still persist postoperatively, the score is designated E-2. When no complications are seen after surgery, the complication score (C) is C-0, while the score is C-2 if troublesome complications remain. In addition, total evaluation of the results (T) is judged by combining the E and C scores. For example, when E is 0, and C is C-2, the total evaluation is scored as T-2, which is diagnosed as fair. The response rate of the questionnaire was 80.7% (109/135). Overall surgical data were evaluated and analyzed using our new scoring system. Analysis of the collected data revealed an outcome of T-0 was 70% (35/50 patients) and T-1 was 24% (12/50) and T-2 was 6% (3/50) in TN, whereas in HFS, T-0 was 61% (36/59) and T-1 was 27.1% (16/59) and T-2 was 6.8% (4/59) and T-3 was 5.1% (3/59). The total results of MVD should be evaluated and analyzed by combining the cure rate of symptoms together with the complication rate. This new scoring system could allow much more objective analysis of the results of following MVD. Adopting this scoring system to objectively judge treatment results for TN and HFS, individual surgeons can compare their own overall surgical results with those of other institutes. Comparative results of MVD can also be provided to patients considering therapy to allow informed decision-making on the basis of good quality evidence.

Surgery of cerebral aneurysm confronts expected difficulty and unexpected happenings. To make difficult surgery easy, a surgical strategy as if operating in a shallow basin with the skull base technique is required. Extradural drilling of the anterior clinoid process is the most basic technique to obtain wide working space by mobilizing the internal carotid artery. We report a case of very high-positioned basilar top aneurysm treated with this technique. Drilling of the anterior clinoid process is a safe and quick technique. On the contrary, drilling of the posterior clinoid process poses the danger of unexpected massive bleeding from the venous plexus of the clivus. Preoperative estimation of how wide and deep the drilling can be performed is not easy. Hesitating go and obligatory stop limit this technique. We report 2 cases that encountered this situation.

Decision making for either surgery or gamma-knife for the treatment of arteriovenous malformations (AVMs) cannot be uniform. The skill of the neurosurgeon in operating on AVMs is now being compared with that of the gamma-knife. The decision varies from case to case and is to be taken by the neurosurgeon. This report presents three cases in which such decision making was not easy. Case 1 was a non-ruptured cingulate AVM of 2.5 cm diameter in the cingulate cortex. The operative field was anticipated to be very narrow between the parietal bridging veins. Case 2 was a tiny ruptured AVM in the speech-motor area which was buried underneath the cortex. Case 3 was a large ruptured thalamo-stiriate-capsular AVM with feeders from the anterior and posterior choroidal arteries. All cases were operated without serious morbidity. A combination of pre-operative intravascular surgery (cases 1 and 3) or postoperative gamma-knife (case 3) was adopted. In conclusion, there is no unitary rule to decide on surgery or gamma-knife for the treatment of AVMs. It depends on what good or harm the responsible surgeon or the gamma-knife does.

BACKGROUND Jugular bulb diverticulum is a rare condition that has never been reported in association with lower cranial nerve palsy. CASE DESCRIPTION A 54-year-old woman developed acute swallowing disturbance and hoarseness. Neuroradiological examinations demonstrated a jugular bulb diverticulum as well as unruptured internal carotid and basilar tip aneurysms on the same side. Laboratory data for both serum and cerebrospinal fluid were normal. Steroids were given, and the cranial nerve palsy disappeared within 1 month. The aneurysms were successfully clipped. During the follow-up period of more than 1 year, the patient has done well and has no neurological deficit. CONCLUSION This is the first reported case of jugular bulb diverticulum associated with a lower cranial nerve palsy and multiple aneurysms. We recommend close observation of patients with this condition regardless of its clinical presentation.

BACKGROUND Whereas the transcranial approach has been regarded as the therapy of choice for transethmoidal encephalocele, its feasibility for transsphenoidal encephalocele has remained controversial, particularly in neonates and infants. CASE REPORT Two cases of transsphenoidal encephalocele operated transcranially are presented. In the first case, this 6-year-old boy underwent a transpalatal operation with repair of a cleft palate in another hospital before admission. Reoperation via the transcranial route was carried out because of postoperative recurrent meningitis. With partial resection of the anterior wall, the encephalocele could be separated from the underlying tissue, and the interspace was filled with the pericranial flap. He made an uneventful recovery and has been well for the past 3 years. The second was a 3-month-old baby with a large encephalocele filling the nasopharyngeal space. As the cleft palate was absent, the transcranial approach was employed. In this case, the herniated tissue was excised at the lowest level possible. Postoperatively, panhypopituitarism became manifest. Re-evaluation of the preoperative magnetic resonance imaging (MRI) disclosed a small mass far below the dorsum sellae, which turned out to be an anomalous pituitary gland on histologic examination. CONCLUSIONS The transcranial approach is considered a valid alternative for the therapy of transsphenoidal encephalocele, particularly when the transpalatal approach is unfeasible. While the anterior wall of the herniated sac may be safely resected, the posterior wall should under no circumstances be sacrificed. The preoperative MRI is essential, as it may provide valuable information as to the location of vital structures within the herniated tissue.

Utilizing a specific polyclonal antibody against a peptide unique for brain-derived neurotrophic factor (BDNF), we investigated the regional and temporal profiles of immunoreactivity of the BDNF protein in the rat hippocampus after transient forebrain ischemia. The pattern of immunoreactivity for the BDNF receptor (TrkB) was also examined and compared with that for BDNF. In the early phase after ischemia, we observed a distinct regional difference in immunoreactivity between the pyramidal cell layer and the stratum radiatum of the CA1 subfield. In the pyramidal cell layer, there was a rapid and transient increase in the positive immunostaining for both BDNF and TrkB. By contrast, in the stratum radiatum there was a marked decrease in BDNF immunoreactivity, but not one in that of TrkB. One week after ischemia, high immunoreactivity for both BDNF and TrkB was observed in the reactive astrocytes in the dendritic field of the CA1 subfield. These findings suggest that a transport of BDNF from the neuronal soma to the dendrites of the stratum radiatum might be ceased after the ischemic insult. Thus, a dysfunctional autocrine mechanism of BDNF within the CA1 neuron may be involved in the pathogenesis of selective neuronal damage after ischemia. J. Neurosci. Res. 53:318–329, 1998. © 1998 Wiley-Liss, Inc.

Using the canine chronic cerebral vasospasm model, we studied the effects of a potent new nonpeptidic endothelin-1 (ET1) receptor antagonist, bosentan (Ro 47-0203, 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'-bipyr imidin-4 - yl]-benzenesulfonamide). Endothelin (ET) receptors are composed of the ETA receptors and the ETB receptors; ET1 acts on both of these receptors. Although it has been previously thought that the ETA receptor mediates vasoconstriction, whereas the ETB receptor mediates vasodilation, recent evidence suggests that ETB receptor also contributes to vasoconstriction. Because bosentan is a mixed antagonist that acts on both receptors, its use might indicate whether or not ET is involved in the pathogenesis of cerebral vasospasm. In this study, beagle dogs received a double injection of autologous arterial blood into the cisterna magna at 2-day intervals (i.e., on Days 0 and 2). The diameter of the basilar artery (BA) was angiographically examined up to Day 7. A total of 24 dogs were randomly allocated to either the treatment group or the no-treatment group. Eight dogs were treated with 10 mg/kg bosentan by a one-dose injection into a central venous catheter. Bosentan was given twice a day starting immediately after the first subarachnoid hemorrhage for 6 days until Day 5. Sixteen dogs served as controls, with untreated subarachnoid hemorrhage. After the injection of bosetan, blood pressure decreased by about 25 mm Hg for a few minutes and then returned to normal. In the dogs treated with bosentan, the BA spasm on Day 7 was significantly ameliorated compared with the BA spasm in the untreated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Extradural removal of the anterior clinoid process (ACP) is useful and essential for approaching aneurysmal and tumor lesions in and around the cavernous sinus. A safe, rapid and less invasive technique is beneficial for this basic skull base surgery. We developed a new technique by sharply cutting the ACP together with the part of the sphenoid ridge bone followed by complete replacement. A series of patients with either basilar top or internal carotid artery aneurysms underwent the present technique. After frontotemporal craniotomy, the lateral frontal and anterior middle cranial fossae are exposed extradurally. The bone was cut using a cutting steel burr from the sphenoid ridge to the superior orbital fissure and to the optic canal. By sharply separating the meningo-orbital band between the dura propria and the periorbital fascia, the ACP is exposed. The cutting burr runs underneath the ACP. By leaving a very thin sheet of bone, the entire bone piece was elevated after fracturing the thin bone using a chisel. By severing the carotid ring, the internal carotid artery is freed and mobile either laterally or medially to obtain an ample basal cistern. After operation, the once removed clinoid process is replaced in situ using a titanium plate screw. Extradural en bloc removal and in situ replacement of the ACP can be safely done by this cutting procedure. This can provide a good cosmetic result without causing enophthalmos or transient oculomotor palsy.

A unique transposition technique in microvascular decompression for hemifacial spasm (HFS) was employed in patients with compression by either the peripheral artery or the main trunk of the vertebral artery. Complete transposition that secured free space between the offending artery and the root exit zone (REZ) was accomplished by introducing GORE-TEX tape around the artery and suturing it to the petrous dura. An adequate working space, as if operating in a shallow basin, was essential. Throughout the procedure, it was not necessary to use a brain retractor. Instead, a gentle wrapping retraction technique using a sucker was employed over the brain covered by a sheet of Gelfoam (Pfizer Japan Inc., Tokyo) and cotton. All patients showed complete cure of HFS immediately after surgery with this technique. The difficulty of transposing the vertebral artery can be overcome by well-designed surgical strategy and skillfulness.

The detailed surgical procedure of the transsphenoidal surgery for pituitary abscess has scarcely been described previously because it is a very rare clinical entity. The authors reported two cases of primary pituitary abscess. In case 1, the anterior wall of the sella turcica was reconstructed with the vomer bone after irrigating the abscess cavity, but the sella was not packed by fat for fear of the persistent infection by devascularized tissues. This led to the postoperative meningocele, the cerebrospinal fluid leak, and bacterial meningitis despite the successful abscess drainage. In case 2, tight sellar packing and reconstruction of the sellar wall were performed to avoid these postoperative complications, which resulted in complete drainage and uneventful postoperative course. Although accumulation of more cases is obviously needed to establish the definitive surgical technique in pituitary abscess surgery, our experience might suggest that packing of the sella is not impeditive for postoperative sufficient drainage.

✓ The role of endothelin, a newly found vasoconstrictor peptide, is examined in the pathogenesis of cerebral vasospasm after experimental subarachnoid hemorrhage (SAH) in the dog. Endothelin immunoreactivity was overexpressed in the endothelium of the vasospastic basilar artery. Because endothelin synthesis is regulated at the messenger ribonucleic acid transcription level, the effect of actinomycin D, a ribonucleic acid synthesis inhibitor, was studied as a means of preventing vasospasm. It was found that treatment with intravenous actinomycin D for 5 days beginning on the day of SAH completely inhibited the development of vasospasm. This novel experimental therapy may lead not only to the elucidation of the pathogenesis of cerebral vasospasm but also to the availability of a prophylactic adjuvant therapy for patients with SAH.

1. The vascular effects of endothelin and localization of endothelin-like immunoreactivity were characterized in isolated cerebral arteries of dogs. 2. Endothelin-like immunoreactivity was detected in a few populations of endothelial cells of dog basilar artery. 3. Endothelin-1, endothelin-2 and endothelin-3 contracted isolated ring preparations of cerebral arteries in a dose-dependent manner independently of the presence of endothelium. The ED50 values (and 95% confidence intervals) for the contraction were 411 pM (242-697 pM) and 478 pM (295-776 pM) for endothelin-1 and endothelin-2, respectively. Endothelin-3 induced vascular contraction at a higher concentration (ED50 = 26.5 nM, 95% confidence interval = 15.7-45.7 nM). 4. The increases in tone induced by endothelin-1 and endothelin-2 did not return to the resting level after repeated washings, while a rinse with Krebs solution reversed the vasoconstrictor response to endothelin-3. The endothelins did not cause any vasodilator response in arteries precontracted with uridine 5'-triphosphate even in the presence of intact endothelial cells. 5. NiCl2 (1 mM) attenuated the contractions induced by endothelin-3 (10-300 nM) and those to relatively low doses (1 nM) but not higher doses (10-100 nM) of endothelin-1 and endothelin-2. The contractions in response to endothelin-1, endothelin-2 and endothelin-3 were greatly attenuated in Ca(2+)-free solutions although high concentrations of endothelin-1 and endothelin-2 still evoked contractions. 6. These results suggest that the vasoconstriction induced by endothelin-3 and lower doses of endothelin-1 and endothelin-2, largely depends on the influx of Ca2+ ions. The apparent insensitivity to Ni2+ shows that additional distinct mechanisms also operate in the vasconstrictor responses to high concentrations of endothelin-1 and endothelin-2. 7. The presence of endothelin-like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen.

A rare case of delayed traumatic intracerebellar hematoma (DTIC1H) in a 54-year-old male achieved an excellent outcome without surgery. Analysis of this case and other reported cases suggests that DTIC1H occurs in two types: Group I with hematoma developing in previously contused areas, and Group II with hematoma developing in areas appearing normal on the initial computed tomographic scan. Group I hematomas occurred in the cerebellar cortex, but Group II hematomas occurred in the subcortical region or vermis where direct impact is less likely to have an effect. This suggests different mechanisms of development for DTIC1H.

Since the discovery of endothelin-1 (ET-1), its involvement in cerebral vasospasm after subarachnoid hemorrhage (SAH) has been suspected. We performed various experiments, first to demonstrate the presence of ET in both patients and dogs with SAH, and second to examine the effects of ET synthesis inhibition in experimental vasospasm. Here we report that ET was present in both plasma and cerebrospinal fluid (CSF) in SAH, but did not correlate with vasospasm. However, ET was locally expressed in the vascular endothelium in vasospasm. Several therapeutic approaches causing the inhibition of ET synthesis were effective in preventing the development of vasospasm. Such approaches utilized drugs that inhibited RNA and DNA synthesis. Among them, actinomycin D treatment was most effective. We also utilized phosphoramidon, a recently found conversion inhibitor of big ET to ET. However, this product failed to ameliorate the development of vasospasm. Therefore, although we cannot yet conclude that ET is the main cause of cerebral vasospasm, it may, at least, act as one of the modifying factors in cerebral vasospasm.

BACKGROUND A more simplified and easier technique for the orbitozygomatic approach is sought. We have developed a new modification to fully expose the temporal base before using one-piece craniotomy. METHODS By transposing the temporalis muscle underneath the zygomatic arch before osteotomy, the temporal base and the inferior orbital fissure can be fully exposed. Craniotomy is made in one piece with the frontotemporal and orbitozygomatic bone together by using a high-speed drill. RESULTS AND CONCLUSIONS Osteotomy was easy and the cosmetic result was satisfactory. This technique also allows better access to the subtemporal region without removing the zygomatic arch.

A 60-year-old man presented with dizziness, dysarthria, and right hemifacial palsy with sudden onset. Computed tomography scan revealed a small cerebellar hematoma near the left flocculus. Since the site of the hemorrhage was atypical for cerebellar hemorrhages, emergency angiography was performed and revealed a pial single-channel arteriovenous fistula (AVF) in the early arterial phase with drainage into the dilated perimedullary vein. The feeding artery was a peripheral branch of the left anterior inferior cerebellar artery. There were no angiographical findings indicating a nidus or capillary network. The patient underwent left lateral suboccipital craniotomy. A small dilated perimedullary vein and an abnormally red spherical varix were found during the operation. A peripheral branch of the left anterior inferior cerebellar artery was thought to be a feeder because it seemed to be firmly attached to the dilated vein. Based on the operative technique for dural AVFs, electrocoagulation of the varix was performed aiming at obliteration of the fistula. The postoperative angiogram demonstrated the obliteration of the fistula and of the early filling vein. Feeders of cerebral AVF are cerebral arteries. A pial single-channel AVF is defined as a vascular malformation with a single venous channel in communication with one or more arteries with no intervening nidus or vessels. To date, reports in the literature of cerebral arteriovenous fistula have been very few. Its clinical entities such as origin, bleeding rate and the necessity of surgery remain subjects of debate. Here we report our experience and discuss its issues of the treatment we used.

Background context For the treatment of irreducible atlantoaxial dislocation (AAD), anterior decompression has been commonly used by removal of the odontoid process and fixation of the vertebral body by means of the transoral approach. Although the transoral approach has been well established, there are some disadvantages. By contrast, there have been few technical case reports of the posterolateral approach, especially for irreducible AAD. Purpose To describe a technical case report of the posterolateral approach for irreducible AAD, demonstrating the specific advantages. Study design/setting Technical case report. Patient sample Case report. Outcome measures Report of postoperative symptoms. Methods/description A 74-year-old woman presented with sudden left hemiparesis because of irreducible AAD. She underwent the odontoidectomy and reduction by means of the posterolateral approach. Posterior fixation with instrumentation and an iliac bone graft was performed 16 days later. The results of radiological examinations were satisfactory. The posterolateral approach takes advantage of the particular features of C1–C2 dislocation of irreducible AAD. Conclusions We suggest the possibility that the posterolateral approach is feasible and effective in most cases with irreducible AAD.

Recurrence of trigeminal neuralgia (TN) or hemifacial spasm (HFS) after microvascular decompression (MVD) is not rare. The prosthesis material eventually adheres to the neurovascular structures and again transmits arterial pulsation to the nerve. A snare ligature technique using a Gore-Tex tape can be used for the transposition of the offending artery. No prosthesis is necessary once the transposition is complete. This technique requires introduction of either Gore-Tex tape or thread around the artery and suture over the petrous dura, so an adequate working space as if operating in a shallow basin is essential. Therefore, the osteoplastic craniotomy is a little larger than usual with the scalp flap entirely reflected using a semicircular skin incision. The Gore-Tex tape can be directly snared around the artery and sutured over the petrous dura. If this procedure is difficult, a thread can be attached to both ends of the Gore-Tex tape to pass the tape around the vessel. Seven patients with TN and 13 patients with HFS have undergone this surgery. Although the follow-up period is not yet long enough, there has been no case of recurrence. The present technique for MVD can provide complete and permanent transposition of the offending artery.

An incidentally found arteriovenous malformation (AVM) of the inferior medullary velum behind the medulla was removed by the lateral approach to the fourth ventricle originally described by Seeger in 1980. A wide posterior fossa craniotomy was performed to move the cerebellar tonsil laterally with C-1 laminectomy. The tela chroidea and inferior medullary velum, the two main sheets of tissue that form the lower half of the roof of the fourth ventricle can be exposed by gently displacing the tonsils laterally without splitting the vermis. Both the cerebellomedullary and uvulotonsillar spaces were exposed. Because the lateral cerebellomedullary cistern was also exposed, the moving of the cerebellar tonsil in a lateral direction was easy to do without injuring the cerebellar tissues. The nidus was located mainly in the extrapial plane that received feeding arteries from the posterior inferior cerebellar artery. The nidus was removed in a dry field without bleeding. This report is the first report of surgical removal of unruptured AVM of the inferior medullary velum through the so-called telovelar or transcerebellomedullary fissure approach. We propose to call this approach the uvulotonsillar approach to emphasize the dissecting plane between the uvula and the tonsil.

A hypertensive 72-year-old male presented with a ruptured arteriovenous malformation (AVM) manifesting as hematoma indistinguishable from common putaminal hemorrhage on precontrast computed tomography scan. The AVM was located in the proximal sylvian region fed by branches of the anterior and middle cerebral arteries. The AVM was totally removed. Although bleeding from AVM in the elderly is uncommon, the cause of even common hypertensive hemorrhage should be identified by other imaging techniques such as magnetic resonance imaging and cerebral angiography to allow the optimum treatment.

BACKGROUND Observation of the surgical field from all directions is essential in microneurosurgery. A tilting operating table operated by the surgeon can satisfy this need. METHODS A tilting operating table operated by the surgeon using a foot switch was developed by modifying the Sugita table incorporating the X-Y shifter. RESULTS AND CONCLUSIONS The modified operating table allows the surgeon to move the patient in the head up or down directions, as well as the left side down or right side down directions, so the surgical field can be inspected from all aspects without changing the vertical axis of the operating microscope.

Involvement of nerve growth factor (NGF) in the pathogenesis of delayed neuronal death (DND) of CA1 neurons in the hippocampus has been suggested. We measured regional changes in the content of tissue NGF of the hippocampus in the Mongolian gerbil after 5 min forebrain ischemia. The NGF content was found to decrease significantly in the CA3 and dentate regions by 32% two days after ischemia. By contrast in the CA1 region, the level of NGF became significantly elevated by 50% two weeks after ischemia or later. The early reduction of NGF content in the afferent area projecting to the CA1 sector might be primarily linked to the pathogenesis of DND, whereas the delayed increase within the CA1 sector might be a secondary local response mainly of reactive astroglia.

Specific regions of brain are known to be especially vulnerable to various insults such as ischemia [Spielmeyer, 1925; Brown and Brierley, 1968]. Patients resuscitated from cardiac arrest often suffer from memory impairment. Even a short cessation of cerebral circulation causes damage to the hippocampus, which is critical to memory function [Brierly and Graham, 1984; Petito, 1984]. Delayed neuronal death of the hippocampus was originally described in rodents model of transient global ischemia [Ito et al. 1975; Kirino, 1982; Pulsinelli et al. 1982]. In gerbils, only 5 minutes of bilateral carotid artery occlusion causes selective neuronal death of the hippocampal CAl sector [Kirino, 1982].

Selective neuronal death in the CA1 sector of the hippocampus [delayed neuronal death (DND)] develops several days after transient global cerebral ischemia in rodents. Because NGF plays a potential role in neuronal survival, it was decided to study its effect in DND. We report here that intraventricular injection of NGF either before or after 5 min forebrain ischemia in the Mongolian gerbil significantly reduced the occurrence of DND. The tissue content of NGF in the hippocampus was decreased 2 d after ischemia and recovered to the preischemic level by 1 week. By the Golgi staining technique, changes first began in the dendrites of affected neurons as early as 3 hr. Such changes could be ameliorated by NGF treatment. Although previous knowledge of NGF is limited to the survival of cholinergic neurons in the CNS, it is assumed that other mechanisms must be operating in the hippocampus, for example, postsynaptic modification at dendrites or aberrant expression of NGF receptors possibly at the initial excitation period by glutamate. Furthermore, because previous work has shown that inhibition of protein synthesis reduces the occurrence of DND, a program leading to cell death might also be operating via de novo synthesis of certain protein(s), collectively termed “killer protein,” because of a lack of NGF.

Brief forebrain ischemia in rodents causes delayed neuronal death selectively in the CA1 pyramidal cells of hippocampus. Treatment with a reversible protein synthesis inhibitor, anisomycin, significantly reduced the occurrence of delayed neuronal death in the Mongolian gerbil. This result indicates that de novo synthesis of certain protein(s), collectively termed ‘killer protein’ is required, possibly due to deprivation of nerve growth factor or other trophic factors.

✓ Cortical and spinal evoked potentials were used to monitor the effect of experimental chronic cord compression in cats. An implantable compression screw made it possible to maintain the animals unrestrained. The mean compression period was 10 weeks (maximum 16.5 weeks). Compression was increased by stepwise tightening of the screw at intervals of 4 to 7 days under ketamine anesthesia. Evoked potentials were monitored before and after each compression step with repeated recordings, and were analyzed in terms of alterations in amplitude, latency, and waveform. Amplitude response curves were plotted where the amount of compression at each recording was expressed as a percentage of total compression. Changes in spinal evoked potentials occurred rather early (mean 36% of total compression), while obvious cortical evoked potential changes appeared rather late (mean 91% of total compression). Neurological alterations appeared later than alterations in spinal evoked response but prior to alterations in cortical evoked response. Thus, alterations in cortical somatosensory evoked potentials in the presence of chronic spinal compression indicate a severe degree of compression and do not seem to be of diagnostic value in the early detection of chronic spinal cord compression. It is suggested that the monitoring of spinal rather than cortical evoked responses would be more useful in locating and detecting chronic compression spinal cord damage.

A total of 128 cases with ruptured cerebral aneurysms were operated on within two weeks after subarachnoid hemorrhage (SAH) . Postoperatively, cerebrospinal fluid (CSF) was continuously drained from the lateral ventricle and the basal cistern. Using the intraventricular catheter, intracranial pressure (ICP) was monitored for an average of three weeks after operation. The development of normal pressure hydrocephalus (NPH) was estimated from ICP pattern and other diagnostic studies such as CT scan, infusion test and RI cisternography. NPH developed in 26% of these cases. Patients who had a large volume of CSF drainage of over 200 ml daily underwent shunt surgery in a higher proportion (56%). It was postulated that the defect of the subarachnoid space might be aggravated by CSF drainage. A total of 49 long-term recordings of ICP was obtained in 31 cases. Within two weeks after SAH, ICP was usually higher than 20 mmHg, but thereafter became lower. This early high pressure was mostly due to acute hydrocephalus and not to the so-called acute brain swelling. However, when mildly elevated ICP with B-wave lasted beyond the third week of SAH, almost all patients developed NPH. This characteristic pattern of ICP plays an important role in the development of NPH and is useful for selecting patients for shunt surgery. Vasospasm was a frequent concomitant of increased ICP, and patients with vasospasm underwent shunt surgery in rather high incidences (34%). Both vasospasm and hydrocephalus could be explained to be the result of blood clots in the subarachnoid space.

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.

The effect of indomethacin on rCBF was studied in cats anesthetized with Nembutal either under resting conditions or with temporary middle cerebral artery (MCA) occlusion. RCBF was measured by the microsphere method. In control animals (n = 3), indomethacin (4 mg/kg, i.v.) significantly reduced rCBF by about 25% in both cortex (from 44 +/- 6 to 32 +/- 3 ml/100 g/min, p less than 0.001) and white matter (from 36 +/- 4 to 26 +/- 2 ml/100 g/min, p less than 0.001). After MCA occlusion rCBF was markedly decreased in the sylvian region ipsilateral to occlusion (ischemic core) (from 38 +/- 4 to 14 +/- 2 ml/100 g/min in cortex, 4 animals). Although pretreatment with indomethacin (4 mg/kg) (4 animals) 30 min prior to occlusion did not alter rCBF during ischemia, a marked enhancement of reactive hyperemia was observed in the ischemic core immediately upon reperfusion following 2 h occlusion (54 +/- 11 untreated vs 95 +/- 13 treated, p less than 0.05). In the delayed postischemic period, namely 2 h after recirculation, rCBF still remained to be higher in the animals treated with indomethacin (40 +/- 6 untreated vs 96 +/- 9 treated, p less than 0.001). Such an effect of indomethacin for ameliorating postischemic blood flow in both the immediate and delayed period was less prominent in the adjacent area (penumbra) ipsilateral to occlusion. In the contralateral hemisphere, indomethacin caused slight reduction in rCBF during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary The in vivo vasoconstrictor effect of endothelin-1 (ET-1) was investigated on feline and canine basilar arteries. The basilar artery caliber was angiographically measured after either vertebral artery perfusion or asternal injection of the peptide. In both cats and dogs, ET-1 (5–500 pmol) induced a dose-dependent basilar artery contraction in vivo when applied intracisternally. The vasoconstriction was extremely long lasting; no significant recovery of vessel caliber was observed up to 12 h after injection. In contrast, bolus injection of ET-1 up to 3 nmol into the vertebral artery had no appreciable effect on the basilar artery caliber. These observations suggest that ET-1 acts in cerebral vessels from the adventitial but not from the luminal side, possibly due to the presence of the blood-brain barrier. The long-lasting nature of the ET-1-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

Selective ischemic damage was produced either involving only the cortex or together with the striatum by occlusion of the middle cerebral artery proximal or distal to the lenticulostriate artery in the rat. The consequences in local cerebral blood flow, local cerebral glucose utilization, and neuropathology were investigated in the acute stage of ischemia. Caudate damage produced by proximal occlusion resulted in such secondary alterations as enhanced blood flow and metabolism in areas remote from the main lesion, such as in the globus pallidus and substantia nigra ipsilateral to occlusion. After distal occlusion, however, there were two patterns distinctly different from each other in the appearance of the autoradiograms. One was ipsilateral and the other was contralateral enhancement of blood flow and metabolism involving the striato-pallido-nigral axis without any striatal damage. We therefore suggest that these secondary alterations in circulation and metabolism contribute to a varied neurological dysfunction after focal cerebral ischemia. Furthermore, our currently introduced model of selective ischemic lesioning is important in studying the roles of cortical and striatal influences in ischemic pathophysiology.

We investigated the in vivo vasoconstrictor effect of endothelin, a recently characterized vasoconstrictor peptide from vascular endothelium, in the basilar arteries of five cats and five dogs. Basilar artery caliber was angiographically measured under anesthesia before (control) and after either vertebral artery infusion or cisternal injection of the peptide. In cats, 5-500 pmol endothelin induced a dose-dependent basilar artery contraction in vivo when injected intracisternally; within 3 minutes after injection of 500 pmol endothelin, basilar artery caliber was decreased by 73 +/- 4% compared with control diameter before injection. The vasoconstriction was extremely long-lasting; no significant recovery of basilar artery caliber was observed for up to 2 hours after injection. In contrast, infusion of up to 3,000 pmol endothelin into the vertebral artery had no appreciable effect on basilar artery caliber. Similar results were obtained in dogs; vasoconstriction was maintained for as long as 12 hours. Our observations suggest that endothelin acts in cerebral vessels from the adventitial side, not from the luminal side, possibly due to the presence of the blood-arterial wall barrier. The long-lasting nature of endothelin-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

✓ The content of norepinephrine (NE) in the ventricular, basal cisternal, and lumbar cerebrospinal fluid (CSF) was determined in 19 patients with ruptured cerebral aneurysms at different intervals according to the presence or absence of vasospasm. Twelve were operated on within 3 days after subarachnoid hemorrhage (SAH), prior to the occurrence of vasospasm. Postoperatively, CSF was continuously drained from a basal cistern or lateral ventricle. Norepinephrine was assayed by the highly sensitive automated fluorometric method. The concentration of NE increased in all sites of CSF sampling along with the appearance of vasospasm. Above all, the cisternal CSF of patients with vasospasm contained significantly higher NE (0.246 ± 0.049 ng/ml, mean ± SEM) compared to those without vasospasm (0.075 ± 0.001 ng/ml) (p < 0.001). However, since this increase cannot be considered to be high enough locally to constrict cerebral arteries, this might be only a secondary phenomenon due to release of NE into CSF from various sources in the brain.

A survey on literature reports and our own experimental studies on the pathogenetic mechanisms underlying ischaemic brain oedema is given and a new concept proposed.

A new variety of primary empty sella syndrome is reported. A partial herniation of the optic chiasm into an enlarged empty sella compressed by a dilated optic recess mimicking a cystic tumor was confirmed at operation. The pathogenesis and the treatment of this type of empty sella syndrome are discussed.

✓ In 44 consecutive cases of ruptured cerebral aneurysm, vasospasm was demonstrated pre- or postoperatively. These cases were examined by bilateral carotid angiography and computerized tomography (CT), and the relationship between the angiographically visualized distribution of vasospasm, the neurological symptoms, and infarction seen on CT was evaluated. Vasospasm occurred in only some intracranial portions of the cerebral arteries that were immersed in blood-stained cerebrospinal fluid. Angiographically, diffuse vasospasm extensively involving bilateral carotid systems indicated the gravest prognosis for patients. Vasospasm affecting one carotid system and the anterior cerebral arteries on the opposite side often produced permanent neurological deficits. On the contrary, when vasospasm was restricted to one carotid system or to bilateral anterior cerebral arteries, it was usually associated with temporary neurological symptoms; however, it always produced residual neurological symptoms if it extended to the ascending branches (M3) of the middle cerebral arteries. Computerized tomography definitely demonstrated a low-density area or infarction in the territory of the spastic arteries in 25 (71%) of 35 cases with vasospasm. A low-density area was always detected when vasospasm occurred in M3 segments.

✓ The microgravimetric technique and the drying-weighing method for the determination of brain water content are analyzed and compared. A new method has been devised for the automatic production of the gradient column. For gravimetry, tissue samples weighing more than 30 mg have proven adequate for measurement. Specific gravity (SG) should be determined as early as 1 minute after tissue is inserted into the gradient column. Calculations of cerebral blood volume (CBV) from changes in SG of both brain tissue and intravascular perfusate have shown that the SG of brain tissue is considerably influenced by changes in CBV. This is because the SG of blood is higher than that of brain tissue, and may lead to a decrease of SG of about 0.002 in anemic cortex and of 0.001 in anemic white matter, which will simulate a false increase in tissue volume as water of 4% and 2%, respectively. This methodological error may be relevant when the early stages of ischemic brain edema development are studied. Water content of brain tissue can also be determined with acceptable accuracy by vacuum freeze-drying samples of brain tissue weighing about 100 mg. In contrast to cortex, white matter shows a wide range of individual and regional differences in water content. Thus, conclusions on the presence of brain edema drawn from tissue water determinations should always be subjected to cautious analysis and criticism.