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A patient with Rasmussen's encephalitis underwent a right central resection at the age of 6 as a treatment for status epilepticus. She became seizure free, but suffered a left hemiplegia which improved so that she could walk. Because of the recurrence of seizures an enlargement of the resection to a hemispherectomy was carried out 17 years after the first operation. Various examinations, including H(2)(15)O PET and amytal testing, performed before this second operation indicated that a compensatory reinforcement of the ipsilateral uncrossed corticospinal and spinocortical pathways had taken place. This was confirmed postoperatively. The patient had no new sensorimotor deficits.

Labor: Normales padiatrisches Routinelabor. Gerinnungsparameter und Thrombophiliediagnostik unauffallig. EKG: Sinusrhythmus. Keine Hypertrophiezeichen, keine Erregungsruckbildungsstorungen. EEG: Altersgemaser Normalbefund ohne Seitendifferenz. Schadel-MRT: Frische Ischamiezone im Mediastromgebiet links (. Abb. 1). Kein Anhalt fur altere Ischamiezonen. MR-Angiographie: Hochgradige Stenosen aller basalen hirnversorgenden Arterien (. Abb. 2). Digitale Subtraktionsangiographie (DSA): Ausgedehnte Kollateralkreislaufe im Bereich der Hirnbasis (. Abb. 3).

A 52-year-old Japanese woman complicated by a sex chromosomal anomaly as a superfemale, a mosaic of XXXXX/XXXX/XXX/XX/XO, with mild mental retardation, was hospitalized for dry mouth, dry eyes, and proteinuria. The sialography of the right parotid gland showed a globular-type gland enlargement. A definite diagnosis of primary Sjögren's syndrome (SS) was made, and further examinations revealed not only typical sicca syndrome but also systemic extraglandular lymphocytic infiltration; interstitial pneumonitis, glomerular- and interstitial nephritis, superficial gastritis, thyroiditis, and a severe excitation conductive impairment of heart. We report a very rare case of superfemale with primary SS which involved systemic organs.

The development of total parenteral nutrition (TPN) has dramatically improved the prognosis of patients afflicted with intestinal failure. However, TPN-related complications, which remain a problem for patients with intestinal failure can be addressed by intestinal transplantation, which can significantly improve their prognosis and quality of life. The first intestinal transplantation in Japan occurred in 1996. Of the 17 intestinal transplantations performed to date, six were obtained from deceased donors and 11 from living donors. The primary indications were: short gut syndrome (n = 8), intestinal function disorder (n = 7), and retransplantation (n = 2). In our experience, the 1-year and 5-year patient survival rates are 87% and 69%. All nine patients receiving transplants in the last 7 years have survived, which seem to be acceptable results for the treatment of intestinal failure. Relatively few intestinal transplantations have been performed to date, mainly due to the lack of national health insurance coverage for the procedure and the ban of the use of donors below 15 years of age. Liver failure patients are also ineligible because liver-intestine or multiorgan transplants are not allowed by current guidelines. Case numbers may increase in the future as the result of allowing for pediatric donors in the new Act on Organ Transplantation, which went into effect in July 2010. We continue to work on reforming national insurance coverage to cover multiorgan transplantations.

Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought-provoking case of HSV hepatitis in a high-risk recipient after living-related liver transplantation (LRLT). A 1-month-old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody-mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real-time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.

The therapeutic idea of anastomosis of the external carotid artery, or one of its branches, with the internal carotid artery above the area of narrowing was advocated by C. Miller Fisher in 1951. This was actually realized in another way than originally suggested at the cervical region, but in the form of superficial temporal artery-middle cerebral artery (STA-MCA) bypass using microsurgical technique by Donaghy and Yasargil in 1967 [22]. Thereafter, applications of the revascularization technique have been reported for one cerebral vascular territory after the other. It was the international cooperative study of extracranial-intracranial (EC-IC) bypass, whose final results in 1985 called the role of the procedure in prevention of further recurrent stroke into question [5]. Most neurosurgeons were disappointed at the results then and apparently have lost interest in performing microvascular anastomosis. This tendency has been enhanced by the development of interventional neuroradiology represented by percutaneous an transluminal dilatation (PTA) pioneered by A. Gruntzig in 1979 and later with additional stenting procedure.

The anterior clinoid process is a part of the sphenoid bone overlying the optic nerve and the carotid artery taking a veer medially to the planum sphenoidale, anterolateraly to the sphenoid ridge and caudally to the optic strut. Partial removal of the process has been recommended for the surgical management of aneurysms of the internal carotid artery (ICA) at its proximal intradural part, already as early as in 1972 [11, 12, 19]. It was however only in 1993 that the method of systematic en bloc removal of the bone fragment including the whole anterior clinoid process (ACP), namely, selective extradural anterior clinoidectomy (SEAC) was carried out, which then was reported in 1997 [22]. With this method one may obviate the more invasive and time consuming technique of extensive orbital roof removal together with anterior clinoidectomy which had been applied in surgical treatment for parasellar and cavernous pathologies pioneered by Dolenc [2, 3]. In this chapter, advantages, indications, technical details and complications are clarified.

We are interested in the userspsila level of understanding of an innovative Japanese portable phone (KEITAI) unit with multiple functions. This research focuses on userspsila knowledge of cellular phone usage and design and practice of the information transfer method for users who need more information. In this article, we conducted several surveys and their data analysis to determine the necessary knowledge about KEITAIpsilas potential and possible risks for the improvement of KEITAIpsilas usability as well as the operation of successful workshop. We further focus on how KEITAI users gain the knowledge of cellular phones (as information tool), and which functions they have concerns about by comparing the results of nationwide Internet survey and regional survey. Based on these results, we review the knowledge users need, as well as the appropriate area and scale of a trial experiment of the workshop for the effective provision of KEITAI knowledge for ldquonot advanced KEITAI userrdquo. We also found that users concerns are focused on security-related functions such as service suspension in case of theft and electric money, regardless of user type. As a solution to bridge such gap, we held a workshop for providing information on a cellular phone including a quiz game and one-on-one lecture, etc. The repetitive training effectively contributed to the userspsila satisfaction and the improvement of their understandings.

The need of an emergency bypass in hazardous situations during treatment of intracranial aneurysms has rarely been addressed in the literature. We report our 10 year experience with emergency bypass for aneurysm treatment. We retrospectively analyzed the data of patients who underwent emergency bypass surgery for the treatment of an intracranial aneurysm and compared the results with patients treated with bypass as a planned procedure during the same time period. Three groups were formed: group I, emergency bypass during clipping procedure; group II, emergency bypass for therapy refractory vasospasm; group III, planned bypass surgery. Sixteen patients (35%) out of 46 were treated with emergency bypass. In group I (11 patients) mortality was 37% and a good outcome (GOS 45) was achieved in 36%. In group II (5 patients) mortality was 20% and good outcome was reached in 60%. In group III (30 patients) mortality was 10% and good outcome was achieved in 86.6%. Outcome was worse in patients with additional SAH. An emergency bypass procedure as part of the aneurysm treatment should be considered in risky situations. Accurate timely decision-making is crucial combined with a fast and secure bypass technique. Treatment of refractory vasospasm with emergency bypasses may help to improve outcome in selected patients.

The number of patients, especially children, diagnosed with Moyamoya angiopathy and being referred to us for treatment from all across Europe, has increased over the last few years. An increase in awareness of the occurrence of stroke in children in the general and medical population might be the main cause of this phenomenon. Increasing awareness does not happen "spontaneously" nor does it manifest overnight! It requires regular platforms of communication between the general population and amongst the different medical specialists mainly neurologists, paediatric neurologists, neuropsychologists, neuroradiologists, neurorehabilitation specialists, nursing staff and neurosurgeons. Presently we were lucky to conduct the first Moyamoya Symposium ever to be conducted at a European-Japanese level with participation of specialists of this particular field from across Europe and Japan. Ever since the first child with Moyamoya was managed at the University hospital in Zurich some 7 years ago the number of patients referred to us from all across Europe increased rapidly. The importance of interdisciplinary communication, trust and support amongst specialists and increasing the awareness of the disease among the patients, medical personnel was and remains to be just as important as making the correct diagnosis and treatment of choice in these patients. We present the lessons we learned during these previous years and look into the future perspectives that require our further and urgent attention.

Multiple aneurysms occur in up to one-third of people with intracranial aneurysms. Of such patients, epidemiological data, clinical information, and aneurysm characteristics (of both unruptured and ruptured aneurysms in the same patients) were gathered in this retrospective review.Ninety-nine patients operated on for multiple intracranial aneurysms at the Department of Neurosurgery, University Hospital Zurich, Switzerland, between 1994 and 2003 were assessed, 90% with subarachnoid hemorrhage (SAH), 10% with incidental aneurysms.The female to male ratio was 3:1, median age was 53 years. SAH symptoms included acute headache (74%), decrease of consciousness (54%), nausea and vomiting (40%), epileptic seizure (11%). Neurological signs were meningism (40%), cranial nerve paresis (12%), none (28%). Chronic headache was the major complaint (40%) in patients with incidental aneurysms, 20% had paresis of extraocular muscles. History of smoking and hypertension was present in 47% and 35%. There were 265 aneurysms (median number per patient, 2; range, 2-8), 95% were small (or = 10 mm), 4.5% large, 0.5% giant (25 mm); 34% were ruptured, 66% unruptured (median size, 7 mm vs. 4 mm; p0.0001). Most aneurysms (27%) were on the middle cerebral artery bifurcation. Most ruptured aneurysms (18%) were on the anterior communicating artery and were 10 mm or smaller. Eighty-one percent of patients had (non-surgery related) SAH complications: cerebral vasospasm (44%), post-SAH hydrocephalus (36%), cerebral infarction (36%), intracerebral (25%) and intraventricular (21%) bleeding. Glasgow Outcome Scale score at 3 months was 4 or 5 in 73%.Ruptured aneurysms were significantly larger than unruptured ones. Although discussed controversially, most of our population's ruptured aneurysms were 10mm or smaller in size. Considering this, our study may contribute to improve the management of patients with intracranial aneurysms.

The thalamic cavernous angioma (CA) represents a neurosurgical challenge because of the critical neurologic functions of the thalamus and its surrounding structures and of their deep location inside the brain. Although the natural history of the thalamic CA remains undefined, several studies suggest the poor outcome of those patients especially if the symptomatic thalamic CA is treated conservatively. We describe the advantage of the paraculminar supracerebellar approach to the lesions in the brainstem.We studied the usefulness and the safety of the paraculminar supracerebellar infratentorial transtentorial approach for the patients with thalamic CA.One hundred and ninety two consecutive patients with CA were treated at the Department of Neurosurgery in the Zurich University Hospital between 1993 and 2003. Among these patients, we analyzed six patients (four female, mean age 43) with thalamic CA who underwent surgical removal with the paraculminar supracerebellar transtentorial approach. We retrospectively reviewed their medical charts, the neuroradiological images, and the operative notes/video records.Four patients of the six presented with thalamic hemorrhage. CA existed in the left thalamus in four patients and in the right in two. Preoperative symptoms included sensorimotor disturbance (three cases), double vision (three cases), Parinaud syndrome (one case), and thalamic pain (one case). All patients had the thalamic CA completely removed without any postoperative deterioration.This study suggests that for the removal of thalamic cavernous angioma the paraculminar supracerebellar infratentorial transtentorial approach provides the spacious surgical field with reduced risks of damaging and sacrificing surrounding vascular and neuronal system. This approach could proffer one of the best and safest surgical routes for the radical removal of thalamic cavernous angioma.

Objective: A safe entry zone to tegmental lesions was identified based on intraoperative electrophysiological findings, the compound muscle action potentials (CMAP) from the extraocular muscles, and anatomic considerations. This entry zone is bordered caudally by the intramesencephalic path of the trochlear, laterally by the spinothalamic tract, and rostrally by the caudal margin of the brachium of the superior colliculus. Methods: Four intrinsic midbrain lesions were operated upon via the safe entry zone using the infratentorial paramedian supracerebellar approach. All lesions involved the tegmentum and included an anaplastic astrocytoma, a metastatic brain tumor, a radiation necrosis, and a cavernous angioma. CMAP were bilaterally monitored from the inferior recti (for oculomotor function) and superior oblique (for trochlear nerve function) muscles. Results: In three of four cases, CMAP related to the oculomotor nerve were obtained upon stimulation at the cavity wall after removal of the tumor. Stimulation at the surface of the quadrigeminal plate, however, did not cause any CMAP response. Using this monitoring as an indicator, the lesions were totally removed. Conclusions: In the surgery of tegmental lesions, CMAP monitoring from extraocular muscles is particularly helpful to prevent damage to crucial neural structures during removal of intrinsic lesions, but less so to select the site of the medullary incision. The approach via the lateral part of the colliculi is considered to be a safe route to approach the tegmental lesions.

Surgical treatment of paraclinoid aneurysms is considered to be difficult due to their complicated anatomical location in the vicinity of important neural, vascular and bony structures. We present our clinical experience of the past 10 years of conventional microsurgical treatment of 81 paraclinoid aneurysms in 75 patients with the use of selective extradural anterior clinoidectomy SEAC and discuss the method of therapy option by reviewing recent reports on results of endovascular coiling method and the combination of these with conventional microsurgical therapy. The favorable surgical results with the use of SEAC and no recurrence of the treated aneurysm after clipping procedure in our series indicate that direct surgery can still be a standard technique for paraclinoid aneurysms in view of the fact that the endovascular aneurysm coiling methods are still associated with a considerable percentage of incomplete occlusion and present the problem of coil packing.

Three special cases of AVM finally treated with conventional microsurgical method are presented. Two cases of medium sized AVMs were located at the central region, one of them was primarily treated with Gamma-knife followed by endovascular embolization having been complicated with growing cyst formation followed ultimately by microsurgical removal. The AVM of another case was embolized three times, followed by removal of the residual nidus under awake surgery. The third AVM located at the hypothalamus in the vicinity of the optic nerve was considered unsuitable for embolization and Gamma-knife therapy, and therefore removed by microsurgery using special approaches after a trial of embolization. In terms of microsurgical removal, preoperative embolization, embolization material, awake surgery and selection of special approaches are discussed.

In patients suffering from subarachnoid haemorrhage (SAH) and presenting with multiple intracranial aneurysms (MIA) two questions have to be decided on: 1st when is the ideal moment to eliminate the ruptured aneurysm and 2nd when to treat the coexisting aneurysms. In our series we retrospectively analysed 124 SAH-patients presenting with a total of 323 aneurysms. In 57 patients the ruptured aneurysm and all coexisting aneurysms were clipped during the first operation, whereas in 9 patients only some of the coexisting aneurysms (group-A; age in median 55 years) were clipped besides the ruptured one. In 55 patients (group-B; age in median 55 years) the first operation was restricted to clipping the ruptured aneurysm, dealing with the coexisting aneurysm subsequently. Immediately after admission 3 patients passed away. One of the 64 patients waiting (average 60 days, median 14 days) for the subsequent clipping of the not yet secured aneurysms suffered a SAH. Six to 12 months after the initial SAH, 78% of the cases in both groups reached a Glasgow Outcome Score of 4 or 5. Even if in patients with coexisting unruptured intracranial aneurysms the elimination of each and every aneurysm is recommended, the advantages of an unstaged procedure versus the additional strain caused by the prolongation of the procedure, e.g. approach over the midline, 2 or more craniotomies, and the risk of additional ischemic damage to the brain, caused by increased manipulation of cerebral arteries and brain tissue, have to be carefully considered. This is of special importance in dealing with patients in higher Hunt and Hess grades.

The treatment and natural course of unruptured cerebral aneurysms were analyzed in 615 patients with 712 unruptured cerebral aneurysms registered from seven Japanese national hospitals and Zurich University hospital. For 209 aneurysms in 181 cases, the natural course of the aneurysms was observed without surgical treatment. During the follow-up period of 3,862 months (321.8 years), 11 of these aneurysms ruptured giving a rupture rate of 3.42%/year. Five of these 11 aneurysms were less than 10 mm in diameter. Seventeen aneurysms of these 209 untreated aneurysms had blebs. Seven of these 17 aneurysms ruptured yielding the high rupture rate of 28.3%/year. The likelihood of unruptured cerebral aneurysms to rupture was not exceedingly low even when the aneurysms were smaller than 10 mm. Since the risk of rupture and morbidity in relation to surgical treatment cannot be predicted by size alone, the morphology, especially the presence of blebs, should be considered when treating unruptured cerebral aneurysms. In 434 patients, 503 cerebral aneurysms were treated surgically either by craniotomy in 472 aneurysms or endovascular coil embolization in 31 aneurysms. Surgical outcome was influenced by the presence of concurrent diseases, patient age, size and location of the aneurysms. Complications after surgical treatment of 128 incidentally found aneurysms were reported in four cases; three cases of hemiparesis and one case showing disturbance of higher brain function, with a morbidity rate of 3.1%. These results suggest that surgical treatment may be acceptable in cases of incidentally found cerebral aneurysms, especially when blebs are present.

Over the past 6 years we at the Neurosurgery Department in Zürich have had the opportunity to manage increasing numbers of patients, especially children, with Moyamoya angiopathy. With increasing awareness of presence of this angiopathy in Europe the number of referrals from all across Europe is constantly on the increase. We have also been able to readdress the presence of the entity of Moyamoya angiopathy i.e. both the Moyamoya disease and the Moyamoya syndrome in the European population. Thorough presurgical workup is mandatory for evaluation of surgical candidates for the type of effective revascularisation procedure and therefore for their successful management. Apart from scrutinizing the routine yet indispensable presenting symptomatology with clinical examination of the patients, our preoperative diagnostic workup mainly consists of a 6 vessel cerebral angiography, cerebral perfusion studies with HMPAO-SPECT and H(2)15O-PET examinations and transcranial Doppler. Longterm follow-up of these patients is indispensable and of great interest to us in terms of etiology and progression of the disease process as well as the choice of effective revascularisation procedure especially in our European population.

To evaluate the outcome of patients with most severe cerebral venous and dural sinus thrombosis (CVT) after decompressive craniectomy. Indications and techniques for decompressive craniectomy and intensive care regimen are discussed.Between 2000 and 2004 15 patients with CVT and intracerebral hemorrhage were treated at the Department of Neurosurgery, University Hospital Zurich. Among them, four patients with the most severe illness course were treated with decompressive craniectomy. Indications for decompressive craniectomy were deterioration of level of consciousness with CT signs of space occupying brain edema, venous infarction and congestional bleeding with mass effect, midline shift and obliteration of the basal cisterns.Among 15 patients with CVT and intraparenchymatous hemorrhage four patients were treated with decompressive craniectomy. Glasgow Coma Scale (GCS) immediately before the operation was in mean 10.2 (range 6 to 13). No patient showed signs of unilateral or bilateral third nerve palsy before surgery. No surgical complications were observed. All four patients who underwent decompressive craniectomy recovered with favourable functional outcome (Glasgow Outcome Scale; GOS 4 and 5). Anticoagulation therapy with heparin was reconvened 12 hours postoperatively with half dosage and 12 hours later with full dosage. No enlargement of existing intraparenchymatous hematoma or other intracranial bleeding complications occurred.Favorable functional outcome in selected patients with most severe courses of CVT can be achieved after decompressive craniectomy. Postoperative anticoagulation therapy with full dose heparin 24 hours after craniotomy seems to be safe. Precise indications and techniques for combined surgical decompression and thrombectomy deserve to be evaluated in future studies.

Basilar bifurcation aneurysms are lately treated frequently with endovascular technique. Microsurgical clipping occlusion technique has, however, still its solid position because of its completeness. This standard technique is required often due to unfeasibility and/or incompleteness at the time of application of the endovascular technique for aneurysms of this location. The authors suggest following strategies and tactics for safe and secure occlusion of aneurysms of this location: pterional approach, selective extradural anterior clinoidectomy SEAC, no transection of the posterior communicating artery, isolation of perforating arteries at the time of neck clipping with oxycellulose and combination of the use of fenestrated clip and conventional clip (especially for aneurysms projected posteriorly), controlled hypotension (systolic pressure of around 100 mmHg), temporary clipping (trapping) procedures of usually less than 15 min. All these are aimed for prevention of intraoperative premature rupture, and of injury of perforating arteries and for complete occlusion of aneurysms in the narrow depth of the operative field.

Symptomatic cerebral vasospasm (CVS) with delayed ischemic neurologic deficits affects about one third of the patients after aneurysmal subarachnoid hemorrhage (SAH). In spite of the lack of definite evidence of large clinical trials, the devastating outcome of the natural history of symptomatic CVS demands an aggressive CVS treatment in a practically oriented, structured multimodal treatment regimen. With our treatment protocol good functional outcome could be reached in 66% of the patients with symptomatic CVS. This policy requires close and fast multidisciplinary collaboration between neurosurgeons, neuroradiologists, competent in endovascular interventions, and specialists for neurointensive care. We report on our experience with 79 cases with symptomatic CVS and delayed ischemic neurologic deficit (DIND) after aneurysmal SAH. The different treatment options with CVS are reviewed and practical guidelines for a step by step treatment are given.

Radiographic cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) do not reflect cerebral hemodynamics and oxygenation and may occur in the absence of clinical deficit and vice-versa. This report is to describe preliminary findings in further development of a non invasive method to estimate regional cerebral oxygenation and perfusion. Measurements were performed with a technique combining near infrared spectroscopy (NIRS) and indocyaningreen (ICG) dye dilution. Successful data analysis has been performed based on the decomposition in pulsatile and non-pulsatile components of NIRS absorption data collected before and during the passage of ICG through the vascular bed under the NIRS-detector. First measurements in patients with CVS suggest that the technique could become a powerful tool in the detection and treatment of CVS. This non invasive technique can be done at the bedside, it seems to be safe, easy to perform and less time-consuming compared to conventional techniques. The influence of extracerebral bone and surface tissue on cerebral NIRS signal has not been clarified yet. Therefore a new subdural NIRS probe has been developed, which gives the opportunity to measure directly the concentration of the chromophores in the brain without the influence of extracerebral contamination. In future comparative measurements with conventional NIRS probes on the scalp will allow to quantify and eliminate extracerebral contamination from the NIRS signal.

The importance of repeat-angiography in patients with acute subarachnoid hemorrhage (SAH) and initial negative angiography has been reviewed in the light of our patient population (19 patients with initial negative angiography/168 patients with SAH). The type of SAH i.e., nontraumatic perimesencephalic SAH versus focal or generalized non perimesencephalic SAH, as well as the amount and distribution of blood on the initial CT examination are important factors in decision making. 3D-Angio-CT, in 3/5 patients, and MR-angiography (MRA) in 1/5 patients were complementary non-invasive methods to diagnose aneurysms on repeated examinations. Repeat-cerebral angiography confirmed the source of hemorrhage in 3 patients.

Special strategies are mandatory for optimal surgical management of aneurysms of special location, size and form. Approaches of extradural selective anterior clinoidectomy, partial occipital condylectomy, transpetrosal approach by anterior petrosectomy and supracerebellar transtentorial approach are discussed among them. Furthermore various types of temporary and permanent clipping procedures are discussed along with mention of intraoperative monitoring.

A series of 40 patients admitted to University Hospital Zurich (1996-97) with unruptured cerebral aneurysms is reported. Fifty-two aneurysms were treated in 40 operations. The age of surgically treated patients ranged from 31 to 78 year old (mean 53.6). The main locations of the aneurysms were: MCA 21 (40.4%), AcomA 10 (19.2%), ICA (posterior communicating and bifurcation) 6 (11.5%), carotid-ophthalmic segment 4 (7.7%), ACA 4 (7.7%), basilar tip 3 (5.8%), vertebral artery 2 (3.8%). The circumstances of diagnosis were: incidental 15 (37.5%), other cranial lesions 9 (22.5%), symptomatic 8 (20%), multiple aneurysm 8 (20%). The overall outcome of surgery was: good recovery in 39 cases (97.5%), moderately disabled in 1 case (2.5%) who was 56 year-old and had three aneurysms including basilar tip. There was no operative mortality. Though this series has small number of patients, it suggests that location of the aneurysm is an important factor affecting surgical outcome among patient age, the circumstances of the diagnosis, size and location of aneurysm.

The fact that neurological status and physical integrity alone do not sufficiently assess the overall state of patients after aneurysmal subarachnoid hemorrhage (SAH) gives rise to the necessity for complementary neuropsychological investigation. Neuropsychological work-up should also cover an emotional state, psychosocial adjustment and competence in everyday life of the patients. In our prospective study we investigated 82 patients three months and one year after SAH and early clipping of the aneurysm. For the evaluation of postoperative neurological functions the Glasgow Outcome Scale (GOS) was used. For the neuropsychological assessment we used standardized measures of verbal and figural learning and memory, verbal and figural fluency, speed of information processing, visuospacial abilities and affective function. One year after SAH 95.6% of patients with HuntHess Grade 1 and 2 on admission showed good neurological results (GOS 4 and 5). However, only 30.1% (18 of 63 patients with a favourable neurological outcome--GOS 4 and 5) did not show any neuropsychological deficit. Localization of the ruptured aneurysm significantly correlated with cognitive measures. The best cognitive outcome was shown in patients with aneurysms on the anterior communicating artery (ACoA) followed by posterior communicating artery (PCoA) and those located on the internal carotid artery (ICA) on the right side.

The supracerebellar transtentorial (SCTT) approach, a modification of the infratentorial supracerebellar approach, facilitates simple and minimally invasive access to posterior temporomedial structures without requiring retraction of the temporal or occipital lobe. The SCTT approach was used in 16 patients over a 3-year period. Eleven patients harbored tumors confined to, or located mainly within, the posterior hippocampal formation, three patients harbored aneurysms (one ruptured posterior cerebral artery [PCA] aneurysm at the P2-P3 junction, one ruptured giant PCA [P2] aneurysm, and one giant basilar artery-superior cerebellar artery aneurysm), one patient had juvenile-type moyamoya disease, and one patient suffered from medically intractable epilepsy. In these patients, the SCTT approach enabled tumor removal, aneurysm clipping, and vascular bypass procedures. The authors' experience suggests that this approach can be used routinely in treating lesions in the posterior temporomedial region.

Diffuse astrocytoma WHO grade II is a well-differentiated, slowly growing tumor that has an inherent tendency to progress to anaplastic astrocytoma (WHO grade III) and, eventually, to glioblastoma (WHO grade IV). Little is known about its molecular basis, except for p53 mutations that are found in60% of cases. In a search for additional genetic alterations, we carried out gene expression profiling of 11 diffuse astrocytomas using cDNA expression arrays. Expression of six genes (TIMP3, c-myc, EGFR, DR-nm23, nm23-H4, and GDNPF) was detected in 64-100% of diffuse astrocytomas, but not in nontumorous brain tissue. Seven genes (AAD14, SPARC, LRP, PDGFR-alpha, 60S ribosomal protein L5, PTN, and hBAP) were found to be up-regulated more than 2-fold in 20-60% of cases, whereas 11 genes (IFI 9-27, protein kinase CLK, TDGF1, BIN1, GAB1, TYRO3, LDH-A, adducin 3, GUK1, CDC10, and KRT8) were down-regulated to less than 50% of normal levels in 64-100% of cases. Semiquantitative conventional reverse transcription-PCR was performed for 11 genes, 9 of which showed an expression profile similar to that obtained with cDNA expression arrays. Immunohistochemical staining for SPARC showed cytoplasmic immunoreactivity of neoplastic cells in all diffuse astrocytomas analyzed. These results indicate significant changes in gene expression in diffuse astrocytomas, but it remains to be shown which of these are causally related to the transformation of glial cells.

Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) therapy was performed in five cases of recurrent glioblastoma multiforme. In the last study, the authors demonstrated response of the HSV-TK/GCV therapy against tumor progression (Adachi N, et al.: No Shinkei Geka). The aim of this study is to estimate the biosafety of in vivo HSV-TK gene transfer and GCV administration in five cases. Six parameters were analyzed sequentially up to the 6th month after the vector producer cells (VPCs) inoculation as follows; i) clinical symptom, ii) vital sign, iii) peripheral blood cell count, iv) blood biochemical analysis, v) serological test, vi) molecular biological test in peripheral leukocytes. In addition, ten systemic organs extracted from the two subjects in whom death occurred were also analyzed biologically. One case suffered from transient deterioration of left hemiparesis on the 34th day, which could be considered a probably-related but not adverse event. Serological tests detected anti-VPC antibody at the 1st month in one case and anti-vector antibody at the 1st and 4th month in another. The other examinations revealed no abnormal findings at all. These data indicate that the HSV-TK/GCV therapy might be a satisfactorily safe approach against glioblastoma multiforme.

Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy was performed in five cases of recurrent glioblastoma multiforme. The mean age of cases, three males and two females, was 60 +/- 5 years old. All of the tumors were confirmed pathologically as glioblastoma multiforme and recurred after the initial treatments (surgery and irradiation). A total number of 1 x 10(9) vector producer cells (VPCs), which produce retroviral vectors containing the HSV-TK gene, was inoculated into the tumor-bed spaces after removal of the recurrent tumors. From the following 14th day to the 27th day, GCV was transfused 5 mg/kg i.v. twice a day. The effect of the HSV-TK/GCV gene therapy was evaluated by the Karnofsky performance scale and MRI findings sequentially, before the therapy and in the 1st, 2nd, 4th and 6th month after the VPCs inoculation. During the follow-up period of 12 months, two cases died (survival period; 8.4 and 9.9 months), whereas the other three are still alive for over 12 months (1-year survival; 60%). Karnofsky performance scale showed the maximum at the 2nd and 4th month in all cases; the mean performance rating of living cases was 80% and that of dead cases was 70%. MRI revealed progression in none of the cases until the 2nd month. These results obtained in five cases suggest that the HSV-TK/GCV gene therapy may promise a feasible approach against glioblastoma multiforme.

Ninety-eight patients with aneurysms of the posterior circulation were admitted to our department from 1993 to 1997. Sixty of them underwent microsurgical treatment, mostly in the acute stage of subarachnoid hemorrhage. Peri- and intraoperative management were carried out according to a structured treatment strategy. Special aspects of surgical technique included extradural selective anterior clinoidectomy for basilar head aneurysms, lateral suboccipital craniotomy and partial condylectomy without laminectomy for aneurysms of the vertebral artery or posterior inferior cerebellar artery, and a trans-Sylvian approach, as used in selective amygdalohippocampectomy, for aneurysms of the posterior cerebral artery. A careful angiographic evaluation of the aneurysms in relation to the neighboring important arteries and bony structures was essential for optimal surgical planning. Forty-nine patients (82%) made a good recovery by 3 months after surgery. The mortality was 7%.

Giant cell glioblastoma is a rare glioblastoma variant characterized by the presence of large, bizarre, multinucleated giant cells. This glioblastoma subtype develops clinically de novo after a short clinical history and contains a high frequency of p53 mutations. In this study, we screened a series of 18 giant cell glioblastomas for additional genetic alterations. PCR-SSCP followed by DNA sequencing revealed PTEN mutations in 5 of 15 tumors (33%). Of these, two mutations were located in exon 5, two mutations in exon 6, and one mutation each in exons 1 and 9. Four mutations were point mutations and two mutations were deletions. One neoplasm contained two PTEN mutations (exons 5 and 6). None of the giant cell glioblastomas showed a homozygous deletion of PTEN orp16, or amplification of MDM2. Immunohistochemically, MDM2 overexpression was either not observed or detected in only a minor fraction of tumor cells. Differential PCR revealed EGFR amplification in only one of 17 tumors (6%). These results indicate that giant cell glioblastomas occupy a hybrid position, sharing with primary (de novo) glioblastomas a short clinical history, the absence of a less malignant precursor lesion and a 30% frequency of PTEN mutations. With secondary glioblastomas that develop through progression from low-grade astrocytomas, they have in common a younger patient age at manifestation and a high frequency (70%) of p53 mutations.

Mutations of the p53 tumor suppressor gene are a genetic hallmark of human astrocytic neoplasms, but their predictive role in glioma progression is still poorly understood. We analyzed 144 biopsies from 67 patients with recurrent astrocytoma by single-strand conformation polymorphism and direct DNA sequencing. We found that 46 of 67 patients (69%) had a p53 mutation in at least one biopsy. In 41 of these (89%), the mutation was already present in the first biopsy, indicating that p53 mutations are early events in the evolution of diffuse astrocytomas. Double mutations of the p53 gene were observed in three tumors and also present from the first biopsy. Of 28 low-grade astrocytomas with a p53 mutation, 7 (25%) showed loss of the normal allele in the first biopsy. The allele status remained the same in 95% of the cases, irrespective of whether the recurrent lesion had the same or a higher grade of malignancy. Progression of low-grade astrocytomas to anaplastic astrocytoma or glioblastoma occurred at a similar frequency in lesions with (79%) and without (63%) p53 mutations (P = 0.32), indicating that this genetic alteration is associated with tumor recurrence but not predictive of progression to a more malignant phenotype. However, the time interval until progression was shorter in patients with low-grade astrocytomas carrying a p53 mutation (P = 0.055).

The presence of gemistocytes in low-grade astrocytomas is regarded as a sign of poor prognosis because the majority of gemistocytic astrocytomas rapidly progress to anaplastic astrocytoma or glioblastoma. To elucidate the role of gemistocytes in astrocytoma progression, we assessed the fraction of neoplastic gemistocytes, bcl-2 expression, p53 mutations, p53 immunoreactivity (PAb 1801), and proliferative activity (MIB-1) in 40 low-grade astrocytomas (World Health Organization (WHO) Grade II) with histologically proven progression to anaplastic astrocytoma (WHC Grade III) or glioblastoma (WHO Grade IV). Astrocytoma progression took significantly less time in patients with a low-grade astrocytoma containing more than 5% gemistocytes (35 months) than in those with lesions containing less than 5% gemistocytes (64 months; p = 0.038). All 11 astrocytomas with more than 5% gemistocytes contained a p53 mutation, whereas the incidence of p53 mutations in astrocytomas with less than 5% gemistocytes was 61% (p = 0.017). In low-grade astrocytomas the p53 labeling index (LI) of gemistocytes (7.4%) was significantly higher than in all tumor cells (3.2%, p = 0.0014). Gemistocytes showed a significantly higher bcl-2 expression than all tumor cells, with a mean bcl-2 1 of 15.6% versus 2.7% in low-grade astrocytomas (p = 0.0004), 20.9% versus 3.0% in anaplastic astrocytoma (p = 0.002), and 30.2% versus 5.2% in glioblastomas (p = 0.0002). In contrast, gemistocytes showed a significantly lower proliferating activity than the mean of all tumor cells, with a mean MIB-1 LI of 0.5% versus 2.6% in low-grade astrocytomas, 1.5% versus 11.6% in anaplastic astrocytoma, and 1.7% versus 16.6% in glioblastomas (p0.0001). These data show that low-grade astrocytomas with a significant fraction of gemistocytes progress more rapidly and typically carry a p53 mutation. The vast majority of gemistocytes are, however, in a nonproliferative state (G0 phase of the cell cycle), which suggests terminal differentiation. Their accumulation within astrocytomas may be due to bcl-2-mediated escape from apoptosis.

Since the first H-mode discharges in 2010, the duration of the H-mode state has been extended and a significantly wider operational window of plasma parameters has been attained. Using a second neutral beam (NB) source and improved tuning of equilibrium configuration with real-time plasma control, a stored energy of Wtot???450?kJ has been achieved with a corresponding energy confinement time of ?E???163?ms. Recent discharges, produced in the fall of 2012, have reached plasma ?N up to 2.9 and surpassed the n?=?1 ideal no-wall stability limit computed for H-mode pressure profiles, which is one of the key threshold parameters defining advanced tokamak operation. Typical H-mode discharges were operated with a plasma current of 600?kA at a toroidal magnetic field BT?=?2?T. L?H transitions were obtained with 0.8?3.0?MW of NB injection power in both single- and double-null configurations, with H-mode durations up to ?15?s at 600?kA of plasma current. The measured power threshold as a function of line-averaged density showed a roll-over with a minimum value of ?0.8?MW at . Several edge-localized mode (ELM) control techniques during H-mode were examined with successful results including resonant magnetic perturbation, supersonic molecular beam injection (SMBI), vertical jogging and electron cyclotron current drive injection into the pedestal region. We observed various ELM responses, i.e. suppression or mitigation, depending on the relative phase of in-vessel control coil currents. In particular, with the 90? phase of the n?=?1 RMP as the most resonant configuration, a complete suppression of type-I ELMs was demonstrated. In addition, fast vertical jogging of the plasma column was also observed to be effective in ELM pace-making. SMBI-mitigated ELMs, a state of mitigated ELMs, were sustained for a few tens of ELM periods. A simple cellular automata (?sand-pile?) model predicted that shallow deposition near the pedestal foot induced small-sized high-frequency ELMs, leading to the mitigation of large ELMs. In addition to the ELM control experiments, various physics topics were explored focusing on ITER-relevant physics issues such as the alteration of toroidal rotation caused by both electron cyclotron resonance heating (ECRH) and externally applied 3D fields, and the observed rotation drop by ECRH in NB-heated plasmas was investigated in terms of either a reversal of the turbulence-driven residual stress due to the transition of ion temperature gradient to trapped electron mode turbulence or neoclassical toroidal viscosity (NTV) torque by the internal kink mode. The suppression of runaway electrons using massive gas injection of deuterium showed that runaway electrons were avoided only below 3?T in KSTAR. Operation in 2013 is expected to routinely exceed the n?=?1 ideal MHD no-wall stability boundary in the long-pulse H-mode (?10?s) by applying real-time shaping control, enabling n?=?1 resistive wall mode active control studies. In addition, intensive works for ELM mitigation, ELM dynamics, toroidal rotation changes by both ECRH and NTV variations, have begun in the present campaign, and will be investigated in more detail with profile measurements of different physical quantities by techniques such as electron cyclotron emission imaging, charge exchange spectroscopy, Thomson scattering and beam emission spectroscopy diagnostics.