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The aryl hydrocarbon receptor interacting protein (AIP) is a tumor-suppressor gene underlying the pituitary adenoma predisposition. Thus far, the exact molecular mechanisms by which inactivated AIP exerts its tumor-promoting action have been unclear. To better understand the role of AIP in pituitary tumorigenesis, we performed gene expression microarray analysis to examine changes between Aip wild-type and knockout mouse embryonic fibroblast (MEF) cell lines. Transcriptional analyses implied that Aip deficiency causes a dysfunction in cyclic adenosine monophosphate (cAMP) signaling, as well as impairments in signaling cascades associated with developmental and immune-inflammatory responses. In vitro experiments showed that AIP deficiency increases intracellular cAMP concentrations in both MEF and murine pituitary adenoma cell lines. Based on knockdown of various G protein α subunits, we concluded that AIP deficiency leads to elevated cAMP concentrations through defective Gαi-2 and Gαi-3 proteins that normally inhibit cAMP synthesis. Furthermore, immunostaining of Gαi-2 revealed that AIP deficiency is associated with a clear reduction in Gαi-2 protein expression levels in human and mouse growth hormone (GH)-secreting pituitary adenomas, thus indicating defective Gαi signaling in these tumors. By contrast, all prolactin-secreting tumors showed prominent Gαi-2 protein levels, irrespective of Aip mutation status. We additionally observed reduced expression of phosphorylated extracellular signal-regulated kinases 1/2 and cAMP response element-binding protein levels in mouse and human AIP-deficient somatotropinomas. This study implies for the first time that a failure to inhibit cAMP synthesis through dysfunctional Gαi signaling underlies the development of GH-secreting pituitary adenomas in AIP mutation carriers. [ABSTRACT FROM AUTHOR]

Background: Both conventional bypass utilizing temporary recipient vessel occlusion and the excimer laser-assisted nonocclusive anastomosis (ELANA) bypass technique are possible strategies in the treatment of giant aneurysms. These treatments have only been studied in single institutional retrospective studies. The potential advantage of the ELANA technique is the absence of temporary occlusion of major arteries, decreasing the risk of intraoperative ischemia., Objective: To investigate the risks and potential benefits of high-flow bypass surgery for giant and complex aneurysms of the anterior cerebral circulation. In addition, the effectiveness of the ELANA bypass procedure in the treatment of these aneurysms is determined., Methods: A total of 37 patients were included in 8 vascular neurosurgical centers in the United States, Canada, and Europe. A 30-d postoperative bypass follow-up was studied by using digital subtraction angiography and/or magnetic resonance angiography and computed tomography angiography to assess patency as well as by clinical monitoring in all patients., Results: In 35 patients, an ELANA high-flow bypass was performed and the aneurysm treated. Four patients had remaining neurological deficits after 30 d caused by stroke (11.4%). These strokes were not related to the ELANA anastomosis device., Conclusion: This study does not prove that the ELANA technique has an advantage over conventional bypass techniques, but it appears to be an acceptable alternative to conventional transplanted high-flow bypass in this very-difficult-to-treat patient group, especially in select patients whom cannot be bypassed using conventional means in which temporary occlusion is considered to be not recommended., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background and Purpose: Moyamoya angiopathy (MMA) is a chronic progressive disorder, but imaging changes observed over time are not yet characterized in European populations. We analyzed the progression of MMA with magnetic resonance imaging and angiography (MRI and MRA) in our Finnish MMA registry. Stage classification based on MRA findings was used to evaluate the progress of the disease., Methods: 32 patients with MMA were evaluated with MRI and MRA and compared to previous imaging. The follow-up imaging was done 103 (range 6-380) months after the MMA diagnosis, and 64 (range 6-270) months after the previous imaging. We graded the disease stage according to the previously described MRA grading scale., Results: No acute lesions, including silent ischemic strokes were found in the follow-up image compared to latest available previous image. One patient had an asymptomatic intracerebral hemorrhage since the last imaging. Ivy sign was observed in 22% of the patients in the follow-up image. Six percent (n = 2) had microhemorrhages and 9% (n = 3) white matter lesions in the follow-up imaging. The MRA grade was evaluated from the follow-up images and it was 3 and 2.5 points (right and left, respectively). Fifty-six percent (n = 18) had old ischemic lesions in the follow-up image. Majority (71%) of the old ischemic lesions were large anterior circulation infarcts., Conclusions: A slow progression of MMA-related changes on MRI/MRA was found, being in line with our previous reports suggesting a rather benign course of the disease in the Finnish population.

Somatic driver mechanisms of pituitary adenoma pathogenesis have remained incompletely characterized; apart from mutations in the stimulatory Gα protein (Gα s encoded by GNAS ) causing activated cAMP synthesis, pathogenic variants are rarely found in growth hormone-secreting pituitary tumors (somatotropinomas). The purpose of the current work was to clarify how genetic and epigenetic alterations contribute to the development of somatotropinomas by conducting an integrated copy number alteration, whole-genome and bisulfite sequencing, and transcriptome analysis of 21 tumors. Somatic mutation burden was low, but somatotropinomas formed two subtypes associated with distinct aneuploidy rates and unique transcription profiles. Tumors with recurrent chromosome aneuploidy (CA) were GNAS mutation negative ( Gsp - ). The chromosome stable (CS) -group contained Gsp + somatotropinomas and two totally aneuploidy-free Gsp - tumors. Genes related to the mitotic G 1 -S-checkpoint transition were differentially expressed in CA- and CS-tumors, indicating difference in mitotic progression. Also, pituitary tumor transforming gene 1 (PTTG1), a regulator of sister chromatid segregation, showed abundant expression in CA-tumors. Moreover, somatotropinomas displayed distinct Gsp genotype-specific methylation profiles and expression quantitative methylation (eQTM) analysis revealed that inhibitory Gα (Gα i ) signaling is activated in Gsp + tumors. These findings suggest that aneuploidy through modulated driver pathways may be a causative mechanism for tumorigenesis in Gsp - somatotropinomas, whereas Gsp + tumors with constitutively activated cAMP synthesis seem to be characterized by DNA methylation activated Gα i signaling. IMPLICATIONS: These findings provide valuable new information about subtype-specific pituitary tumorigenesis and may help to elucidate the mechanisms of aneuploidy also in other tumor types., (©2019 American Association for Cancer Research.)

Objective: Bypass surgery is a special technique used to treat complex internal carotid artery (ICA) aneurysms. The aim of this retrospective study is to provide a comprehensive description of treatment and outcome of complex ICA aneurysms at different ICA segments (cavernous, supraclinoid, ICA bifurcation) treated with bypass procedures., Methods: We identified 39 consecutive patients with 41 complex ICA aneurysms that were treated with 44 bypass procedures between 1998 and 2016. We divided the aneurysms into 3 anatomic subgroups to review our treatment strategy. All the imaging studies and medical records were reviewed for relevant information., Results: The aneurysm occlusion (n = 34, 83%) or flow modification (n = 5, 12%) was achieved in 39 aneurysms (95%). The long-term bypass patency rate was 68% (n = 30). Minor postoperative ischemia or hemorrhage was commonly seen (n = 20, 51%), but large-scale strokes were rare (n = 1, 3%). Preoperative dysfunction of extraocular muscles (cranial nerves III, IV, and VI) showed low-to-moderate improvement rates (20%-50%). Preoperative vision disturbance (cranial nerve II) improved seldom (22%). At the latest follow-up (mean; 51 months) 29 patients (74%) were independent (modified Rankin Scale ≤2)., Conclusions: Bypass surgery for complex ICA aneurysms is a feasible treatment method with an acceptable risk profile. Patients should be informed of the uncertainty related to improvement of pretreatment cranial nerve dysfunctions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose: Moyamoya angiopathy (MMA) is a chronic cerebrovascular disorder predominantly starting in childhood or early adulthood and thus affects the whole lifetime. Little is known on MMAs long-term outcomes in European patients. We report long-term follow-up data on Finnish MMA patients., Methods: We included patients from our Helsinki University Hospital MMA database and arranged long-term follow-up visits for all the patients. This follow-up included a review of the medical records accumulated in due time, detailed neurological and neuropsychological evaluation, and outcome measures modified Rankin Scale (mRS) and Barthel Index (BI)., Results: There were 61 MMA patients with a mean follow-up period of 9.5 years (SD 6.7 years; range 1.3-35.4 years; 581 patient-years). Only two patients had died and two-thirds (n = 40, 65.6%) had no new events during the follow-up period. Eight patients (13.1%) had an ischemic and five patients (8.2%) a hemorrhagic stroke during the follow-up. There were no differences between operated (n = 26) and conservatively (n = 35) treated groups regarding recurrent events or the outcome measured with mRS or BI. Finnish MMA patients reported significantly poorer physical and psychological health aspects of QOL when compared to the general Finnish population. Symptoms of low mood were found in 27 (56%) patients., Conclusions: Finnish MMA patients have a benign and stable course with a ~3.5 % annual stroke risk. We found no differences in the clinical outcomes between the operated and conservative groups, however, the psychosocial well-being requires more attention in MMA patients.

Objective: Recently, mutations in KCNQ1 , a potassium channel gene usually linked to long QT syndrome, were reported to cause maternally inherited gingival fibromatosis and growth hormone deficiency (GHD). Expression of the mutated KCNQ1 with the auxiliary potassium channel subunit KCNE2 was shown to reduce pituitary hormone secretion in functional experiments. Here, we investigated if germline mutations in KCNQ1 and KCNE2 were present in patients with somatotropinomas, which represent a model of growth hormone excess., Design and Methods: KCNQ1 and KCNE2 were screened for germline mutations in 53 patients with acromegaly by Sanger sequencing. Effects of the variants were predicted by in silico tools., Results: Only deep intronic and synonymous polymorphisms were detected in KCNQ1. These findings were likely insignificant based on in silico predictions and the variants' frequencies in the general population. In KCNE2 , a heterozygous c.22A>G, p.(Thr8Ala) mutation with unknown significance was found in three patients. It was present in the database controls with a frequency of 0.0038., Conclusions: KCNQ1 or KCNE2 mutations do not appear to account for somatotropinoma formation, although larger patient series are needed to validate the findings., (© 2018 The authors.)

Background and purpose Moyamoya vasculopathy, a rare steno-occlusive progressive cerebrovascular disorder, has not been thoroughly studied in Caucasian populations. We established a registry of Finnish patients treated at the Helsinki University Hospital, to collect and report demographic and clinical data. Methods We collected data both retrospectively and prospectively from all the patients with a moyamoya vasculopathy referred to our hospital between January 1987 and December 2014. All patients underwent a neurological outpatient clinic visit. Results We diagnosed 61 patients (50 females, 10 children) with moyamoya vasculopathy. The mean age at the disease-onset was 31.5 ± 17.9 years. The two most common presenting symptoms were ischemic stroke (n = 31) and hemorrhage (n = 8). Forty-four percent underwent revascularization surgery, and 70% were prescribed antithrombotic treatment. Conclusions The results support in part the Western phenotype of the disease considering the later presentation and larger female predominance compared to the Asian moyamoya vasculopathy reports. However, the proportion of ischemic strokes and hemorrhagic strokes is closer to Japanese population than German population. The absence of familial cases points to a different genetic profile in the Finnish patients.

Objective: The published data on health-related quality of life (HRQoL) after treatment of nonfunctioning pituitary adenomas (NFPAs) are conflicting. We evaluated HRQoL in a recent series of patients who had surgery for an NFPA., Design: Cross-sectional study including a large control population., Patients and Measurements: A HRQoL questionnaire (15D) was sent to all patients (n = 161) having undergone transsphenoidal surgery for NFPA in the years 2000-2010 at the Helsinki University Hospital. The 15D score and dimension scores of the study population (n = 137) were compared with those of a large (n = 4967) gender- and age-standardized control population. Possible independent predictors of HRQoL in the patients were estimated with multivariate regression analysis., Results: Postoperatively, 57% of the patients had normal visual function. After a mean follow-up of 7·4 ± 3·2 years (mean ± SD), 62% suffered from hypopituitarism. Overall, HRQoL was near-normal in patients compared to controls (15D scores 0·885 ± 0·114 vs 0·903 ± 0·093, respectively, P = 0·07). On single dimensions, patients had impaired vision and sexual activity (both P < 0·0005), more depression and distress (both P < 0·005) and less discomfort and symptoms (P < 0·05). Age, body mass index, diabetes, depression and reoperation were independent predictors of impaired HRQoL (all P < 0·05). Thyroxine substitution was associated with impaired and hydrocortisone and testosterone substitution (males only) with better HRQoL (all P < 0·05)., Conclusions: This recent series of NFPA patients demonstrates that overall HRQoL is near-normal after medium term follow-up; the most impaired dimensions were in vision and sexual activity. Comorbidities are strong predictors of impaired HRQoL., (© 2015 John Wiley & Sons Ltd.)

Context: The somatic landscape of pituitary adenomas is largely unknown. Identification of somatic alterations aims at better understanding of tumor pathology., Objective: The objective of the study was a genome-wide characterization of somatic single-nucleotide variants, structural variants, and copy-number aberrations in somatotropinomas., Design and Setting: Whole-genome sequencing and single-nucleotide polymorphism array analyses were performed on 12 fresh-frozen somatotropinomas and their corresponding blood samples. All the coding somatic variants were confirmed by Sanger sequencing., Patients: Studied tumors were somatotropinomas. Apart from one AIP mutation-positive patient, all cases were mutation negative for the established germline mutations associated with pituitary adenomas., Intervention(s): There were no interventions., Main Outcome Measures: Somatic variants were identified with an established computational pipeline and filtered against germline data. Somatic copy number alteration analyses were performed using segmentation-based approaches., Results: A genome-wide analysis revealed on average 129 somatic single-nucleotide variants per tumor. Further analysis of coding regions showed on average 2.3 single-nucleotide variants per tumor. The only recurrent somatic events were the oncogenic GNAS mutation (p.Arg201Cys) and shared chromosome losses (chromosomes 1, 6, 13, 14, 15, 16, 18, 22). Analysis of somatic structural variants revealed one tumor with a complex chromosomal rearrangement., Conclusions: Somatotropinomas showed a low number of somatic genetic alterations. Whereas no novel recurrently mutated genes could be identified, the somatic landscape has potential to affect the Ca(2+) and ATP pathways known to be involved in the pituitary tumorigenesis. Further studies, eg, methylome and transcriptome analyses, are needed to investigate possible interplay between the recurrent chromosome losses and epigenetic factors.

Objective: At our institution, a total of 320 patients were operated on between 2000 and 2010 for a newly diagnosed pituitary adenoma. In an attempt to improve quality of tumor resection, the transsphenoidal microscopic technique was replaced by the endoscopic technique in June 2008. This retrospective single center study compares the outcomes after microscopic (n = 144) and endoscopic (n = 41) tumor surgery of all patients operated on for a nonfunctional pituitary adenoma., Methods: Tumor size and location, Knosp grade, prevalence of anterior hypopituitarism, diabetes insipidus, visual acuity/fields, complication rates, and operation time were compared between the groups., Results: At the 3-month follow-up, hypopituitarism had improved in 7% of patients in the microscopic group and in 9% in the endoscopic group, and had further impaired in 13% and 9%, respectively. At the 3-month follow-up magnetic resonance imaging, a total tumor removal was achieved in 45% versus 56% of patients, respectively (P = not significant [NS]). Visual fields had normalized or improved in 90% versus 88% of patients, respectively (P = NS). Postoperative cerebrospinal fluid leak occurred in 3.5% versus 2.4% (P = NS), and diabetes insipidus (transient or permanent) in 7.6% versus 4.9% (P = NS) of cases, respectively. Larger tumor size (P < 0.0005) and endoscopic technique (P = 0.03) were independent predictors of increased mean operative time., Conclusions: Initial results with the endoscopic technique were statistically similar to those achieved with the microscopic technique. However, there was a trend toward improved outcomes and fewer complications in the endoscopic group., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Previous studies report impaired health-related quality of life (HRQoL) in patients with functional pituitary adenomas (FPA). We assessed HRQoL in FPA patients having undergone surgery at our University Central Hospital between 2000 and 2010, with combined adjuvant treatment given to achieve strict hormonal control., Design: A cross-sectional study including a large control population., Patients and Methods: HRQoL was assessed by the 15D in 100 FPA patients (acromegaly n = 47, Cushing's disease n = 21, prolactinoma n = 26, TSH-adenoma n = 2, gonadotropinoma n = 4), operated on a mean 7·4 (range 2·1-13·0) years earlier. An age- and gender-standardized sample of the general population (n = 4924) served as controls. HRQoL determinants were assessed by independent samples t-test and multiple regression analysis., Results: Hormonal remission rate was 90·9% and 43·9% of the patients received replacement therapy. The mean 15D scores were similar in patients and controls (0·917 vs 0·922, P = 0·568). On single dimensions, patients were worse off regarding speech and sexual activity (both P < 0·05) and better off regarding discomfort and symptoms (P < 0·05). Age (P = 0·001), co-morbidities (P = 0·009), Cushing's disease (P = 0·034), and thyroxine dose (P = 0·002) predicted impaired HRQoL, but not hypopituitarism, hydrocortisone replacement, radiotherapy, or time after surgery., Conclusions: It is possible to achieve near-normal HRQoL in surgically treated FPA patients given adjuvant treatment to achieve strict hormonal remission. However, in addition to age and co-morbidities, Cushing's disease and need for thyroxine replacement therapy predict impaired HRQoL., (© 2014 John Wiley & Sons Ltd.)

Pituitary adenomas are neoplasms of the anterior pituitary lobe and account for 15-20% of all intracranial tumors. Although most pituitary tumors are benign they can cause severe symptoms related to tumor size as well as hypopituitarism and/or hypersecretion of one or more pituitary hormones. Most pituitary adenomas are sporadic, but it has been estimated that 5% of patients have a familial background. Germline mutations of the tumor suppressor gene aryl hydrocarbon receptor-interacting protein (AIP) predispose to hereditary pituitary neoplasia. Recently, it has been demonstrated that AIP mutations predispose to pituitary tumorigenesis through defective inhibitory GTP binding protein (Gαi) signaling. This finding prompted us to examine whether germline loss-of-function mutations in inhibitory guanine nucleotide (GTP) binding protein alpha (GNAI) loci are involved in genetic predisposition of pituitary tumors. To our knowledge, this is the first time GNAI genes are sequenced in order to examine the occurrence of inactivating germline mutations. Thus far, only somatic gain-of-function hot-spot mutations have been studied in these loci. Here, we have analyzed the coding regions of GNAI1, GNAI2, and GNAI3 in a set of young sporadic somatotropinoma patients (n = 32; mean age of diagnosis 32 years) and familial index cases (n = 14), thus in patients with a disease phenotype similar to that observed in AIP mutation carriers. In addition, expression of Gαi proteins was studied in human growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH)-secreting and non-functional pituitary tumors. No pathogenic germline mutations affecting the Gαi proteins were detected. The result suggests that loss-of-function mutations of GNAI loci are rare or nonexistent in familial pituitary adenomas.

Object: The object of this study was to describe the authors' institutional experience in the treatment of complex middle cerebral artery (MCA) aneurysms necessitating bypass and vessel sacrifice., Methods: Cases in which patients with MCA aneurysms were treated with a combination of bypass and parent artery sacrifice were reviewed retrospectively., Results: The authors identified 24 patients (mean age 46 years) who were treated with bypass and parent artery sacrifice. The aneurysms were located in the M1 segment in 7 patients, MCA bifurcation in 8, and more distally in 9. The mean aneurysm diameter was 30 mm (range 7-60 mm, median 26 mm). There were 8 saccular and 16 fusiform aneurysms. Twenty-one extracranial-intracranial and 4 intracranial-intracranial bypasses were performed. Partial or total trapping (only) of the parent artery was performed in 17 cases, trapping with resection of aneurysm in 3, and aneurysm clipping with sacrifice of an M2 branch in 4. The mean follow-up period was 27 months. The aneurysm obliteration rate was 100%. No recanalization of the aneurysms was detected during follow-up. There was 1 perioperative death (4% mortality rate) and 6 cerebrovascular accidents, causing permanent morbidity in 5 patients. The median modified Rankin Scale score of patients with an M1 aneurysm increased from 0 preoperatively to 2 at latest follow-up, while the score was unchanged in other patients. Most of the permanent deficits were associated with M1 aneurysms. Twenty-one patients (88%) had good outcome as defined by a Glasgow Outcome Scale score of 4 or 5., Conclusions: Bypass in combination with parent vessel occlusion is a useful technique with acceptable frequencies of morbidity and mortality for complex MCA aneurysms when conventional surgical or endovascular techniques are not feasible. The location of the aneurysm should be considered when planning the type of bypass and the site of vessel occlusion. Flow alteration by partial trapping may be preferable to total trapping for the M1 aneurysms.

Cerebral artery bypass surgery makes it possible to improve or replace cerebral circulation by bringing blood flow from extracranial arteries into the cerebral arteries or by creating new flow routes between cerebral arteries. Cerebral artery bypass operations play an important role in the treatment of the rare moyamoya disease causing cerebral artery stenosis and disturbances of the cerebral circulation and in the treatment of cerebral aneurysms that are unamenable to treatment with traditional microsurgical or endovascular techniques. Compared with conservative therapy, bypass surgery does, however, not seem beneficial in the prevention of strokes and hemodynamic disturbances of the cerebral circulation associated with atherosclerotic occlusion of the carotid artery.

During recent decades extra-intracranial and intra-intracranial bypasses have deserved high interest among neurosurgeon, especially in management of giant cerebral aneurysms. Development of microsurgery and neuroanesthesiological techniques, advances in neuroradiology and neurophysiology prerequisite improvement of revascularization surgery. Evolution of competitive endovascular methods pushes the surgeons to improve microneurosurgical technique of revascularization and elaboration of new approaches to management of intracranial aneurysms. In this review we discuss principles of surgery of cerebrovascular bypasses in management of giant aneurysms applied in our clinic.

Background: The excimer laser-assisted nonocclusive anastomosis (ELANA) technique enables large-caliber bypass revascularization without temporary occlusion of the parent artery., Objective: To present the surgical experience of 2 bypass centers using ELANA in the treatment of complex intracranial lesions., Methods: Between July 2002 and December 2007, 64 consecutive patients (37 in Germany and 27 in Finland) were selected for high-flow bypass surgery with ELANA. Modified Rankin Scale, a bypass success rate, and the success rate of the laser arteriotomy were assessed., Results: In 66 surgeries for 64 intent-to-treat patients, 58 ELANA procedures were completed successfully. A favorable outcome (postoperative modified Rankin Scale score less than or equal to preoperative modified Rankin Scale) at 3 months was achieved in 43 of 56 patients (77%) with anterior circulation lesions (37 of the 43 patients had aneurysms, 4 had ischemia, and 2 received a bypass before tumor removal) and only in 2 of 8 patients (25%) with posterior circulation aneurysms. Perioperative (< 7 days) mortality for anterior and posterior circulation aneurysms was 6% and 50%, respectively. At the 3-month follow-up, 12% and 63% of patients with anterior and posterior circulation aneurysms, respectively, were dead. The success rate of the laser arteriotomy was 70%. Another 14% were retrieved manually after a nearly complete laser arteriotomy., Conclusion: The ELANA procedure requires a meticulous and careful operative technique. Morbidity and especially mortality rates, usually unrelated to ELANA, are comparable to those of contemporary series of conventional high-flow revascularization operations. This underscores the overall complexity of treating neurovascular pathologies by high-flow bypasses.

Objective: Anterior choroid artery aneurysms (AChAAs) constitute 2%-5% of all intracranial aneurysms. They are usually small, thin walled with one or several arteries originating at their base, and often associated with multiple aneurysms. In this article, we review the practical microsurgical anatomy, the preoperative imaging, surgical planning, and the microneurosurgical steps in the dissection and the clipping of AChAAs., Methods: This review, and the whole series on intracranial aneurysms (IAs), are mainly based on the personal microneurosurgical experience of the senior author (J.H.) in two Finnish centers (Helsinki and Kuopio) that serve, without patient selection, the catchment area in Southern and Eastern Finland., Results: These two centers have treated more than 10,000 patients with IAs since 1951. In the Kuopio Cerebral Aneurysm Database of 3005 patients with 4253 IAs, 831 patients (28%) had altogether 980 internal carotid artery (ICA) aneurysms, of whom 95 patients had 99 (2%) AChAAs. Ruptured AChAAs, found in 39 patients (41%), with median size of 6 mm (range = 2-19 mm), were associated with intracerebral hematoma (ICH) in only 1 (3%) patient. Multiple aneurysms were seen in 58 (61%) patients., Conclusions: The main difficulty in microneurosurgical management of AChAAs is to preserve flow in the anterior choroid artery originating at the base and often attached to the aneurysm dome. This necessitates perfect surgical strategy based on preoperative knowledge of 3 dimensional angioarchitecture and proper orientation during the microsurgical dissection., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Internal carotid artery bifurcation aneurysms form 2% to 9% of all IAs. They are more frequent in younger patients than other IAs. In this article, we review the practical microsurgical anatomy, the preoperative imaging, surgical planning, and the microneurosurgical steps in the dissection and the clipping of ICAbifAs., Methods: This review and the whole series on IAs are mainly based on the personal microneurosurgical experience of the senior author (JH) in 2 Finnish centers (Helsinki and Kuopio), which serve, without patient selection, the catchment area in Southern and Eastern Finland., Results: These 2 centers have treated more than 11 000 patients with IAs since 1951. In the Kuopio Cerebral Aneurysm Database of 3005 patients with 4253 IAs, 831 (28%) patients had altogether 980 ICA aneurysms, of whom 137 patients had 149 (4%) ICAbifAs. Ruptured ICAbifAs, found in 78 (52%) patients, with median size of 8 mm (range, 2-60 mm), were associated with ICH in 15 (19%) patients. Ten (7%) ICAbifAs were giant (> or = 25 mm). Multiple aneurysms were seen in 59 (43%) patients. The ICAbifAs represented 18% of all IAs ruptured before the age of 30 years., Conclusions: The main difficulty in microneurosurgical management of ICAbifAs is to preserve flow in all the perforators surrounding or adherent to the aneurysm dome. This necessitates perfect surgical strategy based on preoperative knowledge of 3D angioarchitecture and proper orientation during the microsurgical dissection.

Excimer laser-assisted nonocclusive anastomosis (ELANA) has been developed over the past 14 years for assistance in the creation of intracranial bypasses. The ELANA technique allows the creation of intracranial-intracranial and extracranial-intracranial bypasses without the need for temporary occlusion of the recipient artery, avoiding the inherent risk associated with occlusion time. In this review the authors discuss the technique and its indications, while reviewing the clinical results of the procedure. The technique itself is explained using cartoon drawings and intraoperative photographs. Advantages and disadvantages of the technique are also discussed.

Background: The M1As are located in the main trunk (M1) of the MCA, between the bifurcation of the ICA and the main bifurcation of M1. Proximal MCA aneurysms are often small and thin-walled, which makes their proper clipping tedious. There are few reports on their microsurgery., Methods: This review, and the whole series on intracranial aneurysms, is mainly based on the personal microneurosurgical experience of the senior author (JH) in 2 Finnish centers (Helsinki and Kuopio), which serve, without selection, the catchment area in the southern and eastern Finland., Results: These 2 centers have treated more than 10000 patients with aneurysm since 1953. We review the practical anatomy, preoperative planning, and avoidance of complications in the microsurgical dissection and clipping of M1As which form 7.4% of all intracranial and 14% of all MCA aneurysms in our patients., Conclusions: Proximal MCA aneurysms are often wide-necked and intimately connected to an M1 branch at its origin on M1, features that favor exosurgery rather than endosurgery. The direction and course of the parent and branching arteries and the orientation of the fundus are the most important factors affecting the efficacy and safety of clipping.

Since their introduction by Prof. Yaşargil in the 1960s, Microneurosurgical techniques have been the essentials of neurosurgical practice. Principles of Microneurosurgery are mainly based upon handling the lesions of different characteristics that can be localized in any part of the nervous system. Whereas the aim is to treat these lesions with efficacy and precision, the performance should be non-traumatic and minimally invasive. Delicate movements of instruments under the magnification of an operating microscope require a good knowledge of Microneurosurgical anatomy and experience. Professional teamwork is the essential part of Microneurosurgical operations. Fascinating approaches are not practical unless combined with appropriate positioning and optimal conduction of Neuroanesthesia. Although the neurosurgical operations are highly dependent on technological advancements, their use should be adjusted according to personal preferences and financial resources. To keep the operations simple and fast, and appreciate normal anatomy, only a limited array of instruments is preferable for use. The basic principles of Microneurosurgery discussed in this chapter are based on the Helsinki and Kuopio Neurosurgery practices in Finland, as well as the Senior Author's (J.H.) experience in approximately 10,000 microsurgery operations. The question to be addressed is: How does one perform operations safer and faster while preserving the normal anatomy?

Objective: To describe a surgical technique to retract the tentorial edge during the subtemporal approach initially introduced and used widely by Drake and Peerless to treat distal basilar artery aneurysms., Methods: One of the most important parts of the exposure is to reflect the edge of the tentorium downward by 1 cm or more and to tether it with a suture placed lateral to or behind the insertion of the trochlear nerve and then to the dura mater of the floor of the middle fossa. Surgical forceps or a sharp dural hook are used to elevate the tentorial edge, in front of the trochlear nerve. A small incision is made on the surface of the floor of the middle fossa using a sharp bipolar forceps, and a small straight microclip is inserted with one arm through the incision on the surface of the floor of the middle fossa and the other at the free margin of the tentorial edge., Results: The method described has been used by the senior author in more than 100 operations as a simple and fast means of tethering the free margin of the tentorial edge simply and quickly., Conclusion: We inserted a small straight microclip with one arm through the incision on the surface of the floor of the middle fossa and the other at the free margin of the tentorial edge as a fast and simple method of retracting the tentorial edge during a subtemporal approach.

Microneurosurgical techniques introduced by Prof Yasargil in the 1960s have increased the neurosurgeon's ability to operate in small and often very narrow and deep gaps. Microneurosurgical techniques-ensuring an almost bloodless field and mostly obviating need for transfusion-should be atraumatic and noninvasive to the already lesioned central nervous system tissues and structures. Instruments in microneurosurgery range from very short to very long and from sturdy to delicate, depending on the working depth, characteristics of tissues, and the microneurosurgical anatomy. However, to keep it simple and fast, and to appreciate normal anatomy, it is preferable to use only a limited array of instruments. Besides the use of instruments and the operating microscope, everything else in the neurosurgical arena should be optimized and professional, such as the positioning of the patient and the conduct of neuroanesthesia. This review of the very basics is distilled from the Helsinki and Kuopio neurosurgery practices in Finland and from the senior author's (JH) experience of close to 10,000 operations, and this is to encourage young neurosurgeons of the world-most of them working with limited resources-to continue to improve their microneurosurgical skills to serve their patients best.

Objective: To find out the effect of carmustine (bischloroethyl-nitrosourea) combined with a biodegradable polymer in the treatment of malignant (Grades III and IV) gliomas, applied locally, at the time of the primary operation., Methods: Prospective, randomized double-blind study of an active treatment group versus a placebo group. Conducted at the Departments of Neurosurgery of the University Hospitals of Helsinki, Tampere, and Turku in Finland and Trondheim in Norway. The study consisted of 32 patients (16 in each treatment group) enrolled between March 23, 1992, and March 19, 1993. The study was planned to include 100 patients but had to be terminated prematurely, because the drug that was being used had become unobtainable. The main outcome measures included the survival times of patients after the operations and the application of an active drug or placebo., Results: The median time from surgery to death was 58.1 weeks for the active treatment group versus 39.9 weeks for the placebo group (P = 0.012). For 27 patients with Grade IV tumors, the corresponding times were 39.9 weeks for the placebo group and 53.3 weeks for the active treatment group (P = 0.008). At the end of the study, six patients were still alive, five of whom belonged to the active treatment group., Conclusion: Carmustine applied locally in a biodegradable polymer at the time of primary operation, seems to have a favorable effect on the life span of patients with high-grade gliomas.

The octapeptide FLFQPQRF-NH2 or neuropeptide FF ('F8Famide'; FMRFamide-like peptide'; 'morphine-modulating peptide') has been isolated from the bovine brain. In this study, the ultrastructural localization of neuropeptide FF-like immunoreactivity was examined with pre-embedding immuno-electron microscopy in the nucleus of the solitary tract and in the posterior lobe of the pituitary gland of an adult rat. Neuropeptide FF-like immunoreactivity was detected only in neuronal structures of the medial and commissural nuclei of the solitary tract and in the neurohypophysis. In the medulla, the peroxidase-antiperoxidase reaction product was localized in large (100 nm) dense-cored vesicles and in the cytoplasm of the neuronal perikarya, dendrites and axon terminals. In the labeled terminals, small (50 nm) clear vesicles rimmed with the peroxidase-antiperoxidase reaction product were seen. Synaptic contacts of labeled perikarya and dendrites with unlabeled axon terminals were observed. Labeled axon terminals formed contacts with unlabeled dendrites and perikarya. In the posterior lobe of the pituitary gland, neuropeptide FF-like immunoreactivity was localized in nerve terminals frequently associated with blood vessels. The results suggest that neuropeptide FF-like peptides are localized exclusively in neuronal structures and that they are synthesized in cell somata and released from axon terminals. In the brain, neuropeptide FF-like peptides may act as neuromodulators involved in the regulation of autonomic functions. The localization of neuropeptide FF-like immunoreactivity in the neurohypophysis suggests endocrine regulatory functions of these peptides.