Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients: a position paper endorsed by ESMINT and ESNR : part I: Current situation and major research questions.

A new era of stroke treatment may have begun with mechanical thrombectomy (MT) by fully deployed closed-cell self-expanding stents (stent-triever). Multiple case series and the first randomised controlled trials (RCTs) have now been published. More studies are under way involving large numbers of patients, which in turn has resulted in less strict "pragmatic" study protocols. Problems with current trials include a lack of standardisation in the conduct of the recanalisation procedure, the definition of primary endpoints such as the grade of arterial recanalisation and tissue reperfusion, and the post-surgical care provided. In Part 1 of this two part series, we outline the current situation and the major research questions.

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - a position paper endorsed by ESMINT and ESNR : part II: methodology of future trials.

Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.

[Epilepsy surgery--assessment and patient selection]. / Epilepsikirurgi--utredning og pasientseleksjon.

BACKGROUND: Considerable progress in diagnostic imaging and video EEG monitoring has improved the possibilities of localising the epileptogenic zone of the brain in patients with epilepsy. Despite the fact that epilepsy surgery can therefore be offered to more patients today than previously, relatively few patients are referred for an assessment for surgery. The aim of this review is to provide a brief account of the patient selection procedures and the investigations prior to epilepsy surgery. METHOD: The review is based on a literature search in PubMed and the personal experiences of the authors in this field. RESULTS: If the epilepsy does not respond to any kind of pharmacological treatment, and idiopathic generalised epilepsy and pseudoresistance have been ruled out, the patient should be evaluated for surgery. The evaluation is multidisciplinary, and the aim is to localise the epileptogenic zone, which can be identified by both structural and functional abnormalities. It must be determined before the operation whether the zone can be removed without leaving severe neurological or cognitive impairment. The best results after epilepsy surgery are seen in patients with a morphological substrate, particularly temporal lobe epilepsy associated with hippocampal sclerosis. INTERPRETATION: Epilepsy surgery plays an ever more important role in the treatment of patients with drug resistant seizures. Doctors who treat epileptic patients should refer candidates for surgery at an early stage of the disease.

Plea of the defence-critical comments on the interpretation of EVA3S, SPACE and ICSS.

Three randomised controlled trials (RCTs) comparing outcomes after carotid artery stenting (CAS) with carotid endarterectomy (CEA) have recently been published. Recent systematic reviews have recommended that CAS is no longer justified for patients suitable for CEA. Indeed, in many centres, pooled data of RCTs show higher peri-operative risk of performing CAS vs. CEA with comparable long-term efficacy. Due to limitations in SPACE, EVA3S and ICSS study design and conduct, the inferiority of CAS to CEA as a method remains inconclusive. The goal of this review is not to discredit these trials but to develop a more differentiated and critical interpretation of the data and to create more discussion. It will discuss the necessity of RCTs for Interventional Neuroradiology in general and particular problems in study design (non-inferiority design and interpretation of results, clinical equipoise, study endpoints), practical study conduct difficulties (operator and centre experience, antiaggregation, timing of treatment) and the interpretation of the results (relation of internal and external validity, procedural complexity, the 68-year surprise, longer-term outcome). A premature rejection of CAS based on the data from these studies could harm future patients who would have had benefited from this procedure. For the time being, there is no reason why centres with good and independently controlled track records should stop performing CAS. Designing a single cooperative European trial that incorporates the lessons learned would be major step forward.

[Neurofibromatosis type 2 and auditory brainstem implantation]. / Nevrofibromatose type 2 og auditorisk hjernestammeimplantat.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a rare and severe autosomal dominant disorder caused by mutations in a tumour suppressor gene. This article reviews NF2 and its treatment with auditory brainstem implantation. MATERIAL AND METHODS: The review is based on the authors' experience with the disease and literature identified through a non-systematic search of PubMed. RESULTS: NF2 is caused by loss-of-normal function of the tumour suppressor protein merlin. Merlin normally suppresses cell growth and proliferation. The clinical picture is dominated by neurological symptoms, caused by multiple tumours - mainly schwannomas and meningeomas. The hallmark of the disease is development of bilateral vestibular schwannomas, and the most common presenting symptom in adults is progressive hearing loss. Presenile cataract, ocular motility disorders, peripheral neuropathy and skin tumours are other common findings. The majority of patients become deaf, many patients become severely disabled and life expectancy is reduced. The goal of management is conservation of function and maintenance of quality of life. Auditory brainstem implants stimulate the cochlear nucleus directly and provide substantial auditory benefits to patients with NF2. INTERPRETATION: A multidisciplinary approach in specialty centres is recommended. Management by an experienced team reduces mortality and improves outcome after surgery. Auditory brainstem implantation is an important part of the hearing rehabilitation in these patients. Emerging knowledge of the molecular disease mechanisms offers hope for new therapeutic strategies.

[Carotis stenosis-open surgery and endovascular treatment]. / Apen kirurgi og endovaskulaer behandling av carotisstenose.

BACKGROUND: Patients who have a carotid stenosis and suffer a TIA have a high risk of stroke shortly afterwards, and should be offered prophylactic surgery within 2 weeks. We present the results for treatment of carotid stenosis from Oslo University Hospital, Rikshospitalet in the period 2001-2008. MATERIAL AND METHODS: The material comprises all patients treated for carotid stenosis, with either carotid thrombendarterectomy (CEA) or endovascular stenting, in the period 2001-2008. All procedures were prospectively recorded in a database. A neurologist examines the patients before, and 1 and 12 months after treatment. RESULTS: 408 carotid stenoses were treated in the observation period. Median age (range) was 68 years (21-85), and 125 (31 %) patients were women. 206 (64.2 %) of the 321 stenoses treated with CEA were symptomatic as were 53 (61 %) of the 87 who underwent endovascular treatment (87). The rate of serious stroke and/or death within 30 days after CEA was 1.9 % for symptomatic stenoses and 1.1 % for asymptomatic stenoses; after endovascular treatment the corresponding numbers were 1.9 % and 3.8 %. INTERPRETATION: We have offered endovascular treatment to patients in whom surgery would be complicated (restenosis, radiation-induced stenosis etc). Results could therefore not be compared within our material. CEA prevents stroke, and it has been shown that the risk of complications is higher with stenting. Evaluation and treatment of patients with carotid stenosis should be included in the planned National guidelines for stroke treatment.

[Subarachnoid haemorrhage--diagnosis and management]. / Subaraknoidalblødning--diagnostikk og behandling.

INTRODUCTION: Subarachnoid haemorrhage (SAH) causes 3% of all strokes and is caused by a ruptured cerebral aneurysm in four of five cases. This review article presents an update of knowledge on symptoms, diagnosis and management of SAH. MATERIAL AND METHODS: This article is based on selected literature and the authors' clinical experience. RESULTS AND INTERPRETATION: The mortality of SAH is approximately 50% and one out of three survivors have permanent disabling neurological symptoms. Patients with suspected or diagnosed SAH need urgent examination and treatment. A large randomised multicentre study (International Subarachnoid Aneurysm Trial) suggests that endovascular repair with coiling may be less traumatic than microsurgery. Not all patients are suitable for endovascular treatment, despite new tools like balloon- and stent-assisted coiling. Centres that treat patients with SAH should have both methods available at all hours. The management of these patients involves advanced neuro-intensive care, and co-operation between neurosurgeons, neuroradiologists and neuroanestesiologists.

[Operative and endovascular treatment of carotis stenosis--when is it indicated?]. / Operativ og endovaskulaer behandling av carotisstenose--når er det aktuelt?

BACKGROUND: Stroke is the most common cause of disability in Norway. Most strokes are ischemic, and 25-30% are caused by emboli from atherosclerotic plaques in pre-cerebral arteries. The aim of this study was to review the literature on effectiveness of stroke prevention by surgical and endovascular treatment of carotid bifurcation stenoses. MATERIAL AND METHODS: Search of the PubMed and Cochrane Library. Relevant textbook chapters and personal experience have also supported the evaluation. RESULTS AND INTERPRETATION: Prevention of stroke by carotid endarterectomy is documented in several large randomised controlled trials. For carotid stenoses with reduced diameters of more than 50%, a significant reduction of 5-year stroke risk is achieved with surgery and best medical treatment, compared to best medical treatment alone. The benefit is greatest with symptomatic stenoses, especially if surgery is performed shortly after onset of symptoms. Patients with transient ischemic attack (TIA), minor stroke or amaurosis fugax should without delay be referred to an ultrasound examination of the carotid. Surgery as soon as possible is indicated if > 70% stenosis is found, and for men also with moderate stenoses (50-69%). The benefit is less pronounced for women with moderate stenosis and they should be considered individually. In asymptomatic patients, surgery reduces the 5-year stroke risk from 11.8 to 6.4%. The indication for surgery in asymptomatic patients must be balanced against age, co-morbidity, and the quality of surgery at each centre. A low operative morbidity is a prerequisite. No comparable evidence exists for endovascular treatment, and it is recommended that patients eligible for stent treatment are included in ongoing randomised trials comparing stent treatment and endarterectomy.

[Endogenous Cushing's syndrome]. / Endogent Cushings syndrom.

BACKGROUND: Untreated endogenous Cushing's syndrome is a serious condition with high morbidity and mortality. New diagnostic procedures make today's assessment more accurate. We describe which tests should be done when there is suspicion of the syndrome. Treatment options are mentioned. MATERIAL AND METHODS: The paper is based on current international literature and reflects the experience of the authors. RESULTS AND INTERPRETATION: Endogenous Cushing's syndrome is caused by elevated cortisol levels. The reason can be overproduction of ACTH or an adrenocortical pathology. It should be considered when combinations of symptoms like central obesity, proximal muscle weakness, striae and menstrual irregularities are seen. Osteoporosis and impotence are other important symptoms. Diagnosis of Cushing's syndrome is often challenging. Measurement of urinary free cortisol or overnight dexamethasone suppression test has usually been performed initially. Midnight salivary cortisol seems promising as an alternative. The final diagnosis is often made after a combined evaluation of dynamic tests. The first-line treatment of endogenous Cushing's syndrome is surgery.

Cerebral foreign body reaction after carotid aneurysm stenting.

Flow diverter stents are new important tools in the treatment of large, giant, or wide-necked aneurysms. Their delivery and positioning may be difficult due to vessel tortuosity. Common adverse events include intracranial hemorrhage and ischemic stroke, which usually occurs within the same day, or the next few days after the procedure. We present a case where we encountered an unusual intracerebral complication several months after endovascular treatment of a large left internal carotid artery aneurysm, and where brain biopsy revealed foreign body reaction to hydrophilic polymer fragments distally to the stent site. Although previously described, embolization of polymer material from intravascular equipment is rare. We could not identify any other biopsy verified case in the literature, with this particular presentation of intracerebral polymer embolization--a multifocal inflammation spread out through the white matter of one hemisphere without hemorrhage or ischemic changes.

[Hormonally inactive pituitary adenomas]. / Ikke-hormonproduserende hypofyseadenomer.

BACKGROUND: This paper surveys hormonally inactive pituitary tumours on the basis of the current international literature; it also reflects the experience of the authors. INTERPRETATION: Pituitary tumours are frequently diagnosed and usually show a low potential for growth. Although benign they may invade adjacent structures such as the cavernous and sphenoid sinuses. The diagnosis is usually made on the basis of pituitary failure or visual problems, or incidentally. Tumour debulking or removal, usually by transsphenoidal surgery, is indicated if there is a compression of the optic chiasm or if the tumour shows signs of growth on consecutive MRI scans. Surgery is an effective treatment of these tumours, with little risk of complications. Repeated surgery, either transsphenoidally or by craniotomy, is indicated if chiasmal decompression is not achieved initially. Fractionated single beam irradiation or stereotactic radiosurgery is indicated in cases where there is a residual of growing tumours that may not be removed surgically.

Increasing serum levels of vitamin A, D and E are associated with alterations of different inflammation markers in patients with multiple sclerosis.

To explore the relationships between vitamin A, D and E and inflammation in relapsing remitting multiple sclerosis, we assessed their associations with 11 inflammation markers in 9 serial serum samples from 85 patients, before and during interferon-ß1a treatment. A negative association was found between vitamin A and pentraxin 3 independent of interferon-ß1a use, whereas positive associations between vitamin D and interleukin-1 receptor antagonist and secreted frizzled-related protein 3 were seen before, and between vitamin E and chemokine (C-X-C motif) ligand 16 during interferon-ß1a treatment. These findings suggest associations with diverse inflammatory pathways, which may be differentially influenced by interferon-ß1a treatment.

Inflammation markers in multiple sclerosis: CXCL16 reflects and may also predict disease activity.

BACKGROUND: Serum markers of inflammation are candidate biomarkers in multiple sclerosis (MS). ω-3 fatty acids are suggested to have anti-inflammatory properties that might be beneficial in MS. We aimed to explore the relationship between serum levels of inflammation markers and MRI activity in patients with relapsing remitting MS, as well as the effect of ω-3 fatty acids on these markers. METHODS: We performed a prospective cohort study in 85 relapsing remitting MS patients who participated in a randomized clinical trial of ω-3 fatty acids versus placebo (the OFAMS study). During a period of 24 months 12 repeated magnetic resonance imaging (MRI) scans and nine serum samples were obtained. We measured 10 inflammation markers, including general down-stream markers of inflammation, specific markers of up-stream inflammatory pathways, endothelial action, and matrix regulation. RESULTS: After Bonferroni correction, increasing serum levels of CXCL16 and osteoprotegerin were associated with low odds ratio for simultaneous MRI activity, whereas a positive association was observed for matrix metalloproteinase (MMP) 9. CXCL16 were also associated with low MRI activity the next month, but this was not significant after Bonferroni correction. In agreement with previously reported MRI and clinical results, ω-3 fatty acid treatment did not induce any change in the inflammation markers. CONCLUSIONS: Serum levels of CXCL16, MMP-9, and osteoprotegerin reflect disease activity in MS, but are not affected by ω-3 fatty acid treatment. CXCL16 could be a novel biomarker and potential predictor of disease activity in MS.

Reactive expansive intracerebral process as a complication of endovascular coil treatment of an unruptured intracranial aneurysm: case report.

BACKGROUND AND IMPORTANCE: As a consequence of the increased use of endovascular coiling of intracranial aneurysms, a growing number of case reports on complications are being reported. This article presents a case with a previously undescribed complication of coil treatment: a reactive, noninfectious process after coiling of an unruptured intracranial aneurysm CLINICAL PRESENTATION: A 60-year-old hypertensive woman with hypoxic encephalopathy after respiratory arrest following a total thyroidectomy had extensive intentional myoclonus and reduced quality of life as sequelae. An asymptomatic 15-mm internal carotid artery bifurcation aneurysm was discovered on magnetic resonance imaging (MRI) 6 months after the thyroidectomy. After documented growth, the aneurysm was treated endovascularly with bare platinum Guglielmi detachable coils. Three months later, an expansion in the right frontal lobe cranially to the coiled aneurysm was observed. The lesion had grown at the 12-month postcoil MRI and, because of its increasing mass effect, was resected through a craniotomy 2 years after the coiling. As a result of lesion regrowth and cyst formation, she underwent a new craniotomy 5 years later with excision of the now 21-mm large coiled aneurysm, internal carotid artery clip reconstruction, and lesionectomy. Five months postoperatively, the process had not recurred. No signs of malignancy or infection were observed during the histological evaluation of the resected tissue. The tissue is described as a reactive, noninfectious process, most likely resulting from the coils acting as a foreign body. CONCLUSION: This article presents a case with a reactive expansive intracerebral process as a complication to endovascular coil treatment of an unruptured intracranial aneurysm.

Angiographic balloon test occlusion and therapeutic sacrifice of major arteries to the brain.

OBJECTIVE: Treatment of certain cerebral aneurysms, caroticocavernous fistulae, and tumors of the neck or cranial base may involve therapeutic arterial sacrifice, which requires preoperative knowledge of the feasibility of permanent occlusion of the internal carotid artery (ICA) or vertebral artery or arteries. METHODS: Retrospective study of transcranial Doppler ultrasonography-monitored angiographic balloon test occlusion and therapeutic sacrifice of the ICA or vertebral artery. RESULTS: We performed transcranial Doppler-guided balloon test occlusion in 136 patients at a procedural risk equivalent to that of conventional neuroangiography, and with correct prediction of the hemodynamic result of therapeutic arterial sacrifice in all instances. Patients with an immediate drop in ipsilateral middle cerebral artery (MCA) velocity to 65% or more of baseline values upon ICA balloon occlusion tolerated ICA sacrifice well, whereas hemodynamic infarction is likely in those with a corresponding drop in MCA velocity to 54% or less. When ICA balloon occlusion caused a drop in MCA velocity to between 55 and 64% of baseline, the pulsatility of the MCA signal had to be analyzed. Patients who tolerated bilateral vertebral artery closure had reversal of flow and an increase in velocity in the P1 section of the posterior cerebral artery. In 212 patient-years of observation after therapeutic arterial sacrifice, no de novo aneurysms formed. CONCLUSION: Angiographic balloon test occlusion with transcranial Doppler monitoring can be performed ultra-swiftly at a risk equal to conventional neuroangiography and with correct prediction of the hemodynamic outcome of arterial sacrifice. Elective therapeutic arterial occlusion is a safe and efficient treatment of large cerebral aneurysms and caroticocavernous fistulae.

The eyes remember it: oculography and pupillometry during recollection in three amnesic patients.

Two patients (TC and SS) with lesions that included the hippocampal regions (predominantly on the left side) were severely impaired in their recall of simple, verbally stated facts. However, both patients remembered spatial information that was temporally associated with semantic information. Specifically, TC and SS could not recall explicitly the content of an episode, but their spontaneous oculomotor behavior showed that they retained some information about the event as their gaze automatically returned to the locations on the computer screen where visual information had been paired to verbally presented information. Thus, this spatial information is implicit, automatically retrieved, and eye-based, as when one patient (TC) was asked to point with the finger to the same positions he was impaired. In addition, in an old/new recognition task, TC and SS and an additional patient, OB, showed significant changes in eye pupil diameter when viewing novel visual stimuli compared to stimuli that they had previously seen, also when they (incorrectly) declared with confidence that an old item was new. The spared memory of these patients, despite severe amnesia for the learning episodes, is characterized by a re-enactment of previous eye fixations that were associated with each (forgotten) episode and physiological responses (as indexed by pupillometry) to previously seen stimuli. Such spared memory can be seen as a type of "snapshot" memory, which automatically processes eye-based spatial information and whose content remains implicit. Finally, we surmise on the basis of the neuroanatomical findings of these patients, that neural substrates in the spared (right) hemisphere might support both the eye fixations' re-enactment and implicit visual pattern recognition.

Changes in verbal and nonverbal memory following anterior temporal lobe surgery for refractory seizures: effects of sex and laterality.

We studied the effects on verbal and nonverbal memory of anterior temporal lobe (ATL) surgery for epilepsy in 91 patients (46 men, 45 women), all of whom had left-hemisphere dominance for speech. Patients were divided into four groups according to sex and laterality of the excision. The memory tasks were administered shortly before surgery, 6 months postoperatively, and at a 2-year follow-up. Test scores were submitted to repeated-measures analyses of variance. We found that men treated with left temporal resection declined significantly in long-delay verbal memory after surgery, whereas no clear pre- to postoperative sex differences were found with respect to other verbal memory scores. Only the results on long-delay verbal memory confirm previous findings, showing a greater vulnerability of verbal memory to left ATL surgery in men than in women. Women with left temporal excisions obtained particularly poor scores on a long-delay nonverbal memory test preoperatively, but improved their performance on this test significantly after surgery. The seemingly gradual improvement during the 2-year follow-up suggests a plastic process.