Antibodies to Epstein-Barr virus and MRI disease activity in multiple sclerosis.

BACKGROUND: Previous reports indicate an association between Epstein-Barr virus (EBV) antibody levels and multiple sclerosis (MS) disease activity, but the results have been conflicting. OBJECTIVES: The objective of this paper is to study if EBV antibody levels reflect MRI disease activity in MS and examine the potential for EBV antibody levels as biomarkers for treatment response. METHODS: A total of 87 MS patients were followed for two years prior to and during interferon beta (IFNB) treatment, with MRI examinations and serum measurement of IgM and IgG antibodies to viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA-1) and early antigen (EA). Associations between EBV antibody levels and MRI activity were assessed by a logistic regression model. RESULTS: Higher anti-EBNA-1 IgG levels were associated with increased MRI activity, OR = 2.95 (95% CI 1.07-8.10; p = 0.036) for combined unique activity (CUA; the sum of T1Gd+ lesions and new or enlarging T2 lesions). Although most patients were anti-VCA IgM negative, there was an inverse association, OR = 0.32 (95% CI 0.12-0.84; p = 0.021) with CUA during IFNB treatment. CONCLUSIONS: This study supports an association between anti-EBNA-1 IgG levels and MS disease activity. We also found an inverse association with anti-VCA IgM levels during IFNB treatment not previously described, indicating anti-VCA IgM as a possible biomarker for IFNB treatment response.

Retinol levels are associated with magnetic resonance imaging outcomes in multiple sclerosis.

BACKGROUND: Vitamin A has immunomodulatory properties and may regulate the transcription of genes involved in remyelination. OBJECTIVE: To investigate the association between retinol and disease activity in multiple sclerosis (MS). METHODS: Cohort study of 88 relapsing-remitting MS patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS study), followed prospectively for 24 months with repeated assessments of serum-retinol and magnetic resonance imaging (MRI). All patients were initiated on interferon ß-1a after month 6. RESULTS: Each 1 µmol/L increase in serum-retinol reduced the odds (95% confidence interval) for new T1 gadolinium enhanced (Gd(+)) lesions by 49 (8-70)%, new T2 lesions by 42 (2-66)%, and combined unique activity (CUA) by 46 (3-68)% in simultaneous MRI scans, and 63 (25-82)% for new T1Gd(+) lesions, 49 (3-73)% for new T2 lesions and 43 (12-71)% for CUA the subsequent month. Serum-retinol also predicted new T1Gd(+) and T2 lesions six months ahead. The associations were not affected by HLA-DRB1*15, or serum levels of 25-hydroxyvitamin D, eicosapentaenoic acid or docosahexaenoic acid. CONCLUSION: Serum retinol is inversely associated with simultaneous and subsequent MRI outcomes in RRMS.

Cognitive and neurological sequelae after stereoendoscopic disconnection of a hypothalamic hamartoma. A case study.

Hypothalamic hamartomas (HH) are congenital malformations of the hypothalamus, often generating medically refractory gelastic seizures. There is great risk of progression to various complex partial and generalized seizures and of cognitive and behavioral deterioration. Hence, various surgical approaches have been introduced to resect or disconnect the HH from surrounding tissue, and stereoendoscopic disconnection has been advocated as one of the most lenient approaches to sessile HH embedded in the third ventricle. In fact, no long-term neurological or cognitive impairments have hitherto been reported after this procedure. Yet, unforeseen complications may arise in any surgical intervention on this region. We found serious deterioration of memory and reading skills by comprehensive neuropsychological assessments pre- and postoperatively in a child who, before surgery, was age-appropriate with respect to cognitive, emotional, and behavioral development. The child also contracted a permanent oculomotor paresis. Our results are discussed in light of previous relevant findings.

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.

Cerebral microemboli and brain injury during carotid artery endarterectomy and stenting.

BACKGROUND AND PURPOSE: Cerebral microembolic signals detected by transcranial Doppler are frequent during carotid angioplasty with stenting and carotid endarterectomy (CEA). Their potential harmful effects on the brain are, however, unclear. The aim of this study was to relate the frequency and type of per-procedural microembolic signals to procedure-related ipsilateral ischemic strokes and new ipsilateral ischemic lesions on diffusion-weighted cerebral MRI. METHODS: Eighty-five patients who were prospectively treated with CEA (61) or carotid angioplasty with stenting (30) for high-grade (>/=70%) internal carotid artery stenoses were monitored during the procedures using multifrequency transcranial Doppler with embolus detection and differentiation. Pre- and postprocedural cerebral diffusion-weighted cerebral MRIs were performed on a subset of patients. RESULTS: Solid and gaseous microemboli were independently associated with procedure-related ipsilateral ischemic strokes (solid: P=0.027, gaseous: P=0.037) or new ipsilateral diffusion-weighted cerebral MRI lesions (solid: P=0.043, gaseous: P=0.026). Microembolic signals were detected during all procedures except one (CEA); 17% and 21% of all emboli were solid during carotid angioplasty with stenting and CEA, respectively. Patients undergoing carotid angioplasty with stenting had more solid (P<0.001) and gaseous (P<0.001) emboli and more new ipsilateral ischemic strokes (P=0.033) compared with patients undergoing CEA. Echolucent plaques (P=0.020) and preprocedural diffusion-weighted cerebral MRI ischemic lesions (P=0.002) were associated with increased numbers of solid emboli. CONCLUSIONS: Solid and gaseous microemboli were increased in patients with procedure-related ipsilateral ischemic strokes or new diffusion-weighted cerebral MRI lesions, which suggests that both solid and gaseous emboli may be harmful to the brain during CEA and carotid angioplasty with stenting.

[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.

[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.

Blood blister-like aneurysms of the internal carotid artery trunk causing subarachnoid hemorrhage: treatment and outcome.

OBJECT: The object of this study was to evaluate cases of subarachnoid hemorrhage (SAH) from ruptured blood blister-like aneurysms (BBAs) of the internal carotid artery (ICA) trunk. METHODS: The authors performed a single-center, retrospective study. Data analyzed were patient age, sex, Hunt and Hess grade, Fisher grade, time from SAH to hospitalization, aneurysm size and location, collateral capacity of the circle of Willis, time from hospitalization to aneurysm repair, type of aneurysm repair, complications, and Glasgow Outcome Scale (GOS) score at follow-up. RESULTS: A total of 211 patients suffered SAH from ICA aneurysms. Of these, 14 patients (6.6%) had ICA trunk BBAs; 6 men and 8 women. The median age was 47.8 years (range 29.9-67.7 years). The Hunt and Hess grade was IV or V in 7 cases, and SAH was Fisher Grade 3 + 4 in 6. All aneurysms were small (< 1 cm), without relation to vessel bifurcations, and usually located anteromedially on the ICA trunk. Three patients were treated with coil placement and 11 with clip placement. Of the 7 patients in whom the ICA was preserved, only 1 had poor outcome (GOS Score 2). In contrast, cerebral infarcts developed in all patients treated with ICA sacrifice, directly postoperatively in 2 and after delay in 5. Six patients died, 1 survived in poor condition (GOS Score 3; p < 0.001). CONCLUSIONS: Internal carotid BBAs are rare, small, and difficult to treat endovascularly, with only 2 of 14 patients successfully treated with coil placement. The BBAs rupture easily during surgery (ruptured in 6 of 11 surgical cases). Intraoperative aneurysm rupture invariably led to ICA trap ligation. Sacrifice of the ICA within 48 hours of an SAH led to very poor outcome, even in patients with adequate collateral capacity on preoperative angiograms, probably because of vasospasm-induced compromise of the cerebral collaterals.

[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.

Anatomical features of the cervical spinal canal in Chiari I deformity with presyrinx: A case-control study.

Purpose The relationship between syringomyelia and presyrinx, characterized by edema in the spinal cord, has not been firmly established. Patients with syringomyelia have abnormal spinal canal tapering that alters cerebrospinal fluid flow dynamics, but taper ratios in presyrinx have never been reported. We tested the hypothesis that presyrinx patients have abnormal spinal canal tapering. Materials and methods At six medical institutions, investigators searched the PACS system for patients with Chiari I and spinal cord edema unassociated with tumor, trauma, or other evident cause. In each case taper ratios were calculated for C1 to C4 and C4 to C7. In two age- and gender-matched control groups, Chiari I patients with no syringomyelia and patients with normal MR scans, the same measurements were made. Differences between groups were tested for statistical significance with t tests. Results The study enrolled 21 presyrinx patients and equal numbers of matched Chiari I and normal controls. C4 to C7 taper ratios were positive and steeper in presyrinx patients than in the normal controls ( p = 0.04). The upper cervical spine, C1 to C4, tapered negatively in cases and controls without significant differences between the groups. The difference in degree of tonsillar herniation was statistically significant between presyrinx patients and Chiari I controls ( p = 0.01). Conclusions Presyrinx patients have greater than normal positive tapering in the lower cervical spine and greater degree of tonsillar herniation than the controls.

[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.

No association of tobacco use and disease activity in multiple sclerosis.

OBJECTIVE: To study whether tobacco use is associated with MRI and clinical disease activity in patients with multiple sclerosis (MS). METHODS: Prospective cohort study of 87 patients with relapsing-remitting MS originally included in a randomized placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS Study). Serum levels of cotinine (biomarker of tobacco use) were analyzed at baseline and every 6 months for 2 years. MRI activity was assessed at baseline and monthly for 9 months and after 12 and 24 months. RESULTS: Fifty-three patients (61%) had serum cotinine levels ≥85 nmol/L on ≥60% of the measurements and were considered tobacco users and 34 (39%) had cotinine levels <85 nmol/L, consistent with non-tobacco use. There was no association between tobacco use and the occurrence of new gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, or their aggregate (combined unique activity). Furthermore, there was no association between cotinine levels and MRI activity for the tobacco users, and tobacco users did not have more relapses or Expanded Disability Status Scale progression. CONCLUSION: Our results indicate that tobacco use does not directly influence MRI activity or relapse rate in MS. This may implicate that the reported association between smoking and MS disease progression could be mediated through other mechanisms.