Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

Predictors of outcome after endovascular treatment for tandem occlusions: a single center retrospective analysis.

BACKGROUND: The endovascular treatment procedure in tandem occlusions (TO) is complex compared to single occlusion (SO) and optimal management remains uncertain. The aim of this study was to identify clinical and procedural factors that may be associated to efficacy and safety in the management of TO and compare functional outcome in TO and SO stroke patients. METHODS: This is a retrospective single center study of medium (MeVO) and large vessel occlusion (LVO) of the anterior circulation. Clinical, imaging, and interventional data were analyzed to identify predictive factors for symptomatic intracranial hemorrhage (sICH) and functional outcome after endovascular treatment (EVT) in TO. Functional outcome in TO and SO patients was compared. RESULTS: Of 662 anterior circulation stroke patients with MeVO and LVO stroke, 90 (14%) had TO. Stenting was performed in 73 (81%) of TO patients. Stent thromboses occurred in 8 (11%) patients. Successful reperfusion with modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was achieved in 82 (91%). SICH occurred in seven (8%). The strongest predictors for sICH were diabetes mellitus and number of stent retriever passes. Good functional clinical outcome (mRS ≤ 2) at 90-day follow up was similar in TO and SO patients (58% vs 59% respectively). General anesthesia (GA) was associated with good functional outcome whereas hemorrhage in the infarcted tissue, lower mTICI score and history of smoking were associated with poor outcome. CONCLUSIONS: The risk of sICH was increased in patients with diabetes mellitus and those with extra stent-retriever attempts. Functional clinical outcomes in patients with TO were comparable to patients with SO.

Mechanical thrombectomy in acute ischaemic stroke. / Mekanisk trombektomi ved akutt hjerneinfarkt.

Mechanical thrombectomy is now the standard treatment for acute ischaemic stroke with occlusion of a carotid or intercranial artery. With occlusions of this type, thrombolytic treatment often has limited effect. The therapeutic outcome with the use of thrombectomy is time-dependent, and a personalised approach to indication is always necessary. To achieve the best possible results, the main prerequisites are good clinical procedures, an optimal patient pathway, high neuroradiological competence and coordinated, interdisciplinary teams.

Brain monitoring in hospitals needs to be strengthened. / Hjerneovervåking i sykehusene må styrkes.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

Cerebral venous thrombosis after COVID-19. / Cerebral venetrombose etter covid-19.

BACKGROUND: There is emerging evidence of an increased risk of venous thromboembolism as well as several reports of cerebral venous thrombosis in COVID-19. CASE PRESENTATION: A previously healthy man in his fifties was admitted due to sudden confusion and reduced consciousness. One month earlier the patient had symptoms with headache, fever, dry cough, vomiting and diarrhoea and reduced sense of taste and smell. He was diagnosed with COVID-19 and the symptoms were mainly resolved within three weeks. On admission the patient was disorientated with aphasia. Brain imaging revealed a haemorrhagic infarction in the left temporal lobe due to thrombosis of the left transverse sinus and low-molecular weight heparin was instituted. On follow-up four months later, there was clinical improvement with only slight problems with short term memory and concentration. INTERPRETATION: This case illustrates the risk of serious neurological complications due to cerebral venous thrombosis in COVID-19.

Clinical outcome after thrombectomy in patients with MeVO stroke: importance of clinical and technical factors.

BACKGROUND AND AIMS: Whereas high-level evidence has been proven for safety and efficacy of endovascular treatment (EVT) in large vessel occlusion (LVO) stroke, the evidence for EVT in medium vessel occlusion (MeVO) in both sexes and different age groupremains to be answered. The aim of this study was to evaluate the importance of clinical and technical parameters, focusing on sex, age and EVT procedural factors, on functional outcome in primary MeVO (pMeVO) strokes. METHODS: 144 patients with pMeVO in the MCA territory from the Oslo Acute Reperfusion Stroke Study (OSCAR) were included. Clinical and radiological data were collected including 90-day mRS follow-up. RESULTS: Successful reperfusion with modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was achieved in 123 patients (84%). Good functional outcome (mRS ≤ 2) at 90-day follow-up was achieved in 84 patients (61.8%). Two or more passes with stent retriever was associated with increased risk of SAH, poor mTICI and poor functional outcome. In average, women had 62 min longer ictus to recanalization time compared to men. Age over 80 years was significantly associated with poor outcome and death. CONCLUSION: In pMeVO patients, TICI score and number of passes with stent retriever were the main technical factors predicting mRS ≤ 2. Good clinical outcome occurred almost twice as often in patients under 80 years of age compared to patients over 80 years. Women with MeVO strokes had significant longer time from ictus to recanalization; however, this did not affect the clinical outcome.

Seizure control after late introduction of anakinra in a patient with adult onset Rasmussen's encephalitis.

Neuroinflammation has been considered an important pathophysiological process involved in epileptogenesis and may provide possibilities for new treatment possibilities. We present the case of a 45-year-old female with drug resistant epilepsy and progressive right-sided cerebral hemiatrophy associated with adult onset Rasmussen's encephalitis. Over a period of 26 years, she was treated with 14 different antiseizure medications, intravenous immunoglobulins, glucocorticosteroids, underwent two operations with focal resection and subpial transections, and tried out trigeminal nerve stimulation. Extensive blood tests, including antibodies relevant for autoimmune encephalitis, and brain biopsy did not show any signs of neuroinflammation. Eventually, the patient received the interleukin-1 receptor antagonist, anakinra. Within 1-2 days after injection, seizure frequency decreased significantly, and, after one week, the seizures stopped completely. Anakinra treatment was continued for 2 months. Stopping medication led to a relapse of seizures after 2 weeks, with a frequency of up to 45 seizures per day. Reintroduction of anakinra led to rapid recovery. Treatment with anakinra was continued for 7 months. The treatment was discontinued in April 2020, and the patient has been completely seizure free since then. There have been no other changes in antiseizure medication.

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.

Predictive modeling in glioma grading from MR perfusion images using support vector machines.

The advantages of predictive modeling in glioma grading from MR perfusion images have not yet been explored. The aim of the current study was to implement a predictive model based on support vector machines (SVM) for glioma grading using tumor blood volume histogram signatures derived from MR perfusion images and to assess the diagnostic accuracy of the model and the sensitivity to sample size. A total of 86 patients with histologically-confirmed gliomas were imaged using dynamic susceptibility contrast (DSC) MRI at 1.5T. Histogram signatures from 53 of the 86 patients were analyzed independently by four neuroradiologists and used as a basis for the predictive SVM model. The resulting SVM model was tested on the remaining 33 patients and analyzed by a fifth neuroradiologist. At optimal SVM parameters, the true positive rate (TPR) and true negative rate (TNR) of the SVM model on the 33 patients was 0.76 and 0.82, respectively. The interobserver agreement and the TPR increased significantly when the SVM model was based on an increasing sample size (P < 0.001). This result suggests that a predictive SVM model can aid in the diagnosis of glioma grade from MR perfusion images and that the model improves with increasing sample size.

[A ten-year old boy with progressive neurologic outcome]. / En ti år gammel gutt med progredierende nevrologiske utfall.

BACKGROUND: Rasmussen's encephalitis is a rare chronic inflammatory disease with unknown etiology. Patients with this condition have symptoms of intractable partial epilepsy, often with epilepsia partialis continua combined with a progressive hemiparesis. MATERIAL AND METHODS: The history of a Norwegian ten-year old boy with Rasmussen's encephalitis is described. RESULTS AND INTERPRETATION: The patient had clinical symptoms of Rasmussen's encephalitis. He had intractable partial epilepsy including epilepsia partialis continua. Cerebral MRI showed unilateral right-sided cerebral atrophy and foci of increased signal intensity in cortical grey and subcortical white matter. The boy was operated with right-sided hemispherectomy and is postoperatively seizure free. To our knowledge, this is the first published Norwegian child with Rasmussen's encephalitis. The disorder may be underdiagnosed in Norway. It is important to recognise this disease as early as possible.

Comparison of cerebral embolization during off-pump and on-pump coronary artery bypass surgery.

BACKGROUND: Coronary artery bypass surgery with cardiopulmonary bypass carries a significant risk of perioperative brain injury. At least 1% to 5% will suffer a stroke, and at 3-months postoperatively approximately 30% are reported to have cognitive impairment assessed by neuropsychologic testing. In off-pump surgery cardiopulmonary bypass is not used and instrumentation on the ascending aorta is reduced. The main aim of this study was to assess if off-pump surgery reduces intraoperative cerebral embolization. METHODS: This was a prospective and randomized study of two comparable groups with regard to age, sex, years of education, preoperative cognitive functioning, and surgical characteristics. Fifty-two patients (29 off-pump) were monitored by the use of transcranial Doppler ultrasound for cerebral microembolization during surgery. Preoperative and postoperative clinical, cerebral magnetic resonance imaging, and neuropsychologic examinations were also carried out. RESULTS: There was a significant reduction in the number of cerebral microemboli during off-pump compared with on-pump surgery (16.3 [range 0 to 131] versus 90.0 [range 15 to 274], p < 0.0001). No significant difference with regard to the incidence of neuropsychologic performance (decline in 29% off-pump, 35% on-pump) or neuroradiologic findings at 3 months was found, and there was no association between the number of cerebral microemboli and cognitive outcome. CONCLUSIONS: This study clearly demonstrates that off-pump surgery leads to a reduction in intraoperative cerebral microembolization. A significant reduction in the number of off-pump patients with cognitive decline or ischemic brain lesions on cerebral magnetic resonance imaging could not be demonstrated in this relatively small patient population.

Use of miglustat in a child with late-infantile-onset Niemann-Pick disease type C and frequent seizures: a case report.

INTRODUCTION: Niemann-Pick disease type C is a rare genetic lysosomal storage disease associated with impaired intracellular lipid trafficking and a range of progressive neurological manifestations. The influence of seizure activity on disease course and response to miglustat therapy is not currently clear. CASE PRESENTATION: Niemann-Pick disease type C homozygous for NPC1 mutation p.S940L [c. 2819 C>T] was diagnosed in a four-and-a-half-year-old Norwegian Caucasian girl. The patient, who died at eight years and seven months of age, had a history of prolonged neonatal jaundice and subsequently displayed progressive neurological manifestations that started with delayed speech, ataxia, and gelastic cataplexy. A regimen of 100mg of miglustat three times a day was initiated when she was four years and 11 months old. She showed decreased neurological deterioration during about three and a half years of treatment. However, she displayed periods of distinct worsening that coincided with frequent epileptic seizures. Anti-epileptic therapy reduced seizure frequency and severity and allowed re-stabilization of her neurological function. Prior to her death, which was possibly due to acute cardiac arrest, seizure activity was well controlled. CONCLUSIONS: Miglustat delayed the expected deterioration of neurological function in this patient with p.S940L-homozygous late-infantile-onset Niemann-Pick disease type C and provided important quality-of-life benefits. This case demonstrates the importance of effective seizure control therapy in achieving and maintaining neurological stabilization in Niemann-Pick disease type C.

An autostereoscopic 3D display can improve visualization of 3D models from intracranial MR angiography.

PURPOSE: An autostereoscopic display with image quality comparable to ordinary 2D displays has recently been developed. The purpose of our study was to evaluate whether the visualization of static 3D models from intracranial time-of-flight (TOF) MR angiography (MRA) was improved by this display. METHODS: Maximum Intensity Projection (MIP) and Volume Rendering (VR) 3D models of intracranial arteries were created from ten TOF MRA datasets. Thirty-one clinically relevant intracranial arterial segments were marked in the TOF source images. A total of 217 markings were used. The markings were displayed in the 3D models as overlying red dots. Three neuroradiologists viewed the static 3D models on the autostereoscopic display, with the display operating either in autostereoscopic mode or in 2D mode. The task of the neuroradiologists was to correctly identify the marked artery. A paired comparison was made between arterial identification in autostereoscopic and 2D display mode. RESULTS: In 314 MIP 3D models, 233 arterial markings (74%) were correctly identified with the display operating in autostereoscopic mode versus 179 (57%) in 2D mode. Odds ratio for correct identification with autostereoscopic mode versus 2D mode was 2.17 (95% confidence interval 1.55-3.04, P < 0.001). In 337 VR 3D models, 256 markings (76%) were correctly identified using autostereoscopic mode and 229 (68%) using 2D mode (odds ratio 1.49, 95% confidence interval 1.06-2.09, P = 0.021). CONCLUSION: The visualization of intracranial arteries in static 3D models from TOF MRA can be improved by the use of an autostereoscopic display.

A randomized double-blind controlled trial of intra-annular radiofrequency thermal disc therapy--a 12-month follow-up.

The discTRODE probe applies radiofrequency (RF) current, heating the annulus to treat chronic discogenic low back pain. Randomized controlled studies have not been published. We assessed the long-term effect and safety aspects of percutaneous intradiscal radiofrequency thermocoagulation (PIRFT) with the discTRODE probe in a prospective parallel, randomized and gender stratified, double-blind placebo-controlled study. Twenty selected patients with chronic low back pain and a positive one-level pressure-controlled provocation discography were randomized to either intra-annular PIRFT or intra-annular sham treatment. A blinded interim analysis was performed when 20 patients had been followed for six months. The 6-month analysis did not reveal any trend towards overall effect or difference between active and sham treatment for the primary endpoint: change in pain intensity (0-10). The inclusion of patients was therefore discontinued. After 12 months the overall reduction from baseline pain had reached statistical significance, but there was no significant difference between the groups. The functional outcome measures (Oswestry Disability Index, and SF 36 subscales and the relative change in pain) appeared more promising, but did not reach statistical significance when compared with sham treatment. Two actively treated and two sham-treated patients reported increased pain levels, and in both groups a higher number was unemployed after 12 months. The study did not find evidence for a benefit of PIRFT, although it cannot rule out a moderate effect. Considering the high number, reporting increased pain in our study, we would not recommend intra-annular thermal therapy with the discTRODE probe.

Plasma levels of granzyme B are increased in patients with lipid-rich carotid plaques as determined by echogenicity.

Increased echolucency of carotid plaques is associated with an increased risk of ischemic stroke. Inflammation and apoptosis of vascular smooth muscle cells in the arterial wall are involved in the atherosclerotic process and destabilization of the plaque. Granzyme B (GrB) is a key mediator of T cell-mediated cytotoxicity, and we therefore hypothesized that this protease could distinguish echolucent from other plaques. Ultrasound-determined echolucency of atherosclerotic plaques was assessed prior to carotid endarterectomy/angioplasty in 57 consecutively recruited patients with high-grade internal carotid stenosis. Plasma levels of GrB were measured by enzyme immunoassay prior to surgery. Patients with carotid atherosclerosis had significantly higher plasma levels of GrB compared to healthy controls (n=16) (p<0.01), with particularly high levels in those with an echolucent lesion. While there were no differences in traditional cardiovascular risk factors or CRP between those with echolucent (n=16) and those with echogenic/heterogeneous (n=41) plaques, the echolucent group had markedly raised plasma levels of GrB (p<0.01). Patients with high levels of circulating granzyme B also had more ischemic lesions on cerebral MRI prior to surgery. Raised plasma levels of GrB in echolucent carotid plaques with increased frequency of cerebrovascular events suggest that GrB may be a marker of plaque instability.

Fractures in the proximal humerus: functional outcome and evaluation of 70 patients treated in hospital.

INTRODUCTION: Patients with proximal humeral fractures are mostly elderly. In addition to the proximal humeral fracture, they often have other injuries related to poor bone quality. The surgical treatment of proximal humeral fractures in elderly patients with comminuted fractures is associated with several problems and a high frequency of complications. The aims of this study were to evaluate patients with a proximal humeral fracture treated in a hospital, assess the outcome of the fracture treatment, and decide whether surgical treatment of displaced proximal humeral fractures is superior to conservative treatment or not. MATERIALS AND METHODS: Patients with fractures of the proximal part of the humerus treated in our hospital were followed during two different periods (14 and 10 months). The study in the first time period was retrospective in design, while in the second period the patients were followed prospectively. Seventy patients, (71% women) with a mean age of 71 years, were included in the study. A functional test was performed within 12-14 months after the injury using a modified Rowe shoulder score. Surgical treatment was performed in 15 patients (21%). Neither the surgical approach nor the implants used for osteosynthesis were standardized. Fifty-five patients (79%) were treated conservatively with a modified Velpeau bandage or a sling. RESULTS: The fractures were classified according to AO into type A (27%), type B (58%) and type C (14%). Osteoporotic risk factors were present in many of the patients, mainly characterized by other skeletal injuries than the proximal humeral fracture (43%). In the group of complex, displaced, non-impacted fractures B2, B3, C2, C3 included (20 fractures), the group treated conservatively had a mean Rowe score of 48/75 (64% of maximum score) and SD 16.8, while in the surgically treated group the mean score was 28/75 (38% of maximum score) and SD 8.1. The difference between the two treatments was significant, with a p-value of 0.01 in favour of the conservatively treated group. CONCLUSION: The number of patients in each of the fracture groups was low, but surgery did not benefit the patients with complex, displaced fractures in this study.

Cerebral ischemic injury and cognitive impairment after off-pump and on-pump coronary artery bypass grafting surgery.

BACKGROUND: Off-pump coronary artery bypass grafting surgery reduces the intraoperative cerebral embolic load and may therefore cause less brain injury. The main aim of this study was to compare off-pump and on-pump surgery with regard to the frequency of new postoperative cerebral ischemic lesions and the prevalence of postoperative cognitive impairment. We also assessed whether preoperative cerebral ischemic injury predicts the risk for cognitive dysfunction after surgery. METHODS: One hundred twenty patients with ischemic coronary artery disease were prospectively randomized to undergo off-pump or on-pump surgery. A detailed neuropsychological assessment and a cerebral magnetic resonance imaging examination were performed on the day before and at 3 months postoperatively. The neuropsychological assessment was repeated at 12 months. RESULTS: There was no significant (p = 0.17) difference between off-pump (8.2%) and on-pump (17.3%) surgery with regard to new postoperative cerebral lesions. The prevalence of cognitive impairment after surgery was also similar in the two groups (3 months: off-pump 20.4%, on-pump 23.1%, p = 0.74; 12 months: off-pump 24.1%, on-pump 23.1%, p = 0.90). The degree of preoperative cerebral ischemic injury was significantly associated with cognitive dysfunction after on-pump (p = 0.02) but not after off-pump (p = 0.22) surgery. None of the patients with normal preoperative radiologic findings were found to have cognitive impairment at 3 months postoperatively (p = 0.04). CONCLUSIONS: Long-term cognitive function and magnetic resonance imaging evidence of brain injury were similar after off-pump and on-pump coronary artery bypass grafting surgery. Preoperative cerebral magnetic resonance imaging can be used to predict the risk for cognitive dysfunction after coronary artery bypass grafting surgery.

Preoperative cerebral ischemic lesions predict physical health status after on-pump coronary artery bypass surgery.

BACKGROUND: Risk assessment is integral to patient selection and counseling before coronary artery revascularization. We studied the predictive ability of cerebral magnetic resonance imaging of preoperative and postoperative cerebral ischemic injury on self-reported physical and mental health at 3 months after coronary artery bypass surgery with or without use of cardiopulmonary bypass. METHODS: In a prospective clinical trial comparing on-pump and off-pump surgery, 120 patients responded to a questionnaire for self-report of angina (Canadian Cardiovascular Society scale) and physical and mental health status (Short Form 36) at baseline before preoperative cerebral magnetic resonance imaging. Preoperative sets of both magnetic resonance imaging and self-assessments were available for 103 (85.8%) patients. These patients were grouped according to classification of preoperative cerebral magnetic resonance imaging findings. Analysis of covariance determined the association of (1) preoperative magnetic resonance imaging status, (2) new postoperative cerebral lesions, and (3) actual use of cardiopulmonary bypass to physical and mental health. RESULTS: At 3 months after surgical intervention, 98 of 103 patients completed follow-up. The analysis revealed an interaction effect of preoperative cerebral ischemic injury and use of cardiopulmonary bypass on physical health (F = 9.07, P = .003) independent of age. No independent effects on health status were found of baseline magnetic resonance imaging or new cerebral lesions at 3 months. CONCLUSIONS: This study strongly suggests that the combination of preoperative cerebral ischemic injury and use of cardiopulmonary bypass can predict postoperative health status at 3 months. Cerebral magnetic resonance imaging might be a more specific indicator than age for preoperative assessment of vulnerability or resilience during rehabilitation after on-pump cardiac surgery.