[Show description][Hide description] DESCRIPTION: In diabetic sensorimotor neuropathy there is substantial evidence of concomitant cutaneous, cardiac and visceral autonomic neuropathies. The neuropathy may reduce quality of life and explain the higher prevalence of gastrointestinal complaint
[Show abstract][Hide abstract] ABSTRACT: The diagnosis of nonconvulsive status epilepticus (NCSE) relies largely on electroencephalography (EEG) findings. The lack of a unified EEG terminology, and of evidence-based EEG criteria, leads to varying criteria for and ability to diagnose NCSE. We propose a unified terminology and classification system for NCSE, using, as a template, the Standardised Computer-based Organised Reporting of EEG (SCORE). This approach integrates the terminology recently proposed for the rhythmic and periodic patterns in critically ill patients, the electroclinical classification of NCSE (type of NCSE) and the context for the pathologic conditions and age-related epilepsy syndromes. We propose flexible EEG criteria that employ the SCORE system to assemble a database for determining evidence-based EEG criteria for NCSE.
[Show abstract][Hide abstract] ABSTRACT: The electroencephalography (EEG) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis of the recordings. The interobserver agreement in EEG interpretation is only moderate. This is partly due to the method of reporting the findings in free-text format. The purpose of our endeavor was to create a computer-based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video-EEG recordings). A working group of EEG experts took part in consensus workshops in Dianalund, Denmark, in 2010 and 2011. The faculty was approved by the Commission on European Affairs of the International League Against Epilepsy (ILAE). The working group produced a consensus proposal that went through a pan-European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer-based Organised Reporting of EEG (SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, "episodes" (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. The following specific aspects of the neonatal EEGs are scored: alertness, temporal organization, and spatial organization. For each EEG finding, relevant features are scored using predefined terms. Definitions are provided for all EEG terms and features. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer-assisted analysis into the report, it will make possible the build-up of a multinational database, and it will help in training young neurophysiologists.
[Show abstract][Hide abstract] ABSTRACT: Background:
Many patients with acute ischaemic stroke do not receive intravenous thrombolysis due to contraindications. We aimed to assess safety, short-term clinical development, short-term outcome and mortality in patients treated off-label with tissue plasminogen activator (tPA).
Stroke patients treated with tPA within 4.5 h after symptom onset during 2006-2011 were prospectively included. Patients with contraindications to tPA according to national guidelines were compared to patients without any of these contraindications. Separate analyses were performed on patients who had compatible contraindications and did not receive tPA. Primary outcome was rate of symptomatic intracerebral haemorrhage (SICH). Secondary outcomes were short-term clinical development, short-term outcome and 30-day mortality.
Of the 265 patients who received tPA, 135 patients (50.9%) had formal contraindications and 130 patients (49.1%) had no such contraindications. Rates of SICH were similar for patients with or without contraindications (P = 0.305). Patients with contraindications to tPA had a similar rate of clinical improvement (P = 0.504), a trend of less favourable outcome (P = 0.052) and higher mortality (P = 0.005) than patients without contraindications. Logistic regression analysis showed no association between presence of contraindications to tPA and short-term outcome or mortality when adjusted for age, sex and admission National Institute of Health Stroke Scale score. Short-term outcome and mortality were similar in patients with contraindications who received tPA and patients with contraindications who did not receive tPA (n = 134).
Intravenous thrombolysis with tPA may be safe and efficient in stroke patients with a number of formal contraindications to tPA. Prospective randomized trials are imperative to clarify the need for a re-evaluation of the current contraindications to tPA.
No preview · Article · Jan 2013 · Acta Neurologica Scandinavica
[Show abstract][Hide abstract] ABSTRACT: Aims
Gastrointestinal complaints are common in diabetes mellitus. However, its association to peripheral sensorimotor and autonomic neuropathies is not well investigated. The aim was to assess skin, muscle, bone and visceral sensitivity in diabetes patients with sensorimotor neuropathy, and correlate these with gastrointestinal symptoms and degree of cardiac autonomic neuropathy.
Twenty patients with sensorimotor neuropathy (65% type 2 diabetes, aged 58.3 ± 12.0 years, diabetes duration 15.8 ± 10.0 years) and 16 healthy controls were recruited. Cutaneous sensitivity to von Frey filaments, mechanical allodynia, muscle/bone/rectosigmoid sensitivities, and heart rate variability were examined. Gastrointestinal symptom scores (PAGI-SYM) and health-related quality of life (SF-36) were also recorded.
Patients displayed hypesthesia to von Frey filaments (p = 0.028), but no difference to muscle and bone pain sensitivities. Also, patients were hyposensitive to multimodal rectal stimulations (all p < 0.05), although they suffered more gastrointestinal complaints. Heart rate variability was reduced in the patient cohort. Rectal mechanical and cutaneous sensitivities correlated (p < 0.001), and both were associated with heart rate variability as well as PAGI-SYM and SF-36 scores (p < 0.01).
In diabetic sensorimotor neuropathy there is substantial evidence of concomitant cutaneous, cardiac and visceral autonomic neuropathies. The neuropathy may reduce quality of life and explain the higher prevalence of gastrointestinal complaints.
No preview · Article · Jan 2013 · Journal of diabetes and its complications
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The optimal management of patients with recurrent glioblastoma multiforme (GBM) is a subject of controversy. These patients may be candidates for both reoperation and/or gamma knife surgery (GKS). Few studies have addressed the role of GKS for relapsing gliomas, and the results have not been compared with reoperation. To validate the efficacy and safety of GKS, we compared the survival and complication rates of GKS and reoperation for recurrent GBMs. METHODS: This study retrospectively reviewed 77 consecutive patients with histopathologically confirmed GBMs retreated for recurrent GBM between 1996 and 2007. Thirty-two patients underwent GKS, 26 reoperation and 19 both procedures. RESULTS: The median time from the second intervention to tumor progression was longer after GKS than after resection, P = 0.009. Median survival after retreatment was 12 months for the 51 patients receiving GKS compared with 6 months for reoperation only (P = 0.001, hazard ratio [HR] 2.4), and 19 months versus 16 months from the time of primary diagnosis (P = 0.021, HR 1.8). A multivariate analysis adjusted for possible confounding factors (tumor volume, recursive partitioning analysis class, neurological deficits, time to recurrence, adjuvant therapy, and tumor location) showed significantly longer survival for patients treated with GKS, both from retreatment (P = 0.013, HR 4.1) and from primary diagnosis (P = 0.002, HR 5.8). The adjusted results were still significant after separate analysis according to tumor volume <5 mL, 5 to 20 mL, and >20 mL. The complications rate was 9.8% after GKS and 25.2% after reoperation. CONCLUSIONS: GKS may be an alternative to open surgery for small GBMs at the time of recurrences, with a significantly lower complication rate and a possible survival benefit compared with reoperation.
Full-text · Article · Dec 2012 · World Neurosurgery
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Transcranial color-coded sonography (TCCS) and CT-angiography (CTA) are reliable tools for detection of intracranial stenosis. Current ultrasonographic criteria for middle cerebral artery (MCA) stenosis are usually limited to a dichotomized grading (< or ≥ 50 %). As for carotid arteries, continuity equation might provide a more accurate evaluation of degree of MCA stenosis. We aimed to apply continuity equation to calculate degree of MCA stenosis with TCCS and to compare these results with CTA.
Materials and methods:
All patients admitted to our Neurovascular Center with ischemic stroke or TIA underwent TCCS examination. Degree of MCA stenosis was calculated based on continuity equation as (1 - [PSVprestenotic/PSVintrastenotic] × 100) %. CTA was performed when TCCS detected MCA stenosis, and degree of stenosis was calculated by diameter (D) as: (1 - [Dprestenotic/Dintrastenotic] × 100) %. Correlation between TCCS and CTA results was tested. Continuity equation method was compared to cut-off velocity method for detection of ≥ 50 % MCA stenosis. To assess TCCS inter-observer agreement, evaluation of MCA stenosis was repeated by another neurosonographer in a subgroup of patients.
The overall correlation coefficient between TCCS and CTA was 0.85 (p < 0.0001). Correlation coefficient for stenosis defined with CTA as ≥ 50 % was 0.94 (p < 0.0001). TCCS inter-observer agreement on degree of stenosis was 0.85 (p = 0.001). In detection of ≥ 50 % MCA stenosis, continuity equation method showed a sensitivity of 78 % (14/18) and a specificity of 86 % (19/22), while the cut-off velocity method showed a sensitivity of 67 % (12/18) and a specificity of 86 % (19/22).
This study shows that ultrasonographic evaluation of MCA stenosis applying the continuity equation provides reproducible and accurate results, and is more sensitive in detection of ≥ 50 % MCA stenosis than cut-off velocity method.
No preview · Article · Aug 2012 · Ultraschall in der Medizin
[Show abstract][Hide abstract] ABSTRACT: Many patients with cerebral infarction suffer from symptoms such as pain, fatigue, and depression. The aim of this study was to evaluate these symptoms in relation to health-related quality of life (HRQoL) on long-term follow-up.
All surviving stroke patients admitted to the Stroke Unit, Haukeland University Hospital, Norway between February 2006 and November 2008 were sent a questionnaire, including a visual analog pain scale, Fatigue Severity Scale, Depression Subscale of Hospital Anxiety and Depression Scale, Barthel Index, and three measures of HRQoL--15D, EuroQol, and EuroQol Visual Analogue Scale--at least 6 months after stroke onset. Cox regression survival analysis, including EQ-5D, was performed by November 2009.
The questionnaire was returned by 328 patients. All three symptoms were reported by 10.1% of the patients, and 26% reported two symptoms. There was a significant association between worse HRQoL scores and an increasing number of cooccurring symptoms for all three HRQoL scores. Fatigue, depression, pain, functional state, and sleeping disorder on follow-up accounted for 58%-83% of the variability in HRQoL, depending on which HRQoL scale was used. Cox regression analysis showed that mortality was associated with a low EuroQol score (P = 0.016).
Pain, fatigue, and depression were common symptoms among these stroke patients and, to a large extent, they determined the patients' HRQoL. Low HRQoL was associated with increased mortality.
Preview · Article · Jun 2012 · Vascular Health and Risk Management
[Show abstract][Hide abstract] ABSTRACT: Many patients with cerebral infarction suffer from symptoms such as pain, fatigue and depression. Most studies focus on single symptoms, but these symptoms often occur together. Whereas symptom clusters have been studied in cancer patients, little is known about different symptom clusters in patients with cerebral infarction. The aim was to evaluate clusters of co-occurring symptoms in the long term. We hypothesized that patients with cerebral infarction display distinct symptom clusters. Furthermore, we hypothesized that multiple co-occurring symptoms have an adverse effect on patients.
All consecutive patients with acute stroke (the index stroke) admitted to the Stroke Unit, Department of Neurology, Haukeland University Hospital, between February 2006 and July 2008, were prospectively registered in a database. Prior risk factors (including diabetes mellitus, hypertension, smoking, coronary heart disease, atrial fibrillation and prior stroke), prior depression and stroke severity (modified Rankin Scale (mRS) score on day 7) were registered. Patients with cerebral infarction were sent a questionnaire including a visual analogue pain scale (VAS), Fatigue Severity Scale (FSS), depression subscale of the Hospital Anxiety, Depression Scale (HADS-D) and Barthel Index at least 6 months after stroke onset.
The questionnaire was returned by 328 patients (response rate 60%). All three symptoms were reported by 10.1%. Pain and fatigue among nondepressed patients were reported by 19.6%. Pain and depression among nonfatigued patients were reported by 2.0%. Depression and fatigue, and no pain were reported by 4.4%. Single symptoms were reported by 31% whereas 33% reported no symptoms. VAS, FSS and HADS-D score severity increased with the number of co-occurring symptoms. Logistic regression analyses showed that two or three symptoms (versus no symptoms) was associated with high mRS score on day 7 (p = 0.02), prior stroke (p = 0.002), prior diabetes mellitus (p = 0.005) and prior depression (p < 0.001).
Symptom clusters are frequent in patients with cerebral infarction. Fatigue was associated with pain and depression whereas there was little association between depression and pain in nonfatigue patients, indicating distinct symptom clusters. The severity of symptoms increased with the number of co-occurring symptoms.
No preview · Article · Apr 2012 · Cerebrovascular Diseases
[Show abstract][Hide abstract] ABSTRACT: A possible synergic role of serum uric acid (SUA) with thrombolytic therapies is controversial and needs further investigations. We therefore evaluated association of admission SUA with clinical improvement and clinical outcome in patients receiving rt-PA, early admitted patients not receiving rt-PA, and patients admitted after time window for rt-PA.
SUA levels were obtained at admission and categorized as low, middle and high, based on 33° and 66° percentile values. Patients were categorized as patients admitted within 3 hours of symptom onset receiving rt-PA (rt-PA group), patients admitted within 3 hours of symptom onset not receiving rt-PA (non-rt-PA group), and patients admitted after time window for rt-PA (late group). Short-term clinical improvement was defined as the difference between NIHSS on admission minus NIHSS day 7. Favorable outcome was defined as mRS 0 - 3 and unfavorable outcome as mRS 4 - 6.
SUA measurements were available in 1136 patients. Clinical improvement was significantly higher in patients with high SUA levels at admission. After adjustment for possible confounders, SUA level showed a positive correlation with clinical improvement (r = 0.012, 95% CI 0.002-0.022, p = 0.02) and was an independent predictor for favorable stroke outcome (OR 1.004; 95% CI 1.0002-1.009; p = 0.04) only in the rt-PA group.
SUA may not be neuroprotective alone, but may provide a beneficial effect in patients receiving thrombolysis.
[Show abstract][Hide abstract] ABSTRACT: The main objective of this study was to investigate the circadian distribution of subtypes of ischemic stroke. The time of onset of stroke in consecutive stroke patients was registered and categorized into the following time intervals: midnight-6 am, 6 am-noon, noon-6 pm, and 6 pm-midnight. Patients with unknown onset of stroke were categorized as woke up with stroke, found with stroke by others, and miscellaneous. Patients who woke up with stroke, were included in the midnight-6 am interval. Stroke subtypes were categorized according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria and as lacunar or embolic stroke based on diffusion-weighted magnetic resonance imaging (DWI). The study group comprised 1101 patients who sustained ischemic stroke between February 2006 and March 2008. The proportion of lacunar stroke, defined according to both the TOAST criteria and DWI findings, was significantly higher in the midnight-6 am interval compared with the other time intervals. In our study group, the prevalence of lacunar strokes was highest at night.
No preview · Article · Sep 2011 · Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association
[Show abstract][Hide abstract] ABSTRACT: Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experimental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This effect was independent of age at diagnosis, treatment received and hypermethylation of the O6-methylguanine methyltransferase (MGMT) DNA repair gene promoter. NG2 was frequently co-expressed with nestin and vimentin but rarely with CD133 and the NG2 positive tumour cells harboured genetic aberrations typical for GBM. 2D proteomics of 11 randomly selected biopsies revealed upregulation of an antioxidant, peroxiredoxin-1 (PRDX-1), in the shortest surviving patients. Expression of PRDX-1 was associated with significantly reduced products of oxidative stress. Furthermore, NG2 expressing GBM cells showed resistance to ionising radiation (IR), rapidly recognised DNA damage and effectuated cell cycle checkpoint signalling. PRDX-1 knockdown transiently slowed tumour growth rates and sensitised them to IR in vivo. Our data establish NG2 as an important prognostic factor for GBM patient survival, by mediating resistance to radiotherapy through induction of ROS scavenging enzymes and preferential DNA damage signalling.
Electronic supplementary material
The online version of this article (doi:10.1007/s00401-011-0867-2) contains supplementary material, which is available to authorized users.
Full-text · Article · Aug 2011 · Acta Neuropathologica
[Show abstract][Hide abstract] ABSTRACT: To evaluate characteristics and mortality related to post-stroke fatigue (PSF).
All surviving stroke patients admitted to the Stroke Unit, Haukeland University Hospital, between February 2006 and November 2008 were sent a postal questionnaire including the Fatigue Severity Scale (FSS), the hospital anxiety and depression scale (HADSD), and the Barthel Index (BI) at least 6 months after stroke onset. Survival among patients returning the questionnaire was determined by November 2009. PSF was defined as FSS score ≥5.
Among 377 patients returning the questionnaire, 42.3% had PSF. Logistic regression showed that PSF was independently associated with pre-stroke depression, leucoaraiosis, myocardial infarction, diabetes mellitus, pain, and sleeping disturbances. Mean FSS score was lower among TIA patients than among patients with minor cerebral infarction (patients with BI=100) (P=.002). Cox regression analysis showed mortality to be associated with PSF.
There is a multifactorial basis for PSF suggesting different therapy options. Cerebral lesions may cause PSF in some patients. Post-stroke fatigue is associated with higher mortality.
No preview · Article · Aug 2011 · Journal of the neurological sciences
[Show abstract][Hide abstract] ABSTRACT: Treatment of acute cerebral infarction has greatly improved over the last 15 years. The purpose of this article is to describe patients with acute cerebral infarction admitted to a stroke unit from a geographically well defined population between 2007 and 2009.
All patients were included aged over 15 years with acute cerebral infarction living in a well defined geographical area and admitted to Haukeland University Hospital between August 2007 and October 2009. Risk factors, neurological status, treatment, complications, results of evaluation, and outcome were registered in a stroke database (Bergen Stroke Registry). Data on mortality as of November 2009 were provided by the official population registry.
In total, 553 patients with acute cerebral infarction were included: 260 (47%) females and 293 (53%) men. The mean age was 74.2 years. The incidence of patients admitted with acute cerebral infarction was 105 per 100,000 citizens per year. Thrombolysis was administered to 15%. Duplex sonography of neck vessels disclosed plaques in 68%. Atrial fibrillation was known before admission in 20%. Evaluation disclosed atrial fibrillation in another 12%. Recurrence of cerebral infarction occurred in 1% during the hospital stay. Estimated survival after one year was 82%.
The incidence of acute cerebral infarction in Bergen is low. Systematic evaluation discloses risk factors with therapeutic consequences in many patients.
Preview · Article · May 2011 · Tidsskrift for den Norske laegeforening
[Show abstract][Hide abstract] ABSTRACT: Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiother-apy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experi-mental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diag-nosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This effect was independent of age at diagnosis, treatment received and hypermethylation of the O 6 -methylguanine
[Show abstract][Hide abstract] ABSTRACT: Development of stroke units during the last decade has changed management of patients with stroke. The aim of this study is to assess unselected patients admitted to an acute stroke unit with respect to daily functioning (neurological deficits), treatment and 7-day outcome.
All patients with suspected neurovascular disease were admitted to the stroke unit as emergencies. Patients with confirmed cerebrovascular disease were prospectively included in the Bergen Stroke Study in the period 1 February 2006-30 April 2009. Patients who had other diagnoses were not included, but their diagnoses were prospectively recorded in a 3 month-period.
49.8% of the patients had other diagnoses than acute stroke. Of 1101 patients with neurovascular disease; 10% had transient ischemic attacks, 79% had ischemic and 10% had hemorrhagic stroke. On admission, 72% of the patients had none or minor neurological deficits. After one week 63% of the patients were independent, 25% needed long-term rehabilitation and 10% were bedridden.
Most patients in our study had mild deficits and first of all need an exact diagnostic work-up, acute and prophylactic treatment. Rehabilitation is important for a minority of patients.
Preview · Article · Jan 2011 · Tidsskrift for den Norske laegeforening