The assessment of carotid atherosclerosis using a new multipurpose ultrasound probe.

BACKGROUND AND PURPOSE: Multipurpose ultrasound probes combined with ultra-mobile ultrasound instrumentation have the potential to increase the availability and use of ultrasound examinations in the assessment of atherosclerotic burden and cardiac disease. The aim of this study was to compare the agreement of a newly developed multipurpose probe to a standard linear carotid probe in detection of atherosclerosis of the precerebral arteries. METHODS: We examined 103 patients with a multipurpose probe (General Electric, G9L MPP-9 MHz) and a standard linear probe (General Electric, Vivid 7-M12L-14 MHz). Measurements included intima-media thickness (IMT) in the common carotid arteries (CCA), carotid bifurcations (BIF), internal carotid arteries (ICA), and detection of carotid plaques and stenoses. RESULTS: We found a significant level of agreement between the two probes for all IMT measurements with intraclass correlation coefficients (ICC) of: left CCA .91, left BIF .68, left ICA .75, right CCA .84, right BIF .74, and right ICA .59. Agreement with regard to carotid plaque and stenosis detection had kappa values of .94 and .93. CONCLUSION: The multipurpose probe showed agreement with a standard linear probe in detecting atherosclerosis of the carotid arteries and has therefore the potential for use in both cardiac and precerebral ultrasound examinations.

Hereditary motor neuron disease in a large Norwegian family with a "H46R" substitution in the superoxide dismutase 1 gene.

Mutant genes associated with Charcot Marie Tooth type 2, distal hereditary motor neuropathy and familial amyotrophic lateral sclerosis may cause overlapping clinical phenotypes. We performed whole genome linkage analysis, haplotype analysis, sequencing and detailed clinical and neurophysiological investigations in a large Norwegian kindred with a condition that clinically had been classified as Charcot Marie Tooth type 2. The mutation c.140A>G, p.His47Arg (alias p.His46Arg or H46R) in the superoxide dismutase 1 gene (SOD1) segregated with the disease. The patients present a hereditary motor neuropathy-like clinical picture and long survival (mean 29years). To our knowledge, this is the first extensive report describing a large non-Japanese kindred. The prognostic implications of the condition seen in this family have little in common with what is normally associated with sporadic amyotrophic lateral sclerosis and illustrates the complexity of the genetic etiology of lower motor neuron disease.

A novel MYH7 mutation occurring independently in French and Norwegian Laing distal myopathy families and de novo in one Finnish patient.

Laing early-onset distal myopathy is a rare autosomal dominant myopathy and caused by mutations in the MYH7 gene, encoding the slow beta myosin heavy chain. We report the first molecularly verified Laing distal myopathy in a French family caused by a novel p.Glu1508del mutation in the MYH7 gene. Interestingly, we identified the identical mutation in an unrelated Norwegian family and, as a de novo mutation, in one sporadic Finnish patient. Described in detail are the clinical and electrophysiological characteristics of 5 patients from the French family. The phenotype in the Finnish patient and the Norwegian patients is largely similar. This mutation causes a benign myopathy within the range of previously reported Laing myopathy phenotype variations. Onset of weakness in the tibialis anterior (TA) muscles occurred in early childhood in all patients. Finger extensor and neck flexor weakness together with Achilles tendon retractions were other frequent findings. The independent recurrence of the identical mutation without any founder background may reflect a mutational susceptibility of this residue, in accordance with some other MYH7 mutations previously reported. De novo mutations seem to be frequent in Laing distal myopathy. This is of clinical importance since a dominant family history is missing, which may confuse differential diagnostic efforts.

Prevalence, mutation spectrum and phenotypic variability in Norwegian patients with Limb Girdle Muscular Dystrophy 2I.

Mutations in the FKRP (Fukutin Related Protein) gene produce a range of phenotypes including Limb Girdle Muscular Dystrophy Type 2I (LGMD2I). In order to investigate the prevalence, the mutation spectrum and possible genotype-phenotype correlation, we studied a cohort of Norwegian patients with LGMD2I, ascertained in a 4-year period. In this retrospective study of genetically tested patients, we identified 88 patients from 69 families, who were either homozygous or compound heterozygous for FKRP mutations. This gives a minimum prevalence of 1/54,000 and a corresponding carrier frequency of 1/116 in the Norwegian population. Seven different FKRP mutations, including three novel changes, were detected. Seventy-six patients were homozygous for the common c.826C>A mutation. These patients had later disease onset than patients who were compound heterozygous - 14.0 vs. 6.1 years. We detected substantial variability in disease severity among homozygous patients.

Soluble CD36 in plasma is increased in patients with symptomatic atherosclerotic carotid plaques and is related to plaque instability.

BACKGROUND AND PURPOSE: The risk for cardiovascular events is related to the composition and stability of an atherosclerotic plaque driven by inflammation and deposition of lipids. Scavenger receptors are a family of cell surface receptors involved in lipid uptake and inflammation. Recently, we found that soluble CD36 is increased in plasma from patients with diabetes strongly correlated with insulin resistance. METHODS: We tested whether soluble CD36 is a marker of plaque stability in patients with high-grade internal carotid stenoses (n=62). The patients were classified according to plaque symptomatology and plaque echogenicity on ultrasound examination. RESULTS: When patients were divided into 3 groups according to the latest clinical symptoms from plaques (ie, symptoms within the last 2 months [n=16], symptoms within the last 2 to 6 months [n=15], or asymptomatic [n=31]), the former group had significantly raised plasma levels of soluble CD36 as compared with the other 2 groups. In contrast, we found no differences in plasma levels of C-reactive protein, beta-thromboglobulin, lipid parameters, or HbA1C between these groups. The patients with echolucent carotid plaques (n=20) tended to have higher soluble CD36 levels in plasma compared with those with echogenic/heterogenic plaque (n=39; P=0.087). By immunohistochemistry, CD36 was localized to macrophages-rich area of intima within the atherosclerotic lesion. CONCLUSIONS: We propose that sCD36 may be a marker of plaque instability and symptomatic carotid atherosclerosis, possibly at least partly as a result of CD36 release to the circulation from the foam cells within the atherosclerotic lesion.

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.

[Secondary prophylaxis after ischemic stroke and transitoric ischemic attack]. / Sekundaerprofylakse etter hjerneinfarkt og transitorisk iskemisk anfall.

BACKGROUND: Approximately 13,000 persons develop a stroke in Norway each year. 3,000 of these are recurrent strokes. There are also more than 10,000 patients who experience a transitory ischemic attack each year which often immediately precedes a stroke. The aim of this review article is to present updated treatment recommendations for secondary prophylaxis after an ischemic stroke or TIA. MATERIAL AND METHODS: This article is based on the guidelines from the European Stroke Initiative, the American Stroke Association and review articles found by searching Medline and the Cochrane database. New relevant randomized studies are also included and discussed. Therapy guidelines have been modified for Norwegian use. RESULTS AND INTERPRETATION: Individualised secondary prophylaxis following an ischemic stroke or TIA can prevent cerebrovascular disease and death. It is especially important with optimal blood pressure and blood glucose control as well as adequate antithrombotic and lipid-lowering treatment.

[Atherosclerosis and cerebral infarction]. / Aterosklerose og hjerneinfarkt.

BACKGROUND: Approximately half of all cerebral infarctions are caused by artery-to-artery emboli from atherosclerotic plaques in the aorta and pre- or intracranial arteries. This review article presents an update on the development of atherosclerotic plaques, and discusses the diagnostic and therapeutic implications of new pathophysiological knowledge of atherosclerosis in relation to cerebral infarction. MATERIAL AND METHODS: The article is based on our own clinical-neurological experience and publications mainly on intima-media thickness (IMT) and ultrasound in the diagnosis of cerebrovascular disease, identified through a Medline search. RESULTS: Unstable plaques have a thin and vulnerable capsule, inflammatory cells, high fat content and often intra-plaque bleeding. Calcium deposition and organized fibrous tissue have a stabilizing effect. The development of atherosclerosis and biological characteristics of plaques can be explained by known vascular risk factors and genetic disposition. Ultrasound examination of the aorta and pre-cerebral arteries can be used to assess the degree of atherosclerosis and to provide important information regarding patients' risk of cerebrovascular disease. INTERPRETATION: New knowledge regarding the pathophysiology of atherosclerosis can improve prediction of a patient's risk for ischemic stroke. This forms the basis for a better and more individualized prophylactic treatment of cerebrovascular disease.

[Transitory ischemic attack]. / Transitorisk iskemisk anfall.

BACKGROUND: Neurological symptoms rapidly resolve after a transitory ischemic attack (TIA). Diffusion-weighted MRI and new clinical studies have greatly increased our understanding of the pathophysiology and clinical impact of TIA. This review presents an update on pathophysiology, symptoms, diagnosis and treatment of TIA. MATERIAL AND METHODS: This article is based on our clinical experience, European guidelines for acute cerebrovascular disease and recent medical literature found by searching Medline. RESULTS AND INTERPRETATION: TIA is a warning of a potential cerebrovascular disaster. About 10-13% of TIA patients will have a stroke within a few months, half of them within a few days. A more urgent approach to TIA diagnosis and treatment should prevent many strokes and deaths. All TIA patients should therefore be referred as an emergency to a stroke unit.

[Stroke--primary prophylaxis]. / Primaerprofylakse mot hjerneslag.

BACKGROUND: The estimated annual incidence of stroke in Norway is 15,000; 5,000 have a lethal outcome. 11,500 patients are affected for the first time. The incidence of stroke is expected to rise considerably in the future, due to an increasing number of elderly. The aim of this review article is to present updated treatment recommendations for primary prophylaxis of stroke. MATERIAL AND METHODS: This article is based on guidelines from The European Stroke Initiative and the American Stroke Association Guidelines and on literature found in Medline and the Cochrane Library. The results from new randomised clinical studies are also included. Therapeutic guidelines have been modified for Norwegian use. RESULTS AND INTERPRETATION: Active treatment of modifiable risk factors such as hypertension, dyslipidaemia and atrial fibrillation can reduce the number of patients who develop a stroke. There is considerable evidence suggesting that a substantial proportion of the population with high blood pressure receive insufficient treatment. More active treatment of this condition is probably the most efficient single measure. Lifestyle factors such as smoking, diet, physical inactivity and obesity contribute to the relatively high incidence of stroke in Norway.

Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization.

BACKGROUND: Although the participation of inflammation in atherogenesis is widely recognized, the identification of the different components has not been clarified. In particular, the role of inflammation in plaque destabilization is not fully understood. METHODS AND RESULTS: Our main findings were as follows: (1) In a microarray experiment, we identified visfatin, one of the most recently identified adipokines, as a gene that was markedly enhanced in carotid plaques from symptomatic compared with plaques from asymptomatic individuals. This finding was confirmed when carotid plaques from 7 patients with asymptomatic and 14 patients with symptomatic lesions were examined with real-time reverse transcription polymerase chain reaction. (2) Immunohistochemistry showed that visfatin was localized in areas that were rich in lipid-loaded macrophages. (3) The relationship between visfatin and unstable lesions was also found in patients with coronary artery disease, demonstrating a strong visfatin immunostaining in lipid-rich regions within the material obtained at the site of plaque rupture in patients with acute myocardial infarction. (4) Both oxidized low-density lipoprotein and tumor necrosis factor-alpha increased visfatin expression in THP-1 monocytes, with a particularly enhancing effect when these stimuli were combined. (5) Visfatin increased matrix metalloproteinase-9 activity in THP-1 monocytes and tumor necrosis factor-alpha and interleukin-8 levels in peripheral blood mononuclear cells. Both of these effects were abolished when insulin receptor signaling was blocked. CONCLUSIONS: Our findings suggest that visfatin should be regarded as an inflammatory mediator, localized to foam cell macrophages within unstable atherosclerotic lesions, that potentially plays a role in plaque destabilization.

[Can ischaemic stroke be prevented with statins?]. / Kan hjerneslag forebygges med statiner?

BACKGROUND: Statins provide a reduction in the risk for ischaemic stroke in patients with coronary artery disease, known atherosclerotic disease, and in patients with risk factors for arterial vascular disease. There is also considerable interest in whether or not statins should be used as a secondary prophylaxis for stroke. MATERIALS AND METHOD: This review is based on articles included on Medline that consider the association between cholesterol and cerebrovascular disease and the use of statins in ischaemic stroke. RESULTS: Cholesterol is a much weaker risk factor for ischaemic stroke than for coronary heart disease. It is especially associated with thromboembolic stroke due to atherosclerosis of the larger vessels. Meta-analysis of earlier studies in patients with coronary artery disease and several more recent studies which include patients with other atherosclerotic disease and risk factors for atherosclerosis have clearly shown a relative risk reduction for ischaemic stroke of between 20 and 30%. Since these studies were of patients in age groups in which stroke rarely occurs, the relative risk reduction was moderate. Risk reduction seems similar in all age groups with atherosclerotic heart disease and for all cholesterol levels. A reduced risk for a new stroke has to date not been shown for patients with previous stroke. CONCLUSION: Given the fact that stroke is caused by several mechanisms and is often not caused by atherosclerosis of larger vessels, definite advice cannot be given on secondary prevention with statins in all stroke patients. At present there are no results from studies where only ischaemic stroke patients were included and with a sufficient number of older patients.

[Treatment of patients with neuromuscular disease in a warm climate]. / Behandling i varmt klima for pasienter med nevromuskulaere sykdommer.

BACKGROUND: Several patient groups request treatment in a warm climate, in spite of the fact that the effects of such treatment are undocumented. MATERIAL AND METHODS: 47 children and 40 adults with neuromuscular diseases were recruited, stratified according to sex, use or non-use of electric wheelchair, primary myopathy or hereditary neuropathy, and randomised into two adult and two children groups. The patients were treated in a rehabilitation centre, either on Lanzarote or in Norway. All patients were monitored with physical tests and questionnaires at the start of the study, at the end of the treatment period, after three months (all groups) and after six months (adults only). RESULTS: No significant differences in effect between the groups were found. In the warm climate, the adult patient group showed a statistically significant improvement regarding pain, quality of life, depression, and results of physical tests at the end of treatment. After three months, the improvement in physical tests was still present. Among adult patients treated in Norway, improvement in physical tests was statistically significant after three months, but not at the end of the treatment period. INTERPRETATION: This study did not show a statistically significant difference between patients with various neuromuscular diseases treated in a warm climate compared to similar patients treated in Norway.

Symptoms and cognitive dysfunction in patients with the late whiplash syndrome.

The aim of the study was to record the severity of symptoms in patients with the late whiplash syndrome and to assess how the symptom load affected the performance on a simple psychometric test. The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) with an additional question on neck pain, modified RPQ (mRPQ), and the Short Test of Mental Status (STMS) were applied on 40 chronic whiplash patients. Symptoms reported by the whiplash group were compared to those of 50 normal controls. The patients scored significantly higher than the controls on all symptoms listed in the mRPQ. The most frequent symptoms reported.

Genome-wide homozygosity mapping localizes a gene for autosomal recessive non-progressive infantile ataxia to 20q11-q13.

Autosomal recessive ataxias represent genetic and clinical heterogeneity. Unsteady gait is often accompanied by poor coordination of limbs, speech, and eye movements. To date, seven genes have been identified. In addition, five chromosomal loci have been localized in non-related families. Here, we report homozygosity mapping of a novel locus to a 19.5-cM region on chromosome 20q11-q13 in a large inbred Norwegian family with infantile non-progressive ataxia.