Biomedical subjects

S I Mellgren

Publications and source records attributed to S I Mellgren.

At least 19 recordsLinked to original sources

PubMed2004

The effect of age and gender on epidermal nerve fiber density.

OBJECTIVE: Sensory neuropathies often involve small-diameter myelinated and unmyelinated nerve fibers, and neurologic and electrophysiologic findings may be normal unless larger nerve fibers are involved. The small (intra)epidermal nerve fibers (ENFs) now can be visualized with immunohistochemical techniques using the panaxonal marker anti-protein gene product 9.5 (PGP 9.5). Using this technique, the authors have established a reference range for ENF in a healthy white population and evaluated the reliability of the method. METHODS: Two punch biopsies, 3 mm in diameter, were taken from the distal part of the leg in 106 healthy volunteers (mean age, 49.0 +/- 19.6 years). Fifty-micrometer frozen thick sections were incubated with rabbit polyclonal antibodies to human PGP 9.5. The number of ENF/mm then was reported as the mean of counts in six sections (three sections from each of the two biopsies). RESULTS: The mean number of ENFs was 12.4 +/- 4.6 mm. In a multiple regression model, the density of ENF depended on age and gender (Y = 13.92 + 2.25 (gender) - 0.06 x age). The mean difference in ENF by intraobserver analysis was 0.2 +/- 1.2 ENF/mm, and by interobserver analysis, it was 0.4 +/- 1.5 fibers/mm. CONCLUSION: Normal means and ranges for the density of epidermal nerve fibers in a reference population have been established. The density of epidermal nerve fibers decreases with age and is lower in men compared with women. Intraobserver and interobserver analysis proves the reliability of the method.

Adult↗

PubMed2004

Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis.

In order to analyze whether loci in the human leukocyte antigen (HLA) class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis (MS), we examined selected microsatellite markers in 177 Nordic sib-pair families, 222 British sib-pair families, 323 sporadic Norwegian MS patients and 386 Norwegian controls. All samples were, in addition, genotyped for the HLA-DR DQ haplotype, and the Norwegian case-control samples were also typed for HLA-A and -B loci. In the Norwegian sporadic MS patients association was seen with HLA-A, HLA-B, and with the D6S265 marker, located 100 kb centromeric to HLA-A. Associations with HLA-A and D6S265 loci were also suggested when restricting the analysis to HLA-DR15 haplotypes. In the sib-pair data a similar trend was seen with marker D6S265. Higher genotypic relative risk (GRR) was found for individuals who carry both HLA-DR15 and -A3 (GRR = 15), compared to those who carry only HLA-DR15 (GRR = 7), only HLA-A3 (GRR = 3) or none of these alleles (GRR = 1). The highest risk was conferred by a combination of HLA-DR15 and -A3 (odds ratio (OR) = 5.2). These results suggest that HLA-A or a gene in linkage disequilibrium with it may contribute to the HLA class II-associated genetic susceptibility to MS.

Case-Control Studies↗

PubMed2004

Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis.

OBJECTIVE: Interferon (IFN) beta has repeatedly shown benefit in multiple sclerosis (MS) in reducing the rate of relapse, the disease activity as shown with magnetic resonance imaging and, to some degree, the progression of disability; however, it is unknown how much the therapeutic response depends on the dose, the subgroup involved, and the disease stage. This multicentre, double blind, placebo controlled study explored the dose-response curve by examining the clinical benefit of low dose IFN beta-1a (Rebif), 22 micro g subcutaneously once weekly, in patients with secondary progressive MS. METHODS: A total of 371 patients with clinically definite SPMS were randomised to receive either placebo or subcutaneous IFN beta-1a, 22 micro g once weekly, for 3 years. Clinical assessments were performed every 6 months. The primary outcome was time to sustained disability, as defined by time to first confirmed 1.0 point increase on the Expanded Disability Status Scale (EDSS). Secondary outcomes included a sensitive disability measure and relapse rate. RESULTS: Treatment had no beneficial effect on time to confirmed progression on either the EDSS (hazard ratio (HR) = 1.13; 95% confidence interval (CI) 0.82 to 1.57; p = 0.45 for 22 micro g v placebo) or the Regional Functional Status Scale (HR = 0.93; 95% CI 0.68 to 1.28; p = 0.67). Other disability measures were also not significantly affected by treatment. Annual relapse rate was 0.27 with placebo and 0.25 with IFN (rate ratio = 0.90; 95% CI 0.64 to 1.27; p = 0.55). The drug was well tolerated with no new safety concerns identified. No significant gender differences were noted. CONCLUSIONS: This patient population was less clinically active than SPMS populations studied in other trials. Treatment with low dose, IFN beta-1a (Rebif) once weekly did not show any benefit in this study for either disability or relapse outcomes, including a subgroup with preceding relapses. These results add a point at one extreme of the dose-response spectrum of IFN beta therapy in MS, indicating that relapses in this phase may need treatment with higher doses than in the initial phases.

Adjuvants, Immunologic↗

PubMed2002

Beta-CIT-SPECT combined with UPDRS appears to distinguish different parkinsonian conditions.

OBJECTIVES: An earlier study in l-dopa responding patients with idiopathic Parkinson's disease documented that progressive nigro-striatal degeneration shown with single photon emission computed tomography (SPECT) and the cocain analog iodine-123-beta-CIT (beta-CIT) correlated linearly with increasing motor scores in the Unified Parkinson's Disease Rating Scale (UPDRS). Here we have extended the study to include 2 tremor patients with mild parkinsonism, 2 poor l-dopa responders with parkisonism and 2 non l-dopa responders with severe parkinsonism. METHODS: SPECT scanning was performed 20 h after injection of beta-CIT and UPDRS was done at the time of beta-CIT injection. RESULTS: All patients in the present study showed less nigro-striatal degeneration in relation to UPDRS motor scores than the patients with idiopathic Parkinson's disease. CONCLUSION: The results suggest that the the combination of beta-CIT-SPECT and UPDRS motor scores has the potential to differentiate idiopathic Parkinson's disease from other parkinsonian conditions.

Aged↗

PubMed2002

Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study.

OBJECTIVE: To evaluate potential changes in cognitive functions over a 5-yr period in patients with systemic lupus erythematosus (SLE). METHODS: Twenty-eight patients with SLE were examined at baseline and after a mean follow-up of 60.7+/-5.0 months using standardized neuropsychological tests. Group changes in performance over time were measured and the effects of baseline values for subsequent changes in individual variables after 5 yr were evaluated. RESULTS: When all SLE patients were considered as a group, seven out of nine (78%) neuropsychological variables remained unchanged and two (22%) improved significantly during the observation period, possibly due to methodological bias. Analysis of the importance of the level of initial cognitive performance for subsequent changes during the observation period, demonstrated that cognitive changes were not significantly influenced by baseline levels, except for a trend in three of nine variables. Neither demographic nor disease-associated quantitative factors were associated with cognitive changes over time. CONCLUSION: Cognitive dysfunction seems to be a relatively stable feature of central nervous system involvement in SLE. A decrease in performance over time was not demonstrated consistently in the majority of domains.

Adult↗

PubMed2001

[Skin biopsy for quantification of intraepidermal nerve fibers].

BACKGROUND: Skin biopsy for quantification of intraepidermal nerve fibre density has recently been introduced as a method for diagnosis of peripheral neuropathies. Immunostaining by antibody to protein gene product 9.5 has proved particularly useful because it selectively visualizes the epidermal nerve fibres. MATERIAL AND METHODS: We describe the procedure on the basis of relevant literature and our own experience. Results from investigations of 56 healthy individuals and three patients with small fibre involvement as part of their neuropathy are presented. RESULTS: In the healthy individuals, the mean density of epidermal fibres was 12.4 (SD 4.6), median 11.3 and range 6.0-26.1. Three patients with small fibre neuropathy had low intraepidermal nerve fibre density. INTERPRETATION: Skin biopsy for determination of intraepidermal nerve fibre density is a simple and non-painful procedure. Skin biopsies can be done repeatedly and may be used for the purpose of monitoring potential therapeutic agents.

Age Factors↗

PubMed2001

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow.

Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBE Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15% was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17%) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration.

Adult↗

PubMed2001

Peripheral neuropathy in systemic lupus erythematosus--a longitudinal study.

OBJECTIVE: Peripheral neuropathy (PN) is reported to occur in 5-27% of patients with systemic lupus erythematosus (SLE) mostly as a length-dependent sensorimotor axonopathy. Studies over time have not been performed. Design - Longitudinal study. SUBJECTS AND METHODS: Thirty-three Caucasian SLE patients consented to participate in the study and were subjected to clinical examination, laboratory tests, and nerve conduction velocity (NCV) studies. At the follow-up 7 years later, 7 patients (21%) were dead, 4 refused to participate, and 2 did not want to perform NCV studies. Twenty patients were thus available for longitudinal study. RESULTS: When all SLE patients were considered on a group basis at follow-up, 8 (33%) out of 24 NCV parameters showed significant deterioration despite correction for time, while 16 (67%) were unchanged. Analysis of change from baseline showed that, except for F-responses, several NCV changes were highly dependent (negative regression coefficients) on baseline levels at start of study. No demographic, laboratory, or disease associated quantitative factor was associated with these changes in NCV parameters over time. Nor was a consistent effect on NCV parameters from any qualitative demographic or disease associated factor confirmed by Repeated Measures ANOVA analyses. CONCLUSIONS: A modest progressive neuropathic process exists in patients with SLE. Important is also the finding that, over time, the abnormalities of NCV parameters fluctuate in the individual patients, and the impairments are not necessarily irreversible. This study also shows no association to medication, demographic-, or other disease associated factors.

Adolescent↗

PubMed2001

Increased risk of median nerve dysfunction in floor cleaners: a controlled clinical and neurophysiological study.

We studied median nerve involvement in a group of asymptomatic handworkers at risk for carpal tunnel syndrome, and we evaluated damage to thin and thick nerve fibres in the distribution area of the median nerve. Considering floor cleaners as workers at high risk of developing cumulative traumatic disorders in the wrist, we included 42 cleaners and 41 controls. We assessed nerve conduction studies, vibration threshold, and temperature and pain thresholds of the median nerve. The cleaners had significantly impaired motor nerve conduction velocity (p = 0.006), longer sensory distal latency (p = 0.01), lower sensory amplitude (p = 0.0005), and increased difference in heat and cold threshold of the median nerve (p = 0.0002). Increased temperature threshold was associated with prolonged sensory distal latency of the median nerve in the cleaners. In conclusion, impaired neurophysiological variables in the median nerve in floor cleaners compared with controls confirm the hypothesis that those workers are at risk of developing median nerve dysfunction. Sensory nerves seem to be more susceptible to injury than motor branches.

Adult↗

PubMed2001

Transesophageal and transthoracic echocardiography and Doppler-examinations in systemic lupus erythematosus.

OBJECTIVE: To search for cardiac abnormalities in systemic lupus erythematosus (SLE). METHODS: 35 patients examined by 2-D transthoracal Doppler and transesophageal echocardiography. RESULTS: Mitral and aortic valve abnormalities were seen in 12 patients (34%) respectively, and occurred altogether in 16 patients (46%). They were in general significantly associated with longer disease duration, but not with anticardiolipin antibodies (aCL), disease activity, or any other variable, except for time on corticosteroids. which was significantly longer in patients with aortic valve calcifications. CONCLUSION: Valve masses and valve thickening--often in combination--are the most frequent structural findings in SLE, occurring more often on the aortic than on the mitral valves. Factors other than antiphospholipid antibodies, medication, hypertension, or coronary heart disease seem to be responsible for this phenomenon. Drugs that modulate inflammation in endo- and pericardial tissue may, at least in part, be responsible for the observed mitral valve calcifications and pericardial fibrosis.

Adrenal Cortex Hormones↗

PubMed2001

Somatic and psychological features of headache in systemic lupus erythematosus.

OBJECTIVE: Headaches--especially of migrainous type--have been considered part of the disease spectrum of systemic lupus erythematosus (SLE). We wished to characterize prevalence and types of headaches in SLE and find out if headache is associated with disease, personality traits, or other psychological factors. METHODS: Fifty-eight consecutive Caucasian patients with SLE were given a clinical examination. We recorded SLE disease activity according to the SLE Disease Activity Index, types of headache according to International Headache Society criteria, and personality traits and emotional status according to Minnesota Multiphasic Personality Inventory-2 and Beck Depression Inventory (BDI). RESULTS: Thirty-eight SLE patients (66%) were headache sufferers; of these, 22 patients (38%) had migraine and 21 (36%) had tension-type headache. Headaches were not associated with disease activity or any other disease associated variable, including tests for antiphospholipid antibodies. Migraine was associated only with a tendency to social isolation and anxiety, while tension-type headache was associated with psychological distress, such as anxiety, somatic complaints, reduced energy, mental tension, social discomfort and withdrawal, and depressive mood according to the BDI. CONCLUSION; Migraine and tension-type headaches occur frequently in patients with SLE. Migraine shows the same clinical presentation as in a non-SLE population, and may not be part of a neuropsychiatric disease spectrum. This also applies to tension-type headache, which in contrast to migraine shows some associations with emotional and personality traits, and could represent components of a chronic pain syndrome.

Adult↗

PubMed2000

Multiple sclerosis in North Norway, and first appearance in an indigenous population.

This study was performed to determine the prevalence of multiple sclerosis (MS) in 1993 and annual incidence rates 1983-1992, and to examine whether the disease occurs among the Sami people. According to earlier reports the two northernmost counties of Norway, Troms and Finnmark with 225,000 inhabitants, have a relatively low prevalence of MS: 20.6 per 100,000 in 1973 and 31.5 in 1983. Also no person who is of pure Sami heritage (i.e., with both parents speaking Sami natively) has been found with the disease. Except for the introduction of magnetic resonance imaging as a diagnostic tool, there has been no significant change in the neurological service in the area during the past 20 years. Files of patients with the diagnosis of MS were reviewed, and questionnaires were sent to all patients alive on the prevalence day of 1 January 1993. The prevalence in 1993 was 73.0 per 100,000. The mean crude annual incidence rate was 3.5 per 100,000 during the period 1983-1992 compared with 3.0 during 1974-1982. In 1983 there were no pure Sami among the MS patients, but one had a Sami father. On 1 January 1993 there were three patients with both Sami parents and three with only one Sami parent, which is a rate that is still lower than would be expected if the prevalence of MS among the Sami were similar to that in the rest of the Norwegian population. The study shows that the incidence of MS in Troms and Finnmark has been increasing over the past 10 years, but is still lower than on the western coast and in the eastern part of Norway. The lowest incidence is found in Finnmark, where the Sami population is highest. During the past 10 years MS has also been diagnosed among the Sami population.

Adolescent↗

PubMed2000

Recovery of function in adjacent nerve roots after surgery for lumbar disc herniation: use of quantitative sensory testing in the exploration of different populations of nerve fibers.

Results from experimental and clinical studies indicate that adjacent nerve roots may be affected in sciatica because of lumbar disc hemiation. This may be caused by proinflammatory mediators in the epidural space being transported into nerve roots at the same or neighboring lumbar segments. The aim of the present study was to investigate the recovery of function of sensory nerve fibers in the adjacent noncompressed nerve roots. Thirty-nine patients undergoing microdiscectomy for monoradiculopathy were investigated with quantitative sensory testing immediately before surgery, and at 6 weeks, 4 months, and 12 months after the operation. Twenty-one healthy volunteers were used as controls. The patients were classified as having a good or a poor result at the 1-year follow-up according to a clinical score. Significant improvement of function in the noncompressed nerve roots were only observed in the 31 patients with a good result. The improvement in small myelinated nerve fibers came within 12 months in the adjacent nerve roots in both the symptomatic as well as the asymptomatic leg. The improvement of function in small unmyelinated fibers also came within 12 months after surgery; however, significant improvement was only observed in the ipsilateral neighboring nerve root. The function in large myelinated fibers did not improve in any of the adjacent nerve roots during the observation period. The observed recovery of function in adjacent noncompressed nerve roots after successful surgical decompression in monoradiculopathy may be because of less production of proinflammatory mediators when the disc herniation is removed.

Adult↗

PubMed1999

[Nerve biopsy].

Nerve biopsy, if undertaken at centres with appropriate expertise, may be a valuable diagnostic procedure in selected patients with peripheral neuropathy. Sural nerve biopsy and skin biopsy for evaluation of epidermal nerves are described. Indications, surgical procedure, preparation and transport are reviewed. Usually the patient has to be admitted to a hospital with the necessary resources for a comprehensive battery of nerve tissue processing, including teasing and electron microscopical examination, and other investigative procedures. Another option, when practically and economically feasible, is to obtain sural nerve biopsy from several (2-4) patients performed by a skilled surgeon at the local (central) hospital. A technician from a neuromuscular centre or laboratory of neuropathology should be at the site to provide immediate and proper preparation and transport of the tissue samples. An example of peripheral nerve vasculitis with teased nerve fibers in early and late axonal degeneration is presented as an illustration. Sural nerve biopsy is useful in selected cases, particularly in order to demonstrate peripheral nerve vasculitis. For detection of small fiber neuropathy in the investigation of painful neuropathies, skin biopsy for evaluation of epidermal nerves may be an appropriate alternative.

Biopsy↗

PubMed1999

Cerebral computed tomography and electroencephalography compared with neuropsychological findings in systemic lupus erythematosus.

Central nervous system involvement was evaluated in 36 patients with systemic lupus erythematosus (SLE) using cerebral computed tomography (CT), electroencephalography (EEG), and a neuropsychological test battery. The purpose was to investigate whether brain dysfunction as assessed by comprehensive neuropsychological investigation is associated with findings of routine investigation methods such as CT and EEG which are available in most hospitals. Abnormal EEG was found in 19%, and CT revealed cerebral atrophy in 47% of SLE patients. Few neuropsychological functions were affected by the presence of abnormal EEG, cerebral atrophy, or infarcts. Significant associations were found only between cortical atrophy and impairment of tactile spatial problem-solving and motor dexterity, and between cortical infarcts and motor dexterity in the dominant hand. The value of conventional EEG in assessing cerebral SLE is negligible, except for identifying epileptic activity and focal pathology. Cerebral CT has little relevance in predicting brain dysfunction as established by neuropsychological assessment in SLE, except for detecting cortical atrophy and infarcts.

Adult↗

PubMed1999

Relationship between brain structure sizes and performing rapid limb movements. A quantitative magnetic resonance study.

In this study, we aimed to determine the relationship between the size of cerebral structures evaluated by quantitative magnetic resonance technique and the ability of performing rapid-velocity limb movements. Forty-seven healthy women with a mean age of 43.4 years (range 22-68) were included. Exclusion criteria were systemic diseases including alcoholism. Finger and ankle tapping were quantitatively recorded for both right and left extremities. A mean value for the right and left side was calculated. To determine atrophy, we measured the area of the corpus callosum, the cerebrum and the cerebellum on midline sagittal sections. On transverse images, the ventricle-to-brain ratio, the bifrontal ratio and the bicaudate ratio were selected as atrophy parameters. Also, the prevalence of white matter hyperintensities was assessed. Fifteen (32%) had hyperintense white matter lesions. Using simple regression analysis, the frequencies of both finger (r = 0.37, beta = -0.002, p = 0.022) and ankle (r = 0.35, beta = -0.001, p = 0.032) tapping were associated with reduced cerebellar size. No association was found for other atrophy parameters or the number of hyperintense white matter lesions. This study indicates that impaired ability to perform fast limb movements may be related to a relative cerebellar atrophy.

Adult↗

PubMed1999

Myopathy and neuropathy in rheumatoid arthritis. A quantitative controlled electromyographic study.

OBJECTIVE: To test the hypothesis that patients with rheumatoid arthritis (RA) have clinical or subclinical evidence of peripheral neuropathy or myopathy. METHODS: We studied 40 seropositive women with RA, mean age 46.6 years (SD 6.4), and 56 healthy controls, mean age 43.0 years (SD 9.1). Patients had a mean disease duration of 13.0 years (SD 7.8). We performed electromyographic examination of 4 muscles [extensor digitorum communis (EDC), biceps brachii (BB), vastus lateralis (VL), and tibialis anterior (TA)] on the right side in both groups. Quantitative data included percentage of polyphasic potentials, motor unit potential amplitude, area, duration, turns, and number of polyphasic potentials. RESULTS: There were statistically significantly higher proportions of polyphasic potentials in 3 muscles in patients compared with controls. Mean number of phases in EDC was 4.6 (SD 0.4) in the patients and 4.1 (0.5) in controls (p = 0.0001). The values for the VL were 4.1 (SD 0.4) in patients compared with 3.6 (0.4) in controls (p = 0.0001), and in the TA 4.5 (SD 0.5) versus 4.0 (0.4) (p = 0.0001). We also found significantly increased duration of motor unit potentials in the VL and TA of patients. The amplitudes of motor unit action potentials were not significantly different in the 2 groups. CONCLUSION: The study reveals an increased prevalence of neurogenic but not myogenic changes in patients with RA compared with controls.

Adolescent↗

PubMed1998

[Myelin diseases affecting both the central and the peripheral nervous system].

Myelin is synthesized by oligodendrocytes in the central nervous system and by Schwann cells in the peripheral nervous system. A combined dysmyelinating/demyelinating process in the central nervous system and in the peripheral nervous system occurs only rarely. A brief review of these conditions is given in this article. Occasionally, coexistence of multiple sclerosis and chronic inflammatory demyelinating polyneuropathy is reported. Cases of multiple sclerosis, hypertrophic polyneuropathy, and central nervous system demyelination in Miller-Fisher syndrome and Guillain-Barré syndrome have also been reported. Concurrent dysmyelination in the central nervous system and peripheral nerve demyelination are common in metachromatic leukodystrophy, Krabbe disease and adrenoleukodystrophy. A Norwegian family with adult-onset demyelinating disease affecting both the peripheral and central nervous system has recently been described. The mode of inheritance is probably autosomal dominant, but its exact nature remains unknown.

Central Nervous System Diseases↗