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| 2. |
- Bäckström, David, et al.
(author)
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PITX3 genotype and risk of dementia in Parkinson's disease : A population-based study
- 2017
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In: Journal of the Neurological Sciences. - : ELSEVIER SCIENCE BV. - 0022-510X .- 1878-5883. ; 381, s. 278-284
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Journal article (peer-reviewed)abstract
- Dementia is a devastating manifestation of Parkinson's disease (PD). This study investigates whether a common polymorphism in the PITX3 gene (rs2281983), which is of importance for the function of dopaminergic neurons, affects the risk of developing dementia in PD and whether it affects dopamine transporter (DAT) uptake. We PITX3 genotyped 133 patients with new-onset, idiopathic PD, participating in a population-based study in Sweden. Patients were followed prospectively during 6-11 years with extensive investigations, including neuropsychology and DAT-imaging with I-123 FP-CIT. The primary outcome was the incidence of PD dementia (PDD), diagnosed according to published criteria, studied by the Kaplan-Meier method and Cox proportional hazards. Performance in individual cognitive domains, the incidence of visual hallucinations, disease progression and striatal DAT uptake on imaging was also investigated. PD patients carrying the PITX3 C allele had an increased risk of developing PDD (hazard ratio: 2.87, 95% CI: 1.42-5.81, p = 0.003), compared to the PD patients homozygous for the T-allele. Furthermore, the PITX3 C allele carriers with PD had a poorer cognitive performance in the visuospatial domain (p < 0.001) and a higher incidence of visual hallucinations. A trend towards a lower striatal DAT uptake in the PITX3 C allele carriers was suggested, but could not be confirmed. Our results show that a common polymorphism in the PITX3 gene affects the risk of developing PDD and visuospatial dysfunction in idiopathic PD. If validated, these findings can provide new insights into the neurobiology and genetics of non-motor symptoms in PD.
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| 3. |
- Johansson, A, et al.
(author)
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Hypercortisolism after stroke--partly cytokine-mediated?
- 1997
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In: Journal of the Neurological Sciences. - 0022-510X .- 1878-5883. ; 147:1, s. 43-7
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Journal article (peer-reviewed)abstract
- Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis is common early after stroke. Hypercortisolism is a prominent manifestation. Normally the secretion of cortisol is regulated by adrenocorticotrophic hormone (ACTH), but recently an ACTH/cortisol dissociation after stroke was reported. Cytokines may influence the HPA axis, and plasma IL-6 levels are elevated following stroke. We investigated correlations between cortisol, ACTH, and cytokines, and between blood pressure and blood hormone levels early after stroke in seven stroke patients. All had neurological symptoms secondary to brain infarctions. Blood samples for analysis of cortisol, ACTH, IL-6, TNF alpha, norepinephrine, and epinephrine were collected four times daily, and 24-h blood pressure was measured. Plasma IL-6, but not ACTH, correlated significantly to serum cortisol. Catecholamine levels correlated with cytokine and cortisol levels. This study suggests that several routes for HPA-axis dysregulation is present early after stroke. Cytokine release may play an important role in this situation.
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| 4. |
- Lindman, Rolf, et al.
(author)
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Abnormal palatopharyngeal muscle morphology in sleep-disordered breathing
- 2002
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In: Journal of the Neurological Sciences. - : Elsevier. - 1878-5883 .- 0022-510X. ; 195:1, s. 11-23
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Journal article (peer-reviewed)abstract
- The aim of the present study was to investigate whether histopathological changes can be detected in two soft palate muscles, the palatopharyngeus and the uvula, in 11 patients with long duration of sleep-disordered breathing (SDB). Muscle samples were collected froth patients undergoing uvulo-palatopharyngoplasty (UPPP). Reference samples from the corresponding areas were obtained at autopsy froth five previously healthy subjects. Muscle morphology, fibre type and myosin heavy chain (MyHC) compositions were analysed with enzyme-histochemical, immunohistochemical and biochemical techniques. The muscle samples from the patients, and especially those from the palatopharyngeus, showed several morphological abnormalities. The most striking findings were (i) increased amount of connective tissue, (ii) abnormal variability in fibre size, (iii) increased proportion of small-sized fibres, (iv) alterations in fibre type and MyHC compositions, (v) increased frequency of fibres containing developmental MyHC isoforms. Our findings point towards a pathological process of denervation and degeneration in the patient samples. Conclusively. the morphological abnormalities suggest a neuromuscular disorder of the soft palate in SDB patients. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 5. |
- Mezei, M., et al.
(author)
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Motor system abnormalities in heterozygous relatives of a D90A homozygous CuZn-SOD ALS patient of Finnish extraction.
- 1999
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In: Journal of the Neurological Sciences. - 0022-510X .- 1878-5883. ; 169:1-2, s. 49-55
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Journal article (peer-reviewed)abstract
- Presently, 64 mutations in the gene encoding the enzyme CuZn-superoxide dismutase have been found in a small fraction of amyotrophic lateral sclerosis patients worldwide. All but one of these mutations show autosomal dominant inheritance. In Scandinavia, the D90A mutation is inherited as an autosomal recessive trait and patients have an easily recognizable characteristic phenotype with little variation among patients, even amongst different families. Importantly, all D90A heterozygous relatives of Scandinavian D90A homozygous patients have been reported as clinically unaffected. We have investigated a Canadian family of Finnish extraction in which the D90A homozygous proband developed ALS with the characteristic phenotype. Remarkably, two D90A heterozygous relatives show slight symptoms and signs of motor system involvement, suggesting that the final phenotype of an individual with a CuZn-superoxide dismutase mutation is shaped by the combination of the particular CuZn-SOD mutation, other polymorphic modifying genes elsewhere in the genome, stochastics and possible environmental factors.
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| 6. |
- Norman, Holly, et al.
(author)
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Myofibrillar protein and gene expression in acute quadriplegic myopathy
- 2009
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In: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 285:1-2, s. 28-38
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Journal article (peer-reviewed)abstract
- The dramatic muscle wasting, preferential loss of myosin and impaired muscle function in intensive care unit (ICU) patients with acute quadriplegic myopathy (AQM) have traditionally been suggested to be the result of proteolysis via specific proteolytic pathways. In this study we aim to investigate the mechanisms underlying the preferential loss of thick vs. thin filament proteins and the reassembly of the sarcomere during the recovery process in muscle samples from ICU patients with AQM. Quantitative and qualitative analyses of myofibrillar protein and mRNA expression were analyzed using SDS-PAGE, confocal microscopy, histochemistry and real-time PCR. The present results demonstrate that the transcriptional regulation of myofibrillar protein synthesis plays an important role in the loss of contractile proteins, as well as the recovery of protein levels during clinical improvement, myosin in particular, presumably in concert with proteolytic pathways, but the mechanisms are specific to the different thick and thin filament proteins studied.
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| 7. |
- Pontén, Eva, et al.
(author)
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Higher amount of MyHC IIX in a wrist flexor in tetraplegic compared to hemiplegic cerebral palsy
- 2008
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In: Journal of the Neurological Sciences. - : Elsevier. - 0022-510X .- 1878-5883. ; 266:1-2, s. 51-56
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Journal article (other academic/artistic)abstract
- Spastic cerebral palsy can be divided into diagnostic groups by the relative severity of the arm impairment. This study investigates if hemiplegic, tetraplegic or diplegic cerebral palsy (CP) results in different patterns of myosin heavy chain (MyHC) expression in the flexor carpi ulnaris muscle from 17 young patients with CP. Using enzyme-immunohistochemistry and gel electrophoresis techniques we found a higher percentage of fibers expressing fast MyHC IIx (52%) in tetraplegic CP compared to hemiplegic patients (32%), (p < 0.05). Tetraplegic CP also resulted in a lower amount of fibers expressing slow MyHC I (18%) compared to hemiplegic CP (40%), (p < 0.005). The proportion of muscle fibers containing fetal MyHC was higher in tetraplegic CP compared to other groups, (p < 0.005). Taken together theses results indicate that tetraplegic CP is associated with a shift from slow to fast myosins and that regenerative events are more prominent in tetraplegic CP compared with milder brain damage.
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| 8. |
- Pontén, Eva M., et al.
(author)
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Decreased capillarization and a shift to fast myosin heavy chain IIx in the biceps brachii muscle from young adults with spastic paresis
- 2007
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In: Journal of the Neurological Sciences. - : Elsevier. - 0022-510X .- 1878-5883. ; 253:1-2, s. 25-33
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Journal article (peer-reviewed)abstract
- Muscle spasticity and paresis are conditions that occur secondary to upper motor neuron lesions. The co-existence of decreased motor unit recruitment and intermittent over-activity generates confusion concerning the effect on muscle fiber characteristics. In order to increase the knowledge about the effect of upper motor lesion on capillarization and muscle fiber composition, the biceps brachii muscle from seven young adults with long duration of spastic paresis and seven age-matched controls were analyzed using morphological and enzyme- and immuno-histochemical techniques. The spastic muscles had a 38% lower capillary density (p = 0.002), 30% fewer capillaries around each muscle fiber (p = 0.02), and 16% fewer capillaries when related to the fiber size (p = 0.04). The frequency of fibers expressing myosin heavy chain (MyHC) IIx increased (30% vs. 4%, p = 0.006), while the percentage of fibers expressing MyHC I and MyHC IIa, respectively, decreased (22% vs. 46% and 7% vs. 29%, p < 0.01). The high proportion of muscle fibers with low oxidative capacity and low capillary supply indicates that biceps brachii muscle from patients with upper motor lesions fatigue more easily than normal controls. We also observed a significantly higher variability in fiber size for fibers expressing MyHC I (p < 0.04), and, in three of the subjects, a small amount of small fibers expressing developmental MyHCs was found. These results suggest that, although intermittent stretch reflex contractions might have an impact on the muscle characteristics in spastic paresis, the muscle phenotypic properties are more adapted to decreased voluntary motor unit recruitment.
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| 9. |
- Richard, Edo, et al.
(author)
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Methodological challenges in designing dementia prevention trials - The European Dementia Prevention Initiative (EDPI)
- 2012
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In: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 322:1-2, s. 64-70
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Journal article (peer-reviewed)abstract
- Recent epidemiological studies have indicated numerous associations between vascular and lifestyle related risk factors and incident dementia. However, evidence from randomised controlled trials (RCT) showing effectiveness of interventions aimed at these risk factors in preventing or postponing dementia onset is still lacking. Three large RDT on multi-component interventions to prevent dementia (preDIVA, FINGER. MAPT) have been initiated in Europe to address these issues. Irrespective of some methodological differences, all three studies target cardiovascular and lifestyle related risk factors. Collaboration within the newly founded 'European Dementia Prevention Initiative' (EDPI) will allow for a comprehensive exploration of optimal target population, intervention and outcome measures, which are currently unknown. Combining data of the ongoing studies and running simulation analyses will facilitate determining the optimal design including accurate sample-size calculations for future multi-national clinical trials on dementia prevention. Interventions aiming at dementia prevention should be pragmatic and easy to implement on a large scale in different health care systems, without generating high additional costs or burden on participants or physicians. As the optimal age for intervention precedes the optimal age for outcome assessment, traditional trial designs might lead to suboptimal timing of either of the two. Separation of intervention and outcome assessment in time is a potential solution, but requires studies with very long follow-up. International collaboration of research groups with experience in dementia prevention studies and well-organised logistics for these major projects is pivotal to success for future large-scale dementia prevention studies. Founding of EDPI is an important first step in this direction.
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| 10. |
- Rosén, Christoffer, 1986, et al.
(author)
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High levels of neurofilament light and YKL-40 in cerebrospinal fluid are related to poor outcome in ALS
- 2024
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In: Journal of the Neurological Sciences. - : Elsevier. - 0022-510X .- 1878-5883. ; 463
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a neurological disease without effective treatment. No pathognomonic test can diagnose ALS in sporadic cases. Routine investigation in suspected cases includes neurological examination, imaging of the brain and spine and electromyography supported by blood and cerebrospinal fluid (CSF) analyses. The ALS diagnosis is made by clinical judgement and results from examinations. We aimed to study if the CSF biomarkers neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), YKL-40, soluble amyloid precursor protein (sAPP) α and β, and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) were associated with ALS diagnosis and could predict disease progression. Eighty-one patients with suspected ALS were included after referral to the neurological clinic at Sahlgrenska University Hospital. Fifty-nine patients were diagnosed having ALS, while 22 patients were given alternative diagnoses and labeled ALS mimics. Finally, 25 age-matched neurologically intact individuals were used as controls.ALS patients had significantly higher CSF levels of NFL than controls and mimics. Levels of YKL-40 and GFAP were significantly higher in ALS patients compared with controls. No difference was found between study groups when comparing levels of sAPPα, sAPPβ and sTREM2. Further, elevated levels of NFL and YKL-40 were associated with an increased hazard of death and the annual decline in ALSFRS-R. We also found that patients with elevated levels of both NFL and YKL-40 had a particularly poor prognosis. The results demonstrate the usefulness of CSF biomarkers in the diagnosis and prognostication of ALS.
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