| 1. |
- Corcia, Philippe, et al.
(författare)
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Homozygous SMN2 deletion is a protective factor in the Swedish ALS population
- 2012
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 20:5, s. 588-591
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal survival motor neuron 1 (SMN1)-copy number has been associated with an increased risk of amyotrophic lateral sclerosis (ALS) in French and Dutch population studies. The aim of this study was to determine whether SMN gene copy number increases the risk of ALS or modulates its phenotype in a cohort of Swedish sporadic ALS (SALS) patients. In all, 502 Swedes with SALS and 502 Swedish controls matched for gender and age were enrolled. SMN1 and SMN2 gene copy numbers were studied by a semi-quantitative PCR method. A genotype-phenotype comparison was performed in order to determine whether SMN genes modulate the phenotype of ALS. The results were also compared with our previously reported French cohort of ALS patients. There was no difference between Swedish patients and controls in the frequency of SMN1 and SMN2 copy numbers. The frequency of SMN1 gene copies differed significantly between the French and Swedish ALS populations. The duration of the disease was significantly longer in the Swedish cohort with homozygous deletions of SMN2 when compared with the French cohort. Abnormal SMN1 gene copy number cannot be considered as a universal genetic susceptibility factor for SALS and this result underlines the importance of reproducing association gene studies in groups from different origins. We also suggest that SMN2 gene copy number might have different effects on ALS progression in disparate human populations. European Journal of Human Genetics (2012) 20, 588-591; doi:10.1038/ejhg.2011.255; published online 25 January 2012
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| 2. |
- Dispenzieri, Angela, et al.
(författare)
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Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) : 14-year update
- 2022
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Ingår i: Orphanet Journal of Rare Diseases. - : BioMed Central (BMC). - 1750-1172. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs.Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021).Results: This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation.Conclusions: This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease.ClinicalTrials.gov Identifier: NCT00628745.
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| 3. |
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| 4. |
- Eriksson Westblad, Mimmi, et al.
(författare)
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Disability and health status in patients with chronic inflammatory demyelinating polyneuropathy
- 2009
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Ingår i: Disability and Rehabilitation. - London : Taylor & Francis. - 0963-8288 .- 1464-5165. ; 31:9, s. 720-725
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Chronic inflammatory demyelinating polyneuropathy (CIDP) is a disorder affecting the peripheral nerves. The purpose of this study was to describe disability and health status in patients with CIDP in Sweden. Methods. All 22 adult patients with CIDP at the Karolinska University Hospital, Huddinge were invited to participate. Twenty-one patients performed all measures. Their mean age was 54 years. The following measures were used: vibration perception threshold (VPT); the Fatigue Severity Scale (FSS); the Berg Balance Scale; finger dexterity using the Nine-Hole Peg Test (NHPT); functional mobility using the Timed 'Up and Go' Test; health status with the SF-36 questionnaire. Results. Fifty-seven per cent of the patients had a higher thumb and ankle VPT than published normative data. The FSS showed that 38% scored over 5, indicating severe fatigue. The majority of the patients had reduced functional balance. Sixty-two per cent had a subnormal result on the NHPT. Results of the SF-36 showed lower scores than the Swedish norm on the sub-scales describing physical health. Conclusions. The majority of the patients with CIDP had disabilities and decreased physical health status. The presence of fatigue may be taken into consideration in immunomodulatory treatments and during physical rehabilitation.
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| 5. |
- Feresiadou, Amalia, et al.
(författare)
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Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease
- 2019
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 332, s. 31-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discriminate between inflammatory and non-inflammatory neurological diseases.METHODS: The concentration of sCD27 was measured using a commercially available ELISA in 803 well-defined subjects from a study cohort comprised of 338 patients with neuroinflammatory disease, 338 with non-inflammatory neurological disease and 127 controls without neurological disease.RESULTS: The median value of cerebrospinal fluid sCD27 was 64 pg/mL (IQR 0-200) in controls, 58 pg/mL (IQR 0-130) in patients with non-inflammatory disease and 740 pg/mL (IQR 230-1800) in patients with inflammatory disease. The likelihood ratio of having an inflammatory disease was 10 (sensitivity 74% and specificity 93%) if the sCD27 concentration was >250 pg/mL. In patients with a known inflammatory condition, the likelihood ratio of having an infection was 10 (sensitivity 40% and specificity 96%) if the sCD27 concentration was >2500 pg/mL.CONCLUSIONS: The likelihood of having an inflammatory neurological condition is increased with elevated concentrations of sCD27 in cerebrospinal fluid. Rapid tests of sCD27 should be developed to assist clinicians in diagnosis of neuroinflammatory disease.
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| 6. |
- Forsberg, Anette, 1965-, et al.
(författare)
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Disability and health-rated quality of life in Guillain-Barré syndrome during the first two years after onset : a prospective study
- 2005
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Ingår i: Clinical Rehabilitation. - : SAGE Publications. - 0269-2155 .- 1477-0873. ; 19:8, s. 900-909
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe changes in disability and health-related quality of life in patients with Guillain-Barré syndrome in Sweden during the first two years after onset.SUBJECTS: Forty-four patients were recruited from eight different hospitals, and 42 of them (mean age 52 years) were followed for two years. Evaluations were performed, primarily as home visits, at two weeks, two months, six months, one year and two years after onset.MAIN MEASURES: Disability was measured using the Katz Personal and Extended Activities of Daily Living Indexes, the Barthel Index, the Frenchay Activity Index and assessments of work capacity; health-related quality of life using the Sickness impact Profile.RESULTS: At two weeks, one year and two years after onset of Guillain-Barré syndrome, 76%, 14% and 12% of patients were dependent in personal activities of daily life (ADL); and 98%, 28% and 26% were dependent in instrumental ADL. At two weeks, all of the patients that were working before onset were unable to work owing to Guillain-Barré syndrome; at two years, 17% were unable to work. At two weeks, scores on Sickness Impact Profile were elevated in all dimensions; at two years, they remained elevated in the physical dimension and in the categories home management, work and recreation and pastimes.CONCLUSIONS: The impact of Guillain-Barré syndrome on ADL, work, social activities and health-related quality is considerable two years after onset and presumably persists beyond this time point.
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| 7. |
- Forsberg, Anette, 1965-, et al.
(författare)
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Impairment in Guillain-Barré syndrome during the first 2 years after onset : A prospective study
- 2004
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 227:1, s. 131-138
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo provide a comprehensive description of impairment in patients with Guillain–Barré syndrome (GBS) in Sweden during the first 2 years after disease onset.MethodsIn this prospective multi-centre study, 42 patients, mean age 52 years, were evaluated at 2 weeks, 2 months, 6 months, 1 year and 2 years. Evaluations made use of validated, reliable measures of muscle strength, grip strength, finger dexterity, balance, facial-muscle function, respiratory function, gait, motor performance and sensory examination, and included patients' owns assessments of pain, fatigue and paraesthesia.ResultsMechanical ventilation was required in 21% of patients. At 2 weeks, 1 year and 2 years after GBS onset: 100%, 62% and 55% of patients had submaximal overall muscle strength; 98%, 38% and 31% subnormal grip strength; and 38%, 14% and 12% affected facial-muscle function. At the same time points, 62%, 10% and 7% of patients were unable to walk 10 m independently; and affected sensation was detected in 93%, 55% and 52%.ConclusionsRecovery occurred mainly during the first year after onset. At 2 years, motor impairment and sensory impairment were each still detectable in more than 50% of patients. We conclude that residual impairment is significant, somatically widespread and, likely, persistent.
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| 8. |
- Forsberg, Anette, 1965-, et al.
(författare)
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Residual disability 10 years after falling ill in Guillain-Barré syndrome : a prospective follow-up study
- 2012
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Ingår i: Journal of the Neurological Sciences. - Amsterdam, Netherlands : Elsevier. - 0022-510X .- 1878-5883. ; 317:1-2, s. 74-79
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe residual disability 10years after onset of Guillain-Barré syndrome (GBS) and longitudinal changes from 2weeks after onset until 10years afterwards. The Erasmus GBS Outcome score (EGOS) was applied for predicting prognosis at 2 and 10years.Methods: Twenty-nine patients, mean age at onset 49years, were followed prospectively from 2weeks to 10years after GBS onset. Measures included; GBS disability score, EGOS, Barthel Index, Frenchay Activity Index, Sickness Impact Profile (SIP), Overall Neuropathy Limitations Scale (ONLS), Walk-12, and Fatigue Severity Scale.Results: At 10years, the facial paralysis found in 5 participants at 2years was still present, 11 participants (38%) experienced paresthesia, 6 (21%) had limitations in their arms, and 15 (52%) had limitations in walking. Decreased health-related quality of life on comparison to the general population was seen in the physical dimension of SIP at 10years. The median EGOS at 2weeks was 4.5, which correlated highly only with the Barthel Index at 2years and the ONLS arm scale at 10years.Conclusion: The residual disabilities at 1-2years comprised mainly of reduced walking ability, and are still persistent 10years after GBS onset. For some individuals, facial paralysis caused major disability. The EGOS only partly predicted residual disability at 2 and 10years after onset.
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| 9. |
- Ingre, Caroline, et al.
(författare)
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A 50bp deletion in the SOD1 promoter lowers enzyme expression but is not associated with ALS in Sweden
- 2016
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 17:5-6, s. 452-457
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). A 50 base pair (bp) deletion of SOD1 has been suggested to reduce transcription and to be associated with later disease onset in ALS. This study was aimed to reveal if the 50bp deletion influenced SOD1 enzymatic activity, occurrence and phenotype of the disease in a Swedish ALS/control cohort. Blood samples from 512 Swedish ALS patients and 354 Swedish controls without coding SOD1 mutations were analysed for the 50bp deletion allele. The enzymatic activity of SOD1 in erythrocytes was analysed and genotype-phenotype correlations were assessed. Results demonstrated that the genotype frequencies of the 50bp deletion were all found to be in Hardy-Weinberg equilibrium. No significant differences were found for age of onset, disease duration or site of onset. SOD1 enzymatic activity showed a statistically significant decreasing trend in the control group, in which the allele was associated with a 5% reduction in SOD1 activity. The results suggest that the 50bp deletion has a moderate reducing effect on SOD1 synthesis. No modulating effects, however, were found on ALS onset, phenotype and survival in the Swedish population.
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| 10. |
- Ingre, Caroline, 1977-, et al.
(författare)
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A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts
- 2013
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Ingår i: Neurobiology of Aging. - New York : Elsevier. - 0197-4580 .- 1558-1497. ; 34:6
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Tidskriftsartikel (refereegranskat)abstract
- Profilin 1 is a central regulator of actin dynamics. Mutations in the gene profilin 1 (PFN1) have veryrecently been shown to be the cause of a subgroup of amyotrophic lateral sclerosis (ALS). Here, weperformed a large screen of US, Nordic, and German familial and sporadic ALS and frontotemporaldementia (FTLD) patients for PFN1 mutations to get further insight into the spectrum and pathogenicrelevance of this gene for the complete ALS/FTLD continuum. Four hundred twelve familial and 260sporadic ALS cases and 16 ALS/FTLD cases from Germany, the Nordic countries, and the United Stateswere screened for PFN1 mutations. Phenotypes of patients carrying PFN1 mutations were studied. Ina German ALS family we identified the novel heterozygous PFN1 mutation p.Thr109Met, which wasabsent in controls. This novel mutation abrogates a phosphorylation site in profilin 1. The recentlydescribed p.Gln117Gly sequence variant was found in another familial ALS patient from the United States.The ALS patients with mutations in PFN1 displayed spinal onset motor neuron disease without overtcognitive involvement. PFN1 mutations were absent in patients with motor neuron disease anddementia, and in patients with only FTLD. We provide further evidence that PFN1 mutations can causeALS as a Mendelian dominant trait. Patients carrying PFN1 mutations reported so far represent the“classic” ALS end of the ALS-FTLD spectrum. The novel p.Thr109Met mutation provides additional proofof-principle that mutant proteins involved in the regulation of cytoskeletal dynamics can cause motorneuron degeneration. Moreover, this new mutation suggests that fine-tuning of actin polymerization byphosphorylation of profilin 1 might be necessary for motor neuron survival.
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