Genetic Epidemiology of Amyotrophic Lateral Sclerosis in Norway: A 2-Year Population-Based Study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40-70% of familial ALS patients and approximately 5% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of the genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort. METHODS: Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of C9orf72 and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools. RESULTS: A total of 279 ALS patients were included in the study. Of these, 11.5% had one or several family members affected by ALS, whereas 88.5% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1%), among which 18 (58.1%) were familial and 13 (41.9%) were sporadic. The most common genetic cause was the C9orf72 expansion (6.8%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of SOD1 and TBK1 were identified in 10 familial and 2 sporadic cases. C9orf72 expansions dominated in patients from the Northern and Central regions, whereas SOD1 variants dominated in patients from the South-Eastern region. CONCLUSION: In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well.

Factors influencing employment after minor stroke and NSTEMI.

AIM: To study the effect of cognitive function, fatigue and emotional symptoms on employment after a minor ischemic stroke compared to non-ST-elevation myocardial infarction (NSTEMI). MATERIAL AND METHODS: We included 217 patients with minor ischemic stroke and 133 NSTEMI patients employed at baseline aged 18-70 years. Minor stroke was defined as modified Rankin scale (mRS) 0-2 at day seven or at discharge if before. Included NSTEMI patients had the same functional mRS. We applied a selection of cognitive tests and the patients completed questionnaires measuring symptoms of anxiety, depression and fatigue at follow up. Stroke patients were tested at three and 12 months and NSTEMI at 12 months. RESULTS: The patients still employed at 12 monthswere significantly younger than the unemployed patients and the NSTEMI patients employed were significantly older than the stroke patients (59 vs 55 years, p < .001). In total, 82 % of stroke patients and 90 % of the NSTEMI patients employed at baseline were still employed at 12 months (p = 06). Stroke patients at work after 12 months had higher education than unemployed patients. There were no difference between employed and unemployed patients in risk factors or location of cerebral ischemic lesions. Cognitive function did not change significantly in the stroke patients from three to 12 months. For stroke patients, we found a significant association between HADS-depression and unemployment at 12 months (p = 04), although this association was not present at three months. Lower age and higher educational level were associated with employment at 12 months for all patients. DISCUSSION AND CONCLUSION: Age and education are the main factors influencing the ability to stay in work after a minor stroke. Employed stroke patients were younger than the NSTEMI patients, but there was no difference in the frequencies in remaining employed. The employment rate at 12 months was high despite the relatively high prevalence of cognitive impairment in both groups.

Cognitive and Emotional Impairment after Minor Stroke and Non-ST-Elevation Myocardial Infarction (NSTEMI): A Prevalence Study.

AIM: To study the prevalence of cognitive and emotional impairment following a minor ischemic stroke compared to an age-matched group with non-ST-elevation myocardial infarction (NSTEMI). METHODS: We included patients aged 18-70 years with a minor ischemic stroke defined as modified Rankin Scale (mRS) 0-2 at day 7 or at discharge if before and age-matched NSTEMI patients with the same functional mRS. We applied a selection of cognitive tests and the patients completed a questionnaire comprising of Hospital Anxiety and Depression scale (HADS) and Fatigue Severity Scale (FSS) at follow-up 12 months after the vascular event. Results of cognitive tests were also compared to normative data. RESULTS: 325 ischemic stroke and 144 NSTEMI patients were included. There was no significant difference in cognitive functioning between ischemic stroke and NSTEMI patients. Minor stroke patients and to a lesser extent NSTEMI patients scored worse on more complex cognitive functions including planning and implementation of activities compared to validated normative data. For the minor stroke patients the location of the ischemic lesion had no influence on the result. The prevalence of anxiety, depression, and fatigue was significantly higher in the stroke group compared to the NSTEMI group. Depression was independently associated with reduced cognitive function. DISCUSSION AND CONCLUSION: Minor ischemic stroke patients, and to lesser degree NSTEMI patients, had reduced cognitive function compared to normative data, especially executive functioning, on 12-month follow-up. The difference in cognitive function between stroke and NSTEMI patients was not significant. Depression was associated with low scores on cognitive tests highlighting the need to adequately address emotional sequelae when considering treatment options for cognitive disabilities.

Stroke risk after transient ischemic attack in a Norwegian prospective cohort.

BACKGROUND: Transient ischemic attack (TIA) is a risk factor of stroke. Modern treatment regimens and changing risk factors in the population justify new estimates of stroke risk after TIA, and evaluation of the recommended ABCD2 stroke risk score. METHODS: From October, 2012, to July, 2014, we performed a prospective, multicenter study in Central Norway, enrolling patients with a TIA within the previous 2 weeks. Our aim was to assess stroke risk at 1 week, 3 months and 1 year after TIA, and to determine the predictive value of the dichotomized ABCD2 score (0-3 vs 4-7) at each time point. We used data obtained by telephone follow-up and registry data from the Norwegian Stroke Register. RESULTS: Five hundred and seventy-seven patients with TIA were enrolled of which 85% were examined by a stroke specialist within 24 h after symptom onset. The cumulative incidence of stroke within 1 week, 3 months and 1 year of TIA was 0.9% (95% CI, 0.37-2.0), 3.3% (95% CI, 2.1-5.1) and 5.4% (95% CI, 3.9-7.6), respectively. The accuracy of the ABCD2 score provided by c-statistics at 7 days, 3 months and 1 year was 0.62 (95% CI, 0.39-0.85), 0.62 (95% CI, 0.51-0.74) and 0.64 (95% CI, 0.54-0.75), respectively. CONCLUSIONS: We found a lower stroke risk after TIA than reported in earlier studies. The ABCD2 score did not reliably discriminate between low and high risk patients, suggesting that it may be less useful in populations with a low risk of stroke after TIA. TRIAL REGISTRATION: Unique identifier: NCT02038725 (retrospectively registered, January 16, 2014).

Thrombolytic therapy in acute ischaemic stroke.

BACKGROUND: The aim of this study was to assess the feasibility, clinical effect and safety of intravenous thrombolysis with tissue plasminogen activator in patients with acute ischaemic stroke treated in an acute stroke unit. METHODS: All patients admitted within 3 h after an acute ischaemic stroke were considered for thrombolysis. Twenty-four patients were treated. RESULTS: Ten patients demonstrated early clinical improvement compatible with a positive effect of thrombolysis. Five patients demonstrated a substantial but slow clinical improvement with an uncertain relationship to thrombolysis. Nine patients did not improve. One patient developed an intracerebral haematoma and 2 developed a haemorrhagic infarction without clinical deterioration. Five patients (21%) died within the first 3 months. At follow-up after 6 months, 10 patients (42%) had achieved independence [modified Rankin Scale (mRS) 0-2], 9 (33%) had an unfavourable outcome (mRS 3-5) and 5 patients (21%) had died. None of these 5 patients died due to a treatment complication. CONCLUSIONS: This study in a small patient population suggests that thrombolysis may be administered relatively safely in an acute stroke unit without intensive care facilities. The clinical effect and safety were similar to those which have been found in large randomised studies and clinical series.