| 1. |
- Larsson, Jenny, 1990-
(författare)
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Population-based studies of higher-level gait disorders and hydrocephalus : focused on brain ventricular morphometry and patient outcomes following shunt surgery
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: To study gait is of great importance for the health of the aging population. Higher-level gait disorders (HLGD) are characterized by a slow, symmetrical, unsteady gait. Its cause is most often unknown. HLGD in combination with ventriculomegaly (i.e., large brain ventricles) is obligatory for the diagnosis of Idiopathic Normal pressure hydrocephalus (INPH), a syndrome that is sometimes treatable with insertion of a CSF shunt. It is therefore important to investigate the prevalence of HLGD in the population and brain morphometry in individuals with HLGD. Further, self-perceived confidence in gait and balance among patients with HLGD and INPH is unknown and important to study as slow gait velocity is associated with falls, injuries, and death. CSF shunts in INPH are associated with adverse events and little is known about epilepsy after surgery or minor and moderate adverse events such as headache and abdominal pain.Objective: In the older population investigate the prevalence of HLGD, and its association to ventriculomegaly. To investigate quality of life (QoL), depressive symptoms, and balance confidence in an HLGD population. In patients shunted for INPH, assess falls, fear of falling, balance confidence and prevalence of the possible adverse events headache, epilepsy, and abdominal pain after shunt surgery. Methods: Two population-based case-controlled cohorts were studied. In the first study, the "Ventriculomegaly and gait disturbance in the senior population in the region of Västerbotten" (VESPR) study, individuals (65-84 years) were recruited through a questionnaire (n=6467 dispatched). The final population consisted of 798 cases with gait disorders and 249 controls without gait disorders, age- and sex-matched to individuals with HLGD. All had been examined by a physician and were categorized: 1. "HLGD"; 2. "neurological gait disorder"; 3. "non-neurological gait disorder" or; 4. "no gait disorder". Participants were assessed with: the Swedish modification of the Falls-Efficacy Scale (FES(S)), the Modified Gait-Efficacy Scale (mGES), the Euro Quality of Life 5-Dimension 5-Level (EQ5D5L) instrument (EQ5D5L index and Euro Quality of life visual analogue scale (EQ VAS)) and the Geriatric depression scale 15 (GDS-15). Cases and controls had an MRI of the brain and ventricular size was measured. The second study, the "Comorbidities and vascular risk factors associated with idiopathic normal pressure hydrocephalus" (INPH-CRasH) study, consisted of 176 shunted INPH patients and 368 age- and sex-matched controls. Mean age was 74 years in INPH and 73 in controls. All had a visit to a healthcare facility. Information regarding adverse events, falls and fear of falling were gathered through a questionnaire. Additional information on diagnoses and prescribed drugs were obtained from the Swedish national patient- and drug registries. Data was compared between the groups, and before- and after surgery for INPH. Results: In the VESPR study, 87 individuals were categorized as HLGD, corresponding to a prevalence of 5.8% (95% confidence interval (CI) 4.6-7.0) in the older population. A definite cause was found in 13% (n=11) of individuals with HLGD, but ventriculomegaly was present in 63% (n=46/73, controls: 38%, n=70/184; OR 2.8 95% CI 1.6-4.9, p<0.001). HLGD had more depressive symptoms and lower quality of life (QoL), compared with individuals without gait disorder (GDS-15: 3.9±3.4 vs. 2.5±2.8, p=0.004; EQ VAS: 63±17 vs. 71±18; p<0.001; EQ5D5L index: 0.671±0.188 vs. 0.840±0.126, p<0.001). HLGD had low confidence in gait and to avoid falls compared to those without gait disorder (mGES: 60±22 vs. 74±21; p<0.001; FES(S): 93±32 vs. 111±25 p<0.001). The INPH-CRasH study revealed that patients with INPH feared falling more often (3.3±1.1) and had lower balance confidence (78±40) than controls (fear of falling: 1.6±0.9, balance confidence: 126±14; p<0.001 in both comparisons). After surgery, the proportions were reduced in INPH (p<0.001). More INPH than controls were fallers (before surgery: 67% vs. 11% OR 15.48 95% CI 9.85-24.32; after surgery: 35% vs 11% OR 4.15 95% CI 2.65-6.50, p<0.001). The proportion was reduced after surgery (p<0.001). In shunted INPH, epilepsy, antiepileptic drug (AED) treatment and headache was more common than in controls (epilepsy: 4.5% vs. 1.1% OR 4.3, 95% CI 1.3-14.6, p=0.023; AED treatment: 14.8% vs. 7.3% OR 0.5 95% CI 0.3-0.8, p=0.010; headache: 36.1% vs 11.6% OR 0.2 95% CI 0.2-0.4, p<0.001). Forty percent INPH (n=70) had abdominal pain after surgery. Conclusions: HLGD was common in the general older population and associated to ventriculomegaly. HLGD was also associated with low quality of life and depressive symptoms. Both individuals with HLGD and patients with INPH had low confidence in their balance but it was less common after surgery for INPH. However, patients shunted for INPH still had more problems with low balance confidence, falls, and fear of falling than controls. After shunt surgery for INPH, a significant portion of patients developed epilepsy, headache, and abdominal pain. The findings motivate investigations of causal relationships between HLGD and ventriculomegaly and if treatment options exist for HLGD. The observed adverse events in patients shunted for INPH should be considered in pre- and postoperative evaluations of shunt surgery, and in the development of new techniques for shunt placement. Additional interventions directed towards low balance confidence, falls and fear of falling should be considered for patients with INPH, and for individuals with HLGD.
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| 2. |
- Behzadi, Arvin, 1994-
(författare)
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Biomarkers for diagnosis and prognosis in amyotrophic lateral sclerosis
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of upper and lower motor neurons, leading to paresis, muscle atrophy, and respiratory failure. ALS can be difficult to diagnose and prognosticate early.Aim: To investigate the diagnostic and prognostic characteristics of biomarkers in cerebrospinal fluid (CSF), plasma, and skeletal muscle tissue in patients with ALS.Paper I: Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) were analyzed in CSF using enzyme-linked immunosorbent assay (ELISA), and NFL in plasma was analyzed using single-molecule array (SIMOA). CSF NFL, CSF pNFH, and plasma NFL concentrations can differentiate ALS patients from ALS mimics, and were significantly negatively correlated with the disease duration in ALS patients.Paper II: Myosin heavy chain (MyHC) isoforms in extraocular muscles were investigated using immunofluorescence. Control donors had significantly higher proportion of myofibers containing MyHCIIa and significantly lower proportion of myofibers containing MyHCeom in the global layer compared to spinal-onset ALS and bulbar-onset ALS donors. Disease duration in the spinal-onset ALS donors was significantly correlated with the proportion of myofibers containing MyHCIIa in the global layer and MyHCeom in the orbital layer.Paper III: The study combined the neurofilament concentrations from Paper I, with cytokines previously analyzed in CSF and plasma using SIMOA, to investigate distinct molecular phenotypes in ALS. Patients with bulbar-onset ALS had significantly higher concentrations of CSF tumor necrosis factor α (TNF-α) compared to ALS mimics. TNF-α and NFL were significantly correlated with each other in both CSF and plasma in ALS patients. Combined analysis of NFL and IL-6 in plasma identified molecular prognostic subgroups in ALS patients.Paper IV: Creatine kinase (CK), high-sensitivity cardiac troponin T (hs-cTnT), hs-cTnI, and cystatin C (CysC) were analyzed in plasma in a fully accredited laboratory. CK and hs-cTnT concentrations were significantly elevated in limb-onset ALS compared to controls and bulbar-onset ALS. hs-cTnT concentrations were significantly elevated in truncal-onset ALS compared to controls and bulbar-onset ALS. Multivariable Cox proportional hazards models indicated elevated concentrations of CysC as a significant marker for worse prognosis in ALS.Conclusions: The papers report diagnostic and prognostic characteristics of biomarkers in CSF, plasma, and muscle tissue in ALS patients. The significant findings for biomarkers in plasma could be of value since plasma sampling does not involve a lumbar puncture.
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| 3. |
- Björnfot, Cecilia, et al.
(författare)
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Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
- 2024
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
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Tidskriftsartikel (refereegranskat)abstract
- White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
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| 4. |
- Gasslander, Johan, et al.
(författare)
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Risk factors for developing subdural hematoma : a registry-based study in 1457 patients with shunted idiopathic normal pressure hydrocephalus
- 2021
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 134:2, s. 668-677
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Subdural hematomas and hygromas (SDHs) are common complications in idiopathic normal pressure hydrocephalus (iNPH) patients with shunts. In this registry-based study, patients with shunted iNPH were screened nationwide to identify perioperative variables that may increase the risk of SDH.METHODS: The Swedish Hydrocephalus Quality Registry was reviewed for iNPH patients who had undergone shunt surgery in Sweden in 2004-2014. Potential risk factors for SDH were recorded preoperatively and 3 months after surgery. Drug prescriptions were identified from a national pharmacy database. Patients who developed SDHs were compared with those without SDHs.RESULTS: The study population consisted of 1457 patients, 152 (10.4%) of whom developed an SDH. Men developed an SDH more often than women (OR 2.084, 95% CI 1.421-3.058, p < 0.001). Patients on platelet aggregation inhibitors developed an SDH more often than those who were not (OR 1.733, 95% CI 1.236-2.431, p = 0.001). At surgery, shunt opening pressures had been set 5.9 mm H2O lower in the SDH group than in the no-SDH group (109.6 ± 24.1 vs 115.5 ± 25.4 mm H2O, respectively, p = 0.009). Antisiphoning devices (ASDs) were used in 892 patients but did not prevent SDH. Mean opening pressures at surgery and the follow-up were lower with shunts with an ASD, without causing more SDHs. No other differences were seen between the groups.CONCLUSIONS: iNPH patients in this study were diagnosed and operated on in routine practice; thus, the results represent everyday care. Male sex, antiplatelet medication, and a lower opening pressure at surgery were risk factors for SDH. Physical status and comorbidity were not. ASD did not prevent SDH, but a shunt with an ASD allowed a lower opening pressure without causing more SDHs.
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| 6. |
- Aineskog, Helena, et al.
(författare)
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Serum S100B correlates with health-related quality of life and functional outcome in patients at 1 year after aneurysmal subarachnoid haemorrhage
- 2022
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Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:8, s. 2209-2218
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early, objective prognostication after aneurysmal subarachnoid haemorrhage (aSAH) is difficult. A biochemical marker would be desirable. Correlation has been found between levels of the protein S100 beta (S100B) and outcome after aSAH. Timing and clinical usefulness are under investigation.METHODS: Eighty-nine patients admitted within 48 h of aSAH were included. Modified ranking scale (mRS), EuroQoL health-related quality of life measure (EQ-5Dindex) and EuroQoL visual analogue scale (EQ-VAS) values were evaluated after 1 year. S100B was measured in blood samples collected at admission and up to day 10.RESULTS: S100B correlated significantly with EQ-5Dindex and mRS, but not EQ-VAS at 1 year after aSAH. A receiver operating characteristic analysis for peak S100B values (area under the curve 0.898, 95% confidence interval 0.828-0.968, p < 0.0001), with a cutoff of 0.4 μg/l, yielded 95.3% specificity and 68% sensitivity for predicting unfavourable outcome. Dichotomized S100B (> 0.4 μg/l vs ≤ 0.4 μg/l), age and Hunt and Hess grading scale score (HH) were associated with unfavourable mRS outcome in univariate logistic regression analysis. Dichotomized S100B was the only variable independently correlated with unfavourable mRS outcome in a multivariate logistic regression analysis.CONCLUSIONS: For the first time, S100B was shown to correlate with mRS and health-related quality of life at 1 year after aSAH. Peak S100B can be used as a prognostic factor for unfavourable outcome measured as dichotomized mRS after aSAH. A peak value cutoff of 0.4 μg/l is suggested. Ethical approval no: 2013/366-31, 4th of February 2014.
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| 7. |
- Andelic, Nada, et al.
(författare)
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Frequency of fatigue and its changes in the first 6 months after traumatic brain injury : results from the CENTER-TBI study
- 2021
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Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 268:1, s. 61-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities.METHODS: Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported.RESULTS: Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and individuals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue.CONCLUSION: A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study.
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| 8. |
- Arango-Lasprilla, Juan Carlos, et al.
(författare)
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Early Predictors of Employment Status One Year Post Injury in Individuals with Traumatic Brain Injury in Europe
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Sustaining a traumatic brain injury (TBI) often affects the individual’s ability to work, reducing employment rates post-injury across all severities of TBI. The objective of this multi-country study was to assess the most relevant early predictors of employment status in individuals after TBI at one-year post-injury in European countries. Using a prospective longitudinal non-randomized observational cohort (The Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) project), data was collected between December 2014–2019 from 63 trauma centers in 18 European countries. The 1015 individuals who took part in this study were potential labor market participants, admitted to a hospital and enrolled within 24 h of injury with a clinical TBI diagnosis and indication for a computed tomography (CT) scan, and followed up at one year. Results from a binomial logistic regression showed that older age, status of part-time employment or unemployment at time of injury, premorbid psychiatric problems, and higher injury severity (as measured with higher Injury severity score (ISS), lower Glasgow Coma Scale (GCS), and longer length of stay (LOS) in hospital) were associated with higher unemployment probability at one-year after injury. The study strengthens evidence for age, employment at time of injury, premorbid psychiatric problems, ISS, GCS, and LOS as important predictors for employment status one-year post-TBI across Europe.
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| 9. |
- Bockhop, Fabian, et al.
(författare)
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Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is frequently associated with neuropsychiatric impairments such as symptoms of post-traumatic stress disorder (PTSD), which can be screened using self-report instruments such as the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). The current study aims to inspect the factorial validity and cross-linguistic equivalence of the PCL-5 in individuals after TBI with differential severity. Data for six language groups (n ≥ 200; Dutch, English, Finnish, Italian, Norwegian, Spanish) were extracted from the CENTER-TBI study database. Factorial validity of PTSD was evaluated using confirmatory factor analyses (CFA), and compared between four concurrent structural models. A multi-group CFA approach was utilized to investigate the measurement invariance (MI) of the PCL-5 across languages. All structural models showed satisfactory goodness-of-fit with small between-model variation. The original DSM-5 model for PTSD provided solid evidence of MI across the language groups. The current study underlines the validity of the clinical DSM-5 conceptualization of PTSD and demonstrates the comparability of PCL-5 symptom scores between language versions in individuals after TBI. Future studies should apply MI methods to other sociodemographic (e.g., age, gender) and injury-related (e.g., TBI severity) characteristics to improve the monitoring and clinical care of individuals suffering from PTSD symptoms after TBI.
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| 10. |
- Böhm, Julia K., et al.
(författare)
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Extended Coagulation Profiling in Isolated Traumatic Brain Injury : A CENTER-TBI Analysis
- 2022
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Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 36:3, s. 927-941
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury.METHODS: Results from blood samples (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) (n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR < 1.2 and (2) INR ≥ 1.2. An INR > 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick's value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers.RESULTS: Patients with iTBI with INR ≥ 1.2 (n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR < 1.2 (n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15-20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR < 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR < 1.2 to 1,301 mg/L in patients with INR ≥ 1.2.CONCLUSIONS: This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.
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