| 1. |
- Sandling, Johanna K., et al.
(författare)
-
A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE
- 2011
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 19:4, s. 479-484
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (P(meta)=0.00010 and P(meta)=0.00040, respectively). STAT1 was also associated with SLE in this cohort (P(meta)=3.3 × 10(-5)), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis.
|
|
| 2. |
- Behrens, Anders, et al.
(författare)
-
A computerized neuropsychological test battery designed for idiopathic normal pressure hydrocephalus
- 2014
-
Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A tool for standardized and repeated neuropsychological assessments in patients with idiopathic normal pressure hydrocephalus (INPH) is needed. The objective of this study was to develop a computerized neuropsychological test battery designed for INPH and to evaluate its reliability, validity and patient's ability to complete the tests.METHODS: Based on a structured review of the literature on neuropsychological testing in INPH, the eight tests most sensitive to the INPH cognitive profile were implemented in a computerized format. The Geriatric Depression Scale (GDS) was also included. Tests were presented on a touch-screen monitor, with animated instructions and speaker sound. The battery was evaluated with the following cohorts: A. Test-retest reliability, 44 healthy elderly; B. Validity against standard pen and pencil testing, 28 patients with various cognitive impairments; C. Ability to complete test battery, defined as completion of at least seven of the eight tests, 40 investigated for INPH.RESULTS: A. All except the figure copy test showed good test-retest reliability, r = 0.67-0.90; B. A high correlation was seen between conventional and computerized tests (r = 0.66-0.85) except for delayed recognition and figure copy task; C. Seventy-eight percent completed the computerized battery; Patients diagnosed with INPH (n = 26) performed worse on all tests, including depression score, compared to healthy controls.CONCLUSIONS: A new computerized neuropsychological test battery designed for patients with communicating hydrocephalus and INPH was introduced. Its reliability, validity for general cognitive impairment and completion rate for INPH was promising. After exclusion of the figure copy task, the battery is ready for clinical evaluation and as a next step we suggest validation for INPH and a comparison before and after shunt surgery.TRIAL REGISTRATION: ClinicalTrials.org NCT01265251.
|
|
| 3. |
- Behrens, Anders, et al.
(författare)
-
Are intracranial pressure wave amplitudes measurable through lumbar puncture?
- 2013
-
Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 127:4, s. 233-241
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. Methods In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. Results The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9mmHg. At the highest ICP, the difference changed to 0.2mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. Conclusions Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.
|
|
| 4. |
- Behrens, Anders, et al.
(författare)
-
In Reply
- 2010
-
Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 67:6, s. 1864-
-
Tidskriftsartikel (populärvet., debatt m.m.)
|
|
| 5. |
|
|
| 6. |
- Behrens, Anders, 1979-
(författare)
-
Measurements in Idiopathic Normal Pressure Hydrocephalus : Computerized neuropsychological test battery and intracranial pulse waves
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic Normal Pressure Hydrocephalus (INPH) is a condition affecting gait, cognition and continence. Radiological examination reveals enlarged ventricles of the brain. A shunt that drains CSF from the ventricles to the abdomen often improves the symptoms. Much research on INPH has been focused on identifying tests that predict the outcome after shunt surgery. As part of this quest, there are attempts to find measurement methods of intracranial parameters that are valid, reliable, tolerable and safe for patients.Today's technologies for intracranial pressure (ICP) measurement are invasive, often requiring a burr-hole in the skull. Recently, a method for non-invasive ICP measurements was suggested: the Pulsatile Index (PI) calculated from transcranial Doppler data assessed from the middle cerebral artery. In this thesis the relation between PI and ICP was explored in INPH patients during controlled ICP regulation by lumbar infusion. The confidence interval for predicted ICP, based on measured PI was too large for the method to be of clinical utility.In the quest for better predictive tests for shunt success in INPH, recent studies have shown promising results with criteria based on cardiac related ICP wave amplitudes. The brain ventricular system, and the fluid surrounding the spinal cord are in contact. In this thesis it was shown that ICP waves could be measured via lumbar subarachnoid space, with a slight underestimation.One of the cardinal symptoms of hydrocephalus is cognitive impairment. Neuropsychological studies have demonstrated cognitive tests that are impaired and improve after shunt surgery in INPH patients. However, there is currently no standardized test battery and different studies use different tests. In response, in this thesis a fully automated computerized neuropsychological test battery was developed. The validity, reliability, responsiveness to improvement after shunt surgery and feasibility for testing INPH patients was demonstrated. It was also demonstrated that INPH patients were impaired in all subtests, compared to healthy elderly.
|
|
| 7. |
- Behrens, Anders, et al.
(författare)
-
Transcranial Doppler pulsatility index: not an accurate method to assess intracranial pressure.
- 2010
-
Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 66:6, s. 1050-1057
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transcranial Doppler sonography (TCD) assessment of intracranial blood flow velocity has been suggested to accurately determine intracranial pressure (ICP). OBJECTIVE: We attempted to validate this method in patients with communicating cerebrospinal fluid systems using predetermined pressure levels. METHODS: Ten patients underwent a lumbar infusion test, applying 4 to 5 preset ICP levels. On each level, the pulsatility index (PI) in the middle cerebral artery was determined by measuring the blood flow velocity using TCD. ICP was simultaneously measured with an intraparenchymal sensor. ICP and PI were compared using correlation analysis. For further understanding of the ICP-PI relationship, a mathematical model of the intracranial dynamics was simulated using a computer. RESULTS: The ICP-PI regression equation was based on data from 8 patients. For 2 patients, no audible Doppler signal was obtained. The equation was ICP = 23*PI + 14 (R = 0.22, P < .01, N = 35). The 95% confidence interval for a mean ICP of 20 mm Hg was -3.8 to 43.8 mm Hg. Individually, the regression coefficients varied from 42 to 90 and the offsets from -32 to +3. The mathematical simulations suggest that variations in vessel compliance, autoregulation, and arterial pressure have a serious effect on the ICP-PI relationship. CONCLUSIONS: The in vivo results show that PI is not a reliable predictor of ICP. Mathematical simulations indicate that this is caused by variations in physiological parameters.
|
|
| 8. |
- Wang, Chuan, et al.
(författare)
-
Genes identified in Asian SLE GWASs are also associated with SLE in Caucasian populations
- 2013
-
Ingår i: European Journal of Human Genetics. - : Nature Publishing Group: Open Access Hybrid Model Option B. - 1018-4813 .- 1476-5438. ; 21:9, s. 994-999
-
Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies (GWASs) conducted in Asian populations have identified novel risk loci for systemic lupus erythematosus (SLE). Here, we genotyped 10 single-nucleotide polymorphisms (SNPs) in eight such loci and investigated their disease associations in three independent Caucasian SLE case–control cohorts recruited from Sweden, Finland and the United States. The disease associations of the SNPs in ETS1, IKZF1, LRRC18-WDFY4, RASGRP3, SLC15A4, TNIP1 and 16p11.2 were replicated, whereas no solid evidence of association was observed for the 7q11.23 locus in the Caucasian cohorts. SLC15A4 was significantly associated with renal involvement in SLE. The association of TNIP1 was more pronounced in SLE patients with renal and immunological disorder, which is corroborated by two previous studies in Asian cohorts. The effects of all the associated SNPs, either conferring risk for or being protective against SLE, were in the same direction in Caucasians and Asians. The magnitudes of the allelic effects for most of the SNPs were also comparable across different ethnic groups. On the contrary, remarkable differences in allele frequencies between Caucasian and Asian populations were observed for all associated SNPs. In conclusion, most of the novel SLE risk loci identified by GWASs in Asian populations were also associated with SLE in Caucasian populations. We observed both similarities and differences with respect to the effect sizes and risk allele frequencies across ethnicities.
|
|
