To Örebro University

Background: Body temperature and peripheral blood inflammatory markers are often elevated in acute stroke. Whether the increase in inflammatory markers is caused by the stroke itself or is attributable to a complication, is incompletely understood. This uncertainty may hamper the diagnosis and treatment of infections. We aimed to describe the dynamics of inflammatory parameters in a cohort of stroke patients free from complications.

Methods: Acute stroke patients were prospectively included within 48 h of symptom onset and monitored through daily questions of symptoms and clinical examinations to detect complications. Inflammatory parameters in blood and body temperature were measured daily for up to ten days and the 97.5th percentile calculated. Values were compared with paired t-test to measurements at a 90-day follow up.

Results: 70 stroke patients were included. 51 of them were considered complication-free and sampled for a total of 282 days. Body temperature, CRP and WBC were all significantly elevated the first days after stroke, compared to 90-days post stroke. Mean body temperature was highest at 24-48h at 37.1 degrees C, mean WBC was highest at 0-24h at 8.1 x 10<^>9/L, compared to 36.7 degrees C and 6.0 x 10<^>9/L at the 90-day follow-up (p-values < 0.01). Median CRP peaked at 7.0 mg/L 120-144 h after stroke, compared to 0.9 mg/L at follow-up (p-value < 0.01).

Conclusions: Acute stroke may cause mildly elevated levels of CRP, WBC and body temperature. Except for WBC during the first 24h, higher levels (such as CRP > 50mg/L, WBC > 11 x 10<^>9/L or body temp > 38 degrees C) are very uncommon (< 2.5%) and are likely to reflect a complication.

Background and Objective: Brain morphometry is shaped by a complex interplay of genetic and environmental factors, including physiological and neuropsychiatric conditions. These influences can vary across distinct brain regions, yet the precise contributions of genetics and environment to regional variation in healthy brains remain poorly understood. This study examines the heritability of specific brain structures to provide deeper insights into their development.

Materials and Methods: We studied 118 healthy adult twins from the Hungarian Twin Registry using T1-weighted magnetic resonance imaging (T1W MRI) and the volBrain pipeline for structural measurements.

Results: In all regions, monozygotic (MZ) twins showed a higher resemblance than dizygotic (DZ) twins in total brainstem and cerebellar volumes, with significant heritability (A: 90.5-92.6%) and minimal unique environmental effects (E: <1%). For supratentorial regions, regarding the total gray matter volume, all regions exhibited high heritability (A: 74.5-92.4%) and minimal environmental influence (E: <1.5%). In average cortical thickness analysis, the frontal lobe, temporal lobe, and pre-central gyrus were influenced by shared and unique environmental factors (C: 63-66.5%; E: 33.4-37%), whereas genetics were more prominent in the parietal lobe, occipital lobe, and post-central gyrus (A: 67.7-85%; E: 15-32.3%).

Conclusions: Genetics strongly influence cortical gray matter volume in supratentorial regions (both total and regional), as well as the total brainstem volume and the total and cortical gray matter volumes of the cerebellum in infratentorial regions. This genetic influence extends to the average cortical thickness of the parietal lobe, post-central gyrus, and occipital lobe, while the frontal lobe, temporal lobe, and pre-central gyrus are more affected by environmental factors. These findings emphasize the importance of understanding region-specific genetic and environmental contributions to brain structure, which could guide personalized therapeutic and preventive strategies for neurological conditions.

OBJECTIVE: To determine the temporal profiles of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (t-tau), and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in plasma the first week after acute ischemic stroke, and identify the optimal time points for assessing infarct volume by these biomarkers.

PATIENTS & METHODS: In this cohort study, biomarker plasma concentrations were determined daily over the first week and at 90 days after symptom onset in patients with acute ischemic stroke. A brain MRI was performed on day three. Temporal variations in biomarker levels were analyzed using linear mixed-effects models, and optimal time points for infarct volume correlation were identified with continuous Pearson analysis.

RESULTS: 38 patients with a median age of 78 (IQR 72-86) and mean infarct volume of 5.5 (IQR 1.6-17) cm3 were included. We identified three distinct temporal patterns: (1) a parabolic trajectory of GFAP, reaching zenith after three days, (2) a consistent increase in NFL throughout the week, and (3) an initial surge in t-tau and UCHL1 levels, stabilizing by day three. The optimal time point for infarct volume correlation occurred at 119 h for GFAP (r = 0.94, 95% CI: [0.84-0.98]), 144 h for NFL (r = 0.78, [0.47, 0.92]), 122 h for t-tau (r = 0.82, [0.56, 0.93]) and 113 h for UCHL1 (r = 0.83, [0.60, 0.93]).

INTERPRETATION: This high-resolution serial sampling of plasma GFAP, NFL, t-tau, and UCHL1 the first week after acute ischemic stroke identified three distinct temporal profiles. These biomarkers provided the most accurate infarct volume assessment 4-6 days after symptom onset.

CLINICALTRIALS: gov NCT03812666 (registration date 2019-01-23).

INTRODUCTION: The limbic system and the hippocampus are complex brain structures with key roles in memory, emotions, sexual stimulation and learning, with subregion abnormalities associated with a range of disorders and psychopathologies. Our study aimed to explore the heritability of specific subfield structures within the limbic system and hippocampus first in a Caucasian twin sample with volBrain pipeline.

MATERIALS AND METHODS: 59 healthy adult Caucasian twin pairs from the Hungarian Twin Registry without any history of previous neurodegenerative or cerebrovascular diseases underwent brain MRI on a 3.0 T scanner (43 monozygotic, MZ and 16 dizygotic, DZ pairs, with a median age of 50±+27 years). The volBrain automated volumetry pipeline was used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Based on age- and sex-adjusted MZ and DZ intra-pair correlations, the univariate ACE model was applied to calculate additive genetic, shared and unshared environmental influences.

RESULTS: Adjusting for age and sex, moderate to strong heritability (A: 59.7 to 73.1 %) was found for most limbic cortex volumes, except for the volumes of entorhinal area and posterior cingulate gyrus where common environmental contribution was detected (C: 56.6 % and 65.0 %, respectively). A substantial heritability (A: 67.0 to 79.4 %) was estimated for the overall hippocampus and most subfield volumes, except for the CA2-CA3 region which was determinated by common environmental factors (C: 45.7 %). Unique environmental variance was a minor to moderate contributor across all variables (E: 20.6 to 54.3 %).

CONCLUSIONS: Albeit most limbic cortex, overall hippocampus and most subfield volumes are under substantial genetic influence in healthy adult twins, the volumes of entorhinal area, posterior cingulate gyrus and the CA2-CA3 region of the hippocampus are influenced common environmental factors. The findings underline the importance of unique environmental factors which may play a role in the prevention of disorders related to limbic cortex and hippocampus.

Introduction: Postoperative seroma and pain are common problems following laparoscopic intraperitoneal onlay mesh (IPOM) repair of ventral hernias. These advers outcomes may be avoided by dissecting and using the peritoneum in the hernial sac to bridge the hernia defect.

Methods: This was a patient- an and outcome assesor-blinded, parallel-design, randomized controlled trial compairing nonclosure and peritoeal bridging approaches in patients schedueled for elective midline ventral hernia repair. The primary end point was seroma volume on ultrasonography. The secondary end points were postoperative pain, recurrence, and complications.

Results: Between November 2018 and December 2020, 112 patients were randomized of whom 60 were in the nonclosure group and 52 were in the peritoneal bridging group. The seroma volume in the nonclosure and peritoneal bridging groups were 17cm³(6-53cm³) versus 0cm³(0-26cm³) at 1-moth follow-up (P=0.013). The median volume was zero at 3-, 6-, and 12-month follow-ups in both groups. No significant differences were observed in early postoperative pain (P=0.447) and in recurrencerate (P=0.684). There were 4(7%) and 1(2%) perioperative complictions that lead to reoperations in simple IPOM(sIPOM) and IPOM with peritoneal bridging (IPOM-pb), respectively.

Conclusion: Seroma was less prevalent after IPOM-pb at 1-month follow-up compaired with sIPOM, with simillar posoperative pain 1 week after index of surgery in both groups. At subsequent follow-ups, the differences in seroma were not statiscally significant. Further studies are required to confirm these results. Trial registration (NCT04229940)

Keywords: epigastric hernia, incisional hernia, IPOM with fascia closure, IPOM with peritoneal bridging, laparoscopic hernia repair, simple IPOM, umblical hernia, ventral hernia

Introduction: White matter hyperintensities (WMH) indicate white matter brain lesions in magnetic resonance imaging (MRI), which can be used as a marker for brain aging and cerebrovascular and neurodegenerative disorders. Twin studies revealed substantial but not uniform WMH heritability in elderly twins. The objective of our study was to investigate the genetic and environmental components of WMH, as well as their importance in a healthy twin population, utilizing 3T MRI scanners in a middle-aged twin population.

Methods: Brain MRI was performed on 120 healthy adult twins from the Hungarian Twin Registry on a 3T scanner (86 monozygotic, MZ and 34 dizygotic, DZ twins; median age 50 ± 26.5 years, 72.5% female and 27.5% male). The count of WMH on FLAIR images was calculated using an automated volumetry pipeline (volBrain) and human processing. The age- and sex-adjusted MZ and DZ intra-pair correlations were determined and the total variance was decomposed into genetic, shared and unique environmental components using structural equation modeling.

Results: Age and sex-adjusted MZ intrapair correlations were higher than DZ correlations, indicating moderate genetic influence in each lesion (rMZ = 0.466, rDZ = -0.025 for total count; rMZ = 0.482, rDZ = 0.093 for deep white matter count; rMZ = 0.739, rDZ = 0.39 for infratentorial count; rMZ = 0.573, rDZ = 0.372 for cerebellar count and rMZ = 0.473, rDZ = 0.19 for periventricular count), indicating a moderate heritability (A = 40.3%, A = 45%, A = 72.7% and A = 55.5%and 47.2%, respectively). The rest of the variance was influenced by unique environmental effects (E between 27.3% and 59.7%, respectively).

Conclusions: The number of WMH lesions is moderately influenced by genetic effects, particularly in the infratentorial region in middle-aged twins. These results suggest that the distribution of WMH in various brain regions is heterogeneous.

Background and Objectives: Subcortical grey matter structures play essential roles in cognitive, affective, social, and motoric functions in humans. Their volume changes with age, and decreased volumes have been linked with many neuropsychiatric disorders. The aim of our study was to examine the heritability of six subcortical brain volumes (the amygdala, caudate nucleus, pallidum, putamen, thalamus, and nucleus accumbens) and four general brain volumes (the total intra-cranial volume and the grey matter, white matter, and cerebrospinal fluid (CSF) volume) in twins.

Materials and Methods: A total of 118 healthy adult twins from the Hungarian Twin Registry (86 monozygotic and 32 dizygotic; median age 50 ± 27 years) underwent brain magnetic resonance imaging. Two automated volumetry pipelines, Computational Anatomy Toolbox 12 (CAT12) and volBrain, were used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Age- and sex-adjusted monozygotic and dizygotic intra-pair correlations were calculated, and the univariate ACE model was applied. Pearson's correlation test was used to compare the results obtained by the two pipelines.

Results: The age- and sex-adjusted heritability estimates, using CAT12 for the amygdala, caudate nucleus, pallidum, putamen, and nucleus accumbens, were between 0.75 and 0.95. The thalamus volume was more strongly influenced by common environmental factors (C = 0.45-0.73). The heritability estimates, using volBrain, were between 0.69 and 0.92 for the nucleus accumbens, pallidum, putamen, right amygdala, and caudate nucleus. The left amygdala and thalamus were more strongly influenced by common environmental factors (C = 0.72-0.85). A strong correlation between CAT12 and volBrain (r = 0.74-0.94) was obtained for all volumes.

Conclusions: The majority of examined subcortical volumes appeared to be strongly heritable. The thalamus was more strongly influenced by common environmental factors when investigated with both segmentation methods. Our results underline the importance of identifying the relevant genes responsible for variations in the subcortical structure volume and associated diseases.

Background and Objectives: The asymmetrical vertebral artery (VA) flow and diameter are common findings, which can result in an asymmetrical blood flow in the basilar artery (BA), leading to bending of the artery over time. This study investigated whether the variation of the different vertebrobasilar morphological indices that influence flow characteristics might be inherited.

Materials and Methods: We analyzed 200 cerebral magnetic resonance imaging (MRI) scans of healthy Caucasian twins (100 pairs) who underwent time-of-flight MRI. From the scans, we reconstructed the 3D mesh of the posterior circulation from the start of the V4 segment to the basilar tip and subsequently analyzed the morphology of the vertebrobasilar system. The phenotypic covariances of the different morphological parameters were decomposed into heritability (A), shared (C), and unshared (E) environmental effects.

Results: 39% of the twins had left dominant VA, while 32.5% had right dominant. In addition, 28.5% were classified as equal. The vertebral artery V4 segment diameter, curvature, and tortuosity were mainly influenced by shared (C) and unshared (E) environmental factors. A moderate heritability was found for the BA length (A: 63%; 95% CI: 45.7-75.2%; E: 37%; 95% CI: 24.8-54.3%) and volume (A: 60.1%; 95% CI: 42.4-73.2%; E: 39.9%; 95% CI: 26.8-57.6%), while the torsion of both arteries showed no heritability and were only influenced by the unshared environment.

Conclusions: The length and volume of the BA show a moderate genetical influence. However, most of the measured morphological indices were influenced by shared and unshared factors, which highlight the role of the ever-changing hemodynamic influences shaping the geometry of the vertebrobasilar system. 

Background and Objectives: Aortic arch calcification (AoAC) is associated with a variety of cardiovascular complications. The measurement and grading of AoAC using posteroanterior (PA) chest X-rays are well established. The cardiothoracic ratio (CTR) can be simultaneously measured with PA chest X-rays and used as an index of cardiomegaly. The genetic and environmental contributions to the degree of the AoAC and CTR are not well understood. The purpose of this study was to investigate the effect of genetics and environmental factors on the AoAC and CTR.

Materials and Methods: A total of 684 twins from the South Korean twin registry (261 monozygotic, MZ and 81 dizygotic, DZ pairs; mean age 38.6 ± 7.9 years, male/female = 264/420) underwent PA chest X-rays. Cardiovascular risk factors and anthropometric data were also collected. The AoAC and CTR were measured and graded using a standardized method. A structural equation method was used to calculate the proportion of variance explained by genetic and environmental factors behind AoAC and CTR.

Results: The within-pair differences were low regarding the grade of AoAC, with only a few twin pairs showing large intra-pair differences. We found that the thoracic width showed high heritability (0.67, 95% CI: 0.59-0.73, p = 1). Moderate heritability was detected regarding cardiac width (0.54, 95% CI: 0.45-0.62, p = 0.572) and CTR (0.54, 95% CI: 0.44-0.62, p = 0.701). Conclusions: The heritable component was significant regarding thoracic width, cardiac width, and the CTR.