| 1. |
- Tefre, Sondre, et al.
(författare)
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Endoscopic third ventriculostomy for adults with hydrocephalus: creating a prognostic model for success: protocol for a retrospective multicentre study (Nordic ETV)
- 2022
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarni et al created the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for EN and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. Methods and analysis The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients >= 18 years of age treated with EN at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. Ethics and dissemination The study is approved by appropriate ethics or patient safety boards in all participating countries.
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| 2. |
- Abu Hamdeh, Sami, et al.
(författare)
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Brain tissue Aβ42 levels are linked to shunt response in idiopathic normal pressure hydrocephalus
- 2019
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Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 130:1, s. 121-129
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Tidskriftsartikel (refereegranskat)abstract
- Objective The authors conducted a study to test if the cortical brain tissue levels of soluble amyloid beta (Aβ) reflect the propensity of cortical Aβ aggregate formation and may be an additional factor predicting surgical outcome following idiopathic normal pressure hydrocephalus (iNPH) treatment.Methods Highly selective ELISAs (enzyme-linked immunosorbent assays) were used to quantify soluble Aβ40, Aβ42, and neurotoxic Aβ oligomers/protofibrils, associated with Aβ aggregation, in cortical biopsy samples obtained in patients with iNPH (n = 20), sampled during ventriculoperitoneal (VP) shunt surgery. Patients underwent pre- and postoperative (3-month) clinical assessment with a modified iNPH scale. The preoperative CSF biomarkers and the levels of soluble and insoluble Aβ species in cortical biopsy samples were analyzed for their association with a favorable outcome following the VP shunt procedure, defined as a ≥ 5-point increase in the iNPH scale.Rrsults The brain tissue levels of Aβ42 were negatively correlated with CSF Aβ42 (Spearman's r = -0.53, p < 0.05). The Aβ40, Aβ42, and Aβ oligomer/protofibril levels in cortical biopsy samples were higher in patients with insoluble cortical Aβ aggregates (p < 0.05). The preoperative CSF Aβ42 levels were similar in patients responding (n = 11) and not responding (n = 9) to VP shunt treatment at 3 months postsurgery. In contrast, the presence of cortical Aβ aggregates and high brain tissue Aβ42 levels were associated with a poor outcome following VP shunt treatment (p < 0.05).Conclusions Brain tissue measurements of soluble Aβ species are feasible. Since high Aβ42 levels in cortical biopsy samples obtained in patients with iNPH indicated a poor surgical outcome, tissue levels of Aβ species may be associated with the clinical response to shunt treatment.
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| 3. |
- Abu Hamdeh, Sami, 1982-
(författare)
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Clinical Consequences of Axonal Injury in Traumatic Brain Injury
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic brain injury (TBI), mainly caused by road-traffic accidents and falls, is a leading cause of mortality. Survivors often display debilitating motor, sensory and cognitive symptoms, leading to reduced quality of life and a profound economic burden to society. Additionally, TBI is a risk factor for future neurodegenerative disorders including Alzheimer’s disease (AD). Commonly, TBI is categorized into focal and diffuse injuries, and based on symptom severity into mild, moderate and severe TBI. Diffuse axonal injury (DAI), biomechanically caused by rotational acceleration-deceleration forces at impact, is characterized by widespread axonal injury in superficial and deep white substance. DAI comprises a clinical challenge due to its variable course and unreliable prognostic methods. Furthermore, axonal injury may convey the link to neurodegeneration since molecules associated with neurodegenerative events aggregate in injured axons.The aim of this thesis was to study clinical consequences of axonal injury, its detection and pathological features, and potential link to neurodegeneration in severe TBI patients treated at the neurointensive care unit at Uppsala University Hospital. In paper I and IV DAI patients were studied for the relation of elevated intracranial pressure (ICP) and poor outcome to axonal injury on magnetic resonance imaging. In paper II, soluble amyloid-beta aggregates (oligomers and protofibrils), characteristic of AD pathology, were investigated in surgically resected brain tissue from severe TBI patients, using highly-selective Enzyme-Linked ImmunoSorbent Assays. In paper III, brain tissue biopsy samples from TBI patients with either focal injury or DAI were examined for differential proteome profiles using mass spectrometry-based proteomics.The results provide evidence that axonal injury, located in the central brain stem, in substantia nigra and the mesencephalic tegmentum, is particularly related to poor outcome and increased ICP during neurointensive care of DAI patients. A novel classification system for prognostication after DAI is proposed. Furthermore, the thesis shows that severe TBI induces rapid accumulation of neurotoxic soluble amyloid-beta oligomers and protofibrils. In addition, DAI initiates unique proteome profiles different from that of focal TBI in structurally normal-appearing brain. These findings have implication for the clinical management of DAI patients, and provide new insight in the neuropathological consequences of axonal injury.
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| 4. |
- Abu Hamdeh, Sami, et al.
(författare)
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Differential DNA methylation of the genes for amyloid precursor protein, tau, and neurofilaments in human traumatic brain injury
- 2021
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 38:12, s. 1662-1669
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is an established risk factor for neurodegenerative disorders and dementias. Epigenetic modifications, such as DNA methylation, may alter the expression of genes without altering the DNA sequence in response to environmental factors. We hypothesized that DNA methylation changes may occur in the injured human brain and be implicated in the neurodegenerative aftermath of TBI. The DNA methylation status of genes related to neurodegeneration; for example, amyloid beta precursor protein (APP), microtubule associated protein tau (MAPT), neurofilament heavy (NEFH), neurofilament medium (NEFM), and neurofilament light (NEFL), was analyzed in fresh, surgically resected human brain tissue from 17 severe TBI patients and compared with brain biopsy samples from 19 patients with idiopathic normal pressure hydrocephalus (iNPH). We also performed an epigenome-wide association study (EWAS) comparing TBI patients with iNPH controls. Thirty-eight CpG sites in the APP, MAPT, NEFH, and NEFL genes were differentially methylated by TBI. Among the top 20 differentially methylated CpG sites, 11 were in the APP gene. In addition, the EWAS evaluating 828,888 CpG sites revealed 308 differentially methylated CpG sites in genes related to cellular/anatomical structure development, cell differentiation, and anatomical morphogenesis. These preliminary findings provide the first evidence of an altered DNA methylome in the injured human brain, and may have implications for the neurodegenerative disorders associated with TBI.
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| 5. |
- Abu Hamdeh, Sami, et al.
(författare)
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Extended anatomical grading in diffuse axonal injury using MRI : Hemorrhagic lesions in the substantia nigra and mesencephalic tegmentum indicate poor long-term outcome
- 2017
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 5:34, s. 341-352
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Tidskriftsartikel (refereegranskat)abstract
- Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I—hemispheric lesions, stage II—corpus callosum lesions, stage III—brainstem lesions, and stage IV—substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years).
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| 6. |
- Abu Hamdeh, Sami, et al.
(författare)
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Increased CSF Levels of Apolipoproteins and Complement Factors in Trigeminal Neuralgia Patients-In Depth Proteomic Analysis Using Mass Spectrometry
- 2020
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Ingår i: Journal of Pain. - : CHURCHILL LIVINGSTONE. - 1526-5900 .- 1528-8447. ; 21:9-10, s. 1075-1084
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Tidskriftsartikel (refereegranskat)abstract
- The main cause of trigeminal neuralgia (TN) is compression of a blood vessel at the root entry zone of the trigeminal nerve. However, a neurovascular conflict does not seem to be the only etiology and other mechanisms are implicated in the development of the disease. We hypothesized that TN patients may have distinct protein expression in the CSF. In this study, lumbar CSF from TN patients (n = 17), scheduled to undergo microvascular decompression, and from controls (n = 20) was analyzed and compared with in depth mass spectrometry TMTbased quantitative proteomics. We identified 2552 unique proteins, of which 46 were significantly altered (26 increased, and 20 decreased, q-value < .05) in TN patients compared with controls. An over-representation analysis showed proteins involved in high-density lipoprotein, such as Apolipoprotein A4, Apolipoprotein M, and Apolipoprotein A1, and the extracellular region, including proteins involved in the complement cascade to be over-represented. We conclude that TN patients have distinct protein expression in the CSF compared to controls. The pathophysiological background of the protein alterations found in this study warrants further investigation in future studies. Perspective: In this article, cerebrospinal fluid from patients with trigeminal neuralgia was analyzed using in depth shotgun proteomics, revealing 46 differentially expressed proteins compared to controls. Among these, apolipoproteins and proteins involved in the complement system were elevated and signif-icantly over-represented, implying an inflammatory component in the pathophysiology of the disease.
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| 7. |
- Abu Hamdeh, Sami, et al.
(författare)
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Intracranial pressure elevations in diffuse axonal injury : association with nonhemorrhagic MR lesions in central mesencephalic structures
- 2019
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Ingår i: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 131:2, s. 604-611
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in patients with DAI.Methods: Fifty-two patients with severe TBI (median age 24 years, range 9–61 years), who had undergone ICP monitoring and had DAI on MRI, as determined using T2*-weighted gradient echo, susceptibility-weighted imaging, and diffusion-weighted imaging (DWI) sequences, were enrolled. The proportion of good monitoring time (GMT) with ICP > 20 mm Hg during the first 120 hours postinjury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression.Results: All patients had episodes of ICP > 20 mm Hg. The mean proportion of GMT with ICP > 20 mm Hg was 5%, and 27% of the patients (14/52) spent more than 5% of GMT with ICP > 20 mm Hg. The Glasgow Coma Scale motor score at admission (p = 0.04) and lesions on DWI sequences in the substantia nigra and mesencephalic tegmentum (SN-T, p = 0.001) were associated with the proportion of GMT with ICP > 20 mm Hg. In multivariable linear regression, lesions on DWI sequences in SN-T (8% of GMT with ICP > 20 mm Hg, 95% CI 3%–13%, p = 0.004) and young age (−0.2% of GMT with ICP > 20 mm Hg, 95% CI −0.07% to −0.3%, p = 0.002) were associated with increased ICP.Conclusions: Increased ICP occurs in approximately one-third of patients with severe TBI who have DAI. Age and lesions on DWI sequences in the central mesencephalon (i.e., SN-T) are associated with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in patients with DAI.Abbreviations: ADC = apparent diffusion coefficient; CPP = cerebral perfusion pressure; DAI = diffuse axonal injury; DWI = diffusion-weighted imaging; EVD = external ventricular drain; GCS = Glasgow Coma Scale; GMT = good monitoring time; GOSE = Glasgow Outcome Scale–Extended; ICC = intraclass correlation coefficient; ICP = intracranial pressure; MAP = mean arterial blood pressure; NICU = neurointensive care unit; SN-T = substantia nigra and mesencephalic tegmentum; SWI = susceptibility-weighted imaging; TBI = traumatic brain injury; T2*GRE = T2*-weighted gradient echo.
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| 8. |
- Abu Hamdeh, Sami, et al.
(författare)
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Intracranial pressure elevations in diffuse axonal injury are associated with non-hemorrhagic MR lesions in central mesencephalic structures
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Increased intracranial pressure (ICP) in severe traumatic brain injury (TBI) patients with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in DAI patients.Methods: Fifty-two severe TBI patients (median 24, range 9-61 years), with ICP-monitoring and DAI on MRI, using T2*-weighted gradient echo, susceptibility-weighted and diffusion-weighted (DW) sequences, were enrolled. Proportion of good monitoring time (GMT) with ICP>20 mmHg during the first 120 hours post-injury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression. Results: All patients had episodes of ICP>20 mmHg. The mean proportion of GMT with ICP>20 mmHg was 5% and 27% of the patients (14/52) had more than 5% of GMT with ICP>20 mmHg. Glasgow Coma Scale motor score at admission (P=0.04) and lesions on DW images in the substantia nigra and mesencephalic tegmentum (SN-T, P=0.001) were associated with the proportion of GMT with ICP>20 mmHg. In multivariate linear regression, lesions on DW images in SN-T (8% of GMT with ICP>20 mmHg, 95% CI 3–13%, P=0.004) and young age (-0.2% of GMT with ICP>20 mmHg, 95% CI -0.07–-0.3%, P=0.0008) were associated with increased ICP. Conclusions: Increased ICP occurs in ~1/3 of severe TBI patients with DAI. Age and lesions on DW images in the central mesencephalon (SN-T) associate with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in DAI patients.
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| 9. |
- Abu Hamdeh, Sami, et al.
(författare)
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MRI analysis of diffuse axonal injury - Hemorrhagic lesions in the mesencephalon idicate poor long-term outcome
- 2016
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Ingår i: MRI analysis of diffuse axonal injury - Hemorrhagic lesions in the mesencephalon idicate poor long-term outcome. - : Springer.
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Konferensbidrag (refereegranskat)abstract
- Purpose: Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. Three MRI techniques were compared in demonstrating acute brain lesions. Relationship of the anatomical distribution of the lesions in combination with clinical prognostic factors to outcome after 6 months was evaluated. Methods and Materials: Thirty patients, aged 16-60 years (mean 31.2 years) with severe DAI (Glasgow Motor Score = GMS < 6) were examined with MRI at 1.5T within one week after the injury. A diffusion-weighted (DW) sequence (SE-EPI, b value 1000 s/mm2), a T2*-weighted gradient echo (T2*GRE) sequence and a susceptibility-weighted (SWI) sequence were evaluated by two independent reviewers with short and long neuroradiological experiences. Clinical outcome was assessed with Extended Glasgow Outcome Score (GOSE) after ≥ 6 months.Results: Interreviewer agreement for DAI classification was very good (ҡ 0.82 – 0.91) with all three sequences. SWI visualized more lesions than the T2*GRE or DW sequence. In univariate analysis, number of DW lesions in the deep gray matter area including the internal capsules, number of SWI lesions in the mesencephalon, age, and GMS at admission and discharge correlated significantly with poor outcome. Multivariate analysis only revealed an independent relation with poor outcome for age (p = 0.011) and lesions in the mesencephalic region including crura cerebri, substantia nigra and tegmentum on SWI (p = 0.032).Conclusion: SWI is the most sensitive technique to visualize lesions in DAI. Age over 30 years and hemorrhagic mesencephalic lesions anterior to the tectum are indicators of poor long-term outcome in DAI.
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| 10. |
- Abu Hamdeh, Sami, et al.
(författare)
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"Omics" in traumatic brain injury : novel approaches to a complex disease
- 2021
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Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 163:9, s. 2581-2594
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Forskningsöversikt (refereegranskat)abstract
- BackgroundTo date, there is neither any pharmacological treatment with efficacy in traumatic brain injury (TBI) nor any method to halt the disease progress. This is due to an incomplete understanding of the vast complexity of the biological cascades and failure to appreciate the diversity of secondary injury mechanisms in TBI. In recent years, techniques for high-throughput characterization and quantification of biological molecules that include genomics, proteomics, and metabolomics have evolved and referred to as omics.MethodsIn this narrative review, we highlight how omics technology can be applied to potentiate diagnostics and prognostication as well as to advance our understanding of injury mechanisms in TBI.ResultsThe omics platforms provide possibilities to study function, dynamics, and alterations of molecular pathways of normal and TBI disease states. Through advanced bioinformatics, large datasets of molecular information from small biological samples can be analyzed in detail and provide valuable knowledge of pathophysiological mechanisms, to include in prognostic modeling when connected to clinically relevant data. In such a complex disease as TBI, omics enables broad categories of studies from gene compositions associated with susceptibility to secondary injury or poor outcome, to potential alterations in metabolites following TBI.ConclusionThe field of omics in TBI research is rapidly evolving. The recent data and novel methods reviewed herein may form the basis for improved precision medicine approaches, development of pharmacological approaches, and individualization of therapeutic efforts by implementing mathematical “big data” predictive modeling in the near future.
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