| 1. |
- Fytagoridis, Anders, et al.
(författare)
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Deep Brain Stimulation of the Caudal Zona Incerta : Tremor Control in Relation to the Location of Stimulation Fields
- 2016
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 94:6, s. 363-370
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Tidskriftsartikel (refereegranskat)abstract
- Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.
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| 2. |
- Gatzinsky, Kliment, et al.
(författare)
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Repetitive transcranial magnetic stimulation of the primary motor cortex in management of chronic neuropathic pain: a systematic review.
- 2021
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Ingår i: Scandinavian journal of pain. - 1877-8879. ; 21:1, s. 8-21
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Forskningsöversikt (refereegranskat)abstract
- Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) with frequencies 5-20 Hz is an expanding non-invasive treatment for chronic neuropathic pain (NP). Outcome data, however, show considerable inhomogeneity with concern to the levels of effect due to the great diversity of treated conditions. The aim of this review was to survey the literature regarding the efficacy and safety of M1 rTMS, and the accuracy to predict a positive response to epidural motor cortex stimulation (MCS) which is supposed to give a more longstanding pain relief.A systematic literature search was conducted up to June 2019 in accordance with the PRISMA guidelines. We used the PICO Model to define two specific clinical questions: (1) Does rTMS of M1 relieve NP better than sham treatment? (2) Can the response to rTMS be used to predict the effect of epidural MCS? After article selection, data extraction, and study quality assessment, the certainty of evidence of treatment effect was defined using the GRADE system.Data on 5-20 Hz (high-frequency) rTMS vs. sham was extracted from 24 blinded randomised controlled trials which were of varying quality, investigated highly heterogeneous pain conditions, and used excessively variable stimulation parameters. The difference in pain relief between active and sham stimulation was statistically significant in 9 of 11 studies using single-session rTMS, and in 9 of 13 studies using multiple sessions. Baseline data could be extracted from 6 single and 12 multiple session trials with a weighted mean pain reduction induced by active rTMS, compared to baseline, of -19% for single sessions, -32% for multiple sessions with follow-up <30 days, and -24% for multiple sessions with follow-up ≥30 days after the last stimulation session. For single sessions the weighted mean difference in pain reduction between active rTMS and sham was 15 percentage points, for multiple sessions the difference was 22 percentage points for follow-ups <30 days, and 15 percentage points for follow-ups ≥30 days. Four studies reported data that could be used to evaluate the accuracy of rTMS to predict response to MCS, showing a specificity of 60-100%, and a positive predictive value of 75-100%. No serious adverse events were reported.rTMS targeting M1 can result in significant reduction of chronic NP which, however, is transient and shows a great heterogeneity between studies; very low certainty of evidence for single sessions and low for multiple sessions. Multiple sessions of rTMS can maintain a more longstanding effect. rTMS seems to be a fairly good predictor of a positive response to epidural MCS and may be used to select patients for implantation of permanent epidural electrodes. More studies are needed to manifest the use of rTMS for this purpose. Pain relief outcomes in a longer perspective, and outcome variables other than pain reduction need to be addressed more consistently in future studies to consolidate the applicability of rTMS in routine clinical practice.
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| 3. |
- Fytagoridis, Anders, et al.
(författare)
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Surgical Replacement of Implantable Pulse Generator in Deep Brain Stimulation : Adverse Events and Risk Factors in a Multicenter Cohort
- 2016
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger AG. - 1011-6125 .- 1423-0372. ; 94:4, s. 235-239
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deep brain stimulation (DBS) is a growing treatment modality, and most DBS systems require replacement of the implantable pulse generator (IPG) every few years. The literature regarding the potential impact of adverse events of IPG replacement on the longevity of DBS treatments is rather scarce. Objective: To investigate the incidence of adverse events, including postoperative infections, associated with IPG replacements in a multicenter cohort. Methods: The medical records of 808 patients from one Australian and five Swedish DBS centers with a total of 1,293 IPG replacements were audited. A logistic regression model was used to ascertain the influence of possible predictors on the incidence of adverse events. Results: The overall incidence of major infections was 2.3% per procedure, 3.7% per patient and 1.7% per replaced IPG. For 28 of 30 patients this resulted in partial or complete DBS system removal. There was an increased risk of infection for males (OR 3.6, p = 0.026), and the risk of infection increased with the number of prior IPG replacements (OR 1.6, p < 0.005). Conclusions: The risk of postoperative infection with DBS IPG replacement increases with the number of previous procedures. There is a need to reduce the frequency of IPG replacements.
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| 4. |
- Jemt, Elisabeth, et al.
(författare)
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Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element
- 2015
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 43:19, s. 9262-9275
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Tidskriftsartikel (refereegranskat)abstract
- The majority of mitochondrial DNA replication events are terminated prematurely. The nascent DNA remains stably associated with the template, forming a triple-stranded displacement loop (D-loop) structure. However, the function of the D-loop region of the mitochondrial genome remains poorly understood. Using a comparative genomics approach we here identify two closely related 15 nt sequence motifs of the D-loop, strongly conserved among vertebrates. One motif is at the D-loop 5'-end and is part of the conserved sequence block 1 (CSB1). The other motif, here denoted coreTAS, is at the D-loop 3'-end. Both these sequences may prevent transcription across the D-loop region, since light and heavy strand transcription is terminated at CSB1 and coreTAS, respectively. Interestingly, the replication of the nascent D-loop strand, occurring in a direction opposite to that of heavy strand transcription, is also terminated at coreTAS, suggesting that coreTAS is involved in termination of both transcription and replication. Finally, we demonstrate that the loading of the helicase TWINKLE at coreTAS is reversible, implying that this site is a crucial component of a switch between D-loop formation and full-length mitochondrial DNA replication.
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| 5. |
- Liu, Ilon, et al.
(författare)
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The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:12, s. 1881-1894
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Tidskriftsartikel (refereegranskat)abstract
- Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche. Collectively, our study provides a powerful framework for rational modeling and therapeutic interventions.
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| 6. |
- Pennington, Bruce, et al.
(författare)
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Individual prediction of dyslexia by single vs. multiple deficit models.
- 2012
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Ingår i: Journal of Abnormal Psychology. - : American Psychological Association. - 0021-843X .- 1939-1846. ; 121:1, s. 212-224
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Tidskriftsartikel (refereegranskat)abstract
- The overall goals of this study were to test single versus multiple cognitive deficit models of dyslexia (reading disability) at the level of individual cases and to determine the clinical utility of these models for prediction and diagnosis of dyslexia. To accomplish these goals, we tested five cognitive models of dyslexia-two single-deficit models, two multiple-deficit models, and one hybrid model-in two large population-based samples, one cross-sectional (Colorado Learning Disability Research Center) and one longitudinal (International longitudinal Twin Study). The cognitive deficits included in these cognitive models were in phonological awareness, language skill, and processing speed and/or naming speed. To determine whether an individual case fit one of these models, we used two methods: 1) the presence or absence of the predicted cognitive deficits, and 2) whether the individuals level of reading skill best fit the regression equation with the relevant cognitive predictors (i.e., whether their reading skill was proportional to those cognitive predictors.) We found that roughly equal proportions of cases met both tests of model fit for the multiple deficit models (30-36%) and single deficit models (24-28%); hence, the hybrid model provided the best overall fit to the data. The remaining roughly 40% of cases in each sample lacked the deficit or deficits that corresponded with their best-fitting regression model. We discuss the clinical implications of these results for both diagnosis of school-age children and preschool prediction of children at risk for dyslexia.
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| 7. |
- Ruck, Kate, et al.
(författare)
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International access to research infrastructure in the Arctic
- 2022
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Ingår i: Polar Record. - : Cambridge University Press. - 0032-2474 .- 1475-3057. ; 58
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Reliable access to Arctic research infrastructure is critical to the future of polar science. In cultivating proposals, it is essential that researchers have a deep understanding of existing platforms when selecting the appropriate research site and experimental design for projects. However, Arctic infrastructure platforms are often funded as national assets, and choices for what would be the best platform for the project are sometimes at odds with a researcher’s ability to gain access. Researchers from Arctic and non-Arctic nations are poised to benefit from reducing barriers and increasing cooperation around transnational access to Arctic infrastructure, allowing scientists to successfully execute the research that is most needed rather than what is just logistically feasible. This commentary provides a summary of findings from a workshop held at the 2021 Arctic Science Summit Week to discuss navigating “transnational” or “cross-border” access to national research infrastructure. This workshop brought together users and operators of Arctic infrastructure platforms with the three goals of identifying challenges, best practices, and possible next steps for improved collaboration.
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| 8. |
- Samuelsson, Jennifer, et al.
(författare)
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Intra-arterial nimodipine for severe cerebral vasospasm after aneurysmal subarachnoid haemorrhage - neurological and radiological outcome.
- 2022
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Ingår i: The neuroradiology journal. - : SAGE Publications. - 2385-1996 .- 1971-4009. ; 35:2, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral vasospasm is a known complication to aneurysmal subarachnoid haemorrhage, which can lead to severe morbidity. Intra-arterial vasodilation therapy is widely used as a last resort treatment in patients with symptomatic refractory cerebral vasospasm but there is limited data about the outcome. The purpose of this study is to evaluate the neurological and radiological outcome in patients treated with intra-arterial nimodipine in relation to cerebral infarction, procedure-related complications and clinical outcome.Patients with refractory cerebral vasospasm treated with intra-arterial nimodipine during 2009-2020 at Sahlgrenska University Hospital were retrospectively reviewed. Neurological outcome (modified Rankin Scale) at 30 days and 6 months, development of cerebral infarction after intra-arterial nimodipine treatment and procedure-related complications were studied.Forty-eight patients were treated with intra-arterial nimodipine. A good outcome (modified Rankin Scale 0-2) was seen in 25% (n=12) of the patients after 30 days and in 47% (n=22) of the patients after six months. Infarction related to the vasospastic vessel after treatment with intra-arterial nimodipine was seen in 60% (n=29) of the patients. A total of 124 procedures with intra-arterial nimodipine were performed where complications were seen in 10 (21%) patients in 10 (8%) procedures. Four (8%) patients died within 30 days.A majority of patients developed an ischaemic cerebral infarction in spite of intra-arterial nimodipine treatment. However, a good clinical recovery was seen in almost half of the patients after 6 months. Minor complications occurred in one out of five patients.
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| 9. |
- Samuelsson, Jennifer, et al.
(författare)
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Neurological outcome, mental fatigue and occurrence of aneurysms more than 15 years after aneurysmal subarachnoid haemorrhage.
- 2021
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Ingår i: World neurosurgery. - : Elsevier BV. - 1878-8769 .- 1878-8750. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- Long-term data on neurological and radiological outcome after aneurysmal subarachnoid haemorrhage (aSAH) is scarce. The aims of this study were to report neurological and radiological outcome more than 15 years after aSAH.Patients from Western Sweden with aSAH randomized to endovascular (EVT) or microsurgical treatment (MST) from 1997 to 2001 were included. Main end-points were neurological outcome assessed by modified Rankin scale (mRS), fatigue assessed by mental fatigue scale (MFS) and radiological outcome assessed by magnetic resonance angiography (MRA). Results were compared to a control group for MFS.Forty-six patients (62.2%) of the 74 survivors replied after 15-21 years. Eighteen had MST and 28 had EVT. mRS 0-2 was found in 100% of EVT patients and in 88.8 % of MST patients. Moderate or severe mental fatigue was found in 7/28 patients (25 %) in the EVT group and 7/18 patients (38.8 % (p<0.05)) in the MST group, whereas moderate or severe mental fatigue was observed in 3/34 (8.9 %) in the control group. Twenty-nine patients agreed to do an MRA. In the EVT group, new neck remnants were found in 2/16 (12.5%) and de novo aneurysm was found in 2/16 (12.5%). In the MST group de novo aneurysm was found in 1/13 (7.7%).Neurological outcome at long-term follow-up after aSAH was good, however mental fatigue was overrepresented compared to healthy controls, regardless of treatment modality. Residual or de novo aneurysm was found in 17% of patients warranting radiological long-term follow-up.
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| 10. |
- Samuelsson, Jennifer, et al.
(författare)
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Risk of de novo aneurysm formation in patients previously diagnosed with a ruptured or unruptured aneurysm: 18-year follow-up.
- 2023
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Ingår i: Clinical neurology and neurosurgery. - 0303-8467 .- 1872-6968. ; 233
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Tidskriftsartikel (refereegranskat)abstract
- Data on de novo aneurysm formation after treatment for intracranial aneurysms remains scarce. We studied the incidence of de novo aneurysm formation in patients who had undergone aneurysm treatment more than 18 years prior to follow-up. As it is a disease affecting a younger patient population more specific guidelines are needed when planning a follow-up regime.The rate of de novo aneurysm formation was assessed with Magnetic Resonance Angiography (MRA) follow-up >18 years after endovascular or microsurgical treatment for an intracranial aneurysm. Variables associated with de novo aneurysm formation were studied using logistic regression. Missing data were imputed using chained random forests. A data-driven model for the prediction of de novo aneurysm was created to calculate the relative variable importance of ten clinical features.De novo aneurysms were identified in 11/81 (13.6 %) patients, of whom 1 was male, over a median follow-up of 20 years. Sex was the most important variable associated with de novo aneurysm formation. Regarding the development of de novo aneurysm, men displayed an odds ratio (OR) of 0.16 (0.01-0.97), compared with women. OR for mRS score 2 or more was 0.20 (95 % CI 0.01-1.34), and OR for smokers was 3.70 (0.54-31.18). Six out of 11 patients (54.5 %) needed treatment; 1 underwent endovascular treatment (EVT) and 5 underwent microsurgical treatment (MST). The overall annual de novo aneurysm formation rate was 0.92 %.This study highlights the need for a longer follow-up imaging monitoring of patients that have previously undergone treatment for an intracranial aneurysm. These data are useful to take into consideration when planning a follow-up strategy.
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| 11. |
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| 12. |
- Tobieson, Lovisa, et al.
(författare)
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Akuta vaskulära neurokirurgiska tillstånd kräver snabb hantering
- 2023
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Ingår i: Lakartidningen. - 0023-7205. ; 120
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Forskningsöversikt (refereegranskat)abstract
- Conditions involving intracranial vascular anomalies are increasingly diagnosed, not least incidentally, with the increasing availability of neuroradiological investigations. Acute deterioration and development of symptoms due to a vascular condition could require neurosurgical intervention depending on the nature of the condition and status of the patient. On the other hand, asymptomatic patients with incidental findings require careful consideration and risk assessment when deciding on whether or not to treat the condition, and if so, how. In this review article we provide a summary of some of the most common neurosurgical vascular conditions and outline management considerations in both the acute and elective setting.
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| 13. |
- Tobieson, Lovisa, et al.
(författare)
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Akuta vaskulära neurokirurgiska tillstånd kräver snabb hantering : [Considerations when handling common acute intracranial vascular anomalies]
- 2023
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Ingår i: Läkartidningen. - : Sveriges Läkarforbund. - 0023-7205 .- 1652-7518. ; 120
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Forskningsöversikt (refereegranskat)abstract
- Conditions involving intracranial vascular anomalies are increasingly diagnosed, not least incidentally, with the increasing availability of neuroradiological investigations. Acute deterioration and development of symptoms due to a vascular condition could require neurosurgical intervention depending on the nature of the condition and status of the patient. On the other hand, asymptomatic patients with incidental findings require careful consideration and risk assessment when deciding on whether or not to treat the condition, and if so, how. In this review article we provide a summary of some of the most common neurosurgical vascular conditions and outline management considerations in both the acute and elective setting.
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| 14. |
- Tobieson, Lovisa, et al.
(författare)
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Considerations when handling common acute intracranial vascular anomalies : [Akuta vaskulära neurokirurgiska tillstånd kräver snabb hantering]
- 2023
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 120:4-5
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Tidskriftsartikel (refereegranskat)abstract
- Conditions involving intracranial vascular anomalies are increasingly diagnosed, not least incidentally, with the increasing availability of neuroradiological investigations. Acute deterioration and development of symptoms due to a vascular condition could require neurosurgical intervention depending on the nature of the condition and status of the patient. On the other hand, asymptomatic patients with incidental findings require careful consideration and risk assessment when deciding on whether or not to treat the condition, and if so, how. In this review article we provide a summary of some of the most common neurosurgical vascular conditions and outline management considerations in both the acute and elective setting.
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| 15. |
- Uhler, Jay (Jennifer), et al.
(författare)
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The UbL protein UBTD1 stably interacts with the UBE2D family of E2 ubiquitin conjugating enzymes
- 2014
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 443:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- UBTD1 is a previously uncharacterized ubiquitin-like (UbL) domain containing protein with high homology to the mitochondrial Dc-UbP/UBTD2 protein. Here we show that UBTD1 and UBTD2 belong to a family of proteins that is conserved through evolution and found in metazoa, funghi, and plants. To gain further insight into the function of UBTD1, we screened for interacting proteins. In a yeast-2-hybrid (Y2H) screen, we identified several proteins involved in the ubiquitylation pathway, including the UBE2D family of E2 ubiquitin conjugating enzymes. An affinity capture screen for UBTD1 interacting proteins in whole cell extracts also identified members of the UBE2D family. Biochemical characterization of recombinant UBTD1 and UBE2D demonstrated that the two proteins form a stable, stoichiometric complex that can be purified to near homogeneity. We discuss the implications of these findings in light of the ubiquitin proteasome system (UPS). (C) 2013 Published by Elsevier Inc.
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| 16. |
- Åström, Mattias, et al.
(författare)
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Prediction of Electrode Contacts for Clinically Effective Deep Brain Stimulation in Essential Tremor
- 2018
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 96:5, s. 281-288
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Deep brain stimulation (DBS) is an established neurosurgical treatment that can be used to alleviate symptoms in essential tremor (ET) and other movement disorders. The aim was to develop a method and software tool for the prediction of effective DBS electrode contacts based on probabilistic stimulation maps (PSMs) in patients with ET treated with caudal zona incerta (cZi) DBS. Methods: A total of 33 patients (37 leads) treated with DBS were evaluated with the Essential Tremor Rating Scale (ETRS) 12 months after surgery. In addition, hand tremor and hand function (ETRS items 5/6 and 11-14) were evaluated for every contact during stimulation with best possible outcome without inducing side effects. Prediction of effective DBS electrode contacts was carried out in a retrospective leave-one-out manner based on PSMs, simulated stimulation fields, and a scoring function. Electrode contacts were ranked according to their likelihood of being included in the clinical setting. Ranked electrode contacts were compared to actual clinical settings. Results: Predictions made by the software tool showed that electrode contacts with rank 1 matched the clinically used contacts in 60% of the cases. Contacts with a rank of 1-2 and 1-3 matched the clinical contacts in 83 and 94% of the cases, respectively. Mean improvement of hand tremor and hand function was 79 +/- 21% and 77 +/- 22% for the clinically used and the predicted electrode contacts, respectively. Conclusions: Effective electrode contacts can be predicted based on PSMs in patients treated with cZi DBS for ET. Predictions may in the future be used to reduce the number of clinical assessments that are carried out before a satisfying stimulation setting is defined.
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