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- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Bluett, Brent, et al.
(författare)
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Clinical features of idiopathic normal pressure hydrocephalus : critical review of objective findings
- 2023
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Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:1, s. 9-16
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Forskningsöversikt (refereegranskat)abstract
- Background: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the classic clinical triad of gait, cognitive, and urinary dysfunction, albeit incomplete in a relevant proportion of patients. The clinical findings and evolution of these symptoms have been variably defined in the literature.Objectives: To evaluate how the phenomenology has been defined, assessed, and reported, we performed a critical review of the existing literature discussing the phenomenology of iNPH. The review also identified the instrumental tests most frequently used and the evolution of clinical and radiologic findings.Methods: The review was divided into 3 sections based on gait, cognitive, and urinary dysfunction. Each section performed a literature search using the terms “idiopathic normal pressure hydrocephalus” (iNPH), with additional search terms used by each section separately. The number of articles screened, duplicates, those meeting the inclusion criteria, and the number of articles excluded were recorded. Findings were subsequently tallied and analyzed.Results: A total of 1716 articles with the aforementioned search criteria were identified by the 3 groups. A total of 81 full-text articles were reviewed after the elimination of duplicates, articles that did not discuss phenomenological findings or instrumental testing of participants with iNPH prior to surgery, and articles with fewer than 10 participants.Conclusions: “Wide-based gait” was the most common gait dysfunction identified. Cognitive testing varied significantly across articles, and ultimately a specific cognitive profile was not identified. Urodynamic testing found detrusor overactivity and “overactive bladder” as the most common symptom of urinary dysfunction.
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| 3. |
- Capelle, Hans-Holger, et al.
(författare)
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Bilateral deep brain stimulation for cervical dystonia in patients with previous peripheral surgery
- 2012
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 27:2, s. 301-304
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are no data available concerning whether patients with cervical dystonia who have recurrent or new symptoms after peripheral denervation surgery benefit similarly from pallidal deep brain stimulation compared with patients who receive primarily pallidal stimulation. Methods: Data on 7 cervical dystonia patients with recurrent or progressive dystonia after peripheral denervation who underwent pallidal stimulation were prospectively collected. Deep brain stimulation was performed in Mannheim/ Hannover, Germany, or in Umea, Sweden. To the subgroup from Mannheim/Hannover, a second group of patients without previous peripheral surgery was matched. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale and the Burke-FahnMarsden dystonia rating scale, as well as the Tsui scale in the Swedish patients. Results: The 4 patients from Mannheim/Hannover experienced sustained improvement from pallidal stimulation by a mean of 57.5% according to the Toronto Western Spasmodic Torticollis Rating Scale (P <.05) and by a mean of 69.5% according to the Burke-FahnMarsden dystonia rating scale (P <.05) at long-term follow-up of 40.5 months. The patients from Umea had a mean Tsui score of 7 prior to surgery and a mean score of 3 at the mean follow-up of 8 months (62.5%). In the matched group the Toronto Western Spasmodic Torticollis Rating Scale improved by 58.8% and the Burke-Fahn-Marsden dystonia rating scale by 67% (P <.05) at long-term follow-up (mean, 41.5 months). Conclusions: Patients who had prior peripheral surgery for cervical dystonia experience improvement from subsequent pallidal stimulation that is comparable to that of de novo patients. (C) 2011 Movement Disorder Society
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| 7. |
- Krauss, Joachim K., et al.
(författare)
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Technology of deep brain stimulation : current status and future directions
- 2021
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Ingår i: Nature Reviews Neurology. - : Springer Nature. - 1759-4758 .- 1759-4766. ; 17:2, s. 75-87
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Forskningsöversikt (refereegranskat)abstract
- Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.
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| 8. |
- Nuttin, Bart, et al.
(författare)
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Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders
- 2014
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group. - 0022-3050 .- 1468-330X. ; 85:9, s. 1003-1008
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Tidskriftsartikel (refereegranskat)abstract
- Background For patients with psychiatric illnesses remaining refractory to 'tandard' therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. Methods To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. Findings The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered 'stablished' in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient's capacity and autonomy, multifaceted preoperative as well as postoperative long-term follow-p evaluation, and reporting of effects and side effects for all patients. Interpretation This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety.
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| 9. |
- Rzesnitzek, Lara, et al.
(författare)
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Psychosurgery in the History of Stereotactic Functional Neurosurgery
- 2020
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 98:4, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- The paper invites to reappraise the role of psychosurgery for and within the development of functional stereotactic neurosurgery. It highlights the significant and long-lived role of stereotactic neurosurgery in the treatment of severe and chronic mental disorders. Stereotactic neurosurgery developed out of psychosurgery. It was leucotomy for psychiatric disorders and chronic pain that paved the way for stereotactic dorsomedial thalamotomy in these indications and subsequently for stereotactic surgery in epilepsy and movement disorders. Through the 1960s stereotactic psychosurgery continued to progress in silence. Due to the increased applications of stereotactic surgery in psychiatric indications, psychosurgery's renaissance was proclaimed in the early 1970s. At the same time, however, a public fearing mind control started to discredit all functional neurosurgery for mental disorders, including stereotactic procedures. In writing its own history, stereotactic neurosurgery's identity as a neuropsychiatric discipline became subsequently increasingly redefined as principally a sort of "surgical neurology," cut off from its psychiatric origin.
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| 10. |
- Rzesnitzek, Lara, et al.
(författare)
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The Origins of Human Functional Stereotaxis : A Reappraisal
- 2019
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 97:1, s. 49-54
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Forskningsöversikt (refereegranskat)abstract
- In order to shed light on the first application of human functional stereotactic neurosurgery, whether it was in the realm of movement disorders, as has been claimed repeatedly, or in the realm of psychiatry, a review of the original scholarly literature was conducted. Tracking and scrutinising original publications by Spiegel and Wycis, the pioneers of human stereotactic neurosurgery, it was found that its origin and the very incentive for its development and first clinical use were to avoid the side effects of frontal leucotomy. The first applications of functional stereotactic neurosurgery were in performing dorsomedial thalamotomies in psychiatric patients; it was only later that the stereotactic technique was applied in patients with chronic pain, movement disorders and epilepsy. Spiegel and Wycis' first functional stereotactic operations were for obsessive-compulsive disorder, schizophrenia, and other psychiatric conditions.
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