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Improved prediction and monitoring of CNS disorders with advanced neurophysiological and genetic assessment

English title Improved prediction and monitoring of CNS disorders with advanced neurophysiological and genetic assessment
Applicant Fuhr Peter
Number 124115
Funding scheme SPUM
Research institution Abteilung für Klinische Neurophysiologie Neurologische Universitätsklinik Kantonsspital Basel
Institution of higher education University of Basel - BS
Main discipline Neurology, Psychiatry
Start/End 01.04.2009 - 31.03.2012
Approved amount 1'550'527.00
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Lay Summary (English)

Lead
Lay summary
Objective: To establish a numerical model for better characterization and prediction of the course of the two most prevalent chronic neurological disorders with high impact on quality of life in young and elderly human beings, respectively: Multiple Sclerosis (MS) and Alzheimer's disease (AD). The numerical model will contain clinical, neuropsychological, genetic, imaging and neurophysiological data.Background: Although diagnosis of MS has greatly improved over the last decade, reliable prediction of the disease course (prognosis) is still not satisfying. In AD and other dementia types diagnosis is more difficult early in the disorder and depends in part on the course of symptoms. In both disease groups, clinical examination is still the main tool to assess the course of disease and the grade of impairment. Neurophysiological measurements like electroencephalography (EEG) at rest and during visual and sensory stimulation (evoked potentials, EP) represent parameters of impulse propagation in the central nervous system. These measures are likely to be abnormal early in the course of MS and AD. Therefore, they may add important information on the prognosis in MS and AD, and on the differential diagnosis of dementias. Recent technical developments allow the recording of EEG and EP with high resolution (256 channels) resulting in precise identification and localization of pathological changes. Genetic testing is likely to further improve the prediction of the disease course.Methods: In the MS subproject one hundred patients and fifty age-matched healthy controls will be examined three times at yearly intervals. Clinical and neuropsychological examination will be complemented by high-resolution EEG and EP, genetic testing and brain imaging by magnetic resonance tomography.In the AD subproject, forty patients with dementia will be compared to forty age matched healthy controls in regard to their cognitive performance, genetic profile and results of high resolution EEG and EP. All results of the different tests will be analyzed with a statistical model, which summarizes all data of an individual to a score to predict the clinical course in MS and AD.Significance: Reliable markers of disease progression and prognosis would allow to conduct clinical trials with a smaller number of patients or in less time, thus reaching clinically meaningful results more efficiently. This is especially important in MS and AD, where innovative treatment options are entering the phase of clinical testing in coming years. Moreover, improved prediction of the course of MS and AD may be useful even in individual patients for counselling and treatment decisions.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis.
Kuhle J, Hardmeier M, Disanto G, Gugleta K, Ecsedi M, Lienert C, Amato M P, Baum K, Buttmann M, Bayas A, Brassat D, Brochet B, Confavreux C, Edan G, Färkkilä M, Fredrikson S, Frontoni M, D'Hooghe M, Hutchinson M, De Keyser J, Kieseier B C, Kümpfel T, Rio J, Polman C, Roullet E (2016), A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis., in Multiple sclerosis (Houndmills, Basingstoke, England), 22(4), 533-43.
Fluctuations of spontaneous EEG topographies predict disease state in relapsing-remitting multiple sclerosis.
Gschwind Markus, Hardmeier Martin, Van De Ville Dimitri, Tomescu Miralena I, Penner Iris-Katharina, Naegelin Yvonne, Fuhr Peter, Michel Christoph M, Seeck Margitta (2016), Fluctuations of spontaneous EEG topographies predict disease state in relapsing-remitting multiple sclerosis., in NeuroImage. Clinical, 12, 466-77.
Monitoring multiple sclerosis by multimodal evoked potentials: Numerically versus ordinally scaled scoring systems.
Schlaeger Regina, Hardmeier Martin, D'Souza Marcus, Grize Leticia, Schindler Christian, Kappos Ludwig, Fuhr Peter (2016), Monitoring multiple sclerosis by multimodal evoked potentials: Numerically versus ordinally scaled scoring systems., in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiol, 127(3), 1864-71.
Quantitative EEG and Cognitive Decline in Parkinson's Disease.
Cozac Vitalii V, Gschwandtner Ute, Hatz Florian, Hardmeier Martin, Rüegg Stephan, Fuhr Peter (2016), Quantitative EEG and Cognitive Decline in Parkinson's Disease., in Parkinson's disease, 2016, 9060649-9060649.
Reliability of Functional Connectivity of Electroencephalography Applying Microstate-Segmented Versus Classical Calculation of Phase Lag Index.
Hatz Florian, Hardmeier Martin, Bousleiman Habib, Rüegg Stephan, Schindler Christian, Fuhr Peter (2016), Reliability of Functional Connectivity of Electroencephalography Applying Microstate-Segmented Versus Classical Calculation of Phase Lag Index., in Brain connectivity, 6(6), 461-9.
Microstate connectivity alterations in patients with early Alzheimer's disease.
Hatz Florian, Hardmeier Martin, Benz Nina, Ehrensperger Michael, Gschwandtner Ute, Rüegg Stephan, Schindler Christian, Monsch Andreas U, Fuhr Peter (2015), Microstate connectivity alterations in patients with early Alzheimer's disease., in Alzheimer's research & therapy, 7, 78-78.
Correlation of EEG slowing with cognitive domains in nondemented patients with Parkinson's disease.
Zimmermann Ronan, Gschwandtner Ute, Hatz Florian, Schindler Christian, Bousleiman Habib, Ahmed Shaheen, Hardmeier Martin, Meyer Antonia, Calabrese Pasquale, Fuhr Peter (2014), Correlation of EEG slowing with cognitive domains in nondemented patients with Parkinson's disease., in Dementia and geriatric cognitive disorders, 39(3-4), 207-14.
Improved characterization of visual evoked potentials in multiple sclerosis by topographic analysis.
Hardmeier Martin, Hatz Florian, Naegelin Yvonne, Hight Darren, Schindler Christian, Kappos Ludwig, Seeck Margitta, Michel Christoph M, Fuhr Peter (2014), Improved characterization of visual evoked potentials in multiple sclerosis by topographic analysis., in Brain topography, 27(2), 318-27.
Power spectra for screening parkinsonian patients for mild cognitive impairment.
Bousleiman Habib, Zimmermann Ronan, Ahmed Shaheen, Hardmeier Martin, Hatz Florian, Schindler Christian, Roth Volker, Gschwandtner Ute, Fuhr Peter (2014), Power spectra for screening parkinsonian patients for mild cognitive impairment., in Annals of clinical and translational neurology, 1(11), 884-90.
Reliability of fully automated versus visually controlled pre- and post-processing of resting-state EEG.
Hatz F, Hardmeier M, Bousleiman H, Rüegg S, Schindler C, Fuhr P (2014), Reliability of fully automated versus visually controlled pre- and post-processing of resting-state EEG., in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiol, 126(2), 268-74.
Reproducibility of functional connectivity and graph measures based on the phase lag index (PLI) and weighted phase lag index (wPLI) derived from high resolution EEG.
Hardmeier Martin, Hatz Florian, Bousleiman Habib, Schindler Christian, Stam Cornelis Jan, Fuhr Peter (2014), Reproducibility of functional connectivity and graph measures based on the phase lag index (PLI) and weighted phase lag index (wPLI) derived from high resolution EEG., in PloS one, 9(10), 108648-108648.
Slowing of EEG background activity in Parkinson's and Alzheimer's disease with early cognitive dysfunction.
Benz Nina, Hatz Florian, Bousleiman Habib, Ehrensperger Michael M, Gschwandtner Ute, Hardmeier Martin, Ruegg Stephan, Schindler Christian, Zimmermann Ronan, Monsch Andreas Urs, Fuhr Peter (2014), Slowing of EEG background activity in Parkinson's and Alzheimer's disease with early cognitive dysfunction., in Frontiers in aging neuroscience, 6, 314-314.
Quantitative EEG and apolipoprotein E-genotype improve classification of patients with suspected Alzheimer's disease.
Hatz F, Benz N, Hardmeier M, Zimmermann R, Rueegg S, Schindler C, Miserez A R, Gschwandtner U, Monsch A U, Fuhr P (2013), Quantitative EEG and apolipoprotein E-genotype improve classification of patients with suspected Alzheimer's disease., in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiol, 124(11), 2146-52.
Superficial brain stimulation in multiple sclerosis.
Schlaeger Regina, Hardmeier Martin, Fuhr Peter (2013), Superficial brain stimulation in multiple sclerosis., in Handbook of clinical neurology, 116, 577-84.
Cognitive dysfunction in early multiple sclerosis: altered centrality derived from resting-state functional connectivity using magneto-encephalography.
Hardmeier Martin, Schoonheim Menno M, Geurts Jeroen J G, Hillebrand Arjan, Polman Chris H, Barkhof Frederik, Stam Cornelis J (2012), Cognitive dysfunction in early multiple sclerosis: altered centrality derived from resting-state functional connectivity using magneto-encephalography., in PloS one, 7(7), 42087-42087.
Combined evoked potentials as markers and predictors of disability in early multiple sclerosis.
Schlaeger Regina, D'Souza Marcus, Schindler Christian, Grize Leticia, Kappos Ludwig, Fuhr Peter (2012), Combined evoked potentials as markers and predictors of disability in early multiple sclerosis., in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiol, 123(2), 406-10.
Prediction of long-term disability in multiple sclerosis.
Schlaeger R, D'Souza M, Schindler C, Grize L, Dellas S, Radue E W, Kappos L, Fuhr P (2012), Prediction of long-term disability in multiple sclerosis., in Multiple sclerosis (Houndmills, Basingstoke, England), 18(1), 31-8.
Biology of gait control Vitamin D involvement
Beauchet O., Annweiler C., Verghese J., Fantino B., Herrmann F. R., Allali G. (2011), Biology of gait control Vitamin D involvement, in NEUROLOGY, 76(19), 1617-1622.
Clinical EEG in cognitively impaired patients with Parkinson's Disease.
Schlede Nina, Zimmermann Ronan, Ehrensperger Michael M, Gschwandtner Ute, Hardmeier Martin, Hatz Florian, Monsch Andreas U, Naegelin Yvonne, Fuhr Peter (2011), Clinical EEG in cognitively impaired patients with Parkinson's Disease., in Journal of the neurological sciences, 310(1-2), 75-8.
Interest of dual-task-related gait changes in idiopathic normal pressure hydrocephalus.
Armand S, Allet L, Landis T, Beauchet O, Assal F, Allali G (2011), Interest of dual-task-related gait changes in idiopathic normal pressure hydrocephalus., in European journal of neurology : the official journal of the European Federation of Neurological Soci, 18(8), 1081-4.
Test-retest reliability of stride time variability while dual tasking in healthy and demented adults with frontotemporal degeneration
Beauchet O, Freiberger E, Annweiler C, Kressig R, Herrmann F, Allali G (2011), Test-retest reliability of stride time variability while dual tasking in healthy and demented adults with frontotemporal degeneration, in Journal of NeuroEngineering and Rehabilitation, 8(1), 1081-1084.
Association of vitamin D deficiency with cognitive impairment in older women: cross-sectional study.
Annweiler C, Schott A M, Allali G, Bridenbaugh S A, Kressig R W, Allain P, Herrmann F R, Beauchet O (2010), Association of vitamin D deficiency with cognitive impairment in older women: cross-sectional study., in Neurology, 74(1), 27-32.
Frontotemporal dementia: pathology of gait?
Allali Gilles, Dubois Bruno, Assal Frederic, Lallart Elise, de Souza Leonardo C, Bertoux Maxime, Annweiler Cédric, Herrmann Francois R, Levy Richard, Beauchet Olivier (2010), Frontotemporal dementia: pathology of gait?, in Movement disorders : official journal of the Movement Disorder Society, 25(6), 731-7.
Imagined Timed Up & Go test: a new tool to assess higher-level gait and balance disorders in older adults?
Beauchet Olivier, Annweiler Cédric, Assal Frédéric, Bridenbaugh Stephanie, Herrmann François R, Kressig Reto W, Allali Gilles (2010), Imagined Timed Up & Go test: a new tool to assess higher-level gait and balance disorders in older adults?, in Journal of the neurological sciences, 294(1-2), 102-6.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ENS 2011 Poster EEG background activity is correlated to a measure of cognitive speed in MS 28.05.2011 Lisbon, Portugal Rüegg Stephan; Schindler Christian; Hardmeier Martin Ernst; Fuhr Peter; Hatz Florian; Penner Iris-Katharina; Kappos Ludwig;
ECTRIMS 2011 Poster Functional connectivity and Eigenvector centrality mapping in MS using magneto-encephalography (MEG) 28.05.2011 Amsterdam, Netherlands Hardmeier Martin Ernst;
SGKN Tagung 2011 Talk given at a conference resolution visual evoked potentials (VEP) in the assessment of patients with Multiple Sclerosis 19.05.2011 Luzern, Switzerland Seeck Margitta; Hatz Florian; Fuhr Peter; Kappos Ludwig; Hardmeier Martin Ernst; Michel Christoph;


Associated projects

Number Title Start Funding scheme
128775 High-resolution EEG: translation of neuroscience into clinical context 01.12.2009 R'EQUIP
132644 Immune regulation by microRNAs in Multiple Sclerosis - Added value in characterization of disease course and response to treatment 01.01.2011 Project funding (Div. I-III)
159705 Temporal dynamics of whole-brain neuronal networks 01.05.2015 Project funding (Div. I-III)
140338 Improved prediction and monitoring of central nervous system disorders with advanced neurophysiological and genetic assessment. 01.04.2012 SPUM

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