V42. De novo mutations in the FUS gene are a frequent cause of sporadic ALS in very young patients

Society Proceedings / Clinical Neurophysiology 126 (2015) e63–e170

potential of quantitative balance parameters as trait and state markers in the prodromal phase of PD. Further implications and potential clinical impact of this will be discussed. doi:10.1016/j.clinph.2015.04.119

V42. De novo mutations in the FUS gene are a frequent cause of sporadic ALS in very young patients—A. Hübers a, A. Volk b,c, W. Just c, A. Rosenbohm a, N. Bierbaumer d, M. Kathrin c, M. Nicolai c, G. Ingrid c, H. Josef c, A. Janine b,e, T. Holger b,e, P. Nürnberg b,e, J.H. Weishaupt a, C. Kubisch b, A.C. Ludolph a (a Universität Ulm, Klinik für Neurologie, Ulm, Germany, b Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendof, Hamburg, Germany, c Institut für Humangenetik, Universitätsklinikum Ulm, Ulm, Germany, d Institut für medizinische Psychologie und behaviorale Neurobiologie, Universitätsklinikum Tübingen, Tübingen, Germany, e Cologne Center for Genomics, Universität Köln, Köln, Germany) Background: Mutations in C9orf72 and SOD1 account for most of the familial and late-onset sporadic ALS cases. Mutations in FUS can be identified in around 5% of FALS and 1% of overall sporadic ALS cases. Methods: We screened a large cohort of 15 very early onset (onset age <36 years) and 10 middle aged (36–53 years) sporadic ALS patients to determine the frequency of mutations in C9orf72, SOD1 and FUS in this distinct patient cohort. Results: In the cohort of the very early onset patients, we identified 6 subjects (40.0%) carrying a FUS mutation. Genetic testing of the patients’ parents was possible in 5 families and revealed that the mutation in these individuals arose de novo. Two of the identified mutations had not been described before (c.1484delG; c.1504delG). Three patients carried the already in younger ALS patients described FUS mutation p.P525L. No mutations were found in SOD1, C9orf72. Five of the six identified patients presented with rapidly progressive bulbar symptoms. Conclusion: Our study identifies FUS mutations as the most frequent genetic cause in early-onset ALS and suggests that de novo FUSmutations may be more common for sporadic ALS cases than recognized so far. Genetic testing of the FUS gene seems worthwhile in early onset ALS patients showing predominant bulbar symptoms and an aggressive disease course. doi:10.1016/j.clinph.2015.04.120

V43. Vagus somatosensory evoked potentials in elderly: A potential risk marker for neurodegeneration and its relation to Subjective Memory Impairment—F. Metzger a, K. Hagen a, A. Kroczek a, T. Polak b, A.-C. Ehlis a, A.J. Fallgatter a (a Universitätsklinikum Tübingen, Psychiatrie & Psychotherapie, Tübingen, Germany, b Universitätsklinikum Würzburg, Psychiatrie, Psychosomatik & Psychotherapie, Würzburg, Germany) Background: Vagus somatosensory evoked potentials (VSEP) have been shown to have higher latencies with aging, which are even more increased in patients with neurodegenerative or demyelination diseases, which may be related to an early affection of the brain stem and especially of the nuclei of the vagus nerve. Patients with Alzheimer’s disease and subjects with mild cognitive impairment as well as patients with Parkinson’s disease have increased latencies compared to age-matched healthy controls. A further potential risk or prodromal marker for Alzheimer’s (AD) disease being recently focused is subjective memory impairment (SMI). A main research

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question is which marker has the best predictive value for degenerative processes like AD. We investigate this question from both a psychological (SMI) and biological (VSEP) perspective. Methods: The association of VSEP latencies and SMI is studied in a healthy risk cohort, including 358 elderly subjects, who are in a longitudinal study of risk factors for neurodegenerative disorders (TREND study, Tuebinger evaluation of Risk factors for the Early detection of NeuroDegeneration). Results: The results show increased VSEP latencies for peak P2 at Fz-F4 in subjects who report SMI and are worried about it, as compared to subjects who report memory impairment, but are not concerned and to subjects without complaints. These results are in line with the findings during the last years of increased VSEP latencies in neurodegenerative diseases. Conclusion: VSEP are easily and comfortably measureable evoked potentials which may have a correlation to neurodegenerative or demyelinating damage to the brainstem nuclei of the N. Vagus. An important implication of the results is to further examine the predictive value of VSEP for neurodegenerative processes in longitudinal perspective. The present results support a potential role of VSEP for the detection of very early neurodegenerative processes which may precede Alzheimer’s disease. doi:10.1016/j.clinph.2015.04.121

V44. Spatially distinct cortico-thalamic networks identified by parallel iEEG and MEG recordings in patients with tremor—W.- J. Neumann a,b, A. Oswal b,c, A. Jha b,c, T. Foltynie b, P. Limousin b, L. Zrinzo b, M. Hariz b, P. Brown c, V. Litvak b (a Charité – Universitätsmedizin Berlin, Klinik für Neurologie, Berlin, Germany, b University College London, Institute of Neurology, London, United Kingdom, c University of Oxford, Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom) Question: The ventral intermediate nucleus region (VIMr) of the ventrolateral thalamus and the caudal Zona Incerta (cZi) are established targets for deep brain stimulation (DBS) therapy of medication refractory tremor. While the mechanism of action of DBS remains elusive, evidence points to a modulation of a coordinated network of oscillations. Distinct oscillatory activity patterns may allow large scale interactions between different neural structures. Aberrant activity patterns in these oscillatory networks can lead to the manifestation of specific symptoms, such as tremor, that can be treated with DBS. To characterize the oscillatory cortico-thalamic network we performed simultaneous magnetoencephalographic (MEG) and local field potential (LFP) recordings from the VIMr and cZi DBS electrodes in 10 patients (age: 59 ± 2.7 years) with tremor (6 Parkinson’s disease, 3 essential tremor, 1 orthostatic tremor). Methods: Simultaneous MEG-LFP recordings were conducted with the patients at rest with eyes open. LFPs were recorded bipolarly from adjacent contact pairs of the DBS electrodes. The lowermost contact pair was targeted at the cZi (01), while the two upper (12, 23) contact pairs targeted at the VIMr. Dynamic imaging of coherent sources (DICS) beamforming was utilized to visualize peaks of frequency specific cortico-thalamic coherence in Montreal Neurological Institute (MNI) space. Significant clusters were identified using Statistical Parametric Mapping (SPM, FWE corrected threshold p < 0.05). Results: Two spatially distinct beta band (13–30 Hz) clusters of cortico-subcortical oscillatory network activity were found for the cZi and VIMr contact pairs, respectively. Coupling of oscillatory beta band activity from the cZi was focally localized in the central cerebellum. In contrast, cortico-thalamic beta band coupling was