Systematic Analysis of Deep Brain Stimulation and Ethanol Effect in Patients with Essential Tremor

Ein etablierter Ansatz zur Therapie des fortgeschrittenen Essentiellen Tremors (= ET) ist die Tiefe Hirnstimulation des Nucleus ventro intermedius (= Vim-THS) (Rehncrona et al. 2003, Pahwa et al. 2006, Zhang et al. 2010). In der vorliegenden Arbeit soll der Krankheitsprogress und der Habituationseffekt der Langzeit-Vim-THS bei Patienten mit Essentiellem Tremor untersucht werden sowie potentielle, die Validität der Beurteilung beeinflussende Faktoren, wie z. B. der sogenannte Rebound-Effekt. Methoden zur Trennung von Krankheitsprogress und Habituation auf den Verlauf des Tremors existieren bis dato nicht, daher war hier methodische Entwicklung erforderlich. Neben der Vim-THS kann auch durch Alkoholeinnahme eine signifikante Senkung der Tremoramplitude erreicht werden (Growdon et al. 1975, Lou et al. 1991, Knudsen et al. 2011, Hopfner et al. 2015). Die Kombination dieser den Tremor modifizierenden Interventionen ist bis dato durch keine Studie systematisch erfasst worden. Unklar ist auch, in welchem Maß sich diese therapeutischen Effekte additiv oder überadditiv verhalten. Die vorliegende Arbeit soll daher zu einem besseren Verständnis beider Therapieansätze führen und pathophysiologische Überlegungen stimulieren

The solitary nucleus connectivity to key autonomic regions in humans

The nucleus tractus solitarius (NTS) is a key brainstem structure relaying interoceptive peripheral information to the interrelated brain centres for eliciting rapid autonomic responses and for shaping longer-term neuroendocrine and motor patterns. Structural and functional NTS' connectivity has been extensively investigated in laboratory animals. But there is limited information about NTS' connectome in humans. Using MRI, we examined diffusion and resting state data from 20 healthy participants in the Human Connectome Project. The regions within the brainstem (n = 8), subcortical (n = 6), cerebellar (n = 2) and cortical (n = 5) parts of the brain were selected via a systematic review of the literature and their white matter NTS connections were evaluated via probabilistic tractography along with functional and directional (i.e. Granger causality) analyses. The underlying study confirms previous results from animal models and provides novel aspects on NTS integration in humans. Two key findings can be summarized: (1) the NTS predominantly processes afferent input and (2) a lateralization towards a predominantly left-sided NTS processing. Our results lay the foundations for future investigations into the NTS' tripartite role composed of interoreceptors' input integration, the resultant neurochemical outflow and cognitive/affective processing. The implications of these data add to the understanding of NTS' role in specific aspects of autonomic functions

Sensitized vasoactive C-nociceptors: key fibers in peripheral neuropathic pain

Abstract. Introduction:. Multiple mechanisms are involved in the development and persistence of neuropathic pain. Some patients with nerve damage will remain painless and develop a “loss of function” phenotype, whereas others develop painful neuropathies. Objectives:. The aim of this study is to investigate the role of a peripheral nervous system sensitization by analyzing patients with and without pain. Methods:. The topical application of capsaicin was investigated in peripheral nociceptors. Two groups of patients (painful vs painless) with length-dependent neuropathies and small-fiber impairment were tested. Quantitative sensory testing was assessed before and after topical application of 0.6% capsaicin in the affected skin. In addition, blood perfusion measurements and an axon reflex flare assessment were performed. Results:. Quantitative testing revealed that heat hyperalgesia was induced in all patients and volunteers (P < 0.01) without observing any significant differences between patient groups. By contrast, the extent of the axon reflex flare reaction (P < 0.01) as well as the blood perfusion (P < 0.05) was significantly greater in patients with pain than in neuropathy patients not experiencing pain. Conclusion:. Hyperexcitable vasoactive nociceptive C fibers might contribute to pain in peripheral neuropathies and therefore may serve as a key player in separating into a painless or painful condition