Increased EEG power and slowed dominant frequency in patients with neurogenic pain

To study the mechanisms of chronic neurogenic pain, we compared the power spectra of the resting EEG of patients (n = 15, 38-75 years, median 64 years, 6 women) and healthy controls (n = 15, 41-71 years, median 60 years, 8 women). On an average, the patient group exhibited higher spectral power over the frequency range of 2-25 Hz, and the dominant peak was shifted towards lower frequencies. Maximal differences appeared in the 7-9 Hz band in all electrodes. Frontal electrodes contributed most to this difference in the 13-15 Hz band. Bicoherence analysis suggests an enhanced coupling between theta (4-9 Hz) and beta (12-25 Hz) frequencies in patients. The subgroup of six patients free from centrally acting medication showed higher spectral power in the 2-18 Hz frequency range. On an individual basis, the combination of peak height and peak frequency discriminated between patient and control groups: discriminant analysis classified 87% of all subjects correctly. After a therapeutic lesion in the thalamus (central lateral thalamotomy, CLT) we carried out follow-up for a subgroup of seven patients. Median pain relief was 70 and 95% after 3 and 12 months, respectively. The average EEG power of all seven patients gradually decreased in the theta band and approached normal values only after 12 months. The excess theta EEG power in patients and its decrease after thalamic surgery suggests that both EEG and neurogenic pain are determined by tightly coupled thalamocortical loops. The small therapeutic CLT lesion is thought to initiate a progressive normalization in the affected thalamocortical system, which is reflected in both decrease of EEG power and pain relief

Human pallidothalamic and cerebellothalamic tracts: anatomical basis for functional stereotactic neurosurgery

Anatomical knowledge of the structures to be targeted and of the circuitry involved is crucial in stereotactic functional neurosurgery. The present study was undertaken in the context of surgical treatment of motor disorders such as essential tremor (ET) and Parkinson’s disease (PD) to precisely determine the course and three-dimensional stereotactic localisation of the cerebellothalamic and pallidothalamic tracts in the human brain. The course of the fibre tracts to the thalamus was traced in the subthalamic region using multiple staining procedures and their entrance into the thalamus determined according to our atlas of the human thalamus and basal ganglia [Morel (2007) Stereotactic atlas of the human thalamus and basal ganglia. Informa Healthcare Inc., New York]. Stereotactic three-dimensional coordinates were determined by sectioning thalamic and basal ganglia blocks parallel to stereotactic planes and, in two cases, by correlation with magnetic resonance images (MRI) from the same brains prior to sectioning. The major contributions of this study are to provide: (1) evidence that the bulks of the cerebellothalamic and pallidothalamic tracts are clearly separated up to their thalamic entrance, (2) stereotactic maps of the two tracts in the subthalamic region, (3) the possibility to discriminate between different subthalamic fibre tracts on the basis of immunohistochemical stainings, (4) correlations of histologically identified fibre tracts with high-resolution MRI, and (5) evaluation of the interindividual variability of the fibre systems in the subthalamic region. This study should provide an important basis for accurate stereotactic neurosurgical targeting of the subthalamic region in motor disorders such as PD and ET

Loading neurons with BAPTA-AM activates xbp1 processing indicative of induction of endoplasmic reticulum stress

Copyright 2003 CHURCHILL LIVINGSTON

Spinal cord trauma activates processing of xbp1 mRNA indicative of endoplasmic reticulum dysfunction

© 2005 Mary Ann Liebert, Inc. publisher

Supplementary Material for: Effects of Cerebellothalamic Tractotomy on Cognitive and Emotional Functioning in Essential Tremor: A Preliminary Study in 5 Essential Tremor Patients

<p><b><i>Background:</i></b> Subthalamic stereotactic interventions have recently caught renewed interest as a treatment for essential tremor (ET). However, it is not clear whether these interventions are associated with neurocognitive, mood or personality changes. <b><i>Objective:</i></b> To investigate neurocognition, neuropsychiatric functions and personality variables in patients with ET and to explore the neurocognitive and neuropsychiatric effects of cerebellothalamic tractotomy (CTT), a form of subthalamotomy. <b><i>Methods:</i></b> In our study, we investigated cognitive functions, frontal functions, mood and personality variables in 5 patients with intractable ET. Patients were tested before and 3 months after surgery using neuropsychological tests, clinical scales for depression, anxiety, anger regulation and a personality test. <b><i>Results:</i></b> Before surgery, ET patients showed normal neurocognitive function, a slightly elevated frontal lobe score in the dimensions mental control and memory, without being indicative of a frontal lesion, and no elevated depression or anxiety scores compared to norm values. After surgery, there was no change in neurocognitive function and no increase in depression or anxiety scores. <b><i>Conclusion:</i></b> In this exploratory study on 5 ET patients, CTT was not associated with alterations of mood or neurocognitive functions.</p

Supplementary Material for: Autologous Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Drug Induction: A Retrospective Single-Center Analysis

<p>Within this retrospective single-center study, we analyzed the survival of 320 multiple myeloma (MM) patients receiving melphalan high-dose chemotherapy (HDCT) and either single (<i>n</i> = 286) or tandem (<i>n</i> = 34) autologous stem cell transplantation (ASCT) from 1996 to 2012. Additionally, the impact of novel induction regimens was assessed. Median follow-up was 67 months, median overall survival (OS) 62 months, median progression-free survival (PFS) 33 months (95% CI 27-39), and treatment-related death (TRD) 3%. Multivariate analysis revealed age ≥60 years (<i>p = </i>0.03) and stage 3 according to the International Staging System (<i>p = </i>0.006) as adverse risk factors regarding PFS. Median OS was significantly better in newly diagnosed MM patients receiving induction therapy with novel agents, e.g., bortezomib, thalidomide, or lenalidomide, compared with a traditional regimen (69 vs. 58 months; <i>p = </i>0.01). More patients achieved at least a very good partial remission in the period from 2005 to 2012 than from 1996 to 2004 (65 vs. 30%; <i>p</i> < 0.001), with a longer median OS in the later period (71 vs. 52 months, <i>p</i> = 0.027). In conclusion, our analysis confirms HDCT-ASCT as an effective therapeutic strategy in an unselected large myeloma patient cohort with a low TRD rate and improved prognosis due to novel induction strategies.</p

Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis

The unfolded protein response (UPR) is a conserved adaptive reaction that increases cell survival under endoplasmic reticulum (ER) stress conditions. X-box-binding protein-1 (XBP-1) is a key transcriptional regulator of the UPR that activates genes involved in protein folding, secretion, and degradation to restore ER function. The occurrence of chronic ER stress has been extensively described in neurodegenerative conditions linked to protein misfolding and aggregation. However, the role of the UPR in the CNS has not been addressed directly. Here we describe the generation of a brain-specific XBP-1 conditional KO strain (XBP-1Nes−/−). XBP-1Nes−/− mice are viable and do not develop any spontaneous neurological dysfunction, although ER stress signaling in XBP-1Nes−/− primary neuronal cell cultures was impaired. To assess the function of XBP-1 in pathological conditions involving protein misfolding and ER stress, we infected XBP-1Nes−/− mice with murine prions. To our surprise, the activation of stress responses triggered by prion replication was not influenced by XBP-1 deficiency. Neither prion aggregation, neuronal loss, nor animal survival was affected. Hence, this most highly conserved arm of the UPR may not contribute to the occurrence or pathology of neurodegenerative conditions associated with prion protein misfolding despite predictions that such diseases are related to ER stress and irreversible neuronal damage