Combined Short-Pulse and Directional Deep Brain Stimulation of the Thalamic Ventral Intermediate Area for Essential Tremor.

OBJECTIVE: Novel deep brain stimulation (DBS) systems allow directional and short-pulse stimulation to potentially improve symptoms and reduce side effects. The aim of this study was to investigate the effect of short-pulse and directional stimulation, in addition to a combination of both, in the ventral intermediate thalamus (VIM)/posterior subthalamic area (PSA) on tremor and stimulation-induced side effects in patients with essential tremor. MATERIALS AND METHODS: We recruited 11 patients with essential tremor and VIM/PSA-DBS. Tremor severity (Fahn-Tolosa-Marin), ataxia (International Cooperative Ataxia Rating Scale), and paresthesia (visual analog scale) were assessed with conventional omnidirectional and directional stimulation with pulse width of 60 µs and 30 µs. RESULTS: All stimulation conditions reduced tremor. The best directional stimulation with 60 µs reduced more tremor than did most other stimulation settings. The best directional stimulation, regardless of pulse width, effectively reduced stimulation-induced ataxia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. All new stimulation modes reduced occurrence of paresthesia, but only the best directional stimulation with 30 µs attenuated paresthesia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. The best directional stimulation with 30 µs reduced tremor, ataxia, and paresthesia compared with conventional stimulation in most patients. Correlation analyses indicated that more anterior stimulation sites are associated with stronger ataxia reduction with directional 30 µs than with conventional 60 µs stimulation. CONCLUSION: Directional and short-pulse stimulation, and a combination of both, revealed beneficial effects on stimulation-induced adverse effects.

Face-induced gamma oscillations and event-related potentials in patients with epilepsy: an intracranial EEG study.

BACKGROUND: To examine the pathological effect of a mesial temporal seizure onset zone (SOZ) on local and inter-regional response to faces in the amygdala and other structures of the temporal lobe. METHODS: Intracranial EEG data was obtained from the amygdala, hippocampus, fusiform gyrus and parahippocampal gyrus of nine patients with drug-refractory epilepsy during visual stimulation with faces and mosaics. We analyzed event-related potentials (ERP), gamma frequency power, phase-amplitude coupling and phase-slope-index and compared the results between patients with versus without a mesial temporal SOZ. RESULTS: In the amygdala and fusiform gyrus, faces triggered higher ERP amplitudes compared to mosaics in both patient groups and higher gamma power in patients without a mesial temporal SOZ. In the hippocampus, famous faces triggered higher gamma power for both groups combined but did not affect ERPs in either group. The differentiated ERP response to famous faces in the parahippocampal gyrus was more pronounced in patients without a mesial temporal SOZ. Phase-amplitude coupling and phase-slope-index results yielded bidirectional modulation between amygdala and fusiform gyrus, and predominately unidirectional modulation between parahippocampal gyrus and hippocampus. CONCLUSIONS: A mesial temporal SOZ was associated with an impaired response to faces in the amygdala, fusiform gyrus and parahippocampal gyrus in our patients. Compared to this, the response to faces in the hippocampus was impaired in patients with, as well as without, a mesial temporal SOZ. Our results support existing evidence for face processing deficits in patients with a mesial temporal SOZ and suggest the pathological effect of a mesial temporal SOZ on the amygdala to play a pivotal role in this matter in particular.

Short pulse and directional thalamic deep brain stimulation have differential effects in parkinsonian and essential tremor.

The aim of this study was to assess the effects of novel stimulation algorithms of deep brain stimulation (short pulse and directional stimulation) in the ventrointermediate thalamus and posterior subthalamic area (VIM/PSA-DBS) on tremor in Parkinson's disease (PD) and to compare the effects with those in essential tremor (ET). We recruited six PD patients (70.8 ± 10.4 years) and seven ET patients (64.4 ± 9.9 years) with implanted VIM/PSA-DBS in a stable treatment condition (> 3 months postoperatively). Tremor severity and ataxia were assessed in four different stimulation conditions in a randomized order: DBS switched off (STIM OFF), omnidirectional stimulation with 60 µs (oDBS60), omnidirectional stimulation with 30 µs (oDBS30), directional stimulation at the best segment with 60 µs (dDBS60). In both patient groups, all three DBS stimulation modes reduced the total tremor score compared to STIM OFF, whereas stimulation-induced ataxia was reduced by oDBS30 and partially by dDBS60 compared to oDBS60. Tremor reduction was more pronounced in PD than in ET due to a limited DBS effect on intention and action-specific drawing tremor in ET. In PD and ET tremor, short pulse or directional VIM/PSA-DBS is an effective and well tolerated therapeutic option.Trial registration: The study was registered in the DRKS (ID DRKS00025329, 18.05.2021, German Clinical Trials Register, DRKS-Deutsches Register Klinischer Studien).

Subthalamic Deep Brain Stimulation Lead Asymmetry Impacts the Parkinsonian Gait Disorder.

Background: The preferable position of Deep Brain Stimulation (DBS) electrodes is proposed to be located in the dorsolateral subthalamic nucleus (STN) to improve general motor performance. The optimal DBS electrode localization for the post-operative improvement of balance and gait is unknown. Methods: In this single-center, retrospective analyses, 66 Parkinson's disease (PD) patients (24 female, age 63 ± 7 years) were assessed pre- and post-operatively (8.45 ± 4.2 months after surgery) by using MDS-UPDRS, freezing of gait (FoG) score, Giladi's gait and falls questionnaire and Berg balance scale. The clinical outcome was related to the DBS electrode coordinates in x, y, z plane as revealed by image-based reconstruction (SureTune™). Binomial generalized linear mixed models with fixed-effect variables electrode asymmetry, parkinsonian subtype, medication, age class and clinical DBS induced changes were analyzed. Results: Subthalamic nucleus-deep brain stimulation improved all motor, balance and FoG scores in MED OFF condition, however there were heterogeneous results in MED ON condition. DBS electrode reconstructed coordinates impacted the responsiveness of axial symptoms. FoG and balance responders showed slightly more medially located STN electrode coordinates and less medio-lateral asymmetry of the electrode reconstructed coordinates across hemispheres compared to non-responders. Conclusion: Deep brain stimulation electrode reconstructed coordinates, particularly electrode asymmetry on the medio-lateral axis affected the post-operative responsiveness of balance and FoG symptoms in PD patients.

Comparison of Montreal cognitive assessment and Mattis dementia rating scale in the preoperative evaluation of subthalamic stimulation in Parkinson's disease.

INTRODUCTION: The preoperative evaluation of Parkinson's Disease (PD) patients for subthalamic nucleus deep brain stimulation (STN-DBS) includes the assessment of the neuropsychological status of the patient. A widely used preoperative test is the Mattis Dementia rating scale (MDRS). However, the Montreal cognitive assessment (MoCA) has also been proven to be a sensitive, time-sparing tool with high diagnostic validity in PD. We evaluate the utility of the MoCA as a preoperative screening test for PD patients undergoing bilateral STN-DBS. METHODS: In this single-centre, retrospective study, we analysed pre- and postoperative assessments of MoCA, MDRS, Movement disorder society-Unified PD Rating Scale-motor examination, PD Questionnaire-39 and levodopa equivalent daily dose. Longitudinal outcome changes were analysed using paired t-test, Pearson's correlation coefficient, linear regression and CHAID (chi-square automatic interaction detector) regression tree model. RESULTS: Clinical motor and cognitive scores of 59 patients (61.05±7.73 years, 24 females) were analysed. The MoCA, but not the MDRS, identified significant postoperative cognitive decline in PD patients undergoing STN-DBS. The preoperative MoCA score correlated with postoperative quality of life improvement, whereas the MDRS did not. PD patients with a MoCA score ≤ 23 points had a significant decline of quality of life after DBS surgery compared to patients > 23 points. CONCLUSION: This study identifies the MoCA as an alternative test within the preoperative evaluation of PD patients for the detection of neuropsychological deficits and prediction of the postoperative improvement of quality of life.

Combined Subthalamic and Nigral Stimulation Modulates Temporal Gait Coordination and Cortical Gait-Network Activity in Parkinson's Disease.

Background: Freezing of gait (FoG) is a disabling burden for Parkinson's disease (PD) patients with poor response to conventional therapies. Combined deep brain stimulation of the subthalamic nucleus and substantia nigra (STN+SN DBS) moved into focus as a potential therapeutic option to treat the parkinsonian gait disorder and refractory FoG. The mechanisms of action of DBS within the cortical-subcortical-basal ganglia network on gait, particularly at the cortical level, remain unclear. Methods: Twelve patients with idiopathic PD and chronically-implanted DBS electrodes were assessed on their regular dopaminergic medication in a standardized stepping in place paradigm. Patients executed the task with DBS switched off (STIM OFF), conventional STN DBS and combined STN+SN DBS and were compared to healthy matched controls. Simultaneous high-density EEG and kinematic measurements were recorded during resting-state, effective stepping, and freezing episodes. Results: Clinically, STN+SN DBS was superior to conventional STN DBS in improving temporal stepping variability of the more affected leg. During resting-state and effective stepping, the cortical activity of PD patients in STIM OFF was characterized by excessive over-synchronization in the theta (4-8 Hz), alpha (9-13 Hz), and high-beta (21-30 Hz) band compared to healthy controls. Both active DBS settings similarly decreased resting-state alpha power and reduced pathologically enhanced high-beta activity during resting-state and effective stepping compared to STIM OFF. Freezing episodes during STN DBS and STN+SN DBS showed spectrally and spatially distinct cortical activity patterns when compared to effective stepping. During STN DBS, FoG was associated with an increase in cortical alpha and low-beta activity over central cortical areas, while with STN+SN DBS, an increase in high-beta was prominent over more frontal areas. Conclusions: STN+SN DBS improved temporal aspects of parkinsonian gait impairment compared to conventional STN DBS and differentially affected cortical oscillatory patterns during regular locomotion and freezing suggesting a potential modulatory effect on dysfunctional cortical-subcortical communication in PD.

Sex Disparities in the Self-Evaluation of Subthalamic Deep Brain Stimulation Effects on Mood and Personality in Parkinson's Disease Patients.

Changes in personality are one of the main concerns Parkinson's disease (PD) patients raise when facing the decision to undergo neurosurgery for deep brain stimulation (DBS) of the subthalamic nucleus (STN). While clinical instruments for monitoring functional changes following DBS surgery are well-established in the daily therapeutic routine, personality issues are far less systematically encompassed. Moreover, while sex disparities in the outcomes of STN-DBS therapy have been reported, little is known about the different effects that DBS treatment may have on mood and personality traits in female and male patients. To this aim, the effect of STN-DBS on personality traits was assessed in 46 PD patients (12 women and 34 men) by means of the Freiburg Personality Inventory. The Becks Depression Inventory (BDI-I) and the Parkinson's Disease Questionnaire were used to evaluate patients' level of depression and quality of life (QoL). Patients completed the questionnaires a few days before, within the first year, and 2 years after surgery. The 12 personality traits defined by the FPI-R questionnaire did not change significantly after STN-DBS surgery (p = 0.198). Women declared higher depression scores through all study stages (p = 0.009), but also showed a stronger QoL amelioration after surgery than male patients (p = 0.022). The BDI-I scores of female patients clearly correlated with their levodopa equivalent daily dose (LEDD; r = 0.621, p = 0.008). Remarkably, in both male and female patients, higher pre-operative LEDDs were related to worse post-operative QoL scores (p = 0.034). These results mitigate the concerns about systematic personality changes due to STN-DBS treatment in PD patients and encourage an early DBS approach, before severe levodopa-induced sequelae may irreparably compromise the patients' QoL. In the future, more focus should lie on sex-related effects, since female patients seem to profit more than male patients from STN-DBS, in terms of reduced depressive symptoms associated with a reduction of the LEDD and amelioration of QoL. These aspects may help to redress the sex imbalance in PD patients treated with DBS, given that women are still strongly under-represented.

Pallidal lead placement in dystonia: leads of non-responders are contained within an anatomical range defined by responders.

BACKGROUND: Deep brain stimulation (DBS) within the pallidum represents an effective and well-established treatment for isolated dystonia. However, clinical outcome after surgery may be variable with limited response in 10-25% of patients. The effect of lead location on clinical improvement is still under debate. OBJECTIVE: To identify stimulated brain regions associated with the most beneficial clinical outcome in dystonia patients. METHODS: 18 patients with cervical and generalized dystonia with chronic DBS of the internal pallidum were investigated. Patients were grouped according to their clinical improvement into responders, intermediate responders and non-responders. Magnetic resonance and computed tomography images were co-registered, and the volume of tissue activated (VTA) with respect to the pallidum of individual patients was analysed. RESULTS: VTAs in responders (n = 11), intermediate responders (n = 3) and non-responders (n = 4) intersected with the posterior internal (GPi) and external (GPe) pallidum and the subpallidal area. VTA heat maps showed an almost complete overlap of VTAs of responders, intermediate and non-responders. VTA coverage of the GPi was not higher in responders. In contrast, VTAs of intermediate and non-responders covered the GPi to a significantly larger extent in the left hemisphere (p < 0.01). CONCLUSIONS: DBS of ventral parts of the posterior GPi, GPe and the adjacent subpallidal area containing pallidothalamic output projections resulted in favourable clinical effects. Of note, non-responders were also stimulated within the same area. This suggests that factors other than mere lead location (e.g., clinical phenotype, genetic background) have determined clinical outcome in the present cohort.

Mapping stimulation-induced beneficial and adverse effects in the subthalamic area of essential tremor patients.

BACKGROUND: Stimulation of the subthalamic area (STA) is an effective treatment in essential tremor patients, but limited by stimulation induced adverse effects. The aim of this study was to determine the spatial distribution of stimulus related tremor suppression, ataxia induction and paresthesia of the upper limb in the subthalamic area (STA) of essential tremor patients. METHODS: We recruited eight patients with essential tremor in a stable postoperative condition (>3 months after surgery). Stimulation-induced effects were assessed with suprathreshold stimulation. Tremor severity was assessed with the Fahn-Tolosa-Marin tremor rating scale (TRS) and cerebellar impairment was evaluated using the international cooperative ataxia rating scale (ICARS). Patients rated paresthesia intensity with a visual analog scale. Linear regression analysis was performed to associate stereotactic coordinates with tremor, ataxia and paresthesia. RESULTS: Suprathreshold stimulation significantly decreased tremor and elicited ataxia and paresthesia in all patients (P < 0.001). Tremor rating scale (TRS) total score was positively correlated with y-coordinates (r = 0.44, P < 0.05), i.e. anterior stimulation sites were more effective to suppress tremor. Concerning adverse effects, ataxia induction was positively correlated with z-coordinates almost reaching statistical significance (r = 0.50, P = 0.07), i.e. inferior stimulation sites elicit stronger ataxia. Furthermore, paresthesia was positively correlated with y-coordinates (r = 0.66; P < 0.01) and to a lesser degree with x-coordinates (r = 0.32; P = 0.08), i.e. posterior and lateral stimulation sites within the STA caused more paresthesia. CONCLUSION: Antero-dorso-medial stimulation site in the STA were associated with less tremor and adverse effects in our small single-center cohort of ET patients with thalamic DBS.

Seizures as presenting symptom in patients with glioblastoma.

OBJECTIVE: The clinical course and underlying molecular causes in patients with glioblastoma presenting with seizures are poorly understood. Here we investigated clinical features and carrier systems as well as a transaminase relevant in glutamate homeostasis in patients with glioblastoma. METHODS: We performed a retrospective analysis of our clinical glioma database for clinical data during a 2-year period. Patients with glioblastoma were divided into 2 groups: symptomatic and asymptomatic for seizures. Magnetic resonance imaging (MRI) scans and tissue samples from both groups were investigated. A Cox regression analysis was performed for survival and clinical and molecular features. RESULTS: One hundred three patients diagnosed with glioblastoma in this period were identified. Twenty-three patients were symptomatic with seizures (22.3%). All were IDH-1/2 wild-type. We found no significant difference in the tumor localization between the groups. Patients with seizures from glioblastoma had significantly smaller tumors, which caused less edema compared to nonepileptogenic tumors. A significantly increased up-regulation of glutamate carrier systems was evident in symptomatic tumors compared to asymptomatic tumors. Moreover, there seems to be an oversupply of glutamate in symptomatic tumors due to dysregulation in glutamate synthesis. SIGNIFICANCE: Glioblastoma presenting with seizures is morphologically different from asymptomatic tumors. Furthermore, we were able to show that the molecular profile of these tumors, particularly glutamate homeostasis controlling systems, is significantly different.

Towards unambiguous reporting of complications related to deep brain stimulation surgery: A retrospective single-center analysis and systematic review of the literature.

BACKGROUND AND OBJECTIVE: To determine rates of adverse events (AEs) related to deep brain stimulation (DBS) surgery or implanted devices from a large series from a single institution. Sound comparisons with the literature require the definition of unambiguous categories, since there is no consensus on the reporting of such AEs. PATIENTS AND METHODS: 123 consecutive patients (median age 63 yrs; female 45.5%) treated with DBS in the subthalamic nucleus (78 patients), ventrolateral thalamus (24), internal pallidum (20), and centre médian-parafascicular nucleus (1) were analyzed retrospectively. Both mean and median follow-up time was 4.7 years (578 patient-years). AEs were assessed according to three unambiguous categories: (i) hemorrhages including other intracranial complications because these might lead to neurological deficits or death, (ii) infections and similar AEs necessitating the explantation of hardware components as this results in the interruption of DBS therapy, and (iii) lead revisions for various reasons since this involves an additional intracranial procedure. For a systematic review of the literature AE rates were calculated based on primary data presented in 103 publications. Heterogeneity between studies was assessed with the I2 statistic and analyzed further by a random effects meta-regression. Publication bias was analyzed with funnel plots. RESULTS: Surgery- or hardware-related AEs (23) affected 18 of 123 patients (14.6%) and resolved without permanent sequelae in all instances. In 2 patients (1.6%), small hemorrhages in the striatum were associated with transient neurological deficits. In 4 patients (3.3%; 0.7% per patient-year) impulse generators were removed due to infection. In 2 patients electrodes were revised (1.6%; 0.3% per patient-year). There was no lead migration or surgical revision because of lead misplacement. Age was not statistically significant different (p>0.05) between patients affected by AEs or not. AE rates did not decline over time and similar incidences were found among all patients (423) implanted with DBS systems at our institution until December 2016. A systematic literature review revealed that exact AE rates could not be determined from many studies, which could not be attributed to study designs. Average rates for intracranial complications were 3.8% among studies (per-study analysis) and 3.4% for pooled analysis of patients from different studies (per-patient analysis). Annual hardware removal rates were 3.6 and 2.4% for per-study and per-patient analysis, respectively, and lead revision rates were 4.1 and 2.6%, respectively. There was significant heterogeneity between studies (I2 ranged between 77% and 91% for the three categories; p< 0.0001). For hardware removal heterogeneity (I2 = 87.4%) was reduced by taking study size (p< 0.0001) and publication year (p< 0.01) into account, although a significant degree of heterogeneity remained (I2 = 80.0%; p< 0.0001). Based on comparisons with health care-related databases there appears to be publication bias with lower rates for hardware-related AEs in published patient cohorts. CONCLUSIONS: The proposed categories are suited for an unequivocal assessment of AEs even in a retrospective manner and useful for benchmarking. AE rates in the present cohorts from our institution compare favorable with the literature.

Thalamic short pulse stimulation diminishes adverse effects in essential tremor patients.

OBJECTIVE: To investigate the effect of directional current steering and short pulse stimulation in the ventral intermediate thalamic nucleus (VIM) on stimulation-induced side effects in patients with essential tremor. METHODS: We recruited 8 patients with essential tremor in a stable postoperative condition (>3 months after electrode implantation of deep brain stimulation [DBS] electrodes) with segmented contacts implanted in the VIM. Tremor severity on acute stimulation was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale. Cerebellar impairment was evaluated with the International Cooperative Ataxia Rating Scale. Patients rated paresthesia intensity with a visual analog scale. RESULTS: In all patients, tremor was reduced to the same extent by VIM stimulation regardless of pulse width using energy dose-equivalent amplitudes. Short pulse stimulation diminished stimulation-induced ataxia of the upper extremities and paresthesia compared with conventional parameters. Directional steering with monopolar stimulation of single segments successfully suppressed tremor but also induced ataxia. No differences in adverse effects were found between single-segment stimulation conditions. CONCLUSION: These proof-of-principle findings provide evidence that acute short pulse stimulation is superior to directional steering in the subthalamic area to decrease stimulation-induced side effects while preserving tremor suppression effects in patients with tremor. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with tremor with thalamic DBS, acute short pulse stimulation reduces adverse effects, while directional steering does not provide a generalizable benefit regarding adverse effects.

Immunophenotyping of Newly Diagnosed and Recurrent Glioblastoma Defines Distinct Immune Exhaustion Profiles in Peripheral and Tumor-infiltrating Lymphocytes.

Purpose: Immunotherapeutic treatment strategies for glioblastoma (GBM) are under investigation in clinical trials. However, our understanding of the immune phenotype of GBM-infiltrating T cells (tumor-infiltrating lymphocytes; TILs) and changes during disease progression is limited. Deeper insight is urgently needed to therapeutically overcome tumor-induced immune exhaustion.Experimental Design: We used flow cytometry and cytokine assays to profile TILs and peripheral blood lymphocytes (PBLs) from patients with GBM, comparing newly diagnosed or recurrent GBM to long-term survivors (LTS) and healthy donors. TCR sequencing was performed on paired samples of newly diagnosed and recurrent GBM.Results: We identified a clear immune signature of exhaustion and clonal restriction in the TILs of patients with GBM. Exhaustion of CD8+ TILs was defined by an increased prevalence of PD-1+, CD39+, Tim-3+, CD45RO+, HLA-DR+ marker expression, and exhibition of an effector-/transitional memory differentiation phenotype, whereas KLRG1 and CD57 were underrepresented. Immune signatures were similar in primary and recurrent tumors; however, restricted TCR repertoire clonality and a more activated memory phenotype were observed in TILs from recurrent tumors. Moreover, a reduced cytokine response to PHA stimulation in the blood compartment indicates a dysfunctional peripheral T-cell response in patients with GBM. LTS displayed a distinct profile, with abundant naïve and less exhausted CD8+ T cells.Conclusions: TILs and PBLs exhibit contrasting immune profiles, with a distinct exhaustion signature present in TILs. While the exhaustion profiles of primary and recurrent GBM are comparable, TCR sequencing demonstrated a contracted repertoire in recurrent GBM, concomitant with an increased frequency of activated memory T cells in recurrent tumors. Clin Cancer Res; 24(17); 4187-200. ©2018 AACRSee related commentary by Jackson and Lim, p. 4059.

A novel threshold criterion in transcranial motor evoked potentials during surgery for gliomas close to the motor pathway.

OBJECTIVE Warning criteria for monitoring of motor evoked potentials (MEP) after direct cortical stimulation during surgery for supratentorial tumors have been well described. However, little is known about the value of MEP after transcranial electrical stimulation (TES) in predicting postoperative motor deficit when monitoring threshold level. The authors aimed to evaluate the feasibility and value of this method in glioma surgery by using a new approach for interpreting changes in threshold level involving contra- and ipsilateral MEP. METHODS Between November 2013 and December 2014, 93 patients underwent TES-MEP monitoring during resection of gliomas located close to central motor pathways but not involving the primary motor cortex. The MEP were elicited by transcranial repetitive anodal train stimulation. Bilateral MEP were continuously evaluated to assess percentage increase of threshold level (minimum voltage needed to evoke a stable motor response from each of the muscles being monitored) from the baseline set before dural opening. An increase in threshold level on the contralateral side (facial, arm, or leg muscles contralateral to the affected hemisphere) of more than 20% beyond the percentage increase on the ipsilateral side (facial, arm, or leg muscles ipsilateral to the affected hemisphere) was considered a significant alteration. Recorded alterations were subsequently correlated with postoperative neurological deterioration and MRI findings. RESULTS TES-MEP could be elicited in all patients, including those with recurrent glioma (31 patients) and preoperative paresis (20 patients). Five of 73 patients without preoperative paresis showed a significant increase in threshold level, and all of them developed new paresis postoperatively (transient in 4 patients and permanent in 1 patient). Eight of 20 patients with preoperative paresis showed a significant increase in threshold level, and all of them developed postoperative neurological deterioration (transient in 4 patients and permanent in 4 patients). In 80 patients no significant change in threshold level was detected, and none of them showed postoperative neurological deterioration. The specificity and sensitivity in this series were estimated at 100%. Postoperative MRI revealed gross-total tumor resection in 56 of 82 patients (68%) in whom complete tumor resection was attainable; territorial ischemia was detected in 4 patients. CONCLUSIONS The novel threshold criterion has made TES-MEP a useful method for predicting postoperative motor deficit in patients who undergo glioma surgery, and has been feasible in patients with preoperative paresis as well as in patients with recurrent glioma. Including contra- and ipsilateral changes in threshold level has led to a high sensitivity and specificity.

Disease Progression and Changes in Physical Activity in Patients with Chronic Obstructive Pulmonary Disease.

RATIONALE: Little is known about the role of physical activity in the course of chronic obstructive pulmonary disease (COPD). OBJECTIVES: To assess changes in physical activity in COPD in relation to severity stages and changes in other disease components, and to evaluate the longitudinal association between sustained physical inactivity and disease progression. METHODS: In this prospective cohort study, we measured physical activity (multisensory armband), airflow obstruction (FEV1), health status (St. George's Respiratory Questionnaire), exercise capacity (6-min-walk distance [6MWD]), muscle mass (fat-free mass [FFM]), and systemic inflammation (fibrinogen and high-sensitivity C-reactive protein) over a 3-year period in 137 patients with COPD and 26 with chronic bronchitis (normal spirometry). MEASUREMENTS AND MAIN RESULTS: Independent of baseline disease severity, steps per day, total daily energy expenditure, and (daily) physical activity level (PAL) decreased by 393, 76 kcal, and 0.04 per year, respectively. The decline in PAL was significantly associated with a decline in FEV1 and an increase in St. George's Respiratory Questionnaire total score. Changes in 6MWD, FFM, and inflammatory markers were not associated with changes in PAL. Independent of FEV1, sustained physical inactivity (i.e., PAL(T0andT1) < 1.40) was related to a greater decline in 6MWD and FFM compared with that in patients with some level of activity (i.e., PAL(T0and/orT1) ≥ 1.40; difference, 17 m/yr and 0.87 kg/yr, respectively). CONCLUSIONS: Over time, physical activity substantially decreases across all severity stages of COPD, and this decline is paralleled by a worsening of lung function and health status. Sustained physical inactivity is associated with a progression of exercise intolerance and muscle depletion.