Somatosensory evoked potentials recorded from DBS electrodes: the origin of subcortical N18.

The different peaks of somatosensory-evoked potentials (SEP) originate from a variety of anatomical sites in the central nervous system. The origin of the median nerve subcortical N18 SEP has been studied under various conditions, but the exact site of its generation is still unclear. While it has been claimed to be located in the thalamic region, other studies indicated its possible origin below the pontomedullary junction. Here, we scrutinized and compared SEP recordings from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in various subcortical targets. We studied 24 patients with dystonia, Parkinson's disease, and chronic pain who underwent quadripolar electrode implantation for chronic DBS and recorded median nerve SEPs from globus pallidus internus (GPi), subthalamic nucleus (STN), thalamic ventral intermediate nucleus (Vim), and ventral posterolateral nucleus (VPL) and the centromedian-parafascicular complex (CM-Pf). The largest amplitude of the triphasic potential of the N18 complex was recorded in Vim. Bipolar recordings confirmed the origin to be close to Vim electrodes (and VPL/CM-Pf) and less close to STN electrodes. GPi recorded only far-field potentials in unipolar derivation. Recordings from DBS electrodes located in different subcortical areas allow determining the origin of certain subcortical SEP waves more precisely. The subcortical N18 of the median nerve SEP-to its largest extent-is generated ventral to the Vim in the region of the prelemniscal radiation/ zona incerta.

Does Temporary Externalization of Electrodes After Deep Brain Stimulation Surgery Result in a Higher Risk of Infection?

OBJECTIVES: Deep brain stimulation (DBS) is a well-established surgical therapy for movement disorders that comprises implantation of stimulation electrodes and a pacemaker. These procedures can be performed separately, leaving the possibility of externalizing the electrodes for local field potential recording or testing multiple targets for therapeutic efficacy. It is still debated whether the temporary externalization of DBS electrodes leads to an increased risk of infection. We therefore aimed to assess the risk of infection during and after lead externalization in DBS surgery. MATERIALS AND METHODS: In this retrospective study, we analyzed a consecutive series of 624 DBS surgeries, including 266 instances with temporary externalization of DBS electrodes for a mean of 6.1 days. Patients were available for follow-up of at least one year, except in 15 instances. In 14 patients with negative test stimulation, electrodes were removed. All kinds of infections related to implantation of the neurostimulation system were accounted for. RESULTS: Overall, infections occurred in 22 of 624 surgeries (3.5%). Without externalization of electrodes, infections were noted after 7 of 358 surgeries (2.0%), whereas with externalization, 15 of 252 infections were found (6.0%). This difference was significant (p = 0.01), but it did not reach statistical significance when comparing groups within different diagnoses. The rate of infection with externalized electrodes was highest in psychiatric disorders (9.1%), followed by Parkinson's disease (7.3%), pain (5.7%), and dystonia (5.5%). The duration of the externalization of the DBS electrodes was comparable in patients who developed an infection (6.1 ± 3.1 days) with duration in those who did not (6.0 ± 3.5 days). CONCLUSIONS: Although infection rates were relatively low in our study, there was a slightly higher infection rate when DBS electrodes were externalized. On the basis of our results, the indication for electrode externalization should be carefully considered, and patients should be informed about the possibility of a higher infection risk when externalization of DBS electrodes is planned.

Heterozygous UCHL1 loss-of-function variants cause a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy.

PURPOSE: Biallelic variants in UCHL1 have been associated with a progressive early-onset neurodegenerative disorder, autosomal recessive spastic paraplegia type 79. In this study, we investigated heterozygous UCHL1 variants on the basis of results from cohort-based burden analyses. METHODS: Gene-burden analyses were performed on exome and genome data of independent cohorts of patients with hereditary ataxia and spastic paraplegia from Germany and the United Kingdom in a total of 3169 patients and 33,141 controls. Clinical data of affected individuals and additional independent families were collected and evaluated. Patients' fibroblasts were used to perform mass spectrometry-based proteomics. RESULTS: UCHL1 was prioritized in both independent cohorts as a candidate gene for an autosomal dominant disorder. We identified a total of 34 cases from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). Affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17). The mass spectrometry-based proteomics showed approximately 50% reduction of UCHL1 expression in patients' fibroblasts. CONCLUSION: Our bioinformatic analysis, in-depth clinical and genetic workup, and functional studies established haploinsufficiency of UCHL1 as a novel disease mechanism in spastic ataxia.

Improvement of head and neck range of motion induced by chronic pallidal deep brain stimulation for cervical dystonia.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become an accepted treatment for severe cervical dystonia (CD). Assessment of therapeutic efficacy of DBS mostly focused on head position at rest but hardly on limitations of head and neck mobility, which represent a functionally important impairment in CD. OBJECTIVE: We aimed to determine prospectively head and neck range of motion (ROM) preoperatively and during chronic bilateral GPi DBS in a series of 11 patients with idiopathic CD or segmental dystonia with prominent CD using a computerized motion analysis. METHODS: Maximum horizontal rotation of the head in the transverse plane and lateral inclination in the frontal plane were measured preoperatively and at a median of 7 months of chronic GPi DBS, using an ultrasound-based three-dimensional measuring system combined with surface electromyography of cervical muscles. RESULTS: Horizontal rotation of the head increased from 78.8° ± 31.5° (mean ± SD) preoperatively to 100.7° ± 24.7° with GPi DBS (p < 0.01), thereby improvement of head rotation to the anti-dystonic side (+ 14,2° ± 12,2°) was greater than to the pro-dystonic side (+ 7,8° ± 9,2°; p < 0.05). Movement-related agonistic-antagonistic EMG modulation during head rotation was enhanced with GPi DBS in both sternocleidomastoid (modulation index (MI) 35.8% ± 26.7% preoperatively vs. 67.3% ± 16.9% with GPi DBS, p < 0.01), and splenius capitis muscles (MI 1.9% ± 24.5% preoperatively vs. 44.8% ± 11.6% with GPi DBS, p < 0.01). CONCLUSION: Chronic bilateral GPi DBS significantly improves head ROM in CD, likely due to enhanced agonist-antagonist EMG activity with reduced co-contraction. Computerized motion analysis provides an objective measurement to assess the improvement of head and neck mobility in CD.

Deep brain stimulation in patients on chronic antiplatelet or anticoagulation treatment.

BACKGROUND: In the aging society, many patients with movement disorders, pain syndromes, or psychiatric disorders who are candidates for deep brain stimulation (DBS) surgery suffer also from cardiovascular co-morbidities that require chronic antiplatelet or anticoagulation treatment. Because of a presumed increased risk of intracranial hemorrhage during or after surgery and limited knowledge about perioperative management, chronic antiplatelet or anticoagulation treatment often has been considered a relative contraindication for DBS. Here, we evaluate whether or not there is an increased risk for intracranial hemorrhage or thromboembolic complications in patients on chronic treatment (paused for surgery or bridged with subcutaneous heparin) as compared to those without. METHODS: Out of a series of 465 patients undergoing functional stereotactic neurosurgery, 34 patients were identified who were on chronic treatment before and after receiving DBS. In patients with antiplatelet treatment, medication was stopped in the perioperative period. In patients with vitamin K antagonists or novel oral anticoagulants (NOACs), heparin was used for bridging. All patients had postoperative stereotactic CT scans, and were followed up for 1 year after surgery. RESULTS: In patients on chronic antiplatelet or anticoagulation treatment, intracranial hemorrhage occurred in 2/34 (5.9%) DBS surgeries, whereas the rate of intracranial hemorrhage was 15/431 (3.5%) in those without, which was statistically not significant. Implantable pulse generator pocket hematomas were seen in 2/34 (5.9%) surgeries in patients on chronic treatment and in 4/426 (0.9%) without. There were only 2 instances of thromboembolic complications which both occurred in patients without chronic treatment. There were no hemorrhagic complications during follow-up for 1 year. CONCLUSIONS: DBS surgery in patients on chronic antiplatelet or anticoagulation treatment is feasible. Also, there was no increased risk of hemorrhage in the first year of follow-up after DBS surgery. Appropriate patient selection and standardized perioperative management are necessary to reduce the risk of intracranial hemorrhage and thromboembolic complications.

Implementation of New Technology in Patients with Chronic Deep Brain Stimulation: Switching from Non-Rechargeable Constant Voltage to Rechargeable Constant Current Stimulation.

INTRODUCTION: Deep brain stimulation (DBS) for movement disorders has been mainly performed with constant voltage (CV) technology. More recently also constant current (CC) systems have been developed which theoretically might have additional advantages. Furthermore, rechargeable (RC) system implantable pulse generators (IPG) are increasingly being used rather than the former solely available non-rechargeable (NRC) IPGs. OBJECTIVE: To provide a systematic investigation how to proceed and adapt settings when switching from CV NRC to CC RC technology. METHODS: We prospectively collected data from 11 consecutive patients (10 men, mean age at DBS implantation 52.6 ± 14.0 years) with chronic DBS for dystonia (n = 7), Parkinson disease (n = 3), and essential tremor (n = 1) who underwent IPG replacement switching from a CV NRC system (Activa® PC; Medtronic®) to a CC RC system (Vercise® RC; Boston Scientific®). Systematic assessments before and after IPG replacement were performed. RESULTS: DBS technology switching at the time of IPG replacement due to battery depletion was at a mean of 108.5 ± 46.2 months of chronic DBS. No perioperative complications occurred. Clinical outcome was stable with overall mild improvements or deteriorations, which could be dealt with in short-term follow-up. Patients were satisfied with the new RC IPG. CONCLUSIONS: This study confirms both the safety and feasibility of switching between different DBS technologies (CV to CC, NRC to RC, different manufacturers) in patients with chronic DBS. Furthermore, it shows how the management can be planned using available information from the previous DBS settings. Individual assessment is needed and might partly be related to the DBS target and the underlying disease. MR safety might be a problem with such hybrid systems.

Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review.

Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society.

Does being physically active prevent future disability in older people? Attenuated effects when taking time-dependent confounders into account.

BACKGROUND: Causal experimental evidence that physical activity prevents disability in older people is sparse. Being physically active has nonetheless been shown to be associated with disability-free survival in observational studies. Observational studies are, however, prone to bias introduced by time-dependent confounding. Time-dependent confounding occurs when an exposure (e.g. being physically active at some time-point) potentially affects the future status of a confounder (such as depression sometime later), and both variables have an effect on latter outcome (i.e. disability). "Conventional" analysis with e.g. Cox-regression is the mainstay when analyzing longitudinal observational studies. Unfortunately, it does not provide unbiased estimates in the presence of time-dependent confounding. Marginal structural models (MSM) - a relatively new class of causal models - have the potential to adequately account for time-dependent confounding. Here we analyze the effect of older people being physically active on disability, in a large long-term observational study. We address time-dependent confounding by using marginal structural models and provide a non-technical practical demonstration of how to implement this type of modeling. METHODS: Data is from 639 elderly individuals ascertained in the European multi-center Leukoaraiosis and Disability study (LADIS), followed-up yearly over a period of three years. We estimated the effect of self-reported physical activity on the probability to transit to instrumental disability in the presence of a large set of potential confounders. We compare the results of "conventional" modeling approaches to those estimated using marginal structural models, highlighting discrepancies. RESULTS: A "conventional" Cox-regression-like adjustment for salient baseline confounders signals a significant risk reduction under physical activity for later instrumental disability (OR 0.62, 95% CI 0.44-0.90). However, given MSM estimation, the effect is attenuated towards null (OR 1.00, 95% CI 0.57-1.76). CONCLUSIONS: Contrary to most reports, we did not find that physical activity in older people prevents future instrumental disability, when taking time-dependent confounding into account. This result may be due to the characteristics our particular study population. It is, however, also conceivable that previous evidence neglected the effect of this type of bias. We suggest that analysts of longitudinal observational studies consider marginal structural models as a further modeling approach.

Diagnostic and Prognostic Relevance of Magnetic Resonance Imaging and Electrophysiological Findings in Acute Spinal Ischemia.

OBJECTIVE: Our purpose was to classify the rare entity of spontaneous spinal ischemia with clinical, magnetic resonance-tomographic, and electrophysiological parameters to determine criteria for outcome prediction. METHODS: We analyzed the stroke registry database of the University Hospital Mannheim, Germany, from 2004 to 2010 for patients with a diagnosis of vascular spinal cord ischemia. RESULTS: Ten patients were identified (mean age 65 years [range 50-83], 5 women). In 5 patients an etiology was found. Spinal diffusion-weighted magnetic resonance imaging revealed acute ischemia in 7 patients at initial imaging and this diagnosis was confirmed during the first week in the remaining 3 patients. Electrophysiological studies showed abnormal motor evoked potentials (MEPs) in 8 patients and abnormal somatosensory evoked potentials (SSEPs) in 7 patients. After rehabilitation, 5 patients had regained walking ability, whereas 5 patients stayed wheelchair bound. All patients with unfavorable outcome (American Spinal Injury Association (ASIA) Impairment score [AIS] score of ≤C) showed severe pyramidal tract lesions in MEPs during the first week. All patients with normal MEPs had an excellent outcome (AIS of E, P < .05). CONCLUSIONS: Diffusion-weighted imaging (DWI) is a useful tool to confirm acute spinal ischemia suspected in patients within the first days after symptom onset. Poor outcome was associated with severe electrophysiological abnormalities in MEPs and SSEPs. Normal MEPs were significantly predictive of an excellent prognosis. A multimodal diagnostic approach combining DWI and electrophysiological evaluation facilitates the prediction of the individual clinical outcome.

Body weight gain in patients with bilateral deep brain stimulation for dystonia.

In patients with Parkinson's disease, significant weight gain following chronic deep brain stimulation (DBS) has been reported. Recently, relevant weight gain could be demonstrated also following subthalamic nucleus DBS in patients with primary cervical dystonia. Prospective analyses of body weight changes following DBS in patients with dystonia, however, have not been published so far. We aimed to analyse the changes of body weight following DBS in patients with dystonia. The body mass index (BMI) of 17 consecutive patients with segmental or generalised dystonia (mean age 54.6 ± 16.1 years) treated with bilateral DBS of the globus pallidus internus (GPi) (n = 14) or the thalamic ventral intermediate nucleus (n = 3) was measured preoperatively (pre-OP) and at three follow-up (FU) time points post-DBS surgery (FU1 = 7 months, FU2 = 17 months, FU3 = 72 months). All patients benefited from marked improvement in their dystonia. The mean BMI pre-OP (SD) was 22.5 (±3.7) kg/m(2) and increased stepwise to 24.0 (±3.3) kg/m(2) at FU1, 24.4 (±3.7) kg/m(2) at FU2 and 24.9 (±3.7) kg/m(2) at FU3 (p < 0.05 at all three FUs compared to pre-OP). Relative BMI increase and improvement of dystonia were correlated (p = 0.025). Chronic bilateral GPi DBS in patients with dystonia is associated with significant body weight gain, in particular during the first 6 months post-OP. This probably is a result of improvement of dystonic motor symptoms and recovery of eating dysfunction rather than a target-specific phenomenon.

Comparative characterization of single cell activity in the globus pallidus internus of patients with dystonia or Tourette syndrome.

Altered processing in the basal ganglia has been described both in dystonia and Tourette's syndrome (TS). Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become a recognized treatment for dystonia and has been used successfully to alleviate tics in TS. This study evaluates possible differences of GPi linear and nonlinear neuronal discharge characteristics between patients with dystonia and TS. Nine patients with primary dystonia and six patients with TS were studied during functional stereotactic neurosurgical operations for implantation of DBS electrodes under general anesthesia. Six patients with primary dystonia under local anesthesia served as non-anesthetized controls. Single-unit activity recordings in the GPi were obtained during routine microelectrode recording and mapping to delineate nuclear borders and to identify the sensorimotor subregions. Anesthesia profoundly decreased neuronal activity in patients with dystonia. Dystonia patients showed marginally higher mean firing rates in the GPi compared to TS patients (P = 0.06). Although the average total number of bursts and the mean peak frequency in bursts did not differ between groups, the mean spikes in bursts were higher in dystonia patients (P < 0.05). Nonlinear time series analysis metrics, measured as complexity of Lempel-Ziv and maximum approximate entropy, revealed higher randomness in TS compared to dystonia patients (P < 0.05). The percentage of oscillating neurons in spike trains was higher in dystonia compared to TS (P < 0.05). Our data provide evidence for differences of the neuronal dynamic complexity, randomness and oscillatory modulation of spike trains in the GPi between dystonia and TS. Such differences, although subtle, might contribute to the specific clinical phenomenology secondary to disordered neuronal basal ganglia processing.

Shape abnormalities of the caudate nucleus correlate with poorer gait and balance: results from a subset of the LADIS study.

OBJECTIVE: Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in frontostriatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter hyperintensities (WMHs) on magnetic resonance imaging has been found to correlate with poorer performance on measures of gait and balance. This study aimed to determine whether striatal volume and shape changes were correlated with gait dysfunction. METHODS: Magnetic resonance imaging scans and clinical gait/balance data (scores from the Short Physical Performance Battery [SPPB]) were sourced from 66 subjects in the previously published LADIS trial, performed in nondisabled individuals older than age 65 years with WMHs at study entry. Data were obtained at study entry and at 3-year follow-up. Caudate nuclei and putamina were manually traced using a previously published method and volumes calculated. The relationships between volume and physical performance on the SPPB were investigated with shape analysis using the spherical harmonic shape description toolkit. RESULTS: There was no correlation between the severity of WMHs and striatal volumes. Caudate nuclei volume correlated with performance on the SPPB at baseline but not at follow-up, with subsequent shape analysis showing left caudate changes occurred in areas corresponding to inputs of the dorsolateral prefrontal, premotor, and motor cortex. There was no correlation between putamen volumes and performance on the SPPB. CONCLUSION: Disruption in frontostriatal circuits may play a role in mediating poorer physical performance in individuals with WMHs. Striatal volume and shape changes may be suitable biomarkers for functional changes in this population.

Scaling of movement is related to pallidal γ oscillations in patients with dystonia.

Neuronal synchronization in the gamma (γ) band is considered important for information processing through functional integration of neuronal assemblies across different brain areas. Movement-related γ synchronization occurs in the human basal ganglia where it is centered at ~70 Hz and more pronounced contralateral to the moved hand. However, its functional significance in motor performance is not yet well understood. Here, we assessed whether event-related γ synchronization (ERS) recorded from the globus pallidus internus in patients undergoing deep brain stimulation for medically intractable primary focal and segmental dystonia might code specific motor parameters. Pallidal local field potentials were recorded in 22 patients during performance of a choice-reaction-time task. Movement amplitude of the forearm pronation-supination movements was parametrically modulated with an angular degree of 30°, 60°, and 90°. Only patients with limbs not affected by dystonia were tested. A broad contralateral γ band (35-105 Hz) ERS occurred at movement onset with a maximum reached at peak velocity of the movement. The pallidal oscillatory γ activity correlated with movement parameters: the larger and faster the movement, the stronger was the synchronization in the γ band. In contrast, the event-related decrease in beta band activity was similar for all movements. Gamma band activity did not change with movement direction and did not occur during passive movements. The stepwise increase of γ activity with movement size and velocity suggests a role of neuronal synchronization in this frequency range in basal ganglia control of the scaling of ongoing movements.

Deterioration of gait and balance over time: the effects of age-related white matter change--the LADIS study.

BACKGROUND: Cross-sectional studies have shown an association between the severity of age-related white matter change (ARWMC) and lower body motor function. However, the association between prevalent ARWMC and incident deterioration of balance and gait remains insufficiently investigated. This study investigates if the degree of prevalent ARWMC has a differential effect on lower body motor function as it changes over time, hypothesizing that individuals with more severe baseline white matter pathology experience greater clinical deterioration independent of potential confounders. This is of clinical relevance: given the increasing use of neuroimaging, incidental white matter pathology is common; being able to delineate natural trajectories of balance and gait function given ARWMC may improve patient advice and help optimize allocation of care. METHODS: 639 non-disabled elderly individuals with prevalent ARWMC (grading of severity of ARWMC using the Fazekas scale) were followed up yearly for 3 years, as part of the Leukoaraiosis and Disability Study. The primary outcome variable, reflecting the temporal course of gait and balance function, was the change of scores on the Short Physical Performance Battery (SPPB) over time versus the severity of ARWMC. We used linear mixed modelling to analyse change over time. Explorative analysis was carried out investigating the effect of age on potential deterioration of gait and balance function. We used propensity scores to adjust for multiple confounders that affect both the exposure (i.e. ARWMC) and outcome. RESULTS: Subjects' lower body motor function deteriorated by 2.6% per year. However, after adjustment for baseline motor impairment and potential confounders, only subjects with moderate [-0.22 points per year on the SPPB (equals -2.3%); 95% CI -0.35 to -0.09, p < 0.001] or severe [-0.46 points per year (equals -4.7%); 95% CI -0.63 to -0.28, p < 0.0001] ARWMC show a loss of function. Age shows differential effects: relatively younger elderly subjects have similar temporal dynamics in SPPB change independent of their individual degree of ARWMC severity; however, subjects with severe ARWMC and who are older than 75.9 years deteriorate significantly more rapidly than their counterparts with only mild or moderate white matter pathology. CONCLUSION: Only moderate and severe ARWMC is independently associated - on average - with a deterioration of gait and balance. Albeit the possibility of unmeasured confounding and other methodological constraints, there is nonetheless evidence of large interindividual variability: some subjects with moderate or severe ARWMC stay stable over time or even show improvement. Furthermore, there is explorative analysis showing that younger elderly subjects may be able to better compensate even severe ARWMC. These individuals' gait and balance function stays relatively stable over time, whereas their older counterparts deteriorate significantly. This may point towards a threshold effect given ARWMC.

Transient global amnesia associated with accidental high-frequency stimulation of the right hippocampus in deep brain stimulation for segmental dystonia.

We report on a 66-year-old woman with segmental dystonia treated with chronic bilateral deep brain stimulation of the globus pallidus internus, in whom accidental high-voltage, high-frequency stimulation induced an episode of transient global amnesia (TGA) via an electrode contact which was misplaced in the right hippocampus. A possible mechanism underlying this TGA episode may have been the inhibition of local neuronal activity or fiber activation by high current density via direct electrical stimulation of hippocampal structures. While a unifying etiology of TGA has not been proven so far, our case demonstrates a possible link between focal electrical stimulation of hippocampal structures and the full clinical picture of the syndrome.

Microelectrode recording and hemorrhage in functional neurosurgery: a comparative analysis in a consecutive series of 645 procedures.

OBJECTIVE: Functional stereotactic neurosurgery including deep brain stimulation (DBS) and radiofrequency lesioning is well established and widely used for treatment of movement disorders and various other neurological and psychiatric diseases. Although functional stereotactic neurosurgery procedures are considered relatively safe, intracranial hemorrhage resulting in permanent neurological deficits may occur in 1%-3% of patients. Microelectrode recording (MER) has been recognized as a valuable tool for refining the final target in functional stereotactic neurosurgery. Moreover, MER provides insight into the underlying neurophysiological pathomechanisms of movement disorders and other diseases. Nevertheless, there is an ongoing controversy on whether MER increases the risk for hemorrhage. The authors aimed to compare the risk of hemorrhage in functional stereotactic neurosurgical procedures with regard to the use of MER. METHODS: The authors performed a comparative analysis on a consecutive series of 645 functional neurosurgery procedures, including 624 DBS surgeries and 21 radiofrequency lesionings, to evaluate whether the use of MER would increase the risk for hemorrhage. MER was performed in 396 procedures, while no MER was used in 249 cases. The MER technique involved the use of a guiding cannula and a single trajectory when feasible. Postoperative CT scans were obtained within 24 hours after surgery in all patients and screened for the presence of hemorrhage. RESULTS: Twenty-one intracranial hemorrhages were detected on the postoperative CT scans (3.2%). Of the 21 intracranial hemorrhages, 14 were asymptomatic and 7 were symptomatic. Symptoms were transient except in 1 case. There was no statistically significant correlation between hemorrhage and the use of MER at any site (subdural, ventricle, trajectory, target, whether asymptomatic or symptomatic). There were 4 cases of symptomatic hemorrhage in the MER group (1%) and 3 cases in those without MER (1.2%). CONCLUSIONS: Intraoperative MER did not increase the overall risk of hemorrhage in the authors' experience using primarily a single MER trajectory and a guiding cannula.

Physical activity prevents progression for cognitive impairment and vascular dementia: results from the LADIS (Leukoaraiosis and Disability) study.

BACKGROUND AND PURPOSE: We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently. METHODS: The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes on the transition of independent elderly subjects into disability. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and cognitive assessment with classification of cognitive impairment and dementia according to usual clinical criteria. Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study. RESULTS: Six hundred thirty-nine subjects were included (74.1±5 years old, 55% women, 9.6±3.8 years of schooling, 64% physically active). At the end of follow-up, 90 patients had dementia (vascular dementia, 54; Alzheimer disease with vascular component, 34; frontotemporal dementia, 2), and 147 had cognitive impairment not dementia. Using Cox regression analysis, physical activity reduced the risk of cognitive impairment (dementia and not dementia: ß=-0.45, P=0.002; hazard ratio, 0.64; 95% CI, 0.48-0.85), dementia (ß=-0.49, P=0.043; hazard ratio, 0.61; 95% CI, 0.38-0.98), and vascular dementia (ß=-0.86, P=0.008; hazard ratio, 0.42; 95% CI, 0.22-0.80), independent of age, education, white matter change severity, medial temporal atrophy, previous and incident stroke, and diabetes. CONCLUSIONS: Physical activity reduces the risk of cognitive impairment, mainly vascular dementia, in older people living independently.

Bilateral deep brain stimulation for cervical dystonia in patients with previous peripheral surgery.

BACKGROUND: There are no data available concerning whether patients with cervical dystonia who have recurrent or new symptoms after peripheral denervation surgery benefit similarly from pallidal deep brain stimulation compared with patients who receive primarily pallidal stimulation. METHODS: Data on 7 cervical dystonia patients with recurrent or progressive dystonia after peripheral denervation who underwent pallidal stimulation were prospectively collected. Deep brain stimulation was performed in Mannheim/Hannover, Germany, or in Umea, Sweden. To the subgroup from Mannheim/Hannover, a second group of patients without previous peripheral surgery was matched. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale and the Burke-Fahn-Marsden dystonia rating scale, as well as the Tsui scale in the Swedish patients. RESULTS: The 4 patients from Mannheim/Hannover experienced sustained improvement from pallidal stimulation by a mean of 57.5% according to the Toronto Western Spasmodic Torticollis Rating Scale (P < .05) and by a mean of 69.5% according to the Burke-Fahn-Marsden dystonia rating scale (P < .05) at long-term follow-up of 40.5 months. The patients from Umea had a mean Tsui score of 7 prior to surgery and a mean score of 3 at the mean follow-up of 8 months (62.5%). In the matched group the Toronto Western Spasmodic Torticollis Rating Scale improved by 58.8% and the Burke-Fahn-Marsden dystonia rating scale by 67% (P < .05) at long-term follow-up (mean, 41.5 months). CONCLUSIONS: Patients who had prior peripheral surgery for cervical dystonia experience improvement from subsequent pallidal stimulation that is comparable to that of de novo patients.

Are Transventricular Approaches Associated With Increased Hemorrhage? A Comparative Study in a Series of 624 Deep Brain Stimulation Surgeries.

BACKGROUND: Deep brain stimulation (DBS) surgery has advanced tremendously, for both clinical applications and technology. Although DBS surgery is an overall safe procedure, rare side effects, in particular, hemorrhage, may result in devastating consequences. Although there are certain advantages with transventricular trajectories, it has been reasoned that avoidance of such trajectories would likely reduce hemorrhage. OBJECTIVE: To investigate the possible impact of a transventricular trajectory as compared with a transcerebral approach on the occurrence of symptomatic and asymptomatic hemorrhage after DBS electrode placement. METHODS: Retrospective evaluation of 624 DBS surgeries in 582 patients, who underwent DBS surgery for movement disorders, chronic pain, or psychiatric disorders. A stereotactic guiding cannula was routinely used for DBS electrode insertion. All patients had postoperative computed tomography scans within 24 hours after surgery. RESULTS: Transventricular transgression was identified in 404/624 DBS surgeries. The frequency of hemorrhage was slightly higher in transventricular than in transcerebral DBS surgeries (15/404, 3.7% vs 6/220, 2.7%). While 7/15 patients in the transventricular DBS surgery group had a hemorrhage located in the ventricle, 6 had an intracerebral hemorrhage along the electrode trajectory unrelated to transgression of the ventricle and 2 had a subdural hematoma. Among the 7 patients with a hemorrhage located in the ventricle, only one became symptomatic. Overall, a total of 7/404 patients in the transventricular DBS surgery group had a symptomatic hemorrhage, whereas the hemorrhage remained asymptomatic in all 6/220 patients in the transcerebral DBS surgery group. CONCLUSION: Transventricular approaches in DBS surgery can be performed safely, in general, when special precautions such as using a guiding cannula are routinely applied.