Improved gait performance in a patient with hereditary spastic paraplegia after a continuous intrathecal baclofen test infusion and subsequent pump implantation: a case report.

OBJECTIVE: To show the benefits of a continuous intrathecal baclofen (ITB) test infusion in a patient with hereditary spastic paraplegia (HSP), with an improved gait performance after ITB pump implantation. DESIGN: Case report. SETTING: University hospital. PARTICIPANT: A 49-year old man with HSP experiencing progressive walking difficulties because of lower extremity spasticity, which did not respond to oral spasmolytics. INTERVENTIONS: A prolonged, continuous ITB test infusion was started at a low dose and increased gradually, to provide a stable dose of ITB over a prolonged period. The gradual dose increase provided the patient enough time to experience the effects of ITB, because he feared that ITB therapy might cause functional loss. MAIN OUTCOME MEASURES: Modified Ashworth Scale, electromyography, muscle strength, timed Up and Go tests, and the Patient Global Impression of Change. Gait performance before and after ITB pump implantation was assessed in a motion laboratory. RESULTS: During the test infusion, the ITB dose was gradually increased to a continuous dose of 108µg/d. This dose caused the spasticity to decrease, with maintenance of muscle strength. After pump implantation, gait performance was improved, resulting in increased knee flexion during the loading response and a doubled walking speed as compared with baseline. CONCLUSIONS: Patients with HSP who have mild spasticity that does not respond to oral spasmolytics should receive a continuous ITB test infusion, to provide them with enough time to experience the delicate balance between spasmolysis and muscle strength. ITB administration is a suitable therapy to improve gait performance in patients with HSP.

Clinical relevance of pharmacological and physiological data in intrathecal baclofen therapy.

OBJECTIVE: To review all pharmacological and physiological data available on intrathecal baclofen (ITB) therapy and to evaluate its use in clinical practice and future research. DATA SOURCES: PubMed was searched for relevant anatomic, physiological, and pharmacological data available on ITB. STUDY SELECTION: All currently available data on ITB pharmacokinetics (PKs) and pharmacodynamics (PDs) in both human and animal studies were reviewed and combined with the anatomy and physiology of the intrathecal space and cerebrospinal fluid flow. DATA EXTRACTION: Only 4 studies reported PK data on ITB in humans. More studies reported PD data on ITB; however, none were combined with PK data. More detailed data on PK could be gathered from studies using an animal model. DATA SYNTHESIS: ITB does not spread equally over the intrathecal space after injection, but it diffuses according to a concentration gradient. ITB distribution can be influenced by the location of the catheter tip and by changing the infusion mode. CONCLUSIONS: The pharmacological and physiological data on ITB can be used to support decisions in clinical practice concerning drug concentration, infusion regimens, localization of the catheter tip, and management of tolerance; however, some strategies have little evidence in humans.

Modulation of cerebral blood flow with transcutaneous electrical neurostimulation (TENS) in patients with cerebral vasospasm after subarachnoid hemorrhage.

OBJECTIVES: Transcutaneous electrical neurostimulation (TENS) and spinal cord stimulation have been shown to increase peripheral and cerebral blood flow. We postulate that certain pathological conditions attenuate cerebral autoregulation, which may result in a relative increase of the importance of neurogenic regulation of cerebral blood flow, which could be decreased by electrical modulation. We therefore assess the effects of TENS on cerebral blood flow velocities (CBFVs) and cerebral saturation in patients with cerebral vasospasm after subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Cervical TENS was applied in 10 SAH patients with transcranial Doppler (TCD)-proven cerebral vasospasm. Measurements included plethysmography, near-infrared spectroscopy, capnography, and CBFVs by TCD. After determining the optimal frequency and current, patients were treated with cervical TENS for two periods of three days, with a pause of one day in between. RESULTS: The TENS electrodes were not always tolerated by the patients. Higher frequencies demonstrated the most prominent combined effects. ETCO2 was 0.19% lower with TENS off than with TENS on (p = 0.05). Mean arterial blood pressure and pulse were not significantly different over time. CBFV in MCA was decreased (p = 0.07) while cerebral oxygen saturation was increased (p = 0.01) after the use of TENS. CONCLUSIONS: Our data suggest improved cerebral blood flow when using cervical TENS in patients with cerebral vasospasm. Several factors could have attenuated the effects: the electrodes were poorly tolerated, ETCO2 increased during TENS, few vessels showed prolonged vasospasm, and overall flow velocities were low. Still, an on-off effect of TENS over time was detected.

The added value of semimicroelectrode recording in deep brain stimulation of the subthalamic nucleus for Parkinson disease.

OBJECT: Accurate placement of the leads is crucial in deep brain stimulation (DBS). To optimize the surgical positioning of the lead, a combination of anatomical targeting on MRI, electrophysiological mapping, and clinical testing is applied during the procedure. Electrophysiological mapping is usually done with microelectrode recording (MER), but the relatively undocumented semimicroelectrode recording (SMER) is a competing alternative. In this study the added value and safety of SMER for optimal lead insertion in the subthalamic nucleus (STN) in a consecutive cohort of patients with Parkinson disease (PD) was assessed. METHODS: Between 2001 and 2010, a consecutive single-center cohort of 46 patients with PD underwent DBS of the STN (85 lead insertions). After exclusion of 11 lead insertions for mostly technical reasons, 74 insertions were included for the assessment. Anatomical target localization was based on either 1.5-T MRI or fused 3-T MRI with CT, with reference to anterior commissure-posterior commissure coordinates. Electrophysiological mapping was performed with SMER. Intraoperative clinical testing was dominant in determining the final lead position. The target error was defined as the absolute distance between the anatomical or electrophysiological target and the final lead position. The effect of SMER on anatomical target error reduction and final target selection was analyzed. Also, the anatomical and electrophysiological target error was judged against the different imaging strategies. For safety evaluation, the adverse events related to all lead insertions were assessed. RESULTS: The use of SMER significantly reduced the anatomical target error from 1.7 (SD 1.6) mm to 0.8 (SD 1.3) mm (p < 0.0001). In particular, the anatomical target error based on 1.5-T MRI was significantly reduced by SMER, from 2.3 (SD 1.5) mm to 0.1 (SD 0.5) mm (p < 0.001). Anatomical target error reduction based on 3-T MRI fused with CT was not significantly influenced by SMER (p = 0.2), because the 3-T MRI-CT combination already significantly reduced the anatomical target error from 2.3 (SD 1.5) mm to 1.5 (SD 1.5) mm compared with 1.5-T MRI (p = 0.03). No symptomatic intracerebral hemorrhage was reported. Intracerebral infection was encountered in 1 patient following lead insertion. CONCLUSIONS: Semimicroelectrode recording has added value in targeting the STN in DBS for patients with PD based on 1.5-T MRI. The use of SMER does not significantly reduce the anatomical target error in procedures with fused 3-T MRI-CT studies and therefore might be omitted. With the absence of hemorrhagic complications, SMER-guided lead implantation should be considered a safe alternative to MER.

Multimorbidity, the predominant predictor of quality-of-life, following successful spinal cord stimulation for angina pectoris.

BACKGROUND: Patients suffering from severe chronic angina pectoris (AP) that has become therapeutically refractory to medication and revascularization can be adequately treated with spinal cord stimulation (SCS). However, following SCS implantation for angina, not all patients show a consistent improvement in quality of life (QoL). Therefore, we sought to study the association of baseline characteristics and chronic multimorbidities on QoL following SCS implantation. MATERIALS AND METHODS: All patients treated with SCS for refractory AP (rAP) were registered in a local data base. Patients who had discontinued SCS therapy were excluded from further analysis. Baseline characteristics, such as exercise limiting morbidities (chronic obstructive pulmonary disease [COPD], rheumatic disease, diabetes mellitus [DM], obesity expressed as body mass index [BMI]>25) and demographic data, were retrieved from the data base. QoL was studied using the Seattle Angina Questionnaire and the RAND-36 questionnaire. RESULTS: During a 21-year registration period (1986-2008), we enlisted 127 patients with SCS for rAP in our data base. Eighty-two, of whom 59 died, had discontinued SCS and were lost to follow-up. Out of the remaining 45 patients, 33 returned their questionnaires (73.3%). At SCS implantation, 72.7% of the patients were male, mean age 58±8.5 years. Twenty-four patients were in class III-IV angina and nine in class II-III NYHA. After a follow-up of 6.4±4.1 years, men had better physical capacity and experienced less impairment in QoL resulting from physical or emotional restrictions (all p<0.05) compared with women. Patients without COPD reported a better general health compared with those with rAP and COPD (p<0.05). The association of DM on QoL was borderline significant. Patients with lower BMI scored better on emotional well-being and perception of disease than those with a higher BMI (p<0.05 and p<0.05, respectively). None of the patients reported other morbidities limiting their exercise. CONCLUSIONS: Men showed a larger improvement in QoL following SCS implantation, compared with women. As SCS improves rAP, other chronic morbidities such as COPD, DM, and BMI may become the limiting factors for exercise and subsequently adversely affect QoL following implantation of an SCS system. As a consequence of the present relatively small single-center study, we recommend studies regarding rAP and SCS to also address the effect of comorbidities on outcomes.

Subcutaneous electrical nerve stimulation: a feasible and new method for the treatment of patients with refractory angina.

INTRODUCTION: Patients suffering from chronic angina pectoris, insufficiently controllable with medication and revascularization, are an increasing medical and psychosocial problem. Although spinal cord stimulation (SCS) is proven to employ, safe, long-term anti-angina, and anti-ischemic effects for these patients, the use of SCS in this group remains limited. The reason for this restricted use is largely unknown. However, among other reasons, it may be related to the difficulties in positioning an electrode in the epidural space. We studied the feasibility and efficacy of subcutaneous implantation of an entire system. METHODS: Seven male patients, mean age 67 ± 3.6 years, received complete subcutaneously implanted electrical nerve stimulation (SENS) systems, with one or more leads fixed in parallel with the sternum, covering the angina area. At baseline and 2 months follow-up patients performed exercise and quality of life tests (Seattle Angina Questionnaire and diaries number angina attacks and glyceryl trinitrate use). RESULTS: All patients showed clinical relevant improvement (baseline vs. follow-up), in exercise (63%) and quality of life (Seattle Angina Questionnaire 59%). The number of angina attacks dropped 82% and the number of glyceryl trinitrate use decreased by 90%. No major adverse events were observed. CONCLUSION: This small feasibility study demonstrates SENS to be an effective and safe method to treat patients suffering from refractory angina. Furthermore, SENS is less invasive and appears to have less lead migrations compared with SCS.

The distressed (Type D) personality is independently associated with tinnitus: a case-control study.

BACKGROUND: Tinnitus is a common and disturbing condition, reported by 10% to 20% of the general population. OBJECTIVE: The authors sought to determine personality characteristics associated with tinnitus patients versus a control group of ear-nose-throat (ENT) patients without tinnitus. METHOD: Adult chronic tinnitus sufferers (N=265) and ENT patients without tinnitus (N=265) participated in a cross-sectional study. The authors evaluated personality characteristics with tests for distressed personality (Type D), neuroticism, extraversion, and emotional stability. RESULTS: As compared with control subjects, tinnitus patients had statistically significant and clinically relevant higher levels of neuroticism, negative affectivity, and social inhibition, on one hand, and lower levels of extraversion and emotional stability on the other hand. Also, tinnitus patients were more likely to have a type D personality. CONCLUSIONS: Neuroticism, reduced extraversion, and reduced emotional stability were associated with tinnitus, but the level of prediction of the model improved with the addition of type D personality to the single traits. This might indicate that personality characteristics, and type D personality, in particular, are associated with having tinnitus and might contribute to its perceived severity.

The influence of transcutaneous electrical neurostimulation (TENS) on human cerebral blood flow velocities.

BACKGROUND: It has been shown that transcutaneous electrical neurostimulation (TENS) reduces sympathetic tone. Spinal cord stimulation (SCS) has proven qualities to improve coronary, peripheral, and cerebral blood circulation. Therefore, we postulate that TENS and SCS affect the autonomic nervous system in analogous ways. In this line of thought, cervical application of TENS might be a useful and simple adjunct in the treatment of cerebrovascular disease by improving cerebral blood flow. Experiments were performed in order to assess whether cervical TENS is safe and whether an effect on cerebral blood flow velocity (CBFV) can be shown in healthy subjects. METHOD: A controlled, non-randomized, phase 1 study was performed with 20 healthy volunteers. Cervical TENS was applied in several frequencies, with and without hyperventilation. Continuous registration of blood pressure, pulse, CBFV (estimated by transcranial Doppler sonography) and end-tidal carbon dioxide concentration was performed. FINDINGS: Cervical TENS was well-tolerated by all subjects. Despite small effects on heart rate (HR) and mean arterial blood pressure (MAP), a significant effect on middle cerebral artery (MCA) blood flow velocity was not demonstrated. No effect of age, gender, current or session order on MCA, HR, or MAP was found. TENS did not influence the effect of hyperventilation. CONCLUSIONS: In these experiments, application of cervical TENS is proven to be a safe procedure. However, no effects on cerebral blood flow velocity could be detected, perhaps due to the intact cerebral autoregulation in the healthy volunteers.

Avoiding the ventricle: a simple step to improve accuracy of anatomical targeting during deep brain stimulation.

OBJECT: The authors examined the accuracy of anatomical targeting during electrode implantation for deep brain stimulation in functional neurosurgical procedures. Special attention was focused on the impact that ventricular involvement of the electrode trajectory had on targeting accuracy. METHODS: The targeting error during electrode placement was assessed in 162 electrodes implanted in 109 patients at 2 centers. The targeting error was calculated as the shortest distance from the intended stereotactic coordinates to the final electrode trajectory as defined on postoperative stereotactic imaging. The trajectory of these electrodes in relation to the lateral ventricles was also analyzed on postoperative images. RESULTS: The trajectory of 68 electrodes involved the ventricle. The targeting error for all electrodes was calculated: the mean +/- SD and the 95% CI of the mean was 1.5 +/- 1.0 and 0.1 mm, respectively. The same calculations for targeting error for electrode trajectories that did not involve the ventricle were 1.2 +/- 0.7 and 0.1 mm. A significantly larger targeting error was seen in trajectories that involved the ventricle (1.9 +/- 1.1 and 0.3 mm; p < 0.001). Thirty electrodes (19%) required multiple passes before final electrode implantation on the basis of physiological and/or clinical observations. There was a significant association between an increased requirement for multiple brain passes and ventricular involvement in the trajectory (p < 0.01). CONCLUSIONS: Planning an electrode trajectory that avoids the ventricles is a simple precaution that significantly improves the accuracy of anatomical targeting during electrode placement for deep brain stimulation. Avoidance of the ventricles appears to reduce the need for multiple passes through the brain to reach the desired target as defined by clinical and physiological observations.

Detection of tremor bursts by a running second order moment function and analysis using interburst histograms.

INTRODUCTION: Conventional linear signal processing techniques are not always suitable for the detection of tremor bursts in clinical practice due to inevitable noise from electromyographic (EMG) bursts. This study introduces (1) a non-linear analysis technique based on a running second order moment function (SOMF) and (2) auto- and cross-interburst interval histograms (IBIH) showing distributions of interburst interval EMG bursts of pathological tremors illustrating an application of the SOMF. MATERIALS AND METHODS: EMG recordings from extensors and flexors of two patients with Parkinson's disease with a rest tremor and from a healthy subject during sustained muscular contraction were preliminary analyzed in a pilot study. The SOMF was obtained by repeated second order moment calculations within a window of fixed width W (time scale parameter) plotted as a function of time. Minimum SOMF values indicate local "moments of inertia" of each EMG burst. Bursts were detected and located when minimum SOMF values were below level L (decision parameter). Optimal settings of parameters W and L were calculated empirically for pathological tremor EMGs. Auto- and cross-IBIHs were obtained from minimum SOMF values of detected bursts. RESULTS: Tremor frequency and phase relation between EMG bursts from auto- and cross-IBIHs agreed with those derived from spectral analysis. Burst detection by SOMF has a high sensitivity and selectivity even with noisy background. CONCLUSION: The SOMF is appropriate for detection of individual EMG bursts of pathological tremors. The technique is sensitive to non-stationary changes of tremor bursts regardless of their amplitude. IBIHs provide a measure of tremor frequency and phase difference between EMG bursts.

The sustained benefits of long-term neurostimulation in patients with refractory chest pain and normal coronary arteries.

OBJECTIVES: To assess the long-term efficacy of neurostimulation for treating refractory angina pectoris-like chest pain, we followed patients, treated with either transcutaneous electrical nerve stimulation (TENS) or spinal cord stimulation (SCS). METHODS: Neurostimulation was judged successful and subsequently continued when initial pain was reduced at least 50%. All patients started with TENS, but if skin irritation occurred during TENS, a SCS system was implanted. The quality of life was measured at baseline and follow-up with the Seattle Angina Questionnaire. Additional information was gathered concerning anti-anginal medication, complaints, and physical condition. RESULTS: Of 36 patients treated successfully with neurostimulation, we identified 24 patients after a mean (SD) follow-up period of 5.08 (3.86) years; 12 patients dropped out of the study. In 13 of the remaining 24 patients, TENS induced skin irritation. Eight of these 13 patients received successful SCS, while five refused implantation. In the 24 patients, a mean pain reduction of 57% was achieved in conjunction with an increased exercise capacity of 30% and walking distance increased from 0.73 (0.83) to 1.62 (1.62) (p=0.018). Within the Seattle Angina Questionnaire the domain 'disease perception' improved from 38.89 (16.61) to 49.31 (21.83) (p=0.004), the domain 'physical limitation' improved from 29.89 (15.10) to 40.97 (22.63) (p=0.001) and 'anginal frequency' improved from 41.67 (24.08) to 55.00 (23.03) (p=0.005). In addition, nitroglycerin consumption was reduced from 7.85 (8.49) to 1.98 (2.19) (p=0.001). CONCLUSION: Neurostimulation techniques should thus be of widespread value for treating angina pectoris-like chest pain in patients who are refractory to medication.

The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion.

BACKGROUND: Electrical neurostimulation can be used to treat patients with refractory angina, it reduces angina and ischemia. Previous data have suggested that electrical neurostimulation may alleviate myocardial ischaemia through increased collateral perfusion. We investigated the effect of electrical neurostimulation on functional collateral perfusion, assessed by distal coronary pressure measurement during acute coronary occlusion. We sought to study the effect of electrical neurostimulation on collateral perfusion. METHODS: Sixty patients with stable angina and significant coronary artery disease planned for elective percutaneous coronary intervention were split in two groups. In all patients two balloon inflations of 60 seconds were performed, the first for balloon dilatation of the lesion (first episode), the second for stent delivery (second episode). The Pw/Pa ratio (wedge pressure/aortic pressure) was measured during both ischaemic episodes. Group 1 received 5 minutes of active neurostimulation before plus 1 minute during the first episode, group 2 received 5 minutes of active neurostimulation before plus 1 minute during the second episode. RESULTS: In group 1 the Pw/Pa ratio decreased by 10 +/- 22% from 0.20 +/- 0.09 to 0.19 +/- 0.09 (p = 0.004) when electrical neurostimulation was deactivated. In group 2 the Pw/Pa ratio increased by 9 +/- 15% from 0.22 +/- 0.09 to 0.24 +/- 0.10 (p = 0.001) when electrical neurostimulation was activated. CONCLUSION: Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.

Tinnitus and neural plasticity of the brain.

OBJECTIVE: To describe the current ideas about the manifestations of neural plasticity in generating tinnitus. DATA SOURCES: Recently published source articles were identified using MEDLINE, PubMed, and Cochrane Library according to the key words mentioned below. STUDY SELECTION: Review articles and controlled trials were particularly selected. DATA EXTRACTION: Data were selected systematically, scaled on validity and comparability. CONCLUSION: An altered afferent input to the auditory pathway may be the initiator of a complex sequence of events, finally resulting in the generation of tinnitus at the central level of the auditory nervous system. The effects of neural plasticity can generally be divided into early modifications and modifications with a later onset. The unmasking of dormant synapses, diminishing of (surround) inhibition and initiation of generation of new connections through axonal sprouting are early manifestations of neural plasticity, resulting in lateral spread of neural activity and development of hyperexcitability regions in the central nervous system. The remodeling process of tonotopic receptive fields within auditory pathway structures (dorsal cochlear nucleus, inferior colliculus, and the auditory cortex) are late manifestations of neural plasticity. The modulation of tinnitus by stimulating somatosensory or visual systems in some people with tinnitus might be explained via the generation of tinnitus following the nonclassical pathway. The similarities between the pathophysiological processes of phantom pain sensations and tinnitus have stimulated the theory that chronic tinnitus is an auditory phantom perception.

Myocardial perfusion quantification in patients suspected of cardiac syndrome X with positive and negative exercise testing: a [13N]ammonia positron emission tomography study.

BACKGROUND: The combination of angina pectoris, angiographically normal coronary arteries, and a positive exercise stress test (EST) is referred to as cardiac syndrome X. However, a large group of patients suspected of syndrome X reveals a normal exercise stress test and weakens the diagnosis of syndrome X. Previous studies demonstrated an impaired coronary flow reserve on ammonia positron emission tomography (PET) in patients with syndrome X. AIM: To evaluate the coronary flow reserve in patients suspected of syndrome X with positive and negative EST findings, using [(13)N]ammonia PET as the diagnostic aid. METHODS: Forty-two patients with chest pain and a normal coronary angiography, were analysed by exercise stress testing (EST) and the dypyridamole stress test (DST) on [(13)N]ammonia PET. Two subgroups were predefined, based on outcome of EST: an EST positive and negative group. A normal control group was used as the reference method. RESULTS: A total of 24 (57%) out of 42 patients had significant ST-T changes (EST positive). [(13)N]ammonia PET showed a significantly lower rest flow in the EST positive and EST negative group compared to controls (P<0.001 and P=0.0028, respectively). DST [(13)N]ammonia PET perfusion was significantly reduced in flow in both the EST positive and EST negative groups (P<0.001 both), as was the DST/rest [(13)N]ammonia perfusion reserve (P<0.001 for both), compared to normal controls. CONCLUSION: PET demonstrates a reduced coronary flow reserve in patients suspected of syndrome X, irrespective of the EST findings.

Cardiac nociception in rats: neuronal pathways and the influence of dermal neurostimulation on conveyance to the central nervous system.

Neurostimulation for refractory angina pectoris is often advocated for its clinical efficacy. However, the recruited pathways to induce electroanalgesia are partially unknown. Therefore, we sought to study the effect of neurostimulation on experimentally induced cardiac nociception, using capsaicin as nociception-induced substance. Four different groups of male Wistar rats were pericardially infused with either saline or capsaicin with or without neurostimulation. Group StimCap was infused with capsaicin, and group StimVeh was infused with saline. Both groups were treated with neurostimulation. Group ShamCap was only infused with capsaicin without stimulation, whereas group ShamVeh was only infused with saline. Neuronal activation differences were assessed with cytochemical staining, revealing the cellular expression of c-fos. Pain behavior was registered on video and was quantitatively analyzed. In the StimCap and ShamCap groups, all animals exerted typical pain behavior, whereas in the StimVeh group only moderate changes in behavior were observed. Group ShamVeh animals were unaffected by the procedure. The upper thoracic spinal cord showed high numbers of c-fos-positive cells, predominantly in laminae III and IV in both StimCap and StimVeh groups. Almost no c-fos expression was noticed in groups ShamCap and ShamVeh in these sections of the spinal cord. In groups StimCap and ShamCap a significantly higher number of c-fos-positive cells in comparison with groups StimVeh and ShamVeh were noticed in the periambigus region, the nucleus tractus solitarius, and the paraventricular hypothalamus. In the paraventricular thalamus, periaqueductal gray, and central amygdala, no significant differences were noticed among the first three groups, and the c-fos concentration in these three groups was significantly higher than in group ShamVeh. It is concluded that neurostimulation does not influence capsaicin-induced cardiac nociceptive pain pulses to the central nervous system. Furthermore, capsaicin-induced cardiac pain and neurostimulation may utilize two different pathways.

Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial.

BACKGROUND: Patients with advanced Parkinson's disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS. METHODS: We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074. FINDINGS: Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinson's disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups. INTERPRETATION: Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease. FUNDING: Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

Electrical modulation of the sympathetic nervous system in order to augment cerebral blood flow: a protocol for an experimental study.

Introduction Cerebral blood flow (CBF) is regulated by several mechanisms. Neurogenic control has been a matter of debate, even though several publications reported the effects of changes in sympathetic tone on CBF. Transcutaneous electrical nerve stimulation and spinal-cord stimulation have been shown to influence peripheral and cerebral blood flow through a sympathetic pathway. The authors hypothesise that certain pathological conditions result in a relative increase in the neurogenic regulation of CBF and that this regulation can be modulated electrically. Methods and analysis Patients with cerebral vasospasm after subarachnoid haemorrhage will be included. The experimental set-up measures several parameters that are involved in cerebral blood flow regulation in patients with cerebral vasospasm after subarachnoid haemorrhage. Measurements are taken at baseline and with stimulation in several frequencies. An ad hoc statistical analysis is used to evaluate different settings of the electrical stimulation. Autoregulation is evaluated with transfer function analysis and autoregulatory index calculations. Ethics and dissemination Ethical registration was granted by Medical Review Ethics Committee Groningen (ID METc 2010.123). All participants provide written informed consent on participation. Upon finishing a pilot study to investigate feasibility and effect, either future prospective (randomised) studies will be designed, or other modalities of electrical stimulation will be explored using the same set-up. Trial Registration Dutch Trial Registry: NTR2358.

The impact of Type D personality on health-related quality of life in tinnitus patients is mainly mediated by anxiety and depression.

OBJECTIVE: To evaluate the impact of Type D personality on health-related quality of life (HRQoL) and self-reported tinnitus-related distress in chronic tinnitus patients and whether this relationship is mediated by indicators of psychological distress (i.e., vital exhaustion, anxiety, and depression). MATERIALS AND METHODS: Using a cross-sectional study design, 265 consecutive tinnitus patients were asked to complete the Hospital Anxiety and Depression Scale, the Maastricht Questionnaire, the Type D Scale (DS14), the Short-Form Health Survey 36, and the Tinnitus Reaction Questionnaire. RESULTS: The prevalence of Type D was 35.5%. Type D patients were significantly more anxious, depressed, and vitally exhausted, and experienced more impaired HRQoL and increased tinnitus-related distress compared with non-Type D patients. Structural equation modeling showed that Type D personality directly increased symptoms of depression and anxiety, but not vital exhaustion. Type D was also a direct predictor of poor mental and physical HRQoL and increased tinnitus-related distress, although this influence was mainly mediated by symptoms of depression and anxiety. Anxiety, depression, and vital exhaustion had a direct influence on HRQoL and self-reported tinnitus-related distress, with a higher impact on mental HRQoL (R2 = 0.74) compared with physical HRQoL (R2 = 0.33). Vital exhaustion was a predictor of HRQoL and self-reported tinnitus-related distress; however, its influence was moderated by enhanced levels of anxiety and depression. CONCLUSION: Tinnitus patients with a Type D personality were more likely to be anxious and depressed and to experience poor HRQoL and increased self-reported tinnitus-related distress, with the impact of Type D mainly being mediated by symptoms of anxiety and depression, although Type D also exerted a direct influence on these outcomes. These findings underline that to reduce the impact of tinnitus on HRQoL and self-reported tinnitus-related distress, treatment should be directed toward reducing anxiety and depression, especially in patients with a Type D personality.

Personality: predictor of neurostimulation outcomes in patients with chest pain and normal coronary arteries.

Objectives. To study the impact of personality traits on the effect of neurostimulation in patients with chest pain and normal coronary arteries. Materials and Methods. Using the Dutch personality questionnaire, we retrospectively studied the personality traits in 33 patients treated with neurostimulation, either transcutaneous electrical nerve stimulation or spinal cord stimulation after 5 years. Neurostimulation was successful in 21 patients. Baseline characteristics and medication also were assessed for possible interactions with personality traits and neurostimulation outcome. Results. Patients with beneficial neurostimulation scored lower on the "social inadequacy" scale than patients with neurostimulation failure (p = 0.032). In univariate analyses, low scores at the "social inadequacy" scale and the use of calcium antagonists were associated with beneficial outcome of neurostimulation. In multivariate analysis low scores at the "social inadequacy" scale remained an independent predictor for beneficial neurostimulation outcome, when adjusted for other variables. Conclusion. Personality traits are a determining factor in the evaluation of neurostimulation for patients with chest pain and normal coronary arteries.