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Background Intermittent explosive disorder (IED) is a psychiatric disorder characterized by recurrent outbursts of aggressive behavior. Deep brain stimulation (DBS) in the posteromedial nucleus of the hypothalamus (pHyp) is an alternative therapy for extreme cases and shows promising results. Intraoperative microdialysis can help elucidate the neurobiological mechanism of pHyp-DBS. We sought to evaluate efficacy and safety of pHyp-DBS using 8-contact directional leads in patients with refractory IED (rIED) and the accompanying changes in neurotransmitters. Methods This was a prospective study in which patients with a diagnosis of rIED were treated with pHyp-DBS for symptom alleviation. Bilateral pHyp-DBS was performed with 8-contact directional electrodes. Follow-up was performed at 3, 6, and 12 months after surgery. Results Four patients (3 men, mean age 27 ± 2.8 years) were included. All patients were diagnosed with rIED and severe intellectual disability. Two patients had congenital rubella, one had a co-diagnosis of infantile autism, and the fourth presented with drug-resistant epilepsy. There was a marked increase in the levels of gamma-aminobutyric acid and glycine during intraoperative stimulation. The average improvement in aggressive behavior in the last follow-up was 6 points (Δ: 50%, P = 0.003) while also documenting an important improvement of the Short Form Health Survey in all domains except bodily pain. No adverse events associated with pHyp-DBS were observed. Conclusions This is the first study to show the safety and beneficial effect of directional lead pHyp-DBS in patients with rIED and to demonstrate the corresponding mechanism of action through increases in gamma-aminobutyric acid and glycine concentration in the pHyp.

Introduction Hereditary spastic paraplegia is a heterogeneous group of genetic disorders characterized by degeneration of the corticospinal tracts, coursing with progressive weakness and spasticity of the lower limbs. To date, there are no effective treatments for progressive deficits or disease-modifying therapy for those patients. We report encouraging results for spastic paraparesis after spinal cord stimulation. Methods A 51-year-old woman suffering from progressive weakness and spasticity in lower limbs related to hereditary spastic paraplegia type 4 underwent spinal cord stimulation (SCS) and experienced also significant improvement in motor function. Maximum ballistic voluntary isometric contraction test, continuous passive motion test and gait analysis using a motion-capture system were performed in ON and OFF SCS conditions. Neurophysiologic assessment consisted of obtaining motor evoked potentials in both conditions. Results Presurgical Spastic Paraplegia Rating Scale (SPRS) score was 26. One month after effective SCS was initiated, SPRS went down to 15. At 12 months follow up, she experienced substantial improvement in motor function and in gait performance, with SPRS scores 23 (OFF) and down to 20 (ON). There was an increased isometric muscle strength (knee extension, OFF: 41 N m; ON: 71 N m), lower knee extension and flexion torque values in continuous passive motion test (decrease in spastic tone) and improvement in gait (for example, step length increase). Conclusion Despite being a case study, our findings suggest innovative lines of research for the treatment of spastic paraplegia.

Background With application of 3T magnetic resonance imaging (MRI) to functional neurosurgery procedures and given the inherent requirement of millimetric precision, the need to develop a method for correction of geometric image distortion emerged. The aim of this study was to demonstrate clinical safety and practical viability of a correction protocol in patients scheduled to undergo stereotactic procedures using 3T MRI. Methods This prospective study comprised 20 patients scheduled to undergo computed tomography (CT) stereotactic functional procedures or encephalic brain lesion biopsies. The CT images were references for MRI geometric accuracy calculations. For each scan, 2 images were obtained: normal and reversed images. Eight distinct points on CT and MRI were selected summing 152 points that were based on a power analysis calculation value >0.999. One patient was excluded because of the inability to find reliable common landmark points on CT and MRI. Results The distortion range was 0–5.6 mm and increased proportionally with stereotactic isocenter distance, meaning the distortion was greater in the periphery. After correction, the minimum and maximum distortion found was 0 mm and 3.5 mm, respectively. There was no significant difference between CT and MRI corrected x-coordinates (P > 0.05). Conclusions The proposed method can satisfactorily correct geometric distortions in clinical 3T MRI studies. Clinical use of the technique can be practical and efficient after software automation of the process. The method can be applied to all spin-echo MRI sequences.

Aggressiveness has a high prevalence in psychiatric patients and is a major health problem. Two brain areas involved in the neural network of aggressive behavior are the amygdala and the hypothalamus. While pharmacological treatments are effective in most patients, some do not properly respond to conventional therapies and are considered medically refractory. In this population, surgical procedures (ie, stereotactic lesions and deep brain stimulation) have been performed in an attempt to improve symptomatology and quality of life. Clinical results obtained after surgery are difficult to interpret, and the mechanisms responsible for postoperative reductions in aggressive behavior are unknown. We review the rationale and neurobiological characteristics that may help to explain why functional neurosurgery has been proposed to control aggressive behavior.

Motor cortex stimulation via surgically implanted electrodes has been used as an off-label treatment for chronic neuropathic pain, but its efficacy has not been fully established. We aimed to objectively study the efficacy of motor cortex stimulation and characterize potential predictors of response. In this randomized, double-blind, sham-controlled, single centre trial, we recruited 18 patients with chronic neuropathic pain who did not adequately respond to conventional treatment and had a numerical pain rating scale (NRS) score ≥6. Patients were initially assigned to receive 3 months of active (‘on’) or sham (‘off’) stimulation in a double-blind cross-over phase. This was followed by a 3-month single-blind phase, and 6 months of open-label follow-up. A meaningful response in our trial was defined as a ≥30% or 2-point reduction in NRS scores during active stimulation. Using Bayesian statistics, we found a 41.4% probability of response towards on versus off motor cortex stimulation. The probability of improvement during active stimulation (double-blind, single-blind and open-label phases) compared to baseline was 47.2–68.5%. Thirty nine per cent of the patients were considered long-term responders, 71.4% of whom had facial pain, phantom limb pain or complex regional pain syndrome. In contrast, 72.7% of non-responders had either post-stroke pain or pain associated with brachial plexus avulsion. Thirty-nine per cent of patients had a substantial postoperative analgesic effect after electrode insertion in the absence of stimulation. Individuals with diagnoses associated with a good postoperative outcome or those who developed an insertional effect had a near 100% probability of response to motor cortex stimulation. In summary, we found that ∼40% of patients responded to motor cortex stimulation, particularly those who developed an insertional effect or had specific clinical conditions that seemed to predict an appropriate postoperative response.

Hemidystonia (HD) is characterized by unilateral involuntary torsion movements and fixed postures of the limbs and face. It often develops after deleterious neuroplastic changes secondary to injuries to the brain. This condition usually responds poorly to medical treatment, and deep brain stimulation often yields unsatisfactory results. We propose this study based on encouraging results from case reports of patients with HD treated by ablative procedures in the subthalamic region.To compare the efficacy of stereotactic-guided radiofrequency lesioning of the subthalamic area vs available medical treatment in patients suffering from acquired HD.This is an open-label study in patients with secondary HD allocated according to their treatment choice, either surgical or medical treatment; both groups were followed for one year. Patients assigned in the surgical group underwent unilateral campotomy of Forel. The efficacy was assessed using the Unified Dystonia Rating Scale, Fahn-Marsden Dystonia Scale, Arm Dystonia Disability Scale, and SF-36 questionnaire scores.Patients in the surgical group experienced significant improvement in the Unified Dystonia Rating Scale, Fahn-Marsden Dystonia Scale, and Arm Dystonia Disability Scale (39%, 35%, and 15%, respectively) 1 year after the surgery, with positive reflex in quality-of-life measures, such as bodily pain and role-emotional process. Patients kept on medical treatment did not experience significant changes during the follow-up. No infections were recorded, and no neurological adverse events were associated with either intervention.The unilateral stereotaxy-guided ablation of Forel H1 and H2 fields significantly improved in patients with HD compared with optimized clinical treatment.

Background Olfactory dysfunction is a nonmotor symptom of Parkinson disease (PD) associated with reduction in quality of life. There is no evidence on whether improvements in olfaction after subthalamic deep brain stimulation (STN-DBS) may be directly attributable to motor improvement or whether this reflects a direct effect of DBS on olfactory brain areas. The aim of the present study was to evaluate the effect of DBS on olfactory function in PD, as well as to explore the correlation between these changes and changes in motor symptoms and brain metabolism. Methods Thirty-two patients with PD were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. Primary outcome was the change in olfactory function (Sniffin' Sticks odor-identification test [SST]) after surgery among the patients with hyposmia at baseline. Secondary outcomes included the relationship between motor outcomes and olfactory changes and [18F]fluorodeoxyglucose-positron emission tomography analysis between subgroups with improvement versus no improvement of smell. Results STN-DBS improved SST after surgery (preoperative SST, median 7.3 ± 2.4 vs. postoperative SST, median 8.2 ± 2.1; P = 0.045) in a subset of patients among 29 of 32 patients who presented with hyposmia at baseline. The improvement in SST was correlated with DBS response (r = 0.424; P = 0.035). There was also an increase in glucose metabolism in the midbrain, cerebellum, and right frontal lobe in patients with SST improvement (P Conclusions STN-DBS improves odor identification in a subset of patients with PD. Motor improvement together with changes in the brain metabolism may be linked to this improvement.

To compare transcranial sonography (TCS) findings in patients with predominantly neurological Wilson's disease (WD) to those from controls, and to correlate TCS data with the clinical profile of WD. Patients with WD (n=40/f=18) and healthy, matched controls (n=49/f=20) were assessed in terms of TCS, serum copper and iron parameters, and clinical scales, such as the Unified Wilson's Disease Rating Scale (UWDRS), Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini Mental State Examination (MMSE), and Beck Depression Inventory. Lenticular nuclei and substantia nigra echogenic area cut-off values clearly differentiated WD patients from controls (area under the curve: 95.4% and 79.4%). Substantia nigra echogenic area was significantly larger in male than in female patients (p=0.001). Compared with controls, patients showed hyperechogenicity also in thalami and midbrain tegmentum/tectum; third ventricle width was increased and midbrain axial area was reduced. In the WD group, male gender correlated with substantia nigra echogenic area (r=0.515, p=0.0007) and serum ferritin levels (r=0.479, p=0.002); lenticular nuclei hyperechogenicity correlated with dystonia (r=0.326, p=0.04) and dysarthria (r=0.334, p=0.035); third ventricle width correlated with dystonia (r=0.439 p=0.005), dysarthria (r=0.449, p=0.004), parkinsonism (r=0.527, p

Stereotaxy is based on the precise image-guided spatial localization of targets within the human brain. Even with the recent advances in MRI technology, histological examination renders different (and complementary) information of the nervous tissue. Although several maps have been selected as a basis for correlating imaging results with the anatomical locations of sub-cortical structures, technical limitations interfere in a point-to-point correlation between imaging and anatomy due to the lack of precise correction for post-mortem tissue deformations caused by tissue fixation and processing. We present an alternative method to parcellate human brain cytoarchitectural regions, minimizing deformations caused by post-mortem and tissue-processing artifacts and enhancing segmentation by means of modified high thickness histological techniques and registration with MRI of the same specimen and into MNI space (ICBM152). A three-dimensional (3D) histological atlas of the human thalamus, basal ganglia, and basal forebrain cholinergic system is displayed. Structure's segmentations were performed in high-resolution dark-field and light-field microscopy. Bidimensional non-linear registration of the histological slices was followed by 3D registration with in situ MRI of the same subject. Manual and automated registration procedures were adopted and compared. To evaluate the quality of the registration procedures, Dice similarity coefficient and normalized weighted spectral distance were calculated and the results indicate good overlap between registered volumes and a small shape difference between them in both manual and automated registration methods. High thickness high-resolution histological slices in combination with registration to in situ MRI of the same subject provide an effective alternative method to study nuclear boundaries in the human brain, enhancing segmentation and demanding less resources and time for tissue processing than traditional methods.

The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ post-mortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.

Background Intractable aggressive behavior (iAB) is a devastating behavioral disorder that may affect psychiatric patients. These patients have reduced quality of life, are more challenging to treat as they impose a high caregiver burden and require specialized care. Neuromodulatory interventions targeting the amygdala, a key hub in the circuitry of aggressive behavior (AB), may provide symptom alleviation. Objective To Report clinical and imaging findings from a case series of iAB patients treated with bilateral amygdala ablation. Methods This series included 4 cases (3 males, 19-32 years old) who underwent bilateral amygdala radiofrequency ablation for iAB hallmarked by life-threatening self-injury and social aggression. Pre- and postassessments involved full clinical, psychiatric, and neurosurgical evaluations, including scales quantifying AB, general agitation, quality of life, and magnetic resonance imaging (MRI). Results Postsurgery assessments revealed decreased aggression and agitation and improved quality of life. AB was correlated with testosterone levels and testosterone/cortisol ratio in males. No clinically significant side effects were observed. Imaging analyses showed preoperative amygdala volumes within normal populational range and confirmed lesion locations. The reductions in aggressive symptoms were accompanied by significant postsurgical volumetric reductions in brain areas classically associated with AB and increases in regions related to somatosensation. The local volumetric reductions are found in areas that in a normal brain show high expression levels of genes related to AB (eg, aminergic transmission) using gene expression data provided by the Allen brain atlas. Conclusion These findings provide new insight into the whole brain neurocircuitry of aggression and suggest a role of altered somatosensation and possible novel neuromodulation targets.

Deep brain stimulation of the subthalamic nucleus is an effective and established therapy for patients with advanced Parkinson’s disease improving quality of life, motor symptoms and non-motor symptoms. However, there is a considerable degree of interindividual variability for these outcomes, likely due to variability in electrode placement and stimulation settings. Here, we present probabilistic mapping data from a prospective, open-label, multicentre, international study to investigate the influence of the location of subthalamic nucleus deep brain stimulation on non-motor symptoms in patients with Parkinson’s disease. A total of 91 Parkinson’s disease patients undergoing bilateral deep brain stimulation of the subthalamic nucleus were included, and we investigated NMSScale, NMSQuestionnaire, Scales for Outcomes in Parkinson’s disease-motor examination, -activities of daily living, and -motor complications, and Parkinson’s disease Questionnaire-8 preoperatively and at 6-month follow-up after surgery. Leads were localized in standard space using the Lead-DBS toolbox and individual volumes of tissue activated were calculated based on clinical stimulation settings. Probabilistic stimulation maps and non-parametric permutation statistics were applied to identify voxels with significant above or below average improvement for each scale and analysed using the DISTAL atlas. All outcomes improved significantly at follow-up. Significant spatial distribution patterns of neurostimulation were observed for NMSScale total score and its mood/apathy and attention/memory domains. For both domains, voxels associated with below average improvement were mainly located dorsal to the subthalamic nucleus. In contrast, above average improvement for mood/apathy was observed in the ventral border region of the subthalamic nucleus and in its sensorimotor subregion and for attention/memory in the associative subregion. A trend was observed for NMSScale sleep domain showing voxels with above average improvement located ventral to the subthalamic nucleus. Our study provides evidence that the interindividual variability of mood/apathy, attention/memory, and sleep outcomes after subthalamic nucleus deep brain stimulation depends on the location of neurostimulation. This study highlights the importance of holistic assessments of motor and non-motor aspects of Parkinson’s disease to tailor surgical targeting and stimulation parameter settings to patients’ personal profiles.

Key Points Question Is lateral hypothalamic deep brain stimulation (DBS) safe for the treatment of obesity in Prader-Willi syndrome? Findings In this case series of 4 patients with Prader-Willi syndrome treated with lateral hypothalamic DBS, 2 developed stimulation-induced manic symptoms and 2 developed infections, 1 of which was associated with skin picking. No major differences were found when postoperative anthropometric and calorimetric data were compared with baseline; hormonal levels, and results of blood workup, sleep studies, and neuropsychological evaluations also showed no change. Meaning Safety of lateral hypothalamic DBS was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS; however, in the small cohort of patients with Prader-Willi syndrome treated, DBS seemed largely ineffective for the treatment of obesity., This study of a case series of 4 patients investigates the safety and efficacy of deep brain stimulation for obesity associated with Prader-Willi syndrome., Importance Deep brain stimulation (DBS) has been investigated for treatment of morbid obesity with variable results. Patients with Prader-Willi syndrome (PWS) present with obesity that is often difficult to treat. Objective To test the safety and study the outcome of DBS in patients with PWS. Design, Setting, and Participants This case series was conducted in the Hospital das Clínicas, University of São Paulo, Brazil. Four patients with genetically confirmed PWS presenting with severe obesity were included. Exposure Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months). Main Outcomes and Measures Primary outcome measures were adverse events recorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits. Results Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking. Conclusions and Relevance Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in our study, DBS was largely ineffective.

Subthalamic deep brain stimulation (STN-DBS) is used to treat refractory motor complications in Parkinson disease (PD), but its effects on nonmotor symptoms remain uncertain. Up to 80% of patients with PD may have pain relief after STN-DBS, but it is unknown whether its analgesic properties are related to potential effects on sensory thresholds or secondary to motor improvement. We have previously reported significant and long-lasting pain relief after DBS, which did not correlate with motor symptomatic control. Here we present secondary data exploring the effects of DBS on sensory thresholds in a controlled way and have explored the relationship between these changes and clinical pain and motor improvement after surgery. Thirty-seven patients were prospectively evaluated before STN-DBS and 12 months after the procedure compared with healthy controls. Compared with baseline, patients with PD showed lower thermal and mechanical detection and higher cold pain thresholds after surgery. There were no changes in heat and mechanical pain thresholds. Compared with baseline values in healthy controls, patients with PD had higher thermal and mechanical detection thresholds, which decreased after surgery toward normalization. These sensory changes had no correlation with motor or clinical pain improvement after surgery. These data confirm the existence of sensory abnormalities in PD and suggest that STN-DBS mainly influenced the detection thresholds rather than painful sensations. However, these changes may depend on the specific effects of DBS on somatosensory loops with no correlation to motor or clinical pain improvement.

We describe a case of a 30-year-old woman who suffered a traumatic injury of the right brachial plexus, developing severe complex regional pain syndrome type II (CRPS-II). After clinical treatment failure, spinal cord stimulation (SCS) was indicated with initial positive pain control. However, after 2 years her pain progressively returned to almost baseline intensity before SCS. Additional motor cortex electrode implant was then proposed as a rescue therapy and connected to the same pulse generator. This method allowed simultaneous stimulation of the motor cortex and SCS in cycling mode with independent stimulation parameters in each site. At 2 years follow-up, the patient reported sustained improvement in pain with dual stimulation, reduction of painful crises, and improvement in quality of life. The encouraging results in this case suggests that this can be an option as add-on therapy over SCS as a possible rescue therapy in the management of CRPS-II. However, comparative studies must be performed in order to determine the effectiveness of this therapy. Key words: Chronic neuropathic pain, Complex regional pain syndrome Type II, brachial plexus injury, motor cortex stimulation, spinal cord stimulation

Objective Reporting the outcome of two patients who underwent unilateral ablative stereotactic surgery to treat pharmacologic resistant posttraumatic tremor (PTT). Methods We present two patients (31 and 47 years old) with refractory PTT severely affecting their quality of life. Under stereotactic guidance, refined by T2-weighted magnetic resonance imaging and double-channel multiunit microelectrode recording (MER), three sequential radiofrequency lesions were performed in the caudal zona incerta (cZi) up to the base of thalamus (VOP). Effects of cZi/VOP lesion were prospectively rated with a tremor rating scale. Results Both patients demonstrated intraoperative tremor suppression with sustained results up to 18 months follow-up, with improvement of 92% and 84%, respectively, on the tremor rating scale. Tremor improvement was associated with enhancement functionality and quality of life for the patients. The patients returned to their work after the procedure. No adverse effects were observed up to the last follow-up. Conclusion Radiofrequency lesion of the cZi/VOP target was effective for posttraumatic tremor in both cases. The use of T2-weighted images and MER was found helpful in increasing the precision and safety of the procedure, because it leads the RF probe by relying on neighbor structures based on thalamus and subthalamic nucleus.

OBJECT The aim of this study was to show that microendoscopic guidance using a double-channel technique could be safely applied during percutaneous cordotomy and provides clear real-time visualization of the spinal cord and surrounding structures during the entire procedure. METHODS Twenty-four adult patients with intractable cancer pain were treated by microendoscopic-guided percutaneous radiofrequency (RF) cordotomy using the double-channel technique under local anesthesia. A percutaneous lateral puncture was performed initially under fluoroscopy guidance to localize the target. When the subarachnoid space was reached by the guiding cannula, the endoscope was inserted for visualization of the spinal cord and surrounding structures. After target visualization, a second needle was inserted to guide the RF electrode. Cordotomy was performed by a standard RF method. RESULTS The microendoscopic double-channel approach provided real-time visualization of the target in 91% of the cases. The other 9% of procedures were performed by the single-channel technique. Significant analgesia was achieved in over 90% of the cases. Two patients had transient ataxia that lasted for a few weeks until total recovery. CONCLUSIONS The use of percutaneous microendoscopic cordotomy with the double-channel technique is useful for specific manipulations of the spinal cord. It provides real-time visualization of the RF probe, thereby adding a degree of safety to the procedure.

Objective Quantitative data are reported on rapid eye movement (REM) sleep behavior disorder (RBD) in a cohort of predominantly neurological Wilson's disease (WD). Methods A total of 41 patients with WD and 41 healthy, age- and gender-matched controls were studied by conducting face-to-face interviews, neurological and clinical examinations, laboratory tests, and WD- and RBD-specific scales. Video-polysomnography and quantification of REM sleep without atonia (RWA) were conducted in 35 patients and 41 controls. Results Patients with WD showed significantly worse sleep quality, less sleep efficiency, increased wakefulness after sleep onset, and more arousals compared to healthy controls. Five patients with WD (four women) fulfilled the diagnostic criteria for RBD with significantly higher values in RWA, RBD Questionnaire-Hong Kong, and RBD Screening Questionnaire compared to patients with WD without RBD. In three patients with WD, RBD had manifested before any other symptom that could be attributed to WD. Percentage of RWA was significantly lower in WD without RBD than in WD with RBD, but still significantly increased compared to controls. Conclusions RBD can be comorbid with WD. RWA is commonly present in WD, both in the presence or absence of clinical RBD. A causal connection is possible, though retrospective determination of RBD onset and the low number of patients do not allow a definitive conclusion at this point. However, screening for WD in idiopathic RBD is available at low cost and is recommended. Early-stage copper chelation therapy provides a highly effective treatment to prevent further WD manifestations and might also control the comorbid RBD.

Freezing of gait (FoG) in Parkinson’s disease (PD) is an incapacitating transient phenomenon, followed by continuous postural disorders. Spinal cord stimulation (SCS) is a promising intervention for FoG in patients with PD, however, its effects on distinct domains of postural control is not well known. The aim of this study is to assess the effects of SCS on FoG and distinct domains of postural control. Four patients with FoG were implanted with SCS systems in the upper thoracic spine. Anticipatory postural adjustment (APA), reactive postural responses, gait and FoG were biomechanically assessed. In general, the results showed that SCS improved FoG and APA. However, SCS failed to improve reactive postural responses. SCS seems to influence cortical motor circuits, involving the supplementary motor area. On the other hand, reactive posture control to external perturbation that mainly relies on neuronal circuitries involving the brainstem and spinal cord, is less influenced by SCS.

This study aimed to evaluate the relationship between posturography, clinical balance, and executive function tests in Parkinson´s disease (PD). Seventy-one people participated in the study. Static posturography evaluated the center of pressure fluctuations in quiet standing and dynamic posturography assessed sit-to-stand, tandem walk, and step over an obstacle. Functional balance was evaluated by Berg Balance Scale, MiniBESTest, and Timed Up and Go test. Executive function was assessed by Trail Making Test (TMT) and semantic verbal fluency test. Step over obstacle measures (percentage of body weight transfer and movement time) were moderately correlated to Timed Up and Go, part B of TMT and semantic verbal fluency (r > 0.40; p < 0.05 in all relationships). Stepping over an obstacle assesses the responses to internal perturbations. Participants with shorter movement times and higher percentage of body weight transfer (higher lift up index) on this task were also faster in Timed Up and Go, part B of TMT, and semantic verbal fluency. All these tasks require executive function (problem solving, sequencing, shifting attention), which is affected by PD and contribute to postural assessment.

The “direct” and “indirect” pathways play crucial roles in movement disorder pathophysiology. Both traverse from the striatum to the internal pallidum and substantia nigra, the latter detouring to external pallidum and subthalamic nucleus. Anatomically, the pathways manifest within the striatofugal bundle that passes radially through the pallidum in the form of pencil-like tracts (first described by Wilson1; figure 1) before leaving the pallidum toward the substantia nigra in the form of a comb described by Edinger in 18962 (figure 2). A century later, these structures can be visualized in the living human brain (figures 1D and 2A).

High-frequency deep brain stimulation (DBS) is an effective treatment for some movement disorders. Though mechanisms underlying DBS are still unclear, commonly accepted theories include a “functional inhibition” of neuronal cell bodies and the excitation of axonal projections near the electrodes. It is becoming clear, however, that the paradoxical dissociation “local inhibition” and “distant excitation” is far more complex than initially thought. Despite an initial increase in neuronal activity following stimulation, cells are often unable to maintain normal ionic concentrations, particularly those of sodium and potassium. Based on currently available evidence, we proposed an alternative hypothesis. Increased extracellular concentrations of potassium during DBS may change the dynamics of both cells and axons, contributing not only to the intermittent excitation and inhibition of these elements but also to interrupt abnormal pathological activity. In this article, we review mechanisms through which high extracellular potassium may mediate some of the effects of DBS.

Objective Interactions between opioid use and hormonal function are documented in the literature. However, it is unclear if therapeutic intrathecal opioid therapy can induce hormonal changes, compared to oral opioid therapy. Methods The authors studied hormone and metabolic changes in 22 women (18–60 years) and 38 men (18–45 years) who were referred to a pain center. The patients were allocated to different treatment groups (based on assistant physicians' decision), as follows: 20 patients received oral morphine (60–120 mg/day); 20 patients, spinal morphine (0.2–10 mg/day); and 20 patients, nonopioid analgesic treatment. Results All three groups experienced substantial improvement in pain scores during the whole follow-up period. Significantly impaired libido, reduced potency, hot flashes, and menstrual cycle dysfunction occurred more often in both morphine groups than in the nonopioid group. Significantly low serum total testosterone levels were more prevalent in the spinal morphine group and the oral morphine group (58.3% and 70.0%, respectively) than in the control group (16.7%). Total cholesterol values above 200 mg/dL and higher ultrasensitive C-reactive protein levels were significantly more frequent in the morphine groups than in the controls. Total body bone mineral density was below normal in men receiving spinal morphine ( P = 0.014). Conclusions Hypogonadotrophic hypogonadism was more prevalent in the morphine groups and was correlated with clinical findings. Significant bone mass loss occurred in morphine users, even without hormone dysfunction when compared to nonopioid treatment. Growth hormone, thyroid stimulating hormone, adrenocorticotrophic hormones, and cardiovascular risk parameters were less compromised in morphine users.

Neurodegeneration with brain iron accumulation type 1 (NBIA-1) is a rare disorder characterized by progressive extrapyramidal dysfunction and dementia. NBIA-1 encompasses typical iron brain accumulation, mostly in the globus pallidus with secondary dementia, spasticity, rigidity, dystonia, and choreoathetosis. Treatment remains mostly symptomatic and is challenging. We present the case of a 14-year-old boy diagnosed with NBIA-1, presenting intractable progressive generalized dystonia leading to unresponsive status dystonicus (SD). The patient received a SynchroMed II (model 8637) programmable system pump (Medtronic®, Inc.) implant with an Ascenda intrathecal catheter for intrathecal morphine therapy (IMT). The initial dose of morphine was 1.0 mg/day. Overall, we observed no complications with IMT treatment and important improvement of the patient's motor function with stabilization of his incapacitating dystonia and his quality of life. On the Global Dystonia Severity Rating Scale, he presented 52% improvement, 30% improvement on the Unified Dystonia Rating Scale, and 38% improvement on the Fahn-Marsden Rating Scale after 10 months, when the dose was 1.7 mg/day. IMT should be considered as a potential palliative treatment in the management of intractable dystonia and SD secondary to NBIA-1.

Leprosy affects approximately 10-15 million patients worldwide and remains a relevant public health issue. Chronic pain secondary to leprosy is a primary cause of morbidity, and its treatment remains a challenge. We evaluated the feasibility and safety of peripheral nerve stimulation (PNS) for painful mononeuropathy secondary to leprosy that is refractory to pharmacological therapy and surgical intervention (decompression).Between 2011 and 2013 twenty-three patients with painful mononeuropathy secondary to leprosy were recruited to this prospective case series. All patients were considered to be refractory to optimized conservative treatment and neurosurgical decompression. Pain was evaluated over the course of the study using the neuropathic pain scale and the visual analog scale for pain. In the first stage, patients were implanted with a temporary electrode that was connected to an external stimulator, and were treated with PNS for seven days. Patients with 50% or greater pain relief received a definitive implantation in the second stage. Follow-ups in the second stage were conducted at 1, 3, 6, and 12 months.After seven days of trial in the first stage, 10 patients showed a pain reduction of 50% or greater. At 12-month follow-up in the second stage, 6 of the 10 patients who underwent permanent device implantation showed a pain reduction of 50% or greater (75% reduction on average), and two patients showed a 30% reduction in pain. Two patients presented with electrode migration that required repositioning during the 12-month follow-up period.Our data suggest that PNS might have significant long-term utility for the treatment of painful mononeuropathy secondary to leprosy. Future studies should be performed in order to corroborate our findings in a larger population and encourage the clinical implementation of this technique.

Over the last decades, extensive basic and clinical knowledge has been acquired on the use of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson’s disease (PD). It is now clear that mechanisms involved in the effects of this therapy are far more complex than previously anticipated. At frequencies commonly used in clinical practice, neural elements may be excited or inhibited and novel dynamic states of equilibrium are reached. Electrode contacts used for chronic DBS in PD are placed near the dorsal border of the nucleus, a highly cellular region. DBS may thus exert its effects by modulating these cells, hyperdirect projections from motor cortical areas, afferent and efferent fibers to the motor STN. Advancements in neuroimaging techniques may allow us to identify these structures optimizing surgical targeting. In this review, we provide an update on mechanisms and the neural elements modulated by STN DBS.

A 25-year-old woman with severe tardive dyskinesia (TD) due to neuroleptics had substantial improvement of movements while inline skating (video at [Neurology.org][1]). She received pallidal deep brain stimulation (DBS), and gait and inline skating were assessed before and after DBS; her twin sister served as a control (figures 1 and 2). Possible explanations for her improvement include (1) balance stability required by inline skating provides external cues that are less prominent during gait1; and (2) dystonia consistently responds to geste antagoniste.2 Since TD has variable response to treatments, we propose research into alleviating factors in TD that may advance treatment and rehabilitation in this incapacitating disorder. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000004092

In this study, we used electrocorticographic (ECoG) signals to extract the onset of arm movement as well as the velocity of the hand as a function of time. ECoG recordings were obtained from three individuals while they performed reaching tasks in the left, right and forward directions. The ECoG electrodes were placed over the motor cortex contralateral to the moving arm. Movement onset was detected from gamma activity with near perfect accuracy (> 98%), and a multiple linear regression model was used to predict the trajectory of the reaching task in three-dimensional space with an accuracy exceeding 85%. An adaptive selection of frequency bands was used for movement classification and prediction. This demonstrates the efficacy of developing a real-time brain-machine interface for arm movements with as few as eight ECoG electrodes.

To prospectively evaluate the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the different characteristics of pain and other nonmotor symptoms (NMS) in patients with Parkinson disease (PD).Forty-four patients with PD and refractory motor symptoms were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. The primary outcome was change in pain prevalence after surgery. Secondary outcome measures were changes in motor function (Unified Parkinson's Disease Rating Scale), characteristics of pain and other NMS using specific scales and questionnaires, and quality of life.Forty-one patients completed the study. The prevalence of pain changed from 70% to 21% after surgery (p0.001). There were also significant improvements in pain intensity, NMS, and quality of life after STN-DBS (p0.05). Dystonic and musculoskeletal pain responded well to DBS, while central pain and neuropathic pain were not influenced by surgery. There was a strong correlation between the change in pain intensity and the improvement in quality of life (r = 0.708, p0.005). No correlation was found between pain improvement and preoperative response to levodopa or motor improvement during stimulation (r = 0.247, p = 0.197 and r = 0.249, p = 0.193, respectively) or with changes in other NMS.STN-DBS decreased pain after surgery, but had different effects in different types of PD-related pain. Motor and nonmotor symptom improvements after STN-DBS did not correlate with pain relief.This study provides Class IV evidence that in patients with idiopathic PD with refractory motor fluctuations, STN-DBS decreases the prevalence of pain and improves quality of life.

BACKGROUND Image distortion limits application of direct 3-T magnetic resonance imaging for stereotactic functional neurosurgery. OBJECTIVE To test the application of a method to correct and curtail image distortion of 3-T magnetic resonance images. METHODS We used a phantom head model mounted on a platform with the dimensions and features of a stereotactic frame. The phantom was scanned within the head coil of a Philips Achieva 3T X series (Philips Medical Systems, Eindhoven, the Netherlands). For each scan, 2 images were obtained-the normal and the reversed images. We applied the inverted gradient correction protocol to produce a corrected x, y, and z coordinates. We applied the Cronbach test or coefficient of reliability to assess the internal consistency of the data. RESULTS For all analyzed data, the P value was >.05, indicating that the differences among the observers were not statistically significant. Moreover, the data rectification proved to be effective, as the average distortion after correction was 1.05 mm. The distortion varied between 0.7 mm and 3.7 mm, depending on the target location. CONCLUSION This study examined a rectifying technique for correcting geometric distortion encountered in magnetic resonance images related to static field inhomogeneities (resonance offsets), and the technique proved to be highly successful in producing consistently accurate stereotactic target registration. The technique is applicable to all routinely used spin-echo MRI.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked adult-onset neurodegenerative disorder that affects carriers of the fragile X mental retardation 1 ( FMR1 ) gene premutation, which is a 55–200 CGG repeat expansion in the 5ʹ untranslated region of the gene.1 The core symptoms of FXTAS are progressive intention tremor and cerebellar ataxia. These symptoms can be disabling and, when combined, severely reduce the patient's quality of life. Symptomatic control with medication has limited effects.1 Very few cases have been treated with deep brain stimulation (DBS), mostly in the ventrointermediate thalamic (VIM) nucleus. This treatment results in tremor improvement with either no benefit or worsening of the ataxia and balance.2–4 We present a patient who experienced long-term tremor control and ataxia improvement after chronic bilateral stimulation of the ventro-oralis posterior thalamic nucleus and zona incerta (VoP/ZI), which resulted in significant improvement in daily life activities.

There has been renewed interest in decompressive craniectomy as a surgical treatment for elevated intracranial pressure (ICP), although evidence-based clinical data are still lacking and some experimental results are conflicting. Ongoing clinical trials on the use of this operation after traumatic brain injury (TBI) may clarify the clinical application of this technique, however, some pathophysiological issues, such as the timing of this operation, its effect on brain edema formation, and its role for secondary brain damage, are still controversial. This review addresses recent clinical data on the influence of decompressive craniectomy on the brain pathophysiology in TBI. Decompressive craniectomy with dural augmentation enlarges intracranial space so that the swollen cerebral hemisphere could expand out of normal cranial limits, avoiding progression of brain herniation. The gain in intracranial volume results in both the improvement of cerebral compliance and a decrease in ICP; the latter favors a rise in both cerebral blood flow and cerebral microvascular perfusion, which can be accompanied by elevation in brain tissue oxygen tension (PbtO2) as well as the return of abnormal metabolic parameters to normal values in cases of cerebral ischemia. Enhancement of edema formation, impairment of cerebrovascular pressure reactivity, and non-restoration of brain aerobic metabolism due to metabolic crisis may occur after craniectomy and require further investigations. This review suggests that decompressive craniectomy as the sole treatment is likely to be insufficient; efforts must be made to maintain adequate brain hemodynamics, preferably coupled with brain metabolism, in addition to treating brain metabolic abnormalities, during postoperative stages.

For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.

Posteroventral pallidotomy has already been considered the surgical procedure of choice for Parkinson's disease patients with motor complications. Recently, however, several factors led to its replacement by deep brain stimulation. Nevertheless, pallidotomy has a well-documented efficacy and safety evidence regarding the reduction of parkinsonian motor symptoms. Yet, there may be manysituations where it may be considered as a better option than neuromodulation. Herein we review those possible conditions, giving emphasis to the costs, which we found to be the most limiting factor. Importantly, a cost comparison between deep brain stimulation and pallidotomy was also provided.

Deep brain stimulation and levodopatherapy ameliorate motor manifestations in Parkinson's disease, but their effects on axial signs are not sustained in the long term.The objective of this study was to investigate the safety and efficacy of spinal cord stimulation on gait disturbance in advanced Parkinson's disease.A total of 4 Parkinson's disease patients who experienced significant postural instability and gait disturbance years after chronic subthalamic stimulation were treated with spinal cord stimulation at 300 Hz. Timed-Up-GO and 20-meter-walk tests, UPDRS III, freezing of gait questionnaire, and quality-of-life scores were measured at 6 months and compared to baseline values. Blinded assessments to measure performance in the Timed-Up-GO and 20-meter-walk tests were carried out during sham stimulation at 300 Hz and 60 Hz.Patients treated with spinal cord stimulation had approximately 50% to 65% improvement in gait measurements and 35% to 45% in UPDRS III and quality-of-life scores. During blinded evaluations, significant improvements in the Timed-Up-GO and 20-meter-walk tests were only recorded at 300 Hz.Spinal cord stimulation at 300 Hz was well tolerated and led to a significant improvement in gait. © 2016 International Parkinson and Movement Disorder Society.

Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD). This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson’s disease (WD) and in patients with WD with RBD.Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge.Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression.Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD.

The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson's disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off-medication condition with the stimulator turned on or off (on- and off-stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age-matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P=.019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off-stimulation condition. In the on-stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber-mediated sensations.

Background: Low back pain (LBP) is one of the most common and important health problems affecting the population worldwide and remains mostly unsolved. Ozone therapy has emerged as an additional treatment method. Questions persist concerning its clinical efficacy. Objective: The purpose of our study was to evaluate the therapeutic results of percutaneous injection of ozone for low back pain secondary to disc herniation. Study Design: A systematic review and meta-analysis of randomized controlled trials. Methods: A comprehensive literature search was conducted using all electronic databases from 1966 through September 2011. The quality of individual articles was assessed based on the modified Cochrane review criteria for randomized trials and criteria from the Agency for Healthcare Research and Quality. Outcome Parameters: The outcome measure was short-term pain relief of at least 6 months or long-term pain relief of more than 6 months. Results: Eight observational studies were included in the systematic review and 4 randomized trials in the meta-analysis. The indicated level of evidence for long-term pain relief was II-3 for ozone therapy applied intradiscally and II-1 for ozone therapy applied paravertebrally. The grading of recommendation was 1C for intradiscal ozone therapy and 1B for paravertebral ozone therapy. Limitations: The main limitations of this review are the lack of precise diagnosis and the frequent use of mixed therapeutic agents. The meta-analysis included mainly active-control trials. No placebo-controlled trial was found. Conclusions: Ozone therapy appears to yield positive results and low morbidity rates when applied percutaneously for the treatment of chronic low back pain. Key words: Low back pain, oxygen-ozone, ozone therapy, chronic pain, failed back surgery syndrome.

Summary Objective The authors show the clinical evaluation and follow-up results in 56 patients diagnosed with a failed back surgery pain syndrome. Methods Descriptive and prospective study conducted over a one-year period. In this study, 56 patients with a failed back surgery pain syndrome were assessed in our facility. The age ranged from 28 to 76 years (mean, 48.8 ± 13.9 years). The pain was assessed through a visual analog scale (VAS). Results Postoperative pain was more severe (mean VAS score 8.3) than preoperative pain (7.2). Myofascial pain syndromes (MPS) were diagnosed in 85.7% of patients; neuropathic abnormalities associated or not with MPS were found in 73.3%. Drug therapy associated with physical medicine treatment provided ≥ 50% pain improvement in 57.2% of cases; trigger point injection in 60.1%, and epidural infusion of morphine with lidocaina in 69.3% of refractory cases. Conclusion In patients with a post-laminectomy syndrome, postoperative pain was more severe than preoperative pain from a herniated disk. A miofascial component was found in most patients.

Single-session repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) is effective in the treatment of chronic pain patients, but the analgesic effect of repeated ses- sions is still unknown. We evaluated the effects of rTMS in patients with refractory pain due to com- plex regional pain syndrome (CRPS) type I. Twenty-three patients presenting CRPS type I of 1 upper limb were treated with the best medical treatment (analgesics and adjuvant medications, physical therapy) plus 10 daily sessions of either real (r-) or sham (s-) 10Hz rTMS to the motor cortex (M1). Patients were assessed daily and after 1 week and 3 months after the last session using the Visual Analogical Scale (VAS), the McGill Pain Questionnaire (MPQ), the Health Survey-36 (SF-36), and the Hamilton Depression (HDRS). During treatment there was a significant reduction in the VAS scores favoring the r-rTMS group, mean reduction of 4.65 cm (50.9%) against 2.18 cm (24.7%) in the s-rTMS group. The highest reduction occurred at the tenth session and correlated to improvement in the affective and emotional subscores of the MPQ and SF-36. Real rTMS to the M1 produced anal- gesic effects and positive changes in affective aspects of pain in CRPS patients during the period of stimulation. Perspective: This study shows an efficacy of repetitive sessions of high-frequency rTMS as an add-on therapy to refractory CRPS type I patients. It had a positive effect in different aspects of pain (sensory-discriminative and emotional-affective). It opens the perspective for the clinical use of this technique.

INTRODUCTION: Current advances in frame modeling and computer software allow stereotactic procedures to be performed with great accuracy and minimal risk of neural tissue or vascular injury. CASE REPORT: In this report we associate a previously described minimally invasive stereotactic technique with state-of-the-art 3D computer guidance technology to successfully treat a 55-year-old patient with an arachnoidal cyst obstructing the aqueduct of Sylvius. We provide detailed technical information and discuss how this technique deals with previous limitations for stereotactic manipulation of the aqueductal region. We further discuss current advances in neuroendoscopy for treating obstructive hydrocephalus and make comparisons with our proposed technique. CONCLUSION: We advocate that this technique is not only capable of treating this pathology but it also has the advantages to enable reestablishment of physiological CSF flow thus preventing future brainstem compression by cyst enlargement.

This article describes the case of a 67-year-old woman who presented with a typical left hemifacial spasm of 8-month duration. After 2 months, she experienced lacinating and sharp shock-like pain in the left side of her face affecting the V1 and V2 territories and a discrete attenuation of nauseous reflex on the left side. CT angiography and MRI revealed significant compression of left cranial nerves V, VII, VIII, IX and X by a giant and tortuous vertebro-basilar arterial complex. This case illustrates the nonlinearity of the relationship between the presence of the stressor factor and the actual manifestation of the disease.

Cerebral microdialysis is a chemical detection method capable of identifying and simultaneously sampling a wide range of substances in the micromilieu of the monitoring probe. The interstitial space of biological tissues and fluids is sampled through a thin fenestrated dialysis catheter inserted into the brain. The technique has been reported in patients with Parkinson's disease. However, the procedure is not widely used by neurosurgeons, possibly owing to unclear indications and poor effective benefits, mostly secondary to significant pitfalls. In spite of the feasibility of microdialysis in humans, many factors can affect the quality of the process. Possible pitfalls include improperly designed probe, probe insertion effects, ineffective perfusion rate, issues to optimize stabilization period, and insufficient volume sample. This article reviews those key technical features necessary for performing microdialysis in humans during deep brain stimulation for Parkinson's Disease.

OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional stereotactic procedures.

Gliomas are the most common type among all central nervous system tumors. The aggressiveness of gliomas is correlated with the level of angiogenesis and is often associated with prognosis. The aim of this study is to evaluate the novel GX1 peptide and the heterodimer RGD-GX1 radiolabeled with technetium-99m, for angiogenesis detection in glioma models. Radiolabeling and radiochemical controls were assessed for both radioconjugates. In vitro binding studies in glioma tumor cells were performed, as well as biodistribution in SCID mice bearing tumor cells, in order to evaluate the biological behavior and tumor uptake of the radiocomplexes. Blocking and imaging studies were also conducted. MicroSPECT/CT images were acquired in animals with experimentally implanted intracranial tumor. Open field activity was performed to evaluate behavior, as well as perfusion and histology analysis. The radiochemical purity of both radiotracers was greater than 96 %. In vitro binding studies revealed rather similar binding profi le for each molecule. The highest binding was for RGD-GX1 peptide at 120 min in U87MG cells (1.14 ± 0.35 %). Tumor uptake was also favorable for RGD-GX1 peptide in U87MG cells, reaching 2.96 ± 0.70 % at 1 h p.i. with 47 % of blocking. Imaging studies also indicated better visualization for RGD-GX1 peptide in U87MG cells. Behavior evaluation pointed brain damage and histology studies confirmed actual tumor in the uptake site. The results with the angiogenesis seeking molecule (99m)Tc-HYNIC-E-[c(RGDfk)-c(GX1)] were successful, and better than with (99m)Tc-HYNIC-PEG4-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended.

Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain in PD and to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain in PD and the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms. PD patients have altered sensory and pain thresholds in the off-medication state. Both levodopa and DBS improve motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non-motor symptoms do not necessarily share the same mechanisms. Whether dopamine and DBS have a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism-based approach to pain in PD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related to PD before specific treatment can be instituted.

A 48-year-old man developed numbness in the left leg, which progressed gradually to paresis and urinary incontinence. Neurologic examination revealed a left Brown-Sequard syndrome with leg paresis, mild spasticity, reduced proprioception, and contralateral thermal and painful hypoesthesia below T6. MRI revealed a thoracic spinal cord herniation (SCH) (figure). Idiopathic SCH is relatively rare. Pathogenesis involves a dura mater defect (see video on the Neurology ® Web site at [Neurology.org][1]); herniation develops over a progressive pressure gradient through the dural fissure.2 Surgical reduction is typically performed if symptoms progress, but mild symptoms may be eligible for conservative treatment and monitoring. Surgical spinal reduction and dural repair usually reverses neurologic deficits. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000002886

Summary Background Vocal impairment is one of the main debilitating symptoms of Parkinson disease (PD). The effect of levodopa on vocal function remains unclear. Objective This study aimed to determine the effect of levodopa on electromyographic patterns of the laryngeal muscle in patients with PD. Study design This is a prospective interventional trial. Methods Nineteen patients with PD—diagnosed by laryngeal electromyography—were enrolled. Cricothyroid and thyroarytenoid (TA) muscle activities were measured at rest and during muscle contraction (phonation), when participants were on and off medication (12 hours after the last levodopa dose). Results Prevalence of resting hypertonia in the cricothyroid muscle was similar in the off and on states (7 of 19, P = 1.00). Eight patients off medication and four patients on medication had hypertonic TA muscle at rest ( P = 0.289). No electromyographic alterations were observed during phonation for either medication states. Conclusion Despite a tendency for increased rest tracings in the TA muscle when participants were on medication, no association was found between laryngeal electromyography findings and levodopa + carbidopa administration.