Globus pallidus internus neuronal activity: a comparative study of linear and non-linear features in patients with dystonia or Parkinson's disease.

Movement disorders such as Parkinson's disease (PD) and dystonia are associated with alterations of basal ganglia motor circuits and abnormal neuronal activity in the output nucleus, the globus pallidus internus (GPi). This study aims to compare the electrophysiological hallmarks for PD and dystonia in the linear and non-linear time stamp domains in patients who underwent microelectrode recordings during functional stereotactic surgery for deep brain stimulation (DBS) or pallidotomy. We analyzed single-unit neuronal activity in the posteroventral lateral region of the GPi in awake patients prior to pallidotomy or the implantation of DBS electrodes in 29 patients with PD (N = 83 neurons) and 13 patients with dystonia (N = 41 neurons) under comparable conditions. The discharge rate and the instantaneous frequency of the GPi in dystonia patients were significantly lower than in PD patients (P < 0.001), while the total number of bursts, the percentage of spikes in bursts and the mean duration of bursts were higher (P < 0.001). Further, non-linear analysis revealed higher irregularity or entropy in the data streams of GPi neurons of PD patients compared to the dystonia patients group (P < 0.001). This study indicates that both linear and non-linear features of neuronal activity in the human GPi differ between PD and dystonia. Our results may serve as the basis for future studies on linear and non-linear analysis of neuronal firing patterns in various movement disorders.

Relationships and redundancies of selected hemodynamic and structural parameters for characterizing virtual treatment of cerebral aneurysms with flow diverter devices.

BACKGROUND AND PURPOSE: To quantify the relationship and to demonstrate redundancies between hemodynamic and structural parameters before and after virtual treatment with a flow diverter device (FDD) in cerebral aneurysms. METHODS: Steady computational fluid dynamics (CFD) simulations were performed for 10 cerebral aneurysms where FDD treatment with the SILK device was simulated by virtually reducing the porosity at the aneurysm ostium. Velocity and pressure values proximal and distal to and at the aneurysm ostium as well as inside the aneurysm were quantified. In addition, dome-to-neck ratios and size ratios were determined. Multiple correlation analysis (MCA) and hierarchical cluster analysis (HCA) were conducted to demonstrate dependencies between both structural and hemodynamic parameters. RESULTS: Velocities in the aneurysm were reduced by 0.14m/s on average and correlated significantly (p<0.05) with velocity values in the parent artery (average correlation coefficient: 0.70). Pressure changes in the aneurysm correlated significantly with pressure values in the parent artery and aneurysm (average correlation coefficient: 0.87). MCA found statistically significant correlations between velocity values and between pressure values, respectively. HCA sorted velocity parameters, pressure parameters and structural parameters into different hierarchical clusters. HCA of aneurysms based on the parameter values yielded similar results by either including all (n=22) or only non-redundant parameters (n=2, 3 and 4). CONCLUSION: Hemodynamic and structural parameters before and after virtual FDD treatment show strong inter-correlations. Redundancy of parameters was demonstrated with hierarchical cluster analysis.

Rationale, design and critical end points for the Riluzole in Acute Spinal Cord Injury Study (RISCIS): a randomized, double-blinded, placebo-controlled parallel multi-center trial.

BACKGROUND: Riluzole is a sodium channel-blocking agent used in treating amyotrophic lateral sclerosis. It has been approved by the U.S. Food and Drug Administration, Canadian and Australian authorities, and in many other countries. A phase I trial of riluzole for acute spinal cord injury (SCI) provided safety and pharmacokinetic data and suggested neuroprotective benefits. A phase IIB/III double-blinded randomized controlled trial (RCT) started in January 2014 (https://clinicaltrials.gov, NCT01597518). This article describes the pathophysiological rationale, preclinical experience and design of the phase IIB/III RCT of Riluzole in Acute Spinal Cord Injury Study (RISCIS). OBJECTIVES: The primary objective of the trial is to evaluate the superiority of riluzole, at a dose of 100 mg BID in the first 24 h followed by 50 mg BID for the following 13 days post injury, compared with placebo in improving neurological motor outcomes in patients with C4-C8 level, International Standards for Neurological Classification of Spinal Cord Injury Examination (ISNCSCI) grade A, B or C acute (within 12 h post injury) SCI. SETTING: Acute trauma centers worldwideMethods:A double-blind, multi-center, placebo-controlled RCT will enroll 351 participants randomized 1:1 to riluzole and placebo. The primary end point is the change between 180 days and baseline in ISNCSCI Motor Score. This study has 90% power to detect a change of nine points in ISNCSCI Motor Score at one-sided α=0.025. RESULTS: Currently enrolling in 11 centers. CONCLUSION: This study will provide class I evidence regarding the safety and neuroprotective efficacy of riluzole in patients with acute cervical SCI.

Quantitative comparison of hemodynamic parameters from steady and transient CFD simulations in cerebral aneurysms with focus on the aneurysm ostium.

OBJECTIVE: To quantitatively compare hemodynamics simulated with steady-state and transient computational fluid dynamics (CFD) simulations in cerebral aneurysms with single inflow, with focus at the aneurysm ostium. METHODS: Transient and steady-state CFD simulations were performed in 10 cerebral aneurysms. Distributions and average values for pressure, helicity, vorticity, and velocity were qualitatively compared at proximal and distal parent artery locations, at the ostium plane, and in the aneurysm, and scaling factors between the two kinds of simulations were determined. Relative inflow and outflow areas at the ostium were compared, as were average inflow and outflow velocities. In addition, values for the pressure-loss coefficient (PLC), a recently introduced parameter to assess aneurysm rupture risk, were compared for both kinds of simulation. RESULTS: Distributions of hemodynamic parameters had a similar shape but were lower for transient than for steady-state simulations. Averaged scaling factors over cases and anatomical locations showed differences for hemodynamic parameters (0.485 ± 0.01 for pressure, 0.33 ± 0.02 for helicity, 0.58 ± 0.06 for vorticity and 0.56 ± 0.04 for velocity). Good agreement between ratios of inflow and outflow areas at the aneurysm ostium was obtained (Pearson correlation coefficient >0.97, p<0.001) and for the PLC (linear regression slope 0.73 ± 0.14, R(2)=0.75). CONCLUSIONS: Steady-state simulations are a quick alternative to transient simulation for visualizing and quantifying inflow and outflow areas at the aneurysm ostium, potentially of value when planning flow diverter treatment and for quantifying the PLC, a potential indicator of aneurysm rupture.

Predictors of individual visual memory decline after unilateral anterior temporal lobe resection.

BACKGROUND: Different types of neuropsychological visual memory tasks have been created to quantify deficits associated with right hemisphere dysfunction. There are reports of visual memory impairment after right anterior temporal lobe resection (ATR) compared to left ATR for the processing of faces, abstract designs, and spatial locations, but there are also studies showing no between-group differences. One potential reason for the conflicting results is the use of group mean changes, which mask individual differences. METHODS: Proportions of individual subjects with decline, no change, or improvement in memory for spatial locations, abstract designs, and unfamiliar faces were evaluated in 83 individuals who underwent a standard ATR (47 right, 36 left) and were left hemisphere language dominant. RESULTS: Type of visual memory ability was an important factor as there were differential individual declines found for memory for spatial locations after right ATR compared to left ATR (27.3% vs 5.9%), but not memory for abstract designs or face memory. Logistic regression indicated that the odds of a spatial memory decline were six times higher for patients who underwent right ATR than left ATR. CONCLUSIONS: Memory for spatial locations appears to be particularly vulnerable to decline when a patient undergoes right-anterior temporal lobe resection (ATR) and when the patient has better spatial memory before surgery. Results provide proportions of subjects with significant change to help clinicians and patients make better informed decisions about risks associated with undergoing right ATR.

Short and long-term motor and cognitive outcome of staged bilateral pallidotomy: a retrospective analysis.

BACKGROUND: We investigated retrospectively the short and long-term motor and cognitive functioning of staged bilateral pallidotomy using motor testing and a comprehensive neuropsychological battery before and after each procedure. METHODS: Fifteen patients with idiopathic Parkinson's disease were assessed at baseline and at least 3 months after each of their two staged surgeries. Motor and neuropsychological results were compared to 15 non-surgical Parkinson's disease patients matched for disease stage and mental status. In addition, nine bilateral pallidotomy patients were evaluated for long-term cognitive changes (>2 years). FINDINGS: Bilateral pallidotomy patients demonstrated significant improvements in motor functioning in the "on" and "off" states and with dyskinesias after the first surgery, with an additional improvement reported for dyskinesias after the second procedure. On long-term follow-up, dyskinesia improvements were maintained. Bilateral pallidotomy patients did not show significant cognitive declines following both procedures on the short-term follow-up and when compared to the Parkinson's disease group. However, significant cognitive declines were found on the long-term follow-up evaluation. CONCLUSIONS: Parkinson's disease patients received significant short- and long-term motor benefits, particularly reduced dyskinesias, following staged bilateral pallidotomy without significant short-term cognitive consequences. Two years following the second procedure, bilateral pallidotomy patients tended to show an increase in both motor and non-motor symptoms of Parkinson's disease, particularly cognitive decline.

Ischemic injury and faulty gene transcripts in the brain.

The brain has the highest metabolic rate of all organs and depends predominantly on oxidative metabolism as a source of energy. Oxidative metabolism generates reactive oxygen species, which can damage all cellular components, including protein, lipids and nucleic acids. The processes of DNA repair normally remove spontaneous gene damage with few errors. However, cerebral ischemia followed by reperfusion leads to elevated oxidative stress and damage to genes in brain tissue despite a functional mechanism of DNA repair. These critical events occur at the same time as the expression of immediate early genes, the products of which trans-activate late effector genes that are important for sustaining neuronal viability. These findings open the possibility of applying genetic tools to identify molecular mechanisms of gene repair and to derive new therapies for stroke and brain injury.

Comparison of thalamotomy and pallidotomy for the treatment of dystonia.

OBJECTIVE: Thalamotomy and, more recently, pallidotomy have been used to treat selected patients with intractable dystonia, although few studies have compared the effectiveness of these two surgical procedures. In this study, we compare our results using thalamotomy and pallidotomy to treat patients with different forms of dystonia, and we discuss our results in the context of other published series. METHODS: Thirty-two patients with intractable dystonia underwent thalamotomy (n = 18) or pallidotomy (n = 14). Dystonia was classified according to cause and distribution, and each patient was evaluated postoperatively at two or more time points, using a global outcome scale. RESULTS: Although comparisons are limited by differences between the two surgical groups, including longer follow-up periods for the thalamotomy group, differences in symptom distribution, and more bilateral procedures for the pallidotomy group, patients with primary dystonia who underwent pallidotomies demonstrated significantly better long-term outcomes than did patients who underwent thalamotomies (P = 0.0467). Patients with secondary dystonia experienced more modest improvements after either procedure, with little or no difference in outcomes between the two procedures. CONCLUSION: For patients with primary dystonia, pallidotomy seems to result in better outcomes than does thalamotomy.

Aneurysms of the posterior cerebral artery: classification and endovascular treatment.

BACKGROUND AND PURPOSE: We present a retrospective review of our experience in the endovascular treatment of posterior cerebral artery (PCA) aneurysms. We detail the anatomic location of these aneurysms, the technique of endovascular treatment, morphologic results, and clinical outcome. We also discuss the segmental anatomy of the PCA as it relates to the various neurologic deficits that may result from occlusion of the parent artery. METHODS: From 1993 to 1998, 20 patients (12 female, eight male; mean age, 44 yrs) harboring a PCA aneurysm were treated via an endovascular approach. One patient had two aneurysms, comprising a total of 21 lesions. Fourteen (66%) of 21 aneurysms were saccular in nature, five (24%) were giant serpentine aneurysms, and two (10%) were posttraumatic. All aneurysms were treated using Guglielmi detachable coils (GDC) either by selective obliteration of the aneurysm sac or by parent artery occlusion. RESULTS: Fourteen (66%) of the 21 aneurysms were successfully treated with preservation of the parent artery. In the remaining seven (33%), the parent artery was permanently occluded. The overall complication rate in this series was 15%, with a permanent morbidity rate of 10% and a 0% mortality rate. CONCLUSION: Aneurysms of the PCA are rare compared with other locations in the intracranial circulation. Saccular PCA aneurysms can be treated effectively, by use of GDC, to obliterate the aneurysm yet preserve the parent artery. Fusiform and giant serpentine aneurysms of the PCA can effectively be treated by permanent occlusion of the parent artery; in these cases, thorough knowledge of the PCA segmental anatomy is crucial in order to select the site of occlusion and to avoid major neurologic deficits.

Long-term efficacy of posteroventral pallidotomy in the treatment of Parkinson's disease.

The authors describe results of unilateral posteroventral pallidotomy (PVP) in 89 patients with PD. At 3 months after surgery, 81.9% of the patients reported marked or moderate improvement in their parkinsonian symptoms. Postoperative Unified PD Rating Scale "off" state mean total motor score improved by 35.5% and the mean activities of daily living score by 33.7% (p <0.001). Improvements in parkinsonian symptoms were maintained in both"off" and "on" states in 62 patients at 12 months after PVP and in 41 patients who were followed for 18 months or longer (mean 26.6 months).

Corpora amylacea and heat shock protein 27 in Ammon's horn sclerosis.

Increased numbers of corpora amylacea have been observed in the resected mesial temporal lobe of many patients with complex partial seizures (CPS) and Ammon's horn sclerosis (AHS). Several heat shock proteins (HSPs) are induced by seizures and have been suggested as an etiologic factor in the formation corpora amylacea. We quantified corpora amylacea and HSP27-immunoreactive astrocytes in temporal lobe specimens from patients with CPS (28 AHS; 10 non-AHS) and in 5 autopsy controls. Corpora amylacea were increased in each sector of Ammon's horn in the AHS group, significantly so in CA1 and CA3 (p < 0.0001 and p = 0.0097, respectively), compared with the non-AHS group, although there was considerable variability among the specimens. We found HSP27 to be significantly but nonspecifically increased in the resected temporal lobe specimens from all patients with CPS, regardless of the underlying pathology. HSP27 was not, however, expressed within the corpora amylacea, and did not correlate with the number of corpora amylacea in any of the 9 mesial and lateral temporal lobe areas examined.

Neuropsychological outcome after unilateral pallidotomy for the treatment of Parkinson's disease.

OBJECTIVE: To assess the long term cognitive outcome of unilateral posteroventral pallidotomy (PVP) and the overall efficacy of the surgery. METHODS: Forty two (29 left and 13 right PVP) patients with Parkinson's disease underwent neurological and neuropsychological testing before PVP and at 3 and 12 months after PVP. The neuropsychological testing battery emphasised measures of verbal learning and memory, visuospatial abilities, speed of information processing, executive functioning, and affective functioning. RESULTS: All patients demonstrated motor improvements after surgery during their off state, and 86% of patients also showed improvements in motor functioning in their on state. Repeated measures ANOVA showed significant improvements in confrontational naming, visuospatial organisation, and affective functioning 3 months and 12 months after surgery, with inconsistent improvements in executive functioning 12 months post-PVP. Patients demonstrated a transient impairment in verbal memory, with verbal learning performance returning to baseline 12 months post-PVP after a significant decline 3 months after PVP. When three patients with lesions extending outside of the PVP were excluded from the analysis, a decline in verbal fluency performance after PVP was not found to be significant. Differences due to side of lesion placement were not found on any of the cognitive measures. CONCLUSIONS: In the largest long term follow up study reported to date, the cognitive changes found up to a year after PVP are minimal compared with the robust improvements in motor function. The findings highlight the need to investigate the relation between the specific fibre tracts affected by the lesions and cognitive outcome.

Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors.

Between December 1996 and September 1998, 13 patients with advanced recurrent malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3 with anaplastic astrocytoma) were treated with a single intratumoral injection of 2 x 10(9), 2 x 10(10), 2 x 10(11), or 2 x 10(12) vector particles (VP) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was 20:1. Our primary objective was to determine the safety of this treatment. Injection of Adv.RSVtk in doses <==2 x 10(11) VP, followed by GCV, was safely tolerated. Patients treated with the highest dose, 2 x 10(12) VP, exhibited central nervous system toxicity with confusion, hyponatremia, and seizures. One patient is living and stable 29.2 months after treatment. Two patients survived >25 months before succumbing to tumor progression. Ten patients died within 10 months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis. Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site, intratumoral foci of coagulative necrosis, and variable infiltration of the residual tumor with macrophages and lymphocytes.

Neuropsychological outcome following unilateral pallidotomy.

Despite the findings of significantly improved motor functioning following pallidotomy for the treatment of Parkinson's disease, the cognitive sequelae following surgery have yet to be clearly defined. With increasing knowledge of the surgery's effect on frontostriatal circuits, the cognitive processes potentially affected by the procedure require further exploration to evaluate fully the efficacy of the treatment. We reviewed 10 studies on the neuropsychological outcome after pallidotomy that were published in peer-reviewed journals. A general agreement exists that pallidotomy is a relatively safe and effective treatment for ameliorating the motor symptoms of Parkinson's disease, with relatively few cognitive changes reported following surgery. However, a number of conceptual and methodological concerns, including diverse selection criteria, small sample sizes and short follow-up periods, limit the interpretation and generalizability of these findings. These concerns are discussed in detail, along with a summary of the current neuropsychological literature, suggested guidelines for the conduct of research and future research directions. The neuropsychological findings are critically reviewed and tabulated by study, cognitive domain and follow-up period, with particular emphasis on hemisphere-specific cognitive changes.

Prevention of secondary ischemic insults after severe head injury.

OBJECTIVE: The purpose of this study was to compare the effects of two acute-care management strategies on the frequency of jugular venous desaturation and refractory intracranial hypertension and on long-term neurologic outcome in patients with severe head injury. DESIGN: Randomized clinical trial. SETTING: Level I trauma hospital. PATIENTS: One hundred eighty-nine adults admitted in coma because of severe head injury. INTERVENTIONS: Patients were assigned to either cerebral blood flow (CBF)-targeted or intracranial pressure (ICP)-targeted management protocols during randomly assigned time blocks. In the CBF-targeted protocol, cerebral perfusion pressure was kept at >70 mm Hg and PaCO2 was kept at approximately 35 torr (4.67 kPa). In the ICP-targeted protocol, cerebral perfusion pressure was kept at >50 mm Hg and hyperventilation to a PaCO2 of 25-30 torr (3.33-4.00 kPa) was used to treat intracranial hypertension. MEASUREMENTS AND MAIN RESULTS: The CBF-targeted protocol reduced the frequency of jugular desaturation from 50.6% to 30% (p = .006). Even when the frequency of jugular desaturation was adjusted for all confounding factors that were significant, the risk of cerebral ischemia was 2.4-fold greater with the ICP-targeted protocol. Despite the reduction in secondary ischemic insults, there was no difference in neurologic outcome. Failure to alter long-term neurologic outcome was probably attributable to two major factors. A low jugular venous oxygen saturation was treated in both groups, minimizing the injury that occurred in the ICP-targeted group. The beneficial effects of the CBF-targeted protocol may have been offset by a five-fold increase in the frequency of adult respiratory distress syndrome. CONCLUSIONS: Secondary ischemic insults caused by systemic factors after severe head injury can be prevented with a targeted management protocol. However, potential adverse effects of this management strategy may offset these beneficial effects.