Search

Objective: The objective of this study was to determine whether three common genetic polymorphisms [apolipoprotein (APOE) ε4 (rs42938 and rs7412), brain derived neurotrophic factor (BDNF) Met (rs6265), and catechol-O-methyltransferase (COMT) Val (rs4680)] are associated with increased psychiatric symptomatology in individuals with pharmacoresistant epilepsy., Methods: One hundred forty-eight adults (M age  = 38 years; 53% female) with refractory epilepsy completed self-report measures of mood, anxiety, and/or personality/psychopathology. Mann-Whitney U, t-tests, and Fisher's exact tests were used to determine if APOE4, BDNF Val66Met, or COMT Val158Met are associated with increased psychiatric symptomatology in people with epilepsy., Results: As a group, BDNF Met carriers reported greater symptoms of depression on the Personality Assessment Inventory (PAI) than those without a Met allele (p = 0.004); COMT Val carriers reported greater symptoms on the PAI Schizophrenia (p = 0.007), Antisocial Features (p = 0.04), and Alcohol Problems (p = 0.03) scales than noncarriers. On the individual level, a significantly greater proportion of BDNF Met carriers demonstrated elevated PAI Depression scores compared to those without a Met allele (p = 0.046). There was also a larger proportion of COMT Val carriers with elevated PAI Anxiety scores as compared to those without a Val allele (p = 0.036)., Significance: This retrospective cross-sectional study provides preliminary evidence for a genetic basis of psychiatric comorbidities in epilepsy and suggests that BDNF and COMT may play an important role in the pathophysiology of mental health problems in this vulnerable population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A fundamental challenge in the clinical care of Parkinson disease (PD) is the current dependence on subjective evaluations of tremor and bradykinesia. New technologies offer the ability to evaluate motor deficits using purely objective measures. The aim of this study was to develop and evaluate the efficacy of a wireless stylus (Cleveland Clinic Stylus) with an embedded motion sensor to quantitatively assess tremor and bradykinesia in patients with PD with subthalamic nucleus (STN) deep brain stimulation (DBS). Twenty-one subjects were tested in various on and off DBS conditions while holding the Cleveland Clinic Stylus while at rest, maintaining a postural hold, and during a movement task. Kinematic metrics were calculated from the motion sensor data, including 3D angular velocity and 3D acceleration data, and were compared between the on and off conditions. Generalized estimating equations (GEEs) were used to determine the relationship between kinematic metrics and MDS-Unified Parkinson's Disease Rating Scale Motor III (UPDRS-III) subscores. Kinematic metrics from the rest and postural tasks were significantly related to the UPDRS-III subscores of tremor ( p < 0.001 for all metrics), and kinematic metrics from the movement task were significantly related to the UPDRS-III subscore of bradykinesia ( p < 0.001 for 3/7 metrics). Kinematic metrics (7/9) showed a significant effect of stimulation setting (range: p < 0.03- < 0.0001) across the three tasks, indicating significant improvements from DBS in these measures. The Cleveland Clinic Stylus provided quantitative kinematic measures of tremor and bradykinesia severity and detected significant improvements in these measures from medication and DBS therapy. This low-cost, easy-to-use tool can provide objective measures that will improve clinical care of PD patients by providing a more reliable and objective evaluation of movement symptoms, disease progression, and effects of therapy in and outside the clinical setting.

Objective: To examine the convergent and discriminant validity of two brief computerized episodic memory measures in a large, diverse clinical sample of adults undergoing neuropsychological assessment., Method: Computerized measures of word and face memory were administered to 233 adults (age 30 and over) who also completed comprehensive neuropsychological testing., Results: Moderate correlations were observed between the computerized memory tests and a wide range of traditional neuropsychological measures of episodic memory (e.g. word-list learning, story recall, face recognition, design recall). Select measures of visuomotor processing speed and language were also related to performance on the computerized tasks. In contrast, the computerized memory tests showed weak correlations with tests in other cognitive domains (i.e. visuospatial skills, attention/working memory, executive function, motor dexterity, academic skills) and self-report screening measures of mood and anxiety. Similar to traditional measures of episodic memory, the computerized memory measures were sensitive to effects of age and gender., Conclusions: Computerized measures of word and face memory showed good convergent and discriminant validity in this diverse clinical sample supporting the construct validity of these measures. This indicates that it may be feasible to measure memory function in clinical settings using brief, well-designed computerized memory measures.

Background: Deformity reconstruction surgery has been shown to improve quality of life (QOL) in cases of adult spinal deformity (ASD) but is associated with significant morbidity., Objective: To create a preoperative predictive nomogram to help risk-stratify patients and determine which would likely benefit from corrective surgery for ASD as measured by patient-reported health-related quality of life (HRQoL)., Methods: All patients aged 25-yr and older with radiographic evidence of ASD and QOL data that underwent thoracolumbar fusion between 2008 and 2014 were identified. Demographic and clinical parameters were obtained. The EuroQol 5 dimensions questionnaire (EQ-5D) was used to measure HRQoL preoperatively and at 12-mo postoperative follow-up. Logistic regression of preoperative variables was used to create the prognostic nomogram., Results: Our sample included data from 191 patients. Fifty-one percent of patients experienced clinically relevant postoperative improvement in HRQoL. Seven variables were included in the final model: preoperative EQ-5D score, sex, preoperative diagnosis (degenerative, idiopathic, or iatrogenic), previous spinal surgical history, obesity, and a sex-by-obesity interaction term. Preoperative EQ-5D score independently predicted the outcome. Sex interacted with obesity: obese men were at disproportionately higher odds of improving than nonobese men, but obesity did not affect odds of the outcome among women. Model discrimination was good, with an optimism-adjusted c-statistic of 0.739., Conclusion: The predictive nomogram that we developed using these data can improve preoperative risk counseling and patient selection for deformity correction surgery., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Objective: Providing durable long-term pain control for patients with complex regional pain syndrome (CRPS) is challenging. A multidisciplinary approach focused on physical therapy is frequently prescribed, with opioids and invasive procedures reserved for those challenged by functional progression. In this study, we examined the long-term efficacy of intrathecal drug delivery systems (IDDS) in patients with CRPS at our institution., Methods: Patients with CRPS implanted with an IDDS between 2000 and 2013 who had four or more years of continuous follow-up were included in the analysis. The outcome variables of interest were pain intensity and oral opioid intake. The primary predictor of interest was dose of intrathecal opioids, with ziconotide, bupivacaine, and clonidine characterized as binary secondary predictors., Results: Of the 1,653 IDDS identified, 62 were implanted primarily for CRPS-related pain. Of these, 26 had four or more years of complete follow-up data. Pain scores did not significantly decrease over time, and we observed no correlation between pain intensity and use of any intrathecal medication. Although oral opioid intake decreased over time, intrathecal opioid dose did not affect oral opioid consumption. Ziconotide was associated with a hastening of the decrease in oral opioid intake, whereas the presence of bupivacaine paradoxically increased oral opioid intake., Conclusions: Our study demonstrates that intrathecal opioid dose was not associated with long-term decreases in oral opioid intake. Additionally, ziconotide was associated with a decrease in oral opioid intake over the four-year follow-up, and bupivacaine was associated with an increase in oral opioid intake. Our study examines the long-term effectiveness of intrathecal medications in managing pain in patients with complex regional pain syndrome. We present a detailed follow-up over four years for 26 patients, tracking oral opiate intake, pain scores, and intrathecal pump settings. Our findings suggest that intrathecal opiates may not be effective in reducing oral opiate intake, ziconotide may hasten a decrease in intake, and bupivacaine may lead to an increase in intake., (© 2018 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Research in human caregiving shows burden is often present in the caregiver and can be reduced by interventions that increase positive perceptions of caregiving. Recent work suggests burden is also present in owners of a seriously ill companion animal. To help determine if findings from the human caregiving literature are likely to generalize to companion animal caregiving, we undertook a comparison of burden and positive aspects of caregiving in these groups. Material and Methods: Caregivers recruited through social media disease support and information groups completed self-report questionnaires of burden and positive aspects of caregiving in an online research protocol. Owners of a seriously ill companion animal ( n = 117) and caregivers of a family member with dementia ( n = 252) were cross-sectionally compared. Analyses in the full sample were repeated in a subset ( n = 75 per group) of caregivers with blindly matched demographic profiles. Results: Burden was elevated in both dementia and companion animal caregiver groups, though higher overall for dementia caregivers ( p < 0.001 for full and matched samples). In contrast, greater positive aspects of caregiving were reported by companion animal caregivers ( p < 0.001 for full and matched samples). In both groups, positive aspects of caregiving were negatively associated with burden (full sample p < 0.001; matched sample p < 0.05). Exploratory item analyses suggested the two groups show comparable experiences of fearing the future, guilt, and financial strain ( p = ns for full and matched sample). Discussion: Although both groups showed elevated burden, companion animal caregivers reported less burden and a more positive appraisal of caregiving. Elements of burden showing similarities across groups provide a foundation for understanding caregiver burden in the companion animal owner. The inverse correlation between positive aspects of caregiving and burden suggests the impact of positive caregiving experiences should be considered in burden interventions, but because companion animal owners already positively appraise caregiving, enhancing positive aspects of caregiving may not offset burden as it does in human caregiving samples.

Objective: To develop and externally validate models to predict the probability of postoperative naming decline in adults following temporal lobe epilepsy surgery using easily accessible preoperative clinical predictors., Methods: In this retrospective, prediction model development study, multivariable models were developed in a cohort of 719 patients who underwent temporal lobe epilepsy surgery at Cleveland Clinic and externally validated in a cohort of 138 patients who underwent temporal lobe surgery at one of 3 epilepsy surgery centers in the United States (Columbia University Medical Center, Emory University School of Medicine, University of Washington School of Medicine)., Results: The development cohort was 54% female with an average age at surgery of 36 years (SD 12). Twenty-six percent of this cohort experienced clinically relevant postoperative naming decline. The model included 5 variables: side of surgery, age at epilepsy onset, age at surgery, sex, and education. When applied to the external validation cohort, the model performed very well, with excellent calibration and a c statistic (reflecting discriminatory ability) of 0.81. A second model predicting moderate to severe postoperative naming decline included 3 variables: side of surgery, age at epilepsy onset, and preoperative naming score. This model generated a c statistic of 0.84 in the external validation cohort and showed good calibration., Conclusion: Externally validated nomograms are provided in 2 easy-to-use formats (paper version and online calculator) clinicians can use to estimate the probability of naming decline in patients considering epilepsy surgery for treatment of pharmacoresistant temporal lobe epilepsy., (© 2018 American Academy of Neurology.)

Objective: To create a multivariable model to predict early cognitive decline among de novo patients with Parkinson's disease, using brief, inexpensive assessments that are easily incorporated into clinical flow., Methods: Data for 351 drug-naïve patients diagnosed with idiopathic Parkinson's disease were obtained from the Parkinson's Progression Markers Initiative. Baseline demographic, disease history, motor, and non-motor features were considered as candidate predictors. Best subsets selection was used to determine the multivariable baseline symptom profile that most accurately predicted individual cognitive decline within three years., Results: Eleven per cent of the sample experienced cognitive decline. The final logistic regression model predicting decline included five baseline variables: verbal memory retention, right-sided bradykinesia, years of education, subjective report of cognitive impairment, and REM behavior disorder. Model discrimination was good (optimism-adjusted concordance index = .749). The associated nomogram provides a tool to determine individual patient risk of meaningful cognitive change in the early stages of the disease., Conclusions: Through the consideration of easily-implemented or routinely-gathered assessments, we have identified a multidimensional baseline profile and created a convenient, inexpensive tool to predict cognitive decline in the earliest stages of Parkinson's disease. The use of this tool would generate prediction at the individual level, allowing clinicians to tailor medical management for each patient and identify at-risk patients for clinical trials aimed at disease modifying therapies., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Many traumatic brain injury (TBI) survivors live with persistent disability from chronic motor deficits despite contemporary rehabilitation services, underscoring the need for novel treatment., Objective/hypothesis: We have previously shown that deep brain stimulation (DBS) of the lateral cerebellar nucleus (LCN) can enhance post-stroke motor recovery and increase the expression of markers of long-term potentiation in perilesional cerebral cortex. We hypothesize that a similar beneficial effect will be for motor deficits induced by unilateral fluid percussion injury (FPI) in rodents through long-term potentiation- and anti-inflammatory based mechanisms., Methods: Male Long Evans rats with a DBS macroelectrode in the LCN underwent FPI over contralateral primary motor cortex. After 4 weeks of spontaneous recovery, DBS treatment was applied for 4 weeks, with the pasta matrix, cylinder, and horizontal ladder tests used to evaluate motor performance. All animals were euthanized and tissue harvested for further analysis by histology, immunohistochemistry, RNA microarray assay and Western Blot., Results: LCN DBS-treated animals experienced a significantly greater rate of motor recovery than untreated surgical controls, with treated animals showing enhanced expression of RNA and protein for excitability related genes, suppressed expression of pro-inflammatory genes, suppressed microglial and astrocytic activation, but proliferation of c-fos positive cells. Finally, our data suggest a possible role for anti-apoptotic effects with LCN DBS., Conclusion: LCN DBS enhanced the motor recovery following TBI, possibly by elevating the neuronal excitability at the perilesional area and mediating anti-apoptotic and anti-inflammatory effects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: A host of influences contribute to cognitive and behavioral changes following deep brain stimulation. The location of the active cathode is likely an important variable but it has received little attention., Objective: To determine whether active contact location relative to the subthalamic nucleus and other neighboring structures is related to nonmotor outcomes., Methods: We identified a retrospective, cross-sectional sample of 46 patients who underwent subthalamic nucleus deep brain stimulation for treatment of idiopathic Parkinson's disease. T-tests or nonparametric equivalents were used to detect baseline differences between unilateral left, unilateral right, and bilateral surgical groups. Correlation and partial correlational analyses identified relationships between contact location variables and alterations in cognitive, mood, quality of life, motor, and disease variables., Results: Medial contact locations within the left subthalamic nucleus were correlated with improvements in self-reported mood (r12 = -0.78, P = .001; 95% confidence interval [CI] = -0.43 to -0.93) but worsening semantic fluency (r26 = -0.38, P = .048; 95% CI = -0.01 to -0.66). Phonemic fluency worsened with more posterior left placement (r34 = 0.35, P = .036; 95% CI = 0.03 to 0.61). Memory outcome was related to right hemisphere stimulation voltage (r29 = -0.40, P = .022; 95% CI = -0.05 to -0.66), which is likely a proxy for variable electrode location., Conclusion: Location of the active contact is related to nonmotor outcomes, even in electrodes that are adequately placed. This is relevant to clinical care as there appears to be a trade-off between mood and fluency abilities that should be considered during surgical planning according to preoperative patient characteristics.

Objective: Spinal cord stimulation (SCS) is a safe, reversible surgical treatment for complex regional pain syndrome and failed back surgery syndrome refractory to conventional medical management. Paddle electrodes are routinely used for the permanent implant because of the reduced risk of migration, lower energy requirements, and expanded coverage options. The risks associated with paddle lead removal are not well defined in the literature., Methods: We retrospectively reviewed the outcomes of all patients at the Cleveland Clinic who underwent removal of SCS paddle electrodes between 2009 and 2016., Results: We identified 68 patients during this interval who had a paddle electrode removed. The most common reason for removal was loss of coverage or effect (75%), followed by infection (13.24%), and the need for magnetic resonance imaging for diagnostic purposes (8.82%). Postoperative complications occurred in eight patients (11.75%), two of which were classified as major (2.94%). One of these patients developed a postoperative cerebrospinal fluid leak, and another suffered a large suprafascial hematoma. Both patients underwent reoperation. Minor complications were reported in six patients (8.82%) and included wound dehiscence, infection, and prolonged ileus in one case. On average, patients who developed complications lost 20 mL more blood during surgery than those who did not develop complications (p = 0.006)., Conclusion: One of the benefits of SCS therapy is the reversibility of the procedure. However, removal is not without some risk though the overall risk of minor or major complication is low. Patients who are considering removal should be counseled appropriately. Prophylactic removal is not recommended. However, when removal is needed, surgeons and pain specialists must be familiar with these complications and their management., (© 2017 International Neuromodulation Society.)

Background: Medicinal cannabis registries typically report pain as the most common reason for use. It would be clinically useful to identify patterns of cannabis treatment in migraine and headache, as compared to arthritis and chronic pain, and to analyze preferred cannabis strains, biochemical profiles, and prescription medication substitutions with cannabis., Methods: Via electronic survey in medicinal cannabis patients with headache, arthritis, and chronic pain, demographics and patterns of cannabis use including methods, frequency, quantity, preferred strains, cannabinoid and terpene profiles, and prescription substitutions were recorded. Cannabis use for migraine among headache patients was assessed via the ID Migraine™ questionnaire, a validated screen used to predict the probability of migraine., Results: Of 2032 patients, 21 illnesses were treated with cannabis. Pain syndromes accounted for 42.4% (n = 861) overall; chronic pain 29.4% (n = 598;), arthritis 9.3% (n = 188), and headache 3.7% (n = 75;). Across all 21 illnesses, headache was a symptom treated with cannabis in 24.9% (n = 505). These patients were given the ID Migraine™ questionnaire, with 68% (n = 343) giving 3 "Yes" responses, 20% (n = 102) giving 2 "Yes" responses (97% and 93% probability of migraine, respectively). Therefore, 88% (n = 445) of headache patients were treating probable migraine with cannabis. Hybrid strains were most preferred across all pain subtypes, with "OG Shark" the most preferred strain in the ID Migraine™ and headache groups. Many pain patients substituted prescription medications with cannabis (41.2-59.5%), most commonly opiates/opioids (40.5-72.8%). Prescription substitution in headache patients included opiates/opioids (43.4%), anti-depressant/anti-anxiety (39%), NSAIDs (21%), triptans (8.1%), anti-convulsants (7.7%), muscle relaxers (7%), ergots (0.4%)., Conclusions: Chronic pain was the most common reason for cannabis use, consistent with most registries. The majority of headache patients treating with cannabis were positive for migraine. Hybrid strains were preferred in ID Migraine™, headache, and most pain groups, with "OG Shark", a high THC (Δ9-tetrahydrocannabinol)/THCA (tetrahydrocannabinolic acid), low CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with predominant terpenes β-caryophyllene and β-myrcene, most preferred in the headache and ID Migraine™ groups. This could reflect the potent analgesic, anti-inflammatory, and anti-emetic properties of THC, with anti-inflammatory and analgesic properties of β-caryophyllene and β-myrcene. Opiates/opioids were most commonly substituted with cannabis. Prospective studies are needed, but results may provide early insight into optimizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and patterns of use in the treatment of headache, migraine, and chronic pain syndromes.

Objective: The International League Against Epilepsy (ILAE) proposed a classification system for hippocampal sclerosis (HS) based on location and extent of hippocampal neuron loss. The literature debates the usefulness of this classification system when studying memory in people with temporal lobe epilepsy (TLE) and determining memory outcome after temporal lobe resection (TLR). This study further explores the relationship between HS ILAE subtypes and episodic memory performance in patients with TLE and examines memory outcomes after TLR., Methods: This retrospective study identified 213 patients with TLE who underwent TLR and had histopathological evidence of HS (HS ILAE type 1a = 92; type 1b = 103; type 2 = 18). Patients completed the Wechsler Memory Scale-3rd Edition prior to surgery, and 78% of patients had postoperative scores available. Linear regressions examined differences in preoperative memory scores as a function of pathology classification, controlling for potential confounders. Fisher's exact tests were used to compare pathology subtypes on the magnitude of preoperative memory impairment and the proportion of patients who experienced clinically meaningful postoperative memory decline., Results: Individuals with HS ILAE type 2 demonstrated better preoperative verbal memory performance than patients with HS ILAE type 1; however, individual data revealed verbal and visual episodic memory impairments in many patients with HS ILAE type 2. The base rate of postoperative memory decline was similar among all 3 pathology groups., Significance: This is the largest reported overall sample and the largest subset of patients with HS ILAE type 2. Group data suggest that patients with HS ILAE type 2 perform better on preoperative memory measures, but individually there were no differences in the magnitude of memory impairment. Following surgery, there were no statistically significant differences between groups in the proportion of patients who declined. Future research should focus on quantitative measurements of hippocampal neuronal loss, and multicenter collaboration is encouraged., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Introduction: Deep brain stimulation (DBS) is a well-recognized treatment for patients with movement disorders and other neurological diseases. The implantable pulse generator (IPG) is a fundamental component of the DBS system. Although IPG implantation and replacement surgeries are comparatively minor procedures relative to the brain lead insertion, patients often require multiple IPG replacements during their lifetime with each operation carrying a small but possibly cumulative risk of complications. To better educate our patients and improve surgical outcomes, we reviewed our series of patients at our institution., Methods: Using electronic health record data, we retrospectively reviewed all initial and subsequent IPG surgeries from patients who underwent at least one IPG surgery between the years of 2010 and 2015 at the Cleveland Clinic main campus. We calculated infection rates for initial IPG implantation surgeries and the infection rate for subsequent replacements. Fisher's exact tests were used to evaluate the chance of an infection between the initial implantation and replacement. Fisher's exact tests and simple logistic regression analyses were used to determine the predictive ability of selected demographic and clinical variables RESULTS: Our final sample included 697 patients and 1537 surgeries. For all patients, the infection rate at the first surgery was 2.01%; at the second surgery, it was 0.44%; and at the third surgery, it was 1.83%. When considering only patients that underwent at least three replacement surgeries (n = 114) the infection rate did not change in a significant manner with subsequent interventions compared to the first replacement. No other variable of interest was a significant predictor of infection., Conclusion: We did not find increasing rates of infection with subsequent IPG replacement procedures., (© 2017 International Neuromodulation Society.)