Utility of automated memory measures in identifying cognitive impairment in adults with epilepsy.

OBJECTIVE: Cognitive impairment is prevalent in epilepsy and often presents at the time of initial diagnosis. This study sought to validate brief, self-administered, iPad-based recognition memory tasks in a sample of patients with epilepsy and to examine their screening utility in identifying patients with cognitive impairment. METHODS: The Words and Faces tests were administered to 145 adult patients with epilepsy along with a neuropsychological battery. Correlation analyses examined the convergent and divergent validity of the Words and Faces tests, and a series of logistic regression analyses examined discriminative ability in identifying patients with and without cognitive impairments on neuropsychological measures. Patient performance was compared to that of a healthy control group (n = 223), and the relationship between the Words and Faces test performance and disease-related variables (i.e., antiepileptic medication burden, seizure lateralization/localization) was examined. RESULTS: The Words and Faces tests were positively correlated with traditional paper-and-pencil neuropsychological measures of episodic memory, with generally moderate to large effect sizes (r > .40), while correlations between the Words and Faces tests and non-memory measures were generally small in magnitude (r < .30). Patients with epilepsy had significantly lower scores on Words and Faces tests compared to healthy controls, and performance was associated with antiepileptic medication burden and seizure localization. The Words and Faces tests demonstrated good predictive accuracy in identifying any cognitive impairment (concordance (c) statistic = .77) and excellent predictive accuracy (c = .85) in identifying patients with impairments on traditional memory measures. The Words and Faces tests also demonstrated reasonable discrimination for impairments in non-memory domains including executive function, language, attention, processing speed, and visuospatial ability (c = .62 -.70). Importantly, the Words and Faces Immediate Index performed just as well as the Total Score (which included delayed memory performance), suggesting a short version of this measure is sufficient for identifying patients with cognitive impairment. CONCLUSIONS: The Words and Faces tests are valid, computerized tools that can be used to screen for memory and other cognitive impairment in adults with epilepsy.

Cognitive outcomes following frontal lobe resection for treatment of epilepsy in children and adolescents.

OBJECTIVE: To use reliable change indices (RCIs) developed specifically for pediatric patients with epilepsy to examine cognitive outcomes after frontal lobe resection for pharmacoresistant epilepsy. METHODS: Forty-one pediatric patients (25 male, Mage = 10 years) completed comprehensive neuropsychological evaluations before and an average of 6.5 months after frontal lobe resections for treatment of epilepsy. Evaluations included tests of intelligence, attention/working memory, processing speed, language, visuospatial skills, executive function, and episodic memory. Practice effect-adjusted RCIs were used to determine clinically significant postoperative cognitive change. Demographic, disease, and surgical variables were examined to identify factors associated with postoperative cognitive decline or improvement. RESULTS: Within each cognitive domain, there was a large proportion of patients (51-84%) who did not exhibit significant cognitive change. In terms of overall cognitive profile, 44% demonstrated improvement in at least one domain and 69% declined in at least one domain. Postoperative cognitive improvement occurred most commonly in the domain of processing speed, whereas postoperative cognitive decline occurred most frequently in the domain of visuospatial skills. Younger age at surgery was associated with cognitive improvement. Older age at seizure onset and higher baseline cognitive performance were associated with cognitive decline. SIGNIFICANCE: Approximately 6.5 months after frontal lobe resection, only 15% of our sample showed stable performance across all cognitive domains. Seventeen percent of patients showed improvements without declines, 42% showed declines without improvements, and 27% showed a mix of improvements and declines across different cognitive domains. Age and baseline abilities were associated with postoperative cognitive change on multiple measures. With 1 in 8 children demonstrating postoperative decline across three or more domains, further research is needed to identify factors associated with cognitive decline in order to inform clinical decision-making and patient/family counseling.

BDNF and COMT, but not APOE, alleles are associated with psychiatric symptoms in refractory epilepsy.

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 (Mage = 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.

Deep brain stimulation of the ventral striatal area for poststroke pain syndrome: a magnetoencephalography study.

Poststroke pain syndrome (PSPS) is an often intractable disorder characterized by hemiparesis associated with unrelenting chronic pain. Although traditional analgesics have largely failed, integrative approaches targeting affective-cognitive spheres have started to show promise. Recently, we demonstrated that deep brain stimulation (DBS) of the ventral striatal area significantly improved the affective sphere of pain in patients with PSPS. In the present study, we examined whether electrophysiological correlates of pain anticipation were modulated by DBS that could serve as signatures of treatment effects. We recorded event-related fields (ERFs) of pain anticipation using magnetoencephalography (MEG) in 10 patients with PSPS preoperatively and postoperatively in DBS OFF and ON states. Simple visual cues evoked anticipation as patients awaited a painful (PS) or nonpainful stimulus (NPS) to the nonaffected or affected extremity. Preoperatively, ERFs showed no difference between PS and NPS anticipation to the affected extremity, possibly due to loss of salience in a network saturated by pain experience. DBS significantly modulated the early N1, consistent with improvements in affective networks involving restoration of salience and discrimination capacity. Additionally, DBS suppressed the posterior P2 (aberrant anticipatory anxiety) while enhancing the anterior N1 (cognitive and emotional regulation) in responders. DBS-induced changes in ERFs could potentially serve as signatures for clinical outcomes. NEW & NOTEWORTHY We examined the electrophysiological correlates of pain affect in poststroke pain patients who underwent deep brain stimulation (DBS) targeting the ventral striatal area under a randomized, controlled trial. DBS significantly modulated early event-related components, particularly N1 and P2, measured with magnetoencephalography during a pain anticipatory task, compared with baseline and the DBS-OFF condition, pointing to possible mechanisms of action. DBS-induced changes in event-related fields could potentially serve as biomarkers for clinical outcomes.

Effects of surgical side and site on psychological symptoms following epilepsy surgery in adults.

This retrospective study examined the potential role of side and site of surgery in psychological symptom change after epilepsy surgery and determined the base rate of psychological change at the individual level. Two-hundred twenty-eight adults completed the Personality Assessment Inventory (PAI) before and after temporal (TLR; n=190) or frontal lobe resection (FLR; n=38). Repeated measures ANOVAs with bootstrapping examined differences in psychological outcome as a function of surgical site separately in patients who underwent left- versus right-sided resections. Individual's PAI score changes were then used to determine the prevalence of clinically meaningful postoperative symptom change. Following left-sided resections, there were significant group-by-time interactions on Somatic Complaints, Anxiety, and Anxiety Related Disorders. There was also a trend in this direction on the Depression scale. TLR patients endorsed greater preoperative symptoms than FLR patients on all of these scales, except the Somatic Complaints scale. After surgery, TLR patients reported symptom improvement on all four scales, while scores of FLR patients remained relatively stable over time. Endorsement of Mania-related symptoms increased in both TLR and FLR groups from pre-to post-surgical testing. Following right-sided resections, both groups endorsed symptom improvements on Somatic Complaints, Anxiety, and Depression scales following surgery. In addition, the TLR group endorsed more Mania-related symptoms than the FLR group regardless of time. Patterns of meaningful change in individual patients were generally consistent with group findings, with the most frequent improvements observed following TLR. However, there were a small subset of patients who reported symptom exacerbation after surgery. Our results suggest that surgical lateralization and localization are important factors in postoperative psychological outcome and highlight the importance of considering psychological change at the individual patient level. Further research is needed to identify potential risk factors for symptom exacerbation to aid in preoperative counseling and identify those patients most in need of postoperative psychological surveillance.

Pain anticipatory phenomena in patients with central poststroke pain: a magnetoencephalography study.

Central poststroke pain (CPSP) is characterized by hemianesthesia associated with unrelenting chronic pain. The final pain experience stems from interactions between sensory, affective, and cognitive components of chronic pain. Hence, managing CPSP will require integrated approaches aimed not only at the sensory but also the affective-cognitive spheres. A better understanding of the brain's processing of pain anticipation is critical for the development of novel therapeutic approaches that target affective-cognitive networks and alleviate pain-related disability. We used magnetoencephalography (MEG) to characterize the neural substrates of pain anticipation in patients suffering from intractable CPSP. Simple visual cues evoked anticipation while patients awaited impending painful (PS), nonpainful (NPS), or no stimulus (NOS) to their nonaffected and affected extremities. MEG responses were studied at gradiometer level using event-related fields analysis and time-frequency oscillatory analysis upon source localization. On the nonaffected side, significantly greater responses were recorded during PS. PS (vs. NPS and NOS) exhibited significant parietal and frontal cortical activations in the beta and gamma bands, respectively, whereas NPS (vs. NOS) displayed greater activation in the orbitofrontal cortex. On the affected extremity, PS (vs. NPS) did not show significantly greater responses. These data suggest that anticipatory phenomena can modulate neural activity when painful stimuli are applied to the nonaffected extremity but not the affected extremity in CPSP patients. This dichotomy may stem from the chronic effects of pain on neural networks leading to habituation or saturation. Future clinically effective therapies will likely be associated with partial normalization of the neurophysiological correlates of pain anticipation.

Global cognitive scores do not predict outcome after subthalamic nucleus deep brain stimulation.

BACKGROUND: Presence of dementia is a contraindication for DBS treatment of Parkinson's disease. Recent evidence suggests that borderline cognitive function, as measured with a common screening measure, the Mattis Dementia Rating Scale, has a negative impact on quality of life (QoL) after DBS of the STN. METHODS: We attempted to replicate and extend this finding in a larger group of patients with a wider range of preoperative global cognitive performance. RESULTS: Our data indicate that performance on the screening measure is not associated with QoL or medical outcomes, even with scores well below the cutoff for identifying dementia. CONCLUSIONS: This cognitive screening measure lacks sufficient sensitivity to warrant its use in predicting which patients will show QoL benefit from DBS.

Automated detection of cognitive impairment in clinical practice.

OBJECTIVE: Cognitive impairment is now recognized as an impending public health crisis. About one-third of adults are concerned about their cognition, and the prevalence of objective cognitive impairment is much higher among those with neurological disorders. Existing screening tools are narrowly focused on detecting dementia in older adults and must be clinician-administered and scored, making them impractical for many neurology practices. This study examined the utility of a brief, self-administered, computerized cognitive screening tool, the Brief Assessment of Cognitive Health (BACH), in identifying cognitive impairment in adults. METHODS: 912 adults (ages 18-84) completed BACH and a neuropsychological battery. Multivariable models were developed to provide a BACH index score reflecting the probability of cognitive impairment for individual patients. Predictive accuracy was compared to that of the Montreal Cognitive Assessment (MoCA) in a subset of 160 older adults from a Memory Disorders clinic. RESULTS: The final multivariable model showed good accuracy in identifying cognitively impaired individuals (c = 0·77). Compared to MoCA, BACH had superior predictive accuracy in identifying older patients with cognitive impairment (c = 0·79 vs. 0·67) as well as differentiating those with MCI or dementia from those without cognitive impairment (c = 0·86 vs. c = 0·67). CONCLUSIONS: Results suggest that cognitive impairment can be identified in adults using a brief, self-administered, automated cognitive screening tool, and BACH provides several advantages over existing screeners: self-administered; automatic scoring; immediate results in health record; easily interpretable score; utility in wide range of patients; and flags for treatable factors that may contribute to cognitive complaints (i.e., depression, sleep problems, and stress).

Utility of the Brief Assessment of Cognitive Health (BACH) computerized screening tool in identifying MS-related cognitive impairment.

BACKGROUND: Current guidelines recommend that individuals with MS are screened annually for processing speed deficits, often using the Symbol Digit Modalities Test (SDMT). However, given the heterogeneity of cognitive deficits in individuals with MS, other screening measures that assess a range of cognitive domains are necessary. The current cross-sectional study aimed to examine the ability of the computerized, self-administered Brief Assessment of Cognitive Health (BACH) screening measure to detect the presence of cognitive impairment in adults with MS as determined by performance on a standard neuropsychological test battery. METHODS: Seventy-two individuals with MS completed the BACH and a comprehensive neuropsychological test battery. Receiver operating characteristic (ROC) analyses were conducted to investigate the ability of the BACH to identify cognitively impaired and cognitively intact individuals. ROC analyses were also conducted to compare the ability of the SDMT to discriminate between cognitively intact and cognitively impaired groups as a comparison with the BACH. RESULTS: Cognitive impairment was observed in 56 % of the sample. The BACH showed acceptable ability to discriminate between cognitively intact and cognitively impaired groups (AUC = 0.78). Additionally, the BACH was able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.71). The SDMT also demonstrated adequate utility in identifying individuals with cognitive impairment (AUC = 0.73); however, the SDMT was not able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.56). CONCLUSION: The BACH showed adequate ability to detect cognitive impairment in individuals with MS. The BACH was able to identify impairments across various assessed cognitive domains, including individuals with and without processing speed deficits.

Loss of Efficacy in Ventral Intermediate Nucleus Stimulation for Essential Tremor.

OBJECTIVE: The primary aim of this study is to report long-term outcomes associated with deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) performed at our institution. We further aimed to elicit the factors associated with loss of efficacy and to discuss the need for exploring and establishing reliable rescue targets. METHODS: To study long-term outcomes, we performed a retrospective chart review and extracted tremor scores of 43 patients who underwent VIM DBS lead implantation for essential tremor at our center. We further evaluated factors that could influence outcomes over time, including demographics, body mass index, duration of follow-up, degree of parenchymal atrophy indexed by the global cortical atrophy scale, and third ventricular width. RESULTS: In this cohort, tremor scores on the latest follow-up (median 52.7 months) were noted to be worse than initial postoperative scores in 56% of DBS leads. Furthermore, 14% of leads were associated with clinically significant loss of benefit. Factors including the length of time since the lead implantation, age at the time of surgery, sex, body mass index, preoperative atrophy, and third ventricular width were not predictive of long-term outcomes. CONCLUSIONS: Our study identified a substantial subgroup of VIM-DBS patient who experienced a gradual decline in treatment efficacy over time. We propose that this phenomenon can be attributed primarily to habituation and disease progression. Furthermore, we discuss the need to establish reliable and effective rescue targets for this subpopulation of patients, with ventral-oralis complex and dentate nucleus emerging as potential candidates.

Validation of Self-Administered Visual and Verbal Episodic Memory Tasks in Healthy Controls and a Clinical Sample.

This study evaluated the performance characteristics, construct validity, and reliability of two computerized, self-administered verbal and visual recognition memory tests based on the Remember-Know paradigm. Around 250 healthy control participants and 440 patients referred for neuropsychological assessment used an iPad to complete the Words and Faces recognition memory tests before or after concurrent neuropsychological testing. Performance accuracy was high but without ceiling effects. Education, but not age, was related to overall performance for both samples while the influence of gender and race differed across samples. In the clinical sample, overall performance was worse in those patients demonstrating memory impairment on clinical assessment. Words and Faces subtests demonstrated the strongest correlations with neuropsychological measures of verbal and nonverbal memory, respectively. Both showed moderate correlations with processing speed while Faces was also correlated with visuospatial skills. The memory tests showed good test-retest reliability over two testing sessions. These findings demonstrate acceptable psychometric properties in clinical and community samples and suggest that this computerized format is feasible for memory assessment in clinical contexts.

Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial.

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1-3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443 .

Deep cerebellar stimulation enhances cognitive recovery after prefrontal traumatic brain injury in rodent.

Functional outcome following traumatic brain injury (TBI) varies greatly, with approximately half of those who survive suffering long-term motor and cognitive deficits despite contemporary rehabilitation efforts. We have previously shown that deep brain stimulation (DBS) of the lateral cerebellar nucleus (LCN) enhances rehabilitation of motor deficits that result from brain injury. The objective of the present study was to evaluate the efficacy of LCN DBS on recovery from rodent TBI that uniquely models the injury location, chronicity and resultant cognitive symptoms observed in most human TBI patients. We used controlled cortical impact (CCI) to produce an injury that targeted the medial prefrontal cortex (mPFC-CCI) bilaterally, resulting in cognitive deficits. Unilateral LCN DBS electrode implantation was performed 6 weeks post-injury. Electrical stimulation started at week eight post-injury and continued for an additional 4 weeks. Cognition was evaluated using baited Y-maze, novel object recognition task and Barnes maze. Post-mortem analyses, including Western Blot and immunohistochemistry, were conducted to elucidate the cellular and molecular mechanisms of recovery. We found that mPFC-CCI produced significant cognitive deficits compared to pre-injury and naïve animals. Moreover, LCN DBS treatment significantly enhanced the long-term memory process and executive functions of applying strategy. Analyses of post-mortem tissues showed significantly greater expression of CaMKIIα, BDNF and p75NTR across perilesional cortex and higher expression of postsynaptic formations in LCN DBS-treated animals compared to untreated. Overall, these data suggest that LCN DBS is an effective treatment of cognitive deficits that result from TBI, possibly by activation of ascending, glutamatergic projections to thalamus and subsequent upregulation of thalamocortical activity that engages neuroplastic mechanisms for facilitation of functional re-organization. These results support a role for cerebellar output neuromodulation as a novel therapeutic approach to enhance rehabilitation for patients with chronic, post-TBI cognitive deficits that are unresponsive to traditional rehabilitative efforts.

Task context and frontal lobe activation in the Stroop task.

The ability to step outside a routine--to select a new response over a habitual one--is a cardinal function of the frontal lobes. A large body of neuroimaging work now exists pointing to increased activation within the anterior cingulate when stimuli evoke competing responses (incongruent trials) relative to when responses converge (congruent trials). However, lesion evidence that the ACC is necessary in this situation is inconsistent. We hypothesized that this may be a consequence of different task procedures (context) used in lesion and neuroimaging studies. The present study attempted to reconcile the lesion and the fMRI findings by having subjects perform clinical and experimental versions of the Stroop task during BOLD fMRI acquisition. We examined the relationship of brain activation patterns, specifically within the anterior cingulate and left dorsolateral frontal regions, to congruent and incongruent trial types in different task presentations or contexts. The results confirmed our hypothesis that ACC activity is relatively specific to unblocked-uncued incongruent Stroop conditions that have not been used in large neuropsychological studies. Moreover, the size of the behavioral Stroop interference effect was significantly correlated with activity in ACC and left dorsolateral regions, although in different directions. The current results are discussed in terms of previous proposals for the functional roles of these regions in activating, monitoring, and task setting, and the relation of these findings to the disparate reports in recent case series is considered.

Similarities in the patterns of prefrontal cortex activity during spatial and temporal context memory retrieval after equating for task structure and performance.

Event-related functional magnetic resonance imaging was used to assess healthy adults while they performed spatial and temporal context memory tasks matched in task structure. After equating task structure between spatial versus temporal context tasks, subjects reported using similar strategies across tasks and we observed no significant differences in accuracy and reaction time performance between tasks. We used three methods of statistical analysis to interrogate similarities and differences in whole-brain activity across retrieval tasks, while focussing on prefrontal cortex (PFC) activations: multivariate partial least squares analysis (PLS), univariate statistical parametric mapping (SPM) and conjunction analysis. The PLS and conjunction analyses indicated that the overall pattern of PFC activity was similar across both temporal and spatial context retrieval tasks; but the SPM results indicated that some of these PFC regions exhibited differences in the degree to which they were engaged between tasks. However, none of these methods identified unique PFC activations specific to mediating spatial and/or temporal context retrieval. These results indicate that, overall, similar patterns of PFC activity were observed during temporal and spatial context memory retrieval once task structure and performance were equated.

Effect of apolipoprotein ε4 allele on hippocampal and brain volume in intractable temporal lobe epilepsy.

This study investigated the relationship between the apolipoprotein (APOE) ε4 allele and brain volumes in patients with medically intractable temporal lobe epilepsy (TLE). MRI-based volumetric analyses of the hippocampi, cerebral hemispheres, and whole brain were conducted in 59 patients with TLE (31 with left TLE, 28 with right TLE) with hippocampal sclerosis (HS). There were no differences in hippocampal, hemispheric, or whole brain volumes as a function of ε4 status even after correcting for hemispheric and total brain volumes. However, APOE ε4 carriers showed a trend toward having a smaller discrepancy between ipsilateral and contralateral hippocampal volumes than patients without this allele, and post hoc analyses suggest there may be an increased incidence of bilateral HS in ε4 carriers. In summary, APOE ε4 is not associated with significant hippocampal, hemispheric, or whole brain atrophy in patients with medically intractable TLE. However, ε4 carriers may be more likely to have bilateral HS, with an apparent dose-dependent effect.

Neuropsychological outcomes after thalamic deep brain stimulation for essential tremor.

INTRODUCTION: Non-motor DBS outcomes have received little attention in ET relative to PD. This study examines neuropsychological outcomes in ET following thalamic VIM DBS. METHODS: Fifty patients completed neuropsychological evaluations preoperatively and approximately seven months postoperatively. Cognition and mood changes were analyzed at the group level and individual level. Additional associations with treatment, disease, and demographic characteristics were assessed. RESULTS: Significant cognitive decline was not observed at the group level. At the individual level, 46% of patients demonstrated at least subtle overall cognitive decline (≥1SD on at least one test within at least two domains). Mild decline (≥1SD) was seen in 10%-29.17% of patients on individual tests across all cognitive domains, with highest rates in verbal memory. Substantial cognitive decline (≥2SD) occurred in less than 9% of the sample across all tests. Factors related to cognitive decline included higher DBS parameter settings, older age of ET onset, intracranial complications, and inability to reduce ET medications postoperatively. Depression and anxiety did not change when accounting for questionnaire items that could be falsely elevated by tremor. CONCLUSION: Substantial cognitive decline after VIM DBS is rare in patients with ET. However, subtle decrements can occur across cognitive domains and particularly in verbal memory. DBS parameter settings may relate to cognitive decline. Further research is needed to better understand possible associations with electrode lateralization and other variables that could also relate to disease progression and test-retest effects. Symptoms of depression and anxiety remain stable.

Long-Term Neurocognitive Outcome in Patients With Continuous Flow Left Ventricular Assist Device.

OBJECTIVES: The authors sought to examine the long-term cognitive outcome of patients with continuous flow left ventricular assist device (CF-LVAD). BACKGROUND: Data on long-term neurocognitive outcome in LVAD are limited. We examined the neurocognitive outcome of patients who received a CF-LVAD as destination therapy. METHODS: Patients with HeartWare (HVAD) and HeartMate II who were enrolled in the ENDURANCE and ENDURANCE Supplemental trials were eligible. Cognition was evaluated with neuropsychological testing preoperatively and at 6, 12, and 24 months after implantation. General linear models identified demographic, disease, and treatment factors that predicted decline on each neurocognitive measure. RESULTS: Of 668 patients who completed baseline testing and at least 1 follow-up evaluation, 552 were impaired at baseline on at least 1 cognitive measure. At each follow-up, approximately 23% of tested patients declined and 20% improved relative to baseline on at least 1 cognitive measure. Of those who were intact at baseline, only 10%-12% declined in delayed memory and 11%-16% declined in executive function at all 3 follow-ups. For patients impaired at baseline, delayed memory decline was associated with the HVAD device and male sex, whereas executive function decline was associated with the HVAD device and stroke during CF-LVAD support. For patients intact at baseline, male sex and history of hypertension were associated with decline in immediate memory and executive function, respectively. CONCLUSIONS: Neurocognitive function remained stable or improved for most patients (∼80%) with CF-LVAD at 6, 12, and 24 months after implantation. Male sex, hypertension, HVAD, and stroke were associated with cognitive decline.

Cortical thickness in visuo-motor areas is related to motor outcomes after STN DBS for Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) is a widely accepted therapy for Parkinson's disease. While outcome predictors such as levodopa-response are well established, there remains a need for objective and unbiased predictors in clinical practice. We performed an exploratory study to examine whether cortical thickness, derived from preoperative MRI, correlates with postoperative outcome. METHODS: Using freesurfer, we retrospectively measured cortical thickness on the preoperative MRI of 38 patients who underwent bilateral STN-DBS for PD during a 4-year period. The Unified Parkinson Disease Rating motor (UPDRS III) and experiences of daily living subscales (UPDRS II) were collected at baseline and six months after surgery. As an initial analysis, a series of partial correlations was conducted to evaluate the association between postoperative outcome scores and average cortical thickness from predefined regions of interest, adjusting for candidate confounders, without correcting for multiple comparisons. A confirmatory vertex-wise analysis was performed using a cluster-wise correction for multiple comparisons. RESULTS: Based on the ROI analysis, the strongest correlation with motor outcome was found to be with the left lateral-occipital cortex. Patients with greater cortical thickness in this area presented with greater improvements in motor scores. This relationship was also supported by the vertex-wise analysis. Greater cortical thickness in frontal and temporal regions may be correlated with greater post-operative improvements in UPDRS II, but this was not confirmed in the vertex-wise analysis. CONCLUSIONS: Our data indicate that greater cortical thickness in visuo-motor areas is correlated with motor outcomes after DBS for PD. Further prospective investigations are needed to confirm our findings and better-investigate potential image biomarkers.

Factors Associated With Postoperative Confusion and Prolonged Hospital Stay Following Deep Brain Stimulation Surgery for Parkinson Disease.

BACKGROUND: Several patient and disease characteristics are thought to influence DBS outcomes; however, most previous studies have focused on long-term outcomes with only a few addressing immediate postoperative course. OBJECTIVE: To evaluate predictors of immediate outcomes (postoperative confusion and length of postoperative hospitalization) following deep brain stimulation surgery (DBS) in Parkinson disease (PD) patients. METHODS: We conducted a retrospective study of PD patients who underwent DBS at our institution from 2006 to 2011. We computed the proportion of patients with postoperative confusion and those with postoperative hospitalization longer than 2 d. To look for associations, Fisher's exact tests were used for categorical predictors and logistic regression for continuous predictors. RESULTS: We identified 130 patients [71% male, mean age: 63 ± 9.1, mean PD duration: 10.7 ± 5.1]. There were 7 cases of postoperative confusion and 19 of prolonged postoperative hospitalization. Of the 48 patients with tremors, none had postoperative confusion, whereas 10.1% of patients without tremors had confusion (P = .0425). Also, 10.2% of patients with preoperative falls/balance-dysfunction had postoperative confusion, whereas only 1.6% of patients without falls/balance-dysfunction had postoperative confusion (P = .0575). For every one-unit increase in score on the preoperative on-UPDRS III/MDS-UPDRS III score, the odds of having postoperative confusion increased by 10% (P = .0420). The following factors were noninfluential: age, disease duration, dyskinesia, gait freezing, preoperative levodopa-equivalent dose, number of intraoperative microelectrode passes, and laterality/side of surgery. CONCLUSION: Absence of tremors and higher preoperative UPDRS III predicted postoperative confusion after DBS in PD patients. Clinicians' awareness of these predictors can guide their decision making regarding patient selection and surgical planning.