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The primary objective of the study was to determine the risk of postpartum urinary tract infection (UTI) in women exposed to intermittent versus indwelling catheterization in labor. The secondary objective was to identify risk factors for development of postpartum UTI. A case-control study was conducted between 1 January 2013 and 31 December 2016. Cases were defined as patients who were diagnosed with UTI and controls were not diagnosed with UTI. Obstetrical, infectious, and catheterization variables were collected. Univariate and multivariate analyses were performed. A total of 26,517 full-term vaginal deliveries occurred during the study period with a rate of postpartum UTI of 0.7%. There were 166 cases and 695 controls included in the analysis. There was no significant difference in the rate of UTI between patients who underwent indwelling versus intermittent (reference) catheterization (OR 1.05, 95% CI: 0.67–1.64, p =.826). On multivariate analysis, significant risk factors for UTI included the relationship between use of catheterization and duration of labor (p =.026) and history of UTI during the pregnancy (p <.001). In this study, there was no difference in the rate of postpartum UTI based on catheterization method. Further studies are needed to determine the optimal method of catheterization during labor and to enable providers to implement quality improvement strategies aimed at decreasing the risk of infection. [ABSTRACT FROM AUTHOR]

Background: Understanding the neural mechanisms underlying migraine and other primary headache disorders is critical for the development of long-term cures. Magnetoencephalography (MEG), an imaging modality that measures neuronal currents and cortical excitability with high temporal and superior spatial resolution, has been increasingly used in neurological research. Initial MEG studies showed promise in directly recording cortical spreading depression-a cortical correlate of migraine with aura. However, lately MEG technology has highly evolved with greater potential to reveal underlying pathophysiology of migraine and primary headache disorders, and aid in the identification of biomarkers., Objective: To systematically review the use of MEG in migraine and other primary headache disorders and summarize findings., Methods: We conducted a systematic search and selection of MEG studies in migraine and primary headache disorders from inception until June 8, 2023, in Medline, Embase, Cochrane, and Scopus databases. Peer-reviewed English articles reporting the use of MEG for clinical or research purposes in migraine and primary headache disorders were selected., Results: We found 560 articles and included 38 in this review after screening. Twelve studies investigated resting-state, while others investigated a sensory modality using an evoked or event-related paradigm with a total of 35 cohort and 3 case studies. Thirty-two studies focused exclusively on migraine, while the rest reported other primary headache disorders., Conclusion: The findings show an evolution of MEG from a 7- to a 306-channel system and analysis evolving from sensor-level evoked responses to more advanced source-level connectivity measures. A relatively few MEG studies portrayed migraine and primary headache disorders as a sensory abnormality, especially of the visual system. We found heterogeneity in the datasets, data reporting standards (due to constantly evolving MEG technology and analysis methods), and patient characteristics. Studies were inadequately powered and there was no evidence of blinding procedures to avoid selection bias in case-control studies, which could have led to false-positive findings. More studies are needed to investigate the affective-cognitive aspects that exacerbate pain and disability in migraine and primary headache disorders., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background and Objectives: Despite decreasing prevalence of migraine with advancing age, there remains a significant proportion of individuals aged ≥65 years with migraine. Treatment of this population is difficult and they are often excluded from clinical trials, limiting evidence regarding migraine treatment outcomes. Our objective is to assess the efficacy and tolerability of anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) therapies (erenumab, fremanezumab, and galcanezumab) in patients ≥65 years (O65) compared with patients <65 (U65) with daily or nondaily migraine., Methods: This observational study uses retrospective data from the electronic medical records of patients who were treated with an anti-CGRP mAb between June 2018 and November 2021. Efficacy was determined through a reduction in monthly migraine days (MMDs) and Headache Impact Test (HIT-6) scores from baseline to posttreatment. Tolerability was examined through the number of adverse events reported per group. Mann-Whitney tests were used to compare the efficacy and tolerability of U65 and O65 patients overall and separated into daily and nondaily migraine groups., Results: The dataset consisted of U65 (n = 2,707; median [interquartile range]; 45.4 [35.8-53.8] years) or O65 (n = 304; 69.5 [67.3-73.3] years) and further separated into daily (n = 1,303) and nondaily (n = 1,708) migraine. There was no difference ( p = 0.57) in the median MMD reduction between U65 (10 days [0.0-17.0]) and O65 (10 days [0.0-16.5]). Similarly, no difference was found among patients with nondaily migraine ( p = 0.82) and patients with daily migraine ( p = 0.59). HIT-6 scores decreased from severe to moderate/substantial impact for all groups. The daily and nondaily groups showed differences in meeting the 50% improvement threshold (nondaily U65, 67% vs daily U65, 54%, p < 0.0001; nondaily O65, 65% vs daily O65, 49%, p = 0.008). Side effects were reported (829/3,011), with a higher incidence in the U65 (22% O65, 28% U65). The most common side effects for both groups were injection site reaction/rash (40%) and constipation (25%)., Discussion: This retrospective analysis provides real-world evidence that there is no difference in the efficacy and tolerability of treatment with erenumab, fremanezumab, and galcanezumab in patients O65 when compared with patients U65 both with daily or nondaily migraine. These data may help guide the choice of migraine treatment in older populations., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Background: We previously demonstrated that deep brain stimulation (DBS) of lateral cerebellar nucleus (LCN) can enhance motor recovery and functional reorganization of perilesional cortex in rodent models of stroke or TBI., Objective: Considering the treatment-related neuroplasticity observed at the perilesional cortex, we hypothesize that chronic LCN DBS-enhanced motor recovery observed will carry-over even after DBS has been deactivated., Methods: Here, we directly tested the enduring effects of LCN DBS in male Long Evans rats that underwent controlled cortical impact (CCI) injury targeting sensorimotor cortex opposite their dominant forepaw followed by unilateral implantation of a macroelectrode into the LCN opposite the lesion. Animals were randomized to DBS or sham treatment for 4 weeks during which the motor performance were characterize by behavioral metrics. After 4 weeks, stimulation was turned off, with assessments continuing for an additional 2 weeks. Afterward, all animals were euthanized, and tissue was harvested for further analyses., Results: Treated animals showed significantly greater motor improvement across all behavioral metrics relative to untreated animals during the 4-week treatment, with functional gains persisting across 2-week post-treatment. This motor recovery was associated with the increase in CaMKIIα and BDNF positive cell density across perilesional cortex in treated animals., Conclusions: LCN DBS enhanced post-TBI motor recovery, the effect of which was persisted up to 2 weeks beyond stimulation offset. Such evidence should be considered in relation to future translational efforts as, unlike typical DBS applications, treatment may only need to be provided until such time as a new function plateau is achieved., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs. Machado and Baker have intellectual property and distribution rights in Enspire DBS Therapy, Inc., which is a spin-off of the Cleveland Clinic. Drs. Machado and Baker serve on the Scientific Advisory Board of Enspire DBS Therapy, Inc. Dr. Machado holds a patent titled as “Methods of treating medical conditions by neuromodulation of the cerebellar pathways.” US 7,640,063.

Background and Objectives: Deep brain stimulation (DBS) is an established neurosurgical treatment of a variety of neurological disorders. DBS is considered a safe and effective neurosurgical procedure; however, surgical complications are inevitable, and clinical outcomes may vary. The aim of this study was to describe DBS complications at a large clinical center in the United States and to investigate the relationship between patients' baseline characteristics, surgical technique, and operative complications., Methods: We identified all patients who underwent DBS lead implantation at our center between 1st January 2012 and 1st January 2020. We extracted relevant information regarding patient demographics, surgical details, clinical complications, and clinical outcomes from the electronic medical records., Results: A total of 859 leads were implanted in 481 patients (153 men, 328 women). The mean patient age at the time of the surgery was 65 years, with the mean disease duration of 13.3 years. There were no mortalities and 57 readmissions within 30 days (mean = 14.2 days). The most common complications included pneumocephalus (n = 661), edema (n = 78), altered mental state (n = 35), implantable pulse generator discomfort (n = 34), hemorrhage (n = 26), and infection (n = 23). Most notably, the use of general anesthesia, hypertension, heart disease, and depression were associated with significantly longer postoperative stay. High preoperative body mass index was associated with higher rates of surgery-related infections and lead revision/explantation. The intraoperative mean arterial pressure, anesthesia type, and frame apparatus were all important predictors of postoperative pneumocephalus., Conclusion: In this report, we described the rates and types of complications associated with DBS surgery at a large neurosurgical center in the United States. The novel insights highlighted in this study present an opportunity to further improve the clinical outcomes and patient selection in DBS surgery., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

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)., (© 2024. The Author(s).)

While ipsilesional cortical electroencephalography has been associated with poststroke recovery mechanisms and outcomes, the role of the cerebellum and its interaction with the ipsilesional cortex is still largely unknown. We have previously shown that poststroke motor control relies on increased corticocerebellar coherence (CCC) in the low beta band to maintain motor task accuracy and to compensate for decreased excitability of the ipsilesional cortex. We now extend our work to investigate corticocerebellar network changes associated with chronic stimulation of the dentato-thalamo-cortical pathway aimed at promoting poststroke motor rehabilitation. We investigated the excitability of the ipsilesional cortex, the dentate (DN), and their interaction as a function of treatment outcome measures. Relative to baseline, 10 human participants (two women) at the end of 4-8 months of DN deep brain stimulation (DBS) showed (1) significantly improved motor control indexed by computerized motor tasks; (2) significant increase in ipsilesional premotor cortex event-related desynchronization that correlated with improvements in motor function; and (3) significant decrease in CCC, including causal interactions between the DN and ipsilesional cortex, which also correlated with motor function improvements. Furthermore, we show that the functional state of the DN in the poststroke state and its connectivity with the ipsilesional cortex were predictive of motor outcomes associated with DN-DBS. The findings suggest that as participants recovered, the ipsilesional cortex became more involved in motor control, with less demand on the cerebellum to support task planning and execution. Our data provide unique mechanistic insights into the functional state of corticocerebellar-cortical network after stroke and its modulation by DN-DBS., (Copyright © 2024 the authors.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Drs. Floden and Busch would like to disclose the potential for future distributions from Ceraxis Health, Inc. as inventors.]., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.P.F. and R.M.B. would like to disclose the potential for future distributions from Ceraxis Health, Inc. as inventors.

Despite great advances in acute care and rehabilitation, stroke remains the leading cause of motor impairment in the industrialized world. We have developed a deep brain stimulation (DBS)-based approach for post-stroke rehabilitation that has shown reproducible effects in rodent models and has been recently translated to humans. Mechanisms underlying the rehabilitative effects of this novel therapy have been largely focused on the ipsilesional cortex, including cortical reorganization, synaptogenesis, neurogenesis and greater expression of markers of long-term potentiation. The role of subcortical structures on its therapeutic benefits, particularly the striatum, remain unclear. In this study, we compared the motor rehabilitative effects of deep cerebellar stimulation in two rodent models of cerebral ischemia: a) cortical ischemia; and b) combined striatal and cortical ischemia. All animals underwent the same procedures, including implantation of the electrodes and tethered connections for stimulation. Both experimental groups received four weeks of continuous lateral cerebellar nucleus (LCN) DBS and each was paired with a no stimulation, sham, group. Fine motor function was indexed using the pasta matrix task. Brain tissue was harvested for histology and immunohistochemical analyses. In the cortical-only ischemia, the average pasta matrix performance of both sham and stimulated groups reduced from 19 to 24 pieces to 7-8 pieces following the stroke induction. At the end of the four-week treatment, the performance of stimulated group was significantly greater than that of sham group (14 pieces vs 7 pieces, p < 0.0001). Similarly, in the combined cortical and striatal ischemia, the performance of both sham and stimulated groups reduced from 29 to 30 pieces to 7-11 pieces following the stroke induction. However, at the end of the four-week treatment, the performance of stimulated group was not significantly greater than that of sham group (15 pieces vs 11 pieces, p = 0.452). In the post-mortem analysis, the number of cells expressing CaMKIIα at the perilesional cortical and striatum of the LCN DBS treated animals receiving cortical-only stroke elevated but not those receiving cortical+striatal stroke. The current findings suggested that the observed, LCN DBS-enhanced motor recovery and perilesional plasticity may involve striatal mechanisms., Competing Interests: Declaration of competing interest Drs. Machado and Baker have intellectual property and distribution rights in Enspire DBS Therapy, Inc., which is a spin-off of the Cleveland Clinic. Drs. Machado and Baker serve on the Scientific Advisory Board of Enspire DBS Therapy, Inc. Dr. Machado holds a patent titled as “Methods of treating medical conditions by neuromodulation of the cerebellar pathways.”, US 7,640,063., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Many patients with chronic migraine do not achieve clinically meaningful improvement in their headache frequency with monotherapy. The burden associated with chronic migraine calls for a multifaceted treatment approach targeting multiple aspects of migraine pathophysiology., Objective: The aim of this study was to evaluate the effect of concurrent anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) and onabotulinumtoxinA (onabot) treatment on median monthly migraine days (MMD) in patients with chronic migraine, through a retrospective study., Methods: The electronic medical records of Cleveland Clinic patients either concurrently (dual therapy) or consecutively (monotherapy) treated with anti-CGRP mAbs and onabot between June 2018 and November 2021 were extracted. Only adult patients (≥ 18 years of age) were included in this study. MMDs for 194 concurrently treated (86.6% female and a median [interquartile range] age of 51 [41-61] years) and 229 consecutively treated (88.2% female and median age of 47 [IQR 39-57] years) patients were examined at baseline, after first therapy of either anti-CGRP mAb or onabot, and following dual therapy for 3 consecutive months. The reduction of MMDs for each treatment group were compared. The same approach was utilized to compare consecutive monotherapy at separate times (n = 229) and dual-therapy groups., Results: The initial treatment of the dual-therapy group reduced the median (IQR) MMDs from 30 (30-30) to 15 (12-30) [p < 0.0001]. After initiation of dual therapy, the median MMDs was further decreased from 15 (12-30) to 8 (3-22) [p < 0.0001]. A majority [132/194 (68.0%)] of the dual-therapy patients reported a ≥ 50% reduction in MMD and 90/194 (46.4%) reported a ≥ 75% reduction. For the consecutive monotherapy group, median MMDs changed from a baseline of 30 (25-30) to 15 (8-25) from onabot monotherapy and decreased from 25 (15-30) to 12 (4-25) after anti-CGRP mAb monotherapy. Almost half (113/229 [49.3%] from onabot, and 104/229 [45.4%] from anti-CGRP mAb) of these patients achieved a ≥ 50% reduction in MMDs and a minority (38/229 [16.6%] from onabot, and 45/229 [19.7%] from anti-CGRP mAb) achieved a reduction of ≥ 75%. Additionally, dual therapy showed significant improvement in MMDs compared with monotherapy of either treatment (p < 0.0001)., Conclusion: Dual therapy of anti-CGRP mAbs and onabot may be more efficacious than monotherapy, possibly due to their synergistic mechanisms of action., (© 2024. The Author(s).)

We sought to perform a systematic review and individual participant data meta-analysis to identify predictors of treatment response following thalamic neuromodulation in pediatric patients with medically refractory epilepsy. Electronic databases (MEDLINE, Ovid, Embase, and Cochrane) were searched, with no language or data restriction, to identify studies reporting seizure outcomes in pediatric populations following deep brain stimulation (DBS) or responsive neurostimulation (RNS) implantation in thalamic nuclei. Studies featuring individual participant data of patients with primary or secondary generalized drug-resistant epilepsy were included. Response to therapy was defined as >50% reduction in seizure frequency from baseline. Of 417 citations, 21 articles reporting on 88 participants were eligible. Mean age at implantation was 13.07 ± 3.49 years. Fifty (57%) patients underwent DBS, and 38 (43%) RNS. Sixty (68%) patients were implanted in centromedian nucleus and 23 (26%) in anterior thalamic nucleus, and five (6%) had both targets implanted. Seventy-four (84%) patients were implanted bilaterally. The median time to last follow-up was 12 months (interquartile range = 6.75-26.25). Sixty-nine percent of patients achieved response to treatment. Age, target, modality, and laterality had no significant association with response in univariate logistic regression. Until thalamic neuromodulation gains widespread approval for use in pediatric patients, data on efficacy will continue to be limited to small retrospective cohorts and case series. The inherent bias of these studies can be overcome by using individual participant data. Thalamic neuromodulation appears to be a safe and effective treatment for epilepsy. Larger, prolonged prospective, multicenter studies are warranted to further evaluate the efficacy of DBS over RNS in this patient population where resection for curative intent is not a safe option., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Cerebellum shares robust di-synaptic dentato-thalamo-cortical (DTC) connections with the contralateral motor cortex. Preclinical studies have shown that DTC are excitatory in nature. Structural integrity of DTC is associated with better upper extremity (UE) motor function in people with stroke, indicating DTC are important for cerebellar influences on movement. However, there is a lack of understanding of physiologic influence of DTC in humans, largely due to difficulty in accessing the dentate nucleus., Objective: Characterize DTC physiology using dentate nucleus deep brain stimulation (DBS) combined with transcranial magnetic stimulation (TMS) in stroke., Methods: Nine chronic stroke survivors with moderate-to-severe UE impairment (Fugl-Meyer 13-38) underwent a paired DBS-TMS experiment before receiving experimental dentate nucleus DBS in our first-in-human phase I trial (Baker et al., 2023, Nature Medicine). Conditioning DBS pulses were given to dentate nucleus 1 to 10 ms prior to supra-threshold TMS pulses given to ipsilesional motor cortex. Effects were assessed on motor evoked potentials (MEPs). Size of DBS-conditioned MEPs was expressed relative to TMS MEPs, where values >1 indicate facilitation., Results: Dentate nucleus DBS led to facilitation of MEPs at short-latency intervals (3.5 and 5 ms, P  = .049 and .021, respectively), a phenomenon we have termed dentato-cortical facilitation (DCF). Higher DCF was observed among patients with more severe UE impairment. Diffusion tensor imaging revealed microstructure of thalamo-cortical portion of DTC was related to higher corticomotor excitability., Conclusions: Our in vivo investigation reveals for the first time in humans the intrinsic excitatory properties of DTC, which can serve as a novel therapeutic target for post-stroke motor recovery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Andre G. Machado is a consultant and has intellectual property licensed to Enspire DBS. Kenneth B. Baker is a consultant to Enspire DBS. Enspire DBS funded part of the clinical trial. The remaining authors report no competing interests.

Background: During scoliosis surgery, motor evoked potentials (MEP), and somatosensory evoked potentials (SSEP) have been reported to be affected by the use of higher doses of anesthetic agents. Dexmedetomidine, a sympatholytic agent, an alpha-2 receptor agonist, has been used as an adjunctive agent to lower anesthetic dose. However, there is conflicting evidence regarding the effects of dexmedetomidine on the intraoperative neurophysiological monitoring of MEP and SSEP during surgery, particularly among pediatric patients., Objectives: This systematic review aimed to determine whether, during spinal fusion surgery in pediatric patients with scoliosis, dexmedetomidine alters MEP amplitude or SSEP latency and amplitude and, if so, whether different doses of dexmedetomidine display different effects (PROSPERO registration number CRD42022300562)., Methods: We searched PubMed, Scopus, and Cochrane Library on January 1, 2022 and included randomized controlled trials, observational cohort and case-control studies and case series investigating dexmedetomidine in the population of interest and comparing against a standardized anesthesia regimen without dexmedetomidine or comparing multiple doses of dexmedetomidine. Animal and in vitro studies and conference abstracts were excluded., Results: We found substantial heterogeneity in the risk of bias (per Cochrane-preferred tools) of the included articles (n = 5); results are summarized without meta-analysis. Articles with the lowest risk of bias indicated that dexmedetomidine was associated with MEP loss and that higher doses of dexmedetomidine increased risk. In contrast, articles reporting no association between dexmedetomidine and MEP loss suffered from higher risk of bias, including suspected or confirmed problems with confounding, outcome measurement, participant selection, results reporting, and lack of statistical transparency and power., Conclusion: Given the limitations of the studies available in the literature, it would be advisable to conduct rigorous randomized controlled trials with larger sample sizes to assess the effects of dexmedetomidine use of in scoliosis surgery in pediatric patients., (© 2023 John Wiley & Sons Ltd.)

Background and Purpose: Transparent reporting and appropriate interpretation of statistical methods and results are important to facilitate scientific evaluation and enable future replication. The goal of this study was to describe statistical reporting guidance provided to authors by clinical neurology and neuroscience journals., Methods: For first-quartile journals in each discipline (per Clarivate InCites), information collected from Instructions to Authors website sections included whether journals required presentation of sample size justification, estimates of precision, and method of checking assumptions; and guidance for interpretation of p-values and appropriate presentation of descriptive statistics and graphs. Journal endorsement of common but statistically nonspecific published transparent reporting guidelines for human and animal research was also collected, to capture the select statistical reporting items included in each guideline., Results: Journals (n = 85) frequently did not require/recommend sample size justifications (15% not required; 62% only required per external transparent reporting guideline), estimates of precision (15% not required; 41% only required per external guidelines), or disclosure of method of checking assumptions (46%); nor provide guidance for reporting/interpretation of p-values (71%), reporting of descriptive statistics (75%), or use of appropriate graphs (92%). Endorsement of statistically nonspecific standalone reporting guidelines ranged between 52% and 68%, depending on the guideline., Conclusions: There is opportunity for journals to facilitate improvement in transparency of statistical methods and results for clinical neurology and neuroscience studies by providing guidelines and advice to authors at manuscript submission., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Conventional MRI scans have limited usefulness in monitoring Parkinson's disease as they typically do not show any disease-specific brain abnormalities. This study aimed to identify an imaging biomarker for tracking motor symptom progression by using a multivariate statistical approach that can combine gray matter volume information from multiple brain regions into a single score specific to each PD patient., Methods: A cohort of 150 patients underwent MRI at baseline and had their motor symptoms tracked for up to 10 years using MDS-UPDRS-III, with motor symptoms focused on total and subscores, including rigidity, bradykinesia, postural instability, and gait disturbances, resting tremor, and postural-kinetic tremor. Gray matter volume extracted from MRI data was summarized into a patient-specific summary score using Mahalanobis distance, M GMV . MDS-UPDRS-III's progression and its association with M GMV were modeled via linear mixed-effects models over 5- and 10-year follow-up periods., Results: Over the 5-year follow-up, there was a significant increase (P < 0.05) in MDS-UPDRS-III total and subscores, except for postural-kinetic tremor. Over the 10-year follow-up, all MDS-UPDRS-III scores increased significantly (P < 0.05). A higher baseline M GMV was associated with a significant increase in MDS-UPDRS-III total, bradykinesia, postural instability and gait disturbances, and resting tremor (P < 0.05) over the 5-year follow-up, but only with total, bradykinesia, and postural instability and gait disturbances during the 10-year follow-up (P < 0.05)., Conclusions: Higher M GMV scores were linked to faster motor symptom progression, suggesting it could be a valuable marker for clinicians monitoring Parkinson's disease over time., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: High accuracy and precision are essential in stereotactic neurosurgery, as targeting errors can significantly affect clinical outcomes. Image registration is a vital step in stereotaxis, and understanding the error associated with different image registration methods is important to inform the choice of equipment and techniques in stereotactic neurosurgery. The authors aimed to quantify the test-retest reliability and stereotactic accuracy of cone-beam CT (CBCT) compared with the current clinical gold-standard technique (i.e., CT)., Methods: Two anthropomorphic phantom models with 40 independent unique steel spheres were developed to compare CBCT frame and stereotactic space registration with the clinical gold standard (CT). The cartesian coordinates of each sphere were compared between the imaging modalities for test-retest reliability and overall accuracy., Results: Both imaging modalities showed similar levels of fiducial deviation from the expected geometry. The equivalence test demonstrated mean differences between CT and CBCT registration of -0.082 mm (90% CI -0.27 to 0.11), -0.045 mm (90% CI -0.43 to 0.34), and -0.041 mm (90% CI -0.064 to 0.018) for coordinates in the x-, y-, and z-axes, respectively. The mean euclidean distance difference between the two modalities was 0.28 mm (90% CI 0.27-0.29)., Conclusions: Accuracy and precision were comparable between CBCT and CT image registrations. These findings suggest that CBCT registration can be used as a clinically equivalent substitute to gold-standard CT acquisition.

Background: Towards the end of life (EOL), persons with parkinsonism (PwP) have complex needs and can present with unique palliative care (PC) challenges. There are no widely accepted guidelines to aid neurologists, hospitalists, or PC clinicians in managing the symptoms of PwP at EOL. We examined a population of PwP at EOL, aiming to describe trends of in-hospital management and utilization of PC services., Methods: All PwP admitted to two hospitals during 2018 ( N = 727) were examined retrospectively, assessing those who died in hospital or were discharged with hospice (EOL group, N = 35) and comparing them to the main cohort. Their demographics, clinical data, engagement of multidisciplinary and palliative services, code status changes, invasive care, frequency of admissions, and medication administration were assessed., Results: Among the EOL group, 8 expired in hospital, and 27 were discharged to hospice. Forty-six percent of EOL patients received a PC consultation during their admission. The median interval from admission to death was 37 days. Seventy-seven percent had a full code status on admission. Compared to hospice patients, those who expired in hospital had higher rates of invasive procedures and intensive care unit transfers (41% vs. 75%, in both variables), and lower rates of PC involvement (52% vs. 25%). The transition of code status change for the EOL group from Full code to Do Not Resuscitate (DNR) occurred at a median 4-5 days from admission. For patients that passed in the hospital, the median days from transition of code status to death was 0(IQR 0-1). Levodopa dose deviations were frequent in both EOL and non-EOL group, but contraindicated medications were infrequently administered (11% in EOL group vs. 9% in non-EOL group)., Conclusion: Our data suggest a low utilization of PC services and delayed discussions of goals of care. More work is needed to raise awareness of inpatient teams managing PwP regarding the unique but common challenges facing PwP with advanced disease. A brief narrative review summarizing the suggested management of symptoms common to hospitalized PwP near EOL is provided., Competing Interests: BW serves as Section Head of Movement Disorders at the Cleveland Clinic. Over the years, he has received research grants from the NIH and Parkinson’s Foundation. He has served as site investigator and /or co-investigator for clinical research studies sponsored by grants from Industry to Cleveland Clinic. Currently, he site PI for Neuroderm (Mitsubishi Tanabe Pharma), Discern (Great Lakes Neurotech/NIH R44), Tempo2, and Tempo3 studies (Cerevel Therapeutics) and a grant from the Parkinson’s Foundation to improve the inpatient care of People with PD. He has served as a consultant or speaker for Medtronic, Boston Scientific, and Abbott for less than $5,000 in the last year. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Bhansali, Assaedi, Yu, Mandava, Sonneborn, Hogue, Walter, Samala and Margolius.)

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 ., (© 2023. The Author(s).)

Introduction: The therapeutic efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) may be limited for some patients by the presence of stimulation-related side effects. Such effects are most often attributed to electrical current spread beyond the target region. Prior computational modeling studies have suggested that changing the degree of asymmetry of the individual phases of the biphasic, stimulus pulse may allow for more selective activation of neural elements in the target region. To the extent that different neural elements contribute to the therapeutic vs. side-effect inducing effects of DBS, such improved selectivity may provide a new parameter for optimizing DBS to increase the therapeutic window., Methods: We investigated the effect of six different pulse geometries on cortical and myogenic evoked potentials in eight patients with PD whose leads were temporarily externalized following STN DBS implant surgery. DBS-cortical evoked potentials were quantified using peak to peak measurements and wavelets and myogenic potentials were quantified using RMS., Results: We found that the slope of the recruitment curves differed significantly as a function of pulse geometry for both the cortical- and myogenic responses. Notably, this effect was observed most frequently when stimulation was delivered using a monopolar, as opposed to a bipolar, configuration., Discussion: Manipulating pulse geometry results in differential physiological effects at both the cortical and neuromuscular level. Exploiting these differences may help to expand DBS' therapeutic window and support the potential for incorporating pulse geometry as an additional parameter for optimizing therapeutic benefit., Competing Interests: AM was a consultant and had intellectual property licensed to Enspire DBS, had distribution rights in Ceraxis, and was a consultant to Abbott. KB was a consultant for Enspire DBS. AM and KB had intellectual property and distribution rights in Cardionomics. SN consulted for Abbott and was a speaker for Medtronic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Campbell, Favi Bocca, Tiefenbach, Hogue, Nagel, Rammo, Escobar Sanabria, Machado and Baker.)

Background: Functional Neurologic Disorders (FND) are a common but heterogeneous group of disabling conditions. The Emergency Department (ED) is an important venue for care and referral as it is often the first point of contact when patients with FND are faced with a crisis or exacerbation of symptoms., Methods: ED providers (n = 273) practicing in the Cleveland Clinic Foundation Northeast Ohio network were invited to participate through secure web application electronic surveys. Data were collected on practice profiles, knowledge, attitudes, management of FND, and awareness of available resources for FND., Results: Sixty providers completed the survey (22% response rate; n = 50 ED physicians, 10 advanced care providers) with 95.0% (n = 57) reporting a lack of understanding about FND. The terms Psychogenic Nonepileptic Seizures and stress induced/stress related disease were used by 60.0% (n = 36) and 58.3% (n = 35) respectively. Ninety percent (n = 53) rated their experience with managing FND patients as at least more difficult. Eighty- five percent (n = 51) agreed with "rule out others" and 60% (n = 36) agreed with "caused by psych stress". Eighty six percent (n = 50) believe that there is a difference between FND from malingering. Only one respondent was familiar with any FND resources and 79% (n = 47) reported the need for FND specific educational materials., Conclusion: This survey revealed major gaps in knowledge, inaccurate perceptions, and management that differs from the current standard of care among ED providers caring for patients with FND. Educational opportunities are needed to guide diagnosis and evidence-based treatment to optimize management of patients with FND., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The complexity of antiparkinsonian medications makes patients vulnerable to medication deviations. This study examines the frequency and outcomes of deviations between outpatient and inpatient medication administrations in patients with Parkinson's disease (PD)., Methods: We included hospital admissions of patients with PD during a 12-month period at the Cleveland Clinic Main and Fairview campuses. Outpatient regimens were compared with hospital medication administration records to establish rates of deviations in terms of levodopa equivalent daily dose (LEDD) difference, timing deviations/omissions of time-critical medications, substitution of levodopa compounds, and administration of antidopaminergic medications. Logistic regression analyses were used to investigate associations with length of stay (LOS), readmission rates, and mortality., Results: The study included 492 patients with 725 admissions. Of those on time-critical medications, 43% had a LEDD deviation and 19% had levodopa formulation substitutions. Of the admission days with known outpatient timing regimens, 47% had an average deviation of more than 30 min and 22% had at least one missed levodopa dose. LOS was longer with each additional day of over-dose (4%), under-dose (14%), missed dose (21%), timing deviation (15%) and substitution (19%), (all p < 0.0001). Administration of antidopaminergic medications (9.9% of admissions) was associated with increased 30-day readmission/death (OR 1.85, p = 0.041), 90-day mortality (OR 2.2, p = 0.018), and LOS (7.6 vs. 3.8 days, p < 0.0001). LEDD underdose was associated with 30-day readmission/death (OR 1.78, p = 0.025) and 90-day mortality (OR 1.14, CI 1.05-1.24, p = 0.002)., Conclusions: Deviations between outpatient and hospital regimens, and administration of antidopaminergic medications, were associated with poor outcomes., Competing Interests: Declaration of competing interest HHF has received research support from Biogen, Cerevel, Michael J. Fox Foundation, NIH/NINDS, Parkinson Study Group, Parkinson's Foundation, Roche but has no owner interest in any pharmaceutical company; has received honoraria from, Cleveland Clinic as a speaker in CME events; has received honoraria from Amneal, AbbVie, Cerevel, Neurocrine, Parkinson Study Group as a consultant. Elsevier as the Editor-In-Chief of Parkinsonism and Related Disorders Journal; has received royalty payments from Springer for serving as a book author/editor. BW serves as Section Head of Movement Disorders at the Cleveland Clinic. Over the years, he has received research grants from the NIH and Parkinson's Foundation. He has served as site investigator and/or co-investigator for clinical research studies sponsored by grants from Industry to Cleveland Clinic. Currently, he is the site PI for Neuroderm (Mitsubishi Tanabe Pharma), Discern (Great Lakes Neurotech/NIH R44), Tempo 2, and Tempo 3 studies (Cerevel Therapeutics) and a grant from the Parkinson's Foundation to improve the inpatient care of People with PD. He has served as a consultant or speaker for Medtronic, Boston Scientific, and Abbott for less than $5000 in the last year., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Parkinson's disease (PD) affects multiple facets of patients' lives, many of which may not be recognized or addressed by their healthcare team. A growing body of evidence has shown that palliative care improves patients' quality of life with PD; however, little is currently known about how patients with PD perceive palliative care., Methods: An 8-question multiple choice survey was created and given to patients with established care for PD at a movement disorders clinic in a quaternary care center. Patients with less than two years of follow-up or that had atypical features of PD were excluded from the survey., Results: There were 106 respondents to the survey. A third of patients reported having never heard of palliative care and an additional 25% had heard of it but did not know what it was. Eighty-eight percent reported being familiar with or very knowledgeable about hospice, though 50% of respondents did not know the difference between hospice and palliative care. 93% had never been offered either service. 37.7% thought their neurologist should discuss advance care planning early in the course of their disease., Conclusion: Even among established patients with Parkinson's disease in a quaternary center, over half were not familiar with palliative care, and the majority had never been offered palliative or hospice services despite growing evidence that it could improve their quality of life. Additionally, patients would like to be introduced to advanced care planning early in the course of their disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Individuals with PTEN hamartoma tumor syndrome (PHTS) demonstrate a distinct neurobehavioral profile suggesting primary disruption of frontal lobe symptoms, with more severe cognitive deficits in those with associated autism spectrum disorder (ASD) that extend to other areas of neurobehavioral function as well (e.g., adaptive behavior, sensory deficits). The current study sought to characterize longitudinal neurobehavioral profiles in individuals with PHTS who completed serial assessments (2-3 evaluations) over a 2-year time period., Methods: Comprehensive neurobehavioral evaluations were conducted on 92 participants (age range 6-21) with PHTS and/or ASD. Spaghetti plots and linear mixed effects models were used to visualize the individual patient profiles and group trends and examine the group differences in cognitive/behavioral test scores over time. Practice-adjusted reliable change indices (RCIs) and standardized regression-based change scores (SRBs) were calculated for those measures in the battery with adequate sample sizes and test-retest reliabilities for future use in assessing neurobehavioral change in children and young adults with PHTS., Results: Wide individual differences were observed at baseline across all measures. Encouragingly, baseline differences between patient groups persisted at the same magnitude over a 2-year time period with no differences in longitudinal neurobehavioral profiles within any one group. Test-retest reliabilities were generally high, ranging from 0.62 to 0.97, and group mean change from baseline to 12 months was small (range - 3.8 to 3.7). A Microsoft Excel calculator was created that clinicians and researchers can use to automatically calculate RCI and SRB thresholds at both 80% and 90% confidence intervals using test scores from a given child or young adult with PHTS., Conclusions: Our results suggest that the neurobehavioral phenotypes observed in individuals with PHTS remain relatively stable over time, even in those with ASD. The RCIs and SRBs provided can be used in future research to examine patient outcomes at the individual level as well as to detect negative deviations from the expected trajectory that can be used to inform intervention strategies., (© 2022. The Author(s).)

Objective: Seizure outcomes after brain surgery for drug-resistant epilepsy (DRE) are very heterogeneous and difficult to predict with models utilizing the current clinical, imaging, and electrophysiological variables. In this pilot study, we investigated whether genetic and molecular biomarkers (e.g., genomic, transcriptomic) can provide additional insight into differential response to surgery., Methods: Post-operative seizure-outcomes were collected at last follow-up (>6 months) for 201 adult patients with DRE who underwent surgery between 2004 and 2020. Resected tissue was sent for miRNA sequencing ( n = 132) and mRNA sequencing ( n = 135). Following the selection of 10 genes ( SCN1A, NBEA, PTEN, GABRA1, LGL1, DEPDC5, IL1A, ABCB1, C3, CALHM1 ), we investigated SNPs in those 10 genes from previously acquired exome sequencing data ( n = 106). Logistic regression was performed to test for associations between individual features (mRNAs, miRNAs, and SNPs) and post-operative seizure-outcome with an exploratory FDR P < 0.25 as the threshold for significance. Post-operative time-to-seizure analyses were performed for each SNP using a Cox proportional hazards model., Results: The majority of patients (83%) had temporal lobe epilepsy. Mean age at surgery was 38.3 years, and 56% were female. Three SNPs (rs10276036, rs11975994, rs1128503) in multi-drug resistance gene, ABCB1 , were associated with post-operative seizure outcomes. Patients with alternate alleles in ABCB1 were more likely to be seizure-free at last follow-up (52-56% reduction in seizure recurrence; FDR P = 0.24). All three SNPs were in linkage disequilibrium and highly correlated with each other. Median post-operative time-to-seizure was 63 months for patients with 2 alternate alleles, 24-33 months with 1 alternate allele, and 10-11 months with 0 alternate alleles. These SNPs improved outcome prediction beyond MRI and sex alone. No independent miRNAs or mRNAs were significantly associated with seizure-outcome ( P > 0.05). However, pathway analysis identified "cancer drug resistance by drug efflux" (mir-154 and mir-379) as enriched ( P = 0.02), supporting the role of drug response genes in post-operative seizure recurrence., Significance: ABCB1 may have a role in epileptogenesis and surgery outcomes independent of its drug efflux activity necessitating further investigation. SNPs in ABCB1 may serve as independent predictors of post-operative outcome., Competing Interests: Author DR has an equity stake in Clarified Precision Medicine, LLC. DR has received research support from Novo Nordisk, consulting honoraria from Interpares Biomedicine and Pharmazaam, LLC. Author CE is the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine at the Cleveland Clinic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Louis, Busch, Lal, Hockings, Hogue, Morita-Sherman, Vegh, Najm, Ghosh, Bazeley, Eng, Jehi and Rotroff.)

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 p75 NTR 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Normal pressure hydrocephalus (NPH) is characterized by cerebral ventriculomegaly and the triad of magnetic gait, urinary incontinence, and cognitive impairment. Treatment includes ventriculoperitoneal (VP) shunt surgery., Objective: To evaluate complication rates in a cohort of patients undergoing VP shunt surgery with stereotactic proximal catheter navigation and laparoscopic distal catheter placement., Methods: This study was a retrospective consecutive cohort analysis of 117 patients with NPH undergoing VP shunt placement using both stereotactic navigation and laparoscopy from 2015 to 2020. Patients with obstructive hydrocephalus and those with central nervous system infection, intraventricular hemorrhage, Ommaya reservoirs, or undergoing shunt revision at initial encounter were excluded. Variables included demographics and comorbidities, NPH symptoms, operative details, radiographic outcomes, and rates of complications, readmissions, and reoperations within 1, 3, and 12 months. Impact of demographics and comorbidities on complication rates was assessed using Fisher exact tests., Results: Zero patients required reoperation within 30 days. One intracranial hemorrhage was detected on immediate postoperative head computed tomography. Four patients ultimately required revision: 2 for catheter repositioning to alleviate abdominal pain, 1 ligation for a colectomy, and 1 removal for shunt infection. Patients with cardiac or other neurological comorbidities had higher rates of readmission and complications. Systemic complications totaled 12% in the first 30 days., Conclusion: The combination of intraoperative stereotactic navigation and laparoscopic assistance leads to low rates of serious complications and reoperations for VP shunt implantation in patients with NPH. These changes to surgical technique are easy to implement and may reduce the risk for this common operation., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Deep brain stimulation (DBS) of the deep cerebellar nuclei has been shown to enhance perilesional cortical excitability and promote motor rehabilitation in preclinical models of cortical ischemia and is currently being evaluated in patients with chronic, post-stroke deficits. Understanding the effects of cerebellar DBS on contralateral sensorimotor cortex may be key to developing approaches to optimize stimulation delivery and treatment outcomes. Using the naïve rat model, we characterized the effects of DBS of the lateral cerebellar nucleus (LCN) on somatosensory evoked potentials (SSEPs) and evaluated their potential use as a surrogate index of cortical excitability. SSEPs were recorded concurrently with continuous 30 Hz or 100 Hz LCN DBS and compared to the DBS OFF condition. Ratios of SSEP peak to peak amplitude during 100 Hz LCN DBS to DBS OFF at longer latency peaks were significantly>1, suggesting that cortical excitability was enhanced as a result of LCN DBS. Although changes in SSEP peak to peak amplitudes were observed, they were modest in relation to previously reported effects on motor cortical excitability. Overall, our findings suggest that LCN output influences thalamocortical somatosensory pathways, however further work is need to better understand the potential role of SSEPs in optimizing therapy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To characterize and compare the stability of cortical potentials evoked by deep brain stimulation (DBS) of the subthalamic nucleus (STN) across the naïve, parkinsonian, and pharmacologically treated parkinsonian states. To advance cortical potentials as possible biomarkers for DBS programming., Materials and Methods: Serial electrocorticographic (ECoG) recordings were made more than nine months from a single non-human primate instrumented with bilateral ECoG grids spanning anterior parietal to prefrontal cortex. Cortical evoked potentials (CEPs) were generated through time-lock averaging of the ECoG recordings to DBS pulses delivered unilaterally in the STN region using a chronically implanted, six-contact, scaled DBS lead. Recordings were made across the naïve followed by mild and moderate parkinsonian conditions achieved by staged injections of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin. In addition to characterizing the spatial distribution and stability of the response within each state, changes in the amplitude and latency of CEP components as well as in the frequency content were examined in relation to parkinsonian severity and dopamine replacement., Results: In the naïve state, the STN DBS CEP presented as a multiphase response maximal over M1 cortex, with components attributable to physiological activity distinguishable from stimulus artifact as early as 0.45-0.75 msec poststimulation. When delivered using therapeutically effective parameters in the parkinsonian state, the CEP was highly stable across multiple recording sessions within each behavioral state. Across states, significant differences were present with respect to both the latency and amplitude of individual response components, with greater differences present for longer-latency components (all p < 0.05). Power spectral density analysis revealed a high-beta peak within the evoked response, with significant changes in power between disease states across multiple frequency bands., Conclusions: Our findings underscore the spatiotemporal specificity and relative stability of the DBS-CEP associated with different disease states and with therapeutic benefit. DBS-CEP may be a viable biomarker for therapeutic programming., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

The robust, reciprocal anatomic connections between the cerebellum and contralateral sensorimotor cerebral hemisphere underscore the strong physiological interdependence between these two regions in relation to human behavior. Previous studies have shown that damage to sensorimotor cortex can result in a lasting reduction of cerebellar metabolism, the magnitude of which has been linked to poor rehabilitative outcomes. A better understanding of movement-related cerebellar physiology as well as cortico-cerebellar coherence (CCC) in the chronic, poststroke state may be key to developing novel neuromodulatory techniques that promote upper limb motor rehabilitation. As a part of the first in-human phase I trial investigating the effects of deep brain stimulation of the cerebellar dentate nucleus (DN) on chronic poststroke motor rehabilitation, we collected invasive recordings from DN and scalp EEG in participants (both sexes) with middle cerebral artery stroke during a visuo-motor tracking task. We investigated the excitability of ipsilesional cortex, DN, and their interaction as a function of motor impairment and performance. Our results indicate the following: (1) event-related oscillations in the ipsilesional cortex and DN were significantly correlated at movement onset in the low beta band, with moderately and severely impaired participants showing desynchronization and synchronization, respectively; and (2) significant CCC was observed during the isometric hold period in the low beta band, which was critical for maintaining task accuracy. Our findings support a strong coupling between ipsilesional cortex and DN in the low beta band during motor control across all impairment levels, which encourages the exploitation of the cerebello-thalamo-cortical pathway as a neuromodulation target to promote rehabilitation. SIGNIFICANCE STATEMENT Cerebral infarct because of stroke can lead to lasting reduction in cerebellar metabolism, resulting in poor rehabilitative outcomes. Thorough investigation of the cerebellar electrophysiology, as well as cortico-cerebellar connectivity in humans that could provide key insights to facilitate the development of novel neuromodulatory technologies, has been lacking. As a part of the first in-human phase I trial investigating deep brain stimulation of the cerebellar dentate nucleus (DN) for chronic, poststroke motor rehabilitation, we collected invasive recordings from DN and scalp EEG while stroke survivors performed a motor task. Our data indicate strong coupling between ipsilesional sensorimotor cortex and DN in the low beta band across all impairment levels encouraging the exploration of electrical stimulation of the DN., (Copyright © 2022 the authors.)

Longitudinal and behavioral preclinical animal studies generate complex data, which may not be well matched to statistical approaches common in this literature. Analyses that do not adequately account for complexity may result in overly optimistic study conclusions, with consequences for reproducibility and translational decision-making. Recent work interrogating methodological shortcomings in animal research has not yet comprehensively investigated statistical shortcomings in the analysis of complex longitudinal and behavioral data. To this end, the current cross-sectional meta-research study rigorously reviewed published mouse or rat controlled experiments for motor rehabilitation in three neurologic conditions to evaluate statistical choices and reporting. Medline via PubMed was queried in February 2020 for English-language articles published January 1, 2017- December 31, 2019. Included were articles that used rat or mouse models of stroke, Parkinson's disease, or traumatic brain injury, employed a therapeutic controlled experimental design to determine efficacy, and assessed at least one functional behavioral assessment or global evaluation of function. 241 articles from 99 journals were evaluated independently by a team of nine raters. Articles were assessed for statistical handling of non-independence, animal attrition, outliers, ordinal data, and multiplicity. Exploratory analyses evaluated whether transparency or statistical choices differed as a function of journal factors. A majority of articles failed to account for sources of non-independence in the data (74-93%) and/or did not analytically account for mid-treatment animal attrition (78%). Ordinal variables were often treated as continuous (37%), outliers were predominantly not mentioned (83%), and plots often concealed the distribution of the data (51%) Statistical choices and transparency did not differ with regards to journal rank or reporting requirements. Statistical misapplication can result in invalid experimental findings and inadequate reporting obscures errors. Clinician-scientists evaluating preclinical work for translational promise should be mindful of commonplace errors. Interventions are needed to improve statistical decision-making in preclinical behavioral neurosciences research., Competing Interests: the authors have declared that no competing interests exist.

Parkinson's disease is a neurological disease with cardinal motor signs including bradykinesia and tremor. Although beta-band hypersynchrony in the cortico-basal ganglia network is thought to contribute to disease manifestation, the resulting effects on network connectivity are unclear. We examined local field potentials from a non-human primate across the naïve, mild, and moderate disease states (model was asymmetric, left-hemispheric dominant) and probed power spectral density as well as cortico-cortical and cortico-subthalamic connectivity using both coherence and Granger causality, which measure undirected and directed effective connectivity, respectively. Our network included the left subthalamic nucleus (L-STN), bilateral primary motor cortices (L-M1, R-M1), and bilateral premotor cortices (L-PMC, R-PMC). Results showed two distinct peaks (Peak A at 5-20 Hz, Peak B at 25-45 Hz) across all analyses. Power and coherence analyses showed widespread increases in power and connectivity in both the Peak A and Peak B bands with disease progression. For Granger causality, increases in Peak B connectivity and decreases in Peak A connectivity were associated with the disease. Induction of mild disease was associated with several changes in connectivity: (1) the cortico-subthalamic connectivity in the descending direction (L-PMC to L-STN) decreased in the Peak A range while the reciprocal, ascending connectivity (L-STN to L-PMC) increased in the Peak B range; this may play a role in generating beta-band hypersynchrony in the cortex, (2) both L-M1 to L-PMC and R-M1 to R-PMC causalities increased, which may either be compensatory or a pathologic effect of disease, and (3) a decrease in connectivity occurred from the R-PMC to R-M1. The only significant change seen between mild and moderate disease was increased right cortical connectivity, which may reflect compensation for the left-hemispheric dominant moderate disease state., Competing Interests: AM and KB had potential financial conflict of interest with this research related to intellectual property or consulting and distribution rights in Enspire DBS. AM was a consultant to Abbott and Cleveland Clinic receives fellowship support from Medtronic. The Cleveland Clinic Conflict of Interest (COI) committee has approved a plan for managing these conflicts of interest. The authors have adhered to the management plan in the conduct and reporting of research findings. None of these entities had any role in the research or preparation of the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bore, Toth, Campbell, Cho, Pucci, Hogue, Machado and Baker.)

Objectives: Measures of health-related quality of life (HRQOL) are collected throughout healthcare systems and used in clinical, economic, and outcomes studies to direct patient-centered care and inform health policy. Studies have demonstrated increases in stressors unique to the COVID-19 pandemic, however, their effect on HRQOL is unknown. Our study aimed to assess the change in self-reported global health during the pandemic for patients receiving care in a large healthcare system compared with 1 year earlier., Methods: An observational cross-sectional study of 2 periods was conducted including adult patients who had a healthcare appointment and completed the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) as standard care during the COVID-19 pandemic and a year earlier. The effect of time on PROMIS global mental health (GMH) and global physical health (GPH) was evaluated through multiple statistical methods., Results: There were 38 037 patients (mean age 56.1 ± 16.6 years; 61% female; 87% white) who completed the PROMIS GH during the pandemic (August 2020) and 33 080 (age 56.7 ± 16.5 years; 61% female; 86% white) who had completed it 1 year earlier (August 2019). GMH was significantly worse, whereas GPH was similar during the pandemic compared with a year earlier (adjusted estimate [standard error]: -1.21 (0.08) and 0.11 (0.08) T-score points, respectively)., Conclusions: Our study found modest, nonclinically meaningful decreases in GMH and similar GPH during the COVID-19 pandemic compared with a year earlier in patients cared for in a large healthcare system. Nevertheless, healthcare systems are likely seeing a biased sample of patients during these times. Findings from our study have implications for the interpretation of HRQOL during this pandemic., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: Individuals with obesity frequently contend with chronic pain, but few studies address the clinical impact of coordinated pain services on this population. The current study addresses this topic by comparing the effectiveness of a comprehensive pain rehabilitation program for patients with and without obesity., Methods: A retrospective analysis of registry data was conducted. Obesity was considered as one of three weight groups, based on the following body mass index cutoffs: normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2), and obese (> 30 kg/m2). These groups were compared on the Pain Severity Ratings (PSR) Scale, the Pain Disability Index (PDI), and the Depression, Anxiety, Stress Scales-Short Form (DASS-SF)., Results: Groups differed on baseline pain disability and depression. Patients with obesity had higher scores on both the PDI (P = .028) and the DASS-SF depression subscale (P = .006). Contrary to the hypothesis, after controlling for baseline score and sex there were no significant differences between weight groups with regards to PSR, PDI, or any DASS-SF subscale at discharge. At 1-year follow-up, individuals who were overweight and obese had significantly more anxiety compared to individuals whose weight was in the normal range., Conclusions: Multidisciplinary pain rehabilitation programs appear to be an effective treatment intervention for patients who have concomitant chronic pain and obesity, to a degree comparable to patients who have chronic pain but do not contend with obesity. Implications for program development, clinical interventions, and future research are discussed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study aims to evaluate the role of scalp electroencephalography (EEG; ictal and interictal patterns) in predicting resective epilepsy surgery outcomes. We use the data to further develop a nomogram to predict seizure freedom., Methods: We retrospectively reviewed the scalp EEG findings and clinical data of patients who underwent surgical resection at three epilepsy centers. Using both EEG and clinical variables categorized into 13 isolated candidate predictors and 6 interaction terms, we built a multivariable Cox proportional hazards model to predict seizure freedom 2 years after surgery. Harrell's step-down procedure was used to sequentially eliminate the least-informative variables from the model until the change in the concordance index (c-index) with variable removal was less than 0.01. We created a separate model using only clinical variables. Discrimination of the two models was compared to evaluate the role of scalp EEG in seizure-freedom prediction., Results: Four hundred seventy patient records were analyzed. Following internal validation, the full Clinical + EEG model achieved an optimism-corrected c-index of 0.65, whereas the c-index of the model without EEG data was 0.59. The presence of focal to bilateral tonic-clonic seizures (FBTCS), high preoperative seizure frequency, absence of hippocampal sclerosis, and presence of nonlocalizable seizures predicted worse outcome. The presence of FBTCS had the largest impact for predicting outcome. The analysis of the models' interactions showed that in patients with unilateral interictal epileptiform discharges (IEDs), temporal lobe surgery cases had a better outcome. In cases with bilateral IEDs, abnormal magnetic resonance imaging (MRI) predicted worse outcomes, and in cases without IEDs, patients with extratemporal epilepsy and abnormal MRI had better outcomes., Significance: This study highlights the value of scalp EEG, particularly the significance of IEDs, in predicting surgical outcome. The nomogram delivers an individualized prediction of postoperative outcome, and provides a unique assessment of the relationship between the outcome and preoperative findings., (© 2021 International League Against Epilepsy.)

Objective: To develop and externally validate models to predict the probability of postoperative verbal memory decline in adults after temporal lobe resection (TLR) for epilepsy using easily accessible preoperative clinical predictors., Methods: Multivariable models were developed to predict delayed verbal memory outcome on 3 commonly used measures: Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from Wechsler Memory Scale-Third Edition. With the use of the Harrell step-down procedure for variable selection, models were developed in 359 adults who underwent TLR at the Cleveland Clinic and validated in 290 adults at 1 of 5 epilepsy surgery centers in the United States or Canada., Results: Twenty-nine percent of the development cohort and 26% of the validation cohort demonstrated significant decline on at least 1 verbal memory measure. Initial models had good to excellent predictive accuracy (calibration [c] statistic range 0.77-0.80) in identifying patients with memory decline; however, models slightly underestimated decline in the validation cohort. Model coefficients were updated with data from both cohorts to improve stability. The model for RAVLT included surgery side, baseline memory score, and hippocampal resection. The models for LM and VPA included surgery side, baseline score, and education. Updated model performance was good to excellent (RAVLT c = 0.81, LM c = 0.76, VPA c = 0.78). Model calibration was very good, indicating no systematic overestimation or underestimation of risk., Conclusions: Nomograms are provided in 2 easy-to-use formats to assist clinicians in estimating the probability of verbal memory decline in adults considering TLR for treatment of epilepsy., Classification of Evidence: This study provides Class II evidence that multivariable prediction models accurately predict verbal memory decline after TLR for epilepsy in adults., (© 2021 American Academy of Neurology.)

Objective: To characterize seizure and cognitive outcomes of sparing vs removing an magnetic resonance imaging (MRI)-normal hippocampus in patients with temporal lobe epilepsy., Methods: In this retrospective cohort study, we reviewed clinical, imaging, surgical, and histopathological data on 152 individuals with temporal lobe epilepsy and nonlesional hippocampi categorized into hippocampus-spared (n = 74) or hippocampus-resected (n = 78). Extra-hippocampal lesions were allowed. Pre- and postoperative cognitive data were available on 86 patients. Predictors of seizure and cognitive outcomes were identified using Cox-proportional hazard modeling followed by treatment-specific model reduction according to Akaike information criterion, and built into an online risk calculator., Results: Seizures recurred in 40% within one postoperative year, and in 63% within six postoperative years. Male gender (P = .03), longer epilepsy duration (P < .01), normal MRI (P = .04), invasive evaluation (P = .02), and acute postoperative seizures (P < .01) were associated with a higher risk of recurrence. We found no significant difference in postoperative seizure freedom rates at 5 years between those whose hippocampus was spared and those whose hippocampus was resected (P = .17). Seizure outcome models built with pre- and postoperative data had bootstrap validated concordance indices of 0.65 and 0.72. The dominant hippocampus-spared group had lower rates of decline in verbal memory (39% vs 70%; P = .03) and naming (41% vs 79%; P = .01) compared to the hippocampus-resected group. Partial hippocampus sparing had the same risk of verbal memory decline as for complete removal., Significance: Sparing or removing an MRI-normal hippocampus yielded similar long-term seizure outcome. A more conservative approach, sparing the hippocampus, only partially shields patients from postoperative cognitive deficits. Risk calculators are provided to facilitate clinical counseling., (© 2020 International League Against Epilepsy.)

Considerable variability exists in the publication of clinical research study procedures related to study enrollment and participant exit from clinical trials. Despite recent efforts to encourage research data sharing and greater transparency regarding research outcomes, reporting of research procedures remains inconsistent. Transparency about study procedures has important implications for the interpretation of study outcomes and the consistent implementation of best practices in clinical trial design and conduct. This review of publications from clinical trials of deep brain stimulation (DBS) using the MEDLINE database examines the frequency and consistency of publication of research procedures and data related to exit from DBS research. Related considerations, such as device explant or continued use, battery and other device hardware replacements, and post-trial follow-up care are also reviewed. This review finds significant variability in the publication and reporting of study exit procedures. Of the 47 clinical trials included in this review, 19% (9) disclosed procedures related to exit from research. Reporting of other exit-related data and study procedures examined in this review was identified in fewer than half of the included clinical trials. The rate of participant retention and duration of follow-up was reported more than any other category of data included in this review. Results inform efforts to improve consistency in research design, conduct, and publication of results from clinical trials in DBS and related areas of clinical research., (Copyright © 2020 Sankary, Nallapan, Hogue, Machado and Ford.)

Objective: Parkinson's disease (PD) is a progressive neurological movement disorder that is commonly treated with deep brain stimulation (DBS) surgery in advanced stages. The purpose of this study was to investigate factors that affect time to placement of a second-sided DBS lead for PD when a unilateral lead is initially placed for asymmetrical presentation. The decision whether to initially perform unilateral or bilateral DBS is largely based on physician and/or patient preference., Methods: This study was a retrospective cohort analysis of patients with PD undergoing initial unilateral DBS for asymmetrical disease between January 1999 and December 2017 at the authors' institution. Patients treated with DBS for essential tremor or other conditions were excluded. Variables collected included demographics at surgery, time since diagnosis, Unified Parkinson's Disease Rating Scale motor scores (UPDRS-III), patient-reported quality-of-life outcomes, side of operation, DBS target, intraoperative complications, and date of follow-up. Paired t-tests were used to assess mean changes in UPDRS-III. Cox proportional hazards analysis and the Kaplan-Meier method were used to determine factors associated with time to second lead insertion over 5 years., Results: The final cohort included 105 patients who underwent initial unilateral DBS for asymmetrical PD; 59% of patients had a second-sided lead placed within 5 years with a median time of 34 months. Factors found to be significantly associated with early second-sided DBS included patient age 65 years or younger, globus pallidus internus (GPi) target, and greater off-medication reduction in UPDRS-III score following initial surgery. Older age was also found to be associated with a smaller preoperative UPDRS-III levodopa responsiveness score and with a smaller preoperative to postoperative medication-off UPDRS-III change., Conclusions: Younger patients, those undergoing GPi-targeted unilateral DBS, and patients who responded better to the initial DBS were more likely to undergo early second-sided lead placement. Therefore, these patients, and patients who are more responsive to medication preoperatively (as a proxy for DBS responsiveness), may benefit from consideration of initial bilateral DBS.

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., Competing Interests: Declaration of competing interest Andre G. Machado: Consulting fees from St. Jude and has distribution rights from Enspire, ATI, and Cardionomics. The other authors have no disclosures relevant to this study., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Deep brain stimulation (DBS) has been considered for patients with intractable pain syndromes since the 1950s. Although there is substantial experience reported in the literature, the indications are contested, especially in the United States where it remains off-label. Historically, the sensory-discriminative pain pathways were targeted. More recently, modulation of the affective sphere of pain has emerged as a plausible alternative., Objective: To systematically review the literature from studies that used contemporary DBS technology. Our aim is to summarize the current evidence of this therapy., Methods: A systematic search was conducted in the MEDLINE, EMBASE, and Cochrane libraries through July 2017 to review all studies using the current DBS technology primarily for pain treatment. Study characteristics including patient demographics, surgical technique, outcomes, and complications were collected., Results: Twenty-two articles were included in this review. In total, 228 patients were implanted with a definitive DBS system for pain. The most common targets used were periaqueductal/periventricular gray matter region, ventral posterior lateral/posterior medial thalamus, or both. Poststroke pain, phantom limb pain, and brachial plexus injury were the most common specific indications for DBS. Outcomes varied between studies and across chronic pain diagnoses. Two different groups of investigators targeting the affective sphere of pain have demonstrated improvements in quality of life measures without significant reductions in pain scores., Conclusion: DBS outcomes for chronic pain are heterogeneous thus far. Future studies may focus on specific pain diagnosis rather than multiple syndromes and consider randomized placebo-controlled designs. DBS targeting the affective sphere of pain seems promising and deserves further investigation., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Germline mutations in PTEN, the gene that encodes phosphatase and tensin homolog, have been identified in up to 20% of children with autism spectrum disorder (ASD) and macrocephaly and are associated with marked abnormalities in the white matter of the brain. This study sought to characterize the neurobehavioral phenotype of PTEN-ASD. Comprehensive neurobehavioral evaluations were conducted in 36 participants (ages 3-21 years) with PTEN-ASD and compared to two groups of controls: non-syndromic ASD with macrocephaly (Macro-ASD, n = 25) and those with PTEN mutations without ASD (PTEN-no ASD, n = 23). Linear regression analysis or Kruskal-Wallis tests were used to examine group differences on neurobehavioral measures (cognitive, behavioral, sensory, and adaptive functioning) and, for select measures, one-sample t-tests were used to compare group performance to healthy control norms. These analyses revealed a distinct neuropsychological profile associated with mutations in PTEN suggesting primary disruption of frontal lobe systems (i.e., attention, impulsivity, reaction time, processing speed, and motor coordination). Cognitive deficits in PTEN-ASD are more severe than those in PTEN-no ASD and extend to other areas of neurobehavioral function, specifically, adaptive behavior and sensory deficits. While core ASD symptoms are similar in PTEN-ASD and Macro-ASD, PTEN-ASD had lower clinical ratings of autism severity and showed more sensory abnormalities suggestive of less sensory responsiveness. Together, these results suggest that PTEN-ASD has a distinct neurobehavioral phenotype compared to idiopathic ASD that is likely to warrant special consideration for overall assessment and treatment.

Objective: This retrospective, observational study investigated the relationship between objective naming decline and patient report of subjective decline in language functioning following epilepsy surgery. The role of depression in this relationship was also examined., Methods: A total of 429 adults with pharmacoresistant epilepsy completed the Boston Naming Test (BNT) and Memory Assessment Clinics Self-Rating Scale (MAC-S) before and after resective surgery. Multiple regression analyses were used to examine the relationship between objective naming decline and subjective language functioning, while controlling for the confounding effect of depression., Results: Individuals who experienced moderate to severe naming decline (≥11 raw points on BNT) following surgery reported a decline in subjective language functioning (p < .001) and endorsed problems with word-retrieval as well as more general semantic abilities. Those who experienced mild naming decline (5-10 raw points) also reported an increase in subjective language problems (p = .006). Complaints in this group were less severe than in those with more marked naming declines and were primarily related to word-retrieval. Both of these relationships remained significant after controlling for the confounding effect of depression (p < .005-.014)., Conclusions: Individuals with epilepsy who experience naming decline following surgery perceive these declines in their daily life, regardless of whether or not they are depressed. Findings support the utilization of risk models to predict naming outcome and the importance of counseling patients regarding the risk for naming decline following surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: There is a growing attention to determine the factors that predict quality of life (QoL) improvement after deep brain stimulation (DBS) for Parkinson's disease. Prior literature has largely focused on examining predictors one at a time, sometimes controlling for covariates., Objective: To develop a model that could be used as a nomogram to predict improvement in QoL following DBS surgery in patients with Parkinson's disease., Methods: All patients with complete pre- and postoperative movement disorder and neuropsychological testing who underwent DBS at a single institution between 2007-2012 were analyzed. The Parkinson's Disease Questionnaire-39 (PDQ-39) was used to measure QoL. Potential predictive factors, including patient demographics, clinical presentation characteristics, radiographic imaging, and motor and psychological testing were analyzed for impact on QoL., Results: Sixty-seven patients were identified, 36 (53.73%) of whom had meaningfully improved QoL following surgery. Five baseline variables showed significant relationships with the outcome: years since symptom onset, percent change in on/off motor evaluation, levodopa equivalent daily dose, bilateral vs unilateral DBS implantation, and PDQ-39 score. The final model includes PDQ-39, percent change in UPRS-III, and years since symptom onset and is able to predict improvement in QoL with 81% accuracy., Conclusion: Our model accurately predicted whether QoL would improve in patients undergoing subthalamic nucleus DBS 81% of the time. Our data may serve as the foundation to further refine a clinically relevant prognostic tool that would assist the decision-making process for clinicians and DBS multidisciplinary teams assessing patient candidacy for surgery., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Objective: Spinal cord stimulation (SCS) is both relatively safe and reversible. Although SCS is generally regarded as a last resort, some of these patients will undergo additional spinal surgery after the device has been implanted or after its removal. We present a descriptive study of subsequent spinal surgery after SCS implantation., Methods: A retrospective review of patients who had undergone percutaneous or paddle SCS lead placement at our institution from 2009 to 2016 was performed. Patients who had only undergone trials or who had not undergone spine surgery after SCS implantation were excluded., Results: We identified 22 patients (5.7%) who had undergone spine surgery during the course of SCS treatment or after SCS removal, or both, of a total 383 patients who had undergone paddle and/or percutaneous SCS implantation. The most common additional spine interventions included lumbosacral decompression and fusion (n = 15; 42%). Of 36 surgeries, the most frequent indications for subsequent intervention were stenosis or restenosis (n = 16; 73%) and spine deformity (n = 6; 27%). The median EuroQol-5D index was 0.397 preoperatively and 0.678 postoperatively., Conclusions: To the best of our knowledge, the present study is the first to describe spine surgery in the setting of SCS implantation. Our results have indicated that spine surgery subsequent to, or concurrent with, SCS implantation appears to occur in few patients. Our study results suggest a modest improvement in quality of life outcomes. Therefore, clinicians should remember that patients might require further spine surgery despite the use of SCS implantation and, thus, might require reevaluation by the spine team., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Associations between the crude capture of polyallergy-also known as multiple chemical sensitivity or multiple drug intolerance syndrome-and mental health/functional somatic syndrome disorders, healthcare utilization, or other clinical phenomenon have not been examined extensively., Methods: An IRB-approved retrospective chart review of all patients between age 18 and 70 who had a clinical encounter at a large medical center between 2009 and 2014. Patients were stratified into 4 categories based on the absolute number of chart-documented allergies: (1) no allergies; (2) normal allergy (1-4 allergies); (3) polyallergy (5-9 allergies); and (4) "ultrapolyallergy," (≥10 allergies), which were corroborated through a sensitivity analysis. Demographics, comorbidities, and medications were clustered per allergy grouping. Analysis of variance, chi-square, and multivariable logistic regression analyses were employed to test for associations., Results: 2,007,434 patients were examined ("no allergy" group, n = 1,423,631, 70.9%; "normal allergy" group: n = 549,927, 27.4%; "polyallergy" group n = 29,453, 1.5%; "ultrapolyallergy" group, n = 4,423, 0.22%). Proportion of females increased from 51% in the "no allergy" group to 89.6% in the "ultrapolyallergy" group (p < 0.001). Rates of mental health and functional somatic syndrome disorder diagnoses increased significantly across allergy groups (p < 0.001). All psychotropic medication classes were increased significantly across allergy groups (p < 0.001). Healthcare utilization was also significantly elevated across allergy cohorts (p <0.001)., Conclusions: This study demonstrates that polyallergy/multiple chemical sensitivity may serve as a crude yet meaningful indicator of comorbid psychopathology. Drug intolerance mechanisms are reviewed, and both clinical and investigational implications are examined., (Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)