Electrophysiological Correlates of Dentate Nucleus Deep Brain Stimulation for Poststroke Motor Recovery.

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.

Predictors of therapeutic response following thalamic neuromodulation for drug-resistant pediatric epilepsy: A systematic review and individual patient data meta-analysis.

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.

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

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

The effects of dexmedetomidine on intraoperative neurophysiologic monitoring modalities during corrective scoliosis surgery in pediatric patients: A systematic review.

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.

Statistical guidance provided to authors by clinical neurology and neuroscience journals.

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.

Intracranial Bleeding in Deep Brain Stimulation Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Deep brain stimulation (DBS) is a neurosurgical treatment used for the treatment of movement disorders. Surgical and perioperative complications, although infrequent, can result in clinically significant neurological impairment. OBJECTIVES: In this study, we evaluated the incidence and risk factors of intracranial bleeding in DBS surgery. METHOD: Medline, EMBASE, and Cochrane were screened in line with PRISMA 2020 guidelines to capture studies reporting on the incidence of hemorrhagic events in DBS. After removing duplicates, the search yielded 1,510 papers. Abstracts were evaluated by two independent reviewers for relevance. A total of 386 abstracts progressed to the full-text screen and were assessed against eligibility criteria. A total of 151 studies met the criteria and were included in the analysis. Any disagreement between the reviewers was resolved by consensus. Relevant data points were extracted and analyzed in OpenMeta [Analyst] software. RESULTS: The incidence of intracranial bleeding was 2.5% (95% CI: 2.2-2.8%) per each patient and 1.4% (95% CI: 1.2-1.6%) per each implanted lead. There was no statistically significant difference across implantation targets and clinical indications. Patients who developed an intracranial bleed were on average 5 years older (95% CI: 1.26-13.19), but no difference was observed between the genders (p = 0.891). A nonsignificant trend was observed for a higher risk of bleeding in patients with hypertension (OR: 2.99, 95% CI: 0.97-9.19) (p = 0.056). The use of microelectrode recording did not affect the rate of bleeding (p = 0.79). CONCLUSIONS: In this review, we find that the rate of bleeding per each implanted lead was 1.4% and that older patients had a higher risk of hemorrhage.

Stability and Effect of Parkinsonian State on Deep Brain Stimulation Cortical Evoked Potentials.

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.

Improving the prediction of epilepsy surgery outcomes using basic scalp EEG findings.

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.

Evidence of Stability in Patient-Reported Global Health During the COVID-19 Pandemic.

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.

Refractory Chronic Pain and Obesity: Promising Implications for Multidisciplinary Pain Rehabilitation.

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.

Outcomes of resections that spare vs remove an MRI-normal hippocampus.

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.

Polyallergy (Multiple Chemical Sensitivity) is Associated with Excessive Healthcare Utilization, Greater Psychotropic Use, and Greater Mental Health/Functional Somatic Syndrome Disorder Diagnoses: A Large Cohort Retrospective Study.

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.

Naming decline after epilepsy surgery is associated with subjective language complaints.

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.

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

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

Long-term Outcomes Using Intrathecal Drug Delivery Systems in Complex Regional Pain Syndrome.

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

Histopathologic subtype of hippocampal sclerosis and episodic memory performance before and after temporal lobectomy for epilepsy.

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

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal.

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

Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort.

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

Subsequent Pulse Generator Replacement Surgery Does Not Increase the Infection Rate in Patients With Deep Brain Stimulator Systems: A Review of 1537 Unique Implants at a Single Center.

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

Automated detection of cognitive impairment in clinical practice.

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