The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review.

BACKGROUND/IMPORTANCE: Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases. OBJECTIVE: This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults. EVIDENCE REVIEW: The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence. FINDINGS: Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies. CONCLUSIONS: Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings.

Racial and Ethnic Disparities in Inpatient Interventional Pain Management for Lumbar Radiculopathy.

BACKGROUND: Chronic pain is a common reason adults seek care; patients often feel that their pain is inadequately managed. Spine-related pain is the most common chronic pain concern, and lumbar radiculopathy is often the cause. Racial and ethnic disparities in the pharmacologic management of pain are well described, but less is known about these disparities regarding interventional procedures. OBJECTIVE: To study the utilization rates of physical therapy, epidural steroid injection, surgery, and spinal cord stimulation in hospitalized patients with lumbar radiculopathy across different races, ethnicities, and genders. STUDY DESIGN: A retrospective cross-sectional study design. METHODS: The National Inpatient Sample was used to identify 252,790 patients with lumbar radiculopathy, after sample weighting, from 2016-2019. Independent variables were race, ethnicity, age, gender, insurance, geography, year, and severity. Dependent variables were physical therapy, epidural steroid injection, spinal cord stimulator, or surgery (reference group). Conservative management was defined as nonoperative treatment ranging from physical therapy to epidural steroid injection. Data were analyzed with a logistic regression for complex surveys. Regressions were adjusted for age, insurance, geography, and other socioeconomic factors. RESULTS: Most patients were white (78.3%) and received surgery (95.0%). Severe disease was most common among African Americans (9.3%), but was similar across other races, ethnicities, and genders. Medicaid was more common among African Americans and Hispanics. An adjusted analysis showed that African Americans and Hispanics received more epidural steroid injections (odds ratio [OR] = 1.52; 95%CI, 1.3 - 1.8) and (OR = 1.43; 95%CI, 1.1 - 1.8) respectively; and physical therapy (OR = 1.65; 95%CI, 1.1 - 2.5) and (OR = 1.83; 95%CI, 1.2 - 2.8) respectively, than whites compared to surgery. African Americans received a spinal cord stimulator less often than whites compared to surgery (OR = 0.63; 95%CI. 0.4 - 0.9). Women received an epidural steroid injection more frequently than men compared to surgery (OR = 1.29; 95%CI, 1.2 - 1.4). LIMITATIONS: Generalizability is limited because conservative therapies are often outpatient treatments. CONCLUSION: Disparities were observed in lumbar radiculopathy treatment after independent variable adjustment. African Americans received conservative therapy more often than whites despite increased disease severity. Hispanics and women had similar disease severity compared to whites and men, respectively, but received more conservative therapies. Further investigation in outpatient settings is needed to definitively describe these disparities. KEY WORDS: Chronic pain, pain management, back pain, lumbar radiculopathy, epidural steroid injection, spinal cord stimulation, low back surgery, physical therapy, racial disparities, gender disparities.

Low-Dose Naltrexone (LDN) for Chronic Pain at a Single Institution: A Case Series.

Purpose: Low-dose naltrexone (LDN) has increased in popularity as a non-opioid medication that may decrease chronic pain symptoms. LDN is most commonly used to treat fibromyalgia, complex regional pain syndrome (CRPS), and painful diabetic neuropathy. Other studies suggest that LDN provides general symptom reduction in inflammatory conditions such as Crohn's disease and multiple sclerosis. We reviewed our experience with patients to whom we have prescribed LDN to see what types of painful conditions were most responsive to LDN in our patient population. Patients and Methods: Charts from patients who came to the Pain Center between 2014 and 2021 were reviewed. Results: Of the n = 137 patients who were prescribed LDN, 44% had no evidence of ever filling the prescription, and 4.4% of the responses were not charted. Of the remaining who took LDN (n = 70), 64% had some relief and were designated as 'Responders'. The most common pain diagnosis was neuropathic pain which, when added to the diagnosis of complex regional pain syndrome, accounted for 51% of responders to LDN. Patients who experienced greater than 50% pain relief from LDN were more likely to have the diagnosis of neuropathic pain or complex regional pain syndrome (p = 0.038, Fisher's Exact Test). There was a significant difference in the diagnosis of patients who responded to LDN. Patients with spondylosis were much less likely to respond to LDN when compared with other diagnoses (p = 0.00435, Chi-Square Test). Conclusion: Patients with all types of neuropathic pain, including CRPS, were significantly more likely to have pain relief from LDN than patients with spondylosis (p=0.018). The diagnosis of spondylosis was more often associated with a lack of response to LDN than any other diagnosis. Patients may need to have a trial of several weeks before analgesic effects are seen with LDN.

Associations of an eye-tracking task and pupillary metrics with age and ASA physical status score in a preoperative cohort.

Advanced age, American Society of Anesthesiologists physical status (ASA) classification and the presence of cognitive impairment are associated with an elevated risk of postoperative morbidity and mortality. The visual paired comparison (VPC) task, which relies on recognition of novel images, examines declarative memory. VPC scores have demonstrated the ability to detect mild cognitive impairment and track progression of neurodegenerative disease. Quantitative pupillometry may have similar value. We evaluate for associations between these variables of interest and the feasibility of performing these tests in the preoperative clinic. Prospective data from 199 patients seen in the preoperative clinic at a tertiary academic center were analyzed. A 5 min VPC task (Neurotrack Technologies, Inc, Redwood City, CA) was administered during their scheduled preoperative clinic visit. Pupillary light reflexes were measured at the same visit (PLR-3000™, Neuroptics Corp, Irvine, California).Thirty-four percent of patients were categorized as ASA 2 and 58% as ASA 3. Median age was 57 (IQR: 44-69). Associations were demonstrated between age and ASA physical status (Mann-Whitney U Test, p < 0.0001), maximum pupil size (Spearman Rank Correlation, r = - 0.40, p < 0.0001), and maximum constriction velocity (Spearman Rank Correlation, r = - 0.39, p < 0.0001). Our data also revealed an association between VPC score and age (Spearman Rank Correlation, p = 0.0016, r = - 0.21) but not ASA score (Kruskal-Wallis Test, p = 0.14). When compared to a nonsurgical cohort with no history of memory impairment, our population scored worse on the VPC task (Mann-Whitney U Test, p = 0.0002). A preoperative 5 min VPC task and pupillometry are feasible tests in the preoperative setting and may provide a valuable window into an individual's cognition prior to elective surgery.

Opioid-Free Anesthesia for Craniotomy.

BACKGROUND: Perioperative opioids are problematic following craniotomy as they can impede neurological examination because of excessive sedation and mask surgical complications. Multimodal anesthetic techniques including nerve blocks have been used successfully to deliver opioid-free anesthesia in other surgical populations; however, no clinical data evaluating opioid-free anesthesia for craniotomy exists within the current body of literature. MATERIALS AND METHODS: Six prospectively identified patients underwent supratentorial craniotomy at Emory University Hospital using a multimodal opioid-free anesthetic (OFA) technique consisting of preoperative scalp block, dexmedetomidine and intravenous acetaminophen. These opioid-free patients were matched by age, sex, incision length, and incision location to 18 retrospectively identified control patients who underwent craniotomy using conventional, opioid-based anesthetic techniques. Postoperative opioid consumption and pain scores were compared and analyzed for noninferiority. RESULTS: Noninferiority of the OFA technique was demonstrated for opioid consumption at all measured intervals from postanesthesia care unit arrival to 24 hours postoperatively. Noninferiority was also demonstrated with respect to average postoperative pain scores from 0 to 12 hours, 0 to 24 hours, as well as length of postanesthesia care unit stay. Noninferiority was not shown for time to first rescue opioid postoperatively, pain scores for the 12 to 24 hours postoperative period, or time to emergence from anesthesia. CONCLUSIONS: This pilot study demonstrates the feasibility of an OFA technique for patients undergoing supratentorial craniotomy and suggests that larger prospective randomized controlled trials are indicated to examine the role of multimodal anesthetic techniques for craniotomy.

Identifying Barriers to Buprenorphine Treatment for Patients with Opioid Use Disorder Among Anesthesiologists and Pain Practitioners: A Survey Study.

OBJECTIVE: The aim of the study is to investigate barriers to opioid use disorder (OUD) care among acute and chronic pain physicians and advanced practice providers, including hypothesized barriers of lack of interest in OUD care and stigma toward this patient population. METHODS: The study used an anonymous 16-item online survey through Google Forms. Respondents were 153 health practitioners across the United States and Canada, all of whom are registered in one of several pain or anesthesia professional societies. Data were analyzed with descriptive and categorical statistics. RESULTS: The most common barriers include "lack of appropriate clinical environment for prescribing by both acute and chronic pain practitioners" (48%) and "lack of administrative/departmental support" (46%). A total of 32% of respondents reported that OUD care was important but they were not interested in doing more, while 28% of practitioners believed that they treat patients with OUD differently than others in a negative way. More males reported "difficulty" in treating OUD as a barrier (45% vs 25%). Chronic pain practitioners reported poor payor mix as a barrier twice as often as their acute pain colleagues. In free response, lack of multidisciplinary OUD care was a notable barrier. CONCLUSIONS: The top barriers to OUD treatment were clinical environment, departmental support, difficulty in treating the condition, and payor mix, supporting the hypotheses. Given an OUD patient scenario, 55% of acute pain physicians and 73% of chronic pain physicians expressed a willingness to prescribe buprenorphine.

The impact of a postoperative multimodal analgesia pathway on opioid use and outcomes after cardiothoracic surgery.

OBJECTIVE: The Enhanced Recovery after Surgery Cardiac Society recommends using multimodal analgesia (MMA) for postoperative pain however, evidence-based guidelines have yet to be established. This study examines the impact of a standardized postoperative MMA pathway in reducing opioid consumption and related complications after cardiothoracic surgery (CTS). METHODS: Within a multicenter healthcare system, a postoperative MMA pathway was developed and implemented at two CTS intensive care units (ICU) while the other CTS ICU opted to maintain the existing opioid-based pathway. A retrospective chart review was conducted on patients admitted to a CTS ICU within this healthcare system after conventional coronary artery bypass grafting and/or valve surgery from September 1, 2018, to June 30, 2019. Comparative analysis was conducted on patients prescribed MMA versus those managed with an opioid-based pathway. The primary outcome was total opioid consumption, converted to morphine milligram equivalents, 72-h post-surgery. Secondary outcomes included mobility within one-day post-surgery, ICU length of stay (LOS), time to first bowel movement (BM), and time to first zero Richmond Agitation-Sedation Scale (RASS). RESULTS: Seven hundred sixty-two adults were included for final analysis. The MMA group had a higher body mass index, higher percentage of females, were more likely classified as African American and had higher scores for risk-adjusted complications. General Linear Model analysis revealed higher opioid consumption in the MMA group (Est. 0.22, p < 0.0009); however, this was not statistically significant after adjusting for differences in fentanyl usage. The MMA group was more likely to have mobility within one-day post-surgery (OR 0.44, p < 0.0001), have longer time to first BM (OR 1.93, p = 0.0011), and longer time to first zero RASS (OR 1.62, p = 0.0071). The analgesia groups were not a predictor for ICU LOS. CONCLUSIONS: Opioid consumption was not reduced secondary to this postoperative MMA pathway. The MMA group was more likely to have mobility within one-day post-surgery. Patients in the MMA group were also more likely to have prolonged time to first BM and first zero RASS. Development and evaluation of a perioperative MMA pathway should be considered.

Celiac plexus neurolysis for abdominal cancers: going beyond pancreatic cancer pain.

INTRODUCTION: Celiac plexus neurolysis (CPN) has been verified for mitigating pancreatic cancer pain. However, information regarding CPN's use beyond this remains limited. OBJECTIVES: Identify which cancers benefit from CPN, which symptoms improve, and when symptoms improve. METHODS: Retrospective analysis was conducted on 173 patients who received CPN for pain caused by various malignancies. Mean symptom changes on the MD Anderson Symptom Inventory (MDASI) from baseline to 2 weeks, 1 month, and 2 months after CPN were analyzed overall and then by cancer type: pancreatic (all stages and stages III-IV), hepatobiliary, and nonpancreatic, nonhepatobiliary gastrointestinal (NPNH-gastrointestinal). RESULTS: Eighty-two pancreatic, 43 NPNH-gastrointestinal, 14 hepatobiliary, and 34 patients with other cancers met inclusion criteria. Statistically significant changes included decrease in the pain score at 1 month by 1.01 points for all cancers, 1.65 points for all pancreatic cancers, and 1.88 points for late-stage pancreatic cancers. At 2 months, pain decreased by 1.50 points for all cancers, 1.68 points for all pancreatic cancers, 2.37 points for late-stage pancreatic cancers, and 1.50 points in NPNH-gastrointestinal cancers. At 2 months, quality of life improved by 1.07 points for all cancers and 1.53 points for all pancreatic cancers. Sleep improved at 2 months for all cancers by 0.73 points and 1.60 points in late-stage pancreatic cancers. At 2 months, pancreatic cancer patients improved in general activity by 0.93 points, walking by 1.00 points, and working by 1.12 points. CONCLUSION: Celiac plexus neurolysis can decrease cancer symptom burden beyond pain including quality of life and sleep for pancreatic and nonpancreatic cancers, as well as general activity for pancreatic cancers.

A Screening Tool to Detect Chronic Critically Ill Cardiac Surgery Patients at Risk for Low Levels of Testosterone and Somatomedin C: A Prospective Observational Pilot Study.

Objective The neuroendocrine response to critical illness is dichotomous as it is adaptive during the acute phase then transitions to maladaptive as critical illness becomes prolonged in 25-30% of patients. Presently, monitoring all critically ill patients for endocrinopathies is not the standard of care. However, given the negative impact on patient prognosis, a need to identify those at risk for endocrinopathies, may exist. Thus, a screening tool to identify endocrinopathies along the somatotroph and gonadal axes in a cardiothoracic surgery population was developed. Methods A prospective observational pilot study was conducted in two cardiothoracic surgery intensive care units (ICU) within a multi-site healthcare system. Total testosterone and somatomedin C levels were obtained from 20 adult patients who remained in the ICU for greater than seven days after cardiothoracic surgery and were tolerating nutrition, had a risk of malnutrition and a mobility score of moderate to dependent assistance. Results Twenty patients were included for descriptive analysis (seven females). Thirteen patients tested low for total testosterone, with males more likely to have a testosterone-related endocrinopathy as compared to females (100% vs. 0 to 43%, p = 0.0072). A higher proportion of low somatomedin C levels was found in females than males (57% vs. 31%); however, the difference was not statistically significant (p = 0.251). Conclusions The screening tool used in this pilot study accurately predicted low total testosterone in all men and reasonably predicted low somatomedin C in a majority of women. However, the ability of the tool to predict low total testosterone in women and low somatomedin C in men is less certain. A gender-specific screening tool might be necessary to predict hormonal deficiencies.

Erector Spinae Regional Anesthesia for Robotic Coronary Artery Bypass Surgery Is Not Associated With Reduced Postoperative Opioid Use: A Retrospective Observational Study.

OBJECTIVE: Regional anesthesia techniques are gaining traction in cardiac surgery. The aim of this study was to compare the analgesic efficacy of erector spinae plane block catheters (ESPBC), serratus anterior plane block catheters (SAPBC), and paravertebral single-shot block (PVB) versus no block after robotic minimally invasive direct coronary artery bypass (MIDCAB). DESIGN: This was a retrospective observational study of routinely recorded data. SETTING: The study was performed at a single healthcare system. PARTICIPANTS: All patients underwent robotic MIDCAB. INTERVENTION: Data were analyzed from 346 patients during a 53-month period. The clinical data warehouse was queried for all robotic MIDCAB surgeries. Variables abstracted included type of nerve block, age, sex, use of adjuncts, Society of Thoracic Surgeons predicted short length of stay (PSLOS), total opioid consumption during the 72 hours after surgery, and postoperative hospital length of stay (LOS). The primary outcome was total oral morphine milligram equivalents (MME) consumed during the first 72 hours after surgery. The secondary outcome was hospital LOS. MEASUREMENTS AND MAIN RESULTS: In a model adjusting for PSLOS, the authors did not observe an association between ESPBC and the reduction of total administered oral MME within 72 hours after surgery. There was no significant difference in MME when comparing patients who received PVB to patients with ESPBC. Older age and female sex were associated with significantly lower MME. Patients who received ESPBC had a significantly shorter hospital LOS than patients with SAPBC. CONCLUSIONS: These findings suggested that postoperative pain after MIDCAB surgery might not be completely covered by ESPBC. Prospective studies are needed to further elucidate the value of this technique for robotic MIDCAB.

High-Resolution Pulse Oximetry (HRPO): A Cost-Effective Tool in Screening for Obstructive Sleep Apnea (OSA) in Acute Stroke and Predicting Outcome.

INTRODUCTION: Obstructive sleep apnea (OSA) is a well-known risk factor for stroke. This is attributed to multiple mechanisms such as endothelial dysfunction, atrial fibrillation, hypertension, and comorbid obesity. STOP questionnaire alone is unreliable to diagnose OSA and in-hospital sleep study is costly and can be technically challenging. We used high-resolution pulse oximetry (HRPO) to test the feasibility of screening for OSA and predicting outcome. METHODS: Data from 115 stroke patients who underwent HRPO was collected including Oxygen desaturation index (ODI) <4%, pulse rate, arterial oxygen saturation (SaO2), and time spent at SaO2 saturation <88%. We also collected data on various confounders. The outcomes measured were NIHSS (National Institutes of Health Stroke Scale), mRS (modified Rankin Score) on discharge, and discharge disposition. RESULTS: Overall 115 patients with valid HRPO data were included in the study. Mean age was 64±12years with 68% white, 22% black, and 10% Hispanic population. Of this cohort of 115 patients, 56% were males. Of the subjects enrolled 22 had atrial fibrillation, 27 had type 2 diabetes, 7 had resistant hypertension, and 7 had patient foramen ovale. Of the 115 patients, 75 patients were found to have ODI of >10 and the mean ODI was 29±30. The NIHSS on admission was 6.14±6.93 and on discharge was 4.46±4.59, mRS on discharge was 1.70±1.67 with 52% being discharged home, 43% to rehab, 2% nursing home, and 3% to long-term acute care facility. In this study, we show a strong association between atrial fibrillation and increasing ODI (P<.001, OR 1.01, CI 1.00-1.03). In addition, our study also shows an association between discharges outcome of rehab (more deficits leading to higher disability) versus discharge to home (lesser deficits) if ODI was ≤10 (P = 0.005, OR 3.76, CI 1.49-9.52). CONCLUSIONS: Our study showed that there is a significant burden of OSA in acute stroke patients. ODI emerged as a predictor of atrial fibrillation and discharge disposition in our study. HRPO may be a cost-effective tool to screen and evaluate for OSA in acute stroke patients.

Effect of Preoperative Opioid Dosage on Postoperative Period After Thoracic Spinal Cord Stimulator Surgery.

Objective: We aim to study the impact of preoperative opioid dosage on postoperative length of stay (LOS) in patients undergoing thoracic spinal cord stimulator (SCS) placement surgery as a primary objective. Secondary objectives of this study include investigating patient-controlled analgesia (PCA) usage and postoperative complications like fever in relation to patients' preoperative opioid dosage and postoperative LOS. Methods: A total of 47 patients who underwent thoracic SCS for first time were retrospectively studied through chart review. These patients were categorized into two groups, with Group I patients taking a morphine equivalent dose (MED) of less than 100 mg and Group II patients taking an MED of more than 100 mg preoperatively. Results: Group I had 22 patients, and Group II had 25 patients. The average age in Group I was 53.45 years, and the average age in Group II was 50.16 years. There were seven males (38%) and 15 females (62%) in Group I, and in Group II there were 11 males (44%) and 14 females (56%). The average LOS in both groups was two days. In Group I, there were 16 patients (73%) who had an LOS of one day and six patients (27%) who had an LOS of more than one day, and in Group II there were 11 patients (44%) who had an LOS of less than one day and 14 patients (56%) who had an LOS of more than one day, with a P value of 0.047. On univariate analysis, postoperative fever and PCA usage correlated with longer hospital stay, with a P value of < 0.001. Conclusion: Patients on high-dose chronic opioid therapy, defined as an MED greater than 100 mg, who undergo thoracic spinal cord stimulator surgery tend to have longer postoperative hospital stays compared with patients on lower-dose opioid therapy.

Complications of subdural and depth electrodes in 269 patients undergoing 317 procedures for invasive monitoring in epilepsy.

OBJECTIVE: Intracranial monitoring is fundamental to epilepsy surgery, with reported complication rates of 3-17%. We aimed to assess the differences in complication rates between subdural and depth electrodes. METHODS: We conducted a retrospective review of 317 electrode implantation procedures. All documented abnormal postoperative findings were recorded in our study. Those that resulted in a significant alteration of treatment course, including neurologic deficit, long-term medication use, reoperation, or hospital readmission, were deemed clinically significant. When possible, findings were attributed to a particular electrode type based on relative location to each electrode. RESULTS: Postoperative abnormalities were associated with SDE placement in 152 (47.9%) procedures and 40 (25.2%) DE placements (p < 0.001). Twenty-nine (9.1%) clinically significant complications were seen in the subdural electrode (SDE) group compared to 10 associated with DEs (6.3%, p = 0.37). SDEs were associated with increased rates of any postoperative hemorrhage (p < 0.001) or extraaxial collection (p = 0.007). Subdural grid placement was associated with an increased risk of any extraaxial collection (odds ratio [OR 2.42), as well as clinically significant collections (OR 9.47). Previous craniotomy was found to be associated with any abnormal postoperative finding (OR 1.71) as well as radiographic hemorrhage (OR 1.99). Concurrent resection is also associated with abnormal findings (OR 1.83) and extraaxial collections (OR 2.37). The overall complication rate was 9.1%, with 13 procedures (4.1%) resulting in neurologic deficit. However, only two patients (0.6%) had permanent neurologic sequelae resulting from lead placement. SIGNIFICANCE: Subdural electrodes appear to have an increased rate of abnormal postoperative findings, including hemorrhage and extraaxial collections; however, there was no difference in clinically significant findings. Subdural grids also appear to be associated with symptomatic extraaxial collections, and previous craniotomy increases the risk of hemorrhage. Overall, intracranial monitoring remains a safe and effective procedure for localization of operative seizure foci. Patient selection and risk education for various modalities is an essential aspect of preoperative evaluation.

Long-Term Pain Reduction Does Not Imply Improved Functional Outcome in Patients Treated With Combined Supraorbital and Occipital Nerve Stimulation for Chronic Migraine.

BACKGROUND: Dual supraorbital and occipital nerve stimulation (SONS and ONS) have shown promising efficacy in treating primary headaches. However, its functional outcome is not well studied. OBJECTIVE: To present functional outcome studies of combined SONS and ONS for chronic migraine using verified metrics. METHOD: Consecutive patients with both SONS and ONS assessed with Migraine Disability Assessment (MIDAS) and Beck Depression Index (BDI) both preoperatively and postoperatively were studied. Selected predictor variables included patients with ≥50% improvement of pain, disability status, number of years from diagnosis to implantation, and narcotic use. Functional outcome variables included net improvement of ranked MIDAS and BDI scores. Multivariate analysis of variance was performed to assess the correlation between the outcome and predictor variables. RESULTS: Sixteen patients (12 female; average age 52 years old) were studied. Follow-up ranged from 5 to 80 months (average 44.5; σ = 21.4 months). At most recent follow-up, eight patients had a positive response (≥50% improvement in headache), which was the only predictor of functional outcome (total MIDAS, MIDAS-B, and BDI) (p = 0.021). Of note, improvement in functional outcome was only significant during the perioperative 3-6 months period and not throughout long-term follow-up. Among the predictor variables, a strong inverse correlation was found between disability status and positive response to stimulation (r = -0.582). CONCLUSION: There is a paucity of studies in quality of life, productivity, and psychosocial aspects with peripheral nerve stimulation therapy for headache. Patients with a positive response to SONS and ONS also reported overall improvement in their functional status as reflected by MIDAS and BDI in the perioperative period. Unfortunately, this effect waned over the long-term follow-up.

Acute Traumatic Coagulopathy Accompanying Isolated Traumatic Brain Injury is Associated with Worse Long-Term Functional and Cognitive Outcomes.

BACKGROUND: Approximately one-third of patients with isolated traumatic brain injury (iTBI) present with acute traumatic coagulopathy (ATC). ATC is associated with increased morbidity and mortality. Its effects on long-term functional and cognitive outcomes are not as well characterized. METHODS: Data from the Citicoline Brain Injury Treatment Trial (COBRIT) were analyzed retrospectively. Exclusion criteria were renal failure or malignancy, and any extracranial injury severity score >3. ATC was defined as INR > 1.3, PTT > 38 s, or platelets < 100 K, determined at baseline, and during the first 7 days of hospitalization. RESULTS: Six hundred forty-seven patients were included; 21 % were found to have ATC. Highest incidence occurred at baseline, and Day Two. Forty-two percent of ATC patients had a GCS < 8, compared with 11.3 % of non-ATC patients (p < 0.001). A significantly higher proportion of ATC patients was transfused blood products, required greater than 4L of fluids, demonstrated hyperthermia and hypothermia, were hypotensive and demonstrated elevated lactate when compared to non-ATC patients. In-hospital mortality, mean hospital length of stay, incidence of DVT and seizures were also significantly higher in ATC patients. A significantly lower portion of ATC patients had good outcomes on the GOS-E (i.e., score > 6), and the DRS (i.e., score < 2) at 180 days, for which ATC was found to be an independent predictor with binary logistic regression. ATC patients also performed significantly worse on several components of the CVLT-II at 180 days. CONCLUSIONS: ATC accompanying iTBI is associated with worse functional and cognitive outcomes at 180 days.

The effects of anatomic variations on stereotactic laser amygdalohippocampectomy and a proposed protocol for trajectory planning.

BACKGROUND: Stereotactic laser amygdalohippocampectomy (SLAH) is a promising minimally invasive alternative for mesial temporal lobe epilepsy. As seizure outcome has been associated with the extent of amygdalar and hippocampal ablation, it is important to select a safe trajectory optimizing involvement of both structures; however, variations in temporal anatomy significantly affect the overall complexity of planning. OBJECTIVE: To quantify anatomic variables of SLAH and facilitate stereotactic planning by developing a protocol for optimally targeting the amygdalohippocampal complex (AHC). METHODS: We performed a retrospective analysis of 19 SLAHs. Anatomic measurements from preoperative magnetic resonance imaging and laser trajectory measurements from coregistered postoperative magnetic resonance imaging were taken in 11 patients. Simple linear regression analysis was performed to identify significant predictor variables determining ablation extent. Based on these data, a protocol for optimal trajectory planning was developed and subsequently implemented in 8 patients. RESULTS: The medial angle of the laser trajectory correlated with the medial angle of the AHC. The length of amygdalar cannulation was predictive of its ablation volume. All trajectories passed through a posteroinferior corridor formed by the lateral ventricle superiorly and collateral sulcus inferiorly. Our protocol facilitated planning and increased the volume of AHC ablation. CONCLUSION: The medial AHC angle dictates the medial trajectory angle and a path from the posteroinferior corridor through the hippocampus and the center of the amygdala dictates the caudal angle. These observations led to a protocol for long-axis AHC cannulation that maintains an extraventricular trajectory to minimize hemorrhage risk and targets the center of the amygdala to optimize ablation volumes.

Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers.

OBJECTIVE: This study aims to evaluate associations between variations in genes involved in the metabolism of environmental chemicals and steroid hormones and risk of menopause in smokers. METHODS: Survival analysis was performed on 410 eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a cohort study of late-reproductive-age women. Single nucleotide polymorphisms at the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3 Leu432Val, and CYP3A4*1B. RESULTS: Significant interactions between smoking and single nucleotide polymorphisms were observed in European-American carriers of CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR], 2.26; 95% CI, 1.4-3.67; median time to menopause, 10.42 and 11.07 y, respectively). No association between smoking and menopause was identified in CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31-69.2; median time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03-2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54-5.84; median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers (adjusted HR, 17.79; 95% CI, 3.21-98.65; median time to menopause, 5.09 y) had the greatest risk of menopause entry. CONCLUSIONS: Our finding that the risk of menopause entry in European-American smokers varies depending on genetic background represents a novel gene-environment interaction in reproductive aging.

Longitudinal pattern of depressive symptoms around natural menopause.

IMPORTANCE: An increased risk of depressive symptoms has been associated with the transition to menopause, but the risk of depressive symptoms in the early postmenopausal years has not been well characterized. OBJECTIVES: To identify within-woman changes in depressive symptoms during a 14-year period around menopause, determine associations of a history of depression with the pattern of depressive symptoms, and evaluate the rate of change in reproductive hormones as predictors of depressive symptoms following menopause. DESIGN, SETTING, AND PARTICIPANTS: A randomly identified, population-based sample in Philadelphia County, Pennsylvania, of 203 late-reproductive-age women who were premenopausal at baseline and reached natural menopause. MAIN OUTCOMES AND MEASURES: Center for Epidemiologic Studies Depression Scale. RESULTS: The prevalence of high scores on the Center for Epidemiologic Studies Depression Scale decreased from 10 years before to 8 years after the final menstrual period (FMP), with a decrease of approximately 15% of baseline per year (odds ratio, 0.85; 95% CI, 0.81-0.89; P < .001). Relative to the FMP, the risk of depressive symptoms was higher in the years before and lower in the years after the FMP. Among women with a history of depression, the likelihood of depressive symptoms was more than 13 times greater overall and 8 times greater after menopause compared with women with no depression history. Among women who first experienced depressive symptoms approaching menopause, the risk of depressive symptoms declined after the FMP, with a significantly lower risk the second year after menopause. The risk of depressive symptoms after menopause decreased by 35% for each unit (SD) increase before the FMP in the log rate of change of follicle-stimulating hormone (odds ratio, 0.65; 95% CI, 0.46-0.91; P = .01). CONCLUSIONS AND RELEVANCE: The FMP was pivotal in the overall pattern of decreasing depressive symptoms in midlife women, with higher risk before and lower risk after the FMP. A history of depression strongly increased the risk both before and after menopause. Women who had no history of depression before the menopause transition had a low risk of depressive symptoms 2 or more years after the FMP.