National multicentered retrospective review of clinical and intraoperative factors associated with the development of cerebellar mutism after pediatric posterior fossa tumor resection.

BACKGROUND: Cerebellar mutism (CM) is characterized by a significant loss of speech in children following posterior fossa (PF) surgery. The biological origin of CM remains unclear and is the subject of ongoing debate. Significant recovery from CM is less likely than previously described despite rigorous multidisciplinary neuro-rehabilitational efforts. METHODS: A national multi-centered retrospective review of all children undergoing PF resection in four midsized Canadian academic pediatric institutions was undertaken. Patient, tumor and surgical factors associated with the post-operative development of CM were reviewed. Retrospective identification of PF surgery patients including those developing and those that did not (internal control). RESULTS: The study identified 258 patients across the 4 centers between 2010 and 2020 (mean age 6.73 years; 42.2% female). Overall, CM was experienced in 19.5% of patients (N = 50). Amongst children who developed CM histopathology included medulloblastoma (35.7%), pilocytic astrocytoma (32.6%) and ependymoma (17.1%). Intraoperative impression of adherence to the floor of the 4th ventricle was positive in 36.8%. Intraoperative abrupt changes in blood pressure and/or heart rate were identified in 19.4% and 17.8% of cases. The clinical resolution of CM was rated to be complete, significant resolution, slight improvement, no improvement and deterioration in 56.0%, 8.0%, 20.0%, 14.0% and 2.0%, respectively. In the cohort of children who experienced post-operative CM as compared to their no-CM counterpart, proportionally more tumors were felt to be adherent to the floor of the 4th ventricle (56.0% vs 49.5%), intraoperative extent of resection was a GTR (74% vs 68.8%) and changes in heart rate were noted (≥ 20% from baseline) (26.0% vs 15.9%). However, a multiple regression analysis identified only abrupt changes in HR (OR 5.97, CI (1.53, 23.1), p = 0.01) to be significantly associated with the development of post-operative CM. CONCLUSION: As a devastating surgical complication after posterior fossa tumor surgery with variable clinical course, identifying and understanding the operative cues and revising intraoperative plans that optimizes the child's neurooncological and clinical outcome are essential.

Differential Target Multiplexed Spinal Cord Stimulation: A UK Cost-Effectiveness Analysis.

OBJECTIVES: The aim of this economic analysis was to evaluate the cost-effectiveness of differential target multiplexed spinal cord stimulation (DTM-SCS) for treating chronic intractable low back pain, compared with conventional spinal cord stimulation (C-SCS) and conservative medical management (CMM), by updating and expanding the inputs for a previously published cross-industry model. MATERIALS AND METHODS: This model comprised a 12-month decision-tree phase followed by a long-term Markov model. Costs and outcomes were calculated from a UK National Health Service perspective, over a base-case horizon of 15 years and up to a maximum of 40 years. All model inputs were derived from published literature or other deidentified sources and updated to reflect recent clinical trials and costs. Deterministic and one-way sensitivity analyses were performed to calculate costs and quality-adjusted life-years (QALYs) across the 15-year time horizon and to explore the impact of individual parameter variability on the cost-effectiveness results. Probabilistic sensitivity analysis was undertaken to explore the impact of joint parameter uncertainty on the results. RESULTS: DTM-SCS was the most cost-effective option from a payer perspective. Compared with CMM alone, DTM-SCS was associated with an incremental cost-effectiveness ratio (ICER) of £6101 per QALY gained (incremental net benefit [INB] = £21,281). The INB for C-SCS compared with CMM was lower than for DTM-SCS, at £8551. For the comparison of DTM-SCS and C-SCS, an ICER of £897 per QALY gained was calculated, with a 99.5% probability of cost-effectiveness at a £20,000 per QALY threshold. CONCLUSIONS: Among patients with low back pain treated over a 15-year follow-up period, DTM-SCS and C-SCS are cost-effective compared with CMM, from both payer and societal perspectives. DTM-SCS is associated with a lower ICER than that of C-SCS. Wider uptake of DTM-SCS in the UK health care system is warranted to manage chronic low back pain.

Spinal Cord Stimulation Improves Quality of Life for Patients With Chronic Pain-Data From the UK and Ireland National Neuromodulation Registry.

INTRODUCTION: Spinal cord stimulation (SCS) is a well-established treatment for chronic pain and is supported by numerous studies. However, some recent articles have questioned its efficacy. This article examines a cohort of >1800 patients with SCS from the UK and Ireland National Neuromodulation Registry. It is intended to provide a "real-world" assessment of efficacy and compare its effects with other procedures performed for painful indications. MATERIALS AND METHODS: Quality of life (QoL) data (EuroQoL five-level [EQ5D]) and demographic data were extracted from the National Neuromodulation Registry for all patients (N = 1811) who underwent SCS for chronic pain in 27 centers in the UK between February 2018 and July 2022. These were compared with data from the published literature for other commonly performed elective surgical procedures. RESULTS: The EQ5D utility index increased by a mean of 0.202 in the 1236 patients with paired pre- and postoperative utility scores. The median utility was 0.263 (interquartile range [IQR] = 0.384; n = 1811) preoperatively, whereas at six months after the operation, it was 0.550 (IQR = 0.396; n = 1025), p < 0.0001, Wilcoxon rank sum test. The median utility score at 12 months postoperation was 0.548 (IQR = 0.417; n = 970). There was no difference in utility scores at six months and 12 months after implantation (p = 0.15, Wilcoxon rank sum test). There was a significant improvement in QoL in all five domains of the five-level EQ5D tool at six months after baseline (p < 0.01, for all subcategories), and this was sustained at one year after implantation. The baseline utility was lower than in patients who underwent elective surgery for other painful conditions, and the absolute (and proportionate) increase in utility produced by SCS was greater than that achieved with most other interventions. CONCLUSIONS: SCS increases the QoL in patients requiring surgery for pain. Similar results were seen regardless of SCS indication. When comparing analogous data bases, SCS produces a greater percentage improvement in EQ5D utility than do many other elective surgical procedures for painful conditions, including spinal surgery and some joint replacements.

Five-Year Longitudinal Follow-Up of Restorative Neurostimulation Shows Durability of Effectiveness in Patients With Refractory Chronic Low Back Pain Associated With Multifidus Muscle Dysfunction.

BACKGROUND: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology. MATERIALS AND METHODS: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol's "EQ-5D-5L" index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data. RESULTS: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed. CONCLUSION: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354; registration date: October 15, 2016; principal investigator: Christopher Gilligan, MD, Brigham and Women's Hospital, Boston, MA, USA. The study was conducted in Australia (Broadmeadow, New South Wales; Noosa Heads, Queensland; Welland, South Australia; Clayton, Victoria), Belgium (Sint-Niklaas; Wilrijk), The Netherlands (Rotterdam), UK (Leeds, London, Middlesbrough), and USA (La Jolla, CA; Santa Monica, CA; Aurora, CO; Carmel, IN; Indianapolis, IN; Kansas City, KS; Boston, MA; Royal Oak, MI; Durham, NC; Winston-Salem, NC; Cleveland, OH; Providence, RI; Spartanburg, SC; Spokane, WA; Charleston, WV).

Spinal ectopic recurrence of craniopharyngioma in a pediatric patient.

Craniopharyngiomas are rare, benign lesions that can be treated with surgery, radiation therapy, or a combination of these modalities. They have a propensity for local recurrence, but there have also been rare cases reported of ectopic recurrence. Here, we present the case of a 15-year-old girl with a recurrence of craniopharyngioma in the spine, which is the second-ever reported case of recurrence outside of the brain in a pediatric patient, and review the 19 reported cases of ectopic recurrence in pediatric patients due to cerebrospinal fluid dissemination.

Dynamic Brain Imaging Response to Spinal Cord Stimulation Differential Frequencies DiFY SCS-PET Clinical Trial.

OBJECTIVES: This study with sequential 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scanning was designed to investigate any objective measurable effect of differential frequency stimulation (40 Hz, 4000 Hz, and 10,000 Hz) on specific pain matrix areas in patients who underwent spinal cord stimulation (SCS) for intractable lumbar neuropathic pain. MATERIALS AND METHODS: In this single-center, randomized, blinded study, four brain 18F-FDG PET scans were performed for each patient-at baseline before SCS implant and after 40-Hz, 4000-Hz, and 10,000-Hz stimulation. After 40-Hz stimulation for four weeks, patients were randomized 1:1 (4000 Hz/10,000 Hz), crossing over at another four weeks. 18F-FDG PET-CT brain scans acquired on the GE-Discovery 710 PET system (GE Healthcare, Chicago, IL) with 128-slice CT (250-MBq dose) were analyzed using the PMOD software (PMOD Technologies Ltd, Zurich, Switzerland). A total of 18 pain regions, the right and left prefrontal cortex (PFC), insula, anterior cingulate cortex (ACC), hippocampus, amygdala, primary somatosensory cortices, secondary somatosensory cortices (SSCII), thalami, parabrachial, and periaqueductal gray (PAG), were analyzed. RESULTS: A total of 14 patients received 40 Hz for four weeks before crossing over to 10,000 Hz/4000 Hz. A total of 57 PET-CT scans (15 for baseline and 14 each for 40 Hz, 4000 Hz, and 10,000 Hz) were analyzed for maximum standardized uptake value (SUVmax), with a statistically significant difference in SUVmax between 40 Hz and baseline (p = 0.002) and 4000 Hz and baseline (p = 0.001) when pooled across 18 pain matrices. There was no statistical difference in SUVmax between 10,000 Hz and baseline. The pooled analysis showed a proportionately higher thalamic region reduction (59.5%) in metabolic activity than other pain matrices, PFC (52%), insula (50%), ACC (52%), SSCII (49%), and PAG (52%). CONCLUSION: This large cohort of brain PET scans (n = 57) shows statistically significant differences in brain metabolic activity at 40 Hz and 4000 Hz from baseline, with effect on both nociceptive and affect-cognitive pathways (proportionately higher reduction in the thalamus), highlighting the possible mechanism of SCS. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03716557.

Long-Term Outcomes of Restorative Neurostimulation in Patients With Refractory Chronic Low Back Pain Secondary to Multifidus Dysfunction: Two-Year Results of the ReActiv8-B Pivotal Trial.

BACKGROUND: Impaired neuromuscular control and degeneration of the multifidus muscle have been linked to the development of refractory chronic low back pain (CLBP). An implantable restorative-neurostimulator system can override the underlying multifidus inhibition by eliciting episodic, isolated contractions. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward. OBJECTIVE: This study aimed to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Open-label follow-up of 204 participants implanted with a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was performed. Pain intensity (visual analog scale [VAS]), disability (Oswestry disability index [ODI]), quality-of-life (EQ-5D-5L), and opioid intake were assessed at baseline, six months, one year, and two years after activation. RESULTS: At two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of participants had continued device use during the second year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake. CONCLUSIONS: At two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The study is registered on clinicaltrials.gov with identifier NCT02577354.

A Novel Pulsed Stimulation Pattern in Spinal Cord Stimulation: Clinical Results and Postulated Mechanisms of Action in the Treatment of Chronic Low Back and Leg Pain.

OBJECTIVES: The aim of this article is to discuss the possible mechanisms of action (MOAs) and results of a pilot study of a novel, anatomically placed, and paresthesia-independent, neurostimulation waveform for the management of chronic intractable pain. MATERIALS AND METHODS: A novel, multilayered pulsed stimulation pattern (PSP) that comprises three temporal layers, a Pulse Pattern layer, Train layer, and Dosage layer, was developed for the treatment of chronic intractable pain. During preliminary development, the utility was evaluated of anatomical PSP (aPSP) in human subjects with chronic intractable pain of the leg(s) and/or low back, compared with that of traditional spinal cord stimulation (T-SCS) and physiological PSP. The scientific theory and testing presented in this article provide the preliminary justification for the potential MOAs by which PSP may operate. RESULTS: During the pilot study, aPSP (n = 31) yielded a greater decrease in both back and leg pain than did T-SCS (back: -60% vs -46%; legs: -63% vs -43%). In addition, aPSP yielded higher responder rates for both back and leg pain than did T-SCS (61% vs 48% and 78% vs 50%, respectively). DISCUSSION: The novel, multilayered approach of PSP may provide multimechanistic therapeutic relief through preferential fiber activation in the dorsal column, optimization of the neural onset response, and use of both the medial and lateral pathway through the thalamic nuclei. The results of the pilot study presented here suggest a robust responder rate, with several subjects (five subjects with back pain and three subjects with leg pain) achieving complete relief from PSP during the acute follow-up period. These clinical findings suggest PSP may provide a multimechanistic, anatomical, and clinically effective management for intractable chronic pain. Because of the limited sample size of clinical data, further testing and long-term clinical assessments are warranted to confirm these preliminary findings.

Three-Year Durability of Restorative Neurostimulation Effectiveness in Patients With Chronic Low Back Pain and Multifidus Muscle Dysfunction.

BACKGROUND: Restorative neurostimulation is a rehabilitative treatment for patients with refractory chronic low back pain (CLBP) associated with dysfunction of the lumbar multifidus muscle resulting in impaired neuromuscular control. The ReActiv8-B randomized, sham-controlled trial provided evidence of the effectiveness and safety of an implanted, restorative neurostimulator. The two-year analysis previously published in this journal demonstrated accrual of clinical benefits and long-term durability. OBJECTIVE: Evaluation of three-year effectiveness and safety in patients with refractory, disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Prospective, observational follow-up of the 204 implanted trial participants. Low back pain visual analog scale (VAS), Oswestry Disability Index (ODI), EuroQol quality of life survey, and opioid intake were assessed at baseline, six months, and one, two, and three years after activation. The mixed-effects model repeated measures approach was used to provide implicit imputations of missing data for continuous outcomes and multiple imputation for proportion estimates. RESULTS: Data were collected from 133 participants, and 16 patients missed their three-year follow-up because of coronavirus disease restrictions but remain available for future follow-up. A total of 62% of participants had a ≥ 70% VAS reduction, and 67% reported CLBP resolution (VAS ≤ 2.5cm); 63% had a reduction in ODI of ≥ 20 points; 83% had improvements of ≥ 50% in VAS and/or ≥ 20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 71% (36/51) participants on opioids at baseline had voluntarily discontinued (49%) or reduced (22%) opioid intake. The attenuation of effectiveness in the imputed (N = 204) analyses was relatively small and did not affect the statistical significance and clinical relevance of these results. The safety profile remains favorable, and no lead migrations have been observed to date. CONCLUSION: At three years, 83% of participants experienced clinically substantial improvements in pain, disability, or both. The results confirm the long-term effectiveness, durability, and safety of restorative neurostimulation in patients with disabling CLBP associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354.

Effectiveness of high dose spinal cord stimulation for non-surgical intractable lumbar radiculopathy - HIDENS Study.

OBJECTIVES: Spinal cord stimulation (SCS) is being increasingly used in non-surgical intractable low back pain. This study was designed to evaluate the efficacy of high-dose (HD) SCS utilizing sub-perception stimulation with higher frequency and pulse width in non-surgical predominant low-back pain population at 12 months. MATERIALS AND METHODS: A total of 20 patients were recruited (280 screened between March 2017 and July 2018) to undergo percutaneous fluoroscopic-guided SCS (Medtronic 8 contact standard leads and RestoreR IPG), with T8 and T9 midline anatomical parallel placement. Sixteen patients completed 12 months follow-up (500 Hz frequency, 500 µs pulse width, and 25% pulse density). Differences in patients' clinical outcome (NRS back, NRS leg, ODI, PGIC, and PSQ) and medication usage (MQS) at 1, 3, and 12 months from the baseline were assessed using non-parametric Wilcoxon paired test. RESULTS: The mean NRS scores for back pain (baseline 7.53) improved significantly at 1, 3, and 12 months; 2.78 (p < 0.001), 4.45 (p = 0.002), and 3.85 (p = 0.002), respectively. The mean NRS score for leg pain (baseline 6.09) improved significantly at 1 and 3 months; 1.86 (p < 0.001) and 3.13 (p = 0.010), respectively. Mean NRS for leg pain at 12 months was 3.85 (p = 0.057). ODI and sleep demonstrated significant improvement as there was consistent improvement in medication particularly opioid usage (MQS) at 12 months. CONCLUSIONS: This study demonstrates that anatomical placement of leads with sub-perception HD stimulation could provide effective pain relief in patients who are not candidates for spinal surgery.

Opioid sparing strategies for perioperative pain management other than regional anaesthesia: A narrative review.

Opioids play a crucial role in pain management in spite of causing increased hospital morbidity and related costs. It may also cause significant risks such as postoperative nausea and vomiting (PONV), sedation, sleep disturbances, urinary retention and respiratory depression (commonly referred to as opioid related adverse effects) in postoperative patients. In order to evade these opioid related side effects and also improve pain management, multimodal analgesia i.e., combination of different analgesics, was introduced more than a decade ago. Both pharmacological and non-pharmacological techniques are available as opioid sparing analgesia. Research from around the world have proved pharmacological techniques ranging from acetaminophen, NSAIDs (non-steroidal anti-inflammatory drugs), N-methyl-D-aspartate receptor antagonists (NDMA), alpha-2 agonists, anticonvulsants such as gamma aminobutyric acid analogues, beta-blockers, capsaicin, lignocaine infusion to glucocorticoids to be effective. On the other hand, non-pharmacological methods include techniques such as cognitive behavioral therapy, transcutaneous electrical nerve stimulation (TENS), electroanalgesia, acupuncture and hypnosis. However, research regarding the effect of these non-pharmacological techniques on pain management is still needed.

Prevalence of post-traumatic stress disorder in caregivers of pediatric neurosurgical patients.

BACKGROUND: Having a child receive a neurosurgical diagnosis creates significant stress and anxiety in caregivers. The stress of these life-threatening and emotionally charged diagnoses may put caregivers at risk for developing post-traumatic stress disorder (PTSD). While PTSD has been studied in a variety of caregivers of pediatric populations, to the best of our knowledge, it has yet to be examined in caregivers commonly seen in general pediatric neurosurgical practices. This study was designed to gain an understanding of the prevalence of PTSD within this population. METHODS: A cross-sectional survey method was utilized. Participants completed both a survey to provide demographic information, and the Posttraumatic Stress Checklist for DSM-5 (PCL-5) which is used to make a provisional diagnosis of PTSD. Surveys were distributed both in person and online between December 2018 and April 2019. RESULTS: One hundred sixty-eight surveys were included in the study. According to the DSM-5 diagnostic criteria, 44.6% (n = 75) of caregivers screened positively for a provisional diagnosis of PTSD. The specific neurosurgical diagnosis (p = 0.002), number of surgeries (p = 0.008), and category of the last surgery (p = 0.026) impacted the rate of PTSD symptoms in this population. Most caregivers who screened positive for PTSD experience a high level of disturbing memories and physical reactions to the events and avoid reminders of the medical experience. Caregivers also report a loss of interest in activities, feel distant from other people, and have difficulties with concentration and sleep. There was no significant relationship between caregivers who identified having a high level of anxiety before their child was diagnosed and who screened positive for PTSD. CONCLUSION: This study has identified a higher number of caregivers screening positive for PTSD within pediatric neurosurgical patients, than previously reported in other populations. Specific neurosurgical diagnosis, number of surgeries, and category of last surgery all impact a positive screen for the condition. Caregivers who avoid remembering events surrounding their child's diagnosis are at a higher risk of having the condition. The results highlight the need to identify ways to decrease the impact of a pediatric neurosurgical diagnosis on the mental health of caregivers. Future research focused on early mental health intervention for caregivers of pediatric neurosurgical patients may be helpful in reducing the long-term impact of this difficult condition.

Interstitial Lung Disease Associated with Connective Tissue Diseases.

Pulmonary manifestations of connective tissue diseases (CTD) carry high morbidity and potential mortality, and the most serious pulmonary type is interstitial lung disease (ILD). Identifying and promptly intervening CTD-ILD with immune suppressor therapy will change the natural course of the disease resulting in survival improvement. Compared to idiopathic pulmonary fibrosis, the most common presentation of idiopathic interstitial pneumonia (IIP), CTD-ILD carries a better prognosis due to the response to immune suppressor therapy. Nonspecific interstitial pneumonia (NSIP) is the most common type of CTD-ILD that is different from the fibrotic classical presentation of IPF, known as usual interstitial pneumonia (UIP). An exception is rheumatoid arthritis that presents more frequently with UIP type. Occasionally, IPF may not have typical radiographic features of UIP, and a full assessment to differentiate IPF from CTD-ILD is necessary, including the intervention of a multidisciplinary team and the histopathology. Interstitial pneumonia with autoimmune features (IPAF) shows promising advantages to identify patients with ILD who have some features of a CTD without a defined autoimmune disease and who may benefit from immune suppressors. A composition of clinical, serological, and morphologic features in patients presenting with ILD will fulfill criteria for IPAF. In summary, the early recognition and treatment of CTD-ILD, differentiation from IPF-UIP, and identification of patients with IPAF fulfill the assessment by the clinician for an optimal care.

Durability of the Therapeutic Effect of Restorative Neurostimulation for Refractory Chronic Low Back Pain.

OBJECTIVES: The purpose of the ongoing follow-up of ReActiv8-A clinical trial is to document the longitudinal benefits of episodic stimulation of the dorsal ramus medial branch and consequent contraction of the lumbar multifidus in patients with refractory mechanical chronic low back pain (CLBP). We report the four-year outcomes of this trial. MATERIALS AND METHODS: ReActiv8-A is a prospective, single-arm trial performed at nine sites in the United Kingdom, Belgium, and Australia. Eligible patients had disabling CLBP (low back pain Numeric Rating Scale [NRS] ≥6; Oswestry Disability Index [ODI] ≥25), no indications for spine surgery or spinal cord stimulation, and failed conventional management including at least physical therapy and medications for low back pain. Fourteen days postimplantation, stimulation parameters were programmed to elicit strong, smooth contractions of the multifidus, and participants were given instructions to activate the device for 30-min stimulation-sessions twice daily. Annual follow-up through four years included collection of NRS, ODI, and European Quality of Life Score on Five Dimensions (EQ-5D). Background on mechanisms, trial design, and one-year outcomes were previously described. RESULTS: At baseline (N = 53) (mean ± SD) age was 44 ± 10 years; duration of back pain was 14 ± 11 years, NRS was 6.8 ± 0.8, ODI 44.9 ± 10.1, and EQ-5D 0.434 ± 0.185. Mean improvements from baseline were statistically significant (p < 0.001) and clinically meaningful for all follow-ups. Patients completing year 4 follow-up, reported mean (±standard error of the mean) NRS: 3.2 ± 0.4, ODI: 23.0 ± 3.2, and EQ-5D: 0.721 ± 0.035. Moreover, 73% of participants had a clinically meaningful improvement of ≥2 points on NRS, 76% of ≥10 points on ODI, and 62.5% had a clinically meaningful improvement in both NRS and ODI and 97% were (very) satisfied with treatment. CONCLUSIONS: In participants with disabling intractable CLBP who receive long-term restorative neurostimulation, treatment satisfaction remains high and improvements in pain, disability, and quality-of-life are clinically meaningful and durable through four years.

Obstructive coronary artery disease with a coronary artery calcium score of 0: A case report.

Coronary artery calcium (CAC) scoring has emerged as a useful tool in identifying patients who may benefit from more aggressive risk factor modification and for prognostication. Although a CAC score of 0 is associated with a very low prevalence of obstructive epicardial coronary artery disease and low event rates, it can also provide a false sense of reassurance. We present a case of a 39-year-old woman with a CAC score of 0 obtained as part of a coronary computerized tomography angiography study that was ultimately found to have significant left anterior descending artery disease requiring percutaneous coronary intervention and a stent.

Peripheral nerve stimulation registry for intractable migraine headache (RELIEF): a real-life perspective on the utility of occipital nerve stimulation for chronic migraine.

BACKGROUND: Migraine is common and ranked as the first cause of disability in people under fifty. Despite significant advances in its pharmacological treatment, it often remains intractable. Neuromodulation is one option considered in the management of those patients. OBJECTIVE: To assess the safety and efficacy of neuromodulation in the treatment of intractable chronic migraine using the Abbott occipital nerve stimulator. METHODS: Recruitment took place in 18 centres in 6 countries. Patients over the age of 18 who had failed three or more preventative drugs, had at least moderate disability based on MIDAS or HIT-6 score and were implanted with an Abbott neurostimulator were included in the study. Patients were followed up for a maximum of 24 months. Data were collected on adverse events, headache relief, headache days, quality of life, migraine disability, satisfaction and quality of life. RESULTS: One hundred twelve patients were included, 79 female and 33 male, with 45 patients reaching the maximum follow-up of 24 months. At 3 months, 33.7% were satisfied or very satisfied with the procedure with 43.0% reporting improved or greatly improved quality of life. 67.5% indicated that they would undergo the procedure again with satisfaction peaking at 9 months when 49.3% were satisfied or very satisfied with the procedure. At 24 months, 46.7% of available patients were satisfied or very satisfied with the procedure-18% of enrolled patients. The adverse events were however frequent with incidences of 37%, 47% and 31% respectively for hardware-, biological and stimulation-related side effects. CONCLUSION: Neuromodulation can be beneficial for selected patients with intractable chronic migraine although frequent complications have been consistently reported across studies. Further research focusing on development of better hardware and technique optimisation and in particular reliable randomised trials with significantly longer follow-ups are warranted in this field.

Beare-Stevenson Syndrome With Blepharoptosis as a Complication of Front-Orbital Advancement and Remodeling.

Beare-Stevenson syndrome (BSS) is an extremely rare genetic disorder characterized by a broad range of congenital malformations including craniosynostosis, cutis gyrata, facial deformities, and abnormal genitalia. The authors report a case of a 7 month old female who developed a mechanical ptosis secondary to dermatochalasis as a complication of fronto-orbital advancement and remodeling (FOAR) surgery which subsequently required multiple lid surgeries to reverse ptosis. This is the first report of blepharoptosis correction in a child with BSS as a complication of FOAR.

Metabolic Imaging of Pain Matrix Using 18 F Fluoro-deoxyglucose Positron Emission Tomography/Computed Tomography for Patients Undergoing L2 Dorsal Root Ganglion Stimulation for Low Back Pain.

INTRODUCTION: Nociceptive signals from lumbar intervertebral discs ascend in the sympathetic chain via the L2 dorsal root ganglion (L2 DRG), a potential target for discogenic low back pain in neuromodulation. Positron Emission Tomography/Computed Tomography (PET-CT) measures functional changes in the brain metabolic activity, identified by the changes in the regional cerebral blood flow (rCBF) as determined by the changes of F-18 Fluoro-deoxyglucose (18 F FDG) tracer within brain tissues. METHODS AND MATERIALS: Nine patients were recruited to explore the changes in PET-CT imaging at baseline and four-weeks post implantation of bilateral L2 DRG neurostimulation leads and implantable pulse generator (IPG). PET-CT scans were performed 30 min following an IV injection of 250±10% MBq of 18 F FDG tracer. Fifteen frames were acquired in 15 min. PET list-mode raw data were reconstructed and normalized appropriately to a brain anatomical atlas. RESULTS: Nine patients were recruited to the study, where PET-CT imaging data for five patients were analyzed. The right and left insular cortex, primary and secondary somato-sensory cortices, prefrontal cortex, anterior cingulate cortex, thalamus, amygdala, hippocampus and the midline periaqueductal areas, were assessed for any changes in the metabolic activity. A total of 85 pain matrix regions were delineated SUV (standardized uptake value)MAX , SUV MEAN ± SD, and SUVPEAK were calculated for each of these regions of the brain and were compared pre- and post-L2 DRG stimulation. Sixty-one of the 85 matrices showed an increase in metabolic activity whereas 24 matrices showed a reduction in metabolic activity. CONCLUSION: This is the first ever study reporting the changes in cerebral metabolic activity and multi-frame static brain 18 F FDG PET imaging after L2 DRG stimulation for discogenic low back pain. Predominantly an increased metabolic activity in nociceptive brain matrices are seen with an increased in F18 F FDG uptake following L2 DRG stimulation.

Interhypothalamic adhesions in endoscopic third ventriculostomy.

INTRODUCTION: An interhypothalamic adhesion (IHA) is a gray mater-like band of tissue traversing across the third ventricle anterior to the mammillary bodies and is similar but distinct from an interthalamic adhesion. These rare anatomic anomalies can be detected with magnetic resonance imaging or, incidentally, during endoscopic ventricular surgery. METHODS: All cases of interhypothalamic adhesions visualized during endoscopic third ventriculotomy (ETV), outside of the myelomeningocele setting, were identified from two institutions. Retrospective chart and imaging reviews were conducted and compared to intraoperative videos and photos for all cases. IHA variables collected included the following size, location, multiplicity, and associated anatomic anomalies. RESULTS: Four cases of interhypothalamic adhesions were identified during ETV-all of which, either partially or completely, obscured access to the third ventricular floor. The IHAs in our cohort were duplicated in two patients, large (> 3 mm and severely obstructing access to the third ventricular floor) in three patients, and adherent to the floor of the third ventricle in three patients. All four patients had primary absence of the septum pellucidum. Previous reports found associations of IHAs with other congenital, particularly midline, abnormalities. The IHAs in our cohort affected the surgery in three of four cases including misdirecting the ventriculostomy and requiring retraction or division of the IHA. In no case was postoperative pituitary or hypothalamic dysfunction observed. CONCLUSIONS: Although interhypothalamic adhesions are rare, these anomalies must be recognized as they may hinder access to the third ventricular floor. IHAs may be large, multiple, or adherent to adjacent ventricular structures, they can misdirect or occlude the ventriculostomy or impart risk of bleeding and hypothalamic injury. Techniques for management of IHA include aborting the attempt, re-siting the ventriculostomy, or retracting or dividing the IHA, which enabled technically successful ETV in three of four patients in this series.

Characterizing the Somatosensory Profile of Patients With Failed Back Surgery Syndrome With Unilateral Lumbar Radiculopathy Undergoing Spinal Cord Stimulation: A Single Center Prospective Pilot Study.

OBJECTIVES: Currently little objective evidence exists regarding the phenotype or somato-sensory profile of patients with Failed Back Surgery Syndrome (FBSS). The aim of this study is to characterize the somato-sensory profile of the patients with FBSS undergoing spinal cord stimulation (SCS). METHODS: A combined quantitative sensory test and questionnaire approach was used to characterize the somatosensory profiles of patients undergoing SCS. RESULTS: Baseline somatosensory profiles were obtained from 23 patients and full three-month data was obtained from 19 patients. At baseline, there was a high prevalence (>50% prevalence of moderate to severe sensation) of burning, tingling, electric shock, numbness, and pressure pain sensitivity. None of the sensory symptoms were present at significant levels at three months following SCS. At baseline, 65% of patients had an inefficient conditioned pain modulation (CPM). Three months post-SCS, 95% of patients had an efficient CPM. All the patients who had an inefficient CPM at baseline had a successful implant at three months and their CPM became efficient in all but one patient. Only 50% of the patients with an efficient CPM at baseline, had a successful implant at three months post-SCS. CONCLUSION: Although very low numbers, we could demonstrate the somatosensory profiles of patients with FBSS undergoing SCS. Early indication may associate an efficient CPM profile having a higher chance of an unsuccessful implant at three months.