Best Practices from the American Society of Pain and Neuroscience (ASPN) for Clinical Research During a Pandemic or Emergency.

The COVID-19 pandemic caught many areas of medicine in a state of unpreparedness for conducting research and completing ongoing projects during a global crisis, including the field of pain medicine. Waves of infection led to a disjointed ability to provide care and conduct clinical research. The American Society of Pain and Neuroscience (ASPN) Research Group has created guidance for pragmatic and ethical considerations for research during future emergency or disaster situations. This analysis uses governmental guidance, scientific best practices, and expert opinion to address procedure-based or device-based clinical trials during such times. Current literature offers limited recommendations on this important issue, and the findings of this group fill a void for protocols to improve patient safety and efficacy, especially as we anticipate the impact of future disasters and spreading global infectious diseases. We recommend local adaptations to best practices and innovations to enable continued research while respecting the stressors to the research subjects, investigator teams, health-care systems, and to local infrastructure.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations for Surgical Technique for Spinal Cord Stimulation.

INTRODUCTION: The field of neurostimulation for the treatment of chronic pain is a rapidly developing area of medicine. Although neurostimulation therapies have advanced significantly as a result of technologic improvements, surgical planning, device placement, and postoperative care are of equal importance to optimize outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for these often-overlooked areas of neurostimulation practice. MATERIALS AND METHODS: Authors were chosen based on their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from the last NACC publication in 2017 to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on evidence strength and consensus when evidence was scant. RESULTS: This NACC project provides guidance on preoperative assessment, intraoperative techniques, and postoperative management in the form of consensus points with supportive evidence. These results are based on grade of evidence, strength of consensus, and expert opinion. CONCLUSIONS: The NACC has given guidance for a surgical plan that encompasses the patient journey from the planning stage through the surgical experience and postoperative care. The overall recommendations are designed to improve efficacy and the safety of patients undergoing these neuromodulation procedures and are intended to apply throughout the international community.

The impact of the COVID-19 pandemic on patients awaiting spinal cord stimulation surgery in the United Kingdom: a multi-centre patient survey.

INTRODUCTION: Spinal cord stimulation (SCS) is a recommended treatment for chronic refractory neuropathic pain. During the COVID-19 pandemic, elective procedures have been postponed indefinitely both to provide capacity to deal with the emergency caseload and to avoid exposure of elective patients to COVID-19. This survey aimed to explore the effect of the pandemic on chronic pain in this group and the views of patients towards undergoing SCS treatment when routine services should resume. METHODS: This was a prospective, multi-centre telephone patient survey that analysed data from 330 patients with chronic pain who were on an SCS waiting list. Questions focussed on severity of pain, effect on mental health, medication consumption and reliance on support networks during the COVID-19 pandemic. Views towards undergoing SCS therapy were also ascertained. Counts and percentages were generated, and chi-square tests of independence explored the impact of COVID-19 risk (very high, high, low) on survey responses. RESULTS: Pain, mental health and patient's ability to self-manage pain deteriorated in around 47%, 50% and 38% of patients, respectively. Some patients reported increases in pain medication consumption (37%) and reliance on support network (41%). Patients showed a willingness to attend for COVID-19 testing (92%), self-isolate prior to SCS (94%) and undergo the procedure as soon as possible (76%). CONCLUSION: Our findings suggest that even during the COVID-19 pandemic, there remains a strong clinical need for patients with chronic pain identified as likely SCS responders to be treated quickly. The current prioritisation of new SCS at category 4 (delayed more than 3 months) is challenged judging by this national survey. These patients are awaiting SCS surgery to relieve severe intractable neuropathic pain. A priority at category 3 (delayed up to 3 months) or in some selected cases, at category 2 are the appropriate priority categories.

Dorsal Root Ganglion Stimulation for the Treatment of Chronic Neuropathic Knee Pain.

BACKGROUND: To elucidate the efficacy of dorsal root ganglion stimulation in the treatment of chronic neuropathic pain confined to the knee. METHODS: Retrospective analysis of prospectively collected data of 14 consecutive patients undergoing dorsal root ganglion stimulation for chronic knee pain, in a single center. The primary outcome measure was pain reduction assessed by numeric pain rating scale score preoperatively and postoperatively. Secondary outcomes included quantification of percentage of pain area covered by stimulation, and reduction in usage of opioid medications. Responders were defined as patients that experienced a greater than or equal to 50% improvement in their preoperative pain score. RESULTS: Fourteen patients were implanted with dorsal root ganglion stimulator electrodes; 8 had a single L3 lead implanted, 1 patient had a single L4 lead implanted, and 3 patients had 2 leads implanted (L3 and L4). Two patients had their leads explanted: 1 for non-efficacy, and 1 for repeated electrode displacement. The most common indication for surgery was type 2 complex regional pain syndrome, secondary to either trauma or postoperative chronic pain (either knee replacement or arthroscopy). Median preoperative numeric rating scale score was 8.5, median postoperative numeric rating scale score was 2 (P = 0.002, Wilcoxon signed rank test). The median improvement in pain score was 80%. All 12 patients undergoing chronic stimulation were responders. Median coverage of pain area was 85%. All but 1 patient who was on opioid medication prior to surgery had reduced the dosage of regular opioid. CONCLUSIONS: In selected patients, dorsal root ganglion stimulation is an extremely efficacious means of treating otherwise refractory chronic knee pain.

The Importance of the Location of Dorsal Root Ganglion Stimulator Electrodes Within the Nerve Root Exit Foramen.

OBJECTIVE: To quantify the relationship between the electrical power requirement to achieve pain relief and the position of the active electrode of dorsal root ganglion stimulators within the spinal nerve root exit foramen. MATERIALS AND METHODS: Retrospective analysis of prospectively collected data of 92 consecutive patients undergoing dorsal root ganglion stimulation (DRGS) for chronic pain in a single center. Cervical and sacral cases, and failed trials/explanted DRGS were excluded, so we report on 57 patients with 78 implanted leads. Anteroposterior and lateral fluoroscopic images of the lead in the exit foramen were examined, and the active electrode positions were put into categories depending on their location relative to fixed anatomical landmarks. The clinical outcome and the power requirements for each of these groups of electrodes were then analyzed. Overall pain outcome was assessed by numeric pain rating scale score pre-operatively and post-operatively. RESULTS: There was no significant relationship between power requirements and mediolateral electrode position, although the lowest average was observed with electrode positions directly below the center of the pedicle. On lateral x-ray, the lowest power requirements were observed in the electrodes positioned superodorsally or dorsally within the foramen. Importantly, power requirements in this location were consistently low, while the power requirements in other locations were not only higher but also much more variable. Electrodes in the superodorsal position required a median output power almost four times lower than electrodes in other positions (p = 0.002). Clinical outcome was not significantly related to power requirement or foraminal position. CONCLUSION: Aiming for a superodorsal electrode position on lateral intraoperative fluoroscopy is desirable, since siting leads in this location reduces the required stimulator output power very substantially and thus will extend battery life. Position within the foramen does not determine clinical outcome, and so the implanter can safely aim for the low power site without detriment to the analgesic efficacy of the system.

Role of diffusion-weighted imaging in monitoring treatment response following high-intensity focused ultrasound ablation of recurrent sacral chordoma.

Chordoma is the most common malignant tumor of the sacrum and is associated with significant neurologic morbidity. Local recurrence is very common, and the long-term prognosis is poor. High-intensity focused ultrasound (HIFU) is a noninvasive and nonionising ablative therapy that has been successful in treating other tumor types and is being evaluated as a new therapy for sacral chordoma. Contrast-enhanced magnetic resonance imaging is typically used to evaluate tumor perfusion following HIFU; however, its utility is limited in poorly perfused tumors. Diffusion-weighted imaging (DWI) provides tissue contrast based on differences in the diffusion of extracellular water without using gadolinium-based contrast agents. We present novel DWI findings following a planned partial HIFU ablation of a large sacral chordoma which had recurred after radiotherapy. Following HIFU, the treated tumor volume demonstrated loss of restriction on DWI correlating with photopenia on positron emission tomography. This suggests successful ablation and tumor necrosis. This novel finding may provide guidance for sequence selection when evaluating HIFU therapy for sacral chordoma and other tumor types for which contrast-enhanced magnetic resonance imaging may have limited utility.

Burst or Conventional Peripheral Nerve Field Stimulation for Treatment of Neuropathic Facial Pain.

BACKGROUND: Trigeminal Neuropathic Pain (TNP) is a chronic facial pain syndrome caused by a lesion or disease affecting one or more branches of the trigeminal nerve. It may, for example, result from accidental injury to a branch of the trigeminal nerve by trauma or during surgery; it may also be idiopathic. TNP is typically constant, in contrast to most cases of the commoner trigeminal neuralgia. In some cases, pain may be refractory to pharmacological treatment. Peripheral nerve field stimulation is recognized as an effective minimally invasive surgical treatment option for this debilitating condition. To date, stimulation has used conventional tonic waveforms, which generate paraesthesia in the stimulated area. This is the first report of the use of paraesthesia-free burst pattern stimulation for TNP. METHODS: Seven patients were treated at the John Radcliffe Hospital for TNP from 2016 to 2018. Mean duration of preoperative symptoms was five years. All patients had exhausted pharmacological measures to limited effect. The initial three patients had tonic stimulation with the subsequent four having burst stimulation. Outcome was assessed using the numeric pain rating scale preoperatively and postoperatively at three and six months and one year. Side-effects and complications were also assessed as well as reduction in analgesic medication use. RESULTS: All patients achieved pain reduction of at least 50% at 6 months (range 50-100%, mean 81%, p = 0.0082). Those in the burst stimulation group were paraesthesia free. One patient developed a postoperative infection for which the system had to be removed and is awaiting reimplantation. There were no other complications in either group. CONCLUSION: Burst stimulation conferred similar pain control to tonic stimulation in our small cohort, and there were similar reductions in pain medication use. An additional benefit of burst stimulation is freedom from paraesthesia. Larger scale studies are needed to further evaluate burst stimulation and compare its efficacy with that of tonic stimulation.

The Efficacy and Safety of Dorsal Root Ganglion Stimulation as a Treatment for Neuropathic Pain: A Literature Review.

OBJECTIVE: Dorsal root ganglion stimulation (DRGS) received its first regulatory approval (CE marking in Europe) in late 2011, and so its use is now almost six years old. Several thousand patients have already been treated, and a landmark trial in lower limb complex regional pain syndrome (CRPS) and causalgia has recently been published. METHODS: In this review we have summarized the literature to date on the use of DRGS in the treatment of neuropathic pain. RESULTS: The results so far are encouraging, with reports of successful use in treating a wide range of indications including postsurgical pain, CRPS, and phantom pain. Treatment of failed back surgery syndrome (FBSS) appears less successful. The therapy is still young, and long term results are not yet available. There is now good randomized clinical trial (RCT) evidence that DRGS provides superior pain relief to spinal cord stimulation for CRPS and causalgia of the lower limb, and produces stimulation that is more posturally stable, with more precise paraesthesia coverage. However evidence of this quality for other indications and pain locations is lacking. CONCLUSION: There is now Class A RCT evidence that DRGS provides superior pain relief to SCS for CRPS and causalgia of the lower limb. In the coming years we hope that randomized controlled trials will be performed on an indication-by-indication basis, which, together with the publication of longer term follow-up data, will provide a more complete understanding of the role of DRGS in the treatment of neuropathic pain syndromes.

High-intensity focused ultrasonic ablation of sacral chordoma is feasible: a series of four cases and details of a national clinical trial.

High-intensity focused ultrasound describes the use of high-intensity focused ultrasound (HIFU) to ablate tumours without requiring an incision or other invasive procedure. This technique has been trialled on a range of tumours including uterine fibroids, prostate, liver and renal cancer. We describe our experience of using HIFU to ablate sacral chordoma in four patients with advanced tumours. Patients were treated under general anaesthetic or sedation using an ultrasound-guided HIFU device. HIFU therapy was associated with a reduction in tumour volume over time in three patients for whom follow up scans were available. Tumour necrosis was reliably demonstrated in two of the three patients. We have established a national trial to assess if HIFU may improve long-term outcome from sacral chordoma, details are given.

Outcomes of treatment of fractures of the frontal sinus: review from a tertiary multispecialty craniofacial trauma service.

There are no agreed national guidelines for the treatment of fractures of the frontal sinus and the naso-orbitoethmoid complex. The Oxford University Hospitals Craniofacial Trauma unit was set up five years ago as a joint oral and maxillofacial, ENT, and neurosurgical service, and we present our experience to date in the treatment of patients with such fractures. The study includes 91 patients with data collected from a prospective database. Patients underwent cranialisation if they met the criteria of persistent leak of cerebrospinal fluid (CSF), displaced fracture of the posterior wall or obstruction of the nasofrontal outflow tract. The mean follow-up time was 42 months (range 1-10 years). Three groups of patients were analysed. Group 1 met the criteria for, and were treated by, cranialisation (n=50). Group 2 met the criteria for cranialisation, but were treated conservatively because of coexisting conditions (n=8). Group 3 did not match the criteria for treatment, and were managed conservatively (n=33). The numbers of patients with complications or who required further operation were: group 1 (4/50), group 2 (3/8), and group 3 (3/33). There were significantly fewer complications among those patients who met the operative criteria and were treated by cranialisation than among those treated conservatively (p=0.04). These outcomes from one dedicated multispecialist craniofacial trauma unit in the UK may help surgeons who care for patients with this specific group of injuries. Our morbidity was in keeping with published figures.

Yield and complications of frame-based and frameless stereotactic brain biopsy--the value of intra-operative histological analysis.

OBJECTIVES: Image-guided brain biopsy is an established method to obtain histopathological diagnosis and guide management for cerebral lesions. The study aimed to establish negative biopsy and symptomatic haemorrhage rates at a single centre, and to assess the influence of factors such as lesion location, final pathology and the use of intra-operative smears. METHODS: A retrospective analysis of all frame-based and frameless stereotactic biopsies carried out over 57 months from July 2006 to March 2011. RESULTS: A total of 351 biopsies were undertaken, 256 frame-based (73%) and 95 frameless (27%). Mean age was 57 years (range 18-87). Negative biopsy rate was 5.1%. There was a significantly greater negative biopsy rate in deep brain biopsies (p = 0.011) and in the cerebellum (p < 0.001). Intra-operative smear significantly reduced negative biopsy rates from 11.1% to 3.7% (p = 0.011). If repeat smear was requested, yet not provided, then the negative biopsy rate was 57.1% (p = 0.0085). The overall symptomatic haemorrhage rate was 3.7%. There was a significant increase in haemorrhage rate in deep versus superficial biopsies (p = 0.023) and a significantly greater haemorrhage rate in lymphoma biopsies (p = 0.015). There was no significant increase in haemorrhage rate in high-grade compared with low-grade tumour biopsies. Mortality rates at 7 and 30 days post-operatively were 0.6% and 1.7%, respectively, with mortality after 7 days unrelated to biopsy. CONCLUSION: We advocate intra-operative histopathological analysis to decrease negative biopsy rates and advise increased caution when undertaking biopsies of deep lesions or suspected lymphoma cases due to the potentially increased risk of haemorrhage.

Effective management of severe traumatic brain injury in a district hospital.

The authors investigated how effectively adults with severe traumatic brain injury (TBI) can be managed in a district general hospital intensive care unit offering intracranial pressure monitoring (ICPM) receiving advice from a neurosurgical unit. A single-centre case series with retrospective review of prospectively collected information was undertaken of 44 consecutive patients presenting over seven years from January 2003 to January 2010 with severe traumatic brain injury to a single district general hospital intensive care unit serving a population of 500,000 adults. A prospectively entered clinical database was used to obtain information including patient demographics, Glasgow Coma Score (GCS) on admission, ICPM insertion, ICPM-related complications, inpatient mortality and neurosurgical advice. Case notes were used to ratify information and obtain neurorehabilitation clinic functional outcome scores. Forty-four patients were identified (40 male, age range 16-77 years). Mortality in intensive care was 30%. Twenty-eight patients received frontal twist drill ICPM following neurosurgical advice. ICPM had 2 (7%) device malfunctions but no other complications. Twelve additional patients were transferred to tertiary centres. Patients (23 of 31) who survived ICU stay (74%) were referred to neurorehabilitation. Mean clinic follow-up was 14 months. All patients had a Glasgow Outcome Score (GOS) of 3 or 4 at initial clinic assessment. Twenty-two improved to GOS to 4 or 5 at clinic discharge. One patient died prior to clinic discharge. Carefully selected patients with severe TBI can be managed safely and effectively in a district general hospital offering ICPM insertion if transfer to a neurosurgical centre is not possible. Neurosurgical advice regarding patient selection and on-going management is fundamental to provide a good service. Protocol driven therapies provide a useful systematic approach to doctors who do not deal with severe TBI on a routine basis.

Oxford craniotomy infections database: a cost analysis of craniotomy infection.

We describe the process of establishing a large database for the investigation of craniotomy infection and the preliminary results of this database. The initial results have been used to generate a cost analysis for craniotomy infection. The craniotomy infections database prospectively registers craniotomy cases taking place in the John Radcliffe Hospital. In order to achieve this, each patient's details are registered at the time of operation and followed up to identify cases of infection. Infection was defined strictly according to Centre for Disease Control criteria and validated by at least two members of clinical staff. The first 10 months of data are presented here which identifies a total of 245 craniotomies and 20 verified craniotomy infections. An overall infection rate of 8% is identified, and the cost incurred by the neurosurgery department as a result of craniotomy infections is estimated at £1 85 660 for the 10-month period studied. This amounts to a cost per case of infection of £9283.

Endoscopic fenestration of middle cranial fossa arachnoid cysts: does size matter?

The middle cranial fossa (MCF) is the commonest location for intracranial arachnoid cysts and there has long been controversy regarding the optimal surgical management. Over the last 10 years there has been an increased interest in the potential of endoscopic techniques to treat these. In a review of the literature we identified 91 patients with MCF cysts treated with endoscopic techniques. Clinical improvement was seen in 95% of patients and radiological improvement was seen in 74%. The most common complications reported are subdural hygromas (9%) and subdural haematomas (5%). There does not appear to be an undue increased risk of complications compared to open surgical techniques. Reported methods of endoscopic fenestration advocate making as wide an opening as possible without damage to the surrounding neurovascular structures. We consider the possibility that smaller cystocisternostomy may be effective in achieving therapeutic goals while reducing potential risks to the patient.

Rapid development of glioblastoma at the site of atypical meningioma resection.

The authors describe symptomatic presentation of glioblastoma within six months of resection of an atypical meningioma, at the same frontal parafalcine cerebral location. The patient had neither prior nor adjuvant radiotherapy nor known genetic risk factors. Possible links between invasive meningioma and transformation of adjacent glial cells or precursors to malignant glioma are discussed.