Patient-reported outcomes in Primary Spinal Intradural Tumours: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: Primary Spinal Intradural Tumours (PSITs) are rare pathologies that can significantly impact quality of life. This study aimed to review patient reported outcomes (PROs) in PSITs. METHODS: A systematic search of Pubmed and Embase was performed to identify studies measuring PROs in adults with PSITs. PRO results were categorised as relating to Global, Physical, Social, or Mental health. Outcomes were summarised descriptively. RESULTS: Following review of 2382 records, 11 studies were eligible for inclusion (737 patients). All studies assessed surgically treated patients. Schwannoma was the commonest pathology (n = 190). 7 studies measured PROs before and after surgery, the remainder assessed only post-operatively. For eight studies, PROs were obtained within 12 months of treatment. 21 PRO measurement tools were used across included studies, of which Euro-Qol-5D (n = 8) and the pain visual/numerical analogue scale (n = 5) were utilised most frequently. Although overall QoL is lower than healthy controls in PSITs, improvements following surgery were found in Extramedullary tumours (EMT) in overall physical, social, and mental health. Similar improvements were not significant across studies of Intramedullary tumours (IMT). Overall QoL and symptom burden was higher in IMT patients than in brain tumour patients. No studies evaluated the effect of chemotherapy or radiotherapy. CONCLUSION: Patients with PSITs suffer impaired PROs before and after surgery. This is particularly true for IMTs. PRO reporting in PSITs is hindered by a heterogeneity of reporting and varied measurement tools. This calls for the establishment of a standard set of PROs as well as the use of registries.

Microdiscectomy compared with transforaminal epidural steroid injection for persistent radicular pain caused by prolapsed intervertebral disc: the NERVES RCT.

BACKGROUND: Sciatica is a common condition reported to affect > 3% of the UK population at any time and is most often caused by a prolapsed intervertebral disc. Currently, there is no uniformly adopted treatment strategy. Invasive treatments, such as surgery (i.e. microdiscectomy) and transforaminal epidural steroid injection, are often reserved for failed conservative treatment. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of microdiscectomy with transforaminal epidural steroid injection for the management of radicular pain secondary to lumbar prolapsed intervertebral disc for non-emergency presentation of sciatica of < 12 months' duration. INTERVENTIONS: Patients were randomised to either (1) microdiscectomy or (2) transforaminal epidural steroid injection. DESIGN: A pragmatic, multicentre, randomised prospective trial comparing microdiscectomy with transforaminal epidural steroid injection for sciatica due to prolapsed intervertebral disc with < 1 year symptom duration. SETTING: NHS services providing secondary spinal surgical care within the UK. PARTICIPANTS: A total of 163 participants (aged 16-65 years) were recruited from 11 UK NHS outpatient clinics. MAIN OUTCOME MEASURES: The primary outcome was participant-completed Oswestry Disability Questionnaire score at 18 weeks post randomisation. Secondary outcomes were visual analogue scores for leg pain and back pain; modified Roland-Morris score (for sciatica), Core Outcome Measures Index score and participant satisfaction at 12-weekly intervals. Cost-effectiveness and quality of life were assessed using the EuroQol-5 Dimensions, five-level version; Hospital Episode Statistics data; medication usage; and self-reported cost data at 12-weekly intervals. Adverse event data were collected. The economic outcome was incremental cost per quality-adjusted life-year gained from the perspective of the NHS in England. RESULTS: Eighty-three participants were allocated to transforaminal epidural steroid injection and 80 participants were allocated to microdiscectomy, using an online randomisation system. At week 18, Oswestry Disability Questionnaire scores had decreased, relative to baseline, by 26.7 points in the microdiscectomy group and by 24.5 points in the transforaminal epidural steroid injection. The difference between the treatments was not statistically significant (estimated treatment effect -4.25 points, 95% confidence interval -11.09 to 2.59 points). Nor were there significant differences between treatments in any of the secondary outcomes: Oswestry Disability Questionnaire scores, visual analogue scores for leg pain and back pain, modified Roland-Morris score and Core Outcome Measures Index score up to 54 weeks. There were four (3.8%) serious adverse events in the microdiscectomy group, including one nerve palsy (foot drop), and none in the transforaminal epidural steroid injection group. Compared with transforaminal epidural steroid injection, microdiscectomy had an incremental cost-effectiveness ratio of £38,737 per quality-adjusted life-year gained and a probability of 0.17 of being cost-effective at a willingness to pay threshold of £20,000 per quality-adjusted life-year. LIMITATIONS: Primary outcome data was invalid or incomplete for 24% of participants. Sensitivity analyses demonstrated robustness to assumptions made regarding missing data. Eighteen per cent of participants in the transforaminal epidural steroid injection group subsequently received microdiscectomy prior to their primary outcome assessment. CONCLUSIONS: To the best of our knowledge, the NErve Root Block VErsus Surgery trial is the first trial to evaluate the comparative clinical effectiveness and cost-effectiveness of microdiscectomy and transforaminal epidural steroid injection. No statistically significant difference was found between the two treatments for the primary outcome. It is unlikely that microdiscectomy is cost-effective compared with transforaminal epidural steroid injection at a threshold of £20,000 per quality-adjusted life-year for sciatica secondary to prolapsed intervertebral disc. FUTURE WORK: These results will lead to further studies in the streamlining and earlier management of discogenic sciatica. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04820368 and EudraCT 2014-002751-25. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 24. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Sciatica or pain related to nerve irritation travelling down the leg is common in young working adults and most likely to be caused by a 'slipped' (prolapsed) disc. Although the majority of cases get better on their own and within 4­6 weeks, a significant group of patients struggle with disabling symptoms sometimes beyond 1 year. Consequently, patients struggle to maintain their home and working lives. Many treatments are available for sciatica, but simpler treatments (e.g. pain tablets, physiotherapy and changing one's lifestyle) are often not very effective and patients have often tried all of them by the time they are seen in hospital to have tests, such as scans, done. Surgery to remove part of the disc is recommended in cases where the pain is accompanied by severe weakness in one or both legs, or where doctors think that nerves may be damaged because patients have bladder, bowel and sexual functioning difficulties (i.e. red flag symptoms). Surgery works well in alleviation of referred leg pain and also to relieve pressure on a physically compressed nerve that may be showing clinical sign of injury/weakness. An alternative to surgery is to inject a mixture of anaesthetic and steroid close to the site of the disc injury and nerve, but at the moment we do not know whether or not these injections work in the long term. They are cheaper and less invasive, with fewer risks than surgery, such as from anaesthetic or infection. WHAT DID OUR STUDY INVESTIGATE?: This study compared the usefulness of surgery with injections for patients who have had sciatica for < 1 year and who have tried simple remedies but are still in pain. Patients were allocated to have either surgery or the injection. Symptoms (e.g. pain) were assessed after 18 weeks. WHAT DID WE FIND?: We found that there was no significant difference between surgery and injection at the primary end point. Surgery was not significantly different from injection in terms of clinical outcome and was not cost-effective compared with injection. OUR CONCLUSION AND RECOMMENDATION: Given the cost of surgery and the risks to patients, we suggest that further studies should be carried out to explore whether or not all patients with sciatica due to a slipped disc should be considered suitable for an injection, unless there is a good reason not to.

Primary lumbar decompression using ultrasonic bone curette compared to conventional technique.

PURPOSE: The ultrasonic bone curette (Bone Scalpel) is a novel technique in neurosurgery for bony dissection. This study aimed to evaluate its use against conventional techniques for primary lumbar decompression. MATERIALS AND METHODS: This study was a retrospective cohort comparison, using Spine Tango Registry data. All patients undergoing a primary procedure for lumbar decompression secondary to degenerative disease during a 2-year period (2014-2016) were identified, split into age and gender matched cohorts utilising either bone scalpel or conventional techniques intra-operatively. RESULTS: Ninety-three patients were identified within each cohort, which did not differ significantly in terms of age, gender, BMI, number of operative vertebral levels or seniority of the principal surgeon. The incidence of intra-operative blood loss >100 ml was significantly reduced within the bone scalpel cohort (16.1% bone scalpel, 34.4% conventional, p = 0.04). There was no difference in the incidence of iatrogenic dural breach (9.7% bone scalpel, 16.1% conventional, p = 0.27). There was no significant difference in pre-operative Core Outcomes Measures Index (COMI) between the cohorts (7.91 bone scalpel, 8.02 conventional, p = 0.67) and both cohorts demonstrated a significant reduction in mean COMI at 24 months (bone scalpel p = 0.004, conventional p = <0.001). No difference in mean COMI existed between either cohort at any point across the 24-month post-operative period (p = 0.18). CONCLUSIONS: The use of ultrasonic bone curette for primary lumbar decompression is associated with reduced intra-operative blood loss compared to conventional techniques, alongside a comparable safety profile and equivalent patient reported outcomes.

Comparison of clinical outcomes in anterior cervical discectomy versus foraminotomy for brachialgia.

AIM: The choice between anterior cervical discectomy & fusion (ACD) or posterior cervical foraminotomy (PCF) for the treatment of cervical brachialgia is controversial. This study aimes to compare clinical outcomes between these two operative inteventions for brachialgia. METHODS: Retrospective review of prospectively collected data was performed. Patients receiving a primary ACD or PCF to treat brachialgia, in a single tertiary neurosurgical unit were included. Surgical details, and patient reported outcomes (COMI-Neck questionnaire) were extracted from a prospectively maintained spinal procedure database. Minimum clinically important difference (MCID) was defined as a change in COMI score of -2 at 12 months. The student t-test, Chi-square test, and linear regression were used to compare groups. RESULTS: Between June 2011 ad February 2016 there were 634 ACD procedures (Median age 49; 321 Male), and 54 PCF procedures (Median age 50; 37 Male) perfomed for brachialgia. Age, ASA and pre-operative COMI were similar between the groups (p > .05). Complete outcome data was recorded at twelve months in 312 ACD and 36 PCF patients. Both ACD and PCF were associated with an improvement in COMI at 3 and 12 months (all p < .01). Mean change in COMI at 3 months was -2.38 for ACD, versus -2.31 for PCF (p = .88); at twelve months it was -2.94 for ACD, versus -2.67 for PCF (p = .55). MCID was seen in 59% of ACD cases, versus 58% of PCF cases at twelve months (p = .91). CONCLUSION: There was no significant difference between outcomes in the ACD and PCF groups. This is supportive of published literature. The proposed multicenter RCTs may inform further.

Nerve root block versus surgery (NERVES) for the treatment of radicular pain secondary to a prolapsed intervertebral disc herniation: study protocol for a multi-centre randomised controlled trial.

BACKGROUND: Sciatica is a common condition reported to affect over 3% of the UK population at any time and is often caused by a prolapsed intervertebral disc (PID). Although the duration and severity of symptoms can vary, pain persisting beyond 6 weeks is unlikely to recover spontaneously and may require investigation and treatment. Currently, there is no specific care pathway for sciatica in the National Health Service (NHS), and no direct comparison exists between surgical microdiscectomy and transforaminal epidural steroid injection (TFESI). The NERVES (NErve Root block VErsus Surgery) trial aims to address this by comparing clinical and cost-effectiveness of surgical microdiscectomy and TFESI to treat sciatica secondary to a PID. METHODS/DESIGN: A total of 163 patients were recruited from NHS out-patient clinics across the UK and randomised to either microdiscectomy or TFESI. Adult patients (aged 16-65 years) with sciatic pain endured for between 6 weeks and 12 months are eligible if their symptoms have not been improved by at least one form of conservative (non-operative) treatment and they are willing to provide consent. Patients will be excluded if they present with neurological deficit or have had previous surgery at the same level. The primary outcome is patient-reported disability measured using the Oswestry Disability Questionnaire (ODQ) score at 18 weeks post randomisation and secondary outcomes include disability and pain scales using numerical pain ratings, modified Roland-Morris and Core Outcome Measures Index at 12-weekly intervals, and patient satisfaction at 54 weeks. Cost-effectiveness and quality of life (QOL) will be assessed using the EQ-5D-5 L and self-report cost data at 12-weekly intervals and Hospital Episode Statistics (HES) data. Adverse event data will be collected. Analysis will follow the principle of intention-to-treat. DISCUSSION: NERVES is the first trial to evaluate the comparative clinical and cost-effectiveness of microdiscectomy to local anaesthetic and steroid administered via TFESI. The results of this research may facilitate the development of an evidence-based treatment strategy for patients with sciatica. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN04820368 . Registered on 5 June 2014. EudraCT EudraCT2014-002751-25. Registered on 8 October 2014.

A framework for prospectively defining progression rules for internal pilot studies monitoring recruitment.

Just over half of publicly funded trials recruit their target sample size within the planned study duration. When recruitment targets are missed, the funder of a trial is faced with the decision of either committing further resources to the study or risk that a worthwhile treatment effect may be missed by an underpowered final analysis. To avoid this challenging situation, when there is insufficient prior evidence to support predicted recruitment rates, funders now require feasibility assessments to be performed in the early stages of trials. Progression criteria are usually specified and agreed with the funder ahead of time. To date, however, the progression rules used are typically ad hoc. In addition, rules routinely permit adaptations to recruitment strategies but do not stipulate criteria for evaluating their effectiveness. In this paper, we develop a framework for planning and designing internal pilot studies which permit a trial to be stopped early if recruitment is disappointing or to continue to full recruitment if enrolment during the feasibility phase is adequate. This framework enables a progression rule to be pre-specified and agreed upon prior to starting a trial. The novel two-stage designs stipulate that if neither of these situations arises, adaptations to recruitment should be made and subsequently evaluated to establish whether they have been successful. We derive optimal progression rules for internal pilot studies which minimise the expected trial overrun and maintain a high probability of completing the study when the recruitment rate is adequate. The advantages of this procedure are illustrated using a real trial example.

Conservative management of type II and III odontoid fractures in the elderly at a regional spine centre: A prospective and retrospective cohort study.

BACKGROUND: The optimal management of odontoid fractures in the elderly population is unclear and management of this group of patients is complicated by multiple co-morbidities. This study aimed to determine the outcomes after conservative management strategies were applied in this patient group. METHODS: We carried out retrospective and prospective analyses of all patients with axial cervical spine injuries, at a single centre. We included patients aged over 60 years with type II and III odontoid fractures. Information was gathered on demographics, ASA grading-associated injuries and complications. The outcome measures were rates and type of union, pain and neurological functions, specifically ambulation. RESULTS: Fifty-seven adult patients with a median age of 78 years (range 60-92 years) were included. There were 42 type II and 15 type III odontoid fractures. Three patients required surgical fixation due to displaced fractures, which could not be reduced with manual traction. Twenty-four (41%) patients were managed with a rigid pinned halo orthosis to obtain adequate reduction and immobilisation. The remaining 30 (53%) were managed in a hard cervical collar. Patients managed with a halo were significantly younger and had more associated injuries than patients managed in a collar (age: t-test=4.05, p<0.01, associated injuries: Chi-square=4.38, p<0.05). At a mean follow-up of 25 weeks, 87% of type II and 100% of type III fractures had achieved bony union or stable, fibrous non-union. There were no statistical differences in fracture type, follow-up or neurological outcomes between the halo and collar groups. However, overall more patients managed in a collar developed stable fibrous non-union than bony fusion (Fisher's exact test, p<0.05), although this was not significant when analysed by each fracture type individually. A regression model was constructed and identified fracture type as the only independent predictor of time to union, with type III fractures healing faster than type II. CONCLUSIONS: High rates of bony union and stable fibrous non-union with a good functional outcome can be achieved in the elderly population sustaining type II or III odontoid fractures, when managed non-surgically. Halo orthosis may not offer any clear advantage over hard collar in this group. Close follow-up is needed for late complications and there must be a willingness to perform surgery if conservative measures fail.

Is the rate of re-operation after primary lumbar microdiscectomy affected by surgeon grade or intra-operative lavage of the disc space?

STUDY DESIGN. Retrospective audit of consecutive patients. OBJECTIve. To investigate the re-operation rate following elective primary lumbar microdiscectomy and to determine whether principal surgeon grade and/or disc space lavage is a factor in recurrence. SUMMARY OF BACKGROUND DATA. Recurrent herniation of disc material following lumbar microdiscecomy surgery is one of the commonest complications of the procedure. Any reduction in the number of revision microdiscectomies performed per year would have a significant impact on patients' lives and on the health service economy. We undertook this study to ascertain whether principal surgeon grade and/or disc space lavage has an impact in reducing the re-operation rate. METHODS. We undertook a retrospective audit of patients who underwent elective primary lumbar microdiscectomy, over a 3-year period (n = 971). RESULTS. The overall re-operation rate for primary elective microdiscectomy was 3.8%, consistent with the published literature. The relative risk of re-operation in patients primarily operated by registrar surgeons was 1.2 fold the risk in patients operated by consultants (95% CI: 0.62, 2.35) although not statistically significant (p = 0.568). The risk of re-operation in the 'non lavage' group was 2.15 times the risk in the 'lavage' group (95% CI: 0.63, 7.34), but it did not reach significance (p = 0.222). CONCLUSIONS. Principal surgeon grade and intervertebral disc lavage have not been found conclusively to be factors in the rate of recurrence. This information is useful to reassure patients that their outcome from such surgery is not dependent on the grade of surgeon performing the operation. There is a possible trend towards intervertebral disc lavage reducing the rate of recurrence.

Spontaneous spinal epidural hematoma: a case report and literature review.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is a rare cause of spinal cord compression that requires emergency investigation and treatment. Prompt diagnosis is essential to prevent morbidity and mortality. OBJECTIVES: Our goal was to report a case of SSEH, and to review the literature on the topic, looking particularly at the factors influencing post-operative outcome, and the symptoms and signs that would lead one to consider this rare diagnosis. CASE REPORT: A 36-year-old man presented to the Emergency Department with paraplegia and a sensory level at T4. There was no history of trauma and he was not taking any medications. Magnetic resonance imaging revealed a large non-enhancing posterior epidural mass lesion between C7 and upper T4, causing severe cord compression at T1-T3. Post contrast scans revealed no rim enhancement. Blood investigations were unremarkable, with an international normalized ratio of 1.1. He underwent urgent decompression laminectomy within 12 h of symptom onset. Intraoperatively, thick clotted blood and prominent epidural vessels were seen. Histology revealed engorged vessels with hemorrhage and clot in the extravascular tissues. Post-operatively, the impaired neurological status remained unchanged. CONCLUSION: SSEH is a rare cause of spinal cord compression that requires prompt diagnosis and surgical intervention to prevent morbidity. Neurological outcome after surgical decompression depends on the severity of preoperative neurological deficits as well as the time between symptom onset and surgery.

The prevalence and pathogenesis of synovial cysts within the ligamentum flavum in patients with lumbar spinal stenosis and radiculopathy.

STUDY DESIGN: A clinicopathologic study of synovial cysts in the ligamentum flavum (LF) in patients with spinal stenosis. OBJECTIVE: To investigate the pathogenesis of lumbar juxtafacet cysts. SUMMARY OF BACKGROUND DATA: Contradictions in the terminology applied to lumbar juxtafacet cysts arise from the frequent sparsity of synovial lining cells, which has led to synovial cysts often being called "ganglion cysts" despite lacking confirmatory pathology. METHODS: A total of 27 consecutive patients with radiologically confirmed stenosis underwent laminectomy. LF/facet joint (FJ) relationships were retained by en bloc excision of the LF and the medial inferior FJ. Controls were LF/FJ specimens from 47 cadaver lumbar spines. RESULTS: The 27 patients yielded 51 LF/FJ specimens containing 28 synovial cysts, 12 of which were unilateral and 8 were bilateral. Fragments of articular cartilage and bone were embedded in the walls of 89% of cysts and in the walls of a bursa-like channel originating from the medial aspect of the FJ capsule and extending into the LF. Communication with the FJ via this channel was observed in 21 (75%) of the 28 synovial cysts. Extending up to 12 mm in length, the channel was present in nearly all control spines at the L4-L5 level but in only about half at the T12-L1 level. CONCLUSION: Cysts having an extensive or meagre synovial cell lining are common in the LF of patients with symptomatic lateral or central stenosis. The cysts communicate with the FJ by a bursa-type channel within the LF. Advanced osteoarthritis of the FJ causes the liberation of fragments of cartilage and bone into the synovial fluid of the joint space. This enables some fragments to escape from the joint into the channel and become lodged within its wall where they provoke granulation tissue and scar formation. The tissue response to articular debris may block the synovial-lined channel to cause synovial cyst formation.

Transplantation of Schwann cell line clones secreting GDNF or BDNF into the retinas of dystrophic Royal College of Surgeons rats.

PURPOSE: To assess the capacity of a retrovirus-engineered Schwann cell line (SCTM41), transfected with either a glial cell line-derived neurotrophic factor (GDNF) construct or a brain-derived neurotrophic factor (BDNF) construct, to sustain visual function in the dystrophic Royal College of Surgeons (RCS) rat. METHODS: Cell suspensions were injected into the subretinal space of the right eye of 3-week-old dystrophic RCS rats through a transscleral approach. The left eye remained as an unoperated control. Sham-surgery animals received injections of carrier medium plus DNase to the right eye. All animals were placed on oral cyclosporine. At 8, 12, 16, and 20 weeks of age, animals were placed in a head-tracking apparatus and screened for their ability to track square-wave gratings at various spatial frequencies (0.125, 0.25, and 0.5 cyc/deg). At the end of the experiment, the animals were perfused and processed for histologic assessment of photoreceptor survival. RESULTS: Animals with SCTM41-GDNF-secreting cells, on average, head tracked longer than animals with SCTM41-BDNF-secreting cells, and both performed better than those injected with the parent SCTM41 line. All tracked longer than sham-surgery or nonsurgical dystrophic eyes. Each cell type demonstrated preservation of photoreceptors up to at least 4 months of age, over and above the sham-surgery control. CONCLUSIONS: Engineered Schwann cells sustain retinal structure and function in the dystrophic RCS rat. Cells overexpressing GDNF or BDNF had a greater effect on photoreceptor survival than the parent line or sham surgery. This study demonstrates that ex vivo gene therapy and subsequent cell transplantation can be effective in preserving photoreceptors from the cell death that normally accompanies retinal degeneration.

Cost-effective outcome for treating poor-grade subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The goal of this study was to prospectively assess outcome and cost for poor-grade subarachnoid hemorrhage patients presenting to a regional neurosurgical center (Addenbrooke's Hospital, Cambridge, UK) between 1994 and 2001. Outcome measures were clinical outcome at 6 months, number needed to treat (NNT) for favorable outcomes, and cost analysis. METHODS: Poor-grade patients (World Federation of Neurological Surgeons grades 4 and 5) were transferred to the neurocritical care unit after intubation and ventilation. After resuscitation and drainage of ventricular cerebrospinal fluid for 24 hours, sedation was stopped, and patients were assessed clinically. Patients with a Glasgow Motor Score (GMS) > or =4 underwent angiography and surgical treatment of culprit aneurysms. Patients with a subsequent GMS of 6 were not deemed poor grade and were discounted from the study. RESULTS: We deemed 166 ventilated patients genuinely poor grade (mean age, 53.4 years; 94 women [56.6%]). Of these, 88 patients (4