Intrathecal Saline Infusion as an Effective Temporizing Measure in the Management of Spontaneous Intracranial Hypotension.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a rare condition for which no optimal treatment guidelines have been determined. The most common presentation is orthostatic headaches, but patients can present with a variety of symptoms. CASE DESCRIPTION: We present a case of a 34-year-old man who developed progressive orthostatic headaches and bilateral subdural collections. His symptoms along with imaging of his brain and spine were consistent with SIH. Unfortunately, his symptoms continued to progress, and his level of consciousness became affected. The patient did not respond to either conservative management or epidural blood patching. As the result of his worsening condition, a lumbar drain was inserted for the intrathecal infusion of normal saline to prevent tonsillar herniation. Once the infusion was started, his level of consciousness improved. It was discovered that his cerebrospinal fluid leak was due to an osteophyte within his thoracic spine, which was eroding the dura. He underwent a costo-transversectomy with the removal of the osteophyte and repair of the dural defect. The patient had some improvement after this procedure, but he remained more somnolent than expected. On subsequent imaging, it was found that his subdural collections had increased slightly in size and it was decided to drain them. Both collections were released under high pressure, and he went on to make an excellent recovery. CONCLUSIONS: This case demonstrates that an intrathecal saline infusion can be used as an effective temporizing measure in patients with critical symptoms of SIH and it also alerts clinicians that low-pressure subdural collections can progress to subdural collections under high pressure.

Correction: Age-specific global epidemiology of hydrocephalus: Systematic review, metanalysis and global birth surveillance.

[This corrects the article DOI: 10.1371/journal.pone.0204926.].

Intrathecal Morphine Following Lumbar Fusion: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Despite the potential for faster postoperative recovery and the ease of direct intraoperative injection, intrathecal morphine is rarely provided in lumbar spine surgery. OBJECTIVE: To evaluate the safety and efficacy of intrathecal morphine following lumbar fusion. METHODS: We randomly assigned 150 patients undergoing elective instrumented lumbar fusion to receive a single intrathecal injection of morphine (0.2 mg) or placebo (normal saline) immediately prior to wound closure. The primary outcome was pain on the visual-analogue scale during the first 24 h after surgery. Secondary outcomes included respiratory depression, treatment-related side effects, postoperative opioid requirements, and length of hospital stay. An intention-to-treat, repeated-measures analysis was used to estimate outcomes according to treatment in the primary analysis. RESULTS: The baseline characteristics of the 2 groups were similar. Intrathecal morphine reduced pain both at rest (32% area under the curves [AUCs] difference, P < .01) and with movement (22% AUCs difference, P < .02) during the initial 24 h after surgery. The risk of respiratory depression was not increased by intrathecal morphine (hazard ratio, 0.86; 95% confidence interval, 0.44 to 1.68; P = .66). Although postoperative opioid requirements were reduced with intrathecal morphine (P < .03), lengths of hospital stay were similar (P = .32). Other than a trend towards increased intermittent catheterization among patients assigned to intrathecal morphine (P = .09), treatment-related side effects did not significantly differ. The early benefits of intrathecal morphine on postoperative pain were no longer apparent after 48 h. CONCLUSION: A single intrathecal injection of 0.2 mg of morphine safely reduces postoperative pain following lumbar fusion.

Utility of Cervical Collars Following Cervical Fusion Surgery. Does It Improve Fusion Rates or Outcomes? A Systematic Review.

BACKGROUND: The use of postoperative cervical collars following cervical fusions is common practice. Its use has been purported to improve fusion rates and outcomes. There is a paucity in the strength of evidence to support its clinical benefit. Our objective is to critically evaluate the published literature to determine the strength of evidence supporting the use of postoperative cervical collar use following cervical fusions. METHODS: A systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (also known as PRISMA) was performed. An online search using Medline and Cochrane Central Register of Controlled Trials databases was used to query prospective and retrospective clinical trials evaluating cervical fusions with or without postoperative collar. RESULTS: The search identified 894 articles in Medline and 65 articles in the Cochrane database. From these articles, 130 were selected based on procedure and collar use. Only 3 studies directly compared between collar use and no collar use. Our analysis of the mean improvement in neck disability index scores and improvement over time intervals did not show a statistically significant difference between collar versus no collar (P = 0.86). CONCLUSIONS: We found no strong evidence to support the use of cervical collars after 1- and 2-level anterior cervical discectomy and fusion procedures, and no studies comparing collar use and no collar use after posterior cervical fusions. Given the cost and likely impact of collar use on driving and the return to work, our study shows that currently there is no proven benefit to routine use of postoperative cervical collar in patients undergoing 1- and 2-level anterior cervical discectomy and fusion for degenerative cervical pathologies.

Age-specific global epidemiology of hydrocephalus: Systematic review, metanalysis and global birth surveillance.

BACKGROUND: Hydrocephalus is a debilitating disorder, affecting all age groups. Evaluation of its global epidemiology is required for healthcare planning and resource allocation. OBJECTIVES: To define age-specific global prevalence and incidence of hydrocephalus. METHODS: Population-based studies reporting prevalence of hydrocephalus were identified (MEDLINE, EMBASE, Cochrane, and Google Scholar (1985-2017)). Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Two authors reviewed abstracts, full text articles and abstracted data. Metanalysis and meta-regressions were used to assess associations between key variables. Heterogeneity and publication bias were assessed. Main outcome of interest was hydrocephalus prevalence among pediatric (≤ 18 years), adults (19-64 years), and elderly (≥ 65) patients. Annual hydrocephalus incidence stratified by country income level and folate fortification requirements were obtained (2003-2014) from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). RESULTS: Of 2,460 abstracts, 52 met review eligibility criteria (aggregate population 171,558,651). Mean hydrocephalus prevalence was 85/100,000 [95% CI 62, 116]. The prevalence was 88/100,000 [95% CI 72, 107] in pediatrics; 11/100,000 [95% CI 5, 25] in adults; and 175/100,000 [95% CI 67, 458] in the elderly. The ICBDSR-based incidence of hydrocephalus diagnosed at birth remained stable over 11 years: 81/100,000 [95% CI 69, 96]. A significantly lower incidence was identified in high-income countries. CONCLUSION: This systematic review established age-specific global hydrocephalus prevalence. While high-income countries had a lower hydrocephalus incidence according to the ICBDSR registry, folate fortification status was not associated with incidence. Our findings may inform future healthcare resource allocation and study.

Fractures After Removal of Spinal Instrumentation: Revisiting the Stress-Shielding Effect of Instrumentation in Spine Fusion.

BACKGROUND: Many practicing spine surgeons believe that instrumentation can be removed during revision surgery in successful posterolateral or anterior spinal fusions, confirmed by computed tomography and intraoperative exploration. The stress-shielding effect of spinal instrumentation was well described in the late 1980s and 1990s but has not received recent attention. Despite the paucity of recent literature, concepts underlying the biology and biomechanics of the spinal fusion mass remain particularly salient given the increasing incidence of revision spinal fusion surgery. The aim of this study was to highlight a potential complication of instrumentation removal owing to stress shielding of instrumentation on the spinal column and fusion mass. METHODS: A retrospective review was performed, and a small case series was described. RESULTS: In 3 cases, despite apparent solid fusion demonstrated on preoperative computed tomography and confirmed by intraoperative exploration, new fractures developed after removal of instrumentation. In these cases, fracture occurred at the transition zone between the newly rigid instrumented area and previous fusion. This highlights the relative weakness of the fusion and may be explained by the stress-shielding effect of instrumentation within the fusion mass. CONCLUSIONS: Spinal instrumentation revision requires careful consideration, and routine implant removal should not be performed. The presence of a solid fusion on computed tomography and/or at intraoperative exploration may not justify implant removal in these cases. In cases of extension of a fusion, use of a bridging connection to the new implants should be considered. The cases presented demonstrate the consequences of the stress-shielding effect of implants on the spine and fusion mass.

Oblique Intrathecal Injection in Lumbar Spine Surgery: A Technical Note.

OBJECTIVES: Intrathecal morphine (ITM) is an efficacious method of providing postoperative analgesia and reducing pain associated complications. Despite adoption in many surgical fields, ITM has yet to become a standard of care in lumbar spine surgery. Spine surgeons' reticence to make use of the technique may in part be attributed to concerns of precipitating a cerebrospinal fluid (CSF) leak. METHODS: Herein we describe a method for oblique intrathecal injection during lumbar spine surgery to minimize risk of CSF leak. The dural sac is penetrated obliquely at a 30° angle to offset dural and arachnoid puncture sites. Oblique injection in instances of limited dural exposure is made possible by introducing a 60° bend to a standard 30-gauge needle. RESULTS: The technique was applied for injection of ITM or placebo in 104 cases of lumbar surgery in the setting of a randomized controlled trial. Injection was not performed in two cases (2/104, 1.9%) following preinjection dural tear. In the remaining 102 cases no instances of postoperative CSF leakage attributable to oblique intrathecal injection occurred. Three cases (3/102, 2.9%) of transient CSF leakage were observed immediately following intrathecal injection with no associated sequelae or requirement for postsurgical intervention. In two cases, the observed leak was repaired by sealing with fibrin glue, whereas in a single case the leak was self-limited requiring no intervention. CONCLUSIONS: Oblique dural puncture was not associated with increased incidence of postoperative CSF leakage. This safe and reliable method of delivery of ITM should therefore be routinely considered in lumbar spine surgery.

Lumbar Fusion for Degenerative Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Due to uncertain evidence, lumbar fusion for degenerative indications is associated with the greatest measured practice variation of any surgical procedure. OBJECTIVE: To summarize the current evidence on the comparative safety and efficacy of lumbar fusion, decompression-alone, or nonoperative care for degenerative indications. METHODS: A systematic review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (up to June 30, 2016). Comparative studies reporting validated measures of safety or efficacy were included. Treatment effects were calculated through DerSimonian and Laird random effects models. RESULTS: The literature search yielded 65 studies (19 randomized controlled trials, 16 prospective cohort studies, 15 retrospective cohort studies, and 15 registries) enrolling a total of 302 620 patients. Disability, pain, and patient satisfaction following fusion, decompression-alone, or nonoperative care were dependent on surgical indications and study methodology. Relative to decompression-alone, the risk of reoperation following fusion was increased for spinal stenosis (relative risk [RR] 1.17, 95% confidence interval [CI] 1.06-1.28) and decreased for spondylolisthesis (RR 0.75, 95% CI 0.68-0.83). Among patients with spinal stenosis, complications were more frequent following fusion (RR 1.87, 95% CI 1.18-2.96). Mortality was not significantly associated with any treatment modality. CONCLUSION: Positive clinical change was greatest in patients undergoing fusion for spondylolisthesis while complications and the risk of reoperation limited the benefit of fusion for spinal stenosis. The relative safety and efficacy of fusion for chronic low back pain suggests careful patient selection is required (PROSPERO International Prospective Register of Systematic Reviews number, CRD42015020153).

Diagnostic accuracy of intraocular pressure measurement for the detection of raised intracranial pressure: meta-analysis: a systematic review.

OBJECT: Because clinical examination and imaging may be unreliable indicators of intracranial hypertension, intraocular pressure (IOP) measurement has been proposed as a noninvasive method of diagnosis. The authors conducted a systematic review and meta-analysis to determine the correlation between IOP and intracranial pressure (ICP) and the diagnostic accuracy of IOP measurement for detection of intracranial hypertension. METHODS: The authors searched bibliographic databases (Ovid MEDLINE, Ovid EMBASE, and the Cochrane Central Register of Controlled Trials) from 1950 to March 2013, references of included studies, and conference abstracts for studies comparing IOP and invasive ICP measurement. Two independent reviewers screened abstracts, reviewed full-text articles, and extracted data. Correlation coefficients, sensitivity, specificity, and positive and negative likelihood ratios were calculated using DerSimonian and Laird methods and bivariate random effects models. The I(2) statistic was used as a measure of heterogeneity. RESULTS: Among 355 identified citations, 12 studies that enrolled 546 patients were included in the meta-analysis. The pooled correlation coefficient between IOP and ICP was 0.44 (95% CI 0.26-0.63, I(2) = 97.7%, p < 0.001). The summary sensitivity and specificity for IOP for diagnosing intracranial hypertension were 81% (95% CI 26%-98%, I(2) = 95.2%, p < 0.01) and 95% (95% CI 43%-100%, I(2) = 97.7%, p < 0.01), respectively. The summary positive and negative likelihood ratios were 14.8 (95% CI 0.5-417.7) and 0.2 (95% CI 0.02-1.7), respectively. When ICP and IOP measurements were taken within 1 hour of another, correlation between the measures improved. CONCLUSIONS: Although a modest aggregate correlation was found between IOP and ICP, the pooled diagnostic accuracy suggests that IOP measurement may be of clinical utility in the detection of intracranial hypertension. Given the significant heterogeneity between included studies, further investigation is required prior to the adoption of IOP in the evaluation of intracranial hypertension into routine practice.

Carotid endarterectomy versus stenting: a meta-analysis of randomized trials.

BACKGROUND: A meta-analysis of randomized controlled trials (RCTs) was conducted to update the available evidence on the safety and efficacy of carotid endarterectomy (CEA) versus carotid artery stenting (CAS) in the treatment of carotid artery stenosis. METHODS: A comprehensive search was performed of MEDLINE, EMBASE, CENTRAL, bibliographies of included articles and past systematic reviews, and abstract lists of recent scientific conferences. For each reported outcome, a Mantel-Haenszel random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). The I2 statistic was used as a measure of heterogeneity. RESULTS: Twelve RCTs enrolling 6,973 patients were included in the meta-analysis. Carotid artery stenting was associated with a significantly greater odds of periprocedural stroke (OR 1.72, 95% CI 1.20 to 2.47) and a significantly lower odds of periprocedural myocardial infarction (OR 0.47, 95% CI 0.29 to 0.78) and cranial neuropathy (OR 0.08, 95% CI, 0.04 to 0.16). The odds of periprocedural death (OR 1.11, 95% CI 0.56 to 2.18), target vessel restenosis (OR 1.95, 95% CI 0.63 to 6.06), and access-related hematoma were similar following either intervention (OR 0.60, 95% CI 0.30 to 1.21). CONCLUSIONS: In comparison with CEA, CAS is associated with a greater odds of stroke and a lower odds of myocardial infarction. While the results our meta-analysis support the continued use of CEA as the standard of care in the treatment of carotid artery stenosis, CAS is a viable alternative in patients at elevated risk of cardiac complications.

Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials.

BACKGROUND: Many placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation. METHODS: We searched the US Centers for Disease Control and Prevention's Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention. RESULTS: We identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible interval [CrI] 1.91-3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12-5.13), bupropion (OR 2.07, 95% CrI 1.73-2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69-2.62), nicotine tablet (OR 2.06, 95% CrI 1.12-5.13) and nicotine gum (OR 1.71, 95% CrI 1.35-2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95-5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09-4.08). INTERPRETATION: Varenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.

Increased plasticity of genomic imprinting of Dlk1 in brain is due to genetic and epigenetic factors.

The expression of six imprinted genes (Dlk1, Gt12, Igf2r, Kcnq1, Nnat, and Peg1) was examined in brains of 21 mice derived from N2 x N2 intercrosses between C57BL/6 and MOLF/Ei strains. Imprinting of Igf2r, Kcnq1, Gt12, and Dlk1 varied among individuals. As three of these genes are implicated in cell-cell signaling or cell-environment interactions, variation in their imprinting may influence a wide range of biological processes from cell differentiation to behavior. To elucidate the mechanisms underlying the interindividual imprinting variation in the brain, we focused our effort on the paternally expressed gene Dlk1. We investigated expression of Dlk1 in the brains of animals from N9 and N10 backcrosses and found that reactivation of the normally silent maternal Dlk1 allele in the N9 and N10 mice occurred less often than in N2 x N2 animals. Our data suggest that trans-acting genetic factors of MOLF/Ei origin facilitate the reactivation of the normally silent maternal allele of Dlk1. We mapped one of these factors to the proximal part of Chr 7. The results of bisulfite sequencing methylation analysis show that reactivation of the maternal allele was also associated with hypermethylation of the intragenic differentially methylated region (IG DMR), which is the imprinting control region for the Dlk1-Gt12 domain. Thus, the imprinting status of Dlk1 in the brain depends upon trans-acting genetic influences and correlates with the methylation status of a specific subregion of the IG DMR.