Clinical management of contrast-induced neurotoxicity: a systematic review.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is an increasingly recognised complication following endovascular procedures utilising contrast. It remains poorly understood with heterogenous clinical management strategies. The aim of this review was to identify commonly employed treatments for CIN to enhance clinical decision making. METHODS: A systematic search of Embase (1947-2022) and Medline (1946-2022) was conducted. Articles describing (i) patients with a clinical diagnosis of CIN, (ii) with radiological exclusion of other pathologies, (iii) detailed report of treatments, and (iv) discharge outcomes, were included. Data relating to demographics, procedure, symptoms, treatment and outcomes were extracted. RESULTS: A total of 73 patients were included, with a median age of 64 years. The most common procedures were cerebral angiography (42.5%) and coronary angiography (42.5%), and the median volume of contrast administered was 150 ml. The most common symptoms were cortical blindness (38.4%) and reduced consciousness (28.8%), and 84.9% of patients experienced complete resolution at the time of discharge. Management included intravenous fluids to dilute contrast in the cerebrovasculature (54.8%), corticosteroids to reduce blood-brain barrier damage (47.9%), antiseizure (16.4%) and sedative (16.4%) medications. Mannitol (13.7%) was also utilised to reduce cerebral oedema. Intensive care admission was required for 19.2% of patients. No statistically significant differences were observed between treatment and discharge outcomes. CONCLUSIONS: The clinical management of CIN should be considered on a patient-by-patient basis, but may consist of aggressive fluid therapy alongside corticosteroids, as well as other supportive therapy as required. Further examination of CIN management is required to define best practice.

Pathophysiology of Contrast-Induced Neurotoxicity: A Narrative Review of Possible Mechanisms.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is an increasingly observed event following the administration of iodinated contrast. It presents as a spectrum of neurological symptoms that closely mimic ischaemic stroke, however, CIN remains a poorly understood clinical phenomenon. An appreciation of the underlying pathophysiological mechanisms is essential to improve clinical understanding and enhance decision-making. METHODS: A broad literature search of Medline (1946 to December 2022) and Embase (1947 to December 2022) was conducted. Articles discussing the pathophysiology of CIN were reviewed. SUMMARY: The pathogenesis of CIN appears to be multifactorial. A key step is likely blood-brain barrier (BBB) breakdown due to factors including ischaemic stroke, uncontrolled hypertension, and possibly contrast agents themselves, among others. This is followed by passage of contrast agents across the BBB, leading to chemotoxic sequelae on neural tissue. KEY MESSAGES: This review provides a clinically oriented review on the pathophysiology of CIN to enhance knowledge and improve decision-making among clinicians.

Seizure-induced reversible magnetic resonance imaging abnormalities: A retrospective cohort study.

PURPOSE: Seizure-induced reversible magnetic resonance imaging (MRI) abnormalities (SRMA) present challenges in seizure management. We sought to investigate the frequency, risk factors, evolution and prognostic value of SRMA. METHODS: A retrospective observational cohort study of consecutive seizure patients investigated with an MRI of the brain was conducted. Clinical and MRI data were reviewed to determine the clinical characteristics and imaging findings of SRMA. Outcomes (seizure freedom versus uncontrolled seizures and deaths) were assessed upon the last clinic follow-up. Mann-Whitney U test and chi-square test for independence with Bonferroni correction were used to explore the statistical significance of predictive factors. RESULTS: The study included 483 consecutive seizure patients with 7.6% developing SRMA. Patients with SRMA were older (median age 57 years, interquartile range-IQR 52-66, p < 0.001) and experienced longer seizures (median 5 minutes, IQR 2-15, p = 0.002) compared with seizure patients with normal MRI. Seizure type (provoked versus unprovoked), recurrence (first versus recurrent) and epileptiform EEG changes did not demonstrate a significant association. Diffusion restriction and ADC reduction observed in SRMA resolved earlier, while T2, FLAIR hyperintensities and temporal lobes changes persisted longer on follow-up scans. The median time interval from seizure to complete resolution of SRMA was 87 days (IQR 45-225). No statistical difference in outcomes was seen between patients with SRMA and normal MRIs (p = 0.19). CONCLUSIONS: SRMA is an uncommon finding following seizures. It is not associated with poor seizure control or mortality. Risk factors associated with SRMA include older age and longer seizure duration including status epilepticus.

Current knowledge and perspectives of contrast-induced neurotoxicity: A survey of Australian clinicians.

BACKGROUND: Contrast-induced Neurotoxicity (CIN) is an increasingly recognised complication following endovascular procedures. It remains a relatively unexplored clinical entity, and we sought to characterise clinician perspectives towards CIN, as well as identify gaps in knowledge and provide directions for future research. METHODS: An online survey was distributed to members of the Australian and New Zealand Society of Neuroradiology, as well as several Australian tertiary hospitals. Questions related to clinical exposure to CIN, diagnosis, management and pathophysiology were explored. Descriptive analysis was conducted on survey responses, and statistical analysis was performed using Chi-square and Fisher's exact test as appropriate. RESULTS: A total of 95 survey responses were recorded (26.8% response rate). Only 28.4% of respondents were comfortable in diagnosing CIN, and even fewer (24.2%) were comfortable in independently managing CIN patients. Based on clinician opinion, symptoms including impaired consciousness and cortical blindness were thought to be most associated with CIN, whilst the radiological findings of parenchymal oedema and cortical enhancement were considered to be most indicative of CIN. Most clinicians agreed that further investigation is required related to pathophysiology (86.3%), diagnosis (83.2%), and treatment (82.1%). CONCLUSION: CIN is a poorly understood complication following endovascular procedures. Significant gaps in clinical understanding are evident, and further investigation is vital to improve diagnosis and management.

The utility of internal spinal marking for intraoperative localisation: A systematic review.

BACKGROUND: Incorrect level spinal surgery is an avoidable complication, with significant ramifications. Several pre-operative spinal marking techniques have been described to aid intraoperative localisation. METHODS: A systematic search of Ovid MEDLINE, and EMBASE was performed from inception to July 2022. All publications describing cases of internal spinal marking were included for further analysis. 22 articles describing 503 patients satisfied our eligibility criteria. RESULTS: A number of localisation techniques, including endovascular coiling (n = 16), fiducials (n = 177), dye (n = 109), needle/fixed wire (n = 199), cement (n = 4), and gadolinium tubes (n = 1) were described. The highest rates of technical success were observed with endovascular coiling, fiducials, cement and dye (100 %), and complication rates were lowest with endovascular coiling, fiducials and cement (0 %). CONCLUSIONS: Overall, internal spinal marking was effective and safe. When considering practicality and efficacy, fiducial marking appears the optimal technique, as it can be performed in the outpatient setting under local anaesthesia. This review demonstrates the need for more targeted investigation into localisation methods in spinal surgery.

Safety and effectiveness of spinal dural defect repair in the management of superficial siderosis: A systematic review and patient-level analysis.

OBJECTIVE: Superficial siderosis (SS) is a disabling neurodegenerative condition that may be caused by spinal dural defects. Surgical repair is increasingly performed, however clinical outcomes remain unclear. METHODS: A systematic search of PubMed, MEDLINE, and EMBASE was conducted (inception to February 2020). Studies reporting cases of (i) superficial siderosis, (ii) spinal dural defect, (iii) and surgical closure of the defect were included. Demographic characteristics, clinical presentation, operative technique and clinical outcome were extracted for patient-level analysis. RESULTS: A total of 26 publications were included, which reported 38 patients with a median age of 58 years, and a male predominance (78.9 %). Ataxia (85.7 %) and hearing loss (80.0 %) were the most common presenting symptoms. The causative dural defect was most commonly ventral in location (91.7 %) and most commonly identified by CT myelography (48.6 %). Operative technique was highly variable and included primary suture, fibrin glue, dural substitute, or tissue (fat or muscle) graft. Clinical improvement was reported in 21 %, with stabilisation of symptoms in the majority (66 %) and clinical deterioration in 13.2 %. Surgical complications were observed in 7.9 %. CONCLUSION: In patients with superficial siderosis and spinal dural defect, operative closure leads to improvement or stabilisation of symptoms in the vast majority (87%) of patients.

Incidence and risk factors of posttraumatic epilepsy following pediatric traumatic brain injury: A systematic review and meta-analysis.

Posttraumatic epilepsy (PTE) is a well-known chronic complication following traumatic brain injury (TBI). Despite some evidence that age at the time of injury may influence the likelihood of PTE, the incidence of PTE in pediatric populations remains unclear. We therefore conducted a systematic review to determine the overall reported incidence of PTE, and explore potential risk factors associated with PTE after pediatric TBI. A comprehensive literature search of the PubMed, Embase, and Web of Science databases was conducted, including randomized controlled trials and cohort studies assessing the incidence of PTE in TBI pediatric patients. We excluded studies with a sample size of <10 patients and those in which a pediatric cohort was not clearly discernable. The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We found that the overall incidence of PTE following pediatric TBI was 10% (95% confidence interval [CI] = 5.9%-15%). Subgroup analysis of a small number of studies demonstrated that the occurrence of early seizures (cumulative incidence ratio [CIR] = 7.28, 95% CI = 1.09-48.4, p = .040), severe TBI (CIR = 1.81, 95% CI = 1.23-2.67, p < .001), and intracranial hemorrhage (CIR = 1.60, 95% CI = 1.06-2.40, p = .024) increased the risk of PTE in this population. Other factors, including male sex and neurosurgical intervention, were nonsignificantly associated with a higher incidence of PTE. In conclusion, PTE is a significant chronic complication following childhood TBI, similar to in the adult population. Further standardized investigation into clinical risk factors and management guidelines is warranted. PROSPERO ID# CRD42021245802.

Relationship between herniated intervertebral disc fragment weight and pain in lumbar microdiscectomy patients.

OBJECTIVE: The relationship between lumbar disc herniation (LDH) size and the severity of preoperative pain and its impact on postoperative recovery is incompletely understood. This study was conducted to investigate the association between herniated disc fragment weight and pain before and after microdiscectomy. METHODS: A consecutive series of patients from an ongoing randomised controlled trial (ACTRN12616001360404) were included in this study. Included patients were aged between 18 and 75, had a clinical diagnosis of radiculopathy, and MRI evidence of a concordant single-level lumbar disc herniation. All patients underwent standard microdiscectomy without aggressive discectomy or curettage of the endplates. Disc fragment weight was measured intraoperatively. RESULTS: A total of 122 patients with a mean age of 49.5 ± 12.8 years, were included. The median weight of disc fragment was 0.545 g (95% CI 0.364 - 0.654 g). There was no relationship between disc weight and the duration of symptoms (p = 0.409) severity of preoperative leg pain (p = 0.070) or preoperative back pain (p = 0.884). Disc fragment weight was demonstrated to have no correlation with clinically significant postoperative leg pain improvement (p = 0.535) or back pain (p = 0.991). Additional LDH factors, including radiological percentage of canal compromise (p = 0.714), herniation classification (p = 0.462), and vertebral level (p = 0.788) were also shown to have no effect on leg pain outcomes. CONCLUSIONS: Disc fragment weight had no effect on the severity of pain at presentation or after microdiscectomy. Patients benefit from surgery equally, regardless of the size of LDH.

Cumulative Time of Cigarette Smoking Is Associated with a Greater Risk of Aneurysmal Subarachnoid Hemorrhage and Younger Age at Presentation: A Nationwide Observation Study.

BACKGROUND: Smoking is known to be associated with an increased risk of intracranial aneurysm rupture; however, the risk in smokers stratified by age, sex, and aneurysm location is not clear. METHODS: A retrospective study of all aneurysmal subarachnoid hemorrhage (aSAH) cases in Australia between 2008 and 2018 was conducted. The relative risk of aSAH in smokers compared with nonsmokers was calculated on the basis of nationwide smoking statistics and was stratified according to sex, age group, and aneurysm location. RESULTS: Out of 12,915 aSAH patients, 3249 (25.2%) were active smokers. Across both men and women, smoking increased the risk of aSAH by 2.4× in 30- to 39-year-olds (95% CI 2.1-2.7), 2.4× in 40- to 49-year-olds (95% CI 2.2-2.7), 2.3× in 50- to 59-year-olds (95% CI 2.1-2.4), and 1.8× in 60- to 69-year-olds (95% CI 1.7-2.0) with less of an effect in smokers younger than 30 years (RR: 1.2, 95% CI 1.0-1.5) and older than 70 years (RR: 1.0, 95% CI 0.9-1.2). Compared with a nonsmoker younger than 30 years old, the relative risk of aSAH increased by an average of 7.2 for every decade spent smoking in women and an average of 4.0 for every decade spent smoking in men. Additionally, smokers were 5.2× more likely to present before 50 years of age. CONCLUSIONS: Smoking increased the risk of aSAH by 2-fold between the ages of 30 and 60. Smokers experienced aSAH at younger ages.

Influence of socioeconomic status on the incidence of aneurysmal subarachnoid haemorrhage and clinical recovery.

BACKGROUND: The relevance of socioeconomic status (SES) on the incidence of aneurysmal subarachnoid haemorrhage (aSAH) and discharge functional outcomes following treatment is not clear. METHODS: A retrospective cross-sectional study was performed on data retrieved from the Nationwide Hospital Morbidity Database for all aSAH cases in Australia between 2012 and 2018. Information on patient characteristics, procedures performed, discharge disposition and SES were extracted. SES data was derived from classifications by the Australian Bureau of Statistics. Putative risk factors were evaluated with univariate and multivariate logistic regression analysis to identify independent predictor of unfavourable discharge outcomes (defined as death or dependency). RESULTS: A total of 3,591 low SES patients (49.8%) were identified in our study cohort. Average crude incidence of aSAH was persistently higher among the SES disadvantaged (6.6 cases per 100,000 person-years, 95% CI 6.3 - 6.8), compared to the SES advantaged group (4.1 cases per 100,000 person-years, 95% CI 4.0-4.2) (p < 0.0001). Patients in the Low SES group were more likely to be active smokers, have type 2 diabetes mellitus, or live in non-metropolitan residence, and have overall worse discharge functional outcomes (27.7% versus 24.5%, p = 0.0015). Adjusting for well-established risk factors such as older age, and intracranial bleed (ICH and/or IVH), disadvantaged SES remained a significant predictor of poor discharge outcome following aSAH (p = 0.0003). CONCLUSION: aSAH occurs more frequently among low SES communities, and once ruptured, there is a greater risk of poor recovery..

Incidence of post-traumatic epilepsy following paediatric traumatic brain injury: protocol for systematic review and meta-analysis.

INTRODUCTION: Post-traumatic epilepsy (PTE) is a recognised complication of traumatic brain injury (TBI), and is associated with higher rates of mortality and morbidity when compared with patients with TBI who do not develop PTE. The majority of the literature on PTE has focused on adult populations, and consequently there is a paucity of information regarding paediatric cohorts. Additionally, there is considerable heterogeneity surrounding the reported incidence of PTE following childhood TBI in the current literature. The primary aim of our study is to summarise reported PTE incidences in paediatric populations to derive an accurate estimate of the global incidence of PTE following childhood TBI. Our secondary aim is to explore risk factors that increase the likelihood of developing PTE. METHODS AND ANALYSIS: A systematic literature search of Embase (1947-2021), PubMed (1996-2021) and Web of Science (1900-2021) will be conducted. Publications in English that report the incidence of PTE in populations under 18 years of age will be included. Publications that evaluate fewer than 10 patients, report an alternative cause of epilepsy, or in which a paediatric cohort is not discernable, will be excluded. Independent investigators will identify the relevant publications, and discrepancies will be adjudicated by a third independent investigator. Data extracted will include incidence of PTE, time intervals between TBI and PTE, seizure characteristics, injury characteristics, patient demographics and clinical data. Data extraction will be performed by two independent investigators and cross-checked by a third investigator. A descriptive analysis of PTE incidence will be conducted and a weighted mean will be calculated. If sufficient data are available, stratified meta-analysis of subgroups will also be conducted. ETHICS AND DISSEMINATION: Ethics approval was not required for this study. We intend to publish our findings in a high-quality peer-reviewed journal on completion. PROSPERO REGISTRATION NUMBER: CRD42021245802.

Seizure-induced reversible MRI abnormalities in status epilepticus: A systematic review.

In the context of status epilepticus (SE), seizure-induced reversible MRI abnormalities (SRMA) can be difficult to differentiate from epileptogenic pathologies. To identify patterns and characteristics of SRMA, we conducted a systematic review in accordance with the Preferred Items Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included publications describing patients (a) presenting with status epilepticus, (b) exhibiting seizure-induced MRI abnormalities, (c) who demonstrated complete resolution of MRI abnormality at follow-up, and (d) who had availability of descriptive MRI results. A total of 49 cases from 19 publications fulfilled our eligibility criteria. Signal abnormalities were most frequently reported on T2-weighted sequences followed by diffusion-weighted and fluid-attenuated inversion recovery imaging. Both unilateral and bilateral SRMA were reported. Unilateral EEG abnormalities were often associated with ipsilateral SRMA. The signal changes appeared during the ictus itself in some subjects whilst the median time to SRMA appearance and resolution were 24 h and 96.5 days, respectively. Based on the distribution of reversible signal alterations, we identified five 'composite patterns': (1) predominant cortical (with or without subcortical, leptomeningeal or thalamic involvement), (2) hippocampal (with or without cortical, subcortical, leptomeningeal, or thalamic involvement), (3) claustrum, (4) predominant subcortical, and (5) splenium involvement. Amongst treatment-responsive SE patients, the cortical pattern was the most prevalent whereas hippocampal involvement was most frequently reported in refractory SE. Cortical atrophy, hippocampal sclerosis, and cortical laminar necrosis were common long-term sequelae after the resolution of SRMA. In this review, we highlight many limitations of the literature and discuss future directions for research.

Seizure-induced reversible MRI abnormalities in patients with single seizures: a systematic review.

Differentiating seizure-induced reversible MRI abnormalities from MRI changes secondary to underlying cerebral pathologies can be challenging for clinicians in the investigation of seizures. The aim of this study was to delineate the characteristic features of reversible seizure-induced MRI abnormalities. A systematic search of the databases Medline (1946-2020), PubMed (1996-2020), and Embase (1947-2020) was performed in keeping with the Preferred Items Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All publications in English, including case reports, of single unprovoked seizure patients with seizure-induced MRI abnormalities demonstrating complete resolution, were included. Two authors extracted data using a predefined template and evaluated the quality of the included studies. MRI data were additionally reviewed by a neuroradiologist. All data were synthesised qualitatively. There were 11 publications altogether, yielding a total of 27 cases that were pertinent to our research question. Abnormalities were most commonly observed on T2-weighted sequences. The most commonly observed constellations of MRI features ("composite pattern") included the following: cortical or subcortical signal change with or without leptomeningeal enhancement, signal abnormality in the splenium of the corpus callosum, and hippocampal signal abnormality. Seizure-induced reversible MRI abnormalities were observed as early as six hours from seizure onset and resolved completely as early as five days from seizure onset. A key limitation of this systematic review was the variability and incomplete reporting of clinical data, especially with regards to seizure semiology and MRI sequences performed, which may have limited our ability to make more definitive conclusions. Seizure-induced reversible MRI changes may appear within hours of seizure onset and resolve within a variable time frame, ranging from days to weeks. Bilateral seizure-induced reversible MRI abnormalities tend to be associated with generalised seizures while unilateral seizure-induced reversible MRI abnormalities may be associated with focal seizures, usually ipsilateral to the seizure focus.

A Core Outcome Set for Research in Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: A core set of outcomes have been identified and published, which are essential to include in all clinical research evaluating the use of extracorporeal membrane oxygenation in critically ill patients, particularly regarding safety and adverse events. The purpose of this international modified Delphi study was to determine which measurement tools and the timing of measurement should be selected for the core outcome set for research evaluating patients receiving extracorporeal membrane oxygenation. DESIGN: This was a two-round international, multidisciplinary web-based, modified Delphi study. PATIENTS: Participants were identified from the International Extracorporeal Membrane Oxygenation Network and the Extracorporeal Life Support Organization, including consumers, multidisciplinary clinicians, researchers and industry partners. MEASUREMENTS: Measurement tools and the timing of measurement were identified from a systematic review of the literature and clinical trials registrations. The primary outcome was the percentage of respondents who completed each survey and indicated that a measurement tool as well as the timing of the measurement should "always" be included in a core outcome set. MAIN RESULTS: Participant response rates were 46 of 65 (71%) and 40 of 46 (87%) for rounds one and two, respectively, with participants representing, researchers, consumers, and industry partners from 15 countries over five continents. Seven measurement tools were identified for the core outcome set of patients on extracorporeal membrane oxygenation. CONCLUSIONS: This study has identified appropriate measurement instruments and the timing of measurement to include in the core outcome set for research evaluating patients receiving extracorporeal membrane oxygenation. This was an important final step to standardize and synthesize research efforts internationally.