Diagnostic Yield of Decubitus CT Myelography for Detection of CSF-Venous Fistulas.

BACKGROUND AND PURPOSE: Various imaging techniques have been described to detect CSF-Venous Fistulas (CVFs) in the setting of Spontaneous Intracranial Hypotension (SIH), including decubitus CT myelography (dCTM). The expected diagnostic yield of dCTM for CVF detection is not fully established. The purpose of this study was to assess the yield of dCTM among consecutive patients presenting for evaluation of possible SIH, and to examine what impact brain MRI findings of SIH had on diagnostic yield. MATERIALS AND METHODS: Single-center, retrospective cohort of consecutive patients presenting over a one-year period who underwent CTM and had no CSF identified in the epidural space. Patients with epidural CSF leaks were included in a secondary cohort. Subjects were grouped according to positioning for the myelogram, either decubitus or prone, and the presence of imaging findings of SIH on pre-procedure brain MRI. Diagnostic yields for each subgroup were calculated, and the yield of dCTM was compared to prone CTM. RESULTS: The study cohort included 302 subjects, including 247 patients with no epidural fluid. Diagnostic yield of dCTM for CVF detection among subjects with positive brain MRI and no epidural fluid was 73%. No CVFs were identified among subjects with negative brain imaging. Among subjects with epidural leak, brain MRI was negative for signs of SIH in 22%. Prone CTM identified a CVF less commonly than dCTM (43% vs. 73%, p=0.19), although the difference was not statistically significant in this small subgroup. CONCLUSIONS: We found a diagnostic yield of dCTM to be similar to the yield previously reported for digital subtraction myelography among patients with positive brain imaging. No CVFs were identified in patients with negative brain imaging; epidural CSF leaks accounted for all cases of patients who had SIH with negative brain imaging. This study provides useful data for counseling patients and helps establish a general benchmark for dCTM yield for CVF detection.ABBREVIATIONS: SIH = spontaneous intracranial hypotension; CVF = CSF-Venous Fistula; CTM = CT Myelography; dCTM = decubitus CT myelography; EBP = epidural blood patch.

Percutaneous Treatment and Post-treatment Management of CSF Leaks and CSF-Venous Fistulas in Spontaneous Intracranial Hypotension.

Spontaneous intracranial hypotension (SIH) is a treatable cause of orthostatic headaches secondary to pathologic loss of cerebrospinal fluid (CSF) from the subarachnoid space. SIH has several known pathologic causes including dural tears from disc osteophytes, leaks emanating from nerve root sleeve diverticula, and CSF-venous fistulas (CVFs). Depending on the type of leak, surgical repair or endovascular techniques may be options for definite treatment. However, epidural blood patching (EBP) remains first-line therapy for many patients due to its long track record, broad availability, and relatively lower risk profile. This review focuses on indications and techniques for the percutaneous treatment of SIH and provides an overview of post-procedural management of these patients.

Myelography Using Energy-Integrating Detector CT Versus Photon-Counting Detector CT for Detection of CSF-Venous Fistulas in Patients With Spontaneous Intracranial Hypotension.

BACKGROUND. CSF-venous fistulas (CVFs), which are an increasingly recognized cause of spontaneous intracranial hypotension (SIH), are often diminutive in size and exceedingly difficult to detect by conventional imaging. OBJECTIVE. This purpose of this study was to compare energy-integrating detector (EID) CT myelography and photon-counting detector (PCD) CT myelography in terms of image quality and diagnostic performance for detecting CVFs in patients with SIH. METHODS. This retrospective study included 38 patients (15 men and 23 women; mean age, 55 ± 10 [SD] years) with SIH who underwent both clinically indicated EID CT myelography (slice thickness, 0.625 mm) and PCD CT myelography (slice thickness, 0.2 mm; performed in ultrahigh-resolution mode) to assess for CSF leak. Three blinded radiologists reviewed examinations in random order, assessing image noise, discernibility of spinal nerve root sleeves, and overall image quality (each assessed using a scale of 0-100, with 100 denoting highest quality) and recording locations of the CVFs. Definite CVFs were defined as CVFs described in CT myelography reports using unequivocal language and having an attenuation value greater than 70 HU. RESULTS. For all readers, PCD CT myelography, in comparison with EID CT myelography, showed higher mean image noise (reader 1: 69.9 ± 18.5 [SD] vs 37.6 ± 15.2; reader 2: 59.5 ± 8.7 vs 49.3 ± 12.7; and reader 3: 57.6 ± 13.2 vs 42.1 ± 16.6), higher mean nerve root sleeve discernibility (reader 1: 81.6 ± 21.7 [SD] vs 30.4 ± 13.6; reader 2: 83.6 ± 10 vs 70.1 ± 18.9; and reader 3: 59.6 ± 13.5 vs 50.5 ± 14.4), and higher mean overall image quality (reader 1: 83.2 ± 20.0 [SD] vs 38.1 ± 13.5; reader 2: 80.1 ± 10.1 vs 72.4 ± 19.8; and reader 3: 57.8 ± 11.2 vs 51.9 ± 13.6) (all p < .05). Eleven patients had a definite CVF. Sensitivity and specificity of EID CT myelography and PCD CT myelography for the detection of definite CVF were 45% and 96% versus 64% and 85%, respectively, for reader 1; 36% and 100% versus 55% and 96%, respectively, for reader 2; and 57% and 100% versus 55% and 93%, respectively, for reader 3. The sensitivity was significantly higher for PCD CT myelography than for EID CT myelography for reader 1 and reader 2 (both p < .05) and was not significantly different between the two techniques for reader 3 (p = .45); for all three readers, specificity was not significantly different between the two modalities (all p > .05). CONCLUSION. In comparison with EID CT myelography, PCD CT myelography yielded significantly improved image quality with significantly higher sensitivity for CVFs (for two of three readers), without significant loss of specificity. CLINICAL IMPACT. The findings support a potential role for PCD CT myelography in facilitating earlier diagnosis and targeted treatment of SIH, avoiding high morbidity during potentially prolonged diagnostic workups.

Results of an International Survey on Spinal Imaging by the ASNR/ASSR/ESNR/ESSR "Nomenclature 3.0" Working Group.

Our goal was to determine if "Nomenclature 2.0," the classification of lumbar disk pathology consensus, should be updated. We conducted a social media and e-mail-based survey on preferences regarding the use of classification on magnetic resonance spine reporting. Members of the European Society of Neuroradiology, European Society of Musculoskeletal Radiology, American Society of Neuroradiology, and American Society of Spine Radiology received a 15-question online survey between February and March 2022. A total of 600 responses were received from 63 countries. The largest number of responses came from Italy and the United States. We found that 71.28% of respondents used Nomenclature 2.0, Classification of Lumbar Disk Pathology. But classification on stenosis is used less often: 53.94% and 60% of respondents do not use any classification of spinal canal stenosis and foraminal stenosis, respectively. When queried about which part of Nomenclature needs improving, most respondents asked for a Structured Reporting Template (SRT), even though 58.85% of respondents do not currently use any template and 54% routinely use a clinical information questionnaire. These results highlight the importance of an updated Nomenclature 3.0 version that integrates the classifications of lumbar disk disease and spinal canal and foraminal stenosis. Further attention should also be directed toward developing a robust endorsed SRT.

Patient experience of spontaneous intracranial hypotension (SIH): qualitative interviews for concept elicitation.

BACKGROUND & OBJECTIVES: Spontaneous intracranial hypotension (SIH) is an underdiagnosed and debilitating condition caused by a spinal cerebrospinal fluid (CSF) leak. Although SIH can lead to substantial morbidity and disability, little data exists about patients' perspectives. Without hearing directly from patients, our understanding of the full experience of having SIH is limited, as is our ability to identify and use appropriate patient-reported outcome measures (PROMs) within clinical care and research. The purpose of this study was to conduct qualitative interviews with confirmed SIH patients to fully describe their experiences and identify relevant concepts to measure. METHODS: Patients were recruited from an SIH specialty clinic at a large, U.S.-based healthcare center. Patients undergoing an initial consultation who were ≥ 18 years old, English-speaking, met the International Classification of Headache Disorders-3 criteria for SIH, and had a brain MRI with contrast that was positive for SIH were eligible to participate. During semi-structured qualitative interviews with a trained facilitator, participants were asked to describe their current SIH symptoms, how their experiences with SIH had changed over time, and the aspects of SIH that they found most bothersome. Analysts reviewed the data, created text summaries, and wrote analytic reports. RESULTS: Fifteen participants completed interviews. Common symptoms reported by patients included headache, tinnitus, ear fullness/pressure/pain, and neck or interscapular pain. Patients reported that their symptoms worsened over the course of their day and with activity. The most bothersome aspect of SIH was disruption to daily activities and limits to physical activities/exercise, which were severe. With regard to symptoms, the most bothersome and impactful included physical pain and discomfort (including headache), as well as fatigue. CONCLUSIONS: Patients reported a diverse set of symptoms that were attributed to SIH, with devastating impacts on functioning and high levels of disability. Researchers considering use of PROMs for SIH should consider inclusion of both symptom scales and aspects of functioning, and future work should focus on evaluating the validity of existing measures for this patient population using rigorous qualitative and quantitative methods in diverse samples. Additionally, these data can be used to assist clinicians in understanding the impacts of SIH on patients.

Consensus Practice Guidelines on Postdural Puncture Headache From a Multisociety, International Working Group: A Summary Report.

Importance: Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures, such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis, and management of this condition is, however, currently lacking. Objective: To fill the practice guidelines void and provide comprehensive information and patient-centric recommendations for preventing, diagnosing, and managing PDPH. Evidence Review: With input from committee members and stakeholders of 6 participating professional societies, 10 review questions that were deemed important for the prevention, diagnosis, and management of PDPH were developed. A literature search for each question was performed in MEDLINE on March 2, 2022. Additional relevant clinical trials, systematic reviews, and research studies published through March 2022 were also considered for practice guideline development and shared with collaborator groups. Each group submitted a structured narrative review along with recommendations that were rated according to the US Preventive Services Task Force grading of evidence. Collaborators were asked to vote anonymously on each recommendation using 2 rounds of a modified Delphi approach. Findings: After 2 rounds of electronic voting by a 21-member multidisciplinary collaborator team, 47 recommendations were generated to provide guidance on the risk factors for and the prevention, diagnosis, and management of PDPH, along with ratings for the strength and certainty of evidence. A 90% to 100% consensus was obtained for almost all recommendations. Several recommendations were rated as having moderate to low certainty. Opportunities for future research were identified. Conclusions and Relevance: Results of this consensus statement suggest that current approaches to the treatment and management of PDPH are not uniform due to the paucity of evidence. The practice guidelines, however, provide a framework for individual clinicians to assess PDPH risk, confirm the diagnosis, and adopt a systematic approach to its management.

Evidence-based clinical practice guidelines on postdural puncture headache: a consensus report from a multisociety international working group.

INTRODUCTION: Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis or management of this condition is, however, currently lacking. This multisociety guidance aims to fill this void and provide practitioners with comprehensive information and patient-centric recommendations to prevent, diagnose and manage patients with PDPH. METHODS: Based on input from committee members and stakeholders, the committee cochairs developed 10 review questions deemed important for the prevention, diagnosis and management of PDPH. A literature search for each question was performed in MEDLINE (Ovid) on 2 March 2022. The results from each search were imported into separate Covidence projects for deduplication and screening, followed by data extraction. Additional relevant clinical trials, systematic reviews and research studies published through March 2022 were also considered for the development of guidelines and shared with contributors. Each group submitted a structured narrative review along with recommendations graded according to the US Preventative Services Task Force grading of evidence. The interim draft was shared electronically, with each collaborator requested to vote anonymously on each recommendation using two rounds of a modified Delphi approach. RESULTS: Based on contemporary evidence and consensus, the multidisciplinary panel generated 50 recommendations to provide guidance regarding risk factors, prevention, diagnosis and management of PDPH, along with their strength and certainty of evidence. After two rounds of voting, we achieved a high level of consensus for all statements and recommendations. Several recommendations had moderate-to-low certainty of evidence. CONCLUSIONS: These clinical practice guidelines for PDPH provide a framework to improve identification, evaluation and delivery of evidence-based care by physicians performing neuraxial procedures to improve the quality of care and align with patients' interests. Uncertainty remains regarding best practice for the majority of management approaches for PDPH due to the paucity of evidence. Additionally, opportunities for future research are identified.

Enterothecal fistula as a rare cause of adult pneumocephalus and meningitis: a case report.

Background: Enterothecal fistulas are pathological connections between the gastrointestinal system and subarachnoid space. These rare fistulas occur mostly in pediatric patients with sacral developmental anomalies. They have yet to be characterized in an adult born without congenital developmental anomaly yet must remain on the differential diagnosis when all other causes of meningitis and pneumocephalus have been ruled out. Good outcomes rely on aggressive multidisciplinary medical and surgical care, which are reviewed in this manuscript. Case Description: A 25-year-old female with history of a sacral giant cell tumor resected via anterior transperitoneal approach followed by posterior L4-pelvis fusion presented with headaches and altered mental status. Imaging revealed that a portion of small bowel had migrated into her resection cavity and created an enterothecal fistula resulting in fecalith within the subarachnoid space and florid meningitis. The patient underwent a small bowel resection for fistula obliteration, and subsequently developed hydrocephalus requiring shunt placement and two suboccipital craniectomies for foramen magnum crowding. Ultimately, her wounds became infected requiring washouts and instrumentation removal. Despite a prolonged hospital course, she made significant recovery and at 10-month following presentation, she is awake, oriented, and able to participate in activities of daily living. Conclusions: This is the first case of meningitis secondary to enterothecal fistula in a patient without a previous congenital sacral anomaly. Operative intervention for fistula obliteration is the primary treatment and should be performed at a tertiary hospital with multidisciplinary capabilities. If recognized quickly and appropriately treated, there is a possibility of good neurological outcome.

Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy.

PURPOSE: Mendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)-associated acute necrotizing encephalopathy subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype. METHODS: This study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy. RESULTS: All 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family. CONCLUSION: Biallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings.

Image-Guided Spine Interventions for Pain: Ongoing Controversies.

An expanding array of image-guided spine interventions have the potential to provide immediate and effective pain relief. Innovations in spine intervention have proceeded rapidly, with clinical adoption of new techniques at times occurring before the development of bodies of evidence to establish efficacy. Although new spine interventions have been evaluated by clinical trials, acceptance of results has been hindered by controversies regarding trial methodology. This article explores controversial aspects of four categories of image-guided interventions for painful conditions: spine interventions for postdural puncture headache resulting from prior lumbar procedures, epidural steroid injections for cervical and lumbar radiculopathy, interventions for facet and sacroiliac joint pain, and vertebral augmentations for compression fractures. For each intervention, we summarize the available literature, with an emphasis on persistent controversies, and discuss how current areas of disagreement and challenge may shape future research and innovation. Despite the ongoing areas of debate regarding various aspects of these procedures, effective treatments continue to emerge and show promise for aiding relief of a range of debilitating conditions.

Facets of facet joint interventions.

Facet joint (FJ) disease is a common cause of axial low back pain with many minimally invasive image-guided treatment options. This article discusses fluoroscopic and CT-guided intraarticular FJ injections, medial branch (MB) radiofrequency ablation (RFA), and lumbar facet synovial cyst (LFSC) aspiration, rupture, or fenestration. Additionally, the article will highlight medial branch blocks (MBBs) utilized to diagnose facet-mediated pain and to predict outcomes to RFA.

Efficacy of epidural blood patching or surgery in spontaneous intracranial hypotension: an evidence map protocol.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a debilitating disorder caused by non-iatrogenic spinal cerebrospinal fluid leaks. SIH is increasingly recognized as an important treatable cause of secondary headaches. Treatment involves either epidural blood patching or surgery, which have considerable differences in their adverse event rates, recovery times, and cost. The objective of this evidence map is to understand the breadth of studies that investigate SIH treatment efficacy and to identify knowledge gaps to inform future research. METHODS: This review will consider experimental, observational, and systematic review studies that assess the efficacy of epidural blood patching and surgery for the treatment of patients with SIH. Individual case studies, clinical guidelines, editorials, protocols, and studies that do not assess an intervention will not be included. English language studies will be included without limitation based on the date of publication. Databases to be searched include MEDLINE® (via Ovid), EMBASE (via Elsevier), and Web of Science™ (via Clarivate). Study selection will be performed independently by two investigators with extracted data to include study type, the number of patients included, patient descriptors, intervention characteristics, and outcome measure used. Data will be presented through a narrative summary aided by tabular and graphical formats in a manner that aligns with the objective of the evidence mapping review. DISCUSSION: The overarching goal of this evidence map is to provide an improved understanding of the breadth of studies investigating SIH treatment efficacy in the literature and to thereby identify knowledge gaps that can inform future research directions. TRIAL REGISTRATION: OSF Registry https://osf.io/nwju7 .

An Exploratory Analysis of Biomarkers of Perihematomal Edema in the CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial.

OBJECTIVE: To identify biomarkers with potential to indicate severity of perihematomal edema and secondary tissue injury after intracerebral hemorrhage (ICH), and which could be used as surrogate markers in future clinical trials for novel ICH therapeutics. MATERIALS AND METHODS: This exploratory cohort study compared trends in neuroinflammatory biomarker levels in 18 consecutively enrolled patients with acute supratentorial ICH and 16 patients treated with the investigational neuroprotective therapy CN-105 to identify a panel of 10 biomarkers. Biomarker levels over five days post-hemorrhage were then compared with edema volumes in a larger sample of patients treated with CN-105. RESULTS: Mean normalized edema volumes increased over time; higher CRP levels were associated with increased edema volumes (p = 0.006, r = 0.56). Higher IL8, IL10, MCP, and MMP-9 levels were associated with decreased edema volumes (p = 0.005, r =-0.57; p = 0.02, r =-0.51; p = 0.02, r =-0.52; p = .002, r =-0.63, respectively). IL1-RA, IL1-B, IL23, vWF, and IL17 levels were not significantly associated with edema volumes (p > 0.05). CONCLUSIONS: This exploratory study provides some of the first insights into the longitudinal associations between markers of neuroinflammation and development of perihematomal edema and secondary tissue injury in human ICH. We hypothesize that these biomarkers could be used as surrogates for treatment effect in novel therapies intended to limit neuroinflammation after ICH.

Dual energy CT for the identification of CSF-Venous Fistulas and CSF leaks in spontaneous intracranial hypotension: Report of four cases.

Spontaneous intracranial hypotension (SIH) is a debilitating condition caused by spinal CSF leaks or CSF-venous fistulas (CVFs). Localizing the causative CSF leak or CVF is critical for definitive treatment but can be difficult using conventional myelographic techniques because these lesions are often low contrast compared to background, diminutive, and in some cases may be mistaken for calcified structures. Dual energy CT (DECT) can increase the conspicuity of iodinated contrast compared to background and can provide the ability to distinguish materials based on differing anatomic properties, making it well suited to address the shortcomings of conventional myelography in SIH. The purpose of this report is to illustrate the potential benefits of using DECT as an adjunct to traditional myelographic techniques in order to increase the conspicuity of these often-subtle CVFs and CSF leaks. This retrospective case series included 4 adult patients with SIH who demonstrated findings equivocal for either CVF or CSF leak using our institution's standard initial CT myelogram and in whom subsequent evaluation with DECT ultimately helped to identify the CVF or CSF leak. DECT demonstrated utility by increasing the conspicuity of two subtle CVFs compared to background and also helped to differentiate between calcified osteophytes and extradural contrast in 2 CSF leaks, confirming their presence and identifying the causative pathology. Our observations demonstrate the benefit of DECT as a problem-solving tool in the accurate diagnosis and localization of CVFs and CSF leaks.

The microRNA processor DROSHA is a candidate gene for a severe progressive neurological disorder.

DROSHA encodes a ribonuclease that is a subunit of the Microprocessor complex and is involved in the first step of microRNA (miRNA) biogenesis. To date, DROSHA has not yet been associated with a Mendelian disease. Here, we describe two individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. DROSHA is constrained for missense variants and moderately intolerant to loss-of-function (o/e = 0.24). The loss of the fruit fly ortholog drosha causes developmental arrest and death in third instar larvae, a severe reduction in brain size and loss of imaginal discs in the larva. Loss of drosha in eye clones causes small and rough eyes in adult flies. One of the identified DROSHA variants (p.Asp1219Gly) behaves as a strong loss-of-function allele in flies, while another variant (p.Arg1342Trp) is less damaging in our assays. In worms, a knock-in that mimics the p.Asp1219Gly variant at a worm equivalent residue causes loss of miRNA expression and heterochronicity, a phenotype characteristic of the loss of miRNA. Together, our data show that the DROSHA variants found in the individuals presented here are damaging based on functional studies in model organisms and likely underlie the severe phenotype involving the nervous system.

CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial.

BACKGROUND: Endogenous apolipoprotein (apo) E mediates neuroinflammatory responses and recovery after brain injury. Exogenously administered apoE-mimetic peptides effectively penetrate the central nervous system compartment and downregulate acute inflammation. CN-105 is a novel apoE-mimetic pentapeptide with excellent evidence of functional and histological improvement in preclinical models of intracerebral hemorrhage (ICH). The CN-105 in participants with Acute supraTentorial intraCerebral Hemorrhage (CATCH) trial is a first-in-disease-state multicenter open-label trial evaluating safety and feasability of CN-105 administration in patients with acute primary supratentorial ICH. METHODS: Eligible patients were aged 30-80 years, had confirmed primary supratentorial ICH, and were able to intiate CN-105 administration (1.0 mg/kg every 6 h for 72 h) within 12 h of symptom onset. A priori defined safety end points, including hematoma volume, pharmacokinetics, and 30-day neurological outcomes, were analyzed. For clinical outcomes, CATCH participants were compared 1:1 with a closely matched contemporary ICH cohort through random selection. Hematoma volumes determined from computed tomography images on days 0, 1, 2, and 5 and ordinal modified Rankin Scale score at 30 days after ICH were compared. RESULTS: In 38 participants enrolled across six study sites in the United States, adverse events occurred at an expected rate without increase in hematoma expansion or neurological deterioration. CN-105 treatment had an odds ratio (95% confidence interval) of 2.69 (1.31-5.51) for lower 30-day modified Rankin Scale score, after adjustment for ICH score, sex, and race/ethnicity, as compared with a matched contemporary cohort. CONCLUSIONS: CN-105 administration represents an excellent translational candidate for treatment of acute ICH because of its safety, dosing feasibility, favorable pharmacokinetics, and possible improvement in neurological recovery.