Adverse Allergic Reaction to Intrathecally Administered Technetium-99m Diethylenetriamine Pentaacetate: A Case Report.

Intrathecal administration of radiopharmaceuticals is an infrequently performed procedure in most nuclear medicine facilities. It is possible that adverse allergic reactions following the intrathecal administration of radiopharmaceuticals often go unreported. Here we present a case of spontaneous cerebrospinal fluid rhinorrhea with recurrent bacterial meningitis, who underwent radionuclide cisternography for localization of the site of leak and developed an adverse allergic reaction following the intrathecal administration of technetium-99m diethylenetriamine pentaacetate that resolved with appropriate treatment. Imaging, however, could be carried out to our satisfaction and the allergic reaction did not interfere with, or result in discontinuation of the scan procedure.

Radionuclide Cisternography with [64Cu]Cu-DOTA.

Radionuclide cisternography (RNC) is a method for conducting imaging of the cerebrospinal system and can be used to identify cerebrospinal fluid leaks. So far, RNC has commonly employed radiopharmaceutical agents suitable only for single-photon emission tomography techniques, which are thus lacking in terms of image resolution and can potentially lead to false-negative results. Therefore, [64Cu]Cu-DOTA was investigated as an alternative radiopharmaceutical for RNC, employing positron emission tomography (PET) instead of single-photon emission tomography. A formulation of [64Cu]Cu-DOTA was produced according to the guidelines for good manufacturing practice. The product met the requirements of agents suitable for intrathecal application. [64Cu]Cu-DOTA was administered to a patient and compared to the approved scintigraphic RNC agent, [111In]In-DTPA. While no cerebrospinal fluid leak was detected with [111In]In-DTPA, [64Cu]Cu-DOTA RNC exhibited a posterolateral leak between the vertebral bodies C1 and C2. Thus, in this patient, PET RNC with [64Cu]Cu-DOTA was superior to RNC with [111In]In-DTPA. Since radiopharmaceuticals have a very good safety profile regarding the occurrence of adverse events, PET RNC with [64Cu]Cu-DOTA may become an attractive alternative to scintigraphic methods, and also to computed tomography or magnetic resonance imaging, which often require contrast agents, causing adverse events to occur much more frequently.

68Ga-DOTA PET for Diagnosis of Spinal Cerebrospinal Fluid Leaks.

Spontaneous intracranial hypotension due to spinal cerebrospinal fluid (CSF) leakage causes substantial disease burden. In many patients, the course is protracted and refractory to conservative treatment, requiring targeted therapy. We propose PET of the CSF space with 68Ga-DOTA as a state-of-the-art approach to radionuclide cisternography (RC) and validate its diagnostic value. Methods: This study is a retrospective analysis of patients with suspected intracranial hypotension due to spinal CSF leaks and who underwent whole-body PET/CT at 1, 3, and 5 h after intrathecal lumbar injection of 68Ga-DOTA. Two independent raters unaware of the clinical data analyzed all scans for direct and indirect RC signs of CSF leakage. Volume-of-interest analysis was performed to assess the biologic half-life of the tracer in the CSF space and the ratio of decay-corrected activity in the CSF space at 5 and 3 h (simplified marker of tracer clearance). Comprehensive stepwise neuroradiologic work-up served as a reference; additional validation was provided by surgical findings and follow-up. Results: Of 40 consecutive patients, 39 patients with a working diagnosis of intracranial hypotension due to a spinal CSF leak (spontaneous, n = 31; postintervention, n = 8) could be analyzed. A spinal CSF leak was verified by the neuroradiologic reference method in 18 of 39 patients. As the only direct and indirect diagnostic signs, extrathecal tracer accumulation at the cervicothoracic junction (67% sensitivity and 90% specificity) and lack of activity over the cerebral convexities (5 h; 94% sensitivity and 67% specificity) revealed a high diagnostic value for spinal CSF leaks. Their combination provided little improvement (71% sensitivity and 95% specificity). Additional quantitative analyses yielded no benefit (94% sensitivity and 53% specificity for biological half-life; 94% sensitivity and 58% specificity for the ratio of total radioactivity within the CSF space at 5 and 3 h). The location of direct signs (extrathecal tracer accumulation) did not correlate with verified sites of spinal CSF leakage. Conclusion: We propose CSF PET with 68Ga-DOTA as a novel, fast, and convenient approach to RC for verification but not localization of spinal CSF leaks with high sensitivity and specificity. CSF PET may fulfill an important gatekeeper function for stratifying patients toward escalation (ruling in) or deescalation (ruling out) of diagnostic and therapeutic measures. Further prospective studies are needed to validate the present results and determine the potential of the methods to reduce the burden to patients.

Detection of Cerebrospinal Fluid Leaks: Is There a Radiologic Standard of Care? A Systematic Review.

INTRODUCTION: Diagnosis of cerebrospinal fluid (CSF) leaks traditionally involves laboratory testing of markers and appropriate imaging. Surgical localization can be difficult, and the inability to accurately localize skull base defects leads to increased rates of repair failure and complications. Many imaging techniques localizing and identifying CSF leaks have been proposed. Comparisons of current and investigational imaging techniques used to localize CSF leaks are reviewed. METHODS: A comprehensive and systematic search through PubMed, Scopus, and reference lists from relevant articles was completed to identify literature on sensitivities of different imaging methods for localization and detection of CSF leaks. Prospective, retrospective, and case series published since 1995 that addressed imaging techniques for CSF leaks confined to the skull base were included. Sensitivities of each major imaging technique proposed were recorded and analyzed. RESULTS: In total, 133 studies initially were screened from 2125 studies on preliminary search. Of these, 38 studies were included based on inclusion criteria. Studies were segregated by imaging modality. A total of 1000 patients with CSF leaks subsequently were evaluated. CONCLUSIONS: Although radionuclide cisternography has been the historical standard, recent imaging techniques have emerged considering the low sensitivity. Computed tomography cisternography with contrast also has low sensitivity, even in active leaks. Although high-resolution computed tomography is commonly the initial study of choice, magnetic resonance imaging methods, particularly 3-dimensional imaging, may prove to be a more sensitive study of choice. Computed tomography/magnetic resonance imaging combination methods may show promise in localizing CSF leaks. Stratifying by status and etiology may be an important determinant. Further studies investigating various imaging techniques for localizing CSF leaks are needed.

[A modern approach to the diagnosis of nasal liquorrhea]. / Sovremennyi podkhod k diagnostike nazal'noi likvorei.

Nasal liquorrhea is cerebrospinal fluid leakage from cerebrospinal fluid spaces of the cerebral cavity into the nasal cavity or paranasal sinuses due to congenital or acquired abnormalities of the skull base bones and meninges of various etiologies. The severity of liquorrhea varies from hidden manifestations to profuse leakage of cerebrospinal fluid from the nasal cavity. The diagnosis of overt nasal liquorrhea is not problematic, but the diagnosis of latent liquorrhea is a challenge. In this case, the disease leads to potentially fatal complications, such as meningitis (the risk amounts to 10-37%), pneumocephaly, pneumonia, etc. These peculiarites give rise to two main tasks: early diagnosis confirming liquorrhea and accurate identification of the CSF fistula location when planning further surgical management. PURPOSE: The study purpose was to review and comparatively analyze all modern methods of diagnosing nasal liquorrhea as well as to substantiate the most effective and promising approaches and algorithms. MATERIAL AND METHODS: The study included papers in English and Russian found in the Pubmed database and related to the diagnosis of basal liquorrhea of different etiology and localization. RESULTS: This review demonstrates that diagnostic tests vary widely in sensitivity, specificity, accuracy, invasiveness, and cost. Given all the criteria, detection of beta-2 transferrin or beta-trace protein is the best method for confirming nasal liquorrhea, and high-resolution computed tomography is the best technique for localization of the abnormality. CONCLUSION: Based on the review, we suggest a diagnostic algorithm for nasal liquorrhea. However, the evidence presented in this review is unfortunately not very reliable, which indicates the existing need for more accurate studies.

An [18F]-Positron-Emitting, Fluorescent, Cerebrospinal Fluid Probe for Imaging Damage to the Brain and Spine.

Fluorescein is modified to bear 18F so that it can act as both a positron emitter, and a fluorophore, allowing detection by positron emission tomography (PET), scintillation, and fluorescent imaging (FL). [18F]-2 is injected into the intrathecal space of rats and used to observe the cerebrospinal fluid (CSF) that bathes the brain and spine. Injury in three different applications is visualized with [18F]-2: 1) detection of a 0.7 mm paranasal-sinus CSF leak (CSFL); 2) detection of 0.5 mm puncture damage to the thoracic spine (acute spinal cord injury); and 3) detection of intracerebral hemorrhage/edema because of traumatic brain injury. In all models, the location of injury is visualized with [18F]-2 at high resolution. [18F]-2 PET imaging may be a superior alternative to current clinical contrast myelography and 131I, 111In or 99mTc radionuclide cisternography. Like fluorescein, [18F]-2 may also have other uses in diagnostic or fluorescence guided medicine.

C1-C2 cryptic cerebrospinal fluid leak directly identified by pressurized radionuclide cisternography: Case report and review of the literature.

BACKGROUND: Patients with chronic postural headaches may suffer from spontaneous intracranial hypotension (SIH). Trauma, degenerative disc spurring and connective tissue disorders are documented risk factors; in most cases there is no inciting event. Despite sophisticated means of evaluating the neuraxis, many cerebrospinal fluid (CSF) leaks are radiographically occult and treatment is focused on thoracic and cervical-thoracic regions. Although lumbar epidural blood patch (EBP) is the initial treatment of choice after failed conservative management, several studies document the need for treatment aimed at the specific leak area. CASE DESCRIPTION: This report describes the case of a 42-year-old female with scleroderma and sudden onset postural headaches. Magnetic resonance imaging revealed diffuse pachymeningeal enhancement suggestive of intracranial hypotension. Computed tomographic myelography demonstrated a collection of fluid ventral to the cervical thecal sac; an exact location for CSF egress was not identified. Conservative measures followed by lumbar EBP failed to alleviate her symptoms. The patient underwent placement of a lumbar drain and dynamic radionuclide cisternography (RIC). Panoramic images of the spine were taken at the time of the pressurized saline injection. The CSF leak was clearly visualized at C1-2. Treatment was focused at this region using percutaneous injection of autologous blood and fibrin glue. CONCLUSION: SIH is disabling if left untreated. Spinal CSF leaks are often discrete and difficult to identify using static imaging. The use of pressurized, RIC by lumbar drain injection allows for the real-time evaluation of CSF dynamics and can more precisely identify slow flow leaks often missed with static imaging.

Occult spontaneous lateral intrasphenoidal encephalocele: A rare presentation.

Basal encephaloceles are extremely rare congenital malformations. Advanced cross-sectional imaging modalities like computed tomography and magnetic resonance imaging are necessary for diagnosing the asymptomatic, occult basal encephalocele and planning the surgical approach. We present an interesting case of clinically silent right-sided lateral intrasphenoidal encephalocele through a large bony defect.

Radionuclide cisternography: A prudent investigation in diagnosing spontaneous intracranial hypotension.

Spontaneous intracranial hypotension (SIH) is a cause of new persistent headache, which disappears on recumbence and reappears in sitting/standing position (orthostatic headache). We present a case of orthostatic headache, where the patient was suspected to have SIH and was subjected to radionuclide cisternography (RNC) using 99m Technetium Diethylenetriaminepenta acetic acid for confirmation of diagnosis. After due consent from the patient, the radiotracer was injected intra-thecally and serial images were acquired until 24 h. The direct and indirect evidences of Cerebrospinal fluid (CSF) leakage, which were revealed in our study, provided objective evidence to the clinical diagnosis. RNC is an important investigation in diagnosing SIH and also identifying the site of CSF leak, which may aid the management.

Successful treatment of post-dural-puncture headache with surgical dura repair two years after spinal anesthesia.

BACKGROUND: Post-dural-puncture headache (PDPH) can be a highly disturbing complication of elective spinal anesthesia. The incidence of PDPH when small needles are used is estimated to be 0%-14.5%. PDPH usually resolves spontaneously within a few days, but there are rare cases that persist in spite of conventional and epidural blood patch therapy. CASE: A 59-year-old man suffered from persistent postural headache for more than two years after an otherwise uneventful spinal anesthesia. Conventional and minimally invasive treatments were unsuccessful. INTERVENTION/OUTCOME: A neurosurgical procedure was performed, during which a dural leak was identified and repaired. The patient was immediately pain free after surgery and has remained so for the duration of follow-up (more than one year).

Effectiveness of Radionuclide Cisternography to Detect the Leakage Site of CSF in Spontaneous Intracranial Hypotension; Preliminary Report / 핵의학분자영상

PURPOSE: Although radionuclide cisternography (RNC) is an useful study to detect cerebrospinal fluid (CSF) leakage in the patient with spontaneous intracranial hypotension (SIH), it sometimes fails to demonstrate the site of CSF leakage. The aim of the study is to improve the detection of leakage site of CSF and to reduce time for the study in RNC using modified protocol (m-RNC). MATERIALS AND METHODS: The study consists of 8 studies of 7 patients (38+/-8 years, M:F=2:5) with SIH, who underwent m-RNC following administration of 185-222 MBq of 99mTc-DTPA into the lumbar subarachnoid space. Sequential images were obtained the whole spine with the head including urinary bladder at 10 minute, 30 minute, 1 hour, 2 hour, 4 hour and 6 hour. Radioactivity of extradural space and urinary bladder was evaluated. RESULTS: Leakage site of CSF was identified in all 8 cases by m-RNC. Leakage site was cervicothoracic junction (CTJ, n=3), CTJ with C1-2 (n=2), CTJ with thoracic spine, thoracolumbar spine and lumbar spine (each n=1). All cases presented leakage sites within 1 hour and multiple sites, where CTJ was included in 6 cases. Only one case presented additional site in 6 hour image. Early radioactivity within the urinary bladder was noted in 6 cases, but that was following after identification of the leakage site. CONCLUSION: Radionuclide cisternography is sensitive to detect the leakage site of CSF and is expected to improve the detection of CSF leakage site and reduce time for the study using modified protocol.

Evaluation of Spontaneous Intracranial Hypotension Using Radionuclide Cisternography / 대한핵의학회잡지

We report four cases of spontaneous intracranial hypotension that were investigated by radionuclide cisternography Tc-99m-diethylenetriamine pentaacetic acid radionuclide cisternography of all our patients showed direct sign of cerebrospinal fluid leakage as well as indirect signs of less activity than expected over the cerebral convexities and rapid appearance of bladder activity. The headache of all patients was eventually controlled with bed rest and hydration.

A Case of Spontaneous Intracranial Hypotension: Detection of Cerebrospinal Fluid Leakage by Early Dynamic Radionuclide Cisternography / 대한핵의학회잡지

Although cerebrospinal fluid leakage is suggested as one of the causes of spontaneous intracranial hypotension, on]y a few cases with direct evidence of cerebrospinal fluid leakage on radionuclide cisternography have been reported in the literature Indirect evidences of cerebrospinal fluid leakage such as early visualization of the soft tissue and bladder or delayed migration of radiotracer have been observed in most patients with spontaneous intracranial hypotension. We report a case of spontaneous intracranial hypotension in which cerebrospinal fluid leakage was directly demonstrated by early dynamic imaging of spine on radionuclide cisternography. We suggest that early dynamic imaging of spine is an important adjunctive procedure in detecting cerebrospinal fluid leakage in patients with spontaneous intracranial hypotension.

Radionuclide Cisternographic Findings in Patients with Spontaneous Intracranial Hypotension / 대한핵의학회잡지

PURPOSE: Radionuclide cisternography may be helpful in understanding pathophysiology of postural headache and low CSF pressure in patients with spontaneous intracranial hypotension. The purpose of this study was to characterize radionuclide cisternographic findings of spontaneous intracranial hypotension. MATERIALS AND METHODS: The study population consists of 15 patients with spontaneous intracranial hypotension. Diagnosis was based on their clinical symptoms and results of lumbar puncture. All patients underwent radionuclide cisternography following injection of 111 to 222 MBq of Tc-99m DTPA into the lumbar subarachnoid space. Sequential images were obtained between 1/2 hour and 24 hour after the injection of Tc-99m DTPA. Radioactivity of the bladder, soft tissue uptake, migration of radionuclide in the subarachnoid space, and extradural leakage of radionuclide were evaluated according to the scan time. RESULTS: Radionuclide cisternogram showed delayed migration of radionuclide into the cerebral convexity (14/15), increased soft tissue uptake (11/15), and early visualization of bladder activity at 30 min (6/10) and 2 hr (13/13). Cisternography also demonstrated leakage site of CSF in 4 cases and 2 of these were depicted at 30 min. Epidural blood patch was done in 11 patients and headache was improved in all cases. CONCLUSION: The characterstic findings of spontaneous intracranial hypotension were delayed migration of radionuclide and early visualization of the soft tissue and bladder activity. These scintigraphic findings suggest that CSF leakage rather than increased CSF absorption or decreased production may be the main pathophysiology of spontaneous intracranial hypotension. Early and multiple imaging including the bladder and soft tissue is required to observe the entire dynamics of radionuclide migration.