Intrathecal Space Research Articles

Safe subdural administration and retention of a neurotrophin-3-delivering hydrogel in a rat model of spinal cord injury

Neurotrophic growth factor (GF) loaded hydrogels have shown promise as a treatment approach for spinal cord injury (SCI). However, SCI presents complex challenges for the direct administration of treatment due to the spinal cord’s intricate anatomy and highly sensitive environment. Many current hydrogel administration approaches overlook this complexity, limiting their translational potential. To address this, we propose a novel intrathecal administration method using an in situ gelling, hyaluronic acid-modified heparin-poloxamer hydrogel loaded with neurotrophin-3 (NT-3) for the direct delivery of NT-3 to the spinal cord. We injected a NT-3 loaded hydrogel into the intrathecal space immediately after contusion SCI in Sprague Dawley (SpD) rats. Our results indicate that injecting the NT-3 loaded hydrogel into the intrathecal space was safe and that the gel was retained alongside the cord for at least one week. Additionally, no adverse effects were observed on rat behaviour. While functional improvement trends were noted, statistical significance was not reached, and immunohistochemistry results showed no significant difference between treatment groups. Overall, our findings suggest the feasibility, safety, and potential of the developed intrathecal administration technique for delivering diverse therapeutic molecules for SCI recovery.

Active CNS delivery of oxycodone in healthy and endotoxemic pigs

BackgroundThe primary objective of this study was to advance our understanding of active drug uptake at brain barriers in higher species than rodents, by examining oxycodone brain concentrations in pigs.MethodsThis was investigated by a microdialysis study in healthy and endotoxemic conditions to increase the understanding of inter-species translation of putative proton-coupled organic cation (H+/OC) antiporter-mediated central nervous system (CNS) drug delivery in health and pathology, and facilitate the extrapolation to humans for improved CNS drug treatment in patients. Additionally, we sought to evaluate the efficacy of lumbar cerebrospinal fluid (CSF) exposure readout as a proxy for brain unbound interstitial fluid (ISF) concentrations. By simultaneously monitoring unbound concentrations in blood, the frontal cortical area, the lateral ventricle (LV), and the lumbar intrathecal space in healthy and lipopolysaccharide (LPS)-induced inflammation states within the same animal, we achieved exceptional spatiotemporal resolution in mapping oxycodone transport across CNS barriers.ResultsOur findings provide novel evidence of higher unbound oxycodone concentrations in brain ISF compared to blood, yielding an unbound brain-to-plasma concentration ratio (Kp,uu,brain) of 2.5. This supports the hypothesis of the presence of the H+/OC antiporter system at the blood–brain barrier (BBB) in pigs. Despite significant physiological changes, reflected in pig Sequential Organ Failure Assessment, pSOFA scores, oxycodone blood concentrations and its active net uptake across the BBB remained nearly unchanged during three hours of i.v. infusion of 4 µg/kg/h LPS from Escherichia coli (O111:B4). Mean Kp,uu,LV values indicated active uptake also at the blood-CSF barrier in healthy and endotoxemic pigs. Lumbar CSF concentrations showed minimal inter-individual variability during the experiment, with a mean Kp,uu,lumbarCSF of 1.5. LPS challenge caused a slight decrease in Kp,uu,LV, while Kp,uu,lumbarCSF remained unaffected.ConclusionsThis study enhances our understanding of oxycodone pharmacokinetics and CNS drug delivery in both healthy and inflamed conditions, providing crucial insights for translating these findings to clinical settings.

An In Vitro Platform for Pharmacokinetic Quantification and Optimization of Cerebrospinal Fluid Filtration and Drug Circulation

Abstract Background: Modification of cerebrospinal fluid (CSF) transport dynamics is an expanding method for treating central nervous system injury and diseases. One application of this route is to modify the distribution of solutes in the CSF, however few tools currently exist for this purpose. The present study describes the use of a subject-specific in-vitro CSF phantom to perform a parametric evaluation of the Neurapheresis? CSF Management System (NP) for both CSF filtration and intrathecal drug circulation. Methods: An in-vitro CSF phantom was constructed which included realistic anatomy for the complete subarachnoid space. This platform was configured to test multiple parametric modifications of a dual-lumen catheter and filtration system. Calibrated mapping of tracer distribution and area under the curve (AUC) measurements were used to compare filtration and intrathecal-circulation schemes using the NP device versus the clinical standards of care. Results: The NP device showed potential advantages over lumbar drain (LD) for clearance of simulated subarachnoid hemorrhage, especially in the spinal canal. Use of the NP device in combination with simulated intracerebroventricular drug infusion (ICV) resulted in an increased extent and uniformity of tracer spread compared to ICV alone. Conclusion: NP improved clearance of simulated subarachnoid hemorrhage compared to LD and increased uniformity of tracer concentration via simulated ICV, providing support for NP use in these scenarios. The in-vitro CSF phantom system presented here quantitatively described the effects of parametric boundary modification on solute distribution in the intrathecal space.

Intrathecal placement of percutaneous spinal cord stimulation leads: illustrative cases.

Spinal cord stimulation (SCS), including the percutaneous placement of epidural stimulation leads, has been increasingly utilized to treat chronic pain. Although lead migration is a well-characterized complication, few studies have reported on malpositioned leads in the intrathecal space. Here, the authors discuss two cases of intrathecal lead placement necessitating surgical revision. This report is a two-case series on the inadvertent placement of percutaneous SCS leads in the intrathecal space. The authors describe the identification of malpositioned leads, describe the clinical presentation, characterize stimulation parameters, and report improvement following neurosurgical revision for each case. Two patients originally presenting with chronic low-back pain underwent percutaneous SCS lead implantation. Both patients presented with atypical pain symptoms in the acute to subacute postprocedural period, raising suspicion for malpositioned leads. Imaging was consistent with intrathecal malpositioning. Both patients underwent revision surgery resulting in symptomatic improvement. Indicators of malpositioned thoracic SCS leads in the intrathecal space include thoracoabdominal or flank pain exacerbated by movement, insufficient pain relief versus that in the SCS trial, very low electrode impedances, direct visualization on imaging, and lack of epidural lead visualization following laminectomy. Revision options include removal of the intrathecal leads and the surgical placement of a paddle electrode in the epidural space. https://thejns.org/doi/10.3171/CASE24275.

Hepatocyte Growth Factor Delivery to Injured Cervical Spinal Cord Using an Engineered Biomaterial Protects Respiratory Neural Circuitry and Preserves Functional Diaphragm Innervation.

A major portion of spinal cord injury (SCI) cases occur in the cervical region, where essential components of the respiratory neural circuitry are located. Phrenic motor neurons (PhMNs) housed at cervical spinal cord level C3-C5 directly innervate the diaphragm, and SCI-induced damage to these cells severely impairs respiratory function. In this study, we tested a biomaterial-based approach aimed at preserving this critical phrenic motor circuitry after cervical SCI by locally delivering hepatocyte growth factor (HGF). HGF is a potent mitogen that promotes survival, proliferation, migration, repair, and regeneration of a number of different cell and tissue types in response to injury. We developed a hydrogel-based HGF delivery system that can be injected into the intrathecal space for local delivery of high levels of HGF without damaging the spinal cord. Implantation of HGF hydrogel after unilateral C5 contusion-type SCI in rats preserved diaphragm function, as assessed by invivo recordings of both compound muscle action potentials and inspiratory electromyography amplitudes. HGF hydrogel also preserved PhMN innervation of the diaphragm, as assessed by both retrograde PhMN tracing and detailed neuromuscular junction morphological analysis. Furthermore, HGF hydrogel significantly decreased lesion size and degeneration of cervical motor neuron cell bodies, as well as reduced levels surrounding the injury site of scar-associated chondroitin sulfate proteoglycan molecules that limit axon growth capacity. Our findings demonstrate that local biomaterial-based delivery of HGF hydrogel to injured cervical spinal cord is an effective strategy for preserving respiratory circuitry and diaphragm function.

Evaluating the effect of injection protocols on intrathecal solute dispersion in non-human primates: an in vitro study using a cynomolgus cerebrospinal fluid system

BackgroundAchieving effective drug delivery to the central nervous system (CNS) remains a challenge for treating neurological disorders. Intrathecal (IT) delivery, which involves direct injection into the cerebrospinal fluid (CSF), presents a promising strategy. Large animal studies are important to assess the safety and efficacy of most drugs and treatments and translate the data to humans. An understanding of the influence of IT injection parameters on solute distribution within the CNS is essential to optimize preclinical research, which would potentially help design human clinical studies.MethodsA three-dimensional (3D) in vitro model of a cynomolgus monkey, based on MRI data, was developed to evaluate the impact of lumbar injection parameters on intrathecal solute dispersion. The parameters evaluated were (a) injection location, (b) bolus volume, (c) flush volume, (d) bolus rate, and (e) flush rate. To simulate the CSF flow within the subarachnoid space (SAS), an idealized CSF flow waveform with both cardiac and respiratory-induced components was input into the model. A solution of fluorescein drug surrogate tracer was administered in the lumbar region of the 3D in vitro model filled with deionized water. After injection of the tracer, the CSF system wide-solute dispersion was imaged using high-resolution cameras every thirty seconds for a duration of three hours. To ensure repeatability each injection protocol was repeated three times. For each protocol, the average spatial–temporal distribution over three hours post-injection, the area under the curve (AUC), and the percent injected dose (%ID) to extra-axial CSF (eaCSF) at three hours were determined.ResultsThe changes to the lumbar injection parameters led to variations in solute distribution along the neuro-axis. Specifically, injection location showed the most impact, enhancing the delivery to the eaCSF up to + 10.5%ID (p = 0.0282) at three hours post-injection. Adding a post-injection flush of 1.5 ml at 1 ml/min increased the solute delivery to the eaCSF by + 6.5%ID (p = 0.0218), while the larger bolus volume resulted in a + 2.3%ID (p = 0.1910) increase. The bolus and flush rates analyzed had minimal, statistically non-significant effects.ConclusionThese results predict the effects of lumbar injection parameters on solute distribution in the intrathecal space in NHPs. Specifically, the choice of injection location, flush, and bolus volume significantly improved solute delivery to eaCSF. The in vitro NHP CSF model and results offer a system to help predict and optimize IT delivery protocols for pre-clinical NHP studies.

Ultrasound‐assisted and landmark‐based nusinersen delivery in spinal muscular atrophy adults: A retrospective analysis

AbstractIntroduction/PurposeNusinersen, the first treatment approved for all spinal muscular atrophy (SMA) types, is administered intrathecally through lumbar puncture. We used ultrasound assistance or a landmark‐based technique to access the lumbar intrathecal space in adult SMA patients. This study aimed to evaluate the technical success and adverse events (AEs) in such patients using either technique over a long observation period.MethodsFifty‐one adult patients received 507 consecutive interlaminar nusinersen administrations. Patients presented with both ‘uncomplicated spines’ or ‘complicated spines’; two patients had previous back surgery. Technical success and AEs were recorded using either technique. A generalised linear mixed model was applied to evaluate predictors of technical success and complications.ResultsAn overall success rate of 99.6%, with only two procedures failing to reach the intrathecal space, and an overall optimal procedure rate of 90.3% have been reported. A total of 455 procedures (89.7%) were uneventfully performed. One (0.2%) case of severe AE (puncture of a bulky abdominal annexal cyst) was recorded. Twenty‐seven episodes (5.3%) of post‐dural puncture headache (PDPH) and 24 episodes (4.7%) of radicular or back pain, both successfully treated with medical therapy, have also been reported. Technical success was significantly associated with ‘complicated spines’ (P = 0.022) and the use of ultrasound assistance (P = 0.01), and the use of ultrasound was the only independent predictor of uncomplicated procedures (P = 0.007).DiscussionIn adult patients with SMA both landmark‐based and ultrasound‐assisted techniques are safe and effective even in the long term. The use of assistance is associated with technical success and can predict uncomplicated procedures.ConclusionOur results support the use of ultrasonography in order to improve the success and reduce the burden of nusinersen intrathecal administration.

Lumbar Intrathecal Injection in Adult and Neonatal Mice.

This article describes a step-by-step process of lumbar intrathecal injection of Evans blue dye and AAV9-EGFP in adult (2-month-old) and neonatal (postnatal day 10) mice. Intrathecal injection is a clinically translatable technique that has already been extensively applied in humans. In mice, intrathecal injection is considered a challenging procedure that requires a trained and experienced researcher. For both adult and neonatal mice, lumbar intrathecal injection is directed into the L5-L6 intervertebral space. Intrathecally injected material enters the cerebrospinal fluid (CSF) within the intrathecal space from where it can directly access the central nervous system (CNS) parenchyma. Simultaneously, intrathecally injected material exits the CSF with pressure gradient and enters the endoneurial fluid and ultimately the peripheral nerves. While in the CSF, the injectable material also enters the bloodstream and systemic circulation through the arachnoid villi. A successful lumbar intrathecal injection results in adequate biodistribution of the injectable material in the CNS, PNS, and peripheral organs. When correctly applied, this technique is considered as minimally invasive and non-disruptive and can be used for the lumbar delivery of any solute. © 2024 Wiley Periodicals LLC. Basic Protocol 1: C57BL/6 adult and P10 mice lumbar intrathecal injection Basic Protocol 2: Tissue collection and preparation for evaluating Evans blue dye diffusion Basic Protocol 3: Tissue collection and preparation for immunohistochemistry staining Basic Protocol 4: Tissue collection and vector genome copy number analysis.

Crosstalk Inhibition Between 5-HT2A and Adenosine 2A Receptor-Induced Phrenic Motor Facilitation

Episodic spinal serotonin receptor activation elicits phrenic motor facilitation (pMF), a form of respiratory motor plasticity. Although both intermittent 5-HT2 and 5-HT7 receptor activation elicit pMF, they do so via distinct cellular mechanisms known as the Q (5-HT2A/B) and S (5-HT7) pathways. The Q and S pathways interact via powerful crosstalk inhibition; thus, concurrent activation of both receptor subtypes diminishes/abolishes pMF. At least some of the molecules giving rise to mutually inhibitory interactions between 5-HT2 and 5-HT7 receptors have been identified. Although episodic spinal adenosine 2A (A2A) receptor activation also elicits pMF via the S pathway, we do not know: 1) if 5-HT2 and A2A receptors interact via similar crosstalk inhibition, nor 2) if they do so via the same signaling mechanisms. Thus, we tested the hypothesis that concurrent 5-HT2 and A2A receptor activation diminishes pMF via crosstalk inhibition. Selective 5-HT2A (DOI) and A2A receptor agonists (CGS21680) were delivered to the C4 intrathecal space (3, 6 μl injections, 5-min intervals) in urethane anesthetized, artificially ventilated, vagotomized and paralyzed Sprague Dawley rats. Integrated phrenic nerve burst activity was measured before (baseline), during and 90 minutes post-drug injection. Spinal 5-HT2A and A2A receptor activation both increased phrenic nerve burst amplitude when delivered alone (i.e., pMF); however, pMF was no longer apparent with concurrent receptor activation. The magnitude of pMF, expressed as a % change in phrenic burst amplitude from baseline to 90-min post-injection, was significantly lower with concurrent receptor activation (5-HT2A + A2A= 15 ± 7.7%; n=5) versus 5-HT2A (84 ± 12%; n=5, p=0.0047) and A2A (88 ± 16%; n=5, p=0.0085) alone. Thus, 5-HT2A and A2A receptors interact via crosstalk inhibition similar to 5-HT2 and 5-HT7 receptors. However, the mechanism underlying this crosstalk inhibition remains unknown. NIH HL148030. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Atlanto‐occipital fracture: Intrathecal corticosteroid medication of the subarachnoid space—A novel treatment method

SummaryThis case report describes the successful conservative management of a comminuted fracture of the atlas and occiput involving the atlanto‐occipital joint. To the authors' knowledge, treatment of fractures involving the atlanto‐occipital joint in the horse and intrathecal subarachnoid space corticosteroid injection in the standing sedated patient has not been previously reported. Clinical signs following atlanto‐occipital (AO) fracture included acute onset ataxia, proprioceptive deficits and neck stiffness; which developed immediately post‐trauma during head and tail rope‐assisted recovery from general anaesthesia. Radiographic examination was not diagnostic immediately post‐trauma and computed tomography (CT) imaging subsequently identified articular fractures of the atlas and occiput. Treatment included ultrasound‐guided intrathecal medication of the subarachnoid space and intra‐articular medication of the left AO joint under standing sedation. Medication resulted in a marked improvement in clinical signs (grade 4 ataxia to grade 1 ataxia) and a return to ridden exercise 12 months post‐injury.

Comparison of neuraxial acoustic target window of the spine among rider sitting, cross leg, hamstring stretch, and classical sitting position: An observational study.

To compare ultra-sonographic dimensions of acoustic target window of the spine in the participants at four different sitting positions namely cross leg sitting (CLP), hamstring stretch (HSP), classical sitting (CSP) and riders sitting position (RSP). The primary objective of this study was to measure the neuraxial acoustic target window (defined as interlaminar distance between L3-L4 lamina). The secondary objective was to compare ultra-sonographic measurements of the depth of ligamentum flavum from the skin, and to compare the diameter of intrathecal space and comfort score in the four different sitting positions. This study is a prospective observational study. Eighty participants were included and positioned in four different sitting positions to perform an ultra-sonographic scan and measure various parameters of the acoustic neuraxial window. The interlaminar distance, the distance of skin from the ligamentum flavum, and the diameter of the spinal canal or intrathecal space was measured in the L3-L4 intervertebral space in different positions. The mean value of interlaminar distance among four sitting positions was ranging from 1.40 cm to 1.44 cm (P value 0.725.) The distance of ligamentum flavum from skin and diameter of intrathecal space was also comparable in all the groups. The comfort score in CSP was significantly better when compared to other groups with a median score of 4 (P value < 0.001). There is no statistically significant difference in interlaminar distance in various sitting positions. All four positions are equally effective and can be used as an alternative to spinal/epidural intervention, but the CSP came out to be the most comfortable and more emphasis should be given to the comfort as it increases the chance of success rate of the procedure.

Effects of buoyancy on the dispersion of drugs released intrathecally in the spinal canal.

This paper investigates the transport of drugs delivered by direct injection into the cerebrospinal fluid (CSF) that fills the intrathecal space surrounding the spinal cord. Because of the small drug diffusivity, the dispersion of neutrally buoyant drugs has been shown in previous work to rely mainly on the mean Lagrangian flow associated with the CSF oscillatory motion. Attention is given here to effects of buoyancy, arising when the drug density differs from the CSF density. For the typical density differences found in applications, the associated Richardson number is shown to be of order unity, so that the Lagrangian drift includes a buoyancy-induced component that depends on the spatial distribution of the drug, resulting in a slowly evolving cycle-averaged flow problem that can be analysed with two-time scale methods. The asymptotic analysis leads to a nonlinear integro-differential equation for the spatiotemporal solute evolution that describes accurately drug dispersion at a fraction of the cost involved in direct numerical simulations of the oscillatory flow. The model equation is used to predict drug dispersion of positively and negatively buoyant drugs in an anatomically correct spinal canal, with separate attention given to drug delivery via bolus injection and constant infusion.

Intrathecal Vector Delivery in Juvenile Rats via Lumbar Cistern Injection.

Gene therapy is a powerful technology to deliver new genes to a patient for the treatment of disease, be it to introduce a functional gene, inactivate a toxic gene, or provide a gene whose product can modulate the biology of the disease. The delivery method for the therapeutic vector can take many forms, ranging from intravenous infusion for systemic delivery to direct injection into the target tissue. For neurodegenerative disorders, it is often desirable to skew transduction towards the brain and/or spinal cord. The least invasive approach to target the entire central nervous system involves injection into the cerebrospinal fluid (CSF), allowing the therapeutic to reach a large fraction of the central nervous system. The safest approach to deliver a vector into the CSF is the lumbar intrathecal injection, where a needle is introduced into the lumbar cistern of the spinal cord. This technique, also known as a lumbar puncture, has been widely used in neonatal and adult rodents and in large animal models. While the technique is similar across species and developmental stages, subtle differences in size, structure, and elasticity of tissues surrounding the intrathecal space require accommodations in the approach. This article describes a method for performing lumbar puncture in juvenile rats to deliver an adeno-associated serotype 9 vector. Here, 25-35 µL of vector were injected into the lumbar cistern, and a green fluorescent protein (GFP) reporter was used to evaluate the transduction profile resulting from each injection. The benefits and challenges of this approach are discussed.

Encapsulation of the growth factor neurotrophin-3 in heparinised poloxamer hydrogel stabilises bioactivity and provides sustained release

Poloxamer-based hydrogels show promise to stabilise and sustain the delivery of growth factors in tissue engineering applications, such as following spinal cord injury. Typically, growth factors such as neurotrophin-3 (NT-3) degrade rapidly in solution. Similarly, poloxamer hydrogels also degrade readily and are, therefore, only capable of sustaining the release of a payload over a small number of days. In this study, we focused on optimising a hydrogel formulation, incorporating both poloxamer 188 and 407, for the sustained delivery of bioactive NT-3. Hyaluronic acid blended into the hydrogels significantly reduced the degradation of the gel. We identified an optimal hydrogel composition consisting of 20 % w/w poloxamer 407, 5 % w/w poloxamer 188, 0.6 % w/w NaCl, and 1.5 % w/w hyaluronic acid. Heparin was chemically bound to the poloxamer chains to enhance interactions between the hydrogel and the growth factor. The unmodified and heparin-modified hydrogels exhibited sustained release of NT-3 for 28 days while preserving the bioactivity of NT-3. Moreover, these hydrogels demonstrated excellent cytocompatibility and had properties suitable for injection into the intrathecal space, underscoring their suitability as a growth factor delivery system. The findings presented here contribute valuable insights to the development of effective delivery strategies for therapeutic growth factors for tissue engineering approaches, including the treatment of spinal cord injury.

Pneumocephalus after ankle surgery: A Case Report

Introduction: Pneumocephalus, or air in the cranial cavity, can have various causes. Traumatic brain injury is the most common cause of pneumocephalus, accounting for 75% of all cases, particularly in those with skull base fractures. Spinal trauma-related pneumocephalus is rare but has been reported, and patients with this condition are usually treated conservatively. Tumors, infections, and iatrogenic causes are responsible for the remaining 25% of cases. Proper management and a high index of suspicion are critical when considering pneumocephalus as a possible complication, as it can result in significant morbidity and potentially life-threatening consequences. Accidental puncture of the dura mater is a common cause of pneumocephalus secondary to epidural anesthesia, and air entry into the intrathecal space is another known cause. Case presentation: This is a 64-year-old female patient who underwent elective ankle surgery, the anesthetic technique was epidural-spinal block needle on needle, no complications during procedure. She was discharged from the Traumatology and Orthopedics service the next morning, 24 hours after her hospital discharge, she was brought back, in the emergency area, she was found with psychomotor agitation, disorientation, no auditory hallucinations, paresthesias were denied, no mentation disorder, with a score on the Glasgow Coma Scale of 14: Eye opening 4 points, Verbal response 4 points, Motor response 6 points. After 48 hours the CT brain scan revealed absortion of pneumocephalus. Clinical discussion: The causes of neumocephalus resulting from epidural or spinal anesthesia procedures are not entirely understood. However, it is believed to occur due to the introduction of air or gas into the subarachnoid or epidural spaces during the puncture, accidental or not . Given the potential severity of this condition, early diagnosis and appropriate management are crucial, even if the symptoms differ from the most common. Conclusion: This research paper highlights the importance of anesthesiologists being aware of the potential risks associated with epidural or spinal block. Future research could investigate the long-term outcomes of patients who experience pneumocephalus during anesthesia procedures and identify strategies for preventing and managing this complication.

Tranexamic Acid at Cesarean Delivery: Drug-error Deaths

(Am J Obstet Gynecol. 2023;228:1–4) Tranexamic acid plays an important role in reducing bleeding experienced during postpartum hemorrhage. It is recommended by the World Health Organization that tranexamic acid is administered intravenously, over 10 minutes, within 3 hours of delivery to treat postpartum hemorrhage. However, tranexamic acid, although helpful in cases of postpartum hemorrhage, has caused other problems to arise. It has been found that tranexamic acid is toxic when administered intrathecally (IT). Tranexamic acid has components that are known to lead to neuronal excitation when mistakenly administered in the intrathecal space. This most often leads to generalized convulsions and malignant arrhythmias. This has been occurring more frequently secondary to tranexamic acid being stored in labor and delivery operating rooms on anesthetic drug carts for easy access for hemorrhage during cesarean delivery. Both tranexamic acid and the drugs used for spinal anesthesia are stored in look-alike glass vials making this risk even more likely. A review published in 2019 reported 21 cases of inadvertent intrathecal administration of tranexamic acid, 20 of these cases were life-threatening with ten resulting in patient deaths. The accidental administration of tranexamic acid intrathecally most likely occurs more often than it has been reported. The mistake of replacing spinal anesthesia drugs with tranexamic acid most commonly occurs in small hospitals and low-middle-income countries.

Hidden risk of gadolinium-based contrast agents during interventional pain medicine procedures: a retrospective chart review

IntroductionEpidural steroid injections and epidural blood patches commonly involve the injection of a small amount of radiocontrast media under fluoroscopy to properly identify the target tissue or anatomic space and...

Abstract 284: Renal Contrast Excretion After Myelography: A Valuable Tool in The Diagnosis of Cerebrospinal‐Venous Fistulae

Introduction Cerebrospinal‐venous fistulae (CSF‐VFs) represent a pathologic, low‐flow direct connection between the intrathecal space, usually at the level of a diverticular dilation of a nerve root sleeve, and the thoracolumbar venous system. They can cause CSF hypovolemia resulting in an often‐debilitating intracranial hypotension syndrome. Lateral decubitus CT or DSA myelography (CTM, DSM) are the gold‐standard modalities for diagnosing these entities. Their high spatial and temporal resolution allows visualization of the abnormal connection between the two spaces. Yet, the small size and low flow make CSF‐VFs radiographically subtle, and may not be consistently visualized even after a correctly‐performed CTM/DSM, requiring repeated invasive procedures to definitively establish or exclude their presence. Opacification of the renal excretory system 30‐60 minutes after lateral decubitus myelograms is thought to be a highly sensitive and specific indirect sign of the presence of a CSF‐VF 1,2, as this amount of time is considered insufficient to allow arachnoid reabsorption of contrast. Renal pelvises hyperdensity or its absence after a negative decubitus CTM/DSM can prompt further myelographic investigation or definitively rule out the presence of a CSF‐VF on the side of the examination, respectively. Methods We present three patients with severely symptomatic CSF‐VFs treated at our hospital between 2021 and 2023. All patients were females (range: 50‐60 years old). All three patients underwent bilateral diagnostic lateral decubitus DSM/CTM. Exams were performed at least 72 hours apart in order to allow complete clearance of intrathecal contrast. After each myelographic acquisition, patients remained in the lateral decubitus position until abdominal CT imaging was performed at 30 and 45 minutes to detect the presence of contrast in the renal collecting system. Results Patients 1 and 2, had a CSF‐VF between nerve root dural diverticula and the azygos system that was directly visualized on lateral decubitus CTM (patient 1: right T10‐T11, patient 2: left T8‐T9). Contrast was detectable in the renal pelvises after myelography was performed on the affected side, and not detectable after the contralateral investigation. One fistula was treated via CT‐guided targeted blood patch and fibrin glue injection and the other via endovascular Onyx embolization of the tributary Intercostal veins. Patient 3 had an extremely slow flow CSF‐VF at the right T11‐12 level that was identified only after 5 right‐sided decubitus myelograms with both modalities. The repeated exams were based on the presence of contrast in the renal pelvises after each right‐sided procedure and on the absence of renal opacification after the left‐sided myelograms. Eventually, a CSF‐VF was identified. Successful Onyx embolization of the foraminal veins of the R T11‐12 levels was performed. All three patients had complete resolution of symptoms. Conclusion Contrast presence in the renal excretory system after a lateral decubitus CTM/DSM is a potentially highly sensitive and specific indirect diagnostic sign that can establish or exclude the presence of a CSF‐VF on the examined side. It could be particularly helpful when the fistula is not initially detected, as it can prompt aggressive continuation of the myelographic work‐up. Similarly, it can exclude its presence on one side, sparing the patient invasive and low yield diagnostic procedures.

Key Features in the Design and Function of Nanocarriers for Intranasal Administration of Gene Therapy in Huntington Disease.

A major obstacle to fulfilling the therapeutic promise of gene therapies for hereditary brain diseases, such as Huntington' Disease (HD), is the requirement for viral vectors and/or an invasive delivery system (stereotaxic injection into brain or infusion into the intrathecal space). HD is an autosomal dominant neurodegenerative disease for which several clinical trials have demonstrated gene-lowering effects following intrathecal administration. These technical limitations have given impetus to the development of alternative non-invasive delivery systems for gene therapy of brain diseases. The overall objective of this review is to discuss the key features in the design of nanocarriers for intranasal administration of gene-therapy for HD, focusing primarily on our series of published work on the use of nanocarriers for gene therapy. Design and development of nanocarriers packaged with gene-lowering agents represents a significant advance towards non-invasive nose-to-brain delivery of gene therapy for HD and other hereditary brain disorders.

US Guided vs Landmark Guided in Paramedian Spinal in Elderly

Abstract Background The ultrasound-assisted paramedian technique reduces the technical difficulty of spinal anaesthesia in the elderly. Compared with the landmark-guided paramedian technique, the use of ultrasound reduced the number of needle manipulations required for success, increased the firstattempt success rate and reduced block-associated pain and discomfort. Aim of the Work The study aims to evaluate whether ultrasound assisted paramedian spinal anaesthesia in the elderly can achieve successful dural puncture with fewer needle passes compared with the conventional landmark guided paramedian technique. Patients and Methods After obtaining approval from the Research Ethical Committee of Faculty of Medicine, Ain shams University; this study conducted in the operating theatres of Ain Shams University Hospitals with sample size of 10 patients / group will be needed. The patients randomly divided pre-operatively into two groups using their computer-generated random numbers such that „even numbers‟ will be enrolled in “group-L” for patients receive spinal anaesthesia by the paramedian approach by landmark guided palpation and „odd numbers‟ will be enrolled in “group-s” for patients ultrasound assisted approach. Results Ultrasonography might improve the efficacy of spinal anaesthesia by improving the accuracy of identification of intervertebral level, depth measurement of the intrathecal space and location of the interlaminar window that permits needle passage compared with the landmark guided technique, ultrasound assisted spinal anaesthesia decreases the number of puncture attempts and improves the success rate at the first attempt in patients with potential technical difficulties we believe that individualisation is a key element of minimising technical difficulties. Because of the large intersubject variability in anatomy, the blind technique have a theoretical upper limit of success rate. Through which we obtained success rates of 90 and 100% at the first attempt and within two attempts, respectively, in the ultrasound group. Conclusion Ultrasound-assisted paramedian spinal anaesthesia significantly reduces the number of needle manipulations required for success, increases the success rate at first pass and decreases periprocedural pain and patient discomfort compared with the landmark-guided paramedian technique in the elderly. Our results suggest that the neuraxial ultrasonography enhances the efficacy and comfort of spinal anaesthesia in the elderly.