International Journal of Neuroscience, 2014; Early Online: 1–4 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 0020-7454 print / 1543-5245 online DOI: 10.3109/00207454.2014.880436

CASE REPORT

Alternative treatment of intracranial hypotension presenting as postdural puncture headaches using epidural fibrin glue patches: two case reports Antonios Mammis,1,2 Nitin Agarwal,2 and Alon Y. Mogilner1 Int J Neurosci Downloaded from informahealthcare.com by Dalhousie University on 06/02/14 For personal use only.

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Department of Neurosurgery, Harvey Cushing Institute of Neurosciences, Hofstra University School of Medicine and North Shore University Hospital, Manhasset, New York, USA; 2 Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, USA Introduction: Intracranial hypotension is a neurologic syndrome characterized by orthostatic headaches and, radiographically, by dural thickening and enhancement as well as subdural collections. Several of etiologies exist, including surgical dural violations, lumbar puncture, or spontaneous cerebrospinal fluid leak. Current management includes conservative management consisting of bed rest, caffeine, and hydration. When conservative management fails, open surgical or percutaneous options are considered. Currently, the gold standard in percutaneous management of intracranial hypotension involves the epidural injection of autologous blood. Recently, some therapies for intracranial hypotension have employed the use of epidural fibrin glue. Case Presentation: Two cases of patients with persistent postdural puncture headaches are presented. Epidural fibrin glue injection alleviated the orthostatic headaches of two patients with intracranial hypotension. Conclusion: Although consideration must be afforded for the potential risks of viral transmission and aseptic meningitis, the utilization of epidural fibrin glue injection as an alternative or adjunct to the epidural blood patch in the treatment of intracranial hypotension should be further investigated. KEYWORDS: Epidural, fibrin glue, intracranial hypotension

Abbreviations: CSF CT MRI PDPH

Cerebrospinal fluid Computed tomography Magnetic resonance imaging Postdural puncture headache

Introduction Intracranial hypotension is a neurologic syndrome characterized by orthostatic headaches, which are often accompanied by diplopia, visual changes, change in hearing, neck pain, facial numbness, nausea and vomiting [1,2]. There are a number of causes, including dural Received 19 November 2013; revised 28 December 2013; accepted 2 January 2014. Correspondence: Antonios Mammis, M.D., Department of Neurological Surgery, Rutgers New Jersey Medical School, 90 Bergen Street, Suite 8100, P.O. Box 1709, Newark, NJ 07101-1709, USA. E-mail: antonios.mammis@ rutgers.edu

violation during surgery, lumbar puncture, epidural catheter placement, therapeutic epidural injection, and spontaneous cerebrospinal fluid (CSF) leaks. The frequency of persistent CSF leak following lumbar puncture is between 1% and 30%, depending on the technique used [2]. In cases of spontaneous CSF leak, there is no obvious cause. Still, spontaneous intracranial hypotension affects females more than males, and is most common in the fifth or sixth decades of life [1]. The CSF leak is usually due to a dural tear, where the spinal roots leave the subarachnoid space [3]. Recently, a novel hypothesis has been described on the etiology of spontaneous intracranial hypotension. Franzini et al. proposed that negative pressure within the inferior vena cava causes negative pressure within the spinal epidural veins. This contributes to a decrease in spinal epidural pressure, which serves to aspirate CSF into the epidural space and veins [4]. Magnetic resonance imaging (MRI) of the brain can confirm the diagnosis of intracranial hypotension. Imaging characteristics include diffuse pachymeningeal gadolinium enhancement, subdural fluid collections or 1

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hematomas, downward displacement of the cerebellar tonsils, and brain “sagging” [5]. Myelography or magnetic resonance cisternography can be utilized to help identify the CSF leaks yielding intracranial hypotension; however, these methods are not needed for diagnosis [2,5]. Fortunately, most cases of intracranial hypotension will resolve with conservative management. Conservative treatment options include bed rest, hydration, caffeine intake, and use of an abdominal binder [1]. If conservative management fails to resolve the issue, then open surgical or percutaneous options should be entertained. A case with an obvious dural violation from a recent spinal surgery warrants wound exploration and primary dural repair. The current gold standard in percutaneous management of intracranial hypotension involves the epidural injection of autologous blood [5,6]. The function of the epidural blood is likely two-fold – patching any dural defect in the vicinity of the injection and increasing the epidural pressure [4]. Recently, there have been a number of case reports looking at the role of epidural fibrin glue in the treatment of intracranial hypotension [7]. Overall, this clinical presentation serves to present an alternative therapy for intracranial hypotension using epidural fibrin glue patches should conventional treatments fail.

Patients Case 1 A 35-year-old female, with a long history of complex regional pain syndrome and morbid obesity, had both cervical and thoracolumbar spinal cord stimulator systems placed and revised multiple times. After repeated fractures of her cervical stimulator system, she underwent placement of an intrathecal pump, which was removed approximately 4 weeks later due to a Staphylococcus aureus wound infection. After treatment of her infection, she presented for re-implantation, which proceeded uneventfully. Postoperatively, she complained of severe positional headaches, so much so that the head of bed could not be raised greater than 5◦ . These symptoms persisted in spite of intravenous hydration, analgesics and bed rest. At this point, the decision was made to perform an epidural blood patch. The epidural space was entered at the same level as the catheter (L2–3) from the contralateral side, under fluoroscopic guidance. Once the epidural space was entered, the anesthesiologist was unable to draw more than 3 mL of blood due to poor venous access. Therefore, 10 mL of fibrin glue was prepared instead. After injection of 5 mL of the fibrin glue, the patient reported severe band-like lower back pain, so the injection was

terminated. Postoperatively, she was headache free, neurologically intact and had no further issues. She was discharged the following day.

Case 2 A 49-year-old female, with a history of complex regional pain syndrome, had a trial of percutaneous spinal cord stimulation attempted. Her trial was complicated by dural violation with subsequent development of intracranial hypotension. Over a two-month period, she had a series of three epidural blood patches. After the first patch, she did have transient relief; however, the subsequent two did not provide any relief. As her symptoms became increasingly disruptive to her quality of life, she elected to undergo an epidural fibrin glue patch. The patient was positioned prone and sedated. An epidural needle with a glass syringe was introduced into the epidural space at the L1–2 level, under fluoroscopic guidance. As the needle entered, a single drop of what appeared to be spinal fluid was noticed, but this fluid did not persist. The needle was withdrawn and then introduced into the L2–3 epidural space, without difficulty. In order to confirm epidural placement, epidurography was utilized. In an effort to prevent any potential complications of intrathecal contrast loading, the Omnipaque epidurogram was preceded with an air epidurogram, utilizing 2 mL of air. Following the air epidurogram, the contrast study corroborated epidural placement (Figure 1). Upon confirmation, 10 mL of TISSEEL (Baxter, Westlake Village, CA) fibrin glue was injected without difficulty. TISSEEL is a two-component (Sealer Protein and Thrombin) fibrin sealant made from pooled human plasma, which when combined, mimic the final stage of the blood coagulation cascade. Following the injection, the patient was taken to the recovery room, in stable condition. At two weeks follow-up, she reported resolution of her headaches.

Discussion Fibrin glue is a commonly used agent in neurosurgery and is activated by mixing two solutions. The first one is a sealer protein solution consisting of fibrinogen, a synthetic fibrinolysis inhibitor, albumin, tri-sodium citrate, histidine, niacinamide, polysorbate-80, and water. The second solution is a thrombin solution, consisting of thrombin, calcium chloride, albumin, sodium chloride, and water. This mixture serves to simulate the last step of the coagulation cascade, namely the conversion of fibrinogen to fibrin, under the action of thrombin [8,9]. The potential for a fibrin glue patch to treat the symptoms of intracranial hypotension, such as International Journal of Neuroscience

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Epidural fibrin glue patches

Figure 1. Confirmation of epidural placement of needle with contrasted epidurogram. Note epidural collection of contrast (∗) in both AP (A) and lateral (B) views.

postdural puncture headache, was first explored in an in vitro model. Gil et al. simulated the thecal sac by using a fluid filled column with a piece of human dura attached to one end, while the ligamentum flavum was simulated by the use of a paraffin film. Dural punctures were performed with a 17-gauge Tuohy needle, and pressure within the fluid column was transduced. In the five cases studied, Gil et al. found that application of 0.8 mL of fibrin glue to the epidural space sealed the leaking at closing pressures of 25–35 cm H2 O [9]. Encouraging results were obtained in vivo animal studies as well. Kroin et al. studied the effects of epidural injection on intracranial pressure by measuring pressure in the cisterna magna in a rat model of dural puncture. Following lumbar puncture, there was a characteristic decrease in cisterna magna pressure. So, equal volumes of saline, hetastarch 6%, dextran-40, dextran-70, EDTA blood, whole blood, or fibrin glue were injected to compare the preservation of cisterna magna pressure. Only whole blood and fibrin glue were able to maintain an elevated cisterna magna pressure for 240 min [10]. Likewise, in a swine model of dural puncture, the injection of 1.4 mL of fibrin glue was effective in sealing off the CSF leak against pressures of 24.5 cm H2 O. Interestingly, the study also concluded that the relatively large volumes of blood injected for an epidural blood patch increase epidural pressure, but CSF pressure recordings were not significantly altered with the injection of the 1.4 mL of fibrin glue [11]. Perhaps, epidural blood  C

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patches may act, in part, via an increase in epidural pressure, thereby reducing traction on the brain and meningeal structures [12,13]; however, this mechanism of action does not appear to fit for epidural fibrin glue patches. Although percutaneous fibrin glue injections offer therapeutic promise for CSF leaks in humans, there has been a paucity of reports in the neurosurgical literature. Nonetheless, a series of cases from the Netherlands were published in 1997, looking at the use of epidural fibrin glue to stop persistent CSF leak in three cases of long-term intrathecal catheterization. This group reports that 8% of cancer patients with long-term intrathecal catheters develop persistent leakage. Epidural blood patches are often times less likely to be effective in this population. CSF leakage was successfully treated in the three patients described with injections of 4 mL, 4 mL and 3 mL of fibrin glue in patients 1, 2 and 3, respectively [14]. A subsequent case report, by the same group, looked at the successful use of 3 mL of epidural fibrin glue in a woman with persistent postdural puncture headache [8]. Finally, Patel et al. studied 23 patients who had developed persistent CSF leak after surgery. These patients underwent CT guided percutaneous fibrin glue injection with the total volume instilled ranging from 4 mL to 24 mL. Fifteen of these patients had clinical improvement. Although five patients developed aseptic meningitis, this resolved with analgesic therapy and bed rest [15]. Although postdural puncture headaches are typically treated with conservative or, if necessary, aggressive treatment options such as epidural blood patches, exceptions can occur whereby the use of an alternative therapy is necessary [16,17]. Safa-Tisseront et al. demonstrated a 7% failure rate in a prospective observational study on the effectiveness of epidural blood patch in the management of postdural puncture headaches [13]. In such cases, the risks of an alternative therapy, such as fibrin glue patches, must be noted. Since components of fibrin glue are obtained from pooled human plasma, transmission of infectious agents is always a possibility [18]. Moreover, immune reactions are also probable as reported by Mitsuhata et al. after topical fibrin glue application [11,19]. Other studies have also demonstrated similar adverse reactions [20], including a report by Schievink et al., cautioning about the anaphylactic reaction in repeated application of fibrin glue [21]. Lastly, the risk of epidural compression of the spinal cord or nerve roots from the use of fibrin glue must be regarded. The relatively rapid hardening of fibrin glue may augment the risk of focal collection and compression, perhaps yielding the severe band-like lower back pain observed in Case 1. Of note, according to its manufacturer, TISSEEL is expected to be completely resorbed in 10–14 days. Therefore, before administrating

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any fibrin glue injections, the aforementioned risks must be carefully considered.

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Conclusion Percutaneous epidural injection of fibrin glue may be a feasible treatment option for intracranial hypotension, supporting the formation of fibrin at the site of a dural tear. However, its biologic origin implies a theoretical risk for viral transmission. Furthermore, introduction of the fibrin glue into the thecal sac may be associated with aseptic meningitis. Considering the potential risks, treatment with fibrin glue should be limited to cases whereby conventional therapies have failed and an alternative treatment is necessary as demonstrated by the authors in Case 2. As such, in specific cases fibrin glue could be of additional value. Ultimately, further studies, such as case–control studies with placebo controlled design, are needed to prove the safety and efficacy of fibrin glues with at least the same effects as conservative therapy and blood patches.

Declaration of Interest The authors have no personal financial or institutional interest in any of the drugs, material, or devices described in this article. The authors alone are responsible for the content and writing of this paper.

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6. Ferrante E, Arpino I, Citterio A, Wetzl R, Savino A. Epidural blood patch in Trendelenburg position pre-medicated with acetazolamide to treat spontaneous intracranial hypotension. Eur J Neurol 2010;17(5):715–9. 7. Ghavanini AA, Scott CA, Chan DK, Tang-Wai DF. Management of patients with spontaneous intracranial hypotension causing altered level of consciousness: report of two cases and review of literature. Cephalalgia 2013;33(1):43–51. 8. Crul BJ, Gerritse BM, van Dongen RT, Schoonderwaldt HC. Epidural fibrin glue injection stops persistent postdural puncture headache. Anesthesiology 1999;91(2):576–7. 9. Gil F, Garcia-Aguado R, Barcia JA, et al. The effect of fibrin glue patch in an in vitro model of postdural puncture leakage. Anesth Analg 1998;87(5):1125–8. 10. Kroin JS, Nagalla SK, Buvanendran A, et al. The mechanisms of intracranial pressure modulation by epidural blood and other injectates in a postdural puncture rat model. Anesth Analg 2002;95(2):423–9, table of contents. 11. Garcia-Aguado R, Gil F, Barcia JA, et al. Prophylactic percutaneous sealing of lumbar postdural puncture hole with fibrin glue to prevent cerebrospinal fluid leakage in swine. Anesth Analg 2000;90(4):894–8. 12. Vakharia SB, Thomas PS, Rosenbaum AE, et al. Magnetic resonance imaging of cerebrospinal fluid leak and tamponade effect of blood patch in postdural puncture headache. Anesth Analg 1997;84(3):585–90. 13. Safa-Tisseront V, Thormann F, Malassine P, et al. Effectiveness of epidural blood patch in the management of post-dural puncture headache. Anesthesiology 2001;95(2): 334–9. 14. Gerritse BM, van Dongen RT, Crul BJ. Epidural fibrin glue injection stops persistent cerebrospinal fluid leak during long-term intrathecal catheterization. Anesth Analg 1997;84(5):1140–1. 15. Patel MR, Caruso PA, Yousuf N, Rachlin J. CT-guided percutaneous fibrin glue therapy of cerebrospinal fluid leaks in the spine after surgery. Am J Roentgenol 2000;175(2):443–6. 16. Fry RA, Perera A. Failure of repeated blood patch in the treatment of spinal headache. Anaesthesia 1989;44(6):492–3. 17. Stevens RA, Jorgensen N. Successful treatment of dural puncture headache with epidural saline infusion after failure of epidural blood patch. Case report. Acta Anaesthesiol Scand 1988;32(5):429–31. 18. Feinberg EB, Funderburk R. Infectious disease risks of fibrin glue. Ophthalmic Surg 1993;24(3):206. 19. Mitsuhata H, Horiguchi Y, Saitoh J, et al. An anaphylactic reaction to topical fibrin glue. Anesthesiology 1994;81(4):1074–7. 20. Milde LN. An anaphylactic reaction to fibrin glue. Anesth Analg 1989;69(5):684–6. 21. Schievink WI, Georganos SA, Maya MM, et al. Anaphylactic reactions to fibrin sealant injection for spontaneous spinal CSF leaks. Neurology 2008;70(11):885–7.

International Journal of Neuroscience

Alternative treatment of intracranial hypotension presenting as postdural puncture headaches using epidural fibrin glue patches: two case reports.

Intracranial hypotension is a neurologic syndrome characterized by orthostatic headaches and, radiographically, by dural thickening and enhancement as...
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