Novel Dual Lumen Catheter and Filtration Device for Removal of Subarachnoid hemorrhage: First Case Report

Novel Dual Lumen Catheter and Filtration Device for Removal of Subarachnoid hemorrhage: First... Abstract BACKGROUND AND IMPORTANCE The amount of subarachnoid blood and the presence of toxic blood breakdown products in the cerebrospinal fluid (CSF) have long been associated with poor outcomes in aneurysmal subarachnoid hemorrhage. The Neurapheresis™ system (Minnetronix Inc, St. Paul, Minnesota) has been developed to filter CSF and remove blood products, and is being investigated for safety and feasibility in the ExtracorPoreal FILtration of subarachnoid hemorrhage via SpinaL CAtheteR (PILLAR) study. We report the first case using this novel device. CLINICAL PRESENTATION A 65-yr-old female presented with a ruptured left posterior communicating artery aneurysm. Following placement of a ventriculostomy and coil embolization of her aneurysm, the patient underwent placement of a lumbar dual lumen catheter for CSF filtration as part of the PILLAR study. In this case, a total of 9 h of filtration during 31 h of catheter indwelling resulted in 309.47 mL of processed CSF without complication. Computed tomography images demonstrated an interval reduction of subarachnoid hemorrhage immediately after filtration. The patient was discharged home on postbleed day 11 and at 30 d showed good recovery. CONCLUSION Safety of the Neurapheresis procedure was confirmed in this first case, and we will continue to evaluate safety of the Neurapheresis system through the PILLAR trial. Subarachnoid hemorrhage, Lumbar drain, Neurapheresis, Cerebrospinal fluid filtration, Aneurysm ABBREVIATIONS ABBREVIATIONS aSAH aneurysmal subarachnoid haemorrhage BBPs blood breakdown products CSF cerebrospinal fluid CT computed tomography CTA computed tomography angiography DCI delayed cerebral ischemia EVD external ventricular drain HH Hunt–Hess ICPs intracranial pressures LD lumbar drain MRA magenetic resonance angiography RBCs red blood cells SAS subarachnoid space SOC standard of care WFNS World Federation of Neurosurgical Societies Aneurysmal subarachnoid hemorrhage (aSAH) is a catastrophic result of a ruptured aneurysm. There are roughly 30 000 cases/year in the USA, with worldwide incidence between 4.2 and 22.7 people per 100 000.1 Blood and blood breakdown products (BBPs) in the subarachnoid space (SAS) have long been associated with complications leading to poor outcomes after aSAH, including vasospasm, microthrombosis, and delayed cerebral ischemia (DCI).2-4 Hemolysis of red blood cells (RBCs) in the cerebrospinal fluid (CSF) results in release of hemoglobin that triggers oxidative reactions, neuroinflammation, depletion of nitric oxide, and disruption of the blood brain barrier.5-8 There have been a number of studies on removal of blood and BBPs via lumbar drain (LD).9-12 However, LDs are not broadly used in this patient population. A system that removes blood and BBPs from the CSF more quickly and efficiently may reduce delayed complications following aSAH. We introduce the Neurapheresis™ therapy system (Minnetronix Inc, St. Paul, Minnesota), an investigational lumbar dual lumen catheter and filtration system designed to rapidly remove blood from CSF. CSF is simultaneously removed via proximal fenestrations (lumbar cistern) and returned postfiltration into the patient through distal fenestrations (mid-thoracic). This case report represents the first in the ExtracorPoreal FILtration of Subarachnoid Hemorrhage via SpinaL CAtheteR (PILLAR) safety study. CLINICAL PRESENTATION A 65-yr-old female presented to an outside hospital after a thunderclap headache. An external ventricular drain (EVD) was placed and the patient was transferred. On admission, Glasgow Coma Scale was 14, World Federation of Neurosurgical Societies (WFNS) 2, Hunt–Hess (HH) 3. She had neither family history of aSAH or cerebral aneurysm. A brain computed tomography (CT) showed diffuse aSAH (modified Fisher grade 3); computed tomography angiography (CTA) demonstrated a left posterior communicating artery aneurysm confirmed by angiography (7.3 × 4.6 × 2.9 mm) as a wide neck aneurysm. Informed consent for PILLAR was obtained from a legally authorized representative. The aneurysm was secured via coil embolization (Raymond class 2). Neurapheresis (Minnetronix Inc) catheter placement began at 18 h postbleed immediately following coiling. Entry was at L3/L4, and fluoroscopy provided visual confirmation of CSF access and spinal level. The guidewire and catheter were placed without complication, and final placement was verified on fluoroscopy with the proximal radiopaque marker bands at L2/L3 and distal marker bands at T1 (Figure 1). A successful filtration flow test was performed and the catheter was secured using a StayFIX® (Merit Medical, Salt Lake City, Utah), Tegaderm™ (3M, St. Paul, Minnesota), and tape. FIGURE 1. View largeDownload slide X-ray image shows the final location of the Neurapheresis catheter (Minnetronix Inc) in the SAS prior to removal. The two sets of radiopaque marker bands that span the distal fenestrations in the upper thoracic and the proximal fenestrations in the lumbar cistern of the catheter are indicated by the white arrows. FIGURE 1. View largeDownload slide X-ray image shows the final location of the Neurapheresis catheter (Minnetronix Inc) in the SAS prior to removal. The two sets of radiopaque marker bands that span the distal fenestrations in the upper thoracic and the proximal fenestrations in the lumbar cistern of the catheter are indicated by the white arrows. Neurapheresis filtration was initiated at a flow rate of 0.5 mL/min for the first 2 h of pump time and steadily increased until reaching a maximum of 0.8 mL/min and paused during lumbar CSF sampling, or when intracranial pressures (ICPs) were less than 5 mmHg, as directed by the physician. After 9 h 9 min of filtration, 309.47 mL of CSF was processed. Protein levels in the CSF decreased by greater than 5-fold (Figure 2) and CSF RBCs decreased from 5.45 × 105 to 4.88 × 105 cell/μL. Notably, the RBC measurement proved variable due to sampling technique, RBCs settling in coiled tubing, and pump duty cycling. Using system parameters and CSF RBC counts, an estimated 35.2 mL of whole blood was removed from CSF via filtration. FIGURE 2. View largeDownload slide Protein concentration (black solid line) in the CSF during Neurapheresis therapy (Minnetronix Inc), analyzed from protocol-required CSF samples. Time periods when the Neurapheresis pump was turned on are shaded in gray. The horizontal dotted lines represent the normal range of protein concentration in the CSF, the upper limit in red and the lower limit in black. FIGURE 2. View largeDownload slide Protein concentration (black solid line) in the CSF during Neurapheresis therapy (Minnetronix Inc), analyzed from protocol-required CSF samples. Time periods when the Neurapheresis pump was turned on are shaded in gray. The horizontal dotted lines represent the normal range of protein concentration in the CSF, the upper limit in red and the lower limit in black. During filtration, the EVD was clamped and ICP was transduced continuously. ICPs were recorded hourly into the medical record per standard of care (SOC). There did not appear to be a direct relationship between pump time and ICP, though continuous ICP measurement would need to be obtained for comparison (Figure 3). FIGURE 3. View largeDownload slide Hourly ICP (black line) is plotted over the time periods when the Neurapheresis pump (Minnetronix Inc) was turned on (gray shaded areas). The time points of the protocol-required CSF samples (every 4 ± 1 h) are indicated by the red stars. FIGURE 3. View largeDownload slide Hourly ICP (black line) is plotted over the time periods when the Neurapheresis pump (Minnetronix Inc) was turned on (gray shaded areas). The time points of the protocol-required CSF samples (every 4 ± 1 h) are indicated by the red stars. Follow-up and Outcomes Postfiltration, the patient remained in the Neuro intensive care unit until discharge. Transcranial doppler data were collected at regular intervals, and a 7-d angiogram and CT scan were performed (Figure 4). There was no clinical vasospasm and only mild angiographic vasospasm, potentially triggered by the initial hemorrhage or unfinished filtration of the CSF, due to protocol restrictions. Analysis of pre- and postfiltration CTs showed an interval decrease in cisternal blood, denoted by a drop in the Hijdra Score13,14 from 30 to 10. The EVD was removed on day 7. The patient was discharged home on day 11 postbleed. FIGURE 4. View largeDownload slide A representative axial CT slice in this patient at A, baseline, B, immediately after Neurapheresis therapy, and C, at 7-d follow-up. FIGURE 4. View largeDownload slide A representative axial CT slice in this patient at A, baseline, B, immediately after Neurapheresis therapy, and C, at 7-d follow-up. At 30 d, final surveillance found the patient's modified Rankin Scale score stable at 2, Glasgow Outcome Scale score of 5, and Barthel Index of 95. DISCUSSION Despite modern treatments, persistent disability and poor outcome occurs in 20% to 55% of patients that survive aSAH.11,15,16 Studies report clinical vasospasm in 18% to 63%,11,17 with vasospasm-related DCI ranging from 13% to 54%.9,12,18 The percent of patients who go directly home after discharge ranges from 25%9 to 57%,19 and 6-mo mortality is between 2.1% and 15%.10-12 Reducing late morbidity and mortality related to neuroinflammation, clinical vasospasm, DCI, and hydrocephalus remains a top priority. LDs are ubiquitous in neurocritical care and have been shown to reduce the incidence of clinical vasospasm in aSAH patients by as much as 40% compared to controls.9,11 Several attempts have been made to confirm these results, the most recent being the EARLYDRAIN study in which results are pending.20 Despite promising outcomes, the EVD remains the more popular device for hydrocephalus management. Current LDs are hampered by long, inefficient, and manual periods of drainage, but closed loop CSF filtration via the Neurapheresis system may provide rapid, efficient, and controlled removal of hemorrhagic blood and BBPs from the CSF in aSAH, prior to downstream effects. This system can theoretically remove the target particles from CSF faster than LD, where net drainage is limited by natural CSF production rate. The PILLAR study is a 15 patient, nonrandomized, multicenter, first-in-human feasibility, US safety trial. Patients are eligible with aSAH and modified Fisher grade 2, 3, or 4, HH grade I-III, and WFNS grade I-IV (see Table for full inclusion/exclusion criteria). The Neurapheresis catheter (Minnetronix Inc) must be inserted postaneurysm securement but prior to 48 h postbleeding event and may be indwelling for 36 h. TABLE. PILLAR Study Inclusion and Exclusion Criteria Inclusion criteria Exclusion criteria Age: 18 yr or older Patients with a SAH due to mycotic aneurysm or AV malformation Informed consent by the patient or his/her legally authorized representative Patients who present with an acute myocardial infarction or unstable angina Modified Fisher grade 2, 3, or 4 Patients with uncontrolled diabetes Hunt and Hess I-III Patients who present with a creatinine >2.0mg/dl First aneurysmal SAH that has been confirmed by Angio, CTA, or magenetic resonance angiography (MRA) Imaging demonstrates supratentorial mass lesions greater than 50 cc Patient is ≤36 h postbleeding event Imaging demonstrates more than 5 mm of mid-line-shift associated with infarction and or edema WFNS grades I-IV and those grade V patients who improve to grade IV or less after ventriculostomy Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic, and quadrageminal) Vasospasm on admission as defined by angiographic evidence Patients with a coagulopathy that cannot be reversed per the professional discretion of the investigator Thrombocytopenia def. platelet count <100 000 Patients on low molecular weight heparin eg, Love ox Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors Patients with a documented history of cirrhosis Patients who will be managed with supportive care rather than intervention Obstructive hydrocephalus ie noncommunicating Pregnancy History of posterior fusion hardware that would interfere with placement of the catheter Preexisting LD Local skin infections or eruptions over the puncture site Signs of systemic infection/sepsis or pneumonia Lumbar puncture within 6 h Concurrent participation in another study, which is not observational or retrospective in nature without prior approval from the Sponsor Inclusion criteria Exclusion criteria Age: 18 yr or older Patients with a SAH due to mycotic aneurysm or AV malformation Informed consent by the patient or his/her legally authorized representative Patients who present with an acute myocardial infarction or unstable angina Modified Fisher grade 2, 3, or 4 Patients with uncontrolled diabetes Hunt and Hess I-III Patients who present with a creatinine >2.0mg/dl First aneurysmal SAH that has been confirmed by Angio, CTA, or magenetic resonance angiography (MRA) Imaging demonstrates supratentorial mass lesions greater than 50 cc Patient is ≤36 h postbleeding event Imaging demonstrates more than 5 mm of mid-line-shift associated with infarction and or edema WFNS grades I-IV and those grade V patients who improve to grade IV or less after ventriculostomy Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic, and quadrageminal) Vasospasm on admission as defined by angiographic evidence Patients with a coagulopathy that cannot be reversed per the professional discretion of the investigator Thrombocytopenia def. platelet count <100 000 Patients on low molecular weight heparin eg, Love ox Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors Patients with a documented history of cirrhosis Patients who will be managed with supportive care rather than intervention Obstructive hydrocephalus ie noncommunicating Pregnancy History of posterior fusion hardware that would interfere with placement of the catheter Preexisting LD Local skin infections or eruptions over the puncture site Signs of systemic infection/sepsis or pneumonia Lumbar puncture within 6 h Concurrent participation in another study, which is not observational or retrospective in nature without prior approval from the Sponsor This table shows the inclusion and exclusion criteria for the PILLAR study. View Large TABLE. PILLAR Study Inclusion and Exclusion Criteria Inclusion criteria Exclusion criteria Age: 18 yr or older Patients with a SAH due to mycotic aneurysm or AV malformation Informed consent by the patient or his/her legally authorized representative Patients who present with an acute myocardial infarction or unstable angina Modified Fisher grade 2, 3, or 4 Patients with uncontrolled diabetes Hunt and Hess I-III Patients who present with a creatinine >2.0mg/dl First aneurysmal SAH that has been confirmed by Angio, CTA, or magenetic resonance angiography (MRA) Imaging demonstrates supratentorial mass lesions greater than 50 cc Patient is ≤36 h postbleeding event Imaging demonstrates more than 5 mm of mid-line-shift associated with infarction and or edema WFNS grades I-IV and those grade V patients who improve to grade IV or less after ventriculostomy Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic, and quadrageminal) Vasospasm on admission as defined by angiographic evidence Patients with a coagulopathy that cannot be reversed per the professional discretion of the investigator Thrombocytopenia def. platelet count <100 000 Patients on low molecular weight heparin eg, Love ox Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors Patients with a documented history of cirrhosis Patients who will be managed with supportive care rather than intervention Obstructive hydrocephalus ie noncommunicating Pregnancy History of posterior fusion hardware that would interfere with placement of the catheter Preexisting LD Local skin infections or eruptions over the puncture site Signs of systemic infection/sepsis or pneumonia Lumbar puncture within 6 h Concurrent participation in another study, which is not observational or retrospective in nature without prior approval from the Sponsor Inclusion criteria Exclusion criteria Age: 18 yr or older Patients with a SAH due to mycotic aneurysm or AV malformation Informed consent by the patient or his/her legally authorized representative Patients who present with an acute myocardial infarction or unstable angina Modified Fisher grade 2, 3, or 4 Patients with uncontrolled diabetes Hunt and Hess I-III Patients who present with a creatinine >2.0mg/dl First aneurysmal SAH that has been confirmed by Angio, CTA, or magenetic resonance angiography (MRA) Imaging demonstrates supratentorial mass lesions greater than 50 cc Patient is ≤36 h postbleeding event Imaging demonstrates more than 5 mm of mid-line-shift associated with infarction and or edema WFNS grades I-IV and those grade V patients who improve to grade IV or less after ventriculostomy Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic, and quadrageminal) Vasospasm on admission as defined by angiographic evidence Patients with a coagulopathy that cannot be reversed per the professional discretion of the investigator Thrombocytopenia def. platelet count <100 000 Patients on low molecular weight heparin eg, Love ox Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors Patients with a documented history of cirrhosis Patients who will be managed with supportive care rather than intervention Obstructive hydrocephalus ie noncommunicating Pregnancy History of posterior fusion hardware that would interfere with placement of the catheter Preexisting LD Local skin infections or eruptions over the puncture site Signs of systemic infection/sepsis or pneumonia Lumbar puncture within 6 h Concurrent participation in another study, which is not observational or retrospective in nature without prior approval from the Sponsor This table shows the inclusion and exclusion criteria for the PILLAR study. View Large This report details the first patient in the PILLAR trial to receive Neurapheresis therapy. CSF filtration was performed for 9 of the 31 h of indwelling time without complication. There are several advantages to closed loop filtration over LD. First, a filtration system can theoretically remove target particles from the CSF faster, rather than depend on the natural rate of CSF production to slowly drain hemorrhagic CSF. Because the system returns filtered CSF, having removed all cells (eg, RBCs) and most proteins, it can circulate this and potentially provide much more rapid clearance of blood volume. In addition, return of CSF back to the patient postfiltration may help reduce overdrainage complications encountered with traditional LDs. It is well known that a significant volume of blood can exist in the lumbar space, escaping detection on head CT. This pooled blood in the lumbar space will likely be more amenable to clearance with LD than EVD. However, the ability of a filtration device to affect the resolution of blood in the brain is unknown; we interpret, in this report, the drop in Hijdra score, proteins, and RBCs as blood being mobilized caudally and anticipate further clearance of RBCs with longer pump times. This will continue to be investigated in this and subsequent trials to interpret results contextually vs SOC. CONCLUSION In conclusion, this is the first case report of an aSAH patient undergoing Neurapheresis therapy (Minnetronix Inc) as part of a clinical trial. Enrollment and data collection are ongoing for this phase 1 trial. Disclosures This publication is not supported by any company or grant funding. The PILLAR clinical trial is supported by Minnetronix Inc. Two co-authors, Dr Verbick and Dr McCabe, are employed by Minnetronix and facilitated data interpretation and preparation of manuscript and figures. Dr Lad has consulted for Minnetronix Inc. He is the coinventor of the Neurapheresis Therapy and is involved in its scientific development. He is not involved in PILLAR clinical enrollment. Dr Blackburn, Dr Swisher, and Dr Grande are site principal investigators and do not receive compensation for the study other than Institutional Review Board approved study related expenses. Ms Rubi has no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. de Rooij NK , Linn FH , van der Plas JA , Algra A , Rinkel GJ . Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends . J Neurol Neurosurg Psychiatry . 2007 ; 78 ( 12 ): 1365 – 1372 . doi: 10.1136/jnnp.2007.117655 . Google Scholar CrossRef Search ADS PubMed 2. Claassen J , Bernardini GL , Kreiter K et al. Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited . Stroke . 2001 ; 32 ( 9 ): 2012 – 2020 . doi: 10.1161/hs0901.095677 . Google Scholar CrossRef Search ADS PubMed 3. Fisher C , Kistler JP . Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning . Neurosurgery . 1980 ; 6 ( 1 ): 1 – 9 . Google Scholar CrossRef Search ADS PubMed 4. Frontera JA , Claassen J , Schmidt JM et al. Prediction of symptomatic vasospasmafter subarachnoid hemorrhage: the modified Fisher scale . Neurosurgery . 2006 ; 59 ( 1 ): 21 – 27 . Google Scholar CrossRef Search ADS PubMed 5. Pluta RM. Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment . Pharmacol Ther . 2005 ; 105 ( 1 ): 23 – 56 . doi: 10.1016/j.pharmthera.2004.10.002 . Google Scholar CrossRef Search ADS PubMed 6. Rifkind JM , Mohanty JG , Nagababu E . The pathophysiology of extracellular hemoglobin associated with enhanced oxidative reactions . Front Physiol . 2015 ; 5 ( 500 ): 1 – 7 . doi: 10.3389/fphys.2014.00500 . 7. Sehba FA , Mostafa G , Knopman J , Friedrich V , Bederson JB . Acute alterations in microvascular basal lamina after subarachnoid hemorrhage . J Neurosurg . 2004 ; 101 ( 4 ): 633 – 640 . doi: 10.3171/jns.2004.101.4.0633 . Google Scholar CrossRef Search ADS PubMed 8. Vecchione C , Frati A , Di Pardo A et al. Tumor necrosis factor-alpha mediates hemolysis-induced vasoconstriction and the cerebral vasospasm evoked by subarachnoid hemorrhage . Hypertension . 2009 ; 54 ( 1 ): 150 – 156 . doi: 10.1161/HYPERTENSIONAHA.108.128124 . Google Scholar CrossRef Search ADS PubMed 9. Klimo P , Kestle JRW , MacDonald JD , Schmidt RH . Marked reduction of cerebral vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage . J Neurosurg . 2004 ; 100 ( 2 ): 215 – 224 . doi: 10.3171/jns.2004.100.2.0215 . Google Scholar CrossRef Search ADS PubMed 10. Al-Tamimi YZ , Bhargava D , Feltbower RG et al. Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS) . Stroke . 2012 ; 43 ( 3 ): 677 – 682 . doi: 10.1161/STROKEAHA.111.625731 . Google Scholar CrossRef Search ADS PubMed 11. Kwon OY , Kim YJ , Kim YJ , Cho CS , Lee SK , Cho MK . The utility and benefits of external lumbar CSF drainage after endovascular coiling on aneurysmal ubarachnoid hemorrhage . J Korean Neurosurg Soc . 2008 ; 43 ( 6 ): 281 – 287 . doi: 10.3340/jkns.2008.43.6.281 . Google Scholar CrossRef Search ADS PubMed 12. Park S , Yang N , Seo E . The effectiveness of lumbar cerebrospinal fluid drainage to reduce the cerebral vasospasm after surgical clipping for aneurysmal subarachnoid hemorrhage . J Korean Neurosurg Soc . 2015 ; 57 ( 3 ): 167 . doi:10.3340/jkns.2015.57.3.167 . Google Scholar CrossRef Search ADS PubMed 13. Dupont SA , Wijdicks EFM , Manno EM , Lanzino G , Rabinstein AA . Prediction of angiographic vasospasm after aneurysmal subarachnoid hemorrhage: value of the Hijdra sum scoring system . Neurocrit Care . 2009 ; 11 ( 2 ): 172 – 176 . doi:10.1007/s12028-009-9247-3 . Google Scholar CrossRef Search ADS PubMed 14. Hijdra A , Brouwers P , Vermeulen M . Grading the amount of blood on computed tomograms after subarachnoid hemorrhage . Stroke . 1990 ; 21 ( 8 ): 1156 – 1161 . Google Scholar CrossRef Search ADS PubMed 15. Pickard JD , Murray GD , Illingworth R et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial . BMJ . 1989 ; 298 ( 6674 ): 636 – 642 . Google Scholar CrossRef Search ADS PubMed 16. Soppi V , Karamanakos PN , Koivisto T et al. A randomized outcome study of enteral versus intravenous nimodipine in 171 patients after acute aneurysmal subarachnoid hemorrhage . World Neurosurg . 2012 ; 78 ( 1-2 ): 101 – 109 . doi: 10.1016/j.wneu.2011.09.030 . Google Scholar CrossRef Search ADS PubMed 17. Wong GKC , Poon WS , Chan MTV et al. Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage (IMASH): a randomized, double-blinded, placebo-controlled, multicenter phase III trial . Stroke . 2010 ; 41 ( 5 ): 921 – 926 . doi: 10.1161/STROKEAHA.109.571125 . Google Scholar CrossRef Search ADS PubMed 18. Macdonald RL , Higashida RT , Keller E et al. Randomized trial of Clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling . Stroke . 2012 ; 43 ( 6 ): 1463 – 1469 . doi: 10.1161/STROKEAHA.111.648980 . Google Scholar CrossRef Search ADS PubMed 19. Turner CL , Smith C , Murray GD , Hutchinson PJ , Kirkpatrick PJ . 204 simvastatin in aneurysmal subarachnoid haemorrhage (STASH) trial . Neurosurgery . 2014 ; 61 ( suppl 1 ): 228 . doi: 10.1227/01.neu.0000452478.36194.df . Google Scholar CrossRef Search ADS 20. Bardutzky J , Witsch J , Jüttler E , Schwab S , Vajkoczy P , Wolf S . EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial . Trials . 2011 ; 12 : 203 . doi: 10.1186/1745-6215-12-203 . Google Scholar CrossRef Search ADS PubMed Acknowledgment The authors wish to thank Kanako Matsumura for assistance with the PILLAR study and data collection. COMMENTS This is an interesting idea and an innovative system to filter out the blood after subarachnoid hemorrhage. However, neither the safety nor the efficacy are proven, and we need to wait for the results of the phase 1 study of 15 patients. I hope that the authors will be successful. Laligam N. Sekhar Seattle, Washington In this report, the authors provide a case and technical description of the first use of the Neurapheresis therapy (Minnetronix Inc) system for lumbar CSF filtration following aneurysmal subarachnoid hemorrhage (aSAH). This report provides an introduction to this novel therapy and a primer on the pending clinical trial (PILLAR study) that is underway. Like the authors, we are keenly interested to see if implementation of this device in the setting of aSAH can reduce vasospasm or speed recovery in this challenging group of patients. One concern is whether the implementation of CSF filtration in these patients will be “too-little-too-late”; it may be that the inflammatory cascade that is initiated by aneurysmal rupture may persist despite removal of the blood products after the fact. However, if proven efficacious, this strategy hasthe potential to drastically change the clinical management of aSAH patients in the future. We commend the authors for embarking on this interesting undertaking. Michael Mooney Peter Nakaji Phoenix, Arizona The definitive pathophysiology of cerebral vasospasm (delayed cerebral ischemia) remains elusive. Thus, we are left managing the symptoms of this oftentimes deleterious phenomenon. Nevertheless, anecdotally, it seems that the incidence of symptomatic cerebral vasospasm is decreasing. This may be due to multifactorial reasons, however, improvements in the intensive care management of these patients may play a role. Though there may be disagreements regarding the pathophysiology and incidence of this phenomenon, there seems to be overall consensus that substances in the CSF likely contribute to its development. Though the concept of clearing the CSF the authors propose is not novel, they report the first patient treated with a novel device. This paper does not establish neither the safety or efficacy of their device, however, does show that it is feasible in this one patient. I look forward to seeing a larger patient series reported from this group and I congratulate the authors on this interesting and novel device that could potentially have significant clinical benefit. Ketan R. Bulsara Farmington, Connecticut Copyright © 2018 by the Congress of Neurological Surgeons This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Operative Neurosurgery Oxford University Press

Novel Dual Lumen Catheter and Filtration Device for Removal of Subarachnoid hemorrhage: First Case Report

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Abstract

Abstract BACKGROUND AND IMPORTANCE The amount of subarachnoid blood and the presence of toxic blood breakdown products in the cerebrospinal fluid (CSF) have long been associated with poor outcomes in aneurysmal subarachnoid hemorrhage. The Neurapheresis™ system (Minnetronix Inc, St. Paul, Minnesota) has been developed to filter CSF and remove blood products, and is being investigated for safety and feasibility in the ExtracorPoreal FILtration of subarachnoid hemorrhage via SpinaL CAtheteR (PILLAR) study. We report the first case using this novel device. CLINICAL PRESENTATION A 65-yr-old female presented with a ruptured left posterior communicating artery aneurysm. Following placement of a ventriculostomy and coil embolization of her aneurysm, the patient underwent placement of a lumbar dual lumen catheter for CSF filtration as part of the PILLAR study. In this case, a total of 9 h of filtration during 31 h of catheter indwelling resulted in 309.47 mL of processed CSF without complication. Computed tomography images demonstrated an interval reduction of subarachnoid hemorrhage immediately after filtration. The patient was discharged home on postbleed day 11 and at 30 d showed good recovery. CONCLUSION Safety of the Neurapheresis procedure was confirmed in this first case, and we will continue to evaluate safety of the Neurapheresis system through the PILLAR trial. Subarachnoid hemorrhage, Lumbar drain, Neurapheresis, Cerebrospinal fluid filtration, Aneurysm ABBREVIATIONS ABBREVIATIONS aSAH aneurysmal subarachnoid haemorrhage BBPs blood breakdown products CSF cerebrospinal fluid CT computed tomography CTA computed tomography angiography DCI delayed cerebral ischemia EVD external ventricular drain HH Hunt–Hess ICPs intracranial pressures LD lumbar drain MRA magenetic resonance angiography RBCs red blood cells SAS subarachnoid space SOC standard of care WFNS World Federation of Neurosurgical Societies Aneurysmal subarachnoid hemorrhage (aSAH) is a catastrophic result of a ruptured aneurysm. There are roughly 30 000 cases/year in the USA, with worldwide incidence between 4.2 and 22.7 people per 100 000.1 Blood and blood breakdown products (BBPs) in the subarachnoid space (SAS) have long been associated with complications leading to poor outcomes after aSAH, including vasospasm, microthrombosis, and delayed cerebral ischemia (DCI).2-4 Hemolysis of red blood cells (RBCs) in the cerebrospinal fluid (CSF) results in release of hemoglobin that triggers oxidative reactions, neuroinflammation, depletion of nitric oxide, and disruption of the blood brain barrier.5-8 There have been a number of studies on removal of blood and BBPs via lumbar drain (LD).9-12 However, LDs are not broadly used in this patient population. A system that removes blood and BBPs from the CSF more quickly and efficiently may reduce delayed complications following aSAH. We introduce the Neurapheresis™ therapy system (Minnetronix Inc, St. Paul, Minnesota), an investigational lumbar dual lumen catheter and filtration system designed to rapidly remove blood from CSF. CSF is simultaneously removed via proximal fenestrations (lumbar cistern) and returned postfiltration into the patient through distal fenestrations (mid-thoracic). This case report represents the first in the ExtracorPoreal FILtration of Subarachnoid Hemorrhage via SpinaL CAtheteR (PILLAR) safety study. CLINICAL PRESENTATION A 65-yr-old female presented to an outside hospital after a thunderclap headache. An external ventricular drain (EVD) was placed and the patient was transferred. On admission, Glasgow Coma Scale was 14, World Federation of Neurosurgical Societies (WFNS) 2, Hunt–Hess (HH) 3. She had neither family history of aSAH or cerebral aneurysm. A brain computed tomography (CT) showed diffuse aSAH (modified Fisher grade 3); computed tomography angiography (CTA) demonstrated a left posterior communicating artery aneurysm confirmed by angiography (7.3 × 4.6 × 2.9 mm) as a wide neck aneurysm. Informed consent for PILLAR was obtained from a legally authorized representative. The aneurysm was secured via coil embolization (Raymond class 2). Neurapheresis (Minnetronix Inc) catheter placement began at 18 h postbleed immediately following coiling. Entry was at L3/L4, and fluoroscopy provided visual confirmation of CSF access and spinal level. The guidewire and catheter were placed without complication, and final placement was verified on fluoroscopy with the proximal radiopaque marker bands at L2/L3 and distal marker bands at T1 (Figure 1). A successful filtration flow test was performed and the catheter was secured using a StayFIX® (Merit Medical, Salt Lake City, Utah), Tegaderm™ (3M, St. Paul, Minnesota), and tape. FIGURE 1. View largeDownload slide X-ray image shows the final location of the Neurapheresis catheter (Minnetronix Inc) in the SAS prior to removal. The two sets of radiopaque marker bands that span the distal fenestrations in the upper thoracic and the proximal fenestrations in the lumbar cistern of the catheter are indicated by the white arrows. FIGURE 1. View largeDownload slide X-ray image shows the final location of the Neurapheresis catheter (Minnetronix Inc) in the SAS prior to removal. The two sets of radiopaque marker bands that span the distal fenestrations in the upper thoracic and the proximal fenestrations in the lumbar cistern of the catheter are indicated by the white arrows. Neurapheresis filtration was initiated at a flow rate of 0.5 mL/min for the first 2 h of pump time and steadily increased until reaching a maximum of 0.8 mL/min and paused during lumbar CSF sampling, or when intracranial pressures (ICPs) were less than 5 mmHg, as directed by the physician. After 9 h 9 min of filtration, 309.47 mL of CSF was processed. Protein levels in the CSF decreased by greater than 5-fold (Figure 2) and CSF RBCs decreased from 5.45 × 105 to 4.88 × 105 cell/μL. Notably, the RBC measurement proved variable due to sampling technique, RBCs settling in coiled tubing, and pump duty cycling. Using system parameters and CSF RBC counts, an estimated 35.2 mL of whole blood was removed from CSF via filtration. FIGURE 2. View largeDownload slide Protein concentration (black solid line) in the CSF during Neurapheresis therapy (Minnetronix Inc), analyzed from protocol-required CSF samples. Time periods when the Neurapheresis pump was turned on are shaded in gray. The horizontal dotted lines represent the normal range of protein concentration in the CSF, the upper limit in red and the lower limit in black. FIGURE 2. View largeDownload slide Protein concentration (black solid line) in the CSF during Neurapheresis therapy (Minnetronix Inc), analyzed from protocol-required CSF samples. Time periods when the Neurapheresis pump was turned on are shaded in gray. The horizontal dotted lines represent the normal range of protein concentration in the CSF, the upper limit in red and the lower limit in black. During filtration, the EVD was clamped and ICP was transduced continuously. ICPs were recorded hourly into the medical record per standard of care (SOC). There did not appear to be a direct relationship between pump time and ICP, though continuous ICP measurement would need to be obtained for comparison (Figure 3). FIGURE 3. View largeDownload slide Hourly ICP (black line) is plotted over the time periods when the Neurapheresis pump (Minnetronix Inc) was turned on (gray shaded areas). The time points of the protocol-required CSF samples (every 4 ± 1 h) are indicated by the red stars. FIGURE 3. View largeDownload slide Hourly ICP (black line) is plotted over the time periods when the Neurapheresis pump (Minnetronix Inc) was turned on (gray shaded areas). The time points of the protocol-required CSF samples (every 4 ± 1 h) are indicated by the red stars. Follow-up and Outcomes Postfiltration, the patient remained in the Neuro intensive care unit until discharge. Transcranial doppler data were collected at regular intervals, and a 7-d angiogram and CT scan were performed (Figure 4). There was no clinical vasospasm and only mild angiographic vasospasm, potentially triggered by the initial hemorrhage or unfinished filtration of the CSF, due to protocol restrictions. Analysis of pre- and postfiltration CTs showed an interval decrease in cisternal blood, denoted by a drop in the Hijdra Score13,14 from 30 to 10. The EVD was removed on day 7. The patient was discharged home on day 11 postbleed. FIGURE 4. View largeDownload slide A representative axial CT slice in this patient at A, baseline, B, immediately after Neurapheresis therapy, and C, at 7-d follow-up. FIGURE 4. View largeDownload slide A representative axial CT slice in this patient at A, baseline, B, immediately after Neurapheresis therapy, and C, at 7-d follow-up. At 30 d, final surveillance found the patient's modified Rankin Scale score stable at 2, Glasgow Outcome Scale score of 5, and Barthel Index of 95. DISCUSSION Despite modern treatments, persistent disability and poor outcome occurs in 20% to 55% of patients that survive aSAH.11,15,16 Studies report clinical vasospasm in 18% to 63%,11,17 with vasospasm-related DCI ranging from 13% to 54%.9,12,18 The percent of patients who go directly home after discharge ranges from 25%9 to 57%,19 and 6-mo mortality is between 2.1% and 15%.10-12 Reducing late morbidity and mortality related to neuroinflammation, clinical vasospasm, DCI, and hydrocephalus remains a top priority. LDs are ubiquitous in neurocritical care and have been shown to reduce the incidence of clinical vasospasm in aSAH patients by as much as 40% compared to controls.9,11 Several attempts have been made to confirm these results, the most recent being the EARLYDRAIN study in which results are pending.20 Despite promising outcomes, the EVD remains the more popular device for hydrocephalus management. Current LDs are hampered by long, inefficient, and manual periods of drainage, but closed loop CSF filtration via the Neurapheresis system may provide rapid, efficient, and controlled removal of hemorrhagic blood and BBPs from the CSF in aSAH, prior to downstream effects. This system can theoretically remove the target particles from CSF faster than LD, where net drainage is limited by natural CSF production rate. The PILLAR study is a 15 patient, nonrandomized, multicenter, first-in-human feasibility, US safety trial. Patients are eligible with aSAH and modified Fisher grade 2, 3, or 4, HH grade I-III, and WFNS grade I-IV (see Table for full inclusion/exclusion criteria). The Neurapheresis catheter (Minnetronix Inc) must be inserted postaneurysm securement but prior to 48 h postbleeding event and may be indwelling for 36 h. TABLE. PILLAR Study Inclusion and Exclusion Criteria Inclusion criteria Exclusion criteria Age: 18 yr or older Patients with a SAH due to mycotic aneurysm or AV malformation Informed consent by the patient or his/her legally authorized representative Patients who present with an acute myocardial infarction or unstable angina Modified Fisher grade 2, 3, or 4 Patients with uncontrolled diabetes Hunt and Hess I-III Patients who present with a creatinine >2.0mg/dl First aneurysmal SAH that has been confirmed by Angio, CTA, or magenetic resonance angiography (MRA) Imaging demonstrates supratentorial mass lesions greater than 50 cc Patient is ≤36 h postbleeding event Imaging demonstrates more than 5 mm of mid-line-shift associated with infarction and or edema WFNS grades I-IV and those grade V patients who improve to grade IV or less after ventriculostomy Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic, and quadrageminal) Vasospasm on admission as defined by angiographic evidence Patients with a coagulopathy that cannot be reversed per the professional discretion of the investigator Thrombocytopenia def. platelet count <100 000 Patients on low molecular weight heparin eg, Love ox Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors Patients with a documented history of cirrhosis Patients who will be managed with supportive care rather than intervention Obstructive hydrocephalus ie noncommunicating Pregnancy History of posterior fusion hardware that would interfere with placement of the catheter Preexisting LD Local skin infections or eruptions over the puncture site Signs of systemic infection/sepsis or pneumonia Lumbar puncture within 6 h Concurrent participation in another study, which is not observational or retrospective in nature without prior approval from the Sponsor Inclusion criteria Exclusion criteria Age: 18 yr or older Patients with a SAH due to mycotic aneurysm or AV malformation Informed consent by the patient or his/her legally authorized representative Patients who present with an acute myocardial infarction or unstable angina Modified Fisher grade 2, 3, or 4 Patients with uncontrolled diabetes Hunt and Hess I-III Patients who present with a creatinine >2.0mg/dl First aneurysmal SAH that has been confirmed by Angio, CTA, or magenetic resonance angiography (MRA) Imaging demonstrates supratentorial mass lesions greater than 50 cc Patient is ≤36 h postbleeding event Imaging demonstrates more than 5 mm of mid-line-shift associated with infarction and or edema WFNS grades I-IV and those grade V patients who improve to grade IV or less after ventriculostomy Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic, and quadrageminal) Vasospasm on admission as defined by angiographic evidence Patients with a coagulopathy that cannot be reversed per the professional discretion of the investigator Thrombocytopenia def. platelet count <100 000 Patients on low molecular weight heparin eg, Love ox Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors Patients with a documented history of cirrhosis Patients who will be managed with supportive care rather than intervention Obstructive hydrocephalus ie noncommunicating Pregnancy History of posterior fusion hardware that would interfere with placement of the catheter Preexisting LD Local skin infections or eruptions over the puncture site Signs of systemic infection/sepsis or pneumonia Lumbar puncture within 6 h Concurrent participation in another study, which is not observational or retrospective in nature without prior approval from the Sponsor This table shows the inclusion and exclusion criteria for the PILLAR study. View Large TABLE. PILLAR Study Inclusion and Exclusion Criteria Inclusion criteria Exclusion criteria Age: 18 yr or older Patients with a SAH due to mycotic aneurysm or AV malformation Informed consent by the patient or his/her legally authorized representative Patients who present with an acute myocardial infarction or unstable angina Modified Fisher grade 2, 3, or 4 Patients with uncontrolled diabetes Hunt and Hess I-III Patients who present with a creatinine >2.0mg/dl First aneurysmal SAH that has been confirmed by Angio, CTA, or magenetic resonance angiography (MRA) Imaging demonstrates supratentorial mass lesions greater than 50 cc Patient is ≤36 h postbleeding event Imaging demonstrates more than 5 mm of mid-line-shift associated with infarction and or edema WFNS grades I-IV and those grade V patients who improve to grade IV or less after ventriculostomy Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic, and quadrageminal) Vasospasm on admission as defined by angiographic evidence Patients with a coagulopathy that cannot be reversed per the professional discretion of the investigator Thrombocytopenia def. platelet count <100 000 Patients on low molecular weight heparin eg, Love ox Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors Patients with a documented history of cirrhosis Patients who will be managed with supportive care rather than intervention Obstructive hydrocephalus ie noncommunicating Pregnancy History of posterior fusion hardware that would interfere with placement of the catheter Preexisting LD Local skin infections or eruptions over the puncture site Signs of systemic infection/sepsis or pneumonia Lumbar puncture within 6 h Concurrent participation in another study, which is not observational or retrospective in nature without prior approval from the Sponsor Inclusion criteria Exclusion criteria Age: 18 yr or older Patients with a SAH due to mycotic aneurysm or AV malformation Informed consent by the patient or his/her legally authorized representative Patients who present with an acute myocardial infarction or unstable angina Modified Fisher grade 2, 3, or 4 Patients with uncontrolled diabetes Hunt and Hess I-III Patients who present with a creatinine >2.0mg/dl First aneurysmal SAH that has been confirmed by Angio, CTA, or magenetic resonance angiography (MRA) Imaging demonstrates supratentorial mass lesions greater than 50 cc Patient is ≤36 h postbleeding event Imaging demonstrates more than 5 mm of mid-line-shift associated with infarction and or edema WFNS grades I-IV and those grade V patients who improve to grade IV or less after ventriculostomy Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic, and quadrageminal) Vasospasm on admission as defined by angiographic evidence Patients with a coagulopathy that cannot be reversed per the professional discretion of the investigator Thrombocytopenia def. platelet count <100 000 Patients on low molecular weight heparin eg, Love ox Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors Patients with a documented history of cirrhosis Patients who will be managed with supportive care rather than intervention Obstructive hydrocephalus ie noncommunicating Pregnancy History of posterior fusion hardware that would interfere with placement of the catheter Preexisting LD Local skin infections or eruptions over the puncture site Signs of systemic infection/sepsis or pneumonia Lumbar puncture within 6 h Concurrent participation in another study, which is not observational or retrospective in nature without prior approval from the Sponsor This table shows the inclusion and exclusion criteria for the PILLAR study. View Large This report details the first patient in the PILLAR trial to receive Neurapheresis therapy. CSF filtration was performed for 9 of the 31 h of indwelling time without complication. There are several advantages to closed loop filtration over LD. First, a filtration system can theoretically remove target particles from the CSF faster, rather than depend on the natural rate of CSF production to slowly drain hemorrhagic CSF. Because the system returns filtered CSF, having removed all cells (eg, RBCs) and most proteins, it can circulate this and potentially provide much more rapid clearance of blood volume. In addition, return of CSF back to the patient postfiltration may help reduce overdrainage complications encountered with traditional LDs. It is well known that a significant volume of blood can exist in the lumbar space, escaping detection on head CT. This pooled blood in the lumbar space will likely be more amenable to clearance with LD than EVD. However, the ability of a filtration device to affect the resolution of blood in the brain is unknown; we interpret, in this report, the drop in Hijdra score, proteins, and RBCs as blood being mobilized caudally and anticipate further clearance of RBCs with longer pump times. This will continue to be investigated in this and subsequent trials to interpret results contextually vs SOC. CONCLUSION In conclusion, this is the first case report of an aSAH patient undergoing Neurapheresis therapy (Minnetronix Inc) as part of a clinical trial. Enrollment and data collection are ongoing for this phase 1 trial. Disclosures This publication is not supported by any company or grant funding. The PILLAR clinical trial is supported by Minnetronix Inc. Two co-authors, Dr Verbick and Dr McCabe, are employed by Minnetronix and facilitated data interpretation and preparation of manuscript and figures. Dr Lad has consulted for Minnetronix Inc. He is the coinventor of the Neurapheresis Therapy and is involved in its scientific development. He is not involved in PILLAR clinical enrollment. Dr Blackburn, Dr Swisher, and Dr Grande are site principal investigators and do not receive compensation for the study other than Institutional Review Board approved study related expenses. Ms Rubi has no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. de Rooij NK , Linn FH , van der Plas JA , Algra A , Rinkel GJ . Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends . J Neurol Neurosurg Psychiatry . 2007 ; 78 ( 12 ): 1365 – 1372 . doi: 10.1136/jnnp.2007.117655 . Google Scholar CrossRef Search ADS PubMed 2. Claassen J , Bernardini GL , Kreiter K et al. Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited . Stroke . 2001 ; 32 ( 9 ): 2012 – 2020 . doi: 10.1161/hs0901.095677 . Google Scholar CrossRef Search ADS PubMed 3. Fisher C , Kistler JP . Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning . Neurosurgery . 1980 ; 6 ( 1 ): 1 – 9 . Google Scholar CrossRef Search ADS PubMed 4. Frontera JA , Claassen J , Schmidt JM et al. Prediction of symptomatic vasospasmafter subarachnoid hemorrhage: the modified Fisher scale . Neurosurgery . 2006 ; 59 ( 1 ): 21 – 27 . Google Scholar CrossRef Search ADS PubMed 5. Pluta RM. Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment . Pharmacol Ther . 2005 ; 105 ( 1 ): 23 – 56 . doi: 10.1016/j.pharmthera.2004.10.002 . Google Scholar CrossRef Search ADS PubMed 6. Rifkind JM , Mohanty JG , Nagababu E . The pathophysiology of extracellular hemoglobin associated with enhanced oxidative reactions . Front Physiol . 2015 ; 5 ( 500 ): 1 – 7 . doi: 10.3389/fphys.2014.00500 . 7. Sehba FA , Mostafa G , Knopman J , Friedrich V , Bederson JB . Acute alterations in microvascular basal lamina after subarachnoid hemorrhage . J Neurosurg . 2004 ; 101 ( 4 ): 633 – 640 . doi: 10.3171/jns.2004.101.4.0633 . Google Scholar CrossRef Search ADS PubMed 8. Vecchione C , Frati A , Di Pardo A et al. Tumor necrosis factor-alpha mediates hemolysis-induced vasoconstriction and the cerebral vasospasm evoked by subarachnoid hemorrhage . Hypertension . 2009 ; 54 ( 1 ): 150 – 156 . doi: 10.1161/HYPERTENSIONAHA.108.128124 . Google Scholar CrossRef Search ADS PubMed 9. Klimo P , Kestle JRW , MacDonald JD , Schmidt RH . Marked reduction of cerebral vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage . J Neurosurg . 2004 ; 100 ( 2 ): 215 – 224 . doi: 10.3171/jns.2004.100.2.0215 . Google Scholar CrossRef Search ADS PubMed 10. Al-Tamimi YZ , Bhargava D , Feltbower RG et al. Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS) . Stroke . 2012 ; 43 ( 3 ): 677 – 682 . doi: 10.1161/STROKEAHA.111.625731 . Google Scholar CrossRef Search ADS PubMed 11. Kwon OY , Kim YJ , Kim YJ , Cho CS , Lee SK , Cho MK . The utility and benefits of external lumbar CSF drainage after endovascular coiling on aneurysmal ubarachnoid hemorrhage . J Korean Neurosurg Soc . 2008 ; 43 ( 6 ): 281 – 287 . doi: 10.3340/jkns.2008.43.6.281 . Google Scholar CrossRef Search ADS PubMed 12. Park S , Yang N , Seo E . The effectiveness of lumbar cerebrospinal fluid drainage to reduce the cerebral vasospasm after surgical clipping for aneurysmal subarachnoid hemorrhage . J Korean Neurosurg Soc . 2015 ; 57 ( 3 ): 167 . doi:10.3340/jkns.2015.57.3.167 . Google Scholar CrossRef Search ADS PubMed 13. Dupont SA , Wijdicks EFM , Manno EM , Lanzino G , Rabinstein AA . Prediction of angiographic vasospasm after aneurysmal subarachnoid hemorrhage: value of the Hijdra sum scoring system . Neurocrit Care . 2009 ; 11 ( 2 ): 172 – 176 . doi:10.1007/s12028-009-9247-3 . Google Scholar CrossRef Search ADS PubMed 14. Hijdra A , Brouwers P , Vermeulen M . Grading the amount of blood on computed tomograms after subarachnoid hemorrhage . Stroke . 1990 ; 21 ( 8 ): 1156 – 1161 . Google Scholar CrossRef Search ADS PubMed 15. Pickard JD , Murray GD , Illingworth R et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial . BMJ . 1989 ; 298 ( 6674 ): 636 – 642 . Google Scholar CrossRef Search ADS PubMed 16. Soppi V , Karamanakos PN , Koivisto T et al. A randomized outcome study of enteral versus intravenous nimodipine in 171 patients after acute aneurysmal subarachnoid hemorrhage . World Neurosurg . 2012 ; 78 ( 1-2 ): 101 – 109 . doi: 10.1016/j.wneu.2011.09.030 . Google Scholar CrossRef Search ADS PubMed 17. Wong GKC , Poon WS , Chan MTV et al. Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage (IMASH): a randomized, double-blinded, placebo-controlled, multicenter phase III trial . Stroke . 2010 ; 41 ( 5 ): 921 – 926 . doi: 10.1161/STROKEAHA.109.571125 . Google Scholar CrossRef Search ADS PubMed 18. Macdonald RL , Higashida RT , Keller E et al. Randomized trial of Clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling . Stroke . 2012 ; 43 ( 6 ): 1463 – 1469 . doi: 10.1161/STROKEAHA.111.648980 . Google Scholar CrossRef Search ADS PubMed 19. Turner CL , Smith C , Murray GD , Hutchinson PJ , Kirkpatrick PJ . 204 simvastatin in aneurysmal subarachnoid haemorrhage (STASH) trial . Neurosurgery . 2014 ; 61 ( suppl 1 ): 228 . doi: 10.1227/01.neu.0000452478.36194.df . Google Scholar CrossRef Search ADS 20. Bardutzky J , Witsch J , Jüttler E , Schwab S , Vajkoczy P , Wolf S . EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial . Trials . 2011 ; 12 : 203 . doi: 10.1186/1745-6215-12-203 . Google Scholar CrossRef Search ADS PubMed Acknowledgment The authors wish to thank Kanako Matsumura for assistance with the PILLAR study and data collection. COMMENTS This is an interesting idea and an innovative system to filter out the blood after subarachnoid hemorrhage. However, neither the safety nor the efficacy are proven, and we need to wait for the results of the phase 1 study of 15 patients. I hope that the authors will be successful. Laligam N. Sekhar Seattle, Washington In this report, the authors provide a case and technical description of the first use of the Neurapheresis therapy (Minnetronix Inc) system for lumbar CSF filtration following aneurysmal subarachnoid hemorrhage (aSAH). This report provides an introduction to this novel therapy and a primer on the pending clinical trial (PILLAR study) that is underway. Like the authors, we are keenly interested to see if implementation of this device in the setting of aSAH can reduce vasospasm or speed recovery in this challenging group of patients. One concern is whether the implementation of CSF filtration in these patients will be “too-little-too-late”; it may be that the inflammatory cascade that is initiated by aneurysmal rupture may persist despite removal of the blood products after the fact. However, if proven efficacious, this strategy hasthe potential to drastically change the clinical management of aSAH patients in the future. We commend the authors for embarking on this interesting undertaking. Michael Mooney Peter Nakaji Phoenix, Arizona The definitive pathophysiology of cerebral vasospasm (delayed cerebral ischemia) remains elusive. Thus, we are left managing the symptoms of this oftentimes deleterious phenomenon. Nevertheless, anecdotally, it seems that the incidence of symptomatic cerebral vasospasm is decreasing. This may be due to multifactorial reasons, however, improvements in the intensive care management of these patients may play a role. Though there may be disagreements regarding the pathophysiology and incidence of this phenomenon, there seems to be overall consensus that substances in the CSF likely contribute to its development. Though the concept of clearing the CSF the authors propose is not novel, they report the first patient treated with a novel device. This paper does not establish neither the safety or efficacy of their device, however, does show that it is feasible in this one patient. I look forward to seeing a larger patient series reported from this group and I congratulate the authors on this interesting and novel device that could potentially have significant clinical benefit. Ketan R. Bulsara Farmington, Connecticut Copyright © 2018 by the Congress of Neurological Surgeons This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Operative NeurosurgeryOxford University Press

Published: Jun 5, 2018

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