Prospective Evaluation of Icu Neurostimulant Use for Acute Brain Injury (Prevail): A Pragmatic Observational Cohort Study

Prospective Evaluation of Icu Neurostimulant Use for Acute Brain Injury (Prevail): A Pragmatic Observational Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prospective Evaluation of Icu Neurostimulant Use for Acute Brain Injury (Prevail): A Pragmatic Observational Cohort Study Richard Robert Riker, Haley R Torr, Sara Penrod, Stephanie C Chan, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8744330/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Amantadine, an effective neurostimulant for traumatic brain injury, has limited data supporting its use for other acute brain injuries (ABI). This pragmatic study evaluated amantadine for nontraumatic ABI monitored in the ICU with the Coma Recovery Scale-Revised (CRS-R). Methods: This prospective open-label cohort study developed a protocol to treat impaired consciousness after ABI with amantadine, assessing participants with CRS-R as 0-100 Rasch units, monitoring feasibility, safety, and effectiveness. Results: 40 patients (age 64 [52-73] years, 25 [62%] female) were included during this protocol development phase: 13 ischemic stroke, 10 intracerebral hemorrhage, 7 subarachnoid hemorrhage, 4 hypoxic-ischemic encephalopathy, 3 other ABI. The median baseline CRS-R was 11 (IQR 7-16), including 16 meeting criteria for Disorder of Consciousness. Among 30 participants with an adequate amantadine treatment trial, 27 (90%) responded, with disposition to home (1,4%), skilled nursing facility (6,22%), acute inpatient rehabilitation (15,56%), or withdrawal of life support (5,18%). Pre- versus post-treatment CRS-R increased for responders by 8 (6-11), equivalent to 26 (15-45) Rasch units. Among 10 untreated or inadequate trial patients, 3 (30%) were discharged to rehab, 7 (70%) had support withdrawn. Conclusions: It is feasible to measure responsiveness to amantadine using the CRS-R for ICU patients with ABI. acute ischemic stroke intracerebral hemorrhage central nervous system stimulant amantadine brain injuries disorders of consciousness Figures Figure 1 Figure 2 Full Text Clinical practice guidelines and roundtables recommend early rehabilitation after stroke and acute brain injury, 1,2,3 emphasizing multimodal interventions (e.g., medications and therapy); early recovery and pharmacological interventions are priorities for research. 3,4 A recent systematic review examined neurostimulant administration after stroke, suggesting favorable responses in 70% of studies administering amantadine. 5 Many outcome measures were utilized in the 22 studies reviewed, suggesting that no single indication for neurostimulant use nor measure of response has been identified. 5 Among 10 studies administering amantadine in that review, only one publication included 5 patients during their acute post-stroke care. 6 We previously reported our experience with neurostimulant use in 87 acute stroke patients, with 55% of patients receiving amantadine showing early improvement. 7 Among several limitations identified, the Glasgow Coma Scale proved challenging to assess response to therapy, prompting us and others to suggest other tools for future studies. 3,7 Other challenges reported in caring for ICU patients with acute severe brain injuries include identifying Disorders of Consciousness (DoC), monitoring patients serially, identifying common confounders of consciousness assessment, and intervening acutely to improve consciousness. 3 We performed this prospective, single-center, observational cohort study with an interprofessional team to address these concerns, developing an amantadine treatment protocol for impaired consciousness related to acute, nontraumatic brain injuries (Figure 1). The decision to initiate amantadine in this pragmatic trial was made by the bedside team with input from clinical pharmacology, physiatry, physical and occupational therapy, and speech-language pathology. Participants were assessed with the Coma Recovery Scale-Revised (CRS-R), a validated, reliable, and recommended tool performed by trained Speech-Language Pathologists (SLP) experienced in assessing DoC. 3,8 We also monitored the feasibility, safety, and effectiveness of this protocol. The MaineHealth IRB determined this treatment protocol development to be exempt from review [2102955-1]. We included adult patients with impaired consciousness associated with an acute brain injury, primarily focusing on acute ischemic stroke (AIS) or non-traumatic intracranial hemorrhage (ICH). Patients with other acute brain injuries (e.g. subarachnoid hemorrhage [SAH], hypoxic-ischemic encephalopathy [HIE] after cardiac arrest, or other causes) selected to receive amantadine were also monitored. Efforts to improve the clinical status of the patient by identifying and treating reversible causes prior to initiating amantadine therapy were also monitored. 3,7 Based on potential confounders identified in prior studies, 3,5,7 we excluded patients with a premorbid modified Rankin Scale (mRS) score ≥2, elevated intracranial pressure requiring pharmacologic intervention, those receiving amantadine for other indications (e.g., Parkinson’s disease), patients requiring continuous or scheduled sedation, those with active seizures requiring continuous electroencephalographic monitoring, and those with agitation or hyperactive delirium being treated pharmacologically. To provide comparative data during this pragmatic study, those assessed with the protocol but not treated with amantadine or those treated with amantadine for less than 96 hours were included a priori as a comparison group. We aimed to document the CRS-R prior to the first dose of amantadine and every 4-7 days. Descriptive clinical outcomes included maximum amantadine dose, change in CRS-R from pre-treatment scores, and discharge disposition (acute rehabilitation, home, skilled nursing facility, hospice, or death). Severity of acute brain injury was documented with the National Institutes of Health Stroke Scale (NIHSS) for AIS, 9 the ICH score for non-traumatic ICH, 10 the Hunt-Hess score for SAH, 11 the suppression ratio 6-hours after recovery of spontaneous circulation (SR6) for those with HIE after cardiac arrest, 12,13 and pre-treatment admission Glasgow Coma Scale (GCS) for other etiologies of acute brain injury. Amantadine was administered with a starting dose of 100 mg administered twice daily at 06:00 and 14:00 with dose adjustments for renal dysfunction. The primary effectiveness outcome of this pragmatic study was the consensus determination by the bedside clinical and rehabilitation team whether the patient was more responsive after initiating amantadine. We also monitored the CRS-R change from baseline to highest value prior to hospital discharge using the Rasch-transformed 0-100 measures of the CRS-R scores, 14,15 with a threshold of 9 units. 15 Safety parameters included need for new or increased sleep medication, new or worse agitation by Sedation-Agitation Scale scores, 16,17 new myoclonus or seizure, hyperactive delirium requiring new pharmacologic treatment, and amantadine discontinuation or dose adjustment due to a suspected adverse effect. Continuous and ordinal variables are presented as median (interquartile range - IQR), nominal variables as number (%). No inferential statistical comparisons were planned in this observational study. Forty patients were managed with this evolving protocol from January 2021 to February 2024, including 13 with AIS, 10 with ICH, 7 with SAH, 4 with HIE, 3 with infectious encephalitis, and 1 each with brain tumor, toxic ingestion, and severe sepsis encephalopathy. The median age was 64 (52-73) years, and 25 (62%) were female ( Table 1 ). Sixteen (40%) participants met criteria for acute DoC (coma in 1, unresponsive wakefulness syndrome in 6, lower level minimally conscious state in 7, higher level minimally conscious state in 2), and 18 had milder cognitive-linguistic disorders. Amantadine treatment was initiated in 32 participants a median of 9 (6-16) days after admission, but stopped after 4 or less days in two who were considered inadequately treated to assess for responsiveness; 8 patients never received amantadine per bedside team decision. Among the 30 participants with an adequate amantadine treatment course, 27 (90%) were considered responders who were discharged home (1;4%), to skilled nursing (6;22%), rehabilitation (15;56%), or transition to withdrawal of life support (WLS) (5;18%). Six early participants were not assessed at baseline prior to initiating amantadine. The median baseline CRS-R was 11 (7-16) and 20 responders with pre- and post-CRS-R data had a median increase of 8 (6-11), equivalent to 26 (15-45) Rasch units ( Supplemental Table 1 ). Serial CRS-R testing among 4 participants with delayed or no amantadine therapy and 4 with amantadine therapy are shown in Figure 2 as examples. All 20 responders with pre- and post-CRS-R data increased by 9 or more Rasch units, the minimal detectable change previously identified to exceed measurement error. 15 The disposition for the 8 patients not treated with amantadine included 3 (38%) discharged to rehabilitation and 5 (62%) transitioned to WLS; both patients who received inadequate trials of amantadine transitioned to WLS. Among 6 participants with an initial CRS-R arousal subscale of 2, both treated patients were transferred to acute inpatient rehabilitation, while 2 of 4 untreated participants transitioned to WLS. Among 32 participants receiving amantadine, 23 (72%) experienced no adverse drug effects, and 9 experienced one or more adverse drug effect potentially related to amantadine, including agitation in three which improved after amantadine was stopped or dose-reduced, and sleeplessness in three which improved despite continuation in one and after stopping in two. Amantadine was reduced from 200 mg to 150 mg twice daily in one patient due to intermittent myoclonus which improved with the dose reduction but was associated with a reduced CRS-R (Line 6, Figure 2). Seizures were suspected in two patients: amantadine was continued until WLS in one without further events and stopped after 5 days in another without further seizure activity. Several striking and rapid improvements in arousal were observed, including one patient untreated for a week with no improvement prompting a PEG to be scheduled, but then cancelled when wakefulness and swallowing improved dramatically within 48 hours of starting amantadine (Line 39 in Figure 2). Representative quotes from patient assessments are included in Supplemental Table 2 . This open-label, observational study showed that it is feasible to assess ICU patients with the CRS-R, evaluate potential confounders, and suggested that most participants receiving an adequate trial of amantadine for nontraumatic brain injury responded clinically and when comparing pre- and post-treatment assessments with the 0-100 Rasch transformation of the CRS-R. 14,15 The CRS-R has been shown to be more reliable than the Glasgow Coma Scale, 3,18 and SLP professionals were better able to obtain these data after identifying methods to facilitate assessment and communication, including emails and pharmacist contact when amantadine was ordered, SLP contact after amantadine was discussed on rounds, and establishing a larger pool of SLPs trained to perform the CRS-R. These advances to detect DoC among ICU patients, monitor them serially, and address potential confounders are needed for future successful clinical trials. 3 As a non-randomized and unblinded study, potential bias and clinical improvement related to natural history rather than the intervention is possible, and these results must be considered hypothesis generating. We did not require that subjects met formal criteria for DoC to be treated in this cohort study, and many questions remain unanswered regarding use of amantadine during acute care of nontraumatic brain injuries, including disease- and anatomic location-specific responsiveness, severity of impairment most likely to respond, dose escalation and duration strategies, criteria for exclusion (e.g. prior restlessness or seizures, sympathetic storming, etc), 3,7 and patient- and family-centered outcomes. These data and results may guide future neurostimulant trials in the ICU aiming to improve consciousness after brain injury. Declarations This manuscript complies with all instructions to authors Author contributions: RRR, HRT, and DJG conceptualized the study design; RRR, HRT, DJG, and SP collected data; and all authors (RRR, HRT, DJG, SP, SCC, AL, TLM, DBS) contributed to analysis and interpretation of the data; and revision and approval of the manuscript. Authorship requirements have been met and the final manuscript was approved by all authors This manuscript has not been published elsewhere and is not under consideration by another journal We have adhered to ethical guidelines and indicate ethical approvals (IRB) and waiver of informed consent RRR received a research grant from SHINKEI Therapeutics as part of the Phase 2 Clinical Trial of MR-301 in Severe Traumatic Brain Injury. All other authors declare that they have no Conflicts of Interest to disclose. No reporting checklist is required for this Brief Communication Funding : This study was funded by NIH NIGMS P20GM139745 and departmental funds. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the US government. The funders had no role in the design, analysis, preparation, review, approval, or decision to submit this manuscript for publication. References Winstein CJ, Stein J, Arena R, et al. Guidelines for adult stroke rehabilitation and recovery. Stroke 2016;47:e98-169. Powers WJ, Rabinstein AA, Ackerson R, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke. Stroke 2019;50:e344-e418. Bodien YG, Busl KM, Chang CWJ, et al. Disorders of consciousness diagnosis, interventions, and prognostication for the intensivist: Report of the 2025 ISICEM roundtable. Intensive Care Med 2026;52(1):42-62. Vickrey BG, Brott TG, Koroshetz WJ, et al. Stroke research priorities meeting steering committee and the national advisory Neurological Disorders and Stroke Council, National Institute of Neurological Disorders and Stroke. Research priority setting: a summary of the 2012 NINDS Stroke Planning Meeting Report. Stroke 2013;44:2338-42. Gagnon DJ, Leclerc AM, Riker RR, et al. Amantadine and modafinil as neurostimulants during post-stroke care: a systematic review. Neurocritical Care 2020; 33(1):283-97. Akçıl EF, Dilmen ÖK, Vehid H, Tunalı Y. Can amantadine ameliorate neurocognitive functions after subarachnoid haemorrhage? A preliminary study. Turk J Anaesthesiol Reanim 2018;46(2):100–7. Leclerc AM, Riker RR, Brown CS, et al. Amantadine and modafinil as neurostimulants following acute stroke: a retrospective study of intensive care unit patients. Neurocritical Care 2021;34(1):102-11. Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale- Revised: measurement characteristics and diagnostic utility. Archives of Physical Medicine and Rehabilitation 2004;85(12):2020-9. Lindsell CJ, Alwell K, Moomaw CJ, et al. Validity of a retrospective National Institutes of Health Stroke Scale scoring methodology in patients with severe stroke. J Stroke Cardiovasc Dis 2005;14(6):281-3. Hemphill JC, Bonovich DC, Besmertis L, et al. The ICH Score. Stroke 2001;32:891-7. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. Journal of Neurosurgery 1968;28(1):14-20. Seder DB, Fraser GL, Robbins T, Libby L, Riker RR. The bispectral index and suppression ratio are very early predictors of neurological outcome during therapeutic hypothermia after cardiac arrest. Intensive Care Med 2010;36(2):281-8. Riker RR, Craig A, Eubank L, May T, Seder DB. Validation of the suppression ratio from a simplified EEG montage during targeted temperature management after cardiac arrest. Resuscitation 2020;153:1-5. Weaver JA, Cogan AM, Kozlowski AJ, et al. Interpreting change in disorders of consciousness using the Coma Recovery Scale-Revised. Journal of Neurotrauma 2024;41(15-16):e1996-e2008. Cogan AM, Grady-Dominguez P, Dobson CG, et al. Association of patient characteristics with recovery in adults with Disorders of Consciousness. Archives of Physical Medicine and Rehabilitation 2025;S0003-9993(25)00661-6. Riker RR, Fraser GL, Cox PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med 1994;22:433-40. Riker RR, Picard JT, GL Fraser. Prospective evaluation of the sedation-agitation scale in adult ICU patients. Crit Care Med 1999;27:1325-9. Schnakers C, Majerus S, Giacino J, et al. A French validation study of the Coma Recovery Scale-Revised (CRS-R). Brain Inj 2008;22(10):786-92. Table Table 1: Diagnoses, Demographics, Amantadine Dose and Response, Discharge Disposition # Diagnosis Severity Age Gender DOC Respond Start Day* -- Max Dose Rx@DC Comment Dispo 1 West Nile GCS 11 72 M -- Yes 22 -- 100 mg BID No Weaned off (sleep) Rehab 2 ICH ICH 3 35 F MCS+ Yes 11 -- 200 mg BID Yes Emerged DOC Rehab 3 ICH ICH 4 28 F MCS- Yes 9 -- 200 mg BID No Family request to stop SNF 4 ICH ICH 2 46 M -- Yes 3 -- 150 mg BID Yes See Quote Rehab 5 SAH HH 4 61 F MCS- Yes 9 -- 200 mg BID -- Stopped at WLS died WLS 6 CA HIE SR6 50 65 M UWS Yes 6 -- 200 mg BID -- Stopped at WLS Hospice 7 IS NIH 20 48 F UWS Yes 4 -- 150 mg BID No Stopped for seizure risk (no new events) Rehab 8 IS NIH 32 69 M -- Yes 6 -- 150 mg BID Yes Modafinil added Rehab 9 IS NIH 26 60 M MCS- Yes 5 -- 100 mg BID Yes PEG discontinued Rehab 10 ICH ICH 0 61 M -- No 8 -- 200 mg BID -- Stopped at WLS Hospice 11 IVH ICH 5 68 M CLD Not Treated See Quote Hospice 12 SAH ICH 4 64 M CLD Not Treated See Quote Rehab 13 SAH HH 5 77 F CLD Yes 17 -- 100 mg BID Yes Improved - po diet Rehab 14 SAH HH 4 45 F CLD/A Yes 16 -- 100 mg BID Yes See Quote SNF 15 ICH ICH 3 74 M CLD Yes 14 -- 100 mg BID -- Stopped at WLS Hospice 16 IS NIH 13 90 M CLD/A Short Treat 3 -- 100 mg BID -- Stopped at WLS Hospice 17 IS NIH 38 48 F -- Yes 21 -- 200 mg BID Yes Tracheostomy removed PEG discontinued SNF 18 IS NIH 18 78 F CLD Yes 9 -- 150 mg BID Yes PEG discontinued Rehab 19 IS NIH 22 64 M CLD Not Treated See Quote Rehab 20 IS NIH 40 57 F COMA Not Treated Not Rx due to PSH died WLS 21 Brain Mass GCS 9 79 M MCS- Yes 39 -- 200 mg BID -- Continued until death died IHCA 22 VPA Tox GCS 4 54 F -- No 23 -- 100 mg BID No Held after 5 days concern for seizures Home Services 23 ICH ICH 3 73 F MCS- Yes 6 -- 100 mg BID Yes See Quote Rehab 24 CA HIE SR6 99 64 M MCS- Yes 8 -- 100 mg BID -- Stopped at WLS died WLS 25 IS NIH 32 58 F MCS+ Yes 27 -- 100 mg BID No Stopped due to agitation -- not improved after Rehab 26 ICH ICH 3 65 F CLD Yes 6 -- 100 mg BID -- Stopped at WLS Hospice 27 SAH HH 2 29 F CLD/A Yes 8 -- 100 mg BID Yes See Quote Rehab 28 CA HIE SR6 70 31 M CLD Yes 15 -- 100 mg BID Yes Tolerated after ICP and PSH controlled Rehab 29 ICH ICH 3 59 F CLD Yes 9 -- 200 mg BID No Stopped day 22 – delirium, poor sleep Rehab 30 IS NIH 33 85 F CLD Not Treated Recommended by SLP, never started died WLS 31 IS NIH 30 69 F CLD/A Not Treated Transferred out ICU Rehab 32 ICH ICH 4 80 M UWS Short Treat 3 -- 50 mg BID -- “Never wanted this care” died WLS 33 ICH-IVH ICH 3 81 F CLD Not Treated “No escalation care” died WLS 34 Powassan GCS 5 76 F CLD Yes 23 -- 100 mg BID No Stopped on floor – NPO severe ileus Rehab 35 Enceph GCS 6 64 F MCS- Yes 7 -- 200 mg BID Yes See Quote SNF 36 IS NIH 34 73 F UWS Not Treated Transitioned WLS Hospital Day 2 died WLS 37 CA HIE SR6 70 38 F UWS Yes 8 -- 200 mg BID No Agitation improved when weaned off Home Services 38 IS NIH 28 44 F UWS Yes 3 -- 200 mg BID Yes See Quote Rehab 39 SAH HH 2 72 F CLD Yes 18 -- 125 mg BID Yes Improved with RX, PEG cancelled SNF 40 EEE GCS 11 66 F CLD Yes 14 -- 100 mg BID No Stopped at discharge per Neurology SNF *Start Day – number of days from first hospital admission to first dose of amantadine; Max Dose - maximum dose of amantadine BID, twice daily; CA HIE, cardiac arrest hypoxic-ischemic encephalopathy; CLD, cognitive-linguistic disorder; CLD/A, cognitive linguistic disorder with aphasia; DOC; Disorder of Consciousness; Dispo, disposition; EEE, Eastern Equine Encephalitis; Enceph, encephalopathy; F, female; GCS, Glasgow coma scale; HH, Hunt Hess; Home SVC, home with services; ICH, intracranial hemorrhage; ICP, intracranial pressure; IHCA, in-hospital cardiac arrest; IS, ischemic stroke; IVH, intraventricular hemorrhage; M, male; MCS, minimally conscious state; mg, milligrams; NIH, NIH Stroke scale; NPO, nothing by mouth; PEG, percutaneous endoscopic gastrostomy tube; Powassan, Powassan virus encephalitis; PSH, paroxysmal sympathetic hyperactivity; Rehab, inpatient rehabilitation; Rx@DC, Treated at Discharge; SAH, subarachnoid hemorrhage; SLP, Speech-Language Pathologist; SNF, skilled nursing facility; SR6, suppression ratio 6 hours after recovery of spontaneous circulation; UWS, unresponsive wakefulness syndrome; VPA tox, valproic acid toxicity; West Nile, West Nile encephalitis; WLS, Withdrawal of Life Support. Supplementary Files 2026PREVAILSupplementalTable1.docx 2026PREVAILSupplementalTable2.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8744330","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":585940711,"identity":"23aa0be3-987a-41f1-9ff8-17a144c535f5","order_by":0,"name":"Richard Robert Riker","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYFACxmYgYQNhJ5CgJY0kLQzMQHyYBGeZzz7cbPBxz3l53fbTiR8e7rBh4G/vxm+ZzLnE5sQZz24bbjuTu1ki8Uwag8SZsxvwapHgYWw+zHPgdoLZgdwNEolthxkMJHKJ0PLnwLkEs/NvN/9IbPtPnJZkhgMHEsxu5G4D2nKAOC2GPQeSDbfdeLvNIrEtmYcIv7A/lvhxwE7e7Hzu5ps/2+zk+Nt78WvBADykKR8Fo2AUjIJRgBUAAHrSSZbYPxnAAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0682-6204","institution":"Maine Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Richard","middleName":"Robert","lastName":"Riker","suffix":""},{"id":585940712,"identity":"c4665505-8cf3-449d-8d38-9049efdfa993","order_by":1,"name":"Haley R Torr","email":"","orcid":"","institution":"Maine Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Haley","middleName":"R","lastName":"Torr","suffix":""},{"id":585940713,"identity":"8646b30c-482c-493d-8f94-8e1f7862cbdd","order_by":2,"name":"Sara Penrod","email":"","orcid":"","institution":"Maine Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Penrod","suffix":""},{"id":585940714,"identity":"295a1351-4620-4b09-b115-ce91f5ac5dad","order_by":3,"name":"Stephanie C Chan","email":"","orcid":"","institution":"Maine Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Stephanie","middleName":"C","lastName":"Chan","suffix":""},{"id":585940715,"identity":"b7294857-d5bc-42fc-baf8-22e6239be891","order_by":4,"name":"Angela Leclerc","email":"","orcid":"","institution":"Maine Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Angela","middleName":"","lastName":"Leclerc","suffix":""},{"id":585940716,"identity":"f7d0f99d-2bdd-4895-accf-1172f9502027","order_by":5,"name":"Teresa L May","email":"","orcid":"","institution":"Maine Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Teresa","middleName":"L","lastName":"May","suffix":""},{"id":585940717,"identity":"1a479cf5-3bab-40de-817d-8679a9c0bdbe","order_by":6,"name":"David B Seder","email":"","orcid":"","institution":"Maine Medical Center","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"B","lastName":"Seder","suffix":""},{"id":585940718,"identity":"0314c8ae-9984-4e14-978f-ddaba6761ace","order_by":7,"name":"David J Gagnon","email":"","orcid":"","institution":"Maine Medical Center","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"J","lastName":"Gagnon","suffix":""}],"badges":[],"createdAt":"2026-01-30 19:07:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8744330/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8744330/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102260856,"identity":"efb5a927-2caa-46ce-998b-f75469a5c00f","added_by":"auto","created_at":"2026-02-10 00:35:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":123088,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAmantadine Initiation Algorithm\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCAM-ICU, Confusion Assessment Method for the ICU; cEEG, continuous electroencephalography; CrCl, Creatinine Clearance; CRS-R, Coma Recovery Scale-Revised; OT, Occupational Therapy; SLP, Speech-Language Pathology; SAS, Sedation-Agitation Scale;\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8744330/v1/a1c14bd3d4073b77391e6346.png"},{"id":102260855,"identity":"a74a8482-172f-4ddb-8678-5ccb34296795","added_by":"auto","created_at":"2026-02-10 00:35:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":93137,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCRS-R Rasch Unit Over Time for 4 Treated and 4 Untreated or Delayed Treatment Participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNumbers identify participant from Table 1. Dotted lines and open squares represent no treatment periods. Solid circles and lines represent treatment periods. Fatter or skinnier lines represent an increase or decrease in amantadine dose (Line 6). Day represents day after hospital admission.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8744330/v1/6fb80b8114e976f43444aa5f.png"},{"id":104405236,"identity":"e4291f0d-2dfd-4f8c-a75e-3f690da407b3","added_by":"auto","created_at":"2026-03-11 12:22:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":832085,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8744330/v1/8a8a6694-c76d-45cc-9e38-99d4fe047dad.pdf"},{"id":102297580,"identity":"7d475f25-7b72-4930-be82-e4995ec9e5be","added_by":"auto","created_at":"2026-02-10 10:28:20","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":40706,"visible":true,"origin":"","legend":"","description":"","filename":"2026PREVAILSupplementalTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8744330/v1/9c36e0db3da96dff8dd13f14.docx"},{"id":102260858,"identity":"fa0e91f6-cc9e-43d5-85c1-a96a981e8ee8","added_by":"auto","created_at":"2026-02-10 00:35:31","extension":"docx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":49271,"visible":true,"origin":"","legend":"","description":"","filename":"2026PREVAILSupplementalTable2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8744330/v1/10efbdb55a059e76db5b058e.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eProspective Evaluation of Icu Neurostimulant Use for Acute Brain Injury (Prevail): A Pragmatic Observational Cohort Study\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"\u003cp\u003eClinical practice guidelines and roundtables recommend early rehabilitation after stroke and acute brain injury,\u003csup\u003e1,2,3\u003c/sup\u003e emphasizing multimodal interventions (e.g., medications and therapy); early recovery and pharmacological interventions are priorities for research.\u003csup\u003e3,4\u003c/sup\u003e\u0026nbsp; A recent systematic review examined neurostimulant administration after stroke, suggesting favorable responses in 70% of studies administering amantadine.\u003csup\u003e5\u003c/sup\u003e Many outcome measures were utilized in the 22 studies reviewed, suggesting that no single indication for neurostimulant use nor measure of response has been identified.\u003csup\u003e5\u003c/sup\u003e Among 10 studies administering amantadine in that review, only one publication included 5 patients during their acute post-stroke care.\u003csup\u003e6\u003c/sup\u003e\u0026nbsp; We previously reported our experience with neurostimulant use in 87 acute stroke patients, with 55% of patients receiving amantadine showing early improvement.\u003csup\u003e7\u003c/sup\u003e\u0026nbsp; Among several limitations identified, the Glasgow Coma Scale proved challenging to assess response to therapy, prompting us and others to suggest other tools for future studies.\u003csup\u003e3,7\u003c/sup\u003e Other challenges reported in caring for ICU patients with acute severe brain injuries include identifying Disorders of Consciousness (DoC), monitoring patients serially, identifying common confounders of consciousness assessment, and intervening acutely to improve consciousness.\u003csup\u003e3\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe performed this prospective, single-center, observational cohort study with an interprofessional team to address these concerns, developing an amantadine treatment protocol for impaired consciousness related to acute, nontraumatic brain injuries (Figure 1). \u0026nbsp;The decision to initiate amantadine in this pragmatic trial was made by the bedside team with input from clinical pharmacology, physiatry, physical and occupational therapy, and speech-language pathology. \u0026nbsp;Participants were assessed with the Coma Recovery Scale-Revised (CRS-R), a validated, reliable, and recommended tool performed by trained Speech-Language Pathologists (SLP) experienced in assessing DoC.\u003csup\u003e3,8\u003c/sup\u003e We also monitored the feasibility, safety, and effectiveness of this protocol. \u0026nbsp;The MaineHealth IRB determined this treatment protocol development to be exempt from review [2102955-1].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe included adult patients with impaired consciousness associated with an acute brain injury, primarily focusing on acute ischemic stroke (AIS) or non-traumatic intracranial hemorrhage (ICH). Patients with other acute brain injuries (e.g. subarachnoid hemorrhage [SAH], hypoxic-ischemic encephalopathy [HIE] after cardiac arrest, or other causes) selected to receive amantadine were also monitored. \u0026nbsp;Efforts to improve the clinical status of the patient by identifying and treating reversible causes prior to initiating amantadine therapy were also monitored.\u003csup\u003e3,7\u003c/sup\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBased on potential confounders identified in prior studies,\u003csup\u003e3,5,7\u003c/sup\u003e we excluded patients with a premorbid modified Rankin Scale (mRS) score \u0026ge;2, elevated intracranial pressure requiring pharmacologic intervention, those receiving amantadine for other indications (e.g., Parkinson\u0026rsquo;s disease), patients requiring continuous or scheduled sedation, those with active seizures requiring continuous electroencephalographic monitoring, and those with agitation or hyperactive delirium being treated pharmacologically. To provide comparative data during this pragmatic study, those assessed with the protocol but not treated with amantadine or those treated with amantadine for less than 96 hours were included \u003cem\u003ea priori\u0026nbsp;\u003c/em\u003eas a comparison group. We aimed to document the CRS-R prior to the first dose of amantadine and every 4-7 days.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDescriptive clinical outcomes included maximum amantadine dose, change in CRS-R from pre-treatment scores, and discharge disposition (acute rehabilitation, home, skilled nursing facility, hospice, or death). Severity of acute brain injury was documented with the National Institutes of Health Stroke Scale (NIHSS) for AIS,\u003csup\u003e9\u003c/sup\u003e the ICH score for non-traumatic ICH,\u003csup\u003e10\u003c/sup\u003e the Hunt-Hess score for SAH,\u003csup\u003e11\u003c/sup\u003e the suppression ratio 6-hours after recovery of spontaneous circulation (SR6) for those with HIE after cardiac arrest,\u003csup\u003e12,13\u003c/sup\u003e and pre-treatment admission Glasgow Coma Scale (GCS) for other etiologies of acute brain injury. \u0026nbsp; Amantadine was administered with a starting dose of 100 mg administered twice daily at 06:00 and 14:00 with dose adjustments for renal dysfunction.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe primary effectiveness outcome of this pragmatic study was the consensus determination by the bedside clinical and rehabilitation team whether the patient was more responsive after initiating amantadine. \u0026nbsp;We also monitored the CRS-R change from baseline to highest value prior to hospital discharge using the Rasch-transformed 0-100 measures of the CRS-R scores,\u003csup\u003e14,15\u003c/sup\u003e with a threshold of 9 units.\u003csup\u003e15\u003c/sup\u003e Safety parameters included need for new or increased sleep medication, new or worse agitation by Sedation-Agitation Scale scores,\u003csup\u003e16,17\u003c/sup\u003e new myoclonus or seizure, hyperactive delirium requiring new pharmacologic treatment, and amantadine discontinuation or dose adjustment due to a suspected adverse effect. \u0026nbsp; Continuous and ordinal variables are presented as median (interquartile range - IQR), nominal variables as number (%). No inferential statistical comparisons were planned in this observational study. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eForty patients were managed with this evolving protocol from January 2021 to February 2024, including 13 with AIS, 10 with ICH, 7 with SAH, 4 with HIE, 3 with infectious encephalitis, and 1 each with brain tumor, toxic ingestion, and severe sepsis encephalopathy. The median age was 64 (52-73) years, and 25 (62%) were female (\u003cstrong\u003eTable 1\u003c/strong\u003e). \u0026nbsp;Sixteen (40%) participants met criteria for acute DoC (coma in 1, unresponsive wakefulness syndrome in 6, lower level minimally conscious state in 7, higher level minimally conscious state in 2), and 18 had milder cognitive-linguistic disorders.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmantadine treatment was initiated in 32 participants a median of 9 (6-16) days after admission, but stopped after 4 or less days in two who were considered inadequately treated to assess for responsiveness; 8 patients never received amantadine per bedside team decision. Among the 30 participants with an adequate amantadine treatment course, 27 (90%) were considered responders who were discharged home (1;4%), to skilled nursing (6;22%), rehabilitation (15;56%), or transition to withdrawal of life support (WLS) (5;18%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSix early participants were not assessed at baseline prior to initiating amantadine. \u0026nbsp;The median baseline CRS-R was 11 (7-16) and 20 responders with pre- and post-CRS-R data had a median increase of 8 (6-11), equivalent to 26 (15-45) Rasch units (\u003cstrong\u003eSupplemental Table\u003c/strong\u003e \u003cstrong\u003e1\u003c/strong\u003e). Serial CRS-R testing among 4 participants with delayed or no amantadine therapy and 4 with amantadine therapy are shown in \u003cstrong\u003eFigure 2\u0026nbsp;\u003c/strong\u003eas examples. All 20 responders with pre- and post-CRS-R data increased by 9 or more Rasch units, the minimal detectable change previously identified to exceed measurement error.\u003csup\u003e15\u003c/sup\u003e\u0026nbsp; \u0026nbsp;The disposition for the 8 patients not treated with amantadine included 3 (38%) discharged to rehabilitation and 5 (62%) transitioned to WLS; both patients who received inadequate trials of amantadine transitioned to WLS. Among 6 participants with an initial CRS-R arousal subscale of 2, both treated patients were transferred to acute inpatient rehabilitation, while 2 of 4 untreated participants transitioned to WLS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong 32 participants receiving amantadine, 23 (72%) experienced no adverse drug effects, and 9 experienced one or more adverse drug effect potentially related to amantadine, including agitation in three which improved after amantadine was stopped or dose-reduced, and sleeplessness in three which improved despite continuation in one and after stopping in two. Amantadine was reduced from 200 mg to 150 mg twice daily in one patient due to intermittent myoclonus which improved with the dose reduction but was associated with a reduced CRS-R (Line 6, Figure 2). Seizures were suspected in two patients: amantadine was continued until WLS in one without further events and stopped after 5 days in another without further seizure activity. Several striking and rapid improvements in arousal were observed, including one patient untreated for a week with no improvement prompting a PEG to be scheduled, but then cancelled when wakefulness and swallowing improved dramatically within 48 hours of starting amantadine (Line 39 in Figure 2). \u0026nbsp; \u0026nbsp; Representative quotes from patient assessments are included in \u003cstrong\u003eSupplemental Table 2\u003c/strong\u003e. \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis open-label, observational study showed that it is feasible to assess ICU patients with the CRS-R, evaluate potential confounders, and suggested that most participants receiving an adequate trial of amantadine for nontraumatic brain injury responded clinically and when comparing pre- and post-treatment assessments with the 0-100 Rasch transformation of the CRS-R.\u003csup\u003e14,15\u003c/sup\u003e The CRS-R has been shown to be more reliable than the Glasgow Coma Scale,\u003csup\u003e3,18\u003c/sup\u003e and SLP professionals were better able to obtain these data after identifying methods to facilitate assessment and communication, including emails and pharmacist contact when amantadine was ordered, SLP contact after amantadine was discussed on rounds, and establishing a larger pool of SLPs trained to perform the CRS-R. These advances to detect DoC among ICU patients, monitor them serially, and address potential confounders are needed for future successful clinical trials.\u003csup\u003e3\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs a non-randomized and unblinded study, potential bias and clinical improvement related to natural history rather than the intervention is possible, and these results must be considered hypothesis generating. We did not require that subjects met formal criteria for DoC to be treated in this cohort study, and many questions remain unanswered regarding use of amantadine during acute care of nontraumatic brain injuries, including disease- and anatomic location-specific responsiveness, severity of impairment most likely to respond, dose escalation and duration strategies, criteria for exclusion (e.g. prior restlessness or seizures, sympathetic storming, etc),\u003csup\u003e3,7\u003c/sup\u003e and patient- and family-centered outcomes. These data and results may guide future neurostimulant trials in the ICU aiming to improve consciousness after brain injury.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThis manuscript complies with all instructions to authors \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e RRR, HRT, and DJG \u0026nbsp;conceptualized the study design; RRR, HRT, DJG, and SP collected data; and all authors (RRR, HRT, DJG, SP, SCC, AL, TLM, DBS) contributed to analysis and interpretation of the data; and revision and approval of the manuscript. \u0026nbsp;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthorship requirements have been met and the final manuscript was approved by all authors \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript has not been published elsewhere and is not under consideration by another journal \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have adhered to ethical guidelines and indicate ethical approvals (IRB) and waiver of informed consent\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRRR received a research grant from SHINKEI Therapeutics as part of the Phase 2 Clinical Trial of MR-301 in Severe Traumatic Brain Injury. All other authors declare that they have no Conflicts of Interest to disclose. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo reporting checklist is required for this Brief Communication\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This study was funded by NIH NIGMS P20GM139745 and departmental funds. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the US government. The funders had no role in the design, analysis, preparation, review, approval, or decision to submit this manuscript for publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWinstein CJ, Stein J, Arena R, et al. Guidelines for adult stroke rehabilitation and recovery. Stroke 2016;47:e98-169.\u003c/li\u003e\n \u003cli\u003ePowers WJ, Rabinstein AA, Ackerson R, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke. Stroke 2019;50:e344-e418.\u003c/li\u003e\n \u003cli\u003eBodien YG, Busl KM, Chang CWJ, et al. Disorders of consciousness diagnosis, interventions, and prognostication for the intensivist: Report of the 2025 ISICEM roundtable. Intensive Care Med 2026;52(1):42-62.\u003c/li\u003e\n \u003cli\u003eVickrey BG, Brott TG, Koroshetz WJ, et al. Stroke research priorities meeting steering committee and the national advisory Neurological Disorders and Stroke Council, National Institute of Neurological Disorders and Stroke. Research priority setting: a summary of the 2012 NINDS Stroke Planning Meeting Report. Stroke 2013;44:2338-42.\u003c/li\u003e\n \u003cli\u003eGagnon DJ, Leclerc AM, Riker RR, et al. Amantadine and modafinil as neurostimulants during post-stroke care: a systematic review. Neurocritical Care 2020; 33(1):283-97.\u003c/li\u003e\n \u003cli\u003eAk\u0026ccedil;ıl EF, Dilmen \u0026Ouml;K, Vehid H, Tunalı Y. Can amantadine ameliorate neurocognitive functions after subarachnoid haemorrhage? A preliminary study. Turk J Anaesthesiol Reanim 2018;46(2):100\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eLeclerc AM, Riker RR, Brown CS, et al. Amantadine and modafinil as neurostimulants following acute stroke: a retrospective study of intensive care unit patients. Neurocritical Care 2021;34(1):102-11.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGiacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale- Revised: measurement characteristics and diagnostic utility. Archives of Physical Medicine and Rehabilitation 2004;85(12):2020-9.\u003c/li\u003e\n \u003cli\u003eLindsell CJ, Alwell K, Moomaw CJ, et al. Validity of a retrospective National Institutes of Health Stroke Scale scoring methodology in patients with severe stroke. J Stroke Cardiovasc Dis 2005;14(6):281-3.\u003c/li\u003e\n \u003cli\u003eHemphill JC, Bonovich DC, Besmertis L, et al. The ICH Score. Stroke 2001;32:891-7.\u003c/li\u003e\n \u003cli\u003eHunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. Journal of Neurosurgery 1968;28(1):14-20.\u003c/li\u003e\n \u003cli\u003eSeder DB, Fraser GL, Robbins T, Libby L, Riker RR. The bispectral index and suppression ratio are very early predictors of neurological outcome during therapeutic hypothermia after cardiac arrest. Intensive Care Med 2010;36(2):281-8.\u003c/li\u003e\n \u003cli\u003eRiker RR, Craig A, Eubank L, May T, Seder DB. Validation of the suppression ratio from a simplified EEG montage during targeted temperature management after cardiac arrest. Resuscitation 2020;153:1-5.\u003c/li\u003e\n \u003cli\u003eWeaver JA, Cogan AM, Kozlowski AJ, et al. Interpreting change in disorders of consciousness using the Coma Recovery Scale-Revised. Journal of Neurotrauma 2024;41(15-16):e1996-e2008.\u003c/li\u003e\n \u003cli\u003eCogan AM, Grady-Dominguez P, Dobson CG, et al. Association of patient characteristics with recovery in adults with Disorders of Consciousness. Archives of Physical Medicine and Rehabilitation 2025;S0003-9993(25)00661-6.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRiker RR, Fraser GL, Cox PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med 1994;22:433-40.\u003c/li\u003e\n \u003cli\u003eRiker RR, Picard JT, GL Fraser. Prospective evaluation of the sedation-agitation scale in adult ICU patients. Crit Care Med 1999;27:1325-9.\u003c/li\u003e\n \u003cli\u003eSchnakers C, Majerus S, Giacino J, et al. A French validation study of the Coma Recovery Scale-Revised (CRS-R). Brain Inj 2008;22(10):786-92.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1: Diagnoses, Demographics, Amantadine Dose and Response, Discharge Disposition\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"924\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e#\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSeverity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDOC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRespond\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStart Day* -- \u0026nbsp; \u0026nbsp;Max Dose\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRx@DC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDispo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eWest Nile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eGCS 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e22 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eWeaned off (sleep)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eMCS+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e11 -- 200 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eEmerged DOC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eMCS-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e9 -- 200 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eFamily request to stop\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSNF\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e3 -- 150 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eSee Quote\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eSAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHH 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eMCS-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e9 -- 200 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eStopped at WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003edied WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eCA HIE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSR6 50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eUWS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e6 -- 200 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eStopped at WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHospice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eUWS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e4 -- 150 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eStopped for seizure risk (no new events)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e6 -- 150 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eModafinil added\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eMCS-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e5 -- 100 mg BID\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003ePEG discontinued\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e8 -- 200 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eStopped at WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHospice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIVH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 282px;\"\u003e\n \u003cp\u003eNot Treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp; See Quote\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHospice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eSAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 282px;\"\u003e\n \u003cp\u003eNot Treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eSee Quote \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eSAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHH 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e17 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eImproved - po diet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eSAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHH 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e16 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp;See Quote\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSNF\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e14 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eStopped at WLS \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHospice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eShort Treat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e3 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eStopped at WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHospice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e21 -- 200 mg BID\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eTracheostomy removed \u0026nbsp;PEG discontinued\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSNF\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e9 -- 150 mg BID\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003ePEG discontinued\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 282px;\"\u003e\n \u003cp\u003eNot Treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;See Quote\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCOMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 282px;\"\u003e\n \u003cp\u003eNot Treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;Not Rx due to PSH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003edied WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eBrain Mass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eGCS 9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eMCS-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e39 -- 200 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;Continued until death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003edied IHCA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eVPA Tox\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eGCS 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e23 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eHeld after 5 days concern for seizures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHome Services\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eMCS-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e6 -- 100 mg BID\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eSee Quote\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eCA HIE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSR6 99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eMCS-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e8 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;Stopped at WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003edied \u0026nbsp; \u0026nbsp; WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eMCS+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e27 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;Stopped due to agitation -- not improved after\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e6 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eStopped at WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHospice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eSAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHH 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e8 -- 100 mg BID\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;See Quote\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eCA HIE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSR6 70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e15 -- 100 mg BID\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eTolerated after ICP and PSH controlled\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e9 -- 200 mg BID\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;Stopped day 22 \u0026ndash; delirium, poor sleep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 282px;\"\u003e\n \u003cp\u003eNot Treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eRecommended by SLP, never started\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003edied WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 282px;\"\u003e\n \u003cp\u003eNot Treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;Transferred out ICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eUWS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eShort Treat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e3 -- 50 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026ldquo;Never wanted this care\u0026rdquo;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003edied WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eICH-IVH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eICH 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 282px;\"\u003e\n \u003cp\u003eNot Treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026ldquo;No escalation care\u0026rdquo;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003edied WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003ePowassan\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eGCS 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e23 -- 100 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eStopped on floor \u0026ndash; NPO severe ileus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eEnceph\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eGCS 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eMCS-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e7 -- 200 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eSee Quote \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSNF\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eUWS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 282px;\"\u003e\n \u003cp\u003eNot Treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;Transitioned WLS Hospital Day 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003edied WLS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eCA HIE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSR6 70\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eUWS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e8 -- 200 mg BID\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eAgitation improved when weaned off\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHome Services\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNIH 28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eUWS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e3 -- 200 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp;See Quote \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRehab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eSAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHH 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e18 -- 125 mg BID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003eImproved with RX, PEG cancelled\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSNF\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eEEE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eGCS 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e14 -- 100 mg BID\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;Stopped at discharge per Neurology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSNF\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Start Day \u0026ndash; number of days from first hospital admission to first dose of amantadine; Max Dose - maximum dose of amantadine\u003c/p\u003e\n\u003cp\u003eBID, twice daily; CA HIE, cardiac arrest hypoxic-ischemic encephalopathy; CLD, cognitive-linguistic disorder; CLD/A, cognitive linguistic disorder with aphasia; DOC; Disorder of Consciousness; Dispo, disposition; EEE, Eastern Equine Encephalitis; Enceph, encephalopathy; F, female; GCS, Glasgow coma scale; HH, Hunt Hess; Home SVC, home with services; ICH, intracranial hemorrhage; ICP, intracranial pressure; \u0026nbsp; IHCA, in-hospital cardiac arrest; IS, ischemic stroke; IVH, intraventricular hemorrhage; M, male; MCS, minimally conscious state; mg, milligrams; NIH, NIH Stroke scale; NPO, nothing by mouth; PEG, percutaneous endoscopic gastrostomy tube; Powassan, Powassan virus encephalitis; PSH, paroxysmal sympathetic hyperactivity; Rehab, inpatient rehabilitation; Rx@DC, Treated at Discharge; SAH, subarachnoid hemorrhage; SLP, Speech-Language Pathologist; SNF, skilled nursing facility; SR6, suppression ratio 6 hours after recovery of spontaneous circulation; UWS, unresponsive wakefulness syndrome; VPA tox, valproic acid toxicity; West Nile, West Nile encephalitis; WLS, Withdrawal of Life Support.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"acute ischemic stroke, intracerebral hemorrhage, central nervous system stimulant, amantadine, brain injuries, disorders of consciousness ","lastPublishedDoi":"10.21203/rs.3.rs-8744330/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8744330/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e Amantadine, an effective neurostimulant for traumatic brain injury, has limited data supporting its use for other acute brain injuries (ABI). This pragmatic study evaluated amantadine for nontraumatic ABI monitored in the ICU with the Coma Recovery Scale-Revised (CRS-R).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This prospective open-label cohort study developed a protocol to treat impaired consciousness after ABI with amantadine, assessing participants with CRS-R as 0-100 Rasch units, monitoring feasibility, safety, and effectiveness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 40 patients (age 64 [52-73] years, 25 [62%] female) were included during this protocol development phase: 13 ischemic stroke, 10 intracerebral hemorrhage, 7 subarachnoid hemorrhage, 4 hypoxic-ischemic encephalopathy, 3 other ABI. \u0026nbsp;The median baseline CRS-R was 11 (IQR 7-16), including 16 meeting criteria for Disorder of Consciousness. \u0026nbsp;Among 30 participants with an adequate amantadine treatment trial, 27 (90%) responded, with disposition to home (1,4%), skilled nursing facility (6,22%), acute inpatient rehabilitation (15,56%), or withdrawal of life support (5,18%). Pre- versus post-treatment CRS-R increased for responders by 8 (6-11), equivalent to 26 (15-45) Rasch units. Among 10 untreated or inadequate trial patients, 3 (30%) were discharged to rehab, 7 (70%) had support withdrawn.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e It is feasible to measure responsiveness to amantadine using the CRS-R for ICU patients with ABI.\u003c/p\u003e","manuscriptTitle":"Prospective Evaluation of Icu Neurostimulant Use for Acute Brain Injury (Prevail): A Pragmatic Observational Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-10 00:35:26","doi":"10.21203/rs.3.rs-8744330/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"80db6a9f-d5b6-4580-92f5-d0b9f22550a2","owner":[],"postedDate":"February 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T19:00:47+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-10 00:35:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8744330","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8744330","identity":"rs-8744330","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}