Trials and guidelines for neurology and neurosurgery

This compilation of papers is probably not as useful as other better resources which compile this information, such as Critical Care Reviews and The Bottom Line. However, it is probably at least harmless. Wherever possible, the original paper is linked from the name of the study, and the Bottom Line review is linked from the year of publication.

Traumatic brain injury

DECRA - 2011 - decompressive craniectomy vs. standard care; n=155, Au/NZ/Saudi.  Mortality same (19% and 18%) but more severely disabled survivors (70% vs 51%)

BEST:TRIP2012 - ICP monitoring vs. clinical examination and imaging; n=324, in South America. No difference in mortality (39% vs 41%) nor the composite outcome

STITCH2015- early evacuation of parenchymal haematoma; n=170, worldwide. Better mortality (33% vs 15%) and less disability, but underpowered.

Eurotherm32352015 - prophylactic 33°-35°C until ICP controlled, multinational, but 55% of n=387 from the UK. Greater risk of death (54% vs 44%) and lower likelihood of a good functional outcome (25% vs 37%)

RESCUEicp2016 - decompression or thiopentone and standard care? n=408, in 20 countries. Mortality improved with craniectomy (26.9% vs. 48.9%), but it created more severely disabled survivors (and did not change the % of less disabled survivors)

POLAR -  2018 - prophylactic 33°-35°C, for 3-7 days - n=511 all around the world. No difference in mortality (48.8% vs 49.1%), not much effect on ICP, and more complications (pneumonia, ventilation days, bradycardia and noradrenaline use)

COBI2021 - but what if 20% saline, except continuous infusion? n=370, in France. No significant difference in mortality (15.9% vs 20.8%), ICP control or functional outcome. Probably better off as a bolus. 

Intracranial haemorrhage

INTERACT2 - 2013 - SBP under 140 vs SBP under180; n=2839, multinational. No difference in composite mortality or severe disability (52% vs 55.6%).

PATCH 2016 - platelets within 90 minute of imaging; n=190 patients on antiplatelet agents (Netherlands, UK and France). Worse mortality (24% vs 17%).  

ATACH-2 2016 - SBP 110-130, vs SBP 140-180; n=1000 from many countries. No mortality difference (38.7% vs 37.7%), and the low BP group had more renal complications (9% vs 4%).

TICH-22018 - tranexamic acid within 8 hours; n=2325 (12 countries). No effect on mortality (22% vs 21%) or functional outcome, but haematomas expanded less, so at least the radiologist was happy.

Subarachnoid haemorrhage

BRANT - 1989 - The nimodipine trial. n=554 in UK; oral nimodipine for 21 days. Reduced rate of cerebral infarction (22% vs 33%). Subsequent work duplicated their effect size reasonably well, such that for nimodipine NNT = 8.

Bradford 2013 - but what if magnesium? Mg2+ ~ 1.70 mmol/L, n=162 (Australia). Less vasospasm in the magnesium group, but not statistically significant.

ULTRA2021 - super-early tranexamic acid; n=955, in the Netherlands. No difference in chances of a good outcome: 60% vs 64% (but: rebleeding decreased, 10% vs 14%).

Ischaemic stroke

BP targets

  • CATIS - 2014 - BP 140/90, or uncontrolled? n=4071, in China. No difference in composite of mortality and major disability (33.6% vs 33.6%).
  • MAPAS2019 - looked at 3 different ranges of SBP; n=218, in Brazil. Best outcomes seen in the 160-180 range, but only after statistical trickery. No range was clearly superior.

Decompressive craniectomy for malignant MCA infarction:

  • DESTINY - 2007 - n=32; in Germany. Improved survival (88% vs 47%) but stopped early because other trials were concurrently running
  • DECIMAL - 2007 - n=38; in France. Improved survival (75% vs 22%) Stopped early because of slow recruitment.
  • HAMLET - 2009 - n=64, in the Netherlands.  Better survival (absolute risk reduction was 38%)
  • DESTINY II - 2014 - but what if older patients? n=112, over 60s,  in Germany. Better survival (mortality 33% vs 70%), but most of the survivors were severely disabled (60% vs 28% were modified Rankin score 3 or 4)

Endovascular clot retrieval trials:

  • MR CLEAN - 2015 - ECR within 6 hours versus usual care; n=500 (Netherlands). No difference in mortality, but the survivors had better function  (32.6% vs. 19.1%)
  • SWIFT PRIME - 2015 - ECR plus tPA vs. tPA alone, within 6 hours. n=196, in US and Europe Stopped early because of obvious benefit: better function in 60% vs. 35%
  • EXTEND-IA - 2015 - ECR plus tPA vs. tPA alone, n=70 in Australia and NZ; also stopped early because ECR+tPA was clearly superior (better function in  71% vs. 40%)
  • DEFUSE III - 2018 - what if ECR, but later? 6-16 hours, n=182, in the US. Rate of functional independence at 90 days was 45% vs 17%. Mortality also better (14% vs 26%)
  • DAWN - 2018 - what if ECR, but even later? 6 to 24 hours, n=207, in the US.  Rate of functional independence at 90 days was 49% vs 13%. Mortality same (19% vs 18%)
  • Yoshimura et al - 2022 - in very large strokes; n=203 (Japan). Better outcomes in 31% vs 12.7%, but also more serious haemorrhagic transformation (9% vs 4.9%)

Status epilepticus

HYBERNATUS2016 - added hypothermia to standard care? n=270, in France. No difference in good functional outcome (49% vs 43%). Fewer seizures though. 

CERTA2020 - continuous EEG? n=364, in Switzerland. Yes, they picked up more seizures, and changed the AEDs a lot more, but there was no difference in mortality (48.4% vs 48.9%, because 30% of the patients had hypoxic-ischaemic encephalopathy). 


Traumatic brain injury:

Stroke and intracranial haemorrhage of various sorts:

Spinal injury:

Status epilepticus:

Persistent unconsciousness

Various myopathies and neuropathies:

Examination of the unconscious patient

  • Not really guidelines, but as CICM are so fixated on seeing people perform the oculocephalic reflex in the fellowship exam, the candidates should prepare to discuss it. Walker and O'Brien's 1990 paper "Neurological examination of the unconscious patient" is an excellent brief synopsis; it draws its inspiration from the 1980 edition of Plum and Posner's "The Diagnosis of Stupor and Coma", which is essentially the Old Testament for neurological examination of the critically ill. The time-poor candidate will probably be unable to make use of this textbook, but the paper needs to be read through at least once before the exam. The hypothetical exam candidate with infinite time resources may also benefit from exploring The Comatose Patient by Eelco Wijdicks (2014).



Cooper, D. James, et al. "Decompressive craniectomy in diffuse traumatic brain injury." New England Journal of Medicine 364.16 (2011): 1493-1502.

Roquilly, Antoine, et al. "Effect of continuous infusion of hypertonic saline vs standard care on 6-month neurological outcomes in patients with traumatic brain injury: the COBI randomized clinical trial." Jama 325.20 (2021): 2056-2066.

Cooper, D. James, et al. "Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury: the POLAR randomized clinical trial." Jama 320.21 (2018): 2211-2220.

Hutchinson, Peter J., et al. "Trial of decompressive craniectomy for traumatic intracranial hypertension." N Engl J Med 375 (2016): 1119-1130.

Mendelow, A. David, et al. "Early surgery versus initial conservative treatment in patients with traumatic intracerebral hemorrhage (STITCH [Trauma]): the first randomized trial." Journal of neurotrauma 32.17 (2015): 1312-1323.

Andrews, Peter JD, et al. "Hypothermia for intracranial hypertension after traumatic brain injury." New England Journal of Medicine 373.25 (2015): 2403-2412.

Chesnut, Randall M., et al. "A trial of intracranial-pressure monitoring in traumatic brain injury." New England Journal of Medicine 367.26 (2012): 2471-2481.


Sprigg, Nikola, et al. "Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial." The Lancet (2018).

Baharoglu, M. Irem, et al. "Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial.The Lancet 387.10038 (2016): 2605-2613.

Qureshi, Adnan I., et al. "Intensive blood-pressure lowering in patients with acute cerebral hemorrhage." New England Journal of Medicine 375.11 (2016): 1033-1043.

Anderson, Craig S., et al. "Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage." N Engl j Med 368 (2013): 2355-2365.

Pickard, J. D., et al. "Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial." British Medical Journal 298.6674 (1989): 636-642.

Post, René, et al. "Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial." The Lancet 397.10269 (2021): 112-118.

Bradford, Celia M., et al. "A randomised controlled trial of induced hypermagnesaemia following aneurysmal subarachnoid haemorrhage." Critical Care and Resuscitation 15.2 (2013): 119-125.


Nasi, Luiz Antonio, et al. "Early manipulation of arterial blood pressure in acute ischemic stroke (MAPAS): results of a randomized controlled trial." Neurocritical care 30 (2019): 372-379.

He, Jiang, et al. "Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial." Jama 311.5 (2014): 479-489.

Jüttler, Eric, et al. "Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke." New England Journal of Medicine 370.12 (2014): 1091-1100.

Berkhemer, Olvert A., et al. "A randomized trial of intraarterial treatment for acute ischemic stroke." n Engl J Med 372 (2015): 11-20.

Nogueira, Raul G., et al. "Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct." New England Journal of Medicine 378.1 (2018): 11-21.

Campbell, Bruce CV, et al. "Endovascular therapy for ischemic stroke with perfusion-imaging selection." New England Journal of Medicine 372.11 (2015): 1009-1018.

Yoshimura, Shinichi, et al. "Endovascular therapy for acute stroke with a large ischemic region." New England Journal of Medicine 386.14 (2022): 1303-1313.

Albers, Gregory W., Michael P. Marks, and Maarten G. Lansberg. "Thrombectomy for stroke with selection by perfusion imaging." The New England Journal of Medicine 378.19 (2018): 1849-1850.

Saver, Jeffrey L., et al. "Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke." New England Journal of Medicine 372.24 (2015): 2285-2295.

Carney, Nancy, et al. "Guidelines for the management of severe traumatic brain injury." Neurosurgery 80.1 (2017): 6-15.

Status epilepticus

Rossetti, Andrea O., et al. "Continuous vs routine electroencephalogram in critically ill adults with altered consciousness and no recent seizure: a multicenter randomized clinical trial." JAMA neurology 77.10 (2020): 1225-1232.

Legriel, Stephane, et al. "Hypothermia for neuroprotection in convulsive status epilepticus." New England Journal of Medicine 375.25 (2016): 2457-2467.


Hawryluk, Gregory WJ, et al. "A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)." Intensive care medicine 45 (2019): 1783-1794.

Greenberg, Steven M., et al. "2022 guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association." Stroke 53.7 (2022): e282-e361.

Powers, William J., 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: a guideline for healthcare professionals from the American Heart Association/American Stroke Association." Stroke 50.12 (2019): e344-e418.

Gandhi, Chirag D., et al. "Neuroendovascular management of emergent large vessel occlusion: update on the technical aspects and standards of practice by the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery." Journal of neurointerventional surgery 10.3 (2018): 315-320.

Yaghi, Shadi, et al. "Treatment and outcome of hemorrhagic transformation after intravenous alteplase in acute ischemic stroke: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association." Stroke 48.12 (2017): e343-e361.

Sandset, Else Charlotte, et al. "European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage." European stroke journal 6.2 (2021): XLVIII-LXXXIX.

Ferro, J. M., et al. "European Stroke Organization. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis-endorsed by the European Academy of Neurology." Eur J Neurol 24.10 (2017): 1203-1213.

Connolly, E. S., et al. "Council on Cardiovascular Radiology and Intervention, on behalf of the American Heart Association Stroke Council Council on Cardiovascular Nursing, Council on Cardiovascular Surgery and Anesthesia, and Council on Clinical Cardiology. Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association." Stroke 43.6 (2012): 1711-37.

Tracy, Glauser, Shinnar Shlomo, and Gloss David. "Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: Report of the Guideline Committee of the American Epilepsy Society." Epilepsy Currents 16 (2016): 48-61.

Brophy, Gretchen M., et al. "Guidelines for the evaluation and management of status epilepticus." Neurocritical care 17 (2012): 3-23.

Giacino, Joseph T., et al. "Practice guideline update recommendations summary: disorders of consciousness: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research." Archives of physical medicine and rehabilitation 99.9 (2018): 1699-1709.

Narayanaswami, Pushpa, et al. "International consensus guidance for management of myasthenia gravis: 2020 update." Neurology 96.3 (2021): 114-122.

Fan, Eddy, et al. "An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit–acquired weakness in adults." American journal of respiratory and critical care medicine 190.12 (2014): 1437-1446.

Rupp, Rüdiger, et al. "International standards for neurological classification of spinal cord injury: revised 2019." Topics in spinal cord injury rehabilitation 27.2 (2021): 1-22.

Patel, Mayur B., et al. "Cervical spine collar clearance in the obtunded adult blunt trauma patient: A systematic review and practice management guideline from the Eastern Association for the Surgery of Trauma." Journal of Trauma and Acute Care Surgery 78.2 (2015): 430-441.

Leonhard, Sonja E., et al. "Diagnosis and management of Guillain–Barré syndrome in ten steps." Nature Reviews Neurology 15.11 (2019): 671-683.

Chesnut, Randall M., et al. "Consensus-based management protocol (CREVICE Protocol) for the treatment of severe traumatic brain injury based on imaging and clinical examination for use when intracranial pressure monitoring is not employed." Journal of neurotrauma 37.11 (2020): 1291-1299.

Hoh, Brian L., et al. "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association." Stroke (2023).

Hwang. David Y, et al. "Guidelines for Neuroprognostication in Critically Ill Adults with Intracerebral Hemorrhage". Neurocrit Care 2023;epublished November 3rd

Tunkel, Allan R., et al. "2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis." Clinical Infectious Diseases 64.6 (2017): e34-e65.