UMEM Educational Pearls - By WanTsu Wendy Chang

• A number of small studies in the past suggested that cervical collars can increase intracranial pressure (ICP) in patients with traumatic brain injury (TBI).
• In patients with severe head injury with poor intracranial compliance and impaired cerebral autoregulation, compression on the jugular veins may result in an increase in jugular venous pressure, increase in ICP, and decrease cerebral perfusion.
• A recent meta-analysis included 5 studies comprising 86 adult patients with moderate-severe TBI.
• 3 studies used rigid collars (Stifneck), while 1 used semi-rigid, and 1 used a mix of cervical collars.
• All 5 studies monitored ICP before and after collar application, 2 also monitored ICP after collar removal.
• Cervical collar application was associated with an overall ICP increase of approximately 4.4 mmHg (95%CI 1.70, 7.17; p<0.01), while removal was associated with an overall decrease of approximately 3 mmHg (95%CI -5.45, -0.52; p=0.02).
• The use of rigid cervical collars was strongly associated with raised ICP compared to semi-rigid collars (WMD=4.86; 95%CI 2.13, 7.60; p<0.01).

Bottom Line: Cervical collars can increased ICP in moderate-severe TBI.  In patients with poor cerebral compliance and impaired cerebral autoregulation, even a small increase in ICP can affect cerebral perfusion.

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• Human coronaviruses generally cause GI and respiratory diseases.
• However, myocarditis, meningitis, and multi-organ failure have also been reported.
• Like other viruses, human coronaviruses may enter the central nervous system (CNS) hematogenously or through neuronal retrograde.
• The novel coronavirus (SARS-CoV-2) that emerged in Wuhan, China in December 2019 shares similar pathogenesis with SARS-CoV and MERS-CoV, and has been identified to use the same ACE2 receptor as SARS-CoV.
• Experimentally, SARS-CoV has been shown to cause neuronal death by invading the brain close to the olfactory epithelium.
• Patients with SARS have also been found to have the virus in their cerebrospinal fluid (CSF).
• An altered sense of smell, or hyposmia, has been observed in COVID-19 and may warrant an evaluation for potential CNS involvement.

Bottom Line: SARS-CoV has been associated with CNS involvement. Given their similar pathogenesis and finding of hyposmia in COVID-19, SARS-CoV-2 may be associated with risk of CNS involvement.

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• Current ACEP guidelines recommend to consider neuroimaging after blunt head trauma in patients with coagulopathy.
• However, they do not provide guidance specific to antiplatelet vs. anticoagulant medications.
• A recent multicenter prospective observational study of 9070 patients where 14.6% were receiving antiplatelet medications or warfarin found the relative risk of significant intracranial injury was:
  • 1.29 (95% CI 0.88-1.87) for aspirin alone
  • 0.75 (95% CI 0.24-2.30) for clopidogrel alone
  • 1.88 (95% CI 1.28-2.75) for warfarin alone
  • 2.88 (95% CI 1.53-5.42) for aspirin and clopidogrel in combination
• Significant intracranial injury did not include isolated linear or basilar skull fractures or single small cerebral contusions <2 cm in diameter.
• The study only included patients who underwent neuroimaging, though the researchers also looked at 368 consecutive patients with blunt head injury who did not receive neuroimaging and did not find any missed injuries at 3-month follow-up.

Bottom Line: Patients on warfarin or a combination of aspirin and clopidogrel have increased risk of significant intracranial injury after blunt head trauma.  Aspirin or clopidogrel monotherapy do not appear to be risk factors.

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• Neurogenic bladder refers to urinary tract dysfunction associated with neurological conditions.
• There are 3 patterns that can occur depending on the location of the neurological injury (see figure below):
  • Suprapontine lesions (e.g. Parkinson disease) cause involuntary bladder contractions, resulting in urinary incontinence.
  • Infrapontine to suprasacral lesions (e.g. cervical and thoracic spinal cord injuries) cause uncoordinated bladder and urethral sphincter contractions, resulting in incomplete emptying of the bladder and urinary retention.
  • Sacral/infrasacral lesions (e.g. cauda equina syndrome) cause poor bladder contraction and/or nonrelaxing urethral sphincter, resulting in urinary retention.

• Medications such as opiates, anticholinergics, and alpha-adrenoceptor agonists can also cause urinary retention.

Bottom Line: Urinary retention can be seen with neurological injury involving the lower brainstem, spinal cord, cauda equina, and peripheral nerves.

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• Up to 1/3 of status epilepticus do not respond to benzodiazepines.
• Fosphenytoin, valproate, and levetiracetam are 3 antiepileptic medications commonly used to treat benzodiazepine-resistant status epilepticus, though it is unclear which is more effective.
• Results from the long awaited Established Status Epilepticus Treatment Trial (ESETT) has just been released.
• Fosphenytoin, valproate, and levetiracetam each achieved seizure cessation within 1 hour in approximately 50% of patients.
  • 80% of responders had seizure cessation within 20 minutes.
• Seizure recurrence was observed in 10% of each treatment group.
• It is important to note the dosages of antiepileptic medications used were:
  • Fosphenytoin 20 mg PE/kg, max 1500 mg 
  • Valproate 40 mg/kg, max 3000 mg
  • Levetiracetam 60 mg/kg, max 4500 mg

Bottom Line: Fosphenytoin, valproate, and levetiracetaim have similar efficacy in treatment of benzodiazepine-resistant status epilepticus.

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• Cryptococcal meningitis is the most common fungal CNS infection that predominantly affects immunocompromised patients.
• However, cases have been described in immunocompetent patients.
• Clinical presentation may include headache, fever, neck pain, nausea, vomiting, light sensitivity, seizure, or altered mental status.
• Neuroimaging is usually normal, though cryptococcomas, pseudocysts, and obstructing hydrocephalus can be seen.
• Diagnosis with LP include elevated opening pressure, mononuclear predominance of cell count, low glucose, high protein, India ink microscopy, Cryptococcal antigen testing, and CSF culture.
• Subacute symptoms contribute to delay in diagnosis which increases overall morbidity and mortality.

Bottom Line: Consider cryptococcal meningitis even in immunocompetent patients.

• The ACEP clinical policy on the evaluation and management of acute nontraumatic headache in the ED was recently updated.
• Similar to prior policies, it focuses on the diagnosis of subarachnoid hemorrhage (SAH) due to the disproportionate amount of literature in comparison to other high risk etiologies.
• In summary:

• 1. Are there risk-stratification strategies that reliably identify the need for emergent neuroimaging?
     • The Ottawa SAH Rule has a high sensitivity but low specificity for patients presenting with a normal neurological exam and peak headache intensity within 1 hour of symptom onset (Level B recommendation).
     • Caution in application of this rule, as use in the incorrect population may increase unnecessary testing.
  2. Are nonopioids preferred to opioids for treatment of acute primary headache?
     • Preferentially use nonopioid medications in the treatment of acute primary headaches in ED patients (Level A recommendation).
     • Consider discharge medication and education to reduce headache recurrence and repeat ED visit.
  3. Does a normal noncontrast head CT performed within 6 hours of headache onset preclude the need for further diagnostic workup for SAH?
     • Noncontrast head CT using at least a 3rd generation scanner performed within 6 hours of headache onset can be used to rule out nontraumatic SAH (Level B recommendation).
     • If clinical suspicion remains high despite the negative noncontrast head CT, further evaluation may be pursued.
  4. In a patient who is still considered to be at risk for SAH after a negative noncontrast head CT, is CTA as effective as LP to rule out SAH?
     • Use shared decision making to select the best modality for each patient after weighing the potential for false-positive CTA and the pros/cons associated with LP (Level C recommendation).

• This clinical policy does not address the evaluation of other potential etiologies for acute headache, including in the pregnant woman and postpartum woman. 

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• Elevated BP is common with acute ICH and is associated with hematoma expansion and worse outcome.
• Early BP lowering in ICH appear to be safe, though did not improve outcomes in the two largest trials INTERACT2 and ATACH-II.
• A preplanned pooled analysis of 3829 patients from these 2 trials found:
  • Every 10 mmHg reduction in SBP was associated with a 10% increase in odds of better functional recovery.
  • Reduced variability of SBP was associated with improved outcomes.
• The association between BP variability and outcomes in ICH has been observed in several other recent studies.

Bottom Line: Reduced SBP variability is associated with improved outcomes in ICH.

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• Symptoms/signs that suggest serious underlying conditions causing headaches are summarized by the mnemonic SNOOP:
  • S - Systemic symptoms/signs/disease
    • e.g. fever, weight loss, HIV, malignancy, pregnancy
  • N - Neurologic symptoms/signs
    • e.g. altered mental status, diplopia, pulsatile tinnitus, loss of consciousness
  • O - Onset sudden, abrupt, thunderclap
    • i.e. pain reaches maximal intensity instantly after onset
  • O - Older age of onset, especially > 50 years
  • P - Pattern change
    • e.g. change in frequency, severity, clinical features, precipitated by Valsalva, aggravated by postural change
• Consider structural pathologies, vascular disorders, infectious and inflammatory conditions in the evaluation of secondary headache syndromes.

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• Benzodiazepines are first-line treatment for status epilepticus.
• Guidelines for the treatment of status epilepticus recommend dosing as:
  • 10 mg midazolam IM for patients > 40 kg or 5 mg midazolam IM for patients 13-40 kg
  • 0.1 mg/kg lorazepam IV (max 4 mg/dose), can repeat x 1
  • 0.15-0.2 mg/kg diazepam IV (max 10 mg/dose), can repeat x 1
• The recent Established Status Epilepticus Treatment Trial (ESETT) compared the treatment of patients who did not respond to benzodiazepines.
  • Overall, 29.8% of the first dose of benzodiazepines given in the ED met minimum dose recommendations.
  • Dosing for patients < 40 kg more frequently met minimum dose recommendations.
  • This study found a pattern of multiple, small doses instead of a single full dose of benzodiazepine as recommended by guidelines.

Bottom Line: Underdosing of benzodiazepines in status epilepticus may contribute to treatment failure.

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• Hypertonic saline and mannitol are commonly used for management of acute intracranial hypertension and cerebral herniation.
• The choice of medication is often limited by venous access.
• 23.4% NaCl has been shown to decrease intracranial pressure in patients refractory to mannitol.
  • It requires administration through a central line to avoid sclerosis of the peripheral veins and tissue necrosis with extravasation.
• Intraosseous (IO) access provides a more rapid route for 23.4% NaCl administration.
  • No complications were observed relating to IO insertion site.
  • Transient hypotension occurred in more patients who received 23.4% NaCl via IO vs. central line.

Bottom Line: Use of IO allows more rapid administration of 23.4% NaCl with no immediate serious complications.

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• Misdiagnosis of neurologic emergencies can result in serious neurologic dysfunction or death.
• A recent retrospective analysis using AHRQ databases looked at >3 million adults discharged from the ED with diagnoses of atraumatic headache or back pain.
• A serious neurologic condition or death occurred within 30 days after ED discharge in:
  • 0.5% of patients with nonspecific diagnosis of headache
  • 0.2% of patients with nonspecific diagnosis of back pain
• The frequency of adverse outcome was highest between days 1 and 3 after ED discharge.
• The most frequent adverse outcome was ischemic stroke (18.1%) for headache and intraspinal abscess (44%) for back pain.
• Age ≥ 85, male sex, non-Hispanic white, comorbidities such as neurologic disorders, HIV/AIDS, and malignancy were associated with higher incidence of adverse outcome.

Bottom Line: The rate of serious neurologic conditions missed at an initial ED visit is low.  However, the potential harm of misdiagnosis can be substantial.

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• Intracerebral hemorrhage (ICH) volume is a predictor of mortality and clinical outcome.
• Communicating ICH volume to neurosurgical and neurocritical care consultants can help direct treatment decisions.
• ICH volume can be estimated using the ABC/2 formula:
  • Select the CT slice with the largest area of the hemorrhage (reference slice)
  • A = Measure the largest diameter
  • B = Measure the largest diameter perpendicular to A
  • C = Multiply the number of CT slices with the hemorrhage by the slice thickness
    • Slices with 25-75% of the hematoma volume compared to the reference slice count as 1/2 slice
    • Slices with <25% of the hematoma volume compared to the reference slice do not count

• A recent study by Dsouza et al. found that EM attendings as well as EM trainees were reliable in estimating ICH volume using ABC/2 compared to radiologists.

Bottom Line:  EPs can reliably estimate ICH volume using the ABC/2 formula.  Communicating ICH volume to neurosurgical and neurocritical care consultants can help direct treatment decisions.

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• Lumbar punctures (LPs) are a common ED procedure with variable reported success rates.
• A recent systematic review and meta-analysis looked at 12 studies comprising 957 adult and pediatric patients comparing pre-procedural ultrasound-assisted LPs with traditional landmark-based technique.
  • Some studies utilized ultrasound-assistance in all LPs, others selected patients who were anticipated to be difficult LPs.
  • No studies assessed dynamic ultrasound-guided LPs.
• Overall, ultrasound-assisted LP was 90.0% successful compared with landmark-based LP that was 81.4% successful (OR 2.22, 95% CI = 1.03 - 4.77).
• Ultrasound-assisted LP was also associated with reduced rate of traumatic LPs, shorter time to successful LP, and reduced patient pain scores.

Bottom Line: Consider using pre-procedural ultrasound-assistance for all lumbar punctures.

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• The Canadian C-Spine Rule (CCR) has been shown to decrease the use of cervical spine imaging in low-risk trauma patients.
• While developed for use by physicians, CCR has also been validated in ED triage nurses with moderate interrater reliability (kappa 0.78) by Stiell et al. in 2010.
• Stiell’s group has since implemented the use of CCR by ED triage nurses at 9 teaching hospitals in Ontario with a combined annual volume of approximately 670,000 ED visits.
• 180 certified nurses evaluated 1408 patients.
  • 806 (57.2%) arrived with c-spine immobilization.
  • 602 (42.8%) had neck pain but no immobilization.
• Overall, nurses removed immobilization in 331 (41.4%) patients and applied immobilization in 203 (14.4%) patients.
• Diagnostic imaging was performed in 612 (43.4%) patients and found 16 (1.1%) clinically important and 3 (0.6%) clinically unimportant injuries.
• There were no missed c-spine injuries to the knowledge of the authors as the study hospitals were closely connected with the regional spine centers.
• Time from nursing assessment to discharge decreased by 26.0% (3.4h vs. 4.6h)

Bottom Line: ED triage nurses can safely use the Canadian C-Spine Rule.  This approach can improve patient care and decrease length of stay in the ED.

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Does using a combination of aspirin and clopidogrel decrease your patient’s risk of recurrent stroke after a minor ischemic stroke or high risk TIA event?

• The recent international Platelet-Oriented Inhibition in New TIA and Minor Stroke (POINT) trial compared 4881 patients receiving aspirin/clopidogrel vs. aspirin/placebo within 12 hours of symptom onset.
  • Patients who received DAPT had a lower rate of major ischemic events at 90 days compared to aspirin/placebo (5.0% vs. 6.5%, p=0.02).
  • However, patients who received DAPT had a higher rate of major hemorrhage compared to aspirin/placebo (0.9% vs. 0.4%, p=0.02).
• A similar Chinese study, the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial, compared 5170 patients receiving DAPT vs. aspirin/placebo within 24 hours also found lower rate of stroke (8.2% vs. 11.7%, p<0.001) but similar rates of moderate/severe hemorrhage (0.3% vs. 0.3%, p=0.73).
• Major differences between these two trials are the population studied and the duration of DAPT, as POINT utilized DAPT for 90 days while CHANCE utilized DAPT for 21 days.

Bottom Line: The use of DAPT in minor ischemic stroke and high risk TIA reduces the risk of recurrent stroke.  However, the duration of DAPT may affect the risk of major hemorrhage.

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• Anticoagulation is the mainstay for treatment of acute cerebral venous thrombosis (CVT) to prevent clot propagation, recanalize occluded veins and sinuses, and prevent new venous thrombosis.
• A recent meta-analysis of 4 RCTs compared the efficacy and safety of low molecular weight heparin (LMWH) vs. unfractionated heparin (UFH) for the treatment of CVT.
• All studies were small, with 20 to 66 patients each.
• Treatment with LMWH compared with UFH had similar mortality (OR 0.21; 95% CI 0.02-2.44; p=0.21) and disability (OR 0.5; 95% CI 0.11-2.23; p=0.36). 

Bottom Line: LMWH appear to be similar in efficacy and safety compared with UFH for the management of CVT.

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• The use of neuroimaging in syncope-related ED visits increased from 21% in 2001 to 45% in 2010.
• A recent single-center retrospective study of 1114 patients who presented to the ED with syncope found that 62.3% patients underwent CT, while 10.2% underwent MRI.
• A subset of patients (10.4%) sustained mild head trauma (GCS 14-15) due to syncope and all received neuroimaging.
• Neuroimaging studies were not found to be beneficial in patients without features of:
  • Confusion
  • Amnesia
  • Focal neurological deficit
  • Dizziness
  • Severe headache
  • Nausea and vomiting
  • Signs of serious head injury
  • Intracranial malignancies
  • Use of anticoagulant drugs

Bottom Line: Consider obtaining neuroimaging in patients presenting with syncope only if clinical features suggest probable neurological syncope.

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• CT angiography (CTA) spot sign is a strong predictor of intracerebral hemorrhage (ICH) expansion.
• However, since CTA is not part of the routine diagnostic workup of acute ICH, other predictors using noncontrast head CT have been reported in the past.
• A 5-point BAT score can be used to identify patients at high risk of hematoma expansion:

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• Patients with a score ≥ 3 have a higher risk of hematoma expansion. 

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• A recent systematic review evaluated the diagnostic accuracy of 19 prehospital stroke scales.
• Arm motor strength is the most frequently evaluated item by the scales (15/19), followed by gaze (13/19) and language (13/19).
• Only 4 scales (RACE, LAMS, VAN, sNIHSS-EMS) were performed by paramedics in their original studies.
• The NIHSS, LAMS, and VAN appear to have better results in predicting large vessel occlusion.
• The presence of hemineglect, a sign of cortical involvement, improved the accuracy of the scale.

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