UMEM Educational Pearls - Neurology

• Trigeminal neuralgia is diagnosed by:
  • Pain in 1 or more divisions of the trigeminal nerve
  • Paroxysms of pain that are sudden, intense, usually few seconds in duration
  • Pain triggered by innocuous stimuli in the trigeminal nerve territory (91-99% patients)
• 24-49% of patients experience continuous or long-lasting pain
• Exam may reveal forceful contraction of the facial muscles during a paroxysm (tic convulsif)
• Causes include:
  • Intracranial vascular compression of the trigeminal nerve root (most common)
  • Multiple sclerosis, cerebellopontine angle tumor
  • Idiopathic (10% of cases)
• Carbamazepine and oxcarbazepine are first-line treatments
  • They may be poorly tolerated due to side effects including dizziness, diplopia, ataxia, CNS depression, and hyponatremia
  • They also have limited efficacy on continuous pain
• Acute exacerbations may warrant admission for hydration, acute pain control, and titration of antiepileptic drugs
  • Botulinum toxin A was recently added as a treatment option

Bottom Line: New onset trigeminal neuralgia needs workup for its etiology. Carbamazepine and oxcarbazepine can be effective for symptom management though continuous or long-lasting pain exacerbations are difficult to treat.

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• Spontaneous cerebrospinal fluid (CSF) rhinorrhea is rare and usually related to a combination of thinning of the bone and dura and fluctuating intracranial pressure.
• CSF rhinorrhea can be associated with idiopathic intracranial hypertension, skull base tumors, neurosurgical and otolaryngology procedures, and trauma.
• Trauma with fracture of the anterior skull base is the most common cause of CSF rhinorrhea.
• CT and MRI can identify bony defects, whereas cisternography can diagnose occult leaks.
• Fluid containing CSF is classically described to make a “halo” or “double-ring” pattern on gauze or linen.

• However, this sign is not specific to CSF, as mixtures of blood with saline, tears, or rhinorrhea can also produce halos.
• Beta-2 transferrin is a protein found almost exclusively in CSF* thus can be used to diagnose CSF rhinorrhea.

Bottom Line: Beta-2 transferrin is more accurate than the halo sign to identify CSF containing fluid.

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Idiopathic intracranial hypertension (IIH) is a vision-threatening illness with significant morbidity and needs to be considered as a possible headache diagnosis in the ED. Most often, this occurs in women of childbearing age with a BMI >30, but atypical varieties exist.

Symptoms: Headache (90%), visual disturbance, pulsatile tinnitus, horizotal diplopia.

Signs: Papilledema, 6th cranial nerve (abducens) palsy.

Evaluation: Neuroimaging including CTV or MRV to identify alternate cause including cerebral venous outflow obstruction, lumbar puncture with opening pressure >30 cmH₂O (25-30 cmH₂O is gray zone), blood work per clinical presentation, CSF analysis.

Treatment: No clear consensus, but typically acetazolamide. Severe or refractory symptoms may require surgical intervention such as optic nerve sheath fenestration, VP shunt, venous sinus stenting.

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• The hormonal changes and hypercoagulable state associated with pregnancy can contribute to neurological conditions.
• Migraine
  • Migraines decrease in frequency through second trimester with increased estrogen, while increase in frequency postpartum with drop in estrogen, stress, and sleep deprivation.
  • Women with history of migraine have higher risk of preeclampsia (odds ratio 2.87).
• Reversible Cerebral Vasoconstriction Syndrome (RCVS)
  • Pregnancy is a risk factor for RCVS with 2/3 of cases of pregnancy-related RCVS occurring in the postpartum period.
• Cerebral Venous Thrombosis (CVT)
  • CVT is associated with the hypercoagulable state in late pregnancy and postpartum period, though often associated with additional source of hypercoagulability.
  • Other risk factors include older maternal age, cesarean delivery, smoking, and dehydration.
• Bell’s Palsy
  • Bell’s Palsy is more prevalent in pregnancy, occurring in the third trimester and the first week postpartum.

Bottom Line: Pregnancy is associated with an increased risk for RCVS, CVT, and Bell’s Palsy. Pregnancy also affects the frequency of migraines due to hormonal fluctuations.

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• Previous studies suggest more than 1/3 of head CTs are avoidable by evidence-based guidelines.
• It is controversial whether patients respond to financial incentives for healthy behavior.
• A study by Iyengar et al. surveyed 913 ED patients using a hypothetical mild TBI scenario that does not need a head CT by the Canadian CT Head Rule.
• Patients were randomly assigned the consideration of benefit (0.1% of 1%), risk (0.1% or 1%), or financial incentive ($0 or $100) associated with obtaining a head CT.
• Overall, 54.2% (495/913) patients elected to obtain a head CT.
  • An increase in test benefit was associated with a 9.3% increase in CT use (49.6% to 58.9%).
  • An increase in test risk was associated with a 10.2% decrease in CT use (59.3% to 49.1%).
  • An increase in financial incentive was associated with a 11.7% decrease in CT use (60.6% to 48.3%).

Bottom Line: Discussion of benefit/risk and financial incentive associated with head CT in mild TBI affects patient decision. Interestingly in this population studied, more than half of patients will elect to obtain a head CT even in a low-risk scenario.

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• 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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Primary headaches (not secondary to a life-threatening disease) can be challenging to manage. Remember the following pearls:

• Things that DO NOT work: IV fluids, 5-HT3 Antagonists (aka Zofran), diphenhydramine (aka Benadryl), opioids

• Things that KINDA work: oxygen for all headaches, sphenopalatine ganglion block (4% lido spray) 

• Things that REALLY work: ketorolac, metoclopramide, prochlorperazine, triptans and ergots, oxygen for cluster headaches

• Things that PREVENT recurrence: dexamethasone for migraine headaches 

• 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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Back pain with lower extremity symptoms can be concerning for cauda equina. Some pointers regarding the H&P:

• Symptoms develop within less than 24 hours in 90% of patients
• Urinary retention develops before incontinence, but up to 30% of patients will have neither.
• Saddle anesthesia or hypoesthesia is present in 81% of patients. Perineal numbness may be patchy, mild, and unilateral initially, making it difficult to elicit.

None of these symptoms independently predicts cauda equina syndrome with an accuracy greater than 65%.

Bottom Line: do not depend on any one finding to reliably exclude or confirm cauda equina.

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