POTD: Treat methotrexate neurotoxicity with cough syrup!

How do I treat methotrexate neurotoxicity?

(Yes it's a thing) 

Case from today 

12yo M w/ ALL on methotrexate therapy presents with 1 day of worsening R facial droop and R sided weakness. MRI showed non-enhancing, hyperintense signal on T2 and flair consistent with MTX leukoencephalopathy.

Methotrexate

• Folic acid antagonist

• Used as chemotherapeutic agent or DMARD

• May be given orally, IV, or intrathecally

Neurotoxicity

• Can occur anytime after methotrexate use (hours to days to weeks)

• Symptoms include seizure or stroke-like signs: hemiparesis, hemisensory deficits, aphasia, dysarthria, diplopia, dysphagia

Proposed Mechanism

1. Methotrexate interferes with metabolism of homocysteine

2. Homocysteine levels rise in blood and CSF

3. Downstream effect is NMDA receptor agonism as well as neurotoxicity

Treatment: Dextromethorphan

• Theoretically, NMDA inhibitor could counteract these effects...

• Dextromethorphan is a noncompetitive NMDA receptor antagonist.

• Case series show improvement and even resolution of symptoms after administration of dextromethorphan.

• Symptoms may resolve in minutes, but on average took half a day. Some patients still had neuro symptoms months later.
  
  

References

• Afshar, M., Birnbaum, D., & Golden, C. (2014). Review of Dextromethorphan Administration in 18 Patients With Subacute Methotrexate Central Nervous System Toxicity. Pediatric Neurology, 50(6), 625–629. doi:10.1016/j.pediatrneurol.2014.01.048

• Drachtman, R. A., Cole, P. D., Golden, C. B., James, S. J., Melnyk, S., Aisner, J., & Kamen, B. A. (2002). DEXTROMETHORPHAN IS EFFECTIVE IN THE TREATMENT OF SUBACUTE METHOTREXATE NEUROTOXICITY. Pediatric Hematology and Oncology, 19(5), 319–327. doi:10.1080/08880010290057336

• Radiopedia: Methotrexate-related leukoencephalopathy <https://radiopaedia.org/articles/methotrexate-related-leukoencephalopathy?lang=us>

POTD: Peds C Spine Clearance

How do I clear a pediatric C-Spine?

TL;DR

• While c-spine injury in children is rare, children have some anatomical differences that make their c-spines prone to injury

• NEXUS and Canadian C-Spine Rule cannot be used in children  

• PECARN study identified 8 risk factors: 

  • AMS

  • focal neuro deficits

  • torticollis

  • complaint of neck pain

  • significant torso injury, predisposing conditions

  • high risk MVC

  • diving

• If any of the 8 is present, they found a 98% sensitivity for injury. 

• The Pediatric Cervical Spine Clearance Working Group put together an algorithm based on the PECARN study (see graphic)

Anatomy Review 

• Bigger heads

  • Due to the larger head:body mass ratio, children’s natural fulcrums are more caudal, meaning they’re much more likely to sustain high c-spine fractures. 

  • In an infant, this fulcrum is located at around C2-C3 and eventually moves down to C5-C6 by adulthood.

  • Most c-spine injuries occur between the occiput and C3 in children < 8 years of age

• Spinal column flexibility

  • This does not apply to the spinal cord!

  • Meaning you can have significant spinal cord injury without injury to the spinal column

  • This is how SCIWORA happens (spinal cord injury without radiographic abnormality)

• Poor musculature

  • Less protection against injury

• Ossification Centers

  • Can make it difficult to identify injury even with imaging

• Vertebral facet joints

  • More horizontal than adults

  • Requires less force to cause dislocation

NEXUS (2000) and the Canadian Cervical Spine Rule (2001) are the two most frequently used adult scoring systems for risk stratification, but NEXUS only had 9% of patients under 18 and the Canadian completely excluded patients under 18. 

Should we scan every pediatric trauma patient? (Obviously no!)

In 2011, PECARN published a study identifying risk factors that looked at patients with and without c-spine injury and looked at characteristics that were similar among the group with c-spine injury. What they identified were 8 major risk factors that were associated with c-spine injury (using odds ratios with a CI of 95%):

1. Altered mental status

2. Focal neurological deficits

3. Complaint of neck pain

4. Torticollis

5. Substantial injury to the torso

6. Predisposing conditions (e.g. Down Syndrome or other musculoskeletal abnormalities)

7. High risk motor vehicle crash

8. Diving injury

They found that these factors were able to identify c-sine injury with 98% sensitivity when any of the eight were present. Specificity was 26%. They were also able to conclude that this would decrease diagnostic imaging by 25%. 

Keep in mind this study is not perfect and a subsequent validation study only showed 90% sensitivity with a large confidence interval. 

Consensus Statements... 

This year, based on this study, the Pediatric Cervical Spine Clearance Working Group released a consensus statement in the Journal of Bone and Joint Surgery and proposed the following algorithm (PCSCWG algorithm – clearly they need to work on their acronyms). 

Fun EMS related fact: the NAEMSP (National Association of EMS Physicians also released a position statement in 2018 that application of a c-collar is not necessary if a child does not have:

• Complaint of neck pain

• Torticollis

• Neurological deficit

• Altered mental status (including intoxication and other signs of AMS such as agitation, apnea, hypopnea, somnolence, etc.)

• Involvement in a high-risk MVC, high impact diving injury, or substantial torso injury

Resources:

1. Fischer PE, Perina DG, Delbridge TR, et al. Spinal motion restriction in the trauma patient – a joint position statement. Prehospital Emergency Care. 2018;22(8):659-661.

2. Leonard JC,Kuppermann N, Olsen C, et al. Factors associated with cervical spine injury in children after blunt trauma. Annals of Emergency Medicine. 2019;58(2):145-155.

3. Herman MJ, Brown KO, Sponseller PD, et al. Pediatric cervical spine clearance: a consensus statement and algorithm from the pediatric cervical spine clearance working group. J Bone Joint Surg Am. 2019;101;e1(1-9). 

4. Fox SM. Pediatric cervical spine injury. Pediatric EM Morsels. https://pedemmorsels.com/pediatric-cervical-spine-injury/. Published February 8, 2019. Accessed July 5, 2019. 

POTD: Blastomycosis

What's the deal with blasto?

Blastomycosis

• Infection comes from inhalation of Blastomyces dermatitis or Blastomyces gilchristii

• Endemic to soil in Great Lakes, Ohio, Mississippi and Saint Lawrence River valleys

• And now emerging in upstate New York!

Infection

• May be asymptomatic, flu-like illness, to respiratory failure and death

• Lung (91%)

  • Symptoms: cough, fever, sputum production, chest pain, shortness of breath, weight loss, night sweats, chills, hemoptysis

  • Can present as acute or chronic pneumonia that does not respond to treatment

  • May lead to ARDS

• Extrapulmonary disease

  • Skin (18%) - gray to violet verrucous lesions with irregular boarders

    • may be mistaken for pyoderma gangrenosum or squamous cell carcinoma

Diagnosis

• Urine and serum antigens (urine more sensitive), high cross reactivity with histoplasmosis

• Histologic visualization of yeast on sputum, tissue, or purulence sample

• Culture (sputum cultures often contaminated with bacteria that will inhibit growth so should also be cultured on medium with chloramphenicol)

• CT - nodules, consolidation w/ or w/out cavitation, tree-in-bud opacities, LACK of significant hilarity adenopathy (distinguishes it from histoplasmosis)

Treatment

• Severe: Amphotericin B 3-5mg/kg daily for 1-2 weeks until improvement noted, then Itraconazole 200mg TID x 3 days then BID for 6-12 months

• Moderate to mild: Itraconazole 200mg TID x 3 days then BID or QD for 6-12 months

  • Can use fluconazole or ketoconazole but less effective