Episode 916: Central Cord Syndrome

Contributor: Alec Coston, MD Educational Pearls: Disclaimer: this has nothing to do with the ER but is too cool to not talk about. Condition: Carbamoyl phosphate synthetase 1 (CPS1) deficiency Rare inborn error of metabolism Inability to properly break down ammonia Leads to severe hyperammonemia and hepatic encephalopathy Natural history: Without treatment, typically fatal within the first few weeks of life Even with current standard treatments, life expectancy is often limited to ~5–6 years Breakthrough treatment: A team of researchers at the Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania developed the CRISPR-based targeted gene therapy for this patient. First-of-its-kind precision approach tailored to the patient's specific mutation Key components of the therapy: Whole-genome sequencing to identify the exact CPS1 mutation Creation of a custom base-editing enzyme designed to correct that specific mutation Design of a guide RNA to direct the base editor to the precise genomic location Delivery method: Lipid nanoparticles used to deliver the gene-editing machinery Nanoparticles can be targeted to specific tissues Why the liver works well: CPS1 is primarily expressed in hepatocytes The liver is relatively easy to target with lipid nanoparticles Hepatocytes divide frequently, allowing edited genes to be passed on as cells replicate Long-term impact: Once edited, cells continue producing functional CPS1 enzyme Potential for durable, possibly lifelong correction from a single treatment References https://www.nih.gov/news-events/news-releases/infant-rare-incurable-disease-first-successfully-receive-personalized-gene-therapy-treatment Choi Y, Oh A, Lee Y, Kim GH, Choi JH, Yoo HW, Lee BH. Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency. Clin Chim Acta. 2022 Feb 1;526:55-61. doi: 10.1016/j.cca.2021.11.029. Epub 2021 Dec 29. PMID: 34973183. Bharti N, Modi U, Bhatia D, Solanki R. Engineering delivery platforms for CRISPR-Cas and their applications in healthcare, agriculture and beyond. Nanoscale Adv. 2026 Jan 5. doi: 10.1039/d5na00535c. Epub ahead of print. PMID: 41640466; PMCID: PMC12865601. Summarized and edited by Jeffrey Olson MS4 Donate: https://emergencymedicalminute.org/donate/ Join our mailing list: http://eepurl.com/c9ouHf

9 Feb 6min

Contributors: Travis Barlock MD, Ian Gillman PA, Jacob Altholz MD, Jeffrey Olson MS4 In this episode, EM attending Travis Barlock and medical student Jeffrey Olson listen in to the two remaining cases presented from EMM's recent event, Tox Talk 2025.  Talk 1- Methemoglobinemia- Ian Gillman Cyanosis + chocolate-colored blood + normal PaO₂ + pulse ox stuck at ~85% = Methemoglobinemia → Treat with methylene blue The medications that can cause it can be remembered with… Watch out with methylene blue as it can cause serotonin syndrome While treating with methylene blue the pulse ox can drop dramatically but this is not a real drop in oxygenation but rather an effect of how the methylene blue affects the sensor BADNAPS: causes of methemoglobinemia Benzocaine Aniline Dyes Dapsone Nitrites/Nitrates (Found in meds, preservatives, and well water) Antimalarials Pyridium Sulfonamides Talk 2- Intratecal TXA and Hierarchy of Controls for Error Avoidance - Jacob Altholz Hierarchy of Controls in terms of error prevention includes all of the layers of protection which can be categorized as elimination, substitution, engineering controls, administration controls, and PPE References Centers for Disease Control and Prevention. (2022, April 28). Hierarchy of controls. National Institute for Occupational Safety and Health. https://www.cdc.gov/niosh/learning/safetyculturehc/module-3/2.html Pushparajah Mak RS, Liebelt EL. Methylene Blue: An Antidote for Methemoglobinemia and Beyond. Pediatr Emerg Care. 2021 Sep 1;37(9):474-477. doi: 10.1097/PEC.0000000000002526. PMID: 34463662. Produced by Jeffrey Olson, MS4 Donate: https://emergencymedicalminute.org/donate/ Join our mailing list: http://eepurl.com/c9ouHf

4 Feb 41min

Contributor: Alec Coston, MD Educational Pearls: BiPAP is often effective in severe asthma, but many patients struggle with mask tolerance due to intense air hunger–driven anxiety, often compounded by hypoxia. Benzodiazepines are commonly used for anxiety, but they can depress respiratory drive, making clinical improvement difficult to interpret (a lower RR may reflect sedation rather than true physiologic improvement). Low-dose fentanyl is a useful alternative when patients cannot tolerate BiPAP despite coaching. Opioids blunt the perception of dyspnea and are well established for treating air hunger. When carefully titrated, fentanyl provides anxiolysis without significant respiratory suppression. It is rapidly titratable (e.g., 25 mcg IV every 5 minutes). Evidence primarily comes from palliative and oncology literature, but growing clinical experience supports its use in severe asthma to improve BiPAP tolerance. Failure of fentanyl should prompt escalation to ketamine, often signaling impending need for intubation. References Pang GS, Qu LM, Tan YY, Yee AC. Intravenous Fentanyl for Dyspnea at the End of Life: Lessons for Future Research in Dyspnea. Am J Hosp Palliat Care. 2016 Apr;33(3):222-7. doi: 10.1177/1049909114559769. Epub 2014 Nov 25. PMID: 25425740. Summarized and edited by Meg Joyce, MS2 Donate: https://emergencymedicalminute.org/donate/ Join our mailing list: http://eepurl.com/c9ouHf

2 Feb 4min

Contributor: Aaron Lessen, MD Educational Pearls BRASH Syndrome: Bradycardia Renal Failure AV Nodal Blockade Shock Hyperkalemia  Clinical Features: Profound bradycardia and shock in patients on AV nodal blockers: Commonly, Beta Blockers or Calcium Channel Blockers Etiology:  Caused by an inciting kidney injury: Common triggers include precipitating illness, dehydration, or medications  Results in hyperkalemia The enhanced effect of the combination of AV nodal blockade and hyperkalemia leads to a more profound presentation of shock. Treatment:  IV Fluids, unless volume overloaded Epinephrine for bradycardia Lasix for volume overload, only if the patient is still making urine Low threshold to dialyze for hyperkalemia Focus on treating early and more aggressively.  References: Farkas JD, Long B, Koyfman A, Menson K. BRASH Syndrome: Bradycardia, Renal Failure, AV Blockade, Shock, and Hyperkalemia. J Emerg Med. 2020 Aug;59(2):216-223. doi: 10.1016/j.jemermed.2020.05.001. Epub 2020 Jun 18. PMID: 32565167.   Summarized by Ashley Lyons OMS3 Editting by Ashley Lyons OMS3 and Jeffrey Olson MS4   Donate: https://emergencymedicalminute.org/donate/ Join our mailing list: http://eepurl.com/c9ouHf

19 Jan 2min

Contributor: Taylor Lynch, MD Educational Pearls: What is tramadol and how does it work? Tramadol is a Schedule IV opioid analgesic used for moderate pain and is often perceived as safer than other opioids due to lower abuse potential. It is a prodrug with weak direct μ-opioid receptor activity. The parent compound also inhibits serotonin and norepinephrine reuptake, giving it SSRI/SNRI-like properties. Tramadol is metabolized by CYP2D6 into O-desmethyltramadol (ODT), which has significantly stronger μ-opioid receptor agonism than the parent drug. What are the concerns with tramadol? Ultrarapid CYP2D6 metabolizers (more common in Middle Eastern and North African populations) rapidly convert tramadol to ODT, increasing the risk of opioid toxicity. Poor CYP2D6 metabolizers generate little ODT and may experience primarily serotonergic effects, increasing the risk of serotonin syndrome, especially when combined with SSRIs or SNRIs. CYP2D6 inhibitors (e.g., bupropion, paroxetine, terbinafine, celecoxib) can block tramadol's conversion to ODT, potentially precipitating opioid withdrawal or increasing serotonergic toxicity. Tramadol is also associated with an increased risk of first-time seizures, even at therapeutic doses. Key takeaways Tramadol's effects are highly unpredictable, varying from minimal analgesia to exaggerated opioid effects depending on metabolism. Drug–drug interactions can lead to serotonin syndrome or opioid withdrawal. Despite its Schedule IV classification and reputation for safety, alternative analgesics may be preferable in many patients. References DailyMed - TRAMADOL HYDROCHLORIDE tablet, coated. Accessed January 10, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61fb5ba7-6896-4ee4-83de-caee69b06a8e#ID57 Dean L, Kane M. Tramadol Therapy and CYP2D6 Genotype. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, eds. Medical Genetics Summaries. National Center for Biotechnology Information (US); 2012. Accessed January 10, 2026. http://www.ncbi.nlm.nih.gov/books/NBK315950/ Aly SM, Tartar O, Sabaouni N, Hennart B, Gaulier JM, Allorge D. Tramadol-Related Deaths: Genetic Analysis in Relation to Metabolic Ratios. J Anal Toxicol. 2022;46(7):791-796. doi:10.1093/jat/bkab096 Summarized and edited by Dan Orbidan OMS2 Donate: https://emergencymedicalminute.org/donate/ Join our mailing list: http://eepurl.com/c9ouHf

12 Jan 5min

Contributor: Aaron Lessen, MD Educational Pearls: The Case 24F brought in for anxiety. Patient is tearful, not talking, and potentially hyperventilating. History from boyfriend is that she suddenly stopped talking and started crying and it was hard to understand what she was saying. On exam, patient appears anxious and has a gaze preference for the right side and is still having difficulty speaking. Decision is made to stroke alert patient. CT shows early MCA stroke and M2 occlusion. Patient is treated by IR with mechanical thrombectomy. What are the risk factors for strokes in young people ( Traditional risk factors still matter Hypertension  Most important modifiable risk factor, present in 30-50% of young stroke patients Diabetes Especially insulin dependent type 1 HLD Smoking Substance use Cocaine Meth Alcohol, especially binge drinking IV drug use Structural heart disease PFO Valvular heart disease like rheumatic disease Hypercoagulable states Factor V Leiden Protein C or S deficiency Antithrombin III deficiency Vertebral dissections Recent trauma References Aigner A, Grittner U, Rolfs A, Norrving B, Siegerink B, Busch MA. Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults. Stroke. 2017 Jul;48(7):1744-1751. doi: 10.1161/STROKEAHA.117.016599. Epub 2017 Jun 15. PMID: 28619986. Ekker MS, Boot EM, Singhal AB, Tan KS, Debette S, Tuladhar AM, de Leeuw FE. Epidemiology, aetiology, and management of ischaemic stroke in young adults. Lancet Neurol. 2018 Sep;17(9):790-801. doi: 10.1016/S1474-4422(18)30233-3. PMID: 30129475. Khan M, Wasay M, O'Donnell MJ, Iqbal R, Langhorne P, Rosengren A, Damasceno A, Oguz A, Lanas F, Pogosova N, Alhussain F, Oveisgharan S, Czlonkowska A, Ryglewicz D, Yusuf S. Risk Factors for Stroke in the Young (18-45 Years): A Case-Control Analysis of INTERSTROKE Data from 32 Countries. Neuroepidemiology. 2023;57(5):275-283. doi: 10.1159/000530675. Epub 2023 May 17. PMID: 37231971. Summarized and edited by Jeffrey Olson MS4 Donate: https://emergencymedicalminute.org/donate/ Join our mailing list: http://eepurl.com/c9ouHf

5 Jan 3min

Contributor: Aaron Lessen, MD Educational Pearls: A 2025 multistate outbreak of infant botulism has been linked to ByHeart infant formula As of December 10-17th, there have been at least 51 infants with suspected or confirmed botulism who were exposed to this formula across 19 states All reported cases resulted in hospitalization but no deaths reported to date Infant botulism  Occurs when C. botulinum spores germinate in the infant's intestine, producing toxin Spores are classically found in honey but can also be in dirt or contaminated in infant formula Infants are particularly susceptible because their body can't neutralize the spores Symptoms may include initial constipation, poor feeding, weak cry, floppy movements, loss of head control, difficulty swallowing, generalized weakness, and respiratory compromise if progressive Can be treated with antitoxin  Maintain a high index of suspicion for infant botulism in infants fed the recalled formula presenting with neuromuscular symptoms.  References Human Foods Program. Outbreak Investigation of Infant Botulism: Infant Formula. U.S. Food and Drug Administration. Published 2025. https://www.fda.gov/food/outbreaks-foodborne-illness/outbreak-investigation-infant-botulism-infant-formula-november-2025 Summarized by Meg Joyce, MS2 | Edited by Meg Joyce & Jeffrey Olson, MS4 Donate: https://emergencymedicalminute.org/donate/

29 Dec 20252min

Carepoint Journal Club is a quarterly series with discussions about a medical topic, brought to you by Carepoint's Emergency Physicians.

22 Dec 202545min