John Betjemann, MD February 14, 2020 Patient Presentation A 17 - PDF document

John Betjemann, MD February 14, 2020 Patient Presentation A 17 year-old young man presented with altered mental status and depressed respiratory effort. The patient has no known medical history and takes no medications. On the day of admission he was with friends who noted that he may have used some substances and by report he has a history of alcohol and alprazolam (Xanax) abuse. They noted that he was sleeping for a prolonged period of time and became concerned when he appeared to stop snoring. EMS was called and administered naloxone without effect. Upon arrival to the emergency room he was noted to be breathing spontaneously but had a Glasgow Coma Scale of 3. On his initial neurologic exam he was intubated, sedated and paralyzed. He underwent routine laboratory testing that revealed a mildly elevated creatinine, creatine kinase and liver function tests. A non-contrast CT scan of the head was unremarkable. On repeat examination following extubation he was noted to be conversant with fluent speech. He was oriented to the year but not his location or the remainder of the date and frequently answered “I don’t know” when asked other simple orientation questions. The remainder of his neurologic exam including cranial nerves, motor, reflexes, sensation and coordination was unremarkable. Diagnostic procedures were performed. References 1. Somerville NJ, et al. Morb Mortal Wkly Rep 66:382-386, 2017. 2. Barash JA, Somerville N, DeMaria A Jr.. Morb Mortal Wkly Rep 66:76-79, 2017. 3. Barash JA, et al. N Engl J Med 378:1157-1158, 2018. 4. Barash JA, Ganetsky M, DeMaria A Jr. N Engl J Med 378:2247-2248, 2018. 5. Khatri UG, Viner K, Perrone J. N Engl J Med 379:1782, 2018. 6. Frank RG, Pollack HA. N Engl J Med 376:605-607, 2017. 7. Bhattacharyya S, Gholipour T, Colorado DA, Klein JP. J Neuroimaging 27:300- 305, 2017.

John Betjemann, MD February 14, 2020 Case Discussion The patient presented with acute encephalopathy for which the differential diagnosis very broad. Once extubated it became clear that he primarily had an acute amnestic syndrome as well as some disorientation. The MRI was the biggest clue to his diagnosis. The symmetric nature of the MRI changes involving the hippocampi raises suspicion for hypoxia, toxic or metabolic etiologies. The hippocampi are particularly vulnerable to hypoxic-ischemic injury. Neuroimaging studies have demonstrated that bilateral reduced diffusion in the hippocampi often results from hypoxic-ischemic injury, but the underlying causes can be quite varied and include substance abuse (cocaine, opioids, benzodiazepines), cardiac arrest, nonconvulsive seizures and hypoglycemia. Ultimately our patient was diagnosed with fentanyl overdose leading to respiratory compromise, hypoxia, and the hippocampal changes seen on MRI. It is worth noting that in our clinical lab, and likely in many others, it requires an extended toxicology screen to detect fentanyl. Fentanyl overdoses have risen dramatically throughout the country, including in the Bay Area, such that public health interventions are warranted. Fentanyl is being used to cut other illicit drugs such as heroin because it is relatively cheap and potent but is also being used to cut counterfeit oxycodone, alprazolam and hydrocodone/acetaminophen (Norco), often times unbeknownst to the person taking the drug. People who have witnessed a fentanyl overdose describe that symptoms occur rapidly and include blue discoloration of the lips, gurgling sounds, stiffening of the body, foaming at the mouth and confusion. Often a single dose of naloxone is insufficient to reverse the effects of fentanyl. As in this case, fentanyl overdose often causes an acute amnestic syndrome with other areas of cognitive impairment including attention and orientation. The MRI findings in the case presented have been well described in other fentanyl overdoses. The exact mechanism of injury is not known but potential mechanisms include cerebral ischemia, hypoxemia, or excitotoxicity. Other than naloxone, treatment is largely supportive and the amnestic syndrome has been reported to last months or even longer. References 1. Somerville NJ, et al. Characteristics of fentanyl overdose – Massachusetts, 2014- 2016. Morb Mortal Wkly Rep 66:382-386, 2017. 2. Barash JA, Somerville N, DeMaria A Jr. Cluster of an unusual amnestic syndrome – Massachusetts, 2012-2016. Morb Mortal Wkly Rep 66:76-79, 2017. 3. Barash JA, et al. Acute amnestic syndrome associated with fentanyl overdose. N Engl J Med 378:1157-1158, 2018.

4. Barash JA, Ganetsky M, DeMaria A Jr. More on acute amnestic syndrome associated with fentanyl overdose. N Engl J Med 378:2247-2248, 2018. 5. Khatri UG, Viner K, Perrone J. Lethal fentanyl and cocaine intoxication. N Engl J Med 379:1782, 2018. 6. Frank RG, Pollack HA. Addressing the fentanyl threat to public health. N Engl J Med 376:605-607, 2017. 7. Bhattacharyya S, Gholipour T, Colorado DA, Klein JP. Bilateral hippocampal restricted diffusion: same picture many causes. J Neuroimaging 27:300-305, 2017

John Betjemann, MD February 14, 2020 Patient Presentation A 37 year-old transgender woman presents with vision loss, cognitive complaints, and jerking movements that have caused falls. She initially presented with 2 weeks of progressive vision loss of the left eye and was diagnosed with neuroretinitis and macular edema of unclear etiology. She was subsequently lost to follow up. Three years later she presented to clinic with depression, memory complaints and falls. She had a Montreal Cognitive Assessment of 26/30 and was diagnosed with major depressive disorder. Five months later she was seen in the emergency room for worsening depression, worsening cognitive impairment, and new onset insomnia. Reversible causes of dementia labs (B12, HIV, TSH and RPR) were unremarkable. MRI showed trace periventricular T2/FLAIR hyperintensities. She was discharged without a diagnosis. She then returned one month later with continued worsening of all of her symptoms. She was no longer able to work and had noted new gait instability. In particular, she noted jerking movements that would cause her to fall. On her neurologic exam at that time she scored a 13/30 on Montreal Cognitive Assessment (0/5 executive function, 3/3 naming, 3/6 attention, 0/3 language, 1/2 abstraction, 0/5 delayed recall, 6/6 orientation). She was also noted to have hypomimia and hypophonia. Motor exam demonstrated only trace weakness in left hip flexion and rigidity in the left leg. She had diffuse, nonstimulus-dependent myoclonic jerks approximately every 30 seconds. Repeat MRI showed interval worsening of the previously seen periventricular T2/FLAIR hyperintensities bilaterally. Diagnostic procedures were performed. References 1. Holmes BB, Conell-Price J, Kreple CJ, Ashraf D, Betjemann J, Rosendale N. The Neurohospitalist 2019. doi: 10.1177/1941874419869713 2. Garg RK, Mahadevan A, Malhotra HS, Rizvi I, Kumar N, Uniyal R. Rev Med Virol 29(5), 2019. doi: 10.1002/rmv.2058 3. Raut TP, Singh MK, Garg RK, Rai D. BMJ Case Rep 2012. doi: 10.1136/bcr- 2012-007052 4. Colpak AI, Erdener SE, Ozgen B, Anlar B, Kansu T. Curr Opin Ophthalmol 23(6):466-471, 2012