ABSTRACT
TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Guillain Barré Syndrome (GBS) is a syndrome usually consisting of paralyzing illness following an infectious process. SARS-COV-2 virus has well documented complications including pneumonia, ARDS, nephropathy, and thrombosis. Neurologic sequelae of GBS, as described in our case are much less common (1). CASE PRESENTATION: An 85-year-old African American male with recent COVID-19 infection, who presented to the emergency department with bilateral lower extremity weakness and bilateral upper extremity tingling for 24 hours. Vital signs were stable on admission. Physical exam revealed quadriparesis and sensory loss, areflexia of L4 and S1 and no saddle anesthesia. MRI brain and cervical spine revealed no signs of myelitis. Due to concern for COVID-19 post viral syndrome in the setting of new, rapidly progressing neurological symptoms, IVIG therapy was initiated. An EMG study was performed and was consistent with length dependent sensory and motor polyneuropathy, with mixed demyelinating and axonal features. Furthermore, there was minimal to absent recruitment of most muscles, consistent with high severity of disease. Patient's condition continued to worsen. He was intubated and placed on mechanical ventilatory support. While on mechanical ventilation, plasma exchange (PLEX) was initiated with subsequent improvement of his symptoms. Eventually, he was transferred to acute inpatient rehab to continue recovery. DISCUSSION: The most common peripheral nervous system manifestations of COVID-19 usually involve anosmia and chemosensory dysfunction (2). Case reports have shown an association between COVID-19 and GBS. It remains unclear whether humoral molecular mimicry, as seen in C. Jejuni, is also the driving mechanism behind the pathogenesis of GBS in SARS-CoV-2 (3). Reports have highlighted that no known SARS-CoV-2 epitopes have been found to be homologically similar to human peripheral nerve tissue and therefore unable to support immune driven, previously widely described molecular mechanisms of GBS (4). However, this lack of clear genetic similarity does not exclude immune mediated response as it's possible that immunogenic proteins could be modified post-translationally or have non-linear antibody epitopes driving such response (5). In addition, although there has been no evidence of SARS-CoV-2 detection in CSF (6), a small sample size of CSF studies from COVID 19 patients likely points towards overall inflammation caused by virus leading to immune cascade and possible infiltration of immune cells locally leading to CNS injury (7). CONCLUSIONS: Clinicians treating COVID-19 viral syndromes should be aware of the association between COVID-19 and GBS, especially when caring for patients with rapidly progressing neurologic disease. Further work needs to be done to broaden the understanding of pathogenesis of GBS in such cases. REFERENCE #1: Montalvan V, Lee J, Bueso T et al. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clinical Neurology and Neurosurgery 194. REFERENCE #2: Lechner M, Chandrasekharan D, Jumani K, Liu et al. Anosmia as a presenting symptom of SARS-CoV-2 infection in healthcare workers - A systematic review of the literature, case series, and recommendations for clinical assessment and management. Rhinology. 2020 Aug 1;58(4):394-399. REFERENCE #3: Loshaj-Shala A, Regazzoni L, Daci A, Orioli M, Brezovska K, Panovska AP, et al. Guillain Barré syndrome (GBS): new insights in the molecular mimicry between C. Jejuni and human peripheral nerve (HPN) proteins. J Neuroimmunology 2015;289: 168–76. DISCLOSURES: No relevant relationships by Mateusz Gorecki, source=Web Response no disclosure on file for Dean Kalam;No relevant relationships by Ahamed Khalyfa, source=Web Response
ABSTRACT
TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Immunosuppressive therapy is essential for organ transplanted patients. One such broadly used agent is the commonly used macrolide antibiotic tacrolimus. Tacrolimus has several well-known adverse effects including nephrotoxicity, neurotoxicity, infection, diarrhea. Reports of supraventricular tachycardia as a side effect of tacrolimus are rare. CASE PRESENTATION: We present a 48-year-old male with a history of non-ischemic cardiomyopathy status post orthotopic heart transplant who presented to the hospital due to sudden onset palpitations with mild diaphoresis which lasted 30 minutes in duration. Patient reported some mild diaphoresis but no shortness of breath, chest pain, lightheadedness, or dizziness. The patient stated that he had been experiencing episodes of tachycardia for the last few months but none that had persisted to this extent. He reported medication compliance. His vitals were Temp 98.4, BP 140/88, HR 260, RR 20. After review of his EKG, he was diagnosed with supraventricular tachycardia (SVT) (referenced EKG is after adenosine administration). The patient was hospitalized a few months prior to admission for COVID 19 infection and acute pulmonary embolism. His transplant antirejection regimen was changed from sirolimus to tacrolimus during this prior hospitalization due to the increased risk of thrombosis associated with sirolimus in view of the recognized prothrombic effects of COVID-19. Incidentally, the patient started experiencing sporadic episodes of tachycardia since this change in his medication regimen. In the emergency department, diagnostic studies such as troponins, CBC, BMP, magnesium, hepatic panel, TSH, CMV DNA were within normal parameters for the patient. Tacrolimus blood concentration level was found to be 17 with a goal normal level between 4 to 6. The patient had a right/left heart catheterization with endomyocardial biopsy which showed no evidence of coronary artery vasculopathy or acute cellular rejection, thereby ruling out other potential causes of his SVT. His tacrolimus dose was subsequently decreased with significant improvement in the frequency of his symptoms and no further reported episodes of SVT (with further tacrolimus levels not exceeding 7). DISCUSSION: The mechanism by which tacrolimus leads to SVT is not well understood. One purported mechanism is through the inhibition of the calcineurin-calcium-calmodulin complex. Calcium calmodulin is coincidentally also used by smooth muscle cells to contract. It is thought that by inhibiting this system, there is a subsequent increase in vasodilation which leads to the increased sympathetic and adrenergic response, thereby increasing the risk of arrhythmias such as SVT. CONCLUSIONS: Incessant dysrhythmias caused by tacrolimus can be life-threatening, whereby we seek to raise awareness of the importance of carefully monitoring patients on this drug. REFERENCE #1: Kim BR, Shin HS, Jung YS, Rim H. A case of tacrolimus-induced supraventricular arrhythmia after kidney transplantation. Sao Paulo Med J. 2013;131(3):205-207. doi:10.1590/1516-3180.2013.1313472 REFERENCE #2: Pires SDS, Oliveira R, Moradas-Ferreira P, Mendes MV. The Onset of Tacrolimus Biosynthesis in Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status. Antibiotics (Basel). 2020;9(10):703. Published 2020 Oct 15. doi:10.3390/antibiotics9100703 REFERENCE #3: Wojciechowski D, Wiseman A. Long-Term Immunosuppression Management: Opportunities and Uncertainties [published online ahead of print, 2021 Apr 14]. Clin J Am Soc Nephrol. 2021;CJN.15040920. doi:10.2215/CJN.15040920 DISCLOSURES: No relevant relationships by Jamarcus Brider, source=Web Response No relevant relationships by Ahamed Khalyfa, source=Web Response No relevant relationships by Navkiran Randhawa, source=Web Response