Immune checkpoint inhibitor induced myocarditis, myasthenia gravis, and myositis: A single-center case series.

BACKGROUND: Immune checkpoint inhibitors can result in overlap syndrome comprised of myasthenia gravis, myositis and myocarditis. However, the mortality predictors have not been clearly delineated. METHODS: We examined the characteristics of 11 patients diagnosed with overlap syndrome at Cleveland Clinic. All the available clinical, diagnostic, biochemical and disease specific factors were examined. Clinical predictors of increased mortality were using student t-test for parametric data and Wilcoxon-signed rank testing for nonparametric data. RESULTS: Seven patients out of eleven patients were alive during the analysis. Our study did confirm that troponins were indicator of early demise. However, study showed that elevated creatinine, BUN, and decreased hemoglobin were also observed in patients who met early demise. Unlike previously published studies, elevated NT Pro-BNP and reduced left ventricular ejection fraction were not a seen in this study. However, there were higher incidence of electrical abnormalities in deceased patients when compared to alive. CONCLUSION: Our study is first to examine various clinical parameters of overlap syndrome that might be predictive of mortality. This study confirms troponin as possible predictor and adds elevated creatinine, BUN and reduced hemoglobin as possible early biomarkers in deceased patients. The analysis showed that reduced LVEF was not a seen in deceased patients.

Electrodiagnostic Assessment of Radiculopathies.

This article discusses the electrodiagnostic assessment of radiculopathy. Relevant anatomy initially is reviewed followed by discussion surrounding the approach to nerve conduction studies and needle electrode examination when it comes to radiculopathy evaluation. Pitfalls of the electrodiagnosis versus clinical diagnosis of radiculopathy and the definitions of acute versus chronic, and active versus inactive, are reviewed.

Evaluating the frequency of positive paraneoplastic antibodies and associated malignancy risk.

OBJECTIVE: To evaluate the association between malignancy and frequently positive paraneoplastic antibodies. METHODS: A retrospective cohort study was carried out for all patients who received paraneoplastic antibody testing in 2013-2014 at a tertiary referral center. Available medical records on included patients were reviewed through July 2020. Patients were divided into antibody positive and negative subgroups. Focused analysis was performed on the subgroup of patients who received testing via a commonly used antibody panel. RESULTS: A total of 1860 patients (the full cohort) received 19,323 antibody testing via panel or individual antibody testing, and were followed-up for a mean period of 36.2 months (range 0-83 months). Altogether 229 antibodies in 196 patients were positive, and 9 (3.9%) in 7 patients were against onconeuronal antigens. The remaining 220 (96.1%) were positive for mostly antibodies against cell surface or synaptic antigens. A total of 1161 patients received Mayo Clinic paraneoplastic antibody panel tests (the panel cohort), and 14.9% (173) of these patients possessed one or more positive antibodies. For the panel cohort, no difference was found between antibody positive and negative groups with respect to the prevalence of previously existing malignancy (15.6% versus 16.6%, p = 0.745) or incidence of new malignancy (4.0% vs. 3.7%, p = 0.848) during the follow-up period. No difference was observed in the incidence of new malignancy during follow-up between the antibody positive and negative groups for the 7 most frequently positive antibodies. CONCLUSIONS: The presence of frequently positive antibodies, mostly to cell surface or synaptic antigens, is not clearly associated with the development of malignancy in the subsequent three years.

Clinical course of infectious intracranial aneurysm undergoing antibiotic treatment.

INTRODUCTION: Infectious intracranial aneurysm (IIA, or mycotic aneurysm) is a cerebrovascular complication of infective endocarditis. We aimed to describe the clinical course of IIAs during antibiotic treatment. METHODS: We reviewed medical records of persons with infective endocarditis who underwent cerebral angiography at a single tertiary referral center from 2011 to 2016. Aneurysms were followed with subsequent angiography for unfavorable outcome (growth, rupture, no change, or new IIA formation) or favorable outcome (regression or resolution) until endovascular therapy, aneurysm resolution, or end of observation. RESULTS: Of 618 patients included, 40 (6.5%) had 43 IIAs. Eighteen (42%) aneurysms underwent initial endovascular treatment. Twenty-five unruptured aneurysms were followed for a median 18 antibiotic days after IIA discovery (interquartile range [IQR] 4-32). Eleven (44%) aneurysms had unfavorable outcome (1 rupture, 2 new IIA formation, 6 enlargement, and 2 no change) at median 21 days (IQR 5-32). Favorable angiographic outcome was seen in 7 (28%) patients (6 resolution, 1 regression) at median 36 days (IQR 24-41). Seven aneurysms had no angiographic reevaluations but showed no evidence of rupture during clinical follow-up for median 4 days (IQR 3-12) until hospital discharge. Saccular morphology was associated with unfavorable aneurysmal outcome (p = 0.013). Longer duration of antibiotic exposure prior to IIA discovery was associated with favorable aneurysmal outcome (p = 0.046). CONCLUSION: IIAs represent a dynamic disease. Only a quarter of IIAs resolve with antibiotics alone. Saccular aneurysmal morphology might predict unfavorable aneurysmal outcome. IIA found after longer antibiotic therapy has higher likelihood of resolution or regression on antibiotic treatment.

Acute Ischemic Stroke Therapy in Infective Endocarditis: Case Series and Systematic Review.

OBJECTIVES: To evaluate the safety of acute ischemic stroke (AIS) therapy in patients with infective endocarditis (IE) with intravenous thrombolysis (IVT) or endovascular therapy (EVT) such as mechanical thrombectomy. METHODS: We conducted a retrospective study of patients who underwent AIS therapy with IVT or EVT at a tertiary referral center from 2013 to 2017, that were later diagnosed with acute IE as the causative mechanism. We then performed a systematic review of reports of acute ischemic reperfusion therapy in IE since 1995 for their success rates in terms of neurological outcome, and mortality, and their risk of hemorrhagic complication. RESULTS: In the retrospective portion, 8 participants met criteria, of whom 4 received IVT and 4 received EVT. Through systematic review, 24 publications of 32 participants met criteria. Combined, a total of 40 participants were analyzed: 18 received IVT alone, 1 received combined IVT plus EVT, and 21 received EVT alone. IVT compared to EVT were similar in rates of good neurologic outcomes (58% versus 76%, P= .22) and mortality (21% versus 19%, P= .87), but had higher post-therapy intracranial hemorrhage (63% versus 18% [P= .006]). CONCLUSION: IV thrombolysis has a higher rate of post-therapy intracranial hemorrhage compared to EVT. EVT should be considered as first-line AIS therapy for patients with known, or suspected, IE who present with a large vessel occlusion.

Lumbosacral Radiculoplexopathy as the Initial Presentation of Lymphoma: A Report of 4 Cases.

OBJECTIVES: To evaluate the clinical, laboratory, and radiological features of 4 cases of biopsy-proven lymphomatous lumbosacral radiculoplexopathy. METHODS: Retrospective chart review. RESULTS: All patients suffered from diffuse large B-cell lymphoma. A mean diagnostic delay of 10 months was encountered. Presenting symptoms in all 4 patients included back pain, radicular leg pain, and leg weakness, similar to spondylotic radiculopathy. Electrodiagnostic study showed axon loss radiculoplexopathy and magnetic resonance imaging of the lumbar spine or pelvis demonstrated nerve or nerve root enhancement. Increased uptake by lumbosacral roots/plexus on fluorodeoxyglucose-positron emission tomography aided diagnosis in 3 cases. Cytology was positive in 1 of 10 cerebrospinal fluid samples. Combined chemotherapy and radiation treatment led to clinicoradiological improvement, with residual neurological symptoms in all patients. CONCLUSIONS: Lymphomatous lumbosacral radiculoplexopathy should be considered in patients with progressive lumbosacral radicular symptoms. Magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography, but not cerebrospinal fluid, are helpful in achieving early diagnosis. Treatment responses seem favorable.

Pharmacokinetic and Chemical Synthesis Optimization of a Potent d-Peptide HIV Entry Inhibitor Suitable for Extended-Release Delivery.

Peptides often suffer from short in vivo half-lives due to proteolysis and renal clearance that limit their therapeutic potential in many indications, necessitating pharmacokinetic (PK) enhancement. d-Peptides, composed of mirror-image d-amino acids, overcome proteolytic degradation but are still vulnerable to renal filtration due to their small size. If renal filtration could be slowed, d-peptides would be promising therapeutic agents for infrequent dosing, such as in extended-release depots. Here, we tether a diverse set of PK-enhancing cargoes to our potent, protease-resistant d-peptide HIV entry inhibitor, PIE12-trimer. This inhibitor panel provides an opportunity to evaluate the PK impact of the cargoes independently of proteolysis. While all the PK-enhancing strategies (PEGylation, acylation, alkylation, and cholesterol conjugation) improved in vivo half-life, cholesterol conjugation of PIE12-trimer dramatically improves both antiviral potency and half-life in rats, making it our lead anti-HIV drug candidate. We designed its chemical synthesis for large-scale production (CPT31) and demonstrated that the PK profile in cynomolgous monkeys supports future development of monthly or less frequent depot dosing in humans. CPT31 could address an urgent need in both HIV prevention and treatment.

Magnetic Resonance Imaging Susceptibility-Weighted Imaging Lesion and Contrast Enhancement May Represent Infectious Intracranial Aneurysm in Infective Endocarditis.

BACKGROUND: Infectious intracranial aneurysm (IIA) can complicate infective endocarditis (IE). We aimed to describe the magnetic resonance imaging (MRI) characteristics of IIA. METHODS: We reviewed IIAs among 116 consecutive patients with active IE by conducting a neurological evaluation at a single tertiary referral center from January 2015 to July 2016. MRIs and digital cerebral angiograms (DSA) were reviewed to identify MRI characteristics of IIAs. MRI susceptibility weighted imaging (SWI) was performed to collect data on cerebral microbleeds (CMBs) and sulcal SWI lesions. RESULTS: Out of 116 persons, 74 (63.8%) underwent DSA. IIAs were identified in 13 (17.6% of DSA, 11.2% of entire cohort) and 10 patients with aneurysms underwent MRI with SWI sequence. Nine (90%) out of 10 persons with IIAs had CMB >5 mm or sulcal lesions in SWI (9 in sulci, 6 in parenchyma, and 5 in both). Five out of 8 persons who underwent MRI brain with contrast had enhancement within the SWI lesions. In a multivariate logistic regression analysis, both sulcal SWI lesions (p < 0.001, OR 69, 95% CI 7.8-610) and contrast enhancement (p = 0.007, OR 16.5, 95% CI 2.3-121) were found to be significant predictors of the presence of IIAs. CONCLUSIONS: In the individuals with IE who underwent DSA and MRI, we found that neuroimaging characteristics, such as sulcal SWI lesion with or without contrast enhancement, are associated with the presence of IIA.

Neurologic Injuries in Noncontact Sports.

Noncontact sports are associated with a variety of neurologic injuries. Concussion, vascular injury (arterial dissection), and spinal cord trauma may be less common in noncontact sports, but require special attention from the sports neurologist. Complex regional pain disorders, muscle injury from repetitive use, dystonia, heat exposure, and vascular disorders (patent foramen ovale), occur with similar frequency in noncontact and contact sports. Management of athletes with these conditions requires an understanding of the neurologic consequences of these disorders, the risk of injury with return to play, and consideration for the benefits of exercise in health restoration and disease prevention.