Case of Immune Checkpoint Inhibitor Induced Myasthenia Gravis.

An 85-year-old man was diagnosed with hepatocellular carcinoma (HCC) and was initially treated with transarterial chemoembolization (TACE) and sorafenib. He was then switched to nivolumab and ipilimumab in view of sorafenib intolerance and disease progression. Subsequently, he developed dysphagia and generalized dyspnea culminating in hypercapnic respiratory failure requiring intubation. After an extensive workup, the etiology of his fluctuating respiratory issues was narrowed down to a likely neuromuscular process. Although antibodies to acetylcholine receptors (anti-AChR Ab) were negative, he was treated with high-dose steroids due to clinical concern for Immune Checkpoint Inhibitor (ICI) neurotoxicity. His recovery post immune suppression and absence of recurrence after ICI cessation suggested the possibility of this being an ICI neurotoxicity manifesting with myasthenic symptoms. Incidentally, he also had evidence of aseptic meningitis on cerebrospinal fluid analysis further strengthening this diagnosis. This case illustrates the importance of early recognition of ICI toxicity which will in turn lead to initiating treatments sooner and also decreasing the length of illness.

Cerebellar restricted diffusion in Wernicke's encephalopathy.

A 50-year-old woman presented to an outside hospital for acute onset bilateral lower limb pain. She was diagnosed with aortoiliac stenosis and underwent stent placement. Post-procedure, she was noted to have altered mental status, truncal ataxia, neck titubation, and incomplete external ophthalmoplegia. She rapidly declined to a stuporous state. She had a history of uterine cancer treated with chemoradiation which was complicated by chronic radiation enteritis. She was also reported to have poor oral intake, recurrent emesis, and weight loss for a month before her presentation. After an extensive work up, she arrived at our facility where an MRI of the brain showed restricted diffusion and T2-FLAIR sequence showed hyperintensities of bilateral cerebellum. T2-FLAIR hyperintensities of bilateral dorsomedial thalami, fornix, and post-contrast-enhancement of mammillary bodies were also noted. The clinical picture with imaging findings was concerning for possible thiamine deficiency. In Wernicke's encephalopathy, restricted diffusion, T2-FLAIR hyperintensities, and contrast enhancement may be seen in mammillary bodies, dorsomedial thalami, tectal plate, periaqueductal grey matter, and rarely in the cerebellum as well. Her thiamine level was 70 nmol/l (reference range: 70-180 nmol/l). Thiamine levels can be falsely elevated in patients who are on enteral feeds, which was the case in our patient. She was started on high dose thiamine replacement. At time of discharge, repeat MRI brain revealed resolution of cerebellar changes with mild atrophy and patient had subtle neurological improvement including consistent eye opening, tracking, and attending to examiner, as well as mumbling words.

Ticagrelor inhibits platelet aggregation and reduces inflammatory burden more than clopidogrel in patients with stages 4 or 5 chronic kidney disease.

BACKGROUND: No study has compared pharmacologic properties of ticagrelor and clopidogrel in non-dialysis patients with stage 4-5 chronic kidney disease (CKD). METHODS: We conducted a double-blind RCT to compare effects of ticagrelor and clopidogrel in 48 CKD, with the primary outcome of ADP-induced platelet aggregation (WBPA) after 2 weeks of DAPT. In a parallel arm, we compared effects of 2 weeks of ticagrelor plus aspirin on mean changes in WBPA and markers of thromboinflammation among non-CKD controls (n = 26) with that of CKD in the ticagrelor-arm. RESULTS: Average age of CKD was 53.7 years, with 62% women, 54% African American, and 42% with stage 5 CKD. Ticagrelor generated statistically lower WBPA values post treatment [median 0 Ω (IQR 0, 2)] vs. clopidogrel [median 0 Ω (IQR 0, 5)] (P = 0.002); percent inhibition of WBPA was greater (87 ± 22% vs. 63 ± 50%; P = 0.04; and plasma IL-6 levels were much lower (8.42 ± 1.73 pg/ml vs. 18.48 ± 26.56 pg/ml; P = 0.04). No differences in mean changes in WBPA between CKD-ticagrelor and control groups were observed. Ticagrelor- DAPT reduced levels of IL-1α and IL-1ß in CKD-ticagrelor and control groups, attenuated lowering of TNFα and TRAIL levels in CKD-ticagrelor (vs controls), and had global changes in correlation between various cytokines in a subgroup of CKD-ticagrelor subjects not on statins (n = 10). Peak/trough levels of ticagrelor/metabolite were not different between CKD-ticagrelor and control groups. CONCLUSIONS: We report significant differences in platelet aggregation and anti-inflammatory properties between ticagrelor- and clopidogrel-based DAPT in non-dialysis people with stage 4-5 CKD. These notable inflammatory responses suggest ticagrelor-based DAPT might lower inflammatory burden of asymptomatic patients with stage 4 or 5 CKD. (clinicaltrials.gov # NCT03649711).

Coronavirus Disease 2019 in Patients With Prior Ischemic Stroke.

BACKGROUND: It is uncertain if patients with prior ischemic stroke are vulnerable to coronavirus disease 2019 (COVID-19) and its complications. METHODS: We used TriNetX, a global health collaborative clinical research platform with a large global COVID-19 database. COVID-19 infection was identified with a positive lab value for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related ribonucleic acid (RNA). FINDINGS: A total of 604,258 patients with history of ischemic stroke were identified, of which 891 patients (study cohort) were diagnosed with COVID-19. A control cohort with 32,136 patients diagnosed with COVID-19 after January 20th 2020 without a history of ischemic stroke were identified. A comparison between study cohort and control cohort showed patients with prior history of stroke (study cohort) were older (69.5 vs 47.8; p<0.0001) and had more comorbidities contributing to worse clinical outcomes. After propensity matching for demographic variables and comorbidities, only rate of hospitalization (287 vs 231; p=0.0035) and need for critical care services (85 vs 55; p=0.0082) remained statistically significant while intubation (51 vs 43; p=0.39) and death (119 vs 115; p=0.77) showed trends towards worse outcomes but were not statistically significant.  Interpretation: Patients with history of ischemic stroke tend to be significantly older with several comorbid conditions contributing to worse clinical outcomes after COVID-19, which makes them a vulnerable population.

Trends of Industry Payments in Neurology Subspecialties.

Background Open Payments is a national disclosure program to promote transparency by the public disclosure of financial relationships between the pharmaceutical and medical device industries and physicians. Objective To explore payments from the industry to physicians in various neurology subspecialties. Methods Open Payments Program (OPP) data (https://openpaymentsdata.cms.gov) on industry-to-physician payments for the years 2014-2018 were extracted for general neurology, neuromuscular, neurophysiology, and vascular neurology. The data were then analyzed to explore trends in payments for various subspecialties and to identify the possible factors underlying these trends. Results Overall, industry-to-physician payments for neurology subspecialties increased by 16% from 2014 to 2018. The introduction of newer drugs in a subspecialty was likely the driving factor for higher industry payments. Nearly half of the total industry-to-physician payments were for the subspecialty of multiple sclerosis (MS)/Neuroimmunology; this coincided with Aubagio and Copaxone being the top two medications associated with the highest industry payments in 2014, Aubagio, and Lemtrada in 2018. A significant increase in spending percentages for headache, neuromuscular disorders, and movement disorders was observed while a relative decrease in the payments for MS/neuroimmunology and epilepsy was identified; these trends coincide with the introduction of new drugs such as Aimovig, Neuplazid, Nusinersen, and Austedo for headache, neuromuscular and movement disorders. Conclusions From 2014 to 2018, the total industry-to-physician payments for neurology subspecialties increased while the distribution of industry-to-physician payments for various neurology subspecialties showed notable changes. The introduction of newer medications in a subspecialty coincided with higher industry payments. Identification of these trends and potential motives of the industry spending is critical to address any potential physician bias in prescribing medications.

Causes of delayed arrival with acute ischemic stroke beyond the window period of thrombolysis.

CONTEXT: Early thrombolytic therapy in acute ischemic stroke has proven to reduce the associated morbidity. Many factors are in play, delaying the arrival of patients. AIM: To ascertain the factors causing delay in patients with acute ischemic stroke presenting beyond the window period of thrombolysis in and around Chennai, Tamil Nadu, India. SUBJECTS AND METHODS: An observational cross-sectional study involving 200 patients with acute ischemic stroke at Sri Ramachandra Medical College, Chennai, India between June 2015 and July 2016 was conducted. The data was collected by direct interview using a questionnaire designed to study factors such as age, family structure, residence, distance from the hospital, education status, wake-up stroke, transport, symptoms, knowledge about symptoms, seriousness of symptoms, waiting on symptoms, insurance and point of admission. Data was analyzed for means, frequencies, percentages and multiple linear regression analysis was performed to identify factors independently influencing delayed arrival. RESULTS: Mean age of the cohort was 58.08 years: 142 men and 58 women. Mean time of delayed arrival was 13.6 hours. Multiple linear regression analysis revealed that seriousness of symptoms (P = 0.001), residence (P = 0.001), point of admission (P = 0.033) and wake-up stroke (P = 0.005) were statistically significant predictors of delayed arrival. CONCLUSION: Patients not perceiving their symptoms to be serious, residing in a rural area, not arriving to the emergency, and having a stroke while awake were all the significant predictors of pre-hospital delay in our study. Awareness among the masses about symptom recognition and early arrival to a tertiary care center will reduce the delay and associated morbidity. Primary care physicians notably play a significant role in educating patients at risk, identifying the symptoms of stroke and referring them for thrombolysis.

A Young Patient with Stroke and Primary Tuberculosis.

A 21-year-old woman presented with left hemiparesis, fever, dyspnea, tachycardia, and pericardial rub on examination. She was provisionally diagnosed with infective endocarditis and received the final diagnosis of the primary pulmonary tuberculosis (PTB) and extra PTB (EPTB) with pericardial effusion and thoracic lymphadenitis. Left hemiparesis due to a pontine infarct was attributed to TB with neurovasculitis. The diagnosis was supported by findings on imaging studies such as echocardiography, computed tomography of the thorax, and magnetic resonance imaging of the brain. She improved with anti-TB treatment. It is interesting to note that she was not immunodeficient, with the usual suspects such as acquired immunodeficiency syndrome, diabetes mellitus, and renal failure ruled out. We conclude that PTB and EPTB must be considered in any febrile illness, even in patients who are not immunodeficient, considering its atypical presentation and prevalence in India.