Prevalence of objective excessive daytime sleepiness in a cohort of patients with mild obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common, yet the relationship between mild OSA and excessive daytime sleepiness (EDS) is unclear. Our objective was to determine the prevalence of objective EDS in a population with mild OSA using the mean sleep latency (MSL) from the multiple sleep latency test (MSLT). METHODS: We retrospectively analyzed 1205 consecutive patients who underwent a polysomnography and a following day MSLT at a single sleep center. Adult patients who met criteria for mild OSA with an apnea-hypopnea index of 5 to <15 events/h were identified, and the percentage of patients with a MSL ≤ 8 min was determined. Sleep study and demographic variables were examined to evaluate predictors of objective EDS. RESULTS: Of 155 patients with mild OSA, objective EDS was found in 36% (56/155) with an average MSL of 5.6 ± 2.1 min in the objectively sleepy patients. Objectively sleepy patients with mild OSA had greater total sleep time (411.6 ± 48.9 vs. 384.5 ± 61.7 min, p = 0.004), increased sleep efficiency (84.9 ± 9.7 vs. 79.7 ± 12.7%, p = 0.01), and decreased wake after sleep onset time (53.0 ± 36.9 vs. 67.4 ± 46.1 min, p = 0.04) compared to patients with mild OSA but without objective EDS, with total sleep time being an independent predictor of MSL (p = 0.006). The Epworth Sleepiness Scale (ESS) weakly correlated with objective EDS (ρ = - 0.169, p = 0.03). CONCLUSIONS: There is a large subgroup of patients with mild OSA patients who have objective sleepiness. This may represent an ideal subgroup to target for future studies examining the effect of treatment in mild OSA. Additionally, the ESS was a poor predictor of this subgroup with mild OSA and objective EDS.

Stroke Thrombolysis in Patients Taking Ticagrelor -Two Successful Cases and a Review of the Literature.

BACKGROUND: Ticagrelor is a novel antiplatelet agent that is frequently used for secondary prevention in coronary artery disease and has emerging evidence in stroke after the recent results of SOCRATES and THALES trials. The use of intravenous thrombolysis with alteplase in acute ischemic stroke (AIS) patients on ticagrelor is a topic of debate as the safety profile of ticagrelor in this setting is not well established. METHODS: We identified consecutive AIS patients taking ticagrelor who received intravenous alteplase at a comprehensive stroke center from January 2016 to December 2019. We then performed a literature search to capture all known published cases of intravenous thrombolysis in stroke patients on ticagrelor. RESULTS: Of the 3896 patients who were treated for AIS at our local comprehensive stroke center during this time period, two patients received intravenous alteplase while on ticagrelor. Both patients had posterior circulation acute strokes and were successfully treated with intravenous alteplase without a systemic or intracranial bleeding event. Only five other cases of intravenous thrombolysis in AIS patients on ticagrelor have been reported in the literature. Among these cases, four of the five cases had a hemorrhagic complication. CONCLUSION: Despite prior reports of hemorrhagic complications with use of IV alteplase in setting of pre-treatment with ticagrelor, we report the safe use of intravenous thrombolysis in two cases presenting with acute ischemic stroke. Until safety is established in large studies, decision for thrombolysis should be made on case-by-case basis.

Safety of Ticagrelor in Moderate and Severe Acute Ischemic Stroke: A Single-Center Retrospective Review.

OBJECTIVES: Ticagrelor may be superior to aspirin after minor ischemic stroke or TIA, particularly in patients with symptomatic atherosclerotic disease. However, there may be an increased risk of intracerebral hemorrhage in patients with moderate to severe ischemic stroke, and ticagrelor has not been studied in this patient population. Therefore, we sought to evaluate the safety of ticagrelor after moderate or severe ischemic stroke. MATERIALS AND METHODS: Retrospective chart review of all patients admitted with acute ischemic stroke and NIHSS 6 or greater who were discharged on ticagrelor between January 2016 and December 2019. Patients who underwent angioplasty, stenting or carotid revascularization during the hospitalization were excluded. RESULTS: Of 183 patients discharged on ticagrelor, 61 patients were included. Median age was 61 (IQR 52-68); 33 (54%) patients were men. Median NIHSS was 11 (IQR 8-15). Fourteen (23%) patients received IV alteplase and 35 (57%) patients received mechanical thrombectomy. Stroke mechanism was large artery atherosclerosis in 53 (87%) of patients, of which 40 (71%) were deemed intracranial atherosclerosis. Final infarct volume was greater than 10 mL in 32 (52%) patients. Follow-up information was available for 53 (87%) patients; median length of follow-up was 3 (IQR 2-6) months. Six (10%) patients experienced recurrent ischemic stroke. No patients experienced symptomatic intracerebral hemorrhage after initiation of ticagrelor. One (2%) patient experienced major bleeding. CONCLUSIONS: This study provides preliminary evidence supporting the potential safety of ticagrelor following moderate or severe acute ischemic stroke. These findings support the need for future prospective studies.

Baseline Characteristics of Patients with Symptomatic Carotid Webs: A Matched Case Control Study.

BACKGROUND AND PURPOSE: The baseline characteristics of patients with symptomatic carotid web (CaW) are unclear. We investigate demographic and cerebrovascular risk factors in patients with this overlooked stroke etiology. METHODS: We identified consecutive patients diagnosed with symptomatic CaW at a comprehensive stroke center from July 2014-December 2018. These patients were matched at a 1:4 ratio (based on age and NIHSS scores) to create a control group of acute ischemic stroke (AIS) patients with non-CaW etiologies from the local GetWithTheGuidelines stroke database. RESULTS: Thirty patients with symptomatic CaW were compared to 120 AIS patients with non-CaW etiologies. Symptomatic CaW patients were more likely to be female (73.3 vs. 44.2%; p = 0.004) and black (86.7 vs. 64.2%; p = 0.02). Symptomatic CaWs patients had a fewer absolute number of modifiable cerebrovascular risk factors (1.7±1.1 vs. 2.5±1.2; p = 0.002), lower rates of hypertension (43.4 vs. 63.3%; p = 0.04), and a more favorable lipid profile with lower average LDL (89.5±30.3 vs. 111.2±43.7 mg/dL; p = 0.01) and higher average HDL (47.9±11.3 vs. 42.2±13.8 mg/dL; p = 0.01) as compared to strokes with non-CaW etiology. Symptomatic CaW patients were more likely to have a large vessel occlusion (80.0 vs. 51.7%; p = 0.005), despite similar e-ASPECTS between the groups (8.1±2.1 vs. 8.3±2.2; p = 0.30). On multivariable analysis, symptomatic CaW was an independent predictor of independence at discharge (OR 3.72; 95%CI 1.27-10.94). CONCLUSION: A gender and racial predilection of symptomatic CaWs may exist as females and blacks were were found to be more likely affected. Symptomatic CaW patients have a more benign cerebrovascular risk factor profile corroborating the proposed mechanism of local stasis and thromboembolism. Despite presenting more commonly with LVO, symptomatic CaW was associated with good functional outcome, warranting further studies.

Carotid web catheter angiography hemodynamic parameters.

BACKGROUND: Carotid web (CaW)-related contrast stagnation on digital subtraction angiography (DSA) may be a marker supporting the pathophysiological theory of stasis and thrombosis/embolization. We aim to assess the correlation between DSA hemodynamic parameters with CT angiography (CTA) structural measurements and clinical characteristics. METHODS: Cross-sectional analysis of consecutive patients with CaW who underwent CTA+DSA. DSA-derived hemodynamic parameters were calculated based on a region of interest at the carotid bulb (time-density curves; TDC). The correlation between duration of contrast stagnation with CaW structural features and with clinical characteristics was evaluated with a mixed effects model. RESULTS: Sixty patients of mean±SD age 52.2±10.3 years were included, of whom 38 (63.3%) were women, 51 (85%) were black, and 59 (98.3%) had symptomatic lesions. The median CaW base was 2.46 mm (range 1.95-3.76), length 2.7 mm (range 2.15-3.96), thickness (length/base) 1.05 (IQR 0.81-1.36), caudal angle 31.93° (IQR 22.35-43.58), mean±SD distal angle 66.91±15.84°, pocket area 1.62 mm² (0.96-1.62), and pocket perimeter 6.03±2.6 mm. The TDC consistently showed an initial fast decay from the peak concentration followed by a plateau with a negative exponential pattern. The median stagnation time from peak density to 80% contrast clearance was 2.91 s (range 1.81-4.94). No significant associations were observed between the stagnation time and CaW CTA structural measurements (length/base/thickness, caudal and cranial angles web surface angles, web pocket area/perimeter) or clinical characteristics. CONCLUSIONS: A negative exponential pattern in the DSA contrast clearance of the CaW pocket was observed. There were no morphological or clinical features clearly associated with the duration of contrast stagnation on DSA. The hemodynamic disruption caused by CaW and its thrombotic risk may not be appropriately measured by contrast stagnation time.

Symptomatic carotid webs and patent foramen ovale: RoPE score in competing stroke etiologies.

BACKGROUND: Patent foramen ovale (PFO)-associated stroke is diagnosed more frequently in young patients with infrequent vascular risk factors and embolic appearing infarcts. The risk of paradoxical embolism (RoPE) score is used to identify PFO-associated stroke. Patients with symptomatic carotid artery web (CaW) share a very similar risk profile and these lesions are frequently overlooked. In this study, we evaluate the RoPE score profile in patients with suspected symptomatic CaW. METHODS: Retrospective analysis of prospectively collected data of patients with symptomatic CaW as the presumed cause of stroke presenting to 2 comprehensive stroke centers from 2014 to 2021. CaW was diagnosed using computed tomography angiography (CTA) of the neck & head. Shunt study was done using a transthoracic, transesophageal, and/or transcranial-Doppler with bubbles. RoPE score ≥7 was considered high. RESULTS: Seventy-five patients had stroke from a symptomatic ipsilateral CaW. Mean age was 49.7±11.2 years and 74.7 % were females. Median RoPE score was 7 [5-8], and 52.0 % had a high RoPE score. PFO was detected in 13.3 % of the patients and 20.5 % within the high RoPE score group. Ten percent of the cases would have been misclassified as PFO-associated strokes based on RoPE score. CONCLUSION: High RoPE scores were observed in the majority of patients with CaW-attributed stroke, and it should not be used to differentiate CaW- versus PFO-associated stroke. Careful extracranial internal carotid artery evaluation for CaW is warranted in cryptogenic strokes, including in PFO positive patients before defining stroke etiology.

Comparative analysis of stenting for carotid web and atherosclerotic disease.

INTRODUCTION: Carotid Web (CaW) is an increasingly recognized etiology of ischemic stroke, and has been shown to be amenable to endovascular stenting. The technical complexity of stenting for CaW may be lower than for carotid atherosclerotic disease (CAD). We aimed to assess procedural characteristics of stenting for CaW as compared to CAD. METHODS: We retrospectively analyzed a cohort of consecutive patients at a single comprehensive stroke center from 2014 to 2021, who had undergone elective endovascular stent placement for symptomatic CAD or CaW. RESULTS: In total, 118 patients underwent elective stent placement following ischemic stroke/transient ischemic attack; 88 patients had CAD and 30 patients had CaW. CAD patients were older (63.2 vs 51.2 years, p < 0.001), less likely to be female (28.4% vs 73.3%, p < 0.001), and more likely to have pre-existing vascular risk factors. Procedure time (73.0 vs 57.5 min, p = 0.007), radiation exposure (1482 vs 1125 milliGray, p = 0.03), filter time (24 vs 14 min, p = 0.04), and use of pre-stent (68.2% vs 0%, p < 0.001) and post-stent (34.1% vs 3.3%, p < 0.001) balloon angioplasty were higher in CAD cases. There was no significant difference between groups in the rate of periprocedural complications such as hypotension, use of vasopressors, or bradycardia. Recurrent stroke/TIA was reported in five CAD patients and 0 CaW patients by the end of the follow-up period (8.3% vs 0%, p = 0.12). In-stent restenosis was detected in seven CAD patients and 0 CaW patients (10.1% vs 0%, p = 0.09) at a median follow-up of 4 vs 16 months (p = 0.01), respectively. Periprocedural intracranial hemorrhage was not observed in either group. CONCLUSION: Stenting for CaW was found to be technically simpler than CAD and not to confer increased risk of baroreceptor dysregulation. Intimal hyperplasia was uncommon in CaW cases.

Wernicke Encephalopathy From Olfactory Dysfunction After COVID-19 Infection.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide and is caused by infection from the severe acute respiratory syndrome coronavirus-2 pathogen. While COVID-19 most commonly affects the respiratory system, multiple neurological complications have been associated with this pathogen. We report a case of Wernicke encephalopathy in a young girl with poor oral intake secondary to anosmia and dysgeusia after a COVID-19 infection. CASE REPORT: After a recent infection of COVID-19, a 15-year-old girl developed an overwhelming noxious metallic tase resulting in a 30 lb weight loss from being unable to tolerate oral foods. She presented to the hospital 3 months later with bilateral horizontal conjugate gaze palsies, up beating vertical nystagmus, difficulty with limb coordination and gait ataxia. She was found to have a thiamine level of 51 nmol/L (reference range: 70 to 180 nmol/L) and her brain magnetic resonance imaging showed fluid-attenuated inversion recovery and diffusion-weighted imaging changes in the periaqueductal gray and dorsomedial thalami suggestive of Wernicke encephalopathy. She was started on parenteral thiamine replacement and had significant neurological improvement. CONCLUSIONS: As this pandemic continues to progress, more long-term neurological sequelae from COVID-19 such as Wernicke encephalopathy can be expected. Strong clinical suspicion for these complications is needed to allow for earlier diagnosis and faster treatment initiation.

Is Idiopathic Hypersomnia a Circadian Rhythm Disorder?

PURPOSE OF REVIEW: The pathophysiology of idiopathic hypersomnia remains unclear, but some of its clinical features suggest the possibility of circadian dysfunction. This review will provide an overview of recent studies of circadian biology that have begun to elucidate the potential role of circadian rhythm dysfunction in idiopathic hypersomnia. RECENT FINDINGS: Clinically, people with idiopathic hypersomnia tend to have both a late chronotype and prominent sleep inertia or sleep drunkenness. Melatonin and cortisol profiles in people with IH confirm this tendency toward phase delay. More recently, it has been suggested that the night phase as defined by melatonin profile or period length as defined by BMA1 in dermal fibroblasts may also be prolonged in people with IH. Additionally, amplitude of melatonin rhythm and circadian gene expression, particularly BMAL1, PER1, and PER2, may be impaired in this disease. SUMMARY: Clinical features, melatonin profiles, and circadian gene expression all suggest abnormalities of the circadian system may be a contributor to the pathogenesis of IH.

Discovering a critical transition state from nonalcoholic hepatosteatosis to nonalcoholic steatohepatitis by lipidomics and dynamical network biomarkers.

Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for type 2 diabetes and metabolic syndrome. However, accurately differentiating nonalcoholic steatohepatitis (NASH) from hepatosteatosis remains a clinical challenge. We identified a critical transition stage (termed pre-NASH) during the progression from hepatosteatosis to NASH in a mouse model of high fat-induced NAFLD, using lipidomics and a mathematical model termed dynamic network biomarkers (DNB). Different from the conventional biomarker approach based on the abundance of molecular expressions, the DNB model exploits collective fluctuations and correlations of different metabolites at a network level. We found that the correlations between the blood and liver lipid species drastically decreased after the transition from steatosis to NASH, which may account for the current difficulty in differentiating NASH from steatosis based on blood lipids. Furthermore, most DNB members in the blood circulation, especially for triacylglycerol (TAG), are also identified in the liver during the disease progression, suggesting a potential clinical application of DNB to diagnose NASH based on blood lipids. We further identified metabolic pathways responsible for this transition. Our study suggests that the transition from steatosis to NASH is not smooth and the existence of pre-NASH may be partially responsible for the current clinical limitations to diagnose NASH. If validated in humans, our study will open a new avenue to reliably diagnose pre-NASH and achieve early intervention of NAFLD.