Unexplained syncope in a young athlete: the diagnostic process to find the diagnosis-a case report.

BACKGROUND: Differential diagnosis of recurrent syncope is a routine procedure in clinical practice. Most of these syncopes are benign reflex syncopes but identifying patients with cardiac syncope is crucial to prevent fatal outcomes. CASE SUMMARY: In this case report, we present the case of a young athlete with recurrent unexplained syncope referred to us for a second opinion. Despite normal resting-electrocardiography and echocardiography, he developed frequent polymorphic and bidirectional premature ventricular contractions during exercise. Genetic testing confirmed a mutation in the RyR2-gene and the diagnosis of catecholaminergic polymorphic ventricular tachycardia was made. A medical therapy with betablockers was initiated but poorly tolerated, so that an implantable cardioverter-defibrillator was implanted. Furthermore, family screening revealed his mother and his sister to be genetic carriers as well. Implantable cardioverter-defibrillator implantation was performed in both family members. The patient did not experience any syncope or arrhythmic episodes during the follow-up period. DISCUSSION: This case report highlights the importance of thorough diagnostic and potential pitfalls in patients with unexplained syncope. Sometimes, the diagnostic steps need to be extended or repeated to detect rare or potential malignant causes of syncope.

Nurse triage accuracy in the evaluation of syncope according to European Society of Cardiology guidelines.

AIMS: The role of triage for patients admitted to the emergency department (ED) for a syncopal transitory loss of consciousness (TLOC) has not been debated, and no comparisons with the recent European Society of Cardiology (ESC) guidelines are currently available. To verify the ability of triage to correctly prioritize patients with syncopal TLOC. METHODS AND RESULTS: All patients who received a triage assessment at the ED of the Merano Hospital (Italy) between 1 January 2017 and 30 June 2019 for a syncope were considered. All syncope were reclassified according to the aetiology reported in the ESC guidelines. The baseline characteristics of the patients were recorded and divided according to the severity code provided during triage into two study groups: high priority (red/orange) and low priority (yellow/green/blue). The outcome of the study was the presence of a diagnosed cardiac cause within 30 days after the admission. A total of 2066 patients were enrolled (14.3% high priority vs. 85.7% low priority). Cardiac syncope was present in 7.5% of patients. Nurse triage showed a sensitivity for cardiac syncope of 44.8%, a specificity of 88.1%, and an accuracy of 84.9%. The observed discriminatory ability presented an area under the receiver operating characteristic curve of 0.685 (95% confidence interval 0.638-0.732). The possible identification of the aetiology of the syncopal TLOC by the nurse showed good agreement with the medical diagnosis (Cohen's kappa 0.857, P < 0.001). CONCLUSIONS: In cases of syncopal TLOC, nurse triage had a fair specificity but suboptimal sensitivity for cardiac causes. Specific nursing assessments following triage (e.g. precise scores or electrocardiogram) could improve the triage performance.

Triage assessment of transitory loss of consciousness in the emergency department-A retrospective observational study.

AIM: To establish how the Manchester Triage System can correctly prioritize patients admitted to the emergency department for transitory loss of consciousness in relation to their risk of presenting severe acute disease. DESIGN: A observational retrospective study. METHODS: A total of 2291 patients who required a triage evaluation for a transitory loss of consciousness at the emergency department of Merano Hospital between 1 January 2017 and 30 June 2019 were considered. Transitory loss of consciousness was classified according to European Society of Cardiology guidelines. The baseline characteristics of the patients were collected and divided according to the priority level assigned at triage into two different study groups: high priority (red/orange) and low priority (blue/green/yellow). The composite outcome of the study was defined as the diagnosis of a severe acute disease. RESULTS: Of the patients enrolled, 17% (390/2291) had a high-priority code and 83% (1901/2291) received a low-priority code. Overall, a severe acute disease was present in 16.9% of patients (387/2291). The Manchester Triage System had a sensitivity of 42.4%, a specificity of 88.1% and an accuracy of 80.4% for predicting severe acute disease. The discriminatory ability had an area under the receiver operating characteristic curve of 0.651 (CI 95%: 0.618-0.685). CONCLUSIONS: Despite the good specificity, the low sensitivity does not currently allow the Manchester Triage System to completely exclude patients with a severe acute disease who presented in the emergency department for a transitory loss of consciousness. Therefore, it is important to develop precise nursing tools or assessments that can improve triage performance. IMPACT: The assessment of a complex symptom can create difficulties in the stratification of patients in triage, assigning low-priority codes to patients with a severe disease. Additional tools are needed to allow the correct triage assessment of patients presenting with transitory loss of consciousness.

Timing of syncope in ictal asystole as a guide when considering pacemaker implantation.

INTRODUCTION: In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset of asystole and development of syncope in IA, to estimate the frequency with which pacemaker therapy, by preventing severe bradycardia, may diminish syncope risk. METHODS: In this retrospective cohort study, we searched video-EEG databases for individuals with focal seizures and IA (asystole ≥ 3 s preceded by heart rate deceleration) and assessed the durations of asystole and syncope and their temporal relationship. Syncope was evaluated using both video observations (loss of muscle tone) and EEG (generalized slowing/flattening). We assumed that asystole starting ≤3 s before syncope onset, or after syncope began, could not have been the dominant cause. RESULTS: We identified 38 seizures with IA from 29 individuals (17 males; median age: 41 years). Syncope occurred in 22/38 seizures with IA and was more frequent in those with longer IA duration (median duration: 20 [range: 5-32] vs. 5 [range: 3-9] s; p < .001) and those with the patient seated vs. supine (79% vs. 46%; p = .049). IA onset always preceded syncope. In 20/22 seizures (91%), IA preceded syncope by >3 s. Thus, in only two instances was vasodepression rather than cardioinhibition the dominant presumptive syncope triggering mechanism. CONCLUSIONS: In IA, cardioinhibition played an important role in most seizure-induced syncopal events, thereby favoring the potential utility of pacemaker implantation in patients with difficult to suppress IA.

The Longer the Block, the Harder You Fall: Extrinsic Idiopathic Atrioventricular Block Masquerading as Seizures.

History and physical examination are the diagnostic cornerstones of transient loss of consciousness (TLOC). However, details can be scarce and examination unrevealing, thus making the diagnosis elusive. In a case of convulsive TLOC, the initial diagnosis was incorrect, but a fortuitously captured event on telemetry yielded the diagnosis: extrinsic idiopathic atrioventricular block. (Level of Difficulty: Beginner.).

Psychogenic Pseudosyncope: Clinical Features, Diagnosis and Management.

Psychogenic Pseudosyncope (PPS) is the appearance of Transient Loss of Consciousness (TLOC) in which movements are absent, but there are no hemodynamic and electroencephalographic modifications as are induced by gravitational challenges which characterize syncope and true loss of consciousness. For younger and adult populations, a detailed history is crucial for the diagnosis. Clinical clues that should raise the suspicion for PPS include prolonged duration of the LOC, eye closure during the episode, unusual triggers, no recognizable prodromes and the high frequency of attacks. The presence of an established diagnosis of syncope should not deter from the concomitant diagnosis of PPS. The gold standard for a proper diagnosis of PPS is the documentation by a tilt test of normal hemodynamic and electroencephalographic parameters, when recorded during an attack. Treatment of PPS, based on the clear and empathetic communication of the diagnosis, can lead to an immediate reduction of attack frequency and lower the need to call on emergency services. Pharmacological treatment of associated psychiatric disorders and psychological interventions may be beneficial in patients with PPS. Cognitive-behavioural therapy holds the most reliable evidence of efficacy. In the present review, we aimed to address PPS with historical aspects, main clinical features and diagnostic tests, current diagnostic classification, underlying neurobiological abnormalities, management and therapy.

Patterns of neural activity in the mouse brain: Wakefulness vs. General anesthesia.

In light of the general shift from rats to mice as the leading rodent model in neuroscience research we used c-Fos expression as a tool to survey brain regions in the mouse in which neural activity differs between the states of wakefulness and pentobarbital-induced general anesthesia. The aim was to complement prior surveys carried out in rats. In addition to a broad qualitative review, 28 specific regions of interest (ROIs) were evaluated quantitatively. Nearly all ROIs in the cerebral cortex showed suppressed activity during anesthesia. Subcortically, however, some ROIs showed suppression, some showed little change, and some showed increased activity. The overall picture was similar to the rat. Special attention was devoted to ROIs significantly activated during anesthesia, as such loci might actively drive the transition to anesthetic unconsciousness rather than responding passively to inhbitory agents distributed globally (the "wet blanket" hypothesis). Twelve such "anesthesia-on" ROIs were identified: the paraventricular hypothalamic nucleus, supraoptic nucleus, tuberomamillary nucleus, lateral habenular nucleus, dentate gyrus, nucleus raphe pallidus, central amygdaloid nucleus, perifornical lateral hypothalamus, ventro-lateral preoptic area, lateral septum, paraventricular thalamic nucleus and zona incerta. The same primary anti-FOS antibody was used in all mice, but two alternative reporter systems were employed: ABC-diaminobenzidine and the currently more popular AlexaFluor488. Fluorescence tagging revealed far fewer FOS-immunoreactive neurons, sounding an alert that the reporter system chosen can have major effects on results obtained.

A case report of sinoatrial arrest caused by temporal lobe epilepsy in subclinical glioblastoma.

BACKGROUND: Atrial fibrillation with symptomatic bradycardia, higher grade atrioventricular block, and sinus node disease are all common indications for permanent pacemaker implantation. The most frequent causes of sinus node disease treated with pacemaker implantation involve degenerative structural changes of the sinus node; less often, extrinsic causes (such as damage due to myocardial infarction or heightened parasympathetic nervous system activity) lead to pacemaker implantation. CASE PRESENTATION: A 50-year-old patient with syncope and documented sinoatrial arrest was referred. Neurologic exams (including CT and EEG) revealed no pathologies, so a pacemaker was implanted. Postoperatively, syncope occurred again due to a focal seizure during which sinus rhythm transitioned to atrial pacing by the device. Further neurologic testing revealed focal epilepsy. Six months later, stage IV glioblastoma was diagnosed and the patient was treated surgically. CONCLUSION: Intracerebral tumors should be considered in the differential diagnosis for patients with unexplained sinoatrial block, as well as in patients with repeat syncope after pacemaker implantation. Cranial MRI could aid the diagnostic workup of such cases.

Recognition and nursing management of reflex anoxic seizures in children.

Reflex anoxic seizures (RAS) present with a transient loss of consciousness and are triggered by an unexpected stimuli. These are paroxysmal, short-lived episodes of pronounced bradycardia or transient asystole; the episodes are self-limiting, lasting between 15 seconds and 1 minute. RAS are an important differential diagnosis of transient loss of consciousness but they are commonly misdiagnosed as epileptic events. An accurate and focused history is key to the diagnosis. They are mostly managed by performing an ECG to rule out other causes of arrhythmia, with subsequent explanation of the condition and reassurance given to parents. Nurses play an important role in eliciting the history and providing support to parents following the diagnosis. This article addresses the epidemiology and pathophysiology of RAS, with suggestions for management. An illustrative case study is included to highlight some of the challenges that health professionals working in different clinical set-ups are likely to come across while managing a child with RAS.

Role of SEC62 in ER maintenance: A link with ER stress tolerance in SEC62-overexpressing tumors?

Amplification of the candidate oncogene TLOC1/SEC62 in tumors correlates with reduced patient survival. The recently reported role of SEC62 as an autophagy receptor that controls endoplasmic reticulum (ER) size and function might open new scenarios for understanding the phenotypes and treat SEC62high tumors, which are characterized by high ER stress tolerance.

Syncope and Its Impact on Occupational Accidents and Employment: A Danish Nationwide Retrospective Cohort Study.

BACKGROUND: First-time syncopal episodes usually occur in adults of working age, but their impact on occupational safety and employment remains unknown. We examined the associations of syncope with occupational accidents and termination of employment. METHODS AND RESULTS: Through linkage of Danish population-based registers, we included all residents 18 to 64 years from 2008 to 2012. Among 3 410 148 eligible individuals, 21 729 with a first-time diagnosis of syncope were identified, with a median age 48.4 years (first to third quartiles, 33.0-59.5), and 10 757 (49.5%) employed at time of the syncope event. Over a median follow-up of 3.2 years (first to third quartiles, 2.0-4.5), 622 people with syncope had an occupational accident requiring hospitalization (2.1/100 person-years). In multiple Poisson regression analysis, the incidence rate ratio in the employed syncope population was higher than in the employed general population (1.44; 95% confidence interval [CI], 1.33-1.55) and more pronounced in people with recurrences (2.02; 95% CI, 1.47-2.78). The 2-year risk of termination of employment was 31.3% (95% CI, 30.4%-32.3%), which was twice the risk of the reference population (15.2%; 95% CI, 14.7%-15.7%), using the Aalen-Johansen estimator. Factors associated with termination of employment were age <40 years (incidence rate ratio, 1.48; 95% CI, 1.37-1.59), cardiovascular disease (1.20; 95% CI, 1.06-1.36), depression (1.72; 95% CI, 1.55-1.90), and low educational level (2.61; 95% CI, 2.34-2.91). CONCLUSIONS: In this nationwide cohort, syncope was associated with a 1.4-fold higher risk of occupational accidents and a 2-fold higher risk of termination of employment compared with the employed general population.

Temporal Relationship of Asystole to Onset of Transient Loss of Consciousness in Tilt-Induced Reflex Syncope.

OBJECTIVES: The purpose of this study was to investigate the relationship between the onset of asystole and transient loss of consciousness (TLOC) in tilt-induced reflex syncope and estimate how often asystole was the principal cause of TLOC. BACKGROUND: The presence of asystole in vasovagal syncope (VVS) may prompt physicians to consider pacemaker therapy for syncope prevention, but the benefit of pacing is limited in VVS. METHODS: We evaluated electrocardiography, electroencephalography, blood pressure, and clinical findings during tilt-table tests. Inclusion required TLOC (video), electroencephalographic slowing, accelerating blood pressure decrease, and an RR interval ≥3 s. We excluded cases with nitroglycerin provocation. Asystole after onset of TLOC (group A) or within 3 s before TLOC (group B) was unlikely to cause TLOC, but an earlier start of asystole (group C) could be the cause of TLOC. RESULTS: In one-third of 35 cases (groups A [n = 9] and B [n = 3]), asystole was unlikely to be the primary cause of TLOC. The median of the mean arterial pressure at the onset of asystole was higher when asystole occurred early (45.5 mm Hg, group C) than when it occurred late (32.0 mm Hg, groups A and B), which suggests that vasodepression was not prominent at the start of asystole in early asystole, further suggesting that early asystole was the prime mechanism of syncope. CONCLUSIONS: In one-third of cases of tilt-induced asystolic reflex syncope, asystole occurred too late to have been the primary cause of TLOC. Reliance on electrocardiography data only is likely to overestimate the importance of asystole.

Transient loss of consciousness during hypercapnia and hypoxia: Involvement of pathways associated with general anesthesia.

Transient loss of consciousness (TLOC), frequently triggered by perturbation in essential physiological parameters such as pCO2 or O2, is considered a passive consequence of generalized degradation in high-level cerebral functioning. However, the fact that it is almost always accompanied by atonia and loss of spinal nocifensive reflexes suggests that it might actually be part of a "syndrome" mediated by neural circuitry, and ultimately be adaptive. Widespread suppression by molecules distributed in the vasculature is also the classical explanation of general anesthesia. Recent data, however, suggest that anesthesia is due, rather, to drug action at a specific brainstem locus, the mesopontine tegmental anesthesia area (MPTA), with the spectrum of anesthetic effects resulting from secondary recruitment of specific axonal pathways. If so, might the MPTA also be involved in TLOC induced by hypercapnia and hypoxia? We exposed rats to gas mixtures that provoke hypercapnia and hypoxia and asked whether cell-selective lesions of the MPTA affect TLOC. Entry into TLOC, monitored as time to loss of the righting reflex (LORR) was unaffected. However, resumption of the righting reflex (RORR), and of response to pinch stimuli (ROPR), was significantly delayed. The extent of both effects correlated with the extent of damage in the MPTA, but was unrelated to damage that extended beyond the borders of the MPTA. The results implicate neurons in a specific common-core region of the MPTA in TLOC induced by both forms of asphyxia. This is the same area responsible for general anesthesia induced by GABAergic anesthetic agents. This implies the involvement of a common set of brain nuclei and dedicated axonal pathways, rather than nonspecific global suppression, in the mechanism mediating all three instances of TLOC.

Contributions of endothelial nitric oxide synthase, noradrenaline, and neuropeptide Y to local warming-induced cutaneous vasodilatation in men.

We performed a two-part study to determine the roles of endothelial nitric oxide synthase (eNOS) and the vasoconstrictor nerves neurotransmitters noradrenaline (NA) and neuropeptide Y (NPY) in the cutaneous vasodilator response to local skin warming. Forearm skin sites were instrumented with intradermal microdialysis fibres, local heaters, and laser-Doppler flow (LDF) probes. Sites were locally heated from 34 to 42°C. LDF was expressed as cutaneous vascular conductance (CVC; LDF/mean arterial pressure). In Part I, we tested whether sympathetic noradrenergic nerves acted via eNOS. In 8 male participants, treatments were as follows: 1) untreated; 2) bretylium tosylate (BT), preventing sympathetic neurotransmitter release; 3) l-NAA to inhibit eNOS; and 4) combined BT+l-NAA. At treated sites, the initial peak response was markedly reduced, and the plateau phase response to 35min of local warming was also reduced (P<0.05), which was not different among those sites (P>0.05). In Part II, we tested whether NA and NPY were involved in the vasodilator response to local warming. In Part IIa, treatments were: 1) untreated; 2) propranolol and yohimbine to antagonize α- and ß-receptors; 3) l-NAA; and 4) combined propranolol, yohimbine, and l-NAA. In Part IIb, conditions were: 1) untreated; 2) BIBP to antagonize Y1-receptors; 3) l-NAA; and 4) combined BIBP and l-NAA. All treatments caused a reduction in the initial peak and plateau responses to local skin warming (P<0.05). The results of Part II indicate that both NA and NPY play roles in the cutaneous vasodilator response and their actions are achieved via eNOS. These data indicate that NA and NPY are involved in the initial, rapid rise in skin blood flow at the onset of local skin warming. However, their vasodilator actions in response to local skin warming appears to be manifested through eNOS.