Pure downgaze palsy from isolated infarction of the left paramedian thalamic-mesencephalon junction.

A 65-years-old female was hospitalized 24 h after experiencing the sudden onset of subjective reduction in visual acuity and hypersomnia. On admission to the neurological ward, she presented isolated downgaze palsy. A Magnetic Resonance Imaging of the brain disclosed a discrete, ovalar hyperintensity involving the left paramedian thalamic-mesencephalon junction. The lesion was consistent with infarction. Isolated downgaze palsy has been described in thrombosis of Artery of Percheron leading to infarction of bilateral paramedian thalami along with structures from the mesencephalic-diencephalic junction such as the Medial Longitudinal Fasciculus (riMLF). While neurons from the riMLF controlling upward vertical saccades project to either ipsilateral and contralateral oculomotor nuclear complexes, those involved in regulating downgaze descend ipsilaterally in the brain stem. Isolated downgaze palsy has an extreme localizer value to the diencephalic-mesencephalon junction and can arise from a unilateral lesion.

On epilepsy perception: Unravelling gaps and issues.

Epilepsy is one of the most common neurological diseases, but it can sometimes be under-reported or have a time delay in diagnosis. This data is not surprising if we consider that a person often seeks medical attention only after presenting a generalized tonic-clonic seizure. Epilepsy diagnostic delay is caused by several factors: under-reporting by patients, under-diagnosed epileptic manifestations by inexperienced clinicians, and lack of time in the emergency setting. The consequences of this delay are increased accidents, a high rate of premature mortality, and economic expanses for the healthcare system. Moreover, people with epilepsy have a higher probability of comorbidities than the general population, such as mood disorders or cognitive problems. Along with recurrent seizures, these comorbid diseases promote isolation and stigmatization of people with epilepsy, who suffer from discrimination at school, in the workplace, and even in social relationships. Public awareness of epilepsy and its comorbidities is necessary to prevent diagnostic delays and overcome social and professional iniquities for people with epilepsy.

From Goliath to David: Interventricular fibroma.

We describe an interventricular septum mass in 1 years old child, followed during 14 years. The mass did not grow up over time, the patient did not experienced any arrythmia, and did not developed heart failure. A complete diagnosis of interventricular Fibroma was made at the age of 14 years old when the patient underwent to cardiac MRI. A close follow up was in this case the winner strategy, saving him from an early unnecessary cardiac surgery.

Hidden left ventricular sarcoma manifesting itself with cardiogenic shock.

Cardiac sarcomas are rare and aggressive tumors that could have a multiorgan involvement and unfavorable prognosis. We present an extremely rare situation of cardiac sarcoma in a fragile elderly patient with a dramatic presentation of cardiogenic shock.

Endomyocardial fibrosis of the right ventricle: A case report of successful surgery.

AIMS: The case we report, shows a successful treatment of right ventricle endomyocardial fibrosis. MATERIALS AND METHODS: Surgical therapy by endocardial decortication seems to be beneficial for many patients with advanced disease who are in functional-therapeutic class III or IV. The operative mortality rate is high, but successful surgery has a clear benefit on symptoms and seems to favourably affect survival as well.

Left ventricular noncompaction, morphological, and clinical features for an integrated diagnosis.

The presence of myocardial noncompaction (NC), regardless of the criterion used, does not identify cardiomyopathy per se. The distinction between a morphological variant and the presence of an NC cardiomyopathy is challenging. However, thanks to larger cohorts of patients and longer periods of follow-up, better clinical characterization and prognostic evaluation are becoming available. Indeed, the physician is required to integrate the evidence of NC with the clinical history of the patient, which is supplemented by necessary advanced instrumental investigations before a definite diagnosis of NC cardiomyopathy can be made. Therefore, we extensively revised the current literature in order to help the clinicians to identify clinical features which are pivotal supporting diagnostic element for the correct recognition of Left ventricular noncompaction cardiomyopathy and thus highlighting the difference between a form of cardiomyopathy and a mere intraventricular hypertrabeculation.

Cardiac Magnetic Resonance Feature-Tracking Identifies Preclinical Abnormalities in Hypertrophic Cardiomyopathy Sarcomere Gene Mutation Carriers.

BACKGROUND: Assessing myocardial strain by cardiac magnetic resonance feature tracking (FT) has been found to be useful in patients with overt hypertrophic cardiomyopathy (HCM). Little is known, however, of its role in sarcomere gene mutation carriers without overt left ventricular hypertrophy (subclinical HCM). METHODS: Thirty-eight subclinical HCM subjects and 42 healthy volunteers were enrolled in this multicenter case-control study. They underwent a comprehensive cardiac magnetic resonance study. Two-dimensional global radial, circumferential, and longitudinal strain of the left ventricle (LV) were evaluated by FT analysis. RESULTS: The subclinical HCM sample was 41 (22-51) years old and 32% were men. FT analysis revealed a reduction in global radial strain (29±7.2 versus 47.9±7.4; P<0.0001), global circumferential strain (-17.3±2.6 -versus -20.8±7.4; P<0.0001) and global longitudinal strain (-16.9±2.4 versus -20.5±2.6; P<0.0001) in subclinical HCM compared with control subjects. The significant differences persisted when considering the 23 individuals free of all the structural and functional ECG and cardiac magnetic resonance abnormalities previously described. Receiver operating characteristic curve analyses showed that the differential diagnostic performances of FT in discriminating subclinical HCM from normal subjects were good to excellent (global radial strain with optimal cut-off value of 40.43%: AUC, 0.946 [95% CI, 0.93-1.00]; sensitivity 90.48%, specificity 94.44%; global circumferential strain with cut-off, -18.54%: AUC, 0.849 [95% CI, 0.76-0.94]; sensitivity, 88.10%; specificity, 72.22%; global longitudinal strain with cut-off, -19.06%: AUC, 0.843 [95% CI, 0.76-0.93]; sensitivity, 78.57%; specificity, 78.95%). Similar values were found for discriminating those subclinical HCM subjects without other phenotypic abnormalities from healthy volunteers (global radial strain with optimal cut-off 40.43%: AUC, 0.966 [95% CI, 0.92-1.00]; sensitivity, 90.48%; specificity, 95.45%; global circumferential strain with cut-off, -18.44%: AUC, 0.866 [95% CI, 0.76-0.96]; sensitivity, 92.86%; specificity, 77.27%; global longitudinal strain with cut-off, -17.32%: AUC, 0.838 [95% CI, 0.73-0.94]; sensitivity, 90.48%; specificity, 65.22%). CONCLUSIONS: Cardiac magnetic resonance FT-derived parameters are consistently lower in subclinical patients with HCM, and they could emerge as a good tool for discovering the disease during a preclinical phase.

Sudden cardiac death after early-onset myocardial infarction: a multicentre longitudinal cohort study with a 20-year follow-up.

AIMS: Sudden cardiac death (SCD) is a serious consequence of a myocardial infarction (MI), but identifying patients at risk of developing SCD remains a major clinical challenge, especially in the case of juvenile MI. The aim of this study is to identify predictors of SCD after early-onset MI using long-term follow-up data relating to a large nationwide patient cohort. METHODS AND RESULTS: The Italian Genetic Study on Early-onset MI enrolled 2000 patients experiencing a first MI before the age of 45 years, who were followed up for a median of 19.9 years. Fine-Gray proportional hazard models were used to assess the associations between their clinical, demographic, and index event data and the occurrence of SCD. Sudden cardiac death occurred in 195 patients, who were more frequently males, were hypertensive and/or diabetic, had a history of previous thrombo-embolic events with a greater atherosclerotic burden, and had a lower left ventricular ejection fraction (LVEF) after the index event. A multivariable analysis showed that the independent predictors of SCD were diabetes, hypertension, previous thrombo-embolic events, a higher SYNTAX score, and a lower LVEF. There was no clear evidence of the clustering of SCD events during the follow-up. Sudden cardiac death was the first post-MI clinical event in 101 patients; the remaining 94 experienced SCD after a non-fatal MI or hospitalization for coronary revascularization. CONCLUSION: Sudden cardiac death frequently occurs during the 20 years after early-onset MI. The nature of the identified predictors and the absence of clustering suggest that the pathophysiological basis of SCD may be related to progressive coronary atherosclerosis.

Transcatheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: A Multicenter Propensity Score-Based Analysis.

Background: The prognostic impact of catheter ablation (CA) of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients has not yet been satisfactorily elucidated. Objectives: The aim of the study was to assess the impact of CA of AF on clinical outcomes in a large cohort of HCM patients. Methods: In this retrospective multicenter study, 555 HCM patients with AF were enrolled, 140 undergoing CA and 415 receiving medical therapy. 1:1 propensity score matching led to the inclusion of 226 patients (113 medical group, 113 intervention group) in the final analysis. The primary outcome was a composite of all-cause mortality, heart transplant and acute heart failure exacerbations. Secondary outcomes included AF recurrence and transition to permanent AF. Additionally, an inverse probability weighted (IPW) model was examined. Results: At propensity score matching analysis, after a median follow-up of 58.1 months, the primary endpoint occurred in 29 (25.7%) patients in intervention group vs 42 (37.2%) in medical group (P = 0.9). Thromboembolic strokes and major arrhythmic events in intervention vs medical group were 9.7% vs 7.1% (P = 0.144) and 4.4 vs 8.0% (P = 0.779), respectively. Fewer patients in intervention vs medical group experienced AF recurrences (63.7% vs 84.1%, P = 0.001) and transition to permanent AF pattern (20.4% vs 33.6%, P = 0.026). IPW analysis showed consistent results. Severe complications related to CA were uncommon (0.7%). Conclusions: After 5 years of follow-up, CA did not improve major adverse cardiac outcomes in a large cohort of patients with HCM and AF. Nevertheless, CA seems to facilitate the maintenance of sinus rhythm and slow the progression to permanent AF, without significant safety concerns.

Real-world candidacy to mavacamten in a contemporary hypertrophic obstructive cardiomyopathy population.

AIMS: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment. METHODS AND RESULTS: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient ≥30 mmHg at rest or ≥50 mmHg after Valsalva manoeuvre or exercise) despite pharmacological or non-pharmacological therapy. Pharmacological or non-pharmacological therapy resolved LVOTO in 1044 (61.2%) of the 1706 HOCM patients under active follow-up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER-HCM trial population, these real-world HOCM patients were older (62.1 ± 14.3 vs. 58.5 ± 12.2 years, p = 0.02), had a lower body mass index (26.8 ± 5.3 vs. 29.7 ± 4.9 kg/m2 , p < 0.0001) and a more frequent history of atrial fibrillation (21.5% vs. 9.8%, p = 0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66 ± 7% vs. 74 ± 6%, p < 0.0001), higher left ventricular outflow tract gradients at rest (60 ± 27 vs. 52 ± 29 mmHg, p = 0.003), and larger left atrial volume index (49 ± 16 vs. 40 ± 12 ml/m2 , p < 0.0001). Overall, 324 (48.9%) would have been eligible for enrolment in the EXPLORER-HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines. CONCLUSIONS: Real-world HOCM patients differ from the EXPLORER-HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of real-world HOCM patients were found eligible to mavacamten.

A preliminary study investigating the clinical potential of measuring cerebrospinal-fluid lactate levels in patients with narcolepsy type 1 and 2.

STUDY OBJECTIVES: Besides the quantification of orexin-A/hypocretin-1 cerebrospinal fluid (CSF) levels in narcolepsy for diagnostic purposes, several other CSF biomarkers have been evaluated, although with controversial results. Since CSF lactate concentrations fluctuate according to the sleep-wake cycle with higher levels during wakefulness and lower levels during sleep, as documented in animal model studies, the present study aimed at quantifying the CSF lactate levels in patients with narcolepsy type 1 (NT1) and 2 (NT2), which are two sleep disorders featured by excessive daytime sleepiness (EDS). METHODS: Patients with NT1 and NT2 were enrolled in this study and compared to a control group of similar age and sex. All the subjects included in the study underwent a polysomnographic study followed by lumbar puncture for the quantification of CSF lactate levels at awakening. RESULTS: 23 NT1 (43.5 % male; 36.43 ± 11.89 years) and 15 NT2 patients (46.7 % male; 37.8 ± 14.1 years) were compared to 17 controls (58.8 % male; 32.3 ± 8.4 years). CSF lactate concentrations were reduced in patients with NT1 and NT2 compared to controls but no differences were found between the two groups of patients. ROC curves analysis showed that CSF lactate ≤1.3 mmol/l had a sensitivity of 96.49 and a specificity of 82.35 % for discriminating patients with narcolepsy from controls. CONCLUSIONS: The present study showed a decrease in CSF lactate levels in patients with narcolepsy. Notably, the reduction of lactate levels was present in both NT1 and NT2 patients, independently of CSF orexin levels. Narcolepsy patients present EDS with daytime napping and REM-related episodes, possibly substantiating the CSF lactate levels reduction related to the impaired daytime wakefulness which was demonstrated in animal studies. Moreover, CSF lactate levels present a good sensitivity and adequate specificity for differentiating narcolepsy from controls. Further studies are needed to understand the role of CSF lactate and its usefulness for monitoring daytime vigilance in patients with narcolepsy.

When Heart Team Really Counts: Radical Excision of Intracardiac Leiomyomatosis.

Intravenous leiomyomatosis (IVL) are rare and complex tumors, characterized by high rates of recurrences after surgical removal and the capability of multi-organ involvement including pulmonary embolization. Regarding the surgical treatment of Intracardiac Leiomiomatosis (ICL), only few articles have been published and no controlled data are available. A combined approach that involves a Team of Cardiologists, Heart Surgeons, Vascular surgeons and Radiologists seems to be successful in treating ICL.

Treatment with Cenobamate in Adult Patients with Lennox-Gastaut Syndrome: A Case Series.

Background. Lennox-Gastaut syndrome (LGS) is a developmental and epileptic encephalopathy (DEE) in which drug resistance to antiepileptic drugs (AEDs) is common. Focal-onset seizures (FOS) are among the seizure types characterizing LGS. Cenobamate (CNB) is a new AED indicated for the treatment of FOS and it has shown promising results in terms of seizure frequency reduction in both clinical trials and real-world experience. To date, the use of CNB in patients with DEEs is limited to Dravet syndrome. Methods: This was a retrospective study aimed to determine the 12-month effectiveness and tolerability of CNB in patients with LGS following real-world practice. Results: Four patients with LGS receiving CNB treatment were identified. At 12 months from starting CNB, the reduction in baseline seizure frequency ranged from 25 to 74%, with two patients achieving ≥50% seizure reduction. CNB was generally well tolerated and adjustments in doses of concomitant AEDs were required. Conclusions: CNB may represent a promising therapeutic option in patients with drug-resistant epilepsy associated with LGS. Further research is needed to confirm this preliminary evidence.

Paradoxical Pulmonary Embolism in a Patient with Bilateral Renal Infarction: The Role of Contrast-enhanced Ultrasound Imaging.

We present the case of a 52-year-old male who was admitted to the hospital for a bilateral pulmonary embolism. On the 5th day of hospitalization, an acute kidney injury (AKI) occurred. A transesophageal echocardiogram was performed and it demonstrated a large patent foramen ovale with a consistent right-to-left shunt. Contrast-enhanced ultrasound (CEUS) was performed and it demonstrated multiple bilateral renal ischemic areas. CEUS represents a valid alternative to computed tomography or magnetic resonance to confirm the diagnosis of bilateral kidney infarction, especially in patients who experience an AKI.

Unexpected Cause of Pericarditis: Chest Teratoma.

Mediastinal teratoma rarely causes pericarditis. We report a case of a 22-year-old young female admitted to the emergency department for inspiratory chest pain and fever with severe pericardial effusion, unexepectable the cause of pericarditis was a mediastinal teratoma.

Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

Long-term outcomes of early-onset myocardial infarction with non-obstructive coronary artery disease (MINOCA).

BACKGROUND: Acute myocardial infarction with non-obstructive coronary artery disease (MINOCA) is frequent in patients experiencing an early-onset MI, but data concerning its long-term prognosis are limited and conflicting. METHODS: The Italian Genetic Study on Early-onset MI enrolled 2000 patients experiencing a first MI before the age of 45 years, and had a median follow-up of 19.9 years. The composite primary endpoint was cardiovascular (CV) death, non-fatal MI, and non-fatal stroke (MACE); the secondary endpoint was rehospitalisation for coronary revascularisation. RESULTS: MINOCA occurred in 317 patients (15.9%) and, during the follow-up, there was no significant difference in MACE rates between them and the patients with obstructive coronary artery disease (MICAD: 27.8% vs 37.5%; adjusted hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.09;p = 0.15). The CV death rate was lower in the MINOCA group (4.2% vs 8.4%, HR 0.26, 95%CI 0.08-0.86;p = 0.03), whereas the rates of non-fatal reinfarction (17.3% vs 25.4%; HR 0.76, 95%CI 0.52-1.13;p = 0.18), non-fatal ischemic stroke (9.5% vs 3.7%; HR 1.79, 95%CI 0.87-3.70;p = 0.12), and all-cause mortality (14.1% vs 20.7%, HR 0.73, 95%CI 0.43-1.25;p = 0.26) were not significantly different in the two groups. The rate of rehospitalisation for coronary revascularisation was lower among the MINOCA patients (6.7% vs 27.7%; HR 0.27, 95% CI 0.15-0.47;p < 0.001). CONCLUSIONS: MINOCA is frequent and not benign in patients with early-onset MI. Although there is a lower likelihood of CV death,the long-term risk of MACE and overall mortality is not significantly different from that of MICAD patients.

Prognostic role of global longitudinal strain by feature tracking in patients with hypertrophic cardiomyopathy: The STRAIN-HCM study.

BACKGROUND: The assessment of myocardial fiber deformation with cardiac magnetic resonance feature tracking (CMR-FT) has shown to be promising in terms of prognostic information in several structural heart diseases. However, little is known about its role in hypertrophic cardiomyopathy (HCM). Aims of the present study were: 1) to assess the prognostic role of CMR-FT derived strain parameters in patients with HCM. METHODS: CMR was performed in 130 consecutive HCM patients (93 males, mean age (54 ± 17 years) with an estimated 5-year risk of sudden cardiac death (SCD) <6% according to the HCM Risk-SCD calculator. 2D- and 3D-Global Radial (GRS), Longitudinal (GLS) and Circumferential (GCS) Strain was evaluated by FT analysis. The primary outcome of the study was a composite of major adverse cardiac events (MACE) including SCD, resuscitated cardiac arrest due to ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia (VT), and hospitalization for heart failure. RESULTS: After a median follow-up of 51.7 (37.1-68.8) months, 4 (3%) patients died (all of them suffered from SCD) and 36 (28%) were hospitalized for heart failure. After multivariable adjustment for clinical and imaging covariates, among all strain parameters, only GLS remained a significant independent predictor of outcome events in both the model including 2D strain (HR 1.12, 95% CI 1.03-1.23, p = 0.01) and the model including 3D strain (HR 1.14, 95% CI 1.01-1.30, p = 0.04). The addition of 2D-GLS into the model with clinical and imaging predictors resulted in a significant increase in the C-statistic (from 0.48 to 0.65, p = 0.03). CONCLUSION: CMR-FT derived GLS is a powerful independent predictor of MACE in patients with HCM, incremental to common clinical and CMR risk factors including left ventricular ejection fraction and late gadolinium enhancement.