Focal non-motor seizures and subsequent focal motor seizures as the main clinical expression of GLUT-1 deficiency.

The seizure type most frequently described in GLUT1 deficiency is generalized (mainly absence). We report the case of a young boy who, as the main clinical manifestation presented with focal non-motor, and then focal motor seizures. At the age of 3 months episodes of face pallor/cyanosis and hypotonus lasting about 1 min, occurred. They were initially misdiagnosed as gastroesophageal reflux. These episodes disappeared spontaneously at 6 months of age. At 12 months, episodes similar to the previous ones reappeared. A few months later, a cluster of several episodes manifest as impaired responsiveness and vomiting occurred. The patient initially performed long-term video-EEG monitoring (LTVEM) however, no seizures were captured. During a second hospitalization for LTVEM, a focal to bilateral clonic seizure was recorded. Brain MRI was normal. Next Generation Sequencing (NGS) panel for genes associated with epilepsy showed a de novo mutation of SCL2A1 gene. The CSF showed glucose of 41 mg/dL, and the CSF/serum glucose ratio was equal to 0.46. The ketogenic diet was started with optimal efficacy in seizure control. Meal-sensitivity in childhood onset focal seizures may be associated with GLUT-1 deficiency syndrome that can be confirmed by biochemical analysis on blood and CSF following diagnostic genetic study.

Decreased whole-blood global DNA methylation is related to serum hormones in anorexia nervosa adolescents.

OBJECTIVES: The one-carbon metabolism, also known as methionine-homocysteine cycle, governs the dynamics of DNA methylation, epigenetically regulating gene expression, and has been reported altered in anorexia nervosa (AN) adult patients. The aim of this study consisted in assessing whole-blood DNA methylation in adolescent AN patients, assessing its significance in relationship to clinical and hormonal variables. METHODS: Whole-blood global DNA methylation was measured as incorporation of [(3)H]dCTP following HpaII cut in 32 adolescent females affected by restrictive type AN and compared to 13 healthy controls. Homocysteine, vitamin B12 and folate plasma levels were assessed as well as fasting plasma levels of leptin and steroid hormones. Clinical variables, including severity and associate states and traits, were assessed by means of the EDI-3, CDI and STAI-Y scales. RESULTS: We confirm that whole-blood global DNA methylation is modestly albeit significantly reduced in AN adolescents with respect to controls, correlating with plasma leptin and steroid hormone levels. Conversely, clinical traits did not correlate with the outcome variable. CONCLUSIONS: A better definition of the epigenetic dysregulation underlying AN pathology or vulnerability might lead to develop useful markers for diagnosis, prognostic classification and tailored therapeutic interventions in these vulnerable patients since the earliest phases of their disease.

Prevalence of atrial thrombi in patients with atrial fibrillation/flutter and subtherapeutic anticoagulation prior to cardioversion.

AIMS: Thromboembolism may complicate electrical cardioversion (ECV) of atrial fibrillation/flutter (AF). The use of 3 weeks of warfarin before ECV results in a substantial reduction of thromboembolic complications. Nevertheless, in patients scheduled for ECV subtherapeutic INR levels are common. We sought to assess the prevalence and the predictors of atrial thrombi in patients affected with sustained AF in whom subtherapeutic INR values were detected in the 3 weeks preceding scheduled ECV. METHODS AND RESULTS: Forty-one patients with persistent AF and > or =3 weeks warfarin anticoagulation who exhibited subtherapeutic INR values in the last 3 weeks underwent a transoesophageal echocardiogram (TOE) before a scheduled ECV. A left atrial appendage (LAA) thrombus was diagnosed on TOE in four patients (9.8%). Patients with thrombus had lower INR values (1.45+/-0.09 vs 1.72+/-0.20; p=0.0068), lower LAA emptying velocities (13.75+/-4.5 vs 25.86+/-12.4 cm/s; p=0.0313) and higher prevalence of atrial smoke (100 vs 37.8%,p=0.03). CONCLUSIONS: Subtherapeutic levels of anticoagulation before elective ECV of AF may expose patients to post-ECV thromboembolic sequelae, especially in patients with lowest INR values. Current recommendations of a full course of therapeutic anticoagulation before ECV of persistent AF should be firmly observed.

Reproducibility of asystole during head-up tilt testing in patients with neurally mediated syncope.

Tilt induced prolonged asystole has been considered to identify a distinct subgroup of patients with neurally mediated syncope and management including permanent pacemaker implantation has been suggested. To evaluate the reproducibility of asystolic response during head-up tilt testing (HUT), 33 patients with neurally mediated syncope and asystolic response (> or = 3 seconds) during HUT prospectively underwent two consecutive tests 13 +/- 15 days apart. On repeat tilt testing asystole was reproduced in 12 patients (36%), while 8 patients still had a positive HUT, but without asystole. Remarkably, 13 patients (40%) had a negative repeat HUT. Among 12 patients with asystole on both HUTs there was no significant difference in duration of asystole (14 371 +/- 11 430 ms vs 13 707 +/- 10 470 ms, P = ns) and time to syncope (36 +/- 20 min vs 37 +/- 20 min, P = ns) during initial and repeat HUTs. In conclusion, asystole during tilt testing does not seem to be a reproducible response.

Thromboembolic risk in atrial flutter. The FLASIEC (FLutter Atriale Società Italiana di Ecografia Cardiovascolare) multicentre study.

AIMS: Patients with atrial flutter are believed to be at lower risk of thromboembolism than patients with atrial fibrillation. However, the incidence of atrial thrombi and the need for anticoagulation in patients with atrial flutter is not well established. METHODS AND RESULTS: A prospective observational multicentre study was undertaken to assess the frequency of atrial thrombi and spontaneous echocontrast and the prevalence for aortic complex atherosclerotic lesions in a cohort of unselected patients with atrial flutter. We evaluated 134 patients (102 male, aged 70+/-9 years); exclusion criteria were history of atrial fibrillation, rheumatic mitral valve disease and mitral mechanical prosthesis. The median of atrial flutter duration was 33 days. Twelve patients had been taking warfarin for more than 7 days. One hundred and twenty-four patients (94%) underwent a transoesophageal echocardiogram, which revealed left atrial appendage thrombi in two patients (1.6%) and right atrial thrombi in one patient (1%). At least moderate left atrial echocontrast was found in 16/124 patients (13%). Complex atherosclerotic aortic plaques were detected in 10 patients (8%). Atrial flutter conversion was attempted in 93/134 patients (69%). At the 1-month follow-up, two patients experienced a thromboembolic event following restoration of sinus rhythm. CONCLUSIONS: Atrial thrombi and echocontrast, and complex aortic atherosclerotic plaques are relatively uncommon in patients with atrial flutter. Post-cardioversion embolism was observed in two patients in our study population.

Isolated noncompaction of the ventricular myocardium. A study in an adult male and literature review.

Noncompaction of the ventricular myocardium is a rare congenital disorder characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses which communicate with the left ventricular cavity. The disease uniformly affects the left ventricle, sometimes also affecting the right ventricle. Noncompaction of the ventricular myocardium is believed to be a disorder of endomyocardial embryogenesis. Familial occurrence has been observed. It may be accompanied by depressed ventricular function, cardiac arrhythmia and systemic embolism. Although noncompaction of the ventricular myocardium is a congenital myocardial disorder, the onset of symptoms is frequently delayed until adulthood. We describe a case of noncompaction of the ventricular myocardium in a 33-year-old male with the typical echocardiographic and cardiac magnetic resonance imaging features of this disease.

Early cardioversion of atrial fibrillation and atrial flutter guided by transoesophageal echocardiography: a single centre 8.5-year experience.

AIMS: To analyse the safety and impact on maintenance of sinus rhythm of transoesophageal echocardiographically guided early cardioversion associated with short-term anticoagulation in a large series of patients with atrial fibrillation and atrial flutter. METHODS AND RESULTS: Patients who were candidates for cardioversion were eligible for inclusion if they had atrial fibrillation or atrial flutter lasting longer than 2 days or of unknown duration. Patients received short-term anticoagulation with warfarin or heparin and underwent transthoracic echocardiography followed by transoesophageal echocardiography. Early cardioversion was performed if no thrombus was seen on the transoesophageal study. Warfarin was maintained for 1 month after cardioversion. In patients with atrial thrombi, cardioversion was deferred and prolonged anticoagulation was prescribed. The study population included 183 patients. One hundred and sixty nine patients without atrial thrombi underwent early cardioversion. Fourteen patients with atrial thrombi (7.6%) underwent a second transoesophageal echocardiogram after a median of 4 weeks of oral warfarin, and cardioversion was performed if clot regression was documented. No patient in our study population had a clinical thromboembolic event at 1 month follow-up (95% C.I. 0-0.016). The immediate success rate of cardioversion was better among patients with atrial fibrillation < 4 weeks duration compared with patients with atrial fibrillation of longer or of unknown duration: 96.6% vs 85%, respectively (P = 0.014). At 1 month follow-up, the percentage of arrhythmia relapses in patients with initially successful cardioversion was similar in the two groups (29% vs 26%, P = ns); thus the initial better outcome in patients with recent-onset arrhythmia was not lost. CONCLUSION: Transoesophageal echocardiography-guided early cardioversion in concert with short-term anticoagulation is safe. This approach permits abbreviation of the overall duration of atrial fibrillation and has a better impact on the maintenance of sinus rhythm for patients in whom the duration of atrial fibrillation is < 4 weeks.

Reproducibility of head-up tilt testing potentiated with sublingual nitroglycerin in patients with unexplained syncope.

Head-up tilt testing (HUTT) potentiated with sublingual nitroglycerin has gained acceptance as means of diagnosing neurally mediated syncope. To evaluate the reproducibility of HUTT potentiated with sublingual nitroglycerin, 48 patients with unexplained syncope prospectively underwent 2 consecutive tests 1 to 28 days apart. The initial test ended in syncope in 34 patients (71%). In 9 patients (19%) the test was positive during the drug-free phase, whereas 25 patients (52%) had syncope after nitroglycerin administration. Of these 34 patients with an initial positive test result, 27 (79%) had a reproducible outcome on repeat testing. Of 12 patients (25%) with an initial negative test result, 10 (83%) had a reproducible outcome on repeat testing. Of 2 patients (4%) with a first test ending in exaggerated response, both had a negative repeat test response. The overall reproducibility of sublingual nitroglycerin tilt-table testing was 77%. In a group of 23 patients with both positive tests, 19 (83%) had the same response modality (2 vasodepressor, 4 cardioinhibitory, 13 mixed response). In the same group of patients, individual trough heart rates correlated well with each other between tests. Finally, in the 27 patients with both positive tests, intrapatient time of onset of symptoms did not significantly correlate between tests. Thus, in patients with syncope of unknown origin, HUTT potentiated with sublingual nitroglycerin provides an adequate reproducibility when repeated on different days.

Atrial thrombosis in cardiac amyloidosis: diagnostic contribution of transesophageal echocardiography.

Few cases of atrial thrombosis detected by transesophageal echocardiography (TEE) in cardiac amyloidosis have been reported recently. We present the cases of 3 consecutive patients affected by AL-type cardiac amyloidosis, symptomatic for heart failure and in sinus rhythm. All patients had a cardiac restrictive pattern at Doppler examination. TEE showed left atrial thrombus in 2 patients and biatrial thrombi in 1 patient; conventional transthoracic echocardiography detected only 1 left atrial thrombus. Our experience confirms the association between cardiac amyloidosis and atrial thrombosis, even in sinus rhythm. TEE should be considered to assess thromboembolic risk in all cases of cardiac amyloidosis with severe diastolic dysfunction.

Atrial thrombi resolution after prolonged anticoagulation in patients with atrial fibrillation.

BACKGROUND: Cardioversion of atrial fibrillation in nonanticoagulated patients may be associated with clinical thromboembolism. Prolonged anticoagulation with warfarin before cardioversion of atrial fibrillation produces a marked reduction of cardioversion-related thromboembolism. The benefit of anticoagulant therapy is generally believed to be due to atrial thrombi organization. PATIENTS AND METHODS: Transesophageal echocardiography (TEE) is highly accurate for diagnosis of atrial thrombi and gives the possibility to serially evaluate the effects of anticoagulant therapy. One hundred twenty-three patients with atrial fibrillation lasting longer than 2 days underwent TEE before cardioversion. An atrial thrombus was identified in 11 patients (9%), and was always confined to the left atrial appendage. TEE was repeated after a median of 4 weeks of oral warfarin. Atrial thrombus had completely resolved in 9 of 11 patients (81.8%; 95% CI, 48.2 to 97.7%); in two patients, clot was still present. No patient had clinical thromboembolism between the two TEE studies. CONCLUSIONS: In the population of our study, a prolonged course of warfarin therapy was associated with resolution of atrial thrombi in the majority of patients. According to these data, the mechanism of thromboembolism reduction with 4 weeks of anticoagulation before cardioversion in patients with atrial fibrillation seems to be related mainly to thrombus lysis rather than organization. Due to the possibility of thrombus persistence even after prolonged anticoagulation, follow-up with TEE before cardioversion is necessary to document thrombus resolution.

[Pacemaker-induced infection: diagnosis by multi-plane transesophageal echocardiography]. / Infezione di elettrocatetere di pacemaker: diagnosi con ecocardiografia transesofagea multiplana.

We report the identification by multiplane transesophageal echocardiography of a vegetation on a permanent pacemaker lead in a patient with persistent bacteriemia. The lesion could not be visualized with transthoracic echocardiography. The diagnosis of vegetation was based on the visualization of a freely highly mobile mass attached to the pacemaker lead, with different echogenicity from the lead. The entire pacing system was surgically removed through a right atrial approach, and inspection confirmed pacemaker lead vegetation. We conclude that transesophageal echocardiography should be considered to investigate suspected pacemaker lead infection in patients with negative transthoracic echocardiography.

Severe left ventricular dynamic outflow tract gradient secondary to localized septal hypertrophy and concomitant acute ischaemic parietal dyssynergy.

Localized basal septal hypertrophy (LSH) is usually an incidental echocardiographic finding and, as opposed to asymmetric hypertrophic cardiomyopathy (AHC), is of no clinical significance. We report a case of a patient with LSH who developed a severe left ventricular outflow gradient during acute myocardial ischaemia, apical akinesis and compensatory hyperkinesis of basal parietal segments.

[Ultrasonic decalcification in aortic stenosis. Clinical and doppler echocardiographic results]. / Decalcificazione ultrasonica della stenosi aortica. Risultati clinici ed eco-doppler.

Ten elderly patients with aortic valve stenosis and with a small calcified annulus (less than 20 mm) were treated by ultrasonic valve debridement (UVD) while 17 other elderly patients underwent aortic valve replacement (AVR) during the same period. The clinical and doppler results were assessed for a mean follow-up period of 20 months. Patients with significant aortic regurgitation or associated valve disease were excluded. The patients were studied by m-mode, two-dimensional and Doppler echocardiography before, immediately after, and at 6 months interval after the procedure. A successful decalcification was achieved in 8 patients. The valve was replaced in 2 patients because of cusp perforation or unsatisfactory intraoperative result. All patients showed significant postoperative increase in the mobility of the valve cusps, decrease in the amount of calcium, decrease of the aortic mean valve gradient (from 62 +/- 25 to 23 +/- 6 mmHg, p less than 0.001) and increase of the aortic valve area (from 0.49 +/- 0.11 to 1.21 +/- 0.3, p less than 0.001). The mean valve gradient was slightly higher after UVD than after AVR and showed a slight trend to further increase during follow-up, although only one patient had evidence of restenosis. A mild aortic valve insufficiency was present postoperatively in 6 patients. Worsening of insufficiency was noted in 2 patients during the follow-up period and one subject was re-operated on. Surgical ultrasonic debridement of the aortic valve may be effective in selected surgical candidates with small calcified valve and annulus, but subsequent occurrence of aortic insufficiency and restenosis may seriously limit its application.

Unusual origin and course of the first septal branch of the left coronary artery: angiographic recognition.

The anatomical variants of the origin and course of the first septal branch (S1) of the left coronary artery system have received little attention in the literature dealing with coronary angiography. We describe here the angiographic features of the ectopic origin of S1 from epicardial branches of the left coronary artery other than the left anterior descending artery as observed in 8 cases from a series of 700 consecutive patients (1.1%). The S1 originated from the left main coronary artery in 1 case, from a diagonal branch in 4, and from an intermediate branch in 3 cases. Previous reported cases are reviewed. Because the S1 may supply up to 15% of the blood to the myocardium, the recognition of this variable origin may have clinical implications and has to be considered as a part of the complete evaluation of coronary arteriograms of patients referred for coronary artery revascularization.

N-acetyl-beta-D-glucosaminidase (NAG) levels in amniotic fluid or urine in prenatal and postnatal life.

The isoenzyme pattern of N-acetyl-beta-D-glucosaminidase (NAG) was determined in the amniotic fluid of 75 women undergoing amniocentesis for genetic indications. In the amniotic fluid and in the newborn's urine the NAG was completely different from that in adult urine, indicating the presence of a fetal isoenzymatic form also present in the first stage of life.

[Danazol: a new hormonal post-coital contraceptive method]. / Danazol: nouvelle methode de contraception hormonale post-coitale.

During a 9-month period, 84 female patients received post-coital contraception consisting either of an association of ethinyl estradiol/norgestrel or of danazol, in order to compare the safety and any adverse reaction of these 2 treatments. Overall, the patients treated with danazol presented 1/3 as many side effects. Nausea was reduced to 1/3 in frequency and vomiting to 1/9 in this group. 5 pregnancies were confirmed in the ethinyl estradiol/norgesterol group and 2 in the danazol group. Although more cases are needed, it would appear that danazol is characterized by greater efficacy and patient acceptability.

Accuracy of an average ultrasonic laboratory in measurements of fetal biparietal diameter, head circumference and abdominal circumference.

Twenty patients between 14 and 28 gestational weeks were scanned on three occasions during a single day by six operators with different ultrasonic experience (three use a compound scanner and three a real-time equipment). On each occasion every operator had to measure in a "blind" manner the fetal biparietal diameter (BPD), head circumference and abdominal circumference (HC and AC); a coded copy of head and abdominal circumference was subsequently measured by one of the members of the staff. Statistical analysis was carried out on the 1800 measurements, and it was concluded that the accuracy was not dissimilar from that reported by pilot studies. The reproducibility of the parameters studied did not change throughout pregnancy and real-time and compound scanner yielded homogeneous results.

[Pharmacokinetics of amiodarone in one case of acute oral intoxication]. / Farmacocinetica dell'amiodarone in un caso di intossicazione acuta (8 grammi per os).

A wealth of data about the clinical use and the therapeutic efficacy of chronic treatment with amiodarone has been reported, while the acute effects of this agent are less known. In one case of acute oral intoxication with 8 g of amiodarone for suicidal purposes, we have investigated the pharmacokinetics of amiodarone, the thyroid function and the variations of some clinical parameters, such as heart rate and QT interval. Other possible side-effects have been looked for. We have not observed substantial pharmacokinetic differences between our case and studies carried out after chronic oral or intravenous administration. Unlike chronic administration, the acute oral load was not followed by the appearance of toxic effects. The absence of toxic phenomena can be explained by the poor bioavailability of amiodarone, which is known to require long periods for a complete distribution to the tissues and target organs.