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.

Sensitivity Analysis of Single Beat Left Ventricular Elastance Estimation by Chen Method.

INTRODUCTION: Left ventricular (LV) end-systolic elastance (Ees) can be estimated using single-beat (Ees(sb)) Chen method, employing systolic and diastolic arm-cuff pressures, stroke volume (SV), ejection fraction and estimated normalized ventricular elastance at arterial end-diastole. This work aims to conduct a sensitivity analysis of Chen formula to verify its reliability and applicability in clinical scenario. METHODS: Starting from a baseline condition, we evaluated the sensitivity of Ees(sb) to the parameters contained in the formula. Moreover, a mathematical model of the cardiovascular system was used to evaluate the sensitivity of Ees(sb) to end-diastolic LV elastance (Eed), Ees, arterial systemic resistance (Ras) and heart rate (HR). RESULTS: In accordance with Ees definition, Ees(sb) increases by increasing aortic pressure and pre-ejection time, reaching the highest value for a pre-ejection time = 40 ms, and then decreases. In contrast with Ees definition, Ees(sb) increases (from 3.21 mmHg/mL to 12.15 mmHg/mL) by increasing the LV end-systolic volume and decreases by increasing the SV. In the majority of the analysis with the mathematical model, Ees was underestimated using the Chen method: by increasing Ees (from 0.5 to 2.5 mmHg/mL), Ees(sb) passes only from 0.56 to 1.54 mmHg/mL. Ees(sb) increases for higher Eed (from 1.03 to 2.33 mmHg/mL). Finally, Ees(sb) decreases (increases) for HR < 50 bpm (< 50 bpm), and for Ras < 1100 mmHg/gcm4 (> 1100 mmHg/gcm4). CONCLUSION: Unexpectedly Ees(sb) increases for higher LV end-systolic volume and decreases for higher SV. These results contrast with Ees definition, which is the ratio between the LV end-systolic pressure and the LV end-systolic volume. Moreover, Ees(sb) is influenced by cardiocirculatory parameters such as LV Eed, HR, Ras, ejection time, and pre-ejection time. Finally, Ees(sb) computed with the model output often underestimates model Ees.

Non-invasive assessment of myocardial perfusion by intravenous contrast echocardiography: state of the art.

Many technical problems, related to both imaging instrumentation and contrast agents, have to be taken into account before attempting non-invasive evaluation of myocardial perfusion by intravenous contrast media injection. Potentials and pitfalls of first generation contrast agents (i.e. Levovist, Schering AG, Berlin, Germany) using intermittent harmonic angio imaging and of second generation contrast media (i.e. SonoVue, Bracco SpA, Milan, Italy) using real-time perfusion imaging in the non-invasive assessment of myocardial perfusion were described and discussed. We still need more solid data before introducing intravenous myocardial echocardiography into the clinical arena. However, convincing data from several research laboratories are paving the way for the widespread use of this new method in clinical practice.

Mutations at position 1122 in the catalytic domain of the mouse ras-specific guanine nucleotide exchange factor CDC25Mm originate both loss-of-function and gain-of-function proteins.

The role of two residues within the catalytic domain of CDC25Mm, a mouse ras-specific guanine nucleotide exchange factor (GEF), was investigated by site-directed mutagenesis. The function of the mutant proteins was tested in vivo in both a Saccharomyces cerevisiae cdc25 complementation assay and in a mammalian fos-luciferase assay, and in in vitro assays on human and yeast Ras proteins. Mutants CDC25Mm(E1048K) and CDC25Mm(S1122V) were shown to be (partly) inactive proteins, similar to their yeast homologs. Mutant CDC25Mm(S1122A) showed higher nucleotide exchange activity than the wild type protein on the basis of both in vitro and in vivo assays. Thus, alanine and valine substitutions at position 1122 within the GEF catalytic domain originate mutations with opposite biological properties, indicating an important role for position 1122 in GEF function.