In the last decade Ketogenic Diet (KD) came to light as a potential treatment for a wide range of diseases, from neurological to metabolic disorders, thanks to a beneficial role mainly related to its anti-inflammatory properties. The high-fat, carbohydrate-restricted regimen causes changes in the metabolism leading, through the β-oxidation of fatty acids, to the hepatic production of ketone bodies (KBs), used by many extrahepatic tissues as energy fuels. Once synthetized, KBs move through the systemic circulation and reach all the tissues of the organism, affecting their functions and playing pleiotropic roles acting directly and indirectly on various targets as ion channels and neurotransmitters. Moreover, they can operate as signalling metabolites and epigenetic modulators. Therefore, it is limiting to consider that the clinical condition of each single patient could improve after a KD regimen based on its localized effects; rather it is more complete to think about how KBs might affect the organism as a whole. In this minireview, we tried to summarize the recent knowledge of the effects of KBs on various tissues, with a particular attention to the excitable ones, namely the nervous system, heart and muscles.

In myotonic dystrophy type 2 (DM2), an association has been reported between early and severe myotonia and recessive chloride channel (CLCN1) mutations. No DM2 cases have been described with sodium channel gene (SCN4A) mutations. The aim is to describe a DM2 patient with severe and early onset myotonia and co-occurrence of a novel missense mutation in SNC4A. A 26-year-old patient complaining of hand cramps and difficulty relaxing her hands after activity was evaluated at our department. Neurophysiology and genetic analysis for DM1, DM2, CLCN1 and SCN4A mutations were performed. Genetic testing was positive for DM2 (2650 CCTG repeat) and for a variant c.215C>T (p.Pro72Leu) in the SCN4A gene. The variation affects the cytoplasmic N terminus domain of Nav1.4, where mutations have never been reported. The biophysical properties of the mutant Nav1.4 channels were evaluated by whole-cell voltage-clamp analysis of heterologously expressed mutant channel in tsA201 cells. Electrophysiological studies of the P72L variant showed a hyperpolarizing shift (-5 mV) of the voltage dependence of activation that may increase cell excitability. This case suggests that SCN4A mutations may enhance the myotonic phenotype of DM2 patients and should be screened for atypical cases with severe myotonia.

BACKGROUND:The level of language development reached in pre-school age is considered the most reliable predictor of reading acquisition. In normally developing children, learning to read is strongly related to early language skills, and in particular to phonological processing abilities. In dyslexic children, reading abilities seem to show a correlation with phonological awareness.METHODS:A group of 65 children (aged 5-6 years) were recruited and submitted to an in-depth neuropsychological assessment [i.e. metaphonological skills, intelligence, verbal short-term memory (VSTM) and other aspects of receptive and expressive language]. We were able to identify 14 children with significant metaphonological difficulties (MD): 11 children with exclusively MD, and the other three children with specific language impairment. This study compares the neuropsychological profile obtained from children with MD with that of a peer group without any language impairment (N).RESULTS:The performances of the MD were within the normal ability range in almost all the administered tests but significantly lower compared with those of their peers without language impairment (N) in some items of the intelligence scale (Wechsler Preschool and Primary Scale of Intelligence) and in the tests of VSTM and of receptive/expressive language. Nevertheless, there were not statistically significant differences between MD and N in output phonology.CONCLUSIONS:In pre-school age, in a group of non-clinical children, with a range of abilities, those with MD appear to be at the lower end of the normal range in many other verbal skills. These children could be considered at-risk for possible subsequent difficulties learning to read and thus need to be identified and to warrant prompt treatment.

Despite the growing evidence for the positive predictive value of depressed baroreflex sensitivity and/or reduced heart rate variability after myocardial infarction, the mechanisms involved in these autonomic alterations are not fully understood. Specifically, the possible influence of residual ischaemia has not been assessed. To address this problem we studied the spectral analysis of heart rate variability in 21 patients with a first myocardial infarction in whom the only clinical correlate was the presence of residual ischaemia, as documented by the positive response to both an exercise stress test and an echocardiographic stress test. Data from these patients were compared with those obtained in a group of postmyocardial infarction patients similar for several risk factors, age, site of myocardial infarction, but without residual ischaemia. Patients positive for residual ischaemia had lower power in the whole spectrum (1146 +/- 158 vs 1631 +/- 159 ms2, P = 0.032) as well as in the low and high frequency bands of heart rate variability. A nocturnal increase in high frequency was observed in those without residual ischaemia (from 167 +/- 35 to 242 +/- 51 ms2, +45%, P = 0.034), but not in those with residual ischaemia (from 111 +/- 19 to 141 +/- 29 ms2, +27%, ns). Thus, residual ischaemia reduces heart rate variability after myocardial infarction. The autonomic effects of residual ischaemia probably contribute to its negative prognostic value after myocardial infarction.

Interstitial pneumonia is the most common disease caused by infection from cytomegalovirus (CMV) in immunodepressed patients, whereas it is a rare complication in immunocompetent patients. With reference to the second group of patients, little literature has been produced as for the therapy to choose when symptoms are serious. We report the case of immunocompetent adolescent with CMV pneumonitis who responded dramatically to therapy with ganciclovir. For a week B. M., a 15-year-old girl, has been showing fever, cough and boring pain at her left thoracic base. When hospitalized, the girl was suffering and dyspneic, cardio-thoracic conditions were bad. Spleen and liver were palpable two fingers far form costal arch. Hematochemical tests showed an increase in phlogosis and transaminase value. Thoracic X-ray was negative, as well as cultures. Among the serological tests high response of anti-CMV IgM was remarkable. Virological blood test confirmed active CMV infection. On the fifth day, a thoracic radiography showed widespread interstitial infiltrates. Treatment with ganciclovir--i.v. 6 mg/kg/day, twice a day for twelve days--has been then adopted. After two day treatment, the girls was apyretic and eupneic. After ten day treatment, thoracic radiography was negative and a great decrease in CMV antigenic response was given by blood tests. No side effect were observed. According to our experience we can say that treatment with ganciclovir may positively shorten the course of pneumonia caused by CMV in immunocompetent patients.

Background: Human parvovirus (HPV) B19 infection has been shown to be transmissible by clotting factor concentrates, most often resulting in asymptomatic seroconversion. So far, no case of B19 transmission due to single-donor transfusion has been documented.Case Report: A case of transfusion-transmitted HPV B19 infection in a 22-year-old female thalassemia major patient is described. She presented with an aplastic crisis; this was followed 1 week later by transitory heart failure and acute tricuspid incompetence. The echocardiogram revealed a grade III tricuspid regurgitation and a floating vegetation on the atrial face of the tricuspid lateral leaflet. The tricuspid regurgitation and vegetation spontaneously disappeared within 15 days. Blood cultures for bacteria were repeatedly negative. IgM anti-HPV B19 seroconversion was documented in the acute phase. B19 DNA was detected by polymerase chain reaction and remained detectable up to 4 months after diagnosis. High-titer IgM anti-HPV and B19 DNA were also found in serum samples collected at the time of donation from one of the donors of the blood transfused before the onset of clinical symptoms.Conclusion: This case documents the transmission of HPV B19 by the transfusion of 1 red cell unit and the occurrence of possible transient cardiac involvement in this infectious complication.

Thirty-six consecutive patients with idiopathic haemochromatosis (IH) were studied by electrocardiography (ECG), polygraphy, M-mode and 2-D echocardiography and Doppler-echocardiography. No significant correlations were found between ECG, PEP/LVET ratio and echocardiographic measurements. Left ventricular (LV) enlargement with impaired LV systolic function was present only in three patients (5.5%), of whom two died during iron-depleting therapy because of cardiovascular complications. Compared with controls, echocardiographic abnormalities were significantly more frequent and marked in subjects with higher iron overload than in those in whom it was lower. Ten patients were studied before and after iron depletion, nine of whom had only mild echocardiographic abnormalities at baseline examination. Significant reduction of end-diastolic thickness of the interventricular septum and LV mass (P less than 0.01 and less than 0.02 respectively) was observed. Also the end-diastolic thickness of the LV posterior wall and the end-systolic diameter of the left atrium reduced although not to a significant degree. The increased thickness of ventricular walls without impairment of LV systolic function is probably the first and still reversible cardiac alteration due to iron deposition in the myocardium. Later, with increasing iron overload, LV function becomes impaired and dilated cardiomyopathy develops. Early diagnosis and treatment of IH cardiopathy is needed before irreversible cardiac damage occurs.

Forty-four patients with mitochondrial myopathies were treated with Ubidecarenone (CoQ10) for 6 months in an open multi-center trial. No side effects of the drug were observed. Sixteen patients showing at least 25% decrease of post-exercise lactate levels were selected as responders. Responsiveness was apparently not related to CoQ10 level in serum and platelets or to the presence or absence of mtDNA deletions. The responders were treated for a further 3 months with CoQ10 or placebo in the second blind part of the trial; no significant differences were observed between the 2 groups. It is not clear why CoQ10 had therapeutic effects in some patients and not in others with the same clinical presentation and biochemical defect, and we failed to identify candidate responders before treatment. At the dose of CoQ10 used in this study (2 mg/kg/day) the therapy requires a long administration time before a response is seen.

We tested the efficacy of coenzyme Q10 (ubidecarenone, CoQ10) therapy in patients with Kearns-Sayre syndrome and other mitochondrial myopathies with chronic progressive external ophthalmoplegia (CPEO). We treated seven patients for 1 year with daily oral administration of 120 mg of CoQ10. Throughout the treatment most of our patients showed a progressive reduction of serum lactate and pyruvate levels following standard muscle exercise and generally improved neurologic functions. The ECG and echocardiogram showed no significant changes in our patients. None of our patients showed any improvement in ptosis and CPEO.

We describe a patient with a large intramyocardial hydatid cyst lying in the postero-lateral segment of the left ventricle near the atrioventricular groove level which ruptured into the pericardial sac, resulting in cardiac tamponade. Cross-sectional echocardiographic examination from a modified four-chamber apical view showed the multiloculated cyst and the breach connecting it to the pericardial sac, allowing for the definitive diagnosis and indication for emergency cardiac surgery. The risks of pericardiocentesis and invasive diagnostic procedures could thus be avoided.

Cardiac Improvement after Coenzyme Q10 Treatment in Patients with Kearns-Sayre Syndrome: PP286 L. Bet;N. Bresolin;A. Binda;F. Nador;C. Ferrante;G. Comi;G. Scarlato; Neurology

We assessed the relationship between echocardiographic and hemodynamic parameters in 28 patients with documented acute myocardial infarction (AMI), who underwent M-mode echocardiography and Swan-Ganz catheterization during the same hospitalization. Patients with valvular heart disease were excluded from the study. On mitral valve echogram, DE interval was measured and the area enclosed by mitral valve echogram during DE interval (DE subarea ) was calculated in each echocardiogram. DE subarea /DE interval ratio was computed for each measurement set. Hemodynamic parameters were obtained in the usual fashion. Patients with pulmonary artery wedge pressure (PWP) less than 18 mm Hg showed a DE interval markedly longer than patients with PWP greater than 18 mm Hg: 81.72 +/- 15.23 vs 55.12 +/- 9.85 msec (p less than 0.001). Patients with cardiac index greater than 2.2 L min-1 m-2 had a DE subarea /DE interval ratio greater than patients with cardiac index less than 2.2 L min-1 m-2: 0.169 +/- 0.035 vs 0.094 +/- 0.017 dm2 sec-1 (p less than 0.001). Echocardiographic and hemodynamic data were then correlated in the whole study group, and it was found that DE interval was significantly (p less than 0.001) and inversely correlated to PWP; stroke index more than cardiac index was correlated (p less than 0.005) both to DE subarea /DE interval ratio and to DE interval itself; DE interval was not affected by heart rate. We were able to categorize the patients into four subsets on the basis of echocardiographic measurements. Our findings suggest the possibility of providing, through M-mode echocardiography, a noninvasive and accurate evaluation of PWP and stroke index.