Rapid spread of the novel respiratory syncytial virus A ON1 genotype, central Italy, 2011 to 2013.

Respiratory infections positive for human respiratory syncytial virus (RSV) subtype A were characterised in children admitted to hospitals in Rome and Ancona (Italy) over the last three epidemic seasons. Different strains of the novel RSV-A genotype ON1, first identified in Ontario (Canada) in December 2010, were detected for the first time in Italy in the following 2011/12 epidemic season. They bear an insertion of 24 amino acids in the G glycoprotein as well as amino acid changes likely to change antigenicity. By early 2013, ON1 strains had spread so efficiently that they had nearly replaced other RSV-A strains. Notably, the RSV peak in the 2012/13 epidemic season occurred earlier and, compared with the previous two seasons, influenza-like illnesses diagnoses were more frequent in younger children; bronchiolitis cases had a less severe clinical course. Nonetheless, the ON1-associated intensive care unit admission rate was similar, if not greater, than that attributable to other RSV-A strains. Improving RSV surveillance would allow timely understanding of the epidemiological and clinicopathological features of the novel RSV-A genotype.

Human case of autochthonous West Nile virus lineage 2 infection in Italy, September 2011.

On 10 September 2011, a patient in his 50s was admitted to hospital in Ancona, Italy, after six days of high fever and no response to antibiotics. West Nile virus (WNV) infection was suspected after tests to determine the aetiology of the fever were inconclusive. On 20 September, WNV-specific IgM and IgG antibodies were detected in the patient's serum. Genomic sequencing of the viral isolate showed that the virus belonged to WNV lineage 2.

Molecular surveillance of pandemic influenza A(H1N1) viruses circulating in Italy from May 2009 to February 2010: association between haemagglutinin mutations and clinical outcome.

Haemagglutinin sequences of pandemic influenza A(H1N1) viruses circulating in Italy were examined, focusing on amino acid changes at position 222 because of its suggested pathogenic relevance. Among 169 patients, the D222G substitution was detected in three of 52 (5.8%) severe cases and in one of 117 (0.9%) mild cases, whereas the D222E mutation was more frequent and evenly distributed in mild (31.6%) and severe cases (38.4%). A cluster of D222E viruses among school children confirms reported human-to-human transmission of viruses mutated at amino acid position 222.

Episodic spontaneous hypothermia potentially triggered by hyperinsulinemia.

Episodic spontaneous hypothermia is an infrequent disorder, the pathogenic mechanisms of which have not been completely clarified, although alterations in the serotoninergic system have been suggested. We report the history of a girl with episodes of dizziness and shivering associated with a body temperature lower than 35 degrees C since the age of 10 months. At the age of 11 years, she was admitted to a local hospital and an oral glucose tolerance test showed high total insulin levels. Hypoglycemia secondary to hyperinsulinemia was suspected, and a low-carbohydrate (simple) diet was proposed without results. Due to the recurrence of the episodes, episodic spontaneous hypothermia triggered by hyperinsulinemia was suspected, and treatment with flunarizine, a drug considered the first line in the treatment of migraine-related disorders, was started with a resulting reduction in the episodes. A new endocrinological evaluation showed decreased insulin secretion. In our patient, the success of the therapy might be due to the well-known effect of calcium antagonists in inhibiting serotonin uptake and thereby regulating serotonin levels after hyperinsulinism. This case suggests hyperinsulinemia as a potential mechanism for episodic spontaneous hypothermia, probably mediated by an interaction between insulin and the serotoninergic system.

Color vision in epileptic adolescents treated with valproate and carbamazepine.

OBJECTIVE: The aims of our study were to evaluate whether deficits in color vision exist in epileptic adolescents, to study if monotherapy with valproic acid (VPA) and carbamazepine (CBZ) can affect color vision, and to determine the possible relationship between abnormal color vision tests and AEDs dosage and their serum concentrations. PATIENTS: We examined 45 epileptic patients before the beginning of therapy and after 1 year of VPA or CBZ monotherapy and 40 sex- and age-matched healthy controls. METHODS: Color vision was evaluated with Farnsworth Munsell 100 (FM100) hue test and achromatic and short-wavelength automated perimetry (SWAP). STATISTICAL ANALYSIS: To evaluate intergroup differences we used ANOVA with Scheffe's post hoc test, when appropriate. Repeated measures ANOVA was used to evaluate the intragroup modifications of total error score (TES) and perimetric threshold during the follow-up. Pearson's correlation test was performed to correlate chromatic sense and perimetric data and AEDs dosage and serum concentrations. RESULTS: Before the beginning of therapy, there were no differences in central color vision and SWAP between controls and epileptic patients. After 1 year, patients treated with VPA or CBZ showed a deficit in FM100 hue test and SWAP parameters while no significant deficit was found in achromatic perimetry. In particular, with the FM100 hue test a higher number of errors was found in both groups of patients (CBZ patients: 166.00 +/- 27.72 TES; VPA patients: 151.19 +/- 44.09, P < 0.001) in comparison with controls (controls: 109.29 +/- 24.73) and baseline values (CBZ patients: 110.65 +/- 22.9; VPA patients 107.43 +/- 21.70). With SWAP patients of both groups showed significant variation of foveal threshold (controls: 21.07 +/- 2.01 dB; CBZ patients: 19.35 +/- 1.32, P < 0.001; VPA patients: 18.88 +/- 1.89, P < 0.001), full-field mean threshold perimetric sensitivity (controls: 18.50 +/- 1.24 dB; CBZ patients: 16.60 +/- 1.47, P < 0.001; VPA patients: 16.23 +/- 1.55, P < 0.001) and mean threshold perimetric sensitivity of the three evaluated subareas of the visual field (area 1 controls: 21.01 +/- 1.15; CBZ patients: 19.45 +/- 1.74, P = 0.001; VPA patients: 18.25 +/- 1.61, P < 0.001; area 2 controls: 18.40 +/- 1.43; CBZ patients: 16.07 +/- 1.58, P +/- 0.001; VPA patients: 16.13 +/- 1.46, P = 0.001; area 3 controls: 17.20 +/- 1.49; CBZ patients: 14.28 +/- 1.51, P < 0.001; VPA patients: 14.31 +/- 2.90, P = 0.001). CONCLUSIONS: Our study demonstrates that treatment with VPA or CBZ can affect significantly both central and paracentral color vision after a short treatment period.

Macrophagic myofasciitis: an infantile Italian case.

Macrophagic myofasciitis is a recently identified inflammatory myopathy mostly described in adult French patients complaining of arthro-myalgias and fatigue. It is probably due to intramuscular injection of aluminium-containing vaccines and is characterized by a typical muscular infiltrate of large macrophages with aluminium inclusions. We report a 1-year-old Italian child presenting irritability, delayed motor development, hyperCKemia (up to 10 times the normal value), and typical features of macrophagic myofasciitis on muscle biopsy. The child recovered fully after steroid therapy. Macrophagic myofasciitis is a new treatable cause of motor retardation and hyperCKemia in children, and is probably more common than reported. Diagnosis requires a high index of suspicion and can be missed if biopsy is performed outside the vaccination site.

Epilepsy evaluation by electroencephalography and magnetoencephalography in Lafora-body disease: a case report.

UNLABELLED: Lafora-body disease (LBD) is a rare neurometabolic disorder of autosomal recessive inheritance associated with progressive myoclonic epilepsy. We report here the first description of ictal and interictal recording by electroencephalography (EEG) and magnetoencephalography (MEG) of a 15-y-old girl suffering from LBD. CONCLUSIONS: Complementary use of MEG and EEG might be of future help to the clinician in better defining the pathophysiology of complex seizures, and also in patients with progressive neurological disorders, despite the poor prognosis of syndromes such as LBD.

Magnetoencephalographic and electroencephalographic evaluation in patients with cryptogenetic partial epilepsy.

UNLABELLED: Magnetoencephalography (MEG) has been applied for more than 20 years to the localization of the epileptic focus in partial epilepsies, but correlation with electroencephalographic (EEG) data in homogeneous groups of patients is scarce. OBJECTIVE: The aim of our work was to use EEG and MEG for the study of a group of adults and children affected by cryptogenetic partial epilepsy. METHODS: We analyzed the traces obtained from electroencephalographic and magnetoencephalographic recordings of 10 patients of ages ranging from 7 to 38 years affected by cryptogenetic partial epilepsy. We evaluated the presence of commonly detected or uniquely detected spikes, and, whenever possible, we used MEG for localization of the epileptic focus. RESULTS: Three patients showed no epileptic activity during the EEG and MEG sessions. Overall agreement between EEG and MEG (presence of concordant spikes with the same localization shown by both techniques) was obtained in five patients. In one patient the spikes detected by EEG and MEG were different, and in another patient interictal activity was demonstrated exclusively by EEG. CONCLUSIONS: EEG in this series was not inferior to MEG in terms of spike detection. Combination of EEG and MEG is feasible, better than each technique alone, and may be useful for non-invasive diagnosis and monitoring of pediatric and adult patients with partial epilepsies.

Serum leptin levels in girls with precocious puberty.

Few data are available regarding leptin levels in children with different pubertal stages or with precocious puberty (PP). The aim of this study was to assess the changes in serum leptin levels in patients with PP. We studied 20 girls with PP, with Tanner stage II-III; the age at the beginning of pubertal signs ranged from 4.2 to 7.1 yr; all the girls had an advantaged bone age. Controls were subdivided in two groups: group 1: 20 pre-pubertal girls with the same chronological age of the patients, without any signs of pubertal development (Tanner stage I); group 2: 20 additional girls with the same bone age, pubertal stage and body mass index (BMI) of the girls with PP. Serum leptin levels in females with PP are similar to those found in subjects with normal puberty (9.0 +/- 0.8 vs 9.1 +/- 0.9 ng/ml; ns) and different from subjects with the same chronological age without activation of puberty (5.6 +/- 0.9 ng/ml, p < 0.001). In all groups leptin levels correlated significantly with BMI (girls with PP: r = 0.5 1, p < 0.02; control group 1 girls: r = 0.71; p < 0.0001; control group 2 girls: r = 0.49; p < 0.02), there was no significant relationship between leptin and activation of hypothalamic-pituitary-gonadal axis. Our results indicate that the serum leptin levels in the girls with PP are not significantly different from levels in healthy girls at a similar stage of pubertal development, suggesting that the relationship between serum leptin levels and BMI is also present in this pathological situation.

Kidney involvement and disease in patients with diabetes.

Diabetic nephropathy is the leading cause of end-stage renal disease in western or westernised countries and the largest contributor to the total cost of diabetes care around the world. In addition to the development of diabetic nephropathy and end-stage renal failure, diabetic patients with evidence of albuminuria have a much higher risk of developing myocardial infarctions, cerebrovascular accidents, severe progressive retinopathy, and peripheral and autonomic neuropathy. A cumulative incidence of diabetic nephropathy has been documented after duration of diabetes of at least 25 years in both type 1 and type 2 diabetic patients, although more recent studies have demonstrated a substantial reduction of its incidence. Before the onset of overt proteinuria, there are several renal functional changes, including renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules. Basement-membrane thickening and mesangial expansion have long been recognized as pathological hallmark of diabetic nephropathy. It has been postulated that diabetic nephropathy occurs as a result of the interplay of metabolic and haemodynamic factors in the renal microcirculation. Hyperglycaemia plays a pivotal role in the pathogenesis of diabetic renal disease, but genetic factors are also of crucial importance. The accumulation of advanced glycosilation end products (AGEPs), the activation of isoforms of protein kinase C (PKC) and the acceleration of the aldose reductase pathway may explain how hyperglycaemia damages vessels. Growth factors (i.e. TGF-b, IGF-1, VEGF) may also play an important role in the pathogenesis. There is a familial clustering of diabetic kidney disease: a number of gene loci have been investigated to try to explain the genetic susceptibility to this complication. The two main treatment strategies for prevention of diabetic nephropathy are improved glycaemic control and blood pressure lowering, particularly using drugs such angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. Many potential treatment modalities in preventing and treating diabetic nephropathy are presently being evaluated; some of them will possibly be available in the near future in order to try to modify the natural course of kidney involvement and disease in patients with diabetes.

Epilepsy and adolescents.

Anticonvulsant (AEDs) therapy in adolescence is very difficult because there is no-compliance in this special time of life. Many studies show that the factors that assured good compliance were good motivation, a good therapeutic result, the support of parents, medical and assistance personnel and the positive attitude to the disease and its treatment. Moreover, in recent years, many studies have shown the changes in endocrinology function and weight changes in adolescents after AEDs therapy and after long term therapy with valproate (VPA), carbamazepine (CBZ), gabapentin, felbamate and, topiramate. Abnormalities include weight increase, weight loss, polycystic ovaries and bone disease (osteopenia/osteoporosis, osteomalacia, etc). Thyroid hormone concentrations are involved too. Some study report that the children treated with CBZ may have subclinical signs of hypothyroidism, and these changes are more evident if CBZ is given in association with another drug for example with VPA.

New antiepileptic drugs in childhood.

In recent years, many new antiepileptic drugs have been available for the treatment of epilepsy in pediatric age. In this review, we describe these new antiepileptic drugs (vigabatrin, lamotrigine, felbamate, gabapentin, tiagabine, topiramate) which can be used together with "old" antiepileptic drugs (e.g. phenobarbital, valproate, etc.). We report their mechanisms of action, effectiveness, dosage and side effects; moreover, some practical advice for their use in pediatric patients is given.

Photoparoxysmal responses in non-epileptic children in long-term follow-up.

OBJECTIVES: To evaluate the photoparoxysmal responses (PPR) in non-epileptic children and adolescents in long-term follow-up. MATERIALS AND METHODS: We studied 14 non-epileptic children who showed PPR without any other electroencephalographic (EEG) abnormalities. RESULTS: One subjects was lost after 1 year of follow-up. At the final follow-up, four of the 13 patients (approximately 30%) did not show any PPR or other epileptic discharges, while in other children PPR continued to be present. The age of the disappearance of PPR in these four patients ranged from 1.1 to 5.9 years from the first evaluation. No patients suffered from epileptic seizures during the whole period of follow-up. CONCLUSION: Our study confirms that PPR can be present in the EEG of non-epileptic children and adolescents and demonstrates that this EEG change is not related to the presence of seizures and must not be considered a marker for the developing of epilepsy.

Screening for vascular complications in children and adolescents with type 1 diabetes mellitus.

Type 1 diabetes mellitus poses a significant health burden, particularly as a result of its microvascular complications. Clinically evident diabetes-related microvascular complications are extremely rare in childhood and adolescence. However, early functional and structural abnormalities may be present a few years after the onset of the disease. Therefore, regular screening for diabetic microvascular disease, particularly retinopathy and nephropathy, are of foremost importance in paediatric diabetes care. Early detection of diabetic microangiopathy and timely treatment of early signs of these complications have a pivotal role in prevention of blindness and end-stage renal failure in children and adolescents with diabetes.

Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy.

To assess whether epileptic children have abnormal values of serum copper (Cu), zinc (Zn), selenium (Se), glutathione peroxidase (GSH-PX) and superoxide dismutase (CuZn-SOD), and to evaluate the effect of long-term therapy with sodium valproate (VPA) and carbamazepine (CBZ) on these parameters, we studied 36 epileptic patients before the beginning of therapy and after 1 year of therapy with VPA or CBZ. Before the beginning of therapy, there were no differences in levels of all parameters studied between controls and epileptics. After 1 year of therapy, patients treated with VPA and CBZ continued to show normal values. In conclusion our study demonstrates that epilepsy per se and treatment with VPA and CBZ do not affect levels of Cu, Zn, Se, GSH-PX and CuZn-SOD concentrations.

Paroxysmal tonic upgaze of childhood: effect of age-of-onset on prognosis.

UNLABELLED: Paroxysmal tonic upgaze (PTU) is a syndrome of childhood manifesting as sudden ocular movements with sustained upward deviation of the eyes. We describe the outcome of 6 patients, after a follow-up of 10 years, with onset of the disease in childhood. The aims of this study were to clarify some clinical features of this syndrome and to evaluate the long-term prognosis of these children. In all the patients, tonic upgaze episodes disappeared with time to remission, varying from 1 to 4 y, without any therapy and without any change in psychomotor development, EEG and neuroimaging. Only one child had pathologic interictal EEG with temporo-occipital spikes, which persisted after the offset of the disease. CONCLUSION: From a long-term follow-up, we can confirm the good prognosis of PTU and suggest it is possible to define a distinct syndrome of childhood without any neurological abnormalities and with spontaneous resolution.

Effect of anticonvulsant drugs on interleukins-1, -2 and -6 and monocyte chemoattractant protein-1.

In order to evaluate whether treatment with valproic acid or carbamazepine can modify interleukins and monocyte chemoattractant protein-1, we studied 40 epileptic children and adolescents. We evaluated the patients before and after 1 year of therapy. At the end of follow-up, the patients showed a significant increase of the production of interleukin-1alpha, interleukin-1beta, interleukin-6, and monocyte chemoattractant protein-1; interleukin-2 production was significantly higher only in patients receiving carbamazepine. In conclusion, antiepileptic drugs can influence the immune system by modifying interleukin and chemokine concentrations; these changes seem to be independent of the serum concentrations of these drugs.

Effects of antiepileptic drugs on evoked potentials in epileptic children.

To evaluate the visual and auditory function in children and adolescents who are undergoing monotherapy with sodium valproate, carbamazepine, and phenobarbital visual-evoked potentials and brainstem auditory-evoked potentials were measured in 58 epileptic patients (30 males and 28 females), ages 13.7 +/- 6.9 years. Fifty healthy sex- and age-matched children served as controls. The measurements were performed before the beginning of therapy and after 12 months. Before the beginning of therapy, there were no significant differences in visual- and auditory-evoked potentials between the control group and the three groups of epileptic children. After 12 months of therapy, patients treated with carbamazepine demonstrated a significant (P < 0.001) increase of P100 latencies when compared with baseline data and control values; moreover, these patients exhibited a significant increase of peak latencies of waves I-III-V and interpeak interval I-V at auditory second evaluation. The patients treated with sodium valproate manifested a significant (P < 0.05) increase in VEP P100 latencies. On the contrary, children receiving phenobarbital did not manifest any significant abnormality at visual- and auditory-evoked potentials measurements. Our study demonstrates that for patients treated with carbamazepine and sodium valproate, an electrophysiologic dysfunction of visual and auditory sensory pathways can be present after 12 months of treatment.