Complementary and alternative medicine (CAM) in headache of children and adolescents: open-label Italian study.

OBJECTIVE: The aim of the present research is to evaluate and to compare various nutraceuticals and food supplements in the headaches prophylaxis. BACKGROUND: Recently the use of complementary and alternative medicine, nutraceuticals and food supplements, in prophylaxis and attack therapy of headaches is spreading both in adulthood and in childhood age. MATERIALS AND METHODS: 99 children, 6-17 years, females 44 and males 55, suffering from primary headaches and admitted to Headache Center in the years 2016- 2017 are the sample. 7 patients were excluded because they did not adhere to the study due to lack of therapeutic compliance and because they did not return to clinical controls. The patients referred to the Headache Center are selected consecutively. The open-label study evaluating clinical trial concerns the evaluation of the following parameters: headache diagnosis according to International Headache Society criteria (ICHD-III, 2013 beta version), migraine index; the prophylaxis and attack therapies at time zero and after 12 months. The compounds used to prophylaxis therapy are: Mg citrate, Mg oxide and Mg aspartate (compound n°1), Bisglycinate Mg + L-Tryptophan + Niacin + B2 Vitamin + D Vitamin (compound n°2), Oxide Mg + Partenium + Andrographis paniculata + coenzyme Q10, B2 Vitamin (compound n°3). Each compound was compared with the other to evaluate clinical efficacy. Attack therapy: Paracetamol, Ibuprofen, ketoprofen, Indomethacin. Informed consent was obtained for participation in the study by the parents of the children. Statistical analysis is made by Kruskal -Wallis test and analysis post hoc Conover. RESULT: 22 females and 24 males suffer from Migraine without aura, 9 females and 12 males from Migraine with Aura, 11 females and 14 males from Tension Type Frequent Headache. The therapy as with compounds n°1, 2 and 3 is effective in reducing migraine index and reduces the use of attack therapy in all the cases very significantly (p=0.000001). In MwoA the compound n° 1 is less effective than compounds n° 2 and 3(p=0.00089).In MA compound n° 3 is less effective than compounds n° 2 and 1 (p=0.0044). In FETTH, compound n° 3 is less effective compared to compound n° 2 (p=0.052). CONCLUSION: The use of nutraceuticals and food supplements appears to be effective and also encouraging as it is well accepted by parents and children themselves.

A process for energy-efficient high-solids fed-batch enzymatic liquefaction of cellulosic biomass.

The enzymatic hydrolysis of cellulosic biomass is a key step in the biochemical production of fuels and chemicals. Economically feasible large-scale implementation of the process requires operation at high solids loadings, i.e., biomass concentrations >15% (w/w). At increasing solids loadings, however, biomass forms a high viscosity slurry that becomes increasingly challenging to mix and severely mass transfer limited, which limits further addition of solids. To overcome these limitations, we developed a fed-batch process controlled by the yield stress and its changes during liquefaction of the reaction mixture. The process control relies on an in-line, non-invasive magnetic resonance imaging (MRI) rheometer to monitor real-time evolution of yield stress during liquefaction. Additionally, we demonstrate that timing of enzyme addition relative to biomass addition influences process efficiency, and the upper limit of solids loading is ultimately limited by end-product inhibition as soluble glucose and cellobiose accumulate in the liquid phase.

Migraine and obesity: metabolic parameters and response to a weight loss programme.

BACKGROUND AND OBJECTIVE: Weight loss can determine significant improvement of migraine in obese patients. Herein, we evaluated a clinical sample of adolescent migraineurs with obesity who participated in an interdisciplinary programme for weight loss, in order to identify possible metabolic parameters associated with good migraine control. SUBJECTS AND METHODS: Using a cross-sectional design, we evaluated 112 out of 135 adolescents who previously underwent our intervention programme. Based on persistence of headache, subjects for comparison were 40 migraine-free and 72 not migraine-free adolescents. Participants underwent anthropometric evaluations and biochemical tests. RESULTS: Patients with persistence of migraine had significantly higher weight (P < 0.01), body mass index (P < 0.01), waist circumference (P < 0.01), homeostasis model assessment of insulin resistance (P < 0.001), triglyceride (P < 0.05), total cholesterol (P < 0.05) and low-density lipoprotein cholesterol (P < 0.05) values when compared with those who became migraine-free. Between potential predictors, only insulin resistance (odds ratio = 3.5, 95% confidence interval = 1.4-6.1; P < 0.001) was significantly associated with persistence of migraine after intervention programme. CONCLUSIONS: Among obese adolescents with migraine who underwent an intervention programme for weight loss, patients who did not become migraine-free showed higher adiposity values than those who became migraine-free. Patients with insulin resistance had 3.5 times the odds of having persistence of migraine compared with those without.

Impact of a weight loss program on migraine in obese adolescents.

BACKGROUND AND PURPOSE: Increased headache frequency and severity have been observed in obese populations, but the real impact of a weight loss treatment on headache has not been studied. We investigated this issue in a sample of obese adolescents. METHODS: In all, 135 migraineurs, aged 14-18 years, with body mass index (BMI) ≥ 97 th percentile, participating in a 12-month-long program, were studied before and after treatment. The program included dietary education, specific physical training, and behavioral treatment. RESULTS: Decreases in weight (P < 0.01), BMI (P < 0.01), waist circumference (P < 0.01), headache frequency (P < 0.01) and intensity (P < 0.01), use of acute medications (P < 0.05), and disability (P < 0.05) were observed at the end of the first 6-month period and were maintained through the second 6 months. Both lower baseline BMI and excess change in BMI were significantly associated with better migraine outcomes 12 months after the intervention program. CONCLUSIONS: Significant improvements in both adiposity and headache data were observed in obese adolescents with migraine who participated in a 12-month-long interdisciplinary intervention program for weight loss. Initial body weight and amount of weight loss may be useful for clinicians to predict migraine outcomes.

Early-onset absence epilepsy: SLC2A1 gene analysis and treatment evolution.

BACKGROUND AND PURPOSES: To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). METHODS: We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. RESULTS: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). CONCLUSIONS: We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED.

Osmophobia in migraine classification: a multicentre study in juvenile patients.

AIMS: This study was planned to investigate the diagnostic utility of osmophobia as criterion for migraine without aura (MO) as proposed in the Appendix (A1.1) of the International Classification of Headache Disorders (ICHD-II, 2004). METHODS: We analysed 1020 patients presenting at 10 Italian juvenile headache centres, 622 affected by migraine (M) and 328 by tension-type headache (TTH); 70 were affected by headache not elsewhere classified (NEC) in ICHD-II. By using a semi-structured questionnaire, the prevalence of osmophobia was 26.9%, significantly higher in M than TTH patients (34.6% vs 14.3%). RESULTS: Osmophobia was correlated with: (i) family history of M and osmophobia; and (ii) other accompanying symptoms of M. By applying these 'new' criteria, we found an agreement with the current criteria for the diagnosis of migraine without aura (MO) in 96.2% of cases; 54.3% of previously unclassifiable patients received a 'new' diagnosis. CONCLUSIONS: In conclusion, this study demonstrates that this new approach, proposed in the Appendix (A1.1), appears easy to apply and should improve the diagnostic standard of ICHD-II in young patients too.

Levetiracetam monotherapy for childhood occipital epilepsy of gastaut.

OBJECTIVES: The aim of this open label pilot study was to evaluate the efficacy and tolerability of levetiracetam (LEV) as 'de novo' monotherapy in children and adolescents with late onset childhood occipital epilepsy-Gastaut type (COE-G). MATERIAL AND METHODS: Twelve patients suffering from COE-G were enrolled in this prospective study. The age of seizures onset ranged from 6.1 to 16.2 years with a peak of frequency at mean (+/-SD) 10.54 +/- 2.77 years. Therapy with LEV was started at 10 mg/kg/day and, after titration, the final dose was generally achieved within 4 weeks and ranged from 20.7 to 45.2 mg/kg/day. RESULTS: At the 6 month evaluation, 11 (91.6%) of the 12 patients studied were seizure free, and one (8.3%) showed four additional episodes. Electroencephalography (EEG) activity was normal in six (54.5%) patients, unchanged in two (18.1%) children, and in four (33.3%) patients sporadic occipital abnormalities persisted. At the 12-month evaluation all patients were completely seizure free. Four patients (33.3%) continued to show some EEG abnormalities, while eight (72.8%) patients had normal EEG. At the 18-month evaluation all patients were seizure free and 10 patients (83.3%) showed a complete normalization of EEG abnormalities. DISCUSSION: Monotherapy with LEV was effective and well tolerated in patients with COE-G. Nevertheless, prospective, large, long-term double-blind studies are needed to confirm these findings.

Infantile spasms in Down syndrome--effects of delayed anticonvulsive treatment.

To investigate the impact of treatment lag in infantile spasms (IS) on treatment response, occurrence of later epilepsy, and long-term cognition and behavior in patients with one single etiological entity, we examined 18 patients with Down syndrome (DS) and earlier IS retrospectively (follow-up period of 32-180 months with a mean of 85.1 months), and determined their history and present condition, in terms of previously mentioned items. There was a statistically significant correlation between treatment lag and lag to cessation of spasms (R=0.55, P=0.02), developmental quotient (DQ) (R=-0.75, P=0.003), and score of autistic features (AF) (R=0.57, P=0.04). Moreover we found that the later the response to treatment of IS, the lower was the DQ (R=-0.86, P=0.001) and the higher was the score of autistic features (R=0.5, P=0.06). A long duration of spasms also determined a low DQ (R=-0.93, P<0.0001) and a high score of autistic features (R=0.66, P<0.01). All patients with persistent epilepsy (n=5) had had a treatment lag of over 2 months. Conversely, for all children treated within 2 months (n=8) spasms ceased within 3 months of treatment and none of them had later epilepsy. This group of patients with a treatment lag of less than 2 months had earlier treatment response (P=0.002), higher DQ (P=0.004) and lower score of autistic features (P=0.006). The data stress the importance of a short treatment lag in view of mental development and prevention of later epilepsy and autistic features, and raise the question of antiepileptogenic effect in this specific condition.

Spectral analysis of visual potentials evoked by pattern-reversal checkerboard in juvenile patients with headache.

Changes in visual evoked potentials, mainly affecting the amplitude of the major positive wave, are referred to by many authors and are related to the pathophysiological basis of primary headache. We performed both transient pattern-reversal visual evoked potentials and spectral analysis by means of fast Fourier transform of 8-Hz steady-state pattern-reversal visual evoked potentials in 34 children affected with migraine (14 with aura, 20 without aura), and compared them with 14 patients with tension-type headache and 10 healthy subjects. The amplitude of the response to the transient stimulation (P100) was higher and the latency shorter in the patients with headache compared with the controls, but the difference was not statistically significant. The absolute power of the first harmonic (1F) obtained by the spectral analysis of the steady-state stimulation was increased in all the patients with headache compared with the controls, and the increase was significant in patients with migraine. These data seem to confirm the hypothesis of abnormal processing of visual input in migraineurs and could be interpreted as neurophysiological support for the theory that different headache types are related conditions. Furthermore, the spectral analysis of steady-state pattern-reversal visual evoked potentials could be proposed as a test to diagnose migraine.

[Hemicrania and photosensitive epilepsy in pediatric age]. / Emicrania ed epilessia fotosensibile in età pediatrica.

OBJECTIVE: Photosensitive epilepsy is joined to headache. Aim of the present study was the follow up of children suffering from headaches in order to verify if headache can be the only symptom of epileptic photosensitivity. PATIENTS AND METHODS: Thirteen children affected by headache were examined. They were screened on the basis of photosensitivity showed on the EEG. During following 6 patients had seizures. RESULTS: Antiepileptic drugs (VPA, CBZ, CZM) improved seizures and headache. In the others patients migraine therapy improved epileptic photosensitivity on the EEG. CONCLUSIONS: Headache can be the only symptom of epileptic photosensitivity. Migraine and photosensitive epilepsy in childhood are of particular interest because of growing features of occipital lobe. This has therapeutic significance.

Visual evoked potentials and serum magnesium levels in juvenile migraine patients.

Changes in visual evoked potentials and decreased intracellular magnesium levels have been separately described in patients affected by migraine both during the attacks and in the interictal periods. An inverse correlation between increased P100 amplitude and lowered serum magnesium levels was found in children suffering from migraine with and without aura in a headache-free period. A 20-day treatment with oral magnesium pidolate seemed to normalize the magnesium balance in 90% of patients. After treatment, the reduced P100 amplitude confirmed the inverse correlation with the serum magnesium level. These data seem to suggest the hypothesis that higher visual evoked potential amplitude and low brain magnesium level can both be an expression of neuronal hyperexcitability of the visual pathways related to a lowered threshold for migraine attacks.

Platelet responsiveness in migrainous children during headache-free period.

Results of this study confirm the link between migraine and alterations of platelet responsiveness. Our data suggest that in migraineurs the perturbated platelet microviscosity, analyzed by means of fluorescence polarization, appears responsible for the decrease of stimulation-induced influx of external calcium through the platelet membrane. These findings suggest that platelet membrane microviscosity may be considered as a more significant platelet marker of migraine rather than the well-known and nonspecific phenomenon of platelet hyperaggregation, evaluated by time-transmittance variations induced by adenosine diphosphate and collagen.

Influence of a selective 5HT1-receptor agonist GR43175 on platelet responsiveness.

The possible interaction of sumatriptan, a selective 5HT1-receptor agonist, with platelet responsiveness has been investigated. Stimulation of platelet rich plasma with sumatriptan (1-100 microM) did not induce shape change, aggregation or modification of intraplatelet cytosolic calcium levels. Total inhibition of aggregation induced by 20 microM 5HT was observed in platelets preincubated for 20 min with 100 microM sumatriptan. In the same model, platelet stimulation with 4 microM adenosine 5'-diphosphate (ADP), concentration known to induce an irreversible single-phase curve, determined a decrease of aggregatory response. Concentrations from 1 microM to 50 microM of sumatriptan did not influence the aggregatory response induced by 5HT and ADP. These effects appear not to be determined by modifications of platelet calcium homeostasis. The possibility to modulate platelet responsiveness by sumatriptan offers a further approach for evaluating the probable link between platelet behaviour and pathophysiology of migraine.

Rheological features of erythrocytes in acute myocardial infarction.

There is evidence that oxidative insult plays a role in the development of acute myocardial infarction. Significance has also been attributed to changes in viscosity of the blood and in the deformability and aggregation of erythrocytes affecting their rheological behavior. In a group of patients with myocardial infarction we found a decreased erythrocyte filtration and an increased blood viscosity with no significant change in plasma viscosity. These changes were accompanied by alterations in the microviscosity of the erythrocyte membrane assessed by measuring the polarization of specific fluorescent molecules. From our data it is evident that there is an increase in the rigidity of the membrane at the lipid/protein boundary, with an associated increase in the fluidity of the deep lipid core of the membrane, while no changes were observed in the dynamic behavior of the membrane proteins. These physico-chemical perturbations in the membrane could be the basis for the decreased filtration of erythrocytes. We found, however, no evidence of lipid peroxidation in the erythrocyte membrane.

Erythrocyte membrane fluidity in subjects affected with reversible ischemic attacks (RIA).

It is well recognized that in subjects with cerebrovascular disease (CVD), changes in hemorheological properties may occur in about 50% of the patients. This paper concerns a study on microhemorheological perturbations of the erythrocyte membranes in a group of 20 RIA's patients, treated with Pentoxifylline. At the admission of the subjects to the study a trend to an increased whole blood viscosity and erythrocyte aggregation was associated to alterations of membrane fluidity analyzed by means of the fluorescent probes in the patients with respect to the controls. At the end of pharmacological treatment and wash-out, our data indicate a clear modification in erythrocyte membrane which results improved. Our results underline how the improvement of the erythrocyte membrane fluidity, induced by pentoxifylline, is a basic factor of blood flow in the microcirculation.

Effect of exogenous hydrogen peroxide on human erythrocytes.

Circulating erythrocytes are drastically susceptible to peroxidative reactions. To examine the extent of the damage induced by exogenous H2O2 we limited the catalase activity in order to study the extent of lysis, the lipid peroxidation and namely the behaviour of membrane micro-viscosity. Our data showed that the erythrocytes can efficiently scavenge exogenous H2O2 without significant damage of the cells and/or their membranes. These findings could confirm the important role of the erythrocytes as extracellular-antioxidant defense.

In vitro and in vivo effects of erythrocyte phototherapy on newborns.

The photodynamic action of the bilirubin is associated with severe consequences observed during 'in vitro' irradiation of the erythrocytes. This paper is designed to evaluate the bilirubin photodynamic effects which occur 'in vitro' and 'in vivo' on erythrocytes in healthy and jaundiced infants. The in vitro bilirubin sensitized photoreaction damages the erythrocytes mainly at the membrane level. In particular, a dramatic decrease of ATPase activity and an increased susceptibility to lipid peroxidation, expressed as malondialdehyde production, were observed. For in vivo studies, specific fluorescent probes have been used to verify probable changes on the functional architecture of the erythrocyte membrane in the phototherapy-treated infants. Our results showed that specific areas of the membrane are differently affected, mainly at lipid/protein interface. Although the role of the erythrocyte membrane is an important factor of the hemorheological behavior, the measurement of blood viscosity and erythrocyte aggregation and filtration did not show significant alterations during the overall time of phototherapy.

Fluorescence studies of the aged erythrocyte membranes.

The most important purpose of this research is to characterize by means of fluorescence polarization the structural and functional changes which occur in the membrane of the human erythrocytes during aging process. Our results provide evidence of a significant increase of membrane fluidity in the deep lipid core and in the lipid/protein boundary, in the aged erythrocytes. These features are associated with a rigidity of the membrane surface, as revealed by the anisotropy increase of a specific probe suitable for monitoring the membrane protein behaviour. These modifications could be considered as one of the mechanisms which contribute to alter erythrocyte rheological properties sufficiently to be recognised and removed within circulation.