Elisabetta Tozzi

Headache and comorbidity in children and adolescents

Headache is one of the most common neurological symptom reported in childhood and adolescence, leading to high levels of school absences and being associated with several comorbid conditions, particularly in neurological, psychiatric and cardiovascular systems. Neurological and psychiatric disorders, that are associated with migraine, are mainly depression, anxiety disorders, epilepsy and sleep disorders, ADHD and Tourette syndrome. It also has been shown an association with atopic disease and cardiovascular disease, especially ischemic stroke and patent foramen ovale (PFO).

Impact of a weight loss program on migraine in obese adolescents

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.

Levetiracetam in juvenile myoclonic epilepsy: long‐term efficacy in newly diagnosed adolescents

The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in juvenile myoclonic epilepsy (JME). The study group consisted of 32 patients with epilepsy (20 males, 12 females) with a mean age of 13 years 3 months (SD 7y 11mo) at seizure onset. LEV was administered as the first drug; all patients were followed up at 6 and 12 months. The dose that achieved seizure control ranged from 1000 to 2500mg/daily. At 6‐month evaluation: 15 patients were seizure free; 14 patients were responders (>50% reduction in seizures); and three patients had marginal effects (<50% reduction of seizures). At 12‐month evaluation: 29 patients were seizure free; three patients were responders. No patients reported adverse events. These data provide preliminary evidence that LEV may be effective for treating patients with newly diagnosed JME.

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.

Osmophobia as an early marker of migraine: a follow-up study in juvenile patients.

Background: Osmophobia is frequent in children with migraine (20–35%) but can also occur in up to 14% of cases with tension-type headache (TTH). So far, the prognostic role of this symptom in children with primary headaches has never been evaluated. Methods: A longitudinal prospective study was conducted on 90 young patients with TTH (37 with osmophobia, 53 without osmophobia). We evaluated whether osmophobia could predict the diagnosis transformation from TTH to migraine after a 3-year follow-up. Results and Discussion: In our cases the rate of diagnosis change was significantly greater in cases with osmophobia (62%) than in those without (23%). Osmophobia persisted at a 3-year follow-up in the majority of our cases (85%) and it was found to be one of the major predictors for the development of migraine; other predictors of evolution to migraine were phonophobia, a probable rather than certain diagnosis of TTH and olfactory triggers (p < 0.05). Conclusion: Our data confirm that osmophobia has an important diagnostic and prognostic role in children with primary headaches and should be systematically investigated at diagnosis and during follow-up.

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.

Clinical guidelines in pediatric headache: evaluation of quality using the AGREE II instrument

BackgroundThe Appraisal of Guidelines for Research and Evaluation (AGREE II) tool is a validated questionnaire used to assess the methodological quality of clinical guidelines (CGs). We used the AGREE II tool to assess the development process, the methodological quality, and the quality of reporting of available pediatric CGs for the management of headache in children. We also studied the variability in responses related to the characteristics of eleven Italian neuropediatric centers, showing similarities and differences in the main recommendations reported in CGs.MethodsA systematic literature search was conducted from January 2002 to June 2013 on Mediline, the Cochrane database, the National Guideline Clearinghouse website and the NHS evidence search tool, using the following terms: headache, cephalalgia, guidelines and children (MESH or text words). Six CGs providing information on the diagnosis and management of headache and specific recommendations for children were selected. Eleven neuropediatric centers assessed the overall quality and the appropriateness of all available CGs using of the AGREE II instrument.ResultsSix CGs meeting the inclusion and exclusion criteria were identified and assessed by 11 reviewers. Our study showed that the NICE CGs was “strongly recommended” while the French and Danish CGs were mainly “not recommended”. The comparison between the overall quality score of the French CGs and the NICE CGs was statistically significant (6.54 ± 0.69 vs 4.18 ± 1.08; p =0.001). The correlation analysis between quality domain score and guideline publication date showed a statistically significant association only for the “editorial independence” domain (r = 0.842 p = 0.035). The intra-class coefficients showed that the 11 reviewers had the highest agreement for the Lewis CGs (r = 0.857), and the lowest one for the NICE CGs (r = 0.656). Statistical analyses showed that professionals from outpatient services dedicated pediatric headache assigned a higher overall quality score to the NICE CGs as compared to professionals from non-outpatient services (6.86 ± 0.38 vs 6.0 ± 0.82; p = 0.038).ConclusionsCGs resulted definitely of low-moderate quality and non “homogeneous”. Further major efforts are needed to update the existing CGs according to the principles of evidence based medicine.

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).

Epilepsy in the setting of full trisomy 18: A multicenter study on 18 affected children with and without structural brain abnormalities

This paper reports on the clinical aspects, electroencephalographic (EEG) features, and neuroimaging findings in children with full trisomy 18 and associated epilepsy, and compares the evolution and outcome of their neurological phenotype. We retrospectively studied 18 patients (10 males and 8 females; aged 14 months to 9 years) with full trisomy 18 and epilepsy. All patients underwent comprehensive assessment including neuroimaging studies of the brain. We divided patients into two groups according to neuroimaging findings: (Group 1) 10 patients harboring structural brain malformations, and (Group 2) 8 patients with normal brain images. Group 1 had a significantly earlier age at seizure onset (2 months) compared to Group 2 (21 months). The seizure semiology was more severe in Group 1, who presented multiple seizure types, need for polytherapy (80% of patients), multifocal EEG abnormalities and poorer outcome (drug resistant epilepsy in 90% of patients) than Group 2 who presented a single seizure type, generalized or focal, and non‐specific EEG pattern; these patients were successfully treated with monotherapy with good outcome. Imaging revealed a wide and complex spectrum of structural brain abnormalities including anomalies of the commissures, cerebellar malformations, cortical abnormalities, and various degrees of cortical atrophy. Epilepsy in full trisomy 18 may develop during the first months of life and can be associated with structural brain malformations. Patients with brain malformations can show multiple seizure types and can frequently be resistant to therapy with antiepileptic drugs.

Age-dependent changes in human erythrocyte properties

The focus of this paper is mainly directed on the role that the structural and functional perturbations of the erythrocyte membranes could have in the incidence of abnormal microcirculation which occur with the elderly. Rheological parameters of whole blood and the activity of some enzymes involved in erythrocyte metabolism and permeability are studied