Polymorphisms of the SCN1A gene in children and adolescents with primary headache and idiopathic or cryptogenic epilepsy: is there a linkage?

The purpose of this study was to evaluate the distribution of the polymorphisms of the SCN1A gene in a series of children and adolescents with primary headache and idiopathic or cryptogenic epilepsy compared to controls. Five non-synonymous exonic polymorphisms (1748A > T, 2656T > C, 3199A > G, 5771G > A, 5864T > C) of the SCN1A gene were selected and their genotyping was performed, by high resolution melting (HRM), in 49 cases and 100 controls. We found that among the five polymorphisms, only 3199A > G was a true polymorphism. We did not find a statistically significant difference between distribution of 3199A > G genotypes between cases and controls. We excluded the role of the SCN1A gene in the pathogenesis of comorbidity between headache (especially migraine) and epilepsy. The SCN1A gene is a major gene in different epilepsies and epilepsy syndromes; the HRM could be the new methodology, more rapid and efficacious, for molecular analysis of the SCN1A gene

Psychological and behavioral disease during developmental age: the importance of the alliance with parents

The aim of the study is to analyze the clinician’s alliance with parents during the diagnostic process in relation to therapeutic compliance and clinical evolution of individuals aged 0–11 years. The sample was formed by 84 individuals aged 0 to 11 years (18 < 6 years, 66 aged 6 to 11 years; 62 males and 22 females) who came to the Neuropsychiatric Unit for Children and Adolescents for a consultation regarding psychorelational and behavioral problems. Neuropsychiatric consultation took place in five diagnostic interviews with child and parents, separately. The last session was devoted to communication of psychiatric diagnosis (according to ICD 10) and therapeutic suggestions, if any. The clinician’s relationship with parents and patients’ participation were evaluated in terms of collaboration and quality of interaction, on the basis of pre-established criteria. Data about patients’ therapeutic compliance and clinical outcome were collected during a follow-up visit eight months after the last session. Results suggest that the better the alliance between parents and clinician, the higher the therapeutic compliance and the likelihood of a positive outcome for patients. Our data suggest that good communication with parents benefits child patients, both in terms of response to the parents’ need to report their children’s worrying behavior and as a response to the discomfort expressed by children when they come in for consultation

Efficacy and safety of ketamine for neonatal refractory status epilepticus: case report and systematic review

BackgroundEvidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of neonatal SE and to assess its possible role in the treatment of neonatal SE.MethodsWe described a novel case and conducted a systematic literature review on neonatal SE treated with ketamine. The search was carried out in Pubmed, Cochrane, Clinical Trial Gov, Scopus and Web of Science.ResultsSeven published cases of neonatal SE treated with ketamine were identified and analyzed together with our novel case. Seizures typically presented during the first 24 h of life (6/8). Seizures were resistant to a mean of five antiseizure medications. Ketamine, a NMDA receptor antagonist, appeared to be safe and effective in all neonates treated. Neurologic sequelae including hypotonia and spasticity were reported for 4/5 of the surviving children (5/8). 3/5 of them were seizure free at 1–17 months of life.DiscussionNeonatal brain is more susceptible to seizures due to a shift towards increased excitation because of a paradoxical excitatory effect of GABA, a greater density of NMDA receptors and higher extracellular concentrations of glutamate. Status epilepticus and neonatal encephalopathy could further enhance these mechanisms, providing a rationale for the use of ketamine in this setting.ConclusionsKetamine in the treatment of neonatal SE showed a promising efficacy and safety profile. However, further in-depth studies and clinical trials on larger populations are needed

Alexithymia in juvenile primary headache sufferers: a pilot study

Starting in the 1990s, there has been accumulating evidence of alexithymic characteristics in adult patients with primary headache. Little research has been conducted, however, on the relationship between alexithymia and primary headache in developmental age. In their research on alexithymia in the formative years, the authors identified one of the most promising prospects for research, as discussed here. The aim of this study was to verify whether there is: (a) a link between tension-type headache and alexithymia in childhood and early adolescence; and (b) a correlation between alexithymia in children/preadolescents and their mothers. This study was based on an experimental group of 32 patients (26 females and 6 males, aged from 8 to 15 years, mean 11.2 ± 2.0) suffering from tension-type headache and 32 control subjects (26 females and 6 males, aged from 8 to 15 years, mean 11.8 ± 1.6). Tension-type headache was diagnosed by applying the International Headache Classification (ICHD-II, 2004). The alexithymic construct was measured using an Italian version of the Alexithymia Questionnaire for Children in the case of the juvenile patients and the Toronto Alexithymia Scale (TAS-20) for their mothers. Higher rates of alexithymia were observed in the children/preadolescents in the experimental group (EG) than in the control group; in the EG there was no significant correlation between the alexithymia rates in the children/preadolescents and in their mothers

Genomics and premalignant breast lesions: clues to the development and progression of lobular breast cancer

Advances in genomic technology have improved our understanding of the genetic events that parallel breast cancer development. Because almost all mammary carcinomas develop in the terminal duct lobular units of the breast, understanding the events involved in mammary gland development make it possible to recognize those events that, when altered, contribute to breast neoplasia. In this review we focus on lobular carcinomas, discussing the pathology, development, and progression of premalignant lobular lesions from a genomic point of view. We highlight studies utilizing genomic approaches and describe how these investigations have furthered our understanding of the complexity of premalignant breast lesions

COMORBIDIÀ TRA CEFALEA ED EPILESSIA IN ETÀ EVOLUTIVA: ASPETTI CLINICI E ANALISI MOLECOLARE DEL GENE SCN1A

SUMMARY Migraine and epilepsy are both common neurological disorders and can occur as comorbid conditions. The pathogenesis of the common forms of migraine is not completely understood, while many epilepsy syndromes have been pathogenetically linked to channellopaties. A particular migraine form, the familial hemiplegic migraine, is also due to mutations in genes encoding ion channels and is often associated to epileptic seizures. The purpose of this study was to analyse in a large series of children and adolescents with headache (1795 subjects) the comorbidity between primary headache and idiopathic or cryptogenic epilepsy and to evaluate the role of the SCN1A gene in cases with comorbidity. Among the 1795 headache sufferers, there were 1775 subjects diagnosed as primary headache (957 migraine, 686 tension-type headache, 132 other primary headaches) and 20 subjects diagnosed as secondary headache. Fifty-six subjects having comorbidity were selected. The prevalence idiopathic or cryptogenic epilepsy or unprovoked seizures was 3.1% (56/1795) in headache sufferers and 4.8% (46/957) in migraineurs. In subjects with comorbidity, the risk of epilepsy was 3.2-times higher in migraineurs (46/56) compared to tension-type headache sufferers (10/56), without a significant difference between migraine with and without aura (p=0.89); subjects with epilepsy had a 4.5-fold increased risk of developing migraine than tension-type headache. In cases with comorbidity, focal epilepsies prevailed (43/56, 76.8%). Migraineurs affected by focal epilepsies (36/56) had a 3-times higher risk of having a cryptogenic epilepsy (27/36, 75%) than an idiopathic epilepsy (9/36, 25%) (p=0.003). In migraine with aura, epilepsy preceded migraine in 71% of cases, thus excluding a causative role for migraine with aura in epilepsy. In cases with comorbidity, migraineurs did not have a major risk of post-ictal headache compared to tension-type headache sufferers (p=0.58). Post-ictal headache prevailed in subjects affected by cryptogenic temporo-occipital epilepsy (11/18, 61%) than the other types of epilepsy. Photosensitivity (7/56, 12.5%) and positive family history for epilepsy (22/56, 39%) were frequent in cases with comorbidity. In our series nobody experienced episodes of migralepsy or ictal epileptic headache. In conclusions comorbidity between headache and epilepsy is common in children and adolescents and our results confirm a strong association between migraine and epilepsy, without significant difference between migraine with and without aura. Migraine is associated with higher rates of focal epilepsies, in particular cryptogenic epilepsies. The analysis of the clinical relationship between headache (especially migraine) and epilepsy could contribute to understanding the pathogenetic mechanisms of these two conditions, mainly when they are comorbid. Further studies, based on the present diagnostic criteria of both disorders are needed. To the best of our knowledge, this is the first study that evaluated the association between polymorphisms of the SCN1A gene and comorbidity between primary headache (especially migraine) and epilepsy. Five non-synonymous exonic polymorphisms (c.1748A>T of exon 11; c.2656T>C of exon 15; c.3199A>G of exon 16; c.5771G>A of exon 26; c.5864T>C of exon 26) of the SCN1A gene were selected. The single nucleotide polymorphisms (SNPs) genotyping was performed in 49 patients with comorbidity and 100 healthy non migraineurs controls by using a new tecnique, the High Resolution Melting (HRM). Among the five SNPs analyzed, only c.3199A>G of exon 16 was confirmed to be a polymorphism while the other 4 SNPs were not true polymorphisms, because they were not found in the 298 alleles (cases and controls) examined and are not to be further investigated. We didn’t find a statistically significant difference between distribution of c.3199A>G of exon 16 genotypes between cases and controls; therefore our results confirm that the polymorphism c.3199A>G of exon 16 is not associated to pathological phenotypes in headache sufferers and in migraineurs, similarly to that found in other studies conducted on patients with epilepsy. We exclude the role of the SCN1A gene in the pathogenesis of comorbidity between headache (especially migraine) and epilepsy. The SCN1A gene is a major gene in different epilepsies and epilepsy syndromes, and in this field it has to be further investigated. The HRM could be the new methodology, more rapid and efficacious, for molecular analysis of the SCN1A gene. The development of protocols for more efficient and reliable molecular diagnostics would allow a wider appreciation of the role of the SCN1A gene and of other genes encoding for ion channels in different epilepsies and epilepsy syndromes.SOMMARIO L’emicrania e l'epilessia sono disordini neurologici frequenti e possono essere presenti in comorbidità. La patogenesi delle forme comuni di emicrania non è del tutto chiarita, mentre in diverse sindromi epilettiche è noto il ruolo fisiopatologico delle canalopatie. Anche una particolare forma di emicrania, l'emicrania emiplegica familiare, è dovuta a mutazioni di geni codificanti per canali ionici ed è spesso associata a crisi epilettiche. Lo scopo di questo studio è di analizzare, in un'ampia casistica di bambini e adolescenti cefalalgici (1795 soggetti), la comorbidità tra cefalea primaria ed epilessia idiopatica o criptogenetica e di valutare il ruolo del gene SCN1A nei soggetti con comorbidità. Tra i 1795 cefalalgici analizzati, vi erano 1775 soggetti con diagnosi di cefalea primaria (957 emicrania, 686 cefalea tensiva, 132 altre cefalee primarie) e 20 soggetti con diagnosi di cefalea secondaria. Sono stati individuati 56 soggetti con comorbidità. La prevalenza di epilessia idiopatica o criptogenetica o crisi epilettiche isolate è risultata del 3,1% (56/1795) nei cefalalgici e del 4,8% (46/957) negli emicranici. Nei soggetti con comorbidità, il rischio di epilessia era 3,2 volte superiore negli emicranici (46/56) rispetto ai soggetti con cefalea tensiva (10/56), senza differenze significative tra emicrania con e senza aura (p=0.89); i soggetti con epilessia avevano un rischio 4,5 volte maggiore di presentare emicrania rispetto alla cefalea tensiva. Nei casi con comorbidità, erano prevalenti le epilessie focali (43/56, 76,8%). Gli emicranici affetti da epilessie focali (36/56) avevano un rischio 3 volte superiore di presentare un’epilessia criptogenetica (27/36, 75%) rispetto ad un’epilessia idiopatica (9/36, 25%) (p = 0.003). Nell’emicrania con aura, l'esordio dell’epilessia precedeva quello dell’emicrania nel 71% dei casi, escludendo pertanto un ruolo causale dell’emicrania con aura nell’epilessia. Nei casi con comorbidità, gli emicranici non avevano un rischio aumentato di cefalea post-critica rispetto ai soggetti con cefalea tensiva (p=0.58). La cefalea post-critica era più frequente nei soggetti con epilessia temporo-occipitale criptogenetica (11/18, 61%) rispetto agli altri tipi di epilessia. La fotosensibilità (7/56, 12,5%) e la storia familiare positiva per epilessia (22/56, 39%) sono stati frequentemente riscontrati nei casi con comorbidità. Nessuno dei soggetti con comorbidità ha presentato migralepsy o cefalea ictale epilettica. In conclusione la comorbidità tra cefalea ed epilessia è frequente nei bambini e adolescenti e i nostri risultati confermano che vi è una forte associazione tra emicrania ed epilessia, senza differenze significative tra emicrania con e senza aura. L'emicrania è associata ad una maggiore prevalenza di epilessie focali, in particolare criptogenetiche. L'analisi della relazione clinica tra la cefalea (in particolare emicrania) e l'epilessia potrebbe contribuire alla comprensione dei meccanismi patogenetici di queste due condizioni, soprattutto quando presenti in comorbidità. Sono necessari ulteriori studi, basati sugli attuali criteri diagnostici di entrambi i disturbi. A nostra conoscenza, questo è il primo studio che ha valutato l'associazione tra i polimorfismi del gene SCN1A e la comorbidità tra cefalea primaria (in particolare l'emicrania) ed epilessia. Sono stati selezionati cinque polimorfismi esonici non sinonimi (c.1748A>T dell’esone 11; c.2656T>C dell’esone 15; c.3199A>G dell’esone 16; c.5771G> A dell'esone 26; c.5864T> C dell’esone 26) del gene SCN1A. La genotipizzazione dei polimorfismi a singolo nucleotide (SNPs) è stata effettuata in 49 pazienti con comorbidità e 100 controlli sani non emicranici utilizzando una tecnica nuova, l’High Resolution Melting (HRM). Dei cinque SNPs analizzati, solo il c.3199A> G dell’esone 16 è stato confermato come polimorfismo, mentre gli altri 4 SNPs non sono veri polimorfismi perché non sono stati trovati in nessuno dei 298 alleli (tra casi e controlli) esaminati, e pertanto non meritano di essere ulteriormente indagati. Non abbiamo trovato una differenza statisticamente significativa nella distribuzione dei genotipi del polimorfismo c.3199A>G dell’esone 16 tra casi e controlli; quindi i nostri risultati confermano che il polimorfismo c.3199A>G dell’esone 16 non è associato a fenotipi patologici nei soggetti con cefalea ed emicrania, analogamente a quanto riscontrato in altri lavori condotti su soggetti affetti da epilessia. Viene escluso un ruolo del gene SCN1A nella patogenesi della comorbidità tra cefalea primaria (in particolare l'emicrania) ed epilessia. Il gene SCN1A è un gene di primaria importanza nella patogenesi di diverse epilessie e sindromi epilettiche, e in questo campo deve essere ulteriormente indagato. L’analisi HRM potrebbe essere la nuova metodologia, più rapida ed efficace, per l'analisi molecolare del gene SCN1A. Lo sviluppo di protocolli diagnostica molecolare più efficienti e affidabili potrebbe consentire una più ampia valutazione del ruolo del gene SCN1A e di altri geni codificanti per canali ionici nelle diverse epilessie e sindromi epilettiche