Thomas Foiadelli

Omalizumab in Children

Omalizumab is a recombinant humanized monoclonal antibody that reduces levels of circulating immunoglobulin E (IgE) and expression of IgE high-affinity receptors on mast cells and basophils, interrupting the subsequent allergic inflammatory cascade. Current indications for treatment with omalizumab in pediatric patients are clearly defined and are confined to moderate-to-severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU). Any other prescription can only be off label. Data available from clinical trials conducted in children suggest that omalizumab is clinically effective and generally well tolerated. Given its mechanism of action, recent reports have suggested its possible clinical use in other IgE-mediated disorders, such as allergic rhinitis, food allergy, and anaphylaxis. In recent years, several studies have also investigated the possible applications of omalizumab in a number of non IgE-mediated diseases. The aim of the present review is to assess all applications of omalizumab as therapy in the pediatric population. The approved indications—allergic asthma and CSU—are reviewed. Moreover, further potential applications of omalizumab are discussed in both IgE-mediated and non-IgE-mediated diseases.

Epilepsy in patients with Cornelia de Lange syndrome: A clinical series

PURPOSE Cornelia de Lange (CdLS) syndrome is characterized by multiple congenital anomalies and mental retardation. Epilepsy is a clinical feature found in about 20% of cases, but there are no data about its electroclinical features and long-term outcome. METHODS we describe a clinical series of fourteen Caucasian CdLS paediatric patients who developed epilepsy, with special reference to the long term prognosis. RESULTS Epilepsy manifested between age 0.6 and 16.3 years. The majority of patients (64.3%) presented with partial seizures and interictal EEGs mainly revealed focal epileptic paroxysms involving temporal and parietal areas. Thirteen of 14 children became seizure-free with treatment. Valproate monotherapy was used in eight patients (57.1%), controlling seizures in seven. Otherwise monotherapy with topiramate, levetiracetam, carbamazepine and oxcarbazepine appeared to be effective in controlling seizures in four cases. At the end of the follow-up (age range, 7.3-24.2 years; follow-up, 8.2±3.9 years), thirteen patients were seizure free (three still in therapy), while in one patient seizures were not controlled. CONCLUSIONS Partial epilepsy is the most common type of epilepsy in CdLS patients. In the majority of cases the prognosis of this epilepsy is favourable and therapy can be withdrawn after few years of complete seizure control.

Stickler syndrome associated with epilepsy: report of three cases

AbstractStickler syndrome is a genetically heterogeneous collagenopathy characterized by auditory, ocular, musculoskeletal, and orofacial abnormalities. Stickler syndrome type 1 typically presents ophthalmologic involvement and is due to heterozygous defects of the COL2A1 gene, that have been also identified as the molecular cause of a continuous spectrum of different disorders mainly affecting the cartilage and bone (i.e., Kniest dysplasia, achondrogenesis type II, Legg-Calvè-Perthes disease). We report three Caucasian children with: (a) ocular, oral, facial, auditory, and musculoskeletal manifestations of Stickler syndrome type 1; (b) history of generalized and/or partial seizures coupled with abnormal electroencephalographic records; and (c) pathogenic heterozygous mutations of the COL2A1 gene. Epilepsy has been never reported so far in literature as a possible feature of Stickler syndrome, although neurological presentations, including epilepsy and brain abnormalities, have been occasionally described in other COL2A1-related phenotypes (e.g., Legg-Calvè-Perthes disease). Conclusions: This report raises the possibility of a potential occurrence of seizures among the clinical manifestations of Stickler syndrome type 1, suggesting the presence of a continuous neurological spectrum in some individuals harboring heterozygous mutations in COL2A1.What is Known:• Stickler syndrome is a genetically heterogeneous collagenopathy characterized by auditory, ocular, musculoskeletal, and orofacial anomalies.What is New:• Involvement of the nervous central system is not a typical feature of Stickler syndrome and the association with epilepsy has not been reported so far.• This report raises the possibility of a potential occurrence of seizures among the clinical manifestations of Stickler syndrome type 1, suggesting a continuous neurological spectrum in some individuals affected by heterozygous mutations of COL2A1.

Unilateral periventricular heterotopia and epilepsy in a girl with Ehlers–Danlos syndrome

Purpose Ehlers–Danlos syndrome (EDS), comprising a variety of inherited connective tissue disorders, has already been described in association with various neurological features, particularly with epilepsy and periventricular heterotopia (PH). Until now, there are reports of only bilateral periventricular heterotopia associated with Ehlers–Danlos syndrome. Methods and results Here we describe a 1-year, 4-month-old female who came under our care in the Pediatric Emergency Room because of prolonged afebrile generalized seizures, whose clinical picture allowed us to suspect a diagnosis of Ehlers–Danlos syndrome. Neuroradiological investigations showed unilateral periventricular heterotopias, and genetic analyses confirmed the hypothesized diagnosis, identifying in particular a mutation in the COL5A1 gene. After starting anticonvulsant therapy, her seizures showed a good response with seizure control and she had a favorable long-term course. Conclusion To our knowledge, this is the first report of unilateral periventricular heterotopia associated with Ehlers–Danlos syndrome. We first hypothesized a mosaicism as the cause of both, a unilateral localization of the heterotopias and a favorable long-term course with good response to anticonvulsant therapy; however, intriguingly, we could not demonstrate a mosaicism as the genetic condition in our patient and the neuroradiological findings and the favorable clinical outcome still remain unexplained.

Long‐term prognosis of patients with Ehlers‐Danlos syndrome and epilepsy

Epilepsy in Ehlers‐Danlos syndrome (EDS) has been reported in the literature, but there are no studies that have investigated in detail clinical and electroencephalography (EEG) features in patients with EDS, and that have compared the outcome of epilepsy in subjects with or without brain lesions. We report a series of 42 patients with EDS and epilepsy, including data that concern clinical characteristics, EEG abnormalities, brain malformations at magnetic resonance imaging (MRI) and long‐term outcome.

P93 – 2953: Identification of a new mutation of the SCL1A gene in a patient with GLUT1-DS

Objective Diagnostic assessment of a boy of 13 years old. From the age of 16 months, he has showed an isolated oculomotor disorder associated with a delay in acquisition of psychomotor milestones. Furthermore, at 4 years old, he presented absence-like seizures, for whom he has been favourably treated with valproic acid. After 9 years of wellness, when antiepileptic drug was stopped, an effort-related paroxysmal myoclonic dystonia appeared, involving mostly lower limbs. Such episodes have rapidly increased in frequency, becoming truly debilitating for the patient. Methods Suspecting a deficit of the enzyme GLUT1, the patient underwent lumbar puncture, video-EEG and molecular genetic analysis. Physical-chemical analysis of CSF demonstrated a glycorrhachia of 45 mg/dL, lactate at the lower limit of the normal range and a CSF/serum glucose ratio of 0.52. Video-EEG excluded epileptic paroxysms. Results The molecular investigation revealed a point mutation not previously described in literature (c.1199G>A; exon 9 – gene SLC2A1); this mutation was absent in parental alleles and thus it was originated de novo. Conclusion After diagnosis, the patient restarted therapy with valproic acid and began to follow strictly ketogenic diet, getting a complete and persistent clinical remission. In conclusion, this report of a GLUT1-DS case is characterized by an unusual presentation and the description of a new causative mutation. More interestingly, it proves the importance of CSF analysis to potentially reveal treatable diseases in children with undiagnosed movement disorders.

Convulsioni Neonatali Benigne Familiari da mutazione di KCNQ2

Le Convulsioni Neonatali Benigne Familiari sono un raro disordine convulsivo ad ereditarieta AD che si manifesta entro la seconda settimana di vita. Ad oggi sono stati identificati 2 geni responsabili: KCNQ2 e KCNQ3. Riportiamo il caso di F.G., ricoverata per convulsioni neonatali insorte in terza giornata di vita, refrattarie alla terapia antiepilettica. Nella storia clinica del padre emergeva identica sintomatologia (fino al 25° giorno di vita); inoltre, due cugine paterne risultavano affette da differenti disordini comiziali. Anche nel caso di F.G. si verificava una completa risoluzione delle manifestazioni comiziali al compimento del 25° giorno di vita. Ad oggi la bambina (6 mesi di vita) presenta un normale sviluppo psico-motorio. L’analisi genetica Next Generation Sequencing ha potuto evidenziare nella bambina e nel padre una mutazione del gene KCNQ2, a livello dell’esone 5: C.769del. Tale mutazione comporta un frameshift della sequenza codificante con STOP codon prematuro 15 codoni a valle.

Vocal cord dysfunction nel bambino

La vocal cord dysfunction (VCD) e una paradossa adduzione delle corde vocali che si verifica durante l’inspirazione, con conseguenti sintomi di dispnea, respiro sibilante, senso di oppressione al torace o alla gola e tosse. Essendo poco conosciuta, questa condizione viene spesso confusa con l’asma con conseguente utilizzo di trattamento anti-asmatico inefficace. La dimostrazione laringoscopica di adduzione delle corde vocali durante l’inspirazione e considerata il gold standard per la diagnosi di VCD. La logopedia e/o la fisioterapia respiratoria sono spesso utili in questo disturbo. Riportiamo il caso di un ragazzo di 12 anni con persistenti spasmi laringei, giunto alla nostra attenzione dopo diverse visite mediche senza diagnosi. Abbiamo diagnosticato la vocal cord dysfunction associata ad ipotiroidismo autoimmune e ad infezione da Bordetella pertussis, con risoluzione del caso a seguito del trattamento specifico.

Scompenso cardiaco acuto: un caso clinico pediatrico

La crisi ipertensiva e una condizione clinica acuta caratterizzata da un rapido incremento della pressione arteriosa. Puo essere distinta in urgenza ipertensiva ed emergenza ipertensiva. In eta pediatrica la crisi ipertensiva e un evento raro ma potenzialmente fatale, di solito di origine secondaria a patologie sottostanti. La strategia terapeutica prevede l’impiego di farmaci per via parenterale ed enterale con l’obiettivo di ridurre la pressione arteriosa in modo tempestivo per evitare il danno d’organo e graduale per preservare l’autoregolazione dei vasi cerebrali. Il caso clinico descrive una crisi ipertensiva in un bambino di 20 mesi giunto all’attenzione del pronto soccorso Pediatrico per vomito e dispnea. Per il progressivo rapido peggioramento delle condizioni cliniche il bambino e stato trasferito presso il reparto di Rianimazione dove e stato stabilizzato. Il controllo pressorio si e ottenuto con difficolta e la causa eziologica della crisi ipertensiva e stata raggiunta per esclusione di tutte le possibile cause di ipertensione in eta pediatrica. Il Pediatra deve porre molta attenzione alla clinica, correlando segni e sintomi aspecifici e comuni per riconoscere tempestivamente una causa di scompenso cardiocircolatorio per poter intervenire evitando possibili danni irreversibili.

Complessità assistenziali in un nuovo caso di S. di Leigh con mutazione NARP

La Sindrome di Leigh (LS), o encefalopatia necrotizzante subacuta, e una patologia neurodegenerativa con esordio precoce e prognosi grave. La sindrome e determinata da un difetto funzionale riguardante i complessi della catena respiratoria ed e geneticamente eterogenea. L’esordio clinico avviene solitamente con un quadro di: difficolta ad alimentarsi, ipotonia, spasmi infantili o sindrome di West, regressione psicomotoria, atassia. La diagnosi e soprattutto clinica ed e fondata sul rilievo di acidosi lattica, lesioni caratteristiche del SNC alla RMN encefalo e difetto biochimico della catena respiratoria. Le difficolta gestionali nei pazienti affetti sono molteplici: riportiamo qui il caso clinico di una paziente di 8 mesi ricoverata presso la nostra Clinica per grave ipotonia e spasmi infantili, focalizzando l’attenzione sull’aspetto assistenziale relativo ai problemi e alle complicanze cliniche tipici della sindrome di Leigh.