GLUT-1 deficiency syndrome: phenotype-genotype correlations.

La sindrome da deficit di GLUT-1 è una encefalopatia metabolica il cui fenotipo classico configura un quadro clinico caratterizzato dalla presenza di: epilessia ad esordio precoce, di solito farmacoresistente, ritardo mentale, microcefalia acquisita e disturbi del movimento. Nel corso degli anni sono stati descritti circa 200 casi, molti dei quali configurano varianti atipiche. Scopo di questo studio è di ricercare mutazioni nel gene SLC2A1 in una popolazione di pazienti affetti da epilessia ad esordio precoce non inquadrabile in una precisa sindrome epilettica associata o meno a ritardo cognitivo e/o disturbi del movimento. Inoltre, nei pazienti mutati, si propone di studiare la correlazione genotipo-fenotipo attraverso un’attenta valutazione clinica, elettroencefalografica e di neuroimaging funzionale. Step successivo è rappresentato dalla valutazione dell’eventuale penetranza incompleta attraverso lo studio dei familiari dei pazienti affetti. Nel nostro studio sono stati selezionati e studiati 98 pazienti, tra questi sono stati identificati 16 soggetti con 4 differenti mutazioni nel gene SLC2A1. Ad oggi, le correlazioni genotipo-fenotipo sono scarse. I risultati del nostro lavoro corrispondono solo in parte con quanto descritto in letteratura, in particolare: sono state identificate tutte mutazioni eterozigoti missense, mai descritte, associate, ad un fenotipo clinico di sindrome da deficit di GLUT-1 talora piuttosto grave e, comunque, sempre correlato con un’ampia variabilità fenotipica tra pazienti con mutazioni differenti ed in pazienti con la stessa mutazione. Stesse deduzioni emergono dai dati PET. In conclusione, sottolineiamo che l’identificazione e la descrizione di nuovi pazienti e famiglie affetti da sindrome da deficit di GLUT-1 e la caratterizzazione del fenotipo, nonché la precisa correlazione dello stesso con il genotipo è di fondamentale importanza per una migliore definizione di questa sindrome epilettica, del suo spettro clinico, delle possibili implicazioni terapeutiche e prognostiche

Hyperhomocysteinemia and retinal vascular changes in patients with epilepsy.

The possible occurrence of asymptomatic retinal vascular damage was investigated in 87 hyperhomocysteinemic (plasma total homocysteine >13micromol/L) adult epileptic patients (46 M, 41 F; age 34.2+/-7.5 years; mean plasma homocysteine levels 29.8+/-15.4micromol/L; duration of epilepsy 11.5+/-2.4 years) with no other risk factors for atherosclerosis. Plasma total homocysteine (t-Hcy) levels were assayed by high performance liquid chromatography. Retina vascular status was assessed by fundus oculi ophthalmoscopy performed in blind conditions by two skilled ophthalmologists and compared with that obtained from 102 randomly chosen epileptic patients and 94 healthy subjects, matched for age and sex, showing normal t-Hcy levels. No retina abnormality was detected in any of the subjects belonging to the three groups. Based on these results, we conclude that epileptic patients with mild to intermediate hyperhomocysteinemia are not at risk to develop retinal vascular disease

A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy

Objective To evaluate direct medical costs and their predictors in patients with refractory epilepsy enrolled into the SOPHIE study (Study of Outcomes of PHarmacoresistance In Epilepsy) in Italy. Methods Adults and children with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers and followed for 18 months. At entry, all subjects underwent a structured interview and a medical examination, and were asked to keep records of diagnostic examinations, laboratory tests, specialist consultations, treatments, hospital admissions, and day-hospital days during follow-up. Study visits included assessments every 6 months of seizure frequency, health-related quality of life (Quality of Life in Epilepsy Inventory 31), medication-related adverse events (Adverse Event Profile) and mood state (Beck Depression Inventory-II). Cost items were priced by applying Italian tariffs. Cost estimates were adjusted to 2013 values. Results Of 1,124 enrolled individuals, 1,040 completed follow-up. Average annual cost per patient was \ue2\u82\uac 4,677. The highest cost was for antiepileptic drug (AED) treatment (50%), followed by hospital admissions (29% of overall costs). AED polytherapy, seizure frequency during follow-up, grade III pharmacoresistance, medical and psychiatric comorbidities, and occurrence of status epilepticus during follow-up were identified as significant predictors of higher costs. Age between 6 and 11 years, and genetic (idiopathic) generalized epilepsies were associated with the lowest costs. Costs showed prominent variation across centers, largely due to differences in the clinical characteristics of cohorts enrolled at each center and the prescribing of second-generation AEDs. Individual outliers associated with high costs related to hospital admissions had a major influence on costs in many centers. Significance Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second-generation AEDs. Epilepsy-specific costs cannot be easily differentiated from costs related to comorbidities