Chromosome abnormalities are often associated with epilepsy. In particular, Singh et al.  reported 400 different chromosome aberrations associated with epileptic seizures and/or EEG abnormalities. However, only a few chromosome anomalies have a characteristic electroclinical pattern, such as 1 p36, 4p16, 6q terminal, or 15q13.3 deletions, trisomy 12p, Angelman syndrome (AS), inv dup 15, ring 20, Down syndrome, Xp11.22-11.23 duplication, XYY .
An EEG study was carried out in 26 out of 50 patients with PWS and 10 of them (38.5%) showed abnormalities. In particular, five subjects (with or without seizures) presented high voltage 4–6 Hz EEG activities, four (with generalized tonic-clonic seizures) showed focal paroxysmal discharges, and one (with atypical absences) short generalized discharges of polyspike and wave complexes . In other 4 patients with PWS and epilepsy focal or multifocal paroxysmal abnormalities were described .
In a following series of 10 patients with PWS and epilepsy, nine (90%) revealed EEG abnormalities, but only in two cases these were specified as focal left parietal discharges and nonspecific spikes .
Other three subsequent retrospective studies revealed EEG focal, multifocal or generalized paroxysmal abnormalities, respectively in 13 of 23 (56.5%), 13 of 22 (59%), and 38 of 38 (100%) patients with PWS and epilepsy [6–8]. Furthermore, focal epileptiform abnormalities were found in 12 out of 94 subjects (12.8%) collected from an observational cohort study, and a subclinical electrographic seizure pattern was found in 5 of 12 of these cases .
EEG multifocal or focal abnormalities were found in 19 (25.7%) of our 74 patients, epilepsy in 4 (5.4%). This prevalence rates are almost at the lower end of the prevalence ranges reported in previous literature, 12.8–100% for EEG abnormalities, 4–26% for epilepsy; however, this apparent discrepancy in the prevalence rate could be due to the different settings, as all our patients were recruited in Centers specialized in pediatric and endocrinological management of PWS [3–8, 10–12]. Approximately in one quarter of our PWS patients the EEG picture normalized, a finding that could be not compared with literature, since at the best of our knowledge no EEG follow-up studies were conducted in PWS until now. We did not find statistically significant associations between the presence of interictal EEG paroxysmal abnormalities, and some other clinical, genetic and neuroimaging features of the PWS phenotype. Then, interictal EEG abnormalities – and in particular their middle-posterior localization – could represent an important and supportive neurological feature of PWS, but they do not contribute in providing information about genotype, cognitive or behavior endophenotypes, possible MRI structural anomalies, or prognosis.
Both epilepsy and interictal EEG abnormalities are more frequently found in PWS patients than in general population (3.54%) , but they are much less frequent than in AS (85%) which affects the same chromosomal 15q11-q13 region . There is not yet a convincing evidence for this discordance, but it can be hypothesized that in PWS, although the missing paternal 15q11-q13 region includes the genes for the GABA receptor subunit cluster (GABRB3, GABRA5, and GABRG3) receptor, the maternalUBE3A is active, and this could explain the lower rate of epilepsy in PWS . Another alternative genetic mechanism for pathogenesis of EEG abnormalities or epilepsy could be represented by the involvement of other contiguous genes in the region 15q11-q13.
Although our study seems to confirm that a peculiar interictal EEG pattern does not exist in PWS, and paroxysmal abnormalities are mostly focal or multifocal, approximately in two thirds of our patients spikes were localized over the middle-posterior regions. Then, this localization could represent a rather common EEG trait to be considered as a potential marker of PWS.
Brain MRI abnormalities were relatively frequent (59%) and heterogeneous in our cohort of patients with PWS. More frequently we found enlargement of the lateral ventricles (39.1%) and pituitary hypoplasia (39.1%). Dilation of lateral ventricles, a non-specific finding, has been previously observed in patients with PWS, up to approximately 45% of cases, and it can represent the consequence of loss or reduced growth of white or gray matter or both [6, 8, 11, 12]. Pituitary hypoplasia or morphological alterations, but even pituitary autoimmunity, are a very common MRI finding in patients with PWS, in whom hyperphagia, hypogonadism and deficit of growth hormone suggest a possible central hypothalamic/pituitary dysfunction [16–18]. However, no relationship has been reported between pituitary hypoplasia and interictal EEG abnormalities or epilepsy in PWS.
Our study has an important strength. The recruitment of rather large series of patients with PWS, all managed for a long period of time in highly specialized centers allowed us to establish with a certain accuracy the prevalence of interictal EEG abnormalities, considering the great number of EEG recordings carried out. On the other hand, some methodological limitations should be taken into account. In fact, this study was retrospective, all patients were managed in paediatric and endocrinological settings. In addition, brain MRI was available approximately 52% of the sample studied.
In conclusion, we show that about 25% of PWS patients present EEG abnormalities, irrespective of the genetic defect, gender and intellectual disabilities, and about 5% epilepsy. EEG normalized in about 25% of patients with EEG abnormalities. Our study shows that paroxysmal abnormalities are mostly focal or multifocal and localized in two-thirds of the patients over the middle-posterior regions. This localization might be considered a rather common EEG trait and a potential marker of PWS in about 25% of patients during the follow-up. A peculiar interictal EEG pattern does not exist in PWS. Further large prospective studies are needed to clarify pathogenesis of electroclinical findings in PWS, also addressing more strict correlations with molecular genetics and high-definition neuroimaging.