Original article Hemimegalencephaly: foetal tauopathy with mTOR hyperactivation and neuronal lipidosis

Abstract

, , L La au ur ra a F Fl lo or re es s--S Sa ar rn na at t

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…1o) [238,[240][241][242][243][244][245] (for reviews see [233,238] and [239]). The presence of balloon cells has been also reported in HME [244,246]. Moreover, a recent report shows enhanced levels of phosphorylated tau protein and evidence of neuronal lipidosis in 3 male infants with HME [246].…”

“…With the recent advances in fetal imaging HME can be detected prenatally [246], even at a fetal age of 22 weeks [239], supporting the hypothesis of an underlying primary genetic defect that affects the early stages of cortical development (probably between weeks 10 and 20 of human gestation). On the basis of the histopathologic features, it has been suggested as a primary deregulation of proliferation [247], or a disturbance of cellular growth and cellular lineage [233,234].…”

Immunocytochemical markers of neuronal maturation in human diagnostic neuropathology

“…The genetic alterations associated with somatic mutations can also be tested: TSC1 and TSC2 for tuberous sclerosis complex, AKT3 for i s o l a t e d h e m i m e g a l e n c e p h a l y a n d A K T 1 f o r hemimegalencephaly in Proteus syndrome, one of the epidermal naevus syndromes (Lindhurst et al 2011;Poduri et al 2012Poduri et al , 2013Lee et al 2012). Studies of the mTOR (mammalian target of rapomycin) signalling pathway and RAS pathway and also the demonstration of an abnormally phosphorylated and upregulated tau protein can be demonstrated to confirm the diagnosis (Crino 2005(Crino , 2011Sarnat et al 2012;Prabowo et al 2013;Tsai et al 2014;Wang et al 2014). The ultrastructure of the neurons is abnormal (Sarnat et al 2012).…”

Neurological manifestations of Proteus syndrome – review of the literature

“…Although it is evident that those patients could benefit from the surgery, only two such cases are reported. In the first case [19] initial partial hemispherectomy at the age of 8 months had not resulted in a good seizure control and further resection of an epileptic focus in the frontal lobe was performed 10 months later resulting in an improvement. In the second case [20] it was a 3-year-old boy who underwent frontal lobectomy and remained seizure-free for 12 months afterwards.…”

“…Finally, abnormal muscle tone, both hypotonia and hypertonia, were observed [15,18]. [1,[15][16][17][18][19][20][22][23]25,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. Cysts in various locations, calcifications, hypoplastic white matter, lissencephaly, pachygyria, polimycrogyria seem to occur rather sporadically.…”