U ovom radu pružili smo pregled spoznaja o neurobiološkoj osnovi poremećaja migracije koja je važna za njihovu klasifikaciju. Kortikalni neuroni rađaju se u ventrikularnoj i subventrikularnoj zoni te prolaze dugačak put do svojeg konačnog odredišta, rabeći dva osnovna mehanizma i puta migracije: (1) radijalnu migraciju, put uzduž radijalne glije i (2) tangencijalnu, najvjerojatnije “neurofilnu” migraciju. Tijek migracije je složen i može biti poremećen utjecajem različitih genetskih i vanjskih čimbenika. Poremećaj proliferacije u ventrikularnoj zoni dovodi do značajnih malformacija, kao što je shizencefalija, a poremećaj samog početka migracije uslijed genetskih abnormalnosti (mutacija FILAMIN1 gena) dovodi do periventrikularne nodularne heterotopije i strukturnih promjena vidljivih na slikovnim prikazima magnetskom rezonancijom (MRI). Tipični poremećaj migracije je lizencefalija tipa 1 koja se trenutno ubraja u spektar poremećaja agirija-pahigirija-„band“ heterotopija. Ova skupina poremećaja uzrokovana je mutacijama gena LIS1 i DCX (XLIS), a povezana je s Miller-Diekerovim, Lennox-Gastaut sindromom i epilepsijom. Poremećaji kasnijih faza migracije uzrokuju lizencefaliju tipa 2 (kompleks ”cobblestone”), koja je povezana s Walker-Warburgovim sindromom, makrocefalijom, malformacijom mrežnice, poremećajem mišić-oko-mozak i Fukuyama kongenitalnom mišićnom distrofijom. Zellwegerov sindrom je karakteriziran patomorfološki polimikrogirijom i biokemijski grješkom mithondrijskih putova desaturacije. Poremećaji kasne migracije pokazuju strukturne promjene vidljive MRI-om, koje su ograničene na moždanu koru. Drugi migracijski poremećaj, fokalna kortikalna displazija, često je prisutna kod rezistentnih oblika epilepsije, a kod dijagnostike je od posebne koristi MRI visoke rezolucije (3T). Genetski testovi zajedno s MRI-om otvaraju nove mogućnosti za ranu dijagnostiku i poboljšani pristup u liječenju poremećaja migracije.In this review we outline the neurobiological basis for classification of cortical migratory disorders. Neurons of the human cortex are born in the ventricular and subventricular zone and migrate for a long distance to reach their final point of destination in the cortex, using two types of migratory routes and mechanisms: (1) radial migration along radial glia and (2) tangential, presumably “neurophilic” migration. The process of migration is complex and may be disturbed by various genetic and extrinsic factors. The disturbances of proliferation in the ventricular zone result in major malformations such as schizencephaly, while the failure of onset of migration results in periventricular nodular heterotopia with characteristic abnormalities in magnetic resonance imaging (MRI) and with genetic aberration in the background (FILAMIN1 gene mutation). The typical migratory disorder is lissencephaly type I caused by defect of ongoing migration. The lissencephaly type I is currently included in agyria-pachigyria band spectrum disorders. This group of disorders is caused by mutations of LIS1 and DCX (XLIS) gene mutations associated with Miller-Dieker syndrome, Lennox-Gastaut syndrome and epilepsy. The defects of late phases of migration cause lissencephaly type II, cobblestone complex, which is associated with Walker-Warburg syndrome, macrocephaly, retinal malformation, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy. Zellweger syndrome is morphologically characterized by polymicrogyria and biochemically by defects of the mitochondrial desaturation pathway. The disorders with later migration failure show abnormal MRI restricted to the cortex. Another migratory disorder, focal cortical dysplasia, is a frequent cause of drug resistant epilepsy. An especially helpful diagnostic tool for migratory disorders is high resolution (3T) MRI. Genetic testing together with detailed MRI of migratory disorders opens new perspectives for early detection and improved treatment of migratory disorders
