doi: 10.1053/ejpn.2000.0456 available online at http://www.idealibrary.com on Illl~i"
European Journal of Paediatric Neurology 2001 ; 5(Suppl. A): 167-173
ORIGINAL ARTICLE
Northern epilepsy syndrome (NES, CLN8) - MRI and
electrophysiological studies
L LAURONEN, 1"2 P SANTAVUORI, 3 A HIRVASNIEMI, 4 E KIRVESKARI, 5 J HUTTUNEN, 1 T AUTTI 2
1BioMag Laboratory, Medical Engineering Centre, 2Department of Radiology, Helsinki University Central Hospital,
Helsinki, Finland; 3pediatric Neurology, Hospital for Children and Adolescents, Helsinki, Finlanc~ 4Department of
Pediatrics, Kainuu Central Hospital, Kainuu, Finland; 5Department of Clinical Neurophysiology, Helsinki University Central
Hospital, Helsinki, Finland
Northern epilepsy syndrome (NES, EPMR, progressive epilepsy with mental retardation, CLN8), an inherited
childhood-onset epilepsy with mental retardation, has been recently characterized to belong to the family of neuronal
ceroid lipofuscinoses (NCLs). In this study, four patients (ages 26-44 years) with NES and eight healthy controls
underwent magnetic resonance imaging (MRI) and electrophysiological evaluation with somatosensory evoked
magnetic field (SEF) studies. The findings in NES were compared with the known findings in juvenile NCL (JNCL,
CLN3) and Finnish variant late infantile NCL (vLINCLF~N, CLN5) that manifest around the same age as NES. Also post-
mortem MRI was performed on one brain. On the MRIs, slight to moderate cerebellar atrophy was seen in all patients,
whereas only two patients had slightly enlarged cerebral sulci. None of the MRIs demonstrated signal intensity
abnormalities that are commonly seen in JNCL and vLINCLnN and are considered to reflect the Wallerian
degeneration after neuronal death. Generally SEFs in NES were within normal limits, indicating that the disease had
not impaired the function of the neurons on the somatosensory pathway. In conclusion, MRI imaging and SEF findings
suggest that the cerebral neuronal death and dysfunction in NES are minimal compared with JNCL and vLINCLNN.
Keywords: Neuronalceroid lipofuscinoses.Northernepilepsy syndrome.CLN8.MRI. Somatosensory evokedmagneticfields. SEF.
Introduction
Northern epilepsy syndrome, NES, an inherited
childhood epilepsy with mental retardation, has
recently been characterized to belong to the family
of neuronal ceroid lipofuscinoses (NCLs) and has
been denoted as CLN8.1 The NES gene, CLN8,
localized to chromosome 8, encodes a putative
transmembrane protein. 2
The clinical picture of NES can be divided into
three successive stages. The disorder begins with
epilepsy at the mean age of 6.7 years (range 5-10
years); the first stage lasts until puberty and is
characterized by an increasing frequency of gen-
eralized tonic-clonic seizures and borderline or
mild retardation. During the second stage in young
adulthood the frequency of seizures diminishes
and the mental decline is slower, but first signs of
clumsiness in fine motor tasks appear. The third
stage of permanent disability includes few seizures
and continuing retardation, evident clumsiness,
balance difficulties and often decreased visual
acuity. 3
A computer tomography (CT) study of NES
patients revealed cerebral atrophy in all patients
whose epilepsy had lasted more than 12 years. 4
Cerebellar and brain stem atrophy were already
evident in puberty or early adulthood. 4 The
electroencephalogram (EEG) shows slowing of the
background activity, abundant diffuse or inter-
mittent delta and theta activity and scanty
epileptiform activity with varying localization and
form. 5 Visual evoked potentials (VEPs) have been
Correspondence: Leena Lauronen,BioMagLaboratory,PO Box 442, FIN-00029,HUS, Finland
e-maih Isipila@cc.helsinki.fi
1090-3798/01/05/A167+7 $35.00 © 2001 European Paediatric Neurology Society