title: Primary motor cortex alterations in a compound heterozygous form of Unverricht-Lundborg disease (EPM1).
abstract: OBJECTIVE
  Unverricht-Lundborg disease (EPM1) is the most common form of progressive myoclonus epilepsies. The genetic background is a homozygous dodecamer repeat extension mutation in the cystatin B (CSTB) gene. However, mutations occurring in a compound heterozygous form with the expansion mutation have also been reported. In Finland, we have found five EPM1 patients compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutation in the CSTB gene (chEPM1). There are no previous clinical or neurophysiological studies on these patients. Thus, we aimed to characterize possible functional alterations in primary motor cortical areas.
  
  
  METHODS
  Five chEPM1 patients were compared with homozygous patients and healthy controls. All patients underwent a clinical evaluation to characterize the severity of the symptoms. Navigated transcranial magnetic stimulation (TMS) was used to study cortical excitability by determining the motor thresholds (MT), silent periods (SP) and motor evoked potential (MEP) characteristics. Continuous electroencephalography (EEG) was recorded during the measurements. Voxel-based MRI morphometry (VBM) was used to study differences in gray matter volume.
  
  
  RESULTS
  The chEPM1 patients exhibited an inhibitory cortical tonus reflected as elevated MTs and prolonged SPs. EEG showed spontaneous focal epileptiform activity in centro-temporal and parietal areas in addition to more widespread and generalized discharges. VBM revealed loss of gray matter volume in primary motor cortical areas and thalami.
  
  
  CONCLUSIONS
  The chEPM1 patients exhibited functional and structural changes in primary motor cortical areas. The functional changes are more profound as compared to homozygous patients, suggesting a neurophysiological background for the more severe clinical symptoms.
authors.affiliation: Department of Clinical Neurophysiology, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland and Kuopio University Hospital, POB 1777, FIN-70211 Kuopio, Finland. danner@hytti.uku.fi
authors.forename: Nils
authors.initials: N
authors.lastname: Danner
authors.forename: Petro
authors.initials: P
authors.lastname: Julkunen
authors.forename: Mervi
authors.initials: M
authors.lastname: Könönen
authors.forename: Jelena
authors.initials: J
authors.lastname: Hyppönen
authors.forename: Päivi
authors.initials: P
authors.lastname: Koskenkorva
authors.forename: Ritva
authors.initials: R
authors.lastname: Vanninen
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: Reetta
authors.initials: R
authors.lastname: Kälviäinen
authors.forename: Esa
authors.initials: E
authors.lastname: Mervaala
mesh_terms: D000293:Adolescent; D000328:Adult; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies; D020194:Unverricht-Lundborg Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D055815:Young Adult