Acta Neuropathologica

, Volume 121, Issue 3, pp 421–427

New neuropathological findings in Unverricht–Lundborg disease: neuronal intranuclear and cytoplasmic inclusions

  • Nicola R. Cohen
  • Simon R. Hammans
  • James Macpherson
  • James A. R. Nicoll
Case Report


Unverricht–Lundborg disease (EPM1A), also known as Baltic myoclonus, is the most common form of progressive myoclonic epilepsy. It is inherited as an autosomal recessive trait, due to mutations in the Cystatin-B gene promoter region. Although there is much work on rodent models of this disease, there is very little published neuropathology in patients with EPM1A. Here, we present the neuropathology of a patient with genetically confirmed EPM1A, who died at the age of 76. There was atrophy and gliosis affecting predominantly the cerebellum, frontotemporal cortex, hippocampus and thalamus. We have identified neuronal cytoplasmic inclusions containing the lysosomal proteins, Cathepsin-B and CD68. These inclusions also showed immunopositivity to both TDP-43 and FUS, in some cases associated with an absence of normal neuronal nuclear TDP-43 staining. There were also occasional ubiquitinylated neuronal intranuclear inclusions, some of which were FUS immunopositive. This finding is consistent with neurodegeneration in EPM1A as at least a partial consequence of lysosomal damage to neurons, which have reduced Cystatin-B-related neuroprotection. It also reveals a genetically defined neurodegenerative disease with both FUS and TDP-43 related pathology.


Myoclonus Epilepsy Cystatin B Ubiquitin Inclusion Neurodegeneration 



Cystatin B


Epilepsy, progressive, myoclonic, type 1A


Frontotemporal lobar degeneration


Frontotemporal lobar degeneration with ubiquitinylated inclusions


Messenger ribonucleic acid


Neuronal cytoplasmic inclusion


Neuronal intranuclear inclusion


Neuronal intermediate filament inclusion disease


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Nicola R. Cohen
    • 1
  • Simon R. Hammans
    • 2
  • James Macpherson
    • 3
  • James A. R. Nicoll
    • 1
    • 4
  1. 1.Cellular PathologySouthampton General HospitalSouthamptonUK
  2. 2.Wessex Neurological CentreSouthampton General HospitalSouthamptonUK
  3. 3.Wessex Regional Genetics LaboratorySalisbury District HospitalSalisburyUK
  4. 4.Clinical NeurosciencesUniversity of Southampton, Southampton General HospitalSouthamptonUK

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