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

New neuropathological findings in Unverrichta–Lundborg disease: neuronal intranuclear and cytoplasmic inclusions
New neuropathological findings in Unverrichta–Lundborg disease: neuronal intranuclear and cytoplasmic inclusions
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
1432-0533
421-427
Cohen, Nicola R.
17447488-8ddc-43fb-b45b-2e0d9e2d43df
Hammans, Simon R.
6553eac5-9322-4f2b-b677-d4ba698fc10b
Macpherson, James
133e44ad-e114-4732-b28e-0dfa2348d696
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Cohen, Nicola R.
17447488-8ddc-43fb-b45b-2e0d9e2d43df
Hammans, Simon R.
6553eac5-9322-4f2b-b677-d4ba698fc10b
Macpherson, James
133e44ad-e114-4732-b28e-0dfa2348d696
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed

Cohen, Nicola R., Hammans, Simon R., Macpherson, James and Nicoll, James A.R. (2011) New neuropathological findings in Unverrichta–Lundborg disease: neuronal intranuclear and cytoplasmic inclusions. Acta Neuropathologica, 121 (3), 421-427. (doi:10.1007/s00401-010-0738-2). (PMID:20721566)

Record type: Article

Abstract

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

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More information

Accepted/In Press date: 19 August 2010
Published date: March 2011
Keywords: myoclonus, epilepsy, cystatin b, ubiquitin, inclusion, neurodegeneration
Organisations: Human Genetics, Clinical Neurosciences

Identifiers

Local EPrints ID: 162453
URI: http://eprints.soton.ac.uk/id/eprint/162453
ISSN: 1432-0533
PURE UUID: 426bd223-d6a2-4a56-abd0-8957c5a8cfd6
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

Catalogue record

Date deposited: 20 Aug 2010 14:30
Last modified: 14 Mar 2024 02:46

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Contributors

Author: Nicola R. Cohen
Author: Simon R. Hammans
Author: James Macpherson

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