Encephalopathy with neuroserpin inclusion bodies presenting as progressive myoclonus epilepsy and associated with a novel mutation in the Proteinase Inhibitor 12 gene.

Abstract

Neuroserpin encephalopathy is an autosomal-dominant degenerative disease associated with mutations in the Proteinase Inhibitor 12 (PI12) gene. A 26-year-old male presented with progressive myoclonus epilepsy and declining mental status. He had failed in university studies because of impaired attention, memory and concentration. Generalized seizures started to occur approximately once a month, and he developed myoclonus and progressive gait disturbances. Neuroimaging revealed mild atrophy and multiple periventricular white matter lesions, consistent with demyelination. He progressively declined and died at age 34. Neuropathologic examination revealed widespread involvement of the cerebral cortex by numerous round eosinophilic inclusions in neuronal perikarya and neuropil, predominantly within the deep cortical layers. Numerous inclusions were also found in the basal ganglia, thalamus, hippocampus, brain stem, spinal gray matter, and dorsal root ganglia. They were essentially absent from the cerebellum. The inclusions were immunopositive for antibodies raised against neuroserpin. The white matter lesions showed histologic features compatible with multiple sclerosis. Genetic analysis revealed a nucleotide substitution in codon 47 in one allele of the PI12 gene, resulting in a proline for leucine amino acid substitution (L47P). In summary, we report a case of neuroserpin encephalopathy associated with a novel PI12 mutation and complicated by coexistent multiple sclerosis.

• Authors: Matthew C Hagen, Jill R Murrell, Marie-Bernadette Delisle, Eva Andermann, Frederick Andermann, Marie Christine Guiot, Bernardino Ghetti
• Journal: Brain pathology (Zurich, Switzerland) (Brain Pathol) Vol. 21 Issue 5 Pg. 575-82 (Sep 2011) ISSN: 1750-3639 [Electronic] Switzerland
• PMID: 21435071 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2011 The Authors. Brain Pathology © 2011 International Society of Neuropathology.

Chemical References

• Cysteine Proteinase Inhibitors
• Neuropeptides
• Serpins
• neuroserpin

Topics

• Adult
• Autopsy (methods)
• Brain (pathology)
• Cysteine Proteinase Inhibitors (genetics)
• DNA Mutational Analysis
• Humans
• Inclusion Bodies (pathology)
• Magnetic Resonance Imaging (methods)
• Male
• Mutation (genetics)
• Myoclonic Epilepsies, Progressive (complications, genetics, pathology)
• Neuropeptides (metabolism)
• Serpins (metabolism)