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Progressive myoclonus epilepsy in Down syndrome patients with dementia

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Abstract

This study aimed to elucidate the natural history of senile myoclonic epilepsy, a type of myoclonic epilepsy associated with Alzheimer’s disease in adult Down syndrome patients. Twelve Down syndrome patients over the age of 40 years with myoclonic epilepsy and Alzheimer’s disease underwent clinical, neuropsychological, neurophysiological, and neuroradiological study. The kariotypes, APOE polymorphisms, all exons in the PSEN1 and PSEN2 genes, and exons 16 and 17 in the APP gene were determined for all patients. CSF Aβ42, p-tau181, and t-tauAg were determined for two patients. Three main stages appeared during the course of the syndrome. The first stage was characterized by dementia onset (mean age: 51 ± 6.6 years), diffuse EEG abnormalities during sleep, and cerebral atrophy determined using neuroimaging. During the second stage, myoclonic epilepsy manifested (mean age: 51.4 ± 7.2 years) with myoclonic jerks time-locked to diffuse epileptiform abnormalities upon awakening, which was controlled with antiepileptic drugs. During the third stage (mean age: 54.8 ± 7.6 years), myoclonic seizures were replaced with nonepileptic myoclonus, and cerebellar signs, severe dementia, and photosensitivity developed. All patients showed complete trisomy 21. Mutations were ruled out on the APP, PSEN1, and PSEN2 genes, and APOE analysis revealed ε3/ε3 homozygosity. CSF biomarkers showed a decrease in Aβ42 and an increase in p-tau181. The natural history of senile myoclonic epilepsy is consistent with progressive myoclonus epilepsy. Chromosome 21 is implicated in its pathophysiology; however, other genetic and/or environmental risk factors cannot be excluded. The absence of the APOE type 4 allele could predict its progression.

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None of the authors has any conflict of interest to disclose.

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Authors and Affiliations

  1. Department of Neurological Sciences, Epilepsy Centre, Clinic of Nervous System Diseases, Ospedali Riuniti Foggia, University of Foggia, Via Luigi Pinto 1, 71100, Foggia, Italy

    Giuseppe d’Orsi & Luigi M. Specchio

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  1. Giuseppe d’Orsi
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  2. Luigi M. Specchio
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Consortia

On behalf of the Apulian Study Group on Senile Myoclonic Epilepsy

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Correspondence to Giuseppe d’Orsi.

Additional information

A full list of Apulian Study Group on Senile Myoclonic Epilepsy investigators is given in the Appendix.

Appendix

Appendix

Apulian Study Group on Senile Myoclonic Epilepsy:

Chairs: Giuseppe d’Orsi, Luigi M. Specchio (Epilepsy Center, Clinic of Nervous System Diseases, University of Foggia, Ospedali Riuniti, Foggia).

Collaborators: Elena Carapelle, Maria Teresa Di Claudio, Angela Lopopolo, Francesca Pacillo, Maria Grazia Pascarella, Marina Trivisano (Epilepsy Centre, Clinic of Nervous System Diseases, University of Foggia, Ospedali Riuniti, Foggia); Michele Falcone (1st Laboratory analysis, Ospedali Riuniti, Foggia); Gianpaolo Grilli (Radiological Unit, Ospedali Riuniti, Foggia, Italy); Potito Salatto (Department of Anesthesia and Intensive Care, University of Foggia, Foggia); Gabriella De Stefano (Neurology Ward, Opera Don Uva, Foggia); Flavia Meola (Rehabilitation Centre, Manfredonia); Davide Seripa (Geriatric Unit and Gerontology-Geriatric Research Laboratory, Department of Medical Sciences, “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Foggia); Vincenzo Demaio, Mauro Minervini, Salvatore Ottaviano (Neurology Ward, Opera Don Uva, Bisceglie); Teresa Francavilla, Angela La Neve, Concetta Luisi (Epilepsy Centre, Neurology Hospital “Amaducci”, University of Bari, Bari, Italy).

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d’Orsi, G., Specchio, L.M. & On behalf of the Apulian Study Group on Senile Myoclonic Epilepsy. Progressive myoclonus epilepsy in Down syndrome patients with dementia. J Neurol 261, 1584–1597 (2014). https://doi.org/10.1007/s00415-014-7376-x

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  • DOI: https://doi.org/10.1007/s00415-014-7376-x

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