The
progressive myoclonus epilepsies (PMEs) consist of a group of diseases with
myoclonic seizures and progressive neurodegeneration, with onset in childhood and/or adolescence.
Lafora disease is a neuronal
glycogenosis in which normal
glycogen is transformed into
starch-like polyglucosans that accumulate in the neuronal somatodendritic compartment. It is caused by defects of two genes of yet unknown function, one encoding a
glycogen phosphatase (laforin) and the other an
ubiquitin E3 ligase (malin). Early cognitive deterioration,
visual seizures affecting over half, and slowing down of EEG basic activity are three major diagnostic clues.
Unverricht-Lundborg disease is presently thought to be due to damage to neurons by lysosomal
cathepsins and
reactive oxygen species due to absence of
cystatin B, a small
protein that inactivates
cathepsins and, by ways yet unknown, quenches damaging redox compounds. Preserved cognition and background EEG activity,
action myoclonus early morning and vertex spikes in REM sleep are the diagnostic clues.
Sialidosis, with cherry-red spot, neuronopathic
Gaucher disease, with
paralysis of verticality, and
ataxia-
PME, with ataxia at onset in the middle of the first decade, are also lysosomal diseases. How the lysosomal defect culminates in
myoclonus and
epilepsy in these conditions remains unknown.