PROGRESSIVE MYOCLONUS EPILEPSY

 05 November 2004

Myoclonus, epilepsy & progressive neurological deterioration (epilepsy, dementia, ataxia)

Most autosomal recessive

Onset usually late childhood or adolescence

Most due to accumulation of abnormal storage material

Commonest: Unverricht-Lundborg disease, Lafora body disease, neuronal ceroid lipofuschinosis, MERRF, sialidoses, others (Gaucher, DRPLA)

Unverricht-Lundborg disease

Autosomal recessive

1/20,000 births in Finland

major cause of PME in USA

CLINICAL

Onset 6-15 yrs old

Myoclonic jerks:    in 50% first symptoms

                                    Stimulus sensitive

                                    Progressive without treatment

Generalized tonic clonic seizure:

in 50% first symptoms

Infrequently early more frequent for 3-7 years then subside

Neuro findings:      initially normal

                                    Unsteady gait caused by myoclonus

                                    Then ataxia, intention tremor, dysarthria

                                    Slow decline in cognitive function

                                    Labile mood, depression common

INVESTIGATIONS:

EEG:   

always abnormal

Symmetric, generalized, high voltage spike & wave, polyspike & wave paroxysms

marked photosensitivity

epilim has normalizing effect

urinary indican:     50% have increased urinary levels

                                    correlates with amount of myoclonus

SSEP:  P25-N33 > 15 mV (Shibasaki, 1975)

CT, PET: normal

Skin biopsy:

membrane bound vacuoles with clear contents in eccrine clear cells & dark cells

Genetic testing:

founding mutation in Finnish population

Unstable expansion of dodecamer minisatellite repeats in promoter

region of cystatin B gene

reduced level of cystatin B gene product

first case of an unstable repeat unit other than trinucleotide

shows no anticipation

TREATMENT

 PHOTOSENSITIVITY IN PME (PROGRESSIVE MYOCLONUS EPILEPSY)