Progressive Myoclonic Encephalopathies Flashcards
Unverricht disease (Unverricht–Lundborg disease, progressive myoclonic epilepsy 1 (EPM1), Baltic myoclonus, Mediterranean myoclonus)
Semiology
Characterized by:
- cortical myoclonus
- generalised tonic–clonic seizures (GTCSs)
- mild progressive ataxia.
Patients are initially neurologically normal. Mild cognitive deterioration also occurs with time.
A characteristic feature of UL is the relative remission over days.
Unverricht disease (Unverricht–Lundborg disease, progressive myoclonic epilepsy 1 (EPM1), Baltic myoclonus, Mediterranean myoclonus)
Etiology
Autosomal recessive disorder caused by mutations of the CTSB gene (21q22.3), which encodes Cystatin B an inhibitor of lysosomal cysteine proteases.
Lafora disease (Lafora body disease, PME with polyglucosan bodies)
Semiology
Mainly myoclonia and occipital seizures (spontaneous or photic induced), and sometimes GTCS.
Behavioral and cognitive decline may be the initial manifestations
Lafora disease (Lafora body disease, PME with polyglucosan bodies)
Etiology
Autosomal recessive.
Genes: EPM2A (6q24) - protein Laforin
EPM2B (6p22) - protein Malin (milder course)
Lafora bodies are PAS positive diastase resistant polyglucosan inclusions.
Ceroid Lipofuscinoses
Semiology
Rapid and progressive neurocognitive deterioration.
Visual loss due to retinal atrophy is a prominent feature of all but the adult form.
Myoclonia and multiple seizure types occur.
Ataxia, dementia and behavioral problems.
Progressive deterioration of background (“vanishing EEG activity” in infantile NCL).
Ceroid Lipofuscinoses
Etiology
Mainly autosomal recessive. Seven NCL gene loci have been identified:
CLN1 - PPT1 (1p32) - Palmythoil protein thioesterase.
CLN2 - TPP1 (11p15) - Trypeptidyl peptidase I
CLN3 - CLN3 (16p12) - protein CLN3
CLN4- Unknown
CLN5 - CLN5 (13q21) - protein CLN5
CLN6 - CLN6 (15q21) - protein CLN6
CLN8 - CLN8 (8p22) - protein CLN8 CLN10 - CTSD (11p15) - Cathepsin D. In general, the disease is characterized by the intracellular accumulation of lipopigments.
Sialidosis (type I and II)
Semiology
Visual impairment, myoclonus and other seizure types, ataxia. Cherry red spots in the retina. Types I and II have the same clinical manifestations, but type II is more severe
Sialidosis (type I and II)
Etiology
Result from the inherited deficiency of the lysosomal enzyme alpha-N-acetylneuraminidase due to mutations in the gene NEU1 (6p21), which codes for the protein Neuraminidase.
Myoclonic epilepsy associated with ragged red fibers (MERRF)
Semiology
MERRF is characterized by: 1- Cortical Myoclonus 2- Ataxia 3- Mild atrophy 4- Cognitive Impairment Both genders equally affected.
Progressive ataxia is the main cause of disability. Myopathy is mild, but exercise intolerance is prominent. Lactic acidosis, peripheral neuropathy and short stature are common. Strokes may occur (as in MELAS). The phenotype depends on the mutation load.
Myoclonic epilepsy associated with ragged red fibers (MERRF)
Etiology
The gene is MT-TK, which codes for mitochondrial tRNA lysine.
Dentatorubral-pallidoluysian atrophy (DRPLA, Naito-Oyanagi syndrome)
Semiology
Cerebellar ataxia and dementia are the main features.
If onset before early adulthood, cortical myoclonus and other seizure types are observed. In older onsets, seizures may be milder or absent.
Dentatorubral-pallidoluysian atrophy (DRPLA, Naito-Oyanagi syndrome)
Etiology
DRPLA gene ATN1 codes for the protein Atrophin1.
The molecular defect is a trinucleotide expansion. Anticipation is also observed.
Angelman syndrome
Semiology
Defined by:
Severe developmental delay. Severe speech impairment, gait ataxia
Myoclonic jerks
Other epileptic seizures .
Happy demeanor with excessive chortling
Angelman syndrome
Etiology
Failure of expression of the maternal copy of the gene UBE3A (15q11-q13), which encodes Ubiquitin Ligase 3A.
Usually maternal de novo deletion (approximately 70% of cases).