2.3. Progressive Myoclonic Epilepsy
- General features:
- Primarily a heterogenous group of genetic disorders caused primarily by inborn errors of metabolism
- Major clinical features:
- Myoclonus
- Seizures
- Cognitive decline
- Progressive neurologic deficits
- Differential diagnosis:
- Lysosomal storage disease
- Mitochondrial disorders
- Unverricht–Lundborg disease
- Lafora body disease
- Hallervorden–Spatz disease
- Action myoclonus renal failure syndrome
- Dentatorubral pallidal Luysian Sylvian atrophy (DRPLA)
- Sialidosis
- Adult onset polyglucosan body disease
- Gaucher's Disease
- Celiac Disease
- Neuroaxonal dystrophy
- Dawson's encephalopathy
- Biotin responsive encephalopathy
- Familial adult myoclonic epilepsy
Myoclonic Syndromes
- General Features:
- Myoclonic Seizures:
- Sudden, lightening like contractions of groups of muscles
- Faster than contractions of muscles noted with clonic seizures
- Any group of muscles may be affected
- Patients may fall
- Myoclonic jerks may occur as a component of an absence seizure or at the onset of a GTCS
Early Infantile Myoclonic Encephalopathy (Otohara Syndrome)
- General features:
- Initial seizures are myoclonic
- Myoclonic seizures prior to 3 months have severe underlying pathology
- No established link with immunization
- Myoclonic seizures are followed by partial seizures, tonic spasms and GTCS
- Psychomotor deterioration
- EEG:
- Burst suppression
- Neonate presents with burst suppression and evolves to intermittent high amplitude spike and wave complexes
West Syndrome
- Clinical features:
- Infantile spasms
- Arrest of psychomotor development
- Hypsarrhythmia on EEG
- Onset prior to one year (3–7 months)
- Spasms occur in clusters; sudden flexion or extension of the trunk; jack knife pattern (flexion of the head and neck and adduction of the arm)
Familial Adult Myoclonic Epilepsy
- Genetics:
- Chromosome: 8 q 24; AD
- European family described without linkage to 8 q 24
- Baltic familial myoclonic epilepsy and familial adult myoclonic epilepsy are on chromosome 8 q 23.3–q 24.1
- Clinical features of FAME:
- Adult onset of extremity myoclonus
- Infrequent seizures
- Non progressive
- Giant SEP (somatosensory evoked potentials)
- Enhancement of C reflex
- Pre-myoclonus spike
- Onset greater than 30 years of age
- Familial cortical tremor
- Variant of cortical reflex myoclonus
- Some Japanese families have:
- FAME; BAFME (Baltic Familial Myodemic Epilepsy); FCT (familial cortical tremor)
- Lafora body disease
- AR: both sexes equally affected; chromosome 6q
- Clinical features:
- Seizures
- Myoclonus
- Affects any area of the body
- Startle sensitive
- Absent during sleep
- Dysarthria
- Rigidity
- Spasticity
- Dementia follows seizures in two to three years
- Onset in adolescence or in late childhood; progresses to death between 17–24 years in 90% of patients
- Generalized tonic-clonic seizures are presenting features; status epilepticus in terminal stage
- Visual seizures occur in 50% of patients:
- Scotomata
- Simple hallucinations
- Occipital CPS
- Fluctuating course associated with episodes of cortical pseudo blindness
- EEG: bilaterally synchronous spike and wave complexes noted in association with the myoclonic jerks
- Lafora bodies:
- PAS positive intracellular inclusions < 3 μm to 30 μm
- Located in the neuronal perikarya; cerebral cortex, substantia nigra, thalamus and globus pallidus
- Lafora bodies are found in: heart, skeletal muscle, skin, retina, liver
- Branched polysaccharide
Unverricht–Lundborg Disease (Baltic myoclonus)
- Genetics: located on chromosome 21q 22.3; AR
- Mutation in EPM 1 gene
- Encodes cystatin B
- Inhibits cathepsins
- Intralysosomal cystine proteases
- Clinical features:
- Stimulus sensitive; action myoclonus
- Age at onset 8–13; begins insidiously
- Tonic clonic seizures
- Ataxia, dysarthria, decreased swallowing
- Mild dementia
- Exacerbated by phenytoin
- Myoclonus is incapaciting
- MRI:
- Atrophy of the medulla, pons and cerebellar
- OPCA has V shape of the pons hemispheres
- Pathology:
- Loss of Purkinje cells, dentate and olivary neurons
Sialidosis
- Melioidosis 1
- Oligosaccharide sialidosis deficiency
- Genetics: juvenile Type III; chromosome 10
- Clinical features:
- Onset at 6 months
- Mild Hurler's features (facial dysmorphism)
- Corneal clouding
- Macular cherry red spot
- Mental retardation
- Myoclonic jerks
- Seizures
- Neuropathy
MERRF (Mitochondrial Encephalomyopathy with Ragged Fibers)
- Short stature
- Diabetes mellitus
- Sensory neural hearing loss
- Abnormal collection of mitochondria on muscle biopsy
- Proximal weakness
- Progressive myoclonic epilepsy
- Other mitochondrial diseases have myoclonic epilepsy
Neuronal Ceroid Lipofuscinosis
- Juvenile variant (Spielmeyer–Sjögren Disease)
- Genetics: AR; chromosome 16p
- Abnormal lipopigments found in abnormal cytosomes (curvilinear and finger print bodies); abnormalities seen in skin, muscle, peripheral nerve in addition to central nervous system
- Clinical features:
- Onset 5–10 years of age
- Begins with progressive visual loss
- Pigmentary degeneration of the retina
- Myoclonic and generalized seizures
- Death by end of the second decade
- Adult variant (Kufs disease)
- Genetics
- Clinical features:
- Onset in third or fourth decade
- Progressive dementia
- Seizures
- Myoclonus
- Ataxia
- No blindness or retinal degeneration
Rare Causes of Progressive Myoclonic Epilepsy:
- Gaucher's Disease
- GMI gangliosidosis
- Biotin responsive encephalopathy
- DRPLA-SCA-7
- Atypical inclusion body disease (Derision's encephalopathy)
- Action myoclonus renal failure syndrome
- Neuroaxonal dystrophy
- Hallervorden-Spatz Disease
- Celiac Disease
- Dutch mt-DNA deficiency (fatal myoclonus epilepsy)
- HARP
Tonic Seizures
- Clinical Features:
- Brief, usually less than 10 seconds; may last 60 seconds
- Sudden onset of increased tone in extensor muscles; may be preceded by a myoclonic jerk
- Patients fall; may be limited to only this manifestation
- There is impairment of consciousness during the seizure
- Frequently seen with Lennox–Gastaut Syndrome (mental retardation, mixed seizure disorder, slow spike-and-wave EEG pattern)
- Apnea due to involvement of the intercostal muscles
- Long seizures appear to have a clonic component (more frequent at night)
- Only the axial muscles may be involved
Clonic Seizures
- Similar to GTCS
- Rhythmic or semi-rhythmic contractions of a group of muscles
- Jerks can involve any group of muscles: arm, face > legs
Atonic Seizures:
- Begin in the late infancy; may start in adolescence
- Sudden loss of muscle tone; no aura
- Last 1–2 seconds
- No postictal impairment
- If trunk is involved the patient falls; if only the neck extensors are involved there is head drop; may be limited to eye blink
- Longer atonic seizure are associated with loss of consciousness
- May be seen as component of other seizures
- Absence seizures often have an atonic component
- Myoclonic jerk may precede or accompany the seizure
- Long seizures cause seconds of flaccid paralysis
- EEG: poly spike and wave or generalized spike and wave are associated with myoclonic jerks
Focal Akinetic Seizure:
- Focal paresis precedes convulsive activity in the affected part
- Focal paresis may affect one part of the body; convulsive activity may then occur in the affected part
- Somatosensory sensations may occur before or at the onset of the focal paresis in the same body region
- Structural lesions have been documented in central parietal regions
- Patient is motionless with impaired consciousness
Epileptic Negative Myoclonus:
- Action-activated motor activity (jerks) limited to one arm or leg
- Rarely may be multifocal
- Patients may demonstrate motor neglect of the affected part
- Most patients have history of seizures
- Paroxysmal epileptic activity is seen in areas of the sensorimotor cortex
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