Clinical Guidance
Progressive myoclonus epilepsy, Lafora type, also known as Lafora disease, is a rare teenage-onset progressive myoclonus epilepsy. The term "myoclonus" is emphasized because this is a relatively infrequent neurologic symptom in teenagers. When seen in an otherwise healthy adolescent, it strongly suggests a common benign form of epilepsy, juvenile myoclonic epilepsy (JME). For this reason, most individuals with Lafora disease are briefly misdiagnosed with JME. However, while the EEG background in JME is normal, it is already abnormal (slow) when myoclonus appears in individuals with Lafora disease. Lafora disease is associated with inexorable worsening of the epilepsy. Myoclonus gradually becomes near constant. Generalized tonic-clonic seizures gradually become intractable; atypical absences with or without myoclonus eventually take over. The affected individual's interactions become such that every thought, speech, feeding, etc., are interrupted, and each of these and other functions become slow and protracted. Walking ability is lost usually in most affected individuals before age 21 years. Within ten years of disease onset, most individuals are in a vegetative state and usually die in status epilepticus or complications of poor airway control. To date, at least 300 individuals have been identified with Lafora disease [, , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Clinical Findings of Progressive Myoclonus Epilepsy, Lafora Type
Evaluation Type | At Onset | Later in Disease Course |
|---|
General physical exam, incl liver spleen size | Normal | Normal |
Neurologic exam, incl fundi reflexes | Normal | Dysarthria, ataxia, spasticity; fundi remain normal |
Mental state exam | Visual hallucinations, cognitive deficits, depressed mood, headaches | hallucinations, agitation, dementia w/predominantly frontal cognitive impairment affecting mainly performance ability executive function |
EEG | Normal or slow background, occipital discharges | Slow background, paroxysms of generalized irregular spike-wave discharges w/occipital predominance, focal (esp occipital) abnormalities; loss of sleep features; marked photosensitivity |
Visual, somatosensory, auditory brain stem evoked potentials | High-voltage visual somatosensory evoked potentials | Amplitudes may return to normal size; prolongation of brain stem central latencies |
Nerve conduction studies | Normal | Normal |
MRI of brain | Normal | Normal or atrophy |
Proton MR spectroscopy of brain | Data not available | NAA-to-creatine ratio in frontal occipital cortex, basal ganglia, cerebellum; NAA-to-myoinositol ratio in frontal gray white matter; NAA-to-choline ratio in cerebellum; GABA; glutamate/glutamine; UDPG; G6P1 |
Transcranial magnetic stimulation | Not applicable | Defective short-interval intracortical inhibition: inhibition at ISI 6 ms ISI 10 ms; defective long-interval cortical inhibition G6P = glucose-6-phosphate; GABA = gamma-aminobutyric acid; ISI = interstimulus intervals; NAA = N-acetylaspartate; UDPG = uridine diphosphate glucose 1. Age of onset. |
Source: GeneReviews — "Progressive Myoclonus Epilepsy, Lafora Type"
