LD was first described by Lafora and Gluech in 1911.2
Clinical findings often begin at the end of first decade or at the beginning of the second decade; however, onset as late as mid-20s has been reported in four siblings.5
LD is caused by mutation either in gene EPM2A or EPM2B. EPM2A encodes for laforin, a dual-specificity tyrosine phosphatase protein, localised at plasma membrane and endoplasmic reticulum. EPM2B encodes for malin, a putative E3 ubiquitin ligase with a possible role in the ubiquitination pathway. Furthermore, the existence of a third LD locus has also been suggested. It is more frequently seen in India, Pakistan, Middle East and other countries in which consanguineous marriages often occur.6
Although the patient described had no affected siblings, his parents were not related to each other.
Illness begins with epileptic seizures; generalised tonic clonic, diffuse myoclonus and occipital seizures characterised by photoconvulsive reactions, and visual hallucinations and scotoma might also be seen. Visual ictal phenomena appear in half of the cases and are relatively specific clinical clues to the diagnosis of the disease;2 5 6
however, this feature was not seen in our case. Progressive neurological deterioration such as ataxia, dementia, psychosis, dysarthria, amaurosis, mutism, muscle weakness and respiratory failure are associated with seizures, resulting in death within a decade of disease onset.
Diagnosis is confirmed by demonstration of typical PAS-positive spherical inclusion bodies in the brain, spinal cord, skin, liver and skeletal muscle on biopsy or by genetic testing. Axillary skin biopsy is preferred because it is less invasive and gives lower false-negative results.2 6–8
Treatment of seizures in LD has been a therapeutic challenge. Multiple AED drugs including Na valproate, clonazepam, lamotrogine, topiramate and zonisamide have been tried with variable response.9
Piracetam, also a pyyrolidine derivative, though one of the most effective agents for myoclonus, usually requires administration of high doses with no stable and long-term effect in patients with LD.4 9
LEV is chemically similar to piracetam, but has different pharmacological profile, therefore was found effective in controlling seizures, which were refractory to piracetam. Its exact mechanism of action is unknown, possibly including effects on zinc mediation of γ-aminobutyric acid responses, blockade of N-type calcium channels and activation of potassium channels.4
Its broad-spectrum activity and favourable pharmacokinetics have been reported to be successful in the treatment of refractory seizures and status epilepticus due to various epilepsy syndromes other than LD.10–12
Effective doses range from 500 to 6000 mg. It has a rapid onset of action, reducing seizure frequency in 12–96 h, even in intubated patients on nasogastric tube, without interacting with other anticonvulsants and any significant side effects.11 12
Reported patient also showed a rapid response to LEV, and no side effects were noted even on rapid titration. Preliminary studies including open-label trials and multiple case reports have shown efficacy of LEV in controlling myoclonus and thus improving quality of life in patients with PME, mainly Unverricht–Lundborg and myoclonus epilepsy with ragged red fibres, with few case reports of LD.3 4
However, there are few case reports, if any, of status epilepticus due to Lafora body disease, in which LEV was used. Although individual case reports do not prove efficacy beyond doubt, it is important to report individual cases, as patients with various types of PME are rare, making larger randomised trials unfeasible.
- In patients with refractory myoclonic seizures and cognitive decline, consider PME as possible diagnosis.
- Axillary skin biopsy is valuable in the diagnosis of LD, as it is less invasive, has lower false-negative results and especially useful in regions where genetic testing is not available.
- LEV has a significant antimyoclonic activity and one of the few AEDs that is useful in refractory myoclonic seizures and status epilepticus even in oral form.