Lafora disease is a hereditary myoclonic epilepsy, in which there is a deposition of polysaccharide substances in various tissues, primarily in cerebral structures. The clinic is dominated by myoclonic paroxysms, generalized epiprimes, progressive dementia, mental disorders and visual disorders. Diagnostics includes assessment of neurological status, visometry, ophthalmoscopy, EEG, brain tomography, examination of skin biopsies. The treatment is ineffective, it is a combination of anticonvulsant therapy with tetracosactide courses.
ICD 10
G40.8 Other specified forms of epilepsy
General information
Lafora disease got its name thanks to a Spanish neuropsychiatrist who described it in 1911. Along with the clinic of the disease, Rodriguez Lafora gave a description of specific inclusions found in the cytoplasm of cerebral and spinal neurons in this pathology. Later, the inclusions were given the name of the Lafora taurus. They were also detected in other tissues of the body: heart, liver, sweat glands, skeletal muscles.
Lafora disease is a separate type of myoclonus epilepsy, which debuts in the second decade of life and is characterized by myoclonic phenomena, generalized epiprimes, progressive decay of cognitive and mental functions. The steadily worsening course and hereditary nature of the disease formed the basis of its other name — progressive familial myoclonus-epilepsy. In neurology, Lafora disease is also known as Lafora taurus disease and type II myoclonic epilepsy.
Causes
Lafora disease is caused by the presence of gene mutations in the 6th chromosome (loci 6q24 and 6p22.3). In 80% of patients, aberrations affect the EPM2A gene encoding the protein laforin, which is involved in the regulation of glycogen metabolism. In other cases, aberrations are found in the NHLRC1 gene responsible for the production of raspberry protein. Lafora disease has autosomal recessive inheritance. If a child receives a defective gene from both his father and mother, then over time he has carbohydrate metabolism disorders with the deposition of amylopectin-like polysaccharides in the form of Lafora bodies in tissues similar to glycogen. The accumulation of the latter is diffuse, the greatest concentration is observed in the thalamus, hippocampus, the dentate nucleus of the cerebellum, the substantia nigra.
The ongoing metabolic processes leading to the formation of polysaccharide inclusions have not yet been studied. It is known that small glycogen stores in neurons are beneficial because they increase their resistance to hypoxia. Probably, excessive accumulation of amylopectin-like polysaccharides leads to impaired metabolism of neurons and their apoptosis (death). The result is progressive degenerative and atrophic changes in cerebral tissues, causing a steady aggravation of clinical symptoms.
Symptoms
Lafora disease manifests itself in the age range of 10-18 years. The most common onset of the disease is a generalized epiprime, in some cases — a mental disorder. It may begin with myoclonic or focal occipital paroxysms. Myoclonic seizures are characterized by short-term sudden asynchronous and irregular contractions of individual muscle groups. They can be provoked by external influences (a loud sound, a flash of light, a rough touch, an emotional trigger, etc.). Focal myoclonic paroxysms can be mistaken for muscle twitching and initially interpreted as manifestations of neurosis. Common limb myoclonias provoke hyperkinesis and make active movements difficult; they always disappear during sleep. Occipital epiprimes occur with preserved consciousness, transient visual scotomas occur (complete transient blindness is possible) and /or visual hallucinations.
Lafora disease is accompanied by cognitive decline, mental abnormalities and a disorder of visual function. In some children, learning difficulties are noted even before the first symptoms of the onset of the disease. After the onset of the disease, progressive dementia is observed. In the mental sphere, euphoria, aggressiveness, agitation, confusion, hallucinatory syndrome are possible. Visual disorders occur due to optic nerve atrophy and degenerative retinopathy.
With the course of Lafora disease, generalized tonic-clonic seizures become fewer, but myoclonic paroxysms worsen. They are becoming more frequent and bilateral. With the generalization of myoclonia, paroxysm with loss of consciousness is observed. In the expanded stage, there is an increase in intellectual disorders, ataxia appears and worsens, pelvic disorders occur, vision loss progresses up to amaurosis.
Lafora disease lasts on average about 10 years. In the terminal stage, there is deep dementia and almost constant myoclonia. The death of patients occurs from the addition of intercurrent infections. In some cases, when the disease manifests after the age of 20, its duration may be 20-30 years.
Diagnostics
In the neurological status, muscular diffuse hypotension, pronounced ataxia (sharp instability in the Romberg pose, gross violations of the coordination tests), dysarthria are determined. Pyramidal manifestations are not very characteristic. At the consultation of an ophthalmologist, when checking visual acuity, various degrees of its decrease are revealed; ophthalmoscopy diagnoses retinopathy and/ or atrophy of the optic nerves. Perimetry performed during occipital paroxysm can establish the presence of a flickering scotoma.
Electroencephalography determines the presence of synchronous slow alpha rhythm waves along with short-term high-amplitude spikes (peaks). Functional tests show an increase in epi-activity and the occurrence of myoclonic twitching in response to photo- and phonostimulation. CT and MRI of the brain make it possible to visualize diffuse atrophy of the cerebral hemispheres and cerebellar tissues.
The pathognomonic diagnostic criterion is the detection of Lafora bodies in the ducts of sweat glands. To identify this criterion, a histological examination of samples taken by skin biopsy is carried out. Lafora corpuscles can also be detected by muscle biopsy or liver biopsy. Lafora disease should be differentiated from other types of epilepsy in children, primarily from juvenile myoclonic epilepsy, from various encephalopathies, Hunt’s myoclonic cerebellar dissinergia, hereditary metabolic diseases (Andersen’s disease, McArdle’s disease, Tay-Sachs disease with late onset).
Treatment
There is no pathogenetic therapy. The treatment is symptomatic. In the first place comes the relief of epileptic syndrome. To this end, epileptologists use both traditional anticonvulsants (valproic acid) and new generation drugs (levetiracetam, topiramate). Since epilepsy in Lafora disease is difficult to treat with anticonvulsant treatment, these pharmaceuticals are often combined with ethosuximide, phenobarbital, clonazepam.
In parallel with constant antiepileptic therapy, courses of intramuscular tetracosactide administration are prescribed (from 10 to 15 injections per 1 course). Unfortunately, the existing treatment is ineffective and is not able to stop the progression of clinical symptoms.
