Myoclonus is usually a greater problem than Seizures for patients with PME because it is not helped much by the anticonvulsants that do help to control the seizures. The twitching occurs more frequently in the early part of the day or when the patient is under stress of various sorts. Positive myoclonus alludes to jerking of the hands and arms. Negative myoclonus refers to the sudden onset of loss of control of the muscles of the legs that leads to falls and injuries. As the frequency of myoclonic jerks increases, it may build to a “crescendo myoclonus” or a convulsion, after which the condition improves for a few days.
Lack of motor coordination may occur along with myoclonus, even in the absence of seizures. Mental function may be impaired, leading especially to problems with memory. Depression is not uncommon. It can become severe and should not be left untreated.
Other problems may include a bladder abnormality that may be associated with urinary tract infection. Depending on the type of PME, patients may also experience gastrointestinal and thyroid problems, as well as vision or hearing impairment. Weight control may be a problem for inactive patients.
There are many different types of PME, each with a different underlying cause. The types of PME include the following:
EPM1 (epilepsy, progressive myoclonus 1) or myoclonic epilepsy of Unverricht and Lundborg
EPM2A (epilepsy, progressive myoclonus 2) or myoclonic epilepsy of Lafora
Batten disease (neuronal ceroid lipofuscinosis)
Cerebral storage and degenerative disorders
EPM1 (Unverricht-Lundborg disease) usually presents between the ages of six and thirteen with the advent of convulsions. Myoclonus begins one to five years later when Muscle spasms of the limbs and minor twitching motions become obvious. Later, these spasms may become so violent that the patient falls. Mental deterioration accompanies the disease progression. However, the progression of the disease in EPM1 is slower than in most other forms of the syndrome.
The duration and seriousness of EPM1 are variable. In advanced cases, inability to coordinate voluntary muscle movements (cerebellar ataxia) occurs. Very rarely, deafness may occur, especially when cerebellar Ataxia is present. Emotional instability is common. In EPM1, there are no particles in brain or other tissue cells as in Lafora’s disease. However the area of the brain concerned with muscle coordination and balance shows a loss of nerve cells. Changes in the environment like flashing lights or the flickering of sunlight may cause the worst symptoms (stimulus-sensitive myoclonus). Other features are generalized tonic-clonic Seizures that are sometimes combined with absence attacks (petit mal). These types of Seizures may be documented by EEG readings. EPM1 is an autosomal recessive genetic disease caused by mutations in the CSTB gene.
EPM2A (Lafora disease) presents in the form of grand mal Seizures and/or myoclonus, usually during the teen years. It is characterized by the presence of carbohydrate particles (Lafora bodies) in cells of the nervous system (brain, spinal cord, or nerves), muscle (or muscle fibers), and/or skin. The presence of Lafora bodies in biopsied tissue is diagnostic. Over time, Mental deterioration may occur and grand mal Seizures become more frequent. EPM2A is one of the more severe forms of PME. EPM2A is an autosomal recessive genetic disorder caused by mutations in the EPM2A gene or NHLRC1 gene.
Mitochondrial myopathies are a group of neurological and neuromuscular disorders that arise from genetic mutations affecting the function of intracellular (within the cell capsule) energy-producing particles (mitochondria). Since mitochondria are found in the cells of most tissues, diagnosis of these disorders is made though the use of blood chemistry tests or through muscle biopsies.
Batten Disease refers to a family of about seven disorders called the neuronal ceroid lipofuscinoses.
Cerebral storage and degenerative disorders often are accompanied by PME. Among these are several disorders that result from the storage of inappropriate intermediate metabolites in the lysosomes of cells. The accumulation (storage) of these metabolites occurs because an essential enzyme, needed to further metabolize the accumulated chemicals, is not present or is present in insufficient concentration. Gene mutations are the cause of these metabolic disorders. Tay-Sachs disease and Gaucher’s disease are examples of this group of conditions.
Biotin-responsive disorders often present with PME that, in these cases, is frequently reversible. Biotin is essential for several enzymes to keep brain metabolism proceeding smoothly. Normally, biotin is recycled and levels are sustained. If the enzymes required for recycling the biotin are not available, then the condition is called biotinidase deficiency. The condition can be diagnosed through blood chemistry to measure the levels of biotin, biotinidase and biotin-dependent enzymes.