Progressive myoclonus epilepsy

Progressive Myoclonic Epilepsies (PME) are a rare group of inherited neurodegenerative diseases characterized by myoclonus.

PME accounts for less than 1% of epilepsy cases.

PMEs manifest with resistance to treatment, and neurological deterioration.

Most PMEs are caused by autosomal dominant or recessive and mitochondrial mutations.

There is considerable geography and ethnic variations amongst the specific genetic disorders. 

The location of the mutation also affects the inheritance and treatment of PME. 

There is genetic heterogeneity and the lack of a genetic mutation identified in some patients.

There is no current cure for PME and treatment focuses on managing myoclonus and seizures through antiepileptic medication.

PME can affect people of all ages. 

In Unverricht-Lundborg disease (ULD) the age of onset is between 6–15 years, while in Adult Neuronal ceroid lipofuscinoses, adult NCL, the age of onset can be as late as 30.

Symptoms of PME: action or stimuli induced myoclonus, seizures, neuropathy, cognitive decline, and spike and wave or no cerebral discharges.

PME prognosis is poor: often becomes wheelchair bound, enters a vegetative state due to myoclonus, and has shortened life expectancy.

Its most common symptom is myoclonus.

The myoclonus can be fragmented or multifocal.

Its myoclonus can be triggered by posture, actions, and external stimuli such as light, sound, and touch.

Progressive myoclonus epilepsy (PME) is diseases characterized by myoclonus, epileptic seizures, tonic-clonic seizures, and other serious symptoms such as trouble walking or speaking. 

At least three forms of PME exist:

Lafora disease is inherited as an autosomal recessive disorder, characterized by myoclonus, epileptic seizures, and dementia.

Cerebral storage diseases usually involves myoclonus, visual problems, dementia, and dystonia

System degenerations, action myoclonus, seizures, and problems with balance and walking. 

Many of these PME diseases begin in childhood or adolescence. 

Treatment is not normally successful for any extended period of time.

Reticular reflex myoclonus is a type of generalized epilepsy that originates in the brainstem.

Reticular reflex myoclonus myoclonic jerks usually affect the whole body, with muscles on both sides of the body affected simultaneously. 

In some people with reticular reflex myoclonus myoclonic jerks occur in only a part of the body, such as the legs.

Reticular reflex myoclonus can be triggered by either a voluntary movement or an external stimulus.

Diaphragmatic flutter is characterized by  spoken communication that sounds like a short-breathed hiccup.

Diaphragmatic muscle spasms can recur dozens of times per day, ranging between 35 and 480 contractions per minute, with the average rate found to be 150.

Other symptoms of PME include generalized, tonic clonic, tonic, and atypical absence seizures.

In Lafora’s disease the seizures are occipital and the person experiences transient blindness as well as visual hallucinations, and  may also have atypical absences and atonic and complex partial seizures. 

Myoclonus epilepsy with ragged-red fibers (MERRF) is associated with generalized epilepsy along with myoclonus, weakness, and dementia.

Profession of PMEV neurological abilities decreases and myopathy, neuropathy, cognitive decline, cerebellar ataxia, and dementia can occur.


PME diagnosis is dependent on failure to respond to antiepileptic drugs and therapy, and diagnosis of  a specific PME lesion depends on genetic testing, skin and muscle biopsies, EEG, and enzyme measurements.

Gaucher’s disease can be diagnosed through enzyme testing as it is a metabolic disease.

Lafora’s disease can be diagnosed using skin biopsies.

Action myoclonus renal failure (AMRF) syndrome can only be diagnosed using genetic test.

In Lafora’s disease EEGs can show slowing background activity or focal discharges as well as epileptiform discharges.

In ULD EEGs show generalized epileptiform discharges and in MERRF patients show background slowing.

Diagnosis of PME is best made using a combination of signs and symptoms, age of onset, EEG, gene testing, enzyme measurements, and biopsy of skin and muscle.

The main component setting PME apart from other forms of epilepsy is progressive deterioration and resistance to treatment.

The early stages of PME the symptoms and EEG may appear like: Generalized epilepsy, Juvenile myoclonic epilepsy, benign childhood myoclonic epilepsy, and Huntington’s disease.

The is no cure for PME. 

Managing the symptoms: myoclonus and seizures, to prevent harm.

Antiepileptic drugs used in treatment: valproic acid, benzodiazepines, phehobarbital, piracetam, zonisamide, clonazepam, and levetiracetam. 

Some antiepileptic drugs can worsen the symptoms, like vigabatrin, carbamazepine, phenytoin, and gabapentin.

Clonazepam is approved by the FDA for monotherapy treatment of myoclonic seizures.

Deep brain stimulation, vagus nerve stimulation , and diet but they have not been shown to improve seizures.

The prognosis of PME is ultimately dependent on the type of PME. 

Lafora body disease the neurological deterioration progresses until resulting in a vegetative state and death within 10 years of diagnosis.

Unverricht-Lundborg disease (ULD) 

individuals can live up to 60 years of age.

Patients with severe myoclonus can have  injuries by falling and becoming wheelchair bound.

Progressive myoclonic epilepsy disorders:

Unverricht-Lundborg disease (Baltic myoclonus)

Myoclonus epilepsy and ragged red fibers (MERRF syndrome)

Lafora disease

Neuronal ceroid lipofuscinoses


Dentatorubropallidoluysian atrophy (DRPLA)

Noninfantile neuronopathic form of Gaucher disease

Tetrahydrobiopterin deficiencies

Alpers disease

Juvenile Huntington disease

Niemann-Pick disease type C

North Sea progressive myoclonus epilepsy (NSPME)

Unverricht-Lundborg disease: This disease manifests between six and sixteen years and is most prevalent in Scandinavia and the Baltic countries. 

Myoclonus gradually becomes worse and less susceptible to medication. 

Cognitive decline is slow and sometimes mild. 

Patients typically do not live beyond middle-age.

Phenytoin seriously exacerbated the condition. 

Unverricht-Lundborg disease has an 

autosomal recessive inheritance, and is caused by a mutation in the cystatin B (EPM1) gene on chromosome 21q22.3.

It is least severe type of PME.

Myoclonus epilepsy and ragged red fibres (MERRF syndrome) onset may be at any time and the severity and progression are varied. 

In MERRF syndrome tonic-clonic seizures and dementia are less apparent than with other forms of PME. 

MERFF syndrome is caused by a mitochondrial DNA mutation.

Most familial cases of MERFF are transmitted from the mother. 

A skeletal muscle biopsy reveals ragged red fibers.

Lafora disease typically begins between six and nineteen years after apparently normal development and generally results in death within ten years. 

Lafora disease is characterized by the presence of Lafora bodies, which are polyglucosan inclusions in neurons and other body tissue. 

Its generalized seizures are usually well controlled by anticonvulsants.

Associated myoclonus is soon refractory to treatment. 

Within a couple of years, the patient is wheelchair  bound and within five to ten years, the person is confined to bed and is often tube fed. 

The EPM2A gene on chromosome 6q24 encodes for the protein laforin: It is responsible for 80% of cases. 

The EPM2B gene on chromosome 6p22.3 encodes for the protein malin. 

Valproic acid and zonisamide are first choice anticonvulsants.

A ketogenic diet may be helpful in Lafora disease.

An autosomal-recessive genetic defect is responsible, which has been tracked down to the two genes noted.

Neuronal ceroid lipofuscinoses are multiple disorders, each with their own genetic cause and geographical variation.

They result in accumulation of lipopigments (lipofuscin) in the body’s tissues and are inherited in an autosomal-recessive fashion. 

Death usually occurs within five to fifteen years with such  neuronal ceroid lipofuscinoses.

Sialidosis is an autosomal recessive disorder in which the body is deficient in α-neuraminidase.

Myoclonic epilepsy and ataxia due to potassium (K+) channel mutation (MEAK)-a form of progressive myoclonus epilepsy that typically begins between the ages of 3 and 15 years.

The initial symptoms may include ataxia and myoclonus along with generalized tonic-clonic seizures. 

The symptoms are progressive, leading to the use a wheelchair by their late teenage years because of movement difficulties and myoclonus. 

MEAK may be associated with temporary improvement of symptoms with a high fever, and seizures may become less frequent in adulthood, but other neurological complications, including myoclonus, ataxia and tremor, may worsen. 

MEAK is caused by a specific pathogenic mutation in KCNC1.

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