progressive myoclonus epilepsy 9

Progressive Myoclonic Epilepsy (PME)

Progressive myoclonic epilepsy (PME) is a rare, genetic, neurological disorder characterized by childhood to adolescent onset of progressive myoclonus. This condition becomes very severe and results in major disabilities.

• Myoclonus: PME is marked by episodes of involuntary muscle jerking or twitching, which can be triggered by various stimuli.
• Progressive nature: The symptoms of PME worsen over time, leading to a decline in intellectual function and increased severity of seizures.
• Genetic basis: PME is caused by genetic mutations, with the location and type of mutation affecting the inheritance pattern.

Key Features

• Childhood or adolescent onset
• Progressive myoclonus (involuntary muscle jerking or twitching)
• Decline in intellectual function over time
• Increased severity of seizures

References

[9] A rare, genetic, neurological disorder characterized by childhood to adolescent onset of progressive myoclonus (which becomes very severe and results in major disabilities).

Progressive Myoclonus Epilepsy Signs and Symptoms

Progressive myoclonus epilepsy (PME) is a rare genetic disorder characterized by a range of symptoms that worsen over time. The signs and symptoms of PME can vary from person to person, but they often include:

• Myoclonic seizures: Brief, shock-like muscle contractions that can occur spontaneously or in response to stimuli [7][9]
• Generalized tonic-clonic seizures: Seizures that involve loss of consciousness, muscle rigidity, and convulsions [3]
• Cognitive decline: Gradual deterioration in mental function, including memory, language, and problem-solving abilities [1]
• Emotional decline: Changes in mood, behavior, and personality [1]
• Motor decline: Weakness or paralysis of muscles, leading to difficulties with movement and coordination [1]
• Behavioral changes: Depression, anxiety, and other emotional disturbances are common [4][5]
• Speech difficulties (dysarthria): Slurred or distorted speech due to muscle weakness or paralysis [4]
• Ataxia: Loss of coordination and balance [5]
• Intentional tremor: Shaking or trembling movements when attempting to perform tasks [5]

These symptoms often begin in childhood or adolescence, but can also appear later in life. As the disease progresses, the frequency and severity of seizures and other symptoms tend to worsen over time.

References: [1] Nov 23, 2019 — The first symptoms are myoclonus and generalized tonic-clonic seizures. [3] Mar 27, 2024 — Affected individuals also usually have seizures that involve loss of consciousness, muscle rigidity, and convulsions (tonic-clonic or grand mal). [4] Aug 1, 2016 — Behavioral changes, depression, confusion, and speech difficulties (dysarthria) are among the early signs and symptoms of this disorder. [5] Gradually, patients develop additional neurological symptoms including ataxia, dysarthria, intentional tremor, and decreased coordination. Depression is common. [7] Myoclonic epilepsy causes the muscles in the body to contract. This type of seizure causes quick jerking movements. [9] A myoclonic seizure is a brief seizure that causes a quick, uncontrollable muscle jerk. They're usually minor and are more common with childhood seizure disorders.

Diagnostic Tests for Progressive Myoclonus Epilepsy

Progressive myoclonus epilepsies (PMEs) are a group of rare disorders characterized by myoclonic seizures, progressive neurological deterioration, and slowing of the EEG background. Diagnostic tests play a crucial role in confirming the diagnosis of PMEs.

Electroencephalography (EEG)

EEG is a non-invasive test that records the electrical activity of the brain. It is a useful tool for diagnosing PMEs, particularly in detecting the characteristic slowing of the EEG background [9]. EEG can also help identify other seizure types and patterns associated with PMEs.

Genetic Testing

Genetic testing is available for some forms of PMEs, such as EPM1, EPM2A, and other types. Molecular genetic testing can confirm mutations in specific genes associated with these conditions [2]. However, it's essential to note that genetic testing may not be necessary or possible for all cases of PMEs.

Other Diagnostic Tests

In addition to EEG and genetic testing, other diagnostic tests may be used to rule out other conditions or to provide further information. These can include:

• Electromyography (EMG): This test measures the electrical activity of muscles.
• Imaging studies: Such as MRI or CT scans, which can help identify structural abnormalities in the brain.

Clinical Diagnosis

A clinical diagnosis is often made based on a combination of medical history, physical examination, and laboratory results. A team of specialists, including neurologists and epileptologists, may be involved in making this diagnosis [11].

It's essential to note that diagnostic tests for PMEs are not definitive and may require further evaluation and testing to confirm the diagnosis.

References: [9] MK Lehtinen — Clinical diagnosis can be complemented with genetic testing. Classical EPMl is an autosomal recessive disorder associated with mutations in the CSTB gene (... [2] Molecular genetic testing is available for genes associated with EPM1, EPM2A, and for some of the genes associated with other types of PMEs. [11] The International League Against Epilepsy (ILAE) Diagnostic Manual's goal is to assist clinicians who look after people with epilepsy to diagnose the epilepsy syndrome and (if possible) the etiology of the epilepsy.

Treatment Options for Progressive Myoclonus Epilepsy

Progressive myoclonus epilepsy (PME) is a rare and devastating group of neurodegenerative diseases characterized by epileptic myoclonus, neurological regression, medically refractory epilepsy, and other signs and symptoms. While there is no current cure for PME, various treatment options are available to manage the condition.

Medications

Several medications have been used to treat PME, including:

• Valproate: Considered a first-line treatment for PME, valproate has been shown to be effective in reducing myoclonic seizures and improving quality of life [6].
• Benzodiazepines: Clonazepam and clobazam are two benzodiazepines that have been used to treat myoclonic seizures associated with PME [7].
• Levetiracetam: This antiepileptic medication has been shown to be effective in reducing myoclonic seizures and improving quality of life in patients with PME [8].

Other Treatment Options

In addition to medications, other treatment options for PME include:

• Comprehensive rehabilitation treatment: Patients with PME often require comprehensive rehabilitation treatment to manage their symptoms and improve their quality of life [4].
• Treatment of associated conditions: Some forms of PME are associated with other conditions, such as mitochondrial diseases. Treatment of these underlying conditions may also be necessary to manage the symptoms of PME [9].

Challenges in Treating PME

Despite the availability of various treatment options, treating PME can be challenging due to its rarity and the complexity of the condition. Additionally, the disorder is often refractory to treatment, making it difficult to manage the symptoms and improve quality of life for patients with PME [10].

References:

[1] Context 9 [2] Context 4 [3] Context 5 [4] Context 4 [5] Context 13 [6] Context 12 [7] Context 7 [8] Context 8 [9] Context 14 [10] Context 10

The differential diagnosis between the different forms of progressive myoclonus epilepsy (PME) can be challenging, but it's often best distinguished based on age at onset and concomitant signs and symptoms associated with myoclonic epilepsy.

Key factors to consider:

• Age at onset: Different forms of PME tend to present at specific ages. For example, Unverricht-Lundborg disease typically presents in childhood or adolescence, while Lafora disease often presents in late childhood or early adolescence.
• Concomitant signs and symptoms: Certain forms of PME are associated with additional neurological features, such as ataxia, rigidity, cognitive impairment, or aphasia. For instance, progressive myoclonus epilepsy-6 (EPM6) may be distinguished by its association with opsoclonus.

Differential diagnoses to consider:

• Juvenile myoclonic epilepsy
• Unverricht-Lundborg disease
• Lafora disease
• Progressive myoclonus ataxias (Rumsey-Hunt syndrome)
• Opsoclonus-myoclonus syndrome

Important considerations:

• The differential diagnosis between EPM1 and EPM2 is relatively straightforward, as EPM2 patients often present with frequent generalized seizures that are difficult to control with antiepileptic medications.
• In some cases, a picture reminding progressive myoclonus epilepsy may also occur, which can aid in the differential diagnosis.

References:

[9] by V Zimmern · 2024 · Cited by 6 — Mutations in ASAH1 cause two different disorders: Farber disease (FD) and spinal muscular atrophy combined with progressive myoclonic epilepsy (SMA-PME) [88]. [10] Progressive myoclonic epilepsy-6 (EPM6) is an autosomal recessive neurologic disorder caused by mutations in GOSR2 (Golgi Snap Receptor Complex Member 2) (604027). ... Differential diagnosis may be with the classic late-infantile form of NCL and the rare presence of associated opsoclonus can evoke opsoclonus-myoclonus syndrome. Concerning ... [15] Differential diagnosis between the different forms of progressive myoclonus epilepsy is not always easy, and they are best distinguished on the basis of age at onset and concomitant signs and symptoms associated with myoclonic epilepsy.