Unverricht-Lundborg Disease: Symptoms, Causes, Treatment

What are the symptoms of Unverricht-Lundborg disease?

Unverricht-Lundborg disease (ULD) is a rare, inherited form of progressive myoclonic epilepsy. It primarily affects the nervous system and typically begins in childhood or adolescence. The symptoms of ULD include:

Myoclonus: Sudden, involuntary muscle jerks, which may be triggered by movement, stress, or sensory stimuli like light or sound.
Epileptic seizures: Generalized tonic-clonic seizures (convulsions), often occurring alongside the myoclonic jerks.
Ataxia: Difficulty with coordination and balance, which can worsen over time.
Tremors: Shaking, particularly in the hands.
Cognitive decline: Mild to moderate, including memory and learning difficulties, although intelligence is often preserved in early stages.
Emotional and behavioral changes: Anxiety, depression, or irritability, often linked to the challenges of living with the disease.

The severity and progression of symptoms can vary, but they generally worsen over time, affecting daily activities and quality of life.

What are the causes of Unverricht-Lundborg disease?

Unverricht-Lundborg disease (ULD) is caused by mutations in the CSTB gene, which provides instructions for making a protein called cystatin B. This protein plays a role in protecting cells from damage by inhibiting certain enzymes (proteases) that break down proteins. In ULD, mutations in the CSTB gene reduce the amount or function of cystatin B, leading to the gradual degeneration of nerve cells in the brain.

Key points about the causes of ULD:

Genetic inheritance: ULD is inherited in an autosomal recessive manner. This means that an individual must inherit two copies of the mutated CSTB gene (one from each parent) to develop the disease.
Mutation type: The most common mutation is an expansion of a repetitive DNA sequence in the CSTB gene, which disrupts the production of functional cystatin B protein.
Nerve cell degeneration: The deficiency of cystatin B leads to nerve cell damage, particularly in the parts of the brain that control movement and coordination, which causes the characteristic symptoms of the disease.

Since ULD is a genetic disorder, the underlying cause is always linked to the CSTB gene mutations, and it runs in families where both parents are carriers of the mutated gene.

What is the treatment for Unverricht-Lundborg disease?

The treatment for Unverricht-Lundborg disease (ULD) primarily focuses on managing symptoms, as there is currently no cure for the condition. The goal is to control the myoclonic jerks, seizures, and other symptoms to improve the patient’s quality of life. Treatment typically includes:

1. Medications

Antiepileptic drugs (AEDs): These are the mainstay of treatment to control seizures and myoclonus. Commonly used AEDs include:
Valproic acid: Often considered first-line therapy for ULD to control seizures and reduce myoclonus.
Clonazepam: Can help reduce myoclonic jerks.
Levetiracetam: Effective for both myoclonic jerks and seizures with fewer side effects.
Zonisamide: Another option for controlling seizures and myoclonus.
Piracetam: Can be effective for myoclonus in some cases. Note: Certain AEDs, such as phenytoin and carbamazepine, are generally avoided because they can worsen myoclonus.

2. Physical and Occupational Therapy

Physical therapy: Helps improve coordination, strength, and mobility, particularly as myoclonus and ataxia can interfere with movement.
Occupational therapy: Aims to help patients maintain independence in daily activities and manage tasks despite the physical challenges caused by ULD.

3. Speech Therapy

As the disease progresses, some patients may develop speech and swallowing difficulties. Speech therapy can assist in improving communication and ensuring safe swallowing.

4. Psychological Support

Patients with ULD may experience anxiety, depression, or emotional difficulties due to the chronic nature of the disease. Psychological counseling or cognitive behavioral therapy (CBT) can help manage mental health challenges.

5. Lifestyle Modifications

Avoid triggers: Since stress, fatigue, and certain sensory stimuli (like flashing lights or loud sounds) can exacerbate myoclonus or seizures, patients are advised to avoid known triggers.
Good sleep hygiene: Ensuring regular and sufficient sleep can help reduce seizure activity.

6. Regular Monitoring

Since ULD is a progressive disorder, regular follow-up with healthcare providers, including neurologists, is important to adjust treatments and address changes in symptoms over time.

7. Emerging Therapies and Research

Gene therapy: Although not currently available, research into gene therapy for ULD is ongoing. Future treatments may focus on correcting the underlying genetic mutation in the CSTB gene.

Management is typically individualized, depending on the severity of symptoms and the patient’s response to treatment.