Introduction
Unverricht-Lundborg disease(ULD) is a type of progressive myoclonus (contraction of a group of muscles that is spasmodic) and epilepsy (a neurological disorder that causes unusual sensations and behaviors). It is caused by gene mutations encoding the cystatin B gene. There is a deficiency of cystatin B which creates the features of Unverricht-Lundborg disease, including myoclonic seizures, ataxia (loss in muscle control), and neuronal loss. In juvenile myoclonic epilepsy, there is no role of this gene. It is considered a severe and disabling condition. It occurs in adults and at an early age, around twelve to thirteen. Both males and females are equally affected. At the initial stage, generalized tonic-clonic seizures(GTCSs) occur. It involves the symptoms of involuntary muscle movements and tonic-clonic seizures. There is absence of specific clinical or pathological markers. The diagnosis of Unverricht-Lundborg disease is confirmed by genotyping. It totally depends upon molecular biological techniques. For the management of Unverricht-Lundborg disease, social support is important, along with medical treatment. Temporarily alcohol may be used in small amounts to relieve myoclonus.
What Is Unverricht-Lundborg Disease?
Unverricht-Lundborg disease is defined as a neurodegenerative disorder that is an inherited type, and its a form of progressive myoclonus epilepsy. The reactivating factor of this disease is exercise. The person affected with this disease will also develop ataxia, lack of coordination, intention tremor, and difficulty in speaking (dysarthria). Unverricht-Lundborg disease, also known as Baltic myoclonus or progressive myoclonic epilepsy type 1 (EPM1), is a rare genetic disorder that belongs to a group of conditions called the progressive myoclonic epilepsies. It is characterized by a combination of myoclonus (sudden, involuntary muscle jerks) and epilepsy.
What Are the Causes Of Unverricht-Lundborg Disease?
Unverricht-Lundborg disease is mainly caused by a genetic mutation (harmful changes in genes). The most common gene responsible for it is the CSTB gene (cystatin B gene). It is an autosomal recessive inheritance disease. So that the diagnosis of this disease is confirmed by genetic testing. The genes responsible for this disease are CSTB, SCARB2, and PRICKLE1. It becomes triggered by sensory stimulations such as light and touch. Along with genes, other factors are also involved. The person with this disease has more dopamine receptors in certain brain areas. These dopamine are responsible for developing myoclonus.
What Are the Symptoms Of Unverricht-Lundborg Disease?
Unverricht-Lundborg disease is a genetic disease that is caused by one or more genes that are not working properly. The onset of this disease occurs in late childhood and early age. It may appear in childhood and as well as in teenagers. Symptoms may begin in a single age range or during several age ranges. The hallmark symptom of Unverricht-Lundborg disease is myoclonus, which usually begins in childhood or adolescence. Myoclonus can affect various muscle groups and can range from mild to severe, causing significant impairment in daily activities. In addition to myoclonus, individuals with the condition may experience tonic-clonic seizures (also known as grand mal seizures), which involve loss of consciousness, convulsions, and muscle rigidity.
The following are the symptoms of
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GTCS (Generalized Tonic-Clonic Seizures) - It generally occurs at an initial stage, mostly during awakening and less during sleep.
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Cascade Seizures - It is characterized by increasingly intense and violent myoclonic jerks. Some patients become less normal during this type of seizure.
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Myoclonus - It is present in the very early stage, which predominates at the time of awakening. Myoclonus becomes movement-related and increases with stress. This is very much challenging for physically challenged patients. Patients may fear using stairs or physical strain, and bilateral, violent myoclonus becomes less apparent (unless the patient is challenged or stressed). Myoclonus is less severe or even absent at rest or during sleep. Myoclonus causes major disability; a wheelchair may have to be used, and feeding becomes problematic and slow, especially with the intake of liquids (using a straw may be helpful) in severe cases.
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The patient becomes mentally weak and has a fear of using stairs.
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Neurological symptoms like ataxia, impaired walking, and instability.
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Loss of consciousness.
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Feeding problems.
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Suicidal behavior.
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Mental and emotional disturbances.
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Depression.
How To DiagnoseUnverricht-Lundborg DIsease?
The absence of specific clinical markers lacks confirmatory diagnosis. The genotyping of the disease is necessary. The diagnosis of ULD relies on a combination of positive signs and the absence of more specific symptoms and markers. Molecular biological techniques are used to diagnose ULD. It is thought that this procedure, which remains costly, should be justified by solid electro-clinical evidence and should not be performed, together with various tests, to screen all possible genetic causes in poorly assessed subjects with epilepsy and myoclonus.
The following are the ways to diagnose Unverricht-Lundborg disease:
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Clinical Symptoms - A combination of history taking and examination shows the absence of major and progressive cognitive impairment.
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Electrocencephalogram (EEG) - EEG is used to assess brain imaging. A thorough evaluation of the EEG shows the electrical disturbances in the brain.
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Genetic Testing - The genetic test is done to determine the mutation in the gene.
The diagnosis of ULD should not be given to the family before final and definitive confirmation because it may affect the surrounding. The diagnosis should be given to caregivers and patients when it is confirmed.
What Is the Treatment Of Unverricht-Lundborg DIsease?
Several antiepileptic drugs are used for reducing seizures and managing Unverricht-Lundborg disease's other symptoms. The first line of drug choice is Valproic acid. Levetiracetam, Clonazepam, and Piracetam (high dose) can treat seizures. Other common drugs, such as Topiramate and Zonisamide, are suggested for Unverricht-Lundbirg disease.
Conclusion
Increased knowledge about this disease, along with social support and medication, will improve the prognosis of patients with this disease. There is no cure to repair the CSTB gene after mutation. Studies suggest that the absence of cystatin B leads to the death of affected neurons. Cystatin B is a protective molecule of the brain. The prognosis of the disease is very limited, with varying but fairly stable levels of disability. However, the outcome in adults ranges from independent, active life with minimal impairment to severe disability and wheelchair-bound or even bedridden patients. The incidence of death is low or occurs due to accidents or suicide. Little love and care are required for the patient to overcome mental disturbances.
