What is Myoclonic Epilepsy and Ragged Red Fibers?
Myoclonic epilepsy with ragged red fibers (MERRF), also known as Fukuhara syndrome, is a complex disorder that affects multiple body systems. It is primarily known for causing myoclonus (sudden, quick involuntary muscle jerks) and seizures. Other symptoms can include problems with coordination (cerebellar ataxia), muscle weakness (myopathy), irregular heartbeats (cardiac arrhythmia), loss of hearing and sight, and dementia. MERRF results from certain changes in the mitochondrial DNA, the genetic material in the mitochondria, which are like the energy factories of our cells. The most common genetic change occurs in the tRNA (Lys) gene and is found in over 75% of patients. A noticeable sign of MERRF can be seen on a muscle biopsy, where muscle fibers appear as “ragged red.” This condition was first thoroughly described in 1980 by a scientist named Fukuhara and is quite rare. It’s recognized by the National Organization for Rare Disorders (NORD), an organization dedicated to helping people with rare diseases.
What Causes Myoclonic Epilepsy and Ragged Red Fibers?
Mitochondria are tiny parts of the cell that have their own DNA (or genetic material). This specific DNA is a small, circular structure made up of 16,569 components known as base-pairs. This mitochondrial DNA is important because it contains 37 genes that help it produce an energy source for the cell, known as adenosine triphosphate (ATP).
Interestingly, mitochondrial DNA is not passed down from both parents like most genetic material. Only the mother passes it on to her children. So, all your mitochondria are inherited vertically from your mother.
A disease known as MERRF, has been linked to multiple changes or mutations in mitochondrial DNA. In fact, about 80% of patients with MERRF have one specific mutation. Other mutations associated with MERRF have also been identified. Currently, the details of each mutation is not within the scope of this document.
Risk Factors and Frequency for Myoclonic Epilepsy and Ragged Red Fibers
MERRF, or Myoclonic Epilepsy with Ragged Red Fibers, is a condition for which we don’t have a lot of data. However, it’s believed to be pretty rare, affecting fewer than 1 in 100,000 people. Studies conducted in Europe have given us a bit more insight into its prevalence in particular regions. For example, the most prominent mutation associated with MERRF was found in up to 1.5 people in every 100,000 in Northern Finland, and 0.39 in every 100,000 adults in Northern England. Whereas for the pediatric population in western Sweden, the prevalence was up to 0.25 per 100,000.
Importantly, MERRF doesn’t discriminate based on gender; it affects males and females equally. The first symptoms tend to show up in childhood or early adulthood. It’s also worth mentioning that the actual number of people with mitochondrial diseases like MERRF could be higher than these figures suggest, due to many cases likely going undiagnosed.
Signs and Symptoms of Myoclonic Epilepsy and Ragged Red Fibers
MERRF, short for Myoclonic Epilepsy with Ragged Red Fibers, is a specific type of mitochondrial disease. One of the main features that sets it apart from other similar conditions is the progressive development of a certain type of seizure known as myoclonic epilepsy. Usually, the condition begins in childhood and children who have it typically show normal early development. The myoclonus, or involuntary muscle jerks, that these children experience can come and go or be constant. Often, light can trigger these jerks, and they may also get worse with certain actions or stimuli. Patients with MERRF usually have other types of seizures as well.
There are other symptoms that tend to appear in patients with MERRF. These can include issues with balance and coordination (cerebellar ataxia), hearing loss (sensorineural deafness), being shorter than average (short stature), fat under the skin that feels like a lump (cutaneous lipomas), and issues with their muscles (clinical myopathy) that appears similar to limb-girdle muscular dystrophy. Some patients may also develop irregular heartbeats (cardiac arrhythmias), types of heart disease (cardiomyopathy), and cognitive decline or dementia. However, the latter generally occurs later in the disease process.
The symptoms of MERRF can vary greatly from person to person, even among family members with the condition. The balance of normal and abnormal cells within each tissue (mitochondrial heteroplasmy) is a major factor contributing to this variability. Sometimes, patients with MERRF may have symptoms of other, overlapping conditions, such as strokes (in MERRF/MELAS overlap) or issues with their eyes (in MERRF/Kearns-Sayre syndrome overlap). This can complicate the process of diagnosis.
- Myoclonic epilepsy
- Other types of seizures
- Balance and coordination issues (cerebellar ataxia)
- Hearing loss (sensorineural deafness)
- Shorter than average height (short stature)
- Fat under the skin that feels like a lump (cutaneous lipomas)
- Muscle issues similar to limb-girdle muscular dystrophy (clinical myopathy)
- Irregular heartbeats (cardiac arrhythmias)
- Types of heart disease (cardiomyopathy)
- Cognitive decline or dementia (usually appearing later)
Testing for Myoclonic Epilepsy and Ragged Red Fibers
In order to diagnose a condition known as MERRF, doctors might conduct a laboratory test to observe the lactic acid levels in both the blood and cerebrospinal fluid (liquid around the brain and spinal cord). In patients presenting MERRF symptoms, these levels are often increased, especially after physical activity. Additionally, a protein commonly present in cerebrospinal fluid may also show an increase, but it rarely surpasses 100mg/dl. This condition may also cause an increase in creatine kinase, a molecule associated with muscle damage.
However, as other diseases can resemble MERRF, medical professionals strive to rule out potential causes such as autoimmune inflammatory disorders, hormonal imbalances (like diabetes or thyroid disorders), vitamin B12 deficiency, and issues with collagen formation.
Further along the diagnostic road, doctors may use imaging techniques to inspect what’s happening inside the body. Methods like magnetic resonance imaging (MRI) or a computed tomography (CT) scan can show changes in the grey matter of the brain at the early stages of the disease; these changes occur later in the “white matter”. Symptoms visible in scans can extend to cerebral atrophy (brain shrinkage), cerebellar atrophy with calcification (hardening) in a region called the dentate nucleus, and various other alterations due to prolonged neuron loss. Doctors may detect substantial levels of lactic acid with an MRI-associated technique called magnetic resonance spectroscopy (MRS).
Then there are electrophysiological tests, which allow doctors to monitor the electrical activity of your brain and muscles. Through an electroencephalogram (EEG), doctors may note slow activity in the brain along with abnormal electrical discharges potentially induced by light stimulation. Other techniques such as electromyography and nerve conduction studies (EMG/NCS) can reveal signs of muscle disease, and sometimes nerve disease.
Getting a muscle biopsy can help diagnose MERRF. In such a procedure, a small sample of muscle tissue is examined under a microscope. The presence of atypical red-ragged fibers is a common finding with MERRF, seen in over 90% of patients.
Last but not least, genetic testing also plays a vital role in diagnosing MERRF. Certain genetic mutations, like an A-to-G mutation in a specific part of the mitochondrial DNA, are observed in about 80% of MERRF patients. If a mutation is detected in a family member, other at-risk relatives can also be tested.
Treatment Options for Myoclonic Epilepsy and Ragged Red Fibers
MERRF, like many other conditions related to the mitochondria, does not have a specific treatment or cure. However, certain treatments may help slow down its progression. These treatments often include supplements like Coenzyme Q10 (a substance similar to a vitamin), vitamin B-complex which is a group of essential vitamins that play a role in cell metabolism, and L-carnitine, a nutrient that helps the body turn fat into energy.
Symptomatic management, which is addressing the symptoms of the condition, is key for patients with MERRF. For example, antiepileptic drugs are given to help manage myoclonic seizures and epilepsy, two complications that are commonly associated with MERRF. It’s important to note that certain antiepileptic medications, such as sodium valproate, should be used with caution as they can interfere with some body functions and potentially worsen liver function. Other medications may also worsen the seizure episodes, which underscores the need for careful medication choice under professional guidance.
There have been no direct comparisons of different antiepileptic drugs in the treatment of epilepsy in MERRF, but some medical experts recommend levetiracetam, topiramate, clonazepam, or zonisamide. Other complications, like heart rhythm problems, hearing loss, and muscle disease, are treated as per standard protocols.
Additionally, it’s crucial for individuals with MERRF to avoid substances that may adversely affect the mitochondria, such as certain antibiotics, tobacco smoke, and alcohol.
What else can Myoclonic Epilepsy and Ragged Red Fibers be?
MERRF is a type of seizure disorder that can be difficult to tell apart from other similar conditions, like Unverricht-Lundborg, Lafora body disease, neuronal ceroid lipofuscinosis, or sialidoses. Usually, tests for high lactic acid levels, certain features in a muscle biopsy (red-ragged fibers), and genetic testing help to confirm a diagnosis of MERRF.
In some cases, MERRF can also get confused with other disorders related to mitochondria, especially when patients show symptoms common to multiple conditions. Examples of these overlaps include multiple stroke symptoms (MERRF/MELAS overlap) or symptoms relating to deteriorating eye muscles and vision (MERRF/Kearns-Sayre syndrome overlap).
What to expect with Myoclonic Epilepsy and Ragged Red Fibers
MERRF is a long-term, gradually worsening condition. As noted, different people can show different types and severity of symptoms, and at different ages, even within the same family. As a result, it’s challenging to accurately predict the course of the disease, but generally, the outlook is often not positive.
Possible Complications When Diagnosed with Myoclonic Epilepsy and Ragged Red Fibers
People with MERRF, a genetic disorder, face a higher risk of several health problems. These include heart irregularities and weak heart muscle leading to heart failure and sudden death. They are prone to head injuries because of seizures, as well as complications with breathing, spinal curvature, diabetes, and thyroid issues.
Increased Risk Factors for MERRF Patients:
- Heart irregularities
- Weak heart muscle leading to heart failure & sudden death
- Potential head injuries from seizures
- Complications with breathing
- Spinal curvature (kyphoscoliosis)
- Diabetes
- Thyroid issues
Preventing Myoclonic Epilepsy and Ragged Red Fibers
Education about MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a disease that impacts many systems of the body and worsens over time, is vital for the patient and their family. For men who have MERRF with a mutation in their mitochondrial DNA, this disease can’t be passed on to their kids. On the other hand, a woman with this mitochondrial DNA mutation will pass this disease on to all of her children. Also, if a mother has been diagnosed with MERRF, it is possible to identify if the unborn child might also have MERRF.
For those suffering from MERRF and their family members who don’t show symptoms but could potentially develop the disease, it’s necessary to have regular check-ups—preferably every 6 to 12 months in the beginning—to track the progression of the disease and detect any new symptoms. They are also advised to undergo yearly screenings to check for possible complications. These evaluations typically involve examinations from a neurologist (brain and nerve specialist), ophthalmologist (eye specialist), cardiologist (heart specialist), and endocrinologist (hormone specialist).
