What is central core disease (CCD)?

CCD is a congenital myopathy, meaning it is a muscle condition present from birth. It is inherited from a parent, usually by a dominant allele, and is caused by changes in the ryanodine receptor (RYR1) gene, which controls how calcium is released in the muscle cells. Those with this genetic condition often have low muscle tone, weakness in central muscles such as the hips and shoulders, and slow development in motor skills. It also makes them susceptible to malignant hyperthermia, which is a reaction triggered by certain anaesthesia drugs, causing overactivity in the muscles. This occurs as the muscle cells begin to release too much calcium in response to these triggering drugs.¹ 

CCD has slow or static progression, meaning muscle weakness can stay the same throughout many years. Over time, it can slowly progress, and patients may develop other complications, including breathing difficulties and scoliosis (curving of the spine). 

How to detect CCD?

Traditional methods to detect CCD include histopathology, where doctors take a muscle biopsy and examine it under a microscope and look for certain differences, including:

• Cores in the centre of muscle fibres don't have mitochondria and lack oxidative enzyme activity. These changes are mostly detected in type I muscle fibres that are used for endurance and steady movement
• Some of the muscle cells have nuclei in the wrong places (inside the cells instead of at the edge)
• Fat buildup in the muscle²

Whilst histopathology works efficiently, magnetic resonance imaging (MRI) complements clinical and genetic assessments and enables diagnosis to become more efficient, especially as it is non-invasive. 

Typical patterns seen in MRI for CCD include fatty infiltration and wasting, particularly in the vasti, sartorius, and adductor magnus muscles of the thigh, with relative sparing of the rectus femoris and adductor longus. In the lower leg, the soleus and gastrocnemius muscles are typically more affected, with the tibialis anterior often being relatively spared. These patterns can help differentiate CCD from other congenital myopathies.³ Similarly, MRI scans show muscle atrophy, shrinking or thinning of the muscles over time. 

Clinical correlation

1. Patients with more obvious muscle weakness tend to have a classic MRI pattern similar to the one stated above
2. Irregularities may occur in screenings for this with mild or subtle symptoms

MRI sequences

T₁-weighted sequences show how much fat has replaced the muscle, which often happens in CCD. This is shown as bright white areas on MRI images; therefore, the more weight in the muscle, the more muscle loss.

T₂-weighted sequences highlight swelling or inflammation in the muscle. A specific MRI technique is Short Tau Inversion Recovery (STIR), which uses the physical properties of the fat to nullify its signal, enabling fluid and swelling to stand out. This helps detect if the disease is currently active and if there is muscle loss. 

The mercury scale

The Mercuri scale is used to assess the extent of fat that has infiltrated and is detected by MRI.⁵

This is useful in identifying how the disease spreads and allows for comparison with other onset muscle diseases. 

Whole body MRI can take place where the entire body is scanned. An advantage of this is that it shows the overall pattern of muscle involvement across the body, helping to identify muscles that are affected but may not be symptomatic. It also aids doctors in choosing which muscle is best for biopsy, especially for early or mild cases of CCD.⁷

Three MRI techniques 

1. The Dixon technique

This technique measures the exact percentage of fat in the muscles and tracks small changes in fat infiltration over time.

2. T2 relaxation time mapping

This technique can detect inflammation or subtle damage even when there is no visible change. 

3. MRS (Magnetic Resonance Spectroscopy)

This technique analyses the chemical composition of muscle tissue and gives insight into energy use and muscle health, for doctors to determine the trajectory of the disease progression.⁶

Just as with any other technique, MRI has its advantages and limitations, as can be seen in the table below: 

Complete diagnosis of CCD

Diagnosis of CCD involves several assessments and tests, as follows: 

1. Clinical assessment
   • The doctor reviews the patient's symptoms and family history, preceded by a physical exam. The doctor examines you and asks questions about symptoms (what is bothering you, what do you feel is not quite right), when they started and or how often they affect you, if you have or had anyone in the family with similar issues
2. Genetic testing
   • The doctor may prescribe a blood test in order to look for changes in the RYR1 gene, which causes CCD.
3. Muscle biopsy
   • A small piece of a muscle is taken to be examined under a microscope to look for patterns as mentioned above.
4. MRI screening
   • MRI is done to confirm and detect whole-body patterns if previous steps were not clear enough. 

Future MRI techniques that can aid in and better diagnose inherited muscle disorders include diffusion imaging. This can track how water moves inside the muscle tissue to determine the structure of muscle and calculate muscle loss, demonstrating progression of disease. Artificial Intelligence is also being trained to spot patterns faster, for efficiency and accurate diagnosis. 

Summary

Central core disease is an inherited muscle disorder which can be detected using non-invasive MRI, saving time and resources for clinical organisations. It aids in avoiding unnecessary biopsies by providing a detailed image of the muscle and allows for continuous monitoring over time. However, there are some limitations to using MRI over biopsies, which include

+ cost issues, limited access to MRI equipment and the ability to standardise the above-mentioned MRI techniques to ensure diagnoses are performed in a similar way among clinical organisations. Ongoing research and global collaboration are working on helping to solve these issues in order to improve care for those with CCD.