Central core disease (CCD), also known as central core myopathy, is an autosomal dominantly inherited muscle disorder present from birth that negatively affects the skeletal muscles. It was first described by Shy and Magee in 1956. It is characterized by the appearance of the myofibril under the microscope. Signs and symptoms
The symptoms of CCD are variable, but usually involve hypotonia (decreased muscle tone) at birth, mild delay in child development (highly variable between cases), weakness of the facial muscles, and skeletal malformations such as scoliosis and hip dislocation.CCD is usually diagnosed in infancy or childhood, but some patients remain asymptomatic until adulthood to middle age. While generally not progressive, there appears to be a growing number of people who do experience a slow clinically significant progression of symptomatology. These cases may be due to the large number of mutations of ryanodine receptor malfunction, and with continued research may be found to be clinical variants. Pathophysiology
Central core disease is inherited in an autosomal dominant fashion. Most cases have demonstrable mutations in the ryanodine receptor type 1 (RYR1) gene, which are often de novo (newly developed). People with CCD are at increased risk for developing malignant hyperthermia (MH) when receiving general anesthesia. Diagnosis
The diagnosis is made based on the combination of typical symptoms and the appearance on biopsy (tissue sample) from muscle. The name derives from the typical appearance of the biopsy on light microscopy, where the muscle cells have cores that are devoid of mitochondria and specific enzymes.Respiratory insufficiency develops in a small proportion of cases.
In an fMRI study of DPD patients, emotionally aversive scenes activated the right ventral prefrontal cortex. Participants demonstrated a reduced neural response in emotion-sensitive regions, as well as an increased response in regions associated with emotional regulation. In a similar test of emotional memory, depersonalization disorder patients did not process emotionally salient material in the same way as did healthy controls. In a test of skin conductance responses to unpleasant stimuli, the subjects showed a selective inhibitory mechanism on emotional processing.Studies are beginning to show that the temporoparietal junction has a role in multisensory integration, embodiment, and self-other distinction. Several studies analyzing brain MRI findings from DPDR patients found decreased cortical thickness in the right middle temporal gyrus, reduction in grey matter volume in the right caudate, thalamus, and occipital gyri, as well as lower white matter integrity in the left temporal and right temporoparietal regions. However, no structural changes in the amygdala were observed.A PET scan found functional abnormalities in the visual, auditory, and somatosensory cortex, as well as in areas responsible for an integrated body schema.One study examining EEG readings found frontal alpha wave overactivation and increased theta activity waves in the temporal region of the left hemisphere. It is unclear whether genetics plays a role; however, there are many neurochemical and hormonal changes in individuals with depersonalization disorder. DPDR may be associated with dysregulation of the hypothalamic-pituitary-adrenal axis, the area of the brain involved in the "fight-or-flight" response. Patients demonstrate abnormal cortisol levels and basal activity.