A mouse model of focal dystonia due to mutations in DYT-TOR1A is being studied. Humans with this mutation have variable expressivity of diverse forms of dystonia, including cervical dystonia (ie, torticollis), writer's cramp, and lower limb dystonias. Histologic analysis of an affected muscle in one of the experimental mice is most likely to show which of the following?
Focal dystonia | |
Pathophysiology |
|
Clinical features |
|
Dystonia is a neurologic movement disorder characterized by sustained, involuntary muscle contractions, which force certain parts of the body into abnormal, sometimes painful movements or postures. Focal dystonias affect a single muscle or group of related muscles, the most common of which include cervical dystonia (ie, torticollis), blepharospasm (ie, eyelid twitching), and brachial dystonia (ie, writer's cramp).
Focal dystonias are usually classified as idiopathic; however, genetic mutations are becoming increasingly implicated. Focal dystonias are due to abnormal neural signaling pathways, which can arise from multiple locations in the brain (eg, basal ganglia, motor cortex, supplementary motor areas).
Because the dystonia originates from abnormal neural signaling, microscopic examination of the affected muscle is often relatively unremarkable. Histopathology may show normal muscle or muscle fiber hypertrophy (which occurs due to repetitive contractions).
(Choice A) Certain types of glycogen storage diseases (eg, Pompe disease) can lead to weakness and fatigue due to abnormal glycogenolysis in skeletal muscle. Muscle biopsy would show enlarged lysosomes containing periodic acid–Schiff (PAS)-positive material.
(Choice B) Duchenne and Becker muscular dystrophies are caused by mutations affecting dystrophin, a cytoplasmic protein vital for stabilization of the muscle cell membrane. Loss of cell membrane integrity leads to muscle fiber degeneration and progressive fibrofatty replacement.
(Choice C) Autoimmune muscle injury (eg, dermatomyositis, polymyositis) often shows an inflammatory cellular infiltrate (eg, lymphocytes) with muscle fiber necrosis, phagocytosis, and regeneration. Over time, the active inflammation and necrosis may be replaced by fibrosis.
(Choice E) Statin therapy can cause muscle fiber necrosis without a significant associated inflammatory infiltrate. Muscle aches and weakness are the most common complications of statin therapy.
Educational objective:
Focal dystonia is a neurologic movement disorder characterized by sustained, involuntary muscle contractions. Because these contractions are neurologically mediated, muscle biopsy may not show significant histologic changes, although muscle fiber hypertrophy is often present due to repetitive contractions.