The first section of this book covered techniques and general aspects of interpretation of pathological changes. We now turn our attention to specific disorders and the variable role muscle biopsy has in them. In some conditions, such as spinal muscular atrophy, myotonic dystrophy type 1 and facioscapulohumeral muscular dystrophy, molecular analysis is very reliable and a muscle biopsy has very little to contribute from a diagnostic point of view. In other disorders, such as myasthenia gravis, diagnosis is often based on clinical and electrodiagnostic evaluation. In others, however, such as the various muscular dystrophies and the congenital myopathies, there are clinical similarities and a biopsy makes an important contribution to providing a definitive diagnosis.
In addition to the well-defined pathological changes that occur in various neuromuscular disorders, skeletal muscle may also be directly or indirectly involved in many acute or chronic diseases. Biopsy may reveal striking and unexpected changes in situations where involvement of muscle is not clinically apparent. It is also possible that even such common symptoms as the aches and pains that accompany so many illnesses, or the weakness following periods of bedrest, may be associated with marked biochemical, histochemical or structural changes within the muscle.
In this section we try to cover systematically the pathological changes in the known inherited and acquired neuromuscular disorders. As in the previous edition, we include a chapter on the pathological effects of drugs and various toxins as there is a growing awareness of this, and the pathologist needs to bear in mind possible effects of both prescribed drugs and abuse of various substances.
The molecular revolution has led to the identification of many gene defects and protein products responsible for neuromuscular disorders. With the increasing application of whole genome and whole exome sequencing, the clinical and pathological spectra associated with specific genes are constantly evolving and new pathogenic genes identified. The significance of a genetic variant, however, is not always clear, and muscle pathology then has a role in determining if it is pathogenic. Proteins located in every part of a muscle fibre have been found to be responsible for a neuromuscular disorder, the extracellular matrix, the plasma membrane, the cytoskeleton, the Golgi, the internal membrane systems, nuclei, myofibrils, neuromuscular junction and the cytosol (summarized in Figs. 8.1–8.3 ). In addition, many diseases are associated with defects in the mitochondria or glycogen metabolism affecting the energy metabolism of the cells, and defects in autophagocytosis, lysosomes and proteasomes give rise to muscle diseases by failure of the normal turnover of cell components.