Peripheral Neuropathy in Adult-Onset Diabetes Mellitus

The prevalence of peripheral neuropathy in patients with diabetes mellitus depends on the duration of the disease, with up to 50% of diabetic patients having peripheral neuropathy

clinically after 25 years of diabetes and nearly 100% having conduction abnormalities electrophysiologically.[35] Several distinct clinicopathologic patterns of diabetes-related peripheral

nerve abnormalities have been recognized ( Chapter 24 ). They are categorized as distal symmetric sensory or sensorimotor neuropathy, autonomic neuropathy, and focal or multifocal

asymmetric neuropathy. Individuals may develop any combination of these lesions; in fact, the first two (sensorimotor and autonomic) are often found together.

Morphology.

In patients with a distal symmetric sensorimotor neuropathy, the predominant pathologic finding is an axonal neuropathy. As with other chronic axonal neuropathies, there is often some

segmental demyelination. There is a relative loss of small myelinated fibers and of unmyelinated fibers, but large fibers are also affected. Endoneurial arterioles show thickening,

hyalinization, and intense periodic acid-Schiff (PAS) positivity in their walls and extensive reduplication of the basement membrane[36] ( Fig. 27-7 ). Whether the lesions are due to

ischemia[37] or metabolic derangement is unclear.

Clinical Course.

The most common peripheral neuropathy is the symmetric neuropathy that involves distal sensory and motor nerves. Patients with the neuropathy develop decreased sensation in the

distal extremities with less evident motor abnormalities. The loss of pain sensation can result in the development of ulcers that heal poorly because of the diffuse vascular injury in

diabetes, and are a major cause of morbidity. Another manifestation of diabetic neuropathy is dysfunction of the autonomic nervous system; this affects 20% to 40% of diabetics, nearly

always in association with a distal sensorimotor neuropathy.[38] Some patients, especially elderly

Figure 27-7Diabetic neuropathy with marked loss of myelinated fibers, a thinly myelinated fiber (arrowheads), and thickening of endoneurial vessel wall (arrow).

Figure 27-8Traumatic neuroma showing disordered orientation of nerve fiber bundles (purple) intermixed with connective tissue (blue).

Figure 27-9Spinal muscular atrophy with groups of atrophic muscle fibers resulting from denervation atrophy of muscle in early childhood.

Figure 27-10Diagram showing the relationship between the cell membrane (sarcolemma) and the sarcolemmal associated proteins. Dystrophin, an intracellular protein, forms an

interface between the cytoskeletal proteins and a group of transmembrane proteins, the dystroglycans and the sarcoglycans. These transmembrane proteins have interactions with the

extracellular matrix, including the laminin proteins. Dystrophin also interacts with dystrobrevin and the syntrophins, which form a link with neuronal-type nitric oxide synthetase

(nNOS) and caveolin. Mutations in dystrophin are associated with the X-linked muscular dystrophies, mutations in caveolin and the sarcoglycan proteins with the autosomal limb girdle

muscular dystrophies, and mutations in the a2-laminin (merosin) with a form of congenital muscular dystrophy.

Figure 27-11 A, Duchenne muscular dystrophy (DMD) showing variation in muscle fiber size, increased endomysial connective tissue, and regenerating fibers (blue hue). B, Western

blot showing absence of dystrophin in DMD and altered dystrophin size in Becker muscular dystrophy (BMD) compared with control (Con). (Courtesy of Dr. L. Kunkel, Children's

Hospital, Boston, MA.)

TABLE 27-4-- Other Muscular Dystrophies

Date: 2016-04-22; view: 990