Normal peripheral nerve, microscopic

This normal peripheral nerve in longitudinal section shows slightly wavy, elongated cell bodies (axons, ♦) of the fibers. A thin connective tissue layer, the endoneurium (◄), surrounds individual nerve fibers. A perineurium encloses a fascicle of nerve fibers and forms a blood-nerve barrier. The epineurium surrounds a whole nerve. Motor fibers are thickly myelinated. Many sensory fibers are unmyelinated, although fibers for fine discriminatory senses, such as touch and vibration, have myelin. The major axonal myelin sheath component is myelin protein zero; myelin basic protein is the second most common structural protein.

Normal peripheral nerve, microscopic

This normal peripheral nerve in transverse section with toluidine blue stain in the left panel has blue myelin around a normal number and distribution of thickly (▲) and thinly (▼) myelinated fibers. Pale background areas have small unmyelinated fibers; Schwann cell cytoplasm can surround multiple unmyelinated axons but do not wrap them in myelin; in myelinated nerves, Schwann cells associate with only one axon. Overall, unmyelinated axons 0.4 to 2 μm in diameter are more numerous than myelinated axons 1 to 20 μm in diameter. Myelinated fibers transmit impulses with higher conduction velocity (6 to 120 m/s) than nonmyelinated fibers (0.5 to 2 m/s). The larger the fiber, the faster the conduction velocity. Note the even spacing between the dark myelin lamellae around an axon in the electron micrograph in the right panel .

Normal peripheral ganglion, microscopic

This peripheral ganglion has nerve cell bodies (♦) and surrounding satellite cells (▼) and interstitial fibroblasts (■). The nerve cell bodies have fine pink Nissl granules, and some nerve cells display light-brown lipochrome pigment within their cytoplasm. There is no blood-nerve barrier around a ganglion. The sensory and the postganglionic autonomic nerve fibers have neuronal cell bodies located in ganglia associated with cranial nerves, dorsal spinal roots, and autonomic nerves. Ganglia and Schwann cells are embryologically derived from the neural crest.

Normal skeletal muscle, microscopic

Skeletal muscle fibers are seen here in cross-section at low magnification. There are several fascicles. A connective tissue band, the perimysium (♦), surrounds each individual fascicle. An individual muscle fiber within the fascicle is invested by the endomysium (▲). The entire muscle is surrounded by a connective tissue band called the epimysium . The muscle cell nuclei are located at the periphery of the fibers. Each fiber is bounded by a sarcolemma, which projects into the cytoplasm as T tubules containing a high concentration of calcium ions. A nerve impulse causes depolarization with release of the calcium ions to initiate muscle contraction.

Normal skeletal muscle, microscopic

In longitudinal section, these skeletal muscle fibers have prominent cross-striations formed by the Z discs. The thin actin filaments are attached to Z discs and interdigitate with the thick myosin filaments for muscle contraction. The functional contractile unit is a sarcomere between two Z discs. The additional proteins, tropomyosin and troponin complex, regulate actin, myosin, and calcium binding. The skeletal muscle fiber is a multinucleated cell with numerous sarcolemmal nuclei (▲) at the periphery of each muscle fiber. Occasional satellite cells (▼) provide for maintenance, repair, and regeneration of injured fibers.

Normal skeletal muscle, microscopic

In cross-section with adenosine triphosphatase (ATPase) stain at pH 9.4, the normal pattern of type 1 and type 2 skeletal muscle fibers within fascicles is seen. These fibers are intermixed in a checkerboard pattern. The type 1 fibers (slow twitch, oxidative) are light tan, and the type 2 fibers (mainly glycolytic) stain dark brown at this pH. Type 1 fibers have more mitochondria and more myoglobin for sustained contraction. A lower motor neuron innervates a group of myofibers, known as motor units . The motor units are small in number (<50 myofibers) when fine motor control is required (extraocular muscles) and large (hundreds of myofibers) in postural muscles, such as the quadriceps femoris.

Wallerian degeneration, microscopic

Wallerian degeneration occurs distal to the site of an injury with traumatic transection of a peripheral nerve. In this distal nerve segment in longitudinal section, small axonal and myelin fragments lie within myelin ovoids as vacuolar digestion chambers (▲). Regeneration is possible because the proximal nerve stump undergoes axonal sprouting, and Schwann cells proliferate to remyelinate the nerve fiber. Regeneration proceeds along the course of the degenerated axon at a rate of approximately 2 mm/day.

Peripheral nerve with axonal sprouting, microscopic

Here is axonal regrowth in a cross-section of a peripheral nerve following transection (axonotmesis), with clusters of regrowing axons (▼) surrounded by the basement membrane of a Schwann cell. Such small clusters of thinly myelinated fibers represent regrowth (axonal sprouting). With ongoing disease from neuropathies, axonal degeneration and regeneration may coexist.

Denervation atrophy, microscopic

This modified Gomori trichrome stain shows the neurogenic form of skeletal muscle atrophy, with the characteristic pattern of “grouped atrophy” (▼) of muscle fibers that have lost their innervation from a lower motor neuron. These affected muscle fibers do not die, but “downsize” with loss of actin and myosin, becoming small and angular. Denervation could result from traumatic nerve injury, peripheral neuropathy, or a lower motor neuron disease, such as amyotrophic lateral sclerosis. Remaining axons may reinnervate myofibers as a single fiber type (“type grouping”).

Guillain-Barré neuropathy, microscopic

Neuritis secondary to an acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome) is shown in a longitudinal section of peripheral nerve with lymphocytic infiltrates (▲) that damage the nerve, followed by macrophages that strip off the myelin lamellae, leading to demyelination with relative preservation of axons in most cases. There is an acute ascending paralysis that occurs over days, advancing distally to proximally. Respiratory paralysis is life threatening. A bacterial (Campylobacter jejuni) or viral (cytomegalovirus) illness may precede the onset of this disease. Recovery occurs in most patients receiving ventilatory support.

Demyelination, electron microscopy

This peripheral nerve shows a demyelinated axon next to an internode (◄). The axoplasm in the lower demyelinated portion (■) is swollen. The Schwann cell is attracted to the demyelinated axon and remyelinates it. In Guillain-Barré syndrome, there is segmental demyelination between internodes. During recovery from this form of inflammatory neuropathy, these areas become remyelinated. Examination of the cerebrospinal fluid shows few inflammatory cells, little or no pleocytosis, but an elevated protein. Molecular mimicry to antigens of infectious agents, such as Campylobacter jejuni lipopolysaccharide, may elicit antibodies that cross-react with ganglioside GM1 in myelin.

Chronic inflammatory demyelinating polyneuropathy, microscopic