Neuropathology in diabetes: general aspects with emphasis on the autonomic nervous system.
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Biomedical subjects
Publications and source records attributed to N Grover-Johnson.
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The sciatic/tibial/plantar nerve complex of normal aged rats displays striking morphological changes that are most pronounced distally. Nerve fiber abnormalities include: (a) large numbers of axonal glycogenosomes, mitochondria, dense membranous bodies, and decorated particles; (b) adaxonal Schwann cell processes sequestering portions of axoplasm; (c) swollen demyelinated and remyelinated axons, some encircled by supernumerary cellular processes; and (d) collagen pockets, denervated Schwann cell columns, and empty basal laminae. Abnormalities a and b were encountered with increasing frequency on descent through the tibial and plantar nerves. Abnormalities b, c, and d were found in lateral and medial plantar nerves, where they were associated with an enlarged endoneurial space. Found in animals kept in cages with smooth or wire-mesh floors, the incidence of these changes increased with advancing age. They are attributed to trauma and ischemia from chronic pressure on the plantar nerve.
The innervation of lower limb epineurial arterioles, specimens of which were obtained from six patients in the sympathectomy and from six patients in the nonsympathectomy diabetic groups at amputation for ischemic peripheral vascular disease, was compared by quantitative ultrastructural methods. Results demonstrated no statistically significant difference in the number of vasomotor axons present, the average axon to smooth muscle cell distance or the axon distribution pattern in the adventitia between the two diabetic groups of patients. A previous investigation has established that innervation of these arterioles is significantly reduced in patients with diabetes having end-stage ischemia of the lower limb when compared with similar patients without diabetes. The present results demonstrate that surgical lumbar sympathectomy does not significantly further reduce the already severely diminished number of vasomotor nerves in some diabetic arterioles. This observation offers a possible explanation for the poorer success rate of those with diabetes compared with those without diabetes in avoiding amputation of the limb after lumbar sympathectomy.
Intrauterine development and postnatal maintenance of dorsal root ganglion neurons are abnormal in familial dysautonomia, an autosomal recessive disorder associated with autonomic, motor and sensory deficits. Normally, dorsal root ganglion weight increases with age. This does not occur in the cervical plexus ganglia of dysautonomic patients. Neurons in dorsal root ganglia are found to be markedly diminished in the youngest patients and slow degeneration causes further depletion with age. Quantitative studies on C8 dorsal root ganglia show the normal neuron content to be between 42,500 and 53,600. In 3 patients with familial dysautonomia the range was 4,090-8,590 with the smallest number being in the oldest patient. Lateral root entry zones and Lissauer's tracts are severely depleted of axons. In older patients loss of dorsal column myelinated axons becomes evident and is first seen in lumbar fasciculus gracilis, cervical fasciculus cuneatus and interfascicular fasciculus. Temperature sensation is markedly impaired from infancy in familial dysautonomia. Loss of pain sensation is prominent and worsens with age. Vibration sense diminishes in adolescence and coordination of limb movements becomes poor in older patients. Neuron depletion in dorsal root ganglia and the progressive pattern of cord changes correlate well with these clinical observations.
Taste buds occur in the epithelium of the catfish barbel along its entire length. Two major cell types, light and dark cells, occupy the upper two-thirds of the taste bud. A third cell type, the basal cell, lies on the basal lamina and is essentially separated from the light and dark cells by a plexus of unmyelinated nerve fibers. The dark cells have branching processes, both apically and basally whereas the light cells have a single apical process and many basal processes. The apical processes of dark cells contain secretory granules, while the apical processes of light cells contain an abundant agranular endoplasmic reticulum. Light cell nuclei contain bundles of 10 nm filaments, often arranged in the shape of a cup or ring, but nucleoli are rarely seen. It is suggested that this morphology indicates a low degree of RNA synthesis by light cells. The basal cells contain large numbers of vesicles, about 60 nm in diameter, which are sometimes seen in clumps in relation to an adjacent nerve fiber in a configuration resembling a synapse. Curiously, although basal cells present a large surface to the basal lamina, there are no hemidesmosomes. This suggests that the basal cell does not originate from the epidermis.