MACROSCOPIC AND MICROSCOPIC APPEARANCES

In most cases, the brain appears macroscopically normal and scant abnormalities (mild cortical gliosis, slight prominence of microglia) are demonstrable by conventional staining. Use of appropriate silver impregnation techniques reveals argyrophilic material containing aluminum in the choroid epithelium and to a lesser extent in the glia and neurons, particularly in the brain stem nuclei.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The peripheral neuropathy caused by chronic trivalent arsenical intoxication may be associated with chromatolysis and loss of anterior horn cells. In patients with acute hemorrhagic leukoencephalopathy complicating organic pentavalent arsenical administration, the brain is swollen and contains numerous small and occasional larger foci of hemorrhage (Fig. 25.1). Histology reveals fibrinoid necrosis of many parenchymal blood vessels and hemorrhage into the surrounding tissue (Fig. 25.1). Some of the blood vessels are surrounded by a fibrin exudate containing a mixed inflammatory infiltrate. The findings are described in more detail in Chapter 20.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Descriptions of the neuropathologic findings of bismuth toxicity are sparse. Bismuth can be demonstrated histochemically in neurons, glia and the walls of blood vessels. However, most of the described abnormalities such as a loss of Purkinje cells and degeneration of pyramidal cells in the hippocampus are probably due to hypoxia.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Changes reported in acute lead encephalopathy include brain swelling and congestion, and in some cases petechial hemorrhages or hydrocephalus.

Microscopically, endothelial swelling, and capillary necrosis and thrombosis have been reported, with a proteinaceous exudate in the perivascular spaces and extending into the adjacent brain tissue. Periodic acid–Schiff (PAS)-positive globules may be seen within the exudate and in astrocytes. Other reported findings include widespread gliosis, and, in some cases, foci of necrosis or spongiosis.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

In contrast to idiopathic Parkinson’s disease (see Chapter 28), the substantia nigra is preserved, but there is gliosis and a loss of neurons from the pallidum and subthalamic nucleus and, to a lesser extent, from the caudate and putamen.

MACROSCOPIC APPEARANCES

There are no reports of macroscopic abnormalities in the brain following exposure to inorganic mercury. Survivors of methylmercury intoxication develop moderate to marked brain atrophy, particularly of the calcarine cortex and cerebellum.

MICROSCOPIC APPEARANCES

There is preferential loss of small neurons, particularly from the granule cell layer of the cerebellum and the primary visual, auditory, and somatosensory regions of the cerebral cortex, in which small neurons predominate. In severe cases, particularly in children, neuronal loss is more extensive and there is spongiform cortical degeneration. Other features include an associated gliosis and, in acute lesions, infiltration by macrophages. Degeneration of dorsal root ganglion cells results in some loss of nerve fibers from the posterior columns of the spinal cord. Sprouting of Purkinje cell dendrites is a prominent feature in long-term survivors, in whom granular deposits of mercury are demonstrable in astrocytes, microglia, and neurons (Fig. 25.2).

Fetal intoxication can cause neuronal heterotopia and cortical dysplasia in addition to degenerative lesions. Extensive architectural disruption of neuronal elements can be observed within the cerebellum.

 chromatolysis of motor neurons

 degeneration of posterior column fibers.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Triethyltin causes striking white matter edema in brain and spinal cord (Fig. 25.4) due to the accumulation of fluid in vacuoles within the myelin sheaths (Fig. 25.4). The vacuoles are formed by separation of myelin along intraperiod lines (Fig. 25.4). Trimethyltin does not cause intramyelinic edema, but is toxic to neurons in the hippocampus, basal ganglia, entorhinal cortex, and amygdala. It elicits specific apoptotic destruction of pyramidal neurons in the CA3 region of the hippocampus and in other limbic structures.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The brain and spinal cord appear macroscopically normal. Histology reveals swelling and degeneration of the distal part of longer axons in peripheral nerves and the posterior spinal, spinocerebellar, and corticospinal tracts. The swellings contain accumulations of neurofilaments.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The brain and spinal cord appear macroscopically normal, and histologic changes are sparsely documented. In the peripheral nervous system, carbon disulfide intoxication results in axonal swellings (Fig. 25.5), which contain abnormal accumulations of neurofilaments, and distal nerve fiber degeneration. Described CNS abnormalities include distal axonal spinocerebellar degeneration and increased cerebral atherosclerosis. Spinal long tracts contain neurofilamentous axonal swellings (Fig. 25.5). The distal axonopathy is probably secondary to progressive cross-linking and accumulation of neurofilaments during their anterograde transport in long axons.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Published descriptions of the pathologic features of carbon tetrachloride toxicity are scarce. Brain edema, hemorrhages, focal vascular necrosis, venous thromboses, and hemorrhagic infarcts have been reported.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Acute intoxication produces meningeal congestion and cerebral edema, and, occasionally, petechial hemorrhages. Microscopically, birefringent calcium oxalate deposits can usually be demonstrated by polarized light microscopy (Fig. 25.6) in and around vessels in the meninges, brain parenchyma, and choroid plexus. Neurons may show hypoxic change and there is often white matter edema. Scanty perivascular acute inflammatory infiltrates may be seen, but these are not consistently related to the calcium oxalate deposits and may be a reaction to hypoxic brain injury.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The brain and spinal cord appear macroscopically normal. Histologic changes in the human CNS are sparsely documented, but there are many experimental studies demonstrating the formation of neurofilamentous axonal swellings (Fig. 25.7) and distal degeneration of nerve fibers in long ascending (spinocerebellar and posterior column) and descending (corticospinal) spinal tracts, as occur in the peripheral nerves. As in carbon disulfide intoxication, the changes are probably due to progressive cross-linking and accumulation of neurofilaments during their anterograde transport.