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The injection into the cerebrospinal fluid of cats of 52 to 208 gamma of copper in the form of an albumin complex or as cupric sulfate, was followed by small elevations in the content of metal in the neural tissues, but regularly and promptly produced persistent quadriplegia and conspicuous histologic changes. Smaller amounts of copper caused less, or no, neurologic manifestations or histologic alterations. The earliest lesions were essentially unaccompanied by inflammation and were initially characterized by hydropic swelling of the myelin sheaths. They progressed rapidly to focal necrosis of all parenchymal components with marked degeneration of myelin and axis cylinders in the peripheral margins of the spinal cord, brain stem, mid-brain, and cerebrum. These histologic changes did not occur in neural tissues incubated in vitro in solutions of the copper-albumin complex. They did not appear in animals injected intraventricularly with ferric sulfate or saccharated iron. Considered together, the findings make it clear that copper in concentrations comparable to those present in the neural tissues of patients with Wilson's disease has the property of profoundly altering neural function and causing conspicuous morphologic alterations.
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