The risk in immunosuppressed persons of developing a primary lymphoma of the brain or progressive multifocal leukoencephalopathy is well known and has been mentioned in previous chapters. An entirely different encephalopathy that is marked by widespread visual symptoms and edema of the cerebral white matter, evident on the MRI, but mainly occipital, occurs after the administration of cyclosporine and other immunosuppressant drugs. These imaging features of reversible posterior leukoencephalopathy or posterior reversible encephalopathy syndrome (PRES; see Chaps. 33 and 41) are not specific, being seen also in patients with hypertensive encephalopathy, eclampsia, intrathecal methotrexate administration, and other conditions (see Table 41-1 and Figs. 33-35 and 41-2) all of which are probably linked by endothelial dysfunction of cerebral vessels. Systemic fungal infections had in the past been found at autopsy in approximately 45 percent of patients who had had renal transplants and long periods of immunosuppressive treatment; in about one-third of these patients, the CNS was involved. Cryptococcus, Listeria, Aspergillus, Candida, Nocardia, and Histoplasma were the usual organisms. Recent experience suggests a far lower rate of infection but it remains a threat. Other CNS infections that have complicated transplantation are toxoplasmosis and cytomegalovirus (CMV) inclusion disease.
We have found examples of Wernicke-Korsakoff disease and central pontine myelinolysis in uremic patients. A bleeding diathesis may result in subdural or cerebral hemorrhage, as already mentioned.
Bolton and Young (1993) have drawn attention to the frequent occurrence, in severely septic patients, of a drowsy or confusional state that is reversible and not explained by hepatic, pulmonary, or renal failure, electrolyte imbalance, hypotension, drug intoxication, or a primary lesion of the brain. They called the condition “septic encephalopathy.” According to their surveys, 70 percent of patients become disoriented and confused within hours of the onset of severe systemic infection; in a few cases, this state may progress to stupor and coma. Notably there are no signs of asterixis, myoclonus, or focal cerebral disorder but paratonia is common, as is the later development of a polyneuropathy. Rapid changes in water balance may occur, leading to the type of osmotic demyelination discussed below.
The encephalopathic state that occurs with severe systemic infection may also develop independently of sepsis, as a component of a syndrome of multiple organ failure and, according to some authors, a complication of widespread cutaneous burns (Aikawa et al). Others have questioned the validity of this last category and have instead found explanatory electrolyte disorders (particularly hyponatremia), sepsis, or multiple brain abscesses.
It has been useful in clinical work to distinguish these encephalopathies of infection and multiorgan failure from those caused by isolated hepatic or renal disease. The lack of a biochemical marker and the confounding effects of hypotension during sepsis (septic shock) leave doubt as to pathogenesis. Altered phenylalanine metabolism and circulating cytokines have been proposed as causes, without firm evidence. Of interest in 2 of our fatal cases was the presence of brain purpura, but this has otherwise been an infrequent finding. Here, the white matter of the cerebrum and cerebellum was speckled with myriad pericapillary hemorrhages and zones of adjacent necrosis. This pathologic reaction is nonspecific, having also been seen in cases of viral pneumonia, heart failure with morphine overdose, thrombotic thrombocytopenic purpura and arsenic poisoning.
Disorders of Sodium, Potassium, and