Because chronic uremia is so frequently associated with hypertension, a major problem also arises in distinguishing the cerebral effects of uremia from those of severe and accelerated hypertension. Volhard was the first to make this distinction; he introduced the term pseudouremia to designate the cerebral effects of malignant hypertension and to separate them from true uremia. The preferable term, hypertensive encephalopathy, was first used by Oppenheimer and Fishberg. However, the myoclonic-twitch syndrome is not a component of hypertensive encephalopathy. The clinical picture of the latter disorder and its pathophysiology are discussed in “Hypertensive Encephalopathy and Posterior Reversible Encephalopathy Syndrome” in Chap. 33.
Opinions vary widely as to the biochemical basis of uremic encephalopathy and the twitch-convulsive syndrome. Restoration of renal function completely corrects the neurologic syndrome, attesting to the absence of structural change and a functional disorder of subcellular type. Whether caused by the retention of organic acids, elevation of phosphate in the CSF (claimed by Harrison et al), or the action of urea or other toxins, among them parathyroid hormone, has never been settled. The data supporting the causative role of urea itself are also ambiguous, just as they are for other putative endogenous agents (see Bolton and Young (1990) and the review by Burn and Bates). However, it can be stated that urea itself is not the sole inductive agent, as its infusion does not produce the syndrome in humans or animals.
It would appear that every level of the CNS is affected in uremia, from spinal cord to cerebrum. Cellular changes in the brain or spinal cord are limited to mild hyperplasia of protoplasmic astrocytes in some cases, but never of the degree observed in hepatic encephalopathy. Cerebral edema is notably absent. In fact, CT and MRI regularly show an element of cerebral shrinkage. A peripheral neuropathy is also a common complication of uremia and is considered in Chap. 43.
Improvement of encephalopathic symptoms may not be evident for 1 or 2 days after institution of dialysis. Convulsions, which occur in about one-third of cases, often preterminally, may be resistant to treatment until the uremia is addressed. However, some seizures may be suppressed with relatively low-plasma concentrations of antiepileptic drugs, the reason being that serum albumin is depressed in uremia, increasing the unbound, therapeutically active portion of a drug. If there are severe associated metabolic disturbances, such as hyponatremia, the seizures may be difficult to control. One must be cautious in prescribing any of a large number of drugs in the face of renal failure, for inordinately high, toxic blood levels may result. Examples that affect the nervous system are aminoglycoside antibiotics (vestibular damage); furosemide (cochlear damage); and nitrofurantoin, isoniazid, and hydralazine (peripheral nerve damage).