Episodic confusion and stupor and other neurologic symptoms may accompany any form of severe renal disease—acute or chronic. The cerebral symptoms attributable to uremia (first described by Addison in 1832) are discerned in normotensive individuals in whom renal failure develops rapidly. Apathy, fatigue, inattentiveness, and irritability are usually the initial symptoms; later, there is confusion, dysarthria, tremor, and asterixis. Infrequently, this takes the form of a toxic psychosis, with hallucinations, delusions, insomnia, or catatonia (Marshall). These symptoms characteristically fluctuate from day to day, or even from hour to hour. In some patients, especially those who become anuric, symptoms may come on abruptly and progress rapidly to a state of stupor and coma. In others, in whom uremia develops more gradually, mild visual hallucinations and a disorder of attention may persist for several weeks in relatively pure form. The EEG becomes diffusely and irregularly slow and may remain so for several weeks after the institution of dialysis. The CSF pressure is normal and the protein is not elevated unless there is a uremic or diabetic neuropathy. In several reports, meningismus and a low-grade mononuclear pleocytosis have been mentioned (Merritt and Fremont-Smith), but we have not encountered this.
In acute renal failure, clouding of the sensorium is practically always associated with a variety of motor phenomena. These usually occur early in the course of the encephalopathy, sometimes when the patient is still mentally clear. The patient begins to twitch and jerk and may convulse. The myoclonic twitches involve parts of muscles, whole muscles, or entire limbs and are lightning-quick, arrhythmic, and asynchronous on the two sides of the body; they are incessant during both wakefulness and sleep. At times the movements resemble those of chorea or an arrhythmic tremor; asterixis is also readily evoked. The motor phenomena are often difficult to classify. Our predecessor authors described the condition as a uremic twitch-convulsive syndrome.
The resemblance of uremic encephalopathy to hepatic and other metabolic encephalopathies has been stressed by Raskin and Fishman, yet we are more impressed with differences than with similarities. When the twitch-convulsive syndrome is observed in association with other diseases such as widespread neoplasia, delirium tremens, diabetic coma, and lupus erythematosus, the causative factor of renal failure is usually discovered.
As the uremia worsens, the patient lapses into a quiet coma. Unless the accompanying metabolic acidosis is corrected, Kussmaul breathing appears and gives way to Cheyne-Stokes breathing and death.
Encephalopathy and coma in the patient with renal failure may, of course, be a result of disorders other than uremia itself. Because of the similarity of this syndrome to tetany, measurement should be made of serum calcium and magnesium—and, of course, hypocalcemia and hypomagnesemia do occur in uremia. But often the values for these ions are normal or near normal, and the administration of calcium and magnesium salts has little effect. The altered excretion of drugs leads to their accumulation, sometimes evoking excessive sedation. Subdural and intracerebral hemorrhages may complicate uremia (and dialysis) because of clotting defects and hypertension; and uremic patients are prone to infections, including meningitis.