Neurology—Epitomes of Progress: Lithium Toxicity in the Central Nervous System

EPITOMES-NEUROLOGY systemic hypertension develops as well as pul- monary hypertension, and there are significant cardiac arrhythmias, including ventricular tachy- cardia, during the apnea. Apnea occurs during inspiration and a salient clinical sign in these pa- tients is the occurrence of loud snoring. A simple screening procedure consists of recording the sound of the patient's respirations during early sleep by means of a cassette tape recorder at the patient's bedside at home or in the hospital. If findings are suspicious, a polygraphic study of nocturnal sleep is indicated. At present no effec- tive drug therapy has been found and treatment consists of tracheostomy, so prompt otolaryn- gologic consultation is indicated. Symptomatology is totally reversed by this procedure. In the other form of sleep apnea (so-called central apnea), no obstruction is encountered and respiratory effort ceases. In this form of the disorder, tracheostomy is less helpful. JON F. SASSIN, MD REFERENCES Kales A: Sleep disorders: Recent findings in the diagnosis and treatment of disturbed sleep. N Engl J Med 290:487-499, Feb 28, Guilleminault C: Insomnia with sleep apnea, a new syndrome. Science 181:856-858, Aug 31, 1973 Lithium Toxicity in the Central Nervous System LITHIUM CARBONATE is the accepted treatment of acute hypomania and mania. The mild side effects commonly experienced include nausea, vomiting, diarrhea, fatigue and weakness. Polydipsia and polyuria commonly occur and may be due to inhi- bition of the action of antidiuretic hormone. There may be a fine, mild resting tremor of the hands which is responsive to treatment with pro- panolol. The serious signs and symptoms of cen- tral nervous toxicity of lithium usually appear with serum concentrations greater than 1.5 mEq per liter and include lethargy, lightheadedness and confusion, accompanied by ataxia, drowsiness, slurred speech, tinnitus, blurred vision and pro- found weakness. The features of severe intoxica- tion are striking and usually appear either over several days of lithium therapy or following an acute overdose. A patient with severe, acute lithium intoxication presents with tremor, in- creased neuromuscular irritability, increased deep AUGUST 1977 * 127 * 2 tendon reflexes, nystagmus, confusion and even convulsions. Nonneurologic signs of intoxication include vomiting and acute diarrhea. All of these signs may progress to stupor, coma and eventual death. It is generally thought that life-threatening lithium intoxication does not occur below serum levels of 3.0 mEq per liter. However, the thresh- old for intoxication may be lowered in elderly patients and in patients taking other medications including the anticholinesterases and haloperidol. There have been some patients with toxic neuro- logic manifestations in whom serum lithium levels were within the accepted therapeutic range. Alter- ations in lithium tolerance may be produced by trauma, infection and sodium restricted diets. Severe lithium toxicity has been reported in a woman with a viral infection causing high fever and a serum lithium level of 1.0 mEq per liter. An electroencephalogram in a patient who is lithium intoxicated may show a variety of changes. Status epilepticus has been reported in previously nonepileptic patients with lithium con- centrations in the therapeutic range. The rela- tionship of lithium to seizures was studied in 16 epileptics in whom only one instance of increased clinical seizure activity was reported. In ten of the 16 patients there was a clear reduction in seizure frequency during lithium therapy. The continuous use of lithium for more than eight months has been reported to be associated with increased muscle tone. The development of the altered muscle tone appears to be directly re- lated to the duration of lithium maintenance therapy and is not relieved by benztropine, an antiparkinson drug. Rarely, patients taking lithium can develop choreoathetosis. Patients exposed to elevated lithium levels for prolonged periods have survived with permanent damage to the cere- bellum and basal ganglia. In assessing lithium toxicity, the clinical signs are the most important means of detecting in- toxication. Serum levels may be used for con- firmation, but it should always be kept in mind that toxicity may occur with serum levels in the therapeutic range. When signs of serious intoxi- cation are noted, lithium administration should be stopped immedately. As a pharmacologically active cation, lithium is not metabolized in the body, but is excreted by the kidneys. The serum half life of lithium is usually about 16 hours. Hemodialysis, or, if hemodialysis is not available, peritoneal dialysis may be used effectively to lower serum lithium levels. Long-duration hemo-