Tremor in Parkinson's Disease and Its Inhibition by Amyl Nitrite

Abstract

the substantia nigra are now generally accepted as the chief sites of pathological changes in the parkinsonian states (paralysis agitans; postencephalitic and arteriosclerotic parkinsonism). It has been suggested that these changes remove or interfere with an inhibitory function of these parts, the characteristic tremor originating elsewhere or representing the pyramidal system functioning without extrapyramidal constraint.A 6 per second rhythm, known as the theta rhythm, can be recorded from the cerebral cortex. It is believed that this is "paced" by basal ganglia mechanisms. On a few occasions this theta rhythm has been inhibited by the inhalation of amyl nitrite.1 It appeared worth while, therefore, to try the effects of such inhalations on the tremors characteristic of diseases of the basal ganglia, even though abnormal electroencephalograms have been found to occur only in those cases of postencephalitic parkinsonism in which personality changes, and not tremor, were present.1 This paper gives the results of observations on the effects of amyl nitrite and some other vasodilating drugs, namely, sodium nitrite, glyceryl trinitrate (nitroglycerin), octyl nitrite, histamine and nicotinic acid. By testing a variety of vaso¬ dilator drugs, it was hoped to show how far the action of the amyl nitrite depended on this property. A discussion of the pathogenesis of tremor and rigidity, with possible modes of action of amyl nitrite, concludes the paper. METHODSPatients with all forms of the parkinsonian state were investigated except those with advanced arteriosclerosis, who readily become syncopal when given vasodilating drugs.Tremor was recorded by surface electrodes strapped to a forearm, as in electrocardiography. The impulses were fed through the circuits of an electroencephalogram to give a continuous record by means of ink writers. A few records were made by a mechanical system. Amyl nitrite was inhaled from a capsule crushed into a piece of gauze held close to the subject's nose and mouth. Inhalations were continued until an effect on the tremor became obvious or until unpleasantness from the drug resulted.The patient always lay quietly on an examination couch, and the nature of the test had been explained to him. No investigation was commenced unless the patient appeared calm and free from apprehension.Owing to the rapidity and fleeting nature of the effects produced by amyl nitrite, it was often difficult to make rapid and repeated estimations of changes in the blood pressure ; for this reason only systolic readings were taken when fluctuations were believed to be rapid.