The early effects of very small doses are usually tonic in character, there being a general sense of improved power. The same fact was noted when describing effects on the digestive system, and it is possibly not a primary nerve-tonic effect, but rather dependent on improvement in appetite and assimilation of food.

Full medicinal doses, long-continued, give rise to numbness and pricking sensations with tremor or stiffness of limbs.

Irritant doses cause gastric pain, as already described; sometimes headache has been a marked symptom, as, for instance, in a large number of children who each received about 1 gr. of white arsenic in milk ("Taylor on Poisons," p. 295), and in many persons poisoned by the accidental admixture of a small quantity of arsenic in bread: they suffered also from a feeling of constriction over the forehead, vertigo, and tinnitus (Dr. Feltz: Lancet, i., 1880), from visual sensations of light or flame, prostration, and feebleness of lower extremities, and in these, as well as in other cases, pain in the back has been urgent (British Medical Journal, i., 1873). Sometimes the extremities have been very sensitive. Restlessness, insomnia, grinding of teeth, giddiness, irritability, and depression are frequent symptoms.

The effects of poisonous doses (6 to 8 gr.) are often ushered in with rigor, profound depression, and extreme anxiety. Restless tossing of arms is commonly noted, and later, numbness, cramps, and twitchings of all muscles. The oesophageal spasms may simulate those of hydrophobia, and the muscular cramps may amount to opisthotonos - convulsions alternate with delirium, the special senses become impaired or lost, the mental faculties torpid (the stupor may suggest narcotic poisoning), and syncope or collapse may close the scene. There may be local palsies, as of limbs and sphincters in the course of arsenical poisoning, and, as the effect of the drug in this direction is not so generally known, we may, with advantage, speak of it more fully.

Arsenic exerts a paralyzing influence certainly upon sensory and motor, and we may say probably upon vaso-motor nerves also. Dr. Sklarek, experimenting on the frog, found that arsenical injections, in minute quantities, destroyed common sensibility, probably by influence on the cord (Reichert's Archiv, 1866). Lesser, while verifying this, noted a transient increase in reflex irritability, then diminution of it, then cessation; after some time the frog became completely paralyzed.

Drs. Ringer and Murrell, remarking that paralysis occurs in the same order after mechanical arrest of circulation (as by ligature or excision of heart), instituted experiments to show whether the latter was the real factor in Sklarek's results, and concluded that they were due rather to a toxic action on the central nervous system; peripheral motor nerves retained their function for some time, for the muscles continued to contract under direct galvanic stimulus; ultimately both nerves and muscles were paralyzed by arsenic, and they ceased to re-act long before similar muscles did in a brainless frog, and the observers named concluded that "ar-senious acid is a protoplasmic poison, affecting first the more highly organized nervous centres, next the nerves, and last the muscles: . . . that it is a poison to all nitrogenous tissues (Journal of Physiology, i., 1878-79, pp. 227, 228).

Clinical records clearly indicate paralysis as a symptom of arsenical action. So early as 1711 Morgagni notes "tremor of limbs, and palsy of feet" (Op., vol. iii., Trans. Alexander, Letter 59). Mr. Trend reports the case of a pregnant girl, who took 2 gr. twice daily for three months, and besides intestinal symptoms, suffered from pricking pain in both legs, impaired sensation, and loss of power (British Medical Journal, ii., 1858). Partial paralysis and numbness from habitual taking of the drug are recorded in Schmidt (Bd. clxv., p. 238), and tremor and partial palsy from exposure to arsenical vapor in aniline works, by Dr. G. de Mussy (Lancet, i., 1876). Dr. Leroy (d'Etiolles), who has written specially on the subject, describes a case of paraplegia succeeding to acute arsenical symptoms after the application of a caustic paste to a cancerous breast, and another aggravated case of paraplegia, weakness and anaesthesia of arms with diarrhoea, and ultimately death from marasmus (Gazette Hebdom., 1857).

Christison has remarked that arsenical palsy resembles that of lead in its character, and Gubler and Duchenne have found it sometimes indenti-cal. Leroy, however, points out that it not so invariably affects the extensors, and that it is more generalized.

The wasting of limbs is more general, and they may become semiflexed; when all are affected, the upper recover before the lower, - a point of difference from cerebral palsies. An average duration is from four to ten months, and the prognosis is favorable under treatment.

Circulatory System

After administration of arsenic, analysis has detected it in the clot - i.e., united with globules, and not simply dissolved in the serum. Claude Bernard taught that it acted on the corpuscles in such manner as to diminish the activity of interchange of oxygen and carbonic acid (Medical Times, ii., 1861). The experiments of Brodie had already indicated undue fluidity of blood as an effect of arsenic, and modern observations refer this condition to a solvent action on haemoglobin: thus, if arseniuretted hydrogen be passed into defibrinated blood, it becomes black, and gives with the spectroscope one large dark band instead of the two normal ones; by degrees, the spectrum wholly disappears, the haemoglobin is destroyed, and the liquid turns yellowish-green. It seems probable that the same gas is developed to some extent from arseniates absorbed into the living organism, and that it exerts a similar destructive action on the globules; this would explain the anaemia, and the consequent oedema and anasarca, met with after continued use of even medicinal doses, as well as the icteric tint of skin, and the petechiae and hemorrhages in cases of poisoning. Though there is evidence that in certain forms of anaemia the number of the corpuscles is increased under arsenic (Gowers: Practitioner, July, 1878, and Bramwell), there can be no doubt, that an opposite result follows both its long-continued use in disease, and any appreciable quantity of it taken by healthy persons. Thus, Lemare-Piquot (Honfleur), suffering from cerebral congestion, had himself bled many times, and by careful observations of the proportion of clot to serum showed that the continued use of arsenic could markedly lessen the former. The normal maximum proportion of clot he reckoned at 54 per cent.; with any amount above this, cerebral symptoms, such as giddiness and oppression, appeared. In October, 1845, when suffering from such a condition, he found, on being bled, that the proportion of clot was 68 per cent., the serum being at 32 per cent. only. During the next four years he was bled more than twenty times with but partial and temporary relief. In March, 1849, he began the use of arsenical solution in small doses twice daily, at that time his proportion of clot being 69 per cent. After one month's arsenical treatment he felt well, and the proportion found on bleeding was reduced to 52 per cent. In succeeding years the same result occurred several times; he illustrated it also in other cases, and concluded, both from analyses and clinical results, that arsenic always rendered the blood less plastic, and lessened the number of globules (Bulletin de Therapeutique, t. lvii., 1859). More recently Cutler and Bradford also found red and white corpuscles to be diminished in number under arsenical medication, and Malcolm Morris reports diminution in some cases of psoriasis when the general health was good - e.g., F., aged twenty-three, on August 14th, showed 58 corpuscles in each square (of Dr. Gowers' instrument), was ordered Fowler's solution (mv. ter die), and on 21st showed 48 only per square: continuing treatment, on September 11th there were only 37.3 - the eruption was nearly gone (Practitioner, 1S80).

The force and frequency of the heart's action and the activity of the capillary circulation are usually increased by minute doses (Feltz, Har-less) and especially in weakly persons (v. p. 35): larger quantities induce palpitation with quick, small, and irregular pulse; the face is flushed, while the extremities are cold.

Poisonous doses markedly depress the circulation, and ultimately arrest heart-action (in diastole) in the lower animals, as found by Sklarek in batrachia and in cats - there was no previous stage of excitement (Reichert's Archiv, 18G6). Although the frog lives on for ten minutes after arrest of cardiac action, no stimulus will re-excite this, and yet irritability of cardiac muscular tissue persists, so that Sklarek concluded that arsenic paralyzed the motor ganglia of the heart. Unterberger also records a very pronounced fall in the blood-pressure and pulse-rate (Archiv. fur Exper. Pathol., Bd. ii.). There is clearly a direct depressant effect on the heart - in fact, this causes death in cold-blooded animals, though not usually in warm-blooded. Some palsy of vaso-motor nerves is also indicated, and, according to several experiments, this is limited to the abdominal division of those nerves: the exact explanation, however, requires further development. Though Lesser verified Sklarek's observations he did not come to the same conclusion that arsenic causes death by paralysis of the heart, but denies it for the simple reason that frogs survive excision of the heart for more than thirty minutes, while arsenic kills them in ten minutes. Ringer and Murrell found (in frogs) a varying effect upon the heart, it being sometimes completely arrested, sometimes continuing to beat after complete general paralysis, but they explained the difference by a variation in dose; a large one being quickly absorbed and conveyed to the heart arrests it at once, leaving little for the circulation to distribute, while a small dose paralyzes the central nervous system before the heart (loc. cit.). In warm-blooded animals the pulse-rate was increased at first by small and medium doses injected into the veins, afterward it was diminished; by a large dose it was decreased at once, and blood-pressure reduced. The increase of the pulse-rate was traced to lessened influence of the vagus, and increased action of cardiac ganglia, the decrease of pulse-rate to contrary conditions. Stimulation of vaso-motor centres was not marked unless injections were made directly into the carotid, and Lesser could not verify paralysis of those centres under any conditions (Virchow's Archiv, 1878). In the human subject, the pulse usually becomes weak, rapid, and gradually more irregular till heart-action ceases: venous stasis naturally occurs, and there is pallor, lividity, and finally cyanosis of the surface and of visible mucous membranes.