American neurology really began during the Civil War, chiefly through the work of S. Weir Mitchell and William A. Hammond. Appointed as surgeon-general of the U.S. Army Medical Department in 1862, Hammond undertook many projects and reforms, including the establishment of Turner's Lane Hospital outside of Philadelphia. In that 400-bed hospital devoted exclusively to the care of soldiers with neurologic disorders, Mitchell distinguished himself as a clinician with powers of meticulous observation.

Born in Philadelphia in 1821, Mitchell attended the University of Pennsylvania and graduated from Jefferson Medical College in 1850 at age 21. He recalled later, "I made up my mind that by thirty-five I should have a chair in one or the other of the two great schools," a wish that was frustrated all his life. Mitchell was a general practitioner, conducting some research in toxicology, when the Civil War began. His interest in neurologic disorders became evident to his friend Hammond, who appointed him to a small army hospital in Philadelphia devoted to neurologic patients. After the battle of Gettysburg, the hospital was moved to a larger building on Turner's Lane to accommodate the wounded.

With the collaboration of George R. Morehouse and William W. Keen, Mitchell published in 1864 the classic book Gunshot Wounds and Other Injuries of the Nerves. They reported their first 18 months" experience, including a description of the clinical syndrome Mitchell later termed causalgia, a painful condition following injury to a large peripheral nerve. An expanded book written solely by Mitchell, Injuries of the Nerves and Their Consequences, was published in 1872. His son, John Kearsley Mitchell, described Remote Consequences of Injuries to Nerves in 1895, reporting a follow-up of 20 of the original patients. Mitchell and his colleagues recognized the opportunity afforded by Turner's Lane Hospital, writing, "Never before in medical history has there been collected for study and treatment so remarkable a series of nerve injuries" (Mitchell, 1905). Their method of study began with an accurate account of each patient's symptoms and signs:

Keen, Morehouse, and I worked on at notetaking often as late as 12 or 1 at night, and when we got through walked home, talking over our cases. … The cases were of amazing interest. Here at one time were eighty epileptics, and every kind of nerve wound, palsies, choreas, stump disorders. (Mitchell, 1905)

Causalgia was observed in numerous soldiers at Turner's Lane Hospital. The pain was described as an intense, diffuse, burning sensation, subject to exacerbation by stimuli, mental as well as physical. Treatment at the time included water dressings and morphine injections. Mitchell (1872) described causalgia as "the most terrible of all the tortures which a nerve wound may inflict." He was a master of clinical case descriptions, and the following is an account of a case of causalgia in a Union soldier wounded in battle:

H., aged thirty-nine, New York, was shot July 2, 1863, through the inner edge of the right biceps, half an inch above the internal condyle of the humerus; the ball passed backward and downward. The musket fell from his left hand, and the right, grasping the rod, was twisted towards the chest and bent at the elbow. He walked to the rear. He cannot tell how much motion was lost, but he knows that he had instant pain in the median distribution, with tenderness of the palm, even on the first day, and a sense of numbness. My notes described him on entering our wards as presenting the following symptoms: the temperature of the two palms is alike. The back of the hand looks as usual, but the skin of the palm is delicate and thin, and without eruption. The joints of the fingers are swollen, and the hand secretes freely a sour, ill-smelling sweat. The pain is, in the first place, neuralgic, and darting down the median nerve track into the fingers; while in the second place, there is burning in the palm and up the anterior face of the fingers.

Pressure on the cicatrix gave no pain, but the median nerve below that point was tender, and pressure upon it caused pain in the hand. There was slight want of tactile sensibility in the median distribution in the hand, but the parts receiving the ulnar nerve presented no sign of injury. The hyperesthesia of the palm was excessive, so that even to blow on it seemed to give pain. He kept it wrapped up and wet, but could not endure to pour water on to the palm, preferring to wet the dorsum of the hand and allow the fluid to run around, so as by degrees to soak the palm. After a few weeks of this torment he became so sensitive that the rustle of a paper or of a woman's dress, the sound of feet, the noise of a band, all appeared to increase his pain. His countenance at this time was worn, pinched, anaemic, his temper irritable, and his manner so odd that some of the attendants believed him insane. When questioned as to his condition he assured me that every strong moral emotion made him worse,—anger or disappointment expressing themselves cruelly in the aching limb. (Mitchell, 1872)

After the Civil War, Mitchell limited his practice to consultations in neurologic disease, for his reputation was wide and his service in demand. He made much of his living in psychiatry, however, with a particular interest in the treatment of hysteria in women. Friend of Oliver Wendell Holmes, William Osler, William James, and Walt Whitman, Mitchell made his mark in literature as well as medicine, as author of novels, short stories, and poems. In urging him to visit Boston, Holmes wrote to Mitchell, "I am lonely. You are the only friend of distinction left to me."