[1][2] His father Martin Puusepp was a shoemaker who had migrated from Rakvere, Estonia to St. Petersburg where he met and married Victoria-Stephania Goebel.

Here, various operations were performed for conditions such as, epilepsy, hydrocephalus, birth trauma, tumors of the brain and spinal cord, and injuries of the peripheral nervous system.

In 1904 he presented his report 'On Indications and Contraindications for Trephination of the Skull in Epilepsy and Idiocy' at the Ninth Pirogov Congress held in 1904.

During this time, Puusepp and Bekhterev performed an experimental surgical procedure—frontal leucotomy, cutting association fibers in the frontal lobes—on three patients with manic-depressive psychosis with the aim of reducing psychomotor agitation.

Bekhterev had become dissatisfied with the attempts of general surgeons to operate upon the nervous system and felt that neurology should become a surgical specialty like gynecology or ophthalmology: "neurologists will take a knife in their hands and do what they should do".

When the St. Petersburg Psycho-Neurological Institute later that year established a Chair of Surgical Neurology, Bekhterev's protégé Puusepp was named to head the new division.

Puusepp served in the Russian Army Medical Service at the start of World War I, but was discharged and returned to teaching and academic leadership in St. Petersburg after being wounded.

[6] Over the next twenty years he developed a strong neurological and neurosurgical teaching and clinical service with its own operating rooms and neuroradiology support.

Published from 1923 to 1939, it incorporated work not only from other Tartu researchers but also from international authors including Marburg, Freeman, his mentor Bekhterev, Walter Dandy, Walker, Guillain, and Alajouaine.

He also refined the techniques of ventriculography, reviewed the surgical treatment of cerebral aneurysms, experimented with measuring intracranial pressure using a manometer, and investigated nerve compression due to herniated spinal disks.

Some authors have suggested that Puusepp, through the role he played in the advancement of the neurosurgical profession, was Harvey Cushing's counterpart in the Eastern hemisphere.