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Review
. 2016 Jun;30(6):469-80.
doi: 10.1007/s40263-016-0339-2.

Perispinal Delivery of CNS Drugs

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Free PMC article
Review

Perispinal Delivery of CNS Drugs

Edward Lewis Tobinick. CNS Drugs. .
Free PMC article

Abstract

Perispinal injection is a novel emerging method of drug delivery to the central nervous system (CNS). Physiological barriers prevent macromolecules from efficiently penetrating into the CNS after systemic administration. Perispinal injection is designed to use the cerebrospinal venous system (CSVS) to enhance delivery of drugs to the CNS. It delivers a substance into the anatomic area posterior to the ligamentum flavum, an anatomic region drained by the external vertebral venous plexus (EVVP), a division of the CSVS. Blood within the EVVP communicates with the deeper venous plexuses of the CSVS. The anatomical basis for this method originates in the detailed studies of the CSVS published in 1819 by the French anatomist Gilbert Breschet. By the turn of the century, Breschet's findings were nearly forgotten, until rediscovered by American anatomist Oscar Batson in 1940. Batson confirmed the unique, linear, bidirectional and retrograde flow of blood between the spinal and cerebral divisions of the CSVS, made possible by the absence of venous valves. Recently, additional supporting evidence was discovered in the publications of American neurologist Corning. Analysis suggests that Corning's famous first use of cocaine for spinal anesthesia in 1885 was in fact based on Breschet's anatomical findings, and accomplished by perispinal injection. The therapeutic potential of perispinal injection for CNS disorders is highlighted by the rapid neurological improvement in patients with otherwise intractable neuroinflammatory disorders that may ensue following perispinal etanercept administration. Perispinal delivery merits intense investigation as a new method of enhanced delivery of macromolecules to the CNS and related structures.

Figures

Fig. 1
Fig. 1
Cerebrospinal venous system. Detail of plate 5 from Breschet G, Recherches anatomiques physiologiques et pathologiques sur le systáeme veineux. Paris: Rouen fráeres; 1829. Courtesy of the Sidney Tobinick collection
Fig. 2
Fig. 2
Cerebrospinal venous system. Detail of plate from Breschet G, Essai sur les veines du rachis. Paris: Faculte de Medecine de Paris; 1819. Courtesy of the Sidney Tobinick collection
Fig. 3
Fig. 3
Cerebrospinal venous system. Detail of plate III from Breschet G, Recherches anatomiques physiologiques et pathologiques sur le systáeme veineux. Paris: Rouen fráeres; 1829. Courtesy of the Sidney Tobinick collection
Fig. 4
Fig. 4
Cerebrospinal venous system. Detail from Todd RB (ed), The Cyclopaedia of Anatomy and Physiology. 1847, page 630, Fig. 360; after Breschet (1829)
Fig. 5
Fig. 5
Spinal veins. From Gray, 1858. Figure 222, page 416 from Gray H and Carter HV, Anatomy, descriptive and surgical. 1st ed. London: John W. Parker and Son.; 1858; after Breschet (1829)
Fig. 6
Fig. 6
Spinal veins. From Gray, 1858. Figure 222, page 416 from Gray H and Carter HV, Anatomy, descriptive and surgical. 1st ed. London: John W. Parker and Son.; 1858; after Breschet (1829)
Fig. 7
Fig. 7
External vertebral venous plexus in the cervical subcutaneous space. Magnetic resonance image. Courtesy of the Sidney Tobinick Collection
Fig. 8
Fig. 8
Figures from Corning’s 1888 article, Corning JL, XXIA Further Contribution on Local Medication of the Spinal Cord, with Cases. Transactions of the Medical Society of the State of New York for the Year 1888. 1888: pages 260–269. Figure 1 depicts the solid needle, 3 inches in length, utilized in the apparatus depicted in Fig. 2. Figure 2 depicts the spinal canal, the ‘foramen vertebrae’, and the method Corning utilized to estimate the depth of the posterior border of same. Figure 3 depicts the hollow needle Corning utilized to deliver cocaine using the 6.2 ml syringe depicted in Fig. 4
Fig. 9
Fig. 9
Positron emission tomography image, transverse section, of a living rat brain following perispinal extrathecal administration of 64Cu-DOTA-etanercept, imaged 5–10 min following the administration of etanercept. Note enhanced signal in the choroid plexus. Reproduced from Tobinick et al. [18]
Fig. 10
Fig. 10
Positron emission tomography image, transverse, coronal and sagittal sections of a living rat brain following perispinal extrathecal administration of 64Cu-DOTA-etanercept, imaged 5–10 min following the administration of etanercept. Reproduced in part from Tobinick et al. [18]

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