European Journal of NeurologyVolume 8, Issue s4 p. 26-26 Spread of paralytic activity of neurobloc™ (botulinum toxin type B) and botox® (botulinum toxin type A) in juvenile monkeys: an electrophysiological model J. C. Arezzo, J. C. Arezzo Albert Einstein College of Medicine, Bronx, NY;Search for more papers by this authorM. S. Litwak, M. S. Litwak Albert Einstein College of Medicine, Bronx, NY;Search for more papers by this authorF. A. Caputo, F. A. Caputo Sierra Biomedical Inc., Sparks, NV;Search for more papers by this authorC. A. Gasper, C. A. Gasper Elan Pharmaceuticals Inc., South San Francisco, CA, USASearch for more papers by this authorG. M. Shopp, G. M. Shopp Elan Pharmaceuticals Inc., South San Francisco, CA, USASearch for more papers by this authorK. E. Meyer, K. E. Meyer Elan Pharmaceuticals Inc., South San Francisco, CA, USASearch for more papers by this author J. C. Arezzo, J. C. Arezzo Albert Einstein College of Medicine, Bronx, NY;Search for more papers by this authorM. S. Litwak, M. S. Litwak Albert Einstein College of Medicine, Bronx, NY;Search for more papers by this authorF. A. Caputo, F. A. Caputo Sierra Biomedical Inc., Sparks, NV;Search for more papers by this authorC. A. Gasper, C. A. Gasper Elan Pharmaceuticals Inc., South San Francisco, CA, USASearch for more papers by this authorG. M. Shopp, G. M. Shopp Elan Pharmaceuticals Inc., South San Francisco, CA, USASearch for more papers by this authorK. E. Meyer, K. E. Meyer Elan Pharmaceuticals Inc., South San Francisco, CA, USASearch for more papers by this author First published: 01 May 2002 https://doi.org/10.1046/j.1468-1331.2001.00010.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume8, Issues4May 2001Pages 26-26 RelatedInformation

1. The purpose of this study was to evaluate possible changes in brain morphology and evoked potentials associated with daily administration of 300 mg kg-1 vigabatrin in dogs. 2. Somatosensory evoked potentials (SEP) and auditory evoked potentials (AEP) were recorded at baseline and weekly for 12 weeks of treatment and every 2 weeks for 17 weeks of recovery. Morphology was assessed immediately after treatment for two treated dogs and after recovery for the remaining five treated and two control dogs. 3. Vigabatrin produced a significant slowing of the central transmission measure of the SEP with no alteration in the AEP. Vigabatrin was associated with microvacuolation in select regions of the brain including the fornix, septum, optic tract, hypothalamus, thalamus and cortex. In addition, some microglial proliferation was noted. 4. Changes in SEP and the microvacuolation fully recovered after 17 weeks of treatment. 5. The study confirms vigabatrin-induced microvacuolation in the dog and suggests these changes are associated with functional slowing of conduction in the somatosensory pathways.

Epidural visual evoked potentials (VEP) were used to study the role of cytokines in the induction of pathophysiologic changes associated with inflammation in the central nervous system (CNS) of the rabbit. In normal rabbits, intraocular injection of human recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) increased the peak latency of the cortical VEP by more than 2 ms within 3 h of injection; equal volume injections of control substances had no effect. Alterations in conduction induced by IFN-gamma and TNF reversed within 24 h and could be reinduced by reinjection. Intraocular injection of recombinant human interleukin-1 beta (IL-1) induced a more progressive delay in conduction that peaked 24 h after intraocular challenge and reversed over the ensuing 48 h. Pathologic examination of the tissues indicated that the primary effect of these cytokines is on the vasculature and induces changes associated with inflammation. The results suggest that the acute reversible effects of cytokines on CNS function are associated with vascular events; further they support the sensitivity of the 'rabbit eye model' for studies on the pathophysiologic effect of inflammatory mediators on the CNS in vivo.

This study explores the longitudinal assessment of visual evoked potentials (VEPs) in the rabbit as a method for defining factors underlying functional and structural changes associated with optic neuritis and the inflammatory demyelinating diseases. In rabbits with experimental autoimmune encephalomyelitis (EAE) induced by sensitization with guinea pig spinal cord myelin, injection of lymphokines into the posterior chamber of one eye (monocular challenge) produces an early inflammatory response in the retina and optic nerve, and an alteration in the VEP, all limited to the injected eye and its projections. The earliest changes in the timing and distribution of the cortical VEP occur within hours of ocular challenge and precede histopathological evidence of structural demyelination at the light microscope level. Prechallenge assessment allows the induced monocular prechiasmal effects to be distinguished from the more diffuse electrophysiological findings associated with EAE (i.e. those due to sensitization alone). In sensitized/challenged animals there is a clear correspondence between electrophysiological and morphological measures of dysfunction at the time points sampled. These results suggest that this model system affords an excellent opportunity to examine the precise structural correlates of the early functional changes associated with the onset of inflammatory demyelination within the CNS. Furthermore, the stability of the system provides the capacity to monitor alterations over the complete course of inflammation, demyelination and remyelination, induced by experimental manipulations.