Pathogenesis. 447 



found in tlie blood and more remote organs (spleen, brain) 

 and then only in minute quantities (HoMbeck, Dor, Creite, 

 Nicolaier, Haegler, etc., probably they are enclosed in leucocytes 

 and carried there )._ This negative finding harmonizes with the 

 fact that the bacteria exert their pathogenic function indirectly, 

 through the toxic products absorbed from the lymphatic circula- 

 tion. On the other hand, the fact that the symptoms of poison- 

 ing, different from true poisons, such as strychnine, occur after 

 a comparatively long period of incubation (in guinea pigs at 

 least 12, in mice 6 hours) points to the fact that the toxin is 

 carried very slowly to the central nervous system. 



Tetanus toxin exerts a pathogenic effect on the motor nerve 

 cells, primarily those of the spinal cord and medulla oblongata, 

 giving rise to an increased irritability, indirectly however caus- 

 ing contractions of the corresponding muscle groups. If the 

 source of the toxins is on the surface of the body some of them are 

 at once bound by the axis cylinder (nerve endings) and conducted 

 along the nerves to the central motor cells, whose irritation causes 

 local tetanic muscle spasms; the other portion of the toxins 

 enters the blood, is later, however, also bound by constantly in- 

 tercepting nerve fibers and conducted to the motor nerve cells, 

 so that muscle spasms occur in constantly widening areas. If 

 on the other hand, the toxins immediately enter the blood, as 

 would occur in intravenous or intraperitoneal injection, or after 

 an intestinal infection (so called T. splanchnicus), they are 

 almost simultaneously bound by all motor cells and in such cases 

 the muscle spasms occur later, but in almost all the muscles 

 simultaneously (Morax & Marie, Behring). The fact that 

 trismus, in both man and horse, is one of the first symptoms 

 of the clinical picture of tetanus would indicate that the tetanus 

 toxin is more readily bound by the trigeminus neuron than 

 by the other motor neurons. The increased reflex irritation also 

 points to an increased irritation of the sensitive neurons. 



Brusehettini was the first to discover that the tetanus toxin was 

 conducted from the point of infection to the nerve centers mainly- 

 through the nerve channels, and his discovery was confirmed by Meyer 

 & Ransom, Stintzing, v. Behring, Tiberti, etc. According to Meyer 

 & Ransom the toxin is taken up by the nerve endings containing no 

 axis cylinders, according to Pochhammer by the medullary sheaths; 

 Zupnifc, however, thinks that the muscles are directly attacked by the 

 toxin. In the central nervous system the toxin combines eleetively 

 mostly with the motor nerve cells of the spinal cord and medulla 

 oblongata. 



The slow progress of the toxin along the nerve channels explains 

 the relatively long incubation, as the toxin has to be carried to the 

 central nervous system along these paths; when the toxin is brought 

 in direct contact with the nerve centers the incubation is considerably 

 shortened. 



The peculiar action of the tetanus toxin on the nervous system 

 is probably explained by Ehrlich's side chain theory. According to 



