Polymorphonuclear leucocytosis in C.S.F. suggests meningeal involvement Spread of infection and immune response in Lyme disease Lyme disease is caused by Borrelia Burgdorferi. Borrelia burgdorferi is transmitted to humans the bite of ixodes tick vector. Borrelia burgdorferi is inoculated in the skin, where local replication takes place locally and outward migration in the dermis occurs. Days to week after the tick bite, hematogenous dissemination to secondary sites (like joints, hea eye, nervous system) takes place. If untreated, the bacteria may persist in the body for months or even years, despite the production of anti-Borrelia burgodorferi antibodies by the immune system. The following mechanisms have been described - i) Tick saliva, which accompanies the spirochete into the skin during the feeding process, contains substances that disrupt the immune response at the site of the bite. - This provides a protective environment where the spirochete can establish the infect on. ii) Once inside the body, Borrelia burgdorferi becomes a "stealth invader" i.e., it changes shape. In the tick and mice which host the bacterium through most of its life cycle, the bacterium has a thick cell wall and spiral shape. If it maintains its thick cell wall and its spiral shape, immune system can control infection. However, in the human body, it can shed its cell wall and can take a different shape. When under attack from immune system, it simply changes shape so it is not recognized. iii) Borrelia burgdorferi produces antigenic variation in a "cell surface lipoprotein VIsE", during the course of infection The VIsE system presents a challenge to immune system because after an immune response is generated to one version of VIsE protein, a different version is quickly produced. By using this type of antigenic variation, B. burgdorferi can escape the adaptive immune system. Lyme meningitis Meningitis (meningeal involvement) is the most common neurological event that occurs in the setting of early lyme dissemination. - In this clinical setting CSF is always abnormal and shows: I) Pleocytosis with predominantly lymphocytosise (not polymorphonuclear leukocytosis). 2) Increased protein 3) Glucose content is usually normal, but it falls below the serum concentration in 20% of patients. Immunoglobulin abnormalities are common in the CSF of patients with lyme meningitis. - Specific IgM, IgG or IgA antibody against B. burgdorferi appears in CSF and indicates intrathecal antibody synthesis.