Neuroactive kynurenines in Lyme borreliosis.
Although neurologic dysfunction occurs frequently in patients with Lyme borreliosis, it is rarely possible to demonstrate the causative organism within the neuraxis. This discordance could arise if neurologic symptoms were actually due to soluble neuromodulators produced in response to infection. Since immune stimulation is associated with the production of quinolinic acid (QUIN), an excitotoxin and N-methyl-D-aspartate (NMDA) agonist, we measured levels of CSF and serum QUIN, and lymphokines. Samples were obtained from 16 patients with CNS Borrelia burgdorferi infection, eight patients with Lyme encephalopathy (confusion without intra-CNS inflammation), and 45 controls. CSF QUIN was substantially elevated in patients with CNS Lyme and correlated strongly with CSF leukocytosis. In patients with encephalopathy, serum QUIN was elevated with corresponding increments in CSF QUIN. Lymphokine concentrations were not consistently elevated. We conclude that CSF QUIN is significantly elevated in B burgdorferi infection--dramatically in patients with CNS inflammation, less in encephalopathy. The presence of this known agonist of NMDA synaptic function--a receptor involved in learning, memory, and synaptic plasticity--may contribute to the neurologic and cognitive deficits seen in many Lyme disease patients.
Halperin
J J
JJ
Department of Neurology, SUNY, Stony Brook.
Heyes
M P
MP
D001927:Brain Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000382:microbiology; D006801:Humans; D007737:Kynurenine / Q000032:analysis* / Q000134:cerebrospinal fluid / Q000378:metabolism; D008193:Lyme Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008222:Lymphokines / Q000097:blood / Q000134:cerebrospinal fluid; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid / Q000378:metabolism*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D008222:Lymphokines; D011805:Quinolinic Acids; D007737:Kynurenine; D017378:Quinolinic Acid