Syphilis may be a confounding factor, not a causative agent, in syphilitic ALS

Abstract

Based upon a review of published clinical observations regarding syphilitic amyotrophic lateral sclerosis (ALS), I hypothesize that syphilis is actually a confounding factor, not a causative factor, in syphilitic ALS. Moreover, I propose that the successful treatment of ALS symptoms in patients with syphilitic ALS using penicillin G and hydrocortisone is an indirect consequence of the treatment regimen and is not due to the treatment of syphilis. Specifically, I propose that the observed effect is due to the various pharmacological activities of penicillin G ( e.g., a GABA receptor antagonist) and/or the multifaceted pharmacological activity of hydrocortisone. The notion that syphilis may be a confounding factor in syphilitic ALS is highly relevant, as it suggests that treating ALS patients with penicillin G and hydrocortisone—regardless of whether they present with syphilitic ALS or non-syphilitic ALS—may be effective at treating this rapidly progressive, highly devastating disease.

Treatment with penicillin G and hydrocortisone reduces ALS-associated symptoms: a case series of three patients

“…Syphilitic ALS is an intriguing clinical phenomenon, as it is the only form of ALS ever reported to have been cured 9 . Recently, we proposed that the successful treatment of ALS symptoms in these six patients with syphilitic ALS was not directly due to the treatment of syphilis; specifically, we proposed that the penicillin G and/or hydrocortisone treated these patients’ ALS symptoms due to the off-target pharmacological activity of penicillin G (e.g., as a GABA receptor antagonist) and/or the multifaceted pharmacological activity of hydrocortisone (e.g., as an immunosuppressant) 9 . This notion is supported by the three cases reported here, as our patients had no syphilis-related symptoms or history of syphilis.…”

“…This treatment course was recently postulated to be efficacious for treating dysphagia, dysarthria, and other ALS-related symptoms 9 .…”

“…This treatment course was previously reported to be efficacious in six patients with so-called syphilitic ALS in which syphilis was hypothesized to cause ALS 7, 8 . However, we recently proposed that the treatment effect was not due to the treatment of syphilis, but rather was a consequence of the multifaceted pharmacology of penicillin G and/or hydrocortisone 9 . Given that our three patients presented with no evidence of syphilis, our results provide evidence that treating ALS patients with a course of penicillin G and hydrocortisone—regardless of whether they present with syphilitic ALS or non-syphilitic ALS—may effectively treat the symptoms of this rapidly progressive disease.…”

ALSUntangled 46: penicillin G/hydrocortisone

“…Tuk makes the novel proposal that ALS is primarily caused by an increase in inhibitory GABA activity. This results in a compensatory increase of the excitatory neurotransmitter glutamate as a homeostatic response to maintain balance (16)(17)(18). In this scenario, PNG/HC would decrease GABA activity, and in turn decrease the homeostatic increase in glutamate excitotoxicity.…”