Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

Tuk, B.

doi:10.12688/f1000research.8774.1

Cited by 2 publications

(1 citation statement)

References 61 publications

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“…For example, in addition to its antibacterial properties, penicillin G is also a potent antagonist of GABAergic ( i.e ., inhibitory) activity 6 and can induce seizures in patients with renal insufficiency 7 . Interestingly, GABAergic overstimulation was postulated recently to play a role in the pathogenesis of ALS 8 . Furthermore, at sufficient dosages, penicillin G can affect several major bodily functions and/or systems, including the immune system, the cardiovascular system, metabolic function, renal function, liver function, the hematological system, and the urogenital system 7 .…”

Section: Discussion and Conclusion Regarding Syphilitic Alsmentioning

confidence: 99%

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

Tuk

2016

F1000Res

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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.

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Section: Discussion and Conclusion Regarding Syphilitic Alsmentioning

confidence: 99%

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

Tuk

2016

F1000Res

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

Tuk¹,

Jousma²,

Gaillard

2017

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Three male Caucasian patients with ALS were admitted to the hospital due to progressive dysphagia and dysarthria. During two 21-day courses of penicillin G and hydrocortisone, these patients’ dysphagia and dysarthria resolved. The patient’s other ALS-associated symptoms also improved, including respiratory function, coordination, walking, and muscle strength. This is the first report of a treatment with a protocol for treating dysphagia, dysarthria, respiratory depression and other ALS-related symptoms. Furthermore, the observations are consistent with the recent hypothesis that the successful treatment of ALS symptoms with this treatment course in six patients with syphilitic ALS was not directly due to the treatment of syphilis; but that the administered penicillin G and/or hydrocortisone treated these patients’ ALS symptoms due the off-target pharmacological activity of penicillin G and/or hydrocortisone. This report therefore underscores the need to evaluate the efficacy of this treatment course in a clinical trial.

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Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

Cited by 2 publications

References 61 publications

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

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

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

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