William K. ReidSunday, April 3, 2022Amyotrophic Lateral Sclerosis (ALS) remains a terminal disease without an established etiology for the majority of patients. The dominant theory of ALS before 1970’s was the presence of poisons (Wofgram, F. 1973)1. Treatment with plasma exchange to remove poisons was said to have failed (Silani,V. et al1980)2. The exclusion of the theory of poisons in ALS because of the apparent failure of plasma exchange needs reassessment. There is an assumption of a finite body burden of poisons. If, instead, the patient continues to be exposed to poisons after plasma exchange, then the treatment would fail until the source of the poison was removed. There is evidence of chronic fungal infections in ALS patients that secrete neurotoxic mycotoxins. If these neurotoxic mycotoxins are the poisons reported in the old literature, then treatment would require aggressive antifungal therapy along with plasma exchange. There is a third factor complicating therapy. Patients with ALS have significant immune damage and treatment requires repair of the immune system.Introduction :The etiology of ALS has remained elusive. The dominant theory before the 1970’s was the presence of poisons or neurotoxins1. Serum from patients with ALS were toxic to motor neuron cells in culture. Based on this theory multiple institutions treated ALS patients with plasma exchange without apparent improvement2. There is a critical assumption that there is a finite body burden of poison and no further exposures. If, instead, there continues to be exposure to poisons, then treatment would require removal of the source. One source of poisons that could explain all the findings is a chronic fungal infection secreting neurotoxic mycotoxins. The fungal species Fusarium is a likely candidate (Thornton, C.R. 2020, Tortorano, A.M. et al 2014)3,4. Fusarium produces a wide array of mycotoxins of which two have prominent neurotoxicity, trichothecenes or fumonisins. The pathology in humans of trichothecenes mimics the pathology seen in ALS. Fusarium species contaminates water supplies, soil and crops, and are a common cause of onychomycosis, keratitis and sinusitis. Fusarium infections are difficult to treat due to multi-drug resistance. The tools to diagnose Fusarium infections are relatively new and, too often, fungal cultures and tissue hyphae are misdiagnosed as Aspergillus. The most toxic trichothecene produced by Fusarium is T-2 with a pattern of toxicity emblematic of ALS (Dai, C. et al, 2019, Wu, Q. et al 2020)5,6.Fusarium Infections :Fusarium species cause sinusitis, onychomycosis and keratitis in immunocompetent hosts (Thornton, C.R. 2020)3. In the immunocompromised host, Fusarium species cause life-threatening infections, Fusariosis, reported in hematologic cancer patients, HIV, diabetes, liver cirrhosis and especially bone marrow transplant patients. Fusariosis is the second most common invasive mould disease after Aspergillosis with a high mortality rate reaching 75%. Fusarium infections are resistant to almost all the available antifungals. The recommended antifungals are Voraconazole, Amphotericin or combinations. Added to the limited number of antifungals is the impact of mycotoxins that cause immune suppression (Wu, Q. et al 2020)6.
