ALS Abstracts 4

©

 

Chronic mercurialism; a cause of the clinical syndrome of amyotrophic lateral sclerosis.
            (Brown, 1954) Download
The Combination of symptoms referable to the pyramidal system, anterior horn cells, and lower brain stem constitutes the syndrome of amyotrophic lateral sclerosis. The literature contains many case reports of this syndrome in which varied etiologic factors have been determined. Wechsler and associates1 analyzed 81 cases of amyotrophic lateral sclerosis and listed dietary deficiency and inflammatory, vascular, and toxic processes as etiologic factors. This clinical symptom complex has been noted following gastrectomy2 and polyarthritis,3 and in triorthocresyl phosphate poisoning.4 It has recently been considered an atopic-stress disorder, and some improvement has been obtained by the use of adrenocortical extracts.5 Cord tumors, syphilis, and arachnoiditis may also produce this syndrome. It becomes obvious that the physician in his evaluation of such a symptom complex must seek the clue to the etiology by a careful and detailed search into the patient's occupation, contacts, illnesses, and injuries, since one may uncover a factor which can be successfully treated.

The association of exposure to lead, mercury, and selenium and the development of amyotrophic lateral sclerosis and the epigenetic implications.
            (Callaghan et al., 2011) Download
Metal exposures are an intriguing potential culprit in the cause of sporadic amyotrophic lateral sclerosis (ALS). For one, there are numerous case reports linking different metals to an ALS phenotype. Furthermore, some investigators have demonstrated higher levels of certain metals in the blood, bone, cerebrospinal fluid, urine, or spinal cords of patients with ALS compared to controls. There are also many case-control studies looking at the possible association of certain metals with the development of ALS. We have reviewed the relevant literature regarding metal exposures and the risk of developing ALS. We found that many different metals have been implicated as having a role in ALS, but there is more literature investigating the role of lead than any other metal. Despite many studies, the role, if any, of this metal in the pathogenesis of ALS remains unclear. Similarly, other metals either have inconclusive, conflicting, or insufficient results in order to make a definitive conclusion. One explanation for these findings is that metal exposures alone are insufficient for the development of ALS. Perhaps an interaction between the metal exposure and an individual's genetic makeup is required to produce epigenetic changes that ultimately lead to ALS.

ALS, mercury exposure, and chelation therapy.
            (Costa et al., 2008) Download
Re: Praline. Finally, in their discussion, the authors correctly point out that chelation therapy with the dithiol chelator meso-2,3- dimercaptosuccinic acid “DMSA must be initiated shortly after exposure to prevent accumulation and avoid toxic- ity.” However, in their case report, chelation treatment with DMSA was started approximately 7 months after the last mercury vapor exposure. We cast doubts about the efficacy of postexposure treat- ment delay with DMSA to prevent and/or to treat the metallic mercury toxicity. In strikingly contrast, previously published cases of amyotrophic lateral sclerosis after acute overexposure to ele- mental mercury resolved spontaneously without using any chelation treatment, within a few months after removal of sources of mercury. These considerations raise the provocative question of benefits of chelating agents in persons who have sALS associated with overexposure to mercury.

The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity.
            (Geier and Geier, 2005) Download
Autism is a neurodevelopmental disorder that according to the Centers for Disease Control and Prevention (CDC) affects 1 in 150 children in the United States. Autism is characterized by impairments in social relatedness and communication, repetitive behaviors, abnormal movements, and sensory dysfunction. Recently emerging evidence suggests that mercury, especially from childhood vaccines, appears to be a factor in the development of the autistic disorders, and that autistic children have higher than normal body-burdens of mercury. In considering mercury toxicity, it has previously been shown that testosterone significantly potentates mercury toxicity, whereas estrogen is protective. Examination of autistic children has shown that the severity of autistic disorders correlates with the amount of testosterone present in the amniotic fluid, and an examination of a case-series of autistic children has shown that some have plasma testosterone levels that were significantly elevated in comparison neurotypical control children. A review of some of the current biomedical therapies for autistics, such as glutathione and cysteine, chelation, secretin, and growth hormone, suggests that they may in fact lower testosterone levels. We put forward the medical hypothesis that autistic disorders, in fact, represents a form of testosterone mercury toxicity, and based upon this observation, one can design novel treatments for autistics directed towards higher testosterone levels in autistic children. We suggest a series of experiments that need to be conducted in order to evaluate the exact mechanisms for mercury-testosterone toxicity, and various types of clinical manipulations that may be employed to control testosterone levels. It is hoped by devising therapies that address the steroid hormone pathways, in addition to the current treatments that successful lower heavy metal body-burdens of mercury, will work synergistically to improve clinical outcomes. In light of the fact that there are a number of other diseases that may have a chronic mercury toxicity component, such as Alzheimer's disease, heart disease, obesity, ALS, asthma, and other various forms of autoimmune disorders, it is imperative that further research should be conducted to understand mercury-testosterone toxicity.

[Healing of Amyotrophic Lateral Sclerosis: A Case Report].
            (Mangelsdorf et al., 2017) Download
BACKGROUND:  Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to death within 3-5 years in most cases. New approaches to treating this disease are needed. Here, we report a successful therapy. CASE REPORT:  In a 49-year-old male patient suffering from muscle weakness and fasciculations, progressive muscular atrophy, a variant of ALS, was diagnosed after extensive examinations ruling out other diseases. Due to supposed mercury exposure from residual amalgam, the patient's teeth were restored. Then, the patient received sodium 2,3-dimercaptopropanesulfate (DMPS; overall 86 × 250 mg in 3 years) in combination with α-lipoic acid and followed by selenium. In addition, he took vitamins and micronutrients and kept a vegetarian diet. The excretion of metals was monitored in the urine. The success of the therapy was followed by scoring muscle weakness and fasciculations and finally by electromyography (EMG) of the affected muscles. First improvements occurred after the dental restorations. Two months after starting therapy with DMPS, the mercury level in the urine was increased (248.4 µg/g creatinine). After 1.5 years, EMG confirmed the absence of typical signs of ALS. In the course of 3 years, the patient recovered completely. CONCLUSIONS:  The therapy described here is a promising approach to treating some kinds of motor neuron disease and merits further evaluation in rigorous trials.

Mercury and selenium contents in amyotrophic lateral sclerosis in Hokkaido, the northernmost island of Japan.
            (Moriwaka et al., 1993) Download
We evaluated the pathogenicity of mercury (Hg) and selenium (Se) which are supposed to be one of the risk factors in the development of amyotrophic lateral sclerosis (ALS). Hg and Se contents were measured in plasma, blood cells, scalp hair samples of 21 sporadic ALS patients and 36 controls, who included 19 patients with other neurological diseases, in Hokkaido, the northernmost island of Japan. Hg and Se levels in plasma and blood cells of ALS patients were significantly lower in advanced staged ALS patients than controls. Low Hg and Se contents in ALS, being correlated with their disabilities and nutritional conditions, would rather reflect the disease contracted states than the pathogenic roles in ALS.

Caprylic acid in the effective treatment of intractable medical problems of frequent urination, incontinence, chronic upper respiratory infection, root canalled tooth infection, ALS, etc., caused by asbestos & mixed infections of Candida albicans, Helicobacter pylori & cytomegalovirus with or without other microorganisms & mercury.
            (Omura et al., 2011) Download
There are many causes of frequent urination. Whenever water or fluids are consumed, the patient has to urinate within 10 or 20 min. Often urinary bladder examinations & blood tests show no significant abnormalities, & treatment by anti-bacterial or anti-viral agents does not improve the symptoms significantly. In intractable frequent urination with difficulty holding urine, as well as other intractable medical problems such as frequent coughing, white pus in gingiva, infection of the apex of a root canalled tooth, slow-healing wounds, & ALS, the authors often found coexisting mixed infections of Candida albicans (C.A.), Helicobacter pylori (H.P.), & Cytomegalovirus (CMV) with or without additional bacterial (Chlamydia trachomatis, etc.) or viral infections & increased Asbestos, with or without Hg deposits. We often found various degrees of mixed infections with C.A., H.P., & CMV in the external sphincters of the urethra & in the Trigone of the urinary bladder which consists of (1) a horizontal, band-like area between the 2 ureter openings & (2) the funnel shaped part of the Trigone at the lower half of the urinary bladder. In the coexistence of significant amounts of C.A., H.P. & CMV, the infection cannot be reduced by otherwise effective medicines for H.P. & CMV. However, one optimal dose of Diflucan, or Caprylic acid taken orally or externally applied, rapidly reduced the symptoms significantly. We found the best treatment is to give a combination of an optimal dose of Caprylic acid orally in the form of "CaprilyCare" or "Caprylic Acid," with a capsule of Omega-3 Fish Oil as an anti-viral agent, Amoxicillin, Substance Z & a Cilantro tablet. We found that an optimal dose of Caprylic acid increases normal cell telomere (NCT) to a desirable 750 ng BDORT units while Diflucan increases NCT by only 25 ng BDORT units, & with Omega-3 fish oil, leads to a mutual cancellation of both drugs. Thus, Caprylic acid is superior to & less expensive than Diflucan, & has potential application for anti-cancer, anti-aging, anti-Alzheimer's disease, anti-Autism, anti-infection, & general circulatory improvement.

ALS and mercury intoxication: a relationship
            (Praline et al., 2007) Download
We report the case of an 81-year-old woman in whom clinical signs and features of electromyographic activity patterns were consistent with amyotrophic lateral sclerosis (ALS). Increased blood level and massive urinary excretion of mercury proved mercury intoxication. Despite a chelation treatment with Meso 2-3 dimercaptosuccininc acid (DMSA), she died after 17 months. The pathophysiology of sporadic ALS remains unclear. However, the role of environmental factors has been suggested. Among some environmental factors, exposure to heavy metals has been considered and ALS cases consecutive to occupational intoxication and accidental injection of mercury have been reported. Although no autopsy was performed, we discuss the role of mercury intoxication in the occurrence of ALS in our case, considering the results of experimental studies on the toxicity of mercury for motor neuron.

Serum ferritin and metal levels as risk factors for amyotrophic lateral sclerosis.
            (Qureshi et al., 2008) Download
Metal toxicity has been identified as a possible risk factor for amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. We conducted a retrospective chart review of urinary, hair and blood metal levels and serum ferritin in 321 people with ALS seen over a ten-year period at the Massachusetts General Hospital (MGH). We found that hair lead levels and serum ferritin levels were elevated in ALS patients compared to published normal values. Metal levels of arsenic, lead, mercury, cadmium, thallium, cobalt and aluminum in 24-hour urine specimens and lead, mercury and arsenic in serum were within the normal range. We conclude that twenty-four hour urine or blood testing for metals is not warranted as part of the evaluation of ALS. Elevated levels of serum ferritin in ALS population could reflect an underlying perturbation in iron metabolism.

Amyotrophic lateral sclerosis with antecedent poliomyelitis.
            (Roos et al., 1980) Download
Histopathological and virological studies were performed on autopsy tissue from a 47-year-old man who had a history of acute poliomyelitis at age 15 years and died after a three-year course of amyotrophic lateral sclerosis (ALS). The poliovirus serologic tests suggested prior infection with poliovirus type 3 but no ongoing poliovirus infection. The CNS showed typical features of ALS with no inclusion bodies or inflammatory cells. Attempts to isolate poliovirus in the CNS were unsuccessful and results of immunofluorescence studies for poliovirus antigen were negative. Molecular hybridization experiments using a DNA copy of the complete poliovirus genome failed to demonstrate poliovirus-related RNA or DNA sequences in the CNS. These studies, using sensitive techniques, indicate that there was no evidence of the continuing presence of poliovirus in this patient with ALS and antecedent poliomyelitis.


 

Are environmental exposures to selenium, heavy metals, and pesticides risk factors for amyotrophic lateral sclerosis
            (Vinceti et al., 2012) Download
The etiology of sporadic amyotrophic lateral sclerosis (ALS), the most common form of this degenerative disease of the motor neurons, is still unknown, despite extensive investigation of several genetic and environmental potential risk factors. We have reviewed laboratory and epidemiological studies assessing the role of exposure to neurotoxic chemicals (metalloid selenium; heavy metals mercury, cadmium, and lead; pesticides) in ALS etiology by summarizing the results of these investigations and examining their strengths and limitations. Despite limitations in the exposure assessment methodologies typically used in human studies, we found suggestive epidemiological evidence and biologic plausibility for an association between ALS and antecedent overexposure to environmental selenium and pesticides. The relation with mercury, cadmium, and lead appears weaker.

Lead, cadmium and mercury in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: A case-control study.
            (Vinceti et al., 2017b) Download
Exposure to neurotoxic chemicals such as pesticides, selenium, and heavy metals have been suggested to play a role in the etiology of amyotrophic lateral sclerosis (ALS). We assessed exposure to lead, cadmium, and mercury in 38 ALS patients (16 men and 22 females) and 38 hospital-admitted controls by using their cerebrospinal fluid (CSF) content as biomarker. We determined CSF heavy metal levels with inductively coupled plasma sector field mass spectrometry, according to a methodology specifically developed for this biological matrix. ALS patients had higher median values for Pb (155 vs. 132ng/L) but lower levels for Cd (36 vs. 72ng/L) and Hg (196 vs. 217ng/L). In the highest tertile of exposure, ALS odds ratio was 1.39 (95% CI 0.48-4.25) for Pb, 0.29 (0.08-1.04) for Cd and 3.03 (0.52-17.55) for Hg; however, no dose-response relation emerged. Results were substantially confirmed after conducting various sensitivity analyses, and after stratification for age and sex. Though interpretation of these results is limited by the statistical imprecision of the estimates, and by the possibility that CSF heavy metal content may not reflect long-term antecedent exposure, they do not lend support to a role of the heavy metals cadmium, lead and mercury in ALS etiology.


 

Pesticide exposure assessed through agricultural crop proximity and risk of amyotrophic lateral sclerosis.
            (Vinceti et al., 2017a) Download
BACKGROUND:  Epidemiologic studies have raised the possibility that some pesticide compounds induce the neurodegenerative disease amyotrophic lateral sclerosis (ALS), though the available evidence is not entirely consistent. METHODS:  We conducted a population-based case-control study in two Italian populations to assess the extent to which residence in the vicinity of agricultural crops associated with the application of neurotoxic pesticides is a risk factor for ALS, using crop acreage in proximity to the residence as an index of exposure. RESULTS:  Based on 703 cases and 2737 controls, we computed an ALS odds ratio of 0.92 (95% confidence interval 0.78-1.09) for those in proximity to agricultural land. Results were not substantially different when using alternative exposure categories or when analyzing specific crop types, with the exception of a higher risk related to exposure to citrus orchards and olive groves in Southern Italy, though based on few exposed subjects (N = 89 and 8, respectively). There was little evidence of any dose-response relation between crop proximity and ALS risk, and using long-term residence instead of current residence did not substantially change our estimates. CONCLUSIONS:  Though our index of exposure is indirect and subject to considerable misclassification, our results offer little support for the hypothesis that neurotoxic pesticide exposure increases ALS risk.

Preface. Role of reviews. Environmental Contamination and Toxicology.
            (Whitacre, 2014) Download
Reviews of Environmental Contamination and Toxicology [Vol. 1 through 97 (1962–1986) as Residue Reviews] for detailed review articles concerned with any aspects of chemical contaminants, including pesticides, in the total environ- ment with toxicological considerations and consequences.

 


References

Brown, IA (1954), ‘Chronic mercurialism; a cause of the clinical syndrome of amyotrophic lateral sclerosis.’, AMA Arch Neurol Psychiatry, 72 (6), 674-81. PubMed: 13206485
Callaghan, B, et al. (2011), ‘The association of exposure to lead, mercury, and selenium and the development of amyotrophic lateral sclerosis and the epigenetic implications.’, Neurodegener Dis, 8 (1-2), 1-8. PubMed: 20689252
Costa, A, et al. (2008), ‘ALS, mercury exposure, and chelation therapy.’, Clin Neurol Neurosurg, 110 (3), 319-20. PubMed: 18054425
Geier, MR and DA Geier (2005), ‘The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity.’, Med Hypotheses, 64 (5), 946-54. PubMed: 15780490
Mangelsdorf, I, H Walach, and J Mutter (2017), ‘[Healing of Amyotrophic Lateral Sclerosis: A Case Report].’, Complement Med Res, 24 (3), 175-81. PubMed: 28641283
Moriwaka, F, et al. (1993), ‘Mercury and selenium contents in amyotrophic lateral sclerosis in Hokkaido, the northernmost island of Japan.’, J Neurol Sci, 118 (1), 38-42. PubMed: 8229049
Omura, Y, et al. (2011), ‘Caprylic acid in the effective treatment of intractable medical problems of frequent urination, incontinence, chronic upper respiratory infection, root canalled tooth infection, ALS, etc., caused by asbestos & mixed infections of Candida albicans, Helicobacter pylori & cytomegalovirus with or without other microorganisms & mercury.’, Acupunct Electrother Res, 36 (1-2), 19-64. PubMed: 21830350
Praline, J, et al. (2007), ‘ALS and mercury intoxication: a relationship’, Clin Neurol Neurosurg, 109 (10), 880-83. PubMed: 17719172
Qureshi, M, et al. (2008), ‘Serum ferritin and metal levels as risk factors for amyotrophic lateral sclerosis.’, Open Neurol J, 2 51-54. PubMed: 19452011
Roos, RP, et al. (1980), ‘Amyotrophic lateral sclerosis with antecedent poliomyelitis.’, Arch Neurol, 37 (5), 312-13. PubMed: 6247998
Vinceti, M, et al. (2012), ‘Are environmental exposures to selenium, heavy metals, and pesticides risk factors for amyotrophic lateral sclerosis’, Rev Environ Health, 27 (1), 19-41. PubMed: 22755265
Vinceti, M, et al. (2017a), ‘Pesticide exposure assessed through agricultural crop proximity and risk of amyotrophic lateral sclerosis.’, Environ Health, 16 (1), 91. PubMed: 28851431
Vinceti, M, et al. (2017b), ‘Lead, cadmium and mercury in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: A case-control study.’, J Trace Elem Med Biol, 43 121-25. PubMed: 28089071
Whitacre, DM (2014), ‘Preface. Role of reviews. Environmental Contamination and Toxicology.’, Rev Environ Contam Toxicol, 230 vii-ix. PubMed: 24873016