{'fraction_non_alphanumeric': 0.018422991893883568, 'fraction_numerical': 0.014738393515106854, 'mean_word_length': 5.114864864864865, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
THE ALS/PDC SYNDROME OF GUAM AND THE CYCAD HYPOTHESIS

THE ALS/PDC SYNDROME OF GUAM AND THE CYCAD HYPOTHESIS To the Editor: In their review of the amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) syndrome of Guam, Steele and McGeer1 argue against the cycad hypothesis of causation, noting the persistence of this disorder after 1950 when the regular consumption of cycad flour (fadang) among the native Chamorros ceased. The rapid decline in incidence of both ALS and PDC beginning in the 1950s and persisting for more than 50 years is well established.2 The occasional observation of new cases by Steele and McGeer is consistent with a disappearing syndrome resulting from a point exposure in the 1940s. Analysis of the 29 cases of PDC identified in our 2003 island-wide prevalence study reveals that all subjects were born before 1940 and would have had ample opportunity to be exposed to an environmental toxin in the 1940s.3 Steele and McGeer state that our findings of an association of cycad exposure with PDC, MCI, and Guam dementia (GD) “are inconsistent with any reasonable theory regarding fadang toxicity,” because of a protective effect of exposure in childhood and lack of association in adulthood.1 We pointed out that the protective effect in childhood is likely due to recall bias related to study design.4 Our findings of significantly elevated odds ratios for picking, processing, and eating fadang in early adulthood for all three outcomes (GD, MCI, and PDC) are consistent with a point-source exposure. These findings are also consistent with epidemiologic evidence showing a preponderance of affected men as well as reflecting a commonality in causation of all three disorders. The fact that adult exposures were not associated is likely due to the rapid decline in exposure rates of Chamorros to cycad during the 1960s and later when subjects reached adulthood, reducing the statistical power to detect an effect.4 Long-term cycad toxicity is plausible, based on recent studies that implicate toxins other than BMAA. For example, phytosterol glucosides that result in the excitotoxic release of glutamate lead to motor neuron and Parkinsonian phenotypes and pathology in cycad extract-fed mice.5 While alternative hypotheses are welcome, there are negligible data to support them. Steele and McGeer1 suggest that an infection that causes retinopathy may predispose to ALS/PDC. The infectious agent has never been identified, and there is no evidence that infectious retinal diseases trigger tangle formation in widespread regions of brain and spinal cord. Finally, the rapid decline in incidence is inconsistent with either a genetic or persisting environmental exposure.