Toxic models of upper motor neuron disease

Although neurotoxic models for progressive degeneration of both the anterior horn cell and the Betz cell do not exist, (neuro)lathyrism and neurocassavism (konzo) are examples of self-limiting neurotoxic disorders that predominantly target the Betz cell. Both disorders are caused by the continuous intake of neurotoxic plant products (Lathyrus sativus and Manihot esculenta, respectively) which result in a virtually identical clinical picture of spastic paraparesis. A neurotoxic excitatory amino acid and AMPA agonist (β-N-oxalylamino-L-alanine, BOAA) is held largely responsible for lathyrism. Epidemics of konzo are strongly associated with increased intake of the cyanide-liberating glycoside linamarin by protein-poor subjects. Whereas an animal model for neurocassavism does not exist, macaques fed Lathyrus sativus or BOAA develop central motor deficits with corticospinal tract involvement. Estimated dosages of Lathyrus sativus used to induce beginning lathyrism in well-nourished primates are 10-20 fold greater than those associated with irreversible human neurolathyrism. Major unexplained aspects of both diseases are the factors which allow the suspected toxins to target Betz cells (blood-brain barrier, receptor distribution, cellular energy metabolism), the latency to onset in both diseases, and how two separate etiologic factors trigger clinically similar disorders.