Lathyrism, one of the oldest neurotoxic diseases known to Man, results from excessive consumption of the chickling pea, Lathyrus sativus, and certain related species. Once prevalent throughout Europe, N. Africa, Middle East and parts of the Far East, the disease is presently restricted to India, Bangladesh and Ethiopia. Lathyrism is a form of irreversible, non-progressive spastic paraparesis associated with poorly understood degenerative changes in spinal cord. Domestic animals, notably the horse, also develop hindlimb paralysis after prolonged feeding on lathyrus fodder. Experimental animal models of lathyrism have been reported but none has been satisfactorily investigated, and concurrence between these experimental diseases and the human condition is unproven. The culpable agent in lathyrus species that precipitates paralysis also is unknown. Current attention is focused on the glutamate analog, beta-(N)-oxalyl-amino-L-alanine acid (BOAA). While this compound is present in those lathyrus species that induce spastic paraparesis and, in large doses, reportedly causes neuropathological changes similar to glutamate neurotoxicity, there is little to compare these neuropathological changes with those found in human lathyrism.
Konzo and lathyrism are associated with consumption of cassava and grass pea, respectively. Cassava consumption has also been associated with a third disease, tropical ataxic neuropathy (TAN). This review presents a new unifying hypothesis on the causative agents for these diseases: namely, that they are nitriles, compounds containing cyano groups. The diseases may be caused by different but similar nitriles through direct neurotoxic actions not mediated by systemic cyanide release. Both cassava and Lathyrus contain nitriles, and other unidentified nitriles can be generated during food processing or in the human body.
Konzo and lathyrism are associated with consumption of cassava and grass pea, respectively. Cassava consumption has also been associated with a third disease, tropical ataxic neuropathy (TAN). This review presents a new unifying hypothesis on the causative agents for these diseases: namely, that they are nitriles, compounds containing cyano groups. The diseases may be caused by different but similar nitriles through direct neurotoxic actions not mediated by systemic cyanide release. Both cassava and Lathyrus contain nitriles, and other unidentified nitriles can be generated during food processing or in the human body. Available data indicate that several small nitriles cause a variety of neurotoxic effects. In experimental animals, 3,3'-iminodipropionitrile (IDPN), allylnitrile and cis-crotononitrile cause sensory toxicity, whereas hexadienenitrile and trans-crotononitrile induce selective neuronal degeneration in discrete brain regions. IDPN also induces a neurofilamentous axonopathy, and dimethylaminopropionitrile is known to cause autonomic (genito-urinary) neurotoxicity in both humans and rodents. Some of these actions depend on metabolic bioactivation of the parental nitriles, and sex- and species-dependent differences in susceptibility have been recorded. Recently, neuronal degeneration has been found in rats exposed to acetone cyanohydrin. Taken together, the neurotoxic properties of nitriles make them excellent candidates as causative agents for konzo, lathyrism and TAN.
Konzo is a paralytic disease, formerly called epidemic spastic paraparesis, which was first described by Trolli in 1936 in Zaire. During the last decade there has been a number of epidemics of konzo in rural areas of East and Central Africa. These epidemics occur in the dry season among very poor rural populations whose diets for the weeks and months prior to onset consist almost exclusively of roots of bitter cassava. Endemic or sporadic cases also occur in the same areas. The prevalence rate of konzo in affected populations ranges from 1–30 per 1000. Konzo is primarily a disease of children above the age of three, and of women in the fertile age group. The clinical features are characterized by an abrupt onset of a permanent, symmetrical but non-progressive, spastic paraparesis (paralysis of both legs) in a previously healthy person. Associated involvement of the arms and, occasionally, cranial nerves may be present in cases with severe spastic paraparesis. The range of disabilities varies from a slightly spastic gait in mild cases to a complete inability to walk in more severely affected cases. Konzo can be distinguished clinically from the other main tropical myeloneuropathies including tropical ataxic neuropathy (TAN), lathyrism and HTLV-1-associated myelopathy.
Tropical ataxic neuropathy typically occurs in endemic form and has slowly progressive course. In contrast to konzo, tropical ataxic neuropathy is more common in persons greater than 40 years of age. Tropical ataxic neuropathy is a neurologic syndrome of sensory polyneuropathy, gait ataxia, optic atrophy, and neurosensory deafness. Presence of any of the 2 features is considered enough to establish the diagnosis. This syndrome typically begins with dysesthesias in feet, followed by unsteadiness of the gait. There is often loss of vibration and proprioceptive sensations. A Romberg test is often positive. Reflexes in lower limbs are often diminished or absent. Plantar responses are flexor. Spastic paraparesis is present in only 20% of patients . A 2008 study reported, for the first time, evidence for the occurrence of tropical ataxic neuropathy in south India . Authors reviewed the clinical and laboratory profile of 40 tropical ataxic neuropathy cases. The notable demographic characteristics of cases included female preponderance, peak age at onset in the thirties, rural residence, and poor socioeconomic status. The diet in the majority comprised a large amount of tapioca, which was low in protein. In addition to sensory peripheral neuropathy, 90% had decreased hearing, 50% had decreased vision, and 25% had spasticity involving the lower extremities. Compared to the controls, the serum, urine, and sural nerve thiocyanate levels were significantly elevated in the patients. With cessation of cassava intake and better nutrition, improvement of the neurologic disability occurred in the majority.
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