Lathyrism, konzo, and tropical ataxic neuropathy

Ravindra Kumar Garg DM FRCP

General Neurology

Updated 01.08.2024
Released 08.08.2007
Expires For CME 01.08.2027

Lathyrism, konzo, and tropical ataxic neuropathy

Author: Ravindra Kumar Garg DM FRCP

See Contributor Disclosures

Editor: Peter J Koehler MD PhD

Lathyrism, konzo, and tropical ataxic neuropathy

In This Article

Quick Link

Introduction

Overview

Three food-related neurotoxic disorders, lathyrism, konzo, and tropical ataxic neuropathy, are special challenges to mankind because factors producing these disorders are linked to lack of education, poverty, population growth, and certain conditions like drought, trade, and war. High neurolathyrism rates in Ethiopia are linked to diet and demographics; grass pea overconsumption is identified as a key risk factor. Lathyrism is a form of irreversible, non-progressive spastic paraparesis associated with poorly understood degenerative changes in the spinal cord, and it is caused by long-term and excessive consumption of the grass pea Lathyrus sativus. The pathological demyelinating changes in neurolathyrism largely involve pyramidal tracts. The longest pyramidal neurons are more severely affected. The disease is presently restricted to India, Bangladesh, and Ethiopia. In areas of India where a high consumption of Lathyrus sativus was previously reported, increased awareness has led to a marked reduction in lathyrism cases. Nutritional deficiencies of sulfur amino acid methionine and cysteine aggravate the neurotoxicity of beta-N-oxalyl amino-L-alanine. Cassava leaves and roots (Manihot esculenta Crantz) constitute the main daily source of protein as a supplement to the major staple food in remote rural areas of Africa. Ingestion of large amounts of poorly processed cassava roots is associated with the occurrence of an epidemic form of non-compressive myelopathy (konzo) in African countries. Cassava-derived cyanide poisoning and protein malnutrition were two predominant risk factors in the pathogenesis of konzo. A study suggests a possible causal association between konzo and the gut microbiome (09). Konzo is a neurologic entity with selective upper motor neuron damage and is characterized by an abrupt onset of irreversible, non-progressive, and symmetrical spastic paraparesis or tetraparesis. A ‘‘wetting method’’ has been reported to eradicate or markedly reduce konzo outbreaks in the Democratic Republic of Congo. A study on rats noted that Ginkgo biloba extracts can prevent motor changes associated with cassava juice consumption (45). The occurrence of another toxic disease in Africa, tropical ataxic neuropathy, is attributed to prolonged dietary cyanide exposure. Minor improvements in food processing have been found effective in preventing these disabling neurotoxic disorders. In this article, the author provides updated information on epidemiology, clinical features, differential diagnosis, and management of lathyrism, konzo, and tropical ataxic neuropathy. The author also discusses a review that presents a unifying hypothesis on the causative agents for lathyrism, konzo, and tropical ataxic neuropathy.

Key points

	• Three food-related neurotoxic disorders, lathyrism, konzo, and tropical ataxic neuropathy, are linked to illiteracy, poverty, population growth, and conditions like drought, famine, and war.
	• Lathyrism is an irreversible, non-progressive spastic paraparesis resulting from excessive consumption of peas of Lathyrus sativus.
	• Lathyrus sativus contain a neurotoxin, beta-N-oxalyl amino-L-alanine (synonym beta-N-oxalyl-L-alpha,beta-diaminopropionic acid).
	• Konzo is also a distinct form of tropical myelopathy that appears abruptly because of excessive consumption of bitter cassava roots.
	• Tropical ataxic neuropathy is a neurologic syndrome of sensory polyneuropathy, gait ataxia, optic atrophy, and sensory deafness resulting from the dietary use of large quantities of cassava for long periods.
	• There is no specific treatment for any of these entities. A good diet containing high doses of vitamins and physical rehabilitation are required.

Historical note and terminology

Lathyrism results from excessive consumption of the chickling pea, Lathyrus sativus, and certain related species. It is one of the oldest neurotoxic diseases known to mankind. Devastating neurolathyrism epidemics have occurred during major famine crises in various parts of the world. The physicians who wrote the Hippocratic corpus are believed to have been aware of the toxic pea causing persistent paralysis of the legs. In 1873, the Italian scientist Contani coined the term “lathyrismo” (lathyrism) in patients with progressive spastic paraparesis (06). In 1947, Kessler published a vivid account of the toxicity of L sativus among the Romanian prisoners of war during the Second World War (24). The toxic constituent of L sativus is an amino acid identified as beta-N-oxalyl amino-L-alanine. In 1964, two groups of Indian scientists identified beta-N-oxalyl amino-L-alanine after primate feeding studies (33; 46).

Konzo was first described by Trolli in 1936 in Zaire (52). In the Yaka language, konzo means “tied legs,” a description of the spastic gait. This is the name used in Congo, now the official term for this pure motor neuron disorder. Lancaster and colleagues were the first to report that prolonged consumption of cassava caused konzo (27).

The term “tropical ataxic neuropathy” was first used by Osuntokun in Nigeria in 1968 (42). Osuntokun established that this condition developed due to chronic dietary cyanide exposure. A similar form of endemic neuropathy in the Caribbean, which was popularly known as “Jamaican Neuropathy,” was described at least a century ago. Although this condition was thought to have ceased to occur about 2 decades ago, a study has shown that this disease is still endemic in certain areas of the world (39).

Clinical manifestations

Presentation and course

Lathyrism is a form of irreversible, non-progressive spastic paraparesis associated with poorly understood degenerative changes in the spinal cord. Often, the patient awakens one morning to find lower-limb weakness, causing him or her to fall. Severe cramps often accompany or herald the weakness, which can be precipitated by sudden physical exertion or exposure to inclement weather. The acute phase lasts for about a month, and residual symptoms persist. In a few patients, the disease advances subacutely over a month, followed by slow progression. Some patients experience a prolonged slow progression (29; 48). Neurologic examination often reveals a pyramidal pattern of motor weakness combined with marked hypertonia in the thigh extensors and adductors and in the gastrocnemius muscles so that the more severely affected patients walk on the balls of their feet with a lurching scissoring gait. Extensor plantar responses are uniformly present, the knee and ankle tendon reflexes are exaggerated, and clonus is often present. Hoffmann-Trömner sign and exaggerated biceps or triceps tendon jerks are also found in the most severely affected patients. Sensory and bladder manifestations are infrequent (29). Animals fed peas from Lathyrus species develop skeletal deformities and aortic aneurysms rather than neurologic disorders. This animal disease primarily affects collagen tissue and is called osteolathyrism (05). The occurrence of osteolathyrism in humans is poorly documented. Some patients develop bone pain and disfigurement of bones, including vertebrae and pelvis.

Konzo is a neurologic disorder of abrupt onset with selective upper motor neuron damage, characterized by an irreversible, non-progressive, and symmetrical spastic paraparesis or tetraparesis (37; 48). The World Health Organization provided the following criteria for konzo: (1) abrupt onset (less than 1 week) of non-progressive lower limb weakness in a healthy person; (2) symmetric spasticity; and (3) bilaterally increased lower limb reflexes in the absence of signs of spine disease (56). Children and lactating women are the most vulnerable (32; 55). In the majority of patients, the symptoms evolve within a few days. The initial symptoms include cramps, a heavy feeling or weakness in the legs, difficulty standing and walking, and a tendency to fall down. Occasionally, there is lower back pain, blurred vision, speech difficulties, and paresthesias of the legs, but these symptoms are often transient and disappear within a month. In most patients, during the first 2 days, the disease is serious enough to force them to bed. Later on, there may be a partial improvement. Finally, the affected person develops a stable spastic paraparesis, which persists for the remainder of life. After onset, the neurologic signs remain constant or improve minimally if no further cyanide is ingested, unlike, for example, human T-cell lymphotropic virus -I infection, in which further deterioration takes place (41; 21). In addition to motor deficits, konzo-affected children also have cognitive impairment. The determinants of cognitive impairment in these children include female gender and low serum albumin (11). Half the patients with konzo have an optic neuropathy with decreased visual acuity, alterations of the visual fields, and atrophy of the temporal part of the retinal nerve fiber layer linked with temporal pallor of the optic disc. About half of the konzo patients also have abnormal visual evoked potentials, with both delayed latency and reduced amplitude. A few of these patients have an ocular motor disturbance, leading to pendular nystagmus (34). One study demonstrated significant motor and cognitive impairment in boys with konzo. Motor and cognitive testing were done by Bruininks-Oseretsky Test of Motor Proficiency and Kaufman Assessment Battery for Children, respectively (08). Follow-ups were at 2 and 4 years of age. Kaufman Assessment Battery for Children scores of boys with konzo were significantly lower at 2 years of follow-up than the boys who do not have konzo. For boys, increases in urinary thiocyanate concentration were significantly associated with reductions in Bruininks-Oseretsky Test of Motor Proficiency but not for cognitive decline (08; 35).e

Tropical ataxic neuropathy typically occurs in endemic form and has a slowly progressive course. In contrast to konzo, tropical ataxic neuropathy is more common in persons older than 40 years. Tropical ataxic neuropathy is a neurologic syndrome of sensory polyneuropathy, gait ataxia, optic atrophy, and neurosensory deafness. The presence of two of the four features (sensory polyneuropathy, gait ataxia, optic atrophy, and neurosensory deafness) is considered enough to establish the diagnosis. This syndrome typically begins with dysesthesias in the feet, followed by unsteadiness of the gait. There is often a 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 (41; 40; 48). A 2008 study reported, for the first time, evidence for the occurrence of tropical ataxic neuropathy in south India (31). The authors reviewed the clinical and laboratory profiles of 40 tropical ataxic neuropathy cases. The notable demographic characteristics of cases in India 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.

Prognosis and complications

Acton graded the disability of lathyrism into four stages according to the support required in walking. Most patients continue to walk slowly without a stick (no-stick stage); some patients need one or two sticks (one-stick stage or two-stick stage); on further progression, patients can move around on both hands and knees (crawler stage) (01).

In a follow-up study, nine patients with konzo were reexamined after 14 years. This long-term follow-up showed that the neurologic signs in patients with konzo remained constant. Four severely affected patients showed functional improvement (13).

A study showed that endemic ataxic polyneuropathy led to a decrease in the survival of affected patients. In this study, a total of 204 cases and 5766 controls (4000 controls in the endemic community and 1766 controls in the nonendemic community) were followed for 25 months. A total of 153 subjects died during follow-up, including 24 endemic ataxic polyneuropathy cases, 115 controls in the endemic community, and 14 controls in the nonendemic community. Relative risks of death, adjusted for age and gender, were 4.5 for cases (P < 0.0001) but 2.6 for controls living in the endemic community (P = 0.001). Authors were of the opinion that the finding of lower risk of death in the community with higher exposure to cyanide from cassava foods indicated that mortality of endemic ataxic polyneuropathy was not associated with exposure to cyanide from cassava foods (38).

Biological basis

Etiology and pathogenesis

The Lathyrus sativus plant is still cultivated in India, Bangladesh, Nepal, Pakistan, Iran, the Middle East, southern Europe, Ethiopia, and some places in South America. Seeds of this legume plant, which is grown in arid and semi-arid tropical regions, contain beta-N-oxalyl amino-L-alanine (synonym beta-N-oxalyl-L-alpha,beta-diaminopropionic acid). Beta-N-oxalyl amino-L-alanine is a neurotoxin that, when consumed, causes lathyrism. The plant L sativus flourishes in conditions of the most devastating flood and drought, often when no other food crop survives. The product of this especially hardy plant, the chickling pea, historically has served as an inexpensive survival food for the poor population of poor and developing countries (30; 44). An epidemiological study from Ethiopia suggested that in areas with high neurolathyrism prevalence, prevalence is significantly influenced by age, gender, marital status, family size, grass pea production levels, and dietary habits. The study suggests that exclusive consumption of grass pea, particularly immature seeds and in high ratios compared to other cereals, poses a considerable risk for developing neurolathyrism, emphasizing the need for diversified diets and awareness to mitigate this risk (07).

The epidemics of konzo occur in the dry season among very poor rural populations, whose diets for the weeks and months before onset consist almost exclusively of bitter cassava roots. The root of the cassava (Manihot esculenta Crantz) shrub is an important staple food for millions of people in tropical and subtropical countries. Epidemic outbreaks in subtropical and tropical regions are associated with drought-provoked agricultural and social crises, rendering populations dependent on a diet of insufficiently processed bitter cassava. The shortcuts in processing allow large amounts of cyanogens to remain in the cassava consumed; hence, there is a high dietary cyanide exposure. The drought increases the natural occurrence of cyanogenic glucosides in the cassava roots, and the processing procedure normally applied to remove cyanide before consumption is shortened because of food shortage (53; 30; 37). Children with konzo had low levels of selenium, copper, and zinc compared to controls. Motor deficits associated with konzo may be due to a lack of trace elements-induced cyanide-scavenging (10). The diet of konzo-affected patients is usually deficient in protein content (55). A systematic review by Baguma and colleagues revealed that cassava-derived cyanide poisoning and protein malnutrition were two predominant risk factors in the pathogenesis of konzo. Authors further noted that thiocyanate, the biomarker of choice for cyanide exposure, does not accurately estimate the actual level of cyanide poisoning in konzo patients (03).

Tropical ataxic neuropathy is also encountered frequently in malnourished populations. Tropical ataxic neuropathy is frequently observed in populations that use large quantities of cassava in their diets for long periods. Some observations, however, do not suggest that cyanide is the cause of endemic ataxic polyneuropathy (39).

Beta-N-oxalyl amino-L-alanine (synonym beta-N-oxalyl-L-alpha,beta-diaminopropionic acid) is an excitatory amino acid and acts as an agonist at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-kainate receptors located on specific neurons and their dendrites. One of the primary effects of beta-N-oxalyl amino-L-alanine toxicity is the selective inhibition of mitochondrial complex-1 in the motor cortex and lumbar spinal cord (47). Streifler examined the central nervous system of a 67-year-old man who showed symptoms of lathyrism after being imprisoned at the age of 35 and fed a diet of chickling peas, Lathyrus sativus. The most obvious changes were a loss of axons and myelin in the pyramidal tract in the lumbar spinal cord. These alterations correlated with spastic paraparesis. The longest pyramidal neurons are more severely affected (44). Another change at the same level was a mild degree of degeneration of anterior horn cells. A few examples of senile plaques and neurofibrillary tangles were observed in Ammon's horn (50; 17). A report of a patient who had a disease 32 years before death revealed some changes in anterior horn cells with swellings, Hirano bodies, and dispersion of Nissl bodies (20). In a rat model of lathyrism, it was observed that the number and size of motor neurons were decreased only in the lumbar and sacral cord segments (26). In addition, extensive but transient hemorrhage was noted in the ventral spinal cord parenchyma of the rat. Vascular endothelial growth factor receptor levels were significantly lowered in the lumbosacral spinal cord of the paraparetic rats compared with their controls, suggesting a failure of the vascular endothelial growth factor system to protect neurons against beta-N-oxalyl-L-alpha,beta-diaminopropionic acid toxicity. Some studies have indicated that nutritional deficiencies of sulfur amino acid methionine and cysteine aggravate the neurotoxicity of beta-N-oxalyl amino-L-alanine (57).

A number of pathogenic mechanisms for the development of konzo and tropical ataxic neuropathy among inherently susceptible persons have been proposed. The metabolites of linamarin (α-Hydroxyisobutyronitrile β-D-glucopyranoside, dominant cassava cyanogen), cyanide (mitochondrial toxin), thiocyanate (AMPA chaotropic agent), and cyanate (protein carbamylating agent) are considered responsible for the pathogenesis of konzo (23).

The bitter varieties of cassava have a relatively high content of cyanide. Many plants liberate hydrogen cyanide from cyanogenic glycosides, a phenomenon called cyanogenesis, as a defense mechanism against animals and insects. Cassava is by far the most important human food source that uses cyanide as a defense mechanism (37). Cyanide is metabolized to several compounds, such as thiocyanate, cyanate, formate, and 2-iminothiazolidine-4-carboxylic acid, but the major metabolite is thiocyanate. The body uses sulfur-containing amino acids to render cyanide harmless. Thiols, which are sources of sulfur, are required to detoxify cyanide to thiocyanate. It has been hypothesized that the detoxification of cyanide to thiocyanate may be impaired in cases of tropical ataxic neuropathy because of the nutritional deficiency of thiols. If the diet is deficient in sulfur, cyanide will be converted to cyanate, which induces neurodegenerative disease in both animals and humans. Mainly children and ill people, often malnourished (and with kwashiorkor), are not able to detoxify the cyanide sufficiently, consequently developing symptoms of upper motor neuron damage (14; 51). Thiocyanate selectively promotes the action of excitatory amino acid glutamate at AMPA receptors. Some investigators have even suggested that cyanide is a potent inhibitor of mitochondrial enzyme cytochrome-c-oxidase. It has been suggested that cassava contains a chemical known as cyanoglucoside linamarin (alpha-hydroxyisobutyronitrile-beta-d-glucopyranoside). Linamarin is enzymatically converted to cyanide by bacteria in the intestine, and this is absorbed into the blood and then damages neural cells (49). It has been postulated that in Konzo patients, a severe exacerbation of thiamine deficiency results from the inactivation of thiamine that occurs when the sulfur in thiamine is utilized for the detoxification of cyanide consumed in improperly processed bitter cassava (02).

In patients of konzo, the neuronal cells that are most likely affected are Betz cells in the motor cortex. There are no autopsy reports on konzo available. In two original cases, described by Trolli, spinal cords were reported normal. Autopsies performed in ex-prisoners of war suffering from tropical ataxic neuropathy revealed demyelination of the posterior column (particularly of the fasciculus gracilis) and the optic nerves. Nerve biopsy revealed nonspecific patchy demyelination with variable pericapillary cellular reaction and perineural fibrosis (52).

A review presented a unifying hypothesis on the causative agents of lathyrism, konzo, and tropical ataxic neuropathy (28). This review suggested that these diseases may be caused by a group of cyano-containing compounds called nitriles. Direct neurotoxic actions of nitriles are 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, allylnitrile and cis-crotononitrile cause sensory toxicity, whereas hexadienenitrile and trans-crotononitrile induce selective neuronal degeneration in discrete brain regions (28). 3,3'-iminodipropionitrile also induces a neurofilamentous axonopathy, and dimethylaminopropionitrile is known to cause autonomic neurotoxicity in both humans and rodents.

A study suggested a causal association between konzo and the gut microbiome (09). Bramble and colleagues utilized a shotgun metagenomic sequencing technique in 180 individuals in the Democratic Republic of the Congo. Samples were drawn from different geographical regions of Congo, including participants from konzo-prone regions. The gut flora of individuals varied from region to region. Despite similarities in levels of nutritional deficiency, lifestyles, and diets high in cyanogenic cassava, the relative abundance of gut flora in unaffected children from these two konzo-prone areas was significantly different. The authors concluded that the unique gut flora potentially modulates the susceptibility to konzo in konzo-prone regions of the Democratic Republic of the Congo.

Epidemiology

Once prevalent throughout Europe, North Africa, the Middle East, and parts of the Far East, lathyrism is restricted to India, Bangladesh, and Ethiopia. A survey was conducted in an Ethiopian district (a known endemic area for lathyrism), and disease information was obtained for 2987 family members after interviewing 589 randomly selected heads of households. Neurolathyrism patients were detected in 56 households (9.5%, prevalence rate 2.38%). The mean number of affected family members per household was 1.27. The median age at onset of paralysis was 11 years (range 3 to 44 years) (15). Two northwestern districts of Bangladesh with a population of 629,752 were surveyed from June 1991 to March 1993 to detect and follow up with lathyrism patients. Out of 2567 neurologic patients, 882 were diagnosed as having lathyrism, giving a prevalence rate of 14 per 10,000. This prevalence was higher among young males: only 12.9% of the patients were female, and only 19.3% were over 30 years of age at onset of the disease (19). A door-to-door epidemiological survey for the disease was carried out in the major areas of northwest and central Ethiopia where Lathyrus sativus was grown. The survey involved a population of 1,011,272. A total of 3026 affected persons were identified. Variable prevalence rates in different regions, ranging from one per 10,000 to 7.5 per 1000 were observed. The male-to-female ratio of cases was 2.6 to 1; the females exhibited a milder form of the disease (18). An epidemiological study performed in Northeast Ethiopia noted that overall prevalence of lathyrism among 2307 inhabitants was 5.5% (22). Men were more frequently affected than women.

In areas of India where a high consumption of Lathyrus sativus was previously reported, increased awareness of the disease has led to a marked reduction in lathyrism cases. A total of 17,755 (13,129 rural and 4626 urban) inhabitants from 151 villages and 60 wards from urban areas were clinically examined, and only nine old cases of lathyrism were found. Total consumption of Lathyrus sativus had also drastically decreased (25).

The majority of cases of konzo occur during epidemics. In the last decade, several epidemics of konzo have been reported among the African rural populations, including Mozambique, Tanzania, Zaire, and the Central African Republic. Konzo affects mainly women and children. Breastfed children and adults over 50 years of age often remain spared from konzo. A strong familial clustering during epidemics has been noted. The prevalence rate of konzo in affected populations ranges from 1 to 30 per 1000. Two large epidemics have been reported, each of more than 1000 cases. The first was in the Bandundu region in Congo (1936 to 1937), and the second was in the Nampula province of Mozambique (1981). Small outbreaks have been reported from other places. Sporadic cases of konzo also occur. Most cases of konzo occur in the dry season, chiefly during a long drought. Cliff and colleagues reported an epidemic of konzo in which 384 patients were treated in rehabilitation centers. The prevalence rate in a badly affected area was 30 per 1000. Most patients were children over the age of 3 years and women (14). In a report of Médecins Sans Frontières’s demographic data, history, and clinical presentation were recorded for each konzo patient among 60,000 refugees from the Central African Republic who sought refuge in villages in eastern Cameroon (between 2005 and 2007) (12). A total of 469 patients were diagnosed with konzo. Children and women of reproductive age were dominantly affected. Most patients developed symptoms in a seasonal pattern, with most of the cases occurring during the dry winter season. Most of the patients complained about walking difficulties and weight loss and had exaggerated lower limb reflexes and muscle wasting.

The prevalence of tropical ataxic neuropathy in some parts of Africa ranges from 29 to 34 cases per 1000 population. A study determined the prevalence of tropical ataxic neuropathy in southwestern Nigeria. A total of 4583 inhabitants were registered in the census. Of these, 3428 subjects aged 10 years and older were screened. The diagnosis of tropical ataxic neuropathy was made in 206 of 323 subjects who screened positive for tropical ataxic neuropathy. The prevalence of tropical ataxic neuropathy was 6% (4% in males and 7.7% in females). The highest age-specific prevalence was 24% in the 60 to 69 years age group in women (40).

In an epidemiological study in Nigeria, 2392 individuals aged 18 years or older (a country with high consumption of cassava-based meals) were screened for tropical ataxic neuropathy. In this study, 39 cases of tropical ataxic neuropathy were diagnosed with a rough prevalence rate of 16.3 out of 1000. Distal sensory polyneuropathy was the most common clinical manifestation (43).

References

01: Acton HW. An investigation into the causation of the lathyrism in man. Ind Med Gaz 1922;57(7):241-7. PMID 29008389
02: Adamolekun B. Etiology of Konzo, epidemic spastic paraparesis associated with cyanogenic glycosides in cassava: role of thiamine deficiency. J Neurol Sci 2010;296(1-2):30-3. PMID 20619859
03: Baguma M, Nzabara F, Maheshe Balemba G, et al. Konzo risk factors, determinants and etiopathogenesis: What is new? A systematic review. Neurotoxicology 2021;85:54-67. PMID 33964344
04: Banea JP, Bradbury JH, Mandombi C, et al. Effectiveness of wetting method for control of konzo and reduction of cyanide poisoning by removal of cyanogens from cassava flour. Food Nutr Bull 2014;35(1):28-32. PMID 24791576
05: Barceloux DG. Grass pea and neurolathyrism (Lathyrus sativus L.). Dis Mon 2009;55(6):365-72. PMID 19446680
06: Barrow MV, Simpson CF, Miller EJ. Lathyrism: a review. Q Rev Biol 1974;49(2):101-28. PMID 4601279
07: Bimerew M, Gebremeskel T, Beletew B, et al. Prevalence of neurolathyrism and its associated factors in grass pea cultivation areas of Dawunt District, North-Eastern Ethiopia, 2022: a community-based multilevel analysis. BMC Neurol 2023;23(1):357. PMID 37798732
08: Boivin MJ, Okitundu D, Makila-Mabe B, et al. Cognitive and motor performance in Congolese children with konzo during 4 years of follow-up: a longitudinal analysis. Lancet Glob Health 2017;5(9):e936-47. PMID 28807191
09: Bramble MS, Vashist N, Ko A, et al. The gut microbiome in konzo. Nat Commun 2021;12(1):5371. PMID 34508085
10: Bumoko GM, Sadiki NH, Rwatambuga A, et al. Lower serum levels of selenium, copper, and zinc are related to neuromotor impairments in children with konzo. J Neurol Sci 2015;349(1-2):149-53. PMID 25592410
11: Bumoko GM, Sombo MT, Okitundu LD, et al. Determinants of cognitive performance in children relying on cyanogenic cassava as staple food. Metab Brain Dis 2014;29(2):359-66. PMID 24481810
12: Ciglenecki I, Eyema R, Kabanda C, Taafo F, Mekaoui H, Urbaniak V. Konzo outbreak among refugees from Central African Republic in Eastern region, Cameroon. Food Chem Toxicol 2011;49(3):579-82. PMID 20538034
13: Cliff J, Nicala D. Long-term follow-up of konzo patients. Trans R Soc Trop Med Hyg 1997;91(4):447-9. PMID 9373651
14: Cliff J, Nicala D, Saute F, et al. Konzo associated with war in Mozambique. Trop Med Int Health 1997;2(11):1068-74. PMID 9391509
15: Getahun H, Lambein F, Vanhoorne M, Van der Stuyft P. Pattern and associated factors of the neurolathyrism epidemic in Ethiopia. Trop Med Int Health 2002;7(2):118-24. PMID 11841701
16: Getahun H, Lambein F, Vanhoorne M, Van der Stuyft P. Neurolathyrism risk depends on type of grass pea preparation and on mixing with cereals and antioxidants. Trop Med Int Health 2005;10(2):169-78. PMID 15679560
17: Giménez-Roldán S, Morales-Asín F, Ferrer I, Spencer PS. Historical setting an neuropathology of lathyrism: insights from the neglected 1944 report by Oliveras de la Riva. J Hist Neurosci 2019;28(4):361-86. PMID 31268820
18: Haimanot RT, Kidane Y, Wuhib E, et al. The epidemiology of lathyrism in north and central Ethiopia. Ethiop Med J 1993;31(1):15-24. Erratum in: Ethiop Med J 1993;31(2):155-6. PMID 8436097
19: Haque A, Hossain M, Wouters G, Lambein F. Epidemiological study of lathyrism in northwestern districts of Bangladesh. Neuroepidemiology 1996;15(2):83-91. PMID 8684587
20: Hirano A, Llena JF, Streifler M, Cohn DF. Anterior horn cell changes in a case of neurolathyrism. Acta Neuropathol (Berlin) 1976;35(4):277-83. PMID 183453
21: Howlett WP, Brubaker GR, Mlingi N, Rosling H. Konzo, an epidemic upper motor neuron disease studied in Tanzania. Brain 1990;113(Pt 1):223-35. PMID 2302534
22: Hussien FM, Dagnaw MM, Ahmed AY, Hassen HY. Lathyrism and socioeconomic disparities: a neglected public health problem in Northeast Ethiopia. Am J Trop Med Hyg 2021;104(5):1889-94. PMID 33684061
23: Kashala-Abotnes E, Okitundu D, Mumba D, Boivin MJ, Tylleskär T, Tshala-Katumbay D. Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning. Brain Res Bull 2019;145:87-91. PMID 29981837
24: Kessler A. Lathyrismus. Monatsschrift für Psychiatrie und Neurologie 1947;113:76-92. PMID 20270244
25: Khandare AL, Kumar RH, Meshram II, et al. Current scenario of consumption of Lathyrus sativus and lathyrism in three districts of Chhattisgarh State, India. Toxicon 2018;150:228-34. PMID 29908260
26: Kusama-Eguchi K, Yamazaki Y, Ueda T, et al. Hind-limb paraparesis in a rat model for neurolathyrism associated with apoptosis and an impaired vascular endothelial growth factor system in the spinal cord. J Comp Neurol 2010;518(6):928-42. PMID 20058324
27: Lancaster PA, Ingram JS, Lim MY, Coursey DG. Traditional cassava-based foods: Survey of processing techniques. Economic Botany 1982;36:12-45.
28: Llorens J, Soler-Martín C, Saldaña-Ruíz S, Cutillas B, Ambrosio S, Boadas-Vaello P. A new unifying hypothesis for lathyrism, konzo and tropical ataxic neuropathy: nitriles are the causative agents. Food Chem Toxicol 2011;49(3):563-70. PMID 20553991
29: Ludolph AC, Hugon J, Dwivedi MP, Schaumburg HH, Spencer PS. Studies on the aetiology and pathogenesis of motor neuron diseases. 1. Lathyrism: clinical findings in established cases. Brain 1987;110(Pt 1):149-65. PMID 3801847
30: Ludolph AC, Spencer PS. Toxic models of upper motor neuron disease. J Neurol Sci 1996;139 Suppl:53-9. PMID 8899659
31: Madhusudanan M, Menon MK, Ummer K, Radhakrishnanan K. Clinical and etiological profile of tropical ataxic neuropathy in Kerala, South India. Eur Neurol 2008;60(1):21-6. PMID 18437044
32: Mbelesso P, Yogo ML, Yangatimbi E, et al. Outbreak of konzo disease in health region No. 2 of the Central African Republic. [Article in French.] Rev Neurol 2009;165(5):466-70. PMID 19081587
33: Murti VV, Seshadri T, Subramanian V. Neurotoxic compound of seeds of Lathyrus sativus. Phytochemistry 1964;3:73-78.
34: Mwanza JC, Tshala-Katumbay D, Tylleskar T. Neuro-ophthalmologic manifestations of konzo. Environmental Toxicology and Pharmacology 2005;19:491-6. PMID 21783517
35: Newton CR. Cassava, konzo, and neurotoxicity. Lancet Glob Health 2017;5(9):e853-4. PMID 28807173
36: Ngudi DD, Kuo YH, Van Montagu M, Lambein F. Research on motor neuron diseases konzo and neurolathyrism: trends from 1990 to 2010. PLoS Negl Trop Dis 2012;6(7):e1759. PMID 22860149
37: Nzwalo H, Cliff J. Konzo: from poverty, cassava, and cyanogen intake to toxico-nutritional neurological disease. PLoS Negl Trop Dis 2011;5(6):e1051. PMID 21738800
38: Oluwole OS, Onabolu AO. High mortality of subjects with endemic ataxic polyneuropathy in Nigeria. Acta Neurol Scand 2004;110(2):94-9. PMID 15242416
39: Oluwole OS, Onabolu AO, Cotgreave IA, Rosling H, Persson A, Link H. Incidence of endemic ataxic polyneuropathy and its relation to exposure to cyanide in a Nigerian community. J Neurol Neurosurg Psychiatry 2003;74(10):1417-22. PMID 14570837
40: Oluwole OS, Onabolu AO, Link H, Rosling H. Persistence of tropical ataxic neuropathy in a Nigerian community. J Neurol Neurosurg Psychiatry 2000;69(1):96-101. PMID 10864612
41: Osuntokun B. Neurological disorders in Nigeria. In: Spillane J, editor. Tropical neurology. London: Oxford University Press, 1973:161-90.
42: Osuntokun BO. An ataxic neuropathy in Nigeria. A clinical, biochemical and electrophysiological study. Brain 1968;91(2):215-48. PMID 5721927
43: Otubogun FM, Akinyemi RO, Ogunniyi AO. Tropical ataxic neuropathy: findings of a neuroepidemiological survey of Odeda, southwest Nigeria. J Neurol Sci 2019;405:116434. PMID 31520868
44: Parks NE. Metabolic and toxic myelopathies. Continuum (Minneap Minn) 2021;27(1):143-62.** PMID 33522740
45: Rivadeneyra-Domínguez E, Vázquez-Luna A, Rodríguez-Landa JF, Mérida-Portilla CV, Díaz-Sobac R. The protective effect of two commercial formats of Ginkgo biloba on motor alterations induced by cassava juice (Manihot esculenta Crantz) in Wistar rats. Neurologia 2017;32(8):516-22. PMID 27130308
46: Rao SL, Adiga PR, Sarma PS. The isolation and characterization of beta-n-oxalyl-l-alpha, beta-diaminopropionic acid: a neurotoxin from the seeds of Lathyrus sativus. Biochemistry 1964;3:432-6. PMID 14155110
47: Ravindranath V. Neurolathyrism: mitochondrial dysfunction in excitotoxicity mediated by L-beta-oxalyl aminoalanine. Neurochem Int 2002;40(6):505-9. PMID 11850107
48: Román GC. Tropical myelopathies. Handb Clin Neurol 2014;121:1521-48. PMID 24365434
49: Sreeja VG, Nagahara N, Li Q, Minami M. New aspects in pathogenesis of konzo: neural cell damage directly caused by linamarin contained in cassava (Manihot esculenta Crantz). Br J Nutr 2003;90(2):467-72. PMID 12908909
50: Striefler M, Cohn DF, Hirano A, Schujman E. The central nervous system in a case of neurolathyrism. Neurology 1977;27(12):1176-8. PMID 563018
51: Teles FF. Chronic poisoning by hydrogen cyanide in cassava and its prevention in Africa and Latin America. Food Nutr Bull 2002;23(4):407-12. PMID 16619750
52: Trolli G. Paralplégie spastique épidémique, Syndrome æd´wmateux, cutané et dyschrimique. Médecins du Foréami 1936;112:1-38.
53: Tylleskar T, Banea M, Bikangi N, Cooke RD, Poulter NH, Rosling H. Cassava cyanogens and konzo, an upper motoneuron disease found in Africa. Lancet 1992;339(8787):208-11. Erratum in: Lancet 1992;339(8790):440. PMID 1346173
54: Tylleskar T, Howlett WP, Rwiza HT, et al. Konzo: a distinct disease entity with selective upper motor neuron damage. J Neurol Neurosurg Psychiatry 1993;56(6):638-43. PMID 8509777
55: Wood H. Konzo outbreak in Zambia linked to cassava-based diet. Nat Rev Neurol 2020;16(5):242-3. PMID 32203393
56: World Health Organization. Konzo: a distinct type of upper motoneuron disease. Wkly Epidemiol Rec 1996;71(30):225–232.
57: Xu Q, Liu F, Chen P, Jez JM, Krishnan HB. β-N-Oxalyl-l-α,β-diaminopropionic Acid (β-ODAP) Content in Lathyrus sativus: the Integration of nitrogen and sulfur metabolism through β-Cyanoalanine synthase. Int J Mol Sci 2017;18(3). PMID 28264526

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Ravindra Kumar Garg DM FRCP

Dr. Garg of King George's Medical University in Lucknow, India, has no relevant financial relationships to disclose.
See Profile

Editor

Peter J Koehler MD PhD

Dr. Koehler of Maastricht University has no relevant financial relationships to disclose.
See Profile

Patient Profile

Age range of presentation: Lathyrism: 2 to 64 years

Konzo: 2 to 64 years

Tropical ataxic neuropathy: 2 to 65+ years
Sex preponderance: Lathyrism:

male>female, >2:1

Konzo:

male>female, >1:1

Tropical ataxic neuropathy:

female>male, >2:1
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-9: Lathyrism: 988.2

Jamaican neuropathy and Jamaican paraplegic tropical ataxic-spastic syndrome: 349.82
ICD-10: Toxic effect of other noxious substances eaten as food: T62

Toxic effect of other and unspecified substances: T65

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Lathyrism, konzo, and tropical ataxic neuropathy

Associated Disorders

Osteolathyrism
Peripheral neuropathy

Differential Diagnosis

Lathyrism:
primary lateral sclerosis
nutritional myelopathies
hereditary spastic paraplegia
human immunodeficiency virus-myelopathy
- multiple sclerosis
- early spinal cord compression
- Konzo:
- human T-cell lymphotropic virus-associated myelopathy

Lathyrism, konzo, and tropical ataxic neuropathy

Lathyrism, konzo, and tropical ataxic neuropathy

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

References

Contributors

Author

Editor

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Toxic and nutritional deficiency optic neuropathies

Nystagmus

Third nerve palsy

Brain death/death by neurologic criteria

Hormonal contraception and stroke

Hepatic encephalopathy

Cervical spondylotic myelopathy

Bowel dysfunction in neurologic disorders

Lathyrism, konzo, and tropical ataxic neuropathy

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

References

Contributors

Author

Editor

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Toxic and nutritional deficiency optic neuropathies

Nystagmus

Third nerve palsy

Brain death/death by neurologic criteria

Hormonal contraception and stroke

Hepatic encephalopathy

Cervical spondylotic myelopathy

Bowel dysfunction in neurologic disorders

This is an article preview.
Start a Free Account
to access the full version.