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Konzo is characterised by an acute isolated and symmetrical hypertonic paraparesis, which is permanent but non-progressive. The condition is to date only known in poor regions of Africa. In the Yaka valley konzo means "bound legs", a good description of the hypertonic gait. This is the name used in Congo and is now the official term for this motor neuron disorder.
Two large epidemics have been reported, each of more than 1000 cases. The first was in the Bandundu region in Congo (1936-37) and the second in the Nampulla province of Mozambique (1981). Small outbreaks have been reported from Congo, Mozambique, Tanzania and the Central African Republic. Sporadic cases of konzo also occur. The majority of cases of konzo occur in the dry season, chiefly during a long drought. Children who are being breastfed are not affected. Familial clustering is common.
The aetiology of konzo has not yet been fully clarified. At present a toxic/nutritional aetiology is assumed. There is an epidemiological connection between konzo and eating bitter cassava. Nevertheless, konzo only occurs in 1% of the cassava consuming population. Consumption of bitter cassava is a precondition, but not in itself sufficient to induce konzo. Epidemics coincide with periods of food shortage, drought, intense trading in cassava, and war. These are circumstances in which people may be inclined to shorten the long preparation which bitter cassava requires. If shortcuts are taken to process the cassava quickly, large amounts of cyanogens may remain in the food. The disorder can be regarded as a chronic cyanide intoxication, although the final word on this has not yet been spoken.
In many tropical regions cassava, or manioc, is the staple diet. There are various species, all belonging to the Euphorbiaceae: Manihot esculenta, M. aipi and M. utilissima. There are "sweet" and "bitter" varieties. In particular the bitter form survives well under dry conditions. The young leaves and shoots may be eaten as vegetables ("saka saka"). The tubers contain large amounts of starch. This is processed into flour (tapioca). It is an easy plant to grow in all kinds of conditions, and gives a good yield. It is usually harvested after 18 months. The cassava roots, when they are still attached to the stalk, remain good for many months if stored under the earth. Once harvested, however, deterioration begins quite quickly. There is an unwanted conversion of starch to sugar and a number of enzymatic reactions occur which cause discoloration of the product and reduces its value. Bacterial and fungal deterioration also occur. Drying the roots to a moisture content of less than 14% prolongs their storage life considerably. The roots of various plants are able to generate 31-630 mg HCN per kilogram, an enormous range. Low-cyanide varieties have less than 100 mg HCN-equivalent per kg of fresh weight. High-cyanide varieties have higher concentrations. If large amounts of bitter cassava are eaten for long periods, without special precautionary measures being taken to remove the toxin from the plant, and if there is a deficiency in sulphur-containing amino acids, a neurological disorder, known as konzo, results.
The capacity to produce toxic hydrogen cyanide is present in more than 2000 plant species, classified into over 100 plant families. In all cases the HCN is not stored as such in the cells. The plant produces complex molecules, generally glucosides, but also some lipids. From these, HCN can enzymatically be released. The enzyme that accelerates this reaction is physically separated from the cyanogenic substance. If the plant is crushed and its structural integrity is threatened, the enzyme comes into contact with the cyanogenic substance and the reaction can then take place. Teleologically, it can be assumed that the cyanide is intended to protect the plant from damage.
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The bitter varieties contain large amounts of the cyanogenic glucosides linamarin and lotaustralin, in a ratio of 10 to 1. Linamarin is found in vacuoles in the cytoplasm. The concentrations are highest in the peel. Linamarase, the enzyme which breaks down linamarin, is found in the cell wall. When the cells burst (accidental crushing of the plant, being eaten by insects or during processing), the linamarin comes into contact with linamarase. This enzyme splits linamarin into glucose and acetone cyanohydrin. The latter spontaneously releases acetone and HCN. This reaction may be accelerated by the cassava enzyme hydroxynitril lyase. Once HCN has been produced, it spreads in the air as gas (boiling point of HCN = 25.7°C).
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Cyanide (CN-) is normally converted in humans to the less toxic thiocyanate (SCN-) by the enzyme rhodanase, a mitochondrial enzyme which is widely present throughout the human body, with the highest concentrations in the liver and kidneys. Thiocyanate is the chief metabolite of cyanide. Thiocyanate itself has a goitrogenic effect if there is a shortage of iodine in the diet. The body uses sulphur-containing amino acids to render cyanide harmless. If the diet is deficient in sulphur, cyanide will be converted to cyanate (OCN-), which induces neurogenerative disease in both animals and humans. The cells which are most affected are Betz’ cells in the motor cortex.
Konzo begins abruptly, without prodromal signs. In 90% of cases the onset of symptoms takes less than one day. The initial symptoms are described as tremor, cramps, a heavy feeling and/or weakness in the legs, a tendency to fall down and difficulty remaining upright. There is a visible hypertonic gait when walking or running. Occasionally there will be lower back pain, blurred vision, speech difficulties and/or paresthesia of the legs, but they disappear within a month. During the first two days the majority of patients have general muscular weakness and are confined to bed. Hypertonicity is present from day one. Flaccid paralysis of the limbs does not occur. Later there is a slight partial improvement. Finally the affected person develops a stable hypertonic paraparesis, which persists for the remainder of life, or might improve a little. After onset the neurological signs remain constant or improve minimally if no further cyanide is ingested, unlike for example HTLV-1 infection in which further deterioration takes place. Some sufferers will later have a second attack with deterioration of their condition, possibly with dysarthria, abnormalities of eye movement, hypertonicity of the arms. There are indications that cyanide is not the only factor responsible for this disease.
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Note: motor neuron disease
The term "motor neuron disease" includes disorders in which (1) both the upper and the lower motor neurons are affected (amyotrophic lateral sclerosis), (2) disorders in which only the lower motor neurons are abnormal (spinal muscular atrophies, post-poliomyelitis syndrome) and (3) disorders of exclusively the upper motor neurons (neurolathyrism, konzo).
An isolated hypertonic paraparesis is ascertained, with no other neurologic abnormalities. Since this is an upper motor neuron disorder, very brisk reflexes are found in the legs and Babinski’s sign is present. There are no sexual, sphincter, cerebral or sensory abnormalities. Pronounced clonus occurs, or may be triggered by physical examination, e.g. dorsiflexion at the ankle joint.
The following criteria are used for the diagnosis of konzo:
Laboratory tests
Urinary concentrations of thiocyanate and linamarin are elevated. The patient is HTLV-1 negative.
There is no known aetiological treatment for konzo. Treatment with sodium thiosulphate (Na2S2O3), a cyanide antidote, gave disappointing results. A good and varied diet, high dose multivitamins and physical rehabilitation are advised. Since the sufferers have no cognitive defects, affected children should be encouraged to continue their education.
Konzo is not a large public health problem when Africa is regarded as a whole. It is, however, a real problem in the communities affected and of course for the individual patient. The message should be that (1) konzo is not infectious in order to avoid sufferers becoming socially isolated, (2) cassava should be processed correctly without missing out any steps (shortcuts in processing are to be avoided), (3) a varied diet is important. The tubers can be made safe by correct processing. As a first step the cells should be burst in order to bring the linamarin into contact with the endogenous glucosidase. In a second step (drying or heating) cyanohydrin is converted to hydrogen cyanide which then evaporates (this is faster at a higher temperature). The following precautionary measures should be taken when preparing cassava:
