Konzo | |
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A boy affected by konzo displaying the typical gait. The upper motor neuron is the suspected neurodamage site. | |
Specialty | Neurology |
Konzo [1] [2] is an epidemic paralytic disease occurring among hunger-stricken rural populations in Africa where a diet dominated by insufficiently processed cassava [3] results in simultaneous malnutrition and high dietary cyanide intake. [4] [5] Konzo was first described by Giovanni Trolli in 1938 [6] who compiled the observations from eight doctors working in the Kwango area of the Belgian Congo (now Democratic Republic of the Congo).
The onset of paralysis (spastic paraparesis) is sudden and symmetrical and affects the legs more than the arms. The resulting disability is permanent but does not progress. Typically, a patient is standing and walking on the balls of the feet with rigid legs and often with ankle clonus. [7]
Initially, most patients experience generalized weakness during the first days and are bedridden for some days or weeks before trying to walk. Occasional blurred vision and/or speech difficulties typically clear during the first month, except in severely affected patients. Spasticity is present from the first day, without any initial phase of flaccidity. After the initial weeks of functional improvement, the spastic paraparesis remains stable for the rest of life. [8] [2] Some patients may experience an abrupt aggravating episode, e.g. a sudden and permanent worsening of the spastic paraparesis. Such episodes are identical to the initial onset and can therefore be interpreted as a second onset.[ citation needed ]
The severity of konzo varies; cases range from only hyperreflexia in the lower limbs to a severely disabled patient with spastic paraparesis, associated weakness of the trunk and arms, impaired eye movements, speech and possibly visual impairment. Although the severity varies from patient to patient, the longest upper motor neurons are invariably more affected than the shorter ones. Thus, a konzo patient with speech impairment always shows severe symptoms in the legs and arms.[ citation needed ]
Recently, neuropsychological effects of konzo have been described from DR Congo. [9] [ clarification needed ]
The character of the neurological injury is not clear. The disease onset is associated with high intake of cyanide from a diet of mostly bitter cassava, which is low in protein, particularly sulfur amino acids. These are essential for the detoxification in the body of cyanide to thiocyanate, which is removed in the urine. [4] A number of studies implicate the combination of high cyanide intake from bitter cassava and low intake of sulfur amino acids as the cause. It has now been shown that the month by month incidence of konzo is significantly correlated with the percentage of children with high urinary thiocyanate content, which is a measure of their cyanide intake. The importance of an adequate supply of protein sulfur amino acids is shown from three unrelated konzo epidemics in Mozambique, [10] Tanzania [11] and DRC. People of the same ethnic group living only 5 km away from those with konzo had near zero konzo prevalence, because in Mozambique they lived near the sea, in Tanzania they lived near Lake Victoria and had access to fish and in DRC they lived near the forest and had access to animal protein.[ citation needed ]
The dose–response relationship between konzo incidence and cyanide intake, together with the prevention of konzo in many villages by reducing cyanide intake from cassava (see below) and the importance of sulfur amino acids in prevention of konzo, shows that konzo is very likely due to high cyanide/low sulfur amino acid intake in a diet of bitter cassava. Konzo does not occur unless these conditions are met, which occurs only in remote villages in six tropical African countries. The total number of reported cases up to 2009 was 6788, [12] but most cases are never reported and there was an estimate of 100,000 cases in DRC alone in 2002. [13] Konzo is spreading geographically as cassava is being grown in new areas where there is little knowledge of processing methods to remove cyanogens. [12] [14] Konzo epidemics occur due to war which causes disruption of life in poor villages and drought, when the plant increases the cyanogen content of roots 2–4 times [15] and the cyanide content of cassava flour also increases greatly. [16] [17] Konzo is also endemic in certain areas.[ citation needed ]
In East Africa, the traditional methods of processing cassava to remove cyanogens consist of sun drying and heap fermentation, which inadequately remove the cyanogens even in a year of normal rainfall. [17] In Central Africa, soaking (retting) of cassava roots in water for 4–5 days is adequate, but short soaking for only 1–2 days leaves too much cyanogens in the resulting flour and leads to konzo. [18] In West Africa, a roasted product called garri is produced by a different method than that used to produce flour, which reduces the total cyanide content to 10–20 ppm. [17] No cases of konzo are reported west of Cameroon, but another neurological disease called tropical ataxic neuropathy (TAN) occurs amongst older people in West Africa (including south-west Nigeria, Tanzania, Uganda, Kenya, and also in the West Indies and South India). [17] It is probably due to long term intake of cyanogens from cassava at a lower level than that needed to cause konzo. [17]
The WHO has recommended three criteria for the diagnosis of konzo:[ citation needed ]
Depending on its severity, konzo is divided into three categories: mild when individuals are able to walk without support, moderate when individuals need one or two sticks to walk, and severe when the affected person is unable to walk unsupported. [12]
The clinical symptoms are strikingly similar to those of Neurolathyrism. They are also similar to those of viral tropical spastic paraparesis and hereditary spastic paraparesis, but those two disorders have a slow onset. Konzo is clinically distinct from polio which is a flaccid paralysis and which most often affects a person asymmetrically.[ citation needed ]
Konzo is one of several tropical neuropathies. [19] [1] A distinct myeloneuropathy also associated to cyanogen intake from cassava is tropical ataxic neuropathy (TAN), as first described in parts of Nigeria by B. O. Osuntokun in 1968. The disease is still occurring in the same areas. [20] [21]
Konzo can be prevented by use of the "wetting method," [22] [23] [24] [3] which is used to remove residual cyanogens from cassava flour, as an additional processing method. Cassava flour is placed in a bowl and the level marked on the inside of the bowl. Water is added with mixing until the height of the wet flour comes up to the mark. The wet flour is placed in a thin layer on a mat for 2 hours in the sun or 5 hours in the shade to allow the escape of hydrogen cyanide produced by the breakdown of linamarin by the enzyme linamarase. The damp flour is then cooked in boiling water in the traditional way to produce a thick porridge called "fufu" or "ugali", which is flavoured by some means such as a sauce. The wetting method is accepted by rural women because it requires little extra work or equipment and produces fufu which is not bitter, because the bitter tasting linamarin has gone. [25]
In 2010 the wetting method was taught to the women in Kay Kalenge village, Popokabaka Health Zone, Bandundu Province, DRC, where there were 34 konzo cases. The women used the method and during the intervention there were no new konzo cases and the urinary thiocyanate content of the school children fell to safe levels. [26] Konzo had been prevented for the first time ever in the same health zone in which it had first been discovered by Dr Trolli in 1938. Fourteen months after the intervention ceased the village was visited again. It was found that there were no new cases of konzo, the school children had low urinary thiocyanate levels, the wetting method was still being used and it had spread by word of mouth to three nearby villages. [25] It is important to teach the women that konzo is due to a poison present in their food, to get them to regularly use the wetting method and posters are available in 13 different languages as a teaching aid [26] as an additional method to remove residual cyanogens.
The wetting method has now been used in 13 villages in the DRC with a collective population of nearly 10,000 people. The time of the intervention has been reduced from 18 months in the first intervention, [26] to 12 months in the second intervention, [27] to 9 months in the third and fourth interventions. This has reduced the cost per person of the intervention to prevent konzo by removing cyanogens from cassava flour, to $16 per person. This targeted method to reduce cyanide intake is much cheaper and more effective in preventing konzo than broad based interventions.[ citation needed ]
No treatment has been found, but affected individuals benefit considerably from rehabilitation and use of adequate walking aids. In the Central African Republic some children have been operated with an elongation of the Achilles tendon which improved the position of the foot but the long term consequence remains uncertain.[ citation needed ]
Konzo has been reported in outbreaks mainly among women and children in remote rural populations in DR Congo, [28] Mozambique [10] [29] (where it is known as mantakassa), Tanzania, [5] Central African Republic, [30] Cameroon and Angola.
The first reported outbreak occurred in Bandundu Province in present-day DR Congo in 1936–1937 and the second in Nampula Province of Northern Mozambique in 1981. Each of these outbreaks numbered more than 1000 cases. Familial clustering is common. Outbreaks typically occur in the dry season in households living in absolute poverty that have sustained themselves for weeks or months on insufficiently processed bitter cassava. Both smaller outbreaks and sporadic cases have been reported from all the countries above. [31]
"Konzo" means "tied legs" in the Yaka language of southwestern DR Congo and was the designation by the first affected population in DR Congo as reported by Dr G. Trolli in 1938. The name, taken up by Hans Rosling [32] and colleagues, aptly describes the typical spastic gait of those affected.
Manihot esculenta, commonly called cassava, manioc, or yuca, is a woody shrub of the spurge family, Euphorbiaceae, native to South America, from Brazil and parts of the Andes. Although a perennial plant, cassava is extensively cultivated as an annual crop in tropical and subtropical regions for its edible starchy root tuber, a major source of carbohydrates. Cassava is predominantly consumed in boiled form, but substantial quantities are used to extract cassava starch, called tapioca, which is used for food, animal feed, and industrial purposes. The Brazilian farinha, and the related garri of West Africa, is an edible coarse flour obtained by grating cassava roots, pressing moisture off the obtained grated pulp, and finally drying it.
Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditary spastic paraparesis, familial spastic paraplegia, French settlement disease, Strumpell disease, or Strumpell-Lorrain disease. The symptoms are a result of dysfunction of long axons in the spinal cord. The affected cells are the primary motor neurons; therefore, the disease is an upper motor neuron disease. HSP is not a form of cerebral palsy even though it physically may appear and behave much the same as spastic diplegia. The origin of HSP is different from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to treat HSP symptoms.
Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins during the first two years of life. Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size and seizures. The juvenile form of Alexander disease has an onset between the ages of 2 and 13 years. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control. Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder.
Methylenetetrahydrofolatereductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the MTHFR gene. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Natural variation in this gene is common in otherwise healthy people. Although some variants have been reported to influence susceptibility to occlusive vascular disease, neural tube defects, Alzheimer's disease and other forms of dementia, colon cancer, and acute leukemia, findings from small early studies have not been reproduced. Some mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency. Complex I deficiency with recessive spastic paraparesis has also been linked to MTHFR variants. In addition, the aberrant promoter hypermethylation of this gene is associated with male infertility and recurrent spontaneous abortion.
Tropical spastic paraparesis (TSP), is a medical condition that causes weakness, muscle spasms, and sensory disturbance by human T-lymphotropic virus resulting in paraparesis, weakness of the legs. As the name suggests, it is most common in tropical regions, including the Caribbean. Blood transfusion products are screened for human T-lymphotropic virus 1 (HTLV-1) antibodies, as a preventive measure.
Uhthoff's phenomenon is the worsening of neurologic symptoms in multiple sclerosis (MS) and other demyelinating diseases when the body is overheated. This may occur due to hot weather, exercise, fever, saunas, hot tubs, hot baths, and hot food and drink. Increased temperature slows nerve conduction, but the exact mechanism remains unknown. With an increased body temperature, nerve impulses are either blocked or slowed in a damaged nerve. Once the body temperature is normalized, signs and symptoms typically reverse.
Cyanogen bromide is the inorganic compound with the formula (CN)Br or BrCN. It is a colorless solid that is widely used to modify biopolymers, fragment proteins and peptides, and synthesize other compounds. The compound is classified as a pseudohalogen.
Hypertonia is a term sometimes used synonymously with spasticity and rigidity in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate descending pathways gives rise to disordered spinal reflexes, increased excitability of muscle spindles, and decreased synaptic inhibition. These consequences result in abnormally increased muscle tone of symptomatic muscles. Some authors suggest that the current definition for spasticity, the velocity-dependent over-activity of the stretch reflex, is not sufficient as it fails to take into account patients exhibiting increased muscle tone in the absence of stretch reflex over-activity. They instead suggest that "reversible hypertonia" is more appropriate and represents a treatable condition that is responsive to various therapy modalities like drug or physical therapy.
Dominant optic atrophy (DOA), or autosomal dominant optic atrophy (ADOA), (Kjer's type) is an autosomally inherited disease that affects the optic nerves, causing reduced visual acuity and blindness beginning in childhood. However, the disease can seem to re-present a second time with further vision loss due to the early onset of presbyopia symptoms (i.e., difficulty in viewing objects up close). DOA is characterized as affecting neurons called retinal ganglion cells (RGCs). This condition is due to mitochondrial dysfunction mediating the death of optic nerve fibers. The RGCs axons form the optic nerve. Therefore, the disease can be considered of the central nervous system. Dominant optic atrophy was first described clinically by Batten in 1896 and named Kjer’s optic neuropathy in 1959 after Danish ophthalmologist Poul Kjer, who studied 19 families with the disease. Although dominant optic atrophy is the most common autosomally inherited optic neuropathy (i.e., disease of the optic nerves), it is often misdiagnosed.
Hans Rosling was a Swedish physician, academic and public speaker. He was a professor of international health at Karolinska Institute and was the co-founder and chairman of the Gapminder Foundation, which developed the Trendalyzer software system. He held presentations around the world, including several TED Talks in which he promoted the use of data to explore development issues. His posthumously published book Factfulness, coauthored with his daughter-in-law Anna Rosling Rönnlund and son Ola Rosling, became an international bestseller.
Linamarin is a cyanogenic glucoside found in the leaves and roots of plants such as cassava, lima beans, and flax. It is a glucoside of acetone cyanohydrin. Upon exposure to enzymes and gut flora in the human intestine, linamarin and its methylated relative lotaustralin can decompose to the toxic chemical hydrogen cyanide; hence food uses of plants that contain significant quantities of linamarin require extensive preparation and detoxification. Ingested and absorbed linamarin is rapidly excreted in the urine and the glucoside itself does not appear to be acutely toxic. Consumption of cassava products with low levels of linamarin is widespread in the low-land tropics. Ingestion of food prepared from insufficiently processed cassava roots with high linamarin levels has been associated with dietary toxicity, particularly with the upper motor neuron disease known as konzo to the African populations in which it was first described by Trolli and later through the research network initiated by Hans Rosling. However, the toxicity is believed to be induced by ingestion of acetone cyanohydrin, the breakdown product of linamarin. Dietary exposure to linamarin has also been reported as a risk factor in developing glucose intolerance and diabetes, although studies in experimental animals have been inconsistent in reproducing this effect and may indicate that the primary effect is in aggravating existing conditions rather than inducing diabetes on its own.
Professor Benjamin Oluwakayode Osuntokun, was a researcher and neurologist from Okemesi, Ekiti State, Nigeria. Known for discovering the cause of ataxic tropical neuropathy, he was a founding member of the Pan African Association of Neurological Sciences and an early advocate and researcher on tropical neurology.
Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, and in both fatty acid and amino acid metabolism. It is important in the normal functioning of the nervous system via its role in the synthesis of myelin, and in the circulatory system in the maturation of red blood cells in the bone marrow. Plants do not need cobalamin and carry out the reactions with enzymes that are not dependent on it.
Antinutrients are natural or synthetic compounds that interfere with the absorption of nutrients. Nutrition studies focus on antinutrients commonly found in food sources and beverages. Antinutrients may take the form of drugs, chemicals that naturally occur in food sources, proteins, or overconsumption of nutrients themselves. Antinutrients may act by binding to vitamins and minerals, preventing their uptake, or inhibiting enzymes.
Health problems have been a long-standing issue limiting development in the Democratic Republic of the Congo.
A great variety of cassava-based dishes are consumed in the regions where cassava is cultivated, and the ingredient is included many national or ethnic specialities.
Cassava production is important to the economy of Democratic Republic of the Congo (DRC). It is one of the country's principal crops, with per capita consumption of 353 kg per year, which is the highest in the world. Zaire, now the DRC, was the world's largest consumer of cassava with Republic of the Congo ranked second in 1996.
Tropical ataxic neuropathy is a disease or category of diseases that commonly causes disability and increases mortality. The causes of TAN are not understood; there is no generally accepted treatment, and the reported outcomes are inconsistent. The disease affects poor tropical populations; there are no good statistics on how many people are affected worldwide, but in some populations, more than a quarter of people are affected. Malnutrition may play a role.
Tropical neuropathy is a class of illnesses with similar signs and symptoms, including konzo, tropical spastic paraparesis (TSP), and tropical ataxic neuropathy (TAN). TAN is poorly understood, and some researchers subdivide it further into separate illnesses.
Julie Laraine Cliff is an Australian physician and epidemiologist known for her work in the prevention and control of infectious diseases through investigating epidemics and health policy, particularly in Mozambique, where her career spanned around 40 years. There, her investigations revealed that the re-emergence of the paralytic disease konzo in poor rural communities was caused by high levels of cyanide in insufficiently processed cassava, as a result of changes in food preparation practices due to the economic effects of war and drought.
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