Beriberi

Beriberi refers to a cluster of symptoms caused primarily by a nutritional deficit in Vitamin B1 (thiamine). Beriberi has conventionally been divided into three separate entities, relating to the body system involved (nervous or cardiovascular) or age of patient (infantile). Beriberi is one of several thiamine-deficiency related conditions, which may occur concurrently, including Wernicke's encephalopathy, Korsakoff's syndrome, and Wernicke-Korsakoff syndrome.

Historically, Beriberi has been endemic in regions dependent on what is variously referred to as polished, white, or de-husked rice. This type of rice has its husk removed in order to extend its lifespan, but also has the unintended side-effect of removing the primary source of thiamine.

Pathophysiology
Thiamine has a half-life of 18 days and is quickly exhausted, particularly when metabolic demands exceed intake. Thiamine is involved in a variety of glucose metabolism-related and neurological functions. After modification in the body to a diphosphate form, thiamine is involved in a vast array of functions:
 * Carbohydrate metabolism
 * Production of the neurotransmitters glutamic acid and GABA, through the TCA cycle
 * Lipid metabolism, necessary for myelin production
 * Amino acid metabolism
 * Neuromodulation.

Neurons are very sensitive to ionic and metabolic changes produced in their immediate environment, which initially affect metabolism, electrical activity and performance, but then can lead to cell death.

Signs and symptoms
Symptoms of beriberi include weight loss, emotional disturbances, impaired sensory perception, weakness and pain in the limbs, and periods of irregular heart rate. Edema (swelling of bodily tissues) is common. It may increase the amount of lactic acid and pyruvic acid within the blood. In advanced cases, the disease may cause high output cardiac failure and death. Symptoms may occur concurrently with those of Wernicke's encephalopathy, a primarily neurological thiamine-deficiency related condition.

Beriberi is divided into three historical classifications:
 * Dry beriberi affects the nervous system
 * Wet beriberi affects the cardiovascular system and other bodily systems
 * Infantile beriberi affects also the children of malnourished mothers.

Dry beriberi
Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis. It is characterized by:
 * Difficulty in walking
 * Tingling or loss of sensation (numbness) in hands and feet
 * Loss of tendon reflexes
 * Loss of muscle function or paralysis of the lower legs
 * Mental confusion/speech difficulties
 * Pain
 * Involuntary eye movements (nystagmus)
 * Vomiting.

A selective impairment of the large proprioceptive sensory fibers without motor impairment can occur and present as a prominent sensory ataxia, which is a loss of balance and coordination due to loss of the proprioceptive inputs from the periphery and loss of position sense.

Wet beriberi
Wet beriberi affects the heart and circulatory system. It is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become edematous. Wet beriberi is characterized by:
 * Increased heart rate
 * Vasodilation leading to increased arteriovenous shunt
 * Elevated jugular venous pressure
 * Dyspnea (shortness of breath) on exertion
 * Paroxysmal nocturnal dyspnea
 * Peripheral oedema (swelling of lower legs)

Infantile beriberi
Infantile beriberi usually occurs between two and six months of age in children whose mothers have inadequate thiamine intake. In the acute form, the baby develops dyspnea and cyanosis and soon dies of heart failure. The following symptoms may be described in infantile beriberi:
 * Hoarseness, where the child makes moves to mourn but emits no sound or just faint moans, caused by nerve paralysis
 * Weight loss, becoming thinner and then marasmic as the disease progresses
 * Vomiting
 * Diarrhea
 * Occasionally convulsions were observed in the terminal stages
 * Pale skin
 * Edema
 * Ill temper
 * Alterations of the cardiovascular system, especially tachycardia (rapid heart rate).

Inadequate nutrition
Beriberi caused by inadequate nutritional intake is rare today in developed countries because of quality of food and the fact that many foods are fortified with vitamins. There are no reliable statistics for beriberi in developed countries in the 19th century or earlier; neither are statistics available before the last century in countries in extreme poverty.

Beriberi is a recurrent nutritional disease in detention houses even in this century. High rates of illness and death in overcrowded Haitian jails was traced in 2007 to the traditional practice of washing rice before cooking. In the Ivory Coast, among a group of prisoners with heavy punishment, 64% were affected by beriberi. Before beginning treatment, prisoners exhibited symptoms of dry or wet beriberi with neurological signs (swarming: 41%), cardiovascular signs (dyspnoea: 42%, thoracic pain: 35%), and oedemas of the lower limbs (51%). The rate of healing was about 97%.

Populations under extreme stress may be at higher risk for beriberi. Displaced populations, such as war refugees, are susceptible to micronutritional deficiency, including beriberi. The severe nutritional deprivation caused by famine will also cause beriberi, although symptoms may be overlooked in clinical assessment or masked by other famine-related problems. Extreme dieting can also rarely induce a famine-like state and the accompanying beriberi.

Wernicke's encephalopathy
Beriberi may also be caused by shortcomings other than inadequate intake: diseases of or operations on the digestive tract, alcoholism, dialysis, genetic deficiencies, etc. The name that includes all these causes and all symptomatic presentations is Wernicke's disease or Wernicke's encephalopathy.

Wernicke´s disease is one of the most prevalent neurological or neuropsychiatric diseases. In autopsy series, features of Wernicke lesions are observed in approximately 2% of general cases. Medical record research shows that about 85% had not been diagnosed, although only 19% would be asymptomatic. In children, only 58% were diagnosed. In alcohol abusers, autopsy series showed neurological damages at rates of 12,5% or more. Mortality caused by Wernicke's disease reaches 17% of diseases, which means 3.4/1000 or about 25 million contemporaries. The rate of sufferers may be even higher, considering that early stages may have dysfunctions prior to the production of observable lesions at necropsy. In addition, uncounted numbers of persons can experience fetal damage and subsequent diseases.

Etymology
The origin of the term 'beriber' comes from a Sinhalese phrase meaning "weak, weak" or "I cannot, I cannot", the word being duplicated for emphasis.

In 1630, a Dutch physician named Jacob de Bondt (Jacobus Bontius; 1591-1631) encountered the disease while working in Java. In the first known description of beriberi, he wrote, "A certain very troublesome affliction, which attacks men, is called by the inhabitants beriberi (which means sheep). I believe those, whom this same disease attacks, with their knees shaking and the legs raised up, walk like sheep. It is a kind of paralysis, or rather tremor: for it penetrates the motion and sensation of the hands and feet indeed sometimes of the whole body."

Identification
Beriberi was first described over 4,500 years ago, in the Chinese medical book Neichang. In Asia, where polished white rice (milled rice that has had its husk, bran, and germ removed) was the common staple food of the middle class, beriberi resulting from lack of vitamin B1 was endemic.

In the late 1800s, beriberi was studied by Takaki Kanehiro, a British-trained Japanese medical doctor of the Japanese Navy. Beriberi was a serious problem in the Japanese navy: sailors fell ill an average of four times a year in the period 1878 to 1881, and 35% were cases of beriberi. In 1883, Kanehiro learned of a very high incidence of beriberi among cadets on a training mission from Japan to Hawaii, via New Zealand and South America. The voyage lasted more than 9 months and resulted in 169 cases of sickness and 25 deaths on a ship of 376 men. With the support of the Japanese Navy, he conducted an experiment in which another ship was deployed on the same route, except that its crew was fed a diet of meat, fish, barley, rice, and beans. At the end of the voyage, this crew had suffered only 14 cases of beriberi and no deaths. This convinced Kanehiro and the Japanese Navy that diet was the cause. In 1884, Kanehiro observed that beriberi was endemic among low-ranking crew who often were provided nothing but rice, but not among crews of Western navies and nor among Japanese officers who consumed a more varied diet.

In 1897, Dr. Christiaan Eijkman, a Dutch physician and pathologist, demonstrated that beriberi is caused by poor diet, and discovered that feeding unpolished rice (instead of the polished variety) to chickens helped to prevent beriberi. The following year, Sir Frederick Hopkins postulated that some foods contained "accessory factors" – in addition to proteins, carbohydrates, fats, and salt – that were necessary for the functions of the human body. In 1901, Gerrit Grijns (May 28, 1865 – November 11, 1944), a Dutch physician and assistant to Christiaan Eijkman in the Netherlands, correctly interpreted the disease as a deficiency syndrome, and between 1910 and 1913, Dr. Edward Bright Vedder established that an extract of rice bran is a treatment for beriberi.. In 1929, Eijkman and Hopkins were awarded the Nobel Prize for Physiology or Medicine for their discoveries.

Treatment
Many authors agree that patients rarely present with thiamine deficiency alone, and therefore that the disease process in beriberi is multifactorial.

Beriberi is managed with thiamine supplementation. This can be done intravenously or orally. Supplementation can be monitored using blood tests. Patients' health can be improved within an hour of starting treatment, and rapid and dramatic recovery can occur within hours of administration. In situations where concentrated thiamine supplements are unavailable, feeding the patient with a thiamine-rich diet (e.g. whole grain brown bread) will lead to recovery, though at a much slower rate.