Lytico-Bodig disease

Lytico-Bodig disease, sometimes spelled Lytigo-bodig is a neurological disease of uncertain aetiology that exists in the United States territory of Guam.

It resembles Amyotrophic lateral sclerosis (ALS) (more commonly known in North America as Lou Gehrig's disease), Parkinson's Disease, and Alzheimer's. First reports of the disease surfaced in three death certificates on Guam in 1904. These death certificates made some mention of paralysis. The frequency of cases grew amongst the Chamorro people on Guam until it was the leading cause of death between 1940 and 1956.^{[citation needed]} The symptoms range from strongly resembling ALS to those resembling Parkinson's Dementia Complex (PDC). The symptoms tend to show themselves between the ages of 25 and 40. Many victims aren't able to speak of their own accord but they can speak coherently and fluidly when spoken to. It is commonly thought that the disease is caused by toxins in the Cycad trees which are prevalent on Guam.

Neurologist Oliver Sacks detailed this mysterious condition in his book Island of the Colourblind . Sacks wrote that a local species of fruit bat, which is now largely extinct due to over-hunting, had been feeding on Cycads and concentrating β-Methylamino-L-alanine (BMAA), a known neurotoxin, in its body fat. The theory is that consumption of the fruit bat transferred sufficient quantities of the toxin to lead to long term toxicity, although this has not yet been proven.

History

Lytico-bodig is a disease that presents itself in two ways:

• lytico: a progressive paralysis that resembles ALS (amyotrophic lateral sclerosis) which is a disease of the neuron
• bodig: a condition resembling parkinsonism with occasional dementia.

Patients can exhibit one or both of the above portions of the disease, but in order to understand this neurodegenerative phenomenon one must examine the history of the disease itself and the people who are affected.

Lytico-bodig was discovered in 1952 by Koerner and a year later was confirmed by Arnold. The study that led these two scientists to this discovery was an instance that was peculiarly notable on the island of Guam. Both scientists noted a 50 to 100 fold greater occurrence of amyotrophic lateral sclerosis than the rest of the world, and a notable increase in parkinsonism with dementia.

The people who were found to have this disease were the Chamorro people who are native to Guam. Guam has undergone several serious events over the course of its history. In 1668, a near genocide of the Chamorros was started; by 1710, there were almost no Chamorros on the island of Guam. The island was handed over to the United States government in 1898 and after World War II it was retaken from the Japanese by American Forces. After the aforementioned hardships, the Chamorros survived and their living situation improved.

There was no documentation of anything that could resemble lytico-bodig in the entire history of the Chamorros. They were actually described as a very healthy people who live to old age. It was not until 1904 that any cases of death from paralysis occurred. By 1940 this elusive paralysis was the primary cause of death in an adult Chamorros.

Symptoms

There is no standard form of lytico-bodig. It is a disease that can take three, six, or twenty different forms.

Symptoms of Bodig

The symptoms for this disease differ from patient to patient but a good example of what happens to the body once bodig sets in is an excerpt from the book The Island of the Colorblind by Oliver Sacks.

The doctor visited a patient that had just suddenly come down with a virulent form of bodig. His symptoms had begun 18 months ago, starting with a strange immobility, a loss of initiative and spontaneity; he found he had to make a huge effort to walk, to stand, and to make the least movement—his body was disobedient. The immobility attacked with frightening speed and within a year he was unable to stand alone and could not control the posture of his body (2006).

Progressive dementia is also characteristic of bodig. Those who experience dementia are often aphasic, restless, demonstrate irrational behavior such as violence, and deep emotions at odd intervals. They experience highs and lows such as giggling one minute and screaming the next.

Patients in the most virulent stage of bodig have the mouth hang open, drooling with saliva; the palate hangs motionless so that speech and swallowing are impossible. The arms and legs become severely spastic and become bent in immovable tension.

The clinical picture of bodig was often one of a profound motionlessness, almost catatonia, accompanied with a little tremor or rigidity. Except in the cases of those who have dementia coupled with bodig, most patients are capable of lucid thought and speech.

Symptoms of Lytico

As with bodig, the symptoms and forms of lytico present themselves differently from patient to patient.

Symptoms such as muscles wasting away, not being able to move or open the mouths to speak, and choking to death because of the inability to swallow are just some of the things that are prevalent in patients. Some patients retain lucidity throughout the illness until the end.

The muscles of respiration become paralyzed and mechanical ventilation is needed to induce breathing, saliva must be suctioned from the mouth in order to prevent aspiration of the trachea and lungs because the swallowing muscles are locked up.

This form of lytico-bodig is fatal in all cases.

Mechanism

The mechanism is complex and poorly understood. During autopsies, neurofibrillary tangles are found in the brain which are practically congruent to the brain of an Alzheimer's patient.

The following is an excerpt from Island of the Colorblind viewing samples of substantia nigra. "Many of the cells are pale and depigmented. There's a lot of glial reaction, and bits of loose pigment. Shifting to a higher power,he saw a huge number of neurofibrillary tangles, densely staining, convoluted masses, harshly evident within the destroyed nerve cells." Looking at other samples of hypothalamus, spinal cord, and cortex, all were full of neurofibrillary tangles. Neurofibrillary degeneration was everywhere. These slides were similar in appearance to those taken from post-encephalitic parkinsonism.

These slides were also very similar to the neurofibrillary tangles found in Alzheimer's disease, however, in Alzheimer's there are not as many, and they occur in a different distribution. This could be a possible clue as to the process of neurodegeneration but it is still inconclusive.

While neurofibrillary degeneration is a potential cause of the mechanism of lytico-bodig, much is still undiscovered as to what causes the symptoms, the severity, and how the onset of symptoms progresses. However because of the similarities to those of post-encephalitic patients and Alzheimer's patients this could account for the similarities in symptoms of lytico and bodig. Some even wonder if lytico-bodig, post-encephalitis, and Alzheimer's could possibly be the same disease, a viral one, which could take three different forms.

Age of onset seems to be increasing with no more teenage cases and almost no cases in their twenties. Sometimes one form of the disease will present itself chiefly in one decade and then predominately bodig in the next. This is unaccounted for.

No treatment has been found to cure the disease of lytico-bodig. In some cases L-DOPA was given to patients to alleviate some of the symptoms of bodig but this only gave the patient one or two hours of freedom from the complete paralysis and rigidity of limbs. It seems in the case of the Chamorro's, the family is the primary caregiver and that they have accepted those that are ill and provide home care for all those inflicted with lytico-bodig.

An Evolution of Research

Some hypotheses to the cause of the disease include genetics, cycad seeds, and ingested BMAA from the consumption of fruit bats. The actual cause of the disease is as mysterious as the vast manifestations of the disease itself.

Genetics

This was the first hypothesis due to the situation on Guam. Lytico-bodig was found in great numbers on an Island among members of the Chamorro community. It would make sense that it was some sort genetic factor that played a role. This hypothesis was the first to be created and the first to be disproved. There was no Mendellian connection in the disease. It was actually found that only the older generation of Chamorro had the disease, so it had disappeared in one generation. Also, Chamorro who grew up outside of Guam had not developed the disease, and some non-Chamorro who moved to the Island and followed the culture did develop it. Therefore, this hypothesis was quickly dropped. For more information view Pathological Study of Motor Neurone Disease

Cycad Seeds

Cycad seeds are a big part of the Chamorro lifestyle. They are ground to make a flour which is called "fadang", and the flour is then used to make tortillas and dumplings. The flour is soaked and cleaned several times because the seed in is natural form is extremely toxic. One article described that livestock that drink from the water of the first cleaning dropped dead instantly. Much research was done on this the Cycad hypothesis and it was found that cycasin was a component of the seeds. Cycasin was discovered in the 1950s and was once considered one of the most potent carcinogens known. As toxic as it was, it would not be the cause of the symptoms of lytico-bodig. All hope for this hypothesis was not lost, for another toxic substance was found in the seeds. In the 1960s, British biochemists found a substance called beta-N-methylamino-levoalanine or BMAA. Experiments were performed to test the toxicity, and it was found that when monkeys were fed synthetic BMAA they developed symptoms of ALS-PDC and thus of lytico-bodig. However, the treated flour was tested for BMAA, and was not found to contain sufficient quantities.^{[citation needed]}

Fruit Bats

Another theory was introduced by Paul Alan Cox and Oliver Sacks after examining aspects of the Chamorro diet. Fruit bats were a common food for the Chamorro, which often ate cycad seeds themselves. It was found that the bats would bioaccumulate BMAA in their fat, and that eating even a few bats would cause a dose of BMAA similar to levels that produced disease symptoms in the earlier animal models. Cox also observed that there was a matching decline in fruit bat consumption, and in lytico-bodig. This hypothesis is still being investigated.

The actual disease could die off before a cure is found since it is only found in the older generation of people on Guam, and the cause has not yet been found.

Lytico-bodig is isolated to Guam which makes it an excellent opportunity to research neurodegenerative diseases. If a cure was found, it could lead to significant information on other diseases such as Parkinson's and Alzheimers. Only time and future research will tell the outcome of the disease.

See also

• For more information about the Evolution of Research see:

American Journal of Epidemiology

Journal of Neuro-Ophthalmology

• β-Methylamino-L-alanine (BMAA)

References

Wiederholt, W.C. 2000. Guam: the puzzle of Parkinson's. National Institute of Health Report 3:3.

Morris, H.R., Al-Sarraj, S., Schwab, C., Gwinn-Hardy, K., Perez-Tur, J., Wood, N.W., Hardy, J., Lees, A.J., McGreer, P.L., Daniel, S.E., and J.C. Steele. 2001. A clinical and pathological study of motor neurone disease on Guam. Brain 11:2215-2222.

Carrico, C. 2004. Island Lore. Beyond the bench: Representations of pharmacology and science in the media 4:296-297

Sedwick, L.A. 2003. Terry A. Cox, md,PhD, neuro-ophthalmologist, biostatistician, and birdwatcher. Journal of Neuro-Ophthalmology 23:108-110

External links

• Ashland University Ohio Wiki Entry
• Details at National Parkinson's Foundation