Infectious Diseases

Evidence for an Infectious cause of Parkinsons Disease



Tweet
Dr. Bryan Katz's image for:
"Evidence for an Infectious cause of Parkinsons Disease"
Caption: 
Location: 
Image by: 
©  

Parkinson's disease (PD) is a degenerative motor disorder resulting from the progressive loss of dopaminergic neurons in an area of the brain known as the basal ganglia, in particular two clusters of cells called the substantia nigra. The manifestations of PD appear when 80% or more of the dopamine producing neurons have been destroyed. Symptoms of PD include difficulty initiating movement (bradykinesia); a shuffling gait; the classic pill rolling hand tremor; a blank facial expression; muscle rigidity; and in 10-15% of cases, the onset of dementia late in the course of the disease.

Nearly a century ago, in the wake of the 1918 influenza pandemic, which left as many as 50 million people dead worldwide, physicians in the U.S. and Europe reported numerous cases of a Parkinson's-like condition described as postencephalitic parkinsonism, also referred to as Von Economo's encephalopathy. Patients developed a debilitating paralysis, sometimes years after suffering a bout of influenza. Whether the particular strain of influenza virus behind the 1918 pandemic was the culprit in the development of PD symptoms years later remains a mystery, as very few cases of postencephalitic parkinsonism have been diagnosed since 1926.

The enigmatic influenza virus

Although many scientists are now convinced that the genotype of the influenza virus responsible for the 1918 pandemic was H1N1, the mechanism underlying this virus's virulence remains unclear. Part of the reason for this uncertainty stems from the unique nature of the influenza virus itself. Unlike most other viruses, influenza contains a segmented genome comprised of eight distinct sequences of RNA. The virus not only undergoes genetic point mutations, known as antigenic drift, over the course of a flu season but also a phenomenon known as antigenic shift. This occurs when two strains of influenza viruses infect the same cell then proceed to mix and match entire segments of their genomes. This genome swapping ability leads to radically altered (and occasionally deadly) viral progeny, as occurred in later flu epidemics in 1957 and 1968. Incidentally although several hundred thousand Americans died in those epidemics, there was no spike in the number of postencephalitic parkinsonism cases afterwards. 

Another factor complicating the picture is the ability of influenza to hide in hosts other than humans including pigs, chickens, and ducks. All of these animals are capable of spreading the virus to humans; in fact, the H1N1 strain most closely resembles a form of avian influenza. Whether the survivors of the 1918 pandemic who later developed postencephalitic parkinsonism were infected with a unique variant of H1N1 (or perhaps with multiple strains of influenza) will probably never be known for certain.  

In addition to a viral etiology, several other theories have been proposed to account for the pathogenesis of PD. As yet, no consensus has emerged as to a specific cause or causes. In contrast to the etiology, the epidemiology of PD is well characterized: approximately 1% of Americans over age 65 will develop Parkinson's. The disease shows no predilection for any particular ethnic group, and both genders are affected equally. Although PD can strike younger people, they represent roughly 10% of the estimated 3 million cases of PD in the United States.   

Given that 90% of people with PD develop symptomatic disease after age 65, many researchers believe that long term exposure to environmental toxins is the major risk factor for developing PD. Some contend that people who live in rural areas and drink well water are at a higher risk of developing PD. Other researchers focus on exposure to the chemical MPTP, which induces Parkinsonian symptoms in primates. They also point to a high incidence of PD (or a similar disease called PSP) among natives of the island of Guam whose diet formerly included fruit bats. These particular bats allegedly contained high levels of MPTP or similar molecules.  Yet other researchers believe the alpha synuclein gene on chromosome 4 is involved in PD, citing the example of a family with a rare autosomal dominant form of the disease. Nonetheless, most cases of PD occur sporadically, even among identical twins.

The treatment regimen of PD patients consists of the dopamine precursor Levodopa (L-dopa can cross the blood brain barrier where it is converted to dopamine); anticholinergic medications to balance out the relative excess of acetylcholine in the basal ganglia; and several adjunct medications including dopamine receptor agonists like bromocriptine (to mimic the action of dopamine), as well as monoamine oxidase and COMT (catecholamine O-methyltransferase) inhibitors to slow the degradation rate of dopamine throughout the brain. Efforts to replace dopaminergic neurons with stem cell transplants have met with mixed results. Evidence suggests that younger patients tend to benefit more so than elderly ones from cell transplant therapy.


Tweet
More about this author: Dr. Bryan Katz

From Around the Web




ARTICLE SOURCES AND CITATIONS
  • InfoBoxCallToAction ActionArrowhttp://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001762/
  • InfoBoxCallToAction ActionArrowhttp://flu.emedtv.com/1918-flu/1918-flu-p2.html
  • InfoBoxCallToAction ActionArrowhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169890/pdf/v064p00005.pdf
  • InfoBoxCallToAction ActionArrowhttp://www.nejm.org/doi/full/10.1056/NEJMp058281
  • InfoBoxCallToAction ActionArrowhttp://www.virology.ws/2009/05/01/influenza-virus-rna-genome/
  • InfoBoxCallToAction ActionArrowhttp://flu.emedtv.com/flu/flu-outbreaks.html
  • InfoBoxCallToAction ActionArrowhttp://www.environmentalhealthnews.org/ehs/news/parkinsons-and-pesticides
  • InfoBoxCallToAction ActionArrowhttp://www.mydr.com.au/seniors-health/parkinson-s-disease-mptp-and-drug-induced-parkinson-s
  • InfoBoxCallToAction ActionArrowhttp://discover.coverleaf.com/discovermagazine/201105/?pg=45#pg45
  • InfoBoxCallToAction ActionArrowhttp://www.michaeljfox.org/living_viewpoints_researcherAreaPositionPapers_alphaSynuclein.cfm