Question

Which of the following patients most likely suffers from a long-term viral infection?

		Jane, diagnosed with Parkinson's disease
		Jane, diagnosed with Huntington's disease
		Jane, diagnosed with Creutzfeldt–Jakob disease
		Sam, diagnosed with Alzheimer's disease

Answer 1

Answer:

Correct answer is Jane, diagnosed with Parkinson's disease

Parkinson's disease is a most common progressive, neurodegenerative disorder characterized by selective degeneration of dopaminergic neurones in the substantia nigra of the midbrain, resulting in decreased dopamine concentration which intereferes with the inhibition of excitatory impulses. It affects 1-2% of the adult population over 55 years of age.

Despite over 200 years since its first description by James Parkinson in 1817, the cause(s) in most cases of Parkinson’s disease are unknown, although it is generally accepted that there is a genetic susceptibility to a number of environmental agents.

One such agent is viruses. It has been shown that numerous viruses can enter the nervous system, i.e. they are neurotropic, and induce a number of encephalopathies. One of the secondary consequences of these encephalopathies can be parkinsonism, that can be both transient or permanent.

One of the most highlighted and controversial cases of viral parkinsonism is that which followed the 1918 influenza (Spanish flu) outbreak and the subsequent induction of von encephalitis lethargica (Economo's encephalopathy). It was described as a type of ‘sleeping sickness’ characterized by headache, nausea, fever, uncontrollable sleepiness, catatonia, and sometimes coma. Coincidence of encephalitis lethargica epidemic with an equally significant influenza pandemic, lead many clinicians and scientists from that time to believe there was a causal relationship (or at least an epidemiological association) between these conditions. However later on, multiple studies investigating the preserved brain samples of encephalitis lethargica patients found no evidence of the 1918 influenza virus in these tissues.

After that numerous cases of post-encephalitic Parkinsonism after certain viral infections (H5N1, coxsackie virus, Japanese encephalitis B., St. Louis viral encephalopathy, and HIV) have been reported, but these cases of Parkinsonism often do not exhibit the same cellular or molecular pathologies as seen in Parkinson’s disease and are suggested to be ‘phenocopies’ (showing similar features but produced by different cause) of Parkinson’s disease.

Although these acute cases of viral infection did not present with classical Parkinson’s disease but, these findings arouse interest in possible causative relationship between viral infections and Parkinson’s disease and led to multiple clinical studies in the late 1970’s.

Many of these studies found a significant relationship between viruses (herpes simplex virus, measles, influenza A, hepatitis virus) and idiopathic Parkinson’s disease. Upon viral infection, the host immune system usually becomes activated and attempts to remove or destroy the invading pathogen via inflammatory mediators, autophagy degradation, synaptic dysfunction, or sometimes controlled cell death of infected cells and Parkinson’s disease may be a long-term consequence of the viral infections of CNS and resulting changes.

Huntington's disease is an inherited disease caused by mutations in a gene that results in the progressive breakdown (degeneration) of nerve cells in the brain. It is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition). It usually occurs in patient in late 30’s and 40’s.

Creutzfeldt-Jakob disease (CJD) is a rare and fatal condition that causes brain damage that worsens rapidly over time. Symptoms of CJD include loss of intellect and memory, changes in personality, loss of balance and co-ordination, slurred speech, vision problems, jerking movements, and progressive loss of brain function. Most people with CJD die within a year of the symptoms starting, usually from infection by prions. It occurs due to build up of misfolded proteins or ‘prions’ in the brain.

Proteins are made up of a string of amino acids, then they fold themselves into a 3-dimensional shape called prions. Folding allows them to perform useful functions within cells. Normally prion proteins are found in almost all body tissues, but are at the highest levels in brain and nerve cells. The exact role of normal prion proteins is unknown, but it's thought they may play a role in transporting messages between certain brain cells.

Sometimes mistakes occur during protein folding and the prion protein can't be used by the body. Normally, these misfolded prion proteins are recycled by the body, but they can build up in the brain if they aren't recycled. Build-up of misfolded prion proteins in the brain also cause other prion proteins to misfold as well. This causes the brain cells to die, releasing more prions to infect other brain cells.Eventually, clusters of brain cells are killed and deposits of misfolded prion protein called plaques may appear in the brain. The damage to the brain causes the mental and physical impairment associated with CJD, and eventually leads to death.

Alzheimer's disease is the most common type of dementia. The exact cause of Alzheimer's disease is not yet fully understood. Alzheimer's disease is thought to be caused by the abnormal build-up of proteins (amyloid), which form plaques in and around brain cells. Deposits of other protein ‘tau’ form tangles within brain cells.

There's is also a decrease in level of neurotransmitters involved in sending messages between brain cells. Levels of neurotransmitter, acetylcholine, are particularly low in the brains of people with Alzheimer's disease. Over time, different areas of the brain shrink. The first areas usually affected are responsible for memories.

Although it's not known exactly what causes this process to begin, but they begin many years before symptoms appear.

Hence it is clear that long term viral infections are associated with Parkinson’s disease.