Introduction
Shaking Palsy: “Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellects being uninjured.”
Tremors, weakened and rigid muscles, and a stooped posture but the ability to see, hear, feel, taste, and smell intact and with no mental incapacities. These are the words of a man called James Parkinson. In 1817, the apothecary-surgeon published “An Essay on the Shaking Palsy,” wherein he observed the above symptoms in six people and thus defined the syndrome “shaking palsy,” which we now know as Parkinson’s disease.1
Since then, Parkinson’s has been studied and researched profusely. This research has provided many elucidations on the disease, from its pathophysiology to its treatment options. What causes Parkinson’s, though not completely understood, comes under two categories: genetics and environmental factors. One particular environmental factor that has been suggested is infection of adenovirus.
Overview of Parkinson's disease (PD)
In his essay, Parkinson noted that this was a “malady” that was slow in progression, with the first observed symptom being a “proneness to trembling,” particularly in a hand or arm. Over time, Parkinson declared, this trembling worsens and within twelve months the opposite hand or arm also begins to tremble.
Gradually, a person’s posture becomes less upright, they start to tremble in the legs, it becomes challenging to properly carry out daily tasks - eating, defecating, sleeping - and they begin to experience permanent pain in their limbs. According to Parkinson, at the very late stages of the syndrome, a person suffers from drooling, being unable to speak intelligibly, severe bladder and bowel incontinence, and violent trembling on an almost-permanent basis.
The six cases of John Parkinson’s essay
Parkinson based all of this on six cases, which are detailed below:
CASE 1 | - A man of more than 50 years old - A gardener - First experienced trembling in the hands and arms - Suffered limb pain which gradually became worse - Posture was very stooped - Had bladder and bowel dysfunction - Suffered from drooling - Died (the nature of his death, as well as the development of specific symptoms and the small amount of information/knowledge available, led Parkinson to research further) - Had never before suffered from (what would now be called) rheumatoid arthritis or seizures |
CASE 2 | - A 62-year-old man - Formerly an attendant at a magistrate’s office - Had suffered from the syndrome for 8 - 10 years at the time of meeting - Had difficulty speaking - Posture was very stooped – had to be supported entirely by a stick - Experiences gradual onset and worsening of symptoms - Was a heavy drinker - Had never sought medication/help |
CASE 3 | - A 65-year-old man - Previously a sailor - Had completely lost the ability to walk - Suffered from severe shaking of the entire body |
CASE 4 | - A 55-year-old man - Had been suffering from arms trembling for 5 years at the time of meeting - Had considerable degree of inflammation over lower left ribs and growth within the fascia tissue - Moved away meaning progression could not be monitored |
CASE 5 | - Observed at a distance – no age/characteristics were able to be obtained - Had very slow movement - Was able to run 20 paces before he needed catching to prevent a fall - Appeared to require support from another person at all times |
CASE 6 | - A 72-year-old man - Attributed symptoms to old age - Previously had severe lumbago (20 years prior) - Had suffered with “shaking palsy” symptoms for 11 or 12 years at the time of meeting - Trembling had started shortly after a weakness was felt in the left hand and arm and the right arm had started trembling in the subsequent 3 years - It hadn’t taken long until the whole body was affected by trembling, as well as trouble with speech - Had constipation, for which he had been treated with laxatives, which has eased at time of meeting - Had experienced a paralysis of the right side of his body for a fortnight, after which the trembling returned - Struggled eating and sleeping - Had violent shakes which increased in aggression and occurred in the whole body – he seemed to be able to stop it but only for a couple of minutes before it returned in full force |
Although Parkinson had a very small sample size of 6 people, his observations were consistent with what we know now. For example, men are more likely than women to suffer from Parkinson’s disease, and it is more common for patients to be older. In prevalence data from 2020, 69.9% of people who had Parkinson’s in the UK (starting from 50 years of age) were between the ages of 70 and 89.2
Most typically associated with Parkinson’s disease is an area of the brain called the substantia nigra (or “the black stuff”). The substantia nigra is located in the midbrain and is responsible for producing the "happy hormone," dopamine. As well as providing feelings of pleasure, motivation, and focus, dopamine also plays an essential role in movement. Therefore, people with Parkinson’s disease have low levels of dopamine. This is because of sticky, clumped-together structures of the protein alpha-synuclein (called Lewy bodies), which damage the cells of the substantia nigra therefore halting the production of dopamine.3
Overview of adenovirus
Adenoviruses are double-stranded DNA structures without an extra membrane layer. They cause relatively non-serious illnesses unless a person has a weakened immune system or existing respiratory diseases. Adenoviruses are highly contagious and spread through close contact, airborne droplets, surfaces, stool, and water. In 2019, there were approximately 88 strains of human adenovirus, which increased to 113 by June 2023.4,5
If a person is hosting an adenovirus in their body, they may experience the following:
- Common cold/flu symptoms e.g. fever, cough, runny nose, and sore throat
- Pink eye
- Ear infection
- Swollen lymph nodes
- Bronchitis
- Pneumonia
- Diarrhea
- Gastroenteritis - leading to nausea, stomach pain, and vomiting.
- UTIs
Potential links to neurological disorders
The above complications of an adenovirus infection are mainly symptoms of respiratory illnesses or gastrointestinal diseases, which make up the majority of the illnesses caused by adenovirus. However, while it is rare, adenoviruses have also been associated with brain infections such as encephalitis.6,7
This particularly occurs in young children, likely due to them having generally a less developed immune system than adults and therefore a poorer ability to fight infection of the virus. With these brain infections, adenovirus is a direct cause. Adenoviruses can directly invade the CNS by crossing the blood-brain barrier from the bloodstream into the brain.
Adenovirus and Parkinson’s progression
However, adenovirus can also be indirectly associated with brain disorders. When it comes to pre-existing neurological conditions, Parkinson’s in particular has been noted. In this case, adenovirus causes inflammation of the brain through a misdirected immune response which causes the immune system to attack brain cells.
Current evidence linking adenovirus to the progression of Parkinson’s disease
Although there is limited research on Parkinson’s disease progression as a result of adenovirus, one key study found that the disease was exacerbated by reactive astrogliosis (a reaction of astrocytes).
Astrocytes are a type of star-shaped brain cell – glial cells, as opposed to nerve cells – which produce the “calming” neurotransmitter, GABA. GABA is an inhibitory transmitter, meaning it blocks chemical messaging to slow brain function. It also has been found to inhibit dopamine release and production, both of which can result in Parkinson-like motor symptoms.8
Summary
- Parkinson’s disease is an age-related neurological disorder
- One hallmark “umbrella symptom” of Parkinson’s disease is a loss of motor activity. This includes involuntary shaking, slowed movement, and rigid limbs
- The exact cause of Parkinson’s disease is unknown, however, there have been many potential causes suggested which can be categorized into either genetics or environmental factors
- Parkinson’s is associated with the substantia nigra in the brain and low dopamine levels.
- Adenovirus is a very common virus primarily affecting the respiratory system, however, it has been known to invade the brain
- Adenovirus has been associated with the progression of Parkinson’s disease, found to induce reactive astrogliosis which affects dopamine release and production and is suggested to cause Parkinsonian symptoms
References
- James Parkinson essay on the shaking palsy [Internet]. [cited 2024 May 24]. Available from: http://archive.org/details/JamesParkinsonEssayOnTheShakingPalsy
- Parkinson’s UK [Internet]. [cited 2024 May 27]. Reporting on Parkinson’s: information for journalists. Available from: https://www.parkinsons.org.uk/about-us/reporting-parkinsons-information-journalists
- Parkinson’s UK [Internet]. 2024 [cited 2024 May 27]. What areas of the brain are affected in Parkinson’s? Available from: https://www.parkinsons.org.uk/research/research-blog/research-explained/what-areas-brain-are-affected-parkinsons
- Dhingra A, Hage E, Ganzenmueller T, Böttcher S, Hofmann J, Hamprecht K, et al. Molecular evolution of human adenovirus (Hadv) species c. Sci Rep [Internet]. 2019 Jan 31 [cited 2024 May 23];9(1):1039. Available from: https://www.nature.com/articles/s41598-018-37249-4
- Ukuli QA, Erima B, Mubiru A, Atim G, Tugume T, Kibuuka H, et al. Molecular characterisation of human adenoviruses associated with respiratory infections in Uganda. BMC Infectious Diseases [Internet]. 2023 Jun 27 [cited 2024 May 23];23(1):435. Available from: https://doi.org/10.1186/s12879-023-08403-9
- Zhao H, Liu Y, Feng Z, Feng Q, Li K, Gao H, et al. A fatal case of viral sepsis and encephalitis in a child caused by human adenovirus type 7 infection. Virology Journal [Internet]. 2022 Sep 28 [cited 2024 May 24];19(1):154. Available from: https://doi.org/10.1186/s12985-022-01886-z
- Tian J, Wang X, Zhang L, Li Q, Feng G, Zeng Y, et al. Clinical epidemiology and disease burden of adenoviral encephalitis in hospitalized children in China: A nationwide cross‐sectional study. Pediatric Investigation [Internet]. 2023 Dec [cited 2024 May 24];7(4):247–53. Available from: https://onlinelibrary.wiley.com/doi/10.1002/ped4.12396
- An H, Lee H, Yang S, Won W, Lee CJ, Nam MH. Adenovirus-induced reactive astrogliosis exacerbates the pathology of Parkinson’s disease. Exp Neurobiol. 2021 Jun 30;30(3):222–31.