Parkinson's disease series for patients and caregivers. Part 1.

Of the conditions known to impact public health in the USA, the burden of Parkinson’s disease is one of the fastest growing.

In 2020, Yang, Hamilton, and colleagues reported their findings on overall public cost of Parkinson’s in Nature. A staggering $25.4  billion of direct medical costs and $26.5 additional indirect and non-medical cost, such as caregiver costs, disability payments, and others, are projected to only increase in the future.

While Alzheimer’s disease, the most common neurodegenerative disorder in the world, was in the center of attention since the early 90ties, Parkinson’s was less known to the public. Since Dr. James Parkinson first described the condition in mid-19^th century and up until late 20^th century, Parkinson’s disease remained a rare disorder.

This started to change sometime during 2000s. According to Dorsey, Ray, et al, “from 1990 to 2015, the number of people with Parkinson disease doubled to over 6 million”, and this number is projected to double again to over 12 millions by 2040.

Parkinson’s disease affects the lives of the patients profoundly, limiting their ability to perform work, enjoy favorite activities and life, and in later stages, their cognitive function.

In this series of posts, we will review that changes that occur in patient’s bodies and how those changes affect quality of life. We will also outline some of the complementary measures to take that might help the practitioners and patients achieve optimal results. 

First, let’s see what is going on at the level of the nervous system cells called neurons.

When the brains of people who died with Parkinson’s disease are carefully studied, two findings stand out:

1. Look at the picture below. Notice a loss of darkly pigmented areas of the brain?
   
   On the left, brain has distinct, darkly pigmented bands easily visible on the backdrop of much lighter surrounding brain tissue. This is a healthy brain.
   On the right, the bands are blurred out, barely visible, in the brain affected by Parkinson’s disease.
   
   The darkly pigmented areas of a healthy brain are populated by neurons that make large amounts of neurotransmitters called dopamine and norepinephrine.
   
   The loss of those neurons profoundly affects ability of the brain to regulate movements. Dopamine and norepinephrine are also known contributors to mood maintenance and adequate stress response. Dopamine specifically is known to support  daytime alertness and “reward driven” behaviors. 
   
   As dopamine and norepinephrine production drops, people are likely to experience lack of motivation, depression, and decreased enjoyment of life.
   
   
2. Along with loss of neurons, scientists see accumulation of a protein called synuclein in the areas of brain damaged in the course of Parkinson’s disease.
   
   Synuclein forms a special type of formations called “Lewy bodies”. Lewy bodies aggregate in the neurons as “blobs” with a little clearing, or halo around them. Too much synuclein accumulation is directly toxic to neurons and worsens the impact of Parkinson’s on the brain.

When it comes to clinical diagnosis, the following is what practitioners see:

• Bradykinesia, or slow movements, delay in initiating movements.
• Resting tremor, that shows during inactivity, but disappears with movements.
• Rigidity that doesn’t depend on the movement amplitude or velocity.
• Postural and gait changes
• Neurologic changes that include mental and emotional symptoms, gastrointestinal symptoms, and even changes in vision and smell.
• Marked response to dopamine-enhancing medications.

For the doctor to clinically diagnose Parkinson’s disease, a patient must have bradykinesia PLUS one of the three: resting tremor, postural instability, or rigidity.

We will discuss each of these in more detail in future entries. 

Currently, doctors consider diagnosis of Parkinson to be mostly clinical. That is because the changes that happen in the brain are initially on such a small scale, that imaging might not pick it up, but careful physical examination and review of history of patient's symptoms could reveal a recognizable pattern early on. 

By the time when brain imaging findings are notable enough for common imaging techniques, most patients already experience signs and symptoms of Parkinson's that significantly affects their lives. 

In 2011, FDA approved a DaTscan, a type of single photon emission computed tomography (SPECT) scan with the contrast ioflupane iodine-123 injection.

It helps to discriminate between essential tremor and tremor related to depletion in Dopamine transporters in the brain. 

While not specific for Parkinson, the scan picks up dopamine depletion in striatum and helps physicians pick up on pathologies leading to such depletion, of which Parkinson is the most common. Two other major pathologies are Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP). 

The scan is relatively expensive, and will help to diagnose estimated 5% - 15% of patients seen by doctors for movement disorders. Therefore, many doctors do not order DaTscan when they feel that clinical picture is clear enough for diagnosis.