You are a Better Parkinson's Disease Caregiver Than You Think (eBook)

Foreword

It gives me great pleasure to write the foreword for this book by my good friend and colleague, Dr. Kevin Klos. Dr. Klos did his medical training at the Mayo Clinic in Rochester Minnesota. He was a neurology resident, then a Neurology Movement Disorders Fellow in our Movement Disorders Division. During those years, he saw many people with Parkinson’s disease and developed superb expertise in diagnosing and managing that condition. As the Division head at that time, I strongly encouraged him to join our staff at the Mayo Clinic, and I know he thought seriously about doing this. However, his family was a strong priority and for that reason, he moved home to Oklahoma and set up a Parkinson’s disease practice there. Over the years, he has been a very busy clinician and has seen countless people with Parkinson’s disease. I have long contended that expertise in managing Parkinson’s disease is not found in books, but rather seeing patients firsthand in the clinic. He and I both developed our clinical skills doing exactly that.

Somewhat ironically, his beloved mother has developed Parkinson’s disease, giving him an added and personal perspective. We both have had substantial empathy for our patients with Parkinson’s disease but the perspective of having an affected parent provides substantial, additional insight. Dr. Klos writes this book from that perspective.

Parkinson’s disease is fundamentally different from many other cerebral disorders. Conditions such as strokes, encephalitis as well as most autoimmune brain conditions typically start abruptly or over days, weeks or a few months. Parkinson’s disease is a neurodegenerative disorder, which starts and evolves slowly and in fact, much more slowly than most neurodegenerative conditions. Contrast Parkinson’s disease to amyotrophic lateral sclerosis (Lou Gehrig’s disease), which proves fatal after several years. Parkinson’s disease is in distinct contrast. Note that in the current era with the available medications, people with Parkinson’s disease live out a nearly normal life span. In the county in which I live (Olmsted County, Minnesota), the Parkinson’s disease longevity rates are just one year short of the actuarial predictions. Fifty years ago, people with Parkinson’s disease died well before their time. Hence, we have made strides although not nearly as much progress as any of us would like.

The actual duration of Parkinson’s disease (PD) is much longer than most people realize. A number of subtle often symptoms start well before the movement problems that characterize typical Parkinson’s disease (i.e., tremor, slowness, gait problems, etc.). PD-related conditions that may surface years or decades before the visible movement problems of Parkinson’s disease include REM sleep behavior disorder (dream enactment behavior), constipation, anxiety as well as loss of the sense of smell. There are well-documented cases of one or more of these conditions surfacing 20 years or longer before the early tremor or gait problems of Parkinson’s disease.

The typical movement problems characteristic of Parkinson’s disease primarily relate to degeneration of a specific region in the brain called the substantia nigra. This region connects with another area of the brain called the striatum and signals there by way of neurotransmitter release. That signaling chemical of this substantia nigra-striatum connection is dopamine. Dopamine is not a common neurotransmitter in the brain. In fact, it represents less than 1% of all the brain neurotransmitters. However, it is perfectly positioned to modulate the speed, amplitude and likelihood of motor movements. The neurodegenerative loss of this substantia nigra-striatum connection and the loss of the modulatory dopamine influence is responsible for most of the visible symptoms of Parkinson’s disease. Without this dopamine modulation in the striatum, slowness, impaired walking, stiffness or tremor ensue.

The neurodegenerative loss of the substantia nigra and its dopamine modulation of the striatum was recognized years ago to be the substrate for most of the Parkinson’s disease (PD) symptoms. This became the basis for PD treatment, i.e., replenishment of brain dopamine. Oral (and intravenous) dopamine cannot enter the brain and dopamine pills can provide no benefit for people with Parkinson’s disease. However, it was recognized in the 1960’s that the immediate natural precursor of dopamine, levodopa (l-dopa) is transported into the brain and is easily converted into dopamine.

Levodopa administration proved to markedly improve Parkinson’s disease symptoms but the response when this was first introduced was compromised by nausea and vomiting plus the need for very high doses. Scientists quickly appreciated that the problem related to the immediate conversion of levodopa to dopamine in the circulation, prior to brain entry. The enzyme that converts levodopa to dopamine is ubiquitous and present in the circulation (dopa decarboxylase). The solution was to design a molecule that would block that enzyme but not enter the brain. The solution was carbidopa, which cannot enter the brain but blocks the enzyme that converts levodopa to dopamine. (In other countries benserazide serves the same purpose as carbidopa). Hence, the standard of Parkinson’s disease treatment became and remains carbidopa/levodopa.

Carbidopa/levodopa remains the best medication for treating Parkinson’s disease and is responsible for the extension of PD longevity to near normality. However, dopamine is not the entire story and other symptoms occur early and late and do not have a dopamine basis.

Parkinson’s disease (PD) tends to be a decades-long process starting with subtle and non-disabling symptoms, often predating by years the visible, classic PD movement symptoms (gait, tremor, stiffness and slowness). This precursor state is variably characterized by dream enactment behavior (REM sleep behavior), constipation, anxiety or smell loss, which may span up to 20 years and occasionally longer.

These very early symptoms do not reflect loss of brain dopamine. The recognizable Parkinson’s disease state with visible tremor, slowness, etc., represents an intermediate stage characterized by loss of the substantia nigra and the inherent dopamine. In this scenario, this represents the second and third stages of Parkinson’s disease.

Note that the loss of the substantia nigra neurons responsible for the tremor, stiffness and walking problems is slow and visible symptoms are not apparent until dopamine neuron depletion reaches perhaps 50-60%. Estimates suggest that the dopamine neuron loss begins around 5-6 years before the movement symptoms become apparent.

The evolution of Parkinson’s disease obviously does not end with the appearance of PD symptoms. What might be regarded as the 3rd PD stage reflects the ongoing slow additional loss of the dopamine system (dopaminergic substantia nigra). Over several years, the progressive loss of dopamine-containing substantia nigra neurons results in instability of the levodopa treatment response. At that point, there are not enough surviving substantia nigra nerve terminals to maintain a stable level of dopamine at their connection with the striatum. One might speculate that this may occur when the substantia nigra depletion is on the order of 10-20% of baseline. At that juncture, the medication, levodopa (carbidopa levodopa), generates less consistent responses, plus with changing response dynamics. Specifically, this is when people with Parkinson’s disease develop the so-called, “wearing-off” responses and sometimes with involuntary movements called “dyskinesia”. These are treatable by way of medication adjustments but symptom control is often imperfect. This 3rd stage tends to persist for a number of years.

As this third stage continues, the Parkinson’s disease neurodegenerative process slowly starts to extend beyond the dopamine circuits. In other words, brain regions are affected where dopamine is not the signaling neurotransmitter and dopamine replenishment for these accompanying symptoms provides no benefit. Hence, after years in the third stage, the movement response to carbidopa/levodopa becomes less complete (still beneficial but less so than early in the course). .

Through these first 3 stages of Parkinson’s disease, people with PD typically do reasonably well and often do not require much help with activities of daily living. To variable degrees, however, people with long-standing Parkinson’s disease may start to reduce certain activities. At this point, family or spouses may need to take on more of the maintenance of the household. Many tasks and activities that were taken for granted in years past may need to be scaled back, such as landscaping projects or major household repairs. .Also, with more complex medication regimens the spouse or other family members may prove helpful by interceding with the clinician or provide insight about the dosage and timing of medications. However, through these three stages, people with Parkinson’s disease usually do reasonably well.

Not to be forgotten is involvement of the autonomic nervous system, which may become more problematic with passing years of Parkinson’s disease. The autonomic nervous system is responsible for bladder, bowel and blood pressure regulation. Symptoms that may develop include urinary urgency or incontinence, constipation or low blood pressure when standing.

The fourth PD stage is marked by the PD...