What disorders belong to the Parkinson spectrum? - Chapter 21

How is Parkinsonism defined?

Parkinsonism, also known as hypokinetic-rigid syndrome, is a collection of motor symptoms that form the core symptom for a group of progressive neurodegenerative disorders classified as the 'Parkinson spectrum'. Parkinson's disease is the most common disorder in the Parkinson spectrum. Other forms, such as dementia with Lewy bodies (DLB) are less common. Secondary symptoms of Parkinson's disease may also arise as a result of vascular damage: vascular parkinsonism. In contrast to vascular parkinsonism, Parkinson's disease is more progressive, no to little response to specific medication (although patients with vascular parkinsonism often do not respond to this), cognitive decline in the initial phase and a shorter lifespan. This chapter only deals with Parkinson's disease.

What is the clinical picture?

Motor symptoms

According to Wolters (2007), the motor symptoms of Parkinson's disease have four characteristics:

1. Lack of movement/slowness (akinesia, hypokinesia and bradykinesia).

2. Rigidity (movements are stiff and sometimes jerky; 'cogwheel phenomenon').

3. Rest tremor.

4. Postural instability.

Non-motor symptoms

Although there are often more non-motor symptoms, they are usually experienced as secondary. This mainly concerns fatigue, hyposmia (disturbed sense of smell), autonomic disorders, sleep disorders, affective disorders, apathy, cognitive impairment, impulse control disorders, and psychoses and hallucinations. 75% of all patients suffer from pain, which may be caused by muscle spasms or dystonia (persistent muscle contractions): the pain often diminishes once treatment with anti-Parkinson's drugs is started. Autonomic impairments such as blood pressure fluctuations, excessive perspiration, constipation, bladder problems and sexual difficulties occur. Some Parkinson's patients suffer from a sleep disorder (especially sleeping and staying asleep is experienced as difficult). Some suffer from 'REM sleep behaviour disorder' (RSBD): a specific sleep problem characterized abnormal REM sleep. The content of dreams is often extremely vivid, with fearful and aggressive themes: for this reason many couples go to sleep separately because otherwise they can regularly expect an unintended thump or kick.

What are the diagnostic criteria?

Because of the initially non-specific symptoms, the course of the symptoms is an important part of the diagnosis. The brain abnormalities can only be seen at an advanced stage, but the MRI can provide a definitive answer to a vascular disorder or tumors at an early stage. A PET and SPECT scan do not benefit from the differential diagnosis. There must be bradykinesia with one of the following: rigidity, postural instability and / or rest tremor. The motor symptoms should subside after taking antiparkinsonian medication (levodopa). Dementia with Lewy bodies (DLB) is more likely when there have been visual hallucinations in the year that the motor symptoms began. An atypical form of Parkinson's disease is considered if serious autonomic, eye movement or balance disorders are present at an early stage. Within Parkinson's disease there are subtypes such as the balance subtype, tremordominant and hypokinetic-rigid subtype. Each subtype has a different course and treatment. When the symptoms start on the left side of the body, there are often more cognitive problems (Katzen, Levin & Weiner, 2006).

Who develop Parkinson's disease?

Women have a slightly greater chance of developing Parkinson's disease. A higher age is a major risk factor. Every year 8,000 people are diagnosed. The Unified Parkinson Disease Rating Scale (UPDRS) is a multidimensional scale to estimate the severity of Parkinson's disease. This scale consists of six sections, two of which provide insight into the severity: section three (motor symptoms) and section five (the Hoehn & Yahr scale with five stages of severity ranging from symptoms on one side of the body to a severely disabled condition).

What causes Parkinson's disease?

The cause of parkinsonism is the degeneration of dopamine-producing neurons in the compact part (part of the substantia nigra or SN), first in the dorsal striatum and later in the ventral striatum and the mesocorticolimbic dopamine system. The SN is part of the basal ganglia, which interact with the thalamus and the cortex. Reduced dopamine disrupts this entire circuit: in the end, the subthalamic nucleus (STN) becomes hyperactive and causes decreased activation of the motor cortex via the thalamus. As soon as half of the dopamine-producing neurons in the SN have disappeared, the Parkinsonian symptoms begin. Changes within the cholinergic, noradrenergic and serotoninergic systems are also present.

Can Parkinson's disease be treated?

There is currently no treatment to cure Parkinson's disease and the deterioration cannot be slowed down. The antiparkinsonian medication, in particular levodopa and dopamine agonists, suppress motor symptoms. For the remaining symptoms, muscle relaxants and pain medication can be administered (Lohle and colleagues, 2009). Side effects of the antiparkinsonian medication are confusion, delusions, sleep attacks or even a psychosis. Motor side effects are also common over time: in the beginning there is tolerance (which results in a 'wearing off' or 'delayed response' of the medication). Dyskinesias (over-mobility) especially increase when the dose of levodopa is highest. The dopamine agonists cause impulse control problems. Attention and memory disorders, hallucinations and even dementia can be the result of anticholinergic drugs. If the medication is no longer effective, or if the side effects can no longer be tolerated, a brain operation may be considered. In this operation an electrode is implanted in the brain for continuous stimulation ('deep brain stimulation' or DBS), usually in the STN. The battery of the electrode is placed in the chest or abdominal cavity. Eventually, paramedical care (in the form of a multidisciplinary team) is always necessary for the patient to function as independently as possible.

Which cognitive impairments occur?

The majority of patients develop cognitive impairments. During the course of the disease these impairments may gradually develop into dementia. The cognitive impairments are noticeable in attention, mental speed, and memory, as well as in visuospatial deficiencies later in the course of the disease.

What does dementia look like in patients with Parkinson's disease?

Most patients with Parkinson's disease eventually develop dementia. In this case cognitive deterioration is most prominent in the areas of attention and speed. Executive impairments are prominent. Memory is not necessarily impaired (forgetfulness is reported often). Memory problems in patients with Parkinson's disease are less severe than in Alzheimer's disease. In addition, the memory disorders in Parkinson's patients mainly relate to retrieval of information. Another difference is that visual hallucinations are more common in Parkinson's disease patients (even without medication).

What makes Parkinson's disease even more difficult for patients?

Due to the disruption of the dopaminergic frontostriatal circuit, there are mainly problems within the executive functions. Impairments in memory, attention, and visual-spatial functions, and problems in the mental information processing speed. The visual-spatial defects are often secondary to the attention problems. Patients also have difficulty with cognitive flexibility and manipulating information in the working memory. They have a reduced capacity for initiative, increased introversion and less need for change. Levodopa has a positive influence on cognitive flexibility but induces problems within implicit learning as well as impulsive behavior. Patients have difficulty with the internal generation of automatisms: for this reason learning new skills is often disturbed because there is no transition from conscious to unconscious behavior. At a later stage, patients also have difficulty forming a ToM because they can no longer properly process emotional information based on negative emotions and facial expressions. Language problems are rare (there are subtle problems within the complex grammar), but speech problems are common. Sleep disorders increase the chance of developing dementia and a higher debut age and so-called ‘axial’ symptoms increase the chance of cognitive impairment (Wolter & Bosboom, 2007; Muslimovi and colleagues, 2009).

Which mood and behavioral disorders occur?

The amount of dopamine in the brain is related to (common) complaints of anxiety, depression and loss of motivation. The most common depressive symptoms are anhedonia and a depressed mood. In most cases the severity of the depression is mild to moderate. Medication often has a positive influence on these complaints. The psychotic behavior comes at an advanced stage and expresses itself by delusions and visual hallucinations. Initially, the hallucinations are even friendly and patients are fully aware of it. Later the content becomes more threatening and the insight disappears. This is often the reason for admission to a nursing home. The medication and DBS of the STN can lead to impulse control disorders (ICDs), 'punding' (an abnormal fascination and preoccupation with irrelevant activities) and a levodopa addiction. ICDs express themselves in being unable to postpone rewards, less inhibiting control and not having an overview of the consequences of behavior. Common ICDs are pathological gambling and hypersexuality. Punding can express itself, for example, in the urge to clean: the basic needs and social responsibilities are ignored as much as possible.