PARKINSON'S DISEASE

INTRODUCTION

Parkinson’s disease (PD) is the second most common neurodegenerative disorder besides Alzheimer’s disease. There is a heavy burden on those affected and their families. There are no specific diagnostic tests, although a DAT scan may suggest. The diagnosis is critical and remains founded on clinical grounds.

 

Although the clinical picture is usually typical, there may unfortunately be features and symptoms that will in fact guide into one of the many alternative diagnoses.

 

 

HISTORY

James Parkinson in 1817 published his “An Essay on the Shaking Palsy”. In 1879, Charcot recognised the bradykinesia. Brissaud in 1895, drew attention to mid-brain lesions but it wasn’t until Greenfield and Bosanquet in 1953 that confirmed the depigmentation, selective cellular loss and degeneration of the substantia nigra.

 

It was only in the 1960s that Dopamine depletion was identified with a subsequent development of levodopa.

 

 

CLINICAL FEATURES

There are both motor and non-motor features of PD. The cardinal signs of PD are:

 

 

Superimposed on these basic identifying features are dysphagia, dystonia, gait freezing, gait impairment, generalised slowing, hand incoordination, hypomimia, hypophonia, imbalance and falls, leg pipe rigidity, micrographia, tremor of the hands but also other parts of the body and a stooped or tilted truncal posture.

 

The non-motor features include the following:

 

Neuropsychiatric

 

Dysautonomia

 

Sleep Disorders

 

Sensory Dysfunction

 

Pain

 

Fatigue

 

 

MOTOR SYMPTOMS

Bradykinesia refers to a slowness of movement with a progressive loss of amplitude or speed during attempted rapid alternating movements. There are a number of ways in which this can be demonstrated clinically.

 

 

REST TREMOR

The key to the tremor is that it is at rest. The tremor emerges when the affected body part is relaxed and supported by a surface, removing the action of gravitational forces. It vanishes with active movement. It will reappear after a few seconds when the arms are held out stretched which is called re-emergent tremor. The tremor is usually 3-6 Hz. The amplitude is variable from less than 1cm to more than 10cm. The tremor is usually pill-rolling.

 

 

RIGIDITY

Reflects increased muscle tone, felt during examination. Rigidity plus tremor leads to the classical cogwheel rigidity.

 

 

POSTURAL AND GAIT IMPAIRMENT

There tends to be a stooped posture, contributing to falls and an inability to correct a disrupted centre of gravity. There may be camptocormia. The gait is slow on a narrow base characterised by short shuffling steps. This is sometimes referred to as the patient chasing their own centre of gravity. There is decreased arm swing, turning is slow and performed with multiple small steps. Freezing can occur as well, especially in crowded or narrow places. There may be festination.

 

 

NON-MOTOR SYMPTOMS

There would be too much narrative dealing with each of the non-motor symptoms of Parkinson’s disease but good reviews deal with all of the symptoms as listed above.

 

 

THE DIAGNOSIS OF PARKINSON’S DISEASE

The diagnosis of Parkinson’s disease depends on the presence of the cardinal features with three or more required for the diagnosis of the condition.

The UK Parkinson’s disease Society brain bank clinical diagnostic criteria will be discussed but are based on the following (as listed in the article “Cold Spring Harb Perspect Med 2012;2:a008870”).

 

 

Step 1: Diagnosis of parkinsonian syndrome

 

 

Step 2: Exclusion criteria for Parkinson’s disease

 

 

Step 3: Supportive positive criteria of Parkinson’s disease

 

 

DIFFERENTIAL DIAGNOSIS

PD can be confused with many disorders. There may be a whole range of degenerative disorders that superficially might seem similar. Vascular Parkinsonism for instance, can mimic in older people.

 

Drug induced Parkinsonism (DIP) occurs particularly with the use of phenothiazines, though often there are significant dyskinesias, tardive dystonia or akathisia. The diagnosis of DIP is made in the setting of such drug treatment.

 

 

DEMOGRAPHICS

It is thought that there are more than 4 million people with PD in the world. Although it is usually a condition of the 50+ age group, the genetic forms may occur in those as young as 30. Men are more commonly affected than women in a ratio of 3:2.

 

 

TREMOR DISORDERS

The most common tremor disorder misdiagnosed is benign essential tremor and remarkably, such people do see neurologists with a diagnosis of PD when in fact the diagnosis is a much more benign disturbance.

 

 

DEMENTIA WITH LEWY BODIES

Dementia is a fundamental feature of this condition, whereas it would be a side issue with PD.

 

 

MULTIPLE SYSTEM ATROPHY

Is characterised by the more marked dysautonomia, cerebella features and Parkinsonism.

 

Progressive supranuclear palsy that used to be called Steele-Richardson-Olszewski or Richardson’s syndrome has come to the forefront laterally with personalities having developed. The vertical gaze supranuclear palsy is usually the key with pseudobulbar symptoms and a range of other non PD physical features.

 

 

HEREDITARY FORMS OF PARKINSON’S

The last few years have seen an explosion in genomics. The Park syndromes are part of the genetic predisposition to PD.

 

The autosomal dominant forms are Park 1, Park 3, Park 4, Park 5 and Park 8. The autosomal recessive forms are Park 2, Park 6 and Park 7. If there is interest, then again there are excellent reviews of the developing genetics of PD and new identifications on a regular basis. In fact, we are now up to Park 20.

 

 

THE CAUSES OF PARKINSON’S DISEASE

The cause is unknown but a combination of inherited and environmental factors would seem to be significant.

Some people would appear to have had an increased lifetime exposure to well water, head trauma, various dietary influences, rural living and infection. Exposure to rotenone and paraquat may increase the risk. In women, an oophorectomy increases the risk.

 

Protective factors would appear to be smoking, drinking coffee or black tea and possibly the use of non-steroidal anti-inflammatory drugs. High uric acid levels also seem to protect.

 

PAIN IN PARKINSON’S DISEASE

Pain is rarely considered in people with Parkinson’s disease as a significant problem. In reality, it is very difficult to treat in those with the condition. It is always a problem in trying to separate drug or ageing effects from the disease. Pain is more common when motor function declines and dopamine responsiveness diminished. 60-85% of people with PD will have pain, though there are different mechanisms. Recently, a King’s PD pain scale has been validated but is not in general use yet.

 

 

MECHANISMS OF PAIN IN PARKINSON’S DISEASE

 

There are no strategies that actually exist for management. It is very much a try it and see approach.

 

 

THE MANAGEMENT OF PARKINSON’S DISEASE

The diagnosis is always a shock, though many will have made the diagnosis themselves with or without GP assistance.

 

It is best to have time available to break the news and then review with the questions that are bound to be raised. It is a progressive disorder that needs to be emphasised but the rate is variable and the condition is treatable. The advent of treatment has led to an increase in life expectancy of 12 years. Non-motor symptoms need to be managed as appropriate. For instance, impotence drugs and whatever necessary for constipation. When dementia symptoms arise, cholinesterase inhibitors or memantine need to be introduced.

 

With regard to the motor symptoms, the standard levodopa plus peripheral dopa decarboxylase inhibitor (carbidopa or benserazide) or the dopamine agonists which in effect fall into the ergot derivatives, such as bromocriptine, pergolide, cabergoline, dyhydroergocryptine and the non-ergot derivatives, such as ropinirole, pramiprexole, rotigotine and apomorphine will form the initial treatment. There is still no consensus as to the drug choice for therapy initiation in PD or the timing of increase. There is current thinking about delaying dopaminergic therapy but there is some concern as to how that thinking has come about.

 

Further medications include the monoamine oxidase B inhibitors such as selegiline and rasagiline, the catechol-O methyl transferase inhibitors (entacapone, tolcapone) and the anticholinergics, such as benztropine and trihexyphenidyl. Amantadine sits in a group of its own as an anti-viral agent that seems to also reduce tremor. Levodopa carries a higher risk of wearing off and sudden off-states, compared to the dopamine agonists, though it is by far the most effective drug in the control of motor symptoms. The dopamine agonist can cause peripheral edema, fibrotic reactions, excessive daytime somnolence and impulse control disorders.

 

 

ADVANCE TREATMENT FOR PARKINSON’S DISEASE

Functional neurosurgery has become an option, particularly for tremor, as has deep brain stimulation of either the subthalamic nucleus or internal globus pallidus. Various new ways of drug delivery, such as apomorphine infusion and dopamine gel being placed directly into the small intestine continue to be developed, as does the delivery of drugs through the skin.

 

Lifestyle adjustments need to be discussed, as does the driving regulation that is notifying DVLA and the insurance company. Possibly interacting with a driving instructor if necessary.

 

There is a lot of discussion about exercise programmes, showing that people with PD do need to be encouraged to exercise. Tai chi for instance, improves balance. Using visual or other sensory cues, such as striped lines on a floor or walking stick with a bar at the end will improve stride lengths, overall gait and diminished gait freezing. Voice training may also be beneficial.

 

 

THE FUTURE

As is well-known, various experimental treatments are under review. These include neuroprotective agents, spinal cord stimulation, stem cell and foetal adrenal transplants and gene delivery to the subthalamic nucleus. At the moment, none of these treatments are in standard practice and it is very much watch this space.