Definition

Parkinson’s disease (PD) is one of a group of conditions which are thought to be primarily due to the gradual loss of dopamine-producing brain cells, situated in the substantia nigra. It is considered to be a chronic disorder of the motor system primarily causing mobility problems. Postural problems are associated with later stages of the disease.

Incidence

It is unusual to find PD diagnosed before the age of 50 but the prevalence increases with age, becoming as high as 4% in older age groups, particularly in more industrialized countries. The incidence of PD in the UK is 18 per 100 000 population per year, amounting to approximately 10 000 new cases each year [1]. Sex distribution is approximately equal.

Mortality

PD is not generally considered to be a fatal disease. Major morbidity and mortality are less than 1%, having been reduced considerably by the modern drug regimes.

Risk factors

The root cause remains obscure but parkinsonism results from many different pathological processes, including ageing, environmental and genetic factors. Ageing is not thought to be a primary cause of PD, although the substantia nigra containing dopamine-producing neurons declines with age. It is possible that injury or infection in early life may predispose the patient to accelerated loss of this tissue. It has been suggested that PD can be a side-effect of certain psychotropic drugs [2]. Analytic studies generally reveal an inverse association between PD and cigarette smoking, although epidemiologic evidence does not support a direct protective effect of smoking [3].

It has also recently been suggested that gout can protect from PD. The value of the increased uric acid present in the system needs to be fully evaluated but first results are interesting [4]. The association between ischaemic stroke, vascular risk factors and PD has been addressed in several studies [5].

Shy–Drager syndrome is very similar to Parkinson’s in symptomatology but differs in one major respect, respiratory problems. It is described as multiple-system atrophy with autonomic failure and is a progressive disorder but is often first recognized by an increase in loud and strident snoring while the patient is sleeping.

This disorder is generally characterized by postural hypotension – an excessive drop in blood pressure which causes dizziness or momentary blackouts upon standing or sitting up. There are three types of Shy–Drager syndrome: (1) parkinsonian type, which may include symptoms of PD such as slow movement, stiff muscles and mild tremors; (2) cerebellar type, which may include problems such as loss of balance and the tendency to fall; and (3) combination type, which may include symptoms of both types.

There has been some argument over the years about other similar pathologies, known as vascular parkinsonism. The condition has been named and renamed several times, with terms such as arteriosclerotic parkinsonism, arteriosclerotic pseudoparkinsonism and lower-body parkinsonism. Despite the progress in our understanding of other parkinsonian syndromes, such as progressive supranuclear palsy and multiple-system atrophy, and significant developments in neuroimaging techniques, the concept of vascular parkinsonism is still unclear and the clinical diagnosis is often difficult [5], but from a physiotherapy or acupuncture perspective it does not differ greatly from PD.

Differential diagnosis

Early symptoms are subtle and make their appearance gradually, with those closest to the patient often unaware of what the diminished energy and depression may foreshadow. Normal voluntary and spontaneous movements are lacking. In some people the disease progresses more quickly than in others, leading to a rapid decrease in the ability to perform daily activities due to the shaking or tremor.

The definitive symptoms of PD are tremor at rest; involuntary trembling in the hands, arms, legs or jaw; rigidity or stiffness of the limbs and trunk; a general slowness of movement (bradykinesia); and impaired balance and coordination, often involving postural instability. ‘Dropped-head’ syndrome is characterized by severe neck flexion but minor thoracic or lumbar curvature. It results from neck extensor weakness or increased tone of the flexor muscles. This symptom is usually reported in neuromuscular diseases such as amyotrophic lateral sclerosis, myasthenia gravis and polymyositis or in extrapyramidal disorders, but does also occur in PD [6].

Patients may also have difficulty in walking or talking and completing small motor tasks becomes problematic.

In addition to these motor changes, there may be other symptoms, including depression and other emotional changes; difficulty in swallowing, chewing and speaking; urinary problems or constipation; skin problems; and sleep disruptions. There is noticeably decreased facial expression, apathy, fatigue and sometimes pain. This fatigue, combined with worsening functional status, can be a significant contributor to poor quality of life [7].

Some cognitive changes can be suspected early in the disease, particularly frontal lobe executive dysfunction. Parkinsonians find it difficult to turn thought into action. A slowing-down of mental processes is sometimes mistaken for dementia, but as a rule of thumb, if you give a Parkinson’s patient time to answer a question, he or she will answer. A patient suffering from Alzheimer’s will tend to forget the question. As the disease develops psychiatric problems can dominate the clinical picture. Depression is the most common of these, with about a third of patients suffering from depression at some stage in their disease [1].

Tests

The differential diagnosis is based on both medical history and a neurological examination. Early signs of value include infrequent blinking, the lack of arm swinging, and cogwheel or plastic rigidity accentuated when the opposite side is stressed. The disease can be difficult to diagnose accurately in the early stages so doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases.

Pharmacology

Various pharmacologic and surgical therapies have been developed to deal with the dysfunction caused by this disease. A variety of drugs provide some relief from the symptoms. Usually, patients are given levodopa combined with carbidopa. Carbidopa delays the conversion of levodopa into dopamine until it reaches the brain. Nerve cells can use levodopa to make dopamine and replenish the brain’s dwindling supply. Although levodopa helps at least three-quarters of parkinsonian cases, not all symptoms respond equally to the drug. Bradykinesia and rigidity respond best, while tremor may be only marginally reduced.

Problems with balance and other symptoms may not be improved at all. Anticholinergics may be used to help control tremor and rigidity. Other drugs, such as bromocriptine, pramipexole and ropinirole, mimic the role of dopamine in the brain, causing the neurons to react as they would to dopamine. An antiviral drug, amantadine, also appears to reduce symptoms. A relatively new drug, rasagiline (Agilect), can also now be used along with levodopa for patients with advanced PD or as a single-drug treatment for early PD. Constipation is a common problem, often as a result of decreased intestinal peristalsis induced by anticholinergics.

Continuous levodopa treatment for PD patients is frequently associated with the development of motor complications such as dyskinesias and a tailing-off of effect towards the end of the dose. Medical management for this includes careful manipulation of the dose to establish the optimum treatment schedule and improve absorption, incorporating catechol-O-methyl transferase inhibition, monoamine oxidase-B (MAO-B) inhibition, dopaminergic agonists, amantadine and continuous dopaminergic infusions.

Surgery

Surgery was in vogue for PD before the 1970s but became less popular until recently. It may be appropriate if the disease fails to respond to drugs or the effect of the drugs diminishes. Transplanted fetal mesoencephalic cells, harvested from aborted fetuses, grown in cell culture and injected into the brain in a form of cell suspension, have been shown to replace the production of natural dopamine, producing some good results, although the technique itself remains controversial [8]. A technique called deep-brain stimulation uses electrodes implanted into the brain and connected to a small pulse generator which can be externally programmed. This can decrease the need for some of the drugs, reducing the unwanted side-effects, most often the increased involuntary movements associated with levodopa [9]. The deep-brain stimulation can also reduce the fluctuation of symptoms, allowing for greater freedom of movement generally. Early results have been good but the technique is not yet widely used.

Impact on patient

PD is similar to other neurological problems in that it varies widely from patient to patient. With some the tremor is the most limiting factor while others seem untroubled by that, but far more concerned by their lack of mobility or difficulty communicating by facial expression. Clinical experience suggests that there is, however, a great deal of unreported depression and often quite a lot of pain brought about by the rigidity and overall poverty of muscle movement [10].

When investigating the lifestyle impact of PD, Kuopio et al. found that women scored significantly lower on five of the eight dimensions of the SF-36 outcome measure. This study found depression to be more common among women than men [11]. They concluded that, to improve the quality of life in PD patients, it is necessary to recognize and treat the depression. Parkinsonian symptoms and symptoms of autonomic dysfunction such as constipation and sexual impotence in males predominate early in the course of the disease and certainly have an effect on mood. Constipation may be unrelenting and hard to manage in some patients.