The many faces of Parkinson’s disease

Irish Medical Times - Dr Claire Reynolds, Patrick Browne and Prof Tim Counihan examine the challenges in determining a diagnosis of Parkinson’s disease and the main treatment options available to doctors.

With a prevalence rate of around 2 per cent, most physicians in primary care can expect to encounter several patients with Parkinsonism in their practice. For the experienced clinician, recognising the symptoms and signs of Parkinson’s disease (PD) is reasonably straightforward.

The typical patient shuffles into the doctor’s surgery, slightly stooped, looking older than their years. When seated, a coarse tremor affecting one or other hand will emerge, with the hands at rest on the lap. It is this ‘pill-rolling’ rest tremor that is usually the biggest tip-off to the diagnosis. The remaining typical (Table 1) clinical features can then be elicited with more detailed examination.

Table 1: Typical features in early Parkinson’s disease

■Asymmetric tremor at rest
■Stooped posture
■Expressionless face (hypomimia)
■Low-volume monotonous voice (hypophonia)
■Micrographia
■Slowness of movements (bradykinesia)
■Shuffling gait with fragmented turning
■Cog-wheel rigidity of muscle tone
Life, however, is often not quite so simple. Up to 30 per cent of patients with PD do not exhibit tremor at the time of diagnosis. Moreover, other tremor disorders can often be confused with PD, although if the patient exhibits a clear tremor at rest, in the presence of slow movements, the diagnosis is rarely in doubt.

In a recent community-based study of PD misdiagnosis in the west of Scotland, 36 of 610 patients (6 per cent) on treatment for Parkinson’s disease had either essential tremor or vascular Parkinsonism (Newman EJ, Breen K, Patterson J et al, Mov Disord 2009;24:2379-85).

The diagnosis may be further complicated by the difficulty in recognising bradykinesia for both doctor and patient. Many patients attribute stiffness and slowness of movement to advancing age, or arthritis.

Complaints of a persistent ‘frozen shoulder’ are a common early sign of emerging Parkinsonism. One of the most useful markers of bradykinesia is to examine the patient’s handwriting; ask them to write a sentence across the page. Writing that starts reasonably clearly but becomes smaller in amplitude across the page is a reflection of true bradykinesia, distinguishing it from other causes of poor script (such as due to arthritis or other musculoskeletal ailment).

Increasing understanding of the pathological basis for PD has led to greater awareness that it is not simply a disorder of the motor symptom. In fact, non-motor symptoms can actually precede the emergence of motor symptoms by several years.

Non-motor symptoms in early PD include: constipation; loss of sense of smell; postural dizziness; REM sleep behaviour disorder; restless leg syndrome; depression; anxiety; apathy; excessive daytime somnolence; and excessive sweating.

Ensuring diagnosis
It will be seen from this list that common non-motor symptoms include affective, cognitive, autonomic and sleep-related complaints, emphasising the multi-system nature of the disease. Before concluding that the patient has PD, it is particularly important to assiduously review the patient’s list of medications to exclude drug-induced Parkinsonism, the symptoms of which are indistinguishable from idiopathic PD.

Neuroleptic antipsychotics (olanzepine, risperidone in particular) and anti-emetics (metoclopramide, prochlorperazine) are the most frequently encountered causative agents. A radio-isotope dopamine transporter (DATScan) scan may be helpful to distinguish these entities. International best practice recommends that all patients with suspected Parkinson’s disease be referred to a specialist physician with experience in managing the condition.

This should be done ideally prior to any trials of medication, so that the specialist can confirm the diagnosis and also discuss the growing treatment options with the patient.

Not everything that looks like PD turns out to be PD; up to 25 per cent of patients diagnosed with PD in the community ultimately (at necropsy) turn out to have alternative diagnoses. Making an accurate diagnosis early in the disease course is important so as not to give false expectations to patients whose Parkinsonism turns out to be treatment resistant (and hence not idiopathic PD).

A number of factors are important ‘red flags’, suggesting that the Parkinsonism may be atypical.

Should PD be diagnosed and managed entirely in the community, under the guidance of the GP? The European Parkinson’s Disease Association published a charter in 1997 that espoused the following principles that people with PD: be referred to a doctor with a special interest in PD; receive an accurate diagnosis; have access to support services; receive continuous care; and take part in managing the illness.

Bearing in mind that early, accurate diagnosis and institution of appropriate therapy in PD is associated with improved quality of life and possible improved long-term prognosis, the GP retains a vital role in the overall care of such patients.

Treatment options in early PD
It is essential to determine the degree of functional impairment that the symptoms may be causing in our patient. Several studies support the notion that patients with early PD who are left untreated have a poor quality of life. There seems little doubt that early treatment improves patients’ sense of wellbeing, irrespective of the degree of motor impairment at baseline.

Non-motor symptoms need also to be addressed early on, with particular attention to both depression and constipation. Low mood can severely hinder any improvement and needs to be treated as a separate condition. Commonly utilised anti-Parkinson’s medications are mainly absorbed via the duodenum and thus, constipation can impair this process, often leading to acute deteriorations in quality of life. Regular screening for these two possible issues is vital in maintaining a decent quality of life.

Fortunately, treatment options for significant motor impairment are plentiful (Table 5). Which agent to choose will be directed by a number of factors including the degree of functional impairment and, as mentioned earlier, patient age. It is convenient to divide treatment options into low-, medium- and high-potency drugs.

For younger patients (under 60) with mild to moderate motor deficit, it is reasonable to consider an MAO inhibitor or dopamine agonist. Although they lack the degree of efficacy of levodopa, there is a lower risk of motor fluctuations and drug-induced involuntary movements (dyskinesias) at five years. This is rarely a concern in patients 65 or older in whom the five-year risk of dyskinesias is around 20 per cent.

Moreover, dopamine agonists are associated with the potential for significant adverse effects, including sudden onset of sleep, peripheral oedema and hallucinations, as well as a variety of impulse control disorders. In the past decade, it has become apparent that anti-Parkinson’s therapy may worsen, or even be the primary cause of both motor and non-motor symptoms. Motor fluctuations and dyskinesias have been particularly well characterised.

However, a set of complex disinhibitory psychomotor pathologies that relate to aberrant or excessive dopamine receptor stimulation are being increasingly recognised. These behaviours are linked by their repetitive, reward or incentive-based natures, and include impulse control disorders (ICDs), punding, walkabout and dopamine dysregulation syndrome (DDS).

It is important for all health professionals to be able to identify these behaviours and have an understanding of their aetiology and management to limit potential harm. These potential behaviours need to be discussed with the patient and their families after diagnosis, not least due to potential legal implications.

Behaviours
Phenomenology of ICDs typically involves pleasurable behaviours that are performed repetitively, excessively, and/or compulsively, and to an extent that interferes in major areas of life functioning. These behaviours encompass a broad range of compulsive behaviours such as pathological gambling, hypersexuality, compulsive shopping, binge or compulsive eating, and compulsive reckless driving.

Morbid jealousy (Othello syndrome) is not uncommon, in the authors’ experience. Punding refers to behaviours that encompass excessive ‘hobbyism’ to prolonged, disabling, highly stereotyped ritualistic behaviour.

Activities are highly influenced by gender and, in Western societies, are reported to include: collecting or hoarding items; cleaning; repairing things; gardening; writing and categorising information; artistic drawing or craft-making; singing or playing a musical instrument; playing cards; fishing; excessive computer and internet use.

Dopamine dysregulation syndrome refers to the compulsive use of dopaminergic medications well beyond the dose needed to optimally control motor disability and in the face of a mounting number of harmful physical, psychiatric and social sequelae.

Patients may not spontaneously report these behaviours due to shame, denial or not suspecting an association with PD treatment. Direct questioning about a range of behaviours and interviewing a caregiver or informed other is often critical to ensure detection and assessment of severity of impulsive or compulsive behavioural disorders, especially due to the associated lack of insight in many patients.