Parkinson’s disease: overview of diagnosis and management

Introduction

Parkinson’s disease (PD) was initially described by James Parkinson in his 1817 report ‘An essay on the shaking palsy’. Parkinson’s disease is a chronic, progressive neurological disease. It is characterised by the loss of neurons in the substantia nigra and elsewhere, in association with the presence of Lewy bodies and Lewy neurites.¹

Around 145,000 people live with Parkinson’s in the UK. And it is the fastest growing neurological condition in the world.²

There are three main forms of parkinsonism: idiopathic Parkinson’s disease, vascular parkinsonism and drug-induced parkinsonism. This article will be focusing on Parkinson’s disease.

There is no clearly identifiable cause for Parkinson’s disease. It is thought to be due to a blend of genetic and environmental factors. The majority of cases are idiopathic.
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Diagnosis

Parkinson’s disease is predominantly a clinical diagnosis; based on the UK PDS brain bank criteria (Table 1).

The most important symptom for diagnosis is bradykinesia, as well as one of: muscle rigidity, rest tremor (4-6 Hz) and postural instability unrelated to primary visual, cerebellar, vestibular or proprioceptive dysfunction.⁴

As well as the motor symptoms of Parkinson’s disease, it is also important to recognise the non-motor symptoms related to the disease.⁵ The non-motor questionnaire is a useful tool that can be used to quantify the impact these symptoms have on a patient.

There is no one definitive test for Parkinson’s disease, but if the diagnosis is called into question then a Single Photon Emission Computer Tomography SPECT, can be performed.³

Making a correct clinical diagnosis is low, 74% in non-specialists and this increases to 80% among specialists. When Parkinson’s disease is suspected therefore, it is best to refer them, untreated, to a specialist for review.^3,6

Differential diagnoses important to rule out before diagnosing PD include: benign essential tremor, Lewy body dementia, multisystem atrophy, corticobasal atrophy, progressive supranuclear palsy, idiopathic and familial basal ganglia calcification, Huntington’s disease, frontotemporal dementia, and spinocerebellar ataxia.⁷

Review of medications for drug-induced Parkinson’s disease and brain imaging to exclude brain injury and structural brain lesions. Blood test analysis for toxins and metabolic disorders and consideration of CSF sampling to rule out intracerebral infection.⁷

Vascular Parkinsonism presents with the clinical features of parkinsonism that are presumably caused by cerebrovascular disease. It is classically described as symmetrical lower-body parkinsonism with gait unsteadiness and absence of tremors and is usually associated with pyramidal signs.⁸

Treatment of Parkinson’s disease

According to the 2017 NICE guidance on Parkinson’s disease, the first line treatment for people in the early stages of Parkinson’s disease, whose motor symptoms impact on their quality of life, is levodopa. For those whose motor symptoms do not impact their quality of life, consider using dopamine agonists, levodopa or monoamine oxidase B inhibitors instead.

Do not offer ergot-derived dopamine agonists as first-line treatment for PD, due to the increased risk of developing fibrosis.³

Depending on the fluctuation of symptoms, the frequency, dose and formulation of levodopa can be adjusted, in order to reduce ‘off’ periods and dyskinesia.⁹

Offer a choice of dopamine agonists, MAO‑B inhibitors or catechol‑O‑methyl transferase (COMT) inhibitors as an adjunct to levodopa for people with Parkinson’s disease who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy. Again, try and avoid ergot-derived dopamine agonists and only consider them as an adjunct in those who have attempted other drug therapies first.³

If dyskinesia is not adequately managed by modifying existing therapy, consider amantadine.³

As the disease progresses, swallow is often impacted. If this is the case then different medication formulations can be considered, such as transdermal rotigotine patch.¹⁰

Any initiation or changes made to medication should be completed by a PD specialist.³

There are several drug therapies available for the non-motors symptoms associated with Parkinson’s disease, as demonstrated in Figure 1.

Figure 1. Drug therapy for non-motor symptoms³  

Non-motor symptom	Drug therapy – First line	Drug therapy – Second line
Day time sleepiness	Modafinil
Restless legs syndrome and Rapid eye movement sleep  behaviour disorder	Clonazepam Melatonin
Nocturnal akinesia	Levodopa, dopamine agonists	Rotigotine
Orthostatic hypotension	Midodrine	Fludrocortisone
Depression	Antidepressant (SSRI)
Psychotic symptoms	Quetiapine	Clozapine
Parkinson’s disease dementia	Rivastigmine	Other cholinesterase inhibitors Memantine

Long-term levodopa therapy often results in some adverse effects. After five years, the majority of patients suffer fluctuations, dyskinesias, toxicity, or loss of efficacy. Fluctuations can be reduced by changing the drug regimen to a combination therapy of Sinemet and Sinemet controlled-release (CR), or by the addition of deprenyl or a dopamine agonist.⁹

Levodopa holidays have been suggested for dealing with the complications of long term levodopa therapy, however the evidence for this is mixed as to whether this does provide benefit.^11,12

Dopamine receptor agonists, especially at high dosages can be associated with Impulse Control Disorders (ICD) – including pathological gambling, hyper-sexuality, compulsive eating and buying. In addition, other impulsive or compulsive disorders have been reported to occur, including dopamine dysregulation syndrome (compulsive misuse of and addiction to dopamine replacement therapy) and punding (compulsive performance of repetitive, mechanical tasks).¹³

Risk factors for ICDs include male sex, younger age or younger age at PD onset, a pre-PD history of ICD symptoms, history of substance use or bipolar disorder, and a personality profile characterised by impulsiveness.¹³

When starting dopamine agonist therapy NICE recommends giving information to patient’s and family about ICD, how it can present and who to contact if it occurs.

Should ICD occur then reducing dopamine agonist therapy is first line and then cognitive behavioural therapy is second line if this is not effective.³

Non-pharmacological management of Parkinson’s disease is paramount in this chronic disease including involvement of physiotherapy, occupational therapy, dieticians and speech and language therapy.³ They can help with clinical monitoring, motor and balance issues, support for activities of daily living, verbal communication, swallow and saliva issues, as well as nutrition. Integrating care between Parkinson’s disease specialist clinicians and allied healthcare professions is often best done by Parkinson’s Specialist Nurses.

Subcutaneous apomorphine administered either intermittently or continuously can be used in those with advanced Parkinson’s disease, to reduce symptoms of levodopa induced dyskinesia and also reduce the amount of ‘off’ time.¹⁴

Levodopa-carbidopa intestinal gel (LCIG) is a gel containing a combination of Levodopa and Carbidopa.  LCIG is licensed for the treatment of advanced levodopa-responsive PD with severe motor fluctuations and hyper/dyskinesia when available combinations of medicinal products are unsatisfactory. LCIG is an expensive therapy (anticipated annual cost of £28,105 per patient per year); so can only be justifiably used when all other treatment options have been ruled out.¹⁵

Deep brain stimulation (DBS) surgery may be considered in people who have responded poorly to drugs, who have severe side-effects from medication, in particular dyskinesia, or who have severe fluctuations in response to drugs (on-off syndrome) (Figure 2).¹⁶

Figure 2. Inclusion and exclusion criteria for DBS¹⁶

Inclusions: Clinically idiopathic PD Significant improvement with regard to dopaminergic medication (<30%) Refractory motor fluctuations or tremor Only minor symptoms during ON-state Exclusions (relative): Biological age >75yrs Severe/ malignant comorbidity with considerably reduced life-expectancy Chronic immunosuppression Distinct brain atrophy Severe psychiatric disorder

A further surgical option for treatment PD includes pallidotomy; however this is currently not recommended by in the NICE guidance.

Prognosis

There is no cure for Parkinson’s disease, and the mainstay of treatment is to manage the symptoms associated with the disease and to try and maintain quality of life.

It is difficult to estimate the prognosis in Parkinson’s disease and often people have a normal or near-normal life expectancy.¹⁷

Parkinson’s disease does not directly cause death. Common causes of death in Parkinson’s disease include: infection (often aspiration pneumonia), falls, exhaustion and weight loss due to excessive dyskinesia and frailty; and other comorbidities that occur in the aging population.¹⁸

Most people express the wish to die in familiar surroundings, such as at their own home or where they normally reside.¹⁹ However, this goal often is not achieved for people with Parkinson’s disease. Reviewing national mortality data from England (from 1993 to 2010) showed that for patients with Parkinson’s disease, death at home was recorded for only 10%. Most people were recorded as to having died in a nursing or residential care home (46%) or hospital (43%); while few died in hospice (<1%).²⁰

In 1967 Hoehn and Yahr defined five stages of Parkinson’s disease (figure 3), which is based on an increasing motor disability and increased physical dependence as the disease progresses.

Figure 3. Hoehn and Yahr stages of Parkinson’s disease.²¹

Stage	Symptoms
1	Only unilateral involvement, usually with minimal or no functional disability
2	Bilateral or midline involvement without impairment of balance
3	Bilateral disease: mild to moderate disability with impaired postural reflexes; physically independent
4	Severely disabling disease; still able to walk or stand unassisted
5	Confinement to bed or wheelchair unless aided

Complex or advanced Parkinson’s disease is when symptoms are more difficult to control, the patient is no longer able to independently carry out activities of daily living or has developed uncontrollable dyskinesia.¹⁷ At this point, or more appropriately before this point has been reached palliative care or advanced care planning should be discussed. NICE guidance suggest that patient’s with Parkinson’s disease can be referred at any stage of their disease to palliative care.³

As the disease progresses, patients with Parkinson’s disease may face problems with communication, due to impaired speech, bradykinesia, apathy, and cognitive change. Advanced care planning allows patients to express views on the goals of care, future treatments, intensive care unit interventions, resuscitation status, the place of care, the place of death, while the person is able to do so. These wishes can be incorporated into an advance directive to guide health care decision-making when capacity is lost. They may also wish to appoint a lasting power of attorney, who will be able to make decisions on their behalf if they are no longer able to do so.²²

Another consideration for those with PD is donating their brain on death to The Brain Bank, which is the world’s only brain bank solely dedicated to Parkinson’s research. This donation could help ongoing research into the ongoing treatment of Parkinson’s disease.^2,3

Further care

Ultimately, Parkinson’s disease is a progressive neurodegenerative disorder. Education and involvement of patients and their careers are paramount in the ongoing management of this disease. Communication with people with Parkinson’s disease should aim towards empowering them to participate in decision making about their own care. And our role as healthcare professions is to provide honest, realistic information about the condition.³

There is support available not only for patient’s themselves, but for their carer’s also. Parkinson’s UK charity’s website has a fountain of information from diagnosis, treatment and support available.²

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 Dr Zosia Vanessa Beckett, MbCHB, MRCP, DGM, ST5 Geriatric Medicine

[email protected]

No conflict of interest declared

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References

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