Parkinson’s disease in adults

Abstract

Parkinson’s disease (PD) is a common neurodegenerative condition that is characterised by progressive motor dysfunction and associated non-motor features. Affecting up to 160 people in 100 000 in the UK, PD has a profound impact on a patient’s quality of life and that of their carers. With the number of affected patients predicted to rise by 28% by 2020, it is important for GPs to recognise the features of PD and have some understanding of both pharmacological treatment and non-pharmacological management. Increased recognition can achieve timely specialist referral and early initiation of treatment, and may help reduce symptoms, improve the patient’s quality of life and reduce healthcare costs. This article aims to raise awareness of the features of PD and provide a summary of management strategies currently recommended by the National Institute for Health and Care Excellence.

The GP curriculum and Parkinson’s disease

Clinical module 3.18: Care of people with neurological problems lists the learning objectives required for a GP to manage within the community. In particular, GPs are expected to be able to:

Play an essential role in the management of chronic neurological disability in the community

Be able to demonstrate how you manage primary contact with patients who have a neurological problem, including headache, dizziness, tremor, numbness and tingling, weakness, abnormal movement, blackouts and loss of consciousness, and coma

Understand principles of treatment for common conditions that are managed largely in primary care including epilepsy, headaches, vertigo, neuropathic pain, mononeuropathies, essential tremor and Parkinson’s disease

Co-ordinate with other primary care health professionals to enable chronic disease management and rehabilitation

Know the indications for referral to a neurologist for chronic conditions that require ongoing specialist management and conditions that require early treatment to avoid permanent deficit

Pathology

Pathologically, Parkinson’s disease can be defined by a loss of dopamine-producing neurons from the substantia nigra pars compacta with characteristic Lewy bodies (cytoplasmic inclusions) seen within the remaining dopaminergic nerve cells (Dickson, 2012). The substantia nigra is found in the midbrain and forms part of the extrapyramidal nervous system. The substantia nigra sends signals to the striatum via the nigrostiatal pathway, which plays an important role in motor control as it communicates with the basal ganglia. Once approximately 80% of these dopaminergic neurons are lost, there is sufficient disruption of dopaminergic neurotransmitters within the nigrostriatal pathway to give rise to features of Parkinson’s disease such as rigidity, bradykinesia and resting tremor (Cheng, Ulane, & Burke, 2010). Studies have shown that Lewy bodies have also been found outside the dopaminergic system. Although the true function of Lewy bodies remains unknown, it is thought that this may be a cause of the more diverse motor and non-motor manifestations characteristically found in this disorder.

Recognition

Parkinsonism is a clinical syndrome that encompasses clinical signs of tremor, rigidity and slowness of movement (bradykinesia). Although one of the most common causes of parkinsonism, the diagnosis of Parkinson’s disease can prove challenging. Sharing clinical features with other causes of parkinsonism, such as multi-system atrophy, supranucelar palsy and drug-induced parkinsonism, clinicians face the often difficult task of differentiating between these conditions. The diagnosis of Parkinson’s disease is a clinical diagnosis that can be made according to a set criteria based on signs and symptoms. Parkinson’s disease must always be suspected in patients presenting to primary care with tremor, rigidity, postural instability and slowness of movement. The National Institute for Health and Care Excellence (NICE) has published new guidelines for Parkinson’s disease in adults and has recommended the use of the UK Parkinson's Disease Society (PDS) Brain Bank Criteria when the diagnosis of Parkinson’s disease is suspected. This is outlined in Box 1. The UK PDS Brain Bank Criteria also include useful exclusion criteria, which can help clinicians rule out Parkinson’s disease and consider alternative diagnoses. Studies have also found that men are at an increased risk of Parkinson’s disease when compared with women (Wooten, Currie, Bovbjerg, Lee, & Patrie, 2004).

Box 1.

UK PDS criteria for the diagnosis of Parkinson’s disease.

Diagnostic criteria

• Bradykinesia (slowness of movement) and any one of the following:

• Rigidity

• Resting tremor (6–8 Hz)

• Postural Instability

Exclusion criteria

History of:

• Repeated strokes

• Repeated head injury

• Antipsychotic or dopamine-depleting drugs

• Encephalitis

• More than one affected relative

• Sustained remission

• Negative response to large doses of levodopa

• Strictly unilateral features after 3 years

• Exposure to known neurotoxin

• Cerebral tumour or communicating hydrocephalus on neuroimaging

• Other neurological features such as; supranuclear gaze palsy, cerebellar signs, Babinski Sign

Source: Hughes et al. (1992).

At presentation, these diagnostic signs are usually found to be unilateral, but will progress bilaterally over time. The side of onset will usually remain more affected as the disease progresses (Hughes, Daniel, Kilford, & Lees, 1992). Patients may develop non-motor manifestations in the later stages of Parkinson’s disease, such as cognitive impairment, sleep disorders, depression and dysautonomia (orhostatic hypotension, constipation, sexual dysfunction).

Management

Pharmacological management

If Parkinson’s disease is suspected, it is recommended that patients be referred to a specialist without initiating any pharmacological treatment. Before selection of treatment, patient preference, symptoms and co-morbidities must be taken into account. Parkinson’s disease may be treated with levodopa, dopamine agonists and monoamine oxidase-B. Within specialist settings, apomorphine injections and deep brain stimulation may also be available to patients with severe disease. Clinicians must be aware that anti-parkinsonism medication should not be stopped suddenly, due to the risk of akinesia or neuroleptic malignant syndrome. If adjustment to anti-parkinsonism medication is required, discussion with a specialist is recommended.

It must also be noted that impulse control disorders (ICDs) can develop during any stage, as an adverse effect of dopaminergic treatment. ICDs are a group of psychiatric conditions where patients are unable to resist carrying out acts that may be harmful to themselves or others, for example, pathological gambling and hypersexual behaviour. Patients and their carers must be educated in recognising the signs of ICDs so that if such behaviours develop, dopaminergic therapy can be carefully adjusted with admission and specialist supervision. Cognitive behavioural therapy may also be offered if medication adjustment is found to be ineffective.

The recent NICE guideline has also included recommendations for the management of non-motor manifestations in adults with Parkinson’s disease (NICE, 2017a, 2017b). Non-motor manifestations, such as sleep disorders, hallucinations, orthostatic hypotension, drooling of saliva and dementia, can develop in patients with Parkinson’s disease and may require treatment, outlined in Box 2. If there is a new onset of symptoms, always consider the patients medication as a potential cause before initiating new treatment.

Box 2.

Pharmacological management of non-motor symptoms.

• Excessive daytime sleepiness may be managed with the dopamine uptake inhibitor, modafanil. Note this drug is contraindicated in patients with arrhythmias, left ventricular hypertrophy, cor-pulmonale and moderate-to-severe hypertension. Patients on modafanil must be reviewed every 12 months by a specialist

• Rapid eye movement sleep disorder behaviour can be treated with melatonin or clonazepam

• Orthostatic hypotension may be treated with the selective α1 adrenoreceptor agonist midorine. Midorine causes an increase in vascular resistance through vasoconstriction and thus increases blood pressure. If no contraindications are noted such as congestive heart failure, aortic aneurysm or narrow angle glaucoma, for example, treatment can be initiated providing regular monitoring is available

• Hallucinations and delusions should not be treated if well-tolerated by the patient, as antipsychotic medication can worsen symptoms of Parkinson’s disease. Other causes must be ruled out first before initiation of treatment. If further adjustment of anti-Parkinson’s medication or initiation of antipsychotic medication is required, seek specialist advice

• Dementia patients may be offered a cholinesterase inhibitor under specialist guidance in attempts to improve cognitive function

• Drooling of saliva should initially be reviewed by a speech and language therapist. If non-pharmacological management is ineffective, consider the anti-muscarinic agent glycopyrronium bromide, which acts to reduce salivation

It is important to note that patients presenting with excessive daytime sleepiness should be advised to stop driving. People with Parkinson’s disease who do drive should be advised of the need to inform the Department of Vehicle Licensing Agency (DVLA) and insurance providers of their diagnosis. There are also occupational considerations for some, for example, for heavy duty vehicle drivers or those operating machinery.

Non-pharmacological management

People with Parkinson’s disease will require a holistic approach to their management. This should include providing a clear point of access to specialist services, provision of information on the condition for the patient and their relatives, physiotherapy, speech and language therapy, nutritional support and occupational therapy. It is imperative that patients are provided with adequate information regarding their diagnosis and prognosis, so that they can make informed decisions about their own care and participate in planning for the future. This can be achieved through regular consultation and review with primary care providers and specialists, as well as access to specialist nurses, physiotherapists, support groups and provision of high-quality information leaflets. It is important for people with Parkinson’s disease and their carers to have easy access to a specialist nurse who may act as a familiar, ongoing point of contact with specialist services. Also, consider referring people to the palliative care team at any stage of Parkinson’s disease, in order to discuss options for future management, forward planning and to help raise awareness of the support services available to them and their carers.

Summary

NICE have set out clear guidelines that should support GPs in the diagnosis and ongoing management of Parkinson’s disease. The diagnosis of Parkinson’s disease will continue to pose a challenge for many practitioners, considering the number of patients presenting with other causes of parkinsonism.

The main learning points GPs can take into consideration when presented with a patient with possible Parkinson’s disease are listed in the box labelled as key points. The current NICE guideline also identifies evidence gaps where further research is required, including, the effectiveness of combination treatment with cholinesterase inhibitors, identifying the best first line treatment for rapid eye movement sleep deprivation disorder and effectiveness of early physiotherapy. Further details on specialist care can be found in the full NICE guideline (NICE, 2017a, 2017b).

KEY POINTS

Suspect Parkinson’s disease in patients presenting with resting tremor (6–8 Hz), rigidity, slowness of movement (bradykinesia) and postural instability

Before treatment is initiated refer patients with suspected Parkinson’s disease to a specialist in a timely manner

Do not abruptly stop anti-parkinson’s medication and seek specialist advice if dose adjustment is required

Provide patients and carers with both verbal and written information on Parkinson’s disease, including management and prognosis to help patients plan for their future and make informed decisions about ongoing care

Inform patients who drive, that they are required by law to inform the DVLA if they have been diagnosed with Parkinson’s disease

People with Parkinson’s disease should have access to a specialist nurse, physiotherapy, occupational therapy, and national support, and can be referred to the palliative care team at any stage of their disease

References

Cheng

H. C.

Ulane

C. M.

Burke

R. E.

(2010) Clinical progression in Parkinson’s disease and the neurobiology of axons. Annals of Neurology 67(6): 715–725. doi: 10.1002/ana.21995.

Clark

C. E.

(2007) Parkinson’s disease. BMJ. 335. doi: 10.1136/bmj.39289.437454.AD.

Dickson

D. W.

(2012) Parkinson’s disease and parkinsonism: Neuropathology. Cold Spring Harbor Perspectives in Medicine 2(8): a009258. doi: 10.1101/cshperspect.a009258.

DVLA. Parkinson’ s disease and driving. Retrieved from www.gov.uk/parkinsons-disease-and-driving.

Hughes

A. J.

Daniel

S. E.

Kilford

Lees

A. J.

(1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease. A clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery, & Psychiatry 55(3): 181–184. doi: 10.1136/jnnp.55.3.181.

Jankovic

(2008) Parkinson’s disease: Clinical features and diagnosis. Journal of Neurology, Neurosurgery & Psychiatry 79(4): 368–376. doi: 10.1136/jnnp.2007.131045.

NICE. (2017a). Parkinson’s disease in adults. Retrieved from www.nice.org.uk/guidance/ng71.

NICE. (2017b). Parkinsons disease: The final scope. Retrieved from www.nice.org.uk/guidance/cg35/documents/parkinsons-disease-final-scope2.

Parkinson’s UK. (2009). Parkinson’s prevalence in the United Kingdom. Retrieved from www.parkinsons.org.uk/sites/default/files/parkinsonsprevalenceuk_0.pdf.

10.

RCGP. Clinical module 3.18: Care of people with neurological problems. Retrieved from www.rcgp.org.uk/gp-training-and-exams/∼/media/Files/GP-training-and-exams/Curriculum-2012/RCGP-Curriculum-3-18-Neurological-Problems.ashx.

11.

Scottish Intercollegiate Guidelines Network. (2010). Diagnosis and pharmacological management of Parkinson’s disease. Retrieved from www.sign.ac.uk/pdf/sign113.pdf.

12.

Weatherburn

Simon

(2017) Parkinson’s disease: Initial presentation. InnovAiT 7(11): 645–650. doi: 10.1177/1755738014551774.

13.

Wooten

G. F.

Currie

L. J.

Bovbjerg

V. E.

Lee

J. K.

Patrie

(2004) Are men at greater risk for Parkinson’s disease than women? Journal of Neurology, Neurosurgery & Psychiatry 75(4): 637–639. doi: 10.1136/jnnp.2003.020982.