Parkinson’s disease: Core principles and management considerations

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Reference: January 2026 | Issue 1 | Vol 12 | Page 66

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Parkinson’s disease (PD) is a common neurodegenerative disorder affecting an estimated 16,000 individuals in Ireland, although no precise data are available. It can present at any age, and various studies have placed the proportion of cases under age 65 at up to 30 per cent in some series; in this way it diverges from other common neurodegenerative disorders. Prevalence exceeds 1 per cent over age 65, with a male:female ratio in the region of 2:1.

It is important to note that PD is a slowly-evolving condition with pathological features and prodromal symptoms in excess of 10 years prior to clinical presentation to a specialist and formal neurological diagnosis.¹ Understanding the breadth of motor and non-motor features in PD, and their interaction with each other and medications, is critical to understanding this condition.

In 90 per cent of cases, PD is idiopathic with some evidence for an effect from environmental factors and various causative agents. Data implies a lower incidence in smokers and coffee drinkers, and a higher incidence with paraquat herbicide exposure and rural living.¹

In around 10 per cent of cases, a genetic cause is identified and a range of dominant and recessive disorders are recognised. As a rule of thumb, genetic screening is considered in patients with clinical diagnosis under age 40, or under age 50 with a demonstrable inheritance pattern in the family pedigree.

GBA1 heterozygous mutations are likely the most prevalent single entity, resulting in a presentation of a phenotypically typical PD approximately 10 years earlier than average and, in some variants, an earlier cognitive decline.²

Diagnosis

Prodromal features include anosmia, sleep disturbance, mood disturbance, and gastrointestinal
symptoms, especially constipation.

The core clinical features leading to a diagnosis of PD include bradykinesia, rigidity and resting tremor. A fourth feature (postural instability) is no longer considered at presentation as it tends to occur later in the course of typical idiopathic PD (iPD).

The presence of these features is termed ‘parkinsonism’ and always has a differential diagnosis. A significant majority of individuals with classic parkinsonism and lack of additional features or red flags will reach a diagnosis of iPD. Alternative diagnoses are considered below.

Bradykinesia:While any muscle activity can be assessed, specific tasks (eg, finger tapping) are used to demonstrate slowness of movement and decrement (ie, progressive slowing on repetition of the movement). The severity and distribution of same is noted. Presence of bradykinesia with decrement is considered essential by most neurologists to establish a diagnosis.

Rigidity:Demonstration of increased tone consistent with rigidity (as opposed to the velocity-dependent hypertonia seen with spasticity in pyramidal disorders) is important to document.

Resting tremor:Tremor that is most prominent at rest (as opposed to on posture, eg, thyroid disease, or action, eg, essential tremor) is an important observation to make. Indeed, the presence of a true rest tremor is rarely explained by conditions other than PD and its related conditions. Important to note that it is easy to mistake a postural tremor with incomplete muscle relaxation for a resting tremor, and so observing the hand while fully distracted and relaxed during walking can be helpful.

Postural Instability: This symptom relates to loss of postural reflexes, resulting in falls due to lack of correction with major or minor shifts in centre of gravity. It is no longer considered a cardinal feature at presentation as it is rarely evident early in the course of iPD. Indeed, the presence of early significant postural instability is a red flag for a diagnosis other than iPD.

Differential diagnoses

Though the UK Brain Bank criteria are still used, the diagnostic criteria from the Movement Disorders Society (MDS) are often preferred as they are actively maintained. The most recent revision dates from 2015.²

As mentioned above, the presence of parkinsonism does not always mean a diagnosis of typical iPD.^1,2,3 The common differential diagnoses include other primary extrapyramidal disorders (ie, the atypical parkinsonian disorders) and secondary causes of parkinsonism. In the latter group, common entities include drug-induced parkinsonism, ‘vascular’ parkinsonism, and parkinsonism in the setting of another specific diagnosis, eg, Wilson’s disease and other genetic disorders.

General red flags that a patient with parkinsonism is presenting with a diagnosis other than iPD include:

• Symmetric onset
• Rapid progression including early falls
• Lack of immediate and robust response to dopaminergic therapies (a caveat here is patients with tremor-predominant disease – in such cases the response of tremor is quite variable and in the absence of significant issues with gait or ADLs, an effect may not be very noticeable to the patient). 

Drug-induced parkinsonism: The clue here is typically the presence of a causative agent – typical neuroleptics are well recognised, but atypical neuroleptics and a wide range of other agents (eg, valproate) can result in parkinsonism. The other clues are the presence of other extrapyramidal side effects (EPSEs) – tardive dyskinesia, dystonia, akathisia – and lack of typical synucleinopathy non-motor features eg, RBD, autonomic features.

The treatment is reduction or cessation of the causative agent(s) or switch to less detrimental agents – quetiapine or clozapine. Quetiapine is relatively safe and easy to use, but may not be potent enough to cover the psychiatric indication, while clozapine is very effective and the preferred option, but can be limited by the blood monitoring requirements.

Atypical parkinsonian syndromes: This group of conditions, sometimes also referred to as the ‘Parkinson-plus’ disorders, includes other synucleinopathies such as multiple systems atrophy (MSA) and dementia with Lewy Bodies (DLB), as well as tauopathies such as progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).

These syndromes may present initially with general red flags to suggest a non-iPD diagnosis as above. Specific red flags generally evolve over time as outlined in Table 1.

DLB is interesting as it is pathologically identical in many ways to iPD, differing mainly in the distribution and evolution of the pathological changes. There have been proposals to unify PD and DLB into a single entity (neuronal alpha-synuclein disease), but this remains a controversial debate among specialists and academics.

The diagnosis of iPD remains clinical. Essentially, it requires demonstration of parkinsonism (and specifically bradykinesia with decrement) without any clear alternative explanation or red flags/atypical features as outlined above.

Unless patients are presenting extremely early, the overall pattern on examination (reduced facial expression, hypophonia, micrographia, posture, gait, and limb findings) is usually relatively clear in the consultation room.

At the diagnosis stage, presence of suggestive non-motor features, eg, constipation, REM sleep behaviour disorder, etc, can increase confidence.

Where doubt exists, a DaTscan can be performed. This test provides a relatively clear objective assessment of whether there is a primary dopaminergic deficit or not. It is important to note that all causes of primary parkinsonism (iPD and the atypical syndromes) have abnormal DaTscan findings and there is limited usefulness in distinguishing between specific diagnoses within this group.

Where red flags exist, eg, rapid onset, additional unexpected neurological deficits etc, additional tests are indicated. These may include structural brain or cord imaging, blood tests for toxic/metabolic abnormalities, and genetic testing.

Biomarkers will likely become part of the diagnostic work-up over the next few years, particularly when blood-based assessment of alpha-synuclein is available in clinical practice.⁴

Managing motor symptoms

Broadly speaking, the management of iPD falls into medication and non-medication interventions. After initial diagnosis, post-diagnostic support and education are needed to allow patients to engage with the condition and optimise self-management. The role of the nursing team is critical in successful management of PD, facilitating education, self-management, heading-off complications, and admission avoidance.

Motor symptoms result from the combination of the cardinal features of PD – tremor, rigidity and bradykinesia.⁴ The manifestations, and their functional impact, vary enormously between patients. In general, enquiring after gait (including falls) and ADL function (speed and need for assistance) gives a global impression of function.

A range of clinician-facilitated (eg, UPDRS) and patient-reported (eg, PDQ-39) scales provide more objective measures. The UPDRS incorporates clinician-assessed motor function (at the time of assessment) and also prompts for enquiry after non-motor features and motor complications.

The primary dopamine replacement therapies remain levodopa/carbidopa and the dopamine agonists. The former is more effective and better tolerated, while the latter is more convenient (available as once-daily preparations) and historically preferred in younger cases due to concern around dyskinesia risk.

In practice, the target is always to allow patients to engage in their particular daily activities comfortably and reliably, as opposed to aiming for complete absence of symptoms.

An important clinical point is the risk of impulse control disorders with dopaminergic therapies. This is significantly associated with dopamine agonists, and can be very destructive, and may manifest as compulsive gambling, shopping, focus on tasks or hobbies, hypersexuality, excessive eating, and always warrant a review of medication.

The other standard therapies used in PD either augment the core therapies or target specific aspects of disease:

MAO type B inhibitors: These agents augment levodopa/carbidopa by slowing peripheral breakdown of dopamine, allowing more available active drug for CNS entry.

COMT inhibitors: Also reduce dopamine breakdown but are more potent, resulting in greater augmentation of levodopa/carbidopa, but also greater emergence of the relevant side effects.

Amantadine: Used to counter dyskinesia, but commonly associated with neuropsychiatric side effects, limiting usefulness.

Anticholinergic drugs:Specifically used to target tremor, but tolerability is poor, limiting usefulness in all but a minority of cases. In many cases, non-pharmacological treatments provide at least equal if not more benefit for patients. The wider multidisciplinary team is critical to successful PD management.

Physiotherapy: Focus on falls prevention, gait and posture, prevention of sarcopenia. A particular clinical symptom – freezing of gait, where patients become frozen temporarily, often in doorways or tight spaces – is responsive to physiotherapy interventions and not medication changes.

Occupational therapy: Focus on hand function and adaptations, ADLs, engagement with work and other tasks. Driving is another important focus here.

Speech and language therapy:Focus on voice (hypophonia is common and may be disabling) and swallow safety (the presence of any swallow symptoms is usually sufficient to warrant referral).

Medical social work:Critical in supporting and advising patients on social and care supports, financial and related issues, and safeguarding.

Clinical nutrition: Dietary advice and optimisation of bowel management.

Psychology:Neuropsychology is very helpful in identifying and categorising cognitive deficits where present. Clinical psychology is frequently helpful in assisting patients to manage anxiety, mood, adjustment and other symptoms.

Motor complications can arise over time in patients taking oral levodopa/carbidopa. Motor fluctuations may present as a predictable ‘wearing off’ of medication before a next dose or as unpredictable off periods.

Dyskinesia refers to choreiform movements and are classified as disabling if they impair function or non-disabling (no impact on tasks). Important to note that non-motor fluctuations (eg, GI pain and anxiety) also occur in some cases and are at times very disabling.

The presence of motor complications that cannot be resolved by adjusting medication is the primary indication for a device-assisted therapy. Where a patient requires in excess of five dose points in the day, has in excess or two hours of ‘off’ time or one hour of disabling dyskinesia that cannot be improved by adjusting oral therapies, a device therapy can be considered.

The currently available device therapies are subcutaneous apomorphine pump, subcutaneous foslevodopa/foscarbidopa infusion, intra-jejunal levodopa/carbidopa infusion, and functional neurosurgery, such as deep brain stimulation and ultrasound thalamotomy. Such patients should be assessed by a neurologist with subspecialty movement disorders expertise.

Non-motor features

Non-motor features become progressively more prevalent and disabling as PD evolves over time. Many develop as synucleinopathy becomes more widespread and established in the neocortex. As above, prominent early non-motor features may herald the presence of an atypical parkinsonian syndrome eg, autonomic dysfunction in MSA or hallucinations in DLB. Dopaminergic therapies have the capacity to worsen many non-motor features and this often leads to a rationalisation of medication over time, with compromise required in balancing motor and non-motor control.

It is important to take a systematic approach to assessing non-motor features, as patients may not volunteer these symptoms or intuitively associate them with their movement disorder. The more common non-motor features are listed in Table 2 and a selection are discussed further.

Cognition: It is important to note that the features of cognitive impairment associated with PD differ from Alzheimer’s disease or vascular dementia, and may be missed using generic tools like the MMSE.

The term ‘Lewy Body dementias’ encompasses both the specific diagnosis of DLB and PD dementia (PDD).

DLB is characterised by early (generally within a year) cognitive decline and visual hallucinations in the presence of parkinsonism (sometimes minimal).

PDD evolves in iPD in approximately 50 per cent of patients by year 10, and 80 per cent in year 20 post diagnosis. The primary agent used to treat cognitive symptoms is rivastigmine, and an important consideration is that this agent can significantly worsen orthostatic hypotension.

Orthostatic hypotension:This symptom is operationally defined as a drop of 20mmHg systolic or 10mmHg diastolic on standing, with symptoms. It may manifest with presyncope, syncope, or, importantly, with a non-specific sensation of imbalance, and can occur immediately on standing or be delayed over a few minutes.

It is an important cause of falls and injuries in PD. The general approach is to rationalise anti-hypertensives where possible, consider reduction of other relevant agents (specifically considering dopamine agonists, rivastigmine or amantadine from a PD perspective), and encourage conservative measures (eg, aiming for fluid intake towards two litres per day, awareness of the need to stand in two stages and pause before mobilising). Pharmacotherapy can be used in resistant cases (fludrocortisone or midodrine), watching for supine hypertension.

Constipation: This symptom is very common and may predate movement disorder appearance by over a decade. It is important to let the patient know that this is not standard constipation, and a specific and persistent effort is required to maintain control. The general approach is to ensure adequate fluid intake, a balanced diet with adequate fibre, and consider mild and then more aggressive laxative agents as required to maintain regular bowel motions.

REM behaviour disorder: This symptom is ascertained on collateral, with reports that the patient moves and vocalises during sleep. It reflects a failure of normal muscle relaxation during REM sleep, allowing dream enactment. It does not necessarily require treatment, but may do if injury occurs to the patient (or partner). First-line treatment is melatonin, with clonazepam reserved for resistant cases.

Acute decompensations:PD is a slowly progressive neurodegenerative disorder and acute progression or decompensation is usually explained by external factors. Common among these are constipation, acute infection, inpatient admission, missed or changed medications.

Patients with PD admitted to hospital for scheduled (eg, surgery) or unscheduled (eg, pneumonia) will typically note a change or decompensation in their symptoms. It is important to replicate their home situation as much as possible, including taking medications at correct times which may be outside drug round times++. Particular care must be taken where oral medications will be missed, eg, because of fasting for a procedure or acute need for NPO status, and substitution with a rotigotine transdermal patch can be considered. Specific attention is required to facilitate post-acute recovery and rehabilitation, including expectation of a prolonged trajectory.

A range of other medical issues require attention in the management of PD. These include (but are not limited to):

• Bone density management.
• Driving: It is usual to maintain driving in PD if and until significant progression occurs, and partner/caregiver reports and opinion on patient driving ability has good predictive value. An OT assessment and on-the-road driving assessment are both helpful in deciding on medical certification of driving.
• Specific considerations in pre- and peri-menopausal female patients.
• Optimisation of vascular risk factors.
• Specific considerations in young-onset patients, where occupational, childcare and other issues require attention in the co-creation of the management plan. In particular, the legacy concerns around the use of levodopa/carbidopa in younger patients due to the risk of dyskinesia is now considered incorrect, and it should be employed if needed to achieve adequate symptom control (while aiming to use the lowest effective dose).

Future directions

PD is an extremely active area of research and development. A number of themes are consistently represented in scientific reports and clinical trials. These including:

• Re-purposing existing drugs, eg, exenatide
• New delivery systems, eg, subcutaneous foslevodopa/foscarbidopa
• Optimisation of functional neurosurgery, eg, multipolar directional stimulation
• Improved diagnostic accuracy using biomarkers and genetics
• Subgroup optimisations, eg, by sex, age, other factors
• Immunotherapy focused on alpha-synuclein clearance
• Regenerative therapies
• Prevention, eg, physical activity, exposure avoidance, vascular risk factors.

Key points

PD is a slowly progressive neurodegenerative disorder with preclinical, prodromal and clinical stages. Motor and non-motor features are both important targets in patient management. Early specialist review is essential to ensure accurate diagnosis and optimal treatment choices and preventive strategies.

The multidisciplinary team, and particularly specialist nursing, are essential in achieving good patient outcomes. Self-management and education are key. Access to specialist advice on an ongoing basis is required to prevent avoidable complications and admissions. Earlier use of device therapies is now considered appropriate in the correct circumstances.