This article is based on a presentation given by Dr Richard J Davenport, Consultant Neurologist, Edinburgh, at the GM Conference Ageing and Healthcare Today, held in Edinburgh.
Parkinson’s disease can present with both motor and non-motor symptoms. In a number of cases the nonmotor symptoms can precede the motor symptoms by many years.
Parkinsonism is a clinical syndrome and idiopathic Parkinson’s disease is one cause of Parkinsonism. There are no definitive tests so a definitive diagnosis can be difficult to obtain, especially as people get older.
A pathologist would define idiopathic Parkinson’s disease as degeneration of striatonigral pathways predominantly with Lewy bodies. According to the Braak hypothesis, there would be a caudal-rostral pattern of progression and α-synuclein accumulation. Yet, when you deal with a living patient with Parkinson’s disease, it is a clinical syndrome characterised by levodopa responsive Parkinsonism with akinesia or bradykinesia, rigidity, tremor (typically at rest) and postural abnormalities.
Parkinsonism is caused by idiopathic Parkinson’s disease in 80% of cases. In the rest the cause is usually linked to conditions such as: cerebrovascular disease, hydrocephalus, neurodegenerative disorders, inherited degenerative disease (such as Huntington’s disease) or it could be drug-induced (Table 1).
A diagnosis of Parkinson’s disease can be obtained from a history of inclusive and exclusive clues, examination and follow up, which could be for years.
There is also the UK PDS Brain bank clinical criteria that includes three steps.
Step one is bradykinesia (akinesia) plus at least one of the following: rigidity, 4–6 Hz rest tremor and postural instability.
Step two is exclusion criteria such as history of repeated strokes with stepwise progression of Parkinsonism features, history of repeated head injury, strictly unilateral features after three years, supranuclear gaze palsy, early severe dementia with disturbances of memory, language and praxis, or negative response to large doses of levodopa in the absence of malabsorption (Table 2).
Step three is supportive prospective positive criteria that is step one plus at least three of the following: unilateral onset, rest tremor present, progressive disorder, persistent asymmetry affecting side of onset most, excellent response (70–100%) to levodopa, severe levodopa-induced chorea, levodopa response for five years or more and clinical course of ten years or more.
In reality there is a phenotype recognition that is tremor dominant and akinetic/rigid. Early red flags are cognitive decline and behavioural change, autonomic disturbance and falls.
Bradykinesia means slowness of movement and symptoms can include clumsiness, difficulty with buttons and writing. Signs can include finger taps and heel strikes.
Muscular rigidity can be seen unilateral or bilateral. The “cogwheel” phenomenon is a particular type of rigidity occurring in Parkinson’s disease. It is thought to be tremor superimposed on rigidity. There is also leadpipe rigidity, which is sustained resistance to passive movement throughout the whole range of motion, with no fluctuations.
Tremor is one of the main symptoms of Parkinson’s. It can affect just one arm or leg and it can be worse when walking. Less typically it is postural and kinetic. Head tremor is not associated with Parkinson’s disease.
Tremor differentials include physiological, dystonic, drug-induced, neuropathic or caused by cerebellar disease.
Non-motor symptoms (NMS) are increasingly recognised as a significant cause of morbidity in later stages of Parkinson’s disease.
The presenting complaints of 433 cases of pathologically-proven Parkinson’s disease archived at the Queen Square Brain Bank for Neurological Diseases were identified from the clinical case notes. Out of 433 patients with Parkinson’s disease, 91 (21%) presented with non-motor symptoms of which the most frequent were pain (15%), urinary dysfunction (3.9%), anxiety, or depression (2.5%). Presenting with non-motor symptoms is also associated with a delayed diagnosis of PD and initial misdiagnosis may be associated with potentially inappropriate medical interventions.1
|TABLE 1. UK PDS BRAIN BANK CLINICAL CRITERIA STEP 2|
There are three phases of Parkinson’s disease, which are pre-clinical, pre-motor and motor. The pre-motor symptoms can last for years and include hyposmia, REM sleep behavioural disturbance, constipation, depression and anxiety (fatigue, apathy, cognition, personality). Therefore, when taking a history of a patient it is important to also review neuropsychiatric symptoms, cognition/ behaviour, anxiety/depression, compulsiveness and current and previous drugs.
There are no clinical tests to diagnose Parkinson’s disease, but functional imaging can be used and these include:
- nnSPECT (gamma camera)
- Cocaine analogue, binds to dopamine active transporter sites on pre-synaptic terminals
- nPET (PET scanner and cyclotron)
- nn 18F-dopa.
There have been a number of studies that have shown that the diagnosis of Parkinson’s disease is not always straightforward and physicians can often get it wrong.
Not all cases satisfy the established neuropathological criteria for idiopathic Parkinson’s disease. Pitfalls to watch out for are drug-induced Parkinsonism from drugs such as neuroleptics (all except clozapine), metoclopramide and valproate. Gait failure, old age, polymyalgia rheumatica and joint disease can also lead to misdiagnosis.
|TABLE 2. PARKINSONISM CAUSES|
|Idiopathic Parkinson’s disease (80%)
One study found that in 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer’s disease, Alzheimer-type pathology, and basal ganglia vascular disease.2 The finding throws into question many clinical studies that assume that idiopathic Parkinson’s disease. is a specific morbid entity and may be diagnosed on clinical grounds alone.
Parkinson’s disease comes with its own set of management dilemmas such as when to start treatment and with what? What to do when it all starts going wrong? Also, healthcare professionals need to look at non-motor symptoms and cognition.
In conclusion, Parkinsonism and Parkinson’s disease are a clinical diagnosis with motor and nonmotor symptoms. The non-motor symptoms precede the diagnosis by many years. Bradykinesia is the absolute requirement for diagnosis and diagnostic tests are rarely necessary. Follow up is key part of management as is response to treatment.
2. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery, and Psychiatry 1992; 55:181–84