29th April 2024

Parkinson’s-Plus conditions

Background

This refers to other causes of parkinsonism which is not caused by PD itself. Patients often have additional clinical features which suggest a more widespread pathology. Such conditions tend to generally be associated with postsynaptic changes, therefore response to levodopa can be poor or unsustained. The importance of these conditions lies in diagnosis and differentiation from PD.

Differentiating Parkinson’s-Plus conditions

Multiple system atrophy

Multiple system atrophy (MSA) is characterised by parkinsonism in association with autonomic failure. There is no clear etiological factor, and it is generally considered a sporadic disease. Most patients will have a history of prior or concurrent REM behaviour disorder. Patients tend to have a jerky tremor and rigidity is usually symmetrical, though not always. Postural instability is seen early, often within 3 years of onset and is rapidly progressive, and falls are common.   Orthostatic hypertension, erectile dysfunction, urinary incontinence/retention, as well as other autonomic complications are a hallmark.

Progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is caused by abnormal tau protein accumulation, leading to degeneration of neurons in the nuclei in the brainstem and basal ganglia. Clinically, it is characterised by parkinsonism and supranuclear gaze impairment, as well as postural instability and cognitive decline. As well as a resting tremor, patients may present with frequent falls, axial rigidity, dysarthria, dysphagia and cognitive decline. Rigidity and resting tremor tend to be symmetrical. It is distinguished from MSA by the extent of dysautonomia and cerebellar ataxia, which is seen in MSA but less so in PSP.

Dementia with Lewy Bodies

Dementia with Lewy Bodies (DLB) is dementia which occurs concurrently with, or within 1 year, of parkinsonian symptoms. Core features include visual hallucinations, REM sleep behaviour disorder, and parkinsonism in the form of bradykinesia, resting tremor or rigidity. These features often occur early. Lewy bodies, round intracytoplasmic inclusions, aggregate in the nuclei of neurons in the substantia nigra, as well as in the brainstem amongst other places. The importance of recognising the diagnosis of DLB guides management, as it responds to cholinesterase inhibitors, whilst patients with DLB are very sensitive to neuroleptic agents.

Corticobasal degeneration

Corticobasal degeneration is a neurodegenerative condition which leads to asymmetrical neuronal loss and atrophy of the frontoparietal cortex. Clinical features include significantly asymmetrical rigidity and bradykinesia. This typically occurs first in an upper limb and can progress to limb dystonia, with patients exhibiting dystonic limb posturing or alien limb phenomenon. Parkinsonian features include rigidity and bradykinesia, as well as a resting tremor. It is not normally responsive to levodopa administration.

Clinical features are the mainstay of diagnosing Parkinson’s-plus conditions, as well as differentiating between them.

References

• Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremor. From the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord. 2018 Jan;33(1):75-87
• Okun MS, Lang AE. Parkinsonism. In: Goldman L, Schafer AI, editors. Goldman-Cecil Medicine. 26th ed. Philadelphia (US): Elsevier; 2020. p 2416-2423.e3
• Chou KL, Dayalu P. Assessment of tremor. BMJ Best Practice. Sep 2021 https://bestpractice.bmj.com/topics/en-gb/974