20th July 2023

Parkinsonism

Parkinsonism is a term used to describe a group of disorders which cause symptoms similar to those in Parkinson’s disease, such as rigidity, bradykinesia and tremors. Typically, this group of disorders represents up to 15% of all diagnosed cases of Parkinson’s. The disease progression of these syndromes tends to be quicker than PD, and the response to levodopa therapy is either short lived or non-existent.

Multiple System Atrophy (MSA)

A rare neurodegenerative disorder caused by neuronal loss in multiple areas of the brain manifesting as ataxia and Parkinsonism. An important feature is autonomic dysfunction causing postural hypotension and autonomic symptoms.

There are 2 main types; MSA-P (Parkinson’s features) and MSA-C (Cerebellar features); the type depends on which symptoms are predominant at diagnosis. MSA-P is more common, and the symptoms include rigidity, bradykinesia, tremors, posture and balance difficulties. MSA-C includes ataxia, dysarthria, visual disturbances and dysphagia. Symptoms of autonomic dysfunction can overlap in both types and can manifest as postural hypotension, urinary retention/incontinence, sleep disorders, erectile dysfunction, and emotional dysregulation. Autonomic dysfunction tends to present earlier than in Parkinson’s disease. MSA is caused by inclusion bodies containing alpha-synuclein leading to cell loss and reactive changes to glial cells in the CNS. A pathological diagnosis can only be made at autopsy. Management is mainly through an MDT approach, e.g. physios to help with contractures. Postural hypotension can respond to synthetic mineralocorticosteroids such as fludrocortisone. In contrast to Parkinson’s, medications such as levodopa are not found to work as well, and it tends to have a more rapid disease progression, with life expectancy from symptom onset being 6-9 years.

Progressive Supranuclear Palsy (PSP)

PSP is a rare progressive degenerative syndrome characterised by ataxia, vertical gaze palsy and cognitive impairment. It tends to be slightly later onset (60-70 years) than other similar syndromes. Common symptoms include ataxia, frontotemporal dementia, gaze palsy and hypokinesia. Some patients are also noted to have disinhibition and dysphagia. Often a patient complains of difficulty looking down and describes diplopia when reading. PSP is thought to be caused by the accumulation of tau proteins within the brain (described as tufts seen in astrocytes), particularly in the basal ganglia and brainstem. An MRI can be used to diagnose PSP by showing a ‘hummingbird’ and ‘Mickey Mouse’ sign. Management requires an MDT approach, with physio and occupational therapist input. There is currently no thorough research to strongly back medication use.

Lewy body Dementia (LBD)

LBD is a progressive form of dementia caused by the neurodegeneration of the central nervous system manifesting as changes in cognition, motor function, sleep, behaviour and autonomic systems. It is caused by abnormal clumps of Lewy bodies (protein in neurons) being deposited through the brain. This causes neuronal dysfunction, leading to a dopamine dysfunction and a loss of acetylcholine producing neurons.

LBD manifests as motor dysfunction, and autonomic dysfunction, and patients often report visual hallucinations (usually animals and people, often children) and vivid dreams. Patients are often aware that their hallucinations are not real. Autonomic dysfunction typically manifests as postural hypotension. Psychiatric symptoms appear as altered behaviour, depression, apathy, attention deficits, and executive and visuospatial dysfunction.

For diagnosis, cognitive impairment should appear within one year of parkinsonism features. However, a definitive diagnosis is only possible by autopsy. It usually takes years to diagnose, and is commonly misdiagnosed as there is a lot of overlap with other conditions such as Parkinson’s disease and Alzheimers.

Cholinesterase inhibitors such as donepezil and rivastigmine are used to try and help with cognition and function. Melatonin is used for sleep to try to restore the day/night cycle.

Corticobasal Degeneration (CBD)

A rare neurodegenerative disease involving the cerebral cortex and basal ganglia, manifesting as a gradual onset movement and cognitive disorder. It typically occurs in those aged 50-70 years, and it tends to progress over 6-8 years.

Patients find difficulties in cortical processing and basal ganglia dysfunction. Symptoms include bradykinesia, apraxia, aphasia, limb dystonia, parkinsonism, and myoclonus. These can present unilaterally initially, which then become bilateral. Another important feature is alien-limb phenomena. The pathophysiology behind this is an accumulation of tau proteins and astrocyte inclusions, which cause astrocytic plaques which appear as blurry outgrowths from the astrocyte. Unfortunately, there are no known treatments which slow the course of the disease. Parkinson’s drugs don’t show sustained improvement though clonazepam can be used for myoclonus. Otherwise an MDT approach, including speech therapy, is used to try to manage the symptoms of the disease. Patients typically die from complications such as pneumonia.

Drug-Induced Parkinsonism

This is the second most common aetiology of Parkinsonism and is usually caused by medications which antagonise dopamine receptors in the basal ganglia. Culprit medications include antipsychotics, stimulants, GI prokinetics or calcium channel blockers. Usually, the symptoms should improve if the causative medication is stopped, although it can take up to 18 months to do so. If the medication cannot be stopped, it should be reduced where possible. Alternative treatment options are anticholinergics, such as procyclidine.

Clinical symptoms include bilateral and symmetrical Parkinsonism without a resting tremor; however, in practice, a significant portion of patients present with an asymmetrical and resting tremor.