QuestionSBA
QuestionChoice
Dementia symptoms can precede motor symptoms, but if motor symptoms are rapidly followed by dementia onset (within 1 year) this would indicate LBD.
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a
Emergence of dementia 6 months after parkinsonian motor symptom onset
QuestionChoice
Lewy bodies are protein aggregates  (primarily alpha-synuclein) which are characteristic of both Parkinson's Disease and LBD and therefore not a distinguishing feature.
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e
Histological finding of 'Lewy Bodies' in the brain on autopsy
QuestionChoice
This is a motor sign suggestive of Progressive Supranuclear Palsy, a Parkinson's plus syndrome. It is not a feature of LBD.
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d
Vertical gaze palsy
QuestionChoice
Visual hallucinations are found in both LBD and PDD.
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b
Visual hallucinations
QuestionChoice
REM sleep behaviour disorder (acting out dreams) is found in both LBD and PDD
62135
c
REM (rapid eye movement) sleep behaviour disorder
QuestionComment
In LBD don't you get emergence of dementia BEFORE parkinsonian motor symptoms
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# Summary

Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting adults over 65 years characterised by asymmetric tremor, bradykinesia, and rigidity. The condition results from Lewy body formation and neuronal death in the dopaminergic cells of the substantia nigra. Clinical features include assymetric resting tremor, slow shuffling gait, cogwheel rigidity, bradykinesia, and non-motor features such as autonomic dysfunction and psychiatric disturbances. Diagnosis is primarily clinical, supported by response to treatment trials. Pharmacological treatment with Levodopa remains the first-line therapy, with other agents used for specific symptom control or in later disease stages. Surgical interventions such as deep brain stimulation may be considered in certain cases. Prognosis varies, with little impact on overall life expectancy.


# Definition

Parkinson's disease (PD) is a neurodegenerative disorder that presents with generalised slowing of movements (bradykinesia), resting tremor and rigidity.

# Epidemiology

- Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. 
- It affects 0.3% of the UK population.
- It is estimated that PD affects at least 1% of the population over 60


# Aetiology

- The exact cause of Parkinson's disease is unknown. 
- It is believed to result from the accumulation of "Lewy bodies", intracellular inclusions primarily composed of misfolded **alpha synuclein**. 
- These bodies form and lead to neuronal death in the dopaminergic cells of the substantia nigra of the basal ganglia, thereby causing the characteristic symptoms. 
- Both dominant and recessive familial variants of Parkinson's disease have been identified.

# Clinical Features 

Parkinson's disease is characterised by the following core features:

* Bradykinesia
* Asymmetric 3-5Hz "pill-rolling" resting tremor
* Rigidity
	* Often noted to be 'cog-wheeling' which occurs when the tremor coincidees with rigidity
* Gait Disturbance
	 * Small, shuffling steps
	 * Difficult initation and turning 'en bloc turning'

Other features associated with Parkinson's Disease include:

- Hypomimic facies
- Micrographia (secondary to a combination of bradykinesia and rigidity)

Non-motor features of Parkinson's disease are also common and may precede onset of motor symptoms by many years. These include:

* Autonomic dysfunction, leading to constipation, symptomatic orthostasis (postural hypotension), and erectile dysfunction
* Olfactory loss
* Constipation
* Sleep disorders such as REM behavioural disorder 
* Psychiatric features including depression, anxiety, and hallucinations


Postural instability is a late feature of idiopathic Parkinson's disease. This said, very prominent early autonomic dysfunction should raise the suspicion of Multiple System Atrophy.

Early and prominent cognitive dysfunction should raise the suspicion of dementia with Lewy bodies (DLB).

# Differential diagnosis

Key differentials for Parkinson's disease, along with their signs and symptoms, include:

* **Multiple System Atrophy (MSA):** Very prominent autonomic dysfunction, early postural instability, poor response to levodopa
* **Dementia with Lewy Bodies (DLB):** Early and prominent cognitive dysfunction, visual hallucinations, fluctuating cognition
* **Progressive Supranuclear Palsy (PSP):** Early gait instability and falls, vertical gaze palsy, prominent axial rigidity
* **Corticobasilar Degeneration**: May have predominant apraxia, aphasia and 'alien hand' syndrome
* **Wilson's Disease:** Secondary to copper deposition in the Basal Ganglia. May be associated with signs of liver disease
* **Dementia Pugilistica:** Secondary to repeated head trauma
* **Drug Induced Parkinsonism** Secondary to antipsychotic therapy, usually symmetrical tremor and less responsive to Levodopa

# Investigations

Parkinson's disease is primarily a clinical diagnosis, supported by positive response to treatment trials. 

An absolute failure to respond to 1-1.5g of levodopa daily almost excludes a diagnosis of idiopathic Parkinson's disease.

Other investigations such as MRI Head or a Dopamine Transporter Scan (DaT scan) can be considered in atypical cases. 

# Management

Management should by led by a multidisciplinary team of neurologists, nurse specialists, physiotherapists, occupational therapists and other allied healthcare professionals.

## Pharmacological Management

### Levodopa

- Levodopa is the precurser to dopamine
- It is used as a dopamine replacement agent
- Should be started in all patients with **significant functional impairment** according to NICE guidelines
- Typically combined with Carbidopa, which decreases side effects and improves CNS bioavailability), oftern referred to as **Co-careldopa**
- Absolute failure to respond to 1-1.5g of levodopa daily virtually excludes a diagnosis of idiopathic Parkinson's disease, though a response to levodopa does not confirm the diagnosis (as many primary parkinsonian syndromes may also respond).


Side effects can be split into peripheral and central (depending on where the acting dopamine receptor is for the side effect).

Peripheral side effects include:

- Postural hypotension
- Nausea & vomiting*


With time, and as the underlying disease progresses, levodopa may become a less effective and patients may report end-of-dose effects, where motor activity progressively declines as the previous dose wears off, and on-off phenomena, which manifest as seemingly random fluctuations in drug effect.

One of the most disabling side effects is **drug-induced dyskinesia**: writhing and uncoordinated movements of the limbs associated with poorly organised dopaminergic control of motor activity.

It typically takes 2-5 years to develop complete loss of response.

*Domperidone is the anti-emetic of choice in those with Parkinson’s disease which has anti-dopaminergic activity but does NOT cross the blood brain barrier. 

### Dopamine agonists

- Examples include: Ropinirole, rotigotine, Apomorphine. Previous ergot derived formulations (eg cabergoline) as now not widely used as are associated with lung fibrosis. 
- Have a longer half life than levodopa but are not as potent
- Are often used in early disease in those without functional impairment, or late in disease when dyskinesias and motor fluctuations secondary to levodopa is a problem.
- Increases activity of dopamine via the mesolimbic pathway which may affect reward centres and lead to unwanted risk-taking behaviours such as gambling. 
- Apomorphine is the most potent dopamine agonist and is typically given subcutaneously. It works well against motor fluctuations and dyskinesia. Often used late in disease. 


### MAO-B Inhibitors

- Examples include: Selegiline, Rasagiline.
- Reduce dopamine breakdown peripherally & thus increase central update of levodopa. Often used in combination with levodopa later in disease.
- Initial animal studies suggested a "neuroprotective effect" although this has not been seen in human studies.
- Can cause serotonin syndrome. 

### COMT Inhibitors

- COMT inhibitors, or catechol- O -methyltransferase inhibitors include Entacapone and Tolcapone.
- Extend the use of levodopa. Useful in wearing off effect in levodopa use.
- Tolcapone is more potent than entacapone and can result in hepatotoxicity. 

### Amantadine

- NMDA receptor antagonist that has an unclear action in Parkinson's Disease.
- Can be used in those suffering from dyskinesia. 


###  Anticholinergic agents

- Examples include: Procyclidine, Trihexyphenidyl
- Can be used in those with mild tremors. 
- Rarely used in clinical practice 


## Surgical Management

- Deep Brain Stimulation: typically performed by implanting a stimulating device into a target area of the brain, often the thalamus or the subthalamus.

# Prognosis

- Parkinson's disease is typically slowly progressive, but the rate of progression is variable. 
- The mortality rate for elderly people aged 70-89 years with Parkinson's disease is 2-5 times higher than for age-matched controls in some studies. 
- The risk of dementia is about 2-6 times higher in people with Parkinson's disease than in healthy controls
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Which of the following characteristics support diagnosis of Lewy Body Dementia (LBD) rather than Parkinson's disease dementia (PDD)?
a