Parkinson's Disease

Question 1

Describe the key features of Parkinson’s disease and atypical parkinsonisms

Answer 1

Parkinson’s Disease (PD)

Motor Symptoms:

• Bradykinesia: Slowness of movement
• Rest Tremors: circular movement of the thumb and forefinger
• Muscle Rigidity: Increased muscle tone in the limbs
• Postural Instability: Impairment in balance

(Jankovic, 2008)

Non-Motor Symptoms:

• Autonomic Dysfunction: constipation, urinary urgency, erectile dysfunction
• Neuropsychiatric complications: Depression, anxiety, psychosis and cognitive impairment
• Sensory Symptoms and Sleep Disturbance: Pain, restless leg syndrome and REM sleep behaviour disorders are common.

(Chaudhuri, Healy & Schapira, 2006)

Atypical Parkinsonisms

Neurodegenerative disorders that present with parkinsonian features but also with additional signs and symptoms that distinguish them from PD.

Multiple System Atrophy (MSA): Autonomic failure (urinary incontinence), parkinsonism and ataxia (speech). (Gilman et al., 2008)

Progressive Supranuclear Palsy (PSP): Marked by axial rigidity, vertical supranuclear gaze palsy, cognitive dysfunction is more pronounced than in PD (Williams & Lees, 2009).

Dementia with Lewy Bodies: Includes fluctuating cognition, visual hallucinations and parkinsonian motor symptoms (McKeith et al., 2005).

Question 2

Know the clinical symptoms and diagnostic critieria

Answer 2

PD

Motor Symptoms:

• Bradykinesia, rest tremor, rigidity and postural instability.
• Bradykinesia is particularly central, required for diagnosis and involves a decrement in the amplitude and speed of repetitive actions
• UK Brain Bank Criteria Definition of Bradykinesia: Slowness of initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive action (Gibb and Lees, 1988)

Non-Motor Symptoms:

• Olfactory dysfunction, constipation, sleep disturbances like REM sleep behaviour disorder and autonomic dysfunctions (ED)

Diagnostic Criteria:

• The UK Brain Bank Criteria are commonly used for the diagnosis of PD. Requires the presence of bradykinesia and at least one of the following: muscular rigidity, rest tremor or postural instability. Exclusion criteria rule out other causes of parkinsonism (stroke, head trauma, early postural instability, early freezing, early hallucinations and dementia, vertical gaze palsy), and there must be a positive response to dopaminergic therapy (Levodopa).
• The Movement Disorder Society Clinical Diagnostic Criteria for Parkinson’s Disease (2015) offers a structured approach to diagnosing PD, emphasising the importance of parkinsonism being defined as bradykinesia in combination with either rest tremor or rigidity. This criterion also incorporates red flags and supportive criteria to enhance diagnostic accuracy.

Atypical Parkinsonisms

Multiple System Atrophy (MSA): Characterised by autonomic dysfunction, parkinsonism, or cerebellar ataxia. Diagnostic criteria focus on these core features (Gilman et al., 2008)

Progressive Supranuclear Palsy (PSP): Features include vertical supranuclear gaze palsy, axial rigidity and frequent fall. Highlighting gaze palsy as a distinctive feature

Corticobasal Degeneration (CBD): Presents with asymmetric limb rigidity, apraxia and cortical sensory deficits. The alien limb phenomenon is an indicator (Armstrong et al., 2013)

Dementia with Lewy Bodies (DLB): Marked by fluctuating cognition, prominent visual hallucinations, parkinsonism and sensitivity to antipsychotic medication. The diagnostic criteria emphasise these core features along with REM sleep behaviour disorder and severe neuroleptic sensitivity (extrapyramidal side effects from antipsychotic medication). (McKeith et al 2017)

Question 3

Understand key neuropathological aspects of these conditions

Answer 3

PD

Loss of Dopaminergic Neurons: in the substantia nigra pars compacta (SNpc). Depletion of dopamine, a neurotransmitter for controlling movement and coordination

• Lewy Bodies: intracytoplasmic eosinophilic inclusions, composed of alpha-synuclein protein. Lewy bodies are found in the remaining dopaminergic neurons and are thought to contribute to neural death

(Spillantini et al., 1997)

Atypical Parkinsonisms

Multiple System Atrophy (MSA:

• Oligodendroglial cytoplasmic inclusions: presence of alpha-synuclein-positive glial cytoplasmic inclusions in oligodendrocytes
• Neuronal Degeneration and loss in the stratonigral and olivopontocerebellar systems.

Progressive Supranuclear Palsy (PSP):

• Tau Pathology, neurofibrillary tangles made up of tau proteins similar to AD but different tau isoform pattern
• Brainstem and Cortical Degeneration: Especially in the subthalamic nucleus, globus pallidus and dentate nucleus of the cerebellum

Corticobasal Degeneration (CBD):

• Asymmetric Cortical Atrophy: frontal and parietal lobes
• Balloon Cells and Tau-positive atrocytic plaques

Question 4

Know the key symptomatic treatments of movement disorders

Answer 4

1. Dopaminergic Therapies:

• Levodopa, a precursor to dopamine that crosses the blood-brain barrier and is converted to dopamine in the brain. Administered with a dopa-decarboxylase inhibitor to prevent peripheral conversion of levopoda to dopamine, thereby reducing side effects and increasing the amount available in the brain (Olanow et al., 2009).
• Dopamine Agonists: stimulate dopamine receptors, useful in younger patients to delay the initation of levodopa (Schapira et al., 2013). Side effects include sleepiness, leg oedema and impulsive compulsive behaviour

2. MAO-B Inhibitors

• Selegiline and Rasagiline: inhibit monamine oxidase B enzyme which breaks down dopamine in the brain. Have a mild symptomatic effect (Olanow et al., 2009)

3. COMT Inhibitors:

• Entacapone and Tolcapone: Inhibit catechol-O-methylfransferase (COMT) another enzyme that degrades dopamine thereby extending the effect of levodopa (Olanow et al., 2009).

4. Anticholinergic Medications:

• Primarily to control tremors by may have cognitive side effects (Schapira et al., 2013).

Question 5

Know the associated psychological disorders that are associated with movement disorders

Answer 5

1. Depression & Anxiety: linked to neurodegenerative process, involving neurotransmitter imbalances. Anxiety in PD can exacerbate motor symptoms and contribute to fluctuations in motor functions. (Richard & Schiffer, 1996)
2. Cognitive Impairment and Dementia:

• Ranging from mild cognitive impairment to Parkinson’s Disease Dementia (PDD). Executive dysfunction, slowed cognitive speed, memory retrieval issues and visuospatial impairments (Emre =, 2003).

3. Psychosis:

• Hallucinations and delusions, as a side effect of dopaminergic therapies or part of the disease progression (Fenelon et al., 2000)

4. Impulse Control Disorders (ICDs):

• Pathological gambling, hypersexuality, compulsive shopping and binge eating, particularly those with dopamine agonists. (Voon & Fox, 2007)