Parkinosn's Disease Flashcards
How many people in the UK are affected by Parkinson’s Disease?
Approximately 127,000
Parkinson’s Disease is the Second———–
most common neurodegenerative disease, after Alzheimer’s disease
What age are most likely to be affected by Parkinson’s?
Over the age of 50
What gender are more likely to be affected by Parkinson’s?
More men than women
Where do symptoms typically present initially?
On one side
What is heterogeneous Parkinson’s?
considerable variability seen in terms of symptoms and rate of progression
What is progressive Parkinson’s?
no cure, but symptoms managed primarily through medication and therapy
Who published the first medical description of Parkinson’s and when?
James Parkinson in 1817
What is secondary parkinsonism?
Drug induced, vascular
What is Parkinson’s-Plus Syndromes (Atypical Variants)
Multiple System Atrophy (MSA) Progressive Supranuclear Palsy (PSP)
Corticobasal Degeneration (CBD)
What does idiopathic mean?
Exact cause is unknown
How is diagnosis made?
through individuals’ clinical presentation, physical examination and medical history
• SPECT scan may be carried out
• There is currently no ‘test’ for Parkinson’s Disease
• Positive response to levodopa suggestive of Parkinson’s Disease
What are Cardinal Symptoms of Parkinson’s disease?
Tremor
Rigidity
Bradykinesia
Postural Instability
What are some other symptoms?
Masked face Dysarthria Gait disturbance Micrographics Dysphagia Depression Anxiety Apathy Attention deficit Sleep disorders Autonomic symptoms Gastrointestinal symptoms Sensory symptoms Fatigue Dementia Hallucinations
What leads to Parkinson’s disease long before motor symptoms become evident?
Pathological process
What are the 3 phases?
Preclinical
Promotor
Motor Parkinson’s Disease
What is the preclinical phase?
no clinical symptoms, but pathology assumed to be
present
What is the premotor phase?
Early symptoms
What is the motor Parkinson’s disease?
manifestation of classic motor and non-motor symptoms
What can promotor characteristics include?
• Olfactory (smell) deficit
• Sleep disorders
• Constipation
• Mood changes
What can premotor symptoms have potential use for?
Clinical bioamarkers
What other biomarkers have been identified?
Potential neuroimaging, genetic and neurochemical
What is dopamine in relations to the neuropathology of Parkinson’s?
Dopamine - loss of dopamine producing neurons
Typically, there is a 70- 80% reduction in dopamine production by the time of diagnosis
What is lewy body pathology in terms of neuropathology in terms of Parkinson’s?
abnormal aggregates (clumps) of alpha- synuclein protein
What is dopamine?
A neurotransmitter
How many dopaminergic pathways are there?
4
In Parkinson’s when is the loss of dopamine producing neurons is most profound?
within the Substantia Nigra Pars Compacta (SNc) – the origin of the nigrostriatal pathway.
Dopaminergic neurons are also lost in where?
Ventral Tegmental Area (VTA)
What are the basal ganglia?
are a collection of subcortical, grey matter structures, deep within the brain
What are the main structures of the basal ganglia?
Striatum
- Caudate nucleus, putamen and accumbens nucleus • Globus Pallidus (GP)
- Internal (GPi) and external (GPe)
• Substantia Nigra (SN)
-Pars reticulata (SNr) and Pars compacta (SNc)
• Subthalamic Nucleus (STN)
What is the role of the basal ganglia?
Motor control
•Learning
•Cognitive functions
•Emotions
What is the putamen linked with?
motor control (as well as being associated with habit learning)
What is the caudate linked with?
eye movements and cognitive functions
What is the ventral striatum linked with?
The limbic system (emotional behaviour)
What is the input structure?
mainly the Striatum (caudate, putamen and accumbens nucleus)
oReceives projections from the cerebral cortex, brainstem and thalamus
o Input also received through the Subthalamic Nucleus (STN)
What are the output structures?
globus pallidus interna (GPi) and the substantia nigra pars reticulata (SNr).
oProjects initially to the thalamus and brainstem
oThalamus projects principally to widespread areas of the frontal lobe
What is the direct pathway?
Cortex Striatum GPi/SNr Thalamus
What is an indirect pathway?
Cortex striatum GPi Thalamus
What is a hyper direct pathway?
Cortex subthalamic Nucleus Thalamus
Are D1 receptors excitatory or inhibitory?
Excitatory
What does activation of D1 receptors result in?
increased activity of the direct pathway
Are d2 receptors excitatory or inhibitory?
Inhibitory
What does activation of D2 receptors result in?
Decreased activity of the indirect pathway
Reduction in dopamine=?
• Reduction in activation from direct pathway
• Increase in inhibition from indirect pathway
Overall = turning down of “Go” and turning up of “NoGo”
What does previous evidence toward the classical model of the basal ganglia indicate?
that the direct and indirect pathways may be more intertwined than previously thought, both structurally and functionally
What other neurotransmitter systems are also implicated in PD?
Cholinergic Serotonergic Adernergic Glutamatergic GABAergic
What evidence is there proving that the cerebellum also contributes to the clinical symptoms seen in PD?
Reciprocal connections evident between the basal ganglia and cerebellum
Some indication of structural changes in the cerebellum in Parkinson’s Disease
Where do Lewy bodies and Lewy Neurites Present?
SNc
nervous system
Abnormal aggregates (clumps) of alpha-synuclein protein
What has been proposed that lewy body pathology progresses in?
a predictable pattern, divided by Braak and colleagues into 6 stages
• Proposed to begin in structures of the lower brainstem and the olfactory system
What are the 4 ‘Pathways’ stages?
Diagnosed
• Maintenance
• Complex
• Palliative
What is an example of a dopamine agonists?
Ropinrole
What is an example of a Levodopa?
Sinemet
What is an example of an enzyme inhibitor and what do they do?
Prevent breakdown of dopamine
MAO-B inhibitor
What side fears come from increased dopamine?
Hallucinations
What side affects are caused by Levodopa?
Choreic movements
• Abnormal, purposeless involuntary movements
• Dystonic movements
• Muscles tighten, involuntarily (sustained contractions)
When is deep brain stimulation considered?
if side effects of medication are large, or medication no longer working as effectively
What is a deep brain stimulation?
Electrodes placed in specific brain area are connected to a pulse generator
• Electrical impulses sent to the brain when generator turned on
• Bilateral or Unilateral
What are the two types of deep brain stimulation?
STN or GPi
What is the other surgical option beside deep Brian stimulation
Lesioning
How is dysarthria characterised in PD?
Characterised by mono-pitch and mono-loudness, reduced stress, imprecise consonants, short rushes of speech, variable rate, harsh and breathy voice and pitch disturbances
How is language affected by PD?
Link with cognitive changes and dysarthria
