Parkinson's - pathology Flashcards
Who does Parkinson’s most commonly present in?
- 1.5 x more common in MEN than women
- rising prevalence with age (increased population with characteristic as ages)
What is the nature of Parkinson’s?
- chronic progressive neurodegenerative disorder (loss of neural cells in specific brain areas)
- classified as movement disorder but also has non-motor features > often unilateral
- related to other parkinsonism related disorders (movement symptoms associated with several conditions)
What causes Parkinson’s?
- idiopathic PD > unknown cause
- 10-15% hereditary
- 10-20% gene mutation w/wo environmental factors
- may have triggering factors e.g. mild brain injury
- environmental factors > MPTP; neurotoxin related to common pesticides, damage to mitochondrial function from free radicals, oxidative stress in dopamine-producing neurones
Parkinson’s is related to the basal ganglia; what are the basal ganglia’s functions? x5
- subconscious planning and execution of motor programmes > executed through the motor systems of the motor complex and SC
- control of complex unconscious and semi-voluntary movements e.g. walking
- development of body postures/positions needed to perform daily activities/mvms
- regulate muscle tone for specific movements
- inhibit antagonistic or unnecessary movements > perform several movements at once
What is the link between the substantia nigra and Parkinson’s?
- substantia nigra is part of the basal ganglia
- helps to control movements
- PD is caused by a loss of nerve cells the substantia nigra > leads to a reduction in dopamine > which plays a vital role in regulating and fine tuning movement
What is the pathophysiology of PD?
- apoptosis > programmed cell death resulting in death of dopamine cells > initiated by cell itself = dopamine depletion
- dopamine levels fall > compensatory changes in basal ganglia > clinical presentation not usually evident till 69-80% dopamine is lost
- initial pathology in lower brain stem not substantia nigra
- Lewy bodies found in cerebral cortex in later stages > non-motor features of PD
What are Lewy bodies?
- accumulations of the protein alpha synuclein ‘sticky proteins’ > facing/folded the wrong way
- however, can be present in healthy pop too
What are the divisions in PD by stages? x3
- preclinical PD - neurodegeneration present but asymptomatic
- prodromal PD - motor or non-motor symptoms present but clinical criteria not fully met
- clinical PD - motor parkinsonism present
How is PD diagnosed?
- recognition of clinical symptoms following ‘UK PD society brain bank clinical diagnostic criteria’
- absence of absolute exclusion criteria
- at least two supportive criteria
- no red flags
- defined as bradykinesia (slow movements) PLUS rigidity or rest tremor OR both
What are PD motor symptoms?
- bradykinesia
- tremor (70%)
- rigidity
- postural instability > later stages
medically induced:
- on/off states (medicine causing periods of good symptom control and lesser)
- dyskinesias > involuntary, erratic movements
- dystonia > abnormal muscle tone resulting in uncontrolled muscle movements/spasms
What are the other deficits of PD?
- lack of movement definition > no beginning or end
- poor timing
- reduced power
- difficulty with movement transitions/ switching
coordination and thinking:
- initiation
- timing
- dual tasking (multitasking)
- planning
What can occur in gait for those with PD?
- freezing of gait
- festination > multiple short steps with increased gait speed in a sequence with involuntary forward-leaning
- shuffling gait
What are non-motor symptoms of PD? (limbic system - emotion and memory)
- anxiety, depression, hallucinations
- dementia
- frontal lobe executive dysfunction > difficulty starting tasks, staying on track, planning, goal directed behaviour
- autonomic and sensory disturbances (pain)
- sleep disturbances
- restless leg syndrome, day time sleeping, weight loss, postural hypotension
- communication difficulties (facial expression, speech)
- falls and dizziness
- difficulties with eating, swallowing, saliva
- fatigue, general weakness feeling, apathy
What are possible treatments for PD? What is required in this process x3?
- medication
- exercise e.g. walking football
- diet
- stem cells (experimental)
- repurposing drugs (drugs initially used for something different)
- a disease halting Rx > slow down disease progression
- neuro protective agent > protect remaining cells > provide nurturing environment (no.3)
- a cell replacement approach > replace damaged cells
