Parkinsons Disease Lecture Flashcards
What is the incidence and prevalence of Parkinsons disease?
Almost 20,000 new cases a year (relativly common).
Prevlance of around 120,000
Often debate is essential tremor which has a prevalcne of 900,000.
What is the underlying pathophysiology of parkinsons disease?
Risk of genetic and environmental factors.
Misfolding of alpha-synuclein associated with Lewy bodies. Aggergation and accumulation in the brain.
Resutls in neuroinflammation, dysfunctional autopaghy, mitochondrial dysfunction etc
Causes neuronal cell death, particularly in the substantial nigra.
What is the gut brain hypothesis of Parkinson Disease?
Alpha synuclein aggregates are initially formed in the enteric nervous system and spread from the gut to the medulla via the vagus nerve.
Suggests with PD is often associated with exposure to pesticides and other environmental toxins. q
What are the genetic underpinning parkinsons disease?
Parents of children with Gauchers disease are more likely to get PB (homozygous GBA mutation)
Genetic PD is rare but can be caused by
Autosomal dominant
PARK8 (AKA LRRK2)
SNCA (PARK1/4) - alpha synuclein mutation
Autosomal reciessive pattern:
PARK2 (parkin) = problem with clearing toxic proteins.
What system should be used as a reference to diagnose parkisons disease?
What is the basic idea of this system?
UK Brain Bank Criteria
Clinical diagnosis
1 - diagnosis of parkinsonism (quadrant features)
2 - rule out exclusion criteria
3 - confirm supportive criteria for PD for definitive diagnosis.
What are the premotor features of parkinsons disease?
Anosmia - loss of smell
REM sleep behaviour disorder
Constipation
Mood changes.
Why are the premotor functions of parkinsons disease important to detect?
Due to pathology in gut, DMNV and the olfactory bulb 10-15yrs before muscle problems.
Important to identify as pathology not yet causing motor symptoms, may be able to stop progression.
What are the non-motor symptoms of Parkinsons disease?
Swallowing difficulties, speech difficluties, drooling
Congitive impairement, anosmia, apathy, depression/anxiety, sleep disturbances and hallucinations
Orthostatic hypertension, falls, excessive sweating, pain
Constipation, urainry symptoms, gastroparesis, weight loss, weight gain, sexual dysfunction.
What are the main differential diagnosis to consider alongside parkinsons disease?
Essential tremor
Vascular Parkinsons
Parkinsons Plus syndromes
Dementia with Lewy bodies.
What are the key features of vasuclar Parkinsonism?
Stroke of small blood vessels in the brain affecting motor control.
Excluded from parkinson disease because:
Often present with repeated strokes with stepwise progression.
Strictly unilateral features after 3yrs (no progression to bilateral disease). Norm lower limb dominant, gait problems, meds less effective.
What are the main features of parkinsons plus syndrome and how you exclude from parkinsons disease?
Microtubule-associated protein tau disorder - causes neurodegeneration.
Often have supranuclear gaze palsy, eye signs and cerebellar signs
Early severe dysautonomia (poor autonomic function aka urination, erectile dysfunction. sleep patterns, postural hypotension).
Relentlessly progressive - die within 7 years, early swallowing problems, increased falls.
How is Dementia with Lewy Bodies different to Parkinsons’ Disease?
How is this reflected in the exclusion criteria for Parkinson’s disease?
Early severe dementia with disturbances of memory, language or praxis.
Both have the same pathological processes but a different course of disease, cognitive symptoms before parksonism.
What is DAT scan?
Dopamine Active transporter scanner
Nuclear medicine test to highlight hence look at the function of Dopmaine tranpsorters in the brain.
Use to differentiate parkinsons disease from other disorders of movement.
Requires injection of a radioactive tracer.
How can a DAT scan differentiate between parkinsons disease and an essential tremor?
How is dopamine broken down at the synaptic cleft?
Is broken down into homovallinic acid
Either by COMT in the synaptic cleft or by MAOB in the pre-synpatic neuron.
