Parkinson's , dementia - degeneration case unit Flashcards
What is Parkison’s disease ?
- Cause
- Main symptoms
- Risk factors
Progressive Movement disorder - neurodegenerative
- Dopamine producing neurons substansia nigra (or basal ganglia )degenerate.
- start of unilateral but become bilateral
Main symptoms MOTOR SYMPTOMS - Tremor - Bradykinesia - slow movement - Rigidity (stiff & inflexible muscles) - Postural instability * symptoms insidous in nature (gradual , progress ) ------> become disabling.
OTHER SYMPTOMS
- craniofacial
o Hypophonia - loss of voice
o Masked facies - loss of spontaneous facial movement
o Hypokenetic Dysarthria - difficulty speaking - reduced pitch , loudness, variable speaking rate etc. (linked to bradykinesia and rigidity of orobuccolingual & laryngeal musculature )
- Gait (mostly due to rigidity)
o Shuffling gait
o Stooped posture
- Eyes
o eye disorders e.g . hypometric saccades (eye fall short of intended target.) , saccadic eye movement - rapid movement of eye within fixation point.
- Depression
- Anxiety
- higher of developing dementia
RISK FACTORS
STRONG
- Increasing age
- history of familial young onset parkinson’s disease ( young onset - begins under 50 years )
- sufferer / carrier of Gaucher disease gene (mutation in GBA - glucocerebrosidase - so body does make enough of it ) - 5X risk of PD
- MPTP (neurotoxin) exposure - mostly found in labs -so does really affect general population - but high risk
(1- methyl -4-phenyl-1,2,3,6-tetradropyridine)
(Taken up and releases reactive oxygen species ———————-> membrane damage , DNA damage , lipid peroxidation (oxidative degradation of lipids)——————> reduced input / no action potential.
WEAK
- Higher risk in males
- Head trauma
- Toxin exposure
- basal ganglia is a collection of structures.
- akinesia - absence of movement
-
What is the basal ganglia ?
Collection of structures (sub cortical nuclei )
deep to cerebral hemisphere :
- Corpus striatum - largest component
(contains :
o Caudate nucleus
o Lentiform nucleus - contains Putamen , Globus Pallidus (externus & internus ) - Subthalamic nucleus
- Substantia nigra
What is atypical parkinsonism ?
Group of progressive disorders that present with similar symptoms to PD , but do not respond to Levodopa (PD treatment) - usually caused by abnormal build of protein in brain
- Dementia with lewy bodies
- Progressive Supranuclear palsy
- Multiple system atrophy
- Drug induced parkinsonism
- Vascular parkinsonism
- Corticobasal ganglionic degeneration.
SYMPTOMS Prominent postural instablilty - Rigidity - tremour (and resting tremour ) - bradykinesia - severe autonomic dysfunction ( can present as constipation amongst others ) - Cognitive impairment - significant neuropsychiatric features o hallucinations o fluctuating levels of arousal etc.
What causes PD ?
Normally
- Input from cerebral cortex (CC) to Basal Ganglia (BG)
- Output from BG to the thalamus in CC.
- Input from thalamus in CC to skeletal muscle via spinal cord & tractse.g corticospinal tract
PD
- problem with STEP 2 - no output to CC as dopamine receptors in BG degenerate - area is smaller(movements no longer smooth)
- so there is excessive inhibitory input to thalamus as GABA neuron is not inhibited due to lack of dopamine - suppression of Thalamu-cortico-spinal pathway - movement not smooth , controlled etc.
BG role - subconscious control of skeletal muscle , coordination of learned movement patterns
PD vs Parkinsonism ?
Parkinsonism -
umbrella term for the clinical syndrome
involving bradykinesia together with at least one of the following: rigidity, tremor, and postural instability.
PD is the most common form.
Differential diagnosis of PD ?
0 Drug induced Parkinsonism
hard distinguish between Parkinson’s disease and drug-induced Parkinsonism. on the basis of clinical symptoms and signs alone.
Typical presentation:
rapid , bilateral motor symptoms
- no rigidity or resting tremor, may be an action tremor.
Possible causative drugs include: 0 Anti psychotics - symptoms appear within 10 weeks of starting. fluphenazine, trifluorophenazine, haloperidol chlorpromazine flupentixol zuclopenthixol (just for reference ) 0 Antiemetics - ex - Metoclopramide Prochlorperazine
more rarely -
o Antidepressants, ex - (SSRIs). o Calcium-channel blockers. o Cinnarizine. o Amiodarone. o Lithium. o Cholinesterase inhibitors ex- - donepezil -memantine. o Sodium valproate. o Methyldopa. o Pethidine.
0 Parkinsonism - Progressive supranuclear palsy (suggested o early dysphagia o gaze palsy o recurrent falls).
- Multiple system atrophy (suggested by o severe early autonomic involvement o postural hypotension o cerebellar ataxia ATAXIA - degenerative disease of NS - mimic being drunk - slurred speech , stumbling, falling, ;lack of coordination. - Corticobasal degeneration (suggested by asymmetric rigidity and dystonia, with apraxia and cognitive impairment). APRAXIA - desire and capacity to peform movement but cannot carry it out.
0 Wilson’s diseaase - genetic disorde - copper build up in body - excess levels
- uncontrolled movements
- muscle stiffness
(also get jaundice (non -specific liver disease , abdo pain , fatigue , lack of appetite , fluid build up, golden brown eye discolouration(Kayser - Fleischer rings )
Treatment of PD?
1ST LINE - either of these , can be used alone or together + physical activity
- if vomiting & on carbidopa /levodopa - give additional doses of Cabidopa or Domperidone ( reduce stomach contractions )
- if Vomiting & on dopamine agonist - Domperidone
THE FIRST LINE DRUGS -
- Dopaminergic agent - usually 1st intially
e.g . Pramipexole
Ropinirole
(these 2 DOPAMINE AGONISTS)
Levodopa / Carbidopa combination
(Levodopa is converted to dopamine when it reaches brain - Cabidopa - prevent levodopa from being broken down before it reaches the brain.
Help reduce dose of L-dopa needed - Dopamine cant cross Blood brain barrier)
- MAO (monoanime Oxidase B ) inhibitor - ex - Rasagiline secondary option Seregiline
secondary option but still 1st line 0 Trihexyphenidyl - 0 Amantadine anticholengic drugs
- Domperidone - low dose, shortest time possible no longer than week , small risk of life threatening cardiac effects.
CONTRAINDICATED
moderate PD
1st line - same as mild
Difference - if Trihexyphenidyl or amantadine
(caution in patients will cognitive impairment - anticholinergics can make it worse)
if Refactory (non-responsive medication) to all medicine and disabling tremor - Surgery - Deep brain stimulation
if improvement of motor symptoms on levadopa - can add another drug - Dopamine agonist , MOA-B , extended release L/C or COMT inhibitor
- COMT inhibtor if started on Levo then this can improve symptoms further.
(ex - Entacanpone - 1st option
Opicapone - secondary)
if they have Dyskinesia - (involutary erratic writhering movement ) - complication PD drugs e.g L/C therapy
- reduce dopaminergic medications ) or add amantadine
Severe PD - same as mild and moderate Difference : 0 unpredictable off time motor flucations of freezing - PLUS amorphine or L/C as needed
0 refractory dyskineasias - PLUS DBS
if dysphagia - dis-solvable selegiline or L/C or transdermal rotigotine
0 refractory motor flucations
- PLUS -DBS
ADJUCNT- intrajejunal infusion of L/C
What are the different types of Dementia ?
ALzheimer’s disease - most common
(rapid forgetting not as commonly seen in VD)
0 Vascular dementia - 2nd most common
0 Dementia with Lewy bodies
0 Frontotemporal Dementia
What is Alzheimers Disease ?
Most common form of Dementia
Neurodegenerative disease - breakdown of neurons in brain -particularly in cortex.
TYPES
- Sporadic - late onset - most common - risk increases with age.
- Familial - can be early onset
* Deterioration over 8 -10 years.
people with down syndrome can go on to develop AD - Have the same mutation.
CHARACTERISTICS
- Plaque formation
- Neurofibrillary Tangles
- Neurone loss
- Brain atrophu
0 Plaque formation (from insoluble protein (not dispose off or broken down properly - plaque forms btw neurones disrupting nerve transmission) ———————-> plaques can cause inflammation damaging other neurones.
- Plaques can deposits around brain BV weakening the walls — ( Amyloid angiopathy )——-> increased risk of haemorrage , rupture , blood loss.
- Amyloid - what plaque made our off (protein)
0 Neurofillbulary Tangles - found inside neuronal cells
( Plaque build up outside cells initiates pathways activating kinase to Phosphorylate protein tau - ———————-> changes shape ———————–> cant support microtubule stucture ————————————> tau leaves the microtubule and clumps together and tangled —————————–> microtubules break apart , cellular processes cannot functional well, some undergo apoptosis.
- Neurones die
- Brain shrinks & atrophies
- Gyri get narrower
- Sulci & ventricles get wider
TAU- need to hold together microtubule tracts - need for cell movement (organelles ))
- can exist alongside other forms of dementia.
What are the symptoms & signs of Alzheimers ?
Progresses as Plaques & Tangles build up.
0 Memory loss - short memory first ———-> progresses to long term memory.
0 Disorientation ———–> getting loss or misplacing stuff ex.
0 Nominal Dysphasia - difficulty naming things
( Assess in Mini- Mental state Exam)
0 Decline in activities of daily living i.e. first cooking and shopping ———————> later continence , dressing and ambulation (walking without resistance) and verbalisation.
0 Can have personality change / Mood changes
- Apathetic
- Depressed
- Irritable
0 constructional Dyspraxia - difficulty completing task which involve construction i.e. drawing a star etc.
(Parietal lobe deficits)
Dyspraxia / developmental co-ordinatio disorder - condition of physical coordination.
0 Poor abstract thinking ———> organisation & planning different.
Early stages
- might not be detectable —————————> loss of short term memory —————————> loss of motor skills & Language ————————-> Loss of long term memory—————————> disorientated ————————————-> Bed ridden
LATE symptoms
- most common cause of death - infection e.g. pneumonia
Risk factors of AD ?
- Age - increases as age does
0 Fx of AD
0 Down syndrome - linked with plaque build up - (more than 50 % will develop AD cognitive symptoms by 60s )
0 Lifestyle
- smoking
- diabetes
- Hypertension / Pre- hypertension.
*Hyperlpidaemia , Cerebrovascualar disease - higher risk of vascular dementia which can co-exist with AD.
Treatment of AD ?
1st line
0 Carer support - essential + environment control measure (home modification , motion sensors etc,) + Cholinesterase inhibitor
Cholinesterase
0 Donepezil
0 Rivastigimine oral/transdermal
0 Galantamine
Block breakdown of Acetylcholine - neurotransmitter (to preserve memory , functional abilities)
- DONT STOP ABRUPTLY - SYMPTOMS COULD REBOUND.
ADJUNCT - Antidepressants
(Sertaline , Citalopram, escitalopram, mirtazapine)
ADJUNCT - treatment of isomnia
Trazodone - low dose.
ADJUNCT Management of behavioural & psychological symptoms - Citalopram , Carbamazepine
2ND LINE
Memantine - for severe AD - If cholinesterase inhibitors not tolerated or not working.
(Blocks NMDA receptors (N-methyl-d-aspartate - type of glutamate receptor - regulate excitatory function in the brain. ————————-> no calcium influx ———————-> cell protected.
In Alzheimers - abnormal build up of protein causes ———————–> excessive release of Glutamate by glial cells / inhibiting glutamate uptake ———————. overtsimulation of NDMA receptors ————————–> excessive influx of calcium ————————> cell raptures and dies.
too much calcium ———————–> causes death as it over activates enzymes e.g
0 Proteases (damage proteins i.e. in plasma membrane , cytosol)
0 Lipases (damage to cell membrane )
0 overstimulate mitochondria ——————–> produce oxygen reactive species (free radicals ) - damage whatever they come into contact with. - too much activity (excitotoxicity) etc.
What is Vascular dementia ?
Multi- infarct Dementia - progressive loss of brain function because of long term poor blood flow to brain (usally caused by series of strokes. )
Vascular - blood flow to brain
Dementia - difficulty with memory , communicating , learning new info.
What is Vascular dementia ?
2nd most common form of dementia.
Multi- infarct Dementia - progressive loss of brain function because of long term poor blood flow to brain (usually caused by series of strokes. )
Vascular - blood flow to brain
Dementia - difficulty with memory , communicating , learning new info.
lack of blood flow ———————> neurones don’t get oxygen , glucose (they need oxygen and do not store glucose ———————. need constant supply of blood )
Stroke , atherosclerosis - plaque build up blocks artery supplying brain i.e. carotid—————————–> gradual decline in blood flow to brain - Chronic ischemia——————-> plaque break off and block smaller artery completely———————————-> ISCHEAMIC STROKE —> PERMANENT ——————–> BRAIN TISSUE DIES OFF ——————> DEMENTIA .
SYMPTOMS
- Depends on area of brain affected ————–> symptoms appear suddenly —————->function decline withe each stroke.
Function of 4 lobes of brain & stroke in these areas - symptoms ?
0 Frontal lobe - Personality
- movement (motor control - contains primary motor cortex (voluntary movement)-
- language - contains brocas area -
- counting
- spelling
decision making
(Personality changes
- damage to brocas (cant produce words, but can understand ))
0 Parietal lobe
- Sensory lobe
(helps determine physical location , guide movement)
- contain pre somatosensory cortex - processes touch , temperature , pain.
(Aphasia - loss of speech )
0 Occipital
(process visual info)
0 Temporal lobe - Hearing - contain auditory cortex - Smell - memory recognition. - Wernicke's area - language comprehension - damage here - cant understand.
(difficulty remembering- memory loss )
