Unit 14 week 3 Flashcards
Risk factors for PD
increasing age
familial PD
mutation in gene encoding for glucocerebrosidase
Exposure to MPTP (pesticide)
key diagnostic signs/ symptoms (4)
- bradykinesia and one other of
- resting trmor (pill rolling)
- rigidity
- postural instability
bradykinesia
Slowness of movements
Progressive reduction in amplitude of repeated movements
Delay in initiating movements
Freezing of gait eventually seen in all patients
resting tremor
4 or 6 Hz tremor at rest that dissipates with use of the limbs
Asymmetrical onset
rigidity
Hypertonicity is defined as unvarying increased resistance within the range of passive movement about a joint.
Often cogwheeling will be noted, especially (although not only) if tremor is also present.
postural instability
mbalance or falling noted with pull test or spontaneously; retropulsion; common in mid- to late-stage disease.
additional signs and symptoms of pd/ parkinsonism
- masked facial expressions
- hypophonia (low volume)
- micrographia (decreased amplitude of handwriting)
- stooped posture
- shuffling gait
- fatigue
- constipation
- depression
- anxiety
- dementia
- hallucinations
- REM sleep movements
- hypotension
- swallowing difficulties
- visual difficulties
- decreased sense of smell
UK brain bank criteria for PD
guidelines to aid in diagnosis
pathophysiology of PD
pathological hallmark of PD
synuclein is a neuronal.and glial cell protein that can aggregate into insoluble fibrils and form Lewy bodies.
pathological hallmark of PD: synuclein-filled Lewy bodies in the nigrostriatal system
synuclein can aggreagte in other parts of the body; dorsal motor nucelus of vagus nerve, olfactory bulb (loss of smell early sign), neocortex, sympathetic ganglia (hypotension) and the myenteric plexus.
thought that PD is one of the last steps of lewy body deposition.
rarely PD can occur without synuclein ( mutation in PARK2 gene)
pigmented neurones of the substantia nigra degenerate resulting in loss of dopamine in the dorsal aspect of the putamen
PD and vision
dopamine is an important NT in the retina particularly in amacrine cells along the inner border of the inner nuclear layer and also is accumulated by inter-plexiform cells – it has involvement in the organisation of ganglion cells and bipolar cell receptive fields and may modulate the activity of the photoreceptors, as well as interfering with the visual cortex processing.
- difficulty moving eyes
- nystagmus
- blurred vision
- double vision
impulsive episodes in PD
pathophysiolgy
related to medications- dopamine agonists e.g., mirapexin and deep brain stimuilation
hypersexuality, gambling etc.
pathophysiology- dopamine receptors type 3 are expressed in the ventral striatum (major input into basal ganglia) and are linked to reward processing – dopamine agonists are known to overstimulate the D3-mediated reward circuits and excessively disinhibit the D2 mediated indirect pathway
differential diagnoses of PD
essential tremor
drug induced pd- antipsychotic medication eg., skizophrenia
vascualr parkinsonism caused by multiple strokes
multiple sclerosis
lesion to the corticospinal tract
differences between PD nad essential tremor
PD does not affect the voice box
PD is felt more at rest
essential tremor’s symptoms get progressively worse but don’t shorten life
what is a DaTSCAN
how would PD appear on it
Radioactive tracer, Ioflupane123I (DaTSCAN) is injected into the blood. It then circulates around the body and makes its way to the brain.
It is a specific type of single-photo emission computed tomography (SPECT) imaging.
Ioflupane Is used to help diagnose abnormalities in the brain and belongs to the group of medicines, radiopharmaceuticals which contain a small amount of radioactivity.
Binds to the dopamine transporter which is found on dopamine neurones.
It shows up on a scan after several hours and is used to visualise the number of dopaminergic neurones in the substantia nigra.
Any neuronal degeneration will show up as a significantly reduced number of DAT.
People with PD will typically have a smaller signal in the striatum, where the ends of the dopamine neurones are located – decrease in uptake of the radiotracer in the neostriatum.
DaTSCAN can be used to differentiate between PD and similar conditions such as essential tremor. It may also accurately differential between early PD and secondary parkinsonism and ET but it is not enough to diagnose PD.
distinguishing between Musculoskeletal problems and neurological problems (EMG) - upper vs lower motor neuron lesion results
EMG = Electromyography. Diagnostic procedure that evaluates the health condition of the muscles and the nerve cells that control them (motor neurons).
Possible Results EMG: If EMG shows any electrical activity in resting muscle then may have muscle disorder, disorder affecting nerves that connect to muscle and inflammation caused by injury. If abnormal electrical activity when muscle contracts, then may have herniated disc or nerve disorder.
2 components to EMG test: Nerve conduction study and needle EMG.
- Nerve conduction study – placing small sensory called surface electrodes on skin to assess ability of motor neurons to send electrical signals.
- Needle EMG – Uses sensors to electrical signals 9Needle electrodes) that are directly inserted into muscle tissue to evaluate muscle activity at rest and when contracted.
When done together, they help to tell if symptoms are caused by muscle disorder or nerve problem. You may need these when you have muscle weakness tinging or numbness in limbs, muscle cramps, spasms and/or twitching and paralysis of any muscle.
differentiating between upper motor neurone and lower motor neurone
EMG – Diagnose LMN and disorders muscle + peripheral nerves. The electrical activity in muscle is tirggered by LMN.
what is a multicompliance aid
AKA MCCA (multi-compartment compliance aid) – device designed to contain individual doses of multiple medications, organised into compartments or blisters per day.
electrode implants for PD
used to produce DBS (deep brain stimulation)
delivers electrical current via a thin wire into the basal ganglia, which allows the patient to exert more effective control over the symptoms of Parkinson’s they experience.
stimulation given to the brain only when it is needed
Electrode is inserted into the basal ganglia under MRI guidance. IPG (impulse generator, AKA battery) is implanted within subclavicular region
Particularly useful for patients who have seen a plateau or decrease in effectiveness of levodopa medications.
However, does not influence speech or swallowing issues, cognitive flow or freezing of gait
duopa for PD
alternative surgical option
A tube is inserted into the jejunum to allow levodopa to be drip-fed in a gel form over 16 hours, which reduces risk of doses being missed.
Stoma will have to be inserted – increased risk of infection as patients may struggle to care for this
treatment options for PD
carbidopa/ levodopa
amantadine
MAO type b inhibitors
catechol0-methyltransferase inhibitors
surgery if drugs don’t work
exercise and adaptive measures
co-careldopa
dopaminergic medicine
mixture of cardopa and levodopa
clinical use:
Used for symptomatic treatment of parkinsonian syndrome e.g. parkinsonism, idiopathic Parkinson disease
Provides symptomatic relief of akinesia, rigidity, tremor and improves functional ability
MOA:
- Levodopa is a dopamine precursor which crosses the blood brain barrier before being converted into dopamine in the body and therefore helps to restore dopamine levels in the damaged area of the brain
- Carbidopa is a peripheral DOPA-decarboxylase inhibitor which prevents levodopa from being broken down into dopamine in other parts of the body other than the brain this prevents symptoms like emesis
side effects:
loss of appetite
diarrhoea
effectiveness decreases over time. strategy is to adust dosage of levodopa or adding adjunctive antiparkinsonian agents
what are the basal ganglia
function
consists of 5 pairs of nuclei (neurones):
- caudate nucleus (tucked under lateral ventricle)
- putamen (makes up the striatum w caudate)
- globus pallidus (internal and external aspects)
- subthalamic nucleus
- subtsantia nigra
Fine-tune the voluntary movements by receiving the impulses from the cerebral cortex. The basal ganglia convey their instructions to the thalamus and then back to the cortex.
These fine tuned movements are sent via thr corticospinal tract to synapse with the cranial nerve nuclei and the motor neurons of the spinal cord. Therefore important to know if lesion here or basal ganglia.
The basal ganglia also mediated some higher cortical functions such as planning and modulation of movement, memory, eye movements and reward processing
motor function of basal ganglia: direct pathway
resting state: no movement
The thalamus always wants to go ‘go’ and start movement but the globus pallidus internal and the substantia nigra pars reticula are set to inhibit the thalamus through GABA to prevent the initiation of the movement.
when you want to move
cortex sends messages to your striatum (caudate nucleus and putamen) through glutamate to excitate the striatum to send off inhibitory signals to the globus pallidus internal and substantia nigra pars reticula by ways of GABA to turn off the inhibition on the thalamus to allow the go to ‘go’
motor function: indirect pathway
STOP
- the cortex send excitatory signals to the striatum, activating its inhibitory function.
- these inhibitory neurones from the striatum deactivate the globus pallidus ext.
- the globus pallidus can then no longer inhibit the subthalamus, stopping its excitation of the glob pallidus interna and substantia nigra pars reticula which inhibit the thalamus from initiating movement.
- the thalamus is stopped from going go via GABA from the substantia nigra pars reticulum and the globus pallidus interna.
- This inhibitory action by the SNPR and GPI is activated by the SN sending glutamate.
- The SN is activated by glutamate from the cortex and is no longer inhibited by the GABA from the GPE.
- The GPE’s inhibitory effect on the SN is inhibited when the striatum is activated by the cortex
role of dopamine in brain
direct and indirect pathway + pleasure
dopamine is a monoamine catecholamine NT
- dopamine neurones are concentrated in the Substantia nigra and ventral tegmental area, hypothalamus, olfactory bulb and retina
- the largest dopamine pathway is the nigrostriatal pathway (SN–>Stria) which increases the initation of movement
- dopamine receptors are GPCR’s
- dopamine transporters remove dopamine from the synaptic cleft
functions: movement, reward, memory, lactation, sleep regulation, motivation
Depending which receptor it binds to, DA can be excitatory or inhibitory
D1= excitatory direct D2= inhibitory indirect
direct: you want to go from walking to running. Direct pathway kicks in. Substantia nigra sends of dopamine signals to the striatum, more inhibition of GPI, lets thalamus run wild. if you lose dopamine, this extra muscle excitation is lost.
indirect: you want to go from running to walking. substantia nigra finetunes this, prevents you from drastically stopping on spot. lose dopamine, less striatum activation, movement turned out too much
dopamine regulates pleasure in the brain
mesocorticolimbic pathway ( ventral tegmental area prefrontal cortex nucleus accumbens)
more dopamine more pleasure
reveiw anatomy of cerebellum
types of tremor
Essential tremor
Dystonic tremor
Cerebellar tremor
Parkinsonian tremor
physiological
Essential tremor- appears on both sides of the body and is an action tremor.
Dystonic tremor – caused by dystonia (a movement disorder where incorrect messages from the brain cause muscle to be overactive which results in unwanted movements
Cerebellar tremor – slow, high-amplitude tremor of the extremities that occurs at the end of a postural movement (such as trying to press a button)
Parkinsonian tremor – shaking in one or both hands at rest. May initially appear in one limb or just one side of the body (can be made worse by stress)
physiological- everyone has on e
difference between parkinson’s disease and parkinsonism
Parkinsonism (also called atypical Parkinson’s or Parkinson’s plus) refers to a group of neurological disorders that cause problems with movement such as tremors, bradykinesia and stiffness.
Parkinson’s disease is a neurodegenerative brain disorder and is used to describe the idiopathic Parkinsonism syndrome.
Symptoms are similar and early on in the disease it can be hard to differentiate parkinsonism from PD.
However, Parkinsonism’s tend to progress more rapidly and present with additional symptoms such as early falling, dementia or hallucinations and typically do not respond or only for a short time to levodopa therapy.
illicit drug use and parkinsons
Drug-induced parkinsonism can be difficult to distinguish from PD – although tremors and postural instability may be less severe.
Usually due to drugs that affect dopamine levels in the brain such as antipsychotics, some CCBs and stimulants like amphetamines and cocaine.
If individual stops taking the drug symptoms usually subside – may take up to 18 months.
Amphetamine-type stimulants share structural features with catecholamine neurotransmitters such as noradrenaline and dopamine, been found to affect dopaminergic transmission & function and induce dopamine depletion.
PD and driving
- you have to let DVLA know
- you might not lose license if you pass tests to prove that you are competent
- GP has no legal duty if they think that you are ok. if they don’t think that you’ve contacted dvla then they are supposed to
- bus pass
difference between compliance and adherence
Compliance is a passive behavior in which a patient is following a list of instructions from the doctor.
Adherence is a more positive, proactive behavior, which results in a lifestyle change by the patient, who must follow a daily regimen such as wearing a prescribed brace.
upcoming changes to PD detection
Soon, mobile phone speech recognition may diagnose Parkinson’s, not necessarily with the user’s permission to run test
Movement disorders also being detected by
touchscreens, wearables
Valuable data for early detection (treatment?)
of neurological symptoms
Mining stored data post-diagnosis could
determine when changes occurred
Could help research into causes of
neurodegenerative conditions- Often
well- advanced at diagnosis
link between alcohol tremor and PD
alcohol withdrawal can casue a tremo– differential diagnosis
differnce between essential tremor and resting trmor
compare MRI, CT and PET
dopamine production
tryptophan –> l-dopa –> dopamine
what is a neuroleptic
Antipsychotics, also known as neuroleptics,
are a class of psychotropic medication primarily used to manage psychosis
can cause parkinsons if made poorly
stigma with PD
brain works quicker than body- seen as slow
masked facial demeanour- seen as dour personality
all of the hidden non visible symptoms
People with Parkinsons not i have parkinsons
speech and language therapists + physios
importance of PD nurses
