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 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
