5- Neurology (Less acute- Parkinsons, Essential tremor and Multiple Sclerosis) Flashcards
Parkinsons background
Condition where there is a progressive reduction of dopamine in the basal ganglia, leading to disorders of movement
NOT RELATED TO THE CEREBELLUM
Parkinsons Pathophysiology
- Basal ganglia are a group of structures of the brain responsible for coordinating habitual movements such as walking or looking around, controlling voluntary movements and learning specific movement patterns
- The substantia nigra (part of the basal ganglia) produces dopamine
- Dopamine is essential for correct functioning of the basal ganglia
- In Parkinson’s there is a progressive fall in dopamine
Why is Parkinsons asymmetrical?
the initial pathology starts in one hemisphere and initially damages that hemisphere via the predominantly same-sided connections, leading to marked asymmetry
May be symmetrical if drug induce Parkinsons
Related syndromes i.e. Parkinson’s-plus syndromes
- Multiple system atrophy
- Dementia with lewy body
- Progressive supranuclear palsy
- Corticobasal degeneration
Causes/ risk factors for parkinsons
- Advancing age
- Male
presentation of parkinsons : key triad
involves bradykinesia plus at least one of; rigidity, tremor or postural instability
Characteristically asymmetrical triad
- Resting tremor (low frequency- pill rolling)
- Rigidity
- Bradykinesia
other presentations of parkinsons
Others
- Facial masking
- Stooped posture
- Forward tilt
- Reduced arm swing
- Shuffling gait
- Cogwheel rigidity
- Lead pipe
More
- Depression
- Sleep disturbance and insomnia
- Loss of smell – anosmia
- Postural instability
- Cognitive impairment and memory problem
investigations for parkinsons
- Clinical diagnosis
Rhomberg test and parkinsons
If Parkinson’s should not fall over due to not having a problem with vision or proprioception -> wide base
for sensory ataxia e.g. peripheral neuropathy
e.g. if you tell someone to close their eye who has peripheral neuropathy you have taken away 2/3 contributors of balance (vision and proprioception) -> will fall over
unilateral tremor
The tremor in Parkinsons has a frequency of 4-6 Hz, meaning it occurs 4-6 times a second.
- This is described as a “pill rolling tremor” because it looks like they are rolling a pill between their fingertips and thumb.
- It is more pronounced when resting and improves on voluntary movement.
- The tremor is worsened if the patient is distracted. Asking them to do a task with the other hand, such as miming the motion of painting a fence, can exaggerate the tremor.
“Cogwheel” Rigidity
- Rigidity is a resistance to passive movement of a joint.
- If you take their hand and passively flex and extend their arm at the elbow, you will feel a tension in their arm that gives way to movement in small increments (like little jerks).
- This is what leads to the cog wheel description.
Bradykinesia
Bradykinesia describes how their movements get slower and smaller. This presents in a number of ways:
- Their handwriting gets smaller and smaller (this is a classic presenting complaint in exams)
- They can only take small steps when walking (“shuffling gait”)
- They have difficulty initiating movement (e.g. from standing still to walking)
- They have difficulty in turning around when standing, having to take lots of little steps
- They have reduced facial movements and facial expressions (hypomimia)
parkinsons Pathophysiology
When thinking about Parkinsons disease in relation to the basal ganglia circuit start at the Substantia nigra
Parkinsons is caused by a decrease in dopamine
Normal dopamine action on the basal ganglia pathway
Dopamine excites the direct pathway (harbours D1 receptors) and inhibits indirect (harbours D2 receptors) pathway
1) Dopamine is stimulatory to the direct pathway via the D1 receptors
- Increase inhibition to Globus pallidus internus
- Decreasing GPi inhibition to the thalamus
- Overall increasing thalamus stimulation of the cortex
2) Dopamine is inhibitory to the indirect pathway via the D2 receptors
- Inhibition of inhibitory pathway
- Increase level of activity in the cortex
Hence overall excitation
Parkinson’s disease- loss of dopamine
- Therefore if we take dopamine away
- We get decreased cortex activity
Parkinson’s disease (decreased movement)
- Degeneration of dopaminergic neurones present in substantia nigra
- If we remove dopamine provided by the SN, then we lose net excitation on the cortex (dopamine stimulates direct pathway (which increases movement)and inhibits indirect pathway (which decreases movement))
- Therefore cortical activity decreases- corticospinal pathways aren’t stimulating LMN adequately
o Tremor
o Rigidity- reduction in proper coordination in flexors and extensors
o Bradykinesia- most easily explained by this pathway
o Psychiatric features- cognition circuit interlinked with the basal ganglia circuit
management of parkinsons
Aim: manage symptoms and minimise side effects
Patients describe themselves as “on” when the medications are acting and they are moving freely, and “off” when the medications wear out, they have significant symptoms and their next dose is due.
4 main classes of drugs used to treat Parkinsons
- Levodopa
- COMT inhibitors
- Dopamine agonists
- Monoamine Oxidase-B inhibitors
Levodopa
- Synthetic dopamine given orally to boost dopamine levels
- Usually given with carbidopa or benserazide (peripheral decarboxylase inhibitors) – which prevent levodopa being broken down before they cross the BBB. Therefore given as combination drugs
o Co-benyldopa (levodopa and benserazide)
o Co-careldopa (levodopa and carbidopa)
positives of levodopa
most effective treatment for symptoms
negatives of levodopa
- becomes less effective over time- therefore often reserved when other treatments are not working for symptom control
- patients develop dyskinesia
o dystonia- excessive muscle contraction
o chorea- jerking
o athetosis- involuntary twisting or writhing movements in the fingers, hands or feet
COMT inhibitors
- inhibitors of catechol-o-methyltransferase (COMT)
- COMT enzymes metabolise levodopa in the body and brain
- E.g. Entacapone -> usually taken with levodopa (and decarboxylase inhibitor e.g. carbidopa)
- Positive: extends effective duration of levodopa
Dopamine agonists
- Mimic dopamine in the basal ganglia, stimulating dopamine receptors
- Less effective than levodopa in reducing symptoms
- E.g. Bromocryptine, Cabergoline
- Role
o Used to delay use of levodopa
o Then use din combination to reduce dose of levodopa
Negatives
- Pulmonary fibrosis
Monoamine Oxidase-B Inhibitors
- Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline.
o The monoamine oxidase-B enzyme is more specific to dopamine and does not act on serotonin or adrenalin. - These medications block this enzyme and therefore help increase the circulating dopamine.
- Role
o Similarly to dopamine agonists, they are usually used to delay the use of levodopa and then in combination with levodopa to reduce the required dose. - Examples are:
o Selegiline
o Rasagiline
Optic neuritis and MS
Optic neuritis is the most common presentation of multiple sclerosis. It involves demyelination of the optic nerve and loss of vision in one eye. This is discussed in more detail below.
