Neuro Flashcards
Definition of Parkinson’s
Progressive neurodegenerative condition cuased by degeneration of dopaminergic neruons in the substantia nigra
Where is the substantia nigra loacted?
It is a part of the basal ganglia
Main function of basal ganglia?
Motor control
What is the badsal ganglia?
Group of subcortical nuclei responsible for motor learning, executive function, behaviours and emotions
What is required for the functioning of input nuclei?
Dopamine to be released at the input nuclei
-When there is a dopamine dysfunction it can lead to movement disorders such as parkinson’s
What is the role of the substantia nigra?
Produces dopamine
-This controls muscle tone and movement
-It also plays a role in cognitive executive functions, emotional limbic activity and addiction
What happens to the substantia nigra in parkinson disease?
Neurons degenerate leading to loss of dopamine
What is the triad of features of parkinson disease ?
-Bradykinesia
-Tremor
-Rigidity
What is bradykineasia?
-Slowness of movement and speed (can also present as hesitation/halts when movements are continued)
-NOTE - movements also get smaller
What must you have to be considered to have Parkinson’s?
Bradykinesia plus either tremor or rigidity
How does bradykinesia present in someone with Parkinsons?
-Poverty of movement (hypokineasia)
-Short, shuffling steps with reduced arm swing
-Difficulty in initiating movement
Signs of bradykinesia?
-Not crossing arms and legs
-Blinking less often
-Not swinging arms when walking
-Difficulty standing up or rolling over in bed
-Freezing or pausing while moving
-Having trouble clapping hands or tapping finger
Tremor in parkinson’s disease?
-More prominent at rest, usually improves with voluntary movement
-Worse when stressed and tired
-Pill rolling tremor between thumb and index finger
-4-6 herts
Define lead pipe rigidity
Constant resistance to motion throughout the entire range of movement
Define cogwheel rigidity
Resistance that stops and starts as the limb is moved through a range of movement
-This is due to lead-pipe rigidity with tremor
-Due to superimposed tremor
Spascity
-Is a hypertonic state
-Velocity dependent
-Asymmetric
-Muscle movement are restricted in only one specific direction
Why does spasticity arise?
Due to damage of cortico reticulospinal tracts
Why does rigidity arise?
Due to dysfunction of extrapyramidal pathways
What is a festinating gait?
Rapid frequency of steps to compensate for small steps and avoid falling - this is a sign of bradykinesia
Other ways bradykinesia can manifest
-Shuffling gait
-Festinating gait
-Difficulty initiating movement
-Reduced facial movement (hypomimia)
-Small handwriting (microgrpahia)
-Flexed like posture
Other features of parkinson
-Flexed posture (postural instability) - cause falls
-Depression (40%)
-Sleep disturbances and insomnia
-Cognitive impairment and memory problems
-Fatigue
-Autonomic dysfunction (postural hypotension)
-Drooling
-Anosmia
How can you make tremor more pronounced when examining a patient with parkinson’s?
Ge the patient to do a paintbrush motion with the other hand
How does drug induced parkinsonism present?
-Rapid onset and bilateral motor symptoms
-Rigidity and rest tremors are uncommon
What drugs can cause drug induced parkinsonism?
Antipsychotics and antiemetics - they work by blocking dopamine receptors
What are the antiemetics that can cause drug induced parkinsonism?
Metoclopramide and prochlorperazine
What is an antiemetic that can be used in patients with parkinson’s?
Domperidone - does not affect the basal ganglia it selectively blocks receptors in the gut and chemoreceptor trigger zone
-Does not cross blood brain barrier
How is parkinson’s disease diagnosed?
-Diagnosed clinically but if there is difficulty in distinguishing between essential tremor and parkinson’s NICE recommend I-FP–CIT SPECT
What criteria to NICE recommend for clinical diagnosis of parkinson’s?
UK Parkinons Disease Society Brain Bank Clincal Diagnostic Criteria
What is the aim of management in Parkisnons disease?
Controlling symptoms and minimising side effects
First line treatment if motor symptoms are affecting patients quality of life?
Levodopa
Mechanism of action of levodopa?
Levodopa is a precursor to dopamine that crosses the blood brain barrier and is then converted to dopamine (by decarboxylation) (DOPA decarboxylase)
What is levodopa normally given with?
Peripheral decarboxylase inhibitors
-These inhibit
Why are peripheral decarboxylase inhibitors given with Levodopa?
It stops the levodopa being converted into dopamine in peripheral tissues this is important for 2 reasons
1. Dopamine cannot cross BBB, so will not reach the brain and be effective
2. Peripheral dopamine can cause side effects
3. Allows a lower dose of levodopa to be used
What do enzyme do peripheral decarboxylase inhibitors block?
Peripheral DOPA decarboxylase
What is a hallmark feature of Parkinson’s disease that causes degeneration of dopaminergic neurons?
alpha-synuclein aggregation - form lumps called lewy bodies
What are the neurons damaged in parkinsons?
-the primary damage is to dopaminergic neurons in substantia nigra
-As disease progresses more neurons can be impacted such as noraadrenergic (hypotension) , cholinergic (dementia), serotonrgic neurons (depression), autonomic (constipation, urinary dysfunction, sexual dysfunction and temperature)
NOTE: accumulation of alpha-synuclein in other parts brain such as cortex and limbic system lead to other problems
How does levodopa work even when dopamine neurons are depleted?
- There are residual dopaminergic neurons
- Non-dopaminergic cam convert levodopa
This is why as disease progresses and there are less dopaminergic neurones the effectivness of levodopa decreases
Give the names of peripheral decarboxylase inhibitors
- Carbidopa
- Benserazide
Combination drugs with levodopa and peripheral decarboxylas einhibtors?
-Co-beneldopa (levodopa and benserazide) MADOPA
-Co-careldopa (levodopa and carbidopa) SINEMET
What enzymes metabolise doapamine?
-Monoamine oxidase (MAO)
-Catechol-O-methyltransferase (COMT)
What is the main side effect of levodopa?
Dyskinesia - this is abnormal movements due to excessive motor activity
Give examples of dyskinesia
-Dystonia - excessive muscle contraction leadign to abnormal posture
-Chorea - involuntary movements that can be jerking and random
-Athetosis -involuntary twisting or writhing movments usually of fingers, hands or feet
What other disoers that can occur due to levodopa?
Impulse control disorders
What medication can be used to manage dyskinesia associated with levodopa?
Amantadine
What is the first line treatment of Parkinson’s disease if motor symptoms are not affecting the patient’s quality of life?
-Dopamine agonists, levodopa or monoamine oxidase B (MAO-B) inhibitor
How do dopamine agonists work?
They mimic dopamine stimulating dopamine receptors
What are the types of dopamine agonists?
-Ergot derived (from ergot fungus) and non ergot derived
Examples of dopamine agonists
-Bromocriptine (ergot)
-Cabergoline (ergot)
-Apomorphine
-Pergolide
What is a notable effect of prolonged use of ergot dopamine agonists?
Pulmonary fibrosis
How do monoamine oxidase B inhibitors work in the treatment of parkinson’s disease?
They inhibit MAO-BH which is the enzyme that degrades monoamines including dopamine, this increases the availability of dopamine within the brain
What is typical use of dopamine agonists ?
Delay levodopa treatment and use in combination with levodopa
Side effects of dopamine agonists?
Nausease, dizziness, hallucinations, sleep disturbances, impulse control disorders
What other neurotransmitters does monoamine oxidase enzymes break down?
Serotonin and adrenaline however MAO-B is more specific to dopamine
Examples of monoamine oxidase inhibitors ?
Selegiline
Rasagiline
When do NICE recommend adding dopamine agonist, MAO-B inhibitor or COMT inhibitor as an adjunct in parkinson’s disease?
If symptoms continue despite optimal levodopa use or patient has developed dyskinesia
What are the common adverse effects with levodopa?
-Dry mouth
-Anorexia
-Palpitations
-Postural hypotension
-Psychosis
Describe on and off period
-On is when medications are acting and patient is moving freely
-Off is when medications wear off
How does COMT inhibitor work in treatment of parkinson’s disease?
COMT is an enzyme involved in breakdown of dopamine COMT inhibitors slow the breakdown of levodopa in the brain extending the effective duration of levodopa
Example of COMT inhibitor
Entacapone
When are antimuscarinics used in parkinsons?
These are more helpful in drug-induced parkinsonism
-Help tremor and rigidity
-Block cholinergic receptors
What are patients at risk of if medication used to treat PD is not taken in/absorbed?
Acute akinesia or neuroleptic malignant syndrome
Name four kinds of parkinson plus syndromes?
1.Multiple system atrophy
2. Dementia with Lewy body
3. Progressive supranuclear palsy
4. Corticobasal degeneration
Describe multiple system atrophy
-Parkinson plus syndrome
-Various neurons in the brain degenerate
-Degeneration of neurons in the basal ganglia leads to parkinson’s symptoms
-Degeneration in other areas leads to autonomic dysfunction and cerebellar dysfunction
Name signs that are more specific to cerebellar dysfunction
1.Ataxia
2.Dysmetria
3. Intention tremor
4. Dysdiadochokineasia
5. Nystagmus (horizontal)
6. Rebound phenomenon
7. Pendulkar reflexes
8. Wide based staggerign gait
Define ataxia
Cerebellar dysfunction involving uncoordinated movement - drunken or clumsyt appearance
Define dysmetria
-Control range of movements
-May overshoot (hypermetria) or undershoot (hypometria) when reaching for an object
How does an intention tremor differ to other types of tremors ?
Worse with purposeful movements and worsens when hand or limb approaches target
Define dysdiachokinesia
The ability to perform rapid alternating movements - specific motor sign of cerebellar dysfunction
How is nystagmus in cerebellar dysfunction different to other kinds of nystagmus?
Horizontal more common and occurs when the eye moves away from central line of site
Describe pendular reflexes
Instead of a single reflexive movement in cerebellar dysfunction there can be multiple oscillation or “pendulum-like movements after a reflex is triggered)
What are the symptoms associated with dementia with lewy bodies?
-Visual hallucination
-Delusions
-Rem sleep
-Fluctuating consciousness
Progressive supranuclear palsy vs parkinsons disease?
-Parkinson’s symptoms but more symmetrical and postural instability
-Ocular symptoms also occur (brainstem)
-Dementia
Define apraxia
Neurological disorder characterised by the inability to perform learned purposeful movements or tasks
Why does apraxia occur?
Due to damage of areas of the brain that are involved in planning and executing movements - left parietal lobe and frontal lobe
Corticobasal degeneration vs PD?
-Impacts cortex and basal ganglia
-Apraxia and alien limb (dystonia)
What medication can be considered if sleepiness persists with mediation treatment of PD?
Modafinil however first you should review medication
What should you do if orthostatic hypotenison develops?
Look for causes and midodrine can be considered
Define benign essential tremor
-Common disorder associated with older age
-Often hereditary - autosomal dominant
Where is tremor most notable?
In the hands but can cause head tremor (titubation), jaw tremor and vocal tremor
Features of BET
-Fine tremor (6-12hz)
-Symmetricla
-More prominent with voluntary movement
-Worse when stressed, tired or after caffeine
-Improved with alcohol
-Absent in sleep
How is BET diagnosed?
Clinically after excluding other causes such as PD, MS, Huntingtons, hyperthyroidism, fever alcohol withdrawal, caffeien, drug indcued
How is BET managed?
-Can manage symptoms using propranolol
-Primidone can be used
What is a common consequence of subarachnoid haemorrhage?
syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Myasthe
