PD and BG drug therapy COPY Flashcards
(35 cards)
DISORDERS OF MOVEMENT
i) which two categories can these be placed in?
ii) what can hyperkinetic movements be further classified into?
iii) give three examples of hyperkinetic jerky movement disorders
iv) give two examples of hyperkinetic non jerky movements
v) what type of conditions are hypokinetic? give two examples of these and define them
i) hyper or hypokinetic
ii) hyperkinetic can either be jerky or non jerky
iii) hyperkinetic jerky = tics, chorea and myoclonus
iv) hyperkinetic non jerky = dystonia (abnormal posture) and tremor (oscillating movement)
v) hypokinetic conditions = parkinsonian such as ataxia (disturbance of co-ord) and apraxia (disturbance of planning)
HYPOKINETIC MOVEMENTS
i) what is ataxia? disruption in which area causes this?
ii) what is apraxia? disruption in which area causes this?
i) ataxia is disrupted co-ordination = cerebellar disruption
ii) apraxia is disruption in planning therefore disturbance between sensory and motor cortex
BALLISMUS/HEMIBALLISMUS
i) what is seen in ballismus? how does this differ from hemiballismus
ii) what is seen in hemiballismus and what is the most common cause?
iii) in HB what goes wrong in relation to basal ganglia pathways? which pathway is favoured?
iv) explain how this manifests if there is a lesion in the subthalamic nucleus
i) ballismus = high amplitude flailing of limbs and large amplitude PROXIMAL movement of limbs - differs from hemiball as affects both sides of the body and HB only affects one side
ii) hemiballismus = jerky hyperkinetic movements and negative symptoms such as numbness that affect one side of the body
iii) HB = disrupted balance between direct and indirect pathway - the direct pathway is favoured
iv) lesion in the STN will decrease excitation in the GPi therefore the GPi will cause less inhibition on the thalamus and this increases movement
what kind of movement disorder may this cause?
will the abnormal movement be on the same or contralateral side to the lesion?
will this cause positive or negative symptoms?
stroke causes hemiballismus
movement disorder will be on the contralateral side to the lesion
causes negative symptoms such as numbness
TIC DISORDERS
i) what are they?
ii) give an example of a simple or complex associated actions
iii) what other symptom may they be associated with? is this common?
iv) what may make it worse?
v) what makes it better? what does this imply?
vi) name a condition that on the more severe end of the spectrum of tic disorders
i) brief repetitive stereotyped movements with premonitionary urge (eg feel urge to sneeze) plus a motor disorder
ii) simple = blinking or coughing
complex = jumping or twirling
iii) may also be associated with swearing (coprolalia) but this is rare
iv) anxiety or fatigue makes it worse
v) distraction and concentration makes it better - this implies that is not completely under voluntary control
vi) more severe condition = tourettes
CAUSES OF TIC DISORDERS
i) what % of people have ADHD, OCD and anxiety
ii) which basal ganglia loops may be dysfunctioning if the tic disorder is associated with OCD or ADHD?
iii) is more likely due to genes or environment?
iv) after which event may it occur? explain
i) 50% have ADHD, 33% OCD and 50% anxiety
ii) dysfunction in limbic or prefrontal basal ganglia loops may be associated with ADHD or OCD
iii) due to a mix of genes and the environment
iv) may occur after an infection due to molecular mimickry - antibodies are made against neurons
CHOREA
i) what is it?
ii) are the proximal or distal limbs affected?
iii) how will the patient appear?
iv) what will happen if you ask the patient to hold their tongue out? what does this demonstrate?
v) what are the two most common causes? explain why
vi) how will a lesion in the STN cause this? what BG pathway is favoured?
i) jerky, brief, irregulat contractions that are not repetitive or rhymic but flow from one muscle to the next
ii) affects distal limbs - writhing movement
iii) patient will appear fidgety and restless (dance like movment)
iv) ask patient to hold tongue out - cant do it = motor impersistence
v) two most common causes are degerative (HD) or drugs (neuroleptics - DA agonists)
vi) lesion in STN will cause decrease GPi excitation which decreases thalamic inhibition which increases movement - favours the direct pathway
HUNTINGTONS DISEASE GENETICS
i) what is the genetic cause?
ii) is it autosomal dominant or recessive?
iii) is there complete penetrance?
iv) what is anticipation?
v) how does the length of the number of repeats affect disease onset?
vi) how does the repeat sequence change as you go down generations?
i) trinucleotide repeat on chromosome 4
ii) auto dominant
iii) complete penetrance (anyone who carries the gene will express the pheno)
iv) anticipation = the number of repeats increases with generations
v) increase in number of repeats with each generation will cause earlier onset and more severe disease
vi) as you go down generations the repeat sequence tends to enlarge
HUNTINGTONS CLINICAL PRESENTATIONS
give examples of
i) cognitive
ii) behavioural
iii) physical
symptoms
iv) what type of movement disorder is HD? how is this characterised?
v) what is dyskinesia?
vi) which medical team are often required to intervene?
i) cognitive = inability to make decisions or multitask and general slowness of though
ii) behavioural = irritability, depression, apathy, anxiety and delusions
iii) physical = chorea, motor persistence, dystonia, abnormal eye movements due to oculomotor BG loop disruption
iv) HD = chorea (dance like movements) which is characterised by overactive DA
v) dyskinesia is involuntary muscle movements
vi) often requires neuropsychiatry
MYOCLONUS
i) what is the main thing that characterises this?
ii) is it a brief or prolonged movement?
iii) are movements positive or negative?
iv) what will be seen if you ask the patient to lift their hands?
v) what is the possible pathophysiology?
vi) which system is probably affected?
i) jerk
ii) brief movement with rapid onset and offset
iii) movements are both positive (muscle contraction) and negative (muscle inhibitions)
iv) ask patients to lift hands and they will just lose tone
v) possible pathophysiology is an imbalance between excitatory and inhibitory NTs (explains why it can be treated with anti-epileptics)
vi) probably affects the motor control system at multiple levels
CAUSES OF MYOCLONUS
what are the three main causes of myoclonus? what are each of these associated with?
1) juvenile myoclonic epilepsy = early morning jerks
2) brain hypoxia = post cardiac arrest
3) prion disease = cardinal feature is a myoclonic jerk
DYSTONIA
i) what type of movement disorder is this?
ii) what postures are characteristic of dystonia?
iii) what disease is this a feature of?
iv) name three brain areas that may be disrupted in dystonia
v) give five possible causes
vi) blocking of which receptors may cause dystonia? which drug do som dystonias respond to?
i) hyperkinetic non jerky
ii) abnormal twisting, tremor, arm held in flexed position
iii) feature of huntingtons disease
iv) may be due to disruption in motor cortex, supplementary motor areas, cerebellum and basal ganglia
v) possible causes = stroke, brain injury, encephalitis, PD and HD
vi) blocking DA receptors can cause dystonia and some can be LDOPA response (suggests DA pathway plays a part)
TREMOR
i) what kind of movement disorder is this?
ii) give three types based on the moment of occurence
iii) what is the most common type of tremor? what does this particularly affect?
iv) how can this type of tremor be tested?
i) hyperkinetic non jerky
ii) rest, postural or kinetic
iii) most common type is essential tremor = simple kinetic and only really affects the hands
iv) essential tremor can be tested by the finger to nose test
PATHOPHYS OF TREMOR
i) what is the postulated theory?
ii) what causes tremor in PD in relation to NTs/brain area?
iii) dysfunction of which NT/brain area is involved in essential tremor?
iv) how are circuits between flexors and extensors affected?
i) suggested theory is increased activity in the cerebellothalamocortical circuit
ii) tremor in PD due to DA dysfunction in the globus pallidus
iii) essential tremor - due to GABA dysfunction in the cerebellum
iv) oscillating circuits between flexors and extensors are normally dampened
what is a new treatment for essential tremor?
how does this work?
why is it good?
what would previously have been used?
MRI focused ultrasound therpay
works by firing US beams into the head while circulating cooling water to prevent burning - ablates a specific brain area
good because it is non invasive
may have previously done deep brain stimulation
DRUG TREATMENT FOR HYPERKINETIC MOVEMENT DISORDERS
i) which pathway predominates in these disorders?
ii) give three examples of these disorders
iii) what type of agent may be used to treat? give four examples of these drugs
iv) give two other types of agents that may be used to treat and give an example of each
v) give two acute/sub acute/long term problems that these agents may cause
i) the direct pathway predominates
ii) myoclonus, tics, chorea
iii) DA receptor blockers (typical APs) such as haloperidol, chlorpromazine, pimozide and risperidone (EP SEs)
iv) other agents are DA depeleting agents such as tetrabenazine and atypical anti psychotics such as clozapine
v) acute = oculogyric crisis and neuroleptic malignant syndrome
- sub acute (wks and months) = parkinsonism
- long term (months/years) = tardive dyskinesias
ACUTE PROBLEMS FROM DA BLOCKING AGENTS
i) name two acute problems due to DA blockers
ii) how quickly do each of these develop?
iii) how are these characterised?
i) ocuclogyric crisis and neuroleptic malignant syndrome
ii) both start hours to days after treatment
iii) oculogyric crisis - fixed stare, upward dev of eyes, neck/trunk extension, jaw spasm, dystonia
NMS - rigidity/muscle breakdown (raised creat phosphokinase) , fever, autonomic instability (BP and pulse are volatile), confusion
what side effect of DA blockers is this posture characteristic of?
oculogyric crisis
TARDIVE DYSKINESIA
i) define
ii) when may this be seen?
iii) why is this seen?
iv) give three postures that may be observed
v) how is this treated?
vi) movements seen are similar to what other condition?
i) stiff jerky movements of face that cant be controlled, excessive movement
ii) may be seen when taking anti psychotics
iii) seen due to supersensitivity of DA receptors (DA receptors are shut down to they upregulate)
iv) face/mouth movement, dystonic trunk, excess movement
v) treat by gradually withdrawing the offending agent then sub with an atypical AP or DA depleting agent/benzo
vi) movements are similar to those seen in HD
name three jerky hyperkinetic movement disorders
name two non jerky movement disorders
jerky - myclonus, tic, chorea, ballisumus
non jerky - tremor and dystonia
HYPOKINETIC MOVEMENT DISORDERS
i) what is the umbrella term used for the symptoms seen?
ii) name the triad of symptoms. which one of these must be seen to have a hypokinetic disorder?
iii) what is akinesia?
iv) name two physical signs and give examples of each
i) parkinsonism - conditions that can mimic PD (akinetic rigid movement)
ii) bradykinesia, rigidity and tremor
- bradykinesia must be present to have a hypokinetic disorder
iii) akinesia is difficulty initating voluntary movement
iv) slowness and poverty of movement (loss of facial expression and arm swing)
KEY FEATURES OF HYPOKINETIC MOVEMENT DISORDERS
i) name the three key features
ii) which one must be present for a diagnosis?
iii) explain how to test each feature
i) bradykinesia, rigidity and tremor
ii) must have bradykinesia for a diagnosis
iii) bradykinesia - get patient to tap hand and the tap will get slower and smaller over time
rigidity - move arm and you will feel the rigidity
tremor - sit patient down and ask them to close eyes and count from 20-1 (see tremor)
NON MOTOR SYMPTOMS - HYPOKINETIC DISORDERS
i) how are non motor symptoms explained?
ii) give five non motor symptoms
iii) do these occur before or after motor symptoms?
i) explained by different loops travelling through the basal ganglia eg oculomotor and limbic loop
ii) depressed mood, dementia, postural hypertension, hypersalivation (autonomic involvement), sleep disturbance, reduced sense of smell
iii) these occur before motor symptoms
PARKINSONS DISEASE PATHOPHYSIOLOGY
i) what causes reduced movement in relation to BG pathways?
ii) where are DA neurons lost? which BG pathways does this affect?
iii) what will lack of dopamine cause from the striatum onwards? what does this result in?
i) reduced activation of the directt pathway and increased activation of the indirect pathway
ii) DA neurons are lost between the striatum and the substantia nigra
iii) lack of DA causes the striatum to have less inhibition on GPe
- GPe activates the STN
- STN activates GPi which inhibits the thalamus
- Increased thalamic inhibition causes reduced movements
