PBL Topic 3 Case 7 Flashcards
1
Q
Identify three roles of the cerebellum
A
- Timings of motor activities
- Intensity of muscle contraction
- Interplay between agonist and antagonist muscles
2
Q
Identify the three lobes of the cerebellum
A
- Anterior lobe
- Posterior lobe
- Flocculonodular lobe
3
Q
Where is the vermis located and what is its function?
A
- Longitudinal band in the centre of the cerebellum
- Control for muscle movements of the axial body, neck, shoulders and hips
4
Q
Identify the two zones of the cerebellar hemipsheres and their function
A
- Intermediate zone, control of muscle contractions in hands, fingers, feet and toes
- Lateral zone, planning of sequential movements
5
Q
Describe the topographical representation in the cerebellum
A
- Axial portions of the body lie in the vermis
- Limbs and facial regions lie in the intermediate zones
6
Q
Why does the lateral zone of the cerebellar hemisphere not have topographical representations?
A
- It receives signals directly from the cerebral cortex
- For the planning and co-ordination of sequential muscular activities
7
Q
Describe the course of the corticopontocerebellar pathway
A
- Afferent pathway from motor cortex
- Passes by way of pontocerebellar tracts
- Terminates in lateral divisions of the cerebellar hemispheres
- To the opposite side of the brain
8
Q
Describe the course of the olivocerebellar pathway
A
- Afferent pathway from inferior olive
- Which are excited by fibres from motor cortex, basal ganglia, reticular formation and spinal cord
- Terminates on all parts of the cerebellum
9
Q
Describe the course of the vestibulocerebellar fibres
A
- Afferent pathway from vestibular apparatus and brainstem vestibular nuclei
- Terminate in flocculonodular lobe and fastigial nucleus of the cerebellum
10
Q
Describe the course of the dorsal spinocerebellar tract
A
- From muscle spindles, Golgi tendon organs, tactile receptors through dorsal tracts
- Pass into cerebellum through inferior cerebellar peduncle
- Terminates in vermis and intermediate zones
11
Q
Describe the course of the ventral spinocerebellar tract
A
- From motor signals in the anterior horns
- Through corticospinal and rubrospinal tracts
- Tells cerebellum which signals have arrived at anterior horns and which have not
12
Q
What is the speed of conduction in the spinocerebellar tracts?
A
- 120 m/sec
- Most rapid pathway transmission in any pathway in the CNS
13
Q
Identify two other pathways that relay information to the cerebellum
A
- Spinoreticular pathway
- Spino-olivary pathway
14
Q
Identify the four deep nuclei of the cerebellum
A
- Fastigial nucleus, associated with vestibular apparatus
- Globose nucleus, associated with co-ordination of agonist and antagonist muscles
- Emboliform nucleus, associated with co-ordination of agonist and antagonist muscles
- Dentate nucleus, associated with co-ordination of sequential movements
- Globose and emboliform are known collectively as interposed nuclei
15
Q
Outline the three layers of the cerebellar cortex, where are the deep cerebellar nuclei located relative to these layers?
A
- Molecular layer
- Purkinje layer
- Granule cell layer
- Deep cerebellar nuclei are located deep to these layers
16
Q
Identify the efferent outputs of the cerebellum
A
- Purkinje cell
- Deep nuclear cell
17
Q
Identify the afferent inputs to the cerebellum
A
- Climbing fibres from inferior olives of the medulla, which send signals to deep nuclear cells and then to Purkinje cells
- Mossy fibres from higher brain, brainstem and spinal cord, which synapse with granule cells before sending signals to Purkinje cells
18
Q
Describe the impulse from a climbing fibre
A
- Single strong impulse causes a prolonged action potential followed by several weaker spikes
- Known as a complex spike
19
Q
Describe the impulse from a mossy fibre
A
- Impulse duration is much smaller and action potential is less prolonged
- Known as a simple strike
20
Q
How are deep nuclear cells inhibited and what is the importance of this?
A
- Inhibited by Purkinje cells
- So that an inhibitory signal sis to the output motor pathway
- Damping function stops muscle movement overshooting its mark
21
Q
Identify two other inhibitory cells of the cerebellum and in which cell layer they are located
A
- Basket cells
- Stellate cells
- Molecular layer
- Lateral inhibition
22
Q
What is meant by vestibulocerebellum / archicerebellum?
A
- Flocculonodular lobes and vermis
- Involved in equilibrium and agonist/antagonist muscle contractions
23
Q
What is meant by spinocerebellum / paleocerebellum?
A
- Vermis and intermediate zones
- Involved in coordinating movement in distal limbs
24
Q
What is meant by cerebrocerebellum / pontocerebellum / neocerebellum?
A
- Lateral zones
- Motor imagery, planning of movements in advance to the movement
25
With regards to the vestibulocerebellum, what is meant by anticipatory correction?
- Ability of cerebellum to calculate the rate and direction of movement during next few milliseconds
- Based on signals from periphery
26
How does the spinocerebellum co-ordinate movement in distal limbs?
- Receives from motor cortex red nucleus and peripheral proprioceptors
- Deep nuclear cells of interposed nucleus send signals back to cerebral cortex through relay nuclei in the thalamus and through rubrospinal tract
27
Explain the basis of an intention tremor
- Must movements are pendular and thus have a tendency to overshoot due to momentum
- Cerebellum has a damping system to prevent this overshoot
- Failure of which causes limb to oscillate in opposite directions
28
What is meant by ballistic movements and how is this affected by cerebellar destruction?
- Rapid movements such as typing and reading
- That are preplanned, set in to motion for a specific distance then stop
- Cerebellar destruction results in movements that are slow to develop, weak force, and slow termination of movement
29
Describe how the cerebrocerebellum is involved in planning and timing of sequential movements
- Plan begins in sensory and premotor areas
- Two way signals sent between cerebellum and cerebral cortex
30
What is meant by dysdiadochokinesia?
- Impairment of rapidly alternating hand movement
- Because motor system fails to predict where different parts of the body will be at different times
31
What is meant by dysmetria and ataxia?
- Overshoot of movements over intended mark and subsequent overcompensation (dysmetria) resulting in uncoordinated movements (ataxia)
- Due to lesions in the spinocerebellar tract
32
What is meant by nystagmus?
- Tremor of eyeballs when fixating on one side of head
- Damage of flocculonodular lobes, with subsequent loss of equilibrium
33
What is meant by intention tremor?
- Oscillation of movement caused by overshoot followed by back and forth vibration
34
What is meant by scanning dysarthria?
- Failure of intensity or duration of sound results in jerky, explosive or slurred speech
35
What is meant by hypotonia?
- Decreased tone
- Caused by damage to dentate and interposed nuclei on same side of lesion and subsequent loss of facilitation of the motor cortex
36
Identify three roles of the basal ganglia
- Relative intensities of separate movements
- Directions of movements
- Sequencing of successive movements
37
Identify the different structures of the basal ganglia
- Caudate nucleus and putamen (corpus striatum)
- Putamen and globus pallidus [internal and external] (lentiform nucleus
- Substantia nigra [pars reticulata and pars compacta]
- Subthalamic nucleus
38
What is meant by the direct and indirect pathways of the motor loop of the basal ganglia?
- Direct loop: traverses corpus striatum and thalamus and involves consecutive sets of neurons
- Indirect pathway, traverse subthalamic nucleus and involves seven sets of neurons
39
Which neurotransmitter is involved in projections from cerebral cortex and thalamus?
- Glutaminergic
40
Which neurotransmitter is involved in projections from the striatum and globus pallidus?
- GABAergic
41
What are the two different synapses involved in the nigrostriatal pathway?
- Direct pathway = Facilitatory D1 receptors
- Indirect pathway = Inhibitory D2 receptors
42
Which regions of the basal ganglia are somatotopically organised?
- Putamen
- Globus pallidus
43
Outline the direct pathay
- Excitatory signals from sensorimotor cortex to striatum
- This excites the striatum, which sends inhibitory signals to internal globus pallidus
- This inbhits the internal globus pallidus, which inhibits the inhibitory signals to the thalamus
- Disinhibition of the thalamus results in activation of the supplementary motor area
- Which modifies ongoing corticostriate activity and initiates impulse trains along the corticospinal and corticoreticular fibres.
44
Outline the effect of the nigrostriatal system on the direct pathway
- Excitatory dopamine signals from pars compacta to striatum
- This further excites the striatum
- So causes more disinhibition of the thalamus
- Turning up motor activity
45
Outline the indirect pathway
- Excitatory signals from sensorimotor cortex to striatum
- This excites the striatum, which sends inhibitory signals to external globus pallidus
- This inhibits the external globus pallidus, which inhibits the inhibitory signals to the subthalamic nucleus
- The subthalamic nucleus nucleus now sends excitatory signals to the internal globus pallidus
- Which sends inhibitory signals to the thalamus, inhibiting the signals to the supplementary motor area.
46
Outline the effect of the nigrostriatal system on the indirect pathway
- Inhibitory dopamine signals from pars compacta to striatum
- This inhibits the striatum
- So fewer inhibitory signals are sent to the external globus pallidus
- More inhibition of subthalamic nucleus, so it is unable to send excitatory projections to the globus pallidus internus
- So more excitatory projections to thalamus, so more motor activity.
47
Outline 3 abnormalities of the basal ganglia
- Athetosis, lesion in global pallidus, producing spontaneous and continuous writhing movements of the hand
- Hemiballismus, lesions int he subthalamic nucleus, producing sudden flailing movements of the entire limb
- Chorea, a lesion in the putamen, producing a flicking movement of the hand or face
48
Outline the biosynthesis of acetylcholine
- Choline is acetylated by choline acetyltransferase
- Which transfers the acetyl group from acetyl coenzyme A
49
How is acetylcholine inactivated?
- Hydrolysis by acetylcholinesterase
50
Identify two types of acetylcholine receptors
- Nicotinic ACh receptors (nAChRs)
- Muscarinic ACh receptors (mAChRs)
51
What type of receptors are nAChRs?
- Ligand gated ionotropic channels
52
What type of receptors are mAChRs?
- G-protein coupled receptors
53
Outline three main classes of nAChRs
- Muscle receptors confined to neuromuscular junctions
- Ganglionic receptors
- CNS-type receptors
54
Outline the subtypes of muscarinic receptors
- M1-M5
- Odd numbered are excitatory as they excite inositol phosphate pathway allowing calcium influx and depolarisation
- Even numbered are inhibitory as they inhibit adenylyl cyclase pathway allowing potassium efflux with hyperpolarisation
55
Which muscarinic receptor is the neural type, how does it work?
- M1
- Causes a decrease in k+ conductance which causes membrane depolarisation
56
Where are cholinergic neurons located?
- Nucleus basalis of Meynert
- A forebrain nuclei
57
Which nucleus provides the main cholinergic output to the hippocampus and is involved in memory?
- Septohippocampal nucleus
58
Outline three main functions ascribed to cholinergic pathways with relation to each pathway.
- Arousal (nucleus basal to cortex)
- Memory (septum pellucidum to hippocampus)
- Motor control (cholinergic interneurons in striatum)
59
Where is dopamine most abundant in the brain?
- Corpus striatum
60
Outline the biosynthesis of dopamine
- L-tyrosine is converted to dihydroxyphenylalanine (dopa) by tyrosine hydroxylase
- Dopa is then converted to dopamine by dopa decarboxylase.
61
Why do dopaminergic neurons not convert dopamine to noradrenaline?
- They lack dopamine beta-hydroxylase (DBH)
62
How is dopamine metabolised and what is the clinical significance of the product?
- Uptake into presynaptic neuron or glial cell by DAT
- Monoamine oxidase
- Catechol-o-methyl transferase
- Which produces homovanillic acid (HVA)
- Which is used as an index to dopamine turnover
- Drugs that cause the release of dopamine increase HVA
63
Outline the four main dopaminergic pathways in the brain
- Nigrostriatal pathway
- Mesolimbic pathway
- Mesocortical pathway - Tuberohypophyseal pathway
64
Describe the course of the nigrostriatal pathway and its function
- Cell bodies in substantia nigra
- Whose axons run in medial forebrain bundle
- And terminate in corpus striatum
- Involved in motor control
65
Describe the course of the mesolimbic pathway and its function
- Cell bodies in ventral tegmental area
- Whose axons run in medial forebrain bundle
- To nucleus accumbens and amygdaloid nucleus
- Involved in behaviour
66
Describe the course of the mesocortical pathway and its function
- Cell bodies lie in ventral tegmental area
- Whose axons run in medial forebrain bundle
- To prefrontal cortex
- Involved in behaviour
67
Describe the course of the tuberohypophyseal pathway and its function
- Cell bodies lie in hypothalamus
- To pituitary gland
- Involved in endocrine control
68
Identify the two types of dopamine receptor, what kind of receptor are they?
- D1 and D2
- Which are G-protein transmembrane receptors
69
What is the D1 family?
- Contains D1 and D5
- Excitatory, linked to stimulation of adenylyl cyclase
70
What is the D2 family?
- Contains D2, D3 and D4
- Inhibitory, linked to inhibition of adenylyl cyclase, activation of K+ channels and inhibition of Ca2+ channels
71
Identify a dopamine antagonist
- Chlorpromazine an antipsychotic
72
Why must glutamate be synthesised in neurons from local precursors?
- It does not cross the blood brain barrier
73
Identify two local precursors for the synthesis of glutamate
- From glucose, via Krebs cycle, by action of GABA transaminase
- From glutamine, produced by glial cells, which is converted to glutamate by glutaminase
74
How is glutamate recycled?
- Taken up by astrocytes
- And converted into glutamine
75
Identify the three main subtypes of ionotropic glutamate receptors
- NMDA, involved in slower excitatory responses
- AMPA, involved in fast excitatory responses
- Kainate, involved in fast excitatory responses
76
Identify three special features of NMDA receptors
- Highly permeable to Ca2+ so effective in promoting Ca2+ entry
- Blocked by Mg2+ when polarised
- Activation requires glycine and glutamate
77
Identify the metatropic glutamate receptors
- mGlu1-8
- mGlu1 receptors are excitatory postsynaptic receptors
- mGlu2 and mGlu3 receptors are presynaptic inhibitory receptors
78
Outline the biosynthesis of GABA
- Glutamic acid decarboxylase
- Which converts glutamate to GABA
79
Where is GABA most abundant in the CNS?
- Nigrostriatal system
80
How is GABA taken up and how is it destroyed?
- Taken up by GABAergic neurons and astrocytes via specific transporters
- Destroyed by GABA transaminase, converting it to succinic acid.
81
What percentage of neurons in the CNS are GABAergic?
- 20%
82
Identify the two main types of GABA receptors
- GABAA, ligand gated ion channels, postsynaptic fast inhibition
- GABAB, G-protein coupled receptors, presynaptic and postsynaptic inhibition by blocking Ca2+ and increasing K+ conductance
83
Where is glycine most abundant?
- Spinal cord grey matter
84
Describe the glycine receptor
- Resembles GABAA
- Ligand gated postsynaptic channel that causes fast inhibition
85
What are Lewy bodies and how do they form?
- Intracellular protein aggregates
- Caused by mutation of alpha-synuclein, a vesicular protein
- Which becomes resistant to degradation so builds up within cells
86
How do Lewy bodies result in neurotoxicity
- Vesicular storage of dopamine is impaired
- Leading to an increase in cytosolic dopamine
- Degradation of which produces reactive oxygen species
87
Outline the effect of degradation of nigrostriatal neurons on the striatum
- Loss of facilitation of spiny striatal neurons bearing D1 receptors, disengaging the direct pathway
- Loss of inhibition of D2 receptors, engaging the indirect pathway
88
How does engagement of the indirect pathway result in movement problems?
- Sensorimotor cortex strongly activates GABAergic neurons in striatum which act on external globus pallidus
- Causing disinhibition of subthalamic nucleus
- Which discharges glutamine strongly onto internal globus pallidus
- Which discharges GABA strongly onto ventral nucleus of thalamus
- Reduced output to fibres travelling to supplementary motor area
89
What is bradykinesia, what causes bradykinesia and how does it present?
- Suppression of voluntary movement
- Due to muscle rigidity and inertia of motor system (so motor activity is difficult to stop and start)
- Routine activities such as opening a door require deliberate planning
90
What is the frequency of a resting tremor?
- 3-6 hertz
91
What is the commonest sequence of limb involvement of resting tremor in Parkinson's?
- One upper limb to ipsilateral lower limb in 1 year
- Contralateral limb involvement within 3 years
92
What is a pill-rolling movement?
- Index and middle finger move against thumb pad
93
Why do Parkinson's patients have a stooped posture?
- Rigidity mainly affecting flexors
94
What is meant by lead pipe rigidity?
- Limb is rigid throughout entire range of motion
- Cogwheel sensation
95
What is the first line treatment for Parkinson's?
- Levodopa
- Combined with a decarboxylase inhibitor (co-beneldopa)
96
Why is levodopa combined with a decarboxylase inhibitor?
- Reduces dopamine synthesis in periphery
- Which would cause troublesome side effects
97
Why do patients become tolerant to levodopa?
- Reflects natural progression of the disease
98
Identify the main unwanted effects of levodopa
- Involuntary writhing movements (athetosis)
- Rapid fluctuations in clinical state, reflecting the fluctuating plasma concentration of dopamine
- Hypotension, nausea and schizophrenia-like syndrome
99
Identify two dopamine agonists and their troublesome side effects
- Bromocriptine, inhibits prolactin from anterior pituitary gland, causing nausea, vomiting and somnolence
- Pergolide, believed to cause heart disease
100
Identify two replacements of dopamine agonists
- Non-ergot compounds
- Such as pramipexole and ropinirole - Which are better tolerated
101
What is Selegiline and its advantages?
- Selective MAO-B inhibitor which targets mainly dopamine
- So does not provoke cheese reaction or interact with other drugs
- Protects dopamine from extra neuronal degradation
102
Explain one disadvantage of selegiline and name a similar drug that does not cause these side effects
- Metabolised to amphetamine so can cause excitement, anxiety and insomnia
- Rasagiline
103
What does deep brain stimulation involve in the treatment of Parkinson's?
- Paralysis of subthalamic nucleus (inhibiting internal globus pallidus causing disinhibition of the thalamus)
104
What is Complementary and Alternative Medicine?
- Therapies and interventions that are
- Non standard
- Non prescription
- Non surgical
105
How does complementary medicine differ to alternative medicine?
- Complementary medicines are taken as well as conventional treatment
- Alternative medicines are taken instead of conventional treatment.
106
What is a placebo?
- Any therapy that has no specific activity for the condition being treated
- It has no active ingredient and no direct physiological effect
- Example is sugar pill
107
What is the placebo effect?
- Any psychological or psychophysiological effect produced by placebos
- In a clinical trial, this effect can be worked out by excluding the known specific effects of the treatment under investigation.
108
What is the nocebo effect?
- Adverse psychological or psychophysiological effects produced by a placebo
109
What are outcome expectancies with relation to placebo?
- Beliefs that treatment will have positive effects on health status
110
What are self-efficacy expectancies with relation to placebo?
- Beliefs that one can carry out the actions necessary for successful management of a disease
111
Outline four other explanations of the placebo effect
- Conditioning
- Anxiety reduction
- Social support
- Psychophysiological mechanisms
112
Outline four examples of CAM in Parkinson's
- Nicotine
- Cannabis
- Caffeine
- Acupuncture
113
Why are CAM potentially harmful in the treatment of Parkinson's
- Used as alternative to traditional medicine such as levodopa
- Harmful side effects and interactions with prescribed medicines
114
Describe the course of the limbic loop of the basal ganglia
- From prefrontal cortex
- Through the nucleus accumbens (ventral striatum)
- Returns to prefrontal cortex via the mediodorsal nucleus of the thalamus
115
What is the role of the limbic lobe of the basal ganglia?
- Gives motor expression to emotions
- Such as smiling, gesturing, aggressive or submissive posture
116
Outline the epidemiology of Parkinson's disease
- Increases with age (1:200 over 80)
- More common in males (1.5:1 M:F)
- Environmental factors include pesticide exposure, rural living and non-smokers
- Several genetic loci designated PARK-1 to PARK-11
117
Which genetic locus and subsequent protien is responsible for formation of Lewy bodies?
- PARK-1
- Alpha Synuclein
118
Which genetic locus and subsequent protien is responsible for juvenile and early onset of PD?
- PARK-2
- Parkin
119
Outline how PET scanning can be used to detect Parkinson's disease
- [18F]fluorodopa is injected intravenously and binds to dopamine receptors
- In Parkinson's disease there is reduced fluorodopa binding due to reduction in dopamine receptors
- Intensity of uptake is seen as blue / green
120
Identify two dopa decarboxylase inhibitors
- Carbidopa (co-careldopa)
- Benserazide (co-beneldopa)
121
Outline the mechanism of aciton of amantadine and when it is mainly used.
- Advanced disease
- Mainly acts be incresing dopamine release
122
A glycine antagonists will inhibit what type of receptor?
- NMDA
123
Outline the genetic basis of Huntington's disease
- Inherited as autosomal dominant disorder
- Trinucleotide repeat disease, with expansion of CAG repeats
124
How does the number of glutamine residues relate to development of Huntington's disease?
- Huntingtin gene normally possesses fewer than 30 glutamine residues
- In HD there is increased number of glutamine residues on the N-terminal of the expressed protein
- The mutated huntingtin possesses more than 40 glutamine residues
125
What is the main clinical feature of Huntington's? Which region of the basal ganglia is it associated with?
- Chorea
- Flicking moments of the hands, face and other body parts called chorea.
- Putamen
126
Outline the pathology of HD with relation to neurotransmitters
- Reduction of glutamic acid dercarboxylase, the enzyme responbible for GABA synthesis
- Resulting in a hyperactivity of dopaminergic synapses
- Mirror image of Parkinson's
127
Identify 3 drugs used in the management of Huntington's
- Tetrabenazine (inhibits of a vesicular dopamine transporter that reduces dopmaine storage)
- Chlorpromazine (dopamine antagonist)
- Baclofen (GABA agonist)
128
What is athetosis? Which region of the basal ganglia is it associated with? This condition is a side effect of which drug?
- Writhing movements of the hands face and neck
- Globus pallidus
- Levoopa
129
What is hemiballismus and what region of the basal ganglia is it associated with?
- Flailing movements of an entire limb
- Subthalamic nucleus
130
Which genetic locus and subsequent protien is associated with a phenotyope identical to sporadic Parkinson's disease?
- PARK8
- LRRK2
131
Outline the role of ACh in Parkinson's
- ACh release from striatum is normally inhibited by dopamine acting on D2 receptors
- In PD, there is a lack of dopamine in striatum
- So there is increased release of ACh in resutling in abnormal motor activity.
- Originally treated with mAChR antagonists though these had too many side effects e.g. dry mouth, eyes, blurred vision, urinary retention and diarrhoea
132
What is hyoscine and what does it cause?-
- Muscarinic antagonist
- Amnesia
133
Outline the role of the Pars Reticulata in the regulation of movement
- SnPR has GABAergic projections to thalamus that inhibit the thalamus
- As part of the direct pathway, GABAergic projections from the striatum inhibit the SnPR
- There is disinhibition of the thalamus as a result
Same effect as on Globus Pallidus Internus
134
Outline three types of care homes
- Residential home: Aimed at individuals who cannot manage at home on their own
- Nursing home: Aimed at individuals who cannot cope at home on their own and have a condition that requires 24 hour nursing care
- Specilaist care home: Aimed at individuals who cannot cope at home on their own and have a condition that requires specialist trained staff or adapted facilities
135
How does benserazide work?
- Inhibitor of AADC (aromatic L-amino decarboxylase)
- The enzyme responsible for converted levodopa to dopamine in the periphery
136
What does a standards need approach to QoL assume?
- Needs rather than wants are central to quality of life
137
What is the difference between a subjective and objective measure of QoL?
- Objective: Level of functioning
- Subjective: Self-appraisal of one's own wellveing
138
Give an example of a unidimensional and mutlidimensional question that could be asked on a health questionnaire
- Unidimensional: How woudl you rate your mood?
- Multidimensional: How would you rate your health?
