Movement Disorders 1 Flashcards
1
Q
2 medications associated with chorea?
A
OCP
Dopamine agonists
2
Q
2 toxic causes of chorea?
A
Alcohol
Carbon monoxide poisoning
3
Q
2 metabolic disturbances associated with causing chorea?
A
Hypocalcaemia
Hyperthyroidism
4
Q
What is the genetic basis of Huntington’s disease?
A
Prolonged CAG triplet repeat in the huntingtin gene, found on chromosome 4
5
Q
Where is the major pathology in Huntington’s Disease?
A
The striatum (caudate nucleus and putamen), in turn affecting corticostriatal projections
6
Q
What reflexes are present in Huntington’s Disease?
A
Primitive reflexes - pout, grasp, palmomental
Extensor plantars
7
Q
What MRI sign may be present in Huntington’s disease?
A
Increased T2 signal in caudate nucleus
8
Q
What is an unequivocally normal CAG triplet repeat length?
A
Less than 26 repeats
9
Q
What is an unequivocally abnormal CAG triplet repeat length?
A
Over 40
10
Q
What do intermediate CAG triplet repeat lengths signify (26-40)?
A
Reduced penetrance
11
Q
What might a huge CAG triplet repeat length result in?
A
Juvenile onset/Westphal variant HD - onset less than 20 with a more pronounced akinetic-rigid presentation
12
Q
What is interesting about the inheritance of Westphal HD?
A
Typically paternally inherited
13
Q
4 medications of use to treat chorea?
A
Tetrabenzene
Phenothiazones e.g. Risperidone
Benzodiazepines
Haloperidol
14
Q
What is Sydenham’s chorea?
A
Post GAS (strep pneumoniae) infection, like a subacute rheumatic fever (weeks to months after primary infection)
15
Q
What is the pathophysiology behind Sydenham’s chorea?
A
Necrotising arteritis in thalamus, caudate nucleus and putamen
16
Q
Can Sydenham’s chorea recur? When?
A
Yes - during pregnancy or occasionally intercurrent infection
17
Q
At what stage of pregnancy is chorea gravidarum most likely to occur?
A
First trimester
18
Q
What comprises the pyramidal system?
A
Motor cortex
Corticospinal columns
19
Q
What comprises the Extrapyramidal system?
A
Paired subcortical masses/basal ganglia - caudate nucleus, putamen, globus pallidus, subthalamic nuclei and substantia nigra
20
Q
What part of the brain projects information between the basal ganglia and the motor cortex?
A
Thalamus
21
Q
What cells are reduced in number in the substantia nigra pars compacta in PD?
A
Neuromelanin cells
22
Q
What dopaminergic receptor changes occur in striatal cell membranes in PD?
A
Reduced D1 and D2 receptor expression
23
Q
What 2 Sx may precede the movement disorder in PD?
A
Constipation
Anosmia
24
Q
Describe the typical Parkinsonian tremor?
A
Coarse, slow (4-7Hz) resting tremor
Initially unilateral, often in hands, before spreading to all 4 limbs later
Improves with movement, worse with stress
Disappears when asleep
25
Where is the rigidity prominent in PD (in terms of affected muscle groups)?
Flexors - arms, legs, trunk, neck
26
What eye signs may occur in PD?
Loss of ocular convergence
| Loss of upward gaze
27
What autonomic symptoms may occur in PD?
Postural hypotension
Constipation
Seborrhoea
28
Do sleep problems occur in Parkinson's?
They can do - REM sleep behavioural disorders
29
What is the role of SPECT/DAT D2 receptor imaging in differentiating PD from PD mimics?
Normal scan in PD or normal phenotype
| Abnormal in PD mimics
30
What is the role of FP-CIT SPECT in differentiating between PD, mimics and non-PD?
Normal in non-PD
| Abnormal in PD and its mimics
31
Give 6 PD mimics?
```
Multiple systems atrophy (MSA)
Progressive supranuclear palsy PSP
Vascular Parkinsonism
Cortico-basal ganglionic degeneration
Wilson's disease
Drug induced Parkinsonism
```
32
3 types of MSA?
MSA-A(utonomic) - bladder/bowel, postural hypotension, REM sleep disturbances etc. Most prominent
MSA-P(arkinsonism) - Extrapyramidal symptoms most prominent
MSA-C(erebellar) - ataxia, bilateral UMNL signs, cerebellar signs
33
Eye Sx of PSP?
SN gaze palsy - downward eye movement initially impaired, followed by all other voluntary eye movements
Lid retraction common
34
Non-eye Sx of PSP?
```
Extrapyramidal dysfunction
Axial/truncal dystonia
UMNL signs
Dementia
Reduced response to L-Dopa
```
35
What about the distribution of Sx may suggest vascular Parkinsonism?
Predominantly lower limbs affected
36
Sx of CBD?
```
Asymmetric akinetic-rigid syndrome
Marked dyspraxia
Myoclonus
Dementia
Alien hand phenomena relatively common
```
37
What is dystonia?
Sustained abnormal posturing due to contraction of large muscle groups
38
What is cervical dystonia, or spasmodic torticolis?
Primary focal dystonia of sternocleidomastoid
| Causes unilateral head deviation to face opposite side of affected dystonic SCM
39
What is geste antagoniste?
Touching the unaffected side of the chin of a torticolis patient may return head back to normal
40
How is torticolis managed?
Botox injections into affected SCM
41
What is Meige's syndrome?
Cervical dystonia + oromandibular dystonia; blepharospasm and mouth/tongue/jaw dystonia
42
What is dopamine-responsive dystonia?
Childhood-onset dystonia that affects the legs only
| Responds to L-Dopa long term
43
What drug class commonly causes acute dystonic reactions? How do you manage them?
Phenothiazines e.g. Haloperidol, metaclopramide
| Give Anticholinergics e.g. Procyclodine
44
Why does tardive dyskinesia occur?
Long term neuroleptic treatment leads to dopamine depletion and subsequent development of abnormal supersensitive DA receptors
45
How does tardive dyskinesia often manifest?
Orofacial dyskinesia
| Choreoathetoid limb movements
46
3 causes of athetosis?
Hypoxic brain damage/cerebral palsy
Kernicterus
Metabolic storage disorders
47
Relative to the side of the affected subthalamic nucleus or connections, where does Hemiballismus occur?
Contralateral to the affected side
48
Most common causes of Hemiballismus?
POCS vascular disease
MS
DM - HHS
49
What motor GCS score does decorticate posturing represent?
3
50
What does a motor GCS 3 correspond to?
Decorticate posturing
51
Describe decorticate posturing?
Flexed elbows, wrists, fingers
| Extended and internally rotated legs
52
What is the biphasic pathogenesis of decorticate posturing?
Lesions above red nucleus causes its disinhibition and thus rubrospinal tract activation -> medullary reticulospinal activation leading to upper limb flexion
Disruption of lateral corticospinal tract which gives a pyramidal weakness in lower limbs
53
What type of posturing will a lesion of motor tracts above the red nucleus cause?
Decorticate posturing
54
What type of posturing will a lesion of motor tracts at or below the red nucleus cause?
Decerebrate posturing
55
What motor GCS score does decerebrate posturing imply?
2
56
What type of posturing is suggested by a motor GCS of 2?
Decerebrate posturing
57
Describe decerebrate posturing?
Extended upper and lower extremities
| Arched back and head
58
What type of posturing would a brainstem lesion typically cause?
Decerebrate posturing
59
Why does a brainstem lesion cause decerebrate posturing?
The red nucleus remains inactivated, and thus so does the rubrospinal tract - no upper limb flexion + usual pyramidal weakness of lower limbs
60
What does progression from decorticate to decerebrate posturing suggest?
Tonsilar herniation
61
What is opisthotonos caused by?
Extrapyramidal effect caused by axial spinal muscle spasm
| Caused in turn by inactivation of inhibitory corticoreticular fibres which act upon the pons/reticular formation
62
5 causes of opisthotonos in kids?
```
Meningitis
Tetanus
Kernicterus
MSUD
Sandifer syndrome
```
63
2 medications that can cause opisthotonos?
Phenothiazines e.g. Haloperidol, metaclopramide
| Lithium intoxication
64
5 neurological signs of severe heat stroke?
```
Opisthotonos
Hallucinations
Decerebrate posturing
Oculogyric crisis
Cerebellar dysfunction
```
65
What abnormal posturing can occur in near-death drowning?
Opisthotonos
66
What is risus sardonicus/rictus?
Forced grinning - facial muscle spasm
67
What are 3 differentials for risus sardonicus + opisthotonos?
Wilson's disease
Strychnine poisoning
Tetanus
68
What is the fencing response?
Posture that occurs immediately in concussion, often in impact sports
Brainstem trauma causes forearms to extend into the air on side of impact for a few seconds. Unaffected arm stays down by side
69
Why does fencing response occur?
Lateral vestibular nucleus activation causes a primitive reflex (asymmetric tonic neck reflex) which manifests as fencing response
70
What may a coronal MRI of a patient with HD look like in the long term?
Dilatation of the frontal horn of the lateral ventricle, due to atrophy of the caudate nucleus ('butterfly configuration')
Cortical atrophy
71
Differentials for adult-onset chorea that is HD-negative?
```
Neuroacanthocytosis
McLeod syndrome
DRPLA
SCA-17
HD-like syndrome 2
Fahr's syndrome
Senile chorea
```
72
How does tetrabenazine work?
Binds to vesicular monamine transporter type 2 (VMAT2) to prevent NA, DA and 5-HT uptake into intraneuronal storage vesicles, leading to their depletion and an overall reduction in their tone
73
2 types of drugs which may interact with tetrabenazine?
CYP2D6 inhibitors e.g. Sertraline, fluoxetine, paroxetine may increase concentration (enzyme inhibition)
MAOIs e.g. Phenelzine, Rasagiline, selegiline may cause hypertensive crisis due to inhibition of NA uptake
74
What medications are used early on in HD management?
Antipsychotics e.g. Aripiprazole
75
When does choreoacanthocytosis typically onset?
Late 20s - Early 30s
76
What unusual sign, in combination with chorea, tics, dystonia and other movement disorders, may suggest choreoacanthocytosis?
Self-mutilating behaviour e.g. Lip or tongue biting
77
Sx of choreoacanthocytosis?
Chorea, dystonia, tics and other movement disorders
Dementia, personality change or both (frontal type)
Seizures
Peripheral sensorimotor polyneuropathy
78
Lab signs of choreoacanthocytosis?
Raised CK
Caudate nucleus atrophy
Acanthocytosis
79
What 5 disorders make up the neuroacanthocytoses?
```
McLeod syndrome
Huntington's disease-like 2
PKAN
Abetalipoproteinaemia
Choreoacanthocytosis
```
80
What genetic patterns/age of onsets may differentiate the neuroacanthocytoses?
McLeod syndrome is XL
Abetalipoproteinaemia is infant onset
Huntington's disease-like 2 is AD
Choreoacanthocytosis is usually AR
81
What symptoms might suggest choreoacanthocytosis over HD?
Self-mutilating behaviour
| Peripheral neuropathy
82
What disorder is suggested by choreiform movements, dementia/personality disorder, seizures, peripheral neuropathy and a raised CK?
Choreoacanthocytosis
83
What is FXTAS?
Fragile-X associated tremor ataxia syndrome
Gradual onset of intention tremor, ataxia +/- dementia (cognitive impairment/frontal personality change common) in middle aged or older men (often in 60s)
Often peripheral neuropathy, autonomic symptoms e.g. ED and even mild Parkinsonism over time
84
What is the middle cerebellar peduncle sign on MRI and what does it suggest?
Suggests FXTAS
On T1, the middle cerebellar peduncles are hypointense
On T2 they are hyperintense
85
What causes FXTAS?
Secondary to a premutation in the fragile X mental retardation 1 gene (FMR1), present in 1/813 males
A shorter CGG triplet repeat than causes full fragile X syndrome
86
Differentials for FXTAS?
```
SCA syndromes (AD inherited)
MSA-C
```
87
What is benign hereditary chorea?
AD inherited childhood-onset non-progressive chorea with no dementia, but occasionally hypothyroidism and ataxia
88
What are the affected structures in DRPLA?
Dentate nucleus
Red nucleus
Globus pallidus
Corpus Luysii (subthalamic nucleus)
89
How does DRPLA present?
Gradual onset AD inherited myoclonus, ataxia, seizures, chorea and dementia
90
When does Wilson's disease typically present?
Late childhood - early adulthood, average age 15 years
| But can present any time
91
Neurological symptoms of Wilson's disease?
Movement disorder - wing beating tremor, dystonia (including torticolis, oculogyric crisis or 'smile' dystonia), chorea, Parkinsonism or dysarthria
Personality change - often frontal type
Psychosis - hallucinations, delusions and sometimes first rank Sx
Depression
Cognitive impairment
Seizures
92
What is implied by the presence of neuropsychiatric symptoms in Wilson's disease?
Hepatic disease
93
What MRI sign is pathognomonic of Wilson's disease?
Face of the panda - seen in mesencephalon
| Decreased signal intensity in the red nuclei (eyes) and increased signal intensity elsewhere
94
What are the lab signs of Wilson's disease?
```
Low caeruloplasmin
Low total copper
Increased free copper
Elevated 24-hour urine copper excretion
Liver biopsy is gold standard
```
95
What is the hepatic pathology behind Wilson's disease?
Copper is normally taken into hepatocytes and then disposed of in two ways, both mediated by ATP7B - one by binding copper to apocaeruloplasmin to create caeruloplasmin, and the other by vesicular secretions into bile (the main way)
ATP7B is dysfunctional so there is low caeruloplasmin and low total copper (90% of serum copper is usually caeruloplasmin bound) but raised free copper
This copper is then retained in hepatocytes and also deposited in brain, often in a pericapillary distribution
96
What is the mutated protein in Wilson's disease?
ATP7B
97
Where is copper deposited in the eye in Wilson's disease, where is this visible and what is the name of the phenomenon?
Descemet's membrane
Visible in the corneal limbus - golden brown discolouration of the corneal limbus
Kayser-Fleischer rings
98
Important Wilson's disease differential that may mimic lab results?
Hereditary caeruloplasmin deficiency
| Low caeruloplasmin, low total serum copper but also low 24 hour urine excretion (vs high in Wilson's)
99
3 methods of management of Wilson's disease?
Chelation - penicillamine (seldom used now due to side effects), trientine or tetrathiomolybdate (preferred)
Zinc treatment
Limiting copper intake
100
How does zinc therapy work for Wilson's disease?
Induces intestinal metallothionein, which in turn binds copper to prevent its absorption
101
What is a curative surgical procedure for Wilson's disease?
Liver transplant
102
3 AD inherited diseases causing progressive ataxia?
Gerstmann-Straussler-Scheinker disease
DRPLA
SCA
103
Sporadic causes of progressive cerebellar ataxia?
```
B12 deficiency
Hypothyroidism/SREAT
Paraneoplastic degeneration (anti-Hu)
Alcoholic cerebellar degeneration
MSA-C
```
104
What type of disorder is PSP?
Tau-opathy - abnormal tau protein aggregation
105
What is the gene mutation that sometimes causes PSP?
MAPT gene
106
What seemingly asocial symptom can become apparent in PSP?
Inability to hold eye contact during conversation
107
What falling feature may discriminate between PSP and PD?
PSP features axial rigidity and backwards falls, PD is forwards
108
Which Parkinsonism is more likely in a patient with no tremor and bilateral onset disease?
PSP
109
What reflex, normally suppressed, appears in PSP patients?
Oculocephalic response
110
What is Bell's phenomenon?
Palpebral oculogyric reflex - normally when you close your eyes they look up and move out
111
What are square-wave jerks and with what are they most strongly associated?
Saccadic fine movements with no smooth phase, visible when patient fixes on distance
Associated with PSP
112
What is the histopathology in MSA?
Alpha synucleinopathy with aggregates in oligodendrocytes; glial cytoplasmic inclusions (GCIs)
113
With what disorder are glial cytoplasmic inclusions associated?
MSA
114
What are the 3 structural pathways affected in MSA?
Nigrostriatal pathway
Olivopontocerebellar atrophy
Preganglionic autonomic lesions
115
What clinical feature is defining of MSA in the context of Parkinsonism?
Ataxia
116
What tremor is classical of MSA?
Intention
117
What 2 parkinsonisms can feature extensor plantar responses?
MSA and CBD
118
What MRI findings are suggestive of MSA?
Hot cross bun sign in midbrain
| Pontocerebellar atrophy
119
What is suggested by the hot cross bun sign on MRI?
MSA
120
What MRI finding is suggestive of PSP?
Hummingbird/King penguin sign
121
What disorder is suggested by the hummingbird/King penguin sign on MRI?
PSP
122
What is the affected nucleus in MSA responsible for the bladder and bowel disturbances?
Onuf's spinal nucleus
123
What nuclei are affected in MSA and CBD in the cerebellum?
Dentate nuclei
124
What is the pathology of CBD? Where is affected?
Asymmetric atrophy of posterior frontal, inferior parietal and superior temporal cortices
Plus thalamus, substantia nigra and cerebellar dentate nuclei
Tau-opathy, with Pick cells but no argyrophillic Pick bodies
125
Which two parkinsonisms are characterised by tau protein inclusions?
PSP
| CBD
126
Which Parkinsonism is suggested by stimulus sensitive limb myoclonus?
CBD
127
What Parkinsonism does severe ache in limbs suggest, with asymmetrical postural tremor?
CBD
128
What important feature is absent in CBD?
Dysautonomia
129
Which antiemetic is best for patients starting Dopa treatment? What is the risk?
Domperidone
| Risk of prolonging QTc so needs ECG
130
What drug is used for dyskinesias and off period freezing? What are common side effects?
Amantidine
| Side effects include dreams and sleep disturbance
131
What drug is used for RBD in PD?
Clonazepam
132
What DBS can promote freezing in PD?
GPi
133
What drug is used for hallucinations in PD/related?
Rivastigmine
134
What gene mutation is associated with young onset, motor only PD?
Parkin gene mutation
135
What drug is used for PD related pain, depression?
Duloxetine
136
How is sternocleidomastoid innervated? What is the implication of this in DBS for cervical dystonia?
Bilateral cortical innervation (Accessory)
| Therefore always need bilateral GPi DBS
137
What two muscles are involved in retrocolis dystonia?
SCM
| Splenius capitus
138
What drug can falsely raise caeruloplasmin?
OCP
139
Suggestive characteristics of myoclonus-dystonia?
Positive family history
Onset under 12 years
Alcohol improves Sx
140
5 differentials for myoclonus and renal failure?
```
Wilson's disease
Mitochondrial e.g. MERRF
Renal encephalopathy
Vasculitis
Action myoclonus - renal failure syndrome
```
141
What is MERRF and what Sx suggest it?
```
Myoclonic epilepsy with red ragged fibres
Short stature
Deafness
Dementia
Subcutaneous lipomas
```
142
What is suggestive of action-myoclonus renal failure syndrome?
```
Onset in teens/early adulthood
Fine myoclonus (tremor like)
Seizures
Ataxia
Focal glomerulosclerosis
```
143
What mutation causes action myoclonus renal failure syndrome?
SCARB2 mutations
144
What 3 diseases can SCARB2 mutations cause?
Action myoclonus renal failure syndrome
Gaucher's disease
Myoclonus epilepsy
145
What can be a later presentation of methylmelanuric aciduria?
Striatal necrosis - young patients with hyperkinetic chorea/tremor disorder and sometimes Parkinsonism
146
What is the general picture of DYT6 dystonia?
Generalised dystonia starting in 30s, from head/neck and progressing from there
147
What 3 phenotypes can be caused by c9orf72 deficiency?
ALS
FTD
Chorea and fasciculations
148
What are the 3 most common mutations seen in ALS?
c9orf72 mutation
Superoxide dismutase (SOD1)
TAR DNA binding protein 43 (TDP-43)
149
In roughly what percentage of familial ALS is c9orf72 mutation responsible?
40%
150
What SCA is a HD differential?
SCA 17 - late onset dysphagia, dementia, psych Sx, chorea/dystonia, epilepsy or parkinsonism
151
What mutation causes myoclonus dystonia and what inheritance pattern does it show?
Epsilon sarco-glycan (SGCE)
| AD but shows maternal imprinting
152
Which general sort of neuropathy can sometimes cause a tremor?
Demyelinating
153
What type of disorder is CBD?
Tauopathy
154
What is the LRRK2 mutation?
GS2019S
155
3 radiological signs of MSA?
Hot cross bun sign in midbrain
Putaminal rim hyperintensity
Middle cerebellar peduncle hyperintensity
