Movement Disorders 2 Flashcards
What is PSP otherwise known as?
Steele-Richardson-Olszewski syndrome
What is the pathological protein in PSP and CBD?
Tau
What gene mutation is occasionally associated with PSP?
MAPT gene mutation
What is the typical constellation (5 Sx) of eye disorders in PSP?
Restricted and slow eye movements; often starting with downgaze before becoming general vertical impairment
Visual blurring
Eyelid apraxia
Inability to maintain eye contact during conversation
‘Surprised’ look - head movement to change gaze
What non-motor signs are suggestive of PSP?
Behaviour change - almost HD like
Frontal impairment and memory problems
Mood change, apathy
Give some features more suggestive of PSP than PD?
Early gait and balance disturbance with early falls (particularly backwards) More rapid progression Speech and swallowing problems earlier in PSP (growling voice) Eye abnormalities in PSP Tremor unusual in PSP Neck stiffness and dystonia in PSP Minimal/brief dopa responsiveness in PSP PSP often symmetrical ish onset
What is the pathological protein in MSA and what histopathological feature does this result in?
Alpha synuclein
Aggregates particularly in oligodendrocytes, resulting in glial cytoplasmic inclusions (GCIs)
What 3 pathways/areas are affected to cause the symptom combinations in MSA?
Olivopontocerebellar pathway (cerebellar) Nigrostriatal pathway (parkinsonism) Preganglionic ANS lesions (autonomic)
What type of tremor is more suggestive of MSA than PD?
Intention - not at rest
What one symptom area, if present early, is more suggestive of MSA than PSP?
Autonomic disturbance - BP/Orthostatic hypotension particularly
What is the only Parkinsonian syndrome classically associated with upgoing plantars?
MSA
But also CBD
In which Parkinson mimic is antecolis most common?
MSA
4 signs of MSA on imaging?
Hot cross bun sign in midbrain
Small pons
Cerebellar wasting with middle cerebellar peduncle signal change
Putaminal rim
What histopathological bodies are suggestive of CBD?
Pick cells - tau positive neurons in the absence of argyrophillic Pick bodies
Features strongly suggestive of CBD?
Alien hand (usually L) - marked asymmetrical apraxia Astereognosis, simultagnosia, dysgraphaesthesia
Which Parkinsonism may feature stimulus sensitive limb myoclonus?
CBD
Does the presence or absence of autonomic disturbance suggest CBD?
Absence
Which Parkinsonism features marked and often intense limb muscle wasting?
CBD
Which cognitive domain is often affected early in CBD?
Speech and language - dysphasia
What genetic mutation causes paroxysmal kinesigenic dyskinesia?
PRRT2
What movements may be present in paroxysmal kinesigenic dyskinesia?
Chorea, dystonia or even ballism
What are the 3 types of paroxysmal dyskinesia?
Paroxysmal kinesigenic dyskinesia
Paroxysmal non-kinesigenic dyskinesia
Paroxysmal exercise induced dyskinesia
How long can attacks of paroxysmal non-kinesigenic dyskinesia last?
Hours-days
What may precede an attack of paroxysmal kinesigenic dyskinesia?
An ‘aura’
What is the typical movement disorder seen in paroxysmal exercise induced dyskinesia?
Bilateral lower limb dystonia for minutes - hours following 10-15 mins exercise
Which of the paroxysmal dyskinesias often features an AD inheritance pattern?
Paroxysmal non-kinesigenic dyskinesia
What gene mutation causes chorea-acanthocytosis, how is it inherited and what protein does it code for?
VPS13A gene for chorein protein
AR inheritance
What disease does the VSP13A gene mutation cause?
Chorea acanthocytosis
Which neuroacanthocytosis typically has the latest onset?
McLeod syndrome - 40-60
Which is the XL inherited neuroacanthocytosis?
McLeod syndrome
What is the gene mutation and affected protein in McLeod syndrome?
XK gene and Kx antigen
What gene mutation is associated with HDL2 and how is it inherited?
JPH3 gene, AD inheritance
Which neuroacanthocytosis usually presents under 20?
PKAN
At what age does PKAN usually present?
Under 20
What is the affected gene in PKAN and how is it inherited?
PANK2 gene
AR inheritance
Which of the two neuroacanthocytoses most commonly feature Acanthocytosis?
Chorea-acanthocytosis and McLeod syndrome
Which neuroacanthocytosis can commonly feature tics and self-mutilation, as well as Parkinsonism?
Chorea acanthocytosis
What are the characteristic blood findings of McLeod syndrome?
Acanthocytosis
Absent Kx red cell antigen
Weak expression of kell blood group antigens
What is the triplet repeat affected in HDL2?
CTG
What is the most common NBIA?
PKAN
What visual symptoms are characteristic of PKAN?
Peripheral visual loss
Progressive night blindness
Retinopathy
Which neuroacanthocytosis presents earliest with dystonia and spasticity, gait ataxia and visual symptoms?
PKAN
What does the presence of seizures in a suspected HD case suggest the possibility of?
Neuroacanthocytosis
What is the most common genetic cause of dopa responsive dystonia? How is this inherited?
GCH1 gene
AD inheritance
What disease might GCH1 gene mutation cause?
Dopa responsive dystonia
What are the 3 most common genetic causes of dopa responsive dystonia?
GCH1
TH (tyrosine hydroxylase)
SPR
What does GCH1 code for and how does this relate to its pathophysiology?
Codes for GTP-cyclohydrolase
This is involved in early steps of tetrahydrobiopterin (BH4) synthesis
BH4 is involved in the synthesis of dopamine and serotonin
So deficiency of GCH1 causes DA and 5-HT def
What does SPR code for and how does this relate to its pathophysiology?
Codes for sepiapterin reductase, which is involved in the last step of BH4 production (-> DA, 5HT)
What does tyrosine hydroxylase do?
Helps convert tyrosine to dopamine
What is TH deficiency DRD also known as and how does it differ from the other 2 types?
Segawa syndrome
Doesn’t feature the sleep and mood disturbances seen in the others
What is Segawa syndrome?
TH-DRD
How and when does DRD often present?
Around age 6; initially clubfoot development, lower limb dystonia
Progressing to upper limb dystonia by adolescence and whole body if untreated
Sleep and mood Sx if GCH1/SPR
How does DRD progress over the long term?
Parkinsonism; movements worsen over time but stabilise around age 30
Hyperreflexia in LLs
How do Sx vary through the day in DRD?
Vary diurnally - worse late in day and improve in morning after sleep
What might happen to eyes in DRD?
Upwards eye rolling
If DRD presents in adulthood, how does its presentation differ compare to childhood?
Slowly progressive parkinsonism -> dystonia with no diurnal variation
What 2 diseases does severe TH deficiency cause?
Infantile Parkinsonism
Progressive infantile encephalopathy
Ix for suspected DRD?
Genetics for GCH1 SPR and TH
LP for biopterin and neopterin levels
Phenylalanine loading test
MRI for ddx and PET for normal DA uptake
6 major differentials for DRD?
Leigh disease GM2 gangliosidosis PKU PKAN Wilson's disease Juvenile HD
What does LP tell you when investigating for DRD?
Low biopterin normal neopterin suggests early onset Parkinsonism
Low biopterin and low neopterin suggests GCH1 deficiency
Normal biopterin and neopterin suggests TH deficiency
What does phenylalanine loading test show for DRD?
Reduced conversion of phenylalanine to tyrosine (which uses BH4 as a cofactor)
Why is DRD dopa responsive?
Tyrosine is shuttled to L dopa via TH which uses BH4 as a cofactor
So bypasses this
What is a Holmes tremor?
Wing beating UL tremor classically due to cerebellar damage
Combination of rest, action and postural tremor worsened by posture and movement
What 2 components suggests spastic rigidity?
Clasp knife - stretch and sudden give way
Gegenhalten - opposing voluntary resistance
