2nd UK MSA Research Meeting
Clinical aspects of MSA
Dr Helen Ling
Queen Square Brain Bank for
Neurological Disorders
Institute of Neurology
University College London
Possible MSA:
Sporadic, progressive, >30y.o.:
-Parkinsonism with poor L-dopa response or
cerebellar syndrome
-Autonomic failure (urinary symptoms/ED or OH)
Probable MSA:
Possible + ≥ 1 additional features:
Definite MSA:
Additional features (probable):
Babinski sign
Stridor
MSA-P:
Rapidly progressive parkinsonism
Poor L-dopa response
Postural instability <3yrs of onset
Cerebellar signs
Dysphagia <5yrs of onset
MRI: atrophy of putamen, pons,
cerebellum
FDG-PET: hypometabolism in
putamen, brainstem, cerebellum
MSA-C:
Parkinsonism
MRI / FDG-PET findings
DAT-SPECT: reduced uptake
MSA-P
‘Red flag’ features supportive of MSA:
Rapid progression (wheelchair)
Antecollis
L-dopa induced fixed orofacial dystonia
Severe dysarthrophonia
Jerky action tremor
Polyminimyoclonus
Others:
Cold hands, Raynaud’s phenomenon
REM sleep behaviour disorder (early sign)
New snoring, sleep apnoea
Inspiratory stridor/sighs
Pisa syndrome
Emotional incontinence (MSA & PSP)
MSA-C
Differential diagnosis:
Idiopathic late onset cerebellar ataxia
Spinocerebellar ataxia 2, 3, 6
Fragile X premutation (FXTAS)
Primary progressive multiple sclerosis
Pure Autonomic Failure Vs. Premotor MSA
PAF
Premotor
MSA
RBD
-
+
ED
+
+
UD
+
+
OH
+
+
RD/Stridor
-
+
Smell
+
-/+
Prospective f/u of MSA patients for 2 years:
N = 141 (38% MSA-C); moderately severe
Mixed parkinsonism and cerebellar signs in majority of cases
Mean age of onset = 56.2 years
Median survival = 9.8 years (95% CI 8.1 – 11.4)
Unified MSA Rating Scales (UMSARS)
Prospective f/u of MSA patients for 2 years:
N = 141 (38% MSA-C); moderately severe
Mixed parkinsonism and cerebellar signs in majority of cases
Mean age of onset = 56.2 years
Median survival = 9.8 years (95% CI 8.1 – 11.4)
Unified MSA Rating Scales (UMSARS)
Independent predictors of disease
duration in MSA
Early autonomic dysfunction
Older age of onset
Not admitted to residential care
53% of 83 MSA cases developed
autonomic dysfunction within 2
years
Milestones of disease progression
and total disease course
MSA ‘Variants’
Long
Duration
MSA
Minimal
Change
MSA
Classical:
MSA-P
MSA-C
MSA with
Cognitive
Impairment
MSA-P with slow progression: A diagnostic catch
Case 1 (UK)
Case 2 (UK)
Case 3 (UK)
Case 4 (Canada)
Mean
Age at onset
62
50
48
43
50.8
Disease
duration
15
17
19
18
17
Parkinsonism
Parkinsonism
Parkinsonism
Parkinsonism
(Lt hand rest
tremor)
(Lt hand
slowness)
(Lt hand rest
tremor)
(Rt foot and hand
tremor)
11 years
9 years
11 years
14 years
(UI)
(UI)
(UR)
(OH)
No
Ataxic gait and
limbs dysmetria
(14)
Initial
presentation
Latency to
autonomic
dysfunction
Cerebellar
symptoms
(latency in
years)
“Red flags”
latency
(latency in
years)
No
No
Antecollis (8)
Antecollis (8)
Inspiratory
stridor (6)
Dysarthria (10)
Antecollis (9)
Inspiratory stridor
(14)
Dysphagia (9)
Dysphagia (16)
11.3
9
Myoclonus (17)
I Petrovic, H Ling, Y Asi et al. Mov Disord. 2012
MSA-P with slow progression: A diagnostic catch
Classic MSA
Slow progression MSA
Clinical characteristics:
Late onset autonomic dysfunction
All had Ldopa-induced generalised choreiform
dyskinesia despite limited motor benefit
I Petrovic, H Ling, Y Asi et al. Mov Disord. 2012
Pathological findings:
• Neuronal loss in substantia nigra & locus coeruleus
• Glial cytoplasmic inclusions - widespread
Minimal Change MSA
Y Asi, H Ling, I Petrovic et al. Manuscript under review.
MSA-P with slow progression:
2 out of 4 cases had cognitive impairment
Case 1 (UK)
Case 2 (UK)
Case 3 (UK)
Case 4 (Canada)
Age at onset
62
50
48
43
Disease duration
15
17
19
18
Cognitive
impairment
(latency in
years)
No
No
MCI (12)
Dementia (17)
MCI (15)
Petrovic et al. MDJ 2012, Asi and Ling et al, 2014 under review
Summary:
• Diagnostic accuracy of MSA - 75%
• Early autonomic dysfunction and older age of onset are poor
prognostic factors
• A subgroup of MSA-P may have very long disease duration
for up to 19 yrs and autonomic dysfunction only occurs in
the second decade
• Minimal change MSA – a unique subgroup which may
represent early MSA pathology
• Cognitive impairment can be a feature in up to 30% of cases
Acknowledgements
Acknowledgements
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Janice Holton
Yasmine Asi
Igor Petrovic
Andrew Lees
Niall Quinn
Zeshan Ahmed
Tetsutaro Ozawa
Tamas Revesz
Henry Houlden
John Hardy
Nadia Magdalinou
Atbin Djamshidian
Alastair Noyce
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Sean O'Sullivan
Luke Massey
Linda Parsons
Susan Stoneham
Robert Courtney
Kate Strand
Iliyana Komsiyska
Tammaryn Lashley
Queen Square Brain Bank
Patients and family