Progressive supranuclear palsy

Institute of Neurology
Magna Graecia University, Catanzaro
Institute of Molecular Bioimaging and Physiology
National Research Council
Magna Grecia University, Catanzaro
Paralisi Sopranucleare Progressiva
- Casi clinici esemplificativi Maurizio Morelli M.D.
Riunione annuale SIN Calabria
Lamezia Terme 8 Novembre 2014
HISTORICAL
NEUROLOGY
J. Clifford Richardson and 50 years of
progressive supranuclear palsy
Williams D.R. et al
2008;70:566-573
J. Olszewski (1913-1964)
J. C. Steele, 1987
J. C. Richardson (1909-1986)
Steele JC, Richardson JC, Olszewski J.
A heterogeneous degeneration involving the brainstem, basal ganglia and cerebellum with vertical
supranuclear gaze and pseudobulbar palsy, nuchal dystonia and dementia.
Arch Neurol 1964;10:333-359
American Neurological Association - Atlantic City; June 1963
Clinical research criteria for the diagnosis of progressive
supranuclear palsy (Steele-Richardson-Olszewski syndrome):
report of the NINDS-SPSP International Workshop
I. Litvan, Y Agid, D. Calne, G. Campbell, B. Dubois, R.C. Duvoisin, C.G. Goetz, L.I. Golbe,
J. Grafman, J.H. Growdon, M. Hallett, J. Jankovic, N.P. Quinn, E. Tolosa, D.S. Zee.
1996;47:1-9
Postural instability with falls in the first year of onset
and vertical supranuclear gaze palsy
Probable
PSP
Vertical supranuclear gaze palsy
or
Postural instability with falls in the first year of onset
and slowing of vertical saccades
Possible
PSP
Historical Review
Progressive Supranuclear Palsy: New Disease or Variant of
Postencephalitic Parkinsonism?
2004;19:247-252
Adolfo Brusa, MD, Rolf Stoehr, MD, and Peter P. Pramstaller, MD
Reference
Sex/
age (yr)
Age at
onset
Akineticrigid
syndrome
Postural
instability
with falls
Rest
tremor
Posturalkinetic
tremor
Neck
dystonia
Dysphagia
Dysarthria
Ophthalmoparesis
Staring
gaze
Blepharospasm
Eyelid
apraxi
a
Case Report
DidIn Charles
Dickens Describe Progressive
The Lazy Tour of Two Idle Apprentices, Dickens and his
friend Wilkie
Collins, thinly disguised
as Francis
Supranuclear
Palsy in
1857?Goodchild
and Thomas Idle, respectively, describe a journey through the
north of England from Carlisle to Doncaster undertaken in
September 1857. Their account was originally published in
installments, beginning in October 1857, in Dickens’s magazine Household Words.7
At an inn in Lancaster, “Mr Goodchild [Dickens] writes the
present account
of his
experience”
(p. 195),
The
Lazy
Tour of
Tworelating
Idle an encounter with:
4.
5.
6.
7.
8.
Apprentices
“A chilled, slow, earthy, fixed old man. A cadaverous man
of measured speech. An old man who seemed as unable to
wink, as if his eyelids had been nailed to his forehead. An
old man whose eyes—two spots of fire—had no more
motion that [sic] if they had been connected with the back
of his skull by screws driven through it, and rivetted and
bolted outside, among his grey hair.”
“He had come in and shut the door, and he now sat
down. He did not bend himself to sit, as other people do,
but seemed to sink bolt upright, as if in water, until the
chair stopped him.” (p. 194).
Discussion
9.
10.
61:199.
Cosnett
93:200–
Cosnett
Psychia
Garcia-R
perfield
Dickens
thoroug
227.
Steele J
palsy: a
sal gang
palsy, n
333–35
Litvan I
Goetz C
J, Quinn
diagnos
Olszews
Worksh
Lees AJ
supranu
disorder
Pa
2002;17:832-833
Review
Progressive supranuclear palsy: clinicopathological concepts
and diagnostic challenges
David R Williams, Andrew J Lees
A. Richardson’s syndrome (PSP-RS)
B. Atypical PSP
2009;8:270-279
- PSP-P (PSP-Parkinsonism)
- PAGF (Pure Akinesia with Gait Freezing)
- PNFA (Progressive Non-Fluent Aphasia)
- CBS (CorticoBasal Syndrome)
+
PSP-RS
Tau protein
Atypical PSP
-
Published online: 5 Nov 2014
DOI: 10.1002/mds.26054
123I-FP-CIT-SPECT
Parkinson
disease
(DaTSCAN)
Progressive
Supranuclear Palsy
Multiple System
Atrophy
123I-MIBG
myocardial scintigraphy
H/M: 1.05
H/M: 1.16
Parkinson
disease
Myocardium
Myocardium
Early imaging phase
Delayed imaging phase
H/M: 2.08
H/M: 2.31
Myocardium
Progressive
supranuclear
palsy
Myocardium
MIBG scintigraphy for differentiation of PD from PSP and MSA
Authors
Early
H/M ratios
studies
Delayed
H/M ratios
studies
Sensitivity (%)
Specificity (%)
Köllensperger M. Mov Disord 2007;22:1771-1776
88.9
44.4
Shin D.H. J Clin Neurol 2006;2:51-7
67.5
95.7
Kashihara K. J Nucl Med 2006;47:1099-1101
83.8
100.0
Taki J. Eur J Nucl Med 2000;27:566-573
82.9
82.4
Orimo S. J Neurol Neurosurg Psychiatry 1999;67:189-194
80.0
85.7
Yoshita M. J Neurol Sci 1998;155:60-67
92.0
86.2
Pooled
82.6
89.2
Authors
Sensitivity (%)
Specificity (%)
Südmeyer M. J Nucl Med 2011;52:733-740
64.5
88.2
Tateno F. Parkinsonism Relat Disord 2011;17:395-397
92.0
75.0
Fröhlich I. Neurol Sci 2010;31:403-406
80.0
23.1
Köllensperger M. Mov Disord 2007;22:1771-1776
88.9
55.6
Shin D.H. J Clin Neurol 2006;2:51-57
80.0
100.0
Nagayama H. J Neurol Neurosurg Psychiatry 2005;76:249-
87.7
57.1
Courbon F. Mov Disord 2003;18:890-897
94.4
70.0
Taki J. Eur J Nucl Med 2000;27:566-573
90.2
76.5
Reinhardt M.J. Eur J Nucl Med 2000;27:566-573
100.0
100.0
Takatsu H. Jama 2000;284;44-45
92.5
100.0
Yoshita M. J Neurol Sci 1998;155:60-67
100.0
89.7
Pooled
89.7
82.6
251
Parkinson
disease
Midbrain area
SCP width
Progressive
supranuclear
palsy
Single and combined MRI measurements
160
140
120
100
Midbrain to pons area ratio (M/P)
80
60
Midbrain area
0.40
40
mm2
Controls
MSA-P
PD
0.35
PSP
0.30
0.25
4.5
0.20
4
0.15
3.5
0.10
3
Controls
Possible PD
Probable PD
PSP
2.5
Superior cerebellar
peduncle width
2
1.5
mm
Controls
MSA-P
PD
PSP
Quattrone A et al.
2008;246:214-221
Magnetic Resonance Parkinsonism Index (MRPI)
MRPI
40
PSP vs non PSP
30
MRPI cutoff
20
10
Controls MSA-P
(n = 50)
PD
(n = 19) (n = 108)
Probable
PSP
Possible
PSP
(n = 17)
(n = 16)
≥ 13.55
Sensitivity
100%
Specificity
100%
Quattrone A et al.
2008;246:214-221
Combined MRI measurements to distinguish PD from PSP
References
M/P
Comparisons
Sensitivity
(%)
MRPI
Specificity
(%)
Sensitivity
(%)
Specificity
Oba H. (Neurology 2005;64:2050-2055)
- PSP vs PD
- PSP vs MSA
- PSP vs controls
100
100
100
100
100
100
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
Gröschel K. (Neurology 2006;66:949-950)
- PSP vs controls
100
90
n.a.
n.a.
Cosottini M. (Acta Neur Sca 2007;116:37-42)
- PSP vs no PSP
86
100
n.a.
n.a.
Quattrone A.
- PSP vs PD
- PSP vs MSA
- PSP vs controls
90
97
97
93
94
94
100
100
100
100
100
100
- PSP vs probable PD
- PSP vs possible PD
- PSP vs controls
92
88
97
85
88
92
100
100
100
99
99
100
- PSP vs PD
- PSP vs MSA
63
63
94
84
82
82
76
92
Longoni G. (Mov Disord 2011;26:247-255)
- PSP vs PD
- PSP vs controls
90
100
96
87
100
100
92
92
Massey L.A. (Neurology 2013;80:1-6)
- PSP vs no PSP
67
100
n.a.
n.a.
(Radiology 2008;246:214-221)
Morelli M. (Mov Disord 2011;26:527-533)
.
Hussl A
(Mov Disord 2010;25:2444-2449)
(%)
Effect of aging on MR measures differentiating Progressive
Supranuclear Palsy from Parkinson disease
Maurizio Morelli, Gennarina Arabia, Demetrio Messina, Basilio Vescio, Maria Salsone, Carmen Chiriaco,
Paolo Perrotta, Federico Rocca, Lucio Cascini, Gaetano Barbagallo, Salvatore Nigro, Aldo Quattrone.
M/P
MRPI
CTRL
Age
Age
PD
Age
Age
PSP
Age
Age
2014;29:488-495
Patient: B.M.
Sex: Female
Age at Examination: 65 Ys
Disease onset: 62 ys
Family history: negative
Clinical features
- Parkinsonism without LD response
- Early postural instability with falls
- Vertical supranuclear gaze palsy
BRAIN MRI
Pons area: 456 mm2
Midbrain area: 77 mm2
MCP width: 7.9 mm
SCP width: 2.16 mm
M/P: 0.17
MRPI: 21.66
DAT-SPECT
MIBG Scintigraphy
- Pons area: 490 mm2
- Midbrain area: 82 mm2
- MCP width: 8.55 mm
- SCP width: 2.71 mm
- M/P: 0.16
- MRPI: 18.83
Diagnosis ?????
PD ?
PSP ?
Parkinsonian syndromes
According to diagnostic criteria for:
- PD (Gelb DJ 1999)
- PSP (Litvan I 1996)
- MSA (Gilmann S 2008)
- LBD (McKeith IG 2005)
- FTD (Neary D 1998)
- CBD (Boeve BF 2003)
- Vascular parkinsonism (Winikates J 1999)
History of neuroleptic use
within the past 6 months
Gly2019Ser and Ile2020Thr
mutations in the LRRK2 gene
Acanthocytes in peripheral blood
Serum or urinary abnormalities
(iron, ferritin, transferrin, copper, calcium,
parathormone, ceruloplasmin)
Postural instability with
falls in the first year of
disease
Slowness of
vertical saccades
Clinically
unclassifiable
parkinsonisms
Normal striatal uptake in DAT SPECT
Postural instability with
falls after the first year of
disease and slowness of
vertical saccades
Freezing in the first
3 years of disease
MRI measurements predict PSP in unclassifiable parkinsonisms
A cohort study
M. Morelli, G. Arabia, F. Novellino, M. Salsone, L. Giofrè, F. Condino, D. Messina, A. Quattrone.
2011;77:1042-1047
Clinically unclassifiable parkinsonisms
(CUP)
n = 45
Baseline evaluation
Accuracy %
Clinical features
Index test = MRPI
n = 45
MRPI < 13.55
n = 30
MRPI ≥ 13.55
n = 15
Death
n=1
Drop-out
n=2
Follow-up
clinical evaluation*
n = 28
Follow-up
clinical evaluation**
n = 14
Isolated postural instability with falls in
the first year of disease
73.8
Slowness of vertical saccades
61.9
Postural instability with falls after the
first year of the disease and slowness
of vertical saccades
76.2
Freezing in the first 3 years of disease
45.2
MRI features
No PSP (CUP)
n = 28
PSP
n=0
No PSP (CUP)
n=3
PSP
n = 11
* Duration of clinical follow-up: 29.6 ± 10.1 months (range 24-60)
** Duration of clinical follow-up: 26.1 ± 14.6 months (range 6-48)
MRPI value ≥ 13.55
92.9
Follow-up evaluation
Possible PSP for Litvan criteria
PSP-P for Williams criteria
- Pons area: 480 mm2
- Midbrain area: 77 mm2
- MCP width: 8.1 mm
- SCP width: 2.62 mm
- M/P: 0.16
- MRPI: 19.26
Maurizio Morelli
Francesco Fera
Francesco Bono
Alessandra Fratto
Gennarina Arabia
Aldo Quattrone
2014:83;948
Grazie per l’attenzione