Job code: ON/JUN18/UK/255; Date of preparation: June 2018 Do we need to rethink imaging? Donald Grosset Consultant Neurologist - Institute of Neurological Sciences Honorary Professor - University of Glasgow This meeting is sponsored by Bial Pharma UK.
DGG has received grants from Parkinson’s UK, Michael’s Movers, the Paul Hamlyn Foundation, and honoraria from Bial, UCB Pharma, GE Healthcare and Acorda
Functional Structural Normal PD MRI FP-CIT SPECT (DaTSCAN) • Parkinson Plus disorders • The nigrosome Normal AD Amyloid imaging
Putamen Caudate Sulcus Thalamus Lateral ventricle
Putamen Caudate Sulcus Thalamus Lateral ventricle
Normal Abnormal In PD, the DaT loss - is asymmetrical especially at onset - affects putamen > caudate - correlates with clinical asymmetry - correlates with bradykinesia and rigidity
Parkinson’s Plus disorders (eg. PSP, MSA) Presynaptic neurones degenerate Postsynaptic neurones also degenerate Presynaptic degeneration, so DaTSCAN will also be abnormal
Normal Abnormal In PD, the DaT loss - is asymmetrical especially at onset - affects putamen > caudate - correlates with clinical asymmetry - correlates with bradykinesia and rigidity In Parkinson plus disorders, the DaT loss - tends to be more symmetrical - tends to be more severe - this correlates with clinical pattern vs PD
Normal Abnormal Essential tremor Parkinson’s disease Movement Dystonic tremor Progressive supranuclear palsy disorders Drug induced parkinsonism Multiple system atrophy Dementia • Alzheimer’s disease • Dementia with Lewy bodies • Vascular dementia
Normal Abnormal MSA-C (19%) 1 Movement disorders Corticobasal syndrome (39%) 2 Parkinson’s disease – very early (9.1%) 3 1. Muñoz E et al. J Neurol. 2011 Dec;258(12):2248-53. 2. Hammesfahr S et al. Neurodegener Drug unmasked Parkinson’s Dis. 2016;16(5-6):342-7. 3. Nalls MA et al. Lancet Neurol. 2015 Oct;14(10):1002-9. Cerebrovascular disease
MSA MSA-C Cerebellar Parkinsonism and/or Autonomic MSA-P Compared to PD: More symmetrical More rapidly progressive Cerebellar features (speech, gait) Less cognitive Earlier and more severe autonomic symptoms impairment Tremor less marked, sometimes irregular Neck and orofacial dyskinesia (rather than limbs)
CBS Cortical involvement: Parkinsonism Cognitive decline, dysphasia, apraxia, spasticity Compared to PD: More symmetrical More rapidly progressive Earlier cognitive decline Earlier dystonia and blepharospasm Earlier contractures (often asymmetric) Alien limb Myoclonus
Dopamine levels over time Threshold of detection Scans of very early PD normal Incomplete motor features or Only premotor feature eg. RBD 1. Booij et al . Synapse 2001;39: 101-8 2. Winogrodzka et al. J Neural Transm 2001;108: 1011-9
Drug unmasked Parkinson’s – early Presynaptic neurones degenerating Postsynaptic neurones – receptors blocked by offending drug - REVERSIBLE Presynaptic degeneration, so DaTSCAN abnormal But if very early PD, ie. above threshold of detection, DaTSCAN is normal
Vascular (and other structural) lesions can affect DaTSCAN appearance Cerebrovascular disease Displacement or disruption Arteriovenous malformations of the striatum, or along the nigrostriatal Hydrocephalus pathway Tumours
Striatal Infarction - no parkinsonism Abnormal FP- CIT scan But, pattern not that of PD A striatal infarct causes parkinsonism in less than 9% of cases (Bhatia and Marsden, Brain. 1994;117:859-76.)
Lacunar striatal infarcts - vascular parkinsonism MR: widespread vascular disease with lacunar infarcts affecting putamen Abnormal FP-CIT, but not PD or MSA pattern Defect on left suggests focal disruption, possibly infarct
Extra-striatal infarction - vascular parkinsonism Abnormal scan - defect in Infarct in internal capsule right caudate Caudate appears normal Not suggestive of PD pattern DaTSCAN defect resulting from disruption of dopamine projections
Substantia Nigra infarction - vascular hemi-parkinsonism Abnormal FP-CIT scan - no uptake in right striatum Not a PD scan pattern MRI - Striatum completely normal - defect in right substantia nigra (evidence of haematoma)
Normal Abnormal MSA-C (19%) 1 Movement Corticobasal syndrome (39%) 2 disorders Parkinson’s disease – very early (9.1%) 3 1. Muñoz E et al. J Neurol. 2011 Dec;258(12):2248-53. Drug unmasked 2. Hammesfahr S et al. Neurodegener Dis. 2016;16(5-6):342-7. Cerebrovascular disease 3. Nalls MA et al. Lancet Neurol. 2015 Oct;14(10):1002-9. SCA 2 and 3
Cerebrovascular changes • White matter hyperintensities Present in 30% of PD (WMH) cases • Linked to MCI and PDD 2 patients aged 80 • Not just atherosclerotic – Wallerian degeneration – Hypotension – Inflammation Mild Marke d • Associated with more gait and cognitive problems Debette BMJ 2010 Malek et al Mov Dis 2016
Synucleinopathies Tauopathies Parkinson’s disease Progressive supranuclear palsy Dementia with Lewy Bodies Alzheimer’s disease Multiple system atrophy Corticobasal syndrome Amyloid
Amyloid imaging in PD and DLB • Amyloid is often found in PD – its presence and severity relate to progression from PD to PDD • Cortical amyloid deposition is more common and more severe in DLB than PD • For PSP and CBD, it may become feasible to image tau with [ 18 F] T807 and similar ligands Gomperts et al, Neurodegen Dis 2015
Structural imaging: the hippocampus Hippocampus: • consolidates short to long-term memory (experienced events, ie. episodic or autobiographical memory) • role in spatial navigation (eg. London taxi drivers – Maguire et al Proc Natl Acad Sci 2000) • significant atrophy in Alzheimer’s disease
The hippocampus in PD Is it atrophied in PD? Does that correlate with cognitive problems? • CA2-3 and CA4-DG subfields significantly smaller • Subiculum smaller in PD patients with visual hallucinations • Significant correlations between learning performance and CA2-3 and CA4-DG volumes Pereira et al, Hippocampus 2013
Structural imaging in PD extensive findings but largely research domain PD Dementia PD non-demented • Regional cortical thinning • Extensive grey matter atrophy, frontal, • Hippocampus and thalamic temporal and parietal atrophy > occipital • Extensive white matter • Hippocampal atrophy abnormalities of major tracts • Accelerated whole (possibly preceding grey matter atrophy) brain atrophy rates • Increased WMH burden Review: Mak et al (Newcastle group) Park Related 2015
Structural imaging • Diagnosis – Parkinson’s Plus disorders • Diagnosis – Parkinson’s ?
MRI in PSP: The Hummingbird sign Normal PSP Focal atrophy in mid-brain Pons relatively preserved Shukla et al 2009
MRI in PSP: Concave upper border of midbrain Normal PSP Shukla et al 2009
MRI in PSP: Concave upper border of midbrain Normal PSP Shukla et al 2009
MRI in PSP: Concave upper border of midbrain Normal PSP Shukla et al 2009
MRI in PSP: Concave upper border of midbrain Normal PSP Concave Convex Shukla et al 2009
MSA: Pons and cerebellar atrophy Acknowledgment: www.radiologyassistant.nl
MRI in PD: The Nigrosome Visualising the substantia nigra! Acknowledgement: http://radiopaedia.org
Rethinking imaging in parkinsonism Summary • FP-CIT SPECT – Abnormal = presynaptic dopamine system affected by a disease process – Normal = usually healthy (but beware very early disease) • MRI – White matter disease = additive in PD, rather than ‘incidental’ – Atrophy = some diagnostic value in Parkinson’s Plus Imaging of Amyloid, Tau, Sonography of basal ganglia, Nigrosome visualisation, and other approaches remain research tools
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