Do we need to rethink imaging? Donald Grosset Consultant - - PowerPoint PPT Presentation

Donald Grosset

Consultant Neurologist - Institute of Neurological Sciences Honorary Professor - University of Glasgow

Do we need to rethink imaging?

This meeting is sponsored by Bial Pharma UK.

Job code: ON/JUN18/UK/255; Date of preparation: June 2018

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

Structural

MRI

• Parkinson Plus disorders
• The nigrosome

Functional

FP-CIT SPECT (DaTSCAN) Amyloid imaging Normal PD Normal AD

Caudate Putamen Sulcus Lateral ventricle Thalamus

Caudate Putamen Sulcus Lateral ventricle Thalamus

Normal Abnormal In PD, the DaT loss

• is asymmetrical especially at onset
• affects putamen > caudate
• correlates with clinical asymmetry
• correlates with bradykinesia and rigidity

Presynaptic neurones degenerate Postsynaptic neurones also degenerate Parkinson’s Plus disorders (eg. PSP, MSA) Presynaptic degeneration, so DaTSCAN will also be 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 Dystonic tremor Drug induced parkinsonism Parkinson’s disease Progressive supranuclear palsy Multiple system atrophy

• Alzheimer’s disease
• Vascular dementia

Movement disorders Dementia

• Dementia with Lewy bodies

Normal Abnormal

Movement disorders

MSA-C (19%) 1

Normal Abnormal

Corticobasal syndrome (39%) 2 Parkinson’s disease – very early (9.1%) 3 Cerebrovascular disease

1. Muñoz E et al. J Neurol. 2011 Dec;258(12):2248-53. 2. Hammesfahr S et al. Neurodegener

• Dis. 2016;16(5-6):342-7.

3. Nalls MA et al. Lancet Neurol. 2015 Oct;14(10):1002-9.

Drug unmasked Parkinson’s

MSA

Parkinsonism

Cerebellar and/or Autonomic

Compared to PD: More symmetrical More rapidly progressive Cerebellar features (speech, gait) Earlier and more severe autonomic symptoms Tremor less marked, sometimes irregular Neck and orofacial dyskinesia (rather than limbs)

MSA-P MSA-C Less cognitive impairment

CBS

Parkinsonism

Cortical involvement:

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

1. Booij et al. Synapse 2001;39: 101-8 2. Winogrodzka et al. J Neural Transm 2001;108: 1011-9

Threshold

• f

detection Scans of very early PD normal Incomplete motor features

• r

Only premotor feature eg. RBD

Presynaptic neurones degenerating Drug unmasked Parkinson’s – early Presynaptic degeneration, so DaTSCAN abnormal Postsynaptic neurones – receptors blocked by offending drug - REVERSIBLE But if very early PD, ie. above threshold of detection, DaTSCAN is normal

Vascular (and other structural) lesions can affect DaTSCAN appearance

Cerebrovascular disease Arteriovenous malformations Hydrocephalus Tumours Displacement or disruption

• f the striatum, or along the nigrostriatal

pathway

Striatal Infarction - no parkinsonism

A striatal infarct causes parkinsonism in less than 9%

• f cases

(Bhatia and Marsden, Brain. 1994;117:859-76.)

Abnormal FP- CIT scan But, pattern not that of PD

Lacunar striatal infarcts - vascular parkinsonism

Abnormal FP-CIT, but not PD or MSA pattern Defect on left suggests focal disruption, possibly infarct

MR: widespread vascular disease with lacunar infarcts affecting putamen

Extra-striatal infarction - vascular parkinsonism

Abnormal scan - defect in right caudate Not suggestive of PD pattern Infarct in internal capsule Caudate appears normal

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)

Movement disorders

MSA-C (19%) 1

Normal Abnormal

Corticobasal syndrome (39%) 2 Parkinson’s disease – very early (9.1%) 3 Cerebrovascular disease

1. Muñoz E et al. J Neurol. 2011 Dec;258(12):2248-53. 2. Hammesfahr S et al. Neurodegener

• Dis. 2016;16(5-6):342-7.

3. Nalls MA et al. Lancet Neurol. 2015 Oct;14(10):1002-9.

Drug unmasked SCA 2 and 3

Cerebrovascular changes

White matter hyperintensities (WMH)

Mild Marke d Debette BMJ 2010

2 patients aged 80

• Present in 30% of PD

cases

• Linked to MCI and PDD
• Not just atherosclerotic

– Wallerian degeneration – Hypotension – Inflammation

• Associated with more gait

and cognitive problems

Malek et al Mov Dis 2016

Synucleinopathies

Parkinson’s disease Dementia with Lewy Bodies Multiple system atrophy

Tauopathies

Progressive supranuclear palsy Alzheimer’s disease 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 [18F] T807 and similar ligands

Gomperts et al, Neurodegen Dis 2015

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

Structural imaging: the hippocampus

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 non-demented

• Regional cortical thinning
• Hippocampus and thalamic

atrophy

• Extensive white matter

abnormalities of major tracts (possibly preceding grey matter atrophy)

PD Dementia

• Extensive grey matter

atrophy, frontal, temporal and parietal > occipital

• Hippocampal atrophy
• Accelerated whole

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

PSP Normal

Shukla et al 2009 Focal atrophy in mid-brain Pons relatively preserved

MRI in PSP: Concave upper border of midbrain

PSP Normal

Shukla et al 2009

PSP Normal

Shukla et al 2009

MRI in PSP: Concave upper border of midbrain

PSP Normal

Shukla et al 2009

MRI in PSP: Concave upper border of midbrain

PSP Normal

Shukla et al 2009 Concave Convex

MRI in PSP: Concave upper border of midbrain

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