MRI in MS MS Masterclass, Sheffield, March 2019 Dr David Paling - - PowerPoint PPT Presentation

MRI in MS

MS Masterclass, Sheffield, March 2019

Dr David Paling Royal Hallamshire Hospital, Sheffield University of Sheffield

Overview

• Diagnosis (and differential diagnosis of MS)
• Surveillance (Monitoring patients on treatment)
• The future is here (Measuring brain atrophy and other advanced techniques)
• Stamp collecting (weird and wonderful)

Diagnosis

“Odd one in”

Which of the following 8 cases is MS? (Scans courtesy of Dr. Ian Turnbull)

1 2 3

4

5 6 7 8

HIV MS CMV

Lymphoma

Behcet’s CVD IRIS Sarcoid

Diagnosis

Symptoms consistent with inflammatory demyelination Exclude another pathology Classify demyelinating disease

Diagnosis

3 week history of left sided clumbsiness and falls O/E left hemi ataxia

ü û

Diagnosis

12 months ago – subacute left hemisensory disturbance – resolved 8 week history of progressive unsteadiness.

ü û

Diagnosis

12 month history of progressive walking difficulty O/E spastic paraplegia

ü û

Diagnosis

Diagnosis

Periventricular lesions

Juxtacortical lesions

Diagnosis

Callosal lesions and Dawson’s fingers

Diagnosis

Callosal lesions and Dawson’s fingers

Diagnosis

• al. M

Posterior fossa and brainstem

Posterior fossa and brainstem

Temporal lobe

Optic nerve

Spinal cord

MS vs vascular lesions

Vascular Lesions MS lesions Corpus Callosum + +++ U Fibres + +++ Basal ganglia

+++

+ Infratentorial +

+++

Temporal Lobe +

+++

Periventricular +

+++

Spinal cord

• +++

Optic nerve

• +++

Dawsons fingers

• +++

Atypical lesions:

Atypical lesions:

Atypical lesions:

Atypical lesions:

Atypical lesions

Surveillance

Treatment Monitoring

Case St Study

• 29 year old man
• Initial symptoms 3 year ago – left optic neuritis
• Further symptoms 2 years ago – sensory disturbance both legs
• Started on interferon beta-1a 1 year ago
• “Stable”
• Difficult to characterise difficulties at work needing 8 weeks off in the context of mood

disturbance

• Mild increase in tone, brisk reflexes, upgoing plantars, reduction in vibration sensation

below knees, positive rhombergs test.

What would help you.

Enhancing lesions

Enhancing lesions

Monitoring treatment effect

1 1.1 3.3 8.3 9.8 1 0.5 7.1 4.4 6.5 2 4 6 8 10 12 No relapse, progression, new lesions Relapse, no progression, no new lesions Progression with new MRI lesion Relapse and new MRI lesion Relapse, progression and new MRI lesion Odds ratio of further relapses at 3 years Odds ratio of progression at 3 years

Rio et al. Multiple Sclerosis 2009;15:848

Monitoring treatment effect

EDSS increase of at least 1 point Confirmed at 6 months at 5 years

MRI only MS or the tip of the iceberg

• MRI lesions
• ccur 7-9

times more frequently than clinical relapses

Relapses MRI

“MRI only MS” or the whole iceberg?

SDMT: Symbol Digit Modalities Test

“MRI only MS”

20% of people with GAD lesion had reduction in symbol digits modality test

• f at least 4 points

All in frontoparietal areas. Not recognised by patients Some recognised by carers

• 1. Pardini et al. Isolated cognitive relapses and informant based evaluation of

neuropsychological performance in MS. Poster at ECTRIMS 2015

Surveillance

Surveillance

• MRI within the first year can predict longer term response to interferons
• Addition of clinical markers can increase reliability
• “Subclinical” lesions can have demonstrable and persistent effects upon

cognition

Clinical case

• 22 year old man – training to be a solicitor
• Oct 14 Subacute ascending spinal sensory syndrome with ataxia
• March 15 Bilateral leg weakness; uses stick for 6 weeks
• Returns to work, sport, walking unlimited
• Increased tone , mild weakness, reduction in vibration sensation left leg

Clinical case

• Spinal onset and subsequent relapses
• Short duration between first and second relapses
• Poor recovery after second episode (EDSS 1.5)
• Spinal cord and multiple brain lesions including posterior fossa
• Contrast enhancing lesions on MRI scan
• 25 birthday 50% chance of moderate disability (EDSS 3 or higher)
• 27 birthday 1/3 chance walking 100m with stick (or worse)

0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 Annualised Relapse Rate Placebo Natalizumab

Reduction in annualised relapse rate

80%

• 3 years of treatment
• Personality change. Somnolent

Images courtesy of Prof Wattjes

• JC virus
• Asymptomatic infection
• Persists in quiescent state in kidneys,

bone marrow and lymphoid tissue

• Immunosuppresion
• Mutated pathogenic form of virus

• Symptoms of PML
• Subacute (weeks to months)
• Cortical features
• Dysphasia
• Behaviour changes
• Visual field defects
• Hemipareisis
• Seizures

Treatment of PML

• Suspend Natalizumab, Plasma Exchange,

Steroids 1,2

• Short duration symptoms, localised

disease good prognostic factors3,4

5 10 15 20 25 30 Symptoms Asymptomatic

Mortality

Mortality

With great power comes great responsibility

• Presymptomatic MRI phase of PML
• If PML picked up at this stage and treated then
• mortality is less (1 in 30 vs 1 in 4)
• Neurological disability is less
• JC Virus index and length of time on treatment can predict risk which can be

used to determine frequency of scanning

Grey matter

Atrophy

Atrophy

Atrophy

Diffusion tensor imaging

Decreases in fractional anisotropy, and increases in mean and radial diffusivity seen

Sodium MRI

The Future is here

• MRI only visualises a proportion of pathology of MS
• Techniques exist that can image
• Grey matter lesions (DIR, PSIR)
• Neuroaxonal loss (Atrophy)
• White matter microstructural changes below resolution of imaging voxel (DTI and others)
• Neuroaxonal metabolic dysfunction (Sodium imaging and others)
• Of these atrophy is closest to clinical use
• Issues
• Technical – related to scanner and sequence
• Patient related – drugs and hydration

Overview

• Diagnosis and differential diagnosis of MS
• MRI can diagnose MS (even after one relapse)
• Predicting the future (disease course)
• Early MRI has predictive role – number and location of lesions
• Surveillance (Monitoring patients on treatment)
• New lesions on beta interferons, particularly in patients that are felt to be relapsing or

progressing indicates worse outcome

• MRI can detect changes of PML before symptoms – can lead to better outcomes
• The future is here (Measuring brain atrophy and other advanced techniques)
• We need to work out how to integrate into clinical practise

Case 3

• Cerebellar dysarthria
• Nystagmus on lateral gaze + left 6th nerve palsy
• Increased tone in legs
• Gd 4 weakness in legs
• F/N + heel shin ataxia
• Frame to walk

Case 4

Case 3

Case 3

Case 3 4

• What is it?
• What else would help?

Case 3

Case 3 4

• ? diagnosis

Case 3

• CLIPPERS syndrome

Case 3

Case 3

• CLIPPERS

– Pontocerebellar dysfunction – Responsive to steroids – Homogenous GAD enhancing nodules without ring enhancement or mass effect predominant in cerebellum or pons <3mm in diameter

Case 3

• CLIPPERS is very rare

– Largest case series is 19 – Consider if clinical, radiological features add up – Commonly relapses when steroids stopped – Second line immunosuppression

MRI in MS

MS Masterclass, Sheffield, September 2016

Dr David Paling Royal Hallamshire Hospital, Sheffield University of Sheffield