Scott Newsome, DO Director, Neurology Outpatient Services

Director, Neurology Infusion CenterJohns Hopkins School of Medicine

Baltimore, Maryland

Clinical Guidelines:

Disclosures

Outline

Introduction

Evolution of MSPreclinicalRISAge ???

Brain Volume

Contrast enhancing/new MS lesions

Neurodegeneration?Mitochondrial Dysfunction vs Compartmentalized IR

Relapsing-RemittingAge ~10–40

Lesion Load

Clinical Course

CIS

Inflammation/Response to Current Therapy

Secondary ProgressivePrimary ProgressiveAge ~>40

Slide courtesy ofP. Calabresi, MD

Recommended Baseline Studies for CIS and/or Suspected MS

PTM= partial transverse myelitis; LETM= longitudinally extensive transverse myelitisTraboulsee A, et al. AJNR 2015 (in press).

Recommended Timing of a Follow-Up Brain MRI for CIS and/or Suspected MS

RIS= radiologically isolated syndromeTraboulsee A, et al. AJNR 2015 (in press).

Low-Risk and High-Risk CIS

Brain MRI with suspicious lesions?

Low-risk CIS- Watchful waiting- Recommend close monitoring with serial MRIs

High-risk CIS- Strongly consider initiation of MS disease-modifying treatment

NO YES

Marcus J, Waubant E. Neurohospitalist. 2013; 3(2): 65–80. Frohman EM, et al. Arch Neurol. 2006;63(4):614-619.

Risk of MS after CIS

1. Beck et al. NEJM 1993;329:1764-1769, 2. Optic neuritis study group. Arch Ophthalmol 1997;115:1545-1552, 3. Beck et al, Arch Ophthalmol 2003;12:944-949, 4. Optic neuritis study group. Arch Neurol 2008;65:747-732, 5. Morrisey et al, Brain 1993;116:135-146, 6. O’Riordan et al, Brain 1998;121:495-503, 7. Brex et al. NEJM 2002;346:158-164, 8. Fisniku et al. Brain 2008;131:808-817, 9. Perumal et al. J Neurol 2008;255:89–93, 10. Bourre et al. Arch Neurol. 2012;69(3):357-362, 11. Sellner et al. Eur J Neurol. 2008 Apr;15(4):398-405

Radiologically Isolated Syndrome:5-year Risk for an Initial Clinical Event

Okuda et al. PLoS One. 2014;Mar 5;9(3):e90509.

Recommended Timing of Brain MRI for Established MS

Traboulsee A, et al. AJNR 2015 (in press).

Recommended Timing of Brain MRI for Established MS (Round 2)

Traboulsee A, et al. AJNR 2015 (in press).

DMT = disease modifying therapy

One-Year MRI Scan PredictsClinical Response to Interferon-β in MS

Patients with subclinical disease activity were at greatest risk for disability progression (≥1 point in the EDSS):1 new lesion; HR 15.12 new lesions; HR 38.83 or more lesions; HR 44.6

Responders: WhitePoor Responders: Checkerboard

Prosperini et al. Eur J Neurol. 2009;16:1202-1209. For educational purposes only.

HR = hazard ratio.

Early MRI Activity on Interferon Predicts Poor Long-Term Outcome

ASSURANCE Study(15-year follow-up of IM interferon β-1a) ─ Results:

MRI activity and relapses predicted future disability in patients treated with interferon-β

Bermel et al. Ann Neurol. 2013;73:95-103.

ASSURANCE = Assessment of Drug Utilization, Early Treatment, and Clinical Outcomes; IM = intramuscular.

Recommended Timing of Brain MRI for Established MS (Round 3)

Traboulsee A, et al. AJNR 2015 (in press).

SPMS = secondary progressive MS; PPMS = primary progressive MS

Tumefactive MS lesion

Axial FLAIR Axial T1 post contrast

Aggressive MS

Axial FLAIR Axial T1 post contrast

Aggressive MS

Sagittal STIR Axial and Sagittal T1 post contrast

Recommended Timing of PML Surveillance Brain MRI While on Nataluzimab

**Brain MRI protocol for monitoring patients on disease modifying therapies includes the PML surveillance sequences.

Traboulsee A, et al. AJNR 2015 (in press).

PML on Axial FLAIR Sequence

FLAIR = fluid attenuated inversion recovery

The Clinical Requisition for MRI

Traboulsee A, et al. AJNR 2015 (in press).

The Radiology Report

**Radiology report should use standardized terminology and MRI studies stored in DICOM format

Traboulsee A, et al. AJNR 2015 (in press).

Radiology Reportfor a PML Surveillance Study

Traboulsee A, et al. AJNR 2015 (in press).

Conclusions