MS ECHO: Update on MS treatment. Gary Stobbe, MD Medical Director, MS Project ECHO Clinical Assistant Professor, UW Neurology

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1 MS ECHO: Update on MS treatment Gary Stobbe, MD Medical Director, MS Project ECHO Clinical Assistant Professor, UW Neurology

2 Conflict of Interest Dr. Stobbe has no conflicts of interest to disclose

3 Objectives Review MS care in Macedonia Case presentations Highlights from ECTRIMS

4 Case #1 34 year old right handed female accountant No history of smoking, no alcohol and drug abuse June 2014 presents with difficulty walking, unsteadiness, and changes in hand writing Hospitalized in secondary care hospital MRI suspicious for infectious disease and she was referred to our clinic Neurological findings: dysarthria, horizontal nystagmus, deep tendon reflexes brisk, left plantar reflex without flexion, right plantar reflex flexor response. Ataxic gait, tandem gait impossible.

5 Case #1 (cont.) Labs CBC, glucose, hepatic enzymes, lipids and sedimentation rate all in reference ranges. VEP prolonged P100 wave latency on the left CSF elevated IgG, no oligoclonal bands, protein and cells in reference range. MRI white matter many small hypersignal lesions in T2 and FLAIR sequences with slight edema. Similar lesion in inferior coliculi and mesencephalon. After gadolinium the lesions are enhancing with ring enhancement. Diagnosed as multiple sclerosis

6 Case #1 (cont.) Treated with 5gram of methylprednisolone over 5 days Time of discharge gait was still ataxic but improved compared to the start of the disease; mild dysarthria. August 2014 relapse with worsening of the symptoms; loss of vision on the left eye and ataxia. Treated again with methylprednisolone 3gram over 3 days. December 2014 started on Avonex July 2015 had another relapse loss of vision on left eye, prominent dysarthria and ataxia. She was treated as a relapse. Current therapy is Avonex. August 2015 repeat MRI obtained

7 Case #1 August 2015 MRI

8 Treatment Options MS relapse Acute therapy Intravenous methylprednisolone (1000 mg daily for 3 7 days) OR high dose oral prednisone ( mg daily in divided doses for 3 7 days) with or without taper (University of British Columbia protocol prednisone 625 mg twice a day at breakfast and lunch for 3 days, no taper) Dexamethasone ( mg oral in divided doses OR intravenous daily for 3 7 days) ACTH (more expensive, no empirical evidence of superiority) units intramuscular or subcutaneous (up to 2 3 weeks) If ineffective, consider Intravenous immunoglobulin (IVIG; 400 mg/kg qd x 5d) OR plasma exchange (every other day for 5 7 exchanges) 8

9 Case #2 39 year old right handed female, no history of smoking, alcohol and drug abuse. No significant family history Spring 2013 presents with clumsiness with her right extremities, movements were not coordinated; pins and needles in her right hand; loss of strength in her right hand; loss of tactile sense on her left face MRI was done CSF oligoclonal bands present and elevated intrathecal synthesis of IgG. Other labs IgM positive for Borrelia; ANCA, ANA, anti DNA, rheuma factor and lupus cells were all negative Diagnosed with MS Treated with 5 grams over 5 days and recovered well. No medical documentation was presented.

10 Case #2 (Cont.) September 2014 worsening of the symptoms; not treated and the symptoms resolved. She was denying the diagnosis and because she was IgM positive for Borrelia she was consulting an infectious disease specialist September 2015 worsening with loss of strength in both legs, more prominent on the right leg; feeling pins and needles, loss of sensation and inability to walk. She was admitted in the clinic

11 Case #2 (Cont.) Exam spastic paraparesis, motor strength lower on the right leg; DTR brisk in all tendons, plantar response pathological bilaterally; incoordination on finger nose test, ataxia more to the right; loss of sensation to touch on the right, sensory level T5; no urinary incontinence or retention Labs CBC, glucose, urea, enzymes, lipids, in reference range; Repeated IgM for Borrelia was negative. SSEP, VEP were normal

12 Case #2 (Cont.) Brain MRI showed many small hypersignal lesions on T2 and FLAIR in the brain, cerebellum and brain stem. Thoracic MRI showed hypersignal lesion on T2 and FLAIR in level T4 5 and showed hyposignal on T1, without contrast enhancement. Treated with 5 grams of methylprednisolone good recovery. At discharge walking was more stable. One month after discharge the walking is almost normal. Before the admission to hospital she had no MS therapy.

13 Case #2 Imaging

14 Case #3 37 year old female diagnosed with MS at age 21 February 2000 first symptoms began as vision loss on the right eye in February 2000 hospitalized. CSF analysis showed intrathecal synthesis of IgG VEP prolonged latency on the right eye. MRI lesions on T2 sequence in the white matter in the frontal and occipital lobe, right brain stem, and cervical spine. She was diagnosed with MS and she started interferon (Rebif) 6 MIU per protocol.

15 Case #3 (Cont.) October 2000 relapse with sensory symptoms in the right body and loss of tactile and sensation for vibration in the right extremities. She was hospitalized and treated as a relapse. March 2006 second relapse, walking was difficult and unstable, she could not walk without support from companion. Hospitalized and treated as a relapse with slight improvement, she could walk without a support. The gait was with wide base. After one year had worsening of the symptoms, especially walking as support was needed. The leg was spastic, she had difficulty climbing stairs one week before she was hospitalized. Hospitalized and treated with slight improvement, the gait was improved but unstable.

16 Case #3 Cont. May 2008 another relapse mainly with walking difficulty and loss of strength in the legs and instability. Discharged and azathioprine was added another relapse, she was switched on Avonex 2014 another relapse with difficulty walking and urinary incontinence Today neurological finding are spastic quadriparesis more pronounced on the legs, the gait is with bilateral canes on wide base and urinary incontinence. Current therapy is Avonex and baclofen. Question: What is the best therapy strategy from now on?

17 Case #3 Imaging

18 Off label Disease Modifying Therapy Pulse steroids (1000 mg intravenous monthly) Azathioprine Cyclophosphamide Rituxumab Methotrexate Cladribine Mycophenolate Intravenous immunoglobulin Autologous hematopoietic stem cell transplant

19

20 Highlights from ECTRIMS Ocrelizumab shows promise in progressive MS (Montalban X, et al. Efficacy and safety of ocrelizumab in primary progressive multiple sclerosis results of the placebo controlled, double blind, Phase III ORATORIO study.) Similar effects seen for fingolimod and placebo in primary progressive MS (Yaldizli O, et al. Abstract 110, ECTRIMS, Barcelona, 2015)

21 Resources Thrower BW. Relapse management in multiple sclerosis. Neurologist 2009;15(1):1 5. High dose oral prednisone for relapses oralcorticosteroids relapse multiple sclerosis Professional Resource Center Professionals/Clinical Care/Managing MS/Relapse Management Kalb,R. The emotional and psychological impact of multiple sclerosis relapses. Journal of the Neurological Sciences: 256 (2007) S29 S33 The Use of Disease Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. A Consensus Paper by the Multiple Sclerosis Coalition:

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