Michelle H. Cameron, M.D., P.T., M.C.R. Portland VA MS Center of Excellence- West, and Oregon Health & Science University

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1 Michelle H. Cameron, M.D., P.T., M.C.R. Portland VA MS Center of Excellence- West, and Oregon Health & Science University Ileana Howard, M.D. VA Puget Sound, Seattle, WA and University of Washington PVA August 26, 2014

2 Dr. Cameron receives: 1. Research support from: VA Rehabilitation Research & Development Service; Acorda Therapeutics; National MS Society; Collins Medical Trust 2. Has given paid lectures for: NMSS; MS Society of Portland; MSAA; OHSU; Genzyme, Acorda Therapeutics Dr. Howard has nothing to disclose Dr Cameron and Dr. Howard will describe offlabel uses of botulinum toxin

3 This continuing education activity is managed and accredited by Professional Education Service Group (PESG) in cooperation with Paralyzed Veterans of America (PVA). Neither PESG, PVA, nor any accrediting organization supports or endorses any product or service mentioned in this activity PESG and PVA staff has no financial interest to disclose

4 Introduction What is botulinum toxin? Botulinum toxin use in MS: Muscle spasticity, Bladder dysfunction, and Tremor Questions and Answers

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7 3/9/ FDA approved onabotulinumtoxin (Botox) to treat spasticity in the flexor muscles of the elbow, wrist and fingers in adults. Botox is not approved for injection in other arm muscles or in the leg muscles, but it is often used off label for these

8 Local May spread to other areas of the body Take 1-14 days to have full effect Last about 3 months Dose ranges Units/3 months

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10 Increased resistance to rapid stretch May present with muscle tightness of the arms or legs that increases with movement Can alter walking Can alter ADLs Can alter bladder function

11 Prevalence: up to 84% (Rizzo, 2004) patients with MS report some spasticity >30% report moderate to severe symptoms (frequent to daily interference with activities) Males and those with more severe disability had more severe spasticity symptoms

12 Maintains muscle bulk May help with transfers Uninhibited contraction of muscles Difficulty with movement Pain Debility Immobility Ulceration Good Spasticity Bad Spasticity

13 Typical symptoms Muscle tightness jumpy muscles Stiffness Common symptoms Scissor gait from thigh spasticity Toe walking gait from calf spasticity Difficulty with transfers Hygiene concerns Poor seating Skin breakdown

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15 Treatment of Limb Spasticity Patient

16 Examples: baclofen, tizanidine, dantrolene, benzodiazepines, gabapentin Use often limited by adverse effects Poor patient adherence

17 Stretching: Do every day Works best in conjunction with medication Can do with or without help from others Better results with: Weightbearing Prolonged stretching

18 Bracing

19 Ice Vibration Electrical Stimulation

20 Most effective for lower extremity High rates of satisfaction in long term follow-ups

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23 1. Identify patients that may benefit 2. Identify culprit muscle/groups 3. Decide on dosage and dilution 4. Perform injection 5. Arrange follow-up to assess effect

24 Spasticity interfering with comfort, health, or function Patient understands risks and benefits and wishes to proceed Not effective for fixed contracture

25 Preserve desired function Target most accessible muscle Target most active muscle

26 Dosage Consider functional status of the patient Size of muscle Persons with MS may require higher dosage compared to other diagnoses Dilution Generally 100 Units/2-4cc Size of muscle Amount of spread desired More targeted towards endplates= less dilution

27 Adductor longus/brevis/magnus Guidance techniques: Anatomical landmarks EMG guidance Electrical stimulation Ultrasound

28 Gastrocnemius/soleus Flexor digitorum/hallicus

29 Shoulder Wrist/hand

30 2 week clinic follow-up Range of motion Strength Tone Were goals of care met? Ashworth Function Numeric rating scale Telephone follow-up for established patients

31 Thank you to Nina Davis, MD for assistance with this information

32 Urine storage Urine emptying, when you want it to! The sphincters open The bladder contracts These must be coordinated

33 First MS symptom in 0-14% of patients Usually takes ~ 5+ years to develop If left untreated/undertreated, bladder dysfunction can result in urinary tract infections kidney damage (~5%)

34 Urgency Frequency Retention Incontinence Infections Kidney damage

35 The bladder should hold urine until you want to empty it It has TWO related functions Storage Emptying Bladder sphincter stays closed until it is time to urinate and then opens

36 Spastic overactive bladder (62%) contracts when you don t want it to Failure of storage Leads to urgency, frequency, leakage Underactive bladder (20%) doesn t contract when you want it to Failure of emptying Leads to urinary retention, overflow incontinence and frequency Mixed over and underactive bladder rare

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38 Post-void residual Urine lab tests Kidney ultrasound +/- urodynamics

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40 Assesses Post void residual, AND Bladder volume Urethral pressure profile

41 For failure of storage/bladder spasticity Non-medication treatment Oral medications Botulinum toxin Botox- A

42 For night time incontinence: Decrease fluid intake at night Avoid caffeine Catheterize at bedtime FYI: Kegel exercises not helpful for overflow due to overactive bladder

43 Antibiotics for infections Anticholinergics for an overactive bladder, e.g. oxybutynin, tolterodine, hyoscyamine Anticholinergics

44 August 24, 2011 FDA approved botox for injection for treatment of urinary incontinence due to bladder muscle (detrussor) overactivity associated with a neurologic condition (e.g. spinal cord injury, MS) in adults who have an inadequate response to or are intolerant of an anticholinergic medication.

45 A total of units (FDA approved dose is 200 units

46 70-80% of people benefit Usually works immediately but can take up to 2 weeks to work Lasts about 10 months but often exceeds a year May or may not also need antimuscarinics Generally results in weak bladder requiring catheterization

47 Whole body weakness Local bleeding Infection Antibodies to the toxin Contraindications Active UTI Hypersensitivity to BT Baseline urinary retention

48 Thank you to Meredith Frederick, MD for assistance with this information

49 Tremor occurs in 25-58% of patients with MS Often late in the disease Generally of the upper extremities Many types postural, intention, fine, coarse Paucity of effective treatments Assistive devices, splints Beta-blockers, benzodiazepines, antiepileptics Botulinum toxin (off-label)

50 Two recent small trials found modest benefit of BT injections for upper extremity tremor in MS Reduced tremor, but also reduced strength and did not improve QOL Something to consider in the light of limited options and temporary effect

51 Botulinum toxin reduces muscle overactivity In MS, this can help reduce spasticity of skeletal muscles and bladder and may reduce tremor This may improve function but can come at the price of weakness With skill and practice botulinum toxin injections can improve quality of life for people living with MS

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