Prise en charge des sympt�mes de la scl�rose en plaques

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					      Managing Symptoms
      of Multiple Sclerosis

             Dr. Julie Prévost
Neurologist and Director, Neurology Clinic,
      St-Jérôme Regional Hospital

           Dr. Pierre Duquette
Neurologist and Director, CHUM MS Clinic
         Objectives of the Presentation

● Update on treatments for various
  symptoms frequently encountered in
  multiple sclerosis patients
● Walking problems
● Spasticity
● Bladder disorders
● Pain
                 Clinical Case Study

● 40-year-old woman
● Diagnosed with MS at age 25
● Stiffness in her legs causes unsteady gait
● Painful spasms at night
● Uses a walker and a manual wheelchair for
  long distances
● Fatigue severely limits her activities
● Urinary problems: occasional urinary
  incontinence and some urinary infections in
  recent years
Managing walking problems
                 Walking Problems

● What patients fear the most: having to
  use a mobility aid (cane, walker,
● Use is often delayed for fear of social
  stigma, loss of self-esteem, etc.
● Preventing falls means preventing injuries
  (fractures, concussion, etc.)
           Walking Difficulties

● Over 60% of MS patients say they worry
  about falling
● More than 67% limit their activities to
  avoid falling

                                        Phys Ther. 2012 Mar;92(3):407-15. Epub 2011 Dec 1.
                     Understanding falls in multiple sclerosis: association of mobility status,
                                    concerns about falling, and accumulated impairments.
             Symptoms That Can Affect

●   Urinary problems (urinary urgency)
●   Spasticity
●   Muscle weakness
●   Pain
●   Fatigue
●   Depression
●   Balance
●   Obesity
                  Muscle Weakness

● Physiotherapy
● Exercise (walking, swimming,
  yoga, cycling, Tai-Chi)
● Orthotics
  • Static
  • Dynamic
● Mobility aids
  • Cane, walker, wheelchair
                  Dynamic Orthotics

● For Foot Drop
● BionessL300
  • Functional electrical stimulation
    synchronized with the patient’s gait
  • More natural stride
  • Needs adjustment by a physiotherapist and
  • Not reimbursed by the government plan
● Bioness L300 plus
  • Adds thigh support
                  Bioness L300
Bioness L300 plus

                Bioness Dynamic Orthotics

Distributing Orthotists
  – Médicus laboratoire orthopédique
    5135 10th Avenue
    Montreal QC H1Y 2G5
    514 525-3757
  – Laboratoires Bi-Op Inc.
    30 Chemin du Golf Ouest
    Saint-Charles-Borromée QC J6E 8X6
    450 752-2467 and St-Jérôme
  – Slawner Ortho
    5713 Côte-des-Neiges
    Montreal QC H3S 1Y7
    514 731-3378
  – Savard Ortho-Confort
    1350 Cyrille-Duquet
    Corner of St-Sacrement Avenue and Charest Boulevard
    Quebec City QC G1N 2E5
    418 681-6381
         Prolonged-Release Fampridine

● Drug that improves walking speed for
  some MS patients
● Only treats the symptom
  • No impact on progression of the disease
                                            Percentage of Patients Who
                                          Respond to Treatment According
                                              to the Timed Walk Test

                            Grouped results from Fampridine studies
                                        Response Rate

                                                        40%                                                               37.3%



                                                                     Placebo (N=237)                        Fampridine-SR 10mg BID
                                                                                                                         p < 0.001*
  Note 1: The patient was deemed to be responding if they walked faster in at least three of four visits
  during the double-blind treatment compared to the maximum walk speed during four visits before treatment
  and the visit two weeks after treatment ended.

MS-F202: Goodman et al. Dose comparison trial of sustained-release fampridine in multiple sclerosis. Neurology 2008;71:1134-41; MS-F203: Goodman et
al. Sustained-release oral fampridine in multiple sclerosis: a randomised double-blind, controlled trial. Lancet 2009;373:732-8; MS-F204: Goodman et al.
Sustained-release fampridine consistently improves walking speed and leg strength in multiple sclerosis: a phase 3 trial. Multiple Sclerosis 2008;14:S298.
                                     Response to Treatment after the Timed Walk
                                    Test Is Independent of the Type of MS, the
                                        Duration of MS and the EDSS Score

       Variable (Placebo N / F-LP 10 N)
       Diagnosis                                                                                                     P value for diagnosis
       Relapsing MS (61/104)                                                                                         < 0.001
       Progressive MS (34/40)                                                                                        0.001
       Second-progr MS (91/184)                                                                                      < 0.001
       Progr-relapsing MS (4/15)                                                                                     0.151
       Duration of MS                                                                                              P value for MS duration
       Less than 8 years (66/97)                                                                                   < 0,001
       8 to 16 years (65/129)                                                                                      < 0,001
       16 years plus (59/117)                                                                                      < 0,001

       EDSS Score                                                                                                        P value for EDSS score
                                                                                                                         < 0.001
       5.5 or less (54/71)
                                                                                                                         < 0.001
       6 (67/140)                                                                                                        < 0.001
       6.5 or more (69/132)

                               0.10                          1.00                         10.00                     100.00
                                                                                Relative Risk

  Note: P values are descriptive. The subgroup sampled for progressive-relapsing MS had less than 30 subjects.

MS-F202:Goodman et al. Dose comparison trial of sustained-release fampridine in multiple sclerosis. Neurology 2008;71:1134-41; MS-F203: Goodman et al. Sustained-
release oral fampridine in multiple sclerosis: a randomised double-blind, controlled trial. Lancet 2009;373:732-8; MS-F204: Goodman et al. Sustained-release
fampridine consistently improves walking speed and leg strength in multiple sclerosis: a phase 3 trial. Multiple Sclerosis 2008;14:S298.
           Fampridine Prolonged-Release

● Indicated to improve walking in adults with
  multiple sclerosis (MS) who have a walking
  disability (score of 3.5 to 7 on the EDSS scale).
● Treatment must be prescribed for a maximum
  initial period of 4 weeks and the patient’s
  walk checked during that time to see if
  there is any improvement.
● In Quebec, covered by private insurance plans.

                       Fampridine, product data sheet, February 8, 2012 (Canada)
                         Fampridine Prolonged-Release

● Seizures
●  with higher blood levels, related to kidney
   • Monitor kidney function when treatment
     begins and annually
● Risk factors:
   • ≥ age 50
   • Kidney impairment
   • Not only in patients who had prior seizures
     March et al. Assessment of the cardiac safety of fampridine-SR sustained release tablets in a thorough QT/QTc
     evaluation at therapeutic doses in healthy individuals. Expert Opinion on Investigational Drugs 2009;18:1807-15.
Managing spasticity
         Spasticity and Multiple Sclerosis

● ≥60% of people with multiple sclerosis are
  at risk for developing spasticity
  • 34% have spasticity that affects their daily
  • 17% are frequently affected by spasticity
    during their activities
  • 4% avoid some activities because of

             Rizzo MA et al. Prevalence and treatment of spasticity reported by multiple
                                sclerosis patients. Multiple Sclerosis. 2004; 10: 589-95.
               Assessment of Spasticity

● Does spasticity interfere with:
  •   Hygiene
  •   Transfers
  •   Walking
  •   Recreation
  •   Sex
          Modified Ashworth Scale for
        Assessing Muscle Tone Intensity

Score   Description
  0     No increase in resistance

        Slight increase or slight resistance near the end
        of movement

        Greater resistance through most of the range of
        movement, but movement possible and easy
        Considerable increase, passive movement
  4     Limb stays rigid
      When to Treat a Patient Who
            Has Spasticity

● If muscle hyperactivity interferes with:
  •   routine activities
  •   mobility
● When it is painful
● To prevent future complications

         Brin MF, the Spasticity Study Group. Muscle Nerve. 1997;20 (suppl 6):S208-S220.
              Description – Disability Severity     New
                           Scale                  Objective











                 Preventing Spasticity

● Do regular stretching exercises
   • Iyengar Yoga
   • Tai Chi
   • Relaxation and massage therapy
● Avoid urinary infections
   • Analyze urine when odour is bad,
     urination frequency increases
● Avoid constipation
   • Eat properly, laxatives
● Avoid injuries
   • Adjust orthotics regularly
       Importance of Stretching and Placement
       Multidisciplinary Work with Physical and
               Occupational Therapists

● Preserve muscle length
● Maintain normal range of joint
● Reduce risk of contractures
● In a wheelchair
  • Check comfort, adjust the seat and arm rests
● Use an appropriate orthotic
         Oral Treatments for Spasticity

● Baclofen (Lioresal)
  • GABAb receptor agonist
  • Dose 5-10 mg twice a day up to
    80 mg/day
  • Side effects:
    •   Low blood pressure
    •   Weakness
    •   Drowsiness
    •   Confusion
    •   Toxic for the liver
        Oral Treatments for Spasticity

● Tizanidine (Zanaflex)
  • Alpha2 adrenergic agonist
  • Dose: 2 mg twice a day up to
    36 mg/day
  • Side effects:
    •   Low blood pressure
    •   Weakness
    •   Drowsiness
    •   Dry mouth
         Oral Treatments for Spasticity

● Dandrolene (Dantrium)
  • Peripheral action on the muscle
  • Dose: 25 twice a day up to 400
  • Side effects:
    • Toxic for the liver
    • Weak respiratory muscles
    • Drowsiness
            Oral Treatments for Spasticity

● Benzodiazepines (Valium, Rivotril)
  • Increases GABA receptor action
  • Side effects:
    •   Drowsiness
    •   Low blood pressure
    •   Breathing difficulty
    •   Dependency
    •   Depression

CESAMET® (Nabilone),
SATIVEX® (Tetranabinex® and Nabidiolex®)
● Drugs developed to reduce nausea and pain
● Studies report decreased spasticity
  • Multiple Sclerosis and Extract of Cannabis:
    results of the MUSEC trial
    • Patients: 144 THC and 135 placebo,
    • Muscle stiffness reduction 2 x greater

                J Neurol Neurosurg Psychiatry. 2012 Nov;83(11):1125-1132. Epub 2012 Jul 12.

● Smoked cannabis for spasticity in
  multiple sclerosis: a randomized,
  placebo-controlled trial
● Canadian study, 30 patients
● Cannabis smoking reduced pain,
  spasticity in MS patients
● Side effects:
  • Reduced cognitive function (attention,
  • Dizziness
  • Fatigue
  • Nausea
                                             CMAJ 2012. DOI:10.1503
                    Baclofen Pump

● Indications: paralysis in
  spastic legs
● Installed by a neurosurgeon
● Dose: adjust Baclofen
  release into the spinal fluid
  according to the clinical
● Surgery-related risks:
  • infections, meningitis,
    equipment breakdown,
            Chemical Denervation:
            Type A Botulinum Toxin

● Blocks acetylcholine release in the
  neuromuscular junction1
● Physiological effect2 is:
   • reversible
   • temporary
   • dosage to meet patients’ needs
● Treatment by focal intramuscular

                                           1. Brin MF. Muscle Nerve. 1997;20(suppl 6):S146-S168.
              2. Brin MF, the Spasticity Study Group. Muscle Nerve. 1997;20(suppl 6):S208-S220.
        Botulinum Toxin: Clinical Effect
           on Muscle Hyperactivity

● Reduces muscle
  stiffness, discomfort,
  within 3 to 7 days.
● Improvement lasts
  about 3 or 4 months.1

            1. Brin MF, the Spasticity Study Group. Muscle Nerve. 1997;20(suppl 6):S208-S220..
                                   2. Sheean G. Expert Rev Neurotherapeutics. 2003;3:773-785..
          Side Effects of Botulinum Toxin

● Pain at injection sites
● Weakness
  • Toxin spread from the site of desired action
    can inhibit nerve transmission in adjacent
    muscles that we do not want to affect.
● Exacerbation of neuromuscular
  junction disease
● Swallowing disorder (for cervical
● Contraindicated during pregnancy and
                                  Neurology, Guideline AAN 2008

● Diluted botulinum toxin injected
  into spastic muscles
  • Botox: Keep the toxin cold before
    dilution and injection.
  • Xeomin: ambient air
● Procedure with no anesthetic, done
  in the clinic by the physician
  • Local disinfection then injection with
    or without an EMG guide
● Procedure lasts less than 20-30
                Spasticity Clinics in Quebec

● Montreal area
   • Institut réadaptation de Montréal, Dr. Dagher
   • Clinique physiatrie CDN, Dr. Haziza and Dr. Dahan
● North Shore
   • Clinique de spasticité, Centre de réadaptation le Bouclier
     in St-Jérôme; Dr. Prévost and Dr. Dahan
● South Shore
   • Neuro Rive-Sud clinic in Longueil; Dr. Boulanger
● Trois-Rivières
   • Centre de réadaptation l’InterVal; Dr. Charest and Dr.
● Quebec City area
   • IRDPQ, Dr. Naud
Managing bladder disorders
               Charbonneau Commission

● I have no conflict of interest to report regarding
  this presentation.
● I receive sponsorships to attend conferences
  (all companies).
● I organize and participate in numerous
  educational events for all audiences
  (all companies and numerous organizations).
● I receive grants from MS Society of Canada and
  the Canadian Institutes of Health Research
● Biogen-IDEC is sponsoring me for a project I
  designed on MRI and cognition in MS.

● I will make some general comments on how to
  treat the following dysfunctions:
  • bladder, bowel, sexuality
● And I will discuss pain associated with multiple
  sclerosis (MS).
● Remember that each case is different.
● I mainly drew inspiration from recent journal
physiologie de la vessie
Bladder and Clinical Stages
            Retention/Emptying Dysfunctions

•The most common problem is urinary urgency
•Which is partial>complete
Resulting from involuntary bladder contractions
or overflow incontinence
→ Avoid irritants: coffee, tea, soft drinks
especially in the evening
If insufficient: medication (see table)
Retention problems (distended bladder) are less
→ Catheterization or probe
            Bladder-Sphincter Dyssynergia

●   Poor co-ordination
●   between the detrusor
●   and the internal sphincter
●   The ‘door' does not open at the right time
●   Is detected by a urodynamic study
●   Poor response to medication
            Intermittent Catheterization

● Simple method which can solve many problems
● I often recommend the use of a catheter at
● To allow the person to have a restful night
● The risks of infection at home are low
● With the appropriate technique
                Botulinum Toxin

● More recent treatment
● The urologist injects the toxin in the bladder
● The bladder becomes ‘lazier'
● Often effective
● But the treatment is complex and costly
● Must be repeated every 3 to 6 months
● May cause retention
                Bladder Residual Urine

Why measure it with the bladder echo?
Usually, the bladder empties almost completely.
If the voiding is incomplete, a more or less
   significant quantity of residue remains leading
• → Urinary infections
• → Increased frequency, urgency
Female Urine Bag

●   Frequent constipation (even before MS)
●   Normal frequency: 1 to 2 days
●   Ease ≠ frequency
●   The colon likes regularity and discipline
●    Regular times
●    Hydration and fibre
●    Fear of urgency incontinence
●    Know how to detect problems
●    Be patient
●    Do not leave home without emptying your bag

●  We can live without it…
●  But things go better with it.
●  Communication is fundamental.
●  Sexuality is not as natural as some might
● Problems do not usually solve themselves.
● It is up to each couple to determine normal
Managing pain
Important to Remember
Types of Pain
Types of Pain (Cont.)
Pain Scales
Types of Pain
Tic Douloureux (Painful Tic)
Medications for Neuropathic Pain
                         DRUGS TESTED TO CONTROL
                             MS-INDUCED PAIN

    Study                 Number of   Drug            Efficacy     Comments

    Centonze et al           20       Sativex         Not proven   N/A
    (2009) [98]

    Chitsaz et al            27       Nortriptyline   Proven       Average dose 50
    (2009) [121]                                                   mg

                                                                   Effective only on
    Solaro et al             16       Pregabalin      Proven       painful
    (2009) [122]                                                   paroxysmal

    Rossi et al (2009)       20       Levetiracetam   Proven       N/A

    Breuer et al             12       Lamotrigine     Not proven   N/A
    (2007) [90]

    Rog et al (2007)                                               Effective only on
    [89]                     66       Sativex         Proven       dysesthetic
                                                                   painful spasms
      My Attitude Toward Pain

Identify the type of pain.
Quantify it.
Set clear objectives when prescribing
Do not ‘pile up' medications.
First, I try tricyclics.
I am not a big fan of gabapentin.
I then try pregabaline.
I avoid opiates as much as possible.
Nabilone (cesamet) is sometimes useful.
In some cases, I prescribe fentanyl patches.

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