Presentation by Karen Vernon

1. Relapse management in
multiple sclerosis
Karen Vernon
Nurse Consultant

2. ∗ I have received travel & accommodation expenses to
attend meetings or honoraria for speaking or advisory
boards from:
∗ Biogen Idec
∗ Genzyme
∗ Merck Serono
∗ Novartis
∗ Teva Pharmaceuticals
Declarations

3. ∗ A relapse is caused by an area of
inflammation and demyelination in a
particular pathway in the brain an/ or
spinal cord.
What is a relapse?

4. ∗ “………….is something neurologists have been
grappling with for decades.” Gavin Giovannoni 2012
Definition of a relapse

5. Working definitions
∗ A relapse is defined as an
episode of neurological
symptoms that happens at
least 30 days after any
previous episode began, lasts
at least 24 hours and is not
attributable to another cause
and occurs in the absence of an
infection or fever.
∗ CLINICAL TRIALS RELAPSE
DEFINITION - The appearance
of a new neurological
symptom(s) and /or worsening
of a pre-existing one lasting at
least 48 hours in a patient who
is neurologically stable (or
improving) for at least 30 days
and without systemic upset
∗ (some trials do have slight
variations in their definition)

6. Realistic in practice?

7. ∗ Relapses conceptually are distinct neurologic events.
∗ However, in practice relapses often are indistinct or
equivocal
definitions

8. ∗ Relapses of whatever severity indicate ongoing
disease activity
... Even a mild relapse indicates a need for
reassessment of the adequacy of disease control.
Mild relapses (defined perhaps as producing minimal
impairments with full and speedy resolution)
need as much attention as a disabling relapse
∗ (Hutchinson 2012)
view of relapses

9. What’s In a name?
attacks exacerbations
Flare ups
blips
events

10. Relapses are under-reported
Duddy et al. DOI: 10.1016/j.msard.2014.02.006
Patients who have ever
experienced an
MS relapse and not contacted a
health care professional
Patients reporting most recent
relapse to an MS specialist team
n=102 n=101

11. Common symptoms of MS
relapses
Brainstem
Cerebellum
Spinal cord
pain on eye movement,
blurring of vision, red /
blue colour desaturation
Uhthoff’s phenomenon
Sensory – Lhermitte’s
phenomenon, “MS hug”,
neuropathic pain. Motor - upper
and / or lower limb weakness
Bladder, bowels, sexual
dysfunction
relapses are often
polysymptomatic due to
lesions in different pathways
vertigo, slurred speech,
ataxia, incoordination,
double vision

12. ∗Intermittent symptoms occur:
∗ when a damaged nerve pathway recovers, but the
recovery is incomplete.
∗ The partially recovered nerves then become susceptible
to heat and/or fatigue, which results in symptoms
coming and going.
∗ the symptoms usually resolve on rest or cooling and
rarely last more than a few hours.
∗This is not a relapse.
"What about intermittent
symptoms?"

13. For full current starting criteria please consult
http://www.england.nhs.uk/wp-content/uploads/2013/10/d04-p-b.pdf

14. ∗ All relapses are clinically significant, but in usual
practice relapses contributing to the eligibility for
Disease Modifying Therapies are:
∗ Any motor relapse
∗ Any brainstem relapse
∗ A sensory relapse if it leads to functional impairment
∗ Relapse leading to sphincter dysfunction
∗ Optic neuritis
∗ Intrusive pain
∗ - and lasting more than 48 hours.
Clinically Significant Relapse

15. ∗ A disabling relapse is defined as any relapse which
fulfils one or more of the following criteria:
Affects:
∗ patient’s ability to work
∗ patient’s activities of daily living as assessed by an
appropriate method
∗ motor or sensory function sufficiently to impair the
capacity or reserve to care for themselves or others as
assessed by an appropriate method
∗ Needs treatment/hospital admission
What is a “disabling” relapse

16. Detailed clinical history of
current events
Crux of relapse management

17. Timecourse – MS relapse

19. Is it a relapse?

20. Is it a relapse?

21. ∗ Beware :
∗ “My vision went suddenly”
∗ “What do you mean suddenly?”
∗ “It happened suddenly”
∗ “So do you mean it was like being hit on the
head...suddenly
∗ “Yes..I woke up with it, suddenly”
∗ [In reality then the symptoms could have occured at
any point from going to sleep the night before] Time
course (shape) onset
“sudden” onset of symptoms

22. ∗ Demand precision!
∗ Don’t be afraid to ask the same question again..and
again until you are satisfied!
∗ If the patient is an unreliable witness get a
corroborative account
∗ If you don’t take an accurate history it will be like
trying to unravel string
Neurological History Taking

23. ∗ History is the key although not always
straightforward
∗ SHAPE OF TIMECOURSE?
∗ What is their usual level of fluctuation in symptoms?
∗ is this recent deterioration merely an exaggeration of
the norm?
∗ Are they sleeping well / overly fatigued / stressed?
∗ Do they have inter-current infection or evidence of
systemic upset?
Relapse or re-emergence of
previous symptoms?

24. What else could it be?
∗ Transient day-to-day fluctuations in neurologic
symptoms common in MS patients.
∗ Progression – gradual worsening over months.
∗ Pseudo-relapses
∗ metabolic disorder.
∗ Neurologic manifestations due to development of
another medical condition.

25. ∗ Exacerbation of symptoms due to;
∗ Bacterial or viral infection
∗ Fatigue
∗ Heat
∗ Stress
∗ Co-morbidities
∗ Hormonal influences e.g. Menstrual cycle
∗ Medication side effects
What is a pseudo relapse?

26. ∗ Have I had this before?
∗ Have I been exposed to anything that could make my
symptoms worse, such as:
∗ heat – hot baths, hot tubs, or an active day out
∗ Have I done anything different?
∗ Could I have an infection?
∗ Have I taken my medication (old/new) as prescribed?
∗ Have I done too much?
∗ Is there anything happening in my life which makes
me feel like this?
Questions patients can ask
themselves

27. ∗ The patient is evaluated to determine whether the
change in neurologic status represents a relapse.
∗ How this happens will depend upon your service:
∗ Telephone triage
∗ Face to face
∗ other
assessment

28. ∗ Not just about steroids
∗ Treatment of underlying infection (if necessary).
∗ Let it recover on its own
∗ Symptomatic therapy
∗ Rehabilitation /MDT input
∗ Reconsideration of long-term disease therapy.
∗ The occurrence of a relapse may indicate the need to
initiate or escalate disease modifying therapy.
Treatment

29. ∗ Corticosteroids accelerate recovery they do not
influence degree of recovery or long-term
progression of disease
∗ NICE Recommendations:
∗ intravenous methylprednisolone 500mg – 1g for 3 to 5
days
∗ high-dose oral methylprednisolone 500mg – 2g daily for
3 to 5 days
∗ There is no significant differences in clinical,
radiological or pharmacological outcomes in oral
versus intravenous steroids for treatments of
relapses
Steroids

30. ∗ Cochrane review 2009:
∗ There is no significant differences in clinical,
radiological or pharmacological outcomes in oral
versus intravenous steroids for treatments of
relapses.
Intravenous versus Oral

31. ∗ 1st Trimester of pregnancy
∗ Relapse sensory (debatable)
∗ Previous psychosis with steroids?
∗ side effects from previous steroid treatment
∗ Used with caution in people with depression
∗ If the patient has osteoporosis?
∗ pressure sores/ open wounds
∗ Any other noxious stimuli
∗ severe dyspepsia
When not to give steroids?

32. Most common/uncommmon side
effects
∗ Metallic taste
∗ Insomnia
∗ Altered mood (high/low)
∗ Anxiety
∗ Increased appetite
∗ Generalised swelling
∗ Headache
∗ Myalgia
∗ Easy bruising
∗ Acne
∗ GI distress/heartburn
∗ Flushing
∗ palpatations
∗ Anaphylaxis
∗ Osteonecrosis/aseptic necrosis
∗ Psychosis: Euphoria or
depression
∗ Exacerbation of pre-existing
peptic ulcer disease, diabetes
mellitus, hypertension,
affective disorders
∗ Osteoperosis, cataracts, fatty
liver, Cushingoid
∗ habitus, pre dispostion to
infection,& impaired healing.

33. ∗ MRI typically is not necessary to diagnose an acute
relapse.
∗ Unless it is:
∗ 1) to rule-out an alternative explanation for the change in
neurologic status, or
∗ 2) to assess the level of disease activity to help assess the
need to initiate or alter disease therapy
∗ 3) use as a new “baseline”
Is MRI necessary to evaluate a
suspected relapse?

34. ∗ Review after 4 to 8 weeks
∗ Determine level of recovery
∗ Identify residual symptoms
∗ Monitor response if steroids given
∗ Document side effects
∗ monitor response to any symptomatic treatment
∗ Discuss disease modifying therapy initiation/
escalation if applicable
∗ Involve MDT if need
Review post relapse
Just as important

35. Do you offer a specific relapse
service?

36. ∗ Map the patients journey
∗ Identify blocks/ constraints
∗ Audit your service
∗ Makes improvements based on the audit
∗ Benchmark your service as to where it is at the
moment
∗ “Benchmarking best practice in relapse management of
multiple sclerosis” Embrey etal 2002, Nursing Standard,
17,22, 38-42
∗ Collect views of patients.
∗ Develop clinical protocol (auditable)
Points to consider

37. ∗ • Education of people with MS and MS teams
about the management of relapses
∗ • Ensuring a responsive and authoritative point of
contact
∗ • Accurate gathering and recording of information
∗ • Providing a timely assessment
∗ • Providing prompt treatment
∗ • A robust follow up service
∗ • Responsive review of DMT management
∗ • Audit
“best practice”

38. ∗ 4 slots per week: one hour appointment
∗ 1 slot available at 2 other DGH’s weekly (nurse
prescribers)
∗ Many referral pathways to the clinic
∗ KPI : contact patients reporting acute deteriorating
conditions within 48hrs: 98% rate, 2014-2015
∗ Neurological examination
∗ Relapse history
∗ Treatment plan
∗ Audit
Salford relapse service

39. ∗ Time from initial referral to patient contact
∗ Initial outcome: clinic appointment/ watch & wait
∗ Outcomes:
∗ Number of confirmed relapse
∗ Number of UTIs requiring antibiotics
∗ Number of prescriptions issued for :
∗ Methylprednisolone
∗ Symptom management medication
∗ Number of referrals
∗ to MDT
∗ for assessment of DMT eligibility
∗ Number of people requiring escalation of treatment
∗ Patient satisfaction
∗ Number of people attending review appointment
Salford audit

40. ∗How has your service responded to
the changing treatment landscape
in terms of relapse
∗What are your concerns?
Relapse or something else?