Relapse management in multiple sclerosis

Karen VernonNurse Consultant

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

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?

“………….is something neurologists have been grappling with for decades.” Gavin Giovannoni 2012

Definition of a relapse

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)

Realistic in practice?

Relapses conceptually are distinct neurologic events.

However, in practice relapses often are indistinct or equivocal

definitions

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

What’s In a name?

attacks exacerbations

Flare upsblips

events

Relapses are under-reported

Duddy et al. DOI: 10.1016/j.msard.2014.02.006

Patients who have ever experienced anMS relapse and not contacted a health care professional

Patients reporting most recent relapse to an MS specialist team

n=102 n=101

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

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?"

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

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

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

Detailed clinical history of current events

Crux of relapse management

Timecourse – MS relapse

Is it a relapse?

Is it a relapse?

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

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

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?

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.

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?

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

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

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

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

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

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?

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.

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?

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

Do you offer a specific relapse service?

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

• 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”

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

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

How has your service responded to the changing

treatment landscape in terms of relapse

What are your concerns?

Relapse or something else?