Symptomatic treatments

Celia Oreja-Guevara & Gavin Giovannoni

• The numerous symptoms and co-morbidities associated with MS can

negatively impact patient quality of life (QoL), and places a burden on

carers, family, friends and other support networks

• Many MS-related symptoms are frequently ignored in assessments of

disease status and often thought not to be associated with the disease

• Research into how MS-related symptoms can be diagnosed and

treated within the MS population is lacking

de Sá JCC, et al. Ther Adv Neurol Disord 2011; 4:139–168.

The importance of considering MS-related

symptoms

Co-morbidities and MS-related symptoms

Prevalence of co-morbidities and associated

symptoms in patients with MS

a 32% of ataxia will be severe enough to decrease functional abilities. b Mortality ratio for suicide in MS of 2.3 compared with general population. Note: where a range is given in the reference, upper limit of range is plotted. de Sá JCC, et al. Ther Adv Neurol Disord 2011; 4:139–168.

90 90 90 85

80 80 75 75

68 65

50

32

25 20

5.4

0

10

20

30

40

50

60

70

80

90

100

Pati

en

ts (

%)

Epstein Bar Virus

Genetics

Vitamin D

Smoking

Risks

Adverse

events

Differential

Diagnosis

MRI

Evoked

Potentials Lumbar

puncture

Blood

Tests

Diagnostic

Criteria

Cognition

Depression

Fatigue

Bladder

Bowel

Sexual

dysfunction Tremor

Pain Swallowing

Spasticity Falls

Balance

problems Insomnia

Restless

legs Fertility

Clinical trials

Gait

Pressure

sores

Oscillopsia

Emotional

lability

Seizures

Gastrostomy

Rehab

Suprapubic

catheter

Intrathecal

baclofern

Physio-

therapy

Speech

therapy

Occupational

Therapy

Functional

neurosurgery

Colostomy

Tendonotomy

Studying

Employment Relationships

Travel

Vaccination

Anxiety

Driving

Nurse

specialists

Counselling

Family

counselling

Relapses

1st line

2nd line

Maintenance Escalation Induction

Monitoring

Disease-free

Disease

progression

DMTs

Side Effects

Advanced

Directive

Exercise

Diet

Alternative

Medicine

Pregnancy Breast

Feeding

Research

Insurance

Vision

Palliative Care

Assisted

suicide

Social

services

Legal aid Family

counselling

Prevention

Diagnosis

DMT

Symptomatic

Therapist

Terminal

Counselling

0

25

50

75

100

Physical Psychological

Mild (n=35) Moderate (n=52) Severe (n=46)

• The subgroup with mild symptoms had the

highest QoL, whereas the subgroup with severe

symptoms had the lowest QoL

MSIS-29, Multiple Sclerosis Impact Scale-29; lower MSIS-29 scores indicates higher QoL.

Motl RW et al. J Pain Symptom Manage 2010; 39:1025–1032.

Effects of MS-related symptoms on QoL

Single-factor model tested using confirmatory

factor analysis for establishing the symptom cluster

Measures of physical and psychological domains of QoL

based on mild, moderate or severe clusters of symptoms

MSIS-29 subs scale

Me

an

± s

tan

da

rd e

rro

r

Fatigue Depressio

n Pain

Perceived

cognitive

complaints

Symptom

cluster

FSS CES-D MPQ PDQ

.55 .63 .61 .71

• Gender (female), caregiver co-morbidities, age of the caregiver and EDSS score were

the main predictors of caregiver HRQoL

Rivera-Navarro J, et al. Mult Scler 2009; 15:1347–1355.

Burden of MS-related symptoms on caregivers

Scores of SF-36 dimensions of caregivers

59.3 62.3

65.5 65.6 70.7

77.5 80.2 81.9

0

20

40

60

80

100

GeneralHealth

MentalHealth

Bodily Pain Role-emotionalFunctioning

SocialFunctioning

Vitality Role-physicalFunctioning

PhysicalFunctioning

Mean

• Discuss your experiences of diagnosing co-morbidities and

MS-related symptoms

Open discussion

Therapies and unmet needs in

symptomatic management

MS-related symptom treatment

1. de Sá JCC, et al. Ther Adv Neurol Disord 2011; 4:139–168 (the medications listed here have only been investigated for the treatment of MS-related symptoms in experimental settings and sometimes not even in patients with MS. Their inclusion in this table and the broader manuscript should not be taken to imply that the authors are in any way recommending they be used in the clinical setting); 2. Cruccu G, et al. Eur J Neurol 2008; 15:1013–1028.

Symptom Recommended/licensed

Spasticity1

Baclofen

Tizanidine

Intrathecal baclofen (for EDSS > 7)

THC-CBD (Sativex)

Pain

trigeminal neuralgia2

Carbamazepine (stronger evidence)

Oxcarbazepine (better tolerability)

Walking impairment Slow release 4-aminopyridine (fampridine)

Pharmacological agents used in treating

MS-related symptoms with limited efficacy

a without sleepiness, b fatigue with sleepiness, c erectile dysfunction, d vaginal dryness, e low libido, f used for urinary storage, g used in emptying dysfunction, h used in combined dysfunction de Sá JCC, et al. Ther Adv Neurol Disord 2011; 4:139–168 (the medications listed here have only been investigated for the treatment of MS-related symptoms in experimental settings and sometimes not even in patients with MS. Their inclusion in this table and the broader manuscript should not be taken to imply that the authors are in any way recommending they be used in the clinical setting).

Symptom Pharmacological agents with limited evidence of efficacy

Spasticity Dantrolene, tolperisone, benzodiazepines, gabapentin, tetrahydrocannabinol, botulinum

toxin

Pain (trigeminal neuralgia) Misoprostol, baclofen, oxcarbazepine

Fatigue 4-aminopyridine or other K channel blockers, SSRIs, amantadinea, modafinilb

Depression SSRIs, serotonin and noradrenaline reuptake inhibitors

Pain – general Related to suspected cause(s) of the symptom; similar approach as taken with non-MS pts

Cognitive impairment Donepezil, rivastigmine

Sexual problems Phosphodiesterase 5 inhibitorsc, topical lubricantsd, androgen therapye

Dysphagia Anticholinesterases

Dysarthria Therapies treating tremor (in rare cases)

Seizures Standard antiepileptic therapies

Vertigo and dizziness Vestibular blocking agents

Sleep disorders Dopaminergic agonists for restless legs syndrome; modafinil for excessive daytime sleepiness

Urinary Storage/emptying

dysfunction/combined

Antimuscarinic compoundsf,g, alpha blocking agentsg, antispasticity agentsg, Neurotoxin, botulinum

toxin Ah, cannabinoidsh

Bowel dysfunction Laxatives

Tremor and ataxia Isoniazid, carbamazepine, topiramate

Oculomotor Memantine, gabapentin

Alternative therapies used in treating

MS-related symptoms

a Urine storage, b emptying dysfunction, c combined dysfunction 1. de Sá JCC, et al. Ther Adv Neurol Disord 2011; 4:139–168; 2. Apel A, et al. J Neurol 2006; 253:1331–1336; 3. Sastre-Garriga J, et al. Mult Scler 2003; 9:320–322. The medications listed here have only been investigated for the treatment of MS-related symptoms in experimental settings and sometimes not even in patients with MS. Their inclusion in this table and the broader manuscript should not be taken to imply that the authors are in any way recommending they be used in the clinical setting).

Symptom Other interventions

Spasticity Physiotherapy, cooling therapy and hydrotherapy

Pain (trigeminal neuralgia) Thermocoagulation, glycerol instillation, gamma knife radiosurgery, neuroablative

procedures, microvascular decompression

Fatigue Physiotherapy, yoga, cooling therapy, aerobic exercise, energy conservation, coping

strategies

Depression Cognitive behavioural therapy

Psychosocial problems Psychotherapy, stress management, relaxation techniques

Tremor and ataxia Exercise and rehabilitation, forearm cooling, deep brain stimulation, thalamotomy

Pain – general Related to suspected causes(s) of the symptom; similar approach as taken with non-MS patients

Cognitive impairment Cognitive training techniques

Dysphagia Thickening agents in liquids, ‘chin tucking’

Dysarthria Speech therapy, spelling boards, computer-assisted programs

Vertigo and dizziness Physiotherapy, vestibular rehabilitation therapy, repositioning manoeuvres

Urinary Storage/Emptying

dysfunction/combined

Incontinence padsa,b, clean intermittent self-catheterizationb, ileovesicostomyb, permanent

catheterisationb, Sacral nerve stimulationc, hyperbaric oxygen treatmentc

Bowel dysfunction High-fibre diet, increased fluid intake, enemas

• 67.3% of MS patients in Germany reported that they were currently using one or more complementary

of alternative medicines2

• 41% of patients in Spain used unconventional therapies during the previous year3

Improving outcomes in patients with MS:

unmet needs in symptomatic management

Rieckmann et al., J Neurol 2012 (Epub ahead of print).

Area for

development

More therapy options Commitment to

research

Personalized

care

Area for

development

Area for

development

Affording patients psychological and social support as part of their treatment package

Diverse therapies and strategies needed to address the complexity of MS symptoms and challenges

New approaches incorporating a wide range of pharmacological and non-pharmacological strategies need to be developed

Widen the focus of research to ensure the continuous development of better therapy options

Ensure greater access to comprehensive care regimens that include symptomatic care, rehabilitation and psychological support

Research across all domains is key for a better understanding of disease mechanisms

• Discuss case scenarios

– Spasticity

– Fatigue

– Depression

Open discussion

• 46-year-old woman with secondary progressive MS, spastic

paraparesis (3 to 4/5) and painful clonic spasms. Using bilateral

support for walking. Currently on oxybutynin (5 mg TDS) and

intermittent self-catheterisation for urinary symptoms, but no other

medications.

• How are you going to manage her spasticity?

Case scenario: spasticity

• A 28-year-old woman with early relapsing–remitting MS. Little

neurological impairment but suffering from severe fatigue. Recently

split up with long-term partner. Has had to stop work as a bank clerk

because of the fatigue.

• How are you going to manage her fatigue?

Case scenario: fatigue

• A 43-year-old man with relapsing–remitting MS complains of feeling

depressed. He is continuously tired as has no energy. Has difficulty

motivating himself to do any physical chores. He is sleeping poorly,

i.e. early morning waking, has lost his appetite and has no libido.

• How are you going to treat his depression?

Case scenario: depression

Epstein Bar Virus

Genetics

Vitamin D

Smoking

Risks

Adverse

events

Differential

Diagnosis

MRI

Evoked

Potentials Lumbar

puncture

Blood

Tests

Diagnostic

Criteria

Cognition

Depression

Fatigue

Bladder

Bowel

Sexual

dysfunction Tremor

Pain Swallowing

Spasticity Falls

Balance

problems Insomnia

Restless

legs Fertility

Clinical trials

Gait

Pressure

sores

Oscillopsia

Emotional

lability

Seizures

Gastrostomy

Rehab

Suprapubic

catheter

Intrathecal

baclofern

Physio-

therapy

Speech

therapy

Occupational

Therapy

Functional

neurosurgery

Colostomy

Tendonotomy

Studying

Employment Relationships

Travel

Vaccination

Anxiety

Driving

Nurse

specialists

Counselling

Family

counselling

Relapses

1st line

2nd line

Maintenance Escalation Induction

Monitoring

Disease-free

Disease

progression

DMTs

Side Effects

Advanced

Directive

Exercise

Diet

Alternative

Medicine

Pregnancy Breast

Feeding

Research

Insurance

Vision

Palliative Care

Assisted

suicide

Social

services

Legal aid Family

counselling

Prevention

Diagnosis

DMT

Symptomatic

Therapist

Terminal

Counselling