Muscle stiffness and spasm in MS

Miranda Olding RGN MSCNNovember 2012

The nervous system

Made of nerve cells(neurons)and ‘glial cells’(meaning ‘glue’) Neuron.Information passes as an electrical current down the axon,And then electrically, or chemically, as a ‘neuro-tranmitter’, in betweenNeurons.

Neurones

http://www.bbc.co.uk/schools/gcsebitesize/science/aqa/nervesandhormones/thenervoussystemrev2.shtml

http://www.childrenshospital.org/research/_neuron/index.html

Neurotransmitters can be either excitatory (stimulating),or inhibitory, (calming); the amount of excitatory or inhibitory input the cell receives dictates whether the cell fires or the impulse is suppressed.

Biology of muscle spasm & stiffness

• The ability to switch off & calm down is as important as the ability to switch on and rev up

• Excitatory signals fire other neurones into action; inhibitory signals stop them firing. The ‘firing’ is Action Potential – an electrical transfer of energy.

• Spasticity occurs as a result of an imbalance between the excitatory and inhibitory signals from the brain and/or spinal cord.

• The nerve pathway connecting the brain and spinal cord is made of upper motor neurones.

• The pathway between the spinal cord and muscles is made of lower motor neurones.

• In MS, ‘spasticity’ ( muscle spasm & stiffness) is thought to be due to nerve conduction being affected by lesions located in the brain or spinal cord.

• This means that the upper motor neurones struggle to regulate messages to the lower motor neurones.

• The lower motor neurones can then become overactive and hypersensitive, causing stiffness or spasms in the muscles.

Some of you may be familiar with this feeling….

…but you probably don’t make this much fuss

PatientIntrathecalBaclofen

(ITB™)Therapy

OralMedications,Food factors

& herbs

Physiotherapy,Exercise

StretchingManaging MS,Prevention &

Trigger factors

Neurosurgery,Orthopaedic

surgery

InjectionTherapy

Interventions for muscle stiffness and spasm

Trigger factors

• Check you don’t have a urine infection – get your urine dipsticked, and get treatment if leucocytes/nitrites present• Check you don’t have any infection, sore skin,

ingrown toenails, clothing/splint/shoes that are chafing, or constipation – treat immediately if so

• Posture; how are you sitting, moving & sleeping? – all these things can trigger worse spasm/stiffness.

• Interferon therapy, esp high dose• Periods of increased stress

PhysiotherapyAssessment• Inhibitory mobilisation techniques• Normal patterns of movement• Active and passive movements• Positioning / posture

(sitting, wheelchair, lying, standing)• Splinting and orthotics• Proprioceptive neurological • facilitation techniques (PNF)• Bobath technique - uses intensive handling to inhibit

abnormal tone and movement patterns• Stretching• Functional Electrical stimulation• Standing

Your Physio can also teach you self-management techniques like:• Home exercises/stretches• Exercise classes• Appropriate

strengthening• Use of:

– Free weights– Machines– Theraband– Swiss balls– Aquacise classes

Active movement exercise• Recent research showed this to be the most

effective form of exercise for spasm / stiffness.

Stretching & range of movementHelps to keep range of movement & flexibilityCan be done with a practitioner, eg physio, shiatsu,In a class, like yogaOr as a home routine, by oneself or with another person helping.

Muscle relaxant medication – all (except dantrolene) affect neurotransmitters, promoting

increase of inhibitory transmitters like GABA Drug Dose Action Common side effects

Baclofen 5-40mg x 3 daily GABA – B (brain) Sedation, weakness

Tizanidine 2-12mg x 3 daily A adrenergic agonist(brain)

Sedation, dry mouth, low blood pressureLiver toxicity

Diazepam & other benzodiazepines

Depends on drug GABA-A (brain) Sedation, can cause dependency quickly

Dantrolene 25-100mg x 4 a day Ca 2 release (muscles)

Sedation, digestive upset, liver failure

Gabapentin 100-1200mg x 3 a day Vk ch ? GABA (brain) Weight gain, sedation, poor concentration, unsteadiness

Pregabalin Same mode of action as Gabapentin, but lower dose

Same, second-line treatment, more expensive, and

Both drugs are “ off label”

Muscle relaxant basics: ‘start low and go slow’

• If you need to start or increase baclofen muscle relaxant medication, get a tablet cutter, and increase in half tablets, every 3 days, until you find the right dose, a to a max of 90mg a day, in 3 split doses; ask your GP to adjust your prescription.

• See your MS nurse or neurologist again if this doesn’t work – you can go higher with supervision & there are other options.

• If baclofen causes undue drowsiness or weakness, tizanidine may be tried; you’d need a blood test before & for the 1st 3 months to check your liver can process it.

• Initial side-effects may wear off after a couple of weeks• Combinations of drugs may be used if trying them alone has

not, or if top dose is reached without desired effect.

Alt Alternatives?LDN

• Many people with MS report improvements in spasm with LDN; it’s not licensed for MS.

• This means your GP could prescribe it if they want to, but may have to get private & pay

• Licensed drug 50-150mg, for heroin addiction• 1.5 - 4.5mg for MS, 3mg top dose for spasms.• Not be used with Beta-interferons or opioids• An opioid antagonist, stimulates production of body’s own ‘feel

good’ neurotransmitters

Research & Testimonials

• Research is preliminary, not large scale, lack of incentive as drug is already out and cheap

• Use is driven by testimonials and campaigning websites, eg www.LDNResearchTrust.org

• Testimonials and preliminary research report reduction in MS symptoms, most commonly in

• Spasms & fatigue• Also many reports of cessation of relapses• Stopping of progression

How LDN works

• LDN is an opioid antagonist – it blocks the uptake of the body’s own natural endorphins, briefly, at night, and thus stimulates the production of more.

• The interaction of naltrexone with microglial cells results in a reduction of proinflammatory cytokines as well as neurotoxic superoxides, which may be how it affects the immune system (reducing relapses)

• A good essay on LDN is available at http://www.ldnresearchtrust.org/uploadeddocuments/dr-zagon.pdf

Drug free strategies to boost inhibitory neurotransmitters

• Terry Wahls in her book suggests:

• Magnesium supplement 500-800mg daily. Also in: pumpkin seeds, spinach, black beans, chard, pinto beans

• Organic sulphur – needed to generate GABA. Good sources: onion & cruciferous veg/greens

• N-acetylcysteine (NAC) helps generate GABA. 2g a day. Supplement. In: red pepper, garlic, onions, cruciferous veg, oats, wheatgerm.

Drug free

• Almost all functions of the brain require adequate amounts of the vitamin B family – many practitioners recommend supplementation as well as consuming healthy foods containing vitamin B

• www.theworld’shealthiestfoods.org is a great site for finding out where to get different nutrients from foods

IMPORTANT: It’s important that you take responsibility for any supplement or herbal medicine that you take, and check that the product and dose is safe for you to take with any existing conditions, medications, or other supplements.

Meditation

Also has a calming effect on neurotransmitters in the brain, and reduces the effects of stress

References re meditation from PubMed

• Serum hormonal concentrations following transcendental meditation--potential role of gamma aminobutyric acid. Elias AN, Wilson AF. Med Hypotheses. 1995 Apr;44(4):287-91.

• The effects of mind-body training on stress reduction, positive affect, and plasma catecholamines.Jung YH, Kang DH, Jang JH, Park HY, Byun MS, Kwon SJ, Jang GE, Lee US, An SC, Kwon JS. Neurosci Lett. 2010 Jul 26;479(2):138-42. Epub 2010 May 28. Clinical Cognitive Neuroscience Center, Neuroscience Institute, SNU-MRC, Seoul, Republic of Korea

• Yoga Asana sessions increase brain GABA levels: a pilot study.Streeter CC, Jensen JE, Perlmutter RM, Cabral HJ, Tian H, Terhune DB, Ciraulo DA, Renshaw PF. J Altern Complement Med. 2007 May;13(4):419-26. Division of Psychiatry, Boston University School of Medicine, Boston, MA 02118, USA. streeter@bu.edu

Injectable therapies

• Anaesthetic / Diagnostic Nerve Blocks– Procaine– Lignocaine

• Neurolytic Nerve Blocks– Ethanol– Phenol

• Botulinum Toxin• Intrathecal Baclofen• Intrathecal Phenol

InjectionsAdvantages• Not permanent• Evidence to support efficacy in reducing spasticity and improving function• Effects are localized - not systemic

Disadvantages• Not permanent - may need to repeat injections• Ethanol and Phenol: require greater skill to inject, increased risk of

paresthesias, dysesthesias• Botulinum toxin: more expensive than other injections, may develop

antibodies• Only of use in single muscle spasticity• Not appropriate if contracture already present

Botulinum toxin therapy• Naturally occurring substance

produced by bacterium clostridium botulinum

• Powerful neurotoxin (type A)• Blocks release of acetylcholine

at neuromuscular junction• Results in muscle weakness - effect in 4-7 days - peak 4-6 weeks - lasts 3-4 months

Botulinum toxinSide effects• Excessive localised muscle weakness• Flu like symptoms• Fatigue without objective weakness• Dry mouth

Follow up • Must be multi disciplinary • Education • Physiotherapy e.g stretching regime• Splinting / casting• Review goals 4-6 weeks post injection• Medical review 3-4 months

Cannabinoids• Research is mixed, most recent trial, clinical

measures of muscle stiffness did not change• In a 2009 systematic review of RCT trials on

people with MS taking cannabis extracts (THC & CBD) found that 5 out of 6 reported:

• a decrease in spasticity & improved mobility• All reported side effects, related to dosage. • Generally the treatment was well-tolerated.• Study on whether cannabis protects against

progression found it did not. (Cupid)

Cannabinoids

• The cannabinoid medicine Sativex has been licensed and seems to help about 30% of the 30% of people with MS spasms who can tolerate it. As it is so expensive, many PCTs will not fund it.

Cannabis is an illegal drug in the UK, however a study in the Lancet reported lower rates of

harm to health than tobacco or alcohol

Known side-effects of Cannabis• Psychoactive, mildly euphoric ‘high’• Slight changes in psychomotor and cognitive function• Appetite stimulation• Increase in heart rate and decrease in blood pressure• Dry mouth and dizziness• May induce feelings of panic, anxiety and paranoia• Frequent, heavy users may develop an amotivational

syndrome -Baker, Pryce, Givanni & Thompson Neurology (2003)]

Types of cannabis

• There are 3 main types of cannabis• Sativa , Indica and Ruderalis• Sativa is more commonly used for a ‘high’• For body relaxation and muscle spasm,

consensus seems to be to use Indica.• It can be smoked in a joint or pipe, a water pipe,

or inhaled in a vaporiser, or sprayed as tincture• Made into a tea with oil, or a butter

Logistics of using cannabis

• There are many online sites discussing the medical use of marajiauna/cannabis, eg here, making a tincture like Sativex:

• http://patients4medicalmarijuana.wordpress.com/medical-use-of-cannabisvideo/marijuana-tincture

• Excellent article in MS magazine ‘New Pathways’ by a person with MS who uses her home grown cannabis for spasm at http://www.msrc.co.uk/downloads/npwm_2010_0060.pdf

Intrathecal Baclofen (ITB™)

Intrathecal Baclofen

• Surgically implanted pump ( under the skin) delivers tiny doses of baclofen via intrathecal ( into spinal space) catheter

• ITB™ /“Lioresal Intrathecal” administered by programmable infusion system

• Effect 5x greater in legs than in arms• Average dose 300-800 micrograms per day

compared to 30-120 miligrams oral baclofen

Why Intrathecal vs Oral?

• Intrathecal– Lower doses than those required with oral

administration– Potentially fewer systemic side effects

• Oral– Low blood/brain barrier penetration, with high

systemic absorption and low CNS absorption– Lack of preferential spinal cord distribution– Adverse effects, such as drowsiness, for some

patients

Surgical procedures• Invasive. Involves cutting of tendons in bad contractures

– Shouldn’t be necessary if appropriate physical and pharmacological management started early

• Intrathecal pharmacological management requires surgical procedure

• Neuro-surgery and orthopedic surgery can be considered • Advantages

– Effects usually last a few years• Disadvantages

– Anesthesia risks– Non-weight bearing after bony procedures– Risk of weakness, decreased function

Much about MS remains unknown & new theories often emerge… eg

• Will the real multiple sclerosis please stand up?• Peter K. Stys, Gerald W. Zamponi, Jan van Minnen &

Jeroen J. G. Geur• ‘...questions have been raised as to whether

inflammation and/or autoimmunity are really at the root of the disease, and it has been proposed that MS might in fact be a degenerative disorder. We argue that MS may be an 'immunological convolution' between an underlying primary degenerative disorder and the host's aberrant immune response. ..’

• Is multiple sclerosis a mitochondrial disease?Peizhong Maoa and P. Hemachandra Reddya,b

Inflammation and degenerationadapted from Compston A, Coles A. Lancet. 2002;359:1221-1231.

Exciting possibilities

APS therapy

• Based on the function of the cell• Electrically simulates Action Potential• Dr. Lia Van der Plaat in Hull recently having very

positive results with people with MS with pain – but marked improvements in muscle spasm and fatigue also occurred.

• Clinical research project about to start in Hull• MS Therapy Centre in Bedford investing in

machines to pilot therapy clinically

APS therapy logistics• Personal machines cost around £1,200• To be effective, need 3 x treatments of ½ hour

a week, ongoing.• In Hull, clinic delivered a 6 week course• Then helped people to access funding via the

personal health budget scheme• We intended to duplicate this model – but

PHBs not working in our area currently, so will try to help people to access charitable grants.

www.apstherapy.co.nz has good information. Headquarters is www.apstherapy.com

Do everything to stay well now! My favourite info resources for staying well with MS

www.overcomingms.org

www.TerryWahls.com

Stay informed!

• www.mssociety.org.uk/ms-resources/muscle-spasms-and-stiffness-ms-essentials-19

• www.mirandasmsblog.wordpress.com