Pain in MS
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Lecture given to the West of Scotland Pain Group on 27th February 2013 by Consultant Neurologist Dr Colin O'Leary on the clinical features of multiple sclerosis and management of MS pain and spasticity.
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Pain in MS
- 1. Multiple Sclerosis: Management of pain and other symptoms Colin O’Leary Neurologist Institute of Neurological Sciences Southern General Hospital Glasgow
- 2. Robert Carswell (1793-1857) Jean Martin Charcot (1825-1893) c.1838
- 3. Multiple sclerosis defined • A chronic disease of the brain and spinal cord characterised by changes in sensation, visual problems, weakness, depression, difficulties with coordination and speech, impaired mobility and disability • An autoimmune condition in which the immune system attacks the central nervous system, leading to demyelination • A disease of the central nervous system that is an unpredictable condition that can be relatively benign, disabling, or devastating, leaving the patient unable to speak, walk, or write
- 4. Who gets MS 30
- 5. WHO Atlas of MS, 2008
- 6. Source: HES, NHS (England)
- 9. COMMON • Fatigue • Paraesthesias • Weakness • Optic neuritis • Ataxia • Transverse myelitis • Brainstem syndrome • Multiple
- 10. What is an MS relapse (attack)? • Subacute or insidious onset • Appearance of new symptom(s)/ reappearance of old symptoms • Symptom(s) last at least 24 hours − Usually days to weeks • Gradual recovery to pre-relapse state • Possible residual deficit • May take up to 6(+) months for recovery • Pseudo-relapse – due to other stressor eg infection, heat
- 11. MS diagnosis CSF Serum
- 12. 3/12
- 14. Course of MS 80 % 70 %
- 15. MS Variability • Variable presentation • Variable course − Relapsing – variable frequency / severity − Progressive • Variable progression • Variable symptoms
- 16. Treatment of MS • Relapses • Symptoms • Disease process − disease-modifying therapies
- 17. Treatment of Relapses • ? need treating − severity − duration − previous response − frequency − no effect on eventual outcome − is it really a relapse? – cave pseudo-relapse • High dose steroids • Apharesis, Immunoglobulin
- 18. Steroids - Dose & Route • Oral prednisolone only - ?efficacy • Intravenous steroids − Methylprednisolone 1g daily for 3 days − ? tapering course of oral steroids • Oral methylprednisolone − 500mg daily for five days − ? GI protection − Insomnia, dysphoria common
- 19. Steroids for MS relapses CONS PROS Click to edit the • Psychosis format outline text • Speeds recovery • Weight gain • Reduces deficit Second Outline • Fluid retention Level • Reduces spasticity • Immunosuppression − Third Outline • Euphoriant • GI irritation Level − ?protection Fourth (H2blocker) Outline • HirsutismLevel • Aseptic necrosis − Fifth
- 20. Symptom Management • Fatigue • Motor • Sensory • Visual • Cranio-bulbar • Autonomic • Psychological • Others
- 21. Fatigue • ~25% patients - worst symptom • 75% patients - among top 3 symptoms • Associated with − need to rest − loss of patience − loss of motivation − worsening of other symptoms • Invisible symptom
- 22. Fatigue Exacerbated by Alleviated by Click to edit the outline text format • Physical activity • Resting Second Outline • Stress • Sleeping Level • Depression • Positive − Third Outline • Afternoon experience Level • Heat Fourth Outline Level − Fifth
- 23. Level − Eighth Fatigue Management Outline Level • Non • Ninth Outline LevelClick to Pharmacological pharmacological edit Master text styles Click to edit the outline text • Amantadine outline text Click to edit the • Behavioural therapy / format − 100mg mane BD format modification • Modafinil Second Outline Level Second Outline Level • Graded exercise − Third Outline Level 100-200mg mane − − Third Outline Level programs BD Fourth Outline Fourth Outline no later than lunchtime • Psychotherapy Level Level • Emotional support − Fifth Outline Others – − Fifth Outline • Level Avoid exacerbating Level − Sixth Outline − SSRIs − factors Sixth Outline Level − SelegilineLevel 5-15mg − Seventh daily − Seventh
- 24. Motor • Weakness - 60-70% • Spasticity - 90% • Tremor • Ataxia
- 25. Spasticity - oral medication • Baclofen − 15 - 120mg daily in divided doses – usually TID − weakness, sedation, bladder disturbance • Tizanidine − 8 - 36mg daily in divided doses – usually QID − start at 2mg − less weakness, better tolerated − hepatotoxicity – check LFTS at baseline and 4/52 after starting • Others − Benzodiazepines • Clonazepam - useful for spasms – nocte (0.5 - 2mg) − Dantrolene − Gabapentin
- 26. Spasticity - overview • Drugs − Start low-dose / increase slowly − NB weakness/dependence on spasticity • Physiotherapy • Treat / remove trigger factors − bladder & bowel dysfunction − infection − limb positioning • Nerve blocks, surgery − Motor point blocks – phenol, botulinum toxin − Intra-thecal – baclofen, phenol
- 27. Other Motor Weakness Click to edit the − Fampridine (Fampyra®) • 4-aminopyridine outline text format Second Outline Tremor Level − Clonazepam − Gabapentin − Third Outline − Propranolol Level − Isoniazid (+ pyridoxine) − Ondansetron Fourth − DBS (deep brain stimulation) Outline Level
- 28. Sensory • Negative − Loss of sensation, numbness • Positive − Pins and needles, burning etc • Paroxysmal − Lhermitte's phenomenon − Trigeminal neuralgia − Puritus
- 29. Level − Eighth Visual Outline Level Ninth Outline LevelClick to • Optic neuritis • Ocular motility edit Master text styles Click to edit the outline text disorders the outline text Click to edit format format Second Outline Level Second Outline Level − Third Outline Level − Third Outline Level Fourth Outline Fourth Outline Level Level − Fifth Outline − Fifth Outline 60% painful Level Oscillopsia - ? gabapentin Level ?steroids − Sixth Outline memantine Outline − Sixth Level Level − Seventh − Seventh
- 30. Bladder • Common, affects 75%, persistent in 50% • Correlates with pyramidal / spinal involvement • ‘Failure to store’ > ‘failure to empty’ • Maybe combined problems • Exacerbated by urinary sepsis − can be silent Check residual - >100ml risk of retention with anti-cholinergic meds
- 31. Bladder treatment Failure to store Failure to empty Urgency, frequency, nocturia, urge Click to edit the Hesitancy, retention, urgency, frequency incontinence outline text format • Treatment • Second Treatment Outline exclude exacerbating drugs e.g. Level − − fluid management − avoid caffeine anticholinergics, antidepressants, baclofen − − double voiding treat infection − CISC − Third Outline • Drugs • Level Clean intermittent self-catheterisation − anticholinergics • e.g. oxybutynin, teroldoline, Fourth propiverine, trospium, solifenacin, imipramine Outline − nocturia – desmopressin • (desmotabs 200mcg nocte) Level − Fifth
- 32. Bowel • 68 % of MS patients − 51% faecal incontinence ~ constipation − 43% constipation • Treatment − exclude exacerbating drugs • opiates, anti-cholinergics, anti-depressants − reduce caffeine − high roughage diet − laxatives and bulking agents
- 33. Sexual dysfunction MALE FEMALE • 60% • Click 50% to edit the • Erectile dysfunction • Problems text format outline − counselling − failure of lubrication − sildenafil 50 -100 mg − Second anorgasmia Outline • tardalafil, verdanafil − intra-urethral / intra-corporeal − Level loss of / altered sensation prostaglandin or papaverine • Treatment − Third Outline − prostheses − counselling − Level lubricants • Ejaculatory dysfunction − Fourth mechanical devices − ? sildenafil − ? sildenafil Outline Level − Fifth
- 34. Bulbar • Dysphagia - late feature ~ disability • Dysarthria - frequent, mild, fatigable, spastic - ataxic • Treatment − speech therapy − alternative nutritional routes e.g. PEG • Vertigo − usually transient, try labyrinthine sedatives
- 35. Psychological Thymic disturbances Cognitive Memory problems the Click to edit • Depression • • • 25 - 55% outline text format − frequent, early, undiagnosed common early in disease − poor recall of recently acquired information • suicide rate 2-3% Second Outline • amitriptyline, SSRIs − affects management • psychotherapy • Level Impaired concentration − related to fatigue / stress − Third Outline • Dementia Euphoria Level • − late feature • late feature; rare Treatments Fourth • • advanced disease • no treatment − aide memoirs − family andOutline group therapies − Level anticholinergic drugs − Fifth
- 36. Pain in MS ~50% chronic pain ~55% significant pain ever • RFs − F:M 2:1 − Not related to • Age of onset • Duration of disease • Level of disability
- 37. Pain types in MS pins and needles Neuropathic burning Nociceptive Click to edit the tightness − Paraesthesias numbness outline text formatpain) (musculoskeletal prickling − Dysaethesias dull ache Spasticity − − Allodynia itching Second Outline − Spasms and cramp crawling nagging LevelMechanical back pain − − Third Outline Trigeminal neuralgia • Level Others Optic neuritis − Asepticnecrosis Fourth − Constipation ‘MS hug’ Outline − UTI Lhermitte’s sign Level − Pressure areas Pruritus − Fifth
- 38. Pain – Exacerbating Factors Heat – Uhthoff’s phenomenon Cold Poor sleep Fatigue Mobility problems Feelings of low self-esteem Loneliness or isolation Depression Anxiety
- 39. Level − Eighth MS Pain - Pharmacology Outline Level • 1st line • 2nd line Ninth Outline LevelClick to • Anti-convulsants edit Master text styles • Amitriptyline − Lamotrigine Click to edit the outline text Click to edit the outline text − Levetiracetam − Nortriptyline, format − Valproate format − Phenytoin imipramine Second Outline Level Second Outline Level • PregabalinOutline Level − Third / • Anti-depressants − Third Outline Level − Venlafaxine Gabapentin Outline Fourth − Dosulepin Fourth Outline − SSRIs • Carbamazepine Level Others Level Fifth Outline − − Opiates − Fifth Outline Level • Level Codeine, DHC, Tramadol, MST, Fentanyl DuloxetineSixth Outline Local anaesthetics − • − − Sixth Outline − Capsaicin Level − Cannabinoids Level − Seventh − Baclofen − Seventh
- 40. Cannabis • Claimed to improve − painful symptoms − spasticity − fatigue − vertigo − sexual function • ? purely euphoriant / dissociative effect • Sativex® – oral cannabinoid spray − tetrahydrocannabinol (THC) and cannabidiol (CBD) − named patient basis only (IPTR) − licensed as add-on therapy for MS spasticity only • Other cannabinoids − nabilone - used in anaesthesia for nausea
- 41. Principles of MS pain management • Adequate − duration, dose, adherence • Avoid exacerbating co-existing symptoms − e.g. fatigue, bladder, constipation, cognition • Dual effect • Avoid polypharmacy • Consider alternative therapies • Consider alternative diagnoses
- 42. Level − Eighth Pain Management in MS – other Outline Level RxNinth Outline LevelClick to • Non- • Complementary edit Master text styles pharmacological text Click to edit the outline therapies the outline text Click to edit • cognitive behavioural • TENS format format therapy • Second Outline Level Neuromodulatory • distraction Outline Level Second techniques devices Outline Level − Third • magnetic therapy Level − Third Outline spinal Fourth Outline Fourth Outline − • mindfulness Level Level − intracranial, − Fifth Outline • reiki − Fifth Outline peripheralLevel • relaxation techniques Level − Sixth Outline • − Sixth Outline visualisation techniques Level Level • yoga − Seventh − Seventh
- 43. Symptomatic Rx - overview • Breakdown symptoms − ? interactions − cave cognition • Consider referral - ? neurology − PAMS • MS Specialist Nurse • Physio, SALT, OT − Rehab Services • Community Disability Teams − Voluntary sector • ‘Revive Scotland’ − Continence services, Sexual Dysfunction clinics − Pain Clinic − Psychology, psychiatry − Ophthalmology
Editor's Notes
- Robert Carswell was born in Paisley in 1793 and studied medicine at the University of Glasgow. His drawing skills were evident as a student and this ability brought him to the notice of Dr. James Thomson of Edinburgh, one of the foremost physicians of the day. Thomson employed Carswell to make a collection of anatomical drawings for his lectures on the practice of physic. To this end, Carswell went to France in 1822, spending two years working in hospitals in Paris and Lyons. He returned to Scotland and took his degree of MD at Marischal College, Aberdeen, in 1826. He then returned to Paris and resumed his studies in morbid anatomy under the celebrated physician Pierre C.A. Louis. At this time, Paris was a centre of brilliance for pathological research; anatomical lectures were conducted in large amphitheatres with easily obtained admission while, crucially, there was a good supply of cadavers to be obtained from state-run hospitals. One of Carswell's most celebrated achievements was being the first to portray the plaques of multiple sclerosis, although he did not identify them as such. Illustrated here in the section on atrophy is 'a peculiar diseased state of the chord and pons Varolii, accompanied with atrophy of the discoloured portions ... the atrophy was more conspicuous in some points than in others, and is particularly well seen in the figure at H, where it affects a portion of the right olivary body'. Carswell notes in the introductory section that 'I have met with two cases of a remarkable lesion of the spinal cord accompanied with atrophy. One of the patients was under the care of Mons. Louis in the Hospital of La Pitié, the other under the care of Mons. Chomel, in the Hospital of La Charité, both of them affected with paralysis. I did not see either of the patients, but I could not ascertain that there was anything in the character of the paralysis or the history of the cases calculated to throw any light on the nature of the lesion found in the spinal cord'. Although unaware of their cause, Carswell meticulously recorded these strange lesions; their distinctive patterns show a specific damaging of the spinal cord and clearly identify them as multiple-sclerosis lesions.
- Hospital Episode Statistics (HES) is a data warehouse containing details of all admissions to NHS hospitals in England. It includes private patients treated in NHS hospitals, patients who were resident outside of England and care delivered by treatment centres (including those in the independent sector) funded by the NHS. HES also contains details of all NHS outpatient appointments in England. The main unit of recording is the Finished Consultant Episode (a period of admitted patient care under a consultant or allied healthcare professional within an NHS trust). This is not always the same as a single stay (spell) in hospital, because a patient may be transferred from one consultant to another during their stay. In these cases, there will be two or more episode records for the spell of treatment.
- Pathogenesis of MS lesion T-cell activated in peripheral blood by antigen presenting cell (APC) Activated T-cell adhere to endothelial cells and transmigrates blood-brain barrier (BBB) – process is matrix metalloprotease-dependent (MMP) {MMPs neurotoxic} T-cells proliferate in CNS recruiting and activating B-cells, microglia and circulating macrophages T-cells, microglia and macrophages release cytotoxic (neurotoxic) cytokines – Il-1, TNF, and IFN (& MMPs) B-cells produce antibodies facilitating antibody-dependent cellular cytotoxicity (ADCC) – complement cascade ending in membrane attack complex (MAC)
- Suspension apparatus used at the salpetriere for ataxia. MS in Focus, Issue 13, page 6, 2009