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Symptomatic treatments Workshop - 17 Nov 2012

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  • 1. Symptomatic treatmentsCelia Oreja-Guevara & Gavin Giovannoni
  • 2. The importance of considering MS-related symptoms • 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 lackingde Sá JCC, et al. Ther Adv Neurol Disord 2011; 4:139–168.
  • 3. Co-morbidities and MS-related symptoms
  • 4. Prevalence of co-morbidities and associated symptoms in patients with MS 100 90 90 90 90 85 80 80 80 75 75 68 70 65Patients (%) 60 50 50 40 32 30 25 20 20 10 5.4 0a32% of ataxia will be severe enough to decrease functional abilities.bMortality 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.
  • 5. Sexual Balance Restless Emotional Advanced Fertility Pregnancy Bladder dysfunction problems legs Tremor Insomnia lability Directive Breast Feeding Oscillopsia Vaccination Studying Bowel Gait Falls Spasticity Cognition Seizures Employment Swallowing PainRelationships Clinical trials Vision Travel Counselling Fatigue Pressure Driving sores Research Depression Exercise Occupational Nurse Rehab Therapy Anxiety specialists Diet Insurance Maintenance Escalation Induction Family Physio- counselling therapy Side Effects Speech Alternative Risks therapy Palliative Care Medicine 2nd line Adverse Suprapubic DMTs 1st line events catheter Genetics Intrathecal Family Disease baclofern Legal aid counselling Smoking progression Lumbar Evoked Tendonotomy Social puncture Potentials Disease-free services Epstein Bar Virus Colostomy Monitoring Differential Gastrostomy Vitamin D Diagnosis Relapses Functional Assisted neurosurgery suicide Diagnostic Criteria Blood MRI Tests Prevention DMT Terminal Diagnosis Symptomatic Therapist Counselling
  • 6. Effects of MS-related symptoms on QoL Single-factor model tested using confirmatory Measures of physical and psychological domains of QoL factor analysis for establishing the symptom cluster based on mild, moderate or severe clusters of symptoms Mild (n=35) Moderate (n=52) Severe (n=46) 100 Mean ± standard error Symptom cluster 75 50 .55 .63 .61 .71 FSS CES-D MPQ PDQ 25 Perceived 0 Depressio Fatigue n Pain cognitive Physical Psychological complaints MSIS-29 subs scale • The subgroup with mild symptoms had the highest QoL, whereas the subgroup with severe symptoms had the lowest QoLMSIS-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.
  • 7. Burden of MS-related symptoms on caregivers Scores of SF-36 dimensions of caregivers 100 80.2 81.9 80 77.5 70.7 65.5 65.6 59.3 62.3 60 Mean 40 20 0 General Mental Bodily Pain Role-emotional Social Vitality Role-physical Physical Health Health Functioning Functioning Functioning Functioning • Gender (female), caregiver co-morbidities, age of the caregiver and EDSS score were the main predictors of caregiver HRQoLRivera-Navarro J, et al. Mult Scler 2009; 15:1347–1355.
  • 8. Open discussion• Discuss your experiences of diagnosing co-morbidities and MS-related symptoms
  • 9. Therapies and unmet needs in symptomatic management
  • 10. MS-related symptom treatment Symptom Recommended/licensed Baclofen Tizanidine Spasticity1 Intrathecal baclofen (for EDSS > 7) THC-CBD (Sativex) Pain Carbamazepine (stronger evidence) trigeminal neuralgia2 Oxcarbazepine (better tolerability) Walking impairment Slow release 4-aminopyridine (fampridine)1. de Sá JCC, et al. Ther Adv Neurol Disord 2011; 4:139–168 (the medications listed here have onlybeen investigated for the treatment of MS-related symptoms in experimental settings and sometimesnot even in patients with MS. Their inclusion in this table and the broader manuscript should not betaken 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.
  • 11. Pharmacological agents used in treating MS-related symptoms with limited efficacy Symptom Pharmacological agents with limited evidence of efficacy Dantrolene, tolperisone, benzodiazepines, gabapentin, tetrahydrocannabinol, botulinum Spasticity 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 Antimuscarinic compoundsf,g, alpha blocking agentsg, antispasticity agentsg, Neurotoxin, botulinum dysfunction/combined toxin Ah, cannabinoidsh Bowel dysfunction Laxatives Tremor and ataxia Isoniazid, carbamazepine, topiramate Oculomotor Memantine, gabapentina without sleepiness, b fatigue with sleepiness, c erectile dysfunction, d vaginal dryness, e low libido,fused for urinary storage, g used in emptying dysfunction, h used in combined dysfunctionde Sá JCC, et al. Ther Adv Neurol Disord 2011; 4:139–168 (the medications listed here have onlybeen investigated for the treatment of MS-related symptoms in experimental settings and sometimesnot even in patients with MS. Their inclusion in this table and the broader manuscript should not betaken to imply that the authors are in any way recommending they be used in the clinical setting).
  • 12. Alternative therapies used in treating MS-related symptoms Symptom Other interventions Spasticity Physiotherapy, cooling therapy and hydrotherapy Thermocoagulation, glycerol instillation, gamma knife radiosurgery, neuroablative Pain (trigeminal neuralgia) procedures, microvascular decompression Physiotherapy, yoga, cooling therapy, aerobic exercise, energy conservation, coping Fatigue 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 Incontinence padsa,b, clean intermittent self-catheterizationb, ileovesicostomyb, permanent dysfunction/combined 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 year3aUrine 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 sometimesnot 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 anyway recommending they be used in the clinical setting).
  • 13. Improving outcomes in patients with MS: unmet needs in symptomatic management Area for Area for Area for development development development Personalized Commitment to More therapy options care research Affording patients psychological and Widen the focus of research to Research across all domains is key social support as part of their ensure the continuous development of for a better understanding of disease treatment package better therapy options mechanisms Ensure greater access to Diverse therapies and strategies comprehensive care regimens that needed to address the complexity of include symptomatic care, MS symptoms and challenges rehabilitation and psychological support New approaches incorporating a wide range of pharmacological and non- pharmacological strategies need to be developedRieckmann et al., J Neurol 2012 (Epub ahead of print).
  • 14. Open discussion• Discuss case scenarios – Spasticity – Fatigue – Depression
  • 15. Case scenario: spasticity• 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?
  • 16. Case scenario: fatigue• 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?
  • 17. Case scenario: depression• 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?
  • 18. Sexual Balance Restless Emotional Advanced Fertility Pregnancy Bladder dysfunction problems legs Tremor Insomnia lability Directive Breast Feeding Oscillopsia Vaccination Studying Bowel Gait Falls Spasticity Cognition Seizures Employment Swallowing PainRelationships Clinical trials Vision Travel Counselling Fatigue Pressure Driving sores Research Depression Exercise Occupational Nurse Rehab Therapy Anxiety specialists Diet Insurance Maintenance Escalation Induction Family Physio- counselling therapy Side Effects Speech Alternative Risks therapy Palliative Care Medicine 2nd line Adverse Suprapubic DMTs 1st line events catheter Genetics Intrathecal Family Disease baclofern Legal aid counselling Smoking progression Lumbar Evoked Tendonotomy Social puncture Potentials Disease-free services Epstein Bar Virus Colostomy Monitoring Differential Gastrostomy Vitamin D Diagnosis Relapses Functional Assisted neurosurgery suicide Diagnostic Criteria Blood MRI Tests Prevention DMT Terminal Diagnosis Symptomatic Therapist Counselling