Multiple Sclerosis (Diagnosis and Management of Current Therapies) Patient Safety William Sonnenberg, MD, Titusville

Transcription

1 Multiple Sclerosis (Diagnosis and Management of Current Therapies) Patient Safety William Sonnenberg, MD, Titusville Disclosures: Speaker discloses that he is on the Speaker s Bureau for Forest Labs. The speaker has attested that his presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices.

2 Multiple Sclerosis William R. Sonnenberg, MD, FAAFP DISCLOSURE The speaker is on the speaker Bureau for Forrest Pharmaceuticals. Risk factors for multiple sclerosis include all of the following except: 1.Childhood high altitude 2.Female 3.Smoking 4.Alcohol 1

3 Most common type of multiple sclerosis is 1.Relapsing remitting 2.Primary progressive 3.Secondary progressive 4.Progressive relapsing Pathognomonic feature of multiple sclerosis are: 1.Optic neuritis 2.Dawson s fingers 3.Tingling 4.Sexual dysfunction Annette Funicello Showed poor balance during, Back to the Beach Went public in 1991 Final years in wheelchair Could not read nor write 2

4 Definition of Multiple Sclerosis Inflammatory demyelinating disease of CNS with: Dissemination in space Dissemination in time ( 3 months) No alternative neurologic disease MS is a clinical diagnosis Epidemiology years of age Women twice as likely Northern Europeans (>90% white) Scandinavian ancestry High socioeconomic status Northern latitude Epidemiology Incidence is increasing in white women 400,000 Americans 2.5 million worldwide 3

5 Those at Less Risk Gypsies Inuit's Native Americans Japanese MS and Latitude Infection and MS EBV seems prerequisite Clinical mono increases risk 13 fold Less childhood infections increases risk 1/3 of relapses preceded by infectious trigger 4

6 Genetics and MS Risk is 1/500 for Caucasians First degree relative 2% 4% <40% concordance rate for identical twins Vitamin D and MS 50 nmol/l increment in 25(OH)D 57% lower rate new lesions 57% lower relapse 25% lower increase in T2 lesion volume 0.41% lower brain volume loss JAMA Neurol. Published online January 20, 2014 Smoking and MS Current and past smokers Risk of progressing from relapsing intermittent to secondary progressive was 3.6 times higher 30% more likely to get MS Hernan, M. Brain, March 9, Miguel A. Hernan, MD, DrPH, department of epidemiology, Harvard School of Public Health, Boston. Nicholas LaRocca, PhD, director of health care delivery and policy research, National MS Society 5

7 Alcohol and MS Epidemiological Investigation of Multiple Sclerosis (EIMS) Heavy drinkers OR 0.6 women OR 0.5 men Seemed to attenuate effects of smoking Anna Karin Hedström, MD et al. Alcohol as a Modifiable Lifestyle Factor Affecting Multiple Sclerosis Risk. JAMA Neurology, January 2014 Oral Contraceptives 305 women, ages with MS compared to 3050 matched controls 30% increased risk with at least 3 months use Kaiser Permanente, Feb 2014 MS Subtypes Asymptomatic Symptomatic Relapsing remitting (85% at onset) Primary progressive (10%) Secondary Progressive (transitional form) Progressive Relapsing (5%) Lublin F, et al Neurology

8 MS Subtypes Primary Progressive 10% 15% Men = women Older age Late 30 s early 40 s Slowly worsening spinal cord syndrome effecting walking White Matter Disease White Matter Vision Motor skills Sensory skills Gray Matter Dementia Seizure Movement disorder 7

9 Demyelination Conduction block at lesion site Slow conduction on affected nerve Fatigue due to compensation of slow conduction Myelin can regenerate, resulting in remission Symptoms Suggestive of MS Blurred or double vision Lhermitte s sign Fatigue Heat sensitivity Bladder symptoms Depression Numbness, tingling, pain Lhermitte s Sign Barber chair sign Electrical sensation running down back and limbs with neck flexion Not unique to MS Transverse myelitis, trauma, radiation SSRI discontinuation 8

10 Signs of MS Action tremor perception of pain, vibration, position strength Hyperreflexia, spasticity, Babinski s sign Impaired coordination and balance Visual Symptoms Blurred or double vision Impaired acuity Impaired red color perception Optic disc pallor Afferent pupil defect Disconjugate eye movements Nystagmus Emotional Manifestations Anger Depression Euphoria Decreased executive functions 9

11 Neurologic Exam Attention, psychomotor slowing Cranial nerves Visual acuity, fundus, fields, EOM Reflexes Babinski, asymmetry Sensory Gait 25 timed walk Bladder PVR Right Internuclear Ophthalmoplegia Medial longitudinal fasciculus Optic Neuritis 10

12 Optic Neuritis 15 20% presenting feature Occurs 50% at some time during disease course 31% recur in 10 years 10 year follow up, 38% get MS after optic neuritis Laura J. Balcer, M.D., M.S.C.E. N Engl J Med 2006; 354: Symptoms Monocular vision loss, central Color desaturation, especially red Improves within 2 weeks Subtle symptoms persist Never seems right Washed out, blurred Findings Afferent pupillary defect Impaired visual acuity Impaired color vision 11

13 Afferent Pupillary Defect Optic disc in MS Balcer LJ. N Engl J Med 2006;354: Optic Neuritis MRI 12

14 MS Studies MRI in Multiple Sclerosis Most useful confirmatory test, 98% sensitive High signal in white matter or spinal cord on T 2 weighted images Abnormal in almost all MS patients with symptoms 13

15 MRI Brain Lesions for MS High signal on T2 weighted and FLAIR MRI sequences (>9 lesions) When actively inflamed, often enhanced with gadolinium contrast Abuts ventricles (often perpendicular) Juxtacortical position (gray white junction) Involvement of brainstem, cerebellum, or corpus callosum T1 Weighted Images Black holes permanent axonal damage FLAIR MRI Fluid attenuation inversion recovery Digitally subtract out water Most sensitive for MS Not specific for demyelination 14

16 Dawson s Fingers Pathognomonic T 2 Weighted Images Spinal MRI Images 15

17 MRI Progression Sensory Evoked Potential Visual most useful Subclinical lesions in sensory pathways Visual Evoked Potentials 16

18 CSF Analysis Increased IgG concentration Oligoclonal bands not matching serum bands Oligoclonal Bands in CSF Red Flags for Misdiagnosis of MS MRI changes without clinical correlate Known psychiatric disease Normal neurologic examination Atypical clinical features Disease onset at the extremes of age Extraneural systemic disease Prominent gray matter symptoms 17

19 Serologic Testing B 12, TSH, ESR B 12 tends to mimic disease and is low in disease ANA Lyme titer Syphilis, HIV Management of Multiple Sclerosis Treatment Goals No cure Treat relapses Prevent relapses Treat chronic progression 18

20 Acute Exacerbations IV or PO methylprednisolone for 5 days, no taper Anti inflammatory, restores blood brain barrier, reduces edema Shorten duration, accelerate recover Long term benefit unsure Options for Acute Attacks Plasmaphoreisis Immunoglobulin Disease Modifying Meds First Line Interferon 1a Interferon 1b Glatiramer Fingolimod Second Line Natalizumab Mitoxantrone Teriflunomide Dimethyl fumarate 19

21 Immunomodulation Start ASAP after diagnosis of MS with relapsing course Consider after first attack with high risk β Interferons 1/3 reduction of relapses 50 80% reduction in inflammatory lesions on MRI May improve quality of life and cognitive function Avonex, Betaseron, Rebif β Interferons Side Effects Lump at injection site or necrosis Flu like illness 60% Depression, suicidal ideation Neutralizing antibodies 40% Effect is variable 20

22 Glatiramer (Copaxone) Mimic and compete with myelin basic protein SQ once daily relapses by 1/3 inflammation on MRI by 1/3 Glatiramer Panic attacks Chest tightness, Palpitations, Anxiety, Dyspnea Nausea Fingolimod (Gilenya) Fungal derived, sequester lymphocytes in lymph nodes First PO med relapses by ½ 21

23 Fingolimod (Gilenya) Bradycardia EKG monitor before and 6 hours after first dose Vitals hourly Macular edema Basal skin cancer Natalizumab Second Line Monoclonal antibody Monthly IV infusion Progressive multifocal leukoencephalopathy Over 130 cases in MS patients Mitoxantrone Second Line Antineoplastic Irreversible cardiomyopathy in 25% 10% decrease in ejection fraction 22

24 Vitamin D Recommended Doses not determined ,000 IU/day 10 nmol/l increases reduces relapse by 12% 50 nmol/l reduces relapse frequency by 50% Symptom Control Adaptive Equipment Cups with lids Scoop dishes Utensils for eating Elastic shoe laces Reachers Communication keyboards Braces, walkers, wheelchairs, splints 23

25 Spasticity Water therapy, yoga, PT TENS unit Botox Meds Baclofen Tiranidine gabapentin Bladder Dysfunction Rule out infection Oxybutrin or tolterodine for failure to store urine Alpha blockers for urinary retention Sexual Symptoms arousal, sensation, orgasms PDE 5 inhibitors Lubricants Foreplay 24

26 Depression SSRI s Amitriptyline Headache Pain syndromes Fatigue Energy conservation Vitamin D Sleep hygiene Amantadine Modafinil SSRI s Pain Acupuncture Manipulation Tricyclics 25

27 Prognosis Most early cases remitting relapsing Most get secondary progressive in 6 10 years Unaffected by Rx Lifespan not affected 33% can live independently 33% have severe disability Disease course > 30 years Favorable Prognosis Female Low relapses/year Complete recovery after first attack Long interval between first and second attack Low disability at 2 5 years Favorable Prognosis Sensory symptoms Younger age at onset Later cerebellar involvement Involvement of only one CNS system at onset 26

28 Summary Clinical diagnosis MRI supports diagnosis LPs for other diseases No cure Treatment is symptomatic and for tertiary prevention Corticosteroids for acute exacerbations Team approach Risk factors for multiple sclerosis include all of the following except: 1.Childhood high altitude 2.Female 3.Smoking 4.Alcohol Most common type of multiple sclerosis is 1.Relapsing remitting 2.Primary progressive 3.Secondary progressive 4.Progressive relapsing 27

29 Pathognomonic feature of multiple sclerosis are: 1.Optic neuritis 2.Dawson s fingers 3.Tingling 4.Sexual dysfunction Patient Support National MS Society Consortium of MS Centers Multiple Sclerosis Association of America Paralyzed Veterans of America VA MS Centers of Excellence (East & West) 28