Multiple Sclerosis Presentation Bahrain 2023 PDF

MULTIPLE SCLEROSIS CONCEPTS AND UPDATE ON MANAGEMENT Dr. Ali Jaffer Al-Hilly M.B.Ch.B MRCP(UK) SCE(Neurology),FEBN 2023  OUTLINES Definition. Etiology-pathogenesis Burden. Diagnosis Treatment. Future. ...

MULTIPLE SCLEROSIS CONCEPTS AND UPDATE ON MANAGEMENT Dr. Ali Jaffer Al-Hilly M.B.Ch.B MRCP(UK) SCE(Neurology),FEBN 2023  OUTLINES Definition. Etiology-pathogenesis Burden. Diagnosis Treatment. Future.  DEFINITION Multiple Sclerosis is autoimmune inflammatory disorder of the CNS ,of unknown aetiology, characterized by demyelination and axonal loss  Age 20-40. Female:Male is 1.5-3:1 Number two disabling disease in the USA. BURDEN AND 2.8 millions are affected world-wide(under- EPIDEMIOLOGY estimate). Cost 9000-50000 USD per patient per year. High rate of unemployment as disease progress UNEMPLOYMENT RATE IN MS PATIENTS  ETIOLOGY Multifactorial. Interplay of : Genetics-Infection-Geography- Climate-Environmental-Nutrition-Smoking GEOGRAPHY AND CLIMATE Increased prevalence away from equator. Exceptions are many Critical migration age is 14-15 Born on November less affected than those born on May. GEOGRAPHICAL DISTRIBUTION  GENETICS Susceptibility and protective genes some are about HLA. Monozygotic twins 30 percent concordance. Dizygotic twins only 5 percent. Non twins siblings' 2.5 percent. Treatment response genes ??? Genotype phenotype relation ??? EPSTEIN VIRUS INFECTION EB VIRUS MECHANISM EB VIRUS CRTICAL POINTS Should acquire the infection at critical time in genetically susceptible person  Vitamin D is immune modulator and gene regulator Vitamin D supplement is mandatory in MS patient in most experts’ opinions. VITAMIN D High doses vitamin D was found safe in AND certain trials although not universally accepted. MULTIPLE Studies confirmed the relationship between SCLEROSIS low vitamin D level and increasing lesion load and disability progression. Vitamin D found to be protective for CIS patient in some studies. IMMUNE-PATHOGENESIS IN MS Characterised by an imbalance between immunoregulatory and Proinflammatory immune cells PATHOLOGY Start peripherally then reside centrally and shut the BBB and start the destruction  POST MORTEM MS BRAIN  MS causes more extensive demyelination of the grey matter than white matter in the brain GREY MATTER DEMYELIN ATION IN MS  MS PLAQUES OCCUR AROUND VEINS IN THE BRAIN AND CONTAIN BOTH LYMPHOCYTES AND MACROPHAGES MS RESULTS IN DEMYELINATI ON OF BOTH THE BRAIN AND SPINAL CORD CLINICAL PRESENTATION  OPTIC NEURITIS Unilateral visual loss Red vision affected first Pain on eye movement Pain typically does not last more than two weeks RAPD Signs in optic neuritis RAPD Acute signs in optic neuritis: Optic disc swelling Chronic signs in optic neuritis: optic disc pallor  BRAIN STEM/CEREBELLAR Facial palsy Ataxia Diplopia Trigeminal neuralgia  Signs in brain stem syndrome Nystagmus INO Signs in brain stem syndrome INO  Signs in brain stem syndrome One-and-a-half syndrome  Signs in brain stem syndrome Ataxia  SYMPTOMS - SPINAL CORD Lhermitte’s symptom Numbness Urinary urgency Faecal incontinence Sexual dysfunction Spastic paraplegia  SIGNS IN SPINAL CORD SYNDROME Weakness Increased tone +/- clonus Brisk reflexes Upgoing plantar response  SIGNS IN SPINAL CORD SYNDROME Acute transverse myelitis in MS is usually partial Uncommon, to involve more than 3 adjacent segments of the cords (LETM) Brown Sequard syndrome is one of the manifestation  SYMPTOMS CEREBRAL HEMISPHERES Cognitive impairement Hemiparesis Seizures Encephalopathy Signs in cerebral hemisphere syndrome  ACUTE ATTACK Usually more than 24 hours Subacute presentation. Optic neuritis, acute transverse myelitis, brainstem and cerebellar syndromes, and pyramidal syndromes. COURSE OF MS TYPES OF MULTIPLE SCLEROSIS  DIAGNOSIS No diagnostic test McDonald criteria 2017. Clinical + MRI + Ancillary tests. Exclusion of MS mimics (vasculitis, autoimmune disease, vitamin b12 deficiency and NMOSD) Essence is the Dissemination in time and dissemination in space with no better explanation of the patient clinical presentation.  MRI MCP lesion 40-year-old female with right facial numbness Subcortical lesion  MRI 20 year old female with optic neuritis Dawson fingers Corpus callosum involvement. MRI MRI 2017 MC DONALDS CRITERIA MCDONALD'S CRITERIA MC DONALD'S CRITERIA  SECONDARY PROGRESSIVE MS A progressive myelopathy Onset begins when walking distance is restricted to approximately 500m Symptoms include ambulatory dysfunction (stick/wheelchair), urinary dysfunction (catheter), pain, depression, fatigue May experience relapses A clinical diagnosis – no confirmatory tests for diagnosis of SPMS Available treatment Siponimod  SPMS ‘Active’ with or without progression ‘Inactive’ with or without progression Based on relapses and MRI activity  PRIMARY PROGRESSIVE MS Accounts for 15% of cases of MS Progressive myelopathy Begins later in life – mean age onset in 50s Disability accumulates quicker Approximately 10% of cases may have superimposed relapses Male: female ratio closer to 1:1 Only approved treatment so far is Ocrelizumab  PPMS ‘Active’ with or without progression ‘Inactive’ with or without progression Based on relapses and MRI activity  DIAGNOSIS OF PPMS One year of disease progression (retrospectively or prospectively confirmed) Plus 2 of 3 of the following: 1. Evidence of DIS on brain MRI 2. Evidence of DIS in the cord based on ≥2 T2 lesions in the cord 3. Positive unmatched OCBs in the CSF DIS = dissemination in space  CIS & RIS Clinically Isolated Syndrome (CIS) is the first episode of demyelination (ON, TM...etc.) The conversion from CIS to CDMS is 60 percent in 2 years and 80 percent in 20 years. Radiologically Isolated Syndrome(RIS) is the presence of MS suggesting MRI findings in clinically asymptomatic patient (MRI usually done for another reason). Two thirds of RIS will progress radiologically in 5 years and one third will develop symptoms in 3-5 years suggestive of CIS or CDMS.  PROGNOSIS 40-50 percent are 75-90 percent will wheelchair bound be disabled and after 10 years of dependent by 25 diagnosis with years from RRMS. diagnosis of RRMS. MS PROGRESSION  TREATMENT 1. Acute Attack: Methylprednisolone 5 day course +/- plasma exchange 2. Maintenance : Disease specific. Symptomatic  DISEASE SPECIFIC TREATMENT Strategies Wait and see. Hit early. Shift early. Hit strong from the start.  WAIT AND SEE Waiting what? More lesions. More inflammation. Get closer to the turning point TIME –LAPSE 1 YEAR MRI OF PATIENT WITH ASYMPTOMATIC MS 2007  HIT EARLY Five phase III trials showed that there is clear cut benefit from treating patient at the First Clinical Demyelinating Event. Delaying the second attack. Delaying the transformation into Clinically Definite MS. Delaying the turning point  SHIFT EARLY The concept of (no evidence of disease activity). The so-called NEDA-4. NEDA-4 indicates: 1. No new or enlarging T2 lesion. 2. No confirmed clinical relapses. 3. No 6 months disability progression. 4. Annual brain atrophy rate below 0.4%.  HIT STRONG FROM THE START Which patient to treat aggressively. Patient phenotypes. Benign Vs malignant MS. Lack of bio-markers  TREATMENT Disease Symptomatic specific  SYMPTOMATIC Spasticity: baclofen, tizanidine, dantrolene, gabapentin, botulinum, cannabinoids Pain: pregabalin, gabapentin, duloxetine, amitryptilline, carbamazepine, cannabinoids Bladder dysfunction: oxybutinin Sexual dysfunction: sildenafil Depression/anxiety: venlfaxine, citalopram Fatigue: modafinil, amantadine  DISEASE SPECIFIC TREATMENT AGENTS Interferon Beta1 Glatiramer acetate Natalizumab Sphingosine-1-phosphate receptor modulators (Fingolimod, Ozanimod, Siponimod) Teriflunomide. Alemtuzumab. Di-methyl Fumarate Anti CD20 (Rituximab, Ocrelizumab, Ofatumumab and Ublituximab). Cladribine.  INTERFERON BETA 1 Four formulation. Reduce Annual Relapse Rate by 30%. Reduction of sustained disability by 37%. Reasonable safety profile. Injectable  GLATIRAMER ACETATE Nearly equal to interferon in annual relapse rate. No effect on disability Safe. Injectable  NATALIZUMAB Annual relapse rate reduction by 68%. Disability reduction by 42%. Injectable every 4 weeks. Safety issues (PML). NATALIZUMAB  FINGOLIMOD Oral tablet drug Unique mechanism of action. Annual relapse rate reduction by 60-70% in comparison to placebo and interferon. Favourable outcome on MRI parameters. Requires admission for the initiation. Side effect profile. Safety issues (PML, Serious infections).  SIPONIMOD Oral daily medications S-1-P modulator Indicated for RRMS and SPMS Same as fingolimod as efficacy and side effect profile  TERIFLUNAMIDE Oral. Annual relapse rate reduction comparable to interferon. Side effects alopecia and nonlife threatening infection. Teratogenic in both female and male  DI-METHYL FUMARATE Oral capsule Immune modulator and neuroprotective. Annual relapse rate reduction by 45%. Favourable outcome on disability and MRI parameters. Side effect profile acceptable. PML reported  PEG INTERFERON AND HIGH DOSE GA Old soldiers in new outfits. Better tolerance and adherence. Better study designs  ALEMTUZUMAB Anti CD52. Infusion 5 days then 3 days after 12 months. Side effect ITP Thyroid disease including neoplasm and serious infections. For severe nonresponding disease  ANTI CD20 Rituximab chimeric every 6 months for RRMS off-lable Ocrelizumab humanised IV infusion every 6 months for RRMS and SPMS Ofatumumab human once monthly self injectable for RRMS and CIS Side effect profile infusion reactions and infections. RCT against competitor  CLADRIBINE Chemotherapeutic agent Immune reconstitution oral 5 day course per year S/E cytopenia and infection  FUTURE Intra-thecal anti CD20. Stem cells transplant Bruton tyrosine kinase inhibitors. Anti CD 19 monoclonal antibodies. ONCE WAS A DREAM…..  COVID AND MS MS patients are not more prone to COVID 19 infection. Prognosis of COVID 19 infection found to be worse in patient with more disability. Vaccination against covid considered safe and ,so far, not implicated in MS flare. Vaccination can be timed with MS medications in certain circumastances. THANKS FOR LISTENING