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Dr. Jorge Barahona Strauch Director Centro de Esclerosis Múltiple Clínica Alemana de Santiago

Problemas Diagnósticos de la Esclerosis Múltiple en Chile D´une maladie inconnue a une maladie en vogue. Dr. Jorge Barahona Strauch Director Centro de Esclerosis Múltiple Clínica Alemana de Santiago Universidad del Desarrollo UDD.

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Dr. Jorge Barahona Strauch Director Centro de Esclerosis Múltiple Clínica Alemana de Santiago

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  1. Problemas Diagnósticos de la Esclerosis Múltiple en ChileD´unemaladieinconnue a unemaladie en vogue Dr. Jorge Barahona Strauch Director Centro de Esclerosis Múltiple Clínica Alemana de Santiago Universidad del Desarrollo UDD II Jornadas Franco Chilenas de Neurología Valparaíso 14-15 de Marzo 2008

  2. MultipleSclerosis in Latin America ?

  3. Latin America: An overview • Vast continent: over 25 m sq km • Vast latitudes • Border US and Mexico at 32o N • Southermost Argentina and Chile at 56o S • Vast spectrum of climate • Desert to sub-Antarctic • Many different regions • 36 countries • 6 territories

  4. Amerindians in Latin American population • Migration routes : • -The Bering Strait route • 30.000 years ago • from Mongolia and Siberia • -The Trans-Pacific route • 20.000 years ago • from Polynesia to South America • -The Trans-Atlantic route

  5. The origin of the Latin America populations: The Mestizos • Offspring of an European and an Amerindian or children of two mestizo parents

  6. Mulattoes and pure blacks in some Latin American countries (%)

  7. The prevalence of MS in Latin America

  8. MultipleSclerosisstudy (Chile)Barahona J. et al LACTRIMS 2004, ArqNeuropsiquiatr2004 ; 62:1:11 • Population of Chile (2002)15.050.341 inhabitants MULTIPLE SCLEROSIS Estimated: • Prevalence: 11,7 : 100.000 • Incidence: 1.8 : 100.000

  9. Distribution of patientswith MS byage at the diagnosis of thedisease

  10. Easter Island (Isla de Pascua) Chile Population: 3.791 inhabitants Area: 166 Km2

  11. MultipleSclerosis in Easter Island No cases of MS in Easter Island Population: 3.791 inhabitants Area : 166 Km2 * The only case of MS in Easter Island is from a man who travelled from Chile and lived here for more than 15 years ( He died from Multiple Sclerosis 5 years ago )

  12. MultipleSclerosismortality(1970-2002)MS was a prevalentdisease in Chile after 1970 MS Cases / 100.000 Number Cases / Year Instituto Nacional de Estadisticas, Chile

  13. YEAR

  14. The effect of socioeconomic status on susceptibility to autoimmune and allergic diseases J.Bach N Engl J Med 2002;347:12:911

  15. The Effect of Infections on Susceptibility to Autoimmune and Allergic DiseasesJ.Bach N Engl J Med 2002;347:12:911-918 J.Bach N Engl J Med 2002;347:12:911

  16. Increase of AutoimmuneDiseases in Chile 25% 30% Increase of Allergic Diseases in school- children in Chile in the last 15 years 14% 8% Allergic dermatitis Asthma Allergic rhinitis 1990 2005 M.A. Guzman, Allergy & Immunology Society of Chile 2006

  17. MRI in Chile ( 1988-2006) N ° MRI Years

  18. MRI : 39 First MRI in Chile

  19. MS Overdiagnosis MS Subdiagnosis

  20. Changes in theascertainment of MultipleSclerosisMarrie, Neurology 2005: 65: 1066

  21. Multiple Sclerosis Diagnosis in ChileTime until the first MS Diagnosis 1-2 years ND 14,6% 2-3 years 6,25% 3-4 years 6,25% 58,4% 0-1 years 12,5% >5 years Superintendencia de Isapres 1996-2005

  22. Review of 156 personal outpatients records Barahona JA, Clínica Alemana MS Center 2006

  23. Review of Personal Outpatient RecordsCharles M. Poser and Callum C. Ross

  24. Other Diagnoses

  25. The mean age was 42 years • 36% male and 64% female • Unexplained symptoms were a important cause of misdiagnosis • In one large series of patients diagnosed with MS , 9% turned out not to have any organic disease • Hankey GJ et al Pseudo multiple sclerosis: a clinico-epidemiological study Clin Exp Neurol 1987 : 24 ; 15-19

  26. Lack of comfirmation of initial MS suspicionuponexpertreferral

  27. Diagnostic Criteria for Multiple Sclerosis Reason for Referral to a MS Center * Rate of Non - Confirmation of MS Reason for Referral to a MS Center * Rate of Non - Confirmation of MS MS possible ( Clinical findings ) 54% MS possible ( MRI findings ) 89% MRI are not a substitute for a good history and neurological examination in the diagnosis of MS J.Fleming AAN San Diego 2006 * Carmosino, Arch Neurol 2005;62:585-90

  28. LancetNeurol 2006 ; 5 : 841-52

  29. Does MRI allowearlier diagnosis ?

  30. JNNP 2001;70:390-93

  31. Criterios de Barkhof(1997) juxta infra Gd PV

  32. Esclerosis Múltiple: Lesión Periventricular o Juxtacortical No EM EM EM

  33. McDonald 2001 McDonald 2005 Nuevos Criterios Diagnósticos Especificidad 91% 88% 87% Sensibilidad 47% 60% 72% Lancet Neurology 2007

  34. ClinicalSymptom in MultipleSclerosis Symptom Porcentage at onset Porcentage Anytime Sensory 30 - 50 90 Visual loss (ON)15.9 65 Weakness legs 10.0 90 Hemiplegia 2.0 9 Diplopia 6.8 30 Gait disturbance 4.8 50 - 80 Sensory in face 2.8 10 Vertigo 1.7 - 4 5 - 50 Lhermitte´s symptom 1.8 - 3 30 Bladder symptoms 1.0 80 Polysymptomatic onset 13.7 D.W.Paty University of British Columbia

  35. Clinical Symptom : Optic Neuritis

  36. ON ON Myelitis Leber ON MS ADEM MS Devic Lupus ADEM Optic Neuritis

  37. OB Cerebral MRI Normal Cerebral MRI Abnormalities + - 36% (19/53) 64% (34/53) 1 year None Developed MS Multiple Sclerosis 35% (12/34) (3/19) 5 year With silent MRI lesions75% Developed MS Multiple Sclerosis 6 year 81% 5% MS 10% Isolated Optic Neuritis Mc Donald1992, Morrissey 1993, Miller 1988, Stendahl-Brondin 1983

  38. Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profileC Lebrun1, C Bensa2, M Debouverie3, J De Seze4, S Wiertlievski5, B Brochet6, P Clavelou7, D Brassat8, P Labauge9, E Roullet2Journal of Neurology, Neurosurgery, and Psychiatry 2008;79:195-198 • Report a descriptive retrospective study ofclinical and 5 year MRI follow-up in patients with subclinicaldemyelinating lesions fulfilling MRI Barkhof–Tintorécriteria with a normal neurological examination. • 30 patientswere identified and the first brain MRI was performed for variousmedical events: headaches (n = 14), migraine with (n = 2) orwithout (n = 4) aura, craniocerebral trauma (n = 3), depression(n = 3), dysmenorrhoea (n = 2), epilepsy (n = 1) and cognitivechanges (n = 1). • Mean time for the second brain MRI was 6 months(range 3–30). • 23 patients had temporospatial dissemination(eight with gadolinium enhancement). • 11 patients had clinicalconversion: optic neuritis (n = 5), brainstem (n = 3), sensitivesymptoms (n = 2) and cognitive deterioration (n = 1). Eight(72%) already had criteria of dissemination to space and timebefore the clinical event. • Mean time between the first brainMRI and clinically isolated syndrome (CIS) was 2.3 years. • Early treatment should be discussed in view of thepredictive value on conversion of the MRI burden of the disease.

  39. Separating Zebras from Horses The unusual presentation of an common disease is generally more likely than the usual presentation of an uncommon disease When faced with an unusual clinical feature, ask first whether it can be explained by something other than a rare disease Smith J Am Board Fam Pract 13(6):424-429, 2000

  40. Problemswiththe McDonald criteria • 1. PrognosticcriterianotDiagnosticcriteria • 2. Stringency of criteria • ( Recurrentoptic neuritis, recurrentmyelitis, recurrent ADEM ) • MRI • ( Cost and thesensitivitymayvarywithtechnology; 3 Tesla MRI maycreate more false positives ) • 4. Oligoclonalbands • ( Sensitivity and specificity ) • Otherdiseasesmaymeetthecriteriafordissemination in time and spacerequiredfor diagnosis of MS • Impactontreatmentdecisions( Early treatment should be discussed in view of thepredictive value on conversion of the MRI burden of the disease)

  41. MultipleSclerosis • MS is a life-long disease • Multiple Sclerosis is a clinical diagnosis • There is no pathognomonic or perfect laboratory test to diagnose MS • MRI is sensitive but has limited specificity Suspected MS isnotthesame as established MS once diagnosedcan´teasilyretract

  42. Muchas Gracias Merci Disease is very old and nothing about it changes. Its is we who change as we learn to recognize what was formerly imperceptible Jean Martin Charcot ( 1825-1893 )

  43. TheThreeWorlds Third World: "less developed countries", "lesser developed countries"

  44. WATER PROCESSING PLANTS MRI CHOLERA YEAR

  45. Large-scale field trial of live oral typhoid vaccine in Santiago, Chile (1982-1986) Santiago of Chile The Lancet • ** Year Vaccine Placebo • 1982 55.238 27.305 • 1983 44.549 21.904 • 1984 248.544 0 • 1986 84.836 0 • Total 433.167 school-children Typhoid Fever(1980-2002) ** C. Ferreccio personal comunication * Lancet 1987;336:891

  46. TheHygieneHypotesis Multiple Sclerosis

  47. The starting point for diagnosis in the individual patient is the clinical picture Twins : MS & Not MS B A Is the clinical history compatible with MS ?

  48. Epigeneticdifferencesariseduringthelife time of monozigotictwinsM. Fraga PNAS 2005;26:10604-09 Explain why different phenotypes can be originated from the same genotype 3 years old twins 50 years old twins Epigenetic profiles may represent the link bewteen an environmental factor and phenotypic differences in MZ twins

  49. Multiple Sclerosis in the Faroe Islands • The Faroe are a group of 18 Islands in the North Atlantic Ocean, in a semi-independent status, part of the Kindgdon of Denmark • British troops invaded the Faroe Islands in World War II (1940-1945) • The population was 26.232 inhabitant (1943) • Multiple Sclerosis did not exist among resident Faroese before 1943( Except 2 Faroese who lived in Denmark and return to Faroe Islands before the War )

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