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O.O. FernFernáándezndez
MS clinical forms and variantsMS clinical forms and variants
Instituto de Neurociencias Clínicas – Hospital Regional Universitario Carlos Haya – Málaga
Updating Knowledge in MS - Barcelona - June 1 - 2010
30´
Introduction
MS International classification of clinical patterns
• Relapsing- Remitting
• Secondary Progressive MS
• Primary progressive MS
• Progressive relapsing MS
MS variants
Conclusions
MS clinical forms and variantsMS clinical forms and variants
CHARCOTCHARCOT(1825(1825--1893)1893)
LA PITIÉ - SALPETRIÈRE
NistagmusScanning speechIntentional tremor
IntroductionIntroduction
Problems to make a diagnosis of MS
Problems to classify phenotypically the patients (clinical clasif.)
• Classification according to the type of evolution
• Classification according to the severity
IntroductionIntroduction
Fred D. Lublin, M.D. isProfessor of Neurology atMount Sinai School ofMedicine and Director of thenewly endowed CorinneGoldsmith Dickinson Centerfor Multiple Sclerosis at MountSinai.
Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey.Neurology 1996;46:906-911
Classification according to the type of evolution
IntroductionIntroduction
Relapsing-Remitting
PrimaryProgressive
SecondaryProgressive
Progressive-Relapsing
or
or
or
or
Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey.Neurology 1996;46:906-911
Clinical classification according to the type of evolution
IntroductionIntroduction
Marburg Variant
ADEM
RRMS
Neuromyelitis optica(Devic´s disease)
Baló´s concentric sclerosis
Acute transverse myelitis
Recurrent optic neuritisIsolated optic neuritis
PPMS
Severity
Type of EvolutionIdiopathic demyelinating diseases of the CNS
PRMS
IntroductionIntroductionA two dimensional classification (Type of evolution and severity)
SPMSBening MS
Psedotumoral MSShilder´s diffuse sclerosis
Introduction
MS International classification of clinical patterns
• Relapsing- Remitting
• Secondary Progressive MS
• Primary progressive MS
• Progressive relapsing MS
MS variants
Conclusions
MS clinical forms and variantsMS clinical forms and variants
Serie EM completa (N=634)
2,1%
31,4%
6,9%
59,6%
PR
PS
PP
RR
Serie EM completa (N=634)
2,1%
31,4%
6,9%
59,6%
PR
PS
PP
RR
Fernández V, 2001
SP
(12 y evolution)
IntroductionIntroduction
1317939360N =
PRPSPPRR
Age
ofdi
seas
eon
set-
Mea
nan
d95
%IC 50
45
40
35
30
25
20
Fernández V, 2001
Distribution of Pts according to Int. Classification
(12 y evolution)
IntroductionIntroduction
Transitional Progresive MS – TPMS
“Essentially a progressive course with a single relapse before or duringthe progressive phase”. (1)
“This clinical form is defined by a progressive course beginning manyyears after an isolated bout”. (2)
“In conclusion, this study gives some evidence that TPMS is very similarto SPMS from a clinical point of view at the beginning, but suggests thatat the progressive stage it shares similar features with PPMS in terms ofpathological activity and increase in disability”.
1. Ingle, G. T. Stevenson, V. L. Miller, D. H. Leary, S. M. Rovaris, M. Barkhof, F. Brochet, B. Dousset, V. Filippi, M.Montalban, X. Kalkers, N. F. Polman, C. H. Rovira, A. Thompson, A. J. wo-year follow-up study of primary and transitionalprogressive multiple sclerosis. Mult Scler 2002;8:108-1142. Gayou, A. Brochet, B. Dousset, V. Transitional progressive multiple sclerosis a clinical and imaging study. J Neurol NeurosurgPsychiatry 1997;63:396-398
Classification according to the type of evolution
IntroductionIntroduction
Montalbán X. Curr Opin Neurol 2005:18:261–266..
Probably strict adherence to the Lublin and Reingoldclassification should be advised (always same bias)
Classification according to the type of evolution
IntroductionIntroduction
Kutzelnigg A; Brain 2005
NeuropathologyNeuropathology
Inflammation Demyelination Neurodegeneration
EDSS and evolution time
Evolution time (years)
50403020100
Pre
sent
ED
SS
scor
e
10
8
6
4
2
0 Rsq = 0,1922
r=0,44
EDSS and evolution time
Evolution time (years)
50403020100
Pre
sent
ED
SS
scor
e
10
8
6
4
2
0 Rsq = 0,1922
r=0,44
Fernández O, 98
58º CONGRESO CHILENO DE NEUROLOGÍA – XI CONGRESO PANAMERICANO DE NEUROLOGÍA - SANTIAGO DE CHILE 9-11 OCTUBRE - 2003
Instituto de Neurociencias – Hospital Regional Universitario Carlos Haya – Málaga
Progression Index: 0,30 - 0,40 / year
ClinicClinic
00,5
11,5
22,5
33,5
44,5
1 2 3 4 5 6 7 8 9
Years
No. Of years in each EDSS point (Weinshenker et al. 1991)
EDSS
10 years of evolution
ClinicClinic
Disabilityprogression
-Mean time to EDSS 6-(1 cane) since onset is 10-15 years
- 87% alive after 40 years
Weinshenker B.G., et al.The natural history of multiple sclerosis: A geographically base study. Brain 1989;112:133-14658º CONGRESO CHILENO DE NEUROLOGÍA – XI CONGRESO PANAMERICANO DE NEUROLOGÍA - SANTIAGO DE CHILE 9-11 OCTUBRE - 2003
Instituto de Neurociencias – Hospital Regional Universitario Carlos Haya – Málaga
ClinicClinic
Disabilityprogression
-Mean time to EDSS 6-(1 cane) since onset is25 years
58º CONGRESO CHILENO DE NEUROLOGÍA – XI CONGRESO PANAMERICANO DE NEUROLOGÍA - SANTIAGO DE CHILE 9-11 OCTUBRE - 2003
Instituto de Neurociencias – Hospital Regional Universitario Carlos Haya – Málaga
Pittock, S. J. et al. Disability profile of MS did not change over 10 years in a population-based prevalence cohort. Neurology 2004
ClinicClinic
Confavreux C, et al. Relapses and progression of disability in multiple sclerosis. N Engl J Med 2000;343:1430-1438.
ClinicClinic
Degeneraciónaxonal
(Total BrainN-Acetilaspartate)
WBNAA in patients andcontrols. There is anannual reduction of 0.8% inpatients.
Gonen O, et al. Total brain N-acetylaspartate: A new measure of disease load in MS. Neurology 2000;54:15-19
NeuroimageNeuroimage
De Stefano, N. Narayanan, S. Francis, G. S. Arnaoutelis, R. Tartaglia, M. C. Antel, J. P. Matthews, P. M. Arnold, D. L. Evidence ofaxonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol 2001;58:65-70
NeuroimageNeuroimage
fMRI as a surrogate of efficacy of neurorehabilitation
Control
MS patient
Rocca MA. Is a Preserved Functional Reserve a Mechanism Limiting Clinical Impairment in Pediatric MS Patients?.Human Brain Mapping 30:2844–2851 (2009
Hopefully fMRI will help, in the near future, to evaluate the effects of neurorehabilitation
NeuroimageNeuroimage
METHODS: visual, acoustic brainstem, somatosensory and motor evokedpotentials; global evoked potential score
EDSS significantly correlated with global evoked potential score severityPatients with severe baseline global evoked potential score (higher than themedian value) had a risk of 72.5% to progress on disability at follow-up, whereaspatients with multiple sclerosis with lower scores had a risk of 36.3%
CONCLUSION: evoked potential is a good marker of the severity of nervousdamage in multiple sclerosis and may have a predictive value regarding theevolution of disability.
Leocani L, et al. Multimodal evoked potentials to assess the evolution of multiple sclerosis: a longitudinal study.J Neurol Neurosurg Psychiatry. 2006
Evoked potentialsEvoked potentials
Response to therapyResponse to therapy
Clinically isolated syndrome
p = 0.034, log rank testHR = 0.69
Pro
bab
ility
ofC
DM
S
0 1 2 30.0
0.1
0.2
0.3
0.4
0.5
0.6
Placebo
IFNB-1a IM
Year
p = 0.002Risk Ratio = 0.56
.
28%
45%
Placebo
IFNB-1b sc
Risk reduction* of50% over 2 years(Hazard ratio= 0.5)
*by adjusted proportionalhazards regression
days
p<0.0001
Clin
ical
lyD
efin
ite
MS
(%)
Placebo
GA
Day 336 Day 722
+ 386 days: + 115%
Risk Reduction of45%Hazard Ratio= 0.55[95% CI] 0.40-0.77p=0.0005
ETOMS CHAMPS
PRECISEBENEFIT
Response to therapyResponse to therapy
RRMS
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
0.50
0 200 400 600 800 1,000 1,200
Glatiramer AcetatePlacebo
p = 0.004
Time to Worsening (days)
Su
rviv
alF
un
ctio
nE
stim
ate
Patients (%) WorsenedBy 1.5 EDSS StepsGlatiramer Acetate: 21.6%Placebo: 41.6%
p = 0.001
IFNB-1ª imIFNB-1b sc
IFNB-1ª sc AG
Response to therapyResponse to therapy
SPMS
IFNB-1b sc
IFNB-1a sc
ALEMTUZUMABEMRR EMSP
Coles AJ, et al (J Neurol 2005)
Response to TherapyResponse to Therapy
IFNB response is not determined by demographic or HLA variables. The onlyvariable associated with response was the EDDS at onset of therapy (Cuttingpoint = 3), which suggest that early herapy is the best therapeutic strategy
Response to therapyResponse to therapy
3066N =
Response to IFNB therapy
Non-responderResponder
ED
SS
atbe
ginn
ing
ofIF
NB
treat
men
t8
6
4
2
0
-2
Clinical form
SPRR
Nº
ofpa
tient
s
60
50
40
30
20
10
0
Responder
Non-responder
17
13
18
48
Fernández O, et al. Responders and non-responders to interferon beta treatment in multiple sclerosis. Mult Scler2001;7:S52. Fernández O, et al. Rev Neurol 2006
Compensatory Phase• Adaptative Immune S.• Altered BBB
• Restricted focal lesions• High remyelinative capability (80%)• OPC differentiation
MS: a disease in twophases
Non- Compensatory Phase• Innate immune S (mycroglia)• Trapped inflammation behind BBB• B cell follicles• CNS global inflammation• Low remyelinative capability (20%)• Restricted OPC differentiation• Cortical demyelination
Fernández O. 2009
CIS
40-70%
30%
5-10%0%
MS: a disease in two phasesMS: a disease in two phases
Thompson A, et al (2000)
ClinicClinic
Polman, C. H. et al Diagnostic criteria for multiple sclerosis 2005 revisions to the "McDonald Criteria“ Ann Neurol 2005
ClinicClinic
Classification according to the type of evolution
• In patients experiencing a progressive course, median ageat onset of progressive phase was similar in secondaryprogressive cases (SP) and in cases who were progressivefrom onset (PP) (39.1 versus 40.1 years; P = 0.47).1
• The proportion of cases with superimposed relapses duringprogression was 40% in both categories (SP,PP).1
• Relapses in PPMS occurred in 27.8% of patients at somepoint event two to three decades after onset.2
1. Confavreux Ch, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain (2006), 129, 606–616
2. Kremechutzki et al. Brain 1999.
ClinicClinic
Kutzelnigg A; Brain 2005
Inflammation Demyelination Neurodegeneration
PPMS showed a lower load offocal demyelinated plaques inthe white matter and lowernumbers of inflammatoryinfiltrates in the global whitematter in comparison withSPMS.
Diffuse white matter injuryand cortical demyelination inprogressive MS invariablyoccurred on a background ofmeningeal, perivascularand parenchymalinflammation.
NeuropathologyNeuropathology
Confavreux CH and Vukusic . Natural history of multiple sclerosis: a unifying concept. Brain (2006), 129, 606–616
ClinicClinic
Lycklama à Nijeholt GJ, et al (1998)
Lycklama à Nijeholt GJ, et al (1998)
Introduction
MS International classification of clinical patterns
• Relapsing- Remitting
• Secondary Progressive MS
• Primary progressive MS
• Progressive relapsing MS
MS variants
Conclusions
MS clinical forms and variantsMS clinical forms and variants
Concept: MS whose onset, evolution, clinical, pathologic and imagingcharacteristics.differ from the common patterns of conventional MS
Types:
•ADEM (Acute disseminatedencephalomyelitis)
•Fulminant MS or Marburg´s disease•Pseudotumoral MS•Concentric Sclerosis of Baló•Diffuse mielinoclastic sclerosis of Schilder•Neuromielitis óptica (enfermedad de Dévic)
MS variantsMS variants
Clasification according to clinical form and age
Acute fulminant
• Pediatric age : < 16 yearsSchilder´s diseaseADEM
• Young adult: 20-40 yearsBaló´s diseaseMarburg´s disease
SubacutePseudotumoral MS: > 30 años
MS variantsMS variants
Classification accordingTopography
Monofocal:• Marburg´s disease• Pseudotumoral MS• Baló´s disease
Multifocal• ADEM: asymmetric distribution• Schilder´s disease: symmetric distribution
MS variantsMS variants
• Acute onset• Symptoms of intracraneal hipertension• Monophasic course• Severe vital prognosis• Cortical signs: conciousness, seizures, psychiatric symptoms,
aphasia, hemianopsia
General clinical characteristics
MS variantsMS variants
– Frequent and marked pleocitosis ( 50-100 c/mm3)– Total proteins in CSF > than in MS– Low frequency of OB in CSF
General CSF characteristics
MS variantsMS variants
• Extense lesions, predominantly in WM• Moderate mass effect• Frequent Gad enhancement• Asymmetric distribution• GM affected frequently• Concentric circles in Baló´disease
Rovira A et al. Neuroradiology 2007
General image characteristics
MS variantsMS variants
• Pathologic overlap– In brains with concentric sclerosis of Baló there are sometimes
contigous typical MS plaques– In some patients there are, at the same time, lesions typical of
ADEM and MS• Clinical overlap
– Some RRMS patients evolve to fulminant form of Marburg andviceversa
– One third of patients with Schilder´s disease evolve later to classicalRRMS
– Two thirds of pseudotumoral forms evolve to classical MS• Image overlap
– Is relatively frequent to find pseudotumoral lesions close to typicalMS plaques
Lucchinetti CF et al. Brain 2008; 131:1759-1775
Nosologic frontiers
MS variantsMS variants
Malignant and acute MS (1)
Marburg´s Disease: Monophasic, fulminant course. Paraclinical andpathological features similar to common MS, causes death due tobrainstem involvement.
Other cases, not so acute, but severe, causing death in 5 years canalso be considered malignant.
Benign MS (2)
Normal life after 15-20 years of evolution (EDSS≤3) – 20% pts.Eventually they can evolve to produce disability.
1. Marburg O. Die sogennante "acute multiple sklerose". Jahrbucher fur Psychiatre und Neurologie 1906; 27:211-312.2. Hawkins SA, McDonnell GV. Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors.J Neurol Neurosurg Psychiatry 1999; 67(2):148-52.
Classification according to the severity
IntroductionIntroduction
Benign MS is rare
Sayao A, Devonshire V, Tremlett H. NEUROLOGY 2007;68:496–500
Mild (EDSS 0-3)
Moderate (EDSS 3.5-5.5)
Severe (EDSS >6)
• At 10 years: 200 patients diagnosed of benign MS with EDSS<3• At 20 years: Follow up of 84.5% of patients
IntroductionIntroduction
Is “Benign Multiple Sclerosis” really benign?
D. J. Rigotti and O. Gonen Department of Radiology. New York University School of Medicine.Revista Española de Esclerosis Múltiple Nº 14 - Junio de 2010. www.revistaesclerosis.es
NeuroimageNeuroimage
Box plots showing the first, second(median)and third quartiles (box),±95% (whiskers) and outliers (*)of the WBNAA distributions of the17 controls (solid), 24 benign(hatched) and 30 non-benign MSpatients (cross-hatched) groups.Note that both patients groups aresignificantly lower in WBNAA thanthe controls but not statisticallydifferent from each other.
Is “Benign Multiple Sclerosis” really benign?
D. J. Rigotti and O. Gonen Department of Radiology. New York University School of Medicine.Revista Española de Esclerosis Múltiple Nº 14 - Junio de 2010. www.revistaesclerosis.es
NeuroimageNeuroimage
MarburgMarburg´s fulminant form of MSs fulminant form of MS
• It´s MS with an acute evolution and course rapidly progressive.
• Some authors consider this as a pseudotumoral form of MS by its
clinical characteristics (headache, nausea, vomiting, somnolence,
hemiplegia, seizures) and image characteristics (edema, necrosis,
compromise of adjacent structures), afecting generally one
hemisphere, afecting the brainstem and showing diffuse
Gadolinium enhancing
Kleinschmidt-Demaster BK. 2005:181-222. Simon JH. Neuroimag Clin N Am 2008
Pathology
• Massive infiltrate of mononuclear cells and macrophages in the centerand hypertrophic astrocytes in the periphery of the great lesions,particularly in the periventricular WM , with the same chronologic age.Frequent deposit of immunocomplexes with complement activation
• Acute axonal lesions and necrosis. Mild remyelination
Hu W; Lucchinetti C. The pathological spectrum of CNS inflamatory demyelinating diseases. Semin Immunopathol 2009
MarburgMarburg´s fulminant form of MSs fulminant form of MS
• Treatment in the acute phase
– Support measures
– Bad response to steroids
– Plasmapheresis (42% response)
• Maintenance therapy : immunosupressants
– Ciclophosphamyde
– Natalizumab,
– Rituximab can be an alternative
Gladstone DE. AJTherapy 2009
MarburgMarburg´s fulminant form of MSs fulminant form of MS
Treatment
• Marburg´s disease:– Humoral immunity disfunction,
deposit of immunocomplexes andcomplement activation
– ¿ By abnormal myelin?
• Baló´s concentric sclerosis:– Mitochondrial disfunction of
olygodendrocytes (Pattern III ofLucchinetti)
• ¿By hypoxia?• ¿Toxics?
Stadelman. Brain 2005;128:979-987. Mahad Brain 2008
Atypical forms of MSAtypical forms of MS
Pathogenic theories
Refers to the presentation of MS plaques as large space-occupyingmass lesions that mimic brain tumors clinically and radiologically.
Lesions are typically supratentorial and thus may result in hemiparesis,hemisensory loss, visual field deficits, decreased consciousness, orseizures.
Often presents with atypical imaging features including size >2 cm, masseffect, edema, open-ring enhancement
Differentiation from a neoplastic process is more problematic when theinitial presentation is with a solitary mass lesion.
Lucchinetti CF, et al. Brain (2008), 131, 1759-1775
Pseudotumoral MS (Tumefactive MS)Pseudotumoral MS (Tumefactive MS)
Pseudotumoral MS (Tumefactive MS)Pseudotumoral MS (Tumefactive MS)
Lucchinetti CF, et al. Brain (2008), 131, 1759-1775
Pseudotumoral MS (Tumefactive MS)Pseudotumoral MS (Tumefactive MS)
Presents the classic features of active inflammatory demyelinatingdisease including hypercellular confluent demyelinating lesions,inflammatory infiltrates dominated by myelin-laden foamy macrophagesclosely intermingled with reactive astrocytes, variable perivascular andparenchymal lymphocytic inflammation, and ‘relative’ axonal preservation
Biopsy can help confirm the demyelinating nature of the lesion;however, the presence of Creuztfelt–Peters cells (astrocytes withfragmented nuclear inclusions) can be mistaken for mitotic glialcells.
Most patients presenting with tumefactive features later develop typicalRRMS, although monophasic cases have also been reported.
Tumefactive MS cases represent a part of the heterogeneous clinicaland radiographic spectrum of MS,
Lucchinetti CF, et al. Brain (2008), 131, 1759-1775
Pseudotumoral MS (Tumefactive MS)Pseudotumoral MS (Tumefactive MS)
Callen DJA, et al. Role of MRI in the differentiation of ADEM from MS in children. Neurology 2009;72:968–973
ADEM criteriaADEM criteria
Callen DJA, et al. Role of MRI in the differentiation of ADEM from MS in children. Neurology 2009;72:968–973
ADEM criteriaADEM criteria
ADEM criteriaADEM criteria
Krupp LB, et al. Consensus definitions proposed for pediatric multiple sclerosis and related disorders.NEUROLOGY 2007;68(Suppl 2):S7–S12
• Schilder´s diffuse sclerosis has been confounded with cases ofleukodystropy because it appears at earlier ages than MS
• Typically there are headache, afasia, cortical blindness and deafnesswhich are unfrequent in MS
• Pathologically is characterised by great demyelinating plaques,particularlly in the posterior part of the brain hemyspheres
• In the acute phase there is an inflammatory infiltrate totally similar to theacute plaques of MS, and in some cases there are transitional forms withother plaques of small size typical of MS.
Schilder P. Zur Kenntnis der sogenannten difusen Sklerose (uber Encephalitis periaxialis diffusa). Zeitschrift furdie gesamte. Neurologie und Psychiatrie 1912;10:1-60.
Kotil K, Kalayci M, Koseoglu T, Tugrul A. Myelinoclastic diffuse sclerosis (Schilder's disease): report of a caseand review of the literature. Br J Neurosurg 2002 Oct;16(5):516-9.
SchilderSchilder´s diffuse sclerosiss diffuse sclerosis
SchilderSchilder´s diffuse sclerosiss diffuse sclerosis
Diagnosis Clínicla symptoms Diagnosticcriteria
Neuroimage Treatment
ADEM Normallymonophasic andpostinfectious
In childrenyes, no inadults
Multifocal,asymmetricSimultaneous Gdenhancement
CorticoidsPLEX
Marburg Mono o multiphasic,Fulminant onset andevolution
No GreatpseudotumorallesionGM++
CorticoidsPLEX
Baló´sconcentricsclerosis
Monophasic andprogressive
No Alteration of signalin concentriccirclesGM ++
CorticoidsPLEX
Schilder sdiffusesclerosis
Almost alwaysmonophasic andalteration ofconciousness
No Bilateral alterationof WM, symmetric,diffuse, infiltrativeGM ++
CorticoidsPLEX
Atypical forms of MSAtypical forms of MS –– Differential diagnosisDifferential diagnosis
Patología Características
ADEMrecurrente
Nuevo episodio de ADEM, con los mismos síntomas y signos,al menos 3 meses después del inicial, sin relación con laretirada de esteroides
ADEMmultifásica
Nuevos episodios clínicos que cumplan criterios de ADEM,pero implicando zonas ≠clínica o radiológicamente
NMOrecurrente
Brotes de mielitis transversa y neuritis óptica, sin episodios deafectación fuera de la vía óptica o medular
EM pediátrica Dos o más episodios separados en tiempo y espacio, y elprimero no debe ser ADEM. Si el primero fue clínicamentecompatible con ADEM, deben seguir dos después distintos. Enla RM deben aparecer lesiones nuevas al menos 3 mesesdespués.
Krupp LB, Banwel lB, Tenembaum S. International Pediatric MS Study Group. Neurology 2007;68 (sppl 2):S7-S12.
FA: diagnóstico diferencial con otras EIDI:definiciones de consenso
•• Epidemiology• Pathophysiology• Pathology• Clinical features• MRI abnormalities• CSF abnormalities• Outcome• Treatment
responsivenessE. DEVIC(1858 – 1930)
Devic’s NMO and MS are different regarding
NeuromyelitisNeuromyelitis OpticaOptica
NeuromyelitisNeuromyelitis OpticaOptica
• Optic nerves• Spinal cord• Brainstem• Hypothalamus• Periventicular regions
Pathogenesis: NMO lesions occur at sites of high AQP4 expression
NeuromyelitisNeuromyelitis OpticaOptica
• Uni or bilateral optic neuritis
• Acute myelitis
• Usually not simultaneous
• Mostly relapsing
• NMO spectrum disorder
Clinic Characteristics
Courtesy of Regina Papais
NeuromyelitisNeuromyelitis OpticaOptica
• Extension of spinal cord lesions
• Severity of optic nerve lesions
• Severity of brain involvement
• Clinical improvement and stabilization
• Beneficial effect of plasmapheresis
Correlation of serum AQP-4 Abs titers with:
NeuromyelitisNeuromyelitis OpticaOptica
In MS several patterns can be recognized, both from the clinical,pathological and paraclinical point of view.
There exist a certain amount of variability in clinical classification ofprototypic MS (20-40%).
This variability can affect the results of clinical, epidemiological, genetic,paraclinical and therapeutic studies
In the near future, paraclinical or biological markers, will permit to reducethe variability
There are atypical forms which are necessary to know, becauseoccasionally they represent a diagnostic and therapeutic dilemma
Neuromyelitis optica is a disease different from MS
ConclusionsConclusions
Instituto de Neurociencias Clínicas – Hospital Regional Universitario Carlos Haya – Málaga
Thanks for your attention
Updating Knowledge in MS - Barcelona - June 1 - 2010