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Central nervous system
demyelinating diseases
- Multiple sclerosis Amilton Antunes Barreira
Department of Neurology
Faculdade de Medicina and Hospital das
Clínicas de Ribeirão Preto - USP
Diseases of myelin
Autoimmune
Acute hemorrhagic leukoencephalopathy
Multiple sclerosis
Infectious
Progressive multifocal leukoencephalopathy
Toxic/metabolic
Carbon monoxide
Vitamin B12 deficiency
Mercury intoxication (Minnamata disease)
Alcohool/tobacco amblyopia
Central pontine myelinolysis
Machiafava-Bignami syndrome
Hypoxia
Radiation
Vascular
Binswanger’s disease
(chronic microvascular leukoencephalopathy)
Hereditary disorders of myelin metabolism
Adrenoleukodystrophy
Metachromatic leukodystrophy
Krabbe’s disease
Alexander’s disease
Canavan-van-Bogaert disease
Pelizaeus-Merzbacher disease
Phenylketonuria
Multiple sclerosis
Diseases of myelin
Autoimmune
Acute hemorrhagic leukoencephalopathy
Diseases of myelin
Vascular
Binswanger’s disease
Diseases of myelin
Infectious
Progressive multifocal leukoencephalopathy
Diseases of myelin
Hereditary disorders of myelin metabolism
Canavan-van-Bogaert disease
Deficiency of the enzyme aspartoacylase
and the accumulation ofN-acetylaspartic
acid lead to a severe leukodystrophy and
spongy degeneration of the brain,
Canavan disease (McKusick 271900).
Epidemiology
• 1,1 million people with MS worldwide
• 2/3 experiment the first symptom between
the age of 20 and 40
• For a minority MS starts in late adult life
• Women are committed 1.4 to 3.1 times more
• In temperate zones MS is five times more
common than in the tropics
• In Brazil: 20 cases per 100 000 inhabitants
(38 000 cases)
• In Uruguay: 30 000 cases for a population
of 3 000 000 inhabitants
• In United States: 300 000 cases
• MS in first degree relatives is 20 times
higher than in general populations
• Monozygotic twin studies show the
concordance rate of 30%
• Dizygotic twins show concordance rate of
less than 5%
PATHOLOGY
Trapp - 2003
MRI IMAGES
Signs and symptoms
• Visual loss
• Ocular motility
Diplopia
• Trigeminal neuralgia
• Equilibrium alterations
• Ataxia
• Pyramidal signs
Monoplegia
Paraplegia
Hemiplegia
Sphincter disturbances
• Cognitive commitments
Course
DIAGNOSTIC CRITERIA
Diagnosis criteria are very specific and the Brazilian Ministry of
Health recommend that it must be confirmed by neurologists.
An exacerbation (relapse) is defined as:
the appearance of a new clinical
Sign/Symptom
or the clinical worsening of a
previous
sign/symptoms that had
been stable for at least the previous
30 days and which persisted for a
minimum of 24 hours.
International Panel Criteria (McDonald Criteria) for Diagnosis MS
Clinical Presentation
Additional Data Needed for MS Diagnosis
Two or more attacks; objective clinical
evidence of 2 or more lesions
Nonea
Two or more attacks; objective clinical
evidence of 1 lesion
Dissemination in space demonstrated by:
• MRIb, or
• 2 or more MRI lesions consistent with MS plus positive
CSFc, or
• await further clinical attack implicating a different site.
One attack; objective clinical evidence of 2 or
more lesions
Dissemination in time demonstrated by:
• MRIb, or
• second clinical attack.
One attack; objective clinical evidence of 1
lesion (clincally isolated syndrome)
Dissemination in space demonstrated by:
• MRIb, or
• 2 or more MRI lesions consistent with MS plus positive
CSFc
And dissemination in time, demonstrated by:
• MRIb, or
• Second clinical attack
Insidious neurological progression suggestive
of MS
Positive CSFc, and dissemination in space,
demonstrated by:
• 1) 9 or more T2 lesions in brain, or 2) 2 or more lesions in
spinal cord, or 3) 4-8 brain lesions plus 1 spinal cord
lesion; or
• Abnormal visual evoked potentials with MRI
demonstrating 4-8 brain lesions, or fewer than 4 brain
lesions plus 1 spinal cord lesion; and
• Dissemination in time demonstrated by MRIb; or
• Continued progression for 1 year
MRI Criteria for Brain Abnormality:
Space and Time Dissemination
MRI lesions disseminated in space:
At least three of the following criteria must be met:
1. One gadolinium-enhancing lesion or nine T2-hyperintense lesions if there is no
gadolinium-enhancing lesion
2. At least one infratentorial lesion
3. At least one juxtacortical lesion
4. At least three periventricular lesions
MRI lesions disseminated in time:
At least one criterion must be met:
1. If MRI is more than 3 months after clinical event, then a gadolinium-enhancing
lesion at a site different from the original clinical event is sufficient; if there is no
gadolinium enhancement, then a follow-up scan is required (usually > 3 months
later). A new T2 or gadolinium-enhancing lesion on this second or subsequent
MRI fulfills the requirement.
2. If first MRI scan occurs less than 3 months after the onset of the clinical event,
then a second scan > 3 months later showing a new gadolinium-enhancing lesion
fulfills requirement. If no gadolinium enhancement is seen at this second scan, a
further scan not less than 3 months after the first scan that shows a new T2 lesion
or an enhancing lesion will suffice.
Pathogenesis
Specific pharmacologic Treatment
MS – The dimension of the problem
August 2003
- 1 400 patients in São Paulo state use IFN-β
- CEREM of HC de Ribeirão Preto – 140 patients are
using IFN-β
- CEREMs of SP city – More than 200 pacientes in each
center are in IFN-β
MS – The dimension of the problem
US in 1991: - U$ 1 500 000 000,00
US in 2001: 50%: MS chronic progressive (MSCP)
US in 2006: 70% will have EMCP
US in 2016: 85% will have o EMCP
MS – The dimension of the problem
Malignant form (1 a 3% dos pacientes):
- Loss of walk in weeks or months
- Life expectancy for MS patients: 10 years less
than the general population
MS – The dimension of the problem
What is the real cost of the incapacities?
How many working ours are lost?
What is the dimension of the human suffering?
Specific treatment for MS
Relapses
• 
Pulsotherapy with metyil-prednisolone
Different regimens:
l  250mg
l 
• 
(IV) each 6 hours in
1g EV in 4 to 6 hours
Plasmapheresis
Specific treatment for MS
Ø Interfere in the course of MS
l  Preventing
l  Possible
or attenuating the relapses intensity
reduction in the course velocity
Specific treatment for MS
Intérferons β-interferons
Glatiramer acetate
Mitoxantrone
Action of the medicines used for MS
Intérferon β
- change the MHC expression;
- Inhibits the cell trafficking;
- l essens the hemato-encephalic barrier
permeability;
- change the balance between pro and antiinflammatory cytokines
Glatiramer
acetate
- Blockade of the T cells antigen receptors
Mitoxantrone
- cytotoxicity
Collateral effects
- reversible mielotoxicity;
- transitory amenorrhea ;
Mitoxantrone
- nausea;
- alopecia;
- Cardio toxicity ( cardio myopathy –
cumulative effect)
Collateral effects
Intérferon β
(discrete or
moderated)
Glatiramer
- influenza;
- local inflammation (injection);
-  worsening of the previous depression;
- do not approved for use during pregnancy;
- leucopenia, hepatitis, hipo or hypertirheodism;
- uncommon: worsening or starting of asthma or
Raynaud phenomenon,
- myastenia gravis, psoriasis, urticaria, cerebral
hemorrhage;
- Hepatic necrosis, anaphylaxis.
- local pain in the site of injection;
-  thoracic pain;
- death sensation;
-  lynphadenopaty;
- do not approved for use during pregnancy.
EMPP: there is no specific treatment (?)
Thank you very much for
your attention!!!!