6 ms friedreich
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Multiple sclerosis
• chronical disease, characterized bymultiple areas of inflamation anddemielination in the CNS
• One of the major causes of disability in theyoung adult
• Variable clinical picture and evolution
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Epidemiology
• Geographical distribution:
• Average onset age: 24-30 years
– Rarely under 10 or after 60 years old
– In females disease starts 5 years earlier
• Relapsing remiting form: 25-29 years
• Primary progressive: 40-44years• F>M (2-3:1)
• Prevalence: (temperate climate )? 80/ 100000 loc. (Northerneurope)
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• The most widelly accepted hypothesis: – An autoimmune disease that is triggered by un unknown
environmental factor in genetically susceptible persons
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••DemielinationDemielination
is due to anis due to an
autoimmuneautoimmune
reactionreaction
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Patogenical aspects
• Brain-blood barrier breakdown
• Inflamation
• Demielination
• Oligodendrocyte loss
• Reactive gliosis
• Degeneration and axonal loss
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INFLAMATION – DEGENERATION
RelapseAcute clinical
presentation Cronic signs;
increase of disability
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Chronic lesions
• Plaques – Different degrees
of inflammation
– Perivascular
– hyperintense onT2-weighted andFLAIR images andhypointense on T1-weighted scans
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Clinical presentation in MS
• Motor
• Sensory
• Cerebellar
• Brainstem
• Visual
• Sfincterian
• Cognitive
• Functional damage isevaluated by the EDSS(Kurtzke Expanded
Disability Status Scale): – Scale from 0 to 10
– 0 no signs/simptoms
– 10 dead
– 6 – loss of gait autonomy
• Monitoring of diseaseevolution and treatmentefficiency
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Relapse
• Sudden onset of new symptoms orexacerbation of preexistent clinicalsymptoms
– At least 24 hours
– More than 30 days from previous relape
• Duration can extend from days to weeks
• Demyelination areas appear
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McDonald diagnostic criteria
Progression for more than 1year AND MRI + VEP oroligoclonal bands
Slow progression of clinicalpicture
MRI +/- oligoclonal bandsANDtime dissemination (asecond relapse or new MRI
changes)
1relapse + 1 clinical lesion(Clinical isolated syndrome)
MRI or wait for second relapse1 relapse + =2 clinical lesion
IRM +/- oligoclonal bands in
LCR
=2 relapses + 1 clinical lesion
No=2 relapses + =2 clinicallesions
Additional dataClinical
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Updated McDonald criteria(2005)
• Changes regarding:
– Space dissemination: spinal lesions on MRIare accepted
– Time dissemination: new T2 lesions,gadolinofile lesions accepted at 1 monthinterval from baseline
• Allow a more timely diagnosis
• Clinical criteria remain accepted
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Clinical types of MS
• Relapsing/Remitting – RRMS
• Secondary progressive (SPMS)
• Progresive with relapses (PRMS)
• Primary Progressive (PPMS)
http://www.nationalmssociety.org/What%20is%20MS.asp
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Relapsing/Remitting (RRMS)
• 85%
• Twice more infemales
• Relapses followedby remission
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Secondary Progressive (SPMS)
• Approx 50 % of theRRMS patients willchange to this form
after many years ofevolution
• In time recovery afterrelapses is less
complete, leading toprogressiveaggravation
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Progressive Relapsing/Remitting(PRMS)
• Relapses and
remissions exist
• During remissionthere is a slow
progression of
symptoms
• Approximativelly 5%
of cases.
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Primary Progressive (PPMS)
• No relapses/remission
• Gradual aggravation ofsymptoms
• Usually begins during the
end of the 3rd decade• Man=woman
• 10% of the total MSpatients
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MS - onset
• “Clinical isolated syndrome” (CIS) – firsneurological symptoms that last for more than aday, caused by inflamation/demyelination in oneor more sites in the CNS
– monofocal – only one lesion, only one type of clinicaldamage
– multifocal – more than one symptoms, caused bymultiple lesions
• Usually more lesions on the MRI exist at thetime of clinical onset
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Clinical picture
• Motor (pyramidal)involvement
• Sensory
• Cerebellar
• Brainstem
• Visual
• Sphincterian
• Higher functions
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Cerebellar syndrome
• Ataxia, gait trouble
• Limb coordination problems
• Tremor
• Dysmetria
• Dysartria
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Pyramidal syndrome
• Upper motor neuron syndrome:
–Paraparesis
–Hemiparesis
–Tetraparesis
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Vestibular Syndrome
• Static and dynamic balance problems
• Nystagmus
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Visual problems
• Optic neuritis
• Diplopia / internuclaer oculomotricity
paresis
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Optic neuritis
• Retrobulbar
• Pain, sight loss
• Scotoma -> blindness
• Usually unilateral
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Sfincterian abnormalities
• Retention/incontinence
• Disuria
• Constipation
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Cognitive
• Depression
• Euphoria
• Memory impairment
• Fatigue
• In more advanced stades, as degeneration
and atrophy occur, more severe cognitiveproblems may appear
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Multiple sclerosis
• Impossible to predict evolution on anindividual scale
• MRI lesions and clinical symptoms may
not coincide on a temporal scale• Clinical picture may take different aspects,
depending on the location of the lesions
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Evolution
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• MRI
• CSF analysis
• Evoked potentials
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MRI
• Multiple lesions
• Hyperintense in Ts and FLAIR,hypointense in T1
• Round/ovalar, well defined margins• >85% perivenular
• Periventricular, calososeptal, subcortical,
brainstem, spinal chord
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MRI
Aspect patognomonic
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MRI
Spinal chord lesions
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MRI
Localizari infratentoriale
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MRI – gadolinium enhancement
T1 + contrast: ring shaped or nodularenhancement
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IRM – 6&/ ( 5 2 =$ 0 8 / 7,3/ A
• Best imagistic method for white matterevaluation
• MRI aspect allows MS diagnosis
• Gadolinium enhancement allows lesionactivity evaluation
• New MRI tehniques bring moreinformation, allowing for a better clinical-imagistic corelation
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CSF analysis
• Important for differential
diagnostic
• Oligoclonal bands –
accesory diagnostic criteria
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Evoked potentials
• VEP
• AEP
• SSEP
• MEP
Ascending (AEP, VEP, SSEP) and
descending pathways (MEP)
Demyelinations leads to slower conduction
and increased latencies
Functional and not structural information
Longer pathways – improved sensitivity
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Motor evoked potential
• Motor treshold.
• Amplitude and latency
• Central conduction time
• Other TMS techniques –
transcallosal inhibition
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Differential diagnosis
• Other inflamatory diseases (infectious andnon infectious)
• Cranio cerebral or spinal structural
abnormalities• Metabolic and endocrine disorders
• Neoplasic diseases
• Genetic and neurodegenerative disorders
O. Bajenaru: Ghiduri de diagnostic si tratament in neurologie – 2005
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Treatment
• DISEASE MODIFYING THERAPIES
– IMUNOMODULATORY
– IMUNOSUPRESANT
• RELAPSE TREATMENT
• SYMPTOMATIC AND REHABILITATIONTHERAPY
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Imunommodulatory treatment
• Beta interferons:• interferon beta l a (REBIF) s.c. 3 times/week
• interferon beta l a (AVONEX) i.m. 1/week
• interferon beta l b (BETAFERON) s.c., e.a.d.
• Glatiramer acetate ( COPAXONE ), s.c.,daily
• Natalizumab
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?eta interferons
• RRMS
• SPMS (in patient with relapses)
• CSI with high risk to developp MS
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Efect:
• Decrease of relapse rate
• Decrease of disease severity
• Decrease of disability progression rate
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Adverse events
• Flu-like syndrome; skin reactions
• Depression (Ifn beta 1 b)
• Liver function abnormalities
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B. Glatiramer acetate (Copaxone): :
• Decrease of relapse rate
• Decrease of disease severity
• Decrease of disability progression rate
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Contraindications
• Unclear diagnosis• Primary progressive MS• Depression• Pregnancy
• Severe diseases (haematological, liver,neoplasms)
• Intolerance•• Therapeuthic failure: 2-3 relapses in 6 months or
at least 4 relapses in one year
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Monoclonal antibodies
• Natalizumab
– IV, 1/month
– Better efficiency
– Potentially very severe adverse events (LMP)
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Imunosupressants:
• Approved: mitoxantrone (Novantrone,Onkotrone)
• other imunosuppresants: off label, in
special cases – azathioprin, metrothrexate, ciclophosphamide,
cladribine, ciclosporine, etc.
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Relapse treatment
• methil prednisolone 500-1000 mg/day 3-5days, i.v.
• Improvement of post relapse recovery
• No effect on overall long time disabilityprogression
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Rehabilitation and symptomatictreatment
• Adresses specific clinical conditions in MSpatients
• Improvement of quality of life
• Adapted for the clinical stage of thedisease and the disabilities of each patient
• Possibly a diminishment of disability
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Friedreich’s
disease
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• Degeneration of the long spinal
pathways (both ascending and
descending) and the peripheral nerve
fibers
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Clinical presentation
• Gait abnormalities
• Ataxia
• Speech disorders
• Nistagmus
• Hyporeflexia
• Trophic changes – High plantar arches (pes
cavus deformity of the foot)
• Sensory disturbance• Babinski sign
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Clinical presentation
• Symptoms typically beginsometime between the ages of 5to 15 years,
• scoliosis
• Diabetes (about 20% of peoplewith Friedreich's ataxia developcarbohydrate intolerance and 10%develop diabetes mellitus)
• Heart disorders (e.g., atrialfibrillation, and resultanttachycardia (fast heart rate) andhypertrophic cardiomyopathy )
• These symptoms are slow andprogressive. Long-term
observation shows that manypatients reach a plateau insymptoms in the patient's earlyadulthood.
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Genetics
• Autosomal recesive disorder
• Mutation of frataxin gene (9q13-q21)
• Long arm of cromosome 9
• Prevalence 1 : 50.000
• Genetic counselling!
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Treatment
• Physical therapy
• Nerve and muscle trophic drugs
• Treatment of complications
• Treatment of heart disorders
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