6 ms friedreich

8/4/2019 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



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)



• The most widelly accepted hypothesis: – An autoimmune disease that is triggered by un unknown

environmental factor in genetically susceptible persons



••DemielinationDemielination

is due to anis due to an

autoimmuneautoimmune

reactionreaction



Patogenical aspects

• Brain-blood barrier breakdown

• Inflamation

• Demielination

• Oligodendrocyte loss

• Reactive gliosis

• Degeneration and axonal loss



INFLAMATION – DEGENERATION

RelapseAcute clinical

presentation Cronic signs;

increase of disability



Chronic lesions

• Plaques – Different degrees

of inflammation

– Perivascular

– hyperintense onT2-weighted andFLAIR images andhypointense on T1-weighted scans



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



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



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



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



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



Relapsing/Remitting (RRMS)

• 85%

• Twice more infemales

• Relapses followedby remission



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



Progressive Relapsing/Remitting(PRMS)

• Relapses and

remissions exist

• During remissionthere is a slow

progression of

symptoms

• Approximativelly 5%

of cases.



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



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



Clinical picture

• Motor (pyramidal)involvement

• Sensory

• Cerebellar

• Brainstem

• Visual

• Sphincterian

• Higher functions



Cerebellar syndrome

• Ataxia, gait trouble

• Limb coordination problems

• Tremor

• Dysmetria

• Dysartria



Pyramidal syndrome

• Upper motor neuron syndrome:

–Paraparesis

–Hemiparesis

–Tetraparesis



Vestibular Syndrome

• Static and dynamic balance problems

• Nystagmus



Visual problems

• Optic neuritis

• Diplopia / internuclaer oculomotricity

paresis



Optic neuritis

• Retrobulbar

• Pain, sight loss

• Scotoma -> blindness

• Usually unilateral





Sfincterian abnormalities

• Retention/incontinence

• Disuria

• Constipation



Cognitive

• Depression

• Euphoria

• Memory impairment

• Fatigue

• In more advanced stades, as degeneration

and atrophy occur, more severe cognitiveproblems may appear



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



Evolution





• MRI

• CSF analysis

• Evoked potentials



MRI

• Multiple lesions

• Hyperintense in Ts and FLAIR,hypointense in T1

• Round/ovalar, well defined margins• >85% perivenular

• Periventricular, calososeptal, subcortical,

brainstem, spinal chord



MRI

Aspect patognomonic



MRI

Spinal chord lesions



MRI

Localizari infratentoriale



MRI – gadolinium enhancement

T1 + contrast: ring shaped or nodularenhancement



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



CSF analysis

• Important for differential

diagnostic

• Oligoclonal bands –

accesory diagnostic criteria



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



Motor evoked potential

• Motor treshold.

• Amplitude and latency

• Central conduction time

• Other TMS techniques –

transcallosal inhibition



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



Treatment

• DISEASE MODIFYING THERAPIES

– IMUNOMODULATORY

– IMUNOSUPRESANT

• RELAPSE TREATMENT

• SYMPTOMATIC AND REHABILITATIONTHERAPY



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



?eta interferons

• RRMS

• SPMS (in patient with relapses)

• CSI with high risk to developp MS



Efect:

• Decrease of relapse rate

• Decrease of disease severity

• Decrease of disability progression rate



Adverse events

• Flu-like syndrome; skin reactions

• Depression (Ifn beta 1 b)

• Liver function abnormalities



B. Glatiramer acetate (Copaxone): :

• Decrease of relapse rate

• Decrease of disease severity

• Decrease of disability progression rate



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



Monoclonal antibodies

• Natalizumab

– IV, 1/month

– Better efficiency

– Potentially very severe adverse events (LMP)



Imunosupressants:

• Approved: mitoxantrone (Novantrone,Onkotrone)

• other imunosuppresants: off label, in

special cases – azathioprin, metrothrexate, ciclophosphamide,

cladribine, ciclosporine, etc.



Relapse treatment

• methil prednisolone 500-1000 mg/day 3-5days, i.v.

• Improvement of post relapse recovery

• No effect on overall long time disabilityprogression



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



Friedreich’s

disease



• Degeneration of the long spinal

pathways (both ascending and

descending) and the peripheral nerve

fibers



Clinical presentation

• Gait abnormalities

• Ataxia

• Speech disorders

• Nistagmus

• Hyporeflexia

• Trophic changes – High plantar arches (pes

cavus deformity of the foot)

• Sensory disturbance• Babinski sign



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.





Genetics

• Autosomal recesive disorder

• Mutation of frataxin gene (9q13-q21)

• Long arm of cromosome 9

• Prevalence 1 : 50.000

• Genetic counselling!



Treatment

• Physical therapy

• Nerve and muscle trophic drugs

• Treatment of complications

• Treatment of heart disorders

Documents

6 ms friedreich