THE RADIOLOGICALLY ISOLATED THE RADIOLOGICALLY ISOLATED SYNDROME OF DEMYELINATIONSYNDROME OF DEMYELINATION

Is it Early Multiple SclerosisIs it Early Multiple Sclerosis (MS)? What to do (MS)? What to do WWhen hen Confronted by a Patient with Radiologically Isolated Confronted by a Patient with Radiologically Isolated

SyndromeSyndrome (RIS)? To Treat (RIS)? To Treat aand/or to Wait?nd/or to Wait?

Bartko DBartko D..1 2 51 2 5 , Rohalova J , Rohalova J..2 52 5, , Fabcin J Fabcin J..3 53 5,, Kubovicova K Kubovicova K..2 52 5, , Ščerbíkova M.Ščerbíkova M.4 54 5, , Bielikova Bielikova

EE..4 54 5, Latta V., Latta V.66

Institute of Medical Sciences, Neurosciences and Military HealthInstitute of Medical Sciences, Neurosciences and Military Health11, , Dept. of NeurologyDept. of Neurology22, MRI Center, MRI Center33,, Dept. of Ophtalmology Dept. of Ophtalmology44, Central Military University , Central Military University

HosptitalHosptital55, Ružomberok, Dept. of MRI, Ružomberok, Dept. of MRI66, Presov, , Presov, Slovak RepublicSlovak Republic

Suported by EU/gov. grants ITMS2202200099,ITMS 2202200153, INTERREG IIIA Suported by EU/gov. grants ITMS2202200099,ITMS 2202200153, INTERREG IIIA 14140200032, APVV0586-0614140200032, APVV0586-06

IntroductionIntroduction DefinitionDefinition

Radiologically isolated syndrome of Radiologically isolated syndrome of

demyelinationdemyelination ( (RIS Ocuda et al.RIS Ocuda et al. 2009, they2009, they

introduced the term) introduced the term)

has been defined as the unanticipatedhas been defined as the unanticipated• MRI findingsMRI findings of white matter (WM) lesions of white matter (WM) lesions

suggestive of demyelinating disease suggestive of demyelinating disease • in in subjects with a normal neurologicsubjects with a normal neurologic findings and findings and • no medical historyno medical history consistent with multiple sclerosis consistent with multiple sclerosis

(MS).(MS).

Although WM lesions may be detected in Although WM lesions may be detected in asymptomatic subjects asymptomatic subjects (De Stefano et al.(De Stefano et al. 2011),2011),

it is still unclear it is still unclear whether RIS should be considered whether RIS should be considered

a)a) a a subclinical MSsubclinical MS or or b)b) an an independent entityindependent entity or orc)c) it is it is MRI finding withoutMRI finding without any association with any association with

MSMS

There are There are only few studies,only few studies, demonstrating the occurrence of a clinical demonstrating the occurrence of a clinical deterioration deterioration in subjects with in subjects with RIS correlated RIS correlated to the presence of inflammatory markersto the presence of inflammatory markers

(Comi 2009, Trojano et al 2009(Comi 2009, Trojano et al 2009, , Lebrun et al.Lebrun et al. 2008)2008)

They found approximately one-third ofThey found approximately one-third of subjects subjects with with RIS associated later with RIS associated later with a clinically isolated syndrome (CISa clinically isolated syndrome (CIS)) particularly particularly those with those with asymptomatic cervical spinal asymptomatic cervical spinal lesionslesions (Okuda et al.(Okuda et al. 2011)2011)

AimAim

1.1. to present a case report and to discuss to present a case report and to discuss questions:questions:2.2. isis the RIS realy MS the RIS realy MS presenting with RIS? and/or presenting with RIS? and/or 3. it is 3. it is not MS,inot MS,it is t is ONLY RISONLY RIS of of demyelination?demyelination?4. If it is RIS, 4. If it is RIS, should we treatshould we treat the patient according to MS the patient according to MS

guide-line guide-line despite no clinical neurologic symptoms despite no clinical neurologic symptoms exist?exist? or or

5. Should we wait?5. Should we wait?6. What shoud we tell the patient6. What shoud we tell the patient??

Case ReportCase Report HistoryHistory

In 2003In 200318 yrs old girl, uncertain, very mild 18 yrs old girl, uncertain, very mild

sighting problems, occasionally. sighting problems, occasionally.

Ophtalmologist´s Ophtalmologist´s (University Professor)(University Professor)

diagnosis:diagnosis:• uveitisuveitis• Neurologic examination normalNeurologic examination normal

* * Brain MRIBrain MRI T1weighted, T2 weighted, Flair, T1weighted, T2 weighted, Flair, performed at local Faculty Hospital showed performed at local Faculty Hospital showed

5 5 small white matter abnormalitiessmall white matter abnormalities in in

supraventricular and periventricular region supraventricular and periventricular region interpretedinterpreted by radiologist (after Gd) by radiologist (after Gd) as as demyelinating MS.demyelinating MS. Spinal cord MRI not performed.Spinal cord MRI not performed.

CONCLUSION :CONCLUSION : MRI MRI brain lasions are brain lasions are typical typical for MSfor MS

Patient was unsatisfied with this Patient was unsatisfied with this conclusionconclusion

In 2003In 2003

she was admitted to another Univesity Dept. of she was admitted to another Univesity Dept. of Neurology. Neurology. Neurological findings:Neurological findings:• normalnormal, CSF, , CSF, no oligoclonalno oligoclonal bounds. bounds.

• VEPs, SEPs, ABEPs VEPs, SEPs, ABEPs normalnormal findings, findings, • Boreliosis in CSF Boreliosis in CSF negat.negat.• MRI MRI (from 2003): (from 2003): interpreted as no typical for MS interpreted as no typical for MS Diagnosis: Neurasthenia, Diagnosis: Neurasthenia, MS not confirmedMS not confirmed..

In 2011In 2011During period of 8 yrs patient During period of 8 yrs patient • withoutwithout clinical symtoms, clinical symtoms, • no relapses, no relapses, • no remissions, no remissions, • no treatedno treated..

• Neurological status Neurological status normal,normal, • CSFCSF: oligoclonal bounds: : oligoclonal bounds: positive.positive.

• VEPs, SEPs, ABEPs VEPs, SEPs, ABEPs normalnormal findings, findings, • Boreliosis in CSF Boreliosis in CSF negat.negat. • inflammation markers: inflammation markers: normnorm

new MRI:new MRI:

16 16 brain lesions brain lesions interpreted again as interpreted again as

demyelinating.demyelinating.

Patient is unsatisfied again,Patient is unsatisfied again,a little anxious a little anxious (of course, with such unclear diagnosis).(of course, with such unclear diagnosis).

She was admitted at Central Military University She was admitted at Central Military University HospitalHospital

Brain MRIBrain MRI

Brain MRIBrain MRI T2 weigted and Flair. T2 weigted and Flair.

16 16 brain MRI lesions interpreted as brain MRI lesions interpreted as demyelinating. After Gd no symptoms of inflammationdemyelinating. After Gd no symptoms of inflammation

MRI of Cervical MRI of Cervical Spinal CordSpinal Cord

MRI: one lesion (hyperintensity signal) in C2/C3 of spinal cord,23×5

mm, without expansion,without perifocal edem,without activity after Gd. It was interpreted as

demyelinating lesion

Final DiagnosisFinal Diagnosis in Central Military University Hospital:in Central Military University Hospital:

Multiple SclerosisMultiple Sclerosiswith recommendation of DMT therapywith recommendation of DMT therapy despitedespitethe patient showed the patient showed • no clinical symtoms of MS,no clinical symtoms of MS, • no relapses, no relapses, • no remissions,no remissions,• no oligoclonal bandsno oligoclonal bands

• normal VEPs,SEPs,ABEPsnormal VEPs,SEPs,ABEPs DMT therapy was not realizedDMT therapy was not realized

March 2012March 2012Patient want to be again examined byPatient want to be again examined byneurologistneurologist THEREFORETHEREFOREreadmission of patient to hospital (RK)readmission of patient to hospital (RK)

1. Neurological findings:1. Neurological findings:• 9 years no pathological neurologic findings, • no history of attacks, • no history of remissions,• mild problem with visus• no oligoclonal bands in CSF• normal VEPs, SEPs, ABEPsnormal VEPs, SEPs, ABEPs• subjectivelly she is filling healthysubjectivelly she is filling healthy• she is working for full day-timeshe is working for full day-time• At present: normal neurological status

2. Diagnostic programme a) New Brain MRI and new cervical spinal cord MRI b) Optical Coherence Optical Coherence Tomography (Tomography (OCT)OCT) c) c) NeurpsychologicalNeurpsychological Assessment and Assessment and d) d) ADLADL and and QoLQoL Scales Scales Some studies confirmed that Some studies confirmed that

a)a) evaluation of changes in morphology and function of evaluation of changes in morphology and function of optical nerve by mean of highly sophisticated methods optical nerve by mean of highly sophisticated methods ( RNFLT, OCT and others) ( RNFLT, OCT and others)

over time over time was likely one of the best approach was likely one of the best approach to monitor early disease onset and progression to monitor early disease onset and progression in Min MSS

FLAIR tra Rbk FLAIR Rbk

2. New Brain MRI ( March 26. 2012)

Brain MRI T2 weigted and Flair.

16 brain MRI lesions interpreted as demyelinating. After Gd no symptoms of activity, no expansion, no perifocal edema.

Conclusions, the same findings comparing to MRI( 2011), After Gd: no symptoms of infammation, no cortical atrophy

3. New Cervical Spinal Cord MRI

MRI of Cervical part of spinal cord. MRI of Cervical part of spinal cord. MRI :one lesion (hyperintense signal) in C2/C3, MRI :one lesion (hyperintense signal) in C2/C3, 23 × 5 mm, without expansion, without perifocal 23 × 5 mm, without expansion, without perifocal edema and without activity after Gdedema and without activity after Gd

Conclusions:Conclusions: the same findings the same findings comparing to 2011comparing to 2011

Do we knowDo we knowDiagnostic Criteria for RIS ? Diagnostic Criteria for RIS ?

Comparison Comparison of these Criteria of these Criteria with the results with the results

of our patientof our patient

Diagnostic criteria for the RISDiagnostic criteria for the RIS

A.A. MRI criteria: MRI criteria: 1.1. Ovoid,Ovoid, well-circumscribed. and well-circumscribed. and homogeneous focihomogeneous foci

with or with or withoutwithout involvement of the involvement of the corpus callosumcorpus callosum

2.2. T2 hyperintensities measuring T2 hyperintensities measuring >3 mm>3 mm and fulfilling and fulfilling Barkhoft criteria (Barkhoft criteria (at least 3 out of 4)at least 3 out of 4) fo for r dissemination in spacedissemination in space and time and time

3.3.CNS white matter anomalies not consistent with a CNS white matter anomalies not consistent with a vascular patternvascular pattern

B.B. No history of remitting clinical symptoms No history of remitting clinical symptoms consistent with neurologic dysfunction consistent with neurologic dysfunction

C.C. The MRI anomalies do not correlate The MRI anomalies do not correlate

1.1. with impairments in social,with impairments in social,2.2. in occupational, or in occupational, or 3.3. generalized areas of functioninggeneralized areas of functioning

D.D. The MRI anomalies The MRI anomalies are not due toare not due to 1.1. the direct physiologic effects of substances (recreational the direct physiologic effects of substances (recreational drug abuse, drug abuse,

toxic exposuretoxic exposure) ) 2.2. or a medical conditions or a medical conditions

E.E. Exclusion of individuals Exclusion of individuals 1.1. with MRI phenotypes suggestive of with MRI phenotypes suggestive of leukoaraiosisleukoaraiosis 2.2. or extensive white matter pathology or extensive white matter pathology lacking involvement of the lacking involvement of the

corpus callosum corpus callosum

Our patient fulfils all these criteriaOur patient fulfils all these criteriaBUTBUT

BUTBUT

There exist another possibility for explaining There exist another possibility for explaining our main question: our main question: 1.1. Optical Coherence TomographyOptical Coherence Tomography2.2. Neurpsychological Assessment and Neurpsychological Assessment and 3.3. ADL and QoL ScalesADL and QoL Scales

4. Optical Coherence Tomography4. Optical Coherence Tomography

OCT (healthy subject OCT MS patientOCT (healthy subject OCT MS patient

5. Neuropsychological Assessment5. Neuropsychological Assessment

1.1. London Handicap ScaleLondon Handicap Scale: 6 points MS has no infuence : 6 points MS has no infuence on social life of patienton social life of patient

2.2. Fatigue Severity ScaleFatigue Severity Scale 28/63 points (mild signs of 28/63 points (mild signs of fatigue)fatigue)

3.3. Montreal Cognitive AssesmentMontreal Cognitive Assesment (MCCA) 28/30 points (MCCA) 28/30 points (normal findings, without cognitive impairment)(normal findings, without cognitive impairment)

4.4. Intrelect Potential TestIntrelect Potential Test (IPT) 20/29 points (normal (IPT) 20/29 points (normal findings, time perception takes as a stress)findings, time perception takes as a stress)

5.5. Wechsler Memory ScaleWechsler Memory Scale MQ=101, mild deficit in logical MQ=101, mild deficit in logical memorymemory

6.6. Rey Complex FigureRey Complex Figure

7.7. Disjunctive Reaction TimeDisjunctive Reaction Time (DRT) 56/60 (DRT) 56/60 pointsperfect working tempopointsperfect working tempo

8.8. Hospital Anxiety and Depression ScaleHospital Anxiety and Depression Scale

Anxiety Scale ´10 points, Anxiety Scale ´10 points,

Depression Scale = 2 pointsDepression Scale = 2 points

9.9. Beck Depression InventoryBeck Depression Inventory 5/63 points, 5/63 points, normalnormal

10.10. Eisenck Personality InventoryEisenck Personality Inventory Extravesion Scale=10/24, Extravesion Scale=10/24, Neurotiscism Scale =19/24,Neurotiscism Scale =19/24,

11.11. Sensefulness Life ScaleSensefulness Life Scale 76/90 point76/90 point

12.12. MSQOLMSQOL-54 Škala kvality života -54 Škala kvality života 79/100 79/100

13.13. Physical Health Composit ScorePhysical Health Composit Score 82 8214.14. Mental health Composite ScoreMental health Composite Score 76 7615.15. ADL for MSADL for MS 6 points (independant during activity of 6 points (independant during activity of

daily livingdaily living

SummarisingSummarising:: all neuropsychological parameters all neuropsychological parameters showed normal findingsshowed normal findings

COMMENT- DISCUSSIONCOMMENT- DISCUSSION

In 2009,In 2009, Okuda and colleagues" introduced Okuda and colleagues" introduced

the term the term

““radiologically isolated syndrome” (RISradiologically isolated syndrome” (RIS) )

to describe patients who have to describe patients who have a)a) brain MRI abnormalitiesbrain MRI abnormalities

b)b) suggestive of MS suggestive of MS

but but c) c) who have no signs or symptoms of the disease. who have no signs or symptoms of the disease.

d) d) without clinical evidence of MS without clinical evidence of MS

that ful- filled at least 3 of 4 Barkhof criteria.that ful- filled at least 3 of 4 Barkhof criteria.

Table. 1. Table. 1. Barkhof–Tintore criteriaBarkhof–Tintore criteria for anatomic dissemination by brain for anatomic dissemination by brain MRI MRI (greatest accuracy in predicting clinically (greatest accuracy in predicting clinically

definite MS achieved with ≥3positive parameters)definite MS achieved with ≥3positive parameters)

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

1.1. At leastAt least one or more Gdone or more Gd enhancing lesionsenhancing lesions or or

nine T2 hyperintense lesionsnine T2 hyperintense lesions if there is no Gd if there is no Gd enhancing lesionenhancing lesion

2.2. At leastAt least three or morethree or more periventricular lesionsperiventricular lesions

3.3. At leastAt least one or moreone or more infratentorial lesionsinfratentorial lesions

4.4. At leastAt least one or moreone or more juxtacortical lesionsjuxtacortical lesions

5.5. one orone or more spinal cord lesionsmore spinal cord lesions (revisited July 2011)(revisited July 2011)

Two years laterTwo years later (2011) the same (2011) the same

authors described a retrospective studyauthors described a retrospective study

of 71 subjects with RIS of 71 subjects with RIS

who had cervical MRI scanswho had cervical MRI scans performed. performed.

• 3535 %% of the subjects with RIS had T2 hyperintensitiesof the subjects with RIS had T2 hyperintensities in the in the

cervical cord, and cervical cord, and

• 8484 %% of these subsequently developed a CIS. of these subsequently developed a CIS.

This study suggests thatThis study suggests that 1.1. pts who have pts who have RISRIS and and

2.2. spinal cord T2spinal cord T2 hyperintensities hyperintensities

3.3. may be at may be at high risk of developing MShigh risk of developing MS

while while 4.4. those those without spinal cordwithout spinal cord abnormalities abnormalities

may have a may have a very low riskvery low risk. .

5.5. This is an This is an important re-definitionimportant re-definition of the concept of of the concept of RISRIS as a risk factor for developing MS and may prove to be as a risk factor for developing MS and may prove to be important for decision for an early treatment of MSimportant for decision for an early treatment of MS ((Tinton Tinton 2006)2006)

However, However,

a large prospective study is needed to delineate a large prospective study is needed to delineate

accurately the natural history of RISaccurately the natural history of RIS

This contribution revisitedThis contribution revisited

“the term RIS”

BUT despite of this,the decision is not easy.How are the possibilities

for right decision?

There are someThere are some key pointskey points1.1. to findto find new parametersnew parameters which can contribute which can contribute

to decisionto decision

2.2. to findto find new clinical or radiological new clinical or radiological findingsfindings which can bring new dimension for which can bring new dimension for more precise diagnosis of MSmore precise diagnosis of MS

3.3. to findto find new approachnew approach which can increase the which can increase the accuracy of MS diagnosisaccuracy of MS diagnosis

The first key pointThe first key point.. It is well known that It is well known that

the basic characteristic of all diagnostic the basic characteristic of all diagnostic

criteria for MScriteria for MS

requirerequire

the demonstratiothe demonstration n of diseaseof disease

dissemination dissemination

in space and time.in space and time.

i.e. the i.e. the confirmationconfirmation

of two or more of two or more clinical attacksclinical attacks, ,

separated in timeseparated in time, ,

which involve which involve

at least two at least two separatedseparated areas areas

of the CNS of the CNS (space).(space).

Moreover, Moreover,

CNS is not only brain but alsoCNS is not only brain but also

spinal cordspinal cord

Therefore we have performed Therefore we have performed

MRI of the MRI of the cervical spinal cordcervical spinal cord and we have and we have confirmedconfirmed hyperintensities hyperintensities

in cervical spinal cordin cervical spinal cord.. This means This means

a)a) this parameter this parameter can contributecan contribute to the decision to the decision

BUT BUT

a)a) it doesn´t mean that it has to confirmed it doesn´t mean that it has to confirmed the the possibility of subsequent MS.possibility of subsequent MS.

b)b) This is very This is very important to knowimportant to know

Why would spinal cord lesions Why would spinal cord lesions

in RIS in RIS

have such a strong influencehave such a strong influence

on the riskon the risk of developing of developing

symptomatic demyelinating symptomatic demyelinating

disease?disease?

BecauseBecause ddemyelinating brain lesion emyelinating brain lesion can occurcan occur in in

a variety of conditionsa variety of conditions • migraine, migraine, • age related changes, age related changes, • asymptomatic cerebrovascular disease, asymptomatic cerebrovascular disease, • boreliosis,boreliosis,• others (not associated with age),others (not associated with age),

THEREFORETHEREFOREan assumption that the brain abnormalities in RISan assumption that the brain abnormalities in RIS

represent areasrepresent areas of demyelination associated with MS of demyelination associated with MS

is not warranted. is not warranted.

WHY?WHY?

The Barckroft criteria were developed asThe Barckroft criteria were developed as

a means of predictinga means of predicting

which patients with a first clinical demyelinating which patients with a first clinical demyelinating eveneventt

werewere at high riskat high risk of developing MSof developing MS

and not to differentiate and not to differentiate

MS from other causesMS from other causes of white matter abnormalities.of white matter abnormalities.

OUR OPINION

RIS is heterogenic syndrome (not simply presymptomatic MS) consisting of pts 1. with MRI demyelinatig BRAIN

lesions !!! a) without clinical neurologic correlationb) without significant influence c) on functional health of subject

AND/OR

2.2. with MRI demyelinatig with MRI demyelinatig BRAINBRAIN and and also also SPINAL CORDSPINAL CORD lesions!!! lesions!!!

a)a) and therefore withand therefore with possibility possibility to to development of typical development of typical MRIMRI symptoms of symptoms of MS MS

BUTBUTb)b) without without clinical neurologic correlation clinical neurologic correlation

therefore,therefore,

in this group of pts it not possible in this group of pts it not possible

toto use Barkroft criteriause Barkroft criteria

c) c) All diagnostic criteria for MS, including the All diagnostic criteria for MS, including the most recent most recent

McDonald criteria, McDonald criteria,

require at leastrequire at least

one one or two or two clinical eventclinical eventss

consistent with MSconsistent with MS, i.e,, i.e,

disseminated in disseminated in TIMETIME

and SPACEand SPACE

The second key pointThe second key point

is the timeis the time of the starting inflammation orof the starting inflammation or demyelinating processes. demyelinating processes. We should find We should find

the marker or clinical sign of the the marker or clinical sign of the early early stage of the disease.stage of the disease.

There are There are two possibilitiestwo possibilities

a)a) assessment of assessment of neuropsychological profilneuropsychological profil of pts wit of pts wit suspected MS. suspected MS. Cognitive impairment could be the first symptoms of Cognitive impairment could be the first symptoms of the pathological changes in the brain associated the pathological changes in the brain associated with MSwith MS

b)b) assessment of assessment of Optical Coherence TomographyOptical Coherence Tomography (OCT).(OCT). Some studies have employed OCT to evaluate Some studies have employed OCT to evaluate changes in optic nerv associated with multiple changes in optic nerv associated with multiple sclerosis (MS)sclerosis (MS)

c)c) we have used both these possibilities. we have used both these possibilities.

Why?Why?

Approximately Approximately 50 %50 % of patients with MS of patients with MS

havehave

disease-related disease-related cognitive deficits.cognitive deficits.

These deficits significantly interfere These deficits significantly interfere

with with everyday life activitieseveryday life activities at home and at home and

at work at work

and erode and erode quality of lifequality of life (QoL) (QoL)Amato et al Amato et al (2012)(2012) in very well designed in very well designed

ppublicationublication reported cognitive impairment of reported cognitive impairment of

the same profile as that of RRMS in 27.6the same profile as that of RRMS in 27.6 %% of of

subjects with RIS.subjects with RIS.

On On quantitative MRIquantitative MRI they found they found

comparable comparable

levels of lesion loads and levels of lesion loads and brain atrophybrain atrophy

a)a) in subjects with in subjects with RISRIS and and

b)b) well-established well-established RRMSRRMS. .

c)c) in subjects with RIS, high T1 lesion volume in subjects with RIS, high T1 lesion volume (σ = (σ = 0.526,0.526, p = p = 0.025) 0.025) and low and low cortical volume (σ = -0.481, p = 0.043)cortical volume (σ = -0.481, p = 0.043)

They were associated with They were associated with

worse cognitive performanceworse cognitive performance

Figure. MRI data expressed in cm3 in RIS, RRMS, and healthy controls (HCs)

NBV = normalized brain volume; NCV = normalized cortical volume; T1/LV = T1 lesion volume; T2/LV = T2 lesion volume (Amato et al. 2012)

We have performed We have performed in our patientin our patientthe comprehensivethe comprehensive assessment ofassessment of• psychological profil, psychological profil, • ADL and ADL and • QoL in our patientQoL in our patient. . • This consists of 15 scales.This consists of 15 scales.

No significant changes in allNo significant changes in all followed parameters were found.followed parameters were found.

It is well known that It is well known that

MS can result in a variety of ophthalmic MS can result in a variety of ophthalmic

disordersdisorders, including optic neuritis (ON). , including optic neuritis (ON).

MRI is not sufficientMRI is not sufficient modality modality for the for the

detection of detection of a)a) active inflammation, active inflammation,

b)b) chronic post-attack neuro-degeneration and chronic post-attack neuro-degeneration and

c)c) the number and volume of clinically silent lesions,the number and volume of clinically silent lesions,

d)d) tthe correlation between lesion quantification he correlation between lesion quantification

by conventional MRI and morphological and by conventional MRI and morphological and

functional disabilities of optic nerve is relatively poor.functional disabilities of optic nerve is relatively poor.

There exist several There exist several new, highly new, highly sophisticatedsophisticated

ttechniquesechniques (n(n == 5) for quantitative evaluation of 5) for quantitative evaluation of optic nerve: optic nerve: a)a) peri-papillary retinal nerve fibre layer thickness peri-papillary retinal nerve fibre layer thickness

(RNFLT), (RNFLT), b)b) macular volume changes with a variety of techniques, macular volume changes with a variety of techniques,

such as red-free such as red-free fundus photography, fundus photography,

c)c) scanning laser polarimetry, scanning laser polarimetry, d)d) Heidelberg retinal tomography or Heidelberg retinal tomography or

e)e) optical coherence tomographyoptical coherence tomography ( (OCT, OCT, Sic et al. Sic et al. 20102010))

From this point of view, it seems to beFrom this point of view, it seems to be

very useful very useful

to include one of above mentioned to include one of above mentioned

technique in the algorhythm of diagnostic technique in the algorhythm of diagnostic decision of RIS , decision of RIS ,

We have used OTCWe have used OTC. . The results clearly demonstrated the pathological The results clearly demonstrated the pathological

changes on OTC comparing to controls (see figure)changes on OTC comparing to controls (see figure)

BUTBUT

the results are limited by another disease the results are limited by another disease

of the patient “Dysplasia of optic nerve”.of the patient “Dysplasia of optic nerve”.

TherforeTherfore

it is very difficult to take this parameter it is very difficult to take this parameter

as contributing factor for MSas contributing factor for MS

1st QUESTION1st QUESTION

Should we treat

pts with RIS (with only MRI brain lesions) according to MS guidelines?

ANSWER

1. we should not treat pts with RIS without MRI spinal cord lesions

WHY?

a) The pts without spinal cord lesions appear

to have a low risk of

developing MS b) They are more likely to have another

explanation for their brain MRI

abnormalities

2nd2nd QUESTION regarding therapy

What about the pts with RIS and a) MRI brain and spinal cord lesions

b) Gd enhancement,

c) brain atrophy,

d) T1 hypo intensities,

e) new lesions that might be suggestive

of presymptomatic MS?

Should we treat such pts?

ANSWER 1. Not to treat such patients, WHY?

because a) all these findings are laboratory findings b) there are no neurological symptoms Moreover

c) there exist some other markers, they can contribute to decision

Optical Coherence Tomography or other parameters of morphology and function of optic nerve (they can show eary changes of optical nerve)

3rd QUESTION

1. Should we wait?

BUT

waiting can be associated

with the delay of therapy

Treating asymptomatic pts

based on

MRI

"suggestive of MS"

without prospective natural history data

is no clever decision.

We treat the patient,

not the MRI scan !!!!

FINAL QUESTION1. What to do with someone in whom

a) there were identified pathologies that are very suspicious for MS

b) in whom MRI scan progresses over time?

ANSWER

We have no rights that anything what we do,

is right decision

Moreover, „we have not the right to say an individual

with RIS who has collected more MRI lesions

that he/she has MS"

And also,

we cannot advocate and recommend

DMT therapies,

because we don't know to what extent this

diagnosis and this therapy will influence the disease and, above all, the expectations of future life of patient.

Conclusions1. The concept of RIS is an exciting concept for

neurologists, showing patients with evidence of MRI lesions, their dissemination in time and space without clinical correlations,

2. Discussion and decision,

a) if it is early sign of MS and , therefore to treat it or

b) if it is not early sign of MS and therefore not to treat it,

is not easy.

3. MRI of spinal cord can help and should be performed

not only in every subject with suspected MS but also

in every „patient“ with RIS (brain MRI) without clinical correlation

4. The best solution, to perform a) quantatative evaluation of brain volume and cortical

volume

b) to performe very precise and complex evaluation of

neuropsychological profil of pts incl. QoL and ADL

c) and all possible inflammatory markers

5. In our opinion, pts showing only time and space dissemination on MRI without clinical symptoms and cognitive impairemnt would

not be considered to have MS

andtherefore not to be treated

We treat the patient, not the MRl scan!!!

Thank you

very much

for

your attention

LIFE is great LIFE is great miraclemiracle,,

because it is non-because it is non-repetitiverepetitive