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Radiologically isolated syndrome in a 46 year old female


Introduction and objectives

Radiologically isolated syndrome (RIS) refers to the phenomenon whereby individuals without neurologic symptoms are incidentally found to have MRIs with white matter changes suggestive of multiple sclerosis (MS).  This scenario, which is well recognized clinically, and increasingly common due to the prevalence of MRIs ordered for headaches, trauma and other reasons, raises multiple questions including whether the patient will ultimately go on to have symptomatic disease, how should the patients be monitored, and whether and at what point the patient should begin treatment for potential MS.  Risk factors - including radiologic risk factors - for the conversion of RIS into symptomatic disease are just beginning to be elucidated (Okuda et al, 2009; Sellner et al, 2010; Okuda et al, 2014).

Case presentation

A 46 year old female with a history of hypothyroidism presented to our MS center as a referral from her primary doctor.  While at a routine annual checkup she reported dull, holocephalic headaches that had started over the past year and had been increasing in frequency over the past month up to twice weekly.  Her primary doctor ordered a non-contrast MRI of the brain which showed T2 hyperintensities in a pattern concerning for MS.  She was subsequently referred to our MS Center for evaluation.  She was also ordered for an MRI of the brain to be done with contrast and was referred to an ophthalmologist for a visual exam. 

At our office, the patient reported being in overall excellent health and denied signs of systemic illness including rash, arthralgias, fevers, chills, or fatigue.  She reported that her thyroid function had been well controlled on synthroid for many years. The patient denied current or prior neurological symptoms including numbness, paresthesias, weakness, visual loss, or diplopia.  Other than the headaches, her only neurologic history was a peculiar episode of loss of consciousness that occurred 18 years prior.  She recalls waking from sleep with generalized shaking while in bed and then losing consciousness and waking in the bathroom.  She was immediately able to go to resume normal functioning and went to work that morning.  She reported that she subsequently followed up with a neurologist a couple times who “never found anything concerning” and that an EEG was reportedly normal.  (She was not sure whether she ever had an MRI at this time).  She never had any further events, and she stopped following up.

She has no family history of neurologic disease, and no history of toxic substance use. 



Clinical presentation

Upon examination, the patient was a well appearing female with normal vital signs, and a normal neurologic exam.


Above is the patient’s initial MRI.  The follow up MRI done with contrast did not reveal any enhancement.  An MRI of the cervical spine ordered by our center was normal. 

Laboratory studies

Laboratory testing ordered by the referring doctor showed ANA, Lyme Ab, and SSA/SSB that were negative and a CRP, ESR, and ANA that were normal.  TSH was within normal limits. 


A report from the ophthalmologist documented corrected visual acuity of 20/20 OU with normal visual fields.  Optokinetic tomography (OCT) testing demonstrated retinal nerve fiber layer thickness that was within normal limits bilaterally.


Although recent definitions of MS have allowed for increasing use of MRI to establish dissemination in time and space, the diagnosis of MS remains clinically rooted: a patient must have at least one neurologic event suggestive of a clinical relapse to establish a diagnosis.This patient has never had such a clinical event (neither her non-specific headaches nor her peculiar episode of LOC are consistent with a clinical relapse).Her MRI, with multiple juxtacortical and periventricular lesions - many perpendicular to the long axis of the lateral ventricle - are suggestive of MS and would in fact meet criteria for dissemination in space.They differ from the “non-specific”, punctuate, deep white matter lesions that are known to occur in headache patients.There is no better explanation for her white matter lesions as her history and labwork are not suggestive of an alternative disease process. The patient was given a diagnosis of radiologically isolated syndrome.

Question: What proportion of patients with radiologically isolated syndrome will develop a clinical event within 5 years of initial MRI?

a) 1/10 of patients
b) 1/3 of patients
c) 1/2 of patients
d) 2/3 of patients

A large retrospective study of RIS patients found that approximately 1/3 of patients will develop a clinical event within a 5 year period of their initial MRI at which point their diagnosis officially “converted” to multiple sclerosis.  Approximately 90% of those who developed clinical events had a relapse (developed RRMS), the other 10% went on to develop progressive symptoms (developed PPMS).  This study identified several factors that were predictive of 5 year risk: age <37 y, male sex, and spinal cord involvement (cervical or thoracic) increased risk of subsequent relapse (Okuda et al, 2014). 

Initial treatment

The decision was made not to begin the patient on disease modifying therapy (DMT) at this time.  It was decided that she should be monitored clinically and via serial MRI.  An MRI was scheduled 3 months from her initial MRI.  We discussed that if this MRI was unchanged we could space out MRIs further with the subsequent MRI 6 months later and then yearly for several years.  Should the MRI change - show new T2 lesions or enhancing lesions - we would reconsider DMT initiation. 

Outstanding questions

Whether, or in what situation, an RIS patient should begin DMT has not been well established and there are no clinical studies have been done to assess the relative benefits and risks.  However, in attempt to prevent or delay symptom development, some clinicians consider starting such patients on DMTs, especially if there are spinal cord lesions, if the MRI is changing, or if there is other paraclinical evidence of MS (i.e. CSF positive for oligoclonal bands or elevated IgG index). 

More patient cases by rebecca farber


great case!
Although individual practices vary and clinicians might opt to treat (or not treat) based on MRI evidence of cord lesions/CSF data (I typically treat if either test modality points to abnormalities that could be construed as being consistent with MS), it should be stressed that early treatment if at all possible, based on cord lesions/CSF data positivity must be initiated. However, with the new EPIC data from UCSF, a lot of new questions have arisen and it is inescapable that the treatment paradigms in MS must be revisited. Treatment of acute relapses does not seem to affect disability and hence newer agents that arrest neurodegeneration must be sought. Part of the problem is defining neurodegeneration and clinical identification of such changes early.