ClinicSpeak & NeuroSpeak: how to define a relapse or not?

Isn’t it time we cleaned-up our act on defining and assessing relapses? #NeuroSpeak #ClinicSpeak #MSResearch

The study below looks at the utility of emergency MRI to diagnose MS relapses and confirms that it is worthwhile, i.e. 87.5% of MSers with exacerbations, or relapses, had active scans. They also mention that pseudo-exacerbations occurred in 18 patients, with almost all having inactive scans. 

I have problems with this study in that it almost certainly involves a diagnostic tautology; i.e. the neurologists almost certainly took into account the presence of an active MRI, and an inactive MRI, to make the diagnosis of a relapse or pseudorelapse, respectively. Therefore the results are self-fulfilling. What should have been done in this study is a diagnosis of a relapse, or pseudorelapse, should have been made without looking at the MRI and then seen how often the MRI scan was active (positive) or inactive (negative). This is why retrospective studies using chart, or EPR (electronic patient record), review are not as good as prospective studies with a hypothesis. The medical literature is full of tautologies like this. Studies like this, however, may lead to changes in clinical practice; for example, based on this study some neurologists may conclude that they need t o see MRI activity to diagnose a relapse. This is a problem for me, because you can have a relapse without any disease activity on MRI. A small lesion, below the detection threshold of the MRI scanner (3-4 mm), in a strategic location can cause a relapse. I have seen the latter many times in my career; patients with definite signs of a lesion in a particular area, but no lesion on MRI.

I worry that neurology, like so many other areas of medicine, is increasingly becoming dependent on technology rather than clinical skills. Please note that our current definition of a relapse does not require an MRI to confirm the diagnosis of a relapse. In someone with established MS who presents with a relapse do you need an MRI? In the majority of cases you don’t. The question you need to ask yourself is how is the result of the MRI going to change your practice? Will it change your decision to use steroids or not? Will it change your diagnosis from a relapse to a pseudorelapse? If the answer to the latter question is yes then you need to ask what the sensitivity and specificity of MRI in this situation is. I am not aware of any studies that have been done to address this question. These issues raise the question of what is a relapse and what is a pseudorelapse?

I think I know what causes pseudorelapes, but I have difficulty defining it as a clinical entity. Are they all relaspes that don’t fulfil our current definition of a relapse? Now that we are doing annual Gd-enhanced MRI studies on all of our patients on DMTs, t oo many patients with transient, or intermittent, symptoms have evidence of active disease on MRI in the last 12 months. I therefore think that we shouldn’t dismiss transient symptoms as being insignificant and that our current definition of what is a relapse is far too restrictive. At present we define a relapse as ‘the appearance of new symptoms, or the return of old symptoms, for a period of 24 hours or more – in the absence of a change in core body temperature or infection’. This definition does not allow us to make a diagnosis of a relapse in patients presenting with new symptoms, that are not associated with focal neurological signs for example, cognitive issues, fatigue, sleep disorders (e.g. narcolepsy), Lhermitte’s sign, flexor spasms, trigeminal neuralgia, etc. In trial protocols the definition of what is a relapse is even more restrictive and typically require patients to move on the EDSS and/or one of the functional systems (FS) (one FS by at least 2 points or two FS by at 1 point). This is why when you read the results of trials we often discuss protocol and non-protocol defined relapses; the former fulfils a strict definition based on metrics and the second is based on the call of the assessing neurologist. Who do  you believe? I think we need to reassess our definition of what is a relapse and seriously think about how we define pseudo-relapses in MS. 

Pakpoor et al. Emergency Department MRI Scanning of Patients with Multiple Sclerosis: Worthwhile or Wasteful? AMJNR Published online before print October 6, 2016, doi: 10.3174/ajnr.A4953

BACKGROUND AND PURPOSE: The increasing use of the emergency department MR imaging scanner at our institution raises questions about its added value to certain patient groups. We hypothesized that the use of emergency department MR imaging for identifying active demyelination in MS patients presenting with new neurologic symptoms would be of low yield.

MATERIALS AND METHODS: Electronic medical records were reviewed for patients with MS who had emergency department MR imaging scans for a suspected MS exacerbation between March 1, 2014, and March 1, 2016. Details surrounding patient disposition, imaging, diagnosis, and management were determined.

RESULTS: Of 115 patients in our study, 48 (41.7%) were ultimately diagnosed with an MS exacerbation. Nearly all patients with MS exacerbations (87.5%, 42/48) had active demyelination on their emergency department MR imaging, identified on 30.6% (33/108) of brain MRIs and 20.4% (19/93) of spinal MRIs. The presence of active demyelination at MRI was significantly associated with the ultimate diagnosis of an MS exacerbation (P < .001). MR imaging activity isolated to the spinal cord (ie, not found on concurrent brain MR imaging) was present in only 9 of 93 (9.7%) cases. Pseudoexacerbations accounted for 18 of the alternative diagnoses.

CONCLUSIONS: Emergency department MR imaging is a worthwhile endeavor from a diagnostic standpoint for MS exacerbations despite not being part of the diagnostic criteria. This finding has corresponding downstream impact on management decisions to admit and/or administer intravenous steroids. However, we raise the question of whether clinicians over-rely on emergency department imaging for making exacerbation diagnoses. Additionally, spinal MR imaging is of questionable value as an addition to brain MR imaging due to a low yield of isolated spinal disease.

10 thoughts on “ClinicSpeak & NeuroSpeak: how to define a relapse or not?”

  1. Re: "I worry that neurology, like so many other areas of medicine, is increasingly becoming dependent on technology rather than clinical skills."Get used to it, Prof G. I'll argue that your profession won't even exist in the next twenty-five years aa technology usurps most white collar jobs. It will encroach on law, teaching, engineering, accountancy, all of it. 85% of current jobs will be gone by 2050. Seriously.

    1. Hopefully the neurology algorithms will be less conservative regarding treatments for MS, though hopefully MS too will be a thing of the past by then.

  2. I completely agree with all the points raised here. I have had two neurologists. One said "if it's not on the MRI you're faking it" and sent me to a psychiatrist. The second one said "there's obviously disease activity, it's just that the MRI can't see it". I worry that the reliance on technology will mean we will end up with more of the first type of neuros than the second.

  3. How many patients will get diagnosis of SPMS because relapses are diagnosed pseudorelapses? Every time I go to the neurologist with a "relapse" we have the same discussion… Is this a relapse or a pseudorelapse. In the mean time the dammage to my spinal cord is getting bigger and bigger. This is a very important issue.

    1. I think most of us think the clinical definition of what is and what isn't SPMS is a thumb suck. It is clear that it is a very grey area and that is why we need to focus on other markers of of ongoing inflammation.

  4. I would prefer not to have an MRI everytime I have symptoms. Sometimes both me and my neurologist just know it's new disease activity. Why get an MRI? They are not cheap and add to healthcare expenses.

    1. I would like an MRI with new activity as I would want to know if it's time to escalate my DMT. If I have a relapse that lasts several months and is fairly severe I want to know if my DMT has failed. I have had relapses before that last several months but no change on MRI.This then makes me think is that due to quality of MRI machine and the skills of the radiographer and radiologist.

  5. Atos ask 'When was your last relapse?' Given the uncertainty of what is or is not a relapse and the fact that some will not show on MRI, and that recovery is not an exact science anyway, it concerns me that they would ask this question. I wander what their understanding of RRMS is. Even neuros have differing ideas on what is or is not a relapse.

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