Differential
Differential Diagnosis: Multiple Sclerosis (MS)
05 Dec 2025 Author profile image Christoff Trüter Spousal caregiver
2

When my wife's condition initially began to escalate, one of the first diseases considered was Multiple Sclerosis (MS). The neurologist at the time quickly concluded it was functional, ruling out MS due to the absence of appropriate MRI lesions and stating that the clinical signs were insufficient for a definitive MS diagnosis.

That said, MS does not always present dramatically from an imaging perspective, and it can often take many years to be diagnosed. Its presentation is sometimes so subtle that it is detectable only clinically, as in a clinically isolated syndrome (CIS).

In some cases, patients may even be asymptomatic, yet show evidence of MS radiographically, referred to as radiologically isolated syndrome (RIS).

We are therefore not ruling it out completely. In fact, most of my wife's current treatment is based on MS protocols, regardless of an official diagnosis, given that her condition follows a clear progression and relapse pattern consistent with MS (she is experiencing yet another relapse at the time of writing, which is her third in a seven-year period.).

At the initial time of investigation, neurologists were still using the 2017 McDonald criteria, but the 2024 update differs in several respects.


Here is an overview of the current criteria.

  1. Dissemination in Space (where lesions appear)

       MRI image showing typical MS lesions in brain, spinal cord and optic nerve

    Lesions should be present in at least two of five locations, regardless of symptoms: juxtacortical/intracortical (JC/IC), periventricular (PV), infratentorial (IT), spinal cord (SC), and now the optic nerve (ON) as well. The inclusion of the optic nerve is quite helpful. If a neurologist prematurely closes diagnostic doors, an ophthalmologist can perform an OCT or VEP to detect optic nerve damage or optic neuritis and aid in investigations.

  2. Spinal fluid testing (CSF)

    Previously, when examining cerebrospinal fluid, observers would only look for oligoclonal bands. This indicates the presence of immune cells in the brain and spinal cord, suggesting that the patient’s immune system is actively attacking the CNS.

    In addition, Kappa-Free Light Chains (kFLC) can also be tested. Like oligoclonal bands, their presence indicates immune activity in the CNS.

  3. Dissemination in Time (passage of time between symptoms and lesions)

    Previously, there was a period of simmering, waiting and monitoring how the disease progressed over time before clinicians could make a diagnosis. This is no longer required, which speeds up the diagnostic process.

  4. Rule-out requirement

    MS remains a diagnosis of exclusion, meaning other causes, vascular, metabolic, infectious, or structural, must be considered first, including conditions that mimic MS, even other demyelinating diseases, before jumping the gun.

The updated criteria provide clearer tools as we continue treating along MS lines.

Instead of revisiting the diagnosis in light of the new criteria and properly monitoring my wife’s condition, the neurologist at the time continued to double down on their initial conclusion that it was functional. Yet her disease continues to progress consistently and reacts to medication as an organic disease would, realities that contradict FND and render that assessment both inappropriate and medically irresponsible.

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