Diagnosing Multiple Sclerosis (MS)
The diagnosis of multiple sclerosis requires demonstrating dissemination of lesions in both time and space through a combination of clinical assessment, MRI, cerebrospinal fluid analysis, and sometimes evoked potentials, while excluding other conditions that may mimic MS. 1
Core Diagnostic Approach
- MS diagnosis is based on obtaining objective evidence of dissemination in time (DIT) and space (DIS) of lesions typical of MS, while excluding other possible explanations for the clinical features 2
- MRI is the most sensitive and specific paraclinical test for MS diagnosis, showing characteristic lesions in the brain and spinal cord 1
- Clinical evidence depends primarily on objectively determined clinical signs, not just symptoms reported by patients 2
MRI Criteria for MS Diagnosis
- For dissemination in space (DIS), lesions must be detected in at least two of the following locations: periventricular, cortical/juxtacortical, infratentorial, or spinal cord 1
- For dissemination in time (DIT), either the presence of both gadolinium-enhancing and non-enhancing lesions on a single MRI, or a new T2 or gadolinium-enhancing lesion on follow-up MRI compared with baseline is sufficient 1
- RRMS typically shows higher inflammatory activity on MRI with more gadolinium-enhancing lesions, while PPMS shows less inflammatory activity 3
Cerebrospinal Fluid Analysis
- CSF analysis showing oligoclonal bands (detected by isoelectric focusing) that are different from any such bands in serum, or a raised IgG index, provides evidence of inflammation and immunological disturbance 1
- CSF analysis is particularly valuable when clinical presentation is atypical or MRI findings do not fully meet diagnostic criteria 1
- Tests used for MS diagnosis in CSF include Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection 4
Definition of MS Attack
- An "attack" (exacerbation, relapse) refers to an episode of neurological disturbance typical of MS 2
- For diagnostic purposes, an attack should last for at least 24 hours 2
- Separate attacks should be separated by at least 30 days from the onset of the first event to the onset of the second event 2
Visual Evoked Potentials and Other Tests
- Visual evoked potentials showing delay with a well-preserved waveform can provide additional support for diagnosis, particularly in situations with few MRI abnormalities 1
- VEPs are especially useful when MRI findings have less specificity (e.g., in older individuals with risk factors for microvascular ischemic disease) 1
- Other evoked potentials contribute little to the diagnosis of MS 2
Diagnostic Categories
- Following diagnostic evaluation, a patient is classified as having MS, "possible MS" (for those at risk but with equivocal evaluation), or "not MS" 1
- The older terms "clinically definite" and "probable MS" are no longer recommended 1
- MS is classified into four main clinical phenotypes: relapsing-remitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndrome 3
Special Considerations and Pitfalls
- Diagnosis should be made with caution in patients with atypical presentations, such as those with dementia, epilepsy, or aphasia 1
- Special care must be taken in making a diagnosis of MS in those who are younger than 10 or older than 59 years at presentation, those with a progressive onset, and those with unusual features 2
- Differential diagnosis includes conditions that can mimic MS clinically or radiologically, such as multifocal areas of cerebral ischemia, infections (HTLV1, Lyme disease), paraneoplastic disorders, acute disseminated encephalomyelitis, neuromyelitis optica, and leukodystrophies 2, 5
- Misdiagnosis remains a significant issue in MS clinical care, even at MS specialty centers, highlighting the need for careful application of diagnostic criteria 6