In a patient with preserved gray‑white differentiation and punctate, confluent non‑enhancing T2 hyperintensities in the subcortical, periventricular and deep white matter—predominantly frontal and parietal, also temporal—and without a central‑vein sign, could these findings represent multiple sclerosis?

MRI Findings and Multiple Sclerosis Diagnosis

Direct Answer

The absence of the central vein sign is a significant red flag against multiple sclerosis, and these findings are more consistent with small vessel ischemic disease or other non-demyelinating white matter pathology rather than MS. 1

Critical Diagnostic Considerations

The Central Vein Sign: A Key Distinguishing Feature

The central vein sign is emerging as one of the most specific imaging features for MS lesions:

• A substantial proportion (>40%) of MS lesions show a central vein, and recent studies using high-resolution 3D sequences at 3.0T demonstrate venocentric patterns in as many as 95% of MS lesions 1
• Venocentric and hypointense rim lesions are specific findings useful for differentiating patients with clinically isolated syndrome or MS from those with other neurological disorders 1
• The explicit statement that "central vein sign criteria is not felt to be met" in your MRI report argues strongly against MS as the primary diagnosis 1

Lesion Distribution Pattern Analysis

Your MRI shows several features that raise concern for alternative diagnoses:

• The distribution is predominantly frontal and parietal with temporal involvement, but the report does not mention the specific MS-characteristic locations required for diagnosis 1
• For dissemination in space (DIS), MS diagnosis requires ≥3 periventricular lesions, ≥1 infratentorial lesion, ≥1 spinal cord lesion, ≥1 optic nerve lesion, or ≥1 cortical/juxtacortical lesion involving at least 2 of these 5 CNS regions 1
• The description of "punctate and confluent zones" in subcortical and deep white matter is more characteristic of small vessel ischemic disease than the ovoid, perivenular lesions typical of MS 1, 2

Absence of Enhancement: Temporal Considerations

• The lack of gadolinium enhancement does not exclude MS but limits the ability to demonstrate dissemination in time on a single scan 1, 2
• However, non-enhancing lesions in the described distribution pattern, combined with absent central vein sign, significantly reduces MS likelihood 1

Red Flags Against MS in This Case

Pattern Recognition

In challenging situations with low numbers of lesions and confounding comorbidities, both the specific characteristics of each individual lesion and the overall patterns of lesions should be taken into account 1:

• Symmetric central lesions in the pons and deep white matter lesions suggest ischemic small-vessel disease rather than MS 1
• The confluent nature of the lesions described is atypical for MS, which typically presents with discrete, well-demarcated ovoid lesions 1, 2

Age and Vascular Risk Factors

In patients older than 50 years or with vascular risk factors, more stringent criteria should be considered, including a higher number of periventricular lesions abutting the lateral ventricles 1:

• Incidental periventricular lesions can be detected in up to 30% of patients with migraine and in healthy individuals 1
• The prevalence of silent cerebral infarction increases dramatically with age: approximately 11% between ages 55-64 years, reaching 43% beyond age 85 3

Alternative Diagnoses to Consider

Small Vessel Ischemic Disease

Patients with hypertension, diabetes, or hyperlipidemia should be considered at high risk for harboring subclinical microinfarctions even without neurological symptoms 3:

• Lacunar infarcts are small subcortical infarcts (<1.5 cm) located in the basal ganglia, brain stem, or deep white matter supplied by penetrating arteries 3
• The described subcortical and deep white matter distribution matches this pattern 3

Other White Matter Diseases

Different white matter diseases can have similar appearances on MRI, and persistent gadolinium enhancement greater than three months, lesions with mass effect, and meningeal enhancement suggest other disorders 2:

• Cerebrovascular disease and autoimmune inflammatory disorders must be excluded 1
• The absence of typical MS lesion characteristics (ovoid shape, Dawson fingers, corpus callosum involvement) further supports alternative diagnoses 2

Recommended Diagnostic Approach

Additional Imaging

Spinal cord MRI can be helpful when brain MRI results are equivocal or when results are inconclusive, such as the detection of one or more lesions that are typical of MS but do not fulfill the diagnostic criteria for dissemination in space 1:

• In contrast to the brain, the spinal cord rarely exhibits incidental MS-like abnormalities, even in older patients 1
• Detection of spinal cord lesions could facilitate the diagnosis of MS and is predictive for conversion to clinically definite MS 1
• All 20 patients in one series with negative or minimal brain MRI findings but confirmed MS had at least one spinal cord lesion visible (median 2; range 1-6) 4

Clinical Context is Paramount

MRI criteria should only be used in the appropriate clinical context, when onset is characterized by clinical manifestations typical of multiple sclerosis 1:

• MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days 5
• There is no single test that is diagnostic of MS, including MRI; the lesions detected with MRI are pathologically nonspecific 2
• MRI evidence plays a supportive role in what is ultimately a clinical diagnosis of MS, in the appropriate clinical situation, and always at the exclusion of alternative diagnoses 2, 6

Laboratory Evaluation

Examination of cerebrospinal fluid for oligoclonal bands may be helpful in establishing the diagnosis for individual patients when imaging is equivocal 5, 6:

• CSF-specific oligoclonal bands are components of the 2017 McDonald Criteria 5
• In patients not satisfying DIS criteria for MS, the presence of oligoclonal bands combined with age is helpful in identifying those at risk for MS 1

Critical Pitfalls to Avoid

Application of diagnostic criteria in the context of clinical presentations that are not typical of multiple sclerosis increases the risk of misdiagnosis 1:

• In patients with few lesions, there is a particularly increased risk of misdiagnosis based on MRI 1
• A positive test for a putative MS "mimic" does not unto itself exclude the diagnosis of MS, but the constellation of absent central vein sign with atypical lesion distribution strongly favors alternative diagnosis 6
• Increasing the sensitivity of diagnostic tests with more lenient criteria can result in decreased specificity 2