What is the likely diagnosis for a patient with a history of transient neurological symptoms and MRI findings showing T2 hyperintense foci in multiple brain regions?

Likely Diagnosis: Multiple Sclerosis (Relapsing-Remitting)

Based on the clinical history of recurrent neurological episodes with spontaneous recovery and MRI findings showing multifocal T2 hyperintense lesions in characteristic locations (periventricular, brainstem, deep gray matter, and cortical regions), this patient most likely has relapsing-remitting multiple sclerosis. 1

Diagnostic Reasoning

Clinical Features Supporting MS

• Dissemination in time: The patient experienced neurological symptoms last year that resolved spontaneously (first episode), followed by new symptoms this year (blackness, arm clumsiness, sluggish movement), demonstrating temporal separation of at least 30 days between attacks 1

• Relapsing-remitting pattern: The spontaneous recovery from the first episode followed by new symptoms is characteristic of relapsing-remitting MS rather than a progressive course 1

• Age and presentation: The clinical pattern fits the typical MS demographic and presentation style 2, 3

MRI Findings Supporting MS

The T2 hyperintense foci in multiple characteristic locations strongly support MS diagnosis 1:

• Periventricular involvement (bilateral corona radiata): Three or more periventricular lesions are required and highly specific for MS 1

• Infratentorial lesions (pons): Brainstem involvement is one of the four key anatomical regions for demonstrating dissemination in space 1

• Deep gray matter (bilateral caudate and lentiform nuclei): While less typical, deep gray matter involvement can occur in MS 1

• Juxtacortical/cortical involvement (bilateral insular cortex, medial temporal parenchyma): Cortical and juxtacortical lesions are characteristic MS features 1

• No diffusion restriction: The absence of restricted diffusion argues against acute ischemic stroke or abscess, supporting a demyelinating process 1

Applying McDonald 2017 Criteria

This patient satisfies dissemination in space and time 4, 3:

• Dissemination in space: Lesions involve at least 2 of 4 characteristic regions (periventricular, infratentorial/brainstem, and juxtacortical areas) 1

• Dissemination in time: Two separate clinical episodes occurring more than 30 days apart 1, 4

Essential Next Steps for Confirmation

Mandatory Evaluations

• Complete spinal cord MRI (cervical and thoracic): Even without spinal symptoms, 30-40% of patients have asymptomatic cord lesions that strengthen the diagnosis 4, 3

• Lumbar puncture for CSF analysis: Look for oligoclonal bands and elevated IgG index, which provide supportive evidence, particularly if MRI criteria are borderline 4, 3

• Anti-aquaporin-4 (AQP4) antibody testing: Absolutely essential to exclude neuromyelitis optica spectrum disorder (NMOSD), which requires completely different treatment and can be catastrophically worsened by MS therapies 1, 4, 5, 6

• Anti-MOG antibody testing: Should be performed to exclude MOG-associated encephalomyelitis, which has distinct treatment implications 1, 6

Additional Recommended Studies

• Gadolinium-enhanced brain MRI: If not already performed, this can demonstrate acute inflammation and help establish dissemination in time if both enhancing and non-enhancing lesions are present simultaneously 1, 4

• Visual evoked potentials: Can detect subclinical optic nerve involvement, adding evidence for dissemination in space 1, 4

Critical Differential Diagnoses to Exclude

High-Priority Alternatives

NMOSD (Neuromyelitis Optica Spectrum Disorder) 1, 5, 6:

• Test AQP4-IgG antibodies immediately
• NMOSD can present with similar relapsing symptoms but typically shows longitudinally extensive spinal cord lesions (≥3 vertebral segments)
• Brainstem involvement (area postrema) is characteristic
• Critical pitfall: MS disease-modifying therapies can worsen NMOSD 5, 6

MOG-Antibody Disease 1, 6:

• Test MOG-IgG antibodies using cell-based assay
• Can present with optic neuritis, myelitis, and brainstem encephalitis
• May show large, confluent brain lesions
• Often has better prognosis than MS but requires different treatment 1

Acute Disseminated Encephalomyelitis (ADEM) 1, 2, 6:

• Typically monophasic with large, confluent lesions
• More common in children
• The relapsing pattern here argues against ADEM 2

Small Vessel Ischemic Disease 1:

• Consider if patient has vascular risk factors
• Lesions typically spare U-fibers and are more symmetric
• Lack of perivenular distribution
• Age >50 years increases likelihood 1

CNS Vasculitis 1, 7:

• Can mimic MS with multifocal lesions
• Usually has systemic features
• CSF typically shows elevated protein and pleocytosis
• May require angiography or biopsy 7

Neurosarcoidosis 7:

• Can cause multifocal CNS lesions
• Look for systemic sarcoidosis features
• CSF shows elevated ACE levels
• Leptomeningeal enhancement is characteristic 7

Red Flags That Would Challenge MS Diagnosis

Watch for these atypical features 1:

• Progressive course from onset without relapses (would suggest primary progressive MS or alternative diagnosis) 1
• Longitudinally extensive spinal cord lesions (≥3 vertebral segments) suggest NMOSD 1, 4
• Prominent papilledema during acute episodes suggests MOG-EM or NMOSD 1
• Neutrophilic CSF pleocytosis or WCC >50/μl suggests MOG-EM 1
• Symmetric lesion distribution without periventricular predominance suggests vascular disease 1
• Absence of periventricular lesions makes MS less likely 1

Treatment Implications

If MS is confirmed after excluding mimics, early initiation of high-efficacy disease-modifying therapy is recommended to improve long-term outcomes 4. However, do not start MS-specific therapy until NMOSD and MOG-antibody disease are definitively excluded, as some MS therapies can worsen these conditions 5, 6.

Common Diagnostic Pitfalls to Avoid

• Do not diagnose MS based solely on MRI findings without clinical correlation—at least one clinical event compatible with acute demyelination is essential 4, 3

• Do not assume all white matter lesions are demyelinating—nonspecific lesions from vascular disease, migraine, or metabolic causes are common, especially in patients >50 years 1

• Do not skip antibody testing for AQP4 and MOG—these are treatable conditions that require different management and can be worsened by MS therapies 1, 5, 6

• Do not overlook spinal cord imaging—cord lesions provide crucial diagnostic information and are often asymptomatic 4

• Do not ignore CSF analysis when diagnosis is uncertain—oligoclonal bands significantly increase diagnostic confidence 4, 3