What is the appropriate management for a 58‑year‑old woman with multiple sclerosis and cervical spinal cord lesions who has progressive fatigue, cognitive fog, sensory tingling in the hands and feet, and worsening gait over the past five months?

Management of Progressive Multiple Sclerosis with Cervical Cord Involvement

This 58-year-old woman with MS presenting with 5 months of progressive fatigue, cognitive fog, sensory symptoms, and gait deterioration requires urgent brain and cervical spine MRI with contrast to assess for disease activity, followed by escalation or initiation of high-efficacy disease-modifying therapy if active inflammation is confirmed.

Immediate Diagnostic Evaluation

MRI Protocol

• Obtain brain MRI with gadolinium contrast to detect new or enlarging T2 lesions and contrast-enhancing lesions indicating active inflammation 1
• Perform cervical spine MRI with and without contrast as the definitive imaging modality for evaluating suspected cervical myelopathy 2, 3
• The 5-month progressive course with cervical symptoms strongly suggests cervical cord involvement, which occurs in 80-90% of MS patients and most commonly affects the cervical region 2, 4
• Cervical cord gray matter cross-sectional area and lateral funiculi fractional anisotropy are independent predictors of disability and should be assessed 5

Clinical Assessment Priorities

• Examine for upper motor neuron signs including hyperreflexia, Babinski sign, clonus, and spasticity, which distinguish cervical myelopathy from peripheral neuropathy 3
• Assess gait and balance for ataxia or spasticity, as gait involvement is present in 100% of cervical myelopathy cases 3
• The combination of sensory symptoms (tingling in hands/feet), cognitive fog, fatigue, and progressive gait difficulty over 5 months suggests either active relapsing disease or progression to secondary progressive MS 4, 5

Disease Activity Assessment

Distinguishing Active vs. Progressive Disease

• Contrast-enhancing lesions or new/enlarging T2 lesions indicate active inflammation requiring immediate treatment escalation 1
• Cervical cord lesions in MS are typically ≤2 vertebral segments long, located peripherally in lateral and posterior columns, appearing wedge-shaped on axial MRI 2
• The presence of intramedullary T2 signal changes represents myelomalacia and gliosis, serving as prognostic factors 3
• Cervical cord gray matter atrophy (cross-sectional area <11.1 mm²) accurately predicts progressive phenotype with 90% sensitivity and 91% specificity 5

Symptom Correlation with Cord Pathology

• Fatigue correlates with abnormal cervical cord function rather than structural damage alone 6
• Sensory symptoms including tingling and proprioceptive changes are characteristic of posterior column involvement in cervical MS lesions 7, 8
• Cognitive fog and fatigue are associated with diffuse cervical cord recruitment patterns on functional MRI 6
• The 5-month progressive timeline without mention of discrete relapses raises concern for transition to secondary progressive MS 4, 5

Treatment Algorithm

If Active Inflammation is Present (Enhancing Lesions)

• Escalate to high-efficacy disease-modifying therapy immediately if not already on one, as brain volume loss and disability progression correlate with treatment effects 1
• Consider pulse methylprednisolone (1000 mg IV daily for 3-5 days) for acute symptom management if significant functional decline is present 4
• The presence of cervical cord lesions with progressive symptoms indicates high disease activity requiring aggressive treatment 5

If No Active Inflammation (No Enhancing Lesions)

• Evaluate for secondary progressive MS if there is sustained disability progression independent of relapses for ≥6 months 4
• Cervical cord gray matter atrophy is the most accurate predictor of progressive phenotype and should guide this determination 5
• Consider therapies approved for progressive MS if criteria are met 4

Symptomatic Management

Fatigue Management

• Initiate structured rehabilitation with graded exercise programs, as cervical cord dysfunction directly contributes to MS fatigue 6
• The extent of cervical cord recruitment correlates with fatigue severity (r=-0.34), making cord-targeted rehabilitation particularly important 6
• Exclude other causes of fatigue including thyroid dysfunction, anemia, depression, and sleep disorders before attributing solely to MS 8

Sensory Symptom Management

• Neuropathic pain requires specific treatment with gabapentin, pregabalin, or duloxetine, as sensory symptoms represent a significant hidden reservoir of morbidity in MS 8
• The burning, tingling quality described is characteristic of neuropathic pain in MS affecting 50% of patients 8
• Lhermitte's phenomenon (electric shock sensations with neck flexion) occurs in two-thirds of MS patients with cervical involvement 8

Gait and Mobility

• Refer to physical therapy immediately for gait training, balance exercises, and assistive device evaluation 3
• Progressive gait impairment over 5 months with cervical lesions indicates significant functional decline requiring urgent intervention 3, 5

Critical Pitfalls to Avoid

• Do not delay MRI imaging – the 5-month progressive course requires urgent evaluation to distinguish active inflammation from irreversible neurodegeneration 1
• Do not assume progression without confirming absence of active lesions – contrast-enhancing lesions may be present even with seemingly progressive symptoms 1
• Do not overlook cervical cord imaging – brain MRI alone is insufficient as cervical cord involvement has a central role in explaining disability in MS 5
• Do not attribute all symptoms to MS without excluding mimics – vitamin B12 deficiency, neuromyelitis optica, and cervical spondylotic myelopathy can present similarly and require different management 2
• Beware of pseudoatrophy – if initiating or escalating disease-modifying therapy, brain volume may decrease excessively in the first 6-12 months due to resolution of inflammation rather than true neurodegeneration 1

Prognosis and Monitoring

• Cervical cord gray matter lesions may cause subsequent atrophy contributing to evolution to progressive MS, making early aggressive treatment critical 5
• Baseline atrophy and high rates of volume loss are associated with cognitive impairment, fatigue, and long-term disability progression 1
• Serial brain MRI should be performed using the same protocol on the same scanner, ideally every 6-12 months initially to monitor treatment response 1
• The combination of lateral funiculi damage and gray matter involvement in cervical cord predicts worse disability outcomes 5