How to manage headaches and back pain in a patient with relapsing multiple sclerosis and a history of post-operative spinal cord injury at the level of C7-T1, who is being treated with Kesimpta (ofatumumab)?

Management of Headaches and Back Pain in MS Patients on Ofatumumab with Spinal Cord Injury

In a patient with relapsing MS on Kesimpta (ofatumumab) and a history of post-operative spinal cord injury at C7-T1, headaches and back pain require immediate evaluation to distinguish between MS-related symptoms, medication adverse effects, post-procedural complications, and structural issues related to the prior spinal surgery.

Initial Clinical Assessment

Critical Red Flags to Evaluate Immediately

• Assess for orthostatic features: Does the headache worsen when lying down and improve when upright, or vice versa? Orthostatic headaches (worse upright, better recumbent) suggest CSF leak or intracranial hypotension, while reverse orthostatic patterns (worse recumbent, better upright) may indicate rebound intracranial hypertension 1.

• Evaluate temporal relationship to any recent procedures: If the patient had lumbar puncture within the past 5 days, post-dural puncture headache is a primary consideration, with an incidence ranging from 2% to 40% depending on procedural factors 2.

• Screen for neurological deterioration: New focal deficits, progressive weakness, saddle anesthesia, or bowel/bladder dysfunction could indicate cauda equina syndrome, nerve root compression, or MS relapse requiring urgent imaging 3.

• Document headache characteristics: Location (occipital vs. frontal), severity, associated symptoms (nausea, vomiting, visual changes), and any neck stiffness 1.

Differential Diagnosis Framework

1. Ofatumumab-Related Adverse Effects

• Headache is a common adverse event with ofatumumab, reported as one of the most frequent side effects alongside nasopharyngitis and upper respiratory tract infections 4.

• The overall tolerability profile of ofatumumab is generally manageable, with most adverse events being mild to moderate 5, 4.

• Back pain is not specifically highlighted as a common adverse effect of ofatumumab in the pivotal ASCLEPIOS trials 6.

2. Post-Procedural Complications (If Recent LP or Spinal Intervention)

• Post-dural puncture headache presents within 5 days of dural puncture, is characteristically postural (worse upright), and may be accompanied by neck stiffness and auditory symptoms 2.

• At 3 days post-LP with intractable headache, proceed directly to epidural blood patch rather than continuing conservative management, as this timeframe meets the threshold for definitive intervention 2.

• Back pain occurs in 16-17% of patients following lumbar puncture and is associated with younger age, female sex, and fear of the procedure 1.

• Nerve injury after LP typically presents as radicular symptoms (pain, numbness, weakness) in the distribution of affected nerve roots, though most cases resolve spontaneously 3.

3. Structural Issues Related to C7-T1 Spinal Cord Injury

• Given the history of post-operative spinal cord injury at C7-T1, consider mechanical causes such as hardware complications, adjacent segment degeneration, or arachnoiditis.

• MRI of the complete spine (cervical through lumbar) without and with contrast is the preferred imaging modality to evaluate structural abnormalities, CSF leak, or spinal cord pathology 1.

4. MS Disease Activity

• While headache is not a typical MS symptom, MS relapse can present with various neurological symptoms that should be distinguished from other causes.

• The patient's MS is being treated with ofatumumab, which demonstrated superior efficacy in reducing relapse rates (0.10-0.11 annualized relapse rate) compared to teriflunomide 6.

Management Algorithm

Step 1: Rule Out Emergent Conditions

• If age >60 years with new headache after any trauma, obtain noncontrast head CT immediately to exclude intracranial hemorrhage 7.

• If coagulopathy or anticoagulation use, CT is mandatory regardless of other factors due to dramatically increased hemorrhage risk 7.

• If signs of cauda equina syndrome (saddle anesthesia, bowel/bladder dysfunction, bilateral lower extremity weakness), obtain emergent MRI spine and neurosurgical consultation 3.

Step 2: Determine If Post-Procedural

If within 5 days of lumbar puncture or spinal intervention:

• Conservative management initially includes adequate oral hydration, multimodal analgesia (acetaminophen and NSAIDs unless contraindicated), and caffeine up to 900 mg/day in the first 24 hours 2.

• Do NOT prescribe bed rest as there is no evidence it reduces post-LP headache 2.

• If symptoms are severe or persist beyond 2-3 days, proceed to epidural blood patch at the level of the original dural puncture, which achieves complete recovery in >85% of cases 2.

• For rebound headache (occurring 1-2 days post-blood patch with reversed orthostatic pattern), manage conservatively with acetazolamide to lower CSF production; CSF drainage via LP may be needed if refractory 1.

Step 3: Address Ofatumumab-Related Symptoms

• For mild-to-moderate headache attributed to ofatumumab, provide symptomatic treatment with acetaminophen or NSAIDs 4.

• Monitor for infections as ofatumumab is an immunosuppressive therapy; serious infections occurred in 2.5% of patients in clinical trials, though overall infection rates were similar to teriflunomide 6.

• Continue ofatumumab unless headache is severe and clearly temporally related to injections, as the benefit-risk profile remains favorable in the broad RMS population 5, 6.

Step 4: Evaluate Structural Causes

For persistent back pain or radicular symptoms:

• Obtain MRI of the complete spine without and with IV contrast to evaluate the C7-T1 surgical site, assess for hardware complications, adjacent segment disease, arachnoiditis, or CSF leak 1.

• If MRI demonstrates CSF leak without recent intervention, consider dynamic digital subtraction myelography for precise localization if epidural blood patch is being considered 1.

Step 5: Symptomatic Management

For back pain management:

• Use multimodal analgesia including acetaminophen and NSAIDs as first-line 2.

• Consider short-term opioids only if multimodal analgesia is ineffective and after ruling out structural causes requiring intervention 2.

• Physical therapy may be beneficial for mechanical back pain related to prior spinal surgery, though this is based on general medical knowledge rather than the provided evidence.

Common Pitfalls to Avoid

• Do not attribute all symptoms to MS without considering other etiologies, particularly in a patient with complex spinal history 3.

• Do not delay epidural blood patch if post-dural puncture headache is severe or persists beyond 2-3 days, as waiting for spontaneous resolution prolongs suffering unnecessarily 2.

• Do not mistake rebound headache for refractory intracranial hypotension, as this may lead to unnecessary repeat blood patches that worsen the condition 1.

• Do not discontinue ofatumumab prematurely for mild headache, as this is a common and generally manageable adverse effect that does not compromise the favorable benefit-risk profile 5, 4, 6.

• Do not overlook infection risk in an immunosuppressed patient; maintain high suspicion for serious infections including meningitis if headache is accompanied by fever, altered mental status, or meningismus 4, 6.