What are the differential diagnoses and recommended diagnostic work‑up for a previously healthy 48‑year‑old adult with isolated dropped‑head syndrome (neck extensor weakness) without sensory deficits, arm weakness, or ptosis?

Differential Diagnoses and Diagnostic Workup for Isolated Dropped Head Syndrome

In a 48-year-old adult presenting with isolated neck extensor weakness (dropped head syndrome) without sensory deficits, arm weakness, or ptosis, the primary differential diagnosis is isolated neck extensor myopathy (INEM), which should be distinguished from more serious neuromuscular conditions through targeted electrophysiologic studies, muscle biopsy, and cervical spine imaging. 1

Primary Differential Diagnoses

Isolated Neck Extensor Myopathy (Most Likely)

• INEM is a relatively benign, nonprogressive myopathy characterized by severe weakness localized to neck extensor muscles 1
• This condition presents with inability to maintain the head in an upright posture, resulting in a passively correctable chin-on-neck deformity in erect posture 2
• INEM is believed to result from isolated myopathic changes due to chronic injury and overloading of cervical muscles 3
• The pathological spectrum ranges from non-inflammatory muscle necrosis to inflammatory myositis 4
• A subgroup of patients may respond favorably to early immunomodulatory treatment if identified promptly 2

Radiation-Induced Cervicoscapular Muscle Atrophy

• This is a rare delayed complication manifesting decades after high-dose mantle-field radiotherapy (>20 Gy) 5
• Characterized by weakness of neck extensor muscles with inability to extend the neck and head-flexed posture 5
• Pathophysiology involves combination of primary muscle damage and nerve damage 5
• Critical history point: Ask specifically about prior radiation therapy for Hodgkin lymphoma or other malignancies treated in childhood or young adulthood 5

Inflammatory Myopathies

• Polymyositis can present with dropped head syndrome and shows favorable response to corticosteroids 4
• Look for elevated creatine kinase (CK) levels, which are typically markedly elevated (median 2650 IU/L) in inflammatory myositis 5
• Dermatomyositis rarely presents with isolated neck weakness but should be considered if skin changes develop 5

Myotonic Dystrophy

• Can present with concurrent dropped head syndrome and camptocormia (trunk flexion) 6
• Ask about family history, grip myotonia, distal weakness, cataracts, cardiac conduction defects, and frontal balding 6

Cervical Spondylosis with Secondary Denervation

• Degenerative cervical spondylosis can cause DHS through denervation of cervical extensors 3
• This association suggests chronic mechanical injury contributing to muscle weakness 3

Less Likely but Must Exclude

• Motor neuron disease (ALS): Would typically show progressive weakness beyond neck extensors, fasciculations, hyperreflexia, and upper motor neuron signs 2
• Myasthenia gravis: Absence of ptosis, diplopia, and fluctuating weakness makes this unlikely; however, seronegative MG can present atypically 2
• Chronic inflammatory demyelinating polyneuropathy (CIDP): Would show areflexia and sensory involvement 2
• Cancer immunotherapy-related myositis: Only relevant if patient has recent checkpoint inhibitor exposure; presents with proximal weakness, myalgia, elevated CK, and potential myocarditis 5

Recommended Diagnostic Workup

Initial Laboratory Studies

• Creatine kinase (CK) level: Essential first test to distinguish inflammatory from non-inflammatory causes 5, 1
  • Normal or mildly elevated CK suggests INEM
  • Markedly elevated CK (>2000 IU/L) suggests inflammatory myositis 5
• Complete blood count, comprehensive metabolic panel, thyroid function tests 5
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 4

Serological Testing

• Myositis-specific antibodies: Anti-Jo1, anti-PM/Scl, anti-SRP, anti-TIF1 gamma 5
• Acetylcholine receptor antibodies and MuSK antibodies to exclude myasthenia gravis 2
• Antinuclear antibodies (ANA) 5

Electrophysiologic Studies (Critical for Diagnosis)

• Electromyography (EMG) and nerve conduction studies are essential for definitive diagnosis 1
• EMG typically shows myopathic pattern with short-duration, low-amplitude motor unit potentials in neck extensors 1
• Nerve conduction studies help exclude neuropathic causes 1
• These studies can readily identify INEM and distinguish it from motor neuron disease, neuropathy, or neuromuscular junction disorders 1

Imaging Studies

• Cervical spine MRI without and with contrast: To evaluate for cervical spondylosis, spinal cord pathology, and muscle signal abnormalities 3, 1
  • Look for muscle edema or fatty replacement in neck extensors
  • Exclude structural causes of denervation
• Chest radiograph or CT chest: To screen for occult malignancy or prior radiation changes if history suggests 5

Muscle Biopsy (When Indicated)

• Indicated if CK is elevated or if inflammatory myopathy is suspected 4, 1
• Biopsy should target affected neck extensor muscles (semispinalis capitis or splenius capitis) 1
• Histopathology can reveal:
  • Non-inflammatory necrotizing myopathy (INEM) 4
  • Inflammatory infiltrates (polymyositis) 4
  • Dystrophic changes (myotonic dystrophy) 6

Cardiac Evaluation (If Inflammatory Myositis Suspected)

• Electrocardiography and cardiac troponin I (more specific than troponin T in skeletal muscle disease) 5
• Cardiac MRI if troponin elevated or ECG abnormal, as myocarditis can complicate inflammatory myopathy 5

Diagnostic Algorithm

1. Obtain detailed history focusing on:

   • Time course (acute vs. subacute vs. chronic progression) 2
   • Prior radiation therapy for any malignancy 5
   • Recent infections, cancer immunotherapy, or new medications 5, 2
   • Family history of neuromuscular disease 6
   • Systemic symptoms (fever, weight loss, rash) 4

2. Perform focused neurological examination:

   • Assess strength in all muscle groups, not just neck extensors 1
   • Check for fasciculations, muscle atrophy, and reflexes 2
   • Examine for ptosis, diplopia, and bulbar weakness 5
   • Test for grip myotonia 6

3. Order CK level immediately 5, 1:

   • If normal or mildly elevated → proceed with EMG/NCS and consider INEM
   • If markedly elevated (>2000 IU/L) → add myositis antibodies and consider muscle biopsy

4. Obtain EMG/NCS within 1-2 weeks 1:

   • Myopathic pattern confirms muscle disease
   • Neuropathic pattern requires different workup

5. Cervical spine MRI 3, 1:

   • Evaluate for spondylosis and muscle signal changes
   • Exclude structural cord pathology

6. Consider muscle biopsy if:

   • CK elevated and inflammatory myopathy suspected 4
   • Diagnosis remains unclear after EMG/imaging 1
   • Treatment response needed to guide immunotherapy 2

Critical Pitfalls to Avoid

• Do not assume isolated neck weakness is benign without excluding motor neuron disease through EMG 2, 1
• Do not miss occult myasthenia gravis: Even without ptosis, seronegative MG can present with isolated neck weakness 2
• Do not overlook radiation history: Dropped head syndrome from prior mantle-field radiation is irreversible and requires only supportive care 5
• Do not delay muscle biopsy if inflammatory myopathy is suspected: Early immunomodulatory treatment may lead to favorable outcomes in a subgroup of INEM patients 2
• Do not forget cardiac evaluation if myositis is confirmed: Myocarditis significantly increases mortality risk 5

Management Considerations

• If INEM is confirmed and CK is elevated, consider trial of corticosteroids as some patients with inflammatory component respond favorably 2, 4
• If non-inflammatory INEM with cervical spondylosis, manipulative therapies may be beneficial before considering surgical intervention 3
• If radiation-induced, management is limited to supportive care with cervical orthoses 5
• Physical therapy and cervical collar may provide symptomatic relief regardless of etiology 3