How do you differentiate between neuropathy, myopathy, and myelopathy?

Differentiating Neuropathy, Myopathy, and Myelopathy

The differentiation between neuropathy, myopathy, and myelopathy relies on a systematic clinical approach that localizes the pathology to the peripheral nerve, muscle, or spinal cord respectively, using specific patterns of motor, sensory, and reflex findings combined with targeted diagnostic testing.

Clinical Localization Framework

Myelopathy (Spinal Cord Pathology)

Key Clinical Features:

• Motor findings: Upper motor neuron signs including spasticity, hyperreflexia, and pathologic reflexes (Babinski sign) below the lesion level 1
• Sensory findings: Sensory level on the trunk with loss of sensation below a specific dermatome; may include posterior column dysfunction (vibration/proprioception loss) or spinothalamic tract dysfunction (pain/temperature loss) 2
• Sphincter dysfunction: Bladder and bowel symptoms are characteristic of myelopathy 2
• Distribution: Affects trunk, arms, and legs while sparing the head 2
• Pain: Commonly localized over the site of the spinal cord lesion 2

Diagnostic Approach:

• MRI of the spine is the definitive imaging modality due to superior soft-tissue contrast resolution 3, 1
• Image the entire spine even when clinical findings suggest a localized level, as multiple pathologies may coexist 1
• Brain MRI may be indicated when demyelinating disease is suspected 1

Myopathy (Muscle Pathology)

Key Clinical Features:

• Motor findings: Proximal muscle weakness (difficulty rising from chair, climbing stairs, lifting arms overhead) without upper motor neuron signs 3
• Reflexes: Normal to diminished deep tendon reflexes, proportional to weakness 3
• Sensory findings: Sensation is completely preserved (critical distinguishing feature) 3
• Distribution: Symmetric proximal muscle weakness in limb-girdle distribution 3
• Associated findings: Elevated muscle enzymes (CK, aldolase) in inflammatory myopathies 3

Diagnostic Approach:

• EMG shows polyphasic motor unit action potentials of short duration and low amplitude with increased insertional activity, fibrillation potentials, and sharp waves 3
• Muscle biopsy is the gold standard for confirming inflammatory versus noninflammatory myopathy and for subclassification 3
• MRI of proximal muscle groups can identify inflammation and guide biopsy site 3
• Genetic testing for muscular dystrophy (dystrophin gene) when hereditary myopathy is suspected 3

Neuropathy (Peripheral Nerve Pathology)

Key Clinical Features:

• Motor findings: Lower motor neuron signs including weakness, muscle atrophy, fasciculations, and hyporeflexia/areflexia 3
• Sensory findings: Distal sensory loss in a stocking-glove distribution (length-dependent pattern) or specific nerve territory distribution 3
• Reflexes: Diminished or absent, particularly ankle reflexes in length-dependent neuropathies 3
• Distribution: Typically distal-to-proximal gradient; may be asymmetric in mononeuropathies or multifocal patterns 3
• Pain characteristics: Neuropathic pain (burning, shooting, electric) with dysesthesias and allodynia 3

Diagnostic Approach:

• Electrophysiological assessment (nerve conduction studies and EMG) supports diagnosis and distinguishes axonal from demyelinating patterns 3
• Clinical evaluation determines if neuropathy is sensory, motor, or sensorimotor; symmetric or asymmetric; acute or chronic 3
• Identify underlying causes: diabetes, medications (chemotherapy, bortezomib, thalidomide), nutritional deficiencies (B12, copper), autoimmune conditions 3

Critical Distinguishing Algorithm

Step 1: Assess Reflexes

• Hyperreflexia with pathologic reflexes → Myelopathy 1, 2
• Normal to diminished reflexes with preserved sensation → Myopathy 3
• Hyporeflexia/areflexia with sensory loss → Neuropathy 3

Step 2: Evaluate Sensory Examination

• Sensory level on trunk → Myelopathy 2
• Normal sensation with weakness → Myopathy 3
• Distal stocking-glove or nerve territory distribution → Neuropathy 3

Step 3: Determine Weakness Pattern

• Spastic weakness with upper motor neuron signs → Myelopathy 1
• Proximal symmetric weakness → Myopathy 3
• Distal weakness with atrophy → Neuropathy 3

Step 4: Check for Sphincter Dysfunction

• Bladder/bowel dysfunction present → Myelopathy (unless severe peripheral neuropathy) 2
• Sphincter function preserved → Myopathy or Neuropathy 3

Common Pitfalls to Avoid

• Do not confuse proximal neuropathies with myopathy: Some neuropathies (Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy) can cause proximal weakness, but these will have areflexia and sensory involvement 3
• Do not miss coexisting conditions: Patients may have multiple pathologies (e.g., diabetic neuropathy with cervical myelopathy) 1
• Do not delay imaging in suspected myelopathy: Compressive myelopathy requires urgent identification to prevent irreversible cord damage 1
• Do not rely on muscle enzymes alone for myopathy diagnosis: Normal CK does not exclude myopathy; muscle biopsy remains the gold standard 3
• Do not overlook medication-induced causes: Statins (myopathy), chemotherapy agents (neuropathy), and other drugs are common reversible causes 3