Approach to Weakness & Neurologic Localization

Localize Before You Diagnose

One pathway, many levels. Voluntary movement travels through upper motor neurons (UMN), from the motor cortex through the posterior limb of the internal capsule and the brainstem, where most fibers cross at the medullary pyramids, then down the lateral corticospinal tract of the cord. At the anterior horn cell the lower motor neuron (LMN) begins and runs through the root, plexus, and peripheral nerve to the neuromuscular junction (NMJ) and muscle. Lesions above the decussation weaken the opposite side of the body; cord lesions weaken the same side.

Tempo suggests the cause. Onset over seconds to minutes implies a vascular event; hours to days, an inflammatory, infectious, toxic, or metabolic process; weeks to months, compression, tumor, or degeneration. First confirm true weakness rather than fatigue, pain-limited effort, or functional weakness (positive Hoover sign).

Pyramidal pattern. Corticospinal lesions weaken the arm extensors and the leg flexors (hip flexors, hamstrings, ankle dorsiflexors) more than their antagonists, which explains the flexed arm, extended leg, and circumducting gait of chronic hemiplegia. Subtle clues include pronator drift, a Hoffmann sign, and slowed fine finger movements.

Acute UMN injury can masquerade as LMN disease: in spinal or cerebral shock, the limbs are flaccid and areflexic for days to weeks before spasticity and hyperreflexia appear.

Mixed UMN and LMN signs. With normal sensation, wasting and fasciculations alongside brisk reflexes and Babinski signs indicate ALS. With sensory loss, think of B12 deficiency (extensor plantars but absent ankle jerks from combined cord and nerve involvement) or cervical spondylotic myelopathy (LMN signs at the compressed segment, UMN signs below it).

Patterns Along the Neuraxis

Cortex. Middle cerebral artery (MCA) lesions weaken the contralateral face and arm more than the leg and carry cortical signs: aphasia in the dominant hemisphere (nonfluent Broca aphasia with superior-division frontal lesions), neglect in the nondominant hemisphere, gaze deviation toward the lesion, homonymous hemianopia, and cortical sensory loss (astereognosis, agraphesthesia, extinction) with intact primary sensation. Anterior cerebral artery lesions reverse the emphasis: leg more than arm.

Internal capsule. Corticospinal and corticobulbar fibers are packed tightly in the posterior limb, so a small lacunar infarct, typically from hypertensive lipohyalinosis, produces pure motor hemiparesis affecting face, arm, and leg equally, without aphasia, neglect, visual field loss, or sensory change.

Brainstem. Crossed findings, an ipsilateral cranial nerve palsy with contralateral hemiparesis, are the signature. CN III palsy with contralateral hemiparesis localizes to the midbrain (Weber syndrome); CN VI or VII palsy to the pons; CN XII palsy, with the tongue deviating toward the lesion, to the medial medulla. Diplopia, vertigo, dysarthria, dysphagia, and ataxia support a brainstem level.

Spinal cord. Weakness of both legs (or all four limbs) that spares the face, a sensory level on the trunk, bowel or bladder dysfunction, and back pain point to the cord. LMN signs appear at the lesion level and UMN signs below it. Useful landmarks: T4 at the nipple, T10 at the umbilicus, L1 at the inguinal ligament.

Root. Radiculopathy produces radiating pain in a dermatome, weakness in the corresponding myotome, and loss of one reflex: C5–C6 biceps and brachioradialis, C7 triceps, L4 patellar, S1 Achilles; L5 has no routine reflex. Spurling maneuver (neck extension and rotation) and the straight-leg raise (L5/S1) reproduce radicular pain.

Peripheral nerve. Polyneuropathy is length-dependent: symmetric distal sensory loss in a stocking-glove pattern, loss of the ankle reflexes first, then distal weakness; diabetes is the leading cause. A mononeuropathy stays within one nerve's territory. Common fibular (peroneal) palsy at the fibular head, often after weight loss, leg crossing, or prolonged squatting, weakens dorsiflexion and eversion but spares inversion (tibialis posterior, tibial nerve) and the ankle reflex; an L5 root lesion also weakens inversion and hip abduction.

Neuromuscular junction. Myasthenia gravis causes fatigable weakness that worsens with use and toward evening, favoring the eyelids, extraocular and bulbar muscles, and neck and proximal limbs, with normal pupils, sensation, and reflexes. Lambert-Eaton syndrome instead favors the proximal legs, with depressed reflexes that improve after brief exercise and autonomic symptoms such as dry mouth; botulism causes descending paralysis with dilated, poorly reactive pupils.

Muscle. Myopathy produces symmetric proximal weakness (rising from a chair, climbing stairs, lifting the arms overhead) and neck flexor weakness, with normal sensation and reflexes preserved until late. CK is the first test (usually high in inflammatory myopathy, statin myopathy, hypothyroidism, and rhabdomyolysis), followed by EMG, muscle MRI, and biopsy.

Steroid myopathy is the classic proximal myopathy with a normal CK.

Choosing the Right Test

Test the level you localized. Brain: CT when hyperacute, then MRI. Cord: emergent spine MRI, never a head CT. Root: MRI of that segment with or without EMG. Nerve, NMJ, and muscle: nerve conduction studies (NCS), needle EMG, repetitive stimulation, CK, and antibodies. In suspected Guillain-Barré syndrome (GBS), lumbar puncture shows albuminocytologic dissociation (high protein, normal cell count).

A sensory level can lie several segments below the true cord lesion, so imaging must extend above it; image the whole spine when the level is uncertain.

Nerve conduction studies. Axonal injury lowers compound muscle (CMAP) and sensory nerve (SNAP) action potential amplitudes with near-normal velocities: diabetic and toxic neuropathy, the AMAN form of GBS. Demyelination slows velocity, prolongs distal and F-wave latencies, and causes conduction block and temporal dispersion: AIDP, CIDP.

Needle EMG. Denervation produces fibrillation potentials and positive sharp waves, then large, long-duration motor units firing with reduced recruitment. Myopathy produces small, short, polyphasic units with early recruitment. Fibrillations take up to 2–3 weeks to appear after an acute nerve or root injury, so a very early study can be falsely reassuring. In radiculopathy the SNAPs remain normal despite numbness, because the lesion lies proximal to the dorsal root ganglion; SNAPs fall in plexus and nerve lesions.

Repetitive nerve stimulation. In myasthenia gravis, 2–3 Hz stimulation produces a progressive CMAP decrement of more than 10% from a normal baseline. In Lambert-Eaton syndrome, baseline CMAPs are small and rise sharply, by 60% or more (classically 100% or more), after 10 seconds of maximal exercise or high-frequency stimulation. Single-fiber EMG showing increased jitter is the most sensitive test for myasthenia gravis.

Acute Flaccid Weakness and the Airway

Can't-miss causes. Rapidly progressive flaccid weakness is an emergency with a short differential:

• Guillain-Barré syndrome: ascending weakness, areflexia, and distal paresthesias days to weeks after an infection such as Campylobacter; treated with IVIG or plasma exchange, not corticosteroids.
• Acute cord compression: sensory level, bladder dysfunction, back pain; flaccid and areflexic during spinal shock. Malignant compression needs dexamethasone and emergent MRI of the whole spine.
• Botulism: descending paralysis beginning with ptosis, diplopia, and dysphagia, with dilated, poorly reactive pupils and normal sensation.
• Hypokalemic or periodic paralysis: flaccid weakness with normal sensation; check potassium immediately.
• Myasthenic crisis: bulbar and respiratory failure in known or new myasthenia gravis, often triggered by infection, surgery, or drugs.

Pulse oximetry and blood gases stay normal until late in neuromuscular respiratory failure; waiting for hypoxemia or hypercapnia means an emergent rather than elective intubation. Noninvasive ventilation often fails in GBS.