What is the appropriate evaluation and management for a 3-year-old male presenting with bilateral upper and lower extremity weakness?

Evaluation and Management of a 3-Year-Old Male with Bilateral Upper and Lower Extremity Weakness

Immediate Life-Threatening Considerations

The first priority is to exclude Guillain-Barré syndrome (GBS), spinal muscular atrophy, and acute metabolic crises, as these require urgent intervention within hours to prevent respiratory failure or permanent neurological damage. 1, 2

Critical Initial Assessment (Within 5 Minutes)

• Assess respiratory function immediately: Check for tachypnea, use of accessory muscles, paradoxical breathing, or inability to cough effectively, as approximately 20% of GBS patients develop life-threatening respiratory failure 2
• Examine deep tendon reflexes: Areflexia or hyporeflexia suggests lower motor neuron pathology (GBS, spinal muscular atrophy), while hyperreflexia indicates upper motor neuron involvement (spinal cord compression, cerebral palsy) 3, 1
• Check for sensory level or bladder dysfunction: Presence indicates spinal cord pathology requiring urgent MRI spine 1
• Observe for ascending pattern: Progressive weakness starting in legs and moving to arms over days to weeks strongly suggests GBS 1, 2
• Assess cranial nerves: Facial weakness, ptosis, difficulty swallowing, or drooling suggests neuromuscular junction disorders or bulbar involvement 3

Urgent Diagnostic Workup (First 24 Hours)

Laboratory Tests (Order Immediately)

• Creatine kinase (CK): Significantly elevated (>1000 U/L) indicates muscular dystrophy, particularly Duchenne muscular dystrophy, which can present as early as 2-3 years with proximal weakness and calf hypertrophy 3
• Basic metabolic panel, magnesium, phosphate: Hypokalemia, hypophosphatemia, or hypomagnesemia can cause acute flaccid weakness 1, 4
• Thyroid-stimulating hormone (TSH): Hyperthyroidism can cause thyrotoxic periodic paralysis with acute weakness and hypokalemia 3, 4
• Serum bicarbonate and lactate: Elevated lactate with reduced bicarbonate suggests mitochondrial myopathy 5

Imaging (Based on Clinical Findings)

• MRI spine with and without contrast (URGENT): Obtain immediately if hyperreflexia, sensory level, bladder dysfunction, or back pain present to exclude spinal cord compression, transverse myelitis, or tumor 1, 2
• MRI brain with contrast: Consider if cranial nerve involvement, altered consciousness, or asymmetric findings suggest central nervous system pathology 1
• Radiographs lower extremities: Only if trauma suspected or child refuses to bear weight, as toddler's fractures can present with refusal to walk 3

Specialized Testing (If Initial Workup Non-Diagnostic)

• Lumbar puncture for CSF analysis: Look for albumino-cytological dissociation (elevated protein with normal cell count) characteristic of GBS, though protein may be normal in first week 1, 2
• Nerve conduction studies and EMG: Identify sensorimotor polyradiculoneuropathy in GBS or denervation patterns in spinal muscular atrophy 2, 6

Differential Diagnosis by Pattern

Proximal > Distal Weakness with Preserved Reflexes

• Duchenne muscular dystrophy: Check CK first; if elevated >1000 U/L, confirm with DMD gene sequencing 3
• Inflammatory myopathy: Check CK, aldolase, and urinalysis for myoglobin 1
• Pompe disease (glycogen storage disease type II): Consider if cardiomegaly on chest x-ray, hepatomegaly, or feeding difficulties present 3

Ascending Weakness with Hyporeflexia/Areflexia

• Guillain-Barré syndrome: Preceding infection within 6 weeks (gastroenteritis, upper respiratory infection), symmetric ascending weakness, absent reflexes 1, 2, 6
• Spinal muscular atrophy: Progressive proximal weakness, tongue fasciculations, absent reflexes, normal sensation 3

Weakness with Upper Motor Neuron Signs

• Spinal cord compression: Hyperreflexia, sensory level, bladder dysfunction—requires emergency MRI and neurosurgical consultation 1
• Cerebral palsy or central lesion: Static encephalopathy with spasticity, though acute presentation unusual 7

Acute Flaccid Weakness with Normal Reflexes

• Metabolic/electrolyte disorders: Hypokalemia (thyrotoxic periodic paralysis), hypophosphatemia, hypomagnesemia 1, 4
• Mitochondrial myopathy: Elevated lactate, exercise intolerance, may have cardiac involvement 5

Immediate Management Based on Findings

If GBS Suspected (Ascending Weakness + Areflexia)

• Admit to monitored setting with respiratory monitoring capability 2
• Measure vital capacity, negative inspiratory force (NIF), and maximum inspiratory/expiratory pressures to assess respiratory failure risk 2
• Initiate IVIG 2 g/kg over 5 days or plasmapheresis if clinical suspicion high and MRI spine excludes structural lesion 2
• Monitor for dysautonomia (blood pressure and heart rate instability) which can be life-threatening 2

If Elevated CK (>1000 U/L)

• Confirm Duchenne muscular dystrophy with DMD gene sequencing 3
• Avoid beta-blockers if cardiomyopathy develops, as they mask hypoglycemia symptoms in glycogen storage diseases 3
• Initiate glucocorticoid therapy (prednisone or deflazacort) as it slows decline in muscle strength and function in DMD 3

If Spinal Cord Pathology Confirmed

• Emergency neurosurgical consultation for decompression if cord compression identified 1
• High-dose methylprednisolone if transverse myelitis suspected 1

If Metabolic Crisis (Hypokalemia, Hypoglycemia)

• Correct electrolytes cautiously: Avoid rapid potassium repletion in thyrotoxic periodic paralysis as it can cause rebound hyperkalemia 4
• Treat underlying hyperthyroidism with beta-blockers and antithyroid medications 4
• Maintain euglycemia in glycogen storage diseases with frequent feeds or continuous glucose infusion 3

Critical Pitfalls to Avoid

• Never delay MRI spine if hyperreflexia or sensory level present, as spinal cord compression requires decompression within hours to prevent permanent paralysis 1, 2
• Do not dismiss GBS because CSF protein is normal, as protein elevation may not occur until after the first week 1, 2
• Avoid attributing weakness to "functional disorder" or "viral myositis" until all life-threatening causes excluded with appropriate imaging and laboratory studies 1
• Do not wait for EMG or CSF results to initiate GBS treatment if clinical suspicion is high and imaging excludes structural lesion 2
• Never assume "just a toddler's fracture" without checking CK and reflexes, as muscular dystrophy commonly presents at this age with refusal to walk or frequent falls 3

Physical Therapy and Rehabilitation Considerations

• Avoid aggressive weight-bearing activities in children with hypermobility/instability and decreased strength, such as cartwheels or climbing 3
• Provide custom-molded foot orthoses if musculoskeletal malalignment identified (genu valgum, hindfoot valgus) to improve weight-bearing alignment 3
• Standardized gross and fine motor testing recommended to assess function relative to age-level peers and identify specific areas of impairment 3
• Gentle aerobic conditioning may be beneficial in glycogen storage diseases, though maximal effort exercise should be approached with caution due to injury risk 3