Rapid Orientation: Localization and Red Flags

Neuromuscular disorders affect one of the four components of the motor unit: the anterior horn cell, the peripheral nerve, the neuromuscular junction and the muscle. Taken individually each is rare; taken together they account for a substantial part of paediatric neurology practice. Some of these conditions now have licensed disease-modifying treatments, and how early the diagnosis is made directly determines long-term function.

Localization first

In a child with weakness, the first question is not which disease it is but which component of the motor unit is involved. Each component leaves a characteristic clinical signature.

• Anterior horn: proximal, patchy weakness; early areflexia; marked atrophy; tongue fasciculations; normal sensation; creatine kinase normal or mildly raised.
• Peripheral nerve: distal weakness; early loss of reflexes; distal atrophy; sensation IMPAIRED; creatine kinase normal.
• Neuromuscular junction: oculobulbar involvement; fatigable weakness; reflexes preserved; no atrophy; creatine kinase normal.
• Muscle: proximal, symmetrical weakness; reflexes decline late; pseudohypertrophy may be present; normal sensation; creatine kinase markedly raised in most.

Central or peripheral

This distinction comes first, particularly in the infant. In central hypotonia strength is relatively preserved, reflexes are brisk or increased, and there are accompanying features such as seizures, dysmorphism, microcephaly, visual inattention, organomegaly or delay across all developmental domains. In peripheral hypotonia strength is clearly reduced, reflexes are absent, and cognitive interest and eye contact are preserved.

The most misleading situation in practice is that an alert, engaged infant with peripheral hypotonia is taken to be reassuring. In fact preserved alertness is one of the most valuable findings pointing to a peripheral cause.

Situations requiring immediate assessment

• Weakness progressing over hours or days.
• Respiratory distress, paradoxical breathing, breathlessness while speaking, a weak cough.
• Swallowing difficulty, signs of aspiration, choking episodes.
• Morning headache and increasing daytime sleepiness, which may indicate hypercapnia.
• Dark urine and diffuse muscle pain, suggesting rhabdomyolysis.
• Syncope, palpitations or exertional chest pain, suggesting arrhythmia or cardiomyopathy.
• Loss of a previously acquired motor skill.
• Intercurrent illness in a child on corticosteroids, because of the risk of adrenal crisis.

Diagnostic red flags

• Unexplained transaminase elevation with a normal GGT — check creatine kinase.
• Toe walking, frequent falls, a Gowers manoeuvre.
• Preserved alertness and eye contact in a hypotonic infant.
• Generalised areflexia; tongue fasciculations.
• Fatigable ptosis or diplopia.
• Cardiomyopathy in a hypotonic infant — consider Pompe disease.
• Unexplained recurrent apnoeic episodes — consider congenital myasthenic syndrome.
• Difficulty releasing the grip in the mother of a hypotonic newborn — consider myotonic dystrophy.
• Unexpected rhabdomyolysis or cardiac arrest during anaesthesia.