Startle Response in Newborns: Evaluation and Management
A newborn exhibiting an exaggerated or abnormal startle response requires immediate assessment to distinguish normal physiologic startle from hyperekplexia, which is a life-threatening but treatable neurogenetic disorder that demands urgent recognition and intervention. 1, 2
Initial Clinical Assessment
Key Distinguishing Features to Evaluate
Perform the nose-tap test immediately - this is the clinical hallmark of hyperekplexia. Tap the nasal bridge repeatedly and observe for a non-habituating head-retraction reflex (head recoil without habituation to repeated stimulation). 1, 2, 3
Critical red flags that indicate pathologic startle (hyperekplexia): 2, 4, 3
- Generalized muscular rigidity or hypertonia
- Exaggerated startle to trivial auditory, visual, or tactile stimuli
- Sustained tonic spasms that may mimic seizures
- Hyperreflexia and tremor
- Fetal posture with clenched fists and anxious stare
- Episodes of apnea or cyanosis during stiffness
- History of abnormal intrauterine movements
Obtain detailed family history - hyperekplexia is most often autosomal dominant with complete penetrance, and unexplained sudden infant deaths in the family are a critical clue. 4, 3
Differential Diagnosis
The American College of Radiology guidelines emphasize that neonatal seizures must be distinguished from startle syndromes, as hypoxic-ischemic injury is the most common cause of neonatal seizures (46-65% of cases). 1 However, consciousness is preserved in hyperekplexia, which distinguishes it from epileptic seizures. 5
Other conditions to consider: 1, 5
- Benign myoclonus of early infancy (myoclonic jerks in clusters, normal EEG, preserved consciousness)
- Transient dystonia of infancy (abnormal upper limb posture, onset 5-10 months)
- Neonatal seizures (altered consciousness, abnormal EEG)
Diagnostic Workup
Electrophysiologic testing: 3, 5
- EEG may show fast spikes during tonic spasms, followed by background slowing and flattening during apnea/bradycardia phases
- EMG demonstrates characteristic almost permanent muscular activity with periods of electrical quietness
- Normal nerve conduction velocity
Genetic testing should be pursued for mutations in GLRA1 (α1 subunit of glycine receptor on chromosome 5q), which is the most common genetic cause. 6, 2
Neuroimaging is indicated if there is history of perinatal insult, prematurity complications, or abnormal neurologic exam to evaluate for symptomatic causes. 1, 7
Emergency Management
Teach the Vigevano maneuver immediately to all families and healthcare workers - forced flexion of the head and legs toward the trunk is life-saving when prolonged stiffness impedes respiration. 2, 3
If apnea or severe stiffness occurs: 3
- Perform the Vigevano maneuver immediately
- Provide respiratory support as needed
- Administer emergency benzodiazepine if available
Treatment
Clonazepam is the first-choice therapy for hyperekplexia, as it is a GABA receptor agonist that effectively treats hypertonia and apneic episodes, though it may not significantly influence the degree of stiffness. 2, 3, 5
Prognosis: The outcomes in genetic cases are good overall with appropriate treatment and safety interventions. 2
Critical Pitfalls to Avoid
Do not dismiss excessive startle as "normal newborn behavior" - particular attention should be given to any neonate with generalized or episodic stiffness, drug-refractory seizures, recurrent apnea, or stimulus-sensitive behavioral states, as these may represent undiagnosed hyperekplexia. 2
Do not delay treatment while awaiting genetic confirmation - if clinical features are consistent with hyperekplexia, initiate clonazepam therapy immediately, as apneic episodes can be fatal. 2, 3
Eliciting the non-habituating head-retraction reflex to repeated nose tapping should be part of routine examination of all newborns, as early recognition prevents sudden infant death. 2