Treatment of Hyperekplexia
Clonazepam is the first-line treatment for hyperekplexia, effectively controlling hypertonia, exaggerated startle responses, and life-threatening apneic episodes. 1, 2, 3, 4
Acute Management
Emergency Intervention
- The Vigevano maneuver (forced flexion of the head and legs toward the trunk) is life-saving during episodes of prolonged stiffness that impede respiration. 2, 4
- This maneuver should be taught immediately to all families and healthcare workers caring for affected patients as an emergency rescue measure. 4
- Apply this technique whenever tonic spasms cause apnea, bradycardia, or cyanosis. 2
Recognition of Life-Threatening Presentations
- Neonates and infants presenting with generalized or episodic stiffness, recurrent apnea, or stimulus-sensitive behavioral states require immediate evaluation for hyperekplexia. 4
- Tonic spasms can mimic generalized tonic seizures and lead to cardiac arrest and death if unrecognized. 1, 2
- The non-habituating head-retraction reflex to repeated nose tapping is the clinical hallmark and should be part of routine newborn examination. 2, 4
Pharmacological Treatment
First-Line Therapy
- Clonazepam, a GABA receptor agonist, is the treatment of choice for controlling hypertonia and apneic episodes. 1, 2, 3, 4
- Clonazepam effectively reduces the exaggerated startle response and prevents life-threatening complications. 4
- Treatment should be initiated as soon as the diagnosis is confirmed to prevent sudden infant death. 3, 4
Treatment Limitations and Refractory Cases
- Clonazepam may not significantly influence the degree of baseline stiffness in all patients. 2
- Refractory cases exist despite clonazepam therapy, though they are uncommon. 1
- For severe forms resistant to clonazepam, multidisciplinary follow-up with cardiorespiratory monitoring is essential. 3
Monitoring and Long-Term Management
Clinical Surveillance
- Severe cases require multidisciplinary follow-up including cardiorespiratory monitoring to prevent sudden infant death. 3
- Monitor for complications including orthopedic deformities, delayed gross motor development (occurs in 25% of patients), and speech delay (18.75% of patients). 5
- Assess for intellectual disability, which occurs in approximately 44% of patients (defined as total IQ <80). 5
Neuropsychiatric Evaluation
- All patients diagnosed with hyperekplexia should undergo formal neuropsychometric evaluation, as the condition is not always benign. 5
- Delayed speech and motor acquisition can complicate the clinical course. 5
- Intellectual disability may develop despite adequate treatment of the startle symptoms. 5
Genetic Testing and Counseling
- Genetic testing should be provided to all patients with confirmed hyperekplexia to identify mutations in GLRA1 (81% of cases) or SLC6A5 (19% of cases). 5
- Most cases (93.75%) show autosomal recessive inheritance, with rare autosomal dominant patterns. 5
- Genetic confirmation aids in family counseling and prognostication. 5
Prognosis
- The evolution is generally benign with symptoms disappearing within 2-3 years in most cases. 3
- Neuromotor retardation is often present without intellectual deficit in milder cases. 3
- Overall outcomes in genetic cases are good with appropriate clonazepam therapy and behavioral interventions. 4
Common Pitfalls to Avoid
- Misdiagnosis as epilepsy occurs in 56% of cases—avoid initiating antiepileptic drugs without confirming the diagnosis with the head-retraction reflex test and normal EEG. 5
- Do not delay clonazepam initiation while awaiting genetic confirmation in clinically evident cases. 4
- Ensure families are trained in the Vigevano maneuver before hospital discharge. 4