Paroxysmal extreme pain disorder (formerly familial rectal pain syndrome)

Fertleman CR, Ferrie CD, Aicardi J. Neurology 2007; 69:586-595.

A large family describes episodes in affected individuals of excruciating rectal pain, flushing of the buttocks and legs, ocular pain, flushing of the eyelids, and periorbital skin, and submaxillary pain. Tonic atacks with bradycardia in infancy and apnea and cardiac asystole with these tonic nonepileptic seizures may be part of the syndrome. The onset may even be in utero. Newborns may be stiff and red. The precipitant for the first attack is usually defecation. Other triggers might include bathing, sudden loud noises, feeding and perineal toilet, cold , wind, eating and emotion. Painful attacks can be divided into rectal, ocular and jaw. However, pain is not restricted to these sites. Flushing is a constant feature and accompanies pain in younger individuals. The pain starts as an itch like pain then burning lancinate, stabbing, and becomes unbearable, the worst pain imaginable. Flushes may be geographic but not always. "Harlequin" color changes are common but not universal and may affect half the face. Other symptoms may include hypersalivation with jaw attacks, watering of eyes, weakness of the affected foot for 24 hours, episodic vomiting, and prolonged recovery from inhalational anesthetics. Tonic attacks are associated with harlequin color changes, can last up to a minute, and leads to several minutes of nonresponsiveness. Symptoms between attacks include constipation (due to fear of precipitating an attack).

Treatment with carbamazepine has been shown to be at least partly effective, completely so in a few patients. High doses are used. Opiates are not effective, and amitryptilene and clonidine are not effective. Inhaled nitrous oxide (Entonex) is used for some of the most severe attacks. Tests are always normal, except tachycardia with attacks. EEG during attack shows slow--flat -slow pattern. The channelopathy is a mutant sodium 1.7 channel .

Differentiate from hyperekplexia in which infants are high toned with increased reflexes. Hyperekplexia is associated with a glycine channel disorder. Children do not respond to pacers with aystole suggesting they are of respiratory not cardiac origin. It si not clear if tonic seizures with asystole pose a threat or not (anoxic seizures are benign, hyperecplectic can be fatal). Primary erythromalgia is caused by mutations in sodium channel gene SCN9A with severe pain and flushing, but occur in the feet and are triggered by warm temperature and exercise. It usually occurs in adult life and fails to respond to CBZ whereas mexilitene is helpful. The disease is lifelong but attacks lessen over time in adulthood.