The proband 1 is a 24-year-old female with history of episodic loss of coordination, dysarthria, and visual disturbance resembling cataplexy. She was asymptomatic until 5 years when an episode of slurred speech and "wobbly" legs without falling to the ground associated with fever was noted. This first episode resolved spontaneously after a few minutes and without sequelae. Following this, she had very frequent, brief (30 s-2 min) episodes occurring often with playing sports like basketball and cross-country running and associated with the excitement of returning to the basketball court, starting or finishing a cross-country race. During the spells, she could not handle the basketball or felt her knees become weak and her legs "rubbery" causing her to slow down or fall. She also reported spells when sitting in class feeling stressed. She did not take naps and reported no excessive sleepiness. Because of the resemblance of the spells to cataplexy, at age 12, the patient was prescribed clomipramine, 25 mg every night at bedtime. She responded well to treatment without side effects and with abatement of spells and improved sports performance. At age 16, she took herself off clomipramine (75 mg/day) because of depression and emotional lability. History of feeling tired and sleepiness in class prompted a polysomnogram followed by a Multiple Sleep Latency Test (MSLT), while off clomipramine, to investigate the possibility of narcolepsy. Her polysomnogram was essentially normal, and she was given a presumptive clinical diagnosis of isolated cataplexy. Her brain MRI at 12 years age was normal except for a small right subcortical frontal area of gliosis of uncertain significance, essentially unchanged on a follow-up brain MRI 13 months later. At age 21, she presented again with renewed difficulty competing in track events after a relative stability during her first 3 years of college. She was asked to do a strenuous exercise in the office, and a spell was elicited. She had difficulty extending her legs, developed a head tremor, bilateral dysmetria in the arms and legs, tremulous voice, needed to sit down, and was without nystagmus. She was diagnosed with episodic ataxia and started on acetazolamide with a decrease in the frequency of spells, but this was discontinued because of depression. She was then evaluated by the genetics team and serum creatine phosphokinase (CPK), and acylcarnitine and amino acids along with urine organic acids were performed that returned within normal limits.
She has a significant family history of similar episodes on her maternal side, which appears to be inherited in a dominant fashion. Other family members had a similar age of onset as well as a decrease in severity and frequency of episodes over time. In all affected members of this family, the precipitating factors for these episodes appeared to be rapid-onset muscle contractions. The patient and her family members reported an increase in the frequency of these episodes related to the menstrual cycle (for females), inter-current illnesses, particularly with fever, and at times of emotional stress. Caffeine and alcohol also exacerbated the episodes. Additional triggers included cold weather and postural change. Headache, tinnitus, hearing loss, vertigo, and scotomas were not reported (Table 1).