Saturday, March 16, 2019

A pediatric case of narcolepsy treated with sodium oxybate

Miskoff JA, Chaudhri M. A Pediatric Case of Narcolepsy Presenting as Syncope. Cureus. 2018 Dec 31;10(12):e3801.


Narcolepsy is a chronic genetic  and sleep disorder that is caused by a protein deficiency. This may affect the patients' sleep architecture and the brain's ability to control circadian rhythms. Individuals with this condition feel rested after waking but then feel tired and sleepy as the day progresses. Typical onset is during adolescence, but there is often a significant delay in diagnosis, which may markedly hinder an individual's quality of life. This case provides an opportunity to shed light on this often underdiagnosed or misdiagnosed condition by presenting a case of a remarkable individual who has persevered to be successful with the help of a timely diagnosis and aggressive off-label therapy.
The patient was treated with sodium oxybate and modafinil. Sodium oxybate was approved by the FDA for narcolepsy in patients 18 years of age and older; a decision was taken by the treating clinician to start the therapy off-label at a reduced dose for this patient.

From the article:

A 13-year-old female visited a physician in January 2007 for the evaluation of passing out associated with laughing. According to the records, the patient underwent a magnetic resonance imaging (MRI) of the brain with and without contrast, along with an electroencephalogram (EEG), in October 2007 for an evaluation pertaining to a chronic headache and generalized weakness resulting in syncopal episodes triggered by laughter. The results of these diagnostic studies were unremarkable. The patient was seen by a neurologist on September 26, 2007, for persistent symptoms of losing muscle tone triggered by a strong emotional response. The neurologist suggested that the patient should undergo a magnetic resonance angiogram (MRA) of carotid arteries because the symptom of “laughter leading to loss of muscle tone, resulting in the patient losing control and falling” may suggest syncope of a cardiovascular etiology. Furthermore, neurologist records suggest that the patient experienced four episodes of laughter leading to loss of muscle tone while she was at Disneyland, a week later. Lastly, the neurologist concluded his consultation by suggesting that no further workup was needed. Subsequently, the patient underwent an echocardiogram on October 1, 2007, to investigate her continued “syncopal episodes.” According to records, the cardiologist felt that the patient might have vasovagal syncope thus requiring an MRA and MRI of the neck followed by a Holter monitor. The results were all within normal limits as reported by the patient and her mother. Although the cardio-neuro workup was inconclusive, the patient continued to have chronic symptoms and, therefore, sought initial consultation with a sleep specialist.

The patient was seen by our practice on January 11, 2008, and was referred for a nocturnal polysomnogram (NPSG) and a multiple sleep latency test (MSLT) to investigate a probable diagnosis of narcolepsy due to exhibited signs of narcolepsy with cataplexy, sleep paralysis, excessive daytime sleepiness and hypnagogic hallucinations. The PSG results suggested a total sleep of 436.7 minutes with a sleep efficiency of 93 percent (n=89%). Moreover, rapid eye movement (REM) and sleep latencies were 94.5 minutes (n=136-156) and 10 minutes, respectively. The PSG revealed that the patient experienced one obstructive apnea lasting for 11 seconds, five central apneas, and 11 hypopneas with an apnea/hypopnea index of 2.3, which is normal. The patient verbalized not being able to move or talk during sleeping. The patient underwent an MSLT study in February 2008, which revealed a mean sleep latency (MSL) of 4.3 minutes on three 20-minute naps. The diagnostic criterion requires an MSL of ≤8 minutes and ≥2 sleep onset REM periods (SOREMPs) on MSLT. Since our patient satisfied the MSL and SOREMP components on three naps, continuing the study was not needed. Records indicate that the patient had an average sleep lasting 15 minutes, REM sleep lasting five minutes, and eight minutes average latency to REM sleep on the MSLT. A normal REM cycle occurs every 90 minutes after sleep onset, the first REM period lasts 10 minutes with each recurring REM stage lengthening. In addition to the sleep study, laboratory workup for HLA-DR15 and DQ0602 was positive, thus further supporting the diagnosis of narcolepsy.

As the patient was undergoing further studies to confirm her diagnosis, her condition and symptoms became common knowledge among her peers, which led her to be ostracized by fellow students. The situation escalated quickly to the point of feeling like she was bullied on a daily basis. Ultimately, she switched school, which added emotional stress to her life…

As with most patients, a trial and error of sodium oxybate were needed to titrate up to the therapeutic dose. The patient was started on 1.5 milligram (mg) sodium oxybate to be taken twice; however, the dose was decreased to 0.75 mg due to intolerance. In addition, the patient was prescribed 200 mg modafinil to be taken in the morning and an additional dose to be taken in the afternoon if needed. Over time, her sodium oxybate dose was increased to 4 grams taken once at bedtime. Typically, in adults, sodium oxybate is started at 2.25 grams (g) at bedtime and repeated three to four hours later due to its short half-life for a total of 9 g. Most titrations take several weeks to months at times. Along with medication, non-pharmacologic interventions, such as not being able to swim, not being able to enjoy riding a bicycle with her friends, requesting access to medication at all times, and needing extra time for exams, along with many other interventions, were instituted. Basically, she had to avoid all activities where laughter may induce cataplexy, which may increase the risk of bodily harm.

In a recent visit, the patient stated that she is tolerating her sodium oxybate and modafinil at a dose of 4 grams taken once per night without any complications and that her condition has stabilized. Timely management of her condition has improved her day-to-day functionality along with improving her quality of life.


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