Clinical Description
Authoritative source:
Abstracted from authoritative source:
Overview: Narcolepsy is a disorder of rapid onset rapid eye movement (REM) sleep characterized by excessive daytime sleepiness (EDS), frequent uncontrollable sleep attacks as well as sleep fragmentation and can be associated with cataplexy, sleep paralysis, and hypnagogic hallucinations. There are two types: narcolepsy type 1 (formerly narcolepsy with cataplexy) and narcolepsy type 2 (formerly narcolepsy without cataplexy).
The condition is often under-diagnosed and delays of 5-10 years are common before making a firm diagnosis. Close to 50% of patients develop symptoms in their teenage years. Prevalence is 14 per 100,000 people for narcolepsy type 1 and 65.4 per 100,000 people for narcolepsy type 2. Incidence is highest in the late teens to early twenties with a 50% greater female predominance in the U. S. according to data 2008-2010. Associated after vaccination with the H1N1 vaccination in Sweden (Pandemrix) within 2 weeks of vaccination in 2010-2011.
Presentation: The only required symptom for the diagnosis of narcolepsy is daily, irrepressible, rapid lapses into REM sleep known as “sleep attacks” that are present for at least three months.
Diagnostics Evaluation: Sleep studies (polysymnographic testing including the Multiple Sleep Latency Test), CSF evaluation for neuropeptide hypocretin-1 (orexin A) (hyposecretion of this neuropeptide is a diagnostic biomarker for narcolepsy).
Therapy Plan: Treat reversible causes (sleep apnea, infections), withdraw or do not continue to expose to provoking agent, personal safety including driving safety. Stimulants for daytime sleepiness, REM sleep suppressing drugs for cataplexy.
Prognosis: Treatments unfortunately fail to help patients with narcolepsy feel fully alert. Psychosocial support. Weight management. Sleep specialist consult. 2-4 fold increased risk for motor vehicle accident compared to non-narcoleptics.
Differential Diagnosis: sleep apnea, depression, seizure
Regular Expression:
sleep|cataplexy|narcolepsys|rem|paralysis|hallucinat|vaccin|mnograph|csf|cretin|oxrexi|weight|obese|apnea|zepam|epilepsy|seizure
Phenotype Development:
Logic Description: All events of Narcolepsy (includes cataplexy with narcolepsy) with no such events in prior clean window period (365 days). Persons should not be diagnosed with hypersomnia. Persons exit the cohort on end_date + 90 days as persons are assumed to have the condition for at least 90 days.
Source of errors in real world and impact on algorithm:
- Miss rate/False negative rate (missing TRUE cases) We expect clinicians in real world to miss detecting this phenotype or mislabeling persons with this condition as having another disease. It is expected to be underdiagnosed or misdiagnosed. The false negative rate in real world is not known. We probably have to accept this error (i.e. lower expected sensitivity) as there would many persons who are undiagnosed.
- Index date misclassification: we hypothesize that persons with this condition would have significant latency in diagnosis, i.e. the date of initial diagnosis maybe months or years after the origin of the disease in the person.
- Specificity errors: Variability within and between diagnosis clinician: because of the lack of well established and universally agreed objective diagnostics criteria, and diagnosis dependent on clinician experience/opinion - it is possible that persons may be diagnosed when they have a related sleep condition.
Cohort Submission:
This cohort definition has cohort id # 239 in OHDSI Phenotype library (pending peer review). We reviewed two versions of cohort definitions for Narcolepsy and decided to submit only the above cohort definition. The other cohort definitions that were evaluated a) All events of Narcolepsy (includes cataplexy with narcolepsy) with no such events in prior clean window period (365 days). Persons exit the cohort on end_date + 890 days as persons are assumed to have the condition for at least 90 days. The key difference was the use of exclusion criteria for hypersomnia.
Reason: we found that among persons with narcolepsy we observed 3 to 10% also had hypersomnia in 30days prior to index. We hypothesized that this could be misclassification errors. On comparison we inferred that the cohort that did not have hypersomnia appears to have characteristics that suggested it was more specific to the target of narcolepsy as evidenced by higher polysomnography, higher modafinil and armodafinil among persons without hypersomnia. Other than these characteristics, those with narcolepsy without hypersomnia appeared similar to those with narcolepsy and hypersomnia
Phenotype Evaluation:
Insights from Cohort Diagnostics:
Was performed on 10 data sources, available on https://data.ohdsi.org/PhenotypeLibrary/ see cohort id C239: [P] Narcolepsy events (1Pe, 0Era, 365W), with the largest data sources having counts ~ 100,000 persons.
Incidence rate - female preponderance is observed. Incidence rate appears higher in the 20 to 29 age range compared to other age deciles with a numerical rate around 0.5 per 1,000 person years across data sources ~ which in the expected range (reported in clinical description). Rate appears to temporally stable.
Index event breakdown: The most common codes accounting for cohort entry across data sources are Narcolepsy without cataplexy (range: 78% to 85%) or Cataplexy and narcolepsy (range: 19% to 28%). The SNOMED code Narcolepsy accounted for entry in CPRD and IQVIA Ambulatory EHR.
Visit context: Between 90%-98% have an outpatient on visit start
Characterization: On index date - Depressive disorder observed in about 10% to 30%, (obstructive) sleep apnea in about 10% to 20%, anxiety 10%, neurosis 10%. Modafinil ranged from 2 to 5.8% in the 30 days after index; Armodafinil ranged from 1.2% to 3.4% in the 30 days after index and was higher (range: 3.2% to 8.4%) in the 31 to 365 days post index and these are consistent with both definitions.
Overall: we believe that removal of hypersomnia improves specificity of the definition.
Performance characteristics
Pending - PheValuator