"The severity of daytime sleepiness needs to be quantified by subjective scales (at least the Epworth Sleepiness Scale) and objective tests such as the multiple sleep latency test (MSLT)." The Stanford sleepiness scale (SSS) is another frequently-used subjective measurement of sleepiness. After it is determined that excessive daytime sleepiness is present, a complete medical examination and full evaluation of potential disorders in the differential diagnosis (which can be tedious, expensive and time-consuming) should be undertaken. Differential diagnosis<unk>  can be primary (of central/brain origin), or it can be secondary to any of numerous medical conditions. More than one type of<unk>  can coexist in a single patient. Even in the presence of a known cause of<unk> , the contribution of this cause to the complaint of excessive daytime sleepiness needs to be assessed. When specific treatments of the known condition do not fully suppress excessive daytime sleepiness, additional causes of<unk>  should be sought. For example, if a patient with sleep apnea is treated with CPAP (continuous positive airway pressure), which resolves their apneas but not their excessive daytime sleepiness, it is necessary to seek other causes for the excessive daytime sleepiness. Obstructive sleep apnea “occurs frequently in narcolepsy and may delay the diagnosis of narcolepsy by several years and interfere with its proper management.” Primary<unk> s The true primary<unk> s include: * Narcolepsy (with and without cataplexy) * Idiopathic<unk>  * Recurrent<unk> s (like Kleine-Levin syndrome) Primary<unk>  mimics There are also several genetic disorders that may be associated with primary/central<unk> . These include the following: Prader-Willi syndrome; Norrie disease; Niemann–Pick disease, type C; and myotonic dystrophy. However,<unk>  in these syndromes may also be associated with other secondary causes, so it is important to complete a full evaluation. Myotonic dystrophy is often associated with SOREMPs (sleep onset REM periods, such as occur in narcolepsy). There are many neurological disorders that may mimic the primary<unk> s, narcolepsy and idiopathic<unk> : brain tumors; stroke-provoking lesions; and dysfunction in the thalamus, hypothalamus, or brainstem. Also, neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, or multiple system atrophy are frequently associated with primary<unk> . However, in these cases, one must still rule out other secondary causes. Early hydrocephalus can also cause severe excessive daytime sleepiness. Additionally, head trauma can be associated with a primary/central<unk> , and symptoms similar to those of idiopathic<unk>  can be seen within 6–18 months following the trauma. However, the associated symptoms of headaches, memory loss, and lack of concentration may be more frequent in head trauma than in idiopathic<unk> . "The possibility of secondary narcolepsy following head injury in previously asymptomatic individuals has also been reported." Secondary<unk> s Secondary<unk> s are extremely numerous.<unk>  can be secondary to disorders such as clinical depression, multiple sclerosis, encephalitis, epilepsy, or obesity.<unk>  can also be a symptom of other sleep disorders, like sleep apnea. It may occur as an adverse effect of taking certain medications, of withdrawal from some medications, or of substance use. A genetic predisposition may also be a factor. In some cases it results from a physical problem, such as a tumor, head trauma, or dysfunction of the autonomic or central nervous system. Sleep apnea is the second most frequent cause of secondary<unk> , affecting up to 4% of middle-aged adults, mostly men. Upper airway resistance syndrome (UARS) is a clinical variant of sleep apnea that can also cause<unk> . Just as other sleep disorders (like narcolepsy) can coexist with sleep apnea, the same is true for UARS. There are many cases of UARS in which excessive daytime sleepiness persists after CPAP treatment, indicating an additional cause, or causes, of the<unk>  and requiring further evaluation. Sleep movement disorders, such as restless legs syndrome (RLS) and periodic limb movement disorder (PLMD or PLMS) can also cause secondary<unk> . Although RLS does commonly cause excessive daytime sleepiness, PLMS does not. There is no evidence that PLMS plays "a role in the etiology of daytime sleepiness. In fact, two studies showed no correlation between PLMS and objective measures of excessive daytime sleepiness. In addition, EDS in these patients is best treated with psychostimulants—and not with dopaminergic agents known to suppress PLMS." Neuromuscular diseases and spinal cord diseases often lead to sleep disturbances due to respiratory dysfunction causing sleep apnea, and they may also cause insomnia related to pain. "Other sleep alterations, such as periodic limb movement disorders in patients with spinal cord disease, have also been uncovered with the widespread use of polysomnography." Primary<unk>  in diabetes, hepatic encephalopathy, and acromegaly is rarely reported, but these medical conditions may also be associated with<unk>  secondary to sleep apnea and periodic limb movement disorder (PLMD). Chronic fatigue syndrome and fibromyalgia can also be associated with<unk> . Chronic fatigue syndrome is "characterized by persistent or relapsing fatigue that does not resolve with sleep or rest. Polysomnography shows reduced sleep efficiency and may include alpha intrusion into sleep EEG. It is likely that a number of cases labeled as chronic fatigue syndrome are unrecognized cases of upper airway resistance syndrome" or other sleep disorders, such as narcolepsy, sleep apnea, PLMD, etc. As with chronic fatigue syndrome, fibromyalgia may be associated with anomalous alpha wave activity (typically associated with arousal states) during NREM sleep. Also, researchers have shown that disrupting stage IV sleep consistently in young, healthy subjects causes a significant increase in muscle tenderness—similar to that experienced in "neurasthenic musculoskeletal pain syndrome". This pain resolved when the subjects were able to resume their normal sleep patterns. Chronic kidney disease is commonly associated with sleep symptoms and excessive daytime sleepiness. 80% of those on dialysis have sleep disturbances. Sleep apnea can occur 10 times as often in uremic patients than in the general population and can affect up to 30-80% of patients on dialysis, though nighttime dialysis can improve this. About 50% of dialysis patients have<unk> , as severe kidney disease can cause uremic encephalopathy, increased sleep-inducing cytokines, and impaired sleep efficiency. About 70% of dialysis patients are affected by insomnia, and RLS and PLMD affect 30%, though these may improve after dialysis or kidney transplant. Most forms of cancer and their therapies can cause fatigue and disturbed sleep, affecting 25-99% of patients and often lasting for years after treatment completion. "Insomnia is common and a predictor of fatigue in cancer patients, and polysomnography demonstrates reduced sleep efficiency, prolonged initial sleep latency, and increased wake time during the night." Paraneoplastic syndromes can also cause insomnia,<unk> , and parasomnias. Autoimmune diseases, especially lupus and rheumatoid arthritis, are often associated with<unk> . Morvan's syndrome is an example of a rarer autoimmune illness that can also lead to<unk> . Celiac disease is another autoimmune disease associated with poor sleep quality (which may lead to<unk> , "not only at diagnosis but also during treatment with a gluten-free diet." There are also some case reports of central<unk>  in celiac disease. And RLS "has been shown to be frequent in celiac disease," presumably due to its associated iron deficiency. Hypothyroidism and iron deficiency with or without (iron-deficiency anemia) can also cause secondary<unk> . Various tests for these disorders are done so they can be treated.<unk>  can also develop within months after viral infections such as Whipple's disease, mononucleosis, HIV, and Guillain–Barré syndrome. Behaviorally induced insufficient sleep syndrome must be considered in the differential diagnosis of secondary<unk> . This disorder occurs in individuals who fail to get sufficient sleep for at least three months. In this case, the patient has chronic sleep deprivation, although they may not necessarily be aware of it. This situation is becoming more prevalent in western society due to the modern demands and expectations placed upon the individual. Many medications can lead to secondary<unk> . Therefore, a patient's complete medication list should be carefully reviewed for sleepiness or fatigue as side effects. In these cases, careful withdrawal from the possibly offending medication(s) is needed; then, medication substitution can be undertaken. Mood disorders, like depression, anxiety disorder and bipolar disorder, can also be associated with<unk> . The complaint of excessive daytime sleepiness in these conditions is often associated with poor sleep at night. "In that sense, insomnia and EDS are frequently associated, especially in cases of depression."<unk>  in mood disorders seems to be primarily related to "lack of interest and decreased energy inherent in the depressed condition rather than an increase in sleep or REM sleep propensity". In all cases with these mood disorders, the MSLT is normal (not too short and no SOREMPs). Posttraumatic<unk> s In some cases,<unk>  can be caused by a brain injury. Researchers found that the level of sleepiness is correlated with the severity of the injury. Even if patients reported an improvement, sleepiness remained present for a year in about a quarter of patients with traumatic brain injury. Recurrent<unk> s Recurrent<unk> s are defined by several episodes of<unk>  persisting from a few days to weeks. These episodes can occur weeks or months apart from each other. There are 2 subtypes of recurrent<unk> s: Kleine-Levin syndrome and
Hypersomnia
Orthosomnia
Dyssomnia
Parasomnia
Excessive daytime sleepiness
Insomnia
Snatiation
Sleepwalking