Page 187 - ILAE_Lectures_2015

PLMS can be familial, but can also be secondary and associated with iron deficiency,
pregnancy, peripheral neuropathy, neurodegenerative diseases and, rarely, spinal cord
lesions. Antidepressant drugs (SSRIs and tricyclics), neuroleptics, lithium, caffeine and
alcohol may also be associated with PLMS. Patients should have iron and ferritin levels
checked and supplements provided if levels are low or within the lower end of the reference
interval if ferritin <50 μg/litre). Treatment may be required if symptoms are severe and there
are frequent arousals. In the first instance, any medication contributing to the symptoms
should be discontinued if possible. Other treatment options are symptomatic and include
dopamine agonists (ropinirole or pramipexole), anticonvulsants (gabapentin, pregabalin,
carbamazepine), benzodiazepines (clonazepam) or opiates (tramadol).

Narcolepsy

Narcolepsy is a well-defined chronic neurological disorder caused by the brain’s inability to
regulate sleep-wake cycles normally, in particular REM sleep. Features of REM sleep intrude
into wakefulness and other stages of sleep. Patients with narcolepsy hence not only have
difficulties staying awake but also staying asleep.

There is a classical tetrad of symptoms:
1. Excessive daytime somnolence (EDS)
2. Cataplexy
3. Hypnogogic or hypnopompic hallucinations
4. Sleep paralysis.

Only 1015% of patients have the full tetrad. EDS, often in combination with sleep paralysis
and/or hallucinations, is the presenting symptom in around 90%. The sleepiness is continuous
but will intermittently worsen, resulting in an uncontrollable urge to sleep even in
inappropriate situations, and often interferes with normal activities. Even a brief nap is often
refreshing. Around 6070% of patients have cataplexy that can develop years after the initial
presentation, usually within in 35 years. Episodes with cataplexy may be mistaken for
seizures. Cataplexy is a sudden decrease in voluntary muscle tone (especially jaw, neck and
limbs) that is usually precipitated by strong emotions such as laughter, anger or surprise.
Usually events are often partial, only involving for example the face, head and neck muscles
and manifest as drooping of face muscles, jaw dropping, or head nodding. If severe, limbs
may be involved and patients may fall (complete attack). Consciousness is preserved
throughout but if episodes last longer than two minutes, patients may go into REM sleep.
Sleep paralysis and hallucinations are not specific for narcolepsy but can occur in other sleep
disorders and can also occur in people without sleep disorders, particularly following sleep
deprivation. Hypnagogic denotes events associated with sleep onset and hypnopompic events
associated with sleep offset. There may also be episodes with automatic behaviour or micro
sleeps/sleep attacks that occasionally can be mistaken for epileptic seizures or post ictal
behaviour.

Narcolepsy is diagnosed using polysomnography and the multiple sleep latency test (MSLT).
There is a strong association with HLA type, suggesting that narcolepsy is an autoimmune
disorder. Approximately 90% of patients who have narcolepsy with cataplexy have the HLA
allele HLA DQB1*0602. However, this is also frequently found in the general population
(around 25%) and is therefore in general not helpful for diagnosis. Genetic factors may also
be involved but to date no specific gene for narcolepsy has been identified in humans. Loss
of hypocretin (orexin)-producing neurones in the hypothalamus has been shown in patients
with narcolepsy with cataplexy and it is likely that narcolepsy is due to hypocretin (orexin)
deficiency30,31. Low levels of hypocretin have been shown in patients who have narcolepsy
with cataplexy but for patients with narcolepsy without cataplexy, levels are similar to control
subjects32,33 and in this group of patients, CSF analyses are less helpful for the diagnosis.