5 - SLEEP DISORDERS
Sleep in other Neurological Disorders
and sleep disorders are commonly associated with neurological
diseases, and neurological impairments of sleep reveal much
about the brain circuitry involved in sleep regulation. Many
neurological disorders are now recognized to cause disruptions
of sleep. For example, pathological sleepiness is associated
with neurological and neurodegenerative disorders such as Parkinson's
disease (PD), Alzheimer's disease (AD), and progressive supranuclear
palsy. Pathological sleepiness is also associated with neuromuscular
disorders such as myotonic dystrophy, inflammatory conditions
such as encephalitis or multiple sclerosis, and with traumatic
or ischemic injury to the brain. In addition, conditions such
as REM Sleep Behavior Disorder (RBD) are recognized as precursors
of Parkinson's disease. Conversely, Fatal Familial Insomnia
(FFI), a prion disorder related to Creutzfeldt-Jakob disease,
causes prolonged wakefulness.
Sleep is a powerful
modulator of epilepsy, with some epilepsy syndromes occurring
exclusively or predominantly during sleep. These include benign
childhood epilepsy with centrotemporal spikes, autosomal dominant
nocturnal frontal lobe epilepsy, and continuous spike-wave activity
during sleep. Sleep deprivation has also been described as a
risk factor for epileptic seizures, although alcohol use and
work-related stress are confounding factors. Treatment of sleep
disorders that fragment sleep, such as Sleep-Disordered Breathing
(SDB), has improved seizure control in case series.
Sleep disorders can
also occur as a consequence of treating neurological disorders.
For example, pathological sleepiness may occur during treatment
of Parkinson's disease and other movement disorders with dopamine-related
drugs. In addition, many drugs used to treat neurological disorders
can cause excessive sleepiness or wakefulness.
Sleep disorders also
interact in complex ways with neurological disorders, and are
frequent after head trauma, stroke, encephalitis or in association
with neuromuscular disorders. For example, stroke has been shown
to be associated with SDB, and SDB likely decreases potential
for recovery in stroke patients. Stroke may also produce SDB
by interacting with the central regulation of breathing. Similarly,
the intermittent hypoxia that accompanies SDB may hasten the
neurodegenerative cascade in disorders such as PD and AD.
provide models for understanding sleep circuitry in the brain.
In addition, understanding sleep mechanisms and disorders will
be integral to treating these neurological diseases.
In The Last 5 Years
- Studies of patients
with Parkinson's disease reveal a range of sleep disorders,
including PLMS, RBD and daytime sleepiness. These disorders
are part of the disease spectrum, occur commonly, and suggest
an important role for dopaminergic pathways in sleep/wake regulation.
Dopamine-like drugs are useful in treating these disorders,
and it is recognized that when these drugs stimulate dopamine
D2/D3 receptors they can cause "attacks" of excessive
sleepiness and hence result in automobile and other accidents.
- An important advance
has been the empirical application of wake-promoting drugs to
treat sleep disorders in various neurological conditions. The
use of wake-promoting compounds in treating fatigue and sleepiness
in various neurological disorders such as Parkinson's disease,
head trauma and multiple sclerosis is increasing but these treatments
deserve controlled study.
- Vagus nerve stimulation
(VNS), an approved treatment for medically refractory epilepsy,
has been shown to cause apneas and shallow breaths (hypopneas)
during sleep, but these effects are ameliorated by reducing
VNS stimulus frequency. In addition, VNS has been shown to reduce
daytime sleepiness in epilepsy patients. These findings emphasize
the interconnections of the vagus nerve with brainstem networks
that regulate respiration and alertness.
- Advances in all
of these disorders depend upon understanding the brain circuitry
involved in sleep regulation. The last five years have seen
the elucidation of important components of the wake and sleep
promoting circuitry in the hypothalamus and the brainstem. Drug
development is currently under way to take advantage of this
new information in order to treat pathological wakefulness or
sleepiness, and to cause sedation when necessary with fewer
- Evaluate the prevalence
and impact of sleep disorders and disturbances in neurological
conditions, such as neurodegenerative disorders (e.g. Alzheimer's
disease, Parkinson's disease), movement disorders, post head
trauma, encephalitis, stroke, and epilepsy. These studies should
evaluate whether sleep disorders predispose to specific neurological
conditions, whether neurological conditions can produce sleep
disorders, and whether sleep disorders impair recovery from
selected neurological disorders. Studies of sleep in animal
models of neurological disorders should also be conducted.
- Study natural models
of locally disrupting sleep circuits (tumors, trauma, multiple
sclerosis plaques, infarcts, neurodegenerative conditions, paraneoplastic
syndrome, etc.). Studies should be performed that combine imaging
techniques or neuropathology with sleep/sleep disorders analyses.
- Study the impact
of pharmacological and non-pharmacological neurological treatments
on sleepiness and sleep (for example, in epilepsy, multiple
sclerosis, Parkinson's disease).
- Study sleep and
sleepiness in inflammatory states (encephalitis, infarcts, multiple
sclerosis, autoimmune disorders etc.).
- Determine if sleep
disruption due to sleep disorders or sleep deprivation lowers
the threshold for epileptic seizures, and explore the mechanisms
responsible for this effect.
- Perform controlled
studies to determine if treatment of sleep disorders improves