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Monday, January 6, 2014

Willis-Ekbom Disease (restless legs syndrome) research has discovered a possible cause and defined the mechanism that impairs sleep.

Willis-Ekbom Disease (rls) is often seen in fibromyalgia, but may be present in other disease processes or be a primary disease with no relation to other pathology.  In The Journal of Sleep Disorders and Therapy, Vol.2, Issue 6, 9/15/2013 at http://dx.doi.org/10.4172/2167-0277.100139 the pathophysiology of Willis-Ekbom Disease (WED) has been theorized as an imbalance between Dopamine and Thyroid Hormone in a research article "Willis-Ekbom Disease (Restless Legs Syndrome) Pathophysiology: The Imbalance Between Dopamine and Thyroid Hormone Theory".  I would like to summarize the findings of this research.  If you would like additional information you can access this research as provided above.  This is an open access research article.

WED is a sensorimotor disorder that has both sensory and motor components.  Four features of WED need to be present in order to make the diagnosis:
1. An urge to move the legs is usually accompanied or caused by uncomfortable sensations and/or pain in the legs.
2. The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity.
3. The urge to move or unpleasant sensations are partially or totally relieved by intentionally moving the legs or body part that is affected by the unpleasant sensations.
4. The urge to move or unpleasant sensations are worse in the evening or night compared to during the day.

Supportive clinical features of WED are family history of WED, Periodic Limb Movements during Sleep, and periodic limb movements during wakefulness.  In addition, WED symptoms that improve with dopamine therapy is indicative that the patient has WED.  It has been questioned whether WED symptoms originate in the central nervous system or the peripheral nervouse system.  Applying cold packs, massaging the legs or stretching the legs relieves some of the symptoms, indicating that WED symptoms originate in the peripheral nervous system.  Medications that relieve WED symptoms do not cross the blood brain barrier, which also indicates that WED symptoms originate in the periphery.  This research was initiated by the authors due to believing the neurohormone dopamine is released in insufficient quantities to inhibit thyrotropin (thyroid hormone) resulting in excess thyroid hormone.  The increased levels of thyrotropin exceed the threshhold for stimuli perception of the somatosensory receptors located deep inside the leg, and the velocity of signals in the nervous system is also increased, which is felt as unpleasant sensations.  WED symptoms appear or worsen in the evening and at night when thyrotropin levels are increased.  Additional evidence that thyroid hormone is involved with producing WED symptoms is some of the medications used to treat WED symptoms decrease thyroid hormone.  Since research has shown that WED symptoms are worsened with an increase in thyroid hormone, it is thought that WED is actually a very mild form of thyrotoxicosis with a circadian rhythm component.

Thyroid hormone has an effect on mitochondria and the production of ATP or energy.  The mitochondria are the power house in our cells, because they produce ATP.  Thyroid hormone also enhances cognitive or thinking processes in the brain.  ATP has an excitatory mechanism that also increases alertness.  ATP is stored with other neurotransmitters such as GABA or glutamate, a fast-acting excitatory neurotransmitter.  The cascade of thyroid hormone, ATP and glutamate in the somatosensory pathways result in WED sensations and increased arousal that results in shortened sleep.  Some patients have sensations strong enough that result in painful stimuli.  "The pharmacological and therapeutic evidence highlight the importance of a strengthened neurotransmission of sensory inputs to the sensory cortex (of the brain) as the ultimate trigger of WED symptoms."  It is thought that dopamine as a neurohormone and neurotransmitter acts in the brain to contribute to WED pathophysiology due to inadequate dopamine supplies to moderate thyroid hormone.  "It is known that an enhanced tonus of the sympathetic nervous system (fight or flight system) impairs sleep.  As thyroid hormone may inhibit sleep, we believe that one of the mechanisms by which an elevated sympathetic nervous tonus system hampers sleep is through releasing thyroid hormone directly from the thyroid gland via its fibers directed to the gland."

WED is more common in patients with severe iron deficiency; your iron level should be checked by your doctor to rule out iron deficiency as a possible cause.  Supplemental iron will alleviate WED symptoms in those patients with severe iron deficiency.  It is assumed that the lack of iron impairs the balance between thyroid hormone and dopamine.  There is also a genetic influence, which is called primary WED.  It is thought that primary WED patients are born with less dopamine neurons than normal individuals so dopamine is in insufficient quantities to modulate the circadian rise in thyroid hormone.  WED can also be caused by medications that work to augment thyroid hormone.  This is a side effect of some medications.

Up to 90% of WED sufferers present with Periodic Limb Movements in Sleep, which are intermittent repetitive movements of the arms and legs during sleep.  During sleep the spinal cord continues to receive inputs and the spinal reflex is triggered causing limb movement.  Patients with Periodic Limb Movements in Sleep are thought to be more severely effected by WED.

In addition to many drugs that act to worsen the severity of WED, there are also many clinical conditions that either increase the severity of existing WED or triggers a new WED episode.  Other secondary WED episodes may be caused by pregnancy, hyperthyroidism (Grave's disease), diabetes, and chronic renal failure.

This research provides powerful arguments regarding the catalysts responsible for WED symptoms and also provides insight about the nature of the associated, circadian rhythm sleep disorder.  Managing your WED symptoms may mean getting a better night's sleep.  Blessings to you in the new year!
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