Restless Legs Syndrome Foundation Blog

Q&A With Advisory Board Member Dr. Rochelle Zak

Rochelle Zak, MD is an RLS specialist who is board-certified in sleep medicine and neurology and treats patients with sleep disorders at the University of California San Francisco Medical Center. She volunteers on the RLS Foundation Scientific and Medical Advisory Board and is a member of the International RLS Study Group Board. Her research includes a special focus on women’s sleep health, particularly during the perimenopausal transition.

Q. What drew you to sleep medicine, and what motivated your interest in RLS?

I began my career in neuro-ophthalmology, a subspeciality focused on diagnosing and treating vision problems caused by neurological diseases. A close friend of mine was working in sleep medicine at New York Hospital. When one of her colleagues became sick, I was asked to step in and help. That experience sparked an unexpected passion for sleep medicine and ultimately led me to pursue formal training in the field.

My specific focus on RLS grew from a 45-year-old patient I encountered nearly 30 years ago, during my time at New York Hospital. He presented with discomfort on the left side of his chest, which to many would indicate cardiac issues. When extensive testing proved inconclusive, eventually we recognized this as his unique manifestation of RLS.

Through this patient, I learned (almost) everything there was to know about RLS. Working as a team – provider and patient – we trialed many treatment options, but ultimately methadone provided the greatest relief. This experience underscored how RLS does not behave as most medical disorders do, both in how it presents and how it responds to medication. While this presents challenges for both the patient and provider, it is all the more rewarding and meaningful when we find the best course of treatment.

Q. How has our understanding of RLS evolved over the course of your career?

A number of changes have occurred, but the first is a greater sophistication in our understanding of the pathophysiology of RLS. This includes its relationship to iron and various aspects of dopamine dysfunction, as well as the roles of glutamate and adenosine. Current research is establishing connections between imbalances in inhibitory and excitatory dopamine receptors and the interplay between the spinal cord and brain.

The second evolution is our prescribing habits and awareness of the roles of additional supplements. We have moved away from dopamine agonists because of the development of augmentation, with an increased usage of the gabapentinoids and a move from using shorter-acting to longer-acting opiates. In addition, there is now awareness of the role of vitamin D in RLS pathophysiology. The recent American Academy of Sleep Medicine Clinical Practice Guideline on RLS is a must-read and delineates much of this.

Q. Are there specific populations – such as perimenopausal individuals, pregnant people or older adults – where you feel additional RLS research is especially needed?

Given the complexity of managing RLS during pregnancy, there is an absolute need for continued RLS research in pregnant people, although as you can imagine, there are many studies one may want to do that cannot be done. There is also a great lack of general research on menopause, of which there are two stages – the menopausal transition and the postmenopausal state. The menopausal transition can be associated with fragmented sleep, low iron, fluctuating hormones and other exacerbating factors that can worsen RLS symptoms. We also need more research on the postmenopausal stage, when some of these factors have stabilized, so we can record how RLS changes during these two very different periods.

Q. Your research focuses on women’s health during the perimenopausal transition. What should individuals know about how menopause may impact their RLS symptoms?

Sleep fragmentation can occur during menopause from many causes, most notably hot flashes, exacerbating RLS symptoms. Fortunately, gabapentinoids can be used to treat both hot flashes and RLS. However, other medications commonly prescribed during the menopausal transition are known to worsen RLS symptoms. These may include serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine, or selective serotonin reuptake inhibitors (SSRIs) such as paroxetine. The RLS Foundation’s Depression and RLS handout may be helpful during conversations with your physician on medication triggers.

Prolonged or irregular spotting can also occur during menopause, which can be a source of significant iron loss but may not be recognized as such. Iron testing and, if needed, supplementation, can be beneficial. Hormone fluctuations are common during menopause; however, we have very little research on the role hormones may play in RLS symptom onset.

Q. What advancements in RLS treatments or future research do you feel will make the biggest impact on RLS management?

Expanding the range of medications available for RLS management is important. But I would also like to have a greater understanding of the relationship between spinal fluid ferritin levels, which give an indication of the iron available to the brain, versus blood ferritin levels, which is what we can easily monitor. Our current understanding of RLS pathophysiology suggests that there is greater difficulty in getting ferritin from the blood into the brain of individuals with RLS – a transport issue of ferritin across the blood-brain barrier. The blood-brain barrier is a protective layer of cells that controls what enters the brain and allows essential nutrients to pass through. If we could understand whether there is a universal serum ferritin level in individuals with RLS that can guide our therapy and/or understand the mechanism preventing easier transport of ferritin into the brain, we might be able to be more specific and effective in how we treat patients.

Q. How can individuals best support each other when dealing with chronic or invisible illnesses?

I think back to what my father, who was a physician, taught me: It’s all in the history. There is no test for RLS, so it is crucial to find a healthcare provider who is willing to thoroughly investigate a patient’s history. The RLS Foundation resources, including handouts, webinars and the Medical Bulletin, can help educate patients so that they have more effective conversations with their clinician to understand how their medical history informs their present situation.

You can connect with a safe space by joining a support group where you can share wisdom and support each other. The RLS Foundation hosts near-weekly support meetings, which are listed at www.rls.org/get-support.