MJF Foundation Podcast

In this podcast from the Michael J. Fox Foundation, Kevin Kwok discusses his experience after having deep brain stimulation surgery. Advances in the technique promise a future where stimulation can be fine tuned for individual needs and thus, perhaps, reduce the side effects associated with DBS.

While selective activation of the brain has proven to relieve many symptoms of Parkinson’s Disease, such as tremors, rigidity, and gait issues, DBS has obtained very selective application approvals from the FDA. Many new studies look at deep brain stimulation for use with “mental health issues” and is most commonly associated, especially in the Parkinson’s community, with the work of reducing tremors; but it’s also gained some ground in the area of chronic pain relief. It is this application that I think most exciting for the HD community.

Huntington’s patients commonly have uncommon reactions to prescription medications. Sometimes pain relieving medications have limited effectiveness, while others create exaggerated side effects. Add to this the complexity of chronic pain in general, and the HD patient’s increasingly dysfunctional interpretations of pain and neuron messaging, and effectively treating chronic pain in the HD patient can become a series of guesses; in which doctors, patients and caregivers spends months or years testing approach after approach to relieve pain.

But DBS could be exciting for any number of reasons, once its mechanisms are more fully understood. Fox’s foundation is highlighting some really interesting research that is producing real time results with actual patients, not just early stage mouse studies, and this is yet another area that should be given serious attention.

Advertisements

Understanding Circadian Dysfunction and How We Can (Maybe) Slow Its Progression

Sleep is the interest we have to pay on the capital which is called in at death; and the higher the rate of interest and the more regularly it is paid, the further the date of redemption is post-poned.”–Arthur Schopenhauer

The internet is a veritable buffet of lists: 7 Superfoods to Eat, 10 Relationship Red Flags, 12 80’s Movies You Should Watch Again and, more pertinently to today’s blog, lists upon lists about getting sleep, sleeping better, and the detriments of losing sleep. List fatigue or no, sleep research is still churning out some very interesting data. Specifically, research into the complex process of circadian rhythm and hypothalamus dysfunction, which has specific indications for neurodegenerative disorders.

Sleep disturbance can cause a host of negative influences throughout the body. Sleep deprivation leads to increased irritability, agitation, decline of cognitive function, even disrupting the breakdown of sugar. Since behavior, such as eating, television, and exercise habits, can greatly influence the sleep process, we find that correcting detrimental behaviors can increase the amount and quality of our sleep and return our bodies to a healthy schedule and stasis.

For the HD patient recuperating from a bout of sleep dysfunction may not be as easy as catching a few extra hours of sleep. The major effects of sleep deprivation exacerbate mood disorders and cognitive dysfunction that the HD individual is already experiencing. This can create a spiraling situation for the individual, and further aggravate relationships potentially already under strain. Addressing this issue is of great importance; however, these outward behaviors only scratch the surface of how circadian disruption disturbs the body’s entire system. What we’re examining here is not just sleep and sleep dysfunction. Sleep is a circadian behavior, and research suggests that circadian dysfunction is at play in disease dysfunction for neurodegenerative diseases. For instance, sleep dysfunction can appear in Parkinson’s patients years ahead of visible motor dysfunction.

Understanding the Science

Sleep cycles are controlled by the circadian rhythms in the body, all of which are controlled by the suprachiasmatic nucleus (SCN), a small area located in the hypothalamus. Research has shown hypothalamic function is greatly affected by HD, most easily evidenced through weight loss. It is unclear exactly how this occurs, but research shows possible connections with oxidative stress and mitochondrial dysfunction. The SCN is directly above the optic chiasm and utilizes specialized light receptors to dictate the circadian rhythm timing system. The SCN uses hormones, particularly cortisol and melatonin, to regulate the system. The SCN can be considered the body’s master clock, coordinating the cycles of the body’s various other clocks (which regulate specific organs and systems within the body).

This process effects every aspect of the human body, down to transcription of each cell. These active and passive cycles allow our bodies to “time” its efforts. We can think of the circadian rhythm (and the SCN that regulates them) like the shift in objectives at a 24 hour store. Staff that arrives in the morning ensures displays are ready (the body waking up), handles customers and balances product (sorting out the input as we move through our day), while the night shift cleans up (our body processing our meals, eliminating toxins), fills the shelves (we rejuvenate during sleep), etc.

Circadian Dysfunction

Research by Mortin and colleagues has shown a progressive breakdown of circadian and activity cycles for the HD patient. Preliminary research with mice shows SCN neurons firing more sluggish during the day, and less quietly at night as are found in HD-free specimens. This generates a comparatively balanced activity chart, with activity leveling out between cycles. While we may seek balance in many other areas of the body, this activity level is a dysfunction in the system. The body should be highly active at times and quietly resting at others. This dysfunction leads to the hypothesis that HD patients are further hindered in their ability to process hormones, toxins, and metabolize in the manner it typically would, in addition to becoming less and less able to truly rest the body’s systems.

This dysfunction doesn’t just affect the cognitive and emotional processes. Dr. Chris Colwell of UCLA illustrated that mice experiencing this disruption had elevated blood pressure and pumping dysfunction. Further, Colwell’s research indicated molecular physiology that appeared to be working, but a growing drift in the synchronization of the various systems’ clocks. Colwell’s hypothesis, then, is that circadian dysfunction accelerates disease dysfunction.

Adjusting Behavior in the Face of Disease Acceleration

Following the logic of this hypothesis, what are the steps for retarding the dysfunction? First, we must consider the circadian/sleep dysfunction as an integral part of the disease. Second, we should identify some key elements that present environmental barriers to regulating sleep/circadian cycles.

Our body responds to full spectrum natural light (which is not the same as the “full spectrum” marketing term used for light bulbs) and regulates our cycles accordingly. This means that living under strictly fluorescent lighting, which emits ultraviolet light waves, can confuse the SCN. Hospitals and nursing homes typically have poor lighting in this regard. Many retailers now carry light boxes, which emit up to 10,000 lux. Light boxes are used in what is called phototherapy, and is used for people with circadian disorders as well as sufferers of seasonal affective disorder (SAD). Large units (of the 10,000 lux variety) can run several hundred dollars, with smaller units costing less than $100. Utilizing the light box can delay the onset of sleep and activate the SCN to recognize the active part of its cycle. Blue light glasses can also be obtained, which serve to block the blue light and induce the release of melatonin.

Exercise is a vital element for care, for all individuals, but in particular HD patients. According to a study at the University of Georgia, brief periods of exercise for just 20 minutes facilitates information processing and memory functions. Research out of UCLA illustrates that exercise for merely one week of activity presented increased axonal regeneration. Exercise facilitates brain growth and increases sensory neurons’ ability to create new connections and pathways. This function is vital for those with neurodegenerative disorders.It’s also important to schedule exercise for the morning/afternoon portion of the day. Exercising in the evening or after dinner can delay the release of melatonin and onset of sleep.

The body needs to be conditioned to relax into the sleep cycle. To this end, meals should ideally be scheduled allowing enough time for the body to process it before retiring for bed. Snacking late at night is a common behavior for many adults, but especially HD patients. Curbing late night snacking can help the body shut down properly. As Colwell discussed, refraining from eating late not only aids in bringing on sleep but lead to improved performance on motor tasks.

Prescription medications are another element for consideration. Aside from the possible side effects of a given drug, timing of drug treatment matters. Certain medications, such as betablockers for hypertension, should be taken in the morning, while other medications should be taken in the evening, depending on how the body will metabolize those drugs. Adding a supplement of melatonin can help some whose body isn’t producing enough of the hormone. It’s best to discuss the sleep cycle disturbance or concern with the prescribing physician to ensure that all medication directions optimize the goal of regulating the sleep cycle.

The research into circadian dysfunction in Huntington’s Disease is in preliminary stages, but the combined efforts of many past studies lends the belief that this is a promising area of research. If we can aid in the regulating of the circadian cycle, and if this can help slow the progressive deterioration in the brain, then we’ve got a tangible, actionable course of treatment that can have short term and long term benefits.

References:

http://www.ncbi.nlm.nih.gov/pubmed/12595152

http://www.walgreens.com/store/c/home-health-care-solutions-daily-living-aids-light-therapy/ID=364025-tier3

http://www.webmd.com/sleep-disorders/features/important-sleep-habits

http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2265.1999.00763.x/full

http://www.med.upenn.edu/uep/user_documents/VanDongen_etal_Sleep_26_2_2003.pdf

http://hmg.oxfordjournals.org/content/14/1/39.short

Disclaimer: I am not a doctor. All information in this article is purely for educational and enrichment purposes and is not intended to replace or provide medical advice.