The relationship between thermoregulation and REM Sleep Behaviour Disorder in parkinson's Disease

A new study by Zhong and colleagues has found that in patients with PD, sleep problems (specifically RBD) appear to be related to problems in regulating body temperature at night. This gives rise to two interesting questions:

• Could the dysfunction in both the 'sleep' and 'thermoregulatory' systems share a common pathology?

• Could core body temperature profiling help in predicting PD?

What is RBD?
REM-sleep behavior disorder (RBD) is a disorder in which patients act out their dreams during the night. It is associated with PD – patients with RBD have an increased risk of developing PD and patients with PD have an increased risk of going on to develop RBD.

What did the authors do?
This was a case-control study comparing 12 patients with PD (cases) with 11 healthy, age-matched 'controls'. The authors measured core body temperautre over a 24-hour period, rest-activity patterns over the day and night (using actigraphy) and sleep patterns (using polyosmnography).

What the study found We know that body temperature fluctuates over a 24 hour period and should normally be cooler at night and warmer during the day (see fig. 1)

 

Fig 1. Schematic diagram showing a typical nocturnal core-body temperature profile (Zhong et al, 2013)

The authors found that patients with PD showed less of a nocturnal drop in body temperature than age-matched controls. They also found that the 'mesor' core body temperature (the average point around which temperature fluctuates) was lower in the patients with PD.

Among the patients with PD, those with self-reported RBD (higher RBDSQ scores) showed even less of a nocturnal drop in core body temperature (CBT amplitude) See fig 2.

Fig 2. A strong negative correlation was found between the nocturnal drop in core body temperature (CBT amplitude) and self-reported symptoms of RBD (RBDSQ) (Zhong et al, 2013)

Reduced noctunral CBT amplitude was also correlated with a lower fraction of time spent in REM sleep and an increase in sleep onset latency (the amount of time taken to fall asleep after going to bed), which are known to be important aspects of the sleep dysfunction suffered by some patients with PD

Could the dysfunction in both the 'sleep' and 'thermoregulatory' systems share a common pathology?

Lewy body pathology is known to affect key regions in the brainstem (pons and medulla) involved in thermoregulation, circadian rhythms and sleep. See fig 3.

Fig 3. Simplified schematic diagram highlighting the neural circuitry of the circadian-homeostatic-ultradian system and the functional neuroanatomical overlap with the thermoregulatory system.

 Possible links between thermoregulatory system dysfunction and sleep dysfunciton include:

• The Ascending Arousal System (AAS) - the AAS is known to be disrupted in PD and has an improtant role in the initation and maintenace of sleep as well as projections to the ultradian system and the medullary autonomic centers (meaning it may influence both sleep architecture and thermoregulation
• The medullary autonomic region, which plays a role in thermoregulation and is a key link between the SCN, the brain's master pacemaker, and the pineal gland, which secretes melatonin (a key hormone involved in both sleep and circadian rhythms)

It is therefore likely that some sort of common pathology results in the disruption of systems controlling both sleep and thermoregulation, however, it is impossible to conclude this for certain from this data alone.

Could core body temperature profiling help in predicting PD?

This reduced nocturnal drop in body temperature has previously been reported for patients with PD (Pierangeli et al, 2001; Suzuki et al, 2007). If these changes in body temperature regulation begin during the prodromal phase of the dsiease, it may be possible to use body temperature profiling to rpedict the development of PD.

However, in this study, the differnce in nocturnal amplitude between patients with PD and controls only just reached statistical significance (p=0.04) and the size of the effect was not that large either. Therefore, even if prodromal PD patients do have slightly abnormal body temperature profiles, core body temperature is unlikely to deliver much predictive power (at least, not on its own).

Additionally, this study suffers from the limitation of very small sample sizes (only 12 patients and 11 controls). Therefore, the effects observed may be due to chance alone and there may have been additional interesting associations (such as earlier sleep onset among patients with PD) that this study was simply not powered to detect.

Nonetheless, this is a very interesting study which provides new insights into body temperature regulation and sleep disorders in PD.

Jargon-buster:
Ultradian rhythms: Ultradian rhythms are bodily rhythms with a period shorter than 24 hours, including the cycling between REM and NRM stages of sleep (compare with circadian rhythms which occur over a 24 hour period).
Actigraphy: a method of measuring rest-activity patterns throughout the day, usually with a motion-detesting wrist watch.
Polysomnography: the measurement of lots of different physiological variables (heart rate, breathing rate, movement, EEG) to determine sleep patterns
RBDSQ: The RBD Screening Questionaire - a questionaire which has been designed to help diagnose RBD

References:

Pierangeli G, Provini F, Maltoni P, Barletta G, Contin M, Lugaresi E, Montagna P, Cortelli P (2001) Nocturnal body core temperature falls in Parkinson's disease but not in Multiple-System Atrophy. Mov Disord 16: 226-232

Suzuki K, Miyamoto T, Miyamoto M, Kaji Y, Takekawa H, Hirata K (2007) Circadian variation of core body temperature in Parkinson disease patients with depression: a potential biological marker for depression in Parkinson disease. Neuropsychobiology 56: 172-179

George Zhong,, Samuel Bolitho,, Ronald Grunstein,, Sharon Linda Naismith,, & Simon John Geoffrey Lewis (2013). The Relationship between Thermoregulation and REM Sleep Behaviour Disorder in Parkinson’s Disease PLOS ONE DOI: 10.1371/journal.pone.0072661