Narcolepsy is recognized as a disabling sleep disorder which demonstrates sleep paralysis, excessive daytime sleepiness (EDS), indications of abnormal rapid eye movement (REM) sleep, cataplexy, and hallucinations either right before falling asleep or immediately after waking up. Functional imaging studies have shown metabolic (a process within a living organism to maintain life) and perfusion (oxygenated blood being delivered to tissues) abnormalities within the hypothalamus-thalamus-orbitofrontal pathway and other brain areas. The hypothalamus is involved in controlling body temperature, sleep and emotion. Meanwhile, the thalamus is involved in perceiving pain and relays sensory information. These abnormalities in narcolepsy patients indicates changes within the hypocretin pathway. Hypocretin is also referred to as orexin which is a hormone that functions to maintain sleep and appetite.
Structural changes in several brain areas resulting in wake-sleep control issues, attention and memory can be seen in brain magnetic resonance imaging (MRI). Due to the evidence of hypoperfusion (decreased blood flow through an organ) in white matter (WM) results in necessary imaging tests to determine the extent to the WM changes. Multiple MRI tests can be performed on patients. For example, diffusion tensor imaging (DTI) is an MRI technique that measures random water movement within the brain microstructural tissues. Additionally, fractional anisotropy (FA) of DTI measures the scaled parameter of the degree for anisotropy. The mean diffusivity (MD) of DTI measures the average water movement, however it’s affected by the size of the cell.
Voxel-based morphometry (VBM) technique was used by Nakamura et al., 2013; Scherfler et al., 2012 in previous WM changes in narcolepsy patient studies. VBM was initially used to investigate changes in grey matter (GM) density in T1-weighted images. However, debates still continue to determine if there are limitations such as faulty alignment between each patient and the uncertainty when choosing the extent to which smoothing occurs. n the other hand, Menzler et al., 2001 used tract-based spatial statistics (TBSS) with the hopes that there would be less limitations.
Park el al., 2016 had goals to look into the WM alterations and the relationship between these WM changes, cognitive functioning and mood within drug-naïve patients with narcolepsy with cataplexy (partial or total loss of muscle control, usually associated with mood or emotion). To complete this study, a final result of twenty-two narcolepsy patients from a university based sleep clinic and twenty-six healthy control patients from a local community were recruited. In order to participate in the study, the patients had to have no history of using nervous system stimulants or cataplexy medication. Each patient had to answer a sleep questionnaire, participate in a clinical interview and polysomnography (PSG) which is used to diagnose sleep disorders.
Many limitations and conditions were put in place and had to be met to be able to participate. For example, a patient would be excluded if they slept on average less than seven hours per day, had any other sleep disorders, or even alcohol or drug abuse, etc. These limitations are put in place to try and increase the accuracy of the results and to better able explain the hypothesis. All of the participants were right-handed, respectively.
Neuropsychological tests were performed based on working memory, executive functioning, verbal information processing, verbal memory, visual memory and verbal fluency. As stated above, the thalamus is responsible for relaying sensory information. As expected, there was different genders and age groups. As a result, patients were found to have a lower score toward attention, verbal fluency, working memory and verbal information processing. However, executive functioning didn’t have much of a difference. A Chi-square test was used to compare the gender distributions. Furthermore, a t-test was used to compare age differences. Age was considered as a covariate (direct interest) because it’s known from previous studies to have a large impact on FA and MD values. With that being said, the FA doesn’t always change when the MD changes.
The variability between results could have been altered based on the tiredness of the patient during testing. In fact, some patients fell asleep during testing. Hence, the results may not as be as accurate as they could have been. Different methods of calculating the data, interpreting the data, the effect the patient’s nervous system has to stimulants, age and gender may have caused some of the variability.
There may be a close relationship between emotional disturbances and WM changes. There may also be a possibility for narcolepsy and depression to share a pathway. It was found that there are greater changes in MD of the fronto-parietal gyri which is connected to more severe depressive symptoms. In conclusion, more narcolepsy patients were thought to be depressed than the results showed. This could be due to a lower self-evaluation in the emotional questionnaire when comparing with healthy patients. Further studies have shown that hypocretin and their hormonal receptors are associated with the physiopathology of depression.
Source: Park et al., 2016 Oh-Hun. Kwon, E.Y. Joo, Jae-Hun. Kim, J.M. Lee, S.T. Kim, S. Hong. White matter alterations in narcolepsy patients with cataplexy: tract-based spatial statistics. J Sleep Res, 25 (2016), pp 181-189.
