Circadian rhythm studies in neuronal ceroid‐lipofuscinosis (NCL)

Abstract

Sleep disorders are common in NCL patients. The patients have problems such as frequent awakenings, difficulties with sleep onset, nightmares, and night terrors. The aim of the study was to examine whether the sleep disturbance in NCL can be explained on the basis of desynchronised circadian rhythms. Therefore we studied diurnal patterns of melatonin, cortisol, body temperature, and motor activity of 14 patients. The group consisted of 8 JNCL patients, 5 INCL children, and one boy with Jansky-Bielschowsky disease of the variant type. There were healthy age- and sex-matched control subjects. The blood samples for serum melatonin and cortisol were collected every 2 hours during 24-hour periods. Body temperature was recorded continuously for a 24-hour period by a polygraph. Diurnal motor activity was measured by wrist actigraphy for 5 days. In most of our patients sleep was fragmented and the sleep phase was irregular. Disturbances in the daily hormonal rhythms occurred only in the minority of the patients and only at an advanced stage of the disease. Although disturbances in the body temperature rhythm were found in about half of the patients, a general failure in the circadian regulatory system does not explain the frequent disturbances of the sleep-wake cycle of the NCL patients.

Temporal distributions of seizure occurrence from various epileptogenic regions

“…22,23 Furthermore, studies have linked chronic epilepsy to permanent circadian phase shifts, 24,25 with the presence and degree of abnormality likely dependent on the severity of disease. 26 Aggregating data from subjects with large circadian phase differences relative to each other would likely smear the distributions to some degree.…”

Children with Infantile Neuronal Ceroid Lipofuscinosis Have an Increased Risk of Hypothermia and Bradycardia During Anesthesia

“…In support of this hypothesis are studies of circadian temperature recordings in NCL patients showing significant disturbances in body temperature rhythms. Researchers showed that patients with INCL have maximal temperature in the morning, whereas controls had higher temperatures in the afternoon (20). It is also noteworthy that the only INCL patient in our series who did not develop hypothermia was the youngest patient (Patient 8) who had not yet developed neurological deficits at the time of first anesthesia.…”

Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis

“…Most symptomatic treatment studies in NCL have come from what we know from other diseases – but very few studies have been done specifically in NCL patients. In INCL these have been: Lamotrigine for epilepsy [ 19 – 21 ]; Transdermal fentanyl for pain [ 22 ]; Melatonin for sleep/circadian rhythm disturbance [ 23 – 25 ]; and hematopoietic stem cell transplant – umbilical cord blood and bone marrow transplant for disease modification [ 26 ]. These treatments, with a limited number of participants, are difficult to interpret because the studies are occurring at a time of rapid development, which significantly increases the variability between subjects, making outcomes difficult to measure.…”