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  • 1.  Non-24-Hour Sleep-Wake Disorder - Circadian Rhythm Sleep Disorder

    Posted 06-16-2025 03:44

    Dear all,

    The neurologist is about to refer a patient with a suspected circadian rhythm sleep disorder, but the patient has normal eyesight. 

    I have never seen such a patient before, but since melanopsin photoreceptors play a role in circadian rythm, I was wondering if there is a way to examine these?

    Any and all suggestions welcome, of course!

    Kind regards,

    Michel



  • 2.  RE: Non-24-Hour Sleep-Wake Disorder - Circadian Rhythm Sleep Disorder

    Posted 06-16-2025 05:07
    Hi Michel

    The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are so interesting!  The classic ipRGCs project to midbrain to drive pupil light reflexes and to hypothalamus to support circadian entrainment.  The melanopsin on their cell membrane results in a sustained tonic signal to bright blue light, which can be detected clinically as the post-illumination pupil response (persistent pupil constriction in the dark after a very bright blue light stimulus).

    However, as the ipRGCs also transmit signals from the rods and cones to the same destinations in the brain, it can be hard to recognise specific dysfunction of the melanopsin protein signal.  Even someone with complete lack of melanopsin will have circadian entrainment and pupil light reflexes (just not the post-illumination pupil response), and the phenotype of melanopsin dysfunction is fairly subtle.  If there was a condition that specifically affected ipRGCs (so they were worse affected than RGCs of conscious vision), then afferent pupil abnormalities and circadian dysfunction would be more marked.  There was some suggestion that the subtle optic atrophy of Alzheimer disease could affect ipRGC more, but most optic neuropathies spare ipRGC to some extent as they are large and robust compared to other RGCs.

    I think someone with an isolated problem of circadian entrainment is most likely to have normal optic nerves and a pathway-specific abnormality in the suprachiasmatic nucleus (hypothalamus).  But a visual field test and a pupil examination would largely answer the neurologist's question.  

    Warm wishes
    Jesse



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  • 3.  RE: Non-24-Hour Sleep-Wake Disorder - Circadian Rhythm Sleep Disorder

    Posted 06-25-2025 18:00

    Dear Jesse,

    Thank you so much for this extensive reply. This is quite educational. The visual fields turned out to be normal. 

    Kind regards 

    Michel 


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  • 4.  RE: Non-24-Hour Sleep-Wake Disorder - Circadian Rhythm Sleep Disorder

    Posted 06-16-2025 14:11

    Chromatic pupillography with blue light stimulus.



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  • 5.  RE: Non-24-Hour Sleep-Wake Disorder - Circadian Rhythm Sleep Disorder

    Posted 06-25-2025 18:00

    Thank you!


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