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  "notes": "The slide uses a direct quote from a scientific editorial to discredit a previously held hypothesis regarding pitolisant's mechanism of action.",
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      "text": "Editorial introducing the Bioprojet paper that undermines the entire pitolisant mechanism of action",
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      "text": "This should further temper concluding that reduction in CSF histamine bioactivity is the principal arbiter of sleepiness in primary hypersomnias.",
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      "text": "The Bioprojet paper showing no correlation between histamine and sleepiness was a landmark finding and merited an editorial in the journal (SLEEP) in which it was published. The author, a neurology professor and leading scientist in sleep research, called it “a back to the drawing board moment” that undermined the “very seductive tale in which the protagonist is brain histamine.” He slammed the previous pitolisant studies and detailed “additional methodological concerns” with the now-discredited histamine hypothesis, concluding that the finding “is not at all surprising” and that “this should temper concluding that…histamine…is the principal arbiter of sleepiness in primary hypersomnias.”",
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      "text": "the analytical methodology employed. An additional point of agreement between these studies was that CSF histamine and t-MH failed to correlate with any clinical metric of sleepiness. This should further temper concluding that reduction in CSF histamine bioactivity is the principal arbiter of sleepiness in primary hypersomnias. It is also a reminder of the diversity of alternate factors that can influence the complex trait of sleepiness.25,26 Time between CSF sampling and sleep/sleepiness assessments, the inadequacy of metrics to capture sleepiness, the reliance on verbal reports and psychometrics of sleepiness, and individual differences in compensatory wake promoting substances or endogenous somnogens are a few of several factors that could account for the inability to correlate CSF histamine markers with sleepiness metrics. It is safe to say that the findings of Dauvilliers et al.13 point us back to the drawing board in search of a biomarker and mechanistic details with relevance to the diagnosis and treatment of the primary hypersomnias.",
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      "text": "a back to the drawing board moment — Neurology Professor/Author of SLEEP editorial. very seductive tale in which the protagonist is brain histamine. — Neurology Professor/Author of SLEEP editorial. additional methodological concerns — Neurology Professor/Author of SLEEP editorial. is not at all surprising — Neurology Professor/Author of SLEEP editorial. this should temper concluding that...histamine...is the principal arbiter of sleepiness in primary hypersomnias. — Neurology Professor/Author of SLEEP editorial.",
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      "text": "Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443754/pdf/aasm.35.10.1315.pdf",
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      "text": "Inability to Replicate Cerebrospinal Fluid Histamine Deficits in the Primary Hypersomnias: A Back to the Drawing Board Moment",
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