What’s New In The Diagnosis and
Management of Parasomnia and
Hypersomnia?
Chitra Lal, MD, FCCP, FAASM
Assistant Professor of Medicine,
Medical University of South Carolina,
Charleston, SC
Author Disclosures
• I have received grant support from Centocor
and Invado Pharmaceuticals
• I have received from grant support from SCOR
at MUSC
Hypersomnias of Central
Origin
Narcolepsy
Idiopathic
Hypersomnia
Recurrent
Hypersomnia
Parasomnias
NREM
Confusional arousals
Sleepwalking
Sleep Terrors
REM
Other
REM behavior disorder
Nightmares
Isolated sleep paralysis
Narcoplepsy
Excessive
daytime
sleepiness
Sleep
Paralysis
Fragmented
sleep
Cataplexy
Hypnogogic/
hypnopompic
hallucinations
Samson WK et al, Trends Endocrinol Metab, 2000
Ebrahim IO et al, J Neurol Neurosurg Psych 2003
Narcolepsy
without
Cataplexy
CSF
Hypocretin
Low ≤110
pg/ml
Intermediate
111-200
pg/ml
High > 200
pg/ml
Andlauer, O. et al, Sleep 2012
Comparison of Hypocretin groups
127 subjects
recontacted
26 years
post-onset
CSF
hypocretin
low
CSF
hypocretin
normal
Cataplexy
in 48%
Cataplexy
in 2%
Hypersomnolence in
87%
Sleep Medicine 14 (2013), 692-694
Feneberg, E et al, Sleep Medicine 2013
Structural abnormalities
in Narcolepsy,
Desseilles et al, Sleep 2008
Neuroimaging of Narcolepsy, Dang-Vu, TT et al,
CNS & Neurological Disorders-Drug Targets, 2009
Possible pathway for H1N1 and Pandemrix vaccination
and onset of Narcolepsy,
A.K. Singh et al, Journal of Autoimmunity, 2013
Alshaikh, MK et al, JCSM, 2012
Sodium Oxybate in Narcolepsy
Mean weekly Cataplexy attacks
Maintenance of Wakefulness
test
Sodium Oxybate in Narcolepsy
Mean Sleep Attacks
Clinical Global Impression of
Change
Sodium Oxybate in Narcolepsy
Adverse events: GI/Nausea
Vomiting
Sodium Oxybate in Narcolepsy
Adverse events: Dizziness
Enuresis
ICSD-2, Criteria for diagnosis of Idiopathic Hypersomnia
Primary Hypersomnia and GABAA
Receptor
• CSF from 32 hypersomnolent patients
stimulated GABAA receptor in vitro by 84% +/40.7% (SD) as compared to 35.8% +/- 7.5% in
controls (p < 0.0001)
• Bioactive CSF component has a mass of 500 to
3000 daltons and is neutralized by trypsin
• Enhancement was more for the α2 subunit of
GABAA receptor versus the α1 subunit
Primary Hypersomnia and GABAA
Receptor
• Flumazenil reversed enhancement of GABAA
receptor signaling by hypersomnolent CSF in
vitro
• Flumazenil normalized vigilance in 7
hypersomnolent patients
GABAA receptor modulation by CSF of
controls and subjects with hypersomnia
David Rye et al,
Sci Transl. Med, 2012
REM Behavior Disorder
• Presence of REM sleep without atonia
• At least one of the following:
- Sleep related injurious, potentially injurious
or disruptive behavior by history
- abnormal REM sleep behavior as
documented by polysomnography
• Absence of EEG epileptiform activity during REM
sleep
• Disease not explained by another disorder
Hippocampal perfusion in Idiopathic RBD:
with neurodegeneration (RBDEv) and without (RBDSt)
Dang-Vu TT et al,
Neurology, 2012
Nomura T. et al, Ramelteon in Secondary REM Behavior
Disorder, Internal Med, 2013
Conclusions
• Objective (HLA typing, MSLT and sleep studies)
more than subjective (sleepiness, sleep paralysis)
features predict low CSF hypocretin-1 levels in
narcolepsy without cataplexy
• Glial Fibrillary Acidic Protein maybe useful as a
biomarker in narcolepsy
• Narcolepsy maybe an autoimmune disease
• Neuroimaging has revealed structural and
biochemical brain abnormalities in narcolepsy
Conclusions
• Sodium oxybate produces significant reductions
in daytime sleepiness and cataplexy in narcolepsy
patients and is well tolerated
• A naturally occurring substance in CSF augments
inhibitory GABA signaling: ??new
pathophysiology of hypersomnia
• SPECT imaging can identify idiopathic RBD
patients at risk for progression to
neurodegenerative disease
• Ramelteon maybe a useful treatment for
secondary RBD