Diagnostic criteria for Kleine-Levin syndrome
Criteria A to E must be met
A. The patient experiences at least two recurrent episodes of excessive sleepiness and sleep duration, each persisting for two days to five weeks.
B. Episodes recur usually more than once a year and at least once every 18 months.
C. The patient has normal alertness, cognitive function, behavior, and mood between episodes.
D. The patient must demonstrate at least one of the following during episodes:
1. Cognitive dysfunction.
2. Altered perception.
3. Eating disorder (anorexia or hyperphagia).
4. Disinhibited behavior (such as hypersexuality).
E. The hypersomnolence and related symptoms are not better explained by another sleep disorder, other medical, neurologic, or psychiatric disorder (especially bipolar disorder), or use of drugs or medications.
Number of patients
Brain areas showing hypoperfusion or functional imaging abnormalities
Hong et al. 2006 
Thalamus (R&L), basal ganglia, temporal cortex (L), medial and dorsolateral frontal cortex (R&L), hypothalamus (L) show disease episode specific hypoperfusion
Huang et al. 2005 
Symptomatic n = 5
Asymptomatic n = 7
Thalamus, basal ganglia, temporal cortex, occipital cortex, frontal cortex more marked hypoperfusion when symptomatic. All symptomatic patients restudied when asymptomatic with normalisation of perfusion.
Huang et al. 2012 
All patients studied during symptomatic and asymptomatic periods
> 10% reduction when symptomatic in cerebellum, thalamus (L 66.7%, R 11.1%), basal ganglia (L 11.1%, R 22.2%)
Kas 2014 
Asymptomatic n = 41
Control n = 15
Symptomatic n = 11
Compared to controls asymptomatic patients had reduced perfusion in the hypothalamus, thalamus, caudate nucleus, and a number of cortical associative areas.
When symptomatic patients developed additional hypoperfusion in dorsomedial prefrontal cortex and right parieto-temporal Junction,
Landtblom et al. 2002 
Temporal cortex (L>R), frontal cortex (L>R), parietal cortex (R) hypoperfusion. Temporal hypoperfusion persisted when asymptomatic.
Landtblom et al. 2003 
4 (Including patient described in 2002)
Asymptomatic n = 4
2/4 Temporal and fronto-temporal hypoperfusion when asymptomatic
Lu et al. 2000 
Basal ganglia, fronto-temporal cortex, hypothalamus hypoperfusion when symptomatic. Pineal cystic lesion.
Portilla 2002 
Left mesiotemporal structures asymptomatic and symptomatic
Vigren et al. 2014 
Symptomatic n = 16
Asymptomatic n = 9
Temporal +/− fronto-temporal and frontal cortex hypoperfusion. No clear difference between symptomatic and asymptomatic studies
Takayanagi 2017 
Symptomatic: brain MRI indicated decreased diffusion in the splenium of the corpus callosum
Asymptomatic: the splenial lesion resolved completely
Billings 2011 
Reduced perfusion medial thalamus (L). Increased glutamine metabolites thalamus (L) and basal ganglia
Hoexter 2010 
Asymptomatic n = 1
Controls n = 3
TRODAT-1 SPECT: 14% lower striatal DAT in asymptomatic patient compared to controls
Dauvilliers 2014 
Asymptomatic and symptomatic n = 4
Controls n = 15
Symptomatic: higher metabolism in paracentral, precentral and postcentral areas, supplementary motor area, medial frontal gyrus, thalamus, and putamen and decreased metabolism in occipital and temporal gyri.
Asymptomatic: higher metabolism in frontal and temporal cortices, posterior cingulate and precuneus compared to healthy controls.
Haba-Rubio 2012 
Symptomatic n = 2 (One receiving lithium)
Asymptomatic n = 2
Images analysed as averaged images subtracted between symptomatic and asymptomatic periods. Average decrease in metabolic activity in symptomatic periods in hypothalamus, orbitofrontal and frontal parasagittal areas and bilateral posterior regions and a decrease in activity in anterior caudate nuclei, the cingulate and premotor cortex
Lo 2012 
Reduced in symptomatic phase in thalamus (R&L), hypothalamus (L), caudate nuclei (R&L), striatum (R&L)
Xie 2016 
Symptomatic: hypometabolism in the thalamus and hypothalamus. Mild reduction in cortex.
Thalamic/hypothalamic reduction normalised when asymptomatic.
Drouet 2017 
Bilateral activation in thalami, caudate nuclei, and lenticular nuclei during symptomatic phase