Table 3.

The main findings of each study.

Author, Year, Country	Imaging	Hypometabolism/Less Activity/Hypoperfusion	Hypermetabolism/Greater Activity/Hyperfusion
Huang et al., 2005, Taiwan [13]	SPECT with 925 MBq (25 mCi) of technetium-99 m ethyl cysteinate dimer (Tc-99 m ECD)	All the patients had hypoperfusion of both thalami during the symptomatic period. In the symptomatic and asymptomatic period, there was hypoperfusion in the temporal lobe, frontal lobe, and basal ganglia.
Engstrom et al., 2009, England [23]	fMRI—BOLD response 1.5 T body scanner—in the asymptomatic period.	Reduced frontal activity in the anterior cingulate and prefrontal cortex while performing a reading span task.	Increased thalamic activity while performing reading and span tasks.
Vigren et al., 2013, Sweden [15]	fMRI 1.5 T in the asymptomatic period	There was a negative correlation between activity in the thalamus and N.A.A. levels.	Decreased N.A.A. levels when there was high activity in the left thalamus. High activity in the left thalamus while performing W.M. task. Larger activation in bilateral parietal cortex compared to controls.
Engstrom et al., England, 2013 [16]	fMRI-BOLD- 1.5 T body scanner	Salient network: decreased activation of the left insular cortex (A.I.C.).	Salient network: Increased activation of the left thalamus, more activation of the right anterior cingulate cortex (A.C.C.) Executive network, K.L.S. patients had increased activation in the left dorsolateral prefrontal cortex (DLPFC) and increased left hemisphere activation in the region of the posterior parietal cortex (P.P.C.) tested.
Kas et al., 2014, France [18]	SPECT Tc-99 m ECD- in the symptomatic and asymptomatic phase	Compared to control, K.L.S. patients had hypoperfusion in the hypothalamus, the thalamus, mainly the right posterior part, the caudate nucleus, and cortical associative areas including the anterior cingulate, the orbitofrontal, and the right superior temporal cortices during the asymptomatic period, while hypoperfusion in the right dorsomedial prefrontal cortex and the right parietal-temporal junction was noted during the symptomatic period.	Depersonalization/derealization- temporal-occipital relation, r = −0.79.5, p = 0.01) in the asymtomatic period. Depersonalization/derealization- temporal-occipital relation, r = −0.45, p = 0.05) in the asymtomatic period. The perfusion during the asymptomatic period in the right parieto-temporal r = 0.53, p = 0.05 decreased with each episode.
Vigren et al., 2014, Sweden [17]	SPECT with 650 MBq 99 m-Tc-HMPAO	A total of 48% have abnormal perfusion. Severe patients: 5/13 had temporal and/or frontal hypoperfusion. Non-severe patients: 7/12 had temporal and/or frontal hypoperfusion. Patients with active disease: 7/16 had temporal and/or frontal hypoperfusion. Patients with remission: 5/9 had temporal and/or frontal hypoperfusion.
Dudoignon et al., 2021, France [19]	FDG-PET FDG-PET/CT using Gemini Dual PET/CT 30 min post- injection of 2 MBq/kg FDG -in the asymptomatic period	A total of 70% of 138 had hypometabolism in the left temporo-occipital junction A total of 63% hypometabolism bilaterally posterior associative cortex A total of 50% have the entire homolateral, bilateral posterior associative cortex, and hippocampus.	Prefrontal, dorsolateral cortex was noted in 34.8% of patients, more often on the right than the left side.
Engstrom 2014 [22]	fMRI 1.5 T- in the asymptomatic period in the asymptomatic state	K.L.S. patients illustrated reduced activation in the medial frontal and anterior cingulate cortices during (p < 0.001).	Increased thalamic activation in 61.4% of patients.
Engstrom et al., 2016, England [20]	fMRI/SPECT in asymptomatic patients	Patients with Kleine–Levin syndrome showed less activity in between the pons and the frontal eye fields as compared to controls at the asymptomatic period (p = 0.041).
Dauvillers et al., 2014, France [21]	PET with F-fluorodeoxy glucose (F-FDG)	K.L.S. patients exhibited hypometabolism in occipital and temporal gyri and in the inferior parietal areas compared to control during the symptomatic phase.	As compared to healthy individuals, the 4 K.L.S. patients demonstrated hypermetabolism in paracentral, precentral, postcentral areas, medial frontal gyrus, thalamus, and putamen during symptomatic periods. In the asymptomatic phase, the 4 K.L.S. patients revealed having more hypermetabolism in frontal and temporal cortices, posterior cingulate, and precuneus as compared to controls.