Bassetti, C.

Boesiger, P.

Poryazova, R.

Schnepf, B.

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J Neurol (2007) 254:1445–1446DOI 10.1007/s00415-007-0531-xRositsa PoryazovaBetina SchnepfPeter BoesigerClaudio L. BassettiMagnetic resonancespectroscopy in a patient with Kleine-LevinsyndromeReceived: 18 September 2006Received in revised form:29 December 2006Accepted: 16 January 2007Published online: 15 October 2007Sirs: Kleine-Levin syndrome (KLS)is a rare recurrent hypersomnia as-sociated with behavioural, cogni-tive, eating and sexual disturbances[1, 2]. A recent SPECT study in 7patients with (KLS) showed de-creased thalamic perfusion duringthe hypersomnolent attacks [3].These findings were later con-firmed in a case report by Honget al. [4]. Proton magnetic reso-nance spectroscopy (1H MRS) is anoninvasive method of obtainingmetabolic information. By meansof MRS, different compounds canbe measured including N-acetylas-partate (NAA), a marker of neu-ronal integrity and glutamate-glut-amine (Glu-Gln), which plays animportant role in excitatory neuro-transmission and mitochondrialmetabolism [5].We present a 19-year-old patientwith idiopathic, classical KLS. Overa 4-year period he suffered 19stereotypical hypersomnolentepisodes. The attacks were alwayspreceded or accompanied by feverup to 39 °C, sore throat or stomachpain. At the beginning of theepisodes mood depression was ob-served, the patient was melan-cholic, sad and withdrew socially.Sleep behaviour reached 20hours/day, interrupted by compul-sive eating, 7–8/days without anyspecific food preference resultingin a weight gain of approximately 5kg/attack. Sexual disinhibition withmasturbation, irritability, aggres-siveness, cognitive and concentra-tion disturbances were frequent.The attacks usually ended with in-somnia lasting 2–3 days and a sub-sequent gradual improvement ofemotional state and cognition. Thepatient described this phase asawakening from a dream and haddifficulty recalling the events thathad occurred during the attack. Inthe first year before treatment 12attacks were observed. Under ther-apy with lithium 30 mg/day andvalproic acid 2000 mg/day a re-markable reduction in frequencyand severity of the episodes (7 at-tacks over a period of 2.5 years)was noted. The duration of the hy-persomnolent episodes remainedunchanged, 10 days on average.Hypocretin-1 in the cere-brospinal fluid during an attackwas in the normal range, 530 pg/ml.The patient underwent 1H MRSin an asymptomatic period and amonth later during a typicalepisode. Because of presumed hy-pothalamic [6] or thalamic [3, 4]dysfunction in KLS we chose threeregions of interest: hypothalamusand both thalami. MRS was per-formed on a Philips Achieva 3.0 Tscanner. Single-voxel proton MRspectra, voxels of 17 x 14 x 15 mmin both thalami (3.57 cm3) and of10  10  10 mm (1 cm3) in the hy-pothalamus, were acquired andprocessed to determine metaboliteconcentration ratios. A remarkablechange between the two examina-tions was observed in the concen-tration ratios of NAA-NAAG, (totalNAA)/Cr and Glu-Gln/Cr (Fig. 1).During the attack lower (totalNAA)/Cr ratios in the right(–25.7 %) and left (–13.2 %) thal-ami were observed. In the hypo-thalamus the (total NAA)/Cr ratiowas slightly higher in the secondscan during the hypersomnolentattack. The Glu-Gln/Cr ratio washigher during the attack – in boththe right (59.8 %) and left (52.3 %)thalamus. In hypothalamus a reli-able value for Glu-Gln/Cr ratio wasobtained only during the secondscan and it was similar to the val-ues in both thalami.Different values for intraindi-vidual metabolite ratio, variabilityand reproducibility of the resultsare reported in the literature, de-pending on the technical parame-ters of the acquisition and on theregion of interest. For example anintraindividual temporal corticalvariation up to 12 % was observedfor (total NAA)/Cr and up to 29 %for Glu-Gln/Cr on a 3T scanner [7].The decrease in the (total NAA)/Crconcentration ratio in both thalamiduring the hypersomnolentepisode in our patient exceeds thenormal range of the intraindivid-ual variability at 3T. Our findingsupports the hypothesis of a thala-mic dysfunction in KLS, recentlysuggested by other authors [3, 4].This hypothesis is indirectly sup-ported also by the observation ofKLS-similar symptoms (reducedalertness, impaired sleep and be-havioural changes) following para-median thalamic strokes [8]. Theobserved high Glu-Gln/Cr concen-tration ratio in all regions of inter-est during the episode points to ad-ditional, global metabolic changesin the brain. Glutamate is a pri-mary excitatory neurotransmitter.Decreased NAA/Cr and increasedLETTER TO THE EDITORSJON 2531R. Poryazova · Prof. Dr. C. L. Bassetti ()Department of NeurologyUniversity Hospital of ZurichFrauenklinikstrasse 26CH-8091 Zurich, SwitzerlandTel.: +41-12555503Fax: +41-12554649E-Mail: claudio.bassetti@usz.chB. Schnepf · P. BoesigerInstitute for Biomedical EngineeringUniversity and ETH ZurichGloriastrasse 358092 Zurich, Switzerland1446Glu + Gln/Cr ratios have been re-ported in focal epilepsies in areaswithout structural abnormalities,linked to ictal and interictal epilep-tiform activities [9] as well as inthe thalamus of patients with idio-pathic generalised epilepsy, possi-bly related to excitotoxicity [10].The neuronal pathophysiology ofepilepsy is however different fromthat of KLS. The remarkable in-crease in Glu-Gln/Cr in our patientmay account for a depolarisationblock and post-excitatory suppres-sion of various thalamic nuclei. Aconsequence of the large corticalprojections of the thalamus may bethat it leads to a widespread corti-cal suppression. As we report a sin-gle case, a confirmation of our hy-pothesis is needed.■ Acknowledgments Dr. Pierluigi Pedrazzi,Hospital “San Giovanni” Bellinzona whokindly referred the patient.References1. Bassetti C, Billiard M, Mignot E, ArnulfI (2006) Kleine-Levin syndrome andother recurrent hypersomnia. In: Bas-setti C, Billiard M, Mignot E (eds) Nar-colepsy and hypersomnia. DekkerPublishing, NYC, NY, pp 89–952. Arnulf I, Zeitzer JM, File J, Farber N,Mignot E (2005) Kleine-Levin syn-drome: a systematic review of 186cases in the literature. Brain 128:2763–27763. Huang YS, Guilleminault C, Kao PF,Liu FY (2005) SPECT findings in theKleine-Levin syndrome. Sleep 28:955–9604. Hong SB, Joo EY, Tae WS, Lee J, Han SJ,Lee HW (2006) Episodic diencephalichypoperfusion in Kleine-Levin syn-drome. Sleep 29:1091–10935. Rubaek E, Ross D (1999) Magneticresonance spectroscopy diagnosis ofneurological diseases. Dekker Publish-ing, NYC, NY6. Malhotra S, Das MK, Gupta N, Mu-ralidharan R (1997) A clinical study ofKleine-Levin syndrome with evidencefor hypothalamic-pituitary axis dys-function. Biol Psychiatry 42:299–3017. Wellard RM, Briellmann RS, JenningsC, Jackson GD (2005) Physiologicvariability of single-voxel proton MRspectroscopic measurements at 3T.Am J Neuroradiol 26:585–5908. Bassetti C, Mathis J, Gugger M, LovbladKO, Hess CW (1996) Hypersomniafollowing paramedian thalamic stroke:a report of 12 patients. Ann Neurol39:471–4809. Guye M, Ranjeva JP, Le Fur Y, Bar-tolomei F, Confort-Gouny S, Regis J,Chauvel P, Cozzone PJ (2005) 1H-MRSimaging in intractable frontal lobeepilepsies characterized by depthelectrode recording. Neuroimage26:1174–118310. Helms G, Ciumas C, Kyaga S, Savic I(2006) Increased thalamus levels ofglutamate and glutamine (Glx) inpatients with idiopathic generalizedepilepsy. J Neurol Neurosurg Psychia-try 77:489–494Fig. 1(total) NAA/Cr (total) NAA/Cr (total) NAA/CrGlu + Gln/Cr Glu + Gln/Cr Glu + Gln/CrRight thalamus Hypothalamus left thalamusfree of symptoms hypersomnolent attack1.320.981.472.350.961.242.151.291.121.362.06a c eb d f

Magnetic resonance spectroscopy in a patient with Kleine-Levin syndrome

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Magnetic resonance spectroscopy in a patient with Kleine-Levin syndrome

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