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On the Kleine-Levin Syndrome
Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [sv]

Populärvetenskaplig sammanfattning på svenska

Kleine-Levins syndrom är en sömnsjukdom som beskrevs av Willi Kleine 1925 och därefter utvecklades i fallbeskrivningar av Max Levin och McDonald Chritchley. De symptom som beskrevs var återkommande sömnperioder (periodisk hypersomnia), en tendens att äta mycket i samband med dessa perioder (hyperfagi) och ökad sexdrift i samband med perioderna (hypersexualitet) och, i senare beskrivningar, kognitiva och beteendemässiga störningar. Enligt tidigare beskrivningar var patienterna återställda mellan sömnperioderna. Dessa varade i dagar-veckor och återkom flera gånger årligen. Sjukdomen debuterade vanligtvis i tonåren och beskrevs gå över efter åtta år.

d avhandling beskriver diagnosens utveckling över tid och sätter forskningen i sitt teoretiska sammanhang. Med det senare menas att det diskuteras hur forskningen förhåller sig till en diagnos som förändras över tid och där olika läkare kan ha olika kunskap kring och förhållningssätt till diagnosen.

De studier som ingår i avhandlingen har undersökt flera olika aspekter av Kleine-Levins syndrom. Den första studien undersökte arbetsminnet hos patienterna och kunde påvisa att det var nedsatt jämfört med friska försökspersoner, även mellan sömnperioderna, något som inte var visat systematiskt tidigare. Dessutom sågsandra aktiveringsmönster i hjärnan när patienterna försökte klara arbetsminnesuppgiften, jämfört med aktiveringsmönstren hos friska försökspersoner. Hos hälften av patienterna sågs dessutom avvikande blodflöde i delar av hjärnan även när ingen särskild arbetsuppgift utfördes. Detta sågs även hos patienter som tillfrisknat.

Då det funnits hypoteser i annan forsking att sjukdomen kan ha ett genetiskt/ärftligt inslag undersöktes huruvida patienterna hade en gen som tidigare har kopplats till sjukdomen. I den grupp av patienter som undersöktes i avhandlingens sista artikel kunde dock ingen sådan koppling ses.

Slutsatsen av forskningsresultaten är att (1) patienter med Kleine-Levins syndrom har en störning av arbetsminnet som verkar konstant. (2) De uppvisar andra hjärnaktiveringsmönster än friska personer som gör samma arbetsminnesuppgift. (3) Hälften av patienterna har ett avvikande blodflödesmönster även i vila och efter tillfrisknande. (4) En eventuell ärftlig komponent kan inte påvisas avseende de undersökta generna.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2017. , 52 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1588
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-141282ISBN: 9789176854464 (print)OAI: oai:DiVA.org:liu-141282DiVA: diva2:1145371
Public defence
2017-09-30, Digitalissalen, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2017-09-28 Created: 2017-09-28 Last updated: 2017-10-04Bibliographically approved
List of papers
1. Working Memory in 8 Kleine-Levin Syndrome Patients: An fMRI Study
Open this publication in new window or tab >>Working Memory in 8 Kleine-Levin Syndrome Patients: An fMRI Study
2009 (English)In: SLEEP, ISSN 0161-8105, Vol. 32, no 5, 681-688 p.Article in journal (Refereed) Published
Abstract [en]

Study Objectives: The objectives of this study were to investigate possible neuropathology behind the Kleine-Levin Syndrome (KLS), a severe form of hypersomnia with onset during adolescence.

Design: Functional magnetic resonance imaging (fMRI) applying a verbal working memory task was used in conjunction with a paper-and-pencil version of the task. Participants: Eight patients with KLS and 12 healthy volunteers participated in the study.

Results: The results revealed a pattern of increased thalamic activity and reduced frontal activity (involving the anterior cingulate and adjacent prefrontal cortex) while performing a reading span task.

Discussion: This finding may explain the clinical symptoms observed in KLS, in that the thalamus is known to be involved in the control of sleep. Given the increasing access to fMRI, this investigation may aid clinicians in the diagnosis of patients suffering from severe forms of hypersomnia.

Keyword
fMRI, Kleine-Levin Syndrome, working memory, hypersomnia, thalamus
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18262 (URN)000265541900015 ()
Available from: 2009-05-16 Created: 2009-05-15 Last updated: 2017-09-28
2. Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome
Open this publication in new window or tab >>Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome
Show others...
2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 2Article in journal (Refereed) Published
Abstract [en]

Background

Kleine Levin Syndrome (KLS) is a rare disorder of periodic hypersomnia and behavioural disturbances in young individuals. It has previously been shown to be associated with disturbances of working memory (WM), which, in turn, was associated with higher activation of the thalamus with increasing WM load, demonstrated with functional magnetic resonance imaging (fMRI). In this study we aimed to further elucidate how these findings are related to the metabolism of the thalamus.

Methods

fMRI and magnetic resonance spectroscopy were applied while performing a WM task. Standard metabolites were examined: n-acetylaspartate (NAA), myo-inositol, choline, creatine and glutamate-glutamine. Fourteen KLS-patients and 15 healthy controls participated in the study. The patients with active disease were examined in asymptomatic periods.

Results

There was a statistically significant negative correlation between thalamic fMRI-activation and thalamic NAA, i.e., high fMRI-activation corresponded to low NAA-levels. This correlation was not seen in healthy controls. Thalamic levels of NAA in patients and controls showed no significant differences between the groups. None of the other metabolites showed any co-variation with fMRI-activiation.

Conclusion

This study shows negative correlation between NAA-levels and fMRI-activity in the left thalamus of KLS-patients while performing a WM task. This correlation could not be found in healthy control subjects, primarily interpreted as an effect of increased effort in the patient group upon performing the task. It might indicate a disturbance in the neuronal networks responsible for WM in KLS patients, resulting in higher effort at lower WM load, compared with healthy subjects. The general relationship between NAA and BOLD-signal is also discussed in the article.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85927 (URN)10.1371/journal.pone.0056279 (DOI)000316849500009 ()
Available from: 2012-12-03 Created: 2012-12-03 Last updated: 2017-09-28Bibliographically approved
3. SPECT in the Kleine–Levin syndrome, a possible diagnostic and prognostic aid?
Open this publication in new window or tab >>SPECT in the Kleine–Levin syndrome, a possible diagnostic and prognostic aid?
2014 (English)In: Frontiers in Neurology, ISSN 1664-2295, Vol. 5, no 178Article in journal (Refereed) Published
Abstract [en]

Introduction: Kleine–Levin syndrome (KLS) is a rare syndrome of periodic hypersomnia and behavioral and cognitive symptoms based on clinical criteria. In the setting of differential diagnosis of hypersomnia disorders, an objective diagnostic aid is desirable. A promising modality is single photon emission computed tomography (SPECT). As intraepisodal investigations are difficult to perform, an interepisodal investigation would be very helpful. Another aim of the study was to correlate SPECT findings to prognosis.

Methods and Materials: Twenty-four KLS-patients were categorized as severe or non-severe based on clinical characteristics. The clinical characteristics were analyzed in relation to SPECT-examinations performed between hypersomnia periods (interepisodal) or after remission, as a clinical routine investigation.

Results: Forty-eight percent of the KLS-patients have hypoperfusion in the temporal or fronto-temporal regions. In patients that have undergone remission, 56% show that pattern. There were no specific findings related to prognosis.

Discussion/Conclusion: SPECT might be a diagnostic aid, in a setting of hypersomnia experience. With a sensitivity of 48%, interepisodal SPECT alone cannot be used for diagnosing KLS.

Place, publisher, year, edition, pages
Switzerland: Frontiers Research Foundation, 2014
Keyword
single photon emission tomography, sleep disorders, brain perfusion, Kleine–Levin syndrome, sleep
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-110858 (URN)10.3389/fneur.2014.00178 (DOI)25295028 (PubMedID)
Available from: 2014-09-24 Created: 2014-09-24 Last updated: 2017-09-28Bibliographically approved

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