Huzursuz bacak sendromunda serebellar beyaz cevher kaybı psikiyatrik semptom düzeyiyle bağlantılıdır

Year 2025, Volume: 50 Issue: 1, 63 - 72, 31.03.2025

Olga Bayar Kapıcı , Yaşar Kapıcı , Ali Arık , Mehmet Şirik , Atilla Tekin , Dilek Örüm

https://doi.org/10.17826/cumj.1588490

Abstract

Amaç: Huzursuz bacak sendromunda (HBS), merkezi sinir sistemi ve periferik sinir sisteminin çok sayıda biyokimyasal yolak ve nörotransmitter aracılığıyla etkili olduğu olası değişiklikleri araştırmak amacıyla çeşitli görüntüleme yöntemleri uygulanmıştır. Bu çalışmada, HBS'li tedavi almamış hastaların serebellar hacimleri incelendi ve sağlıklı kontrol grubuyla karşılaştırıldı. Ek olarak, psikiyatrik semptom şiddeti ile serebellar beyaz cevher (BC) hacmi arasındaki ilişki incelendi.
Gereç ve Yöntem: Bu çalışmaya 44 HBS hastası ve yaş ve cinsiyete göre eşleştirilmiş 53 sağlıklı kontrol dahil edildi. HBS grubunun semptom şiddeti Uluslararası Huzursuz Bacak Sendromu Çalışma Grubu Derecelendirme Ölçeği (HBSDÖ) ve Belirti Kontrol Listesi-90-Revize (BKL-90-R) kullanılarak değerlendirildi. Beyin manyetik rezonans görüntüleme (MRG) hacimleri Volbrain yazılımı ile hesaplandı.
Bulgular: Hasta grubunda 24 erkek ve 20 kadın, sağlıklı kontrol grubunda 29 erkek ve 24 kadın vardı. Hasta grubunda ortalama yaş 36,23±5,43 yıl, sağlıklı kontrol grubunda ise 34,20±5,22 yıl olarak bulundu. Hasta grubunun sağ serebellum BC (1.10±0.26) ve sol serebellum BC (0.90±0.23) yüzdeleri sağlıklı kontrol grubundan (sağ serebellum BC=1.27±0.31; sol serebellum BC=1.03±0.26) anlamlı olarak düşüktü. Hasta grubunun sağ serebellum BC (15.41±4.03) ve sol serebellum BC (12.63±3.05) hacmi sağlıklı kontrol grubundan (sağ serebellum BC=17.49±4.12; sol serebellum BC=14.25±3.53) anlamlı olarak düşüktü. HBS grubunda serebellum BC hacim ve yüzdeleri ile BKL-90-R ve HBSDÖ skorları arasında anlamlı negatif korelasyon bulundu.
Sonuç: Bu çalışma, tedavi almamış HBS’nin önemli derecede serebellar BC hacim kaybı ile ilişkili olduğunu ve bunun erken yapısal beyin anormalliklerine işaret edebileceğini göstermektedir. Serebellar BC değişiklikleri ile psikiyatrik semptom şiddeti arasındaki korelasyon, HBS’deki nörolojik ve psikiyatrik etkileşimin daha ayrıntılı araştırılması gerektiğini vurgulamaktadır.

Keywords

Beyaz cevher, serebellum, huzursuz bacak sendromu, manyetik rezonans görüntüleme

Cerebellum white matter reductions in restless legs syndrome are associated with psychiatric symptom severity

Abstract

Purpose: Various imaging techniques were used to examine putative changes in restless legs syndrome (RLS), in which the central nervous system and peripheral nervous system play a role by using many biochemical pathways and neurotransmitters. In this study, the cerebellar volumes of drug-naive patients with RLS were examined and compared with healthy control groups. Additionally, the relationship between psychiatric symptom severity and cerebellar white matter (WM) volume was examined.
Materials and Methods: The current study included 44 RLS patients and 53 age- and gender-matched healthy controls. The symptom severity of RLS group was assessed by using the International Restless Legs Syndrome Study Group Rating Scale (RLSRS) and the Symptom Checklist-90-Revised (SCL-90-R). Brain magnetic resonance imaging (MRI) volumes were calculated with Volbrain software.
Results: The patient group consisted of 24 males and 20 females, while the control group included 29 males and 24 females. The mean age in the patient cohort was 36.23±5.43 years, compared to 34.20±5.22 years in the control cohort. The right cerebellum WM (1.10±0.26) and left cerebellum WM (0.90±0.23) percentages of the patient group were significantly lower than the healthy control group (right cerebellum WM=1.27±0.31; left cerebellum WM=1.03±0.26). The right cerebellum WM (15.41±4.03) and left cerebellum WM (12.63±3.05) volumes of the patient group were significantly lower than those of the healthy control group (right cerebellum WM=17.49±4.12; left cerebellum WM=14.25±3.53). In the RLS group, a significant negative correlation was found between cerebellum WM volumes and percentages and SCL-90-R and RLSRS scores.
Conclusion: This study demonstrates that drug-naive RLS is associated with significant cerebellar WM volume reductions, which may indicate early structural brain abnormalities. The observed correlation between cerebellar WM changes and psychiatric symptom severity highlights the need for further research into the neurological and psychiatric interplay in RLS.

Keywords

White matter, cerebellum, restless legs syndrome, magnetic resonance imaging

References

• Garcia-Malo C, Romero-Peralta S, Cano-Pumarega I. Restless legs syndrome - clinical features. Sleep Med Clin. 2021;16:233-47.
• Belke M, Heverhagen JT, Keil B, Rosenow F, Oertel WH, Stiasny-Kolster K et al. DTI and VBM reveal white matter changes without associated gray matter changes in patients with idiopathic restless legs syndrome. Brain Behav. 2015;5:e00327.
• Rist PM, Tzourio C, Elbaz A, Soumaré A, Dufouil C, Mazoyer B et al. Structural brain lesions and restless legs syndrome: a cross-sectional population-based study. BMJ Open. 2014;4:e005938.
• Provini F, Chiaro G. Neuroimaging in restless legs syndrome. Sleep Med Clin. 2015;10:215-26.
• Paulus W, Dowling P, Rijsman R, Stiasny-Kolster K, Trenkwalder C. Update of the pathophysiology of the restless-legs-syndrome. Mov Disord. 2007;22:431-9.
• Benarroch E. What is the involvement of the cerebellum during sleep? Neurology. 2023;100:572-7.
• DelRosso LM, Hoque R. The cerebellum and sleep. Neurol Clin. 2014;32:893-900.
• Chang Y, Chang HW, Song H, Ku J, Earley CJ, Allen RP et al. Gray matter alteration in patients with restless legs syndrome: a voxel-based morphometry study. Clin Imaging. 2015;39:20-5.
• Park KM, Kim KT, Lee DA, Cho YW. Redefining the role of the cerebellum in restless legs syndrome. Sleep Med. 2023;112:256-61.
• Lebel C, Deoni S. The development of brain white matter microstructure. Neuroimage. 2018;182:207-18.
• Filley CM, Fields RD. White matter and cognition: making the connection. J Neurophysiol. 2016;116:2093-104.
• Park HR, Kim HR, Oh S, Seong JK, Joo EY. White matter tract-specific alterations in patients with primary restless legs syndrome. Sci Rep. 2021;11:16116.
• Mackie S, Winkelman JW. Restless legs syndrome and psychiatric disorders. Sleep Med Clin. 2015;10:351-7.
• Winkelmann J, Prager M, Lieb R, Pfister H, Spiegel B, Wittchen HU et al. Depression and anxiety disorders in patients with restless legs syndrome. J Neurol. 2005;252:67-71.
• Kalaydjian A, Bienvenu OJ, Hening WA, Allen RP, Eaton WW, Lee HB. Restless legs syndrome and the five-factor model of personality: results from a community sample. Sleep Med. 2009;10:672-5.
• Scholz H, Benes H, Happe S, Bengel J, Kohnen R, Hornyak M. Psychological distress of patients suffering from restless legs syndrome: a cross-sectional study. Health Qual Life Outcomes. 2011;9:73.
• Godau J, Spinnler N, Wevers AK, Trenkwalder C, Berg D. Poor effect of guideline based treatment of restless legs syndrome in clinical practice. J Neurol Neurosurg Psychiatry. 2010;81:1390-5.
• Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4:101-19.
• Veale JF. Edinburgh Handedness Inventory - Short Form: a revised version based on confirmatory factor analysis. Laterality. 2014;19:164-77.
• Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003;4:121-32.
• Kılıç M. Validity and reliability of the Symptom Screening List (SCL-90-R). Journal of Psychological Counseling and Guidance. 1991;1:45-52.
• Zhang J, Zhang J, Sun H, Yang J, Ma Y, Chen K et al. Cerebellum drives functional dysfunctions in restless leg syndrome. Sleep Med. 2023;110:172-8.
• Song B, Zhu JC. A Narrative Review of cerebellar malfunctions and sleep disturbances. Front Neurosci. 2021;15:590619.
• D'Angelo E, Casali S. Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition. Front Neural Circuits. 2013;6:116.
• Depping MS, Schmitgen MM, Kubera KM, Wolf RC. Cerebellar contributions to major depression. Front Psychiatry. 2018;9:634.
• Doubliez A, Nio E, Senovilla-Sanz F, Spatharioti V, Apps R, Timmann D et al. The cerebellum and fear extinction: evidence from rodent and human studies. Front Syst Neurosci. 2023;17:1166166.
• Connor JR, Ponnuru P, Lee BY, Podskalny GD, Alam S, Allen RP et al. Postmortem and imaging based analyses reveal CNS decreased myelination in restless legs syndrome. Sleep Med. 2011;12:614-9.
• Earley CJ, Jones BC, Ferré S. Brain-iron deficiency models of restless legs syndrome. Exp Neurol. 2022;356:114158.
• Möller HE, Bossoni L, Connor JR, Crichton RR, Does MD, Ward RJ et al. Iron, myelin, and the brain: Neuroimaging meets neurobiology. Trends Neurosci. 2019;42:384-401.
• Ozdogar AT, Kalron A. Restless legs syndrome in people with multiple sclerosis: An updated systematic review and meta-analyses. Mult Scler Relat Disord. 2021;56:103275.
• Sparaco M, Lavorgna L, Bonavita S. Psychiatric disorders in multiple sclerosis. J Neurol. 2021;268:45-60.
• Rizzo G, Li X, Galantucci S, Filippi M, Cho YW. Brain imaging and networks in restless legs syndrome. Sleep Med. 2017;31:39-48.
• Wang Z, Li Z, Wang J, Gao J, Li Y. Exploring the pathophysiology of restless leg syndrome: focus on white matter structure and function. Postgrad Med J. 2024:qgae156.
• Tuovinen N, Stefani A, Mitterling T, Heidbreder A, Frauscher B, Gizewski ER et al. Functional connectivity and topology in patients with restless legs syndrome: a case-control resting-state functional magnetic resonance imaging study. Eur J Neurol. 2021;28:448-58.
• Sechi G, Agnetti V, Galistu P, Murgia B, Marrosu F, Puligheddu M et al. Restless legs syndrome and periodic limb movements after ischemic stroke in the right lenticulostriate region. Parkinsonism Relat Disord. 2008;14:157-60.
• Stefani A, Mitterling T, Heidbreder A, Steiger R, Kremser C, Frauscher B et al. Multimodal magnetic resonance ımaging reveals alterations of sensorimotor circuits in restless legs syndrome. Sleep. 2019;42:zsz171.
• Kamali A, Kramer LA, Frye RE, Butler IJ, Hasan KM. Diffusion tensor tractography of the human brain cortico-ponto-cerebellar pathways: a quantitative preliminary study. J Magn Reson Imaging. 2010;32:809-17.
• Dimitrova A, Kolb FP, Elles HG, Maschke M, Gerwig M, Gizewski E et al. Cerebellar activation during leg withdrawal reflex conditioning: an fMRI study. Clin Neurophysiol. 2004;115:849-57.
• Tully PJ, Kurth T, Elbaz A, Tzourio C. Convergence of psychiatric symptoms and restless legs syndrome: A cross-sectional study in an elderly French population. J Psychosom Res. 2020;128:109884.
• Kılınçarslan MG, Ocak Ö, Şahin EM. The impact of neuropsychiatric burden on Restless Legs Syndrome (RLS) disease severity. Sleep Med. 2024;126:82-7.
• Xu Y, Wen H, Li J, Yang J, Luo K, Chang L. The relationship between sleep disorders, anxiety, depression, and cognitive function with restless legs syndrome (RLS) in the elderly. Sleep Breath. 2022;26:1309-18