Altered Somatosensory Neurovascular Response in Patients with Becker Muscular Dystrophy

Overview

Journal Brain Behav

Specialty Psychology

Date 2018 Aug 15

PMID 30106246

Citations 1

Authors

Ulrich Lindberg

Christina Kruuse

Nanna Witting

Stine Lundgaard Jorgensen

John Vissing

Egill Rostrup

Henrik Bo Wiberg Larsson

Affiliations

Soon will be listed here.

Abstract

Introduction: Patients with dystrophinopathies show low levels of neuronal nitric oxide synthase (nNOS), due to reduced or absent dystrophin expression, as nNOS is attached to the dystrophin-associated protein complex. Deficient nNOS function leads to functional ischemia during muscle activity. Dystrophin-like proteins with nNOS attached have also been identified in the brain. This suggests that a mechanism of cerebral functional ischemia with attenuation of normal activation-related vascular response may cause changes in brain function.

Methods: The aim of this study was to investigate whether the brain response of patients with Becker muscular dystrophy (BMD) is dysfunctional compared to that of healthy controls. To investigate a potential change in brain activation response in patients with BMD, median nerve somatosensory evoked stimulation, with stimulation durations of 2, 4, and 10 s, was performed while recording electroencephalography and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging.

Results: Results in 14 male patients with BMD (36.2 ± 9.9 years) were compared with those of 10 healthy controls (34.4 ± 10.9 years). Compared to controls, the patients with BMD showed sustained cortical electrical activity and a significant smaller BOLD activation in contralateral primary somatosensory cortex and bilaterally in secondary somatosensory cortex. In addition, significant activation differences were found after long duration (10 s) stimuli in thalamus.

Conclusion: An altered neurovascular response in patients with BMD may increase our understanding of neurovascular coupling and the pathogenesis related to dystrophinopathy and nNOS.

Citing Articles

Altered somatosensory neurovascular response in patients with Becker muscular dystrophy.

Lindberg U, Kruuse C, Witting N, Jorgensen S, Vissing J, Rostrup E Brain Behav. 2018; 8(6):e00985.

PMID: 30106246 PMC: 5991560. DOI: 10.1002/brb3.985.

References

Bushby K, Finkel R, Birnkrant D, Case L, Clemens P, Cripe L . Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2009; 9(1):77-93. DOI: 10.1016/S1474-4422(09)70271-6. View

Bushby K, Goodship J, Nicholson L, Johnson M, Haggerty I, Gardner-Medwin D . Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 1993; 3(1):57-64. DOI: 10.1016/0960-8966(93)90042-i. View

Young H, Barton B, Waisbren S, Portales Dale L, Ryan M, Webster R . Cognitive and psychological profile of males with Becker muscular dystrophy. J Child Neurol. 2007; 23(2):155-62. DOI: 10.1177/0883073807307975. View

Witting N, Kruuse C, Nyhuus B, Prahm K, Citirak G, Lundgaard S . Effect of sildenafil on skeletal and cardiac muscle in Becker muscular dystrophy. Ann Neurol. 2014; 76(4):550-7. DOI: 10.1002/ana.24216. View

Attwell D, Buchan A, Charpak S, Lauritzen M, MacVicar B, Newman E . Glial and neuronal control of brain blood flow. Nature. 2010; 468(7321):232-43. PMC: 3206737. DOI: 10.1038/nature09613. View

Li B, Freeman R . High-resolution neurometabolic coupling in the lateral geniculate nucleus. J Neurosci. 2007; 27(38):10223-9. PMC: 6672682. DOI: 10.1523/JNEUROSCI.1505-07.2007. View

Doorenweerd N, Straathof C, Dumas E, Spitali P, Ginjaar I, Wokke B . Reduced cerebral gray matter and altered white matter in boys with Duchenne muscular dystrophy. Ann Neurol. 2014; 76(3):403-11. DOI: 10.1002/ana.24222. View

Lv S, Zou Q, Cui J, Zhao N, Hu J, Long X . Decreased gray matter concentration and local synchronization of spontaneous activity in the motor cortex in Duchenne muscular dystrophy. AJNR Am J Neuroradiol. 2011; 32(11):2196-200. PMC: 7964380. DOI: 10.3174/ajnr.A2718. View

Yayla V, Oge A, Deymeer F, Gurvit H, Akca-Kalem S, Parman Y . Cortical excitability in Duchenne muscular dystrophy. Clin Neurophysiol. 2007; 119(2):459-65. DOI: 10.1016/j.clinph.2007.09.125. View

10.

Logothetis N, Pauls J, Augath M, Trinath T, Oeltermann A . Neurophysiological investigation of the basis of the fMRI signal. Nature. 2001; 412(6843):150-7. DOI: 10.1038/35084005. View

11.

Lee J, Pfund Z, Juhasz C, Behen M, Muzik O, Chugani D . Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a pet study. Muscle Nerve. 2002; 26(4):506-12. DOI: 10.1002/mus.10238. View

12.

Anthony K, Cirak S, Torelli S, Tasca G, Feng L, Arechavala-Gomeza V . Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials. Brain. 2011; 134(Pt 12):3547-59. PMC: 3235564. DOI: 10.1093/brain/awr291. View

13.

Backes W, Mess W, van Kranen-Mastenbroek V, Reulen J . Somatosensory cortex responses to median nerve stimulation: fMRI effects of current amplitude and selective attention. Clin Neurophysiol. 2000; 111(10):1738-44. DOI: 10.1016/s1388-2457(00)00420-x. View

14.

Birn R, Bandettini P . The effect of stimulus duty cycle and "off" duration on BOLD response linearity. Neuroimage. 2005; 27(1):70-82. DOI: 10.1016/j.neuroimage.2005.03.040. View

15.

Buxton R, Uludag K, Dubowitz D, Liu T . Modeling the hemodynamic response to brain activation. Neuroimage. 2004; 23 Suppl 1:S220-33. DOI: 10.1016/j.neuroimage.2004.07.013. View

16.

Yeh H, Chen Y, Chen W, Wang H, Chiu H, Lien L . Perfusion status of the stroke-like lesion at the hyperacute stage in MELAS. Brain Dev. 2012; 35(2):158-64. DOI: 10.1016/j.braindev.2012.03.017. View

17.

Lindberg U, Witting N, Jorgensen S, Vissing J, Rostrup E, Larsson H . Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy. Neurotherapeutics. 2016; 14(1):182-190. PMC: 5233618. DOI: 10.1007/s13311-016-0467-x. View

18.

Emery A . The muscular dystrophies. Lancet. 2002; 359(9307):687-95. DOI: 10.1016/S0140-6736(02)07815-7. View

19.

Martin E, Barresi R, Byrne B, Tsimerinov E, Scott B, Walker A . Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy. Sci Transl Med. 2012; 4(162):162ra155. PMC: 3935430. DOI: 10.1126/scitranslmed.3004327. View

20.

Melo M, Lauriano V, Gentil V, Eggers S, Del Bianco S, Gimenez P . Becker and limb-girdle muscular dystrophies: a psychiatric and intellectual level comparative study. Am J Med Genet. 1995; 60(1):33-8. DOI: 10.1002/ajmg.1320600107. View