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01-12-2013

Migraineurs Without Aura Show Microstructural Abnormalities in the Cerebellum and Frontal Lobe

Authors: C. Granziera, D. Romascano, A. Daducci, A. Roche, M. Vincent, G. Krueger, N. Hadjikhani

Published in: The Cerebellum | Issue 6/2013

Abstract

The involvement of the cerebellum in migraine pathophysiology is not well understood. We used a biparametric approach at high-field MRI (3 T) to assess the structural integrity of the cerebellum in 15 migraineurs with aura (MWA), 23 migraineurs without aura (MWoA), and 20 healthy controls (HC). High-resolution T1 relaxation maps were acquired together with magnetization transfer images in order to probe microstructural and myelin integrity. Clusterwise analysis was performed on T1 and magnetization transfer ratio (MTR) maps of the cerebellum of MWA, MWoA, and HC using an ANOVA and a non-parametric clusterwise permutation F test, with age and gender as covariates and correction for familywise error rate. In addition, mean MTR and T1 in frontal regions known to be highly connected to the cerebellum were computed. Clusterwise comparison among groups showed a cluster of lower MTR in the right Crus I of MWoA patients vs. HC and MWA subjects (p = 0.04). Univariate and bivariate analysis on T1 and MTR contrasts showed that MWoA patients had longer T1 and lower MTR in the right and left pars orbitalis compared to MWA (p < 0.01 and 0.05, respectively), but no differences were found with HC. Lower MTR and longer T1 point at a loss of macromolecules and/or micro-edema in Crus I and pars orbitalis in MWoA patients vs. HC and vs. MWA. The pathophysiological implications of these findings are discussed in light of recent literature.

Lipton RB, Stewart WF. Migraine headaches: epidemiology and comorbidity. Clin Neurosci. 1998;5(1):2–9.PubMed

Roncolato M et al. An epidemiological study to assess migraine prevalence in a sample of Italian population presenting to their GPs. Eur Neurol. 2000;43(2):102–6.PubMedCrossRef

Warshaw LJ, Burton WN. Cutting the costs of migraine: role of the employee health unit. J Occup Environ Med. 1998;40(11):943–53.PubMedCrossRef

Stewart WF et al. Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors. JAMA. 1992;267(1):64–9.PubMedCrossRef

Vincent M, Hadjikhani N. The cerebellum and migraine. Headache. 2007;47(6):820–33.PubMedCrossRef

Sandor PS et al. Subclinical cerebellar impairment in the common types of migraine: a three-dimensional analysis of reaching movements. Ann Neurol. 2001;49(5):668–72.PubMedCrossRef

Wieser T et al. Persistent ocular motor disturbances in migraine without aura. Neurol Sci. 2004;25(1):8–12.PubMedCrossRef

Harno H et al. Subclinical vestibulocerebellar dysfunction in migraine with and without aura. Neurology. 2003;61(12):1748–52.PubMedCrossRef

Rossi C et al. Balance disorders in headache patients: evaluation by computerized static stabilometry. Acta Neurol Scand. 2005;111(6):407–13.PubMedCrossRef

10.

Ishizaki K et al. Static stabilometry in patients with migraine and tension-type headache during a headache-free period. Psychiatry Clin Neurosci. 2002;56(1):85–90.PubMedCrossRef

11.

Arkink EB et al. Cerebral perfusion changes in migraineurs: a voxelwise comparison of interictal dynamic susceptibility contrast MRI measurements. Cephalalgia. 2012;32(4):279–88.PubMedCrossRef

12.

Crawford JS, Konkol RJ. Familial hemiplegic migraine with crossed cerebellar diaschisis and unilateral meningeal enhancement. Headache. 1997;37(9):590–3.PubMedCrossRef

13.

Lee TG et al. Reversible cerebellar perfusion in familial hemiplegic migraine. Lancet. 1996;348(9038):1383.PubMedCrossRef

14.

Kruit MC et al. Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: the population-based MRI CAMERA study. Cephalalgia. 2010;30(2):129–36.PubMed

15.

van den Maagdenberg AM et al. A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron. 2004;41(5):701–10.PubMedCrossRef

16.

Hadjikhani N et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci USA. 2001;98(8):4687–92.PubMedCrossRef

17.

Woods RP, Iacoboni M, Mazziotta JC. Brief report: bilateral spreading cerebral hypoperfusion during spontaneous migraine headache. N Engl J Med. 1994;331(25):1689–92.PubMedCrossRef

18.

Vincent MB, Hadjikhani N. Migraine aura and related phenomena: beyond scotomata and scintillations. Cephalalgia. 2007;27(12):1368–77.PubMedCrossRef

19.

Gold L, Lauritzen M. Neuronal deactivation explains decreased cerebellar blood flow in response to focal cerebral ischemia or suppressed neocortical function. Proc Natl Acad Sci USA. 2002;99(11):7699–704.PubMedCrossRef

20.

Moskowitz MA, Macfarlane R. Neurovascular and molecular mechanisms in migraine headaches. Cerebrovasc Brain Metab Rev. 1993;5(3):159–77.PubMed

21.

Jacquin MF et al. Trigeminal primary afferents project bilaterally to dorsal horn and ipsilaterally to cerebellum, reticular formation, and cuneate, solitary, supratrigeminal and vagal nuclei. Brain Res. 1982;246(2):285–91.PubMedCrossRef

22.

Huerta MF, Frankfurter A, Harting JK. Studies of the principal sensory and spinal trigeminal nuclei of the rat: projections to the superior colliculus, inferior olive, and cerebellum. J Comp Neurol. 1983;220(2):147–67.PubMedCrossRef

23.

Kruit MC et al. Brain stem and cerebellar hyperintense lesions in migraine. Stroke. 2006;37(4):1109–12.PubMedCrossRef

24.

Jin C et al. Structural and functional abnormalities in migraine patients without aura. NMR Biomed. 2013;26(1):58–64.PubMedCrossRef

25.

International Headache Conference (IHC). The international classification of headache disorders: 2nd edition. Cephalalgia. 2004;24 suppl 1:9–160.

26.

Klein S et al. elastix: a toolbox for intensity-based medical image registration. IEEE Trans Med Imaging. 2010;29(1):196–205.PubMedCrossRef

27.

Diedrichsen J et al. A probabilistic MR atlas of the human cerebellum. NeuroImage. 2009;46(1):39–46.PubMedCrossRef

28.

Diedrichsen J. A spatially unbiased atlas template of the human cerebellum. NeuroImage. 2006;33(1):127–38.PubMedCrossRef

29.

Diedrichsen J et al. Imaging the deep cerebellar nuclei: a probabilistic atlas and normalization procedure. NeuroImage. 2011;54(3):1786–94.PubMedCrossRef

30.

Bullmore ET et al. Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain. IEEE Trans Med Imaging. 1999;18(1):32–42.PubMedCrossRef

31.

Kober T et al. MP2RAGE multiple sclerosis magnetic resonance imaging at 3 T. Investig Radiol. 2012;47(6):346–52.CrossRef

32.

Krienen FM, Buckner RL. Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity. Cereb Cortex. 2009;19(10):2485–97.PubMedCrossRef

33.

Roche A et al. On the convergence of EM-like algorithms for image segmentation using Markov random fields. Med Image Anal. 2011;15(6):830–9.PubMedCrossRef

34.

Henkelman RM, Stanisz GJ, Graham SJ. Magnetization transfer in MRI: a review. NMR Biomed. 2001;14(2):57–64.PubMedCrossRef

35.

Deoni SC. Quantitative relaxometry of the brain. Top Magn Reson Imaging. 2010;21(2):101–13.PubMedCrossRef

36.

Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex. 2010;46(7):831–44.PubMedCrossRef

37.

Moulton EA et al. Aversion-related circuitry in the cerebellum: responses to noxious heat and unpleasant images. J Neurosci. 2011;31(10):3795–804.PubMedCrossRef

38.

Baumann O, Mattingley JB. Functional topography of primary emotion processing in the human cerebellum. NeuroImage. 2012;61(4):805–11.PubMedCrossRef

39.

Kringelbach ML, Rolls ET. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog Neurobiol. 2004;72(5):341–72.PubMedCrossRef

40.

Anders S et al. Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele. Brain. 2012;135(Pt 4):1128–40.PubMedCrossRef

41.

Sprengelmeyer R et al. Neural structures associated with recognition of facial expressions of basic emotions. Proc Biol Sci. 1998;265(1409):1927–31.PubMedCrossRef

42.

Wildgruber D et al. Distinct frontal regions subserve evaluation of linguistic and emotional aspects of speech intonation. Cereb Cortex. 2004;14(12):1384–9.PubMedCrossRef

43.

Ethofer T et al. Decoding of emotional information in voice-sensitive cortices. Curr Biol. 2009;19(12):1028–33.PubMedCrossRef

44.

Lotze M et al. Reduced ventrolateral fMRI response during observation of emotional gestures related to the degree of dopaminergic impairment in Parkinson disease. J Cogn Neurosci. 2009;21(7):1321–31.PubMedCrossRef

45.

Eck J et al. Affective brain regions are activated during the processing of pain-related words in migraine patients. Pain. 2011;152(5):1104–13.PubMedCrossRef

46.

Moskowitz MA. Basic mechanisms in vascular headache. Neurol Clin. 1990;8(4):801–15.PubMed

47.

Lauritzen M. Pathophysiology of the migraine aura. The spreading depression theory. Brain. 1994;117(Pt 1):199–210.PubMedCrossRef

48.

Boulloche N et al. Photophobia in migraine: an interictal PET study of cortical hyperexcitability and its modulation by pain. J Neurol Neurosurg Psychiatry. 2010;81:978–84.PubMedCrossRef

49.

Denuelle M et al. A PET study of photophobia during spontaneous migraine attacks. Neurology. 2011;76(3):213–8.PubMedCrossRef

50.

Lai KL et al. Subcortical hyperexcitability in migraineurs: a high-frequency oscillation study. Can J Neurol Sci. 2011;38(2):309–16.PubMed

51.

Rogawski MA. Common pathophysiologic mechanisms in migraine and epilepsy. Arch Neurol. 2008;65(6):709–14.PubMedCrossRef

52.

Ayata C et al. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol. 2006;59:652–61.PubMedCrossRef

53.

Merkler D et al. Propagation of spreading depression inversely correlates with cortical myelin content. Ann Neurol. 2009;66(3):355–65.PubMedCrossRef

54.

Ambrosini A et al. Familial basilar migraine associated with a new mutation in the ATP1A2 gene. Neurology. 2005;65(11):1826–8.PubMedCrossRef

55.

Ophoff RA et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 1996;87(3):543–52.PubMedCrossRef

56.

Ducros A et al. Mapping of a second locus for familial hemiplegic migraine to 1q21-q23 and evidence of further heterogeneity. Ann Neurol. 1997;42(6):885–90.PubMedCrossRef

57.

Vanmolkot KR et al. Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions. Ann Neurol. 2003;54(3):360–6.PubMedCrossRef

58.

Kruit MC et al. Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain. 2005;128(Pt 9):2068–77.PubMedCrossRef

59.

Lotze M, Sauseng P, Staudt M. Functional relevance of ipsilateral motor activation in congenital hemiparesis as tested by fMRI-navigated TMS. Exp Neurol. 2009;217(2):440–3.PubMedCrossRef

60.

Lehericy S et al. Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans. Ann Neurol. 2004;55(4):522–9.PubMedCrossRef

Title: Migraineurs Without Aura Show Microstructural Abnormalities in the Cerebellum and Frontal Lobe
Authors: C. Granziera
D. Romascano
A. Daducci
A. Roche
M. Vincent
G. Krueger
N. Hadjikhani
Publication date: 01-12-2013
Publisher: Springer US
Published in: The Cerebellum / Issue 6/2013
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI: https://doi.org/10.1007/s12311-013-0491-x

At a glance: The STEP trials

Springer Medicine

Migraineurs Without Aura Show Microstructural Abnormalities in the Cerebellum and Frontal Lobe

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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