Top

Published in:

17-09-2022 | Migraine | Original Article

Functional connectivity alterations in migraineurs with Alice in Wonderland syndrome

Authors: Claudia Piervincenzi, Nikolaos Petsas, Alessandro Viganò, Valentina Mancini, Giulio Mastria, Marta Puma, Costanza Giannì, Vittorio Di Piero, Patrizia Pantano

Published in: Neurological Sciences | Issue 1/2023

Abstract

Background and purpose

Alice in Wonderland syndrome (AIWS) is a neurological disorder characterized by erroneous perception of the body schema or surrounding space. Migraine is the primary cause of AIWS in adults. The pathophysiology of AIWS is largely unknown, especially regarding functional abnormalities. In this study, we compared resting-state functional connectivity (FC) of migraine patients experiencing AIWS, migraine patients with typical aura (MA) and healthy controls (HCs).

Methods

Twelve AIWS, 12 MA, and 24 HCs were enrolled and underwent 3 T MRI scanning. Independent component analysis was used to identify RSNs thought to be relevant for AIWS: visual, salience, basal ganglia, default mode, and executive control networks. Dual regression technique was used to detect between-group differences in RSNs. Finally, AIWS-specific FC alterations were correlated with clinical measures.

Results

With respect to HCs, AIWS and MA patients both showed significantly lower (p < 0.05, FDR corrected) FC in lateral and medial visual networks and higher FC in salience and default mode networks. AIWS patients alone showed higher FC in basal ganglia and executive control networks than HCs. When directly compared, AIWS patients showed lower FC in visual networks and higher FC in all other investigated RSNs than MA patients. Lastly, AIWS-specific FC alterations in the executive control network positively correlated with migraine frequency.

Conclusions

AIWS and MA patients showed similar FC alterations in several RSNs, although to a different extent, suggesting common pathophysiological underpinnings. However, AIWS patients showed additional FC alterations, likely due to the complexity of AIWS symptoms involving high-order associative cortical areas.

Available only for authorised users

Todd J (1955) The Syndrome of Alice in Wonderland. Can Med Assoc J 73:701–704

Carroll L (1865) Alice’s adventures in wonderland. MacMillan and Co., London

Blom JD (2016) Alice in Wonderland syndrome: a systematic review. Neurol Clin Pract 6:259–270. https://doi.org/10.1212/CPJ.0000000000000251CrossRef

O’Toole P, Modestino EJ (2017) Alice in Wonderland Syndrome: a real life version of Lewis Carroll’s novel. Brain Dev 39:470–474. https://doi.org/10.1016/j.braindev.2017.01.004CrossRef

Blom JD (2020) Alice in Wonderland syndrome. Springer Nature, Cham. https://doi.org/10.1007/978-3-030-18609-8

Podoll K, Ebel H, Robinson D, Nicola U (2002) Obligatory and facultative symptoms of the Alice in wonderland syndrome. Minerva Med 93:287–293

Lanska JR, Lanska DJ (2013) Alice in Wonderland Syndrome: somesthetic vs visual perceptual disturbance. Neurology 80:1262–1264. https://doi.org/10.1212/WNL.0b013e31828970aeCrossRef

Liu AM, Liu JG, Liu GW, Liu GT (2014) “Alice in wonderland” syndrome: presenting and follow-up characteristics. Pediatr Neurol 51:317–320. https://doi.org/10.1016/j.pediatrneurol.2014.04.007CrossRef

Mastria G, Mancini V, Viganò A, Di Piero V (2016) Alice in Wonderland Syndrome: a clinical and pathophysiological review. Biomed Res Int 2016:8243145. https://doi.org/10.1155/2016/8243145CrossRef

10.

Mastria G, Mancini V, Cesare MD et al (2021) Prevalence and characteristics of Alice in Wonderland Syndrome in adult migraineurs: perspectives from a tertiary referral headache unit. Cephalalgia 41:515–524. https://doi.org/10.1177/0333102420968245CrossRef

11.

Petrusic I, Viana M, Zecca C, Zidverc-Trajkovic J (2020) Dysphasia and other higher cortical dysfunctions during the migraine aura-a systematic review of literature. Curr Pain Headache Rep 24:3. https://doi.org/10.1007/s11916-020-0836-3CrossRef

12.

Piervincenzi C, Petsas N, Giannì C, Di Piero V, Pantano P (2022) Alice in Wonderland Syndrome: a lesion mapping study. Neurol Sci 43(5):3321–3332. https://doi.org/10.1007/s10072-021-05792-0

13.

Kuo Y-T, Chiu N-C, Shen E-Y et al (1998) Cerebral perfusion in children with Alice in Wonderland syndrome. Pediatr Neurol 19:105–108. https://doi.org/10.1016/S0887-8994(98)00037-XCrossRef

14.

Gencoglu EA, Alehan F, Erol I et al (2005) Brain SPECT findings in a patient with Alice in Wonderland syndrome. Clin Nucl Med 30:758–759. https://doi.org/10.1097/01.rlu.0000182278.13389.a3CrossRef

15.

Brumm K, Walenski M, Haist F et al (2010) Functional MRI of a child with Alice in Wonderland syndrome during an episode of micropsia. J AAPOS 14:317–322. https://doi.org/10.1016/j.jaapos.2010.03.007CrossRef

16.

Biswal B, Yetkin FZ, Haughton VM, Hyde JS (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34:537–541CrossRef

17.

Chong CD, Schwedt TJ, Hougaard A (2019) Brain functional connectivity in headache disorders: a narrative review of MRI investigations. J Cereb Blood Flow Metab 39:650–669. https://doi.org/10.1177/0271678X17740794CrossRef

18.

Brooks JBB, Prosdocimi FC, da Rosa PB, Fragoso YD (2019) Alice in Wonderland syndrome: who in the world am I? Arq Neuropsiquiatr 77:672–674CrossRef

19.

Kumral E, Evyapan D, Sirin T, Alpaydin S (2012) Hyposchematia without spatial neglect in 2 patients with lesions involving the insula. Cogn Behav Neurol 25:149–153. https://doi.org/10.1097/WNN.0b013e31826b70deCrossRef

20.

Saj A, Wilcke JC, Gschwind M et al (2013) Spatial hyperschematia without spatial neglect after insulo-thalamic disconnection. PLoS ONE 8:e79938. https://doi.org/10.1371/journal.pone.0079938CrossRef

21.

ElTarhouni AH, Beer L, Mouthon M et al (2020) The right thalamic ventral posterolateral nucleus seems to be determinant for macrosomatognosia: a case report. BMC Neurol 20:393. https://doi.org/10.1186/s12883-020-01970-3CrossRef

22.

Weijers NR, Rietveld A, Meijer FJA, de Leeuw FE (2013) Macrosomatognosia in frontal lobe infarct-a case report. J Neurol 260:925–926. https://doi.org/10.1007/s00415-012-6827-5CrossRef

23.

Mancini V, Mastria G, Frantellizzi V et al (2018) Aripiprazole-triggered Alice in Wonderland Syndrome episodes studied with 99mTc-HMPAO brain SPECT. Eur Neurol 79:333–334. https://doi.org/10.1159/000490902CrossRef

24.

Beh SC, Masrour S, Smith SV, Friedman DI (2018) Clinical characteristics of Alice in Wonderland syndrome in a cohort with vestibular migraine. Neurol Clin Pract 8:389–396. https://doi.org/10.1212/CPJ.0000000000000518CrossRef

25.

Mastria G, Mancini V, Cesare MD, Puma M, Alessiani M, Petolicchio B, Viganò A, Piero VD (2021) Prevalence and characteristics of Alice in Wonderland Syndrome in adult migraineurs: perspectives from a tertiary referral headache unit. Cephalalgia 41(5):515–524. https://doi.org/10.1177/0333102420968245

26.

Hansen JM, Baca SM, Vanvalkenburgh P, Charles A (2013) Distinctive anatomical and physiological features of migraine aura revealed by 18 years of recording. Brain 136:3589–3595. https://doi.org/10.1093/brain/awt309CrossRef

27.

Esteban O, Markiewicz CJ, Blair RW et al (2019) fMRIPrep: a robust preprocessing pipeline for functional MRI. Nat Methods 16:111–116. https://doi.org/10.1038/s41592-018-0235-4CrossRef

28.

Esteban O, Blair R, Markiewicz CJ, Berleant SL, Moodie C, Ma F, Ilkay Isik A et al (2018) FMRIPrep. Software. Zenodo. https://doi.org/10.5281/zenodo.852659

29.

Gorgolewski K, Burns CD, Madison C, Clark D, Halchenko YO, Waskom ML, Ghosh S (2011) Nipype: a flexible, lightweight and extensible neuroimaging data processing framework in Python. Front Neuroinform 5:13. https://doi.org/10.3389/fninf.2011.00013

30.

Gorgolewski KJ, Esteban O, Markiewicz CJ, Ziegler E, Ellis DG, Notter MP, Jarecka D et al (2018) Nipype. Software. Zenodo. https://doi.org/10.5281/zenodo.596855

31.

Beckmann CF, DeLuca M, Devlin JT, Smith SM (2005) Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond, B, Biol Sci 360:1001–1013. https://doi.org/10.1098/rstb.2005.1634CrossRef

32.

Smith SM, Fox PT, Miller KL et al (2009) Correspondence of the brain’s functional architecture during activation and rest. Proc Natl Acad Sci. https://doi.org/10.1073/pnas.0905267106CrossRef

33.

Tong Y, Hocke LM, Nickerson LD et al (2013) Evaluating the effects of systemic low frequency oscillations measured in the periphery on the independent component analysis results of resting state networks. Neuroimage. https://doi.org/10.1016/j.neuroimage.2013.03.019CrossRef

34.

Piervincenzi C, Petsas N, De Giglio L et al (2021) Increased within-network functional connectivity may predict NEDA status in fingolimod-treated MS patients. Front Neurol 12:632917. https://doi.org/10.3389/fneur.2021.632917CrossRef

35.

Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, Roffman JL, Smoller JW, Zöllei L, Polimeni JR, Fischl B, Liu H, Buckner RL (2011) The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol 106(3):1125–1165. https://doi.org/10.1152/jn.00338.2011

36.

Filippini N, MacIntosh BJ, Hough MG et al (2009) Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proc Natl Acad Sci U S A 106:7209–7214. https://doi.org/10.1073/pnas.0811879106CrossRef

37.

Nickerson LD, Smith SM, Öngür D, Beckmann CF (2017) Using dual regression to investigate network shape and amplitude in functional connectivity analyses. Front Neurosci 11:115. https://doi.org/10.3389/fnins.2017.00115CrossRef

38.

Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25CrossRef

39.

Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc: Ser B (Methodol) 57:289–300. https://doi.org/10.1111/j.2517-6161.1995.tb02031.xCrossRef

40.

Kruit M, van Buchem M, Launer L et al (2010) 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 30:129–136. https://doi.org/10.1111/j.1468-2982.2009.01904.xCrossRef

41.

Eikermann-Haerter K, Huang SY (2021) White matter lesions in migraine. Am J Pathol 191:1955–1962. https://doi.org/10.1016/j.ajpath.2021.02.007CrossRef

42.

Tessitore A, Russo A, Conte F et al (2015) Abnormal connectivity within executive resting-state network in migraine with aura. Headache 55:794–805. https://doi.org/10.1111/head.12587CrossRef

43.

Tedeschi G, Russo A, Conte F et al (2016) Increased interictal visual network connectivity in patients with migraine with aura. Cephalalgia 36:139–147. https://doi.org/10.1177/0333102415584360CrossRef

44.

Seeley WW, Menon V, Schatzberg AF et al (2007) Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 27:2349–2356. https://doi.org/10.1523/JNEUROSCI.5587-06.2007CrossRef

45.

Seeley WW (2019) The salience network: a neural system for perceiving and responding to homeostatic demands. J Neurosci 39:9878–9882. https://doi.org/10.1523/JNEUROSCI.1138-17.2019CrossRef

46.

Faragó P, Tuka B, Tóth E et al (2017) Interictal brain activity differs in migraine with and without aura: resting state fMRI study. J Headache Pain 18:8. https://doi.org/10.1186/s10194-016-0716-8CrossRef

47.

Niddam DM, Lai K-L, Fuh J-L et al (2016) Reduced functional connectivity between salience and visual networks in migraine with aura. Cephalalgia 36:53–66. https://doi.org/10.1177/0333102415583144CrossRef

48.

Lo Buono V, Bonanno L, Corallo F et al (2017) Functional connectivity and cognitive impairment in migraine with and without aura. J Headache Pain 18:72. https://doi.org/10.1186/s10194-017-0782-6CrossRef

49.

Veréb D, Szabó N, Tuka B et al (2020) Temporal instability of salience network activity in migraine with aura. Pain 161:856–864. https://doi.org/10.1097/j.pain.0000000000001770CrossRef

50.

Silvestro M, Tessitore A, Di Nardo F et al (2022) Functional connectivity changes in complex migraine aura: beyond the visual network. Eur J Neurol 29:295–304. https://doi.org/10.1111/ene.15061CrossRef

51.

Centeno M, Carmichael DW (2014) Network connectivity in epilepsy: resting state fMRI and EEG-fMRI contributions. Front Neurol 5:93. https://doi.org/10.3389/fneur.2014.00093CrossRef

52.

Lin L, Xing G, Han Y (2018) Advances in resting state neuroimaging of mild cognitive impairment. Front Psychiatry 9:671. https://doi.org/10.3389/fpsyt.2018.00671CrossRef

53.

Rocca MA, Schoonheim MM, Valsasina P et al (2022) Task- and resting-state fMRI studies in multiple sclerosis: from regions to systems and time-varying analysis Current status and future perspective. Neuroimage Clin 35:103076. https://doi.org/10.1016/j.nicl.2022.103076CrossRef

54.

Hillary FG, Roman CA, Venkatesan U et al (2015) Hyperconnectivity is a fundamental response to neurological disruption. Neuropsychology 29:59–75. https://doi.org/10.1037/neu0000110CrossRef

55.

Coppola G, Di Renzo A, Petolicchio B et al (2019) Aberrant interactions of cortical networks in chronic migraine: a resting-state fMRI study. Neurology 92:e2550–e2558. https://doi.org/10.1212/WNL.0000000000007577CrossRef

56.

Hougaard A, Amin FM, Magon S et al (2015) No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura. Eur J Neurol 22:702-e46. https://doi.org/10.1111/ene.12636CrossRef

57.

Benarroch EE (2019) Insular cortex: functional complexity and clinical correlations. Neurology 93:932–938. https://doi.org/10.1212/WNL.0000000000008525CrossRef

58.

Borsook D, Veggeberg R, Erpelding N et al (2016) The insula: a “hub of activity” in migraine. Neuroscientist 22:632–652. https://doi.org/10.1177/1073858415601369CrossRef

59.

de Tommaso M, Vecchio E, Quitadamo SG et al (2021) Pain-related brain connectivity changes in migraine: a narrative review and proof of concept about possible novel treatments interference. Brain Sci 11:234. https://doi.org/10.3390/brainsci11020234CrossRef

60.

Zhang J, Su J, Wang M et al (2016) Increased default mode network connectivity and increased regional homogeneity in migraineurs without aura. J Headache Pain 17:98. https://doi.org/10.1186/s10194-016-0692-zCrossRef

61.

Mastria G, Mancini V, Viganò A et al (2018) Temporal-occipital glioblastoma presenting with Alice in Wonderland Syndrome in a patient with a long-time history of migraine without aura. Neurocase 24:242–244. https://doi.org/10.1080/13554794.2018.1562079CrossRef

62.

Tokida H, Takeshima S, Takeshita J et al (2018) A case of various illusion, and hallucination caused by occipital lobe infarction. Rinsho Shinkeigaku 58:556–559. https://doi.org/10.5692/clinicalneurol.cn-001081CrossRef

63.

Cohen L, Gray F, Meyrignac C et al (1994) Selective deficit of visual size perception: two cases of hemimicropsia. J Neurol Neurosurg Psychiatry 57:73–78CrossRef

64.

Hong YH, Lim T-S, Yong SW, Moon SY (2010) Ipsilateral visual illusion after unilateral posterior cerebral artery infarction: a report of two cases. J Neurol Sci 295:114–116. https://doi.org/10.1016/j.jns.2010.05.015CrossRef

65.

Coven I, Horasanlı B, Sönmez E et al (2013) The Alice in Wonderland syndrome: an unusual in acute disseminated encephalomyelitis. Am J Emerg Med 31:638.e1–3. https://doi.org/10.1016/j.ajem.2012.10.029CrossRef

66.

Rode G, Vallar G, Revol P et al (2012) Facial macrosomatognosia and pain in a case of Wallenberg’s syndrome: selective effects of vestibular and transcutaneous stimulations. Neuropsychologia 50:245–253. https://doi.org/10.1016/j.neuropsychologia.2011.11.018CrossRef

67.

Coppola G, Di Renzo A, Tinelli E et al (2021) Thalamo-cortical networks in subtypes of migraine with aura patients. J Headache Pain 22:58. https://doi.org/10.1186/s10194-021-01272-0CrossRef

68.

Zwijnenburg PJG, Wennink JMB, Laman DM, Linssen WHJP (2002) Alice in Wonderland syndrome: a clinical presentation of frontal lobe epilepsy. Neuropediatrics 33:53–55. https://doi.org/10.1055/s-2002-23599CrossRef

69.

Morland D, Wolff V, Dietemann J-L et al (2013) Robin Hood caught in Wonderland: brain SPECT findings. Clin Nucl Med 38:979–981. https://doi.org/10.1097/RLU.0000000000000230CrossRef

70.

Urbanski M, Thiebaut de Schotten M, Rodrigo S et al (2008) Brain networks of spatial awareness: evidence from diffusion tensor imaging tractography. J Neurol Neurosurg Psychiatry 79:598–601. https://doi.org/10.1136/jnnp.2007.126276CrossRef

71.

Schwedt TJ, Dodick DW (2009) Advanced neuroimaging of migraine. Lancet Neurol 8:560–568. https://doi.org/10.1016/S1474-4422(09)70107-3CrossRef

72.

Dalkara T, Nozari A, Moskowitz MA (2010) Migraine aura pathophysiology: the role of blood vessels and microembolisation. Lancet Neurol 9:309–317. https://doi.org/10.1016/S1474-4422(09)70358-8CrossRef

Title: Functional connectivity alterations in migraineurs with Alice in Wonderland syndrome
Authors: Claudia Piervincenzi
Nikolaos Petsas
Alessandro Viganò
Valentina Mancini
Giulio Mastria
Marta Puma
Costanza Giannì
Vittorio Di Piero
Patrizia Pantano
Publication date: 17-09-2022
Publisher: Springer International Publishing
Keywords: Migraine
Aura
Published in: Neurological Sciences / Issue 1/2023
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-022-06404-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Functional connectivity alterations in migraineurs with Alice in Wonderland syndrome

Abstract

Background and purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2023

Sleep disorders in Wilson’s disease: a questionnaire study

Optimal MoCA cutoffs for detecting biologically-defined patients with MCI and early dementia

Fibrocartilaginous embolism: a rare cause leading to spinal cord infarction?

Advanced molecular therapies for neurological diseases: focus on stroke, alzheimer's disease, and parkinson's disease

REM sleep behavior disorder correlates with constipation in de novo Chinese Parkinson’s disease patients

The use of dual antiplatelet therapy for ischemic cerebrovascular events