Is unilateral cerebellum sufficient? Insights from new cases of cerebellar agenesis and literature review

Abstract

The clinical manifestations of adult-acquired cerebellar diseases often surpass those of congenital cerebellar diseases, suggesting the significant role of the cerebellum in the developing brain. Moreover, emerging evidence from structural and functional magnetic resonance imaging indicates that the cerebellum is implicated not only in motor functions but also in non-motor domains such as cognition, emotion, and language. However, delineating the specific extent of cerebellar development required to prevent deficits in either motor or non-motor functions remains challenging. In this study, we present two new cases of unilateral cerebellar agenesis. One individual leads a nearly normal life, while the other exhibits mild cognitive impairment, mild depression, and severe autism, but maintains normal motor function. Van der Heijden et al. (2023) revealed that the brain can compensate for some, but not all, perturbations to the developing cerebellum, including motor deficits and impairments in social behaviors. Therefore, we hypothesize that comparing structural images from our patients and reviewing pertinent literature may elucidate the reasons for the varied clinical manifestations observed in patients with cerebellar agenesis.

Author contributions

Dingmei Deng (Writing - original draft), Bo Tao (Methodology), Yizhi Yuan (Methodology), Yongsheng Ao (Formal analysis), and Lihua Qiu (Writing - review & editing)

Conflict of interest

None declared.

Acknowledgments

We thank the two patients for allowing us to report on their cases.

References

[1] Bigl V, Woolf NJ, Butcher LL. (1982) Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a combined fluorescent tracer and acetylcholinesterase analysis. Brain Res Bull 8:727-49.

[2] Boddaert N, Klein O, Ferguson N, et al. (2003) Intellectual prognosis of the Dandy-Walker malformation in children: the importance of vermian lobulation. Neuroradiology 45:320-4.

[3] Churchill L, Zahm DS, Kalivas PW. (1996) The mediodorsal nucleus of the thalamus in rats-I. forebrain gabaergic innervation. Neuroscience 70:93-102.

[4] Combettes M. (1831) Absence complete du curvelet, des pédoncules postérieus et de la proturbérance cérebrale chez une jeune fille morte dans sa onzieme anneé. Bull Soc Anat Paris 5: 148-57.

[5] Erdogan N, Kocakoc E, Bekar D, et al. (2002) Unilateral absence of cerebellar hemisphere: a case report. Neuroradiology 44: 49-51.

[6] Hong JS, Lee D, Han DH, et al. (2024) Development and validation of the trauma-specific emotional counting stroop paradigm for fMRI study. J Affect Disord 350:118-24.

[7] Jiang S, Li H, Liu L, et al. (2022) Voxel-wise functional connectivity of the default mode network in epilepsies: a systematic review and meta-analysis. Curr Neuropharmacol 20: 254-66.

[8] Kenzie JM, Rajashekar D, Goodyear BG, et al. (2024) Resting state functional connectivity associated with impaired proprioception post-stroke. Hum Brain Mapp 45:e26541.

[9] Kilickesmez O, Yavuz N, Hoca E. (2004) Unilateral absence of cerebellar hemispheres: incidental diagnosis with magnetic resonance imaging. Acta Radiol 45:876-7.

[10] Kolc KL, Sadleir LG, Scheffer IE, et al. (2019) A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psy-chiatric comorbidities, and association of seizure onset and disease severity. Mol Psychiatry 24:241-51.

[11] Lee DH, Chung CK, Kim JS, et al. (2023) Unraveling tactile categorization and decision-making in the subregions of supramarginal gyrus via direct cortical stimulation. Clin Neurophysiol 158:16-26.

[12] Liu Y, Zhang B, Zhou Y, et al. (2024) Plasma oxidative stress marker levels related to functional brain abnormalities in firstepisode drug-naive major depressive disorder. Psychiatry Res 333: 115742.

[13] Pirot S, Jay TM, Glowinski J, et al. (1994) Anatomical and electrophysiological evidence for an excitatory amino acid pathway from the thalamic mediodorsal nucleus to the prefrontal cortex in the rat. Eur J Neurosci 6:1225-34.

[14] Poretti A, Limperopoulos C, Roulet-Perez E, et al. (2010) Outcome of severe unilateral cerebellar hypoplasia. Develop Med Child Neuro 52:718-24.

[15] Tavano A, Grasso R, Gagliardi C, et al. (2007) Disorders of cognitive and affective development in cerebellar malformations. Brain 130:2646-60.

[16] Van Der Heijden ME, Rey Hipolito AG, Kim LH, et al. (2023) Glutamatergic cerebellar neurons differentially contribute to the acquisition of motor and social behaviors. Nat Commun 14:1-18.

[17] Xue Y, Yan H, Hao G, et al. (2023) Symptomatic responses elicited by electrical stimulation of the cingulate cortex: study of a cohort of epileptic patients and literature review. Hum Brain Mapp 44:4498511.

[18] Zahm DS. (2000) An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbens. Neurosci Biobehav Rev 24:85-105.