Impairment of motor skills in children with achondroplasia—usefulness of brain and cranio-cervical junction evaluation by quantitative magnetic resonance imaging: a case-control study

Abstract

Background

Most infants and children with achondroplasia show delayed motor skill development; however, some patients may have clinical consequences related to cranio-cervical junction stenosis and compression.

Purpose

To assess, using brain magnetic resonance imaging (MRI), quantitative variables linked to neuromotor impairment in achondroplasic children.

Material and Methods

In total, 24 achondroplasic children underwent pediatric neurological assessment and were grouped in two cohorts according to relevant motor skill impairment. Achondroplasic children with (n=12) and without (n=12) motor symptoms were identified, and brain MRI scans were quantitatively evaluated. 3D fast spoiled gradient echo T1-weighted images were used to assess: supratentorial intracranial volumes (SICV); supratentorial intracranial brain volume (SICBV); SICV/SICBV ratio; posterior cranial fossa volume (PCFV); posterior cranial fossa brain volume (PCBFV); PCFV/PCFBV ratio; ventricular and extra-ventricular cerebrospinal fluid (CSF) volumes; foramen magnum (FM) area; and jugular foramina (JF) areas.

Results

In both groups, SICV/SICBV ratio, supratentorial ventricular and extra-ventricular space volumes were increased while SICBV was increased only in the asymptomatic group (P < 0.05). PCFV/PCFBV ratio, IV ventricle, infratentorial extra-ventricular spaces volumes were reduced (P < 0.05) in the symptomatic group while PCFBV was increased only in the asymptomatic group (P < 0.05). Foramen magnum (FM) area was more reduced in the symptomatic group than the asymptomatic group (P < 0.05) but no correlation between FM area and ventriculomegaly was found (P > 0.05).

Conclusion

Evaluation of the FM area together with infratentorial ventricular and extra-ventricular space volume reduction may be helpful in differentiating patients at risk of developing motor skill impairment. Further investigation is needed to better understand the temporal profile between imaging and motor function in order to propose possible personalized surgical treatment.

Keywords

achondroplasia motor skill impairment quantitative brain magnetic resonance imaging foramen magnum jugular foramina

Get full access to this article

View all access options for this article.

References

Zucconi

Weber

Castronovo

, et al. Sleep and upper airway obstruction in children with achondroplasia. J Pediatr 1996;129:743–749.

Moritani

Aihara

Oguma

, et al. Magnetic resonance venography of achondroplasia: correlation of venous narrowing at the jugular foramen with hydrocephalus. Clin Imaging 2006;30:195–200.

Ryken

Menezes

. Cervicomedullary compression in achondroplasia. J Neurosurg 1994;81:43–48.

Ruiz-Garcia

Tovar-Baudin

Del Castillo-Ruiz

, et al. Early detection of neurological manifestations in achondroplasia. Childs Nerv Syst 1997;13:208–213.

Wang

Rosenbaum

Reid

, et al. Pediatric patients with achondroplasia: CT evaluation of the craniocervical junction. Radiology 1987;164:515–519.

Song

S-H

Balce

GCE

Agashe

, et al. New proposed clinico-radiologic and molecular criteria in hypochondroplasia: FGFR 3 gene mutations are not the only cause of hypochondroplasia. Am J Med Genet A 2012;158A:2456–2462.

Ireland

Donaghey

McGill

, et al. Development in children with achondroplasia: a prospective clinical cohort study. Dev Med Child Neurol 2012;54:532–537.

Hoover-Fong

Scott

Jones

, et al. Health supervision for people with achondroplasia. Pediatrics 2020;145:e20201010.

Borkhuu

Nagaraju

Chan

, et al. Factors related to progression of thoracolumbar kyphosis in children with achondroplasia: a retrospective cohort study of forty-eight children treated in a comprehensive orthopaedic center. Spine (Phila Pa 1976) 2009;34:1699–1705.

10.

Bauer

Mueller

Oró

. Arachnoid cyst resulting in tonsillar herniation and syringomyelia in a patient with achondroplasia. Case report. Neurosurg Focus 2005;19:E14.

11.

Bagley

Pindrik

Bookland

, et al. Cervicomedullary decompression for foramen magnum stenosis in achondroplasia. J Neurosurg 2006;104:166–172.

12.

Hecht

Horton

Reid

, et al. Growth of the foramen magnum in achondroplasia. Am J Med Genet 1989;32:528–535.

13.

Keiper

Koch

Crone

. Achondroplasia and cervicomedullary compression: prospective evaluation and surgical treatment. Pediatr Neurosurg 1999;31:78–83.

14.

Sanders

Sheldon

Charrow

. Cervical spinal cord compression in infants with achondroplasia: should neuroimaging be routine? Genet Med 2019;21:459–463.

15.

Tasker

Dundas

Laverty

, et al. Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study. Arch Dis Child 1998;79:99–108.

16.

Baujat

Legeai-Mallet

Finidori

, et al. Achondroplasia. Best Pract Res Clin Rheumatol 2008;22:3–18.

17.

Tenconi

Khirani

Amaddeo

, et al. Sleep-disordered breathing and its management in children with achondroplasia. Am J Med Genet A 2017;173:868–878.

18.

Cohen

Rosenthal

Matson

. Neurological abnormalities in achondroplastic children. J Pediatr 1967;71:367–376.

19.

Yamada

Nakamura

Tajima

, et al. Neurological manifestations of pediatric achondroplasia. J Neurosurg 1981;54:49–57.

20.

Pauli

Horton

Glinski

, et al. Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia. Am J Hum Genet 1995;56:732–744.

21.

Haga

. Management of disabilities associated with achondroplasia. J Orthop Sci 2004;9:103–107.

22.

Guarnieri

Brant

, et al. Living with achondroplasia: quality of life evaluation following cervico-medullary decompression. Am J Med Genet A 2004;131:163–167.

23.

Yamada

Ito

Otsubo

, et al. Surgical management of cervicomedullary compression in achondroplasia. Childs Nerv Syst 1996;12:737–741.

24.

Reid

Pyeritz

Kopits

, et al. Cervicomedullary compression in young patients with achondroplasia: value of comprehensive neurologic and respiratory evaluation. J Pediatr 1987;110:522–530.

25.

Benglis

Sandberg

. Acute neurological deficit after minor trauma in an infant with achondroplasia and cervicomedullary compression. Case report and review of the literature. J Neurosurg 2007;107:152–155.

26.

Ozcetin

Arslan

Karapinar

. An achondroplasic case with foramen magnum stenosis, hydrocephaly, cortical atrophy, respiratory failure and sympathetic dysfunction. Iran J Pediatr 2012;22:121–124.

27.

Calandrelli R, Panfili M, D'Apolito G, et al. Quantitative approach to the posterior cranial fossa and craniocervical junction in asymptomatic children with achondroplasia. Neuroradiology 2017;59:1031–1041.

28.

Vatansever

Kyriakopoulou

Allsop

, et al. Multidimensional analysis of fetal posterior fossa in health and disease. Cerebellum 2013;12:632–644.

29.

Yushkevich

Piven

Hazlett

, et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage 2006;31:1116–1128.

30.

Fornarino

Rossi

Severino

, et al. Early impairment of somatosensory evoked potentials in very young children with achondroplasia with foramen magnum stenosis. Dev Med Child Neurol 2017;59:192–198.

31.

Kao

Waziri

Smith

, et al. MR Imaging of the craniovertebral junction, cranium, and brain in children with achondroplasia. AJR Am J Roentgenol 1989;153:565–569.

32.

Pascoe

Yang

JY-M

Chen

, et al. Macrocerebellum in achondroplasia: a further CNS manifestation of FGFR3 mutations? AJNR Am J Neuroradiol 2020;41:338–342.

33.

Yaguchi

Ahmed

, et al. Fibroblast growth factor (FGF) gene expression in the developing cerebellum suggests multiple roles for FGF signaling during cerebellar morphogenesis and development. Dev Dyn 2009;238:2058–2072.

34.

Shazeeb

Cox

Gupta

, et al. Skeletal characterization of the Fgfr3 mouse model of achondroplasia using micro-CT and MRI volumetric imaging. Sci Rep 2018;8:469.

35.

Pannier

Mugniery

Jonquoy

, et al. Delayed bone age due to a dual effect of FGFR3 mutation in achondroplasia. Bone 2010;47:905–915.

36.

Wyrobek

Eskenazi

Young

, et al. Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proc Natl Acad Sci USA 2006;103:9601–9606.

37.

Shiang

Thompson

Zhu

, et al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 1994;78:335–342.

38.

Pauli

. Achondroplasia: a comprehensive clinical review. Orphanet J Rare Dis 2019;14:1.

39.

Jha

Klimo

Smith

. Foramen magnum stenosis from overgrowth of the opisthion in a child with achondroplasia. J Neurosurg Pediatr 2008;2:136–138.

40.

Cheung

Irving

Cocca

, et al. Achondroplasia foramen magnum score: screening infants for stenosis. Arch Dis Child 2021;106:180–184.

41.

Fehlings

Skaf

. A review of the pathophysiology of cervical spondylotic myelopathy with insights for potential novel mechanisms drawn from traumatic spinal cord injury. Spine (Phila Pa 1976) 1998;23:2730–2737.

42.

Karadimas

Gatzounis

Fehlings

. Pathobiology of cervical spondylotic myelopathy. Eur Spine J 2015;24:132–138.

43.

Sarioglu

Guleryuz

. Neuroimaging and calvarial findings in achondroplasia. Pediatr Radiol 2020;50:1669–1679.

44.

Steinbok

Hall

Flodmark

. Hydrocephalus in achondroplasia: the possible role of intracranial venous hypertension. J Neurosurg 1989;71:42–48.

45.

Bosemani

Orman

Hergan

, et al. Achondroplasia in children: correlation of ventriculomegaly, size of foramen magnum and jugular foramina, and emissary vein enlargement. Childs Nerv Syst 2015;31:129–133.

46.

Shim

Cho

T-J

, et al. Predictors of cervical myelopathy and hydrocephalus in young children with achondroplasia. Orphanet J Rare Dis 2021;16:81.