MRI with fibre tracking in Cogan congenital oculomotor apraxia

Abstract

Background Congenital ocular motor apraxia (COMA) occasionally shares with Joubert syndrome (JS) and related disorders (JSRDs) a peculiar malformation, the 'molar tooth sign' (MTS). In JSRDs, the absence of superior cerebellar peduncles (SCP) decussation is reported. Objective To investigate whether COMA demonstrates similar abnormal axonal pathways. Materials and methods Eight healthy age-matched controls, three children with clinical COMA and one child with clinical JSRD underwent examination with a 1.5-T MRI scanner. Diffusion-weighted imaging (DWI), colour-coded fractional anisotropy maps and three-dimensional diffusion tensor imaging (DTI) tractography of the cerebellorubral network were analyzed. Results On DTI cartography, the 'red dot' originally supposed to represent the SCP decussation in the midbrain was present in controls as well in those with COMA but absent in the single case with JS. In none of the subjects including controls was 3-D FT able to depict the SCP decussation. When seeded, the red dot resulted in the ventral tegmental decussation (VTD). It was normal in controls and in patients with COMA but was absent in our single patient with JSRD. MTS was identified in alla patients with COMA and in the patient with JSRD. Conclusion MTS can be present in both COMA and JSRD but the underlying anatomy depicted by fibre tracking is distinct. The main difference is the integrity of the VTD in COMA.

High-Resolution Diffusion Tensor Imaging and Tractography in Joubert Syndrome: Beyond Molar Tooth Sign

“…14e16 Abnormal decussation of the two fiber tracts SCP and CST have been described in Joubert syndrome. 8,9,11 We were able to confirm the previously documented absence of SCP decussation in the midbrain characterized by the absence of the red dot sign in the interpeduncular fissure of the midbrain. 8,9,11 The absence of SCP decussation and pontocerebellar fiber abnormalities are also seen in two other brainstem malformations: pontine tegmental cap dysplasia and horizontal gaze palsy with progressive scoliosis (HGPPS).…”

“…8,9,11 We were able to confirm the previously documented absence of SCP decussation in the midbrain characterized by the absence of the red dot sign in the interpeduncular fissure of the midbrain. 8,9,11 The absence of SCP decussation and pontocerebellar fiber abnormalities are also seen in two other brainstem malformations: pontine tegmental cap dysplasia and horizontal gaze palsy with progressive scoliosis (HGPPS). 14,15,17 Although these condition share minor overlapping features, pontine tegmental cap dysplasia can be distinguished from Joubert syndrome by the characteristic dorsal pontine vaulting with presence of ectopic commissural fibers and multiple cranial nerve neuropathies.…”

Visual Neuropsychology in Development: Anatomo-Functional Brain Mechanisms of Action/Perception Binding in Health and Disease

“…Optic apraxia refers to the impossibility to perform eye movements, resulting in the so-called "sticky" vision: the impossibility to voluntarily shift gaze between different objects (Pena-Casanova et al, 1985). At the neural level, bilateral lesions in a fronto-parietal network comprising the frontal eye fields are considered at the origin of oculomotor apraxia, which therefore would not be necessarily associated strictly with dorsal stream damage (Leigh and Zee, 2015), extending to malformations/dysfunctions in the cerebellum (Shahwan et al, 2006) and midbrain (Jissendi-Tchofo et al, 2009;Merlini et al, 2010). In children, oculomotor apraxia can be present already around the 10th year of life (Tsao and Paulson, 2005), with a mean age of about 7 years and comprised between 2 and 18 years (Le Ber et al, 2003).…”

SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum

“…Of note, diffusion-tensor imaging tractography ('fibre tracking') failed to show evidence of disturbed axonal guidance in two affected siblings from family COR280. 12 Eight carrier parents were interviewed. All reported normal development, did not need extra help in school and denied any neurological issues, with the exception of one mother who reported mild clumsiness and ataxia during school age.…”

“…19 Experience with fibre tracking in patients with SUFU variants is very limited, and axon guidance defects, which are well documented in JS, need to be evaluated in future studies. 12 We were able to interview eight reportedly asymptomatic carrier parents. They all denied COMA, developmental delay and any neurological issues, with the exception of one who complained of mild ataxia/clumsiness in infancy.…”