Comment: Another Piece of the Puzzle of Anomalous Connectivity in Joubert's Syndrome

Reply to Letter to the Editor

We read with great interest the recently published article “Another Piece of the Puzzle of Anomalous Connectivity in Joubert's Syndrome” by Meoded et al.[1] Using diffusion tensor tractography (DTT), the authors have shown the midline crossing fibers, connecting the bilateral middle cerebellar peduncles and the bilateral corticospinal tracts (CSTs) passing through aberrant courses. Additionally, they described that the CST fibers, through which CST normally passes, were not found in the anterior brainstem. However, some issues should be considered while interpreting the DTT results for a patient with Joubert's syndrome.

The deterministic approach used by Meoded et al is the most commonly chosen method for depicting neural tracts using DTT. It is primarily based on streamlined algorithms, where the local tract direction is defined by the major eigenvector of the diffusion tensor.[2] [3] However, this analysis method has some limitations, majorly, the false-positive tracts in the crossing fiber regions and the false disruption of the neural tracts using the partial volume effect.[2] [3] A voxel frequently contains multiple fiber populations in areas referred to as the crossing fiber regions.[2] Approximately 90% of the white matter voxels in the brain were found in the crossing fiber regions.[3] These regions can cause reconstruction of false-positive tracts, such as the crossing fibers and false connections.[3] In the study by Meoded et al, the midline crossing fibers connecting the bilateral middle cerebellar peduncles could be a false-positive tract. Likewise, the authors should have considered the possibility that the CST fibers passing through aberrant courses could be neural tracts other than CST connecting to the crossing fibers or false connections. Moreover, partial volume effects prevent neural tracts from being depicted completely.[2] [3] Accordingly, intact neural tracts of patients can appear damaged on DTT. This limitation, due to partial volume effects, can produce false-positive results. Therefore, the absence of CST fibers in the anterior brainstem, mentioned in the study, could be developed using partial volume effects, even if they were not actually damaged.

Due to these limitations, clinicians and researchers should be careful not to overdiagnose and misinterpret DTT results. Likewise, the findings of this study should be interpreted considering these limitations of DTT.

Publication History

Received: 12 November 2021

Accepted: 10 March 2022

Article published online:
17 July 2022

• References

• 1 Meoded A, Kukreja M, Orman G, Boltshauser E, Huisman TAGM. Another piece of the puzzle of anomalous connectivity in Joubert's syndrome. Neuropediatrics 2022; 53 (03) 195-199
• 2 Calamante F. The seven deadly sins of measuring brain structural connectivity using diffusion MRI streamlines fibre-tracking. Diagnostics (Basel) 2019; 9 (03) 115
• 3 Shin SS, Verstynen T, Pathak S. et al. High-definition fiber tracking for assessment of neurological deficit in a case of traumatic brain injury: finding, visualizing, and interpreting small sites of damage. J Neurosurg 2012; 116 (05) 1062-1069