Cerebral Diffusion Tensor MR Tractography in Tuberous Sclerosis Complex: Correlation with Neurologic Severity and Tract-Based Spatial Statistical Analysis

Wong, Alex Mun-Ching; Wang, H.-S.; Schwartz, Emily; Toh, Cheng Hong; Zimmerman, Robert A.; Liu, P.-L.; Wu, Yi-Ming; Ng, Shu Hang; Wang, J.-J.

doi:10.3174/ajnr.a3507

Cited by 33 publications

(39 citation statements)

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“…Although there is no clear relationship between the extent and the degree of WM alterations and the clinical phenotype, there is some evidence that the more the WM is disrupted, the more severe the neurological phenotype might be [24,25,30]. Therefore, it is noteworthy to emphasize that we observed a statistically significant thinning of RNFL, even if our sample was constituted by patients who presented a relatively mild neurological phenotype.…”

Section: Discussionmentioning

confidence: 62%

“…The low fractional anisotropy frequently observed in neuroimaging studies of TSC strongly supports disorganized and poorly myelinated axons, while a primary poor integrity of the axons themselves is suggested by lower axial diffusivity [22,23]. Although an axonal involvement has been hypothesized after analyzing neuroimaging data [24,25], in humans, axonal structure has never been studied in detail before. Animal models showed that there is a primary axonal developmental defect caused by the genetic mutation in the TSC genes, which leads to a secondary myelination failure [26]; the TSC/mTOR pathway appears to limit multiple axon formation and acts to confine polarized growth within a single axon in the mammalian brain, and its deregulation likely contributes to the neurological symptoms commonly observed in TSC patients [8].…”

Section: Discussionmentioning

confidence: 94%

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Reduction in retinal nerve fiber layer thickness in tuberous sclerosis complex

et al. 2015

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Since a reduced RNFL thickness might be seen as an indicator of chronic axonal degeneration or lack of appropriate neuronal development, our results support the presence of axonal alterations in TSC and also that white matter disorganization could be much more diffuse than originally thought. Since axonal alterations directly derive from mammalian target of rapamycin (mTOR) overactivation, which occurs early during fetus development, the RNFL thinning we observed could represent one of the facets of such early neurodevelopmental abnormalities.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 94%

Reduction in retinal nerve fiber layer thickness in tuberous sclerosis complex

et al. 2015

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“…Based on the most recent neurological evaluation, each patient was assigned a score of neurological outcome (0–8); the scoring method outlined by Wong et al . was used.…”

Section: Methodsmentioning

confidence: 99%

Cerebellar lesions as potential predictors of neurobehavioural phenotype in tuberous sclerosis complex

Toldo

Bugin

Perissinotto

et al. 2019

Develop Med Child Neuro

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ASDAutism spectrum disorder SEN Subependymal nodule TAND Tuberous sclerosis complexassociated neuropsychiatric disorders TSC Tuberous sclerosis complex AIM To improve the genetic, clinical, and neuroradiological characterization of cerebellar involvement in tuberous sclerosis complex (TSC) and determine whether cerebellar lesions could be a reliable biomarker of neurological impairment.METHOD This retrospective cohort study, held at two tertiary paediatric university centres, was conducted on patients with a confirmed diagnosis of TSC who underwent brain magnetic resonance imaging between October 2009 and May 2016. The study population consisted of 112 patients with TSC (median age 10y; range 5mo-38y; 61 females, 51 males). RESULTSThe results from multivariable statistical analysis indicated that cerebellar involvement (34 out of 112 patients, none carrying a TSC1 mutation) was the most powerful predictor of supratentorial cortical tuber load; however, cerebellar involvement was not the best predictor of clinical phenotype when supratentorial tuber load and TSC2 mutations were taken into consideration. The association between cerebellar lesions and a more severe clinical and neuroradiological phenotype was statistically significant and may be due to its strong association with TSC2 mutations and higher cortical tuber load.INTERPRETATION Cerebellar involvement is not the best predictor of neurobehavioural outcome, including TSC-related autism, after adjusting for TSC2 and the number of cortical tubers. Its role in the TSC clinical phenotype needs to be investigated further.In tuberous sclerosis complex (TSC), a multisystem autosomal dominant genetic disorder with neurological involvement in about 90% of cases, structural alterations of the brain (mainly cortical tubers, radial migration lines, and subependymal nodules [SENs]) typically involve the supratentorial regions. 1,2 However, cerebellar involvement has been documented in patients with TSC, with a prevalence varying from 8% to 46%. 3-25 Cerebellar lesions are thought to be predominantly tubers, 5,6,8,20,26 although they are sometimes associated with dystrophy-like focal cerebellar atrophy; 3,4,7,8,20 partial or total cerebellar hypoplasia has also been reported. 9 With regard to contrast enhancement, calcifications, or lesion size, 10,11,27 recent studies have recorded changes in cerebellar lesions in 20% to 46% of patients with TSC. 6,7,14 These changes manifest themselves during the first 8 years of life; 6 however, the underlying biological mechanism remains unclear. Cerebellar lesions have been associated with older age, 4,12 autism spectrum disorder (ASD), 13 and TSC2 mutations; 12,14,17,18 TSC2 is highly expressed in the cerebellum. 14 Patients with TSC with cerebellar lesions generally have more cortical tubers than patients with only supratentorial lesions 4,6,8,12,25 and a greater association with subependymal giant cell astrocytoma. 7,25 Conditional knockout mouse models of TSC1 and TSC2 support the link between cerebellar circuitry and the develo...

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“…This finding is significant in that other investigators have found that abnormalities in FA in normal-appearing white matter correlate with the presence and severity of cognitive impairment in TSC patients. This suggests that mTOR inhibitors may reverse microscopic structural abnormalities, resulting in improved cognition and/or seizure control, in addition to effects on cortical tubers and SEGAs [51,52]. Furthermore, no patients developed new lesions or worsening hydrocephalus or required additional surgery intervention for SEGA during the evaluation phase of the trial or during the extension study [47,49].…”

Section: Pharmacotherapymentioning

confidence: 92%

Pharmacologic management of tuberous sclerosis complex-associated subependymal giant cell astrocytomas

Franz¹

2013

Expert Opinion on Orphan Drugs

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Cerebral Diffusion Tensor MR Tractography in Tuberous Sclerosis Complex: Correlation with Neurologic Severity and Tract-Based Spatial Statistical Analysis

Cited by 33 publications

References 40 publications

Reduction in retinal nerve fiber layer thickness in tuberous sclerosis complex

Reduction in retinal nerve fiber layer thickness in tuberous sclerosis complex

Cerebellar lesions as potential predictors of neurobehavioural phenotype in tuberous sclerosis complex

Pharmacologic management of tuberous sclerosis complex-associated subependymal giant cell astrocytomas

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