Cerebellar radiological abnormalities in children with neurofibromatosis type 1: part 1 - clinical and neuroimaging findings

Abstract

BackgroundMany children with neurofibromatosis type 1 (NF1) have focal abnormal signal intensities (FASI) on brain MRI, whose full clinical impact and natural history have not been studied systematically. Our aims are to describe the clinical and neuroradiological features in children with NF1 and cerebellar FASI, and report on the natural history of FASI that display atypical features such as enhancement and mass effect.MethodA retrospective review of the hospital charts and brain MRIs was performed on children from Manitoba diagnosed between 1999 and 2008 with NF1, who also had cerebellar FASI on MRI.ResultsFifty patients (mean age: 16.1y, minimum-maximum: 6.4 - 30y, 27 M) were identified. Mean duration of follow up was 10.1y. Developmental delay, learning disabilities, tumors, and visual signs occurred commonly. Cerebellar signs were not reported. Mean age of the patients at baseline MRI was 7.8 (SD: 4.5) years. FASI occurred in several brain locations and were rarely confined to the cerebellum. FASI displayed mass effect and enhancement infrequently but were associated with malignancy only once. The number of FASI at baseline MRI was significantly less in patients with attention deficient hyperactivity disorder and more if a first degree relative had NF1 or if they had decreased visual acuity.DiscussionPatients with NF1 and cerebellar FASI do not have motor or consistent non-motor (e.g. developmental delay or learning disabilities) cerebellar features. The number of FASI may correlate with some clinical features. FASI may display enhancement and mass effect but they rarely become malignant.

Genetic Counseling for Neurofibromatosis 1, Neurofibromatosis 2, and Schwannomatosis—Practice Resource of the National Society of Genetic Counselors

“…About 20% of children with NF1 are diagnosed with a specific learning disorder (Vogel et al., 2017), but academic skills are affected in the majority (Lehtonen et al., 2015), which may necessitate accommodations or support. There has been no concrete evidence to suggest an association between learning issues and T2 hyperintensities seen on brain MRI (also referred to as NF spots, UBOs, or FASI) (Roy et al., 2015; Salman, Hossain, Alqublan, Bunge, & Rozovsky, 2018).…”

Non-Oncological Neuroradiological Manifestations in NF1 and Their Clinical Implications

“…Found in about 90% of lifelong NF1 patients, these alterations are most frequently detected in the cerebellum, brainstem and basal ganglia (Figure 1); however, hemispheric and hippocampal lesions may appear over time, suggesting a different pathogenic mechanism compared to other localizations [14][15][16]. FASIs vary in number and size over time, with the highest lesion burden detected in early childhood and the fastest decline observed in the thalami and cerebellum; hemispheric and deep FASIs tend to decrease in number with age, whereas diffuse lesions seem to be more stable over time [17][18][19][20]. Even if the sensitivity of FASI presence in NF1 is high, today they have just been proposed (and not yet accepted) as additional diagnostic criteria due to their relatively low specificity and variable localization; indeed, sensitivity and specificity of FASIs for NF1 averaged 97% and 79%, respectively [21].…”

“…FASIs vary in number and size over time, with the highest lesion burden detected in early childhood and the fastest decline observed in the thalami and cerebellum; hemispheric and deep FASIs tend to decrease in number with age, whereas diffuse lesions seem to be more stable over time [ 17 , 18 , 19 , 20 ]. Even if the sensitivity of FASI presence in NF1 is high, today they have just been proposed (and not yet accepted) as additional diagnostic criteria due to their relatively low specificity and variable localization; indeed, sensitivity and specificity of FASIs for NF1 averaged 97% and 79%, respectively [ 21 ].…”

“…In this light, advanced techniques can help in the differential diagnosis from glial tumors [ 15 , 19 , 26 ]. Perfusion-weighted MRI may allow for the detection of tumor-related angiogenesis and increased vascular permeability, features that are usually absent in the case of FASIs and not always present in the case of low-grade glioma.…”

“…At the MRI examination, FASIs are hyperintense on T2w images and iso-hyperintense on T1w, with no mass effect or post-contrast enhancement. It should be noticed that hyperintensity on T1w is generally limited to FASIs within the basal ganglia, and far less common in the posterior fossa and cerebral white matter, thus suggesting a difference in these localizations [24]; FASIs vary in number and size over time, with the highest lesion burden detected in early childhood and the fastest decline observed in the thalami and cerebellum; hemispheric and deep FASIs tend to decrease in number with age, whereas diffuse lesions seem to be more stable over time [17][18][19][20]. Even if the sensitivity of FASI presence in NF1 is high, today they have just been proposed (and not yet accepted) as additional diagnostic criteria due to their relatively low specificity and variable localization; indeed, sensitivity and specificity of FASIs for NF1 averaged 97% and 79%, respectively [21].…”