Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders

Abstract

Bilateral basal ganglia abnormalities on MRI are observed in a wide variety of childhood disorders. MRI pattern recognition can enable rationalisation of investigations and also complement clinical and molecular findings, particularly confirming genomic findings and also enabling new gene discovery. A pattern recognition approach in children with bilateral basal ganglia abnormalities on brain MRI was undertaken in this international multicentre cohort study. 305 MRI scans belonging to 201 children with 34 different disorders were rated using a standard radiological scoring proforma. In addition, literature review on MRI patterns was undertaken in these 34 disorders and 59 additional disorders reported with bilateral basal ganglia MRI abnormalities. Cluster analysis on first MRI findings from the study cohort grouped them into four clusters: Cluster 1—T2-weighted hyperintensities in the putamen; Cluster 2—T2-weighted hyperintensities or increased MRI susceptibility in the globus pallidus; Cluster 3—T2-weighted hyperintensities in the globus pallidus, brainstem and cerebellum with diffusion restriction; Cluster 4—T1-weighted hyperintensities in the basal ganglia. The 34 diagnostic categories included in this study showed dominant clustering in one of the above four clusters. Inflammatory disorders grouped together in cluster 1. Mitochondrial and other neurometabolic disorders were distributed across clusters 1, 2 and 3, according to lesions dominantly affecting the striatum (cluster 1: glutaric aciduria type 1, propionic acidaemia, 3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome (MEGDEL) and thiamine responsive basal ganglia disease associated with SLC19A3), pallidum (cluster 2: methylmalonic acidaemia, Kearns Sayre syndrome, pyruvate dehydrogenase complex deficiency and succinic semialdehyde dehydrogenase deficiency) or pallidum, brainstem and cerebellum (cluster 3: vigabatrin toxicity, Krabbe disease). The cluster 4 pattern was exemplified by distinct T1-weighted hyperintensities in the basal ganglia and other brain regions in genetically determined hypermanganesemia due to SLC39A14 and SLC30A10. Within the clusters, distinctive basal ganglia MRI patterns were noted in acquired disorders such as cerebral palsy due to hypoxic ischemic encephalopathy in full-term babies, kernicterus and vigabatrin toxicity and in rare genetic disorders such as MEGDEL, thiamine responsive basal ganglia disease, pantothenate kinase associated neurodegeneration, TUBB4A and hypermanganesemia. Integrated findings from the study cohort and literature review were used to propose a diagnostic algorithm to approach bilateral basal ganglia abnormalities on MRI. After integrating clinical summaries and MRI findings from the literature review, we developed a prototypic decision-making electronic tool to be tested using further cohorts, and clinical practice.

Biotin-thiamine-responsive basal ganglia disease: A case report

“…As was the case with our patient, despite the presence of classical radiological changes, there may be a delay in diagnosis for many years in patients with BTBGD, likely due in part to the rarity of this disease, along with an extensive differential diagnoses for bilateral basal ganglia T2 hyperintensity on MRI. One of the top differential considerations in BTBGD is viral encephalitis, particularly Ebstein-Barr virus which also demonstrates multifocal cortical, subcortical, and bilateral deep grey matter T2-FLAIR hyperintensities [8] . Autoimmune-mediated etiologies of encephalitis can also present with bilateral basal ganglia involvement, however some potentially helpful distinguishing features include cortical thickening and involvement of mesial temporal lobes and limbic systems [ 8 , 9 ].…”

“…One of the top differential considerations in BTBGD is viral encephalitis, particularly Ebstein-Barr virus which also demonstrates multifocal cortical, subcortical, and bilateral deep grey matter T2-FLAIR hyperintensities [8] . Autoimmune-mediated etiologies of encephalitis can also present with bilateral basal ganglia involvement, however some potentially helpful distinguishing features include cortical thickening and involvement of mesial temporal lobes and limbic systems [ 8 , 9 ]. Another important differential consideration is mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), which clinically presents very similarly to BTBGD with a relapsing-remitting course, seizures, encephalopathy.…”

“…Another important differential consideration is mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), which clinically presents very similarly to BTBGD with a relapsing-remitting course, seizures, encephalopathy. MR findings in MELAS tend to resemble multifocal predominantly cortical ischemic insults or stroke-like lesions of various ages, frequently in nonvascular territories, often with subsequent development of brain atrophy [ 8 , 10 ]. Stroke-like lesions most frequently occur in the temporo-occipital region, although frontal and parietal regions can be involved [11] .…”

“…In October 2020, Mohammad et al. completed an international multicenter cohort study retrospectively examining 305 MRI scans of children with bilateral basal ganglia abnormalities, with the aim of recognizing clusters of neuroimaging patterns to guide clinicians in differentiating conditions [8] . This study established 4 distinct clusters: Cluster 1) T2-weighted hyperintensities in the putamen; Cluster 2) T2-weighted hyperintensities or increased MRI susceptibility in the globus pallidus; Cluster 3) T2-weighted hyperintensities in the globus pallidus, brainstem and cerebellum with diffusion restriction; Cluster 4) T1- weighted hyperintensities in the basal ganglia.…”

Towards Precision Therapies for Inherited Disorders of Neurodegeneration with Brain Iron Accumulation

“…These disorders have the common neuroradiological feature of signal hypointensity of the basal ganglia on specific MR sequences known to demonstrate the magnetic resonance phenomenon of susceptibility which indicates excess mineralization (T2-weighted, T2*-weighted, susceptibility-weighted and echo-planar imaging b0-diffusion imaging data sets) [ 1 ] with some disorders also clearly associated with neuropathological findings of iron accumulation on post-mortem analysis. Over time, it is increasingly apparent that such radiological features are associated with a broad spectrum of neurological and neurodegenerative disorders including the mitochondrial cytopathies, genetic dystonias (such as those due to KMT2B and VPS16 mutations) and lysosomal disorders (GM1 gangliosidosis, alpha fucosidosis) [ 2 3 4 5 ], although for many of these disorders, correlation with post-mortem studies is not yet reported. As a result, precise classification of what comprises an NBIA disorder remains uncertain.…”