MRI T2 Hypointensities in basal ganglia of premanifest Huntington's disease

Abstract

Increased iron levels have been demonstrated in the basal ganglia of manifest Huntington's disease (HD). An excess in iron accumulation correlates with MRI T2-weighted hypointensity. Determination of the amount of hypointensities in the basal ganglia in the premanifest phase of HD may give more insight in the role of iron in the pathogenesis of HD. Therefore, the present study assessed whether the degree of hypointensities on T2-w MRI in the basal ganglia of premanifest gene carriers differs from non-carriers. Seventeen HD gene carriers without clinical motor signs and 15 non-carriers underwent clinical evaluation and MRI scanning. The amount of T2-w hypointensities was determined using a computer-assisted quantitative method that classified each pixel in the basal ganglia as hypointense or not, resulting in a total of hypointense pixels for each individual. Carriers showed an increased amount of hypointensities in the basal ganglia compared to non-carriers. More hypointensities were furthermore associated with a higher UHDRS total motor score, a longer CAG repeat length and a greater probability of developing symptoms within 5 years. We concluded that the increased amount of hypointensities in the basal ganglia of premanifest carriers of the HD gene may reflect excessive iron deposition and a role for iron in the neuropathology of HD. Furthermore, this phenomenon is associated with clinical and biological disease characteristics. An increased amount of hypointensities on T2-w MRI in the basal ganglia may be considered a biomarker for HD.

Elevated brain iron is independent from atrophy in Huntington's Disease

“…However, this report was based on a group with less stringent inclusion criteria of individuals, namely without overt motor signs as opposed to a UHDRS cut-off point of 5. The correlation which Jurgens et al (2010) found between the number of hypointense pixels and total motor score, demonstrates that all of the participants with higher iron levels would have been classified as having early manifest HD under our criteria (Jurgens et al, 2010). It is certainly possible that the iron levels are not high enough for MFC, or any other existing imaging techniques, to pick up small changes in premanifest gene carriers, or that abnormal iron depositions do not occur until later in the disease process.…”

“…No significant differences in iron were observed between premanifest gene carriers and healthy controls. The only other report in premanifest gene carriers found elevated iron in the globus pallidus (Jurgens et al, 2010). However, this report was based on a group with less stringent inclusion criteria of individuals, namely without overt motor signs as opposed to a UHDRS cut-off point of 5.…”

“…Given that both prior to, and after, disease onset, brain changes in the form of volumetric reductions have been systematically reported (Aylward et al, 1997;Paulsen et al, 2006;Tabrizi et al, 2009;van den Bogaard et al, 2010), it is possible that iron levels change both in the premanifest and in the manifest stages of the disease. However, this hypothesis has only been examined previously in one group of premanifest gene carriers of HD (Jurgens et al, 2010). It has been suggested that increases in iron could promote neurotoxicity through the induction of oxidative reactions (Brass et al, 2006;Stankiewicz and Brass, 2009).…”

Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in theHFEgene

“…Brain iron regulation is disrupted in several neurodegenerative diseases. Neuroimaging methods reveal abnormally high brain iron concentrations in Alzheimer's disease (5), Parkinson disease (6), and Huntington disease (7). High iron concentrations may even cause neuronal death (8,9).…”

Neuroimaging of Rapidly Progressive Dementias, Part 1: Neurodegenerative Etiologies

“…Moreover, the basal ganglia may be hypointense on FLAIR and T2-weighted images due to iron deposition, and this finding is thought to constitute an early biomarker for the disease. 49 Other advanced MR imaging methods such as MR spectroscopy at a high-field strength may aid in showing changes associated with HD with decreased NAA and creatine within the caudate nucleus and putamen. 50 Neuroimaging may prognosticate the onset of disease progression in HD before the development of symptoms.…”