Brain parenchyma sonography detects preclinical parkinsonism

Abstract

Substantia nigra (SN) hyperechogenicity on brain parenchyma sonography (BPS) is highly characteristic for idiopathic PD. We studied 7 symptomatic and 7 asymptomatic parkin mutation carriers (PMC) from a large kindred with adult-onset parkinsonism. BPS revealed larger SN echogenic sizes in PMC with parkin mutations on both alleles (homozygous, compound-heterozygous), compared to PMC with only one mutated allele (Mann-Whitney U test, P = 0.007). In symptomatic PMC, larger SN echogenic size was correlated with younger age at onset of the disease (Spearman rank correlation, Rho = -0.937, P = 0.002) but not with age, disease duration, or disease severity. BPS demonstrated SN hyperechogenicity, in concordance with abnormal nigrostriatal (18)F-dopa positron emission tomography (PET), in all symptomatic and 3 asymptomatic PMC. In 2 asymptomatic PMC, PET and BPS were normal. However, in another 2 asymptomatic PET-normal PMC, SN hyperechogenicity could be detected. Data suggest SN hyperechogenicity as an early marker to detect preclinical parkinsonism.

Imaging Approaches to Parkinson Disease

“…It has been suggested that the presence of midbrain hyperechogenicity is a trait rather than a state marker for susceptibility to parkinsonism and may reflect midbrain iron deposition (13). In support of this viewpoint, midbrain hyperechogenicity has been reported in premanifest monogenic forms of parkinsonism including carriers of a-synuclein, lysine-rich repeat kinase (LRRK2), parkin, and DJ1 mutations (14,15).…”

PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism

“…10,14,16,29 -31 In addition, preclinical changes have been detected in asymptomatic carriers of heterozygous Parkin mutations using positron emission tomography (PET) 32,33 or transcranial ultrasound. 34 Interestingly, haploinsufficiency or a dominant-negative effect have been suggested for heterozygous PINK1 mutations even prior to the identification of the PARK6-related gene: asymptomatic, heterozygous carriers of the PARK6-associated haplotype revealed a significant reduction in caudate (18)F-dopa uptake in a PET study in comparison with controls. 35 However, the potential pathogenic role of heterozygous mutations in 'recessive genes' remains a matter of vivid debate.…”

Imaging of genetic and degenerative disorders primarily causing Parkinsonism

“…This finding is not specific for PD, however, as 10% of elderly normals and 15% of essential tremor cases have also been reported show increased midbrain echogenicity. TCS has also been reported to be abnormal in clinically affected GBA mutation carriers (SaundersPullman et al, 2010) and homozygous or compound heterozygote symptomatic parkin gene carriers (Walter et al, 2004). In a five year follow up study of PD cases, however, it was noted that no significant change in TCS signal occurred (Berg et al, 2005).…”

“…However, the positive predicitive value of abnormal TCS in healthy elderly subjects for subsequent development of PD has been estimated to be only 3%. Increased midbrain echogenicity has been reported in asymptomatic parkin gene carriers but only one third of these were found to also have reduced striatal 18 F-dopa uptake (Walter et al, 2004). Subjects who developed idiopathic hyposmia have been investigated with TCS.…”