Transcranial brain sonography findings in Parkinson’s disease: implications for pathogenesis, early diagnosis and therapy

Abstract

In Parkinson’s disease (PD) transcranial sonography (TCS) reveals changes of several deep brain structures that are related to distinct motor and nonmotor features. Approximately 90% of PD patients exhibit substantia nigra (SN) hyperechogenicity, which is stable over time and discriminates PD from atypical parkinsonian disorders. Since this TCS feature is also present in 9% of healthy adults aged 18–80 years, and is associated with a subclinical malfunction of the nigrostriatal dopaminergic system, it is considered to be a risk marker for PD. SN hyperechogenicity is caused by increased amounts of iron, probably in abnormal protein bindings, and could be related in some cases to mutations of genes involved in iron metabolism. Influencing the disturbances of iron metabolism reflected by SN hyperechogenicity early in life might become a future therapeutic target for PD. Longitudinal studies currently assess the value of SN hyperechogenicity in combination with clinical and other neuroimaging findings in predicting an individual high risk of PD. TCS has the potential of a cost–effective, quick and mobile screening tool for risk populations within a stepwise diagnostic scheme to select individuals for upcoming neuroprotective therapies. This review summarizes TCS findings, shedding light on the pathophysiology of PD, and discusses their potential therapeutic relevance.

Keywords::

• atypical parkinsonian syndromes
• brainstem raphe
• caudate nucleus
• disease progression
• iron metabolism
• monogenic parkinsonism
• neuroprotection
• Parkinson’s disease
• substantia nigra
• transcranial ultrasound

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

^*In patients with dementia with Lewy bodies and patients with corticobasal degeneration a bilateral symmetric marked SN hyperechogenicity is usually found [71,111].

^‡Approximately a third of patients with progressive supranuclear palsy exhibit moderate-to-marked SN hyperechogenicity; sonographic discrimination from PD is usually possible by the combined finding of lenticular nucleus hyperechogenicity and dilatation of third ventricle >10 mm (minimally measured width) [21].

PD: Parkinson’s disease; SN: Substantia nigra.