Transcranial sonography in pantothenate kinase-associated neurodegeneration

Abstract

After it was reported that increased tissue iron concentrations were associated with increased echogenicity of the substantia nigra (SN) obtained with transcranial sonography (TCS) in animal and postmortem studies, our goal was to use this method in a disorder characterized with iron accumulation in human brain tissue. Therefore, magnetic resonance imaging (MRI) and TCS were conducted in 5 unrelated patients with pantothenate kinase-associated neurodegeneration (PKAN), caused by PANK2 mutations. All patients had an eye of the tiger sign. Hypointense lesions on the T2-weighted MRI images were restricted to the globus pallidus (GP) and SN. TCS also revealed bilateral hyperechogenicity restricted to the LN and SN, with normal DTV values. Both TCS and MRI studies in PKAN patients are in accordance with the pathological findings that accumulation of iron, even in advanced cases, is restricted to the GP and SN, suggesting selective involvement of these structures.

Transcranial Brain Parenchymal Sonography in Neurodegenerative and Psychiatric Diseases

“…Our group conducted MRI parallel to transcranial sonography in 5 unrelated patients with pantothenate kinaseassociated neurodegeneration, caused by pantothenate kinase-associated neurodegeneration 2 gene mutations. 26 All patients in our study had an eye of the tiger sign on MRI. Hypointense lesions on the T2-weighted MRI images were restricted to the globus pallidus and substantia nigra.…”

“…Similar findings were observed in some other neurodegenerative diseases with trace metal accumulation. Our group conducted MRI parallel to transcranial sonography in 5 unrelated patients with pantothenate kinase–associated neurodegeneration, caused by pantothenate kinase–associated neurodegeneration 2 gene mutations 26 . All patients in our study had an eye of the tiger sign on MRI.…”

Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)

“…Dopamine transporter (DaT) SPECT imaging, a measure of striatal dopamine function, is generally normal in PKAN, [56,57] although abnormal findings have been reported [42] in line with the clinical experience that PKAN may manifest as parkinsonism [58-61] Cardiac 123I-meta-iodobenzylguanidine (MIBG) imaging which is used to assess postganglionic neuronal function of the sympathetic nervous system was also normal in PKAN, in contrast to PD and other Lewy body disorders where uptake is typically reduced [62]. Transcranial sonography [63,64] demonstrated bilateral hyperechogenicity in the SN and lenticular nucleus. It was thus suggested that transcranial sonography may be used as an inexpensive and simple screening method for the diagnosis of NBIA.…”

Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)

“…Dopamine transporter (DaT) SPECT imaging, a measure of striatal dopamine function, is generally normal in PKAN, [56,57] although abnormal findings have been reported [42] in line with the clinical experience that PKAN may manifest as parkinsonism [58][59][60][61] Cardiac 123I-meta-iodobenzylguanidine (MIBG) imaging which is used to assess postganglionic neuronal function of the sympathetic nervous system was also normal in PKAN, in contrast to PD and other Lewy body disorders where uptake is typically reduced [62]. Transcranial sonography [63,64] demonstrated bilateral hyperechogenicity in the SN and lenticular nucleus. It was thus suggested that transcranial sonography may be used as an inexpensive and simple screening method for the diagnosis of NBIA.…”