T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation.
BACKGROUND
Neurodegeneration with brain iron accumulation (NBIA) defines a group of genetic disorders characterized by brain iron deposition and associated with neuronal death. The known causes of NBIA include pantothenate kinase-associated neurodegeneration (PKAN), neuroferritinopathy, infantile neuroaxonal dystrophy (INAD), and aceruloplasminemia.


OBJECTIVE
To define the radiologic features of each NBIA subtype.


METHODS
Brain MRIs from patients with molecularly confirmed PKAN (26 cases), neuroferritinopathy (21 cases), INAD (four cases), and aceruloplasminemia (10 cases) were analyzed blindly to delineate patterns of iron deposition and neurodegeneration.


RESULTS
In most cases of PKAN, abnormalities were restricted to globus pallidus and substantia nigra, with 100% having an eye of the tiger sign. In a minority of PKAN cases there was hypointensity of the dentate nuclei (1/5 on T2* sequences, 2/26 on fast spin echo [FSE]). In INAD, globus pallidus and substantia nigra were involved on T2* and FSE scans, with dentate involvement only seen on T2*. By contrast, neuroferritinopathy had consistent involvement of the dentate nuclei, globus pallidus, and putamen, with confluent areas of hyperintensity due to probable cavitation, involving the pallida and putamen in 52%, and a subset having lesions in caudate nuclei and thalami. More uniform involvement of all basal ganglia and the thalami was typical in aceruloplasminemia, but without cavitation.


CONCLUSIONS
In the majority of cases, different subtypes of neurodegeneration associated with brain iron accumulation can be reliably distinguished with T2* and T2 fast spin echo brain MRI, leading to accurate clinical and subsequent molecular diagnosis.
McNeill
A
A
Department of Neurology, Regional Neurosciences Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Birchall
D
D
Hayflick
S J
SJ
Gregory
A
A
Schenk
J F
JF
Zimmerman
E A
EA
Shang
H
H
Miyajima
H
H
Chinnery
P F
PF
D000293:Adolescent; D000328:Adult; D000368:Aged; D001052:Apoferritins; D001923:Brain Chemistry; D002570:Ceruloplasmin / Q000172:deficiency; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005060:Europe; D005260:Female; D005293:Ferritins / Q000235:genetics; D054522:Group VI Phospholipases A2 / Q000172:deficiency / Q000235:genetics; D006801:Humans; D007501:Iron / Q000032:analysis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D019150:Neuroaxonal Dystrophies / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009656:North America; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies
C507433:FTL protein, human; D005293:Ferritins; D001052:Apoferritins; D007501:Iron; D002570:Ceruloplasmin; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human