Neurodegeneration with Brain Iron Accumulation (NBIA): MRI

Case Report: 

32 yr old lady of non consanguineous parents  with  two decades history of seizures, altered behavior (no   definite extrapyramidal symptoms) , shows on MRI , symmetrical regions of  relative low signal foci on all sequences  including SWI ,in basal ganglia  (globus pallidi  more than others),  midbrain in the substantial nigra  location (possible red nuclei ) with  non age matched ex vacuo findings  of ventricles, hippocampi, sulcal spaces , with  focal  band of differential signal in  midbrain component and unremarkable cerebellar hemispheres, suggesting  possible heavy metal accumulation  including  NBIA (Neuro degeneration with brain iron accumulation). Systemic work up including heart, liver and kidneys align with  genetic profiling would help.

Discussion by Dr MGK Murthy,  Dr A Satish &  Dr GA prasad 

Neurodegeneration with brain iron accumulation (NBIA) - NBIA  disorders  have typically symmetrical accumulation of Iron in  parts of grey matter  which  normally are  rich in  Iron content , i. e. Basal ganglia (Globi pallidi /Putamen) / Thalamus / Midbrain (Substantia nigra / Red nuclei) cerebellum (Dentate nuclei)  with each of the appx 10 varieties  demonstrating  relatively unique pattern , Permitting imaging  classification

This group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. At least ten types and their associated genes are recognized. The age of onset ranges from infancy to late adulthood; the rate of progression varies. Generalized cerebral atrophy and cerebellar atrophy are also frequently observed. The diagnosis is usually first suspected when brain MRI findings suggest abnormal brain iron accumulation.

An important initial distinction between NBIA and other conditions that lead to both extrapyramidal findings and abnormal basal ganglia signal is the nature of the T2 signal. NBIA disorders produce a characteristic hypointensity of the basal ganglia, while other disorders, such as mitochondrial encephalopathies, organic acidurias, and abnormalities of cofactor metabolism, feature T2 hyperintensity . Furthermore, NBIA typically leads to a symmetric, homogeneous hypointensity, in contrast to the pattern seen with extravasated blood products. Furthermore, iron deposition typically also appears hypointense on both DWI and ADC sequences, which can further confirm the diagnosis.

Other metal accumulation disorders -

Wilson disease can also be associated with T2 hypointensity of the deep gray nuclei, although typically the signal change associated with Wilson's is more heterogeneous and may feature prominent concurrent hyperintensities.

Calcium can also produce T2 hypointensity. In ambiguous cases, CT may be of great use in distinguishing calcium (hyperdense) from iron (isodense). Symmetric deposition of calcium may occur in inherited calcinoses (Fahr disease) or in hyper- or hypoparathyroidism and can be associated with extrapyramidal findings on examination.

Inherited disorder of manganese accumulation - leads to T1 hyperintensity of the caudate, putamen, and globus pallidus, similar to the pattern seen in environmental manganism.

Management.

• Treatment of manifestations: Intrathecal or oral baclofen, oral trihexyphenidyl, intramuscular botulinum toxin, and deep brain stimulation to treat dystonia; services for the blind, educational programs, assistive communication devices; adaptive aids (walkers, wheelchairs) for gait abnormalities.
• Prevention of secondary complications: Adequate nutrition through swallowing evaluation, dietary assessment, gastrostomy tube feeding as needed.
• Surveillance: Evaluation for treatable causes of pain during episodes of extreme dystonia; monitoring of height and weight; routine ophthalmologic assessment; regular assessments of ambulation and speech abilities