Neurodegeneretaion with Brain Iron Accumulation (NBIA) and Normal Brain Iron Accumulation on MRI

Neuromeet

Dr. Tushar Patil

Dept. of Radio Diagnosis

Jehangir Hospital, Pune

16/09/2015

• 59 years / Male

• Presented with vague symptoms

• Generalised weakness

• Bodyache

• MRI brain was done

Axial T2

Axial T2 Axial T1

Axial T2 Axial T1

Axial SW

Differential Diagnosis

• Normal Brain Aging

• Normal Brain Iron Accumulation

• Neurodegeneration with Brain Iron Accumulation (NBIA)

Normal Brain Iron Accumulation

• Iron accumulates in the brain during the process of ageing, corresponds to intraneuronal ferritin.

• May also occur in conjunction with other compounds, such as lipofuscin.

• It may generate local oxidative stress by increasing the concentration of oxygen free radicals and may lead to lipid peroxidation and neurotoxicity.

Normal Brain Iron Accumulation

• Iron accumulation in the brain prominently involves areas related to motor functions, such as

• Basal ganglia, in particular the globus pallidus, as well as the striatum

• Subthalamic nucleus

• Substantia nigra

• Dentate nucleus of the cerebellum

• Also found in the cerebral white matter and cortex

Normal Brain Iron Accumulation

• Iron accumulation in the brain is seen as a T2 hypointensity

• In biologic iron-oxides, Fe+2 typically has fewer unpaired electrons than Fe+3 and is less effective in quenching T2-weighted signal intensity.

• As paramagnetic, Fe+3 catalyzes the nuclear spin relaxation of neighboring water protons.

• SWI can differentiate iron deposition from calcification – iron is associated with a paramagnetic phase shift, whereas calcification causes an opposite diagmagnetic phase shift.

Normal Brain Iron Accumulation

Normal Brain Iron Accumulation

• Iron is normally deposited first within the globuspallidus, then the medial substantia nigra, then the red nucleus, and then the dentate nucleus of the cerebellum.

• With age, iron also accumulates progressively within the putamen and then the caudate nucleus

• Putamen - it usually starts posteriorly, progressing anteriorly with age

Stages of Iron Deposition on MRI

• Initially hyperintense compared with white matter (stage I)

• Isointense (stage II)

• Hypointense compared with both gray and white matter (stage III)

Pathophysiology

• Intracellular iron has an important role in the metabolism of neurotransmitters

• Iron is taken up by capillary endothelial cells in the thalamus and extrapyramidal system via transferrin.

• Iron is subsequently transported along neuronal axons to their sites of projection.

• Iron continues to accumulate at sites of uptake.

• Accumulate proximally due to interruptions of specific axonal projections by multiple causes.

Factors affecting signal

• Greater concentration of paramagnetic substance

• Increased signal/noise ratio (e.g., increasing the TR)

• Prolonged TE

• Longer interecho interval

• Gradient reversal for signal acquisition

• Higher-field-strength scanners

2 years

27 years

80 years

0.5 T

1.5 T

3 T

7 T

Neurodegeneration with Brain Iron Accumulation (NBIA)• NBIA characterizes a class of neurodegenerative

diseases that feature a prominent extrapyramidal movement disorder, intellectual deterioration, and a characteristic deposition of iron in the basal ganglia.

• The diagnosis of NBIA is made on the basis of the combination of representative clinical features along with MR imaging evidence of iron accumulation.

Neurodegeneration with Brain Iron Accumulation (NBIA)• All of the NBIA disorders feature iron deposition

in the globus pallidus but differ in the co-occurrence of other findings.

• All are autosomal recessive except for neuroferritinopathy.

• Disease onset is variable and may range from early childhood to old age.

Pantothenate Kinase Associated Neurodegeneration (PKAN)• Hallervorden Spatz syndrome

• Caused by mutations in PANK2.

• Begins in childhood

• Profound dystonia, dysarthria, spasticity and pyramidal tract signs

• Pigmentary retinopathy, leading to night blindness and visual field constriction

Pantothenate Kinase Associated Neurodegeneration (PKAN)• MR reveals Eye-of-the-tiger Sign.

• Iron deposition in the GP, sometimes in SN.

• Peripheral hypointensity - Preserved iron-laden neuropil, neurons, and astrocytes.

• Central hyperintensity - Gliosis, increased water content, and neuronal loss with disintegration, vacuolization, and cavitation of the neuropil.

Neuroaxonal dystrophy (NAD)

• Mutations in the gene encoding calcium-independent phospholipase A2 (PLA2G6)

• Progressive spasticity, ataxia, and dystonia

• Optic atrophy, peripheral neuropathy, and cognitive impairment

• MRI reveals – Iron deposition in GP

• Significant atrophy of both the cerebellar vermisand hemispheres

• Confluent T2 hyperintensities in white matter

Neuroferritinopathy (NFT)

• Only autosomal dominant form of NBIA

• Caused by mutations in the FTL gene

• Present in adolescence to older adulthood

• Extrapyramidal features like parkinsonism, choreoathetosis, dystonia, tremor, and ataxia.

• MRI reveals - Iron deposition in the putamen, GP and DN

• T2 hyperintensity in the basal ganglia - Cystic cavitation

Aceruloplasminemia (ACP)

• Loss of function mutations in the CP gene, encoding the protein ceruloplasmin

• Present in mid-adulthood

• Blepharospasm, chorea, craniofacial dyskinesias, ataxia, and retinal degeneration

• MRI reveals iron deposition in CN, putamen, GP, thalamus, RN, and DN

• Juxtaposed confluent white matter T2 hyperintensities

• Cerebellar atrophy

Fatty Acid Hydroxylase associated Neurodegeneration (FAHN)• Caused by mutations in FA2H

• Begins with focal dystonia and gait impairment

• MRI reveals iron deposition in GP

• Confluent subcortical and periventricular white matter T2 hyperintensities

• Thinning of the corpus callosum

• Cerebellar and brain stem atrophy

Kufor-Rakeb syndrome (KRS)

• Caused by mutations in the ATP13A2 gene

• Parkinsonism, anarthria, spastic paraparesis, and pyramidal tract signs

• Facial-faucial finger mini-myoclonus

• MRI reveals GP, CN and putamen

• Generalized cerebral, cerebellar, and brain stem atrophy, along with progressive atrophy of the pyramids

Woodhouse-Sakati syndrome (WSS)• Mutations in c2orf37, encoding a nucleolar

protein

• progressive dystonia, with or without choreoathetosis

• Endocrine dysfunction, alopecia, SNHL

• MRI reveals GP

• Widespread confluent and marked periventricular T2 white matter hyperintensities

Static Encephalopathy of childhood with NeuroDegeneration in Adulthood (SENDA)

• Begins with early childhood intellectual impairment

• In adulthood, affected patients develop severe dystonia-parkinsonism

• MRI reveals iron deposition in the GP and SN

• T1 hyperintensity of the SN with a central band of T1 hypointensity

• Significant cerebral and milder cerebellar atrophy

Thank you