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399 lines
34 KiB
Markdown
399 lines
34 KiB
Markdown
---
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title: "Neurodegeneration With Brain Iron Accumulation (NBIA)"
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docid: "8e3465d1-d058-48d8-863c-1fd85cc6caee"
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authors:
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- key: "b2e6dabb-ee1c-42a4-a332-9f0814c1c607"
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value: "Surjith Vattoth, MD, FRCR"
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breadcrumbs:
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name: "Brain"
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slug: "brain"
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name: "Diagnosis"
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slug: "diagnosis"
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treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
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name: "Pathology-Based Diagnoses"
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slug: "pathology-based-diagnoses"
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treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
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-
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name: "Inherited Metabolic/Degenerative Disorders"
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slug: "inherited-metabolicdegenerative-di-"
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treeNodeId: "84bf5d29-d01f-4001-8f6b-51ceefdbf32d"
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name: "Miscellaneous"
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slug: "miscellaneous"
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treeNodeId: "d463e98a-acd6-436d-9bc5-1ef8c667dd95"
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-
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name: "Neurodegeneration With Brain Iron Accumulation (NBIA)"
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slug: "neurodegeneration-with-brain-iron--"
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treeNodeId: null
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category: "Brain"
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cmeTopicId: "30331746-4ad3-456c-9296-1df20916ce7d"
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documentVersionId: "46d35d10-d80a-4d5f-9d42-d9c0b2cbf934"
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imageCount: 15
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lastUpdated: "08/04/20"
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pageDescription: "Neurodegeneration With Brain Iron Accumulation (NBIA)"
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pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Inherited Metabolic/Degenerative Disorders, Miscellaneous, Neurodegeneration With Brain Iron Accumulation (NBIA)"
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pageTitle: "Neurodegeneration With Brain Iron Accumulation (NBIA) | STATdx"
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enhancedTitle: "Neurodegeneration With Brain Iron Accumulation (NBIA)"
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type: "DX"
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references: true
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breadcrumbs:
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- "Brain"
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- "Diagnosis"
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- "Pathology-Based Diagnoses"
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||
- "Inherited Metabolic/Degenerative Disorders"
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- "Miscellaneous"
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- "Neurodegeneration With Brain Iron Accumulation (NBIA)"
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---
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# KEY FACTS
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- ## Terminology
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- Neurodegeneration with brain iron accumulation (NBIA)
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- ## Imaging
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- Characteristic findings of 10 NBIA subtypes, in addition to excess iron hypointense in T2/GRE/SWI
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- Pantothenate kinase-associated neurodegeneration **(PKAN)**: "Eye of tiger sign" in globus pallidus (GP)
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- Phospholipase-associated neurodegeneration **(PLAN)**: Cerebellar vermis & hemisphere atrophy in 95%
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- Fatty acid hydroxylase-associated neurodegeneration **(FAHN)**:****Progressive brainstem & cerebellum atrophy
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- β-propeller protein-associated neurodegeneration **(BPAN)**: Iron earliest & maximum in substantia nigra (SN)
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- Pathognomonic oblique T1 high signal in SN
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- Mitochondrial membrane protein-associated neurodegeneration **(MPAN)**: Characteristic linear T2 hyperintensity in medial medullary lamina in GP
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- Woodhouse-Sakati syndrome **(WSS)**:****Confluent ↑ T2 periventricular & deep white matter frequent
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- Kufor-Rakeb disease **(KRD)**:****↓ striatal uptake in 123-Ioflupane (DaT scan) SPECT (like Parkinson/-plus)
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- Aceruloplasminemia **(ACP)**:****Widespread excessive iron; maximum degree of deposition among all NBIAs
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- Neuroferritinopathy **(NFT)**: Bilateral symmetric cystic degeneration lined by iron deposits in basal ganglia
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- Coenzyme A synthase (COASY) protein-associated neurodegeneration **(CoPAN)**: Early in disease, swollen, ↑ T2 caudate & putamina, & mild ↑ T2 in thalami
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- ## Top Differential Diagnoses
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- Wilson disease, Huntington disease, normal aging
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- ## Pathology
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- Genetic mutations specific for each subtype
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- PKAN: Pantothenate kinase 2 (*PANK2*) gene
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- Iron directly causes or facilitates cellular injury, or is consequence of axonal disruption
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- ## Clinical Issues
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- Extrapyramidal signs; NFT & ACP in adults, others younger
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- Most common is PKAN
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- ## Diagnostic Checklist
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- Look for characteristic imaging signs to differentiate subtypes when excessive iron deposition noted in T2/GRE/SWI
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# TERMINOLOGY
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- ## Abbreviations
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- Neurodegeneration with brain iron accumulation (NBIA)
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- Pantothenate kinase-associated neurodegeneration (PKAN)
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- Phospholipase-associated neurodegeneration (PLAN)
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- Fatty acid hydroxylase-associated neurodegeneration (FAHN)
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- β-propeller protein-associated neurodegeneration (BPAN)
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- Mitochondrial membrane protein-associated neurodegeneration (MPAN)
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- Woodhouse-Sakati syndrome (WSS)
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- Kufor-Rakeb disease (KRD)
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- Aceruloplasminemia (ACP)
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- Neuroferritinopathy (NFT)
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- Coenzyme A synthase (COASY) protein-associated neurodegeneration (CoPAN)
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- ## Synonyms
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- PKAN: **Hallervorden-Spatz syndrome**
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- PLAN: **Infantile neuroaxonal dystrophy (INAD)** or **Seitelberger disease**
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- Atypical PLAN: Atypical neuroaxonal dystrophy **(ANAD)**
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- BPAN: Static encephalopathy of childhood with neurodegeneration in adulthood******(****SENDA****)**
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- ## Definitions
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- Group of neurologic disorders with progressive extrapyramidal symptoms, intellectual impairment, & excessive brain iron deposition in MR
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# IMAGING
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- ## General Features
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- ### Best diagnostic clue
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- **PKAN**: Eye of tiger sign: Bilateral ↓ T2/GRE/SWI in globi pallidi (GP) with central focus of ↑ signal
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- Normal to excessive iron in substantia nigra (SN)
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- White matter (WM) abnormality typically absent
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- **PLAN:****Cerebellar**vermis & hemisphere **atrophy** in 95% (precedes iron deposition) in **INAD**; not early in ANAD
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- Abnormal posterior aspect of corpus callosum constant finding; **thin splenium**, can be vertical
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- **Enlarged clava** (dorsal bulge in medulla by gracile nucleus) may be 1st MR finding in INAD
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- **Optic atrophy**; ↑ T2 cerebellum & putamen
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- Excessive **iron in 50%**; typically in GP
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- May have excessive iron in SN & subthalamic nuclei in INAD; not commonly in ANAD
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- **FAHN**: Excessive iron in bilateral GP, may be in SN also
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- **Optic atrophy**; ↑ T2 subcortical & periventricular WM
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- Mild cortical atrophy &**callosal**thinning
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- Progressive **brainstem** & cerebellum atrophy
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- **BPAN**: Excessive iron **earliest & maximum in SN** (compared to GP); brain atrophy common
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- Pathognomonic bilateral symmetric linear **oblique** **T1 high signal in SN** with central low-T1 band
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- **MPAN**: Excessive iron in GP always, SN almost always
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- **Linear** **T2 hyperintensity in medial medullary lamina** between GP interna & externa (in 1/5 of cases)
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- Cortical & cerebellar atrophy less common
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- **Optic atrophy** in juvenile-onset MPAN (like PLAN)
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- **WSS**: Excessive iron in GP inconsistently; may show hyperintense medial medullary lamina (like MPAN)
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- Confluent ↑ T2 periventricular & deep WM frequent
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- **KRD**: Generalized cerebral & cerebellar atrophy
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- Excessive iron in GP, SN, putamen, & caudate in some
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- **Markedly reduced** bilateral symmetrical striatal uptake in dopamine transporter imaging with **123-Ioflupane (DaT scan)**SPECT (like parkinsonism/Parkinson-plus)
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- **ACP: Widespread** excessive iron**(maximum degree among all NBIAs)**in GP, putamen, caudate, thalamus, SN, red nuclei, dentate nuclei (DN)
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- May see iron in cerebral & cerebellar**cortex**
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- Prominent T2 hyperintensity in WM common
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- Cerebral & cerebellar atrophy common
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- **NFT**: Bilateral symmetric **cystic** degeneration **lined by iron** deposits in caudate, putamen, GP, SN, & DN
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- Iron deposition in **frontal lobe** may be seen
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- Mild cerebral & cerebellar atrophy may be seen
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- Rarely, eye of tiger sign
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- **CoPAN**: Extremely rare NBIA;****excessive iron in GP & SN
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- Early in disease, swollen, ↑ T2 bilateral caudate & putamina, & mild ↑ T2 in dorsomedial thalami
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- Disappear later when iron deposition predominates
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- Calcification in CT mimicking eye of tiger in MR
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- ## Imaging Recommendations
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- ### Best imaging tool
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- MR with T2* (gradient echo) or SWI
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- ## CT Findings
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- ### NECT
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- Cerebellar & cerebral atrophy
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- Identify calcifications in basal ganglia & cortical/subcortical regions which may mimic hypointensity of iron in T2/GRE/SWI MR
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- ## MR Findings
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- ### T1WI
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- Pathognomonic bilateral symmetric linear oblique T1 high signal in SN, with central low-T1 band in BPAN
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- ### T2WI
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- GP hypointensity with central hyperintensity of GP interna: Eye of tiger sign in PKAN
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- Can see only T2 hyperintensity early in disease
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- May also be seen in NFT
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- GP, ± other deep nuclei & cortex dark in varying patterns, without eye of tiger = other NBIA
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- GP normally hypointense on T2, at 3T, or above
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- ### T2* GRE
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- Accentuated T2-hypointense findings; maximum in SWI
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- Imaging findings do not always correlate with clinical symptoms
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# DIFFERENTIAL DIAGNOSIS
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- [Eye of Tiger (PKAN) in Other Disorders](/document/parkinson-disease/0bc3188a-935b-416d-b1a0-25b2d52c6399)
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- Rarely reported in NFT, corticobasal degeneration, multiple system atrophy, healthy adults
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- ## Cerebellar Atrophy & Cortical T2 Hyperintensity (PLAN) in Other Disorders
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- Congenital disorder of glycosylation, neuronal ceroid lipofuscinosis, GM2 gangliosidosis
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- ## Cerebellar & Optic Atrophy (PLAN) in Other Disorders
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- Juvenile MPAN, FAHN, Wolfram syndrome, optic atrophy 1
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- ## Cystic Changes in Basal Ganglia (NFT) in Other Disorders
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- Hypoxic-ischemic encephalopathy, carbon monoxide poisoning, chronic lacunar infarcts, chronic microhemorrhages, enlarged perivascular spaces
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- [Deep Brain Nuclei Iron Deposition in Other Disorders](/document/multiple-sclerosis/7892b2a2-f52a-4d7f-9858-a326f2b7ab04)
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- Iron accumulation in basal ganglia associated with MS
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- Wilson disease, Huntington disease ↑ iron in deep nuclei
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- [Superficial Siderosis](/document/superficial-siderosis-classical/e3125353-614e-43ce-a00d-eeefedbd9d9b)
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- Hemosiderin deposits in subpial layers of brain & spinal cord
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- May mimic cortical iron deposits in ACP & NFT
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- ## Hemochromatosis
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- Liver & spleen usually affected before CNS
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- [Normal Iron Deposition](/document/normal-aging-brain/2a315550-b2ea-4afe-a2ef-f93a2209f276)
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- Imaging at 3T, with normal aging
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# PATHOLOGY
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- ## General Features
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- ### Genetics
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- **Autosomal recessive:** **PKAN**: Pantothenate kinase 2 (*PANK2*) gene on chromosome 20p13
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- **PLAN**: Calcium-independent phospholipase A2 (*PLA2G6*) gene on chromosome 22q13.1
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- **FAHN**: Fatty acid 2 hydroxylase (*FA2H*) gene on chromosome 16q23.1
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- **MPAN**: *C19orf12*gene on chromosome 19q12
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- **WSS**:****C2orf37 (*DCAF17*) gene on chromosome 2q31.1
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- **KRD**: *ATP13A2* gene on chromosome 1p36.13
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- **ACP**:****Ceruloplasmin (*CP**)*gene on chromosome 3q24-q25.1
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- **CoPAN**:****Coenzyme A synthase**(*COASY*) gene on chromosome 17q21.2
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- **Autosomal dominant:******NFT**:**Ferritin light-polypeptide (*FTL*) gene on chromosome 19q13.33
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- **X-linked dominant: BPAN**: Heterozygous mutation of *WDR45*gene on Xp11.23
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- ## Gross Pathologic & Surgical Features
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- **Eye of tiger in PKAN**: GP central T2 hyperintensity due to neuronal loss, gliosis, & cavitation of neuropil
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- Central T2 hyperintensity can be predominant MR finding in presymptomatic patients (iron deposition may be cause or effect); surrounding GP T2 hypointensity develops gradually as PKAN progresses, becoming dominant MR finding later
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- **SN linear high T1 in BPAN**: Iron binding to neuromelanin released from dying SN pars compacta pigmented cells
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- ## Microscopic Features
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- Iron accumulation in GP & SN, neuronal loss, axonal swellings (spheroids)
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- Neurofibrillary tangles & Lewy bodies suggest shared pathway with Alzheimer & Parkinson diseases
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- Iron in liver greater than that in basal ganglia in ACP
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# CLINICAL ISSUES
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- ## Presentation
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- ### Most common signs/symptoms
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- **PKAN: Typical**: (< 6 years, 90% of cases) presents with gait or postural difficulties; later both pyramidal & extrapyramidal symptoms with oromandibular dystonia
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- Night blindness & visual field constriction common; 2/3 have abnormal electroretinograms
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- Clinical signs of pigmentary retinal degeneration in 40% only
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- Wheelchair bound by 10-15 years
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- **Atypical**: Mutations allowing partial enzyme function; delayed onset, milder disease
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- Mainly speech & neurocognitive symptoms
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- Rather than extrapyramidal symptoms
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- **PLAN: INAD**: Asymptomatic at birth; developmental delay starts at 6-18 months
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- Rapid progression with language & motor regression, muscular weakness, hypotonia → spastic quadriplegia
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- Muscular weakness → feeding/breathing difficulty → frequent pneumonia
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- Visual symptoms due to optic atrophy, nystagmus, strabismus
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- Cerebellar signs, sensory abnormalities, including peripheral neuropathy
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- **ANAD**: Presents between 1.5-6.5 years with parkinsonism & dystonia
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- Pyramidal symptoms, abnormal eye movements, cognitive decline
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- Subacute onset of dystonia-parkinsonism linked to *PLA2G6* gene mutation presenting in late adolescence or early adulthood described
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- **FAHN**:****Early-onset gait abnormalities, spastic quadriparesis, ataxia, dystonia, seizures, strabismus
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- *FA2H*-gene mutations have association with leukodystrophies & hereditary spastic paraplegia with clinical picture overlaps
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- **BPAN: SENDA**: Global developmental delay in early childhood (static encephalopathy of childhood)
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- Seizures, spasticity, & sleep disorders may be seen in early childhood
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- Neurodegeneration in early adulthood with parkinsonian features, dystonia, & cognitive decline
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- **MPAN**: Presents at 4-30 years (mean: 11 years)****with cognitive decline, neuropsychiatric disorders, motor neuronopathy, & peripheral neuropathy
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- **Juvenile onset** with optic atrophy or **adult onset** with parkinsonian features
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- **WSS**: Progressive dystonia ± choreoathetosis; progressive cognitive decline
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- Specific flat T wave in ECG, polyendocrinopathy (diabetes, hypogonadism), dysmorphic facies, alopecia, sensorineural hearing loss
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- **KRD**:****Originally described in Jordanian family from Kufor-Rakeb village; adolescent patients with levodopa-responsive parkinsonism & pyramidal signs; psychotic episodes with visual hallucinations
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- **ACP:****Adult-onset triad** of diabetes, retinal degeneration, & neurologic symptoms (movement disorders & dementia)
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- Low-serum copper & iron, **high-serum ferritin**, extremely low ceruloplasmin
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- Microcytic anemia responsive to ceruloplasmin rather than iron
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- **NFT: Adult-onset**extrapyramidal features & spasticity
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- Neurocognitive decline is usually late
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- **Low-serum ferritin** (ACP has high-serum ferritin)
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- **CoPAN**: Early-onset spastic-dystonic paraparesis
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- Later develop parkinsonian features, cognitive decline, obsessive-compulsive behavior, axonal neuropathy
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- *COASY* gene can be associated with pontocerebellar hypoplasia type 12
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- ## Treatment
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- Symptom palliation: Medications & deep brain stimulator
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- ACP: Iron chelation with desferrioxamine & ceruloplasmin from fresh frozen plasma
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6495a951-3f64-4979-ad63-60cd111bff50
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## References
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# Selected References
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1. [Brezavar D et al: Incidence of PKAN determined by bioinformatic and population-based analysis of ~140,000 humans. Mol Genet Metab. ePub, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31540697%5Bpmid%5D)
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1. [Christoforou S et al: Early-onset presentation of a new subtype of β-Propeller protein-associated neurodegeneration (BPAN) caused by a de novo WDR45 deletion in a 6 year-old female patient. Eur J Med Genet. 103765, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31536831%5Bpmid%5D)
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1. [Dusek P et al: Brain iron and metabolic abnormalities in C19orf12 mutation carriers: a 7.0 tesla MRI study in mitochondrial membrane protein-associated neurodegeneration. Mov Disord. 128(4):463-9, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31518459%5Bpmid%5D)
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1. [Levi S et al: Iron pathophysiology in neurodegeneration with brain iron accumulation. Adv Exp Med Biol. 1173:153-77, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31456210%5Bpmid%5D)
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1. [Arber C et al: Insights into molecular mechanisms of disease in neurodegeneration with brain iron accumulation; unifying theories. Neuropathol Appl Neurobiol. 42(3):220-41, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=25870938%5Bpmid%5D)
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1. [Amaral LL et al: Neurodegeneration with brain iron accumulation: clinicoradiological approach to diagnosis. J Neuroimaging. 25(4):539-51, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25545045%5Bpmid%5D)
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1. [Dusek P et al: Wilson disease and other neurodegenerations with metal accumulations. Neurol Clin. 33(1):175-204, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25432729%5Bpmid%5D)
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1. [Hogarth P: Neurodegeneration with brain iron accumulation: diagnosis and management. J Mov Disord. 8(1):1-13, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25614780%5Bpmid%5D)
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1. [Levi S et al: Neuroferritinopathy: from ferritin structure modification to pathogenetic mechanism. Neurobiol Dis. 81:134-43, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25772441%5Bpmid%5D)
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1. [Miyajima H: Aceruloplasminemia. Neuropathology. 35(1):83-90, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25168455%5Bpmid%5D)
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1. [Vroegindeweij LH et al: Aceruloplasminemia: neurodegeneration with brain iron accumulation (NBIA) associated with parkinsonism. J Inherit Metab Dis. 38(2):375-6, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25413956%5Bpmid%5D)
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1. [Gregory A et al: Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet. 46(2):73-80, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=18981035%5Bpmid%5D)
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1. [Gregory A et al: Neurodegeneration associated with genetic defects in phospholipase A(2). Neurology. 71(18):1402-9, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18799783%5Bpmid%5D)
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1. [Kurian MA et al: Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN). Neurology. 70(18):1623-9, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18443314%5Bpmid%5D)
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1. [McNeill A et al: T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation. Neurology. 70(18):1614-9, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18443312%5Bpmid%5D)
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1. [Hartig MB et al: Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. Ann Neurol. 59(2):248-56, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16437574%5Bpmid%5D)
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1. [Hayflick SJ et al: Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations. AJNR Am J Neuroradiol. 27(6):1230-3, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16775270%5Bpmid%5D)
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1. [Matarin MM et al: PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease. Neurosci Lett. 407(2):162-5, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16962235%5Bpmid%5D)
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## Images
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### Selected Images
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*Axial T2WI MR in PKAN (Hallervorden-Spatz syndrome), the most common NBIA, shows classic eye of the tiger sign. Note globi pallidi (GP) hypointensity <img src='img/arrows/CC.png'/> due to iron deposition with central hyperintensity <img src='img/arrows/CS.png'/> due to neuronal loss, gliosis, & cavitation of neuropil. The central T2 hyperintensity can be predominant MR finding initially with surrounding GP T2 hypointensity developing later.*
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*Axial T2WI MR in PKAN (Hallervorden-Spatz syndrome), the most common NBIA, shows classic eye of the tiger sign. Note globi pallidi (GP) hypointensity <img src='img/arrows/CC.png'/> due to iron deposition with central hyperintensity <img src='img/arrows/CS.png'/> due to neuronal loss, gliosis, & cavitation of neuropil. The central T2 hyperintensity can be predominant MR finding initially with surrounding GP T2 hypointensity developing later.*
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*Axial T2WI MR in PKAN (Hallervorden-Spatz syndrome), the most common NBIA, shows classic eye of the tiger sign. Note globi pallidi (GP) hypointensity <img src='img/arrows/CC.png'/> due to iron deposition with central hyperintensity <img src='img/arrows/CS.png'/> due to neuronal loss, gliosis, & cavitation of neuropil. The central T2 hyperintensity can be predominant MR finding initially with surrounding GP T2 hypointensity developing later.*
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*Axial T2WI MR in PKAN (Hallervorden-Spatz syndrome), the most common NBIA, shows classic eye of the tiger sign. Note globi pallidi (GP) hypointensity <img src='img/arrows/CC.png'/> due to iron deposition with central hyperintensity <img src='img/arrows/CS.png'/> due to neuronal loss, gliosis, & cavitation of neuropil. The central T2 hyperintensity can be predominant MR finding initially with surrounding GP T2 hypointensity developing later.*
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*Axial T2WI MR in PKAN (Hallervorden-Spatz syndrome), the most common NBIA, shows classic eye of the tiger sign. Note globi pallidi (GP) hypointensity <img src='img/arrows/CC.png'/> due to iron deposition with central hyperintensity <img src='img/arrows/CS.png'/> due to neuronal loss, gliosis, & cavitation of neuropil. The central T2 hyperintensity can be predominant MR finding initially with surrounding GP T2 hypointensity developing later.*
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*Axial SWI MR in an 8-year-old boy with MPAN shows excess iron in GP with characteristic hyperintensity in medial medullary lamina <img src='img/arrows/CC.png'/>.*
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*Axial SWI MR (left) in a 14-year-old girl with BPAN shows excessive iron, maximum in substantia nigra (SN) <img src='img/arrows/CC.png'/>, compared to GP <img src='img/arrows/CO.png'/>. Axial T1WI MR (right) shows the pathognomonic bilateral symmetric linear oblique T1 high signal in SN with central low-T1 band <img src='img/arrows/CS.png'/>.*
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*Axial FLAIR MR in a 20-month-old boy with PLAN (INAD) shows progressive cerebellar atrophy with increased cortical signal <img src='img/arrows/CS.png'/>. This can also be seen in CDG1A, NCL, GM2 gangliosidosis, etc. Abnormal iron is seen in 50% PLAN patients only (not in this case).*
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*Coronal T2WI MR in an 18-year-old woman with Woodhouse-Sakati syndrome (WSS) shows mild confluent hyperintensities in the cerebral periventricular <img src='img/arrows/CS.png'/> & cerebellar peridentate white matter <img src='img/arrows/CO.png'/>.*
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*Axial SWI MR in the same patient shows bilateral mild increased GP iron deposition <img src='img/arrows/CC.png'/>. Note the hyperintense medial medullary lamina <img src='img/arrows/CS.png'/> in between GP interna & externa (like in MPAN). Also notice the excessive iron deposition in the bilateral lateral ventricle trigone choroid plexus <img src='img/arrows/CO.png'/> in this WSS patient.*
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*Axial T2WI MR in a 43-year-old woman with neuroferritinopathy (NFT) shows cystic degeneration lined by iron deposits in the bilateral putamina <img src='img/arrows/CC.png'/> & GP <img src='img/arrows/CS.png'/>. Bilateral caudate nuclei also had similar findings (not shown).*
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*Axial SWI MR in the same patient shows excess iron deposition in the GP & putamina, which also lines the cystic degeneration. Iron deposition in frontal lobes & mild cerebral & cerebellar atrophy may be seen. Rarely, eye of the tiger sign (characteristic of PKAN) may be seen in NFT.*
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*Axial T2* GRE MR in an adult with aceruloplasminemia (ACP) shows marked hypointensity related to iron deposition in the dentate nuclei <img src='img/arrows/CS.png'/> of cerebellum.*
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*Axial SWI MR in the same patient shows diffuse linear hypointense iron deposition in the cortex <img src='img/arrows/CS.png'/>, basal ganglia <img src='img/arrows/CO.png'/>, & thalami <img src='img/arrows/CC.png'/>. ACP shows widespread excessive iron deposition, maximum degree among all NBIAs. Prominent T2 hyperintensity in WM & brain atrophy are common. Serum ferritin is high in ACP but low in NFT, both adult-onset NBIA.*
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### Additional Images
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*Axial DWI with zero B value MR shows symmetric hypointensity within the GP with subtle "blooming" secondary to susceptibility artifact from iron. These findings are characteristic of NBIA, an umbrella term that includes former Hallervorden-Spatz syndrome without "eye of the tiger."*
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*Axial T1WI MR shows hyperintensity in the GP <img src='img/arrows/WS.png'/> related to iron deposition in this patient with ACP.*
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*Axial FLAIR MR demonstrates the eye of the tiger appearance in a 5-year-old boy diagnosed with cerebral palsy. The hypointense signal <img src='img/arrows/WS.png'/> surrounding the central pallidal hyperintensity is somewhat subtle. The findings are typical of PKAN, formerly known as Hallervorden-Spatz syndrome.*
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*Axial zero B DWI MR accentuates the T2 hypointensity <img src='img/arrows/WS.png'/> of the iron deposition in this patient with PKAN. Note the classic eye of the tiger appearance. This sequence is often referred to as the "poor man's GRE" as it shows "blooming" of blood products and mineral deposition, similar to the T2* sequences.*
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*Axial T2WI MR shows symmetric hypointensity within the GP <img src='img/arrows/WO.png'/>. The eye of the tiger sign is absent; therefore, this is not PKAN. These findings are characteristic of NBIA.*
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