Differential Diagnosis of Intra-Axial Brain Tumor based on appearance in Adults

Intra-axial: 75% astrocytic tumor or mets

Tumors that invade the corpus callosum and cross midline
- GBM (rarely has leptomeningeal spread)
- Lymphoma (can have leptomeningeal spread, typically homogenously enhancing but in immunocompromised hosts can appear ring-enhancing or heterogenous)
- Mets (can have leptomeningeal enhancement, often cystic)

Multiple lesions
- usually mets
- multifocal GBM - rarer but exists
- gliomatosis cerebri
- lymphoma can appear as multiple lesions
- CNS metatstases - i.e. medulloblastoma, ependymoma, oligodendro
Genetic diseases that cause multiple tumors :
- NF1 (optic glioma, astrocytoma)
- NF2 (meningiomas, schwannoma, ependymoma of brain and spinal cord)
- Tuberous Sclerosis (SEGA, ependymoma)
- VHL (cerebellar/retinal/spinal cord hemangioblastomas, endolymphatic sac tumor)

Cortical-based

Oligodendro
- often cortical/subcortical, and are shown on MRI "extending all the way to the cortex"
- classically frontal but can be in any lobe.
- 70-90% calcified.
- usually T1 dark, T2 bright (except calcified areas - which will show up as T2 dark/T2* blooming
- 50% will enhance with Gad - usually heterogenously. Gad enhancement is not a reliable indicator of grade.
- Typically do not restrict on DWI. Often older people (40-50s+)

Ganglioglioma
- mix of glial and neuronal cells (if the glial component de-differentiates it turns into a GBM; if the neuronal component de-differentiates it turns into a neuroblastoma).
- 45% of the time it will appear as a cyst with mural nodule in a cortical area, but it can be very variable in appearance--- simple cyst with small mural nodule, complex cyst with large, heterogenous mural nodule, solid tumor only.
- The mural nodule has variable enhancement - sometimes enhances vividly
- not much edema.
- Usually affects children and young adults.

DNET:
- arise from cortical or deep grey matter.
- Predilection for temporal lobes.
- often associated with cortical dysplasia
- often cause intractable seizures.
- May be cyst with mural nodule.
- Enhances 20-30% of the time.
- T1 isodense, T2 bright with sometimes "bubbly" appearance 
- not much peritumoral edema.
- Rarely grow in size over time, excellent oncologic prognosis but often removed because of the intractable seizures they cause - seizures often stop when the tumor is resected.
- Typically affects children and young adults.

Of note: in clinical practice, DNETs and GG often appear very similar radiographically, are both T1-dark, T2-bright tumors that rarely enhance (DNET can sometimes appear as ring-enhancing but not commonly, GG are a little more likely to be cystic with mural nodule, etc), with predilections for the temporal lobe, cause seizures, and have excellent seizure freedom outcomes with resection. See this retrospective series from Turkey with 52 patients.

PXA:
- cortical tumors with cystic component and vivid enhancement with Gad. 
- 98% supratentorial. Mostly temporal.
- Often low grade/slow growing without much edema.
- T1 iso/hypointense. 50-60% cyst with mural nodule that enhances strongly. T2 - cyst often looks different than CSF due to proteinacious content.
- Avascular on angio despite vidid enhancement.
- Often affects kids and young adults.

Contain T1-bright tissue that resembles fat 

Lipoma
- always located in subarachnoid spaces - believed to be from maldevelopment of meninx primativa (subarachnoid precursor)
- pericallosal (can wrap around corpus callosum - associated with agensis of corpus callosum in 50% of cases) - 45%
- quadrigeminal cistern (associated with underdevelopment of inferior colliculus) - 35%
- suprasellar cistern - 15%
- CP angle - 10%
- sylvian fissure - 5%

Dermoid:
- Can be thought of as on the spectrum from epidermoid (only squamous epithelial tissue) to dermoid (ectodermal only) to teratomas (contain tissue from all 3 embryonic layers)
- They appear bright on T1 but there is actually no fat in them. They contain squamous epithelial tissue + ectodermal appendages like hair follicles, sweat glands, sebaceous glands - which secrete sebum which looks T1 bright (from cholesterol and other things). Technically no adipose tissue, because that is from mesenchymal tissue so it would technically be a teratoma if there was mesenchyme
- Often midline - suprasellar, subfrontal, cerebellar vermis
- They can rupture and cause a chemical meningitis - leptomeningeal enhancement
- Very rarely will transform into squamous carcinoma

Teratoma - contains tissue from all 3 embryonic layers.
- rare in general population - however 25-50% of fetal brain tumor
- usually pineal or suprasellar
- T1 bright from fat, can enhance

Contain Calcifications

- Oligodendro - rare, but often calicfied

- Astrocytoma - common, but infrequently calcified 

- Pinealcytoma - are not calcified in and of themselves, but contain the inherent calcifications of the pineal gland 

- Craniopharyngioma - suprasellar 

Cystic lesions with same intensity as CSF 

- Arachnoid
- Neurenteric cyst 

- Enlarged virchow-robin space 

Bright on T1

- most tumors are isodense or slightly hypodense on T1. T1 hyperintensity implies presence of one of the elements which are hyperintense on T1, which include the following: 

- Fat -> Lipoma, Teratoma 

- Cholesterol -> Craniopharyngioma, Dermoid, colloid cyst 

- Melanin -> Melanoma met

- Subacute blood (intracellular or extracellular metHb) -> Hemorrhagic tumor - melanoma met, breast/lung (uncommonly bleed), follicular thyroid met, renal cell met, choriocarcinoma met. pituitary apoplexy 

- Mineralization with paramagnetic divalent cations ( Ca, Copper, manganese )

- Proteinaceous fluid - neurentetic cyst 

Dark on T2

- Most tumors are bright on T2 dude to high water content. Low T2 signal implies:

- hypercellularity -> PNET/medullo, lymphoma, mucinous adenoCA mets, high-cellularity parts of GBM (although GBM is usually T2 bright) 

- calcifications -> oligo, astro, craniopharyngioma 

- many flow voids -> hemangioblastoma

Contrast enhancement: 

- Fundamentally based on the integrity of the BBB

Tumors that do not have a BBB will enhance vividly 

- extra-axial masses like meningioma, schwannoma

- non-CNS tumors like lymphoma, metastatic lesions (breast, lung, etc)

- CNS tumors derived from tissue that does not have a BBB - pituitary, pineal (including germinoma and other pineal gland tumors), choroid plexus 

Homogenous enhancement

- Mets

- Lymphoma (non immunocompromised) 

- Meningioma - and its great mimics, hemangiopericytoma and dural based MALT lymphomas 

- Schwannoma/neurofibroma 

- Mural nodule of hemangioblastoma, JPA

- Germinoma, other pineal gland tumors

- Pituitary adenoma

- Ganglioglioma 

Patchy Enhancement

- Mets

- GBM

- Non tumor things (like radiation necrosis) 

Ring Enhancement

- MAGICALDR

- Mets

- Abscess

- GBM

- Ischemia (subacute stroke), Infection (neurocystercercosis, toxoplasma, TB, blasto/histo/crypto, nocardia, listeria) 

- Contusion

- Alternative weird stuff (sarcoid, vasculitis, behcets) 

- Lymphoma 

- Demyelination (MS, ADEM) 

- Radiation necrosis 

Leptomeningeal Enhancement 

- leptomeningeal carcinomatosis (breast, lung, melanoma, leukemia/lymphoma) 

- from CNS tumors - GBM, medullo/PNET, ependymoma, choroid plexus carcinoma. 

- infectious - meningitis (bacterial, viral, crypto, TB)

- sarcoid 

- post-LP (<5%), post-surgery/hemorrhage/trauma 

Sources:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876643/
http://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.html
http://radiopaedia.org/articles/dysembryoplastic-neuroepithelial-tumour
http://radiopaedia.org/articles/ganglioglioma
http://radiopaedia.org/articles/pleomorphic-xanthoastrocytoma
http://radiopaedia.org/articles/intracranial-dermoid-cyst-1
http://radiopaedia.org/articles/gliomatosis-cerebri
http://radiopaedia.org/articles/leptomeningeal-enhancement

	Bright	Dark
T1	- contrast - fat/cholesterol (lipoma, teratoma, dermoid, lipomatous ependymoma, cholesteatoma) ** to differentiate fat from other T1-bright lesions, look for chemical shift artifact (dark band at edge of fat on one side, light band at the other)  - melanin - early subacute blood (intracellular metHb 3-7 days) and late subacute blood (extraceullar metHb, 1-4 weeks) - subacute thrombus (i.e. venous sinus) - protein-rich fluid (colloid, rathke’s cleft, ectopic posterior pituitary, craniopharyngioma – also cholesterol and blood) - minerals (microcalcifcations, iron, manganese – hepatic encephalopathy, copper) - laminar necrosis (from global hypoxemia or immunosuppression – appears 2 weeks after insult) – may appear as cortical ribbon - slowly flowing fluid	- CSF - Edema    - flow voids - calcium (bone) – although microcalcifications often appear as bright on T2 due to their interaction of water molecules
T2	- Edema (from tumor, infection, inflammation, ischemia, vasculitis, radiation-induced, chemo-induced, migraines, etc) - late subacute blood (extracellular metHb) - CSF (virchow robin spaces) - Demyelination - Myelinolysis  - Degeneration	- contrast - acute blood (deoxy Hb)/early subactue blood (intracellular metHb), chronic blood (hemosiderin)   - melanin - mucous/protein (i.e. colloid/rathke cyst - hypercellular tumors (high nucleus to cytoplasm ratio – medullo, lymphoma, highest grade parts of high grade gliomas) ** - tends to be dark but not black - minerality (iron, copper, calcium) - flow voids/turbulent flow – of blood  and CSF (jets can appear dark) - air - fibrous tissue/bone
Diffusion	- T2 shine through - acute ischemia (<2-3 weeks) - highly cellular tumors (lymphoma, medullo/PNET, meningioma, chordoma, germinoma, hemangiopericytoma, pinealblastoma, cortical part of high-grade gliomas – cyst part typically does not restrict in gliomas) - abscess (cystic part restricts 2/2 pus) - mucinous metastasis like breast or colon adenocarcinoma (mucus restricts) - epidermoid - prion disease (CJD, kuru – cortical ribboning) - toxic (carbon monoxide, methanol, Wernicke, maple syrup urine, gluteric aciduria, methyl malonic aciduria other inborn errors of metabolism diseases) - adrenoleukodystrophy	- old stroke (> 3 weeks) - necrosis (i.e. core of GBM/mets)
GRE/SWI		Blooming - air - blood of any age - mineralization - inflammation

Source papers:

Clinical applications of diffusion weighted MR imaging: A review

Differential Diagnosis of Bright Lesions on Diffusion-weighted MR Images

Intracranial Lesions with High Signal Intensity on T1-weighted MR Images: Differential Diagnosis

Differential diagnosis of intracranial lesions with high signal on T1 or low signal on T2-weighted MRI.

GRE T2-Weighted MRI: Principles and Clinical Applications

MRI of the Brain: a primer 

Sympathetic storming 

Epidemiology 
- Typically occurs in young patients with significant/diffuse brain injury - TBI/DAI, SAH, big IPH, etc.
- Archetypally a young male with bad DAI -- likely no true gender predilection but rather trauma tends to affect male > female. And perhaps age predilection because young people have a more robust sympathetic response, or maybe because the degree of neurological injury that is typically associated tends to be mortal in older adults, or maybe because high grade SAH or IPH or diffuse injury occurs more in middle age than late age

Pathophys
- Poorly understood
- Originally believed to be exclusively a function of deep white matter injury; however its also seen in bilateral/diffuse cortical injury
- Perhaps decrease in the dampening signals? exaggerated sympathetic response to all stim, instead of only to severe/noxious stim.

Clinical Presentation 
- Paroxysmal bouts of tachycardia, hypertension, diaphoresis, fever, mydriasis
- Characteristically waxing/waning, rather than constant (i.e. alcohol withdrawal)
- Typically occurs 3-5 days after the initial injury, and resolves on the scale of days to weeks but can start as early as immediately after the injury and last for years

Treatment 
- Very severe (i.e. uncontrollable blood pressures leading to problematic sequelae) - precedex gtt and/or esmolol gtt
- Less severe/transitioning off gtts/on the floor - clonidine, propanolol, gabapentin (especially useful for controlling storming that directly follows stim - like turning/bathing/etc)
- Some people believe that opiates like morphine are an integral part of treating storming, some people don't.
- You can always snow people into the ground with propofol or drips of benzos or narcotics, but it's an inelegant solution and some people believe that they are suboptimal ways of treating storming.