University of Texas Medical Branch Baylor College of Medicine CSF a pathophysiology review: The obstructed, non-obstructed, not understood, and the leaky. Rami Eldaya¹, Stephen Herrmann¹, Aditya Durgam¹, Omar Eissa¹, Tomas Uribe² University of Texas Medical Branch Baylor College of Medicine Control #: 1779 eEdE#: eEdE-14

Disclosure: None

Purpose CSF pathology is common but poorly understood among radiology residents with primary and secondary extrinsic and intrinsic pathophysiology. The purpose of this exhibit is to discuss obstructive and non-obstructive pathology of CSF though pictorial guide with emphasis on classic imaging findings and pathophysiological correlation.

Approach/Method CSF anatomy, production, pathway, and absorption. Cases of obstructive hydrocephalus (Foramen of Monro, Sylvian Aqueduct, extrinsic mass effect, intrinsic mass effect). Cases of Non obstructive Hydrocephalus (NPH, etc…). Cases of CSF flow dynamic changes (idiopathic intracranial hypertension, intracranial hypotension, etc…).

CSF anatomy, production, pathway, and absorption. CSF Facts: Produced by Choroid Plexus within the ventricles Normal CSF production = 0.20-0.35 mL/min Total CSF volume produced in a day is 500 ml 120-150 ml of CSF are within circulation at anytime The rest is constantly absorbed by the arachnoid granulations into the venous sinuses.

CSF anatomy, production, pathway, and absorption. CSF Flow: Lateral ventricles Intraventricular Foramen Third Ventricle Cerebral Aqueduct Fourth Ventricle CPA via Foramen of Luschka Spinal Cord Via Foramen of Magande Arachnoid Granulation to systemic venous circulation Please note that there are other theories for CSF flow, but this is the most understood at this time.

CSF Lesions Intraventriclar Obstructive: Extrinsic compression: At the Intraventricular Foramen At the Aqueduct At the fourth ventricle or its lateral and medial outflows Extrinsic compression: From any Mass effect (ex: trauma, abscess, or mass) Non communicating Hydrocephalus Hemorrhage, infection, Carcinomatous CSF flow dynamic changes

Peri-foramen of Monro Lesions Colloid Cyst Subependymal Giant Cell Astrocytoma Neurocysticercosis Metastases Subependymoma Central Neurocytoma VertebroBasilar Dolicoectasia Choroid Plexus Papilloma

Colloid Cyst Figure 1 NECT Fast Facts: Location is Pathognomonic Typically Hyperdense on CT 1/3 are isodense on CT, can be easily missed if small or there is no Hydrocephalus Approximately 50% are symptomatic Treatment is typically surgical Figure 1 NECT Figure 1 NECT demonstrate hyperdense lesion at the level of the Foramen of Monro (arrowhead) resulting in hydrocephalus as suggested by ballooning of the anterior horns. Location is almost pathognomonic for the diagnosis

Colloid Cyst Figure 2A Sagittal T1C+ Figure 2B Coronal T1C+ Figure 2C Fast Facts: -Most are T1 hyperintense - More variable on T2 depending on protein content - Remember to check T1 prior to suggesting enhancement Figure 2A Sagittal T1C+ Figure 2B Coronal T1C+ Figure 2C Axial T1C+ Figure 2 contrast enhance MRI demonstrate hyperintense lesion at the foramen of monro (arrow) resulting in obstructive hydrocephalus (arrowhead). This lesion did not enhance as it was hyperintnese on T1 (not shown).

Subependymal Giant Cell Astrocytoma (SEGA) Fast Facts: Almost never exist without the background of Tuberous sclerosis 15% of Tuberous sclerosis patients have it Calcifications are common Almost always near foramen on monro Figure3A FLAIR Figure3B T2 Figure3C T1C+ Figure 3A. Axial Flair demonstrate multiple cortical hyperintnese lesions consistent with Tuber (arrows) with dilated ventricles (arrowheads). Figure 3B axial demonstrate iso to mildly hyperintnese mass at the level of the foramen. Figure 3C exhibit expected robust enhancement.

Central Neurocytoma Fast Facts: Figure 4A Figure 4A Figure 4B Arise mostly from lateral ventricle body or frontal horn Attach to septum pellucidim near the foramen Bubbly appearance Common age of presentation 20-40 years Figure 4A Axial T1C+ Figure 4B Coronal T1C+ Figure 4A Sagittal T1C+ Figure 4. Multiplaner post contrast MRI demonstrate mildly enhancing lateral ventricle mass (arrow) that expands the ventricles and result in dilated right ventricle (arrowhead).

Periaqueductal/Aqueductal Lesions Aqueductal Stenosis Tectal/quadrigeminal Glioma Neurocysticercosis Enlarged Perivascular Space Pineal Masses Meningioma

Quadrigeminal Plate Lipoma Fast Facts: Constitute 10-15% of intracranial Lipomas Exhibits fat density on CT T1 hyperintense No enhancement or restriction Figure 5. T1 hyperintnese lesion is identified at the level of the tectal plate(vermis/collicus) resulting on mass effect on the tectum and effacement of the aqueduct (arrow). This results in hydrocephalus. Figure 5 Sagittal T1 MRI

Pineoblastoma Fast Facts: Figure 6 Figure 7 Sagittal NECT Axial FLAIR Helpful to divide lesions into germ cell or parenchymal origin. Germ cell lesions typically engulf the calcifications Parenchymal lesions typically extrude the masses to periphery. Figure 6 Sagittal NECT Figure 7 Axial FLAIR Figure 6 NECT demonstrate hyperdense pineal mass with peripheral calcifications (arrow) resulting in mass effect on the tectum and effacement of the aqueduct with hydrocephalus (arrowhead). Figure 7 axial FLAIR confirm the mass (arrow) with obstructive hydrocephalus and transependymal flow (arrowhead)

Aqueduct Stenosis Figure 7A Axial FLAIR Figure 7B Sagittal T2 Figure 7C Sagittal T2 Figure 7A axial FLAIR demonstrate obstructive hydrocephalus with transependymal flow (arrowheads) Figure 7B and C demonstrate narrowing of the aqueduct without evidence of flow (arrow).

Fourth Ventricle and Its Outflow Fourth Ventricle lesions and outflow lesions: Medulloblastoma Ependymoma Pilocytic astrocytoma -Brain Stem Glioma Subependymoma Neurocysticrosis Choroid plexus papilloma Epidermoid/Dermoid Cyst Hemngioblastoma Atypical Teratoid-Rhabdoid Tumor Ependymal Cyst

Neurocysticercosis Fast Facts: Figure 9A Figure 9B Figure 9C Most common Intraventricular location is fourth ventricle Typically an isolated cyst Diagnosis confirmed by CSF ELISA Figure 9A Axial FLAIR Figure 9B Axial FLAIR Figure 9C Sagittal T2 Figure 9A axial FLAIR image demonstrate hydrocephalus. Figure 9B axial FLAIR at the level of the fourth ventricle demonstrate a cystic lesion in the fourth ventricle resulting in narrowing of the fourth ventricle (arrow). Figure 9C Sagittal T2 demonstrate cyst within the 4th ventricle (arrow). Neurocysticercosis was confirmed on CSF studies.

Neurocysticercosis Figure 10A Sagittal T2 Figure 10B Axial FLAIR Figure 10A Sagittal T2 demonstrate cyst within the 4th ventricle (arrow). Neurocysticercosis was confirmed on CSF studies. Obstructive Hydrocephalus is present (arrowhead). Figure 10B axial FLAIR at the level of the fourth ventricle demonstrate a cystic lesion in the fourth ventricle resulting in narrowing of the fourth ventricle (arrow).

Ependymoma Fast Facts: Figure 11A Sagittal T1 Figure 11B Axial T1C+ Lobulated Mass in the 4th ventricle Soft “squeezes through the midline and lateral foramena More common to calcify that medulloblastoma Does not restrict unlike medulloblastoma Figure 11A Sagittal T1 Figure 11B Axial T1C+ Figure 11C Coronal T1C+ Figure 11A. Sagittal T1 demonstrate isointense mass on T1 situated within the fourth ventricle and extending through the foramen of Magande. Mild hydrocephalus is present (arrow head). Figure 11B and 11C axial and coronal post contrast demonstrate mild to moderate contrast enhancement (arrows).

Extrinsic Obstructive Hydrocephalus Extrinsic Obstructive Hydrocephalus Lesions: Any mass occupying lesion resulting in compression of the ventricles: Malignancies Benign Masses Perivascular Cyst Hematoma Abscess Pneumocephalus

Glioblastoma resulting in extrinsic Hydrocephalus Fast Facts: Most common and aggressive primary brain tumor Thick enhancing rind of tissue surrounding a necrotic center Survival is around a year One of the few lesions that cross midline Figure 12A Axial FLAIR Figure 12B Axial T1C+ Figure 12C Coronal T1C+ Figure 12A axial FLAIR demonstrate abnormal signal intensity within the brainstem with associated obstructive hydrocephalus as suggested by transependymal flow (arrowhead) Figure 12B axial T1C+ and 12C coronal T1C+ demonstrate a rim enhancing necrotic multifocal mass resulting in mass effect on the third ventricle (arrow) resulting in hydrocephalus.

Tension pneumocephalus Fast Facts: Pneumocephalus is common after trauma and surgery and is rarely of clinical importance in it self Typically suggestive of underling abnormality that requires detection Tension pneumocephalus Mount Fuji" sign Subdural air separates/compresses frontal lobes, creates widened interhemispheric space between frontal lobe tips, mimicking silhouette of Mount Fuji± mass effect (frontal horns of lateral ventricles displaced posteriorly) Figure 13A Axial NECT Figure 13B Axial NECT NECT axial Figure 13A demonstrate tension pneumocephalus with “Mount Fuji sign) (arrow) resulting in mass effect on the left frontal lobe and midline shift. NCET axial Figure 13B more caudal images demonstrate midline shift and mass effect on the third ventricle resulting in obstructive hydrocephalus (arrowhead)

Extra ventricular Obstructive Hydrocephalus (Communicating Hydrocephalus) Any lesion resulting in mismatch between production and absorption of CSF Subarachnoid Hemorrhage Meningitis Leptomeningeal Carcinomatosis.

Subarachnoid Hemorrhage (SAH) Fast Facts: Impaired absorption of CSF distal to the fourth ventricle Typically a mismatch between the production and absorption of CSF SAH is the most common cause Figure 14A Axial NECT Figure 14B Coronal CTA Figure 14A NECT axial demonstrate SAH within the basil cisterns (arrow). Figure 14B CTA coronal demonstrate basilar tip aneurysm (arrow) with partially visualized dilated lateral ventricles (arrowhead)

Meningitis Fast Facts: Similar pathophysiology as SAH - Basilar leptomeningeal enhancement carries a broad diagnosis including if infectious TB and fungal infections Figure 15A Axial FLAIR Figure 15B Axial T1C+ Figure 15C Coronal T1C+ Figure 15A demonstrate abnormal basilar cisterns leptomeningeal signal (arrow) abnormality with corresponding enhancement on post contrast axial (15B) and coronal (15C) images (arrows). Mild ventricular dilation has developed (arrow heads).

Leptomeningeal Carcinomatosis Fast Facts: Similar pathophysiology as SAH - Bimodal distribution following tumors common presenting age - Obstructive hydrocephalus can be first presenting symptoms Figure 16A Axial T1C+ Figure 16B Sagittal T1C+ Figure 16A axial and 16B coronal post contrast demonstrate leptomeningeal enhancement in patient with breast cancer (arrows) within the cerebellum with mild lateral ventricular dilation (arrowhead).

CSF overproduction CSF overproduction: Choroid plexus papilloma (CPP)(WHO grade I) Atypical choroid plexus papilloma (aCPP)(grade II) Choroid plexus carcinoma (CPCa)(grade III)

Choroid Plexus Papilloma Fast Facts: Child with enhancing lobulated (cauliflower-like) mass in atrium of lateral ventricle Occurs in portion to choroid plexus: lateral ventricles, then fourth ventricle, then third ventricle. Most common brain tumor in children less than a year Overproduction of CSF → obstruction Can be as much as 800-1,500 mL/day Figure 17A Axial T1 Figure 17B Axial T1C+ Figure 17A axial T1 demonstrate cauliflower like mass expanding the right lateral ventricle (arrowhead) Figure 17B axial T1C+ this mass exhibits mild enhancement.

Atypical choroid plexus papilloma Fast Facts: Imaging can not distinguish between all 3 subtypes CSF dissemination can occur in all 3 subtypes. Therefore, imaging the whole neuroaxis is a must Hydrocephalus is likely a combination of overproduction of CSF, obstruction, and impaired absorption secondary to hemorrhage. Figure 18A Axial T1 Figure 18B Axial T1C+ Figure 18A axial non contrast demonstrate mild expansion of the right ventricle with isointense mass (arrow). The ventricles are mildly prominent for age Figure 18B axial T1C+ demonstrate homogenous robust enhancement of the cauliflower like mass. The mass is in a classical location within the right atria (arrow)

Choroid Plexus Carcinoma Figure 19 A axial NECT and 19 B T1C+ demonstrate an enhancing cauliflower like mass within the right lateral ventricle resulting in mass effect on the left lateral ventricle and obstruction as suggested by the transependymal flow and extensive parenchymal edema (arrow). Figure 19A Axial NECT Figure 19B Axial T1C+

Impaired/Altered CSF flow dynamics Some of these tend to be the most poorly understood Some of the common pathologies include: Intracranial Hypotension Idiopathic intracranial hypertension Normal Pressure Hydrocephalus

Intracranial Hypotension Fast Facts: Typically present as headache secondary to decreased intracranial pressure. Decrease pressure could be secondary to CSF leak idiopathic, post traumatic, or iatrogenic (LP or overshunting) Ultimately this lead to alteration of Monro-Kelli Douctrine Figure 20A Axial T2 Figure 20B Axial T1C+ Figure 20C Sagittal T1 Figure 20A axial T2 demonstrate subdural fluid collections consistent with subdural fluid (arrows). Figure 20B axial T1C+ demonstrate diffuse enhancement of the thickened dura (arrows). Figure 20C sagittal T1 demonstrate “sagging” of the mid brain (arrow) and engorgement of the superior sagittal sinus (arrowhead).

Intracranial Hypotension Fast Facts: Classic imaging - Diffuse dural thickening/enhancement - Smooth, not nodular or "lumpy-bumpy“ - Downward displacement of brain through incisura ("slumping" midbrain) - Veins, dural sinuses distended ± subdural hygromas/hematomas Figure 21A Axial T2, pretreatment Figure 21B Axial T2, posttreatment Figure 21A axial T2 of the same patient demonstrate subdural effusions. Figure 21B post treatment images demonstrate resolution of the subdural collections (off note patient nuclear medicine study demonstrated right nasal leak, not shown)

Idiopathic Intracranial Hypertension Fast Facts: Etiology (non consensus) 5 different proposed mechanisms resulting in ↑ ICP ↑ cerebral volume Possible etiology: ↑ interstitial fluid, ↑blood volume, ↑ tissue volume ↑ CSF volume Possible etiology: ↑ CSF production rate, ↑ CSF outflow resistance ↑ cerebral arterial pressure  Possible etiology: Loss of cerebral autoregulation ↑ venous blood volume and interstitial fluid Possible etiology: ↑ cerebral venous pressure ↓ CSF outflow and ↑ CSF volume Figure 22A Axial T2 Figure 22B Sagittal T2 Figure 22A axial T2 demonstrate flattening of the sclera (arrowhead) and thickened tortuous optic nerves with increase CSF spaces (arrows) Figure 22B coronal T2 demonstrate empty Sella configuration (arrow)

Idiopathic Intracranial Hypertension Fast Facts: Imaging Findings: Empty or partially empty sella Posterior globe flattening Intraocular protrusion of optic nerve head Optic nerve sheath enlargement: Increase CSF around optic nerve Optic nerve tortuosity Slit-like ventricles(debatable) MRV: Often shows transverse sinus stenosis Clinical presentation is papilledema or headache Treatment: CSF shunting Figure 23 Axial T2 Figure 23 axial T2 images demonstrate protrusion of the optic nerve into the globe (arrowheads) and increase CSF spaces around both optic nerves (arrows)

NPH Fast Facts: Figure 24C Sagittal T1 Figure 24A FLAIR T2 Figure 24B Imaging Findings: Enlarged lateral and third ventricles Relatively normal fourth ventricle The ventricular enlargement is more prominent that cortical sulci enlargement Pathophysiology poorly understood Possibly related to poor superior sagittal sinus compliance resulting in poor CSF absorption. The Sylvain Fissure and basal cistern are also dilated relative to the cortical sulci. Figure 24C Sagittal T1 Figure 24A FLAIR T2 Figure 24B Axial T2 Figure 24A FLAIR and Figure 24B axial T2 demonstrate dilation of the ventricles (arrows) and Sylvain fissures (arrowheads) out of proportion to the cortical sulci (green arrows). Note periventricular fluid (orange arrows). Figure 24C sagittal T1 demonstrate the dilated lateral ventricles (arrow) and the normal fourth ventricle

NPH Fast Facts: Suggested quantification methods for dilations include the ratio of frontal horn diameter to the brain (Evan’s angle) Alternatively measurement of the angle between the lateral ventricles is applied (Callosal angle) Figure 25 FLAIR T2 Figure 25 FLAIR and Figure 24B axial T2 demonstrate dilation of the ventricles (arrows) out of proportion to the cortical sulci (orange arrows). Note periventricular fluid (arrowhead).

Findings/Discussion CSF flow is one of the more challenging concepts of neuroradiology given the CSF dynamic nature and complex normal pathway. In addition its complex, varied, and rich pathology makes it a very challenging topic for radiology residents and non- neuroradiologists. Furthermore, poorly understood pathologies such as normal pressure hydrocephalus, idiopathic intracranial hypertension, and intracranial hypotension add to the complexity of the topic. Appreciation of these limitations while understanding the classical imaging findings of the pathologies and their associated complications is integral in appreciating CSF and its pathologies. The purpose of this exhibit is to expose the radiology resident to the most common pathologies with emphasis on pathognomonic imaging findings and most plausible pathophysiology of each entity.

Summary Abnormalities within the CSF system are complex ranging from simple straightforward obstructive lesions to abnormalities without definitive underlying lesions. Appreciation of this complexity helps in detecting CSF abnormalities and strengths the radiology resident grasp of this topic

References Statdx: https://my.statdx.com/search accessed 5/1/16 Bradley WG Jr: CSF Flow in the Brain in the Context of Normal Pressure Hydroce Yuh EL et al: Imaging of ependymomas: MRI and CT. Childs Nerv Syst. 25(10):1203-13, 2009phalus. AJNR Am J Neuroradiol. 36(5):831-838, 2015 Passi N et al: MR imaging of papilledema and visual pathways: effects of increased intracranial pressure and pathophysiologic mechanisms. AJNR Am J Neuroradiol. 34(5):919-24, 2013

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