neurosarcoidosis: a patient's journey

Victor Babatunde, Harvard Medical School Year III

Gillian Lieberman, MD

NEUROSARCOIDOSIS:

A PATIENT’S JOURNEY

Victor Babatunde, 2016 Gillian Lieberman, MD

Outline

• Brief initial patient presentation

• Review Anatomy of the Ventricular system and Cisterns

• Radiologic Tests for Evaluating Neurosarcoidosis

• Highlight Patient’s course through presentation and

diagnosis

• Brief review of Sarcoidosis and different organ

manifestations

• Brief overview Neurosarcoidosis and typical presentations

• Discuss Differential diagnosis of Neurosarcoidosis

• Discuss criteria for diagnosis of Neurosarcoidosis

• Treatment of Neurosarcoidosis and patient’s outcome

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Initial Patient Presentation

40 year old woman presents with 5 days of dizziness, headache with associated confusion, nausea and vomiting. Denies double or blurry vision, numbness, weakness or tingling.

PMH: Vestibular Neuritis, Depression

Physical Exam: Vitals signs are normal. Exam notable for lethargy but easily arousable. Non focal neurological examination.

CBC and metabolic panel are normal.

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Anatomy of the Ventricles

Felten et al 2015 4 Lee and Srinivasan 2014


Anatomy of the Subarachnoid Cisterns

5 Felten et al 2015 Felten et al 2015


Our Patient: Hydrocephalus on Head CT

1.There is severe dilation of the

lateral ventricles, and global

effacement of sulci consistent with

severe hydrocephalus

2.There is also periventricular white

matter hypodensities representing

transependymal migration of CSF

due to acute dilation and

increased pressures in ventricles

3.No definite obstructing mass seen

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6 Axial Noncontrast Head CT


Our Patient: MRI s/p VP Shunt

Axial T1 weighted MRI Axial T2 weighted MRI

1.Marked decreased

enlargement of

lateral ventricles post

shunt placement

2.VP Shunt tip seen in

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Second Presentation of Our Patient

• 7 months later, our 42 year old patient with history of hydrocephalus s/p VP shunt placement now presents with progressive cognitive decline, gait difficulties, and intermittent diplopia for several weeks.

• MRI of Head was obtained

• After imaging, Lumbar puncture was obtained with CSF findings remarkable for lymphocytic pleocytosis, low glucose and high protein. CSF showed negative culture and normal ACE levels.

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Our Patient: MRI showing Leptomeningeal enhancements

Extensive nodular leptomeningeal enhancements in bilateral Sylvian fissures, along subarachnoid cisterns.

Contrast-enhanced Axial T1 weighted images

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Extensive nodular enhancements along the cerebellar folia and

subarachnoid cisterns adjacent to brain stem. Not shown in this image are

enhancements in the third and fourth ventricles.

Contrast-enhanced Sagittal T1-weighted

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Our Patient: MRI showing Leptomeningeal enhancements

Differential Diagnosis of Leptomeningeal Enhancements • Leptomeningeal Carcinomatosis ( from carcinoma of breast, lung,

melanoma)

• Leptomeningeal Lymphomatosis ( from Lymphoma)

• Bacterial Meningitis

• Viral Meningitis

• HIV Meningitis

• Tuberculous Meningitis

• CNS Cryptococcus

• Neurosyphilis

• Neurosarcoidosis

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Menu of Radiologic Tests for diagnosis

• Radiographs

• CT

• MRI

• MRCP

• PET-CT

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Our Patient: Normal Chest Radiograph

There are NO opacities, nodules, hilar lymphadenopathy, pleural effusion.

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AP Supine


Our Patient: Normal Chest CT

There are NO hilar or mediastinal lymphadenopathy, no nodules or masses in the lungs

Axial Chest CT with contrast

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Our Patient: Lesion in Periportal Area on CT Abdomen

There is a 1.5cm by 2.7cm well-circumscribed hypodense cystic lesion within the porta hepatitis There is an enlargement of the aortocaval lymph node

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Because the periportal lesion seen on CT Abdomen was difficult to characterize, MRCP was recommended and obtained.

Our Patient: Normal Biliary System seen on MRCP

There is no intra or extrahepatic biliary duct dilation. The gallbladder is normal. No stones are identified.

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There are enlarged lymph nodes in the periportal area and in gastrohepatic ligament.

Axial LAVA seq Contrast-enhanced Axial DWI Axial T2-weighted (SSFSE)

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Our Patient: Lymphadenopathy on MRCP


Our Patient: Focal Lesions along Spinal Nerve Roots

There are T2 hypointense foci along the nerve roots in the lumbar spine

Axial T2-weighted (SSFSE)

Coronal T2-weighted (SSFSE)

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Given concerning focal lesions seen on MRCP, whole spine MRI was obtained.


Our Patient: Nodular Lesions on Lumbar Spine MRI

Sagittal T2-weighted Sagittal T1-weighted post contrast

There are multiple nodular enhancing lesions along cord and cauda equina

Sagittal T1-weighted post contrast

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Our Patient: Nodular lesions on Cerv./Thor. Spine MRI

There are extensive nodular enhancing lesions along the cervical and thoracic spinal cords. No cord compression

Cervical Sagittal T1

weighted post

contrast

Cervical Sagittal T2 weighted Thoracic Sagittal T1

weighted post

contrast

Thoracic Sagittal T2

weighted

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Given leptomeningeal enhancements on imaging, leptomeningeal carcinomatosis from a primary malignancy needed to be ruled out. Lung, pancreatic and colon cancers were unlikely based on CT and MRI obtained. Full skin exam was negative for melanoma-like lesions. A diagnostic Mammogram was ordered to assess her breast for any malignancy.


Our Patient: Normal Diagnostic Mammogram

Right CC Left CC Right MLO Left MLO

There is no dominant mass, unexplained architectural distortion or

suspicious grouped microcalcifications. No evidence of malignancy. Bi-

RADS 1- Negative.

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To further evaluate for any metastatic processes, PET-CT was obtained


Our Patient: FDG avid Lymphadenopathy on PET-CT

There are periportal, gastrohepatic and aortocaval lymphadenopathy with increased FDG avidity.

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Axial FDG PET w/ CT of Abdomen/Pelvis


Increased FDG avidity is seen throughout the course of the spinal

cord

extending from the cervical cord down to the cauda equina, consistent

with

leptomeningeal disease as characterized by the prior MRI. 27

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Our Patient: FDG avid Cord lesions on PET-CT Axial FDG PET w/ CT of Chest


Summary of Imaging Findings

• Extensive nodular enhancements in leptomeninges of brain and throughout spinal cord seen on MRI, and lymphadenopathy in periportal, gastrohepatic and aortocaval areas with increased FDG uptake on PET-CT in those nodes.

• CT-guided biopsy of periportal lymph nodes was obtained

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Our Patient: CT-Guided Biopsy

Under CT guidance, a 19 gauge coaxial needle was introduced into the

lesion. An 20 gauge core biopsy device with a 11 mm throw was used to

obtain

four core biopsy specimens, which were sent to pathology. 29

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• Periportal Lymph Node Biopsy showed Non-Necrotizing Granulomas.

Our Patient: Periportal Lymph Node Biopsy Result

• Biopsy was negative for fungal infections and lymphoma.


Companion slide: Photomicrographs (H&E 20X) in a patient with Neurosarcoidosis

reveal leptomeningeal inflammation (arrowheads) and granuloma formation (arrows) (a)

along with perivascular spread of the disease (arrowheads) (b).

Bathla G, et al Imaging of neurosarcoidosis: common, uncommon, and rare. Clin Radiol. 2016

Companion Patient: Neural Tissue Pathology



Sarcoidosis

• Idiopathic non-infectious inflammatory disorder characterized by formation of non-caseating granulomas

• Commonly affects African-Americans and persons of Scandinavian descent.

• Female predominance, often seen in females between ages of 30-40s.

• Pathophysiology is still elusive but may involve an antigen provoked inflammatory response with CD4 lymphocyte predominance. CD4+ T cells interact with APC to form and maintain granulomas.

• Multisystem disorder with varying presentations depending on organ(s) involved

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Companion Patients: Radiologic Manifestations of sarcoidosis

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Pulmonary Sarcoidosis. Chest radiograph

showing Bilateral Hilar lymphadenopathy

(arrows)

Koyama T, Ueda H, Togashi K, Umeoka S, Kataoka M, Nagai S. Radiologic manifestations of sarcoidosis in various organs. Radiographics. 2004 Jan-Feb;24(1):87-104.

Ocular Sarcoidosis: Axial contrast-enhanced fat-

suppressed T1-weighted MR image shows diffuse,

prominent enhancement of the lacrimal glands (arrows).


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Splenic Sarcoidosis. Contrast-enhanced abdominal CT scan

shows multiple small, hypoattenuating nodules scattered

diffusely throughout the spleen.

Hepatic Sarcoidosis. Contrast-

enhanced abdominal CT scan shows

multiple, irregularly shaped nodules of

variable size in the liver.

Koyama T, Ueda H, Togashi K, Umeoka S, Kataoka M, Nagai S. Radiologic manifestations of sarcoidosis in various organs. Radiographics. 2004 Jan-Feb;24(1):87-104.




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Muscle Sarcoidosis. T2-weighted and contrast-enhanced MR

images demonstrate a nodular type muscle lesion (arrows),

with a central area of decreased signal intensity and periphery

demonstrating prominent enhancement.

Bone sarcoidosis. Close-up view from a

radiograph of the right hand reveals a radiolucent

lesion in the middle phalanx of the third finger.

The lesion has a lacelike appearance and is

accompanied by a soft-tissue mass

(arrowheads).

Koyama T, et al. Radiologic manifestations of sarcoidosis in various organs. Radiographics. 2004


Neurosarcoidosis

• Neurosarcoidosis occurs in 5-15% of those with sarcoidosis.

• It may represent the first manifestation of sarcoidosis.

• Presentation of neurosarcoidosis varies widely deepening on the part of CNS involved.

• Presenting signs and symptoms include: seizures, meningitis, hydrocephalus, peripheral neuropathy, psychiatric symptoms, endocrinal disturbances.

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Contrast-enhanced sagittal T1WI

reveals diffuse thickening and

enhancement involving the pituitary–

infundibulum–hypothalamus axis

(arrow), extending posteriorly along the

clivus (arrowhead).

Cranial Nerve Involvement. Contrast-enhanced axial

T1WIs reveals diffuse thickening and enhancement of

bilateral optic (arrowheads in a) and trigeminal nerves

(arrows in b).

Intraparenchymal.

Solitary Granulomatous

Lesion on Axial T2WI


Companion Patients: Radiologic Manifestations of Neurosarcoidosis


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Differential diagnosis for Neurosarcoidosis (1)Infectious diseases: Tuberculosis, Progressive multifocal

leukoencephalopathy

(2)Granulomatous diseases: GPA, Churg–Strauss syndrome

(3)Tumors: Neurolymphomas, Meningioma, Leptomeningeal metastases

(4) Vasculopathies: Vasculitis, Behcet’s disease

(5)Systemic diseases: Amyloidosis

(6)Neurological diseases: Multiple sclerosis, Acute demyelinating

encephalomyelitis

Hoitsma E, et al. A Pragmatic Approach to Diagnosing and Treating Neurosarcoidosis in the 21st Century. Curr Opin Pulm Med. 2010


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Diagnostic criteria for neurosarcoidosis

Zajicek criteria

I. Definite diagnosis if presence of positive nervous system histology

II. Probable diagnosis if evidence of CNS inflammation on MRI or CSF AND positive histology for a systemic lesion, or at least 2 positive tests on indirect indicators such as chest films, FDG-PET, Gallium scan, serum ACE.

III. Possible diagnosis if above criteria are not met but other inflammatory pathologies were ruled out.

Hoitsma E, et al. A Pragmatic Approach to Diagnosing and Treating Neurosarcoidosis in the 21st Century. Curr Opin Pulm Med. 2010


Treatment for Neurosarcoidosis

• Corticosteroids are the drugs of first choice.

• Immunomodulating and cytotoxic agents such as Methotrexate, Cyclophosphamide, Azathioprine, Infliximab.

• When refractory to medications, neurosurgery and radiation therapy may be appropriate for certain lesions.

40 Tavee JO, Stern BJ. Neurosarcoidosis. Clin Chest Med. 2015


Our Patient’s Outcome

• Imaging findings of CNS leptomeningeal enhancements and positive histology of Sarcoidosis in lymph nodes were consistent with a probable diagnosis of Neurosarcoidosis according to Zajicek criteria

• Our patient received corticosteroids with some resolution of her symptoms.

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Tavee JO, Stern BJ. Neurosarcoidosis. Clin Chest Med. 2015


Conclusion

• Examined a case from presentation to diagnosis of Neurosarcoidosis

• Reviewed Anatomy of the Ventricular system and Cisterns Menu of Radiologic Tests for Evaluating Neurosarcoidosis

• Discussed Sarcoidosis and different organ manifestations

• Brief Overview of Neurosarcoidosis and typical presentations

• Listed differential diagnosis of Neurosarcoidosis

• Outlined criteria for diagnosis of Neurosarcoidosis

• Treatment of Neurosarcoidosis and patient’s outcome

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• Feltern DL, O’Banion ML, Maida MS. Netters Neuroscience 3rd Edition. 2015

• Lee TC, Mukundan S. Netter’s Correlative Imaging: Neuroanatomy 2014.

• Lower EE, Weiss K. Neurosarcoidosis. Clin Chest Med. 2008 Sep;29(3):475-92

• Bathla G, Singh AK, Policeni B, Agarwal A, Case B. Imaging of neurosarcoidosis: common, uncommon, and rare. Clin Radiol. 2016 Jan;71(1):96-106.

• Hoitsma E, Drent M, Sharma OP. A Pragmatic Approach to Diagnosing and Treating Neurosarcoidosis in the 21st Century. Curr Opin Pulm Med. 2010;16(5):472–479

• Koyama T, Ueda H, Togashi K, Umeoka S, Kataoka M, Nagai S. Radiologic manifestations of sarcoidosis in various organs. Radiographics. 2004 Jan-Feb;24(1):87-104.

• Hebel R, Dubaniewicz-Wybieralska M, Dubaniewicz A. Overview of neurosarcoidosis: recent advances. J Neurol. 2015 Feb;262(2):258-67.

• Tavee JO, Stern BJ. Neurosarcoidosis. Clin Chest Med. 2015 Dec;36(4):643-56.

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References


Acknowledgements

• Dr. Gillian Lieberman

• Dr. Ning Lu

• Dr. Chris Hostage

• Dr. Alexei Kudla

• Joanna Babatunde

• BIDMC Core Radiology Rotation Students

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neurosarcoidosis: a patient's journey

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