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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Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
Anatomy of the Ventricles
Felten et al 2015 4 Lee and Srinivasan 2014
Victor Babatunde, 2016 Gillian Lieberman, MD
Anatomy of the Subarachnoid Cisterns
5 Felten et al 2015 Felten et al 2015
Victor Babatunde, 2016 Gillian Lieberman, MD
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
Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
Menu of Radiologic Tests for diagnosis
• Radiographs
• CT
• MRI
• MRCP
• PET-CT
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Victor Babatunde, 2016 Gillian Lieberman, MD
Our Patient: Normal Chest Radiograph
There are NO opacities, nodules, hilar lymphadenopathy, pleural effusion.
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AP Supine
Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
Victor Babatunde, 2016 Gillian Lieberman, MD
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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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Victor Babatunde, 2016 Gillian Lieberman, MD
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
Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
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Given concerning focal lesions seen on MRCP, whole spine MRI was obtained.
Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
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.
Victor Babatunde, 2016 Gillian Lieberman, MD
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
Victor Babatunde, 2016 Gillian Lieberman, MD
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
Victor Babatunde, 2016 Gillian Lieberman, MD
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
Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
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.
Victor Babatunde, 2016 Gillian Lieberman, MD
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
Victor Babatunde, 2016 Gillian Lieberman, MD
Bathla G, et al Imaging of neurosarcoidosis: common, uncommon, and rare. Clin Radiol. 2016
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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Victor Babatunde, 2016 Gillian Lieberman, MD
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).
Victor Babatunde, 2016 Gillian Lieberman, MD
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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.
Companion Patients: Radiologic Manifestations of sarcoidosis
Victor Babatunde, 2016 Gillian Lieberman, MD
Victor Babatunde, 2016 Gillian Lieberman, MD
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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
Companion Patients: Radiologic Manifestations of sarcoidosis
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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Victor Babatunde, 2016 Gillian Lieberman, MD
Bathla G, et al Imaging of neurosarcoidosis: common, uncommon, and rare. Clin Radiol. 2016
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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
Bathla G, et al Imaging of neurosarcoidosis: common, uncommon, and rare. Clin Radiol. 2016
Companion Patients: Radiologic Manifestations of Neurosarcoidosis
Victor Babatunde, 2016 Gillian Lieberman, MD
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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
Victor Babatunde, 2016 Gillian Lieberman, MD
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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
Victor Babatunde, 2016 Gillian Lieberman, MD
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
Victor Babatunde, 2016 Gillian Lieberman, MD
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
Victor Babatunde, 2016 Gillian Lieberman, MD
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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Victor Babatunde, 2016 Gillian Lieberman, MD
• 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
Victor Babatunde, 2016 Gillian Lieberman, MD
Acknowledgements
• Dr. Gillian Lieberman
• Dr. Ning Lu
• Dr. Chris Hostage
• Dr. Alexei Kudla
• Joanna Babatunde
• BIDMC Core Radiology Rotation Students
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Victor Babatunde, 2016 Gillian Lieberman, MD