History Recent Advances in Neurology 66 yo man with referred for - - PowerPoint PPT Presentation

2/10/2017 1

Recent Advances in Neurology Difficult Cases

Nancy Ann Oberheim Bush MD PhD February 10, 2017

History

• 66 yo man with referred for low back pain,

weakness and numbness

• History of papillary thyroid cancer
• 2009: History of right MCA stroke due to a

carotid artery dissection

• Persistent Left-sided weakness following his

stroke

History continued

• Due to persistent weakness, sought treatment

with stem cell therapy

• 2011 (China): intrathecal injection of embryonic

stem and mesenchymal stem cells

• 2012 (Argentina) arterial injection of autologous

iliac crest stem cells

• 2014 (Mexico) intrathecal injection of

mesenchymal and neuronal stem cells

• 2014 (Mexico) intrathecal injection of

mesenchymal and neuronal stem cells

History Continued

• 2015
• Development of low back pain
• Development of progressive right arm and leg

weakness

• Development of urinary incontinence
• No cognitive changes
• No difficulty swallowing, altered speech, or

language difficulty

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Examination

• Well appearing man in no acute distress in a wheelchair.
• Mental status : normal cognition and language. He has

left hemi neglect.

• Cranial nerves: upper motor neuron left facial droop
• Motor : spastic left hemiparesis with a paretic right leg.
• Reflexes: knee jerks were 3+ bilaterally, clonus in the

ankles bilaterally. Plantar responses were extensor bilaterally.

• Coordination: normal bilaterally in arms
• Sensory: marked hyperesthesia with paresthesias in the

left arm and leg with a T4 sensory level on right. No vibratory sensation in the legs.

Investigations MRI brain with and without contrast

T1-weighted with contrast T2-weighted FLAIR

Investigations MRI spine with contrast Question 1

What is the least likely etiology of this lesion?

• A. A) Myxopapillary Ependymoma
• B. B) Glioblastoma
• C. C) Intramedullary metastasis
• D. D) Lymphoma

8% 10% 17% 65%

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Intramedullary Lesions

• Spinal cord tumors can be within or adjacent

to the spinal cord

• Primary spinal cord tumors account for 2-4%
• f all primary CNS tumors
• 1/3 of Spinal cord tumor are intramedullary
• Ependymomas
• Astrocytoma
• Metastases

Ependymomas

• Ependymoma
• Myxopapillary ependymoma
• Subependymoma
• Anaplastic ependymoma

Ependymoma

• Most common intramedullary tumors in adults
• Peak age 30-40 years
• Presentation with localized pain, followed by

neurologic deficits (occur centrally within the cord, expanding it symmetrically as they grow)

• Tumor-associated cyst (syrinx) is common
• Generally enhance intensely on MRI
• Treatment: gross total resection, if partial

resection, consider treatment with radiation

Myxopapillary ependymoma

• Commonly arise in the lumbosacral spinal cord

and filum terminale

• median age at diagnosis is 35 to 37 years
• Present most commonly with pain, neurologic

deficits less common

• propensity for seeding of the neuroaxis, complete

brain and spine MR imaging and cerebrospinal fluid analysis should be done

• Treatment: gross total resection, if partial

resection, radiation

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Astrocytoma

• Occur throughout the spinal cord
• ½ are pilocytic astrocytomas

– well circumscribed and low grade with nonaggressive clinical behavior. – enhance intensely with gadolinium

• ½ are infiltrative astrocytomas

– nonencapsulated lesions that enhance minimally or heterogeneously on MRI – 1/3 are high grade: anaplastic astrocytoma or GBM

• 50% of the high grade tumors have the H3K27M mutations
• Treatment: surgical resection, followed by radiation +/-

chemotherapy in high grade.

Metastases

• Rare
• ½ are associated with lung cancer.

– Breast cancer, renal cell carcinoma, Iymphoma, and melanoma

• Usually observed in patients with widespread

metastatic disease.

• Typically present with weakness, numbness, and

pain

• Treatment: fractionated radiation

Gross Image from Biopsy Pathology

H&E Olig2 MIB-1 SOX2

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Pathology

Question 2

What is the pathologic diagnosis?

• A. Glioblastoma
• B. Glioproliferative Lesion
• C. Anaplastic Astrocytoma
• D. Pilocytic Astrocytoma

4% 12% 43% 41%

Next Generation Sequencing Further investigations

• Next generation sequencing: no cancer-

associated genetic aberrations detected

• Short tandem repeat DNA fingerprinting

analysis

• 62% of the cells contained non-host DNA

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Pathology

• Glioproliferative lesion

Treatment

• Fractionated Radiation therapy was given to

48.6 Gy to the mid C-spine through sacrum

• Improvement in Pain
• No improvement in Neurologic function

Post-treatment imaging Clinical Implications

• Primary spinal cord tumors account for 2-4% of

all primary CNS

• 1/3 of Spinal cord tumor are intramedullary and

include ependymomas, astrocytomas, and metastases

• Stem-Cell therapy is current being used in much
• f the world for therapy in an unregulated

fashion

• Patients should show caution with using these

treatments

• There is promise for stem cell therapy, but it

should continue to be studied in a controlled manner

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References

• Berkowitz Al. Et al. Glioproliferative Lesion of the Spinal Cord as a

Complication of “Stem-Cell Tourism. N England J Med. 2016 Jul 14;375(2):196-8.

• Bowman M, Racke M, Kissel J, Imitola J. Responsibilities of health care

professionals in counseling and educating patients with incurable neurological diseases regarding “stem cell tourism”: caveat emptor. JAMA Neurol 2015;72:1342-1345

• Amariglio N, Hirshberg A, Scheithauer BW, et al. Donor-derived brain

tumor following neural stem cell transplantation in an ataxia telangiectasia

• patient. PLoS Med2009;6:e1000029-e1000029
• Fox IJ, Daley GQ, Goldman SA, et al. Use of differentiated pluripotent

stem cells as replacement therapy for treating disease.Science 2014;345:127391-127391

Clinical Neuro-Oncology Program and Brain Tumor Research Center

400 Parnassus Avenue A808 San Francisco, CA 94143 Phone: (415) 353-2966Fax: (415) 353-2167 http://neurosurgery.ucsf.edu/index.php/brain_tumor_center.html

Nicholas Butowski, MD Susan Chang, MD Jennifer Clarke, MD Manish Aghi, MD, PhD Philip Theodosopoulos, MD Michael McDermott, MD Mitchel Berger, MD Jennie Taylor, MD Nancy Ann Oberheim- Bush MD, PhD