Thanks and Disclosures UCSF Neurology Outpatient Conference - PowerPoint PPT Presentation

2/15/2019 Thanks and Disclosures UCSF Neurology Outpatient Conference Thanks! John Engstrom, M.D. Dr. Cynthia Chin-Neuroradiology February 15, 2019 Dr. Line Jacques-Neurosurgery Dr. Sean Ferris-Neuropathology 49 yo woman with Numb Chin Disclosures Syndrome and a Left Brachial Plexopathy Sadly, I have no conflicts to disclose 49 yo woman with weakness, Topics Covered numbness, pain in left arm/hand • Patient history and current exam • 2012 Left leg weakness/numbness-left leg • Review outside info + initial info at UCSF buckled with walking and numbness over • Initial localization and differential diagnosis knee and medial calf • Neuroradiology and Neurosurgery • 2013 Numb left chin • Neuropathology – Spread to chin on right – Brain MRI normal • Clinical Features and Management – IEP: IgM monoclonal gammopathy • Clinical Course – Bone marrow “smoldering” Waldenstrom’s • Take Home Points macroglobulinemia 1

2/15/2019 Localization 49 yo woman with weakness, numbness, pain in left arm/hand • 8/15-Left 5 th finger and medial forearm itching and tingling • Numbness medial hand, forearm, arm • Burning pain-kept awake at night • Left hand weakness and wasting-unable to use word processer with left hand Localization Q1: Numb chin syndrome is caused by which of the following? • Weakness in APB, EIP, FCU, ADM-share the medial cord (MC) and lower trunk (LT) A. Metastatic tumor affecting the 91% of the brachial plexus; C8 root and C8 AHC third division of the 5th cranial nerve • Weakness EIP-shares LT, C8 root, C8 AHC B. Trauma to the 5th cranial nerve • Numbness medial forearm-medial ante- C. Infection contiguous to the third brachial cutaneous nerve-MC/LT/C8 root 6% 3% division of the 5 th cranial nerve 0% • Numbness medial arm-medial cutaneous e D. All of the above . . . v . . . . o i a t t b nerve of arm-MC/LT/C8 root c n i o e a f a t f s e a r c u h o t r h o t u f m 5 o g i l u e t l h n A t c t o c t i o t n a t a o s a m t i c t u e e M a f r n T I :01 2

2/15/2019 “Numb Chin” Syndrome Outside Evaluation • Charles Bell in 1830s-patient with numb chin and breast cancer • Outside EMG 1/16-“C7 radiculopathy” • Unilateral in 90%, can involve the gingiva • MRI-left C6-7 foraminal narrowing • Only neurologic sign of lymphoproliferative • Left C7 nerve root block-not helpful disorder or part of mononeuritis multiplex • TFTs, B12, CBC (wbc, rbc, plt) normal • Broad differential diagnosis • Anti-MAG antibody-negative • Consider brain MRI (trigeminal nerve protocol), PET/CT, or CSF examination • Rx underlying etiology EMG/NCVs at UCSF Differential Diagnosis-Related to WM • Neurolymphomatosis-lymphomatous • Absent left ulnar and medial antebrachial cutaneous SNAPs and left ulnar CMAPs infiltration of the plexus • Needle EMG results • WM with axonal polyneuropathy – Denervation and chronic partial reinnervation • WM with demyelinating polyneuropathy of the left APB, EIP, and ADM muscles • Unrelated brachial plexopathy – Old left femoral neuropathy • Brachial plexopathy associated with WM? • Conclusion: left lower trunk/medial cord brachial plexopathy – No association with plexus • No definitive electrodiagnostic findings of – 2 cases of mononeuritis multiplex-both with acquired demyelination CN and limb nerve palsies 3

2/15/2019 C6-7 C6-7 6 7 C7-T1 6 C7-T1 C6 7 C7 Brachial Plexus MRI Coronal T2 Brachial Plexus C7 Normal right plexus C8 Maravilla KR AJNR 1998 Coronal Left plexus C8 T1 Axial 4

2/15/2019 Nerve MR Correlation Q2-Reduced diffusion on MR • mechanisms increase water content: Neurography DOES NOT indicate which one of the following? • Interrupt axoplasmic flow A. Inflammation 32% • Increase endoneurial B. Hypercellularity 25% fluid C. Infarction 14% 16% 14% • Increase Schwann cell population D. Large molecule retention E. All of the above • Increase permeability of endothelial tight n y n e n o t o o v i r i i i o junctions t a t t a c n b m u l r a a e m l f t e e l n e h a c I r t l r e f e f n p u l o I y c l l H e A l o m e :01 g r a L http://humanphysiology.academy/Neurosciences Q3-The brachial plexus can be Diffusion Weighted Image: DWI biopsied without producing a • Cellularity: many cells neurologic deficit? lower diffusion • Cell membrane integrity: infarct – retain ions and water A. True 65% reduce diffusion B. False • Large vs small 35% molecules: larger molecules reduce diffusion membrane Large molecules e e s :01 u l r a T F A. van der Plas StartRadiology MRI Technique www.startradiology.com 5

2/15/2019 Infraclavicular Approach for Medial Cord Biopsy and Repair with MEP, SSEP, EMG Nerve Monitoring helps identify the plexus elements and map proximal the nerve to choose the biopsy site The medial cord is found medial to the axillary artery medial clavicle axilla Medial Cord Left arm Toluidine blue thin section– Normal peripheral nerve Patient Toluidine Blue thin section – Severe axonal loss Myelin sheaths Axon s 6

2/15/2019 Patient Electron Microscopy (EM) – endoneurial dense material Patient EM – dense material not assoc. with myelin sheaths Overview of Waldenstrom’s WM-Clinical Features Macroglobulinemia (WM) • “Smoldering WM”-marrow abnl and • Defn-Lymphoplasmacytic infiltration of elevated IgM without other clin findings bone marrow associated with IgM • Etiology unknown-solvents, farming? monoclonal gammopathy • B symptoms-fevers, sweats, weight loss • 1400 new cases/year; < 10% under age 50 • Lymphadenopathy, organomegaly • Assoc MYD88 mutation-gene promotes B- • Bone pain/lytic lesions rare (vs. MM) cell survival and growth • Cytopenias-anemia most common (38%) • Low enthusiasm for bone marrow biopsy in • Lymphocytosis/monocytosis common absence of decr rbc, wbc, or platelet count 7

2/15/2019 IgM Pathogenesis Q4-Which neuropathy is most commonly associated with WM? • MGUS IgM may convert to hematologic malignancy at rate of 1-3%/year A. Mononeuritis multiplex – Risks IgM > 1.5 g/dl B. Distal sensory axonal polyneuropathy – Elevated kappa/lambda light chain ratio 40% 39% C. Brachial plexopathy • IgM often directed against MAG, but can D. CIDP bind other nerve tissue components 16% – Ab deposits in skin, kidneys, GI tract 6% – Subperineurial space, epineurium CIDP Mononeuritis multiplex Brachial plexopathy Distal sensory axonal po... :01 WM Management Associated Neuropathy Features in Patients with Neuropathy with WM (n = 30) • No active Rx in “smoldering”-follow with • 28/30 with sensory symptoms in the feet CBC and quantitative IgM every 6 months • 2/30 with postural hand tremor • Search for systemic involvement • 8/30 with demyelination on NCV (vs. 62% – PET/CT with MGUS-IgM); 22/30 axonal PN – LDH, LFTs, BUN/Cr, CBC • Most common presenting sympts are distal • Ibrutinib-daily oral agent binds to Bruton’s sensory loss and gait ataxia in both groups tyrosine kinase permanently in B cells • Clinical evidence of predominant axonal – Often combined with Rituximab loss favors WM – Partial response: 50-90% reduction of IgM 8

2/15/2019 CNS Complications of Plasma Cell Disorders (MM, WM, Amyloidosis) RH: Clinical Course • Spinal cord compr-plasmacytoma, path fx • Repeat marrow bx UCSF confirms WM • Neoplastic meningitis • Staged with PET/CT-negative • Hyperviscosity syndrome-HA, vertigo, • Pain Rx with gabapentin + ataxia, confusion, hearing loss, strokes • Started on Ibrutinib 400 mg/day-IgM decr • Bing-Neel syndrome: Leukoencephal- from 1g/dl to 0.2 g/dl opathy with sz, alt MS, paralysis • Recently added Rituximab • Amyloidoma/cerebral amyloid angiopathy- stroke, mass effect, cog decline, dementia What I Don’t Understand Take Home Points • Accurate initial localization drives imaging, • Is the antibody deposition in this patient diagnostic studies, saves time, and saves $ pathogenic or an epiphenomenon? • Mononeuropathy multiplex can be indolent • What accounts for the regional specificity • If an IgM monoclonal gammopathy is of tissue involvement in her clinical accompanied by focal neuropathy (even if neurologic syndrome? CBC nl)-discuss marrow bx w hematology • What was the role of her numb chin? • Brachial plexus can be biopsied (carefully) • Unique case or another variation of WM without producing a new neurologic deficit with mononeuritis multiplex? • When perplexed, explore the neuro hx again 9