Thanks and Disclosures UCSF Neurology Outpatient Conference - - PowerPoint PPT Presentation

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Thanks and Disclosures UCSF Neurology Outpatient Conference - - PowerPoint PPT Presentation

Aug 25, 2022 538 likes •641 views

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

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SLIDE 1

2/15/2019 1 UCSF Neurology Outpatient Conference John Engstrom, M.D. February 15, 2019 49 yo woman with Numb Chin Syndrome and a Left Brachial Plexopathy

Thanks and Disclosures

Thanks!

  • Dr. Cynthia Chin-Neuroradiology
  • Dr. Line Jacques-Neurosurgery
  • Dr. Sean Ferris-Neuropathology

Disclosures Sadly, I have no conflicts to disclose

Topics Covered

  • Patient history and current exam
  • Review outside info + initial info at UCSF
  • Initial localization and differential diagnosis
  • Neuroradiology and Neurosurgery
  • Neuropathology
  • Clinical Features and Management
  • Clinical Course
  • Take Home Points

49 yo woman with weakness, numbness, pain in left arm/hand

  • 2012 Left leg weakness/numbness-left leg

buckled with walking and numbness over knee and medial calf

  • 2013 Numb left chin

– Spread to chin on right – Brain MRI normal – IEP: IgM monoclonal gammopathy – Bone marrow “smoldering” Waldenstrom’s macroglobulinemia

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SLIDE 2

2/15/2019 2

49 yo woman with weakness, numbness, pain in left arm/hand

  • 8/15-Left 5th 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 Localization

  • Weakness in APB, EIP, FCU, ADM-share

the medial cord (MC) and lower trunk (LT)

  • f the brachial plexus; C8 root and C8 AHC
  • Weakness EIP-shares LT, C8 root, C8 AHC
  • Numbness medial forearm-medial ante-

brachial cutaneous nerve-MC/LT/C8 root

  • Numbness medial arm-medial cutaneous

nerve of arm-MC/LT/C8 root

Q1: Numb chin syndrome is caused by which of the following?

  • A. Metastatic tumor affecting the

third division of the 5th cranial nerve

  • B. Trauma to the 5th cranial nerve
  • C. Infection contiguous to the third

division of the 5th cranial nerve

  • D. All of the above

M e t a s t a t i c t u m

  • r

a f f e c t i . . T r a u m a t

  • t

h e 5 t h c r a n i a . . . I n f e c t i

  • n

c

  • n

t i g u

  • u

s t

  • t

. . A l l

  • f

t h e a b

  • v

e

6% 91% 3% 0%

:01

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SLIDE 3

2/15/2019 3

“Numb Chin” Syndrome

  • Charles Bell in 1830s-patient with numb

chin and breast cancer

  • Unilateral in 90%, can involve the gingiva
  • Only neurologic sign of lymphoproliferative

disorder or part of mononeuritis multiplex

  • Broad differential diagnosis
  • Consider brain MRI (trigeminal nerve

protocol), PET/CT, or CSF examination

  • Rx underlying etiology

Outside Evaluation

  • Outside EMG 1/16-“C7 radiculopathy”
  • MRI-left C6-7 foraminal narrowing
  • Left C7 nerve root block-not helpful
  • TFTs, B12, CBC (wbc, rbc, plt) normal
  • Anti-MAG antibody-negative

EMG/NCVs at UCSF

  • Absent left ulnar and medial antebrachial

cutaneous SNAPs and left ulnar CMAPs

  • Needle EMG results

– Denervation and chronic partial reinnervation

  • f the left APB, EIP, and ADM muscles

– Old left femoral neuropathy

  • Conclusion: left lower trunk/medial cord brachial

plexopathy

  • No definitive electrodiagnostic findings of

acquired demyelination

Differential Diagnosis-Related to WM

  • Neurolymphomatosis-lymphomatous

infiltration of the plexus

  • WM with axonal polyneuropathy
  • WM with demyelinating polyneuropathy
  • Unrelated brachial plexopathy
  • Brachial plexopathy associated with WM?

– No association with plexus – 2 cases of mononeuritis multiplex-both with CN and limb nerve palsies

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2/15/2019 4

C6-7 C7-T1 C6 C7 C6-7 C7-T1 6 7 6 7

Brachial Plexus MRI

Coronal Axial

Maravilla KR AJNR 1998

C7 C8 C8 T1 Coronal T2 Brachial Plexus Normal right plexus Left plexus

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2/15/2019 5

Q2-Reduced diffusion on MR Neurography DOES NOT indicate which

  • ne of the following?
  • A. Inflammation
  • B. Hypercellularity
  • C. Infarction
  • D. Large molecule retention
  • E. All of the above

I n f l a m m a t i

  • n

H y p e r c e l l u l a r i t y I n f a r c t i

  • n

L a r g e m

  • l

e c u l e r e t e n t i

  • n

A l l

  • f

t h e a b

  • v

e

14% 16% 32% 14% 25%

:01

Nerve MR Correlation

  • mechanisms increase water content:
  • Interrupt axoplasmic

flow

  • Increase endoneurial

fluid

  • Increase Schwann cell

population

  • Increase permeability
  • f endothelial tight

junctions

http://humanphysiology.academy/Neurosciences

  • A. van der Plas StartRadiology MRI Technique www.startradiology.com

Diffusion Weighted Image: DWI

  • Cellularity: many cells

lower diffusion

  • Cell membrane

integrity: infarct – retain ions and water reduce diffusion

  • Large vs small

molecules: larger molecules reduce diffusion

membrane

Large molecules

Q3-The brachial plexus can be biopsied without producing a neurologic deficit?

  • A. True
  • B. False

T r u e F a l s e

65% 35%

:01

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2/15/2019 6

Infraclavicular Approach for Medial Cord Biopsy and Repair with MEP, SSEP, EMG

proximal medial clavicle Left arm axilla Medial Cord Nerve Monitoring helps identify the plexus elements and map the nerve to choose the biopsy site The medial cord is found medial to the axillary artery Myelin sheaths Axon s

Toluidine blue thin section– Normal peripheral nerve Patient Toluidine Blue thin section – Severe axonal loss

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2/15/2019 7

Patient Electron Microscopy (EM) – endoneurial dense material

Patient EM – dense material not assoc. with myelin sheaths

Overview of Waldenstrom’s Macroglobulinemia (WM)

  • Defn-Lymphoplasmacytic infiltration of

bone marrow associated with IgM monoclonal gammopathy

  • 1400 new cases/year; < 10% under age 50
  • Assoc MYD88 mutation-gene promotes B-

cell survival and growth

  • Low enthusiasm for bone marrow biopsy in

absence of decr rbc, wbc, or platelet count

WM-Clinical Features

  • “Smoldering WM”-marrow abnl and

elevated IgM without other clin findings

  • Etiology unknown-solvents, farming?
  • B symptoms-fevers, sweats, weight loss
  • Lymphadenopathy, organomegaly
  • Bone pain/lytic lesions rare (vs. MM)
  • Cytopenias-anemia most common (38%)
  • Lymphocytosis/monocytosis common
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2/15/2019 8

IgM Pathogenesis

  • MGUS IgM may convert to hematologic

malignancy at rate of 1-3%/year

– Risks IgM > 1.5 g/dl – Elevated kappa/lambda light chain ratio

  • IgM often directed against MAG, but can

bind other nerve tissue components

– Ab deposits in skin, kidneys, GI tract – Subperineurial space, epineurium

Q4-Which neuropathy is most commonly associated with WM?

  • A. Mononeuritis multiplex
  • B. Distal sensory axonal polyneuropathy
  • C. Brachial plexopathy
  • D. CIDP

Mononeuritis multiplex Distal sensory axonal po... Brachial plexopathy CIDP

40% 16% 6% 39%

:01

Neuropathy Features in Patients with WM (n = 30)

  • 28/30 with sensory symptoms in the feet
  • 2/30 with postural hand tremor
  • 8/30 with demyelination on NCV (vs. 62%

with MGUS-IgM); 22/30 axonal PN

  • Most common presenting sympts are distal

sensory loss and gait ataxia in both groups

  • Clinical evidence of predominant axonal

loss favors WM

WM Management Associated with Neuropathy

  • No active Rx in “smoldering”-follow with

CBC and quantitative IgM every 6 months

  • Search for systemic involvement

– PET/CT – LDH, LFTs, BUN/Cr, CBC

  • Ibrutinib-daily oral agent binds to Bruton’s

tyrosine kinase permanently in B cells

– Often combined with Rituximab – Partial response: 50-90% reduction of IgM

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2/15/2019 9

CNS Complications of Plasma Cell Disorders (MM, WM, Amyloidosis)

  • Spinal cord compr-plasmacytoma, path fx
  • Neoplastic meningitis
  • Hyperviscosity syndrome-HA, vertigo,

ataxia, confusion, hearing loss, strokes

  • Bing-Neel syndrome: Leukoencephal-
  • pathy with sz, alt MS, paralysis
  • Amyloidoma/cerebral amyloid angiopathy-

stroke, mass effect, cog decline, dementia

RH: Clinical Course

  • Repeat marrow bx UCSF confirms WM
  • Staged with PET/CT-negative
  • Pain Rx with gabapentin +
  • Started on Ibrutinib 400 mg/day-IgM decr

from 1g/dl to 0.2 g/dl

  • Recently added Rituximab

What I Don’t Understand

  • Is the antibody deposition in this patient

pathogenic or an epiphenomenon?

  • What accounts for the regional specificity
  • f tissue involvement in her clinical

neurologic syndrome?

  • What was the role of her numb chin?
  • Unique case or another variation of WM

with mononeuritis multiplex?

Take Home Points

  • Accurate initial localization drives imaging,

diagnostic studies, saves time, and saves $

  • Mononeuropathy multiplex can be indolent
  • If an IgM monoclonal gammopathy is

accompanied by focal neuropathy (even if CBC nl)-discuss marrow bx w hematology

  • Brachial plexus can be biopsied (carefully)

without producing a new neurologic deficit

  • When perplexed, explore the neuro hx again