Advances in the Treatment of Autoimmune Neuromuscular Disease

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Advances in the Treatment of Autoimmune
Neuromuscular DiseaseFrom Diagnostic
Challenges to Long-Term Management
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Faculty
Chairperson Gil I. Wolfe, MD Professor and Chief
of the Neuromuscular Section Department of
Neurology University of Texas Southwestern
Medical Center University of Texas Southwestern
Hospital Dallas, Texas

• Erik R. Ensrud, MD
• Board certified in PMR/EMG/Neurology/
• Neuromuscular Disease
• Director, Neuromuscular Center and EMG Laboratory
• VA Boston Healthcare System
• Associate Neurologist
• Brigham and Womens Hospital
• Boston, Massachusetts

Gregory T. Carter, MD, MS Clinical Professor of
Physical Medicine and Rehabilitation and of
Neuromuscular Medicine University of California
Davis Sacramento, California Medical
Director Regional Neuromuscular Center Providence
St. Peter Hospital Olympia, Washington
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Topics

• Diagnostic criteria for autoimmune neuromuscular
  diseases (NMD)
• Making treatment decisionsusing experience,
  exploring the evidence
• Role of rehabilitation in autoimmune NMD

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Objectives

• On completion of this activity, participants
  should be able to
• Recognize the clinical presentations and key
  diagnostic features of autoimmune NMD
• Select appropriate therapies and recognize
  potential treatment failures on the basis of
  patient history and available clinical evidence
• Determine appropriate timing, dosage, and
  duration of therapies used in the treatment of
  autoimmune NMD
• Recognize the long-term implications of NMD and
  become proficient in applying appropriate
  rehabilitative strategies

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Barohn RJ, Saperstein DS. Semin
Neurol.19981849-61.
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• Dyck at Mayo Clinic, 1975
• Acquired neuropathy that shares a similar
  pathology and autoimmune etiology with GBS
• Different from GBS
• Usually, but not always, in the manner of
  presentation
• Natural history of the disease
• Rarely associated with antecedent infection
• Responds to prednisone
• Peak incidence at 4060 yrs old

Dyck PJ et al. Mayo Clin Proc. 197550621-637
Burns T, Ensrud E. (Producers). (17 Aug 2007).
Chronic inflammatory polyradiculoneuropathy with
Peter J. Dyck, MD Available at
http//beta.aanem.org/Education/Products/PhyPodcas
ts.aspx?page3fileid355.
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• Slow onset of progressive symmetric muscle
  weakness
• Both proximal and distal weakness
• Progresses for gt2 months may be
  relapsing-remitting
• 60 slowly progressive course
• 35 relapsing-remitting
• Sensory loss less prominent than weakness
  paresthesias and numbness, but rarely significant
  pain
• Large-fiber sensory modalities are more affected
• Diffuse decreased or absent reflexes
• 35 have evidence of CNS demyelination
• Pathology
• Multifocal demyelination
• No vasculitic changes
• Sural nerve biopsy is rarely necessary

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Ensrud ER, Krivickas LS. Phys Med Rehabil Clin N
Am. 200112321-334.
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Alberti MA et al. J Peripher Nerv Syst.
201116136-142.
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AIDP

• Prolonged distal motor and F-wave (early)
  latencies
• Absent or impersistent F-waves
• Slowing of CV and/or conduction block
• Reduction of CMAPs /- temporal dispersion
• Abnormal or absent median SNAP normal sural
  SNAP (AMNS) 39

Alberti MA et al. J Peripher Nerv Syst.
201116136-142.
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Very Early EDX Findings in GBS (Within 4 Days of
Clinical Onset)

• Abnormally late responses in 77
• Prolonged distal motor latency in 55
• Cranial nerve study abnormality in 44
• Motor nerve conduction velocity slowing in 23

Alberti MA et al. J Peripher Nerv Syst.
201116136-142.
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Barohn RJ et al. Arch Neurol. 198946878-884.
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• Complex topic
• Need to study multiple nerves, MS of PNS
• Correct temperature (gt32.00C) is crucial
• NCS shows electrophysiologic evidence of
  demyelination
• Distal motor latency gt125 normal
• Conduction velocity lt70 normal (lt80 if CMAP amp
  80 normal)
• Conduction block
• Temporal dispersion
• Needle EMG tends to show more prominent
  reinnervation changes than acute denervation
  changes, consistent with slow temporal nature of
  pathology
• EMG may look axonal because of secondary axonal
  damage

Barohn RJ, Saperstein DS. Semin Neurol
.19981849-61.
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GBSEarly Recognitionof Poor Prognosis

• A recent paper looked at 397 GBS patients
• Which patients were unable to walk at 4 weeks, 3
  months, and 6 months?
• Three important factors
• Older age (gt60)
• Preceding diarrhea
• MRC scores averaged 3 or less when the following
  were tested
• Shoulder abd/elb flexion/wrist ext hip
  flexion/knee ext/ankle dorsiflexion
• MRC scores were most predictive at 7 days after
  admission

Walgaard C et al. Neurology. 201176968-975.
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CIDP With Acute Onset(A-CIDP)

• 170 patients with GBS
• 1-year follow-up
• Treatmentrelated fluctuation (TRF) in GBS always
  occurred within 8 weeks of symptom onset
• Always 1 or at the most 2 TRFs
• Consider A-CIDP when a patient thought to have
  AIDP/GBS deteriorates 8 weeks from onset or has 3
  or more TRFs
• Start maintenance therapy for CIDP when A-CIDP is
  recognized

Ruts L et al. Neurology. 2010741680-1696
Ensrud E. (Producer). (25 May 2010).
Distinguishing acute-onset CIDP from fluctuating
Guillain-Barré syndrome a prospective study
with Dr. Pieter van Doorn. Available at
http//www.aan.com/rss/?eventfeedchannel1.
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GBSRehabilitative Strategies

• ICU setting
• Passive ROM, prevent joint contracture
• Active assisted ROM as tolerated
• Close monitoring
• Medical-surgical setting
• Increase intervention
• Isometric exercises while the patient is
  nonambulatory (Delorme technique)
• Physical therapy

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CIDP

• Evidence-based treatments
• Prednisone 60100 mg per day, followed by taper
• IVIG 2 g/kg as induction therapy
• Plasma exchange 56 treatments

Hughes RA et al. Cochrane Database Syst Rev.
2004(4)CD003280. Mehndiratta MM et al. Cochrane
Database Syst Rev. 2004(3)CD003906. van Schaik
IN et al. Cochrane Database Syst Rev.
2002(2)CD001797.
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MGRoutine Diagnostic Work-up

• Repetitive nerve testing (3 Hz)
• U-shaped decrement
• Reproducible
• Partially repairable
• Anti-acetylcholine receptor antibodies (IgG)
• Antimuscle-specific tyrosine kinase (anti-MUSK)
  antibodies
• Chest CT to look for thymoma

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Autoimmune NMDRehabilitative Strategies

• MG patients who are adequately medicated may have
  minimal rehabilitative needs
• During an acute crisis, passive limb exercises
  lower the risk of deep vein thrombosis (DVT)
• DVT prophylaxis is recommended
• Bulbar dysfunction increases the risk of
  aspiration

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• Anticholinesterase agents (pyridostigmine) for
  symptomatic relief
• Corticosteroids
• Immunosuppressants for steroid-sparing effect
  (azathioprine, mycophenolate mofetil,
  cyclosporine, tacrolimus, rituximab)
• Plasma exchange or IVIG for a crisis before
  thymectomy for severe exacerbations or in
  refractory patients
• IVIG is more accessible
• Plasma exchange may work faster
• Thymectomy
• Removal of thymoma
• Thymectomy is a treatment option in
  nonthymomatous MG1

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Adapted from Grob D et al. Muscle Nerve.
200837141.
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MGSelection of SteroidSparing Agents

• Azathioprine (may be used in conjunction with
  prednisone)
• At least 1 year to see a full effect
• Often seenan increase of at least 10 from
  baseline MCV in CBC in responders
• Mycophenolate
• Tacrolimus

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GBSTreatment of Pain

• Almost 90 of GBS patients experience pain
• 66 have very severe pain
• Gabapentin or pregabalin
• Tricyclic antidepressants
• Opioid analgesics

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GBSBiPAP for Respiratory Support

• Respiratory failure is a significant cause of
  morbidity and mortality in GBS
• 33 of GBS patients require intubation
• Average time to intubation is 7 days after
  symptom onset
• Little clinical experience with BiPAP in GBS
  (used more commonly in MG)

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GBSRehabilitative Approachto Pain Management

• Topical agents (capsaicin, lidocaine gel)
• Desensitization techniques (pressure garment)
• Transcutaneous electrical nerve stimulation (TENS)

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NMDRehabilitative Strategies

• Isotonic exercise
• Isokinetic exercise
• Occupational therapyaddress activities of daily
  living (ADLs), functional concerns
• Speech therapy if necessary
• Assistive devices (walker, canes, etc)

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NMDExercise as a Precautionary Step

• Watch for weakness as a sign of overwork
• Exercise level should be submaximal
• Higher repetition, lower weight
• Endurance trainingwater exercise for uniform
  resistance
• Monitor serum creatine kinase monitor for
  myoglobinurea watch for delayed-onset muscle
  soreness or pain

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Key PointsSummary

• Autoimmune NMD
• Diagnostic criteria
• Treatment decisions
• Role of rehabilitation
• Diagnostic approachtypical presentations of GBS
  and CIDP
• Acute presentation of CIDP with treatmentrelated
  fluctuations timing could lead to diagnosis of
  acute-onset CIDP
• Diagnostic elements of MG long-term management
  and outcomes
• Role of physical medicine and rehabilitative
  strategies in autoimmune NMD in the acute and
  chronic setting

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