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Disease/ Disorder

See Part 1: AIDP/CIDP Part 1: Evaluation and Diagnosis.

Essentials of Assessment

See Part 1: AIDP/CIDP Part 1: Evaluation and Diagnosis.

Rehabilitation Management and Treatments

At different disease stages

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)

AIDP can be a life-threatening medical emergency that often requires ICU admission. As approximately 10–30% of patients with GBS require ventilation within the first week of admission, patients at risk of respiratory failure should be identified promptly.1,2 The Erasmus GBS Respiratory Insufficiency Score (EGRIS) prognostic tool can be used to calculate the probability (1–90%) of a patient requiring ventilation within 1 week of assessment.2,3 Ventilatory parameters including vital capacity (VC) should be monitored every 1–3 hours initially. If the patient develops hypercarbia, hypoxemia, or a significant drop in VC to < 15 mL/kg body weight, mechanical ventilation may be required.3,4

Additionally, cardiac and hemodynamic monitoring is indicated, as autonomic instability may cause labile blood pressures and life-threatening cardiac arrhythmias. Pharmacologic treatment or cardiac pacing may be necessary.4

Early treatment of acute demyelination is paramount to limiting functional decline, hastening recovery, and preventing axonal damage, as ‘time is nerve.’5  Long-term mobility prognosis, defined as the probability of being able to walk unaided at 4 and 26 weeks can be calculated by the modified Erasmus GBS Outcome Score (mEGOS).6 First-line disease-modifying treatments include the use of intravenous immunoglobulin and plasma exchange (also referred to as plasmapheresis), which have equivalent efficacy in Guillain–Barré syndrome (GBS).7,8

Plasma Exchange (PLEX)/Plasmapheresis for AIDP:

PLEX was first described for the treatment of GBS in 1978 and consists of separating plasma from cells using membrane filtration or centrifugation. Its mechanism of action is presumed to involve the removal of soluble factors and, in particular, complement components and circulating autoantibodies. Albumin diluted with gelatin or fresh frozen plasma is simultaneously reinfused to maintain plasma volume and osmotic equilibrium.9

PLEX has largely fallen out of favor in the US owing to multiple factors,10 including the fact that clinical efficacy depends upon the volume of plasma exchanged, the number and frequency of treatments, as well as the replacement solution and separating technique.9 Additionally, PLEX requires access to two veins, one of which has to permit high flow volumes (often requiring insertion of a central venous line), a PLEX machine, and personnel trained in extracorporeal circulation.9 Serious side effects are uncommon but may include hypotension or hypertension, bradycardia or tachycardia, immunosuppression, hypocalcemia, local catheter-related hematoma or infection, hemolysis, deep venous thrombosis, and the inherent risk of potential exposure to blood products.11

Summary of PLEX data in AIDP:

  • PLEX should be started within 2–4 weeks of symptom onset.4
  • The number of treatments and scheduling regimens vary and should be tailored to the patient’s disease status. Ideally, PLEX should be administered at 200–250 mL/kg x 5 sessions over 7–14 days.4,5
  • PLEX significantly hastens recovery compared to supportive care alone in adults with AIDP:9,12
    • improved time to recover walking with aid
    • improved time to recover walking unaided
    • improved time to improve by one or more disability grades
    • improved time on ventilator
    • reduced risk of cardiac arrhythmias
  • After one year, full recovery of muscle strength was more likely, and severe residual weakness less likely.9,12
  • There is a small but significant increase in the risk of relapse at 6–12 months in patients treated with PLEX compared to those not treated.9
  • Level A evidence supports the use of PLEX in patients with AIDP that is “severe enough to impair independent walking or require mechanical ventilation” and is most effective when treatment is started within 2 weeks of symptom onset.4,13,14
  • Level B evidence suggests the use of PLEX in mild to moderate AIDP in “which ambulation is preserved.”13,14

Intravenous immunoglobulin (IVIg) for AIDP

Human immunoglobulin therapies are derived from purified plasma pooled from multiple donors and can be administered intravenously (IVIg) or subcutaneously (SCIg). The first reported use of IVIg in the treatment of AIDP was in 1988. It requires only a single peripheral vein and no special equipment or specially trained staff. Despite the lack of studies comparing IVIg with a placebo, it is easier to administer and generally more widely available than plasma exchange, making it the preferred treatment of choice.2,7

Common side effects following the administration of IVIg include headache, myalgia, transient hypertension or hypotension, and flushing. These can be addressed by slowing the infusion rate.7 Pre-infusion antipyretics and antihistamines mitigate reactions such as fever, mild arthralgias, and minor allergic/skin reactions (urticaria, eczema).15 There is a risk of anaphylaxis in patients with severe immunoglobulin A deficiency, which is best prevented by investigating quantitative serum immunoglobulins prior to administering IVIg.  More significant adverse events, such as neutropenia, pancytopenia, infection, aseptic meningitis, renal tubular necrosis, worsening of renal failure, electrolyte imbalances, alopecia, as well as thromboembolic events and stroke-like episodes (attributable to hyperviscosity and coagulopathy), have rarely been reported.7,15

Summary of IVIg data in AIDP:

  • IVIg commencing within two weeks of symptom onset hastens recovery as much as PLEX.12
  • IVIg is typically administered at a dose of 2.0 g/kg of body weight divided across 5 consecutive days (0.4 g/kg daily for five days).4,7
  • There is no significant difference between PLEX and IVIg in the frequency of adverse events, but treatment with IVIg is significantly more likely to be completed than PLEX.
  • IVIg infusion following PLEX confers no benefit over PLEX alone.
  • In children with AIDP, IVIg hastens recovery compared to supportive care alone and tends to be preferred over PLEX.5
  • Disadvantages of IVIg include high cost and the potential for repeat infusion(s) due to duration of benefit spanning 2–6 weeks.
  • Development of hypoalbuminemia after treatment with IVIg is associated with a more severe clinical course and a poorer outcome.16

Other immunotherapies for AIDP

Besides IVIg and plasma exchange, no other procedures or drugs have been proven effective.2

Eight randomized controlled trials on the efficacy of corticosteroids for GBS showed no significant benefit, and treatment with oral corticosteroids was even shown to have a negative effect on outcome.2,17 Insufficient evidence is available for the efficacy of add-on treatment with intravenous methylprednisolone in IVIg-treated patients.2

Studies are underway to investigate new immunological strategies including beta interferon alone or combined with IVIg, cyclophosphamide, rituximab, and eculizumab.12

Measuring Prognosis in AIDP

Poor prognosis is associated with older age, rapid progression, preceding Campylobacter jejuni infection with severe diarrhea, and positive CMV serology.  Gender, bulbar and facial weakness, sensory deficit, and pain did not correlate with outcome. Many studies support the prognostic value of EMG.18

Patients with GBS may develop hypoalbuminemia after treatment with IVIg, which is related to a more severe clinical course and a poorer outcome. Low serum levels of albumin may herald the need for mechanical ventilation, but further studies are required to confirm the efficacy of serum albumin as a biomarker to monitor disease activity and treatment response to IVIg.19

A high Erasmus GBS respiratory insufficiency score (EGRIS) can predict need for mechanical ventilation. The modified Erasmus GBS outcome scale (mEGOS) administered upon hospital admission and at day 7 can predict functional outcomes at 6 months and is based on age, preceding diarrhea, and GBS disability score.  Both are easily accessed via a simple online calculator.20

Pediatric Considerations for treatment of AIDP

Patients should be closely monitored for motor, respiratory and autonomic function. Treatment should be considered in severe cases involving progressive weakness, respiratory compromise or bulbar symptoms. There is no difference between IVIG and plasma exchange; however, IVIG is typically chosen for ease of administration. Children typically have better prognosis than adults, with over 80% of children with good long term recovery.21

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

The majority of patients with CIDP experience chronic onset of a progressive or relapsing phase of over 8 weeks.  However, up to 16% of all patients with CIDP present with acute onset of prominent sensory symptoms and signs resembling GBS, but deterioration continues >2 months from onset or 3 or more treatment-related fluctuations occur.22 Hospitalization is less common and supportive care is less aggressive compared with AIDP.

There are many disease-modifying treatments for CIDP, but first-line therapies include IVIg, corticosteroids, and PLEX. The mechanism of action of these treatments is not completely understood, as the mechanism of CIDP is not completely understood. According to a Cochrane systematic review, comparative effective studies demonstrate no clear difference in short-term improvement in impairment with IVIg when compared with intravenous methylprednisolone and probably no improvement when compared with either oral prednisolone or PLEX.15 A more recent review from the Netherlands suggests that, compared with corticosteroids, IVIg has fewer adverse events and leads to faster improvement (within 6 weeks). Corticosteroids seemed to induce remission over a longer period of time, but adverse events of long-term corticosteroid use should be balanced against the high costs of IVIg.23

IVIg for CIDP

There is level A evidence to recommend IVIg as first-line treatment for CIDP with a NNTB (number needed to treat for benefit) of three.22,24 The pooled immunoglobulins are thought to interfere with the complement system and compete with the autoantibodies.15 Additionally, IVIg should be considered as the initial treatment in pure motor CIDP.22 Multiple trials have demonstrated improvement of short-term disability with IVIG compared to placebo, and patients had fewer relapses.15

Although IVIg has been used in CIDP for over 30 years, there limited evidence to guide maintenance dosages and intervals.22 The EFNS Task Force recommends a loading dose of 2.0 g/kg divided over 2 to 5 days, followed by a maintenance dose every three weeks of 1.0 g/kg infused over 1 to 2 days.22,23 Dyck et al proposed a dosing regimen of 0.4 g/kg once weekly for 3 weeks followed by a lower dose of 0.2 g/kg weekly for the next 3 weeks, which showed similar efficacy.23 Some authorities advocate for a second loading dose before transitioning to maintenance therapy, or even continuing therapy at higher loading doses for a period of up to 6 months for severely affected patients.23

If effective, IVIg infusions should be continued, commonly at 1.0 g/kg every 3 weeks until maximum benefit is achieved, followed by individualized downward titration to the lowest effective maintenance dose.  In one study, lowering the dose while maintaining the same infusion interval was better tolerated than extending the interval between infusions while maintaining the same dose.23 One recommended downward titration redefines the interval between infusions as the time to deteriorate after the loading dose. Thereafter, two courses of 2 g/kg are infused, and subsequent courses are reduced by 20% until arriving at a minimal dose at which relapse occurs.23

A single longitudinal study demonstrated IVIg improved disability over placebo at 24 and 48 weeks, yet practically, patients receive infusions for years to decades.  Unfortunately, the only way to determine IVIg-dependency is to stop infusions and monitor for deterioration, which typically manifests within 4 months.  One authority recommends trials of IVIg withdrawal at ~6 months, 1 year and every 1-2 years thereafter.23 Preliminary studies suggest that sonographic variability in intra-nerve cross-sectional area25 as well as proximally-evoked CMAP amplitudes may be useful to measure response to treatment26, yet no reliable biomarkers exist to guide treatment decisions.23

Higher infusion rates (>80 to 120 g/day) are safe and allow doses to be administered in a shorter number of days but may be associated with higher rates of IgG catabolism.23 There is an increasing trend to use lower IVIg doses at more frequent intervals in an effort to maintain more constant serum IgG levels rather than higher peak serum levels during maintenance therapy.23

Mild or transient adverse events were reported in 49%, with only 0.5-4% reporting serious adverse events.24 Long-term side effects include decline in hematocrit and glomerular filtration rate, emphasizing need for observation of hematologic and renal function in patients treated with chronic IVIg.27 One retrospective uncontrolled study demonstrated no differences in response to therapy according to manufacturer or brand of IVIg.28

Corticosteroids for CIDP

There is level C evidence recommending corticosteroids in the treatment of CIDP.8 It is thought that corticosteroids suppress genes that are commonly activated in inflammatory conditions.15 Corticosteroids are inexpensive and easy to administer, and multiple clinical trials have investigated types of corticosteroid, routes of administration, and dosing schedules. Prednisone is converted into prednisolone in the liver with little difference in effect, whereas dexamethasone is more potent and used in smaller doses.29 Despite its widespread use, there have only been two random controlled trials. A low-quality evidence demonstrated functional improvements with daily oral prednisone compared to placebo.  And a moderate-quality evidence trial demonstrating no difference between high dose monthly dexamethasone compared to daily prednisolone.30

The European Federation of Neurological Societies (EFNS) Task Force suggests starting prednisolone at 60 mg per day (children: 1.5 mg/kg) and then slowly tapering the dose over months to years.22 Six months’ treatment with high-dose monthly oral dexamethasone does not improve disability more than daily oral prednisolone.15 Whether to use daily or alternate day prednisolone or prednisone or intermittent high-dose monthly intravenous or oral regimens hinges largely upon prescriber opinion.22

Recent randomized trials31 suggest pulsed corticosteroids have higher potential to achieve therapy-free remission or longer remission-free periods compared with IVIg, with relatively low rates of serious side effects when administered as pulsed intravenous infusions over short durations, such as IV methylprednisolone 2-5 g over 2-5 days followed by 1-2 g per month for 2-3 months. Pulsed steroids could be considered first, rather than second choice immunomodulation, with a goal of achieving remission after short-term use.31

Despite the lack of high-quality evidence, corticosteroids are still widely used due to global availability, ease of administration, low cost and familiarity. The duration of corticosteroid treatment for CIDP often last months to years; therefore, clinicians should take steps to mitigate the adverse sequelae of chronic corticosteroids.22 Serious side effects of long-term use include Cushing syndrome, adrenal insufficiency, diabetes mellitus, gastritis/esophagitis and ulcer, increased blood pressure, osteoporosis, psychosis, weight gain, and cataracts. Long-term use of corticosteroids in the pure motor variant of CIDP and multifocal motor neuropathy may actually be harmful.22

PLEX for CIDP

There is level A evidence recommending PLEX if IVIg and corticosteroids are ineffective.22 There is moderate to high-quality evidence that twice-weekly PLEX produces short-term improvements in disability, but effects are not long lasting, and rapid deterioration may occur after cessation of treatments within 1 to 5 weeks.13,22,32 Therefore, PLEX is recommended as a short-term treatment option for CIDP.13 The largest observation study of PLEX cited a 3.9% complication rate.15

Other immunotherapies for CIDP

Combination treatments or augmentation with an immunosuppressant or immunomodulatory agent should be considered if response to monotherapy is inadequate, or the maintenance doses are unacceptably high.22

There is low-quality evidence that adjunctive azathioprine (2 mg/kg) added to prednisone may improve impairment compared with prednisone alone, with adverse effects reported in 10%.15,33

Low-quality evidence failed to demonstrate a 20% reduction in corticosteroid or IVIg doses with the addition of methotrexate 15mg/kg, yet with the added known methotrexate risks of teratogenicity, abnormal liver function, and pulmonary fibrosis.15

Trials with interferon beta-1a (in comparison to placebo), failed to to show improvement at 12 weeks and 32 weeks. Serious adverse events were no more common than placebo15

Observational studies of these and other drugs, including cyclophosphamide, cyclosporine, mycophenolate mofetil, etanercept, rituximab, alemtuzumab, natalizumab, peripheral blood stem cell transplantation, and alpha interferon are of insufficient quality to determine potential benefit.22,33

Coordination of care

In the acute setting, multidisciplinary treatment involves a neurologist, intensivist, rehabilitation medicine physician, physical therapist, occupational therapist, speech therapist, and respiratory therapist.

In addition to the above disease-modifying therapies, the following general rehabilitation management principles are applicable to the acute care setting:

  • Prophylaxis for deep vein thrombosis
  • Management of potential bladder and/or bowel dysfunction
  • Proper positioning, weight shifts, and skin monitoring to prevent skin breakdown and decubitus ulcer formation in immobile patients
  • Initiation of therapy services with a focus on early mobility.
  • Psychosocial support
  • Pain management using neuropathic pain medications, nonsteroidal anti-inflammatories (NSAIDs), and/or opiates. High-quality studies of pharmacotherapy of pain in GBS are lacking, but low-quality evidence exists in support of gabapentin and carbamazepine, limited only by sedation.34

In the ambulatory/chronic care setting, patients with residual deficits from AIDP or CIDP may also benefit from:

  • Orthotic management (ankle foot orthoses) for foot drop
  • Pain management using neuropathic pain medications, nonsteroidal anti-inflammatories (NSAIDs), and/or opiates.

Patient & family education

Patients with AIDP and their families should be counseled early in the disease course about prognosis, various treatment options, and long-term management. In severe cases, proper education on mechanical ventilation, tracheostomy care, bowel and bladder management, skin monitoring, pain management, orthotics, household modification, contracture prevention, exercise, diet and lifestyle management, fall prevention and recovery, driving safety, and foot care should be included.

Additionally, since CIDP may be associated with peripheral nerve and/or nerve root hypertrophy due to redundant layers of myelin, patients should be cautioned and educated regarding:

  • Neuroprotective strategies, owing to potential increased likelihood of peripheral compression mononeuropathies, and
  • Monitoring for development of neurogenic claudication from lumbar spinal stenosis caused by potential root enlargement.

Additionally, studies demonstrate that up to 6% of patients with AIDP may relapse, and up to 10% may exhibit new symptoms or fluctuations in their disease state while undergoing IVIg or PLEX treatment.35 Therefore, patient and family should be counseled regarding signs/symptoms of medical complications or disease recurrence/relapse which should prompt follow-up.

Patients with CIDP may find additional social support locally or online. One such online organization is the GBS-CIDP Foundation International (http://www.gbs-cidp.org/).

Pediatric considerations for treatment of CIDP

Childhood CIDP is rare with an estimated 1in 200,000 cases. First line treatment options include IVIG or corticosteroids. IVIG is typically preferred given side effects of steroids, including osteoporosis. For relapsing cases, some new studies have suggested pulsed weekly corticosteroid can be effective. However, nonsteroidal immunosuppressive agents have not shown to be effective. Childhood CIDP tends to have more favorable outcome than adult CIDP, with most children having minimal residual weakness.36

Emerging/unique interventions

Home IVIg infusion

A pair of Canadian studies demonstrated that IVIg infused both in patient homes and in ambulatory/outpatient infusion centers is feasible and safe for CIDP maintenance therapy. Both studies reported high patient satisfaction and preference for non-inpatient treatments.37,38 A preliminary study in the US demonstrated favorable tolerability even for IVIg-naïve individuals, with an adverse effect rate 4.7%.39 For chronic neuromuscular conditions the UK, home infusion is a first-line preferred treatment option.37

Subcutaneous immunoglobulin (SCIg) for CIDP

The half-life of SCIg does not differ appreciably from that of IVIg, and it can be administered at lower dosages and more frequent intervals than IVIg resulting in higher and more stable serum IgG levels, potentially improving efficacy and reducing adverse effects and ‘end-of-dose’ effect (treatment wearing-off before the next dose is due).40,41 Patient self-administered dosing is well-tolerated up to 50 grams per week administered in 2-3 injections.42 Data from a recent RCT supports maintenance therapy with a weekly subcutaneous dose of 0.2–0.4 g/kg of SCIg.43 Disadvantages include local injection site reactions.  Studies of cost-effectiveness and health-related quality of life favor SCIg infusion.42,44 A small random control trial (n=29) demonstrated greater improvement in motor strength with SCIg compared to IVIG. A random control trial of 69 patients who responded initially to IVIG compared placebo vs low dose SCIg (0.2g/kg) vs high dose SCIg (0.4g/kg) weekly for 24 weeks to analyze efficacy for maintenance therapy. This study demonstrated SCIg is effective with absolute risk reduction of 25% for low dose group and 30% for high dose group.43

Pump-delivered SCIg may be the next frontier of independent home administration options.

Outcomes measures for both AIDP and CIDP have been proposed to quantify response to therapeutic interventions and may be increasingly used by payers to justify ongoing value of pharmacotherapy.

GBS:

Clinical trials have used the GBS disability score, time to recover unaided walking, Sickness Impact Profile, Medical Outcomes Study 36-Item Short-Form Health Survey, and the EuroQol-5D to measure the patient’s activity and health-related quality of life.45

CIDP:

Recent clinical trials have assessed disability in patients with CIDP using the Inflammatory Neuropathy Cause and Treatment overall disability severity score (INCAT-ODSS) and physical impairment using the Medical Research Council strength sum score and/or INCAT sensory sum score.46

The Rasch-built Overall Disability Scale (R-ODS) is a 24-item functional questionnaire that can easily be completed by patients in a clinical practice setting. R-ODS is more sensitive for detection of clinically meaningful changes over time than the Inflammatory Neuropathy Cause and Treatment-Overall Neuropathy Limitation Scale (INCAT-ONLS) in patients with CIDP or GBS.47

Promising therapies using monoclonal antibodies, such as rituximab and natalizumab and stem cell therapies for treatment of CIDP warrant further research.48

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Immunotherapy

  • IVIg and PLEX are first-line treatments for AIDP. Up to 6% of patients with AIDP may relapse and up to 10% exhibit new symptoms or fluctuations in their disease state while undergoing IVIg or PLEX.35
  • Corticosteroids should not be used in the treatment of AIDP.49
  • IVIg, PLEX, and corticosteroids are mainstay treatments for CIDP. Approximately 30% to 60% of patients with CIDP treated with mainstay therapies will substantially improve.50,51 If corticosteroids are used in the management of CIDP, the treating physician should mitigate long-term adverse effects.
  • In CIDP, IVIg was more frequently effective (NNTB of 3) and tolerated (87.5%) than corticosteroids (47.6%) during the first 6 months of treatment. When effective however, corticosteroids had higher potential to achieve and maintain drug-free remission and less frequently associated with deterioration than IVIg in the 6 months following therapy discontinuation.31,52
  • IVIg is still recommended as first line in motor-predominant and rapidly-progressive forms of CIDP, and in those for whom corticosteroids are contraindicated.31
  • Functional outcomes measures such as the INCAT-ODSS or R-ODS should be administered to objectively measure treatment responses and have potential to become a required part of payer authorization for costly immunotherapy.
  • Potential benefits of new immune therapies await confirmation from randomized studies.52

Misdiagnosis of CIDP

It is estimated that 15–55% of patients may receive unnecessary IVIg treatments for misdiagnosed CIDP.23 This may be perpetuated by (1) heterogeneity of disease, (2) fear of deterioration after stopping IVIg, (3) subjective patient reports of treatment benefit, (4) liberal electrodiagnostic interpretation of demyelination, and (5) overreliance on CSF findings.23,53 Furthermore, misinterpretation of electrodiagnostic data as ‘demyelinating’ may occur in the setting of: (1) amplitude-dependent conduction velocity slowing in length-dependent axonopathy, (2) amplitude-independent slowing in diabetics, (3) overreliance on fibular CMAP from the EDB, (4) absent conduction block, and (5) velocity slowing limited to compressible sites.54 Strict adherence to published EFNS/PNS diagnostic criteria of demyelination is crucial.

Cutting Edge/ Emerging and Unique Concepts and Practice

Preliminary studies of complement inhibitors nafamostat mesilate (in anti-GM1 rabbits) and eculizumab (in anti-GQ1b mice) appear promising.  Furthermore, combination therapy with complement inhibitors and IVIg is being considered.55

Eculizumab and IdeS (IgG-degrading enzyme of Strepotococcus pyogenes) are promising agents to rapidly suppress MAC formation and axonal loss. Clinical trials are expected to improve the prognosis of GBS patients.56

A novel treatment modality (“zipper method”) was studied in children diagnosed with severe GBS.57 PLEX was started immediately, followed by an IVIg infusion and a second PLEX session 24 hours later. This plasma exchange–IVIg cycle was repeated 5 times and seemed to reduce mortality, speed weaning from mechanical ventilation, and shorten the hospital stay in patients with severe GBS who required intensive care.57

Gaps in the Evidence-Based Knowledge

Further research is needed to identify which factors predict response and deterioration after various therapies. Comparative effectiveness studies are urgently needed to determine cost-effectiveness of corticosteroids, IVIg, and SCIg, and whether adjunctive treatment with immunosuppressive agents is superior to monotherapy.29

Future trials should have improved designs and longer treatment durations, and should measure function and other outcomes relevant to patients with CIDP.33

Large, well-designed RCTs are required to further investigate the efficacy and safety of potential interventions for patients with pain in both GBS and CIDP.

References

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 Original Version of the Topic

Jeremy I. Simon, MD, Joshua Armstrong, DO. AIDP/CIDP Part 2: Treatment. 9/20/2014.

Previous Revision(s) of the Topic

Jeremy I. Simon, MD, Joshua Armstrong, DO. AIDP/CIDP Part 2: Treatment. 6/29/2018

Author Disclosure

Amanda Ly, MD
Nothing to Disclose

Nikhil Gopal, MBBS
Nothing to Disclose

Rajashree Srinivasan, MD, MBBS
Nothing to Disclose