Immune Mediated Neuropathies

Author(s): Samuel S. Murala, MD and Se Won Lee, MD

Originally published:12/27/2012

Last updated:3/6/2018

1. DISEASE/DISORDER:

Definition

Immune mediated neuropathies are a diverse group of disorders caused by immune-mediated damage to peripheral nerves. These can range from a fulminant, life-threatening crisis to an asymptomatic, minimally progressive process. Some are part of a larger systemic autoimmune process, and others an isolated peripheral nerve disorder.

The major groupings include

  • Acute immune mediated neuropathy (Guillain-Barré Syndromes [GBS] include following subtypes)1
  • Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
  • Acute motor and sensory axonal neuropathy (AMSAN)
  • Acute motor axonal neuropathy (AMAN)
  • Miller-Fisher syndrome (MFS)
  • Sensory ataxic GBS
  • Other acute variants such as Acute pandysautonomic neuropathy

Chronic immune mediated polyneuropathy1,2

  • Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); pure motor form and sensory CIDP
  • Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), Lewis-Summer Syndrome
  • Multifocal motor neuropathy (MMN)
  • Distal acquired demyelinating symmetrical (DADS)
  • Chronic immune sensory polyradiculopathy
  • Neuropathy associated with POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin abnormalities) syndrome
  • Neuropathy associated with monoclonal IgM anti- MAG (Myelin Associated Glycoprotein) antibodies or Anti-MAG neuropathy
  • Other immune mediated neuropathies related to systemic immune disorders, and rarer types such as paraneoplastic neuropathies associated with anti-Hu antibodies and vasculitic neuropathies.

Epidemiology including risk factors

The annual incidence of immune-mediated neuropathies (IN) varies among specific types with most common being GBS and subtype AIDP as well as CIDP, MMN and POEMS syndrome.

GBS

  • The annual incidence is reported to be 1.2-2.3 per 100,000, with men more often affected than women.3 The incidence increases in older age.
  • AIDP is the major occurring subtype of GBS in Europe and North America while axonal forms such as AMAN and AMSAN are found more commonly in China and Japan (50% of cases).
  • GBS is commonly precipitated by an infection with incidence varying depending on geographic locations and infectious outbreaks.
    • Campylobacter jejuni (most common identifiable antecedent infection), Cytomegalovirus (CMV), Epstein-Barr virus (EBV) predominate as infectious pathogens. Other organisms implicated are influenza A, Mycoplasma pneumoniae, Hemophilus influenzae, Hepatitis A, B and C.2,4 Connection between C.jejuni and GBS is strong, particularly the AMAN variant (67%-92%).
    • Zika virus is the most recently identified antecedent infection with several-fold increased incidence reported in several countries as of 2016.4
    • The swine flu vaccine was felt to be a potential risk factor in 1976; however, in 2009 the risk in China was lower in those vaccinated than in those who were not.5
  • Other risk factors include autoimmune disorders, malignancy and surgery.

Chronic acquired demyelinating neuropathies

  • Overall prevalence of around 6 cases per 100,000 individuals, the most common type being CIDP with estimated prevalence rate of 1.0 to 8.9 cases per 100,000.6
  • MMN is a rare motor asymmetric neuropathy affecting no more than 1-2 individuals per 100,0006 affecting male more than female by 3 times
  • All chronic demyelinating neuropathies affect males more commonly and typically occur in middle to old age.6

Etiology and pathogenesis

Immune mediated neuropathies most commonly occur when immunologic tolerance to key antigenic sites on myelin, axon, nodes of Ranvier or ganglionic neurons is lost.

  • Demyelinating neuropathies (occurring at myelin) are the most common type.
    • Either isolated demyelination or a combination of axonal injury and demyelination.
  • Current evidence supports the notion that IN is mediated by antibodies directed against myelin antigens, along with autoreactive T cells and macrophages that invade the myelin sheath, axonal membranes or the nodes of Ranvier. In certain disorders the triggering factors have been identified and progress made in the understanding of immunopathologic process and in many others the exact mechanisms remain unclear.7
  • GBS [8]
    • AIDP – the main target appears to be the myelin
    • AMAN- where primary pathology is in the axon, either due to massive acute demyelination and inflammation or due to a primary attack on axons and nodes of Ranvier mediated by macrophages and antibodies.
    • AMSAN- which is like AMAN but with concurrent involvement of sensory axons.
    • Miller-Fisher syndrome- the presence of IgG antibodies against GQ1b ganglioside.
    • Sensory ataxic GBS- probably occurs due to the involvement of dorsal roots and ganglionic neurons. Some of these patients have also IgG antibodies to GQ1b or GQ1B ganglioside.
    • Acute pandysautonomic neuropathy- where the target antigen is probably in the sympathetic ganglionic neurons.
  • CIDP
    • The pathogenesis is poorly understood.
    • The demyelination in CIDP is multifocal, like the one seen in GBS, affecting roots, plexuses and proximal nerve trunks accounting for variable distribution of symptoms.
    • Cellular immunity process involving activated T cells and macrophage mediated stripping of myelin lamellae
    • Humoral immunity process demonstrated by induction of demyelination in animals by IgG or sera from CIDP patients and by finding of antibodies against P0, myelin P2 protein, peripheral myelin protein 22 (PMP22) as well as an antibody-mediated process (immunoglobulin and complement deposits in myelinated fibers).
    • Antibodies to glycolipids LM1, GM1 or GD1b were subsequently detected in some patients with CIDP.
    • Several studies suggest that genetically determined factors contribute to development of CIDP. The SH2 domain Protein A (SH2DA) gene has a low number of GA repeats that may result in defective elimination of activated T cells.8
  • MMN
    • IgM antibodies against GM1 were found in 20-80% of patients with MMN.
    • Presence of anti-GM1 antibodies also revealed severe axon loss on nerve conduction studies (NCS) than patients without antibodies.
    • Pathological studies of nerves revealed loss of myelinated axons as well as axonal degeneration and regeneration. One study suggested that primary pathology of MMN was axon related rather than myelin related.x
  • POEMS syndrome
    • Pathogenesis is not well understood, but overproduction of VEGF, probably secreted by plasmacytomas neovascularization is associated.x

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

New onset/Acute

  • GBS is a self-limited acute neuropathy characterized by symmetric flaccid paralysis, areflexia and sensory deficits that start 1-3 weeks after an infection. Symptoms develops hours to weeks and reach a nadir within 4 weeks, but often less than 2 weeks.
  • Between 4-15% of patients die and up to 20% are disabled after a year despite modern treatment with worsening prognosis with advanced age.
  • In children, clinical course is more rapid with likely complete recovery.2,8

Subacute

  • Subacute neuropathies (i.e.. SIDP or subacute inflammatory demyelinating polyradiculoneuropathy) are defined as progressing for 4-8 weeks.3

Chronic/Stable

  • CIDP is characterized by the occurrence of chronic progressive, relapsing or monophasic symmetrical weakness in both proximal and distal muscles, impaired sensation and paresthesia due to distal fiber sensory loss and absent or diminished reflexes which progress over 2 months.6,8
    • CIDP has an unpredictable course, although majority of patients have a severe motor, sensory, or sensorimotor disabling status after several years. In a recent population-based study, the nadir overall neuropathy limitation scale score was 5, and 58 % of patients were unable to walk independently at some points of their illness.9,10
  • MMN presents with asymmetric weakness often related to the distribution of individual nerves. Arms are usually affected earlier and more severely than legs with more than 80% of patients initially affected in forearm or hand muscles along with a patchy reduction of reflexes or sometimes even brisk reflexes (often confused with motor-neuron disease).2,8
  • POEMS syndrome is characterized by a chronic progressive demyelinating neuropathy associated with an underlying plasma cell dyscrasia and multi-organ disorder.2 The estimated median survival time in patients with POEMS syndrome is 14 years.

2. ESSENTIALS OF ASSESSMENT

History and Physical Examination

  • Acute (GBS)
    • Progressive bilateral weakness in GBS with difficulty in climbing stairs, getting out of chair are most notable 1-2 days after paresthesias.[2]
    • Cranial nerves including facial, bulbar and ocular motor nerves are commonly involved in GBS (especially in MFS).
    • MFS may present with ophthalmoplegia, ataxia and areflexia.2 Sensory ataxia is common in MFS.
    • Respiratory muscles are commonly affected and 25% of patients may need artificial ventilation. Autonomic dysfunction such as cardiac arrhythmias, arterial hypertension or hypotension, abnormal sweating, GI dysmotility may occur in two-third of patients
    • Bowel or bladder complaints are rare.
    • Autonomic complaints are common in GBS and variants.
  • Chronic
    • Weakness is proximal and distal in typical CIDP.
    • Fasciculations common in MMN.
    • The typical presentation of anti-MAG neuropathy is that of distal, predominantly sensory large fiber ataxic neuropathy, like DADS phenotype of CIDP. Some patients may also exhibit a neurogenic tremor in the arms.8
  • Muscle stretch reflexes are diminished in GBS and CIDP by definition, except for the AMAN variant which can have increased reflexes in the recovery phase.

Differential diagnosis

  • GBS: transverse myelitis, myasthenia gravis, botulism, carcinomatous or lymphomatous meningitis, toxin related neuropathy, vasculitis related neuropathy.
  • CIDP
    • IgA, IgM or IgG monoclonal gammopathies
    • Neuropathy related to human immunodeficiency virus (HIV), hepatitis C, Sjogren’s disease, lymphoma, ulcerative colitis and Crohn disease, melanoma and diabetes.
    • Secondary immune mediated neuropathies are associated with vasculitic disease such as polyarteritis nodosa (PAN), Wegener granulomatosis, Churg-Strauss syndrome (CSS), microscopic polyangiitis, temporal arteritis, drug-induced vasculitis, nonsystemic vasculitis neuropathy), connective tissue disease, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome, systemic sclerosis, cryoglobulinemia), sarcoidosis, or malignancies2

Electrodiagnosis

Electrodiagnostics (EDX) is an important clinical tool for distinguishing demyelinating and axonal types.8

  1. Electrodiagnostic criteria for demyelination
    1. Partial motor conduction block and temporal dispersion reduced motor conduction velocity (60% of the normal mean8, prolonged motor latencies and F wave latencies.2
    2. Conduction block 8
  2. Typical EDX findings in GBS
    1. Test results can be normal early in acute disease.
    2. The first abnormalities are prolonged motor distal latencies and decreased amplitudes.
    3. Prolonged F wave may be the only confirmatory finding if the patient is tested early.4
    4. In AIDP, electrodiagnostics performed within 2-15 days after onset may shows motor conduction blocks (CB) in approximately 60% of patients. Conduction block resolves with the appearance of CMAPs with slow initial components and increased duration on stimulation proximal to the site of block, consistent with remyelinating slowly conducting axons.3
    5. Classification of GBS subtypes depends on the timing of NCS relative to disease onset. Serial NCS lead to reclassification in as many as 40% of patients, especially from AIDP to an axonal form. Thus, classification may differ among studies that employ single or repeated NCS.3
    6. AMAN: decreased distal CMAPs, prolonged distal motor latency (DML), CB, and conduction slowing in forearm segments in first week.8
  3. CIDP: [11]
    1. American Academy of Neurology Ad Hoc Subcommittee Criteria in 1991 (requiring 3 of 4 following criteria)
    2. (1) Reduced conduction velocities (CVs; e.g. <80% of the lower limit of normal [LLN] if the distal motor amplitude is normal, and <70% of LLN if the amplitude is substantially reduced)
    3. (2) Prolonged DMLs
    4. (3) Prolonged F-wave latencies (FLs; e.g.>125% of the upper limit of normal [ULN] if the distal motor amplitude is normal, and >150% of ULN if the amplitude is reduced for distal latencies and F-waves)
    5. (4) CB/temporal dispersion (TD); e.g. CB is >50% reduction of proximal/distal [p/d] amplitude and abnormal temporal dispersion is >130% increase of p/d duration)
    6. European Federation of Neurological Societies/Peripheral Nerve Society Guideline in 2010
      1. Definite: at least one of the following:
        1. At least 50% prolongation of DML above ULN in two nerves
        2. At least 30% reduction of motor CV below LLN in two nerves
        3. At least 20% prolongation of F-wave latency above ULN in two nerves (>50% if amplitude of distal negative peak CMAP <80% of LLN)
        4. Abnormal temporal dispersion (>30% duration increase between the proximal and distal negative peak CMAP) in at least two nerves
        5. Absence of F-waves in two nerves if these nerves have amplitudes of distal negative peak CMAPs at least 20% of LLN + at least one other demyelinating parameter in at least one other nerve
        6. Partial motor CB: at least 50% amplitude reduction of the proximal negative peak CMAP relative to distal, if distal negative peak CMAP at least 20% of LLN, in two nerves, or in one nerve + at least one other demyelinating parameter in at least one other nerve, or
        7. Distal CMAP duration of at least 9 ms in at least one nerve + at least one other demyelinating parameter in at least one other nerve
      2. Probable
        1. At least 30% amplitude reduction of the proximal negative peak CMAP relative to distal, excluding the posterior tibial nerve, if distal negative peak CMAP at least 20% of LLN, in two nerves, or in one nerve + at least one other demyelinating parameter in at least one other nerve
      3. Possible
        1. As in ‘I’ but in only one nerve.
  4. MMN
    1. Presence of motor CB with weakness in 2 or more nerves outside common entrapment sites,
    2. Absence of upper motor neuron signs or significant sensory loss, and with normal sensory nerve conduction in typical cases.1
  5. In ant-MAG neuropathy, patients often have a disproportionate prolongation of distal latencies compared with patients who have CIDP 1
  6. POEMS syndrome affects predominantly intermediate nerve segments and nerve trunks.
    1. NCS in POEMS syndrome shows demyelination in forearm and upper arm segments and signs of axon loss in lower limb nerves. Conduction blocks are rarely seen.3

Laboratory studies and supplementary tests

  • Autoantibodies are variably associated, immune mediated clinical syndromes; highest associations are:
    • anti-GQ1b in MFS
    • anti-GM1 in MMN
    • anti-MAG in the DADS
    • anti-Hu in paraneoplastic ganglionopathies
    • IgM monoclonal gammopathies may be associated with anti-MAG neuropathies3
  • Campylobacter jejuni serology is positive in 44%-88% of GBS cases.1
  • Elevated CSF protein and normal cell count is seen particularly in GBS, CIDP and variants (except MMN).
  • Approximately 90% of patients with anti-MAG neuropathy have elevated CSF protein concentration with normal CSF cell counts.8
  • Nerve biopsy can be useful to confirm vasculitic neuropathies. In patients with equivocal electrodiagnostic findings, nerve biopsies can help distinguish between primary demyelinating and axonal neuropathy.
    • Motor nerve biopsy can help distinguish between MMN and motor neuron disease
    • Sensory nerve biopsy can aid diagnosis of CIDP, anti-MAG neuropathy or POEMS syndrome6
  • Autonomic testing can confirm autonomic involvement.
  • Pulmonary function tests and telemetry are necessary in severe cases that have autonomic and diaphragmatic involvement, particularly in GBS.

Imaging

  • Imaging is useful primarily to exclude other diagnoses.
  • An MRI can show enhancement and enlargement of nerve roots and peripheral nerves in AIDP and CIDP.
  • Chest imaging can detect small cell lung or other cancer in anti-Hu syndrome.

Ultrasonography in CIDP:

  • Typical findings with prognostic implications
    • Combining nerve/fascicle size with echo intensity and histology at baseline, nerves showed hypoechoic enlargement, reflecting active inflammation and onion bulbs or showed nerve enlargement with additional hyperechogenic fascicles/perifascicular tissue, possibly reflecting axonal degeneration and some showing almost no enlargement, reflecting “burned-out” or “cured” disease without active inflammation.
    • Based on nerve echogenicity though Ultrasound, nerves were classified into 3 classes
    • Class 1: large nerves, with hypoechoic segments and increased nerve Cross- sectional Area (CSA). Enlarged fascicles may be seen or the nerve may appear enlarged and hypoechoic without fascicular structure. Enlarged and hypoechoic nerves (class 1); correlate with good responses to treatment.
    • Class 2: large nerve, with segments with increased nerve CSA and coexistence of hyper- and hypoechogenic enlarged (or normal) fascicles (fascicles with hyperechoic structure and other fascicles with hypoechoic structure).
    • Class 3: normal nerve size, but changes in echogenicity (nerve appears hyperechoic with reduced CSA, as in class 1 or 2). [The edge of the nerve and surrounding is not clear. The hyperechoic rim of epineurium is not clearly identified. Fascicles are not well visualized].
    • The results of the above reported classification were correlated with clinical data, namely, age of patient, duration of disease, muscle strength and lower and upper limbs disability score.
    • Increase in nerve vascularization; uncertain clinical implication.12
  • Aid in differential diagnosis; “Bochum ultrasound score” (BUS) to differentiate CIDP from other chronic immune-mediated neuropathies. The BUS included evaluation of cross-sectional area (CSA) in the a) ulnar nerve in the Guyon canal b) ulnar nerve in the upper arm c) radial nerve in the spiral groove and d) sural nerve between the lateral and medial heads of gastrocnemius muscle. 1 point allotted to each anatomical site.
    • Typical BUS finding suggestive of CIDP was pathological CSA enlargement at all 4 anatomical sites compared to reference values. CIDP was highly suggestive in BUS score ≥ 2.
    • For BUS score ≤ 2, other anatomical sites such as median and ulnar nerves in the forearm and tibial nerve at ankle were evaluated. If the patient had pathological enlargement in atleast 1 of the aforementioned sites then MMN is diagnosed. If the above 3 sites were normal and BUS was ≤ 2, then median nerve in carpal tunnel and ulnar nerve at the elbow were evaluated. CSA enlargement in atleast 1 of these sites was highly suggestive of MADSAM.
    • The study showed an 88% sensitivity and 84.6% specificity in distinguishing CIDP from other diagnoses of symmetrical demyelinating polyneuropathies. MMN and MADSAM could both be diagnosed with sensitivity of 100% and specificity of 83.3%.[13]

Early predictions of outcomes

GBS

  • Early predictors of bad prognosis: older age (over 50), rapid onset of profound weakness, mechanical ventilation, distal compound muscle action potential (CMAP) amplitude less than 10% of normal 4
  • Long term outcomes are worse in AMAN, better in MFS than classic AIDP. Disability remains in 10% of patients. 4

CIDP

  • 1) Early predictors of bad prognosis: Mode of onset, progression time from onset to nadir, asymmetrical symptoms, and upper limb predominant weakness, involvement of distal and intermediate nerve segments19

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

  1. According to the Practice Parameter: Immunotherapy for Guillain-Barré Syndrome developed by the Quality Standards Subcommittee of the American Academy of Neurology:
    1. In GBS, plasma exchange (PE) is recommended in non-ambulant patients within four weeks of treatment (level A, class 2) or ambulant within two weeks (level B, limited class 2).
    2. IVIG is recommended within 2 weeks for non-ambulant patients (level A).
    3. PE and IVIG are equivalent (class 1) and steroids are ineffective (level A ,class 1).6

At different disease stages

  • New onset/Acute demyelinating neuropathies
    • In GBS, treatment should begin within two weeks if possible.
    • Multidisciplinary care for the prevention of potentially fatal complications such as respiratory failure, cardiac arrhythmias, infections and thromboembolism.
    • Immunomodulatory treatment consists of plasma exchange and IVIG. The usual regimen is a total exchange of about 5 plasma volumes for 1-2 weeks. Plasma exchange (PE) is recommended in non-ambulant patients within four weeks of treatment.2 The efficacy of IVIG has been proven in Guillain-Barre syndrome (level A)14
    • Plasmapheresis is established as effective and should be offered in severe AIDP/GBS (Class I studies, Level A).15
    • Cost containment can be an issue, since intravenous immunoglobulin (IVIG) can be prohibitively expensive, with some conditions requiring treatment every two weeks. This is a particularly true when IVIG is the preferred first option in the absence of any definite benefit over less costly treatments
    • Autonomic instability may necessitate admission to an intensive care unit (ICU) and telemetry; impending respiratory distress requires pulmonary function monitoring and mechanical ventilation.
  • Chronic/stable
    • Primary treatments for CIDP are corticosteroids, IVIG and plasma exchange (Level A)14,15. Refractory patients with CIDP may benefit from other immunosuppressive agents such as azathioprine, cyclophosphamide, entercept, mycophenolate mofetil and others.
    • Others
      • Anti-MAG neuropathy: rituximab, or combination with fludarabine are often first line treatments
      • MMN: IVIG is first line therapy (level A).
      • POEMS syndrome: melphalan with autologous BMT, Lenalidomide are often first line treatments for POEMS syndrome. Treatment for this condition targets the underlying myeloma. Radiation therapy can be curative in solitary plasmacytomas. To date, no placebo-controlled trials have been conducted, but in disseminated cases, systemic therapies can be beneficial. Currently, experience is limited mostly to alkylating agents with peripheral blood stem cell transplantation, and lenalidomide with dexamethasone. In five patients with POEMS syndrome who received autologous stem cell transplants, improvements in disability scores, strength and nerve conduction at 6 and 12 months were reported in all cases. In a recent systematic review of 51 patients treated with lenalidomide, progression-free survival at 12 months was 93.9%, with the neuropathy improving in 92% of the patients and stabilizing in 8%.
      • Radiation may be used in POEMS syndrome with solitary plasmacytomas.6,2

Rehabilitation

  • Needs: At least a third of people with Immune-mediated neuropathies experience long-term activity limitations. Residual symptoms may be present many years after recovery from GBS syndromes or CIDP. Persistent residual disability and fatigue are the most common long-term consequences which adversely affect ADLs, IADLs, social and family activities.
  • Goal is to stabilize, prevent complication related to immobilization such as venous thromboembolism, contracture and so forth and optimize function and prepare for further interventions at later disease stages
  • Inpatient rehabilitation may be necessary for patients with functional deficits. Aerobic conditioning, resistance exercises, gait training, transfers and activities of daily living are emphasized in physical and occupational therapy. Tilt table training may be necessary for orthostasis. Speech and language therapy are prescribed as necessary. Orthotics are often necessary, particularly ankle-foot orthotics (AFO)11
  • Symptomatic medications are available to offer relief of neuropathic and mechanical pain, fatigue, and alleviate depression and anxiety, but none have been studied in a rigorous fashion in patients with CIDP 11
  • Several Studies including a large multicenter trial in UK demonstrated significant functional gains with in-patient rehabilitation among Patients with acute (GBS) and chronic inflammatory neuropathies with both physical and cognitive disabilities. The study also demonstrated significant reduction in on-going care-costs, especially for highly dependent patients, thus supporting new evidence for cost efficiency of rehabilitation in this group of patients. 14 

Coordination of care

  • Interdisciplinary approach involves neurology, physical medicine and rehabilitation, hospitalists and intensivists, as well as other specialists and disciplines (physical and occupational therapy, speech and language therapy, respiratory therapy, nursing, orthotists).

Patient & family education

  • Patients and families should be educated on the generally good prognosis of GBS, and the potentially recurrent nature of CIDP.
  • Educate regarding complications of treatment such as prednisone and other immunomodulating treatments.
  • Prevention of the complications of immobilization in the outpatient setting will largely fall on caregivers.
  • Patients and families should be educated on the of proper Assistive Devices (AD) and orthotic devices.

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

  • Identifying that a neuropathy is immune mediated is important because of the potential for treatment.
  • Early diagnosis of GBS is complicated by its variable presentation and the lack of reliable, objective testing within the first week of treatment (In the first week of the disease, CSF protein is normal in one-third of patients; 50% have normal CMAP amplitude). GBS is best treated within two weeks of onset of symptoms, sometimes necessitating empiric treatment.
  • Of the several idiopathic neuropathies referred to tertiary centers, 10%-33% are later felt to be CIDP. CIDP should be in the differential of unexplained neuropathies.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

EMERGING/UNIQUE INTERVENTIONS

  1. Immunomodulating agents used in the transplant, rheumatological, and oncology setting are being used but are not yet an established standard of care.
  2. Different regimens of currently used drugs such as pulsed dose dexamethasone have shown efficacy in CIDP.7

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Emerging concepts and practice

  • There is a need for more effective and specific therapies for all immune-mediated neuropathies because- a) A number of patients with GBS and CIDP do not adequately respond to available therapies and are left with significant disability; b) Because some CIDP patients respond only to steroids, while others with pure motor disease worsen with steroids and still others respond only to plasmapheresis or IVIG, biomarkers predicting response to therapies from the outset are needed. c) A number of patients with MMN do not adequately respond to IVIG or the efficacy wanes with time; and d) Very few patients with ant-MAG neuropathy respond only to Rituximab.1
  • Emerging therapeutic agents in the form of new biologic agents, monoclonal antibodies or fusion proteins offer target-specific therapy and are currently used in other autoimmune disorders. 1
  • Albiol-Perez et al. demonstrated a novel Virtual Motor Rehabilitation (VMR) in patients with GBS to test a balance disorder aimed at improving the patients’ motor recovery using Virtual Motor Rehabilitation (VMR) system composed of customizable virtual games to perform static and dynamic balance rehabilitation. 16
  • R. Sendhilkumar et al demonstrated significant improvement in quality of sleep with yogic relaxation, pranayama, and meditation among GBS patients.17

REFERENCES

  1. Dalakas, M.C., Pathogenesis of immune-mediated neuropathies. Biochim Biophys Acta, 2015. 1852(4): p. 658-66.
  2. Eldar, A.H. and J. Chapman, Guillain Barre syndrome and other immune mediated neuropathies: diagnosis and classification. Autoimmun Rev, 2014. 13(4-5): p. 525-30.
  3. Dimachkie, M.M. and R.J. Barohn, Guillain-Barre syndrome and variants. Neurol Clin, 2013. 31(2): p. 491-510.
  4. Wijdicks, E.F. and C.J. Klein, Guillain-Barre Syndrome. Mayo Clin Proc, 2017. 92(3): p. 467-479.
  5. Liang, X.F., et al., Safety of influenza A (H1N1) vaccine in postmarketing surveillance in China. N Engl J Med, 2011. 364(7): p. 638-47.
  6. Latov, N., Diagnosis and treatment of chronic acquired demyelinating polyneuropathies. Nat Rev Neurol, 2014. 10(8): p. 435-46.
  7. Franssen, H. and D.C. Straver, Pathophysiology of immune-mediated demyelinating neuropathies-part I: neuroscience. Muscle Nerve, 2013. 48(6): p. 851-64.
  8. Franssen, H. and D.C. Straver, Pathophysiology of immune-mediated demyelinating neuropathies–Part II: Neurology. Muscle Nerve, 2014. 49(1): p. 4-20.
  9. Mahdi-Rogers, M. and R.A. Hughes, Epidemiology of chronic inflammatory neuropathies in southeast England. Eur J Neurol, 2014. 21(1): p. 28-33.
  10. Leger, J.M., R. Guimaraes-Costa, and C. Muntean, Immunotherapy in Peripheral Neuropathies. Neurotherapeutics, 2016. 13(1): p. 96-107.
  11. Gorson, K.C., An update on the management of chronic inflammatory demyelinating polyneuropathy. Ther Adv Neurol Disord, 2012. 5(6): p. 359-73.
  12. Padua, L., et al., Heterogeneity of root and nerve ultrasound pattern in CIDP patients. Clin Neurophysiol, 2014. 125(1): p. 160-5.
  13. Kerasnoudis, A., et al., Nerve ultrasound protocol in differentiating chronic immune-mediated neuropathies. Muscle Nerve, 2016. 54(5): p. 864-871.
  14. Elovaara, I., et al., EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol, 2008. 15(9): p. 893-908.
  15. Cortese, I., et al., Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, 2011. 76(3): p. 294-300.
  16. Fardoun, H.M., A.S. Mashat, and B. Lange, New methodologies for patients rehabilitation. Methods Inf Med, 2015. 54(2): p. 111-3.
  17. Sendhilkumar, R., et al., “Effect of pranayama and meditation as an add-on therapy in rehabilitation of patients with Guillain-Barre syndrome–a randomized control pilot study”. Disabil Rehabil, 2013. 35(1): p. 57-62.
  18. Kerasnoudis A, et al., Nerve ultrasound score in distinguishing chronic from acute inflammatory demyelinating polyneuropathy.  Clin Neurophysiol. 2014 Mar;125(3):635-41
  19. S Kuwabara, et al., Long term prognosis of chronic inflammatory demyelinating polyneuropathy: a five year follow up of 38 cases. J Neurol Neurosurg Psychiatry. 2006 Jan; 77(1): 66–70.

Original Version of the Topic

Shawn Jorgensen, MD. Immune Mediated Neuropathies. 12/27/2012.

Author Disclosure

Samuel S. Murala, MD
Nothing to Disclose

Se Won Lee, MD
Nothing to Disclose

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