Chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy
Specialty Neurology

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy (because it involves the nerve roots).[1] CIDP is closely related to Guillain–Barré syndrome and it is considered the chronic counterpart of that acute disease.[2] Its symptoms are also similar to progressive inflammatory neuropathy. An asymmetrical variant of CIDP is known as Lewis-Sumner Syndrome.[3]

Signs and Symptoms

Diagnosis is typically made on the basis of presenting symptoms in tandem with electrodiagnostic testing or a nerve biopsy. Doctors may use a lumbar puncture to verify the presence of increased cerebrospinal fluid protein. Symptoms such as diminished or absent deep-tendon reflexes and sensory ataxia are common. Other symptoms include proximal and distal muscle weakness in the limbs.

Cause

Structure of a typical neuron
Neuron

Chronic inflammatory demyelinating polyneuropathy (or polyradiculoneuropathy) is considered an autoimmune disorder destroying myelin, the protective covering of the nerves. Typical early symptoms are "tingling" (sort of electrified vibration or paresthesia) and/or numbness in the extremities, frequent (night) leg cramps, loss of reflexes (in knees), muscle fasciculations, "vibration" feelings, loss of balance, general muscle cramping and nerve pain. [4] [5] CIDP is extremely rare but under-recognized and under-treated due to its heterogeneous presentation (both clinical and electrophysiological) and the limitations of clinical, serologic, and electrophysiologic diagnostic criteria. Despite these limitations, early diagnosis and treatment is favoured in preventing irreversible axonal loss and improving functional recovery.[6]

There is a lack of awareness and treatment of CIDP. Although there are stringent research criteria for selecting patients for clinical trials, there are no generally agreed-upon clinical diagnostic criteria for CIDP due to its different presentations in symptoms and objective data. Application of the present research criteria to routine clinical practice often misses the diagnosis in a majority of patients, and patients are often left untreated despite progression of their disease.[7]

CIDP has been associated with diabetes mellitus, HIV infection, and paraproteinemias.

Diagnosis

There are several types of immune-mediated neuropathies recognised.[8][9] These include

  • Chronic inflammatory demyelinating polyneuropathy (CIDP) with subtypes:
    • Classical CIDP
    • CIDP with diabetes
    • CIDP/monoclonal gammopathy of undetermined significance
    • Sensory CIDP
    • Multifocal motor neuropathy
    • Multifocal acquired demyelinating sensory and motor neuropathy (Lewis-Sumner syndrome)
    • Multifocal acquired sensory and motor neuropathy
    • Distal acquired demyelinating sensory neuropathy
  • Guillain-Barre syndrome with subtypes:
    • Acute inflammatory demyelinating polyradiculoneuropathy
    • Acute motor axonal neuropathy
    • Acute motor and sensory axonal neuropathy
    • Acute pandysautonomia
    • Miller Fisher syndrome
  • IgM monoclonal gammopathies with subtypes:
    • Waldenstrom's macroglobulinemia
    • Mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome
    • Myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome (POEMS)

For this reason a diagnosis of chronic inflammatory demyelinating polyneuropathy needs further investigations.

The diagnosis is usually provisionally made through a clinical neurological examination. Patients usually present with a history of weakness, numbness, tingling, pain and difficulty in walking. They may additionally present with fainting spells while standing up or burning pain in extremities. Some patients may have sudden onset of back pain or neck pain radiating down the extremities, usually diagnosed as radicular pain. These symptoms are usually progressive and may be intermittent.

Autonomic system dysfunction can occur; in such a case, the patient would complain of orthostatic dizziness, problems breathing, eye, bowel, bladder and cardiac problems. The patient may also present with a single cranial nerve or peripheral nerve dysfunction.

On examination the patients may have weakness, and loss of deep tendon reflexes (rarely increased or normal). There may be atrophy (shrinkage) of muscles, fasciculations (twitching) and loss of sensation. Patients may have multi-focal motor neuropathy, as they have no sensory loss.

Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.

Typical diagnostic tests include:

  • Electrodiagnostics – electromyography (EMG) and nerve conduction study (NCS). In usual CIDP, the nerve conduction studies show demyelination. These findings include:
    1. a reduction in nerve conduction velocities;
    2. the presence of conduction block or abnormal temporal dispersion in at least one motor nerve;
    3. prolonged distal latencies in at least two nerves;
    4. absent F waves or prolonged minimum F wave latencies in at least two motor nerves. (In some case EMG/NCV can be normal).
  • Serum test to exclude other autoimmune diseases.
  • Lumbar puncture and serum test for anti-ganglioside antibodies. These antibodies are present in the branch of CIDP diseases comprised by anti-GM1, anti-GD1a, and anti-GQ1b.
  • Sural nerve biopsy; biopsy is considered for those patients in whom the diagnosis is not completely clear, when other causes of neuropathy (e.g., hereditary, vasculitic) cannot be excluded, or when profound axonal involvement is observed on EMG.
  • Ultrasound of the peripheral nerves may show swelling of the affected nerves[10][11][12]
  • MRI can also be used in the diagnosic workup[13][14]

In some cases electrophysiological studies fail to show any evidence of demyelination. Though conventional electrophysiological diagnostic criteria are not met, the patient may still respond to immunomodulatory treatments. In such cases, presence of clinical characteristics suggestive of CIDP are critical, justifying full investigations, including sural nerve biopsy.[15]

Differential diagnosis

Treatment

First-line treatment for CIDP is currently intravenous immunoglobulin (IVIG) and other treatments include corticosteroids (e.g. prednisone), and plasmapheresis (plasma exchange) which may be prescribed alone or in combination with an immunosuppressant drug.[16] Recent controlled studies show subcutaneous immunoglobin (SCIG) appears to be as effective for CIDP treatment as IVIG in most patients, and with fewer systemic side effects.[17]

IVIG and plasmapheresis have proven benefit in randomized, double-blind, placebo-controlled trials. Despite less definitive published evidence of efficacy, corticosteroids are considered standard therapies because of their long history of use and cost effectiveness. IVIG is probably the first-line CIDP treatment, but is extremely expensive. For example, in the U.S., a single 65 g dose of Gamunex brand in 2010 might be billed at the rate of $8,000 just for the immunoglobulin—not including other charges such as nurse administration. Gamunex brand IVIG is the only U.S. FDA approved treatment for CIDP, as in 2008 Talecris, the maker of Gamunex, received orphan drug status for this drug for the treatment of CIDP.

Immunosuppressive drugs are often of the cytotoxic (chemotherapy) class, including rituximab (Rituxan) which targets B cells, and cyclophosphamide, a drug which reduces the function of the immune system. Ciclosporin has also been used in CIDP but with less frequency as it is a newer approach.[18] Ciclosporin is thought to bind to immunocompetent lymphocytes, especially T-lymphocytes.

Non-cytotoxic immunosuppressive treatments usually include the anti-rejection transplant drugs azathioprine (Imuran/Azoran) and mycophenolate mofetil (Cellcept). In the U.S., these drugs are used as "off-label" treatments for CIDP, meaning that their use here is accepted by the FDA, but that CIDP treatment is not explicitly indicated or approved in the drug literature. Before azathioprine is used, the patient should first have a blood test that ensures that azathioprine can safely be used.

Anti-thymocyte globulin (ATG), an immunosuppressive agent that selectively destroys T lymphocytes is being studied for use in CIDP. Anti-thymocyte globulin is the gamma globulin fraction of antiserum from animals that have been immunized against human thymocytes. It is a polyclonal antibody.

Although chemotherapeutic and immunosuppressive agents have shown to be effective in treating CIDP, significant evidence is lacking, mostly due to the heterogeneous nature of the disease in the patient population in addition to the lack of controlled trials.

A review of several treatments found that azathioprine, interferon alpha and methotrexate were not effective.[19] Cyclophosphamide and rituximab seem to have some response. Mycophenolate mofetil may be of use in milder cases. Immunoglobulin and steroids are the first line choices for treatment.

In severe cases of CIDP, when second-line immunomodulatory drugs are not efficient, autologous hematopoietic stem cell transplantation (HSCT) is sometimes performed. The treatment may induce long-term remission even in severe treatment-refractory cases of CIDP. To improve outcome, it has been suggested that HSCT should be initiated before irreversible axonal damage has occurred. However, a precise estimation of the clinical efficacy of HSCT for CIDP is not available, as randomized controlled trials have not been performed.[20]

Physical therapy and occupational therapy may improve muscle strength, activities of daily living, mobility, and minimize the shrinkage of muscles and tendons and distortions of the joints.

Prognosis

As in multiple sclerosis, another demyelinating condition, it is not possible to predict with certainty how CIDP will affect patients over time. The pattern of relapses and remissions varies greatly with each patient. A period of relapse can be very disturbing, but many patients make significant recoveries.

If diagnosed early, initiation of early treatment to prevent loss of nerve axons is recommended. However, many individuals are left with residual numbness, weakness, tremors, fatigue and other symptoms which can lead to long-term morbidity and diminished quality of life.[1]

It is important to build a good relationship with doctors, both primary care and specialist. Because of the rarity of the illness, many doctors will not have encountered it before. Each case of CIDP is different, and relapses, if they occur, may bring new symptoms and problems. Because of the variability in severity and progression of the disease, doctors will not be able to give a definite prognosis. A period of experimentation with different treatment regimens is likely to be necessary in order to discover the most appropriate treatment regimen for a given patient.

Epidemiology

In 1982 Lewis et al. reported a group of patients with a chronic asymmetrical sensorimotor neuropathy mostly affecting the arms with multifocal involvement of peripheral nerves.[21] Also in 1982 Dyck et al reported a response to prednisolone to a condition they referred to as chronic inflammatory demyelinating polyradiculoneuropathy.[22] Parry and Clarke in 1988 described a neuropathy which was later found to be associated with IgM autoantibodies directed against GM1 gangliosides.[23][24] This latter condition was later termed multifocal motor neuropathy[25] This distinction is important because multifocal motor neuropathy responds to intravenous globulin alone while chronic inflammatory demyelinating polyneuropathy responds to intravenous globulin, steroids and plasma exchanges.[26] It has been suggested that multifocal motor neuropathy is distinct from chronic inflammatory demyelinating polyneuropathy and that Lewis-Sumner syndrome is a distinct variant type of chronic inflammatory demyelinating polyneuropathy.[27]

The Lewis-Sumner form of this condition is considered a rare disease with only 50 cases reported up to 2004.[28] A total of 90 cases had been reported by 2009[29]

See also

References

  1. 1 2 Kissel JT (2003). "The treatment of chronic inflammatory demyelinating polyradiculoneuropathy". Semin Neurol. 23 (2): 169–80. doi:10.1055/s-2003-41130. PMID 12894382.
  2. ↑ "GBS (Guillain-Barré Syndrome) - CIDP Neuropathy". cidpneuropathysupport.com. Retrieved 2017-12-14.
  3. ↑ http://www.cidpusa.org/LEWIS%20SUMMER.dwt
  4. ↑ "C.I.D.P. Log". cidplog.com. Retrieved 2018-09-27.
  5. ↑ Latov, Norman (2014-07-01). "Diagnosis and treatment of chronic acquired demyelinating polyneuropathies". Nature Reviews Neurology. 10 (8): 435–446. doi:10.1038/nrneurol.2014.117.
  6. ↑ Toothaker TB, Brannagan TH (2007). "Chronic inflammatory demyelinating polyneuropathies: current treatment strategies". Curr Neurol Neurosci Rep. 7 (1): 63–70. doi:10.1007/s11910-007-0023-5. PMID 17217856.
  7. ↑ Latov, Norman (2002). "Diagnosis of CIDP". Neurology. 59 (12 Suppl 6): S2–6. doi:10.1212/wnl.59.12_suppl_6.s2. PMID 12499464.
  8. ↑ Finsterer J (2005) Treatment of immune-mediated, dysimmune neuropathies. Acta Neurol Scand 112(2):115-125
  9. ↑ Ensrud ER, Krivickas LS (2001) Acquired inflammatory demyelinating neuropathies. Phys Med Rehabil Clin N Am 12(2):321-334
  10. ↑ Herraets IJT, Goedee HS, Telleman JA, van Asseldonk JH, Visser LH, van der Pol WL, van den Berg LH (2017) High-resolution ultrasound in patients with Wartenberg's migrant sensory neuritis, a case-control study. Clin Neurophysiol 129(1):232-237. doi: 10.1016/j.clinph.2017.10.040
  11. ↑ Goedee HS, van der Pol WL, van Asseldonk JH, Franssen H, Notermans NC, Vrancken AJ, van Es MA, Nikolakopoulos S, Visser LH, van den Berg LH (2017) Diagnostic value of sonography in treatment-naive chronic inflammatory neuropathies. Neurology 88(2):143-151. doi: 10.1212/WNL.0000000000003483
  12. ↑ Décard BF, Pham M, Grimm A (2017) Ultrasound and MRI of nerves for monitoring disease activity and treatment effects in chronic dysimmune neuropathies - Current concepts and future directions. Clin Neurophysiol 129(1):155-167. doi: 10.1016/j.clinph.2017.10.028
  13. ↑ Shibuya K1, Sugiyama A, Ito S, Misawa S, Sekiguchi Y, Mitsuma S, Iwai Y, Watanabe K, Shimada H, Kawaguchi H, Suhara T, Yokota H, Matsumoto H, Kuwabara S (2015) Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy. Ann Neurol 77(2):333-337. doi: 10.1002/ana.24314
  14. ↑ Rajabally YA, Knopp MJ, Martin-Lamb D, Morlese J (2014) Diagnostic value of MR imaging in the Lewis-Sumner syndrome: a case series. J Neurol Sci 342(1-2):182-185. doi: 10.1016/j.jns.2014.04.033
  15. ↑ Azulay JP (2006). "[The diagnosis of chronic axonal polyneuropathy: the poorly understood chronic polyradiculoneuritides]". Rev. Neurol. (Paris) (in French). 162 (12): 1292–5. PMID 17151528.
  16. ↑ Hughes RA (2002). "Systematic reviews of treatment for inflammatory demyelinating neuropathy". Journal of Anatomy. 200 (4): 331–9. doi:10.1046/j.1469-7580.2002.00041.x. PMC 1570692. PMID 12090400.
  17. ↑ Hadden, Robert D. M.; Marreno, Fabrizio (2016-12-28). "Switch from intravenous to subcutaneous immunoglobulin in CIDP and MMN: improved tolerability and patient satisfaction". Therapeutic Advances in Neurological Disorders. 8 (1): 14–19. doi:10.1177/1756285614563056. ISSN 1756-2856. PMC 4286942. PMID 25584070.
  18. ↑ Odaka M, Tatsumoto M, Susuki K, Hirata K, Yuki N (2005). "Intractable chronic inflammatory demyelinating polyneuropathy treated successfully with ciclosporin". J. Neurol. Neurosurg. Psychiatry. 76 (8): 1115–20. doi:10.1136/jnnp.2003.035428. PMC 1739743. PMID 16024890.
  19. ↑ Rajabally YA (2017) Unconventional treatments for chronic inflammatory demyelinating polyneuropathy. Neurodegener Dis Manag 7(5):331-342. doi: 10.2217/nmt-2017-0017
  20. ↑ Burman, Joachim; Tolf, Andreas; Hägglund, Hans; Askmark, Håkan (2018-02-01). "Autologous haematopoietic stem cell transplantation for neurological diseases". J Neurol Neurosurg Psychiatry. 89 (2): 147–155. doi:10.1136/jnnp-2017-316271. ISSN 0022-3050. PMID 28866625.
  21. ↑ Lewis RA, Sumner AJ, Brown MJ, Asbury AK (1982) Multifocal demyelinating neuropathy with persistent conduction block. Neurology 32: 958–964
  22. ↑ Dyck PJ, O'Brien PC, Oviatt KF, Dinapoli RP, Daube JR, Bartleson JD, et al. Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment. Ann Neurol 11: 136–141
  23. ↑ Parry GJ, Clarke S. Multifocal acquired demyelinating neuropathy masquerading as motor neuron disease. Muscle Nerve 11: 103–107
  24. ↑ Pestronk A, Cornblath DR, Ilyas AA, Baba H, Quarles RH, Griffin JW, et al. A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside. Ann Neurol 24: 73–78
  25. ↑ Nobile-Orazio E. Multifocal motor neuropathy. J Neuroimmunol 115: 4–18
  26. ↑ Van Doorn PA, Garssen MP (2002) Treatment of immune neuropathies. Curr Opin Neurol 15: 623–631
  27. ↑ Lewis RA (2007) Neuropathies associated with conduction block. Curr Opin Neurol 20(5):525-530
  28. ↑ Viala K, Renié L, Maisonobe T, Béhin A, Neil J, Léger JM, Bouche P (2004) Follow-up study and response to treatment in 23 patients with Lewis-Sumner syndrome. Brain 127(Pt 9):2010-2017
  29. ↑ Rajabally YA, Chavada G (2009) Lewis-Sumner syndrome of pure upper-limb onset: diagnostic, prognostic, and therapeutic features. Muscle Nerve 39(2):206-220. doi: 10.1002/mus.21199
Classification
External resources

My CIDP Record 2013 through 2018 - CIDP Experience Log CIDPlog - My CIDP Record 2013 through 2018 - CIDP Experience Log

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