Chronic inflammatory demyelinating polyneuropathy – CIDP-
Management and treatment
Lewis-Sumner syndrome = Multifocal acquired demyelinating sensory and motor neuropathy
Lewis-Sumner syndrome (LSS or MADSAM) is a rare acquired demyelinating polyneuropathy characterized by asymmetrical distal weakness of the upper or lower extremities and motor dysfunction with adult onset. It is considered to be a variant of chronic inflammatory demyelinating polyneuropathy.
Guillain-Barré syndrome (GBS) is the term used to describe a spectrum of rare post-infectious neuropathies that usually occur in otherwise healthy patients. GBS is clinically heterogeneous and encompasses acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN), Miller-Fisher syndrome (MFS; see these terms) and some other regional variants.
Management and treatment
Miller Fisher syndrome
Polyneuropathy associated with IgM monoclonal gammapathy with anti-MAG
Polyneuropathy associated with IgM monoclonal gammapathy (MG) with anti-MAG (myelin-associated-glycoprotein) activity is a demyelinating polyneuropathy characterized clinically by sensory ataxia, tremor, paresthesia, and impaired gait.
MAG is a membrane glycoprotein found within the noncompact myelin of Schmidt-Lanterman paranoids and incisions (Figure 1). It plays a role in the compaction of myelin, in the adhesion between the axon and the Schwann cell and in the control of the axonal diameter. Anti-MAG antibodies are immunoglobulins of IgM isotype directed against MAG. They are produced by a clonal population of plasma B cells (Figure 1), either as part of a so-called benign monoclonal gammopathy (MGUS), or as part of a Waldenström disease.
This is a rare neuropathy. It affects men more frequently (sex ratio of about 2-3 / 1). It often starts late in the 6th decade. Classically, polyneuropathy is of slow and progressive evolution, with a predominance of sensory symptoms (numbness, tingling of the extremities, disturbance of equilibrium or coordination = ataxia). Sometimes, he associates an attitude and action tremor. A motor deficit can appear during the evolution (deficit of the relievers of the feet, to see weakness of the muscles of the hands). About 25% of patients have a significant functional disability after 10 years of evolution.
The diagnosis is made using the clinical, biological (anti-MAG antibodies in the blood by ELISA) and electroneuromyographic (EMG) arguments. EMG shows a demyelinating neuropathy reflecting the dysfunction of nerve conduction related to the alteration of the myelin sheath. Axonal loss is often marked. Rarely, a nerve biopsy can be helpful to the diagnosis. It shows specific alterations (demyelination with appearance of decompaction of the outer lamellae of myelin and deposits of IgM on the myelin sheath).
Many immunomodulatory or immunosuppressive therapies have been tested in therapeutic trials in order to decrease the amount and / or activity of anti-MAG antibodies and / or producing lymphoplasmocytes. The results are quite disappointing …
Immunoglobulins showed a difference in the short term compared to placebo but the clinical benefit appears limited. The rituximab studied in 2 trials (anti-CD20 monoclonal antibody targeting B cells) has shown in some patients an improvement of several secondary endpoints compared to placebo but there are methodological limitations. When Waldenström’s disease is symptomatic, chemotherapy is offered to the patient by hematologists. “Lure” polymers resembling MAG and allowing binding to anti-MAG ACs present in the blood are being developed.
Symptomatic management includes physiotherapy and the treatment of possible neuropathic pain.
Expert reviewer(s): Dr [Juliette] Svahn – Last update: June 2018