Multifocal Motor Neuropathy, Multifocal Acquired Demyelinating Sensory and Motor Neuropathy, and Other Chronic Acquired Demyelinating Polyneuropathy Variants

Abstract

Chronic acquired demyelinating neuropathies (CADP) are an important group of immune neuromuscular disorders affecting myelin. These are distinct from chronic inflammatory demyelinating polyneuropathy (CIDP). Classically, CIDP is characterized by proximal and distal weakness, large fiber sensory loss, elevated cerebrospinal fluid (CSF) protein content, demyelinating changes nerve conduction studies or nerve biopsy, and response to immunomodulating treatment. In this chapter we discuss CADP with emphasis on multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), distal acquired demyelinating symmetric (DADS) neuropathy and conclude with less common variants. While each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Unlike CIDP, MMN is typically asymmetric and affects only the motor nerve fibers. MMN is a rare disease that presents chronically, over several years of progression affecting the arms are more commonly than the legs. Men are more likely than women to develop MMN. MADSAM should be suspected in patients who have weakness and loss of sensation in primarily one arm or leg which progresses slowly over several months to years. It is important in patient with multifocal demyelinating clinical presentation to distinguish MMN from MADSAM since corticosteroids are not effective in MMN where the mainstay of therapy is intravenous gammaglobulin (IVIg). DADS can be subdivided into DADS-M (associated woth M-protein) and DADS-I which is idioapthic. While DADS-I patients respond somewhat to immunotherapy, DADS-M patients present with distal predominant sensorimotor demyelinating neuropathy phenotype and are notoriously refractory to immunotherapies regardless of antibodies to myelin-associated glycoprotein (MAG). Our knowledge regarding pathogenesis, diagnosis and management continues to expand, resulting in improved opportunities for identification and treatment.

Immunotherapy-responsive allodynia due to distal acquired demyelinating symmetric (DADS) neuropathy

“…Anti‐MAG antibodies are positive in half to two‐thirds of DADS‐M neuropathy patients . DADS‐M neuropathy typically occurs in elderly men and is generally refractory to immunosuppressive therapy regardless of the anti‐MAG antibody status . DADS‐I neuropathy, similar to our patients, does not have the typical older age and male predominance of DADS‐M patients.…”

“…DADS‐I neuropathy, similar to our patients, does not have the typical older age and male predominance of DADS‐M patients. Response to immunomodulatory therapy of DADS‐I neuropathy is somewhere between DADS‐M and classical CIDP . It has been suggested that the response to immunotherapy in DADS‐I patients with pure sensory syndrome or sensory CIDP is difficult to measure, because there are only sensory manifestations .…”

Composite ganglioside autoantibodies and immune treatment response in MMN and MADSAM

“…As a result, clinicians should not assume that their presence rules out a MADSAM diagnosis in favor of MMN. Similarly, the composite autoantibody profile between MMN and MADSAM patients may be in keeping with prior discussion of a potential overlap between the 2 conditions; however, the histopathologic findings of MADSAM are more in keeping with CIDP …”

Pattern-Recognition Approach to Neuropathy and Neuronopathy

“…Rarely, idiopathic pandysautonomic syndrome can be the only manifestation of a peripheral neuropathy without other motor or sensory findings. 25, 26 …”