How Do the Experts Diagnose MMN?                     IVIG                 Homepage FOR MORE INFO.

NeuroCAST has asked a group of neuromuscular specialists how they diagnose and treat MMN. Their responses to six key questions about MMN provide various perspectives on the challenge of diagnosing this disorder. We thank the following panel of neurologists for their participation.

Neil Busis, MD Pittsburgh Neurology Group Pittsburgh, PA Michael Swenson, MD Professor and Chairman Dept. of Neurology University of Louisville Louisville, KY Florian Thomas, MD Associate Professor of Neurology St. Louis University St. Louis, MO

Bashar Katirji, MD University Hospitals of Cleveland Cleveland, OH Jonathan Katz, MD Dept. of Neurology Stanford University Palo Alto, CA Glenn Lopate, MD Barnes Hospital Washington University School of Medicine St. Louis, MO Gil Wolfe, MD Dept. of Neurology University of Texas Southwestern Medical Center Dallas, TX

The Experts' Responses

1) How would you describe the presentation of a "typical" MMN patient?
"Generally middle-aged patients, slightly more common in men, with slowly progressive, asymmetric distal weakness, more frequently in the arms than legs. Over time, other extremities may become involved, but not in all cases. Cramping and muscle twitching may be associated symptoms."
          Gil Wolfe, MD, University of Texas Southwestern Medical Center

"Asymmetrical hand weakness, slowly progressive and indolent, with minimal atrophy."
          Bashar Katirji, MD, University Hospitals of Cleveland

"MMN most commonly begins with weakness in the hands, although virtually any muscle may be affected. In mild cases, one can usually recognize weakness in the distribution of individual named peripheral nerves. In more severe cases the distributions may overlap, causing more widespread weakness. In some cases, the demyelinating nature of the condition is evidenced by the degree of weakness being disproportionate to the degree of atrophy."
          Jonathan Katz, MD, Stanford University

2) What diseases do you include in the differential diagnosis of MMN?
"Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), mononeuritis multiplex, and multiple entrapments."
          Neil Busis, MD, Pittsburgh Neurology Group

"The differential would include motor neuron disease, vasculitic neuropathies, hereditary neuropathy with liability to pressure palsy (HNPP), and other neuropathic disorders that can present with asymmetric weakness initially."
          Gil Wolfe, MD, University of Texas Southwestern Medical Center

"Motor neuron diseases including monomelic amyotrophy and amyotrophic lateral sclerosis, and the multifocal motor variant of CIDP."
          Glenn Lopate, MD, Washington University School of Medicine

"ALS, CIDP, Syrinx, entrapments."
          Michael Swenson, MD, University of Louisville

"CIDP, ALS, and various other forms of neuropathies (due to diabetes, lymphoproliferative disorders, infections, vasculitis, cryoglobulinemia, HNPP, and entrapment) can resemble MMN clinically."
          Florian Thomas, MD, St. Louis University

3) Why differentiate MMN from other disorders?
"MMN is treatable, and while CIDP is also treatable, therapies most likely to benefit the patient will be different."
          Glenn Lopate, MD, Washington University School of Medicine

"Some autoimmune conditions that can resemble MMN respond to different forms of immunomodulatory therapy. Other non-autoimmune conditions in the differential diagnosis, such as HNPP or other multiple entrapments, must be approached differently."
          Florian Thomas, MD, St. Louis University

4) What can electrophysiology and/or nerve biopsy reveal about MMN?
"Electrophysiology reveals features of a demyelinating polyneuropathy, limited to motor neurons. Conduction block is often present, although other features of demyelination such as temporal dispersion of waveforms and conduction slowing are also helpful. Nerve biopsy is not useful in this disorder."
          Jonathan Katz, MD, Stanford University

"[EMGs] reveal motor conduction blocks at sites not prone to compression."
          Bashar Katirji, MD, University Hospitals of Cleveland

"Diagnosis still may be clinical, but EMG is extremely helpful if it shows block. Nerve biopsy is not helpful."
          Michael Swenson, MD, University of Louisville

"We do not perform nerve biopsies on patients when we are confident about the diagnosis on the basis of other testing. Electrophysiology is essential to look for conduction block and/or demyelinating features, which we encounter in nearly all patients. Sensory nerve conduction studies are unaffected."
          Gil Wolfe, MD, University of Texas Southwestern Medical Center

"Nerve conduction studies should show conduction block, but may also show other features of demyelination, including prolonged F-waves and slowed conduction velocities."
          Glenn Lopate, MD, Washington University School of Medicine

5) Do you use autoantibody testing in diagnosing MMN? If so, how?
"Anti-GM1 antibodies are present in between 50-85% of patients, depending on the methodology."
          Glenn Lopate, MD, Washington University School of Medicine

"In straightforward cases with conduction block, no [I do not use autoantibody testing]. In cases where I cannot identify conduction block, I routinely order anti-GM1 antibodies. From my perspective, high titers of these antibodies are a valuable marker for potentially treatable, motor-predominant neuropathies."
          Gil Wolfe, MD, University of Texas Southwestern Medical Center

"Finding evidence for an autoimmune etiology provides support for using immunosuppressive therapy. Response to immunosuppressive treatment can also be monitored with autoantibody testing."
          Florian Thomas, MD, St. Louis University

"GM-1 autoantibodies are not sensitive, although they are specific and therefore are quite useful for confirming a suspected diagnosis."
          Jonathan Katz, MD, Stanford University

6) What therapies have you found successful in treating MMN?
"IVIg is the mainstay of therapy. Most patients respond."
          Jonathan Katz, MD, Stanford University

"Cyclophosphamide and human immune globulin are helpful in 50-75% of patients."
          Glenn Lopate, MD, Washington University School of Medicine

Summary

As described by these neuromuscular specialists, MMN is a treatable neurological disorder. It presents with signs and symptoms that may resemble other conditions, some of which have very different treatment options. First and foremost, MMN must be distinguished from degenerative motor neuron diseases, such as ALS, because of the dramatically different prognosis and therapy. MMN should also be differentiated from CIDP since patients with MMN will respond favorably to intravenous immunoglobulin (IVIg) or cyclophosphamide. In contrast, those with CIDP may benefit from corticosteroids, a medication which can actually exacerbate the weakness seen in MMN.²

The clinical work up of a patient with MMN consists of various components, each of which can affect proper patient management. Categorizing the cause of the neuropathy, through routine lab analysis, electrophysiological studies, and antibody testing, can help diagnose the illness, determine the most appropriate treatment, and can increase the probability of a positive clinical outcome.

Table 1: Differential Diagnosis of Multifocal Motor Neuropathy

NCS = nerve conduction study
SNAP = sensory nerve action potential
 
Chart adapted from: Bosch, E.P. and Smith, B.E. Disorders of Peripheral Nerves. In Neurology in Clinical Practice, 2^nd ed., ed. W.G. Bradley et al., 2091. 2000. Boston: Butterworth-Heinemann.