Supporting diagnosis of neurological diseases - primarily motor

neuron disease and motor neuropathies

Ganglioside antibodies are polyclonal autoantibodies produced at

high levels directed against ganglioside (GM1 and GD1b) antisera.

Gangliosides are sphingolipids that are important components of

neural cell membranes.

Several centers have reported that increased levels of antibodies

directed against gangliosides may be markers of certain types of

motor neuropathy. Very high titers have been found in some patients

with multifocal weakness.

Typically, multifocal motor neuropathy begins with asymmetric

upper limb weakness which becomes more generalized over many

years. Sensory function is spared and reflexes are normal. The weak

limbs may have atrophic muscles with fasciculation. On a clinical

basis, these patients may be mistakenly diagnosed as suffering from

amyotrophic lateral sclerosis (ALS). Patients with multifocal motor

neuropathy do not have prominent upper motor neuron signs

(spasticity) and bulbar weakness is extremely unusual. The multifocal

motor neuropathy may be associated with characteristic

electrophysiologic changes of conduction block in motor nerve

pathways

In the clinical evaluation of patients with lower motor neuron disease

or motor neuropathy, measurement of antiganglioside antibodies has

become part of the diagnostic evaluation. In patients with a confirmed

diagnosis of multifocal motor neuropathy, biopsy of affected nerve has

shown an intensive inflammatory infiltrate in the area of conduction block.

The implication of the antiganglioside antibodies and the inflammatory

infiltrates in nerve is that this disorder represents an immune-mediated

neuropathy which may respond to immunosuppression. Reports from

other institutions and experience at Mayo Clinic have confirmed that some

patients with multifocal motor neuropathy do respond well to

immunosuppression. It is, therefore, important to distinguish clearly

between patients with motor neuron disease and those with motor

neuropathy. The estimation of antiganglioside antibodies provides 1

component of the evaluation.

99% OF NORMALS FALL AT OR BELOW THIS TITER                             

      IgG Monosialo GM1          1:500                                        

      IGM Monosialo GM1         1:1,000                                        

      IgG Asialo GM1                   1:4,000                                        

      IgM Asialo GM1                  1:4,000                                        

      IgG Disialo GD1b               1:1,000                                        

      IgM Disialo GD1b               1:1,000

This represents a normal result.  

BORDERLINE RANGES                                                     

      IgG Monosialo GM1          =1:1,000                                        

      IgM Monosialo GM1          =1:2,000                                        

      IgG Asialo GM1                   =1:8,000                                        

      IgM Asialo GM1                  No borderline range (normal < or = 4,000)       

      IgG Disialo GD1b               No borderline range (normal < or = 1,000)       

      IgM Disialo GD1b               No borderline range (normal < or = 1,000)

There is a borderline elevation of titers against                      

ganglioside epitopes. This may be seen in patients                     

with motor neuron disease or motor neuropathy. 

ABNORMAL RESULTS                                                       

      IgG Monosialo GM1          >1:1,000                                        

      IgM Monosialo GM1          >1:2,000                                        

      IgG Asialo GM1                   >1:8,000                                        

      IgM Asialo GM1                  >1:4,000                                        

      IgG Disialo GD1b               >1:1,000                                        

      IgM Disialo GD1b               >1:1,000

The ganglioside antibody titers are elevated. This                     

is usually only seen in patients with multifocal                       

motor neuropathy or motor variant of chronic  

inflammatory polyradiculoneuropathy.

Reference values apply to all ages.

High titers (>1:2,000) have been found only in patients with multifocal

motor neuropathy and not with motor neuron disease. About 30% to 50%

of patients with these clinical syndromes or the pure motor variant

of chronic inflammatory demyelinating polyneuropathy have

increased antibody titers. Increased antibody titers, therefore, appear

to be a specific but not sensitive marker of those related disorders.

For IgG and IgM antibodies directed against monosialo GM1 and

disialo GD1b, 99% of 182 age- and sex-stratified normal individuals

had titers <1:1,000; 99% of 121 patients with well-defined motor

neuron disease had titers <1:2,000; and all patients with titers >1:2,000

had motor neuropathy.

Titer values of 1:250 to 1:2,000 (modest elevations) are found in

5% of patients with motor neuron disease.

Patients with ALS may have modest elevations of antiganglioside

antibody titer.  

High titers have been found only in patients with multifocal motor

neuron neuropathy.

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      specificity of anti-GM1 antibody testing. Neurology 1996;47:951-955

2.   Pestronk A, Cornblath DR, Ilyas AA, et al:  A treatable multifocal

      motor neuropathy with antibodies to GM1 ganglioside. Ann Neurol

      1988;24:73-78

3.   Pestronk A, Chaundhry V, Feldman EL, et al:  Lower motor neuron

      syndromes defined by patterns of weakness, nerve conduction

      abnormalities, and high titers of antiglycolipid antibodies. Ann

      Neurol 1990;27:316-326

4.   Sadiq SA, Thomas FP, Kilidireas K, et al:  The spectrum of

      neurologic disease associated with anti-GM1 antibodies.  

      Neurology 1990;40:1067-1072

5.   Nobile-Orazio E, Carpo M, Legname G, et al:  Anti-GM1 IgM

      antibodies in motor neuron disease and neuropathy. Neurology

      1990;40:1747-1750

6.   Pestronk A, Adams RN, Clawson L, et al:  Serum antibodies to

      GM1 ganglioside in amyotrophic lateral sclerosis. Neurology

      1998;38:1457-1461

7.   Pestronk A, Adams RN, Cornblath D, et al:  Patterns of serum IgM

      antibodies to GM1 and GD1a gangliosides in amyotrophic lateral

      sclerosis.  Ann Neurol 1989;25:98-102

8.   Krarup C, Stewart JD, Sumner AJ, et al:  A syndrome of asymmetric

      limb weakness with motor conduction block. Neurology 40:

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9.   Pestronk A, Adams RN, Kuncl RW, et al:  Differential effects of

      prednisone and cyclophosphamide on autoantibodies in human

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