Final Diagnosis -- Acute Motor Axonal Neuropathy

FINAL DIAGNOSIS: - ACUTE MOTOR AXONAL NEUROPATHY (AMAN)

DISCUSSION:

Guillain-Barré Syndrome (GBS) is classically described as an acute predominantly demyelinating polyneuropathy, but more recent descriptions included purely axonal forms of GBS.(1-6) There is debate over whether the axonal forms are the same or different disorders than traditional GBS. Most descriptions of the acute axonal neuropathies come from northern China.(2-4,6) In fact, a preponderance of all GBS cases in China are axonal in nature.(3) These disorders have been further subdivided based on the electrophysiology and pathology into acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN).(4) A recently identified clue to their pathogenesis is the identification of periaxonal macrophages in motor or sensory and motor roots without lymphocytic inflammation.(4,6) Examples of AMAN are uncommon in North America,(5) and autopsy studies are rare.

We describe a patient with AMAN and include the clinical, electrophysiologic, and pathologic (from autopsy) findings. This patient had a rather acute onset, predominately proximal, motor axonal polyneuropathy. The clinical, electrophysiologic, and pathologic features were consistent with "AMAN", and they were similar to those reported by McKhann, Griffin et al.(2-4,6) The lack of an inflammatory CSF and giant cells in the motor roots excluded a direct viral infection such as CMV which can affect motor roots rather selectively.(7) The lack of any sensory involvement (clinically or by EMG) excludes AMSAN, and the lack of both sensory involvement and electrophysiologic findings of demyelination are against the diagnosis of typical GBS. Cranial nerves and respiratory function may be affected by AMAN, and they were in our patient. The significant motor but lack of sensory nerve involvement was striking. The anterior horn cell changes were probably secondary to the axonal degeneration. There was no significant primary anterior horn cell degeneration or inflammation as might be seen in poliomyelitis from polio or enteroviruses.

Pathologic findings in AMAN and AMSAN include axonal degeneration of the affected nerves and the presence of periaxonal macrophages (in motor roots in AMAN and in motor and sensory roots in AMSAN).(4,6) We identified macrophages within residual Schwann cell tubes, but plastic sections were not available; thus, we could not confirm whether the macrophages were exactly periaxonal, but it is likely that they were. In addition, we cannot exclude a component of demyelination early on due to the unavailability of teased fibers, but the lack of conduction block or other features of demyelination on nerve conduction studies supports a purely axonal pathogenesis.

The cause of AMAN is unknown. As in our patient, lymphocytic endoneurial inflammation has not been identified. It has been postulated that certain epitopes on motor axons in AMAN or on sensory and motor axons (in AMSAN) may serve as targets of an autoimmune response. These epitopes include glycolipids and glycoproteins such as GM1 and GD1a.(8,9) Campylobacter infections, present in some patients with AMAN and in other forms of GBS, may play a role in triggering such a process possibly by "molecular mimicry".(8) Our patient had a flu-like illness prior to the onset of the neuropathy, but the cause of that illness is unknown. Her death preceded the discovered association of GBS-like illnesses with Campylobacter, and Campylobacter and anti-glycolipid antibodies were not measured. Lastly, our patient had an occult colon adenocarcinoma, and one might speculate a paraneoplastic cause of the neuropathy. Since the neoplasm was occult, "paraneoplastic antibodies" were not measured in the serum or CSF, but a paraneoplastic process is unlikely anyway given the lack of T-cell mediated inflammation, the fact that adenocarcinoma is an unlikely cause of a paraneoplastic neuropathy, and because the patient had a relatively acute neuropathy after a flu-like illness- the more likely trigger.

REFERENCES

1. Feasby TE, Gilbert JJ, Brown WF, Bolton CF, Hahn AF, Doopman WF, Zochodne DW. (1986) An acute axonal form of Guillain-Barré polyneuropathy. Brain 109;1115-1126
2. McKhann GM, Cornblath DR, Ho TW, Li CY, Bai AY, Wu SW, Yei QF, Zhang WC, Zhaori G, Jiang Z, Griffin JW, Asbury AK (1991) Clinical and electrophysiological aspects of acute paralytic disease of children and young adults in northern China. Lancet 338:593-597
3. McKhann GM, Cornblath DR, Griffin JW, Ho TW, Li CY, Jiang Z, Wu SW, Zhaori G, Liu Y, Jou LP, Liu TC, Gao CY, Mao JY, Blaser MJ, Mishu B, Asbury AK (1993) Acute motor axonal neuropathy: A frequent cause of acute flaccid paralysis in China. Ann Neurol 33:333-342
4. Griffin JW, Li CY, Ho TW, Xue P, Macko C, Gao CY, Yang C, Tian M, Mishu B, Cornblath DR, McKhann GM, Asbury K (1995) Guillain-Barré syndrome in northern China. The spectrum of neuropathological changes in clinically
5. Jackson CE, Barohn RJ, Mendel JR (1993) Acute paralytic syndrome in three American men. Comparison with Chinese cases. Arch Neurol 50:732-735
6. Griffin JW, Li CY, Ho TW, Tian M, Gao CY, Xue P, Mishu B, Cornblath Dr, Macko C, McKhann GM, Asbury K (1996) Pathology of the motor-axonal Guillain-Barré syndrome . Ann Neurol 39:17-28.
7. Behar R, Wiley C, McCutchan JA (1987) Cytomegalovirus polyradiculopathy in acquired immune deficiency syndrome. Neurology 37:557-561
8. Ho TW, Mishu B, Li CY, Cornblath DR, Griffin JW, Asbury AK, Blaser MJ, McKhann GM (1995) Guillain-Barré syndrome in northern China. Relationship to Campylobacter jejuni infection and anti-glycolipid antibodies. Brain 118:597-6059.
9. Yuki N, Yoshino H, Sato S, Shinozawa K, Miyatake T (1992) Severe acute axonal form of Guillain-Barré syndrome associated with IgG anti-GD1a antibodies. Muscle Nerve 15:899-903

Contributed by Gloria Galloway, MD*, Michael J. Giuliani, MD, and David Lacomis, MD