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Neurology 2002;58:730-735
© 2002 American Academy of Neurology

Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy

A. Di Rocco, MD, T. Bottiglieri, PhD, P. Werner, PhD, A. Geraci, MD, D. Simpson, MD, J. Godbold, PhD and S. Morgello, MD

From the Department of Neurology (Drs. Di Rocco and Werner), Albert Einstein College of Medicine and Beth Israel Medical Center, New York, NY; Institute of Metabolic Diseases (Dr. Bottiglieri), Baylor University Medical Center, Dallas, TX; and Departments of Community Medicine and Statistics (Dr. Godbold), Neurology (Drs. Geraci and Simpson), and Pathology (Dr. Morgello), Mount Sinai School of Medicine, New York, NY.

Address correspondence and reprint requests to Dr. Alessandro Di Rocco, Department of Neurology, Albert Einstein College of Medicine–Beth Israel Medical Center, PACC, 10 Union Square East, #2R, New York, NY 10003; e-mail: adirocco{at}aecom.yu.edu

Background: White matter vacuolization of the spinal cord is common in patients with AIDS and may lead to clinical manifestations of myelopathy. The pathogenesis of AIDS-associated myelopathy (AM) is unknown and may be related to metabolic abnormalities rather than to direct HIV infection. The striking pathologic similarity between AM and the vacuolar myelopathy associated with vitamin B12 deficiency suggests that abnormal metabolism of the B12-dependent transmethylation pathway may be important in the pathogenesis of AM.

Methods: The authors compared S-adenosyl-methionine (SAM), methionine, homocysteine, and glutathione in serum and CSF of 15 patients with AM vs 13 HIV-infected controls without myelopathy (HWM). They also compared the results with a non-HIV–infected reference population (NC). All patients had normal B12, folate, and methylmalonic acid levels.

Results: There was a decrease in CSF SAM in the AM group compared with the HWM group (p < 0.0001) and the NC group (p < 0.0001). CSF SAM in the HWM group was also lower than that in the NC group (p = 0.015). Serum methionine was also reduced in serum of the myelopathic group compared with the NC group (p = 0.006).

Conclusions: AM is associated with an abnormality of the vitamin B12-dependent transmethylation pathway.




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