PMID- 15477550
OWN - NLM
STAT- MEDLINE
DCOM- 20050608
LR  - 20190514
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 63
IP  - 7
DP  - 2004 Oct 12
TI  - Treatment of AIDS-associated myelopathy with L-methionine: a placebo-controlled 
      study.
PG  - 1270-5
AB  - BACKGROUND: The histopathology of AIDS-associated myelopathy (AM) closely 
      resembles that of myelopathies due to cobalamin or folate deficiency, with white 
      matter vacuolization in the spinal cord. The pathogenesis of AM appears unrelated 
      to direct HIV infection of the spinal cord. There is abnormal trans-methylation 
      metabolism in AM, with decreased availability of the methyl group donor 
      S-adenosyl-methionine (SAM). The authors hypothesized that treatment with 
      l-methionine, the direct metabolic precursor of SAM, might improve AM. OBJECTIVE: 
      To determine the safety and efficacy of l-methionine treatment in AM. METHODS: 
      Fifty-six patients with clinical diagnosis of AM were randomized to a Phase II, 
      double-blind, placebo-controlled study comparing the effect of l-methionine 6 
      g/day in two divided doses with that of placebo. Study duration was 12 weeks. All 
      patients had somatosensory evoked potentials with prolonged central conduction 
      time (CCT) at entry. Change in CCT was the primary endpoint of the study. 
      Frequency of adverse events (AEs) was used to assess safety. Secondary endpoints 
      were strength, spasticity, and urinary function. Biochemical measurements 
      included serum methionine and homocysteine and CSF SAM. RESULTS: There were no 
      significant differences in AEs between the two groups. Serum homocysteine 
      increased in l-methionine-treated patients from 7.2 (+/-5.2 SD) to 12.6 (+/-6.15 
      SD) micromol/L. The mean CCT at baseline was 25.9 milliseconds (+/-7.3 SD) for 
      the treatment group and 24.1 milliseconds (+/-7.0 SD) for the placebo group. At 
      completion, it was 3.0 milliseconds (+/-6.1 SD) for the treatment group and 23.6 
      milliseconds (+/-5.5 SD) for the placebo group (p = 0.17). In a subset of 15 
      patients with CSF studies, SAM levels increased in the l-methionine but not in 
      the placebo group (p = 0.07). There was no significant effect of treatment on 
      strength, spasticity, or urinary function. CONCLUSIONS: l-methionine was safe and 
      well tolerated although in some patients induced an increase of serum 
      homocysteine. There was a nonsignificant improvement in CCT in treated patients 
      but no benefit in any of the clinical measures.
FAU - Di Rocco, A
AU  - Di Rocco A
AD  - Department of Neurology, Albert Einstein College of Medicine-Beth Israel Medical 
      Center, PACC, 10 Union Square East, 2R, New York, NY 10003, USA. 
      adirocco@aecom.yu.edu
FAU - Werner, P
AU  - Werner P
FAU - Bottiglieri, T
AU  - Bottiglieri T
FAU - Godbold, J
AU  - Godbold J
FAU - Liu, M
AU  - Liu M
FAU - Tagliati, M
AU  - Tagliati M
FAU - Scarano, A
AU  - Scarano A
FAU - Simpson, D
AU  - Simpson D
LA  - eng
GR  - NS-35745/NS/NINDS NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 7LP2MPO46S (S-Adenosylmethionine)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Acquired Immunodeficiency Syndrome/*complications
MH  - Adult
MH  - Antiretroviral Therapy, Highly Active
MH  - Double-Blind Method
MH  - Female
MH  - Homocysteine/blood
MH  - Humans
MH  - Male
MH  - Methionine/adverse effects/blood/*therapeutic use
MH  - Middle Aged
MH  - Muscles/drug effects/physiopathology
MH  - Neural Conduction/drug effects
MH  - S-Adenosylmethionine/cerebrospinal fluid
MH  - Spinal Cord Diseases/*drug therapy/physiopathology/virology
MH  - Urination/drug effects
EDAT- 2004/10/13 09:00
MHDA- 2005/06/09 09:00
CRDT- 2004/10/13 09:00
PHST- 2004/10/13 09:00 [pubmed]
PHST- 2005/06/09 09:00 [medline]
PHST- 2004/10/13 09:00 [entrez]
AID - 63/7/1270 [pii]
AID - 10.1212/01.wnl.0000140469.18782.05 [doi]
PST - ppublish
SO  - Neurology. 2004 Oct 12;63(7):1270-5. doi: 10.1212/01.wnl.0000140469.18782.05.