HIV-infected patients may develop a myelopathy without the neuropsychological signs and symptoms of HIVE, labelled HIV associated myelopathy (HIVM). The histopathological hallmark are vacuoles most prominent in the cervical and thoracic parts of the spinal cord and lipid-laden macrophages, hence the term "vacuolar myelopathy" (Petito 1985). These changes are reminiscent of severe combined degeneration and may occur with HIV-negative patients. As HIV viral products have only inconsistently been shown to be part of the lesions, the role of the virus for the disease is uncertain. Pathogenetically, a disturbance of cobalamin-dependent trans-methylation has been discussed. Like HIVE, HIVM occurs mainly with advanced immunosuppression. Only a proportion of patients with the autoptic finding of vacuolar myelopathy shows clinically apparent myelopathy during life (dal Pan 1994).

Diagnostic workup

A patient may be suspected of having HIVM if he has a spastic-atactic gait, hyperreflexia with positive Babinski sign, disturbance of sphincter control, erectile dysfuntion, and slight signs of sensory dysfunction in a glove and stocking distribution. The diagnosis of an independent HIVM should only be made when a concomittant cognitive impairment is significantly less prominent than the myelopathy. Electrophysiological tests which show increased latencies of somatosensory evoked potentials (SEP) and the motor evoked potentials on transcranial magnetic stimulation are compatible with the diagnosis. CSF, microbiological and spinal imaging studies are inconspicuous or unspecific, and they have their importance in the exclusion of differential diagnosis, as listed in Table 4. Spinal imaging should include MRI of the cervical and, possibly the thoracic cord.

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Table 5: Differential diagnoses of HIV myelopathy and diagnostic workup condition adequate diagnostic step (commentary) Mechanic compresssion of the myelon (cervical myelopathy, disk herniation) degenerative changes of the cervical spine MRI shows reduced CSF spaces around the spinal cord with hyperintense lesions of the cord parenchyma Neurosyphilis Antibody testing and CSF analysis (pleocytosis >45/3) (serological findings may be atypical for active neurosyphilis) CMV myelopathy CSF (signs of inflammation) PCR for CMV in CSF antibody testing in blood and CSF (IgG and antibody index may be increased) Toxoplasmosis contrast enhancing cord lesion on MRI VZV myelitis CSF (marked inflammatory signs) VZV specific IgG in blood and CSF (IgM may be absent) VZV PCR in CSF Mostly antecedent or accompanying cutaneous zoster lesions HSV myelitis CSF (inflammatory signs may be absent), HSV PCR in CSF HTLV-1 (tropical spastic paraparesis) travel to the Carribean, West Africa or East Asia slow evolution of symptoms, bladder dysfunction characteristic, CSF inflammation, HTLV-1 specific antibodies Severe combined degeneration Vitamin B12 levels, increased erythrocyte volume heredo-degenerative diseases (hereditary spastic parapa-resis, adrenoleukodystrophy, Friedreich ataxia etc.) appropriate tests Treatment Early observations of significant improvement with zidovudine monotherapy (Oksenhendler 1990) were later confirmed with HAART. This is why any patient with HIVM should be offered effective HAART. A controlled trial showed L-methionin to bring about improvement on electrophysiological but not clinical parameters. References 1. Brew B, Fulham M, Garsia R. Factors Associated with AIDS Dementia Complex. 9th CROI 2002, Seattle. http://www.retroconference.org/2002/Abstract/13381.htm 2. Cysique L, Maruff P, Brew B. Variable benefit in neuropsychological function in HIV-infected HAART-treated patients. Neurology 2006;66:1447-1450. http://amedeo.com/lit.php?id=16682686 3. dal Pan GJ, Glass JD, McArthur JC. Clinicopathologic correlations of HIV-1-associated vacuolar myelopathy: an autopsy-based case-control study. Neurology 1994; 44:2159-2164. http://amedeo.com/lit.php?id=7969977 4. de Luca A, Ciancio BC, Larussa D, et al. Correlates of independent HIV-1 replication in the CNS and of its control by antiretrovirals. Neurology 2002; 59:342-347. http://amedeo.com/lit.php?id=12177366 5. Eggers C, Hertogs K, Stuerenburg HJ, van Lunzen J, Stellbrink HJ. Delayed CNS virus suppression during HAART is associated with HIV encephalopathy, but not with viral drug resistance or poor CNS drug penetration. AIDS 2003; 17:1897-1906. http://amedeo.com/lit.php?id=12960822 6. Letendre SL, McCutchan JA, Childers ME, Woods SP, Lazzaretto D, Heaton RK, Grant I, Ellis RJ. Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Annals of Neurology 2004;56:416-423. http://amedeo.com/lit.php?id=15349869 7. Marra CM, Lockhart D, Zunt JR, Perrin M, Coombs RW, Collier AC. Changes in CSF and plasma HIV-1 RNA and cognition after starting potent antiretroviral therapy. Neurology 2003;60:1388-1390. http://amedeo.com/lit.php?id=12707454 8. Oksenhendler E, Ferchal F, Cadranel J, Sauvageon-Martre H, Clauvel JP. Zidovudine for HIV-related myelopathy [letter]. Am J Med 1990; 88:65N-66N. 9. Petito CK, Navia BA, Cho ES, Jordan BD, George DC, Price RW. Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome. NEJM 1985; 312:874-849. http://amedeo.com/lit.php?id=3974673 10. Sacktor N, Wong M, Nakasujja N, Skolasky R, Selnes O, Musisi S, Robertson K, McArthur JC, Ronald A and Katabira E. The International HIV Dementia Scale: a new rapid screening test for HIV dementia. AIDS 2005;19:1367-1374. http://amedeo.com/lit.php?id=16103767 11. Price RW, Brew BJ. The AIDS dementia complex. J Infect Dis 1988; 158:1079-1083. http://amedeo.com/lit.php?id=3053922 12. Valcour V, Shikuma C et al. Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort. Neurology 2004;63:822-827. http://amedeo.com/lit.php?id=15365130