eMedicine Specialties > Neurology > Neurological Infections

HIV-1 Associated Vacuolar Myelopathy

Niranjan N Singh, MD, DNB, Fellow in Neurophysiology, Department of Neurology, St Louis University School of Medicine
Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Associate Program Director, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University

Updated: Mar 14, 2007

Introduction

Background

Vacuolar myelopathy is the most common chronic myelopathy associated with HIV infection. It occurs during the late stages of HIV infection, when CD4⁺ lymphocyte counts are very low, often in conjunction with AIDS dementia complex, peripheral neuropathies, and opportunistic central nervous system and peripheral nervous system infections or malignancies (eg, cytomegalovirus, progressive multifocal leukoencephalopathy, lymphoma).

Pathophysiology

Several hypotheses have been proposed to explain the development of this common complication of HIV-1 infection.

One hypothesis is infiltration by HIV-infected mononuclear cells that secrete neurotoxic factors including cytokines, possibly in conjunction with neurotoxic astrocyte factors. A significant amount of scientific support exists for this paradigm.
Neurotoxic HIV proteins: Transgenic mice that express HIV gene products in oligodendrocytes develop clinical and histologic features that resemble the human disease.
Direct HIV infection of astrocytes and neurons: While this is reported in the brain and dorsal root ganglia, it is not a major feature in vacuolar myelopathy.
The impaired ability to utilize vitamin B-12 as a source of methionine in transmethylation metabolism for myelin maintenance in the spinal cord may be a contributing factor.

Frequency

United States

Before the introduction of highly active antiretroviral therapy (HAART), vacuolar myelopathy was seen in 5-20% of adult HIV patients in clinical studies and in 25-55% of adult HIV patients in histologic studies.

Since the introduction of HAART, it is estimated that fewer than 10% of AIDS patients develop HIV myelopathy.

Mortality/Morbidity

Most patients die within 6 months of developing symptoms of myelopathy.

Clinical

History

Patients have a history of slow progression, painless leg weakness, stiffness, sensory loss, imbalance, and sphincter dysfunction.
Relapsing-remitting courses have also been described.
Vacuolar myelopathy is often seen in conjunction with cognitive decline, distal limb pain, and numbness from peripheral neuropathy.
Back pain is not a prominent feature.
Arm function is usually normal except for advanced vacuolar myelopathy.

Physical

Slowly progressive spastic paraparesis
Hyperreflexia and extensor plantar responses
Sensory ataxia
Incontinence
Rarely, asymmetric features and involvement of upper extremities
Often associated with AIDS dementia complex and neuropathy
A discrete sensory level is usually absent; if present, this strongly suggests other causes of myelopathy.

Differential Diagnoses

Neurosyphilis

Workup

Laboratory Studies

CSF analysis is indicated to identify or rule out other potential causes of myelopathy like cytomegalovirus, varicella-zoster virus, herpes simplex virus, HTLV-1, and HTLV-2. In HIV-1–associated vacuolar myelopathy, CSF results are usually normal.
Serum studies
- Determine vitamin B-12 and folic acid levels. In borderline low B-12 levels, elevated homocysteine and methylmalonic acid levels are better indicators of a deficiency. B-12 levels are usually normal in vacuolar myelopathy.
- A Schilling test may be indicated.
Hematologic studies
CD4⁺ lymphocyte counts

Imaging Studies

MRI or CT scan are often noncontributory but may reveal unsuspected coexisting conditions such as extramedullary or intramedullary infections, neoplasms, degenerative disk disease, or degenerative joint disease of the spine.
Spinal cord atrophy is the most common abnormal finding involving the thoracic cord with or without cervical cord involvement.
T2-weighted MRI often shows usually symmetric nonenhancing high-signal areas present on multiple contiguous slices, which may result from extensive vacuolation. This may be confined to the posterior columns, especially the gracile tracts, or may be diffuse.

Other Tests

Electrophysiologic tests can confirm a clinical diagnosis of vacuolar myelopathy.
Somatosensory evoked potential (SSEP) may be a valuable tool in the diagnosis of AIDS-associated myelopathy, particularly when myelopathy and peripheral neuropathy coexist.

Histologic Findings

Multifocal, occasionally asymmetric vacuolation and myelin pallor involving the dorsal and lateral more than the anterior and anterolateral tracts, and involving the cervical and thoracic more than the lumbar segments or the brainstem, accompanied by astrogliosis
By electron microscopy, intramyelinic or periaxonal vacuoles and rarely disrupted axons
HIV-infected, activated, lipid-laden macrophages and microglia expressing interleukin-1 and/or tumor necrosis factor-alpha
Resembles subacute combined degeneration from vitamin B-12 deficiency

Treatment

Medical Care

Once other treatable causes of myelopathy have been excluded, options for further therapy for this syndrome are limited, and care is primarily supportive.

Anecdotal reports show improvement and remission with HAART.

In a randomized, double-blind, placebo-controlled study of 56 patients, L-methionine was of no benefit.

Consultations

Refer the patient to physical medicine for spinal cord treatment and follow-up care.

Medication

Although no specific treatment is currently approved for this syndrome, viral control tailored to the individual patient's medical and viral history is important.

Follow-up

Further Outpatient Care

Coordinate care with the primary care physician and an infectious disease specialist.

Prognosis

The prognosis is poor.

Patient Education

For excellent patient education resources, visit eMedicine's Immune System Center, Dementia Center, and Sexually Transmitted Diseases Center. Also, see eMedicine's patient education articles Dementia Due to HIV Infection and HIV/AIDS.

Miscellaneous

Medicolegal Pitfalls

Failure to exclude other causes of myelopathy related or unrelated to HIV infection, since HIV-related vacuolar myelopathy is a diagnosis of exclusion

Multimedia

Media file 1: Spinal cord from patient with vacuolar myelopathy that shows extensive spongiform changes in the white matter (Luxol fast blue stain) (contributed by Dr. Beth Levy, Saint Louis University School of Medicine, St. Louis, MO).

Media file 2: Marked vacuolation is apparent in this Luxol fast blue stained photomicrograph (contributed by Dr. Beth Levy, Saint Louis University School of Medicine, St. Louis, MO).

Media file 3: High-intensity lesion in the C2-C5 posterior spinal cord on T2-weighted sagittal MRI image consistent with HIV myelopathy

Media file 4: High-intensity lesion in the posterior cervical cord on T2-weighted axial MRI image consistent with HIV myelopathy

References

Anneken K, Fischera M, Evers S. Recurrent vacuolar myelopathy in HIV infection. J Infect. Jun 2006;52(6):e181-3. [Medline].
Chong J, Di Rocco A, Tagliati M, et al. MR findings in AIDS-associated myelopathy. AJNR Am J Neuroradiol. Sep 1999;20(8):1412-6. [Medline].
Di Rocco A, Tagliati M, Danisi F, et al. A pilot study of L-methionine for the treatment of AIDS-associated myelopathy. Neurology. Jul 1998;51(1):266-8. [Medline].
Di Rocco A, Werner P, Bottiglieri T, et al. Treatment of AIDS-associated myelopathy with L-methionine: a placebo-controlled study. Neurology. Oct 12 2004;63(7):1270-5. [Medline].
DiRocco A. HIV-associated myelopathy. Current Treatment Options in Infectious Diseases. Vol 5. 2003:457-465.
Eilbott DJ, Peress N, Burger H, et al. Human immunodeficiency virus type 1 in spinal cords of acquired immunodeficiency syndrome patients with myelopathy: expression and replication in macrophages. Proc Natl Acad Sci U S A. May 1989;86(9):3337-41. [Medline].
Fernandez-Fernandez FJ, de la Fuente-Aguado J, Ocampo-Hermida A. Remission of HIV-associated myelopathy after highly active antiretroviraltherapy. J Postgrad Med. 2004;50(3):195-6. [Medline].
Gendelman HE, Lipton SA, Epstein L. The Neurology of AIDS. New York: Chapman & Hall;1998.
Petito CK, Navia BA, Cho ES, et al. Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome. N Engl J Med. Apr 4 1985;312(14):874-9. [Medline].
Price RW, Perry SW. HIV, AIDS, and the Brain. New York: Raven Press;1994.
Said G, Saimont AG, Lacroix C. Neurological Complications of HIV and AIDS. Philadelphia, Pa: WB Saunders;1998.
Santosh CG, Bell JE, Best JJ. Spinal tract pathology in AIDS: postmortem MRI correlation with neuropathology. Neuroradiology. Feb 1995;37(2):134-8. [Medline].
Sartoretti-Schefer S, Blattler T, Wichmann W. Spinal MRI in vacuolar myelopathy, and correlation with histopathological findings. Neuroradiology. Dec 1997;39(12):865-9. [Medline].
Staudinger R, Henry K. Remission of HIV myelopathy after highly active antiretroviral therapy. Neurology. Jan 11 2000;54(1):267-8. [Medline].
Tagliati M, Di Rocco A, Danisi F, Simpson DM. The role of somatosensory evoked potentials in the diagnosis of AIDS-associated myelopathy. Neurology. Apr 11 2000;54(7):1477-82. [Medline].
Tyor WR, Glass JD, Baumrind N, et al. Cytokine expression of macrophages in HIV-1-associated vacuolar myelopathy. Neurology. May 1993;43(5):1002-9. [Medline].
de Gans J, Portegies P. Neurological complications of infection with human immunodeficiency virus type 1. A review of literature and 241 cases. Clin Neurol Neurosurg. 1989;91(3):199-219. [Medline].

Keywords

HIV-1 associated myelopathy, AIDS myelopathy, AIDS dementia complex, peripheral neuropathies, opportunistic central nervous system infections, opportunistic peripheral nervous system infections, central nervous system malignancies, cytomegalovirus, progressive multifocal leukoencephalopathy, lymphoma, HIV-1 infection complications, neuropathy, HAART, highly active antiretroviral therapy

Contributor Information and Disclosures

Author

Niranjan N Singh, MD, DNB, Fellow in Neurophysiology, Department of Neurology, St Louis University School of Medicine
Niranjan N Singh, MD, DNB is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Coauthor(s)

Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Associate Program Director, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Paraplegia Society, and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.

Medical Editor

Michael J Schneck, MD, Associate Professor, Department of Neurology and Neurosurgery, Loyola University Chicago, Stritch School of Medicine
Disclosure: boehringer-ingelheim Honoraria Speaking and teaching; sanofi/bms Honoraria Speaking and teaching; pfizer Honoraria Speaking and teaching; genentech Honoraria Speaking and teaching; ucb pharma Honoraria Speaking and teaching; talecris Consulting fee Other; nmt medical Independent contractor; NIH Grant/research funds Independent contractor; vernalis Grant/research funds Independent contractor; sanofi Grant/research funds Independent contractor

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St Louis ConnectCare, Consulting Staff, Barnes Jewish Hospital
Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

Further Reading