Diagnosis: HIV-Associated Vacuolar Myelopathy

I've waited two days to say anything after my Cleveland Clinic Visit for the chest and back pain, as well as my current and re-accuring problems with balance and walking.  I've gone 12 years without a diagnosis.  12 long years of misdiagnosis, pain killers and medication that didn't work and the brush off when nothing could be found.  It's been emotionally exhaustive.  I've currently been with a home visiting nurse, a home physical therapist and a social worker.  I've also was fortunate enough to get an adjustable hospital bed, which I love by the way.  But it has been unbearable since the middle of January.  

It's felt very lonely.  It's been emotionally, physically, and spiritually draining.  I feel lost. 

Now though I have a diagnosis.  One I'm not overly thrilled with, but at least a diagnosis.  One that technically can not be treated except for what I am doing now by being on morphine and a course of HIV anti-retrovirals.  I saw a psychologist today who wants me to up the strength of my Zoloft and he is going to help me find a grief group.

I'm at a point right now in my life where I'm going to beg for people to talk to me about this.  Help me through this.  Help me cope, and as the psychologist said today "to find my sense of freedom."  There are things I need to figure out.  Beyond teaching what can I do with my MFA.  I'm not opposed to teaching, I would just like to know my options.  Should I continue on and earn my Doctorate in Modern African American Literature or do I immediately enroll in the government school program to teach and in 5 years would forgive my student loans.  I have personal issues I have to work through as well and I don't have the answer to those either.  BUT:

On a positive note I did graduate from Kent with Full Honors with a document that is now my first self-published book, I have had two articles about my writing recently, I have had rave reviews of my book, I'm enrolled in one of the best grad schools in the country and will have my MFA in Creative writing the beginning of January 2016.  I will have a second completed manuscript when I leave Fairfield that could become my third book.  I'm finishing my second now.  I won second place in poetry contest my first semester at Fairfield.  On July 16th of this year I celebrate 25 yrs. with AIDS.  So I know I have a lot going for me.  Yet, somehow, I have to begin to embrace and acknowledge what I have done and while living with a chronic illness.

I ask for your support, your love, your friendship and your prayers.  I'm so very grateful and blessed to have the people I do in my life.

Charlie

HIV-Associated Vacuolar Myelopathy

Overview

Vacuolar myelopathy is the most common chronic myelopathy associated with HIV infection. HIV-associated vacuolar myelopathy 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 infections or malignancies of the central or peripheral nervous system (eg, cytomegalovirus, progressive multifocal leukoencephalopathy, lymphoma).
For patient education information, see the Immune System Center, Dementia Center, and Sexually Transmitted Diseases Center, as well as Dementia Due to HIV Infection and HIV/AIDS.

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. Transgenic mice that express HIV gene products in oligodendrocytes develop clinical and histologic features that resemble the human disease.
Although direct HIV infection of astrocytes and neurons 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.

Epidemiology and Prognosis

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.

The prognosis in HIV patients with vacuolar myelopathy is poor.

Clinical Presentation:

Vacuolar myelopathy typically presents as a slow progression of painless leg weakness, stiffness, sensory loss, imbalance, and sphincter dysfunction. Relapsing-remitting courses have also been described.^[1]

 Arm function is usually normal except for advanced vacuolar myelopathy.
Vacuolar myelopathy is often associated with AIDS dementia complex and peripheral neuropathy. In such cases, patients have cognitive decline and distal limb pain and numbness.

Physical examination:

The following may be noted on physical examination:

• Slowly progressive spastic paraparesis
• Hyperreflexia and extensor plantar responses
• Sensory ataxia
• Incontinence
• Rarely, asymmetric features and involvement of upper extremities

A discrete sensory level is usually absent; if present, this strongly suggests other causes of myelopathy.

Diagnostic Considerations

The differential diagnosis includes neurosyphilis. Other problems to be considered in the differential diagnosis of HIV-related vacuolar myelopathy include the following:

• Herpes simplex virus infection
• Cytomegalovirus infection
• Cervical disk syndromes
• HIV-1 associated conditions (eg, Kaposi sarcoma, lymphoma, toxoplasmosis) in the spinal canal
• Mycobacterium tuberculosis infection
• Compressive myelopathy (eg, tumor, abscess, herniated disc, arteriovenous malformation)
• Human T-cell lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (can co-exist with HIV infection)
• Spinal epidural abscess in HIV-infected parenteral drug users
  
  
  Diagnostic 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.^[2]

Serum studies can determine vitamin B-12 and folic acid levels. In patients with 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.

CT scan results 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.

Magnetic Resonance Imaging:

MRI scans 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 symmetric nonenhancing high-signal areas, which are present on multiple contiguous slices and are usually symmetrical; these may result from extensive vacuolation.^{[3, 4, 5]}

Care for patients with HIV-associated vacuolar myelopathy is primarily supportive. Although no specific treatment is currently approved for this syndrome, viral control tailored to the individual patient's medical and viral history is important, as case reports showing clinical and radiologic improvement with highly active retroviral therapy (HAART) have been described.^{[9, 10, 11, 2]}


Author

Niranjan N Singh, MD, DM, Associate Professor of Neurology, University of Missouri-Columbia School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Florian P Thomas, MD, MA, PhD, Drmed:

Director, Regional MS Center of Excellence, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Director, Neuropathy Association Center of Excellence, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, St Louis University School of Medicine

References

1. Anneken K, Fischera M, Evers S. Recurrent vacuolar myelopathy in HIV infection. J Infect. Jun 2006;52(6):e181-3. [View Abstract]
2. 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. [View Abstract]
3. 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. [View Abstract]
4. Santosh CG, Bell JE, Best JJ. Spinal tract pathology in AIDS: postmortem MRI correlation with neuropathology. Neuroradiology. Feb 1995;37(2):134-8. [View Abstract]
5. Sartoretti-Schefer S, Blattler T, Wichmann W. Spinal MRI in vacuolar myelopathy, and correlation with histopathological findings. Neuroradiology. Dec 1997;39(12):865-9. [View Abstract]
6. 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. [View Abstract]
7. 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. [View Abstract]
8. 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. [View Abstract]
9. Bizaare M, Dawood H, Moodley A. Vacuolar myelopathy: a case report of functional, clinical, and radiological improvement after highly active antiretroviral therapy. Int J Infect Dis. Jul 2008;12(4):442-4.[View Abstract]
10. DiRocco A. HIV-associated myelopathy. Current Treatment Options in Infectious Diseases. Vol 5. 2003:457-465.
11. 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. [View Abstract]
12. 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. [View Abstract]
13. 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. [View Abstract]
14. Staudinger R, Henry K. Remission of HIV myelopathy after highly active antiretroviral therapy. Neurology. Jan 11 2000;54(1):267-8. [View Abstract]