AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Multiple peripheral mononeuropathies can occur in the setting of HIV-1 disease. The presentation can be similar to multiple mononeuropathies in the non-HIV population.

Pathophysiology

These neuropathies are typically inflammatory in nature and may involve single or multiple cranial or peripheral nerves. EMG and nerve conduction studies show asymmetric multifocal involvement with axonal degeneration, and CSF will show elevated protein level and pleocytosis. They vary with the stage of HIV infection. Early multiple mononeuropathy (MM) is usually self limited. Late MM in a patient with a CD4 count <50 is usually related to CMV infection and can progress rapidly; PCR for CMV should be sent if HIV-associated MM is suspected. Anti-CMV therapy must be initiated. The practitioner should also consider complications of herpes or lymphoma when treating this disease.

Mortality/Morbidity

Mortality and morbidity are dependent on the etiology.

• The autoimmune form may undergo spontaneous remission or respond to immunomodulation, especially when the condition presents early during HIV infection.
• The cytomegalovirus (CMV)-related form may respond to ganciclovir and/or foscarnet if started expeditiously.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The patient describes multifocal asymmetric sensory and motor complaints in the distribution of cranial nerves, peripheral nerves, or nerve roots.

Physical

• Physical findings include asymmetric weakness and reflex and sensory loss.
• More severe involvement suggests CMV.
• Progression may change presentation from multifocal mononeuropathies to a more generalized polyneuropathy.

Causes

A limited form (1-2 nerves) presents in HIV-seropositive patients without AIDS and may have an autoimmune origin.

A more generalized form (>2 nerves) presents in patients with AIDS. While CMV is often shown to be the cause, the occurrence of clinical CMV in AIDS has declined with the advent of highly active antiretroviral therapy several years ago.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Cervical disk syndromes

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Cerebral spinal fluid
• • Nonspecific
  • Mononuclear pleocytosis
  • Elevated protein
• Electromyography/nerve conduction studies
• • Reduced amplitudes of sensory nerve and compound muscle action potentials
  • Mildly reduced conduction velocities
  • Denervation
  • Asymmetric distribution
• Correlation with stage of HIV infection and CD4⁺ lymphocyte counts
• • More than 200 in patients with the limited autoimmune form
  • From 50-200 in patients with more widespread involvement related to autoimmunity
  • Less than 50 in patients with the more widespread form and evidence of CMV infection

Procedures

• Nerve biopsy

Histologic Findings

Histologic findings show axonal degeneration with perivascular mononuclear infiltrates. Occasionally, the infiltrate is predominantly polymorphonuclear. CMV inclusions can be seen in mononuclear and endothelial cells, and CMV can be identified by culture or polymerase chain reaction. Occasionally, a prominent necrotizing arteritis can be seen.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Intravenous immunoglobulin (IVIG) and plasmapheresis (plasma exchange) are preferred to immunosuppression.
• During a 7- to 10-day period, 4-5 plasmaphereses may be performed, as described in standard protocols. Potential complications include autonomic instability, hypercalcemia, and bleeding from depletion of clotting factors.
• Base the decision to use IVIG, plasmapheresis, or steroids on the individual patient.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The more extensive disease state, resulting from CMV, can be treated with ganciclovir and/or foscarnet if instituted early. Conversely, the limited autoimmune form can be treated with IVIG, plasmapheresis, or steroids. These treatments have proven efficacious in some studies but not in others.

Drug Category: Antivirals

Goal is to shorten the clinical course, prevent complications, prevent the development of latency and/or subsequent recurrences, decrease transmission, and eliminate established latency. These agents usually inhibit DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase.

Drug Category: Immune globulin

Has demonstrated efficacy in treatment of autoimmune neuropathies and reduction in duration of hospitalization and need for mechanical ventilation.

Drug Category: Glucocorticoids

These agents modify the body's immune response to diverse stimuli. Possible mechanisms of action include stabilization of blood-nerve barrier, enhancement of nerve conduction, inhibition of synthesis and/or secretion of TNF-alpha, IL-6, IL-2, and IFN-gamma, and modulation of serum and leukocyte-bound levels of cell adhesion molecules.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

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

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to promptly make the diagnosis and provide treatment, in particular of CMV-associated neuropathies, can lead to significant morbidity and death

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• 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;91:199-219. [Medline].
• Gendelman HE, Lipton SA, Epstein L. The Neurology of AIDS. New York: Chapman & Hall;1998.
• Luciano C, Pardo C, McArthur J. Recent developments in the HIV neuropathies. Current Opinion in Neurology. 2003;16:403-409.
• Mancall E ed., Lippincott Williams & Wilkins. Neuromuscular disorders in HIV-1 infection. Continuum. 2000;6 number 5 Part A:73-79.
• Maschke M, Kastrup O, Diener HC. CNS manifestations of cytomegalovirus infections: diagnosis and treatment. CNS Drugs. 2002;16:303-315. [Medline].
• Said G, Saimont AG, Lacroix C. Neurological Complications of HIV and AIDS. Philadelphia, PA: WB Saunders;1998.
• Simpson DM, Olney RK. Peripheral neuropathies associated with human immunodeficiency virus infection. Neurol Clin. Aug 1992;10(3):685-711. [Medline].
• Whitley RJ, Jacobson MA, Friedberg DN, et al. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA. Arch Intern Med. May 11 1998;158(9):957-69. [Medline].

Article Last Updated: May 3, 2006