Progressive Polyradiculopathy in HIV

Updated: Mar 18, 2015
  • Author: Florian P Thomas, MD, PhD, MA, MS; Chief Editor: Niranjan N Singh, MD, DM  more...
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Overview

Overview

Progressive polyradiculopathy occurs late in the course of HIV infection, unlike inflammatory demyelinating polyradiculoneuropathies in HIV, which usually occur earlier in the course of disease. [1, 2, 3]

HIV-infected patients become susceptible to progressive polyradiculopathy in advanced immunosuppression when the CD4 T-cell count is less than 50/µL. [4]

Polyradiculopathy typically results from cytomegalovirus (CMV) infection. The most common manifestation of neurological CMV disease in HIV infection is retinitis followed by encephalitis, myelitis, multifocal polyneuropathy, and polyradiculopathy. [5, 6] CMV co-infection of the retina and other sites is common. An idiopathic form of polyradiculopathy exists, which has a better prognosis than the CMV-related form.

Less common causes of polyradiculopathy in HIV infection include spinal lymphomas and CNS infections such as tuberculosis, syphilis, cryptococcosis, herpes simplex virus type 2, varicella-zoster virus, and toxoplasmosis.

Histologically, polyradiculopathy typically features necrosis of nerve roots and endoneurial and epineurial blood vessels, along with marked inflammation (most pronounced in the lumbar region). In CMV-associated cases, cytoplasmic and nuclear CMV inclusions may be apparent in Schwann cells and fibroblasts.

CMV polyradiculopathy is rapidly fatal without treatment. Treatment with foscarnet or ganciclovir may improve or stabilize the condition. Clinical stabilization often occurs after initial worsening during the first 2 weeks of treatment. [2] Even with treatment, mortality is 22%. In idiopathic polyradiculopathy, spontaneous improvement without treatment is common. [7]

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Clinical Presentation

Polyradiculopathy presents as a cauda equina syndrome. CMV-related polyradiculopathy is characterized by rapidly progressive ascending numbness, pain, and weakness affecting the legs and later occasionally also the arms. [8] With idiopathic polyradiculopathy, symptoms are more benign and the clinical progression is slower. [9]

Physical examination

The following may be noted in CMV-related polyradiculopathy:

  • Rapidly progressive, ascending course
  • Paresthesias
  • Sensory loss
  • Rarely, sensory level suggestive of spinal cord involvement
  • Flaccid paraparesis
  • Areflexia
  • Urinary retention, constipation, or incontinence
  • Rarely, cranial neuropathies
  • Often asymmetrical
  • Late involvement of the upper extremities

Herpes zoster is characterized by pain and itching followed by rash. Trigeminal and thoracic dermatomes are most commonly affected. [10]

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CSF Analysis

Cerebrospinal fluid analysis may be useful for differentiation between the various etiologies: the infectious forms (eg, CMV, cryptococcosis, tuberculosis, toxoplasmosis), the idiopathic form, and the neoplastic form (ie, lymphoma). In addition to routine studies, analysis of the CSF for cytology, CMV, Venereal Disease Research Laboratory test (VDRL), and cryptococcal antigen may be performed. The most sensitive techniques, including polymerase chain reaction (PCR), are required to rule out specific treatable infections.

In CMV-related polyradiculopathy, typical CSF findings are as follows:

  • Decreased glucose level
  • Markedly elevated protein level
  • Polymorphonuclear neutrophil (PMN)–predominant pleocytosis
  • Positive PCR for CMV
  • Absence of malignant cells

Pleocytosis usually comprises more than 60% PMNs, but the percentage is sometimes lower. In one study, only 50% of patients had PMN-preponderant pleocytosis. Positive CMV-PCR and elevated protein were the most common CSF findings. [11]

PCR of CSF has a 92% sensitivity and a 94% specificity in CMV-associated progressive polyradiculopathy. CMV culture is positive in only 50% of cases.

CSF findings in idiopathic disease may include the following:

  • Moderate mononuclear pleocytosis
  • Mildly elevated protein
  • Absence of identifiable infectious agents or malignant cells
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Other Tests

A complete blood count may indicate very low CD4 lymphocyte counts. Blood and urine cultures may indicate CMV and other possible etiologic agents.

MRI or myelography is useful to exclude cauda equina or spinal cord compressive lesions resulting from lymphoma, syphilis, or toxoplasmosis. Possible findings include the following:

  • Meningeal enhancement consistent with arachnoiditis
  • Thickened nerve roots

Electromyography and nerve conduction studies may indicate the following:

  • Differentiation from other rapidly progressive neuropathies such as Guillain-Barré syndrome
  • Widespread denervation
  • Prolonged or absent F-waves
  • Low-amplitude or unobtainable tibial or peroneal compound muscle action potentials and sural nerve action potentials
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Treatment & Management

Treatment strategies depend on the etiology. In idiopathic polyradiculopathy, spontaneous improvement without treatment is common. [7]

CMV polyradiculopathy requires treatment that is different from that for similar syndromes caused by lymphoma or other infections. For CMV infection, prompt initiation of therapy is critical. Combination treatment with ganciclovir and foscarnet might be preferred as initial therapy to stabilize disease and maximize response, although it has substantial rates of adverse effects. [12] Ganciclovir-resistant CMV may respond to foscarnet but still carries a high mortality.

Reports exist that CMV polyradiculopathy responds to cidofovir in combination with highly active antiretroviral therapy (HAART). [13] Acyclovir inhibits activity of both HSV-1 and HSV-2.

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