Cytomegalovirus polyradiculopathy

To the Editor:

The relatively recent advent of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) has affected every specialty of medicine and health care today. HIV itself, and in combination with opportunistic infections, has spurred syndromes that have become major killers and cripplers. Some of these syndromes affect the lower extremity, and podiatric physicians must recognize these conditions in patients. One such condition in which foot pain and weakness are major presenting symptoms is cytomegalovirus polyradiculopathy.

Painful distal symmetrical peripheral neuropathy is the most frequent neuropathy in patients with AIDS. The presenting symptoms are subacute onset of pain in the feet, mild sensory changes, and axonal atrophy on nerve biopsy. Lumbosacral radiculopathy occurs in approximately 1% of patients with AIDS. It is a rapidly progressive syndrome that initially presents with low back pain, sphincter disturbance, progressive flaccid paraparesis, and neutrophil cerebrospinal fluid pleocytosis.[1]

Often, weakness of the lower extremities is the initial symptom and can progress to complete irreversible paralysis within days. If antiviral treatment is not started promptly, this syndrome invariably leads to death.

Human cytomegalovirus is classified as a herpesvirus, and is implicated in the pathogenesis of many conditions including atherosclerosis, tumors, and neurologic degeneration. Close contact is required for the spread of cytomegalovirus, which occurs particularly through the shedding of oral and genital secretions. It is spread by both sexual and nonsexual contact. It is mainly the immunocompromised patient who exhibits pathologic disease.[2]

The most common cytomegalovirus-related neuropathy is a painful peripheral neuropathy, which occurs in approximately 15% of patients with AIDS. It is subacute in onset, and usually does not appear until the patient’s CD4+ count drops below 50 µl. The pain, which is usually limited to the feet, occurs over a period of weeks. The pain is increased by direct contact and is usually accompanied by mild numbness. On physical examination, loss of ankle reflexes, mild distal sensory loss, and sometimes distal weakness are noted.

Sural nerve biopsy shows a 40% decrease in myelinated fiber density, and no inflammation is present. Axonal atrophy is present with the axon diameter reduced in relation to the myelin sheath, which is diagnostic for this condition.[3]

The most severe cytomegalovirus-related neuropathy is cytomegalovirus lumbosacral polyradiculopathy. This syndrome has had many different names over the years, including polyradiculoneuropathy, progressive polyradiculopathy, spinal cord syndrome, acute myeloradiculitis, and cauda equina syndrome. Because of the similarity of clinical symptoms, some cases may have been misdiagnosed as Guillain-Barré syndrome.[3]

This syndrome occurs in approximately 1% of patients with AIDS, and may be the first opportunistic infection to be detected.[4] One of the major presenting symptoms of this syndrome is progressive areflexic paraplegia, which is why it is important for the podiatric physician to be able to recognize this syndrome. Often lower extremity weakness can be the presenting complaint of this syndrome which, in turn, may be the initial opportunistic infection of AIDS. If it is diagnosed and appropriate antiviral treatment is initiated promptly, the progression can be arrested. If the condition proceeds untreated, complete irreversible paraplegia, possibly within days, followed by death is a certainty.

Other symptoms are low back pain, often with radicular perianal radiation, sphincter disturbance, urinary retention, and fecal incontinence. In making a diagnosis, it is often helpful to look for evidence of cytomegalovirus infection at other sites, such as cytomegalovirus retinitis. The polymorphonuclear counts in the cerebrospinal fluid are usually between 99 and 5,000 µl. The cytomegalovirus cultures are only occasionally positive for unknown reasons. Deterioration is rapid and death usually occurs from 3 to 12 weeks (mean = 7 weeks) from the onset of symptoms.[1]

The only treatments known are ganciclovir, foscarnet, or a combination of the two. Treatment must be instituted early, as any neurologic loss is permanent and progression is rapid.[7]

Case Report

A 41-year-old female presented to the Cooper Hospital emergency department complaining of pain in her feet, difficulty with walking, headache, urinary retention, and mild neck stiffness. Her past medical history is remarkable for asthma and HIV since 1991. Her last CD4 count was 29. She also had a history of pneumonia and esophageal candidiasis treated with fluconazole. Chest x-ray showed left lower lobe atelectasis, elevation of the left hemi diaphragm, and possible left plural effusion. She refused lumbar puncture at that time, and was treated with amoxicillin/ clavulanate potassium. She refused admission and left the emergency department.

The patient presented again the following day with a worsening of all symptoms. Her difficulty with walking had progressed to an inability to walk. Her temperature was 100° F, pulse 103, respirations 18, blood pressure 99/59. Motor strength was 5/5 bilaterally in the upper extremities, 3/5 on the right lower extremity, and 2/5 on the left lower extremity. The results of the spinal tap showed glucose of 15, protein 234, cell count of 386, cloudy, 96 neutrophils, and 4% lymphocytes. The white blood count was 10.3 and the red blood count was 10.3. The Gram’s stain of the cerebrospinal fluid had many polymorphonucleocytes, no organisms, and was DNA negative. The patient was then admitted to the hospital.

The computed tomography of the head was within normal limits. The magnetic resonance imaging scan of the lumbar spine showed lumbar spondylosis with a small central disk herniation at L4-L5, causing mild spinal stenosis. The chest x-ray showed elevated left diaphragm. The lungs were clear and mild cardiomegaly was present. Abdominal computed tomography showed some small retroperitoneal nodes, but was otherwise normal. Magnetic resonance imaging of the cervical and lumbar spines showed no evidence of either intrinsic lesions or extrinsic compression. Alteration in signal intensity of the posterior aspect of the midthoracic region was present possibly from an inflammatory process of the meninges.

She continued to have fever of 102.1° F. All blood cultures were negative, and initially there was no evidence of cytomegalovirus retinitis. The electromyogram findings were most consistent with cytomegalovirus myelitis.

Six days after admission, the patient was started on ganciclovir, 300 mg intravenously every 12 hr. Repeat spinal tap showed increasing glucose, protein, and white blood counts in the cerebrospinal fluid. At this point, all cytology results were negative. The cerebrospinal fluid was tested for cytomegalovirus analysis. The patient continued to lose strength and sensation in her lower extremities.

Ten days after admission, her lower extremities were without strength, movement, or reflexes bilaterally. Upper extremity strength remained at 4/5. She had no sensation below the level of the umbilicus. Retinal abnormalities were found that were classified as nonspecific.

Fourteen days after admission, the cytomegalovirus protein catabolic rate came back positive. At this point, foscarnet was added to the treatment in addition to ganciclovir. The patient stabilized and no longer deteriorated, but did not improve. She underwent Hickman catheter placement 6 days later. Three days later, she was discharged to hospice care with prescriptions of foscarnet and ganciclovir. Her condition at discharge was flaccid paralysis in both lower extremities, with no sensation below the level of T-10.

Discussion

The case shows the importance of early diagnosis and early treatment in patients with cytomegalovirus polyradiculopathy. The sooner treatment is started, the more neurologic function is preserved. The key clinical findings to look for are: 1) known infection with HIV, 2) low back pain, 3) pain or weakness in the lower extremities, 4) loss of sensation to the lower extremities, 5) difficulty walking, 6) urinary retention, 7) headache, 8) neck stiffness, and 9) retinal abnormalities.