Fainting with HIV
Article Outline
Presentation
When a man with untreated human immunodeficiency virus (HIV) infection presented with recurrent episodes of syncope, magnetic resonance imaging (MRI) yielded a novel etiology.
The patient, a 51-year-old Puerto Rican man, presented to our clinic with cough, hemoptysis, night sweats, and recurrent syncopal episodes. He described intermittent episodes of fainting, increasing in frequency, for 3 months prior to presentation. In the previous week alone, he had suffered 3 such episodes. His daughter, who had witnessed several of the fainting episodes, had called for emergency medical services after his most recent episode, which had resulted in a fall. She reported that the syncopal episodes were accompanied by convulsions during and after loss of consciousness and by a period of confusion after regain of consciousness. The episodes were not accompanied by bowel or bladder incontinence.
The patient had been diagnosed with HIV in 1994 but had no history of acquired immune deficiency syndrome (AIDS)-defining illnesses. He had discontinued his antiretroviral therapy in 2003 because of pill burden. His medical history was otherwise significant for a severe burn to the lumbar spine, which had left him paraplegic and wheelchair-bound at baseline.
Assessment
At his admission examination, the patient exhibited word-finding difficulties. His cranial nerves were intact. His strength was 5/5 bilaterally in the upper extremities but 0/5 bilaterally in the lower extremities. The response to pinprick and light touch was intact above the lumbar spine and absent below the lumbar spine. The oropharynx exhibited no signs of thrush. The lung exam revealed decreased breath sounds at the right base. Blood analyses revealed a CD4+ T-cell count of 4/μL and an HIV viral load of 22.4
×104 copies/mL. Repeated tests for acid-fast bacilli in bronchoalveolar lavage samples were negative.
MRI of the patient's brain showed prominent bilateral, asymmetric, periventricular white-matter lesions (Figure 1, Figure 2, Figure 3) on T2-weighted images. An electroencephalogram revealed no evidence of seizure or epileptiform activity. A chest x-ray revealed a lobar consolidation consistent with pneumonia.
Figure 1.
T2-weighted MRI showing a transverse view of the brain. Note asymmetric, bilateral, white-matter changes without mass effect.
Figure 2.
Pericortical white-matter disease is evident in a T2-weighted MRI of the brain (transverse view).
Figure 3.
T2-weighted MRI showing coronal view of the brain.
Analysis of cerebrospinal fluid obtained by lumbar puncture showed a protein level of 104 mg/dL, glucose level of 46 mg/dL, and red blood cell count (in the 4th sample tube) of 657 per high-power field. Polymerase chain reaction (PCR) tests of the cerebrospinal fluid were negative for JC polyomavirus, cytomegalovirus, herpes simplex virus, and Epstein-Barr virus. Acid-fast and Gram staining and mycobacterial culture of the cerebrospinal fluid also were negative. Additionally, a serum viral hepatitis panel and serum tests for syphilis antibodies (Venereal Disease Research Laboratory), toxoplasmosis immunoglobulin G (IgG), and cryptococcus antigen were negative. Serum tests were positive for cytomegalovirus IgG but not for cytomegalovirus immunoglobulin M (IgM).
Diagnosis
Studies of diagnostic outcomes among patients who present with syncope have suggested that 34% of syncope evaluations are ultimately nondiagnostic1 and that neurological disease accounts for 10% of syncope cases. An electroencephalogram is diagnostic in only 2% of syncopal episodes, and the majority of these diagnostic electroencephalograms are from patients with known seizure disorders. Syncope and drop attacks also can result from transient ischemic attacks, typically through transient vertebrobasilar ischemia.1
The etiology of our patient's syncopal episodes was elucidated by brain MRI, which yielded findings most consistent with progressive multifocal leukoencephalopathy. In this condition, T2-weighted MRI scans exhibit increased signals in a pericortical and periventricular distribution that is typically asymmetric and bilateral, with no mass effect. Our patient's syncopal episodes were probably caused by partial seizures resulting from pericortical involvement of the disease process or from extensive cell destruction in the vertebrobasilar distribution, either of which can occur with progressive multifocal leukoencephalopathy.
The differential for a T2-enhanced signal with no mass effect in a patient with AIDS also includes cytomegalovirus encephalitis and AIDS-dementia complex. In cytomegalovirus encephalitis, however, the T2 signal enhancement is more often multinodular, and ventricular enlargement also is seen. AIDS-dementia complex yields MRI findings similar to those of progressive multifocal leukoencephalopathy, but 2 diseases are most readily differentiated by the symmetry of the lesions. Although the lesions seen in progressive multifocal leukoencephalopathy are asymmetric, the lesions seen in AIDS-dementia complex are classically symmetric.
Because of the sporadic nature of the white-matter lesions typically seen in progressive multifocal leukoencephalopathy, the initial presentation is often nonspecific. In a review of 7 articles assessing symptoms seen in patients with progressive multifocal leukoencephalopathy, Weber documented (in decreasing order of occurrence) mono/hemiparesis, cognitive deficits, visual disturbances, speech deficits, and limb ataxia as the most common initial symptoms.2 Seizure activity is seen less frequently, and tends to coincide with MRI findings indicating cortical or pericortical lesions.3
In our patient, the JC virus PCR did not yield a confirming diagnosis or progressive multifocal leukoencephalopathy. However, tests for JC virus can be negative in up to one-third of patients with a tissue diagnosis of progressive multifocal leukoencephalopathy;4 as a result, many cases are diagnosed clinically. The clinical history and exam findings in our patient, including the new-onset neurological symptoms, the lack of laboratory findings supporting another diagnosis, the low CD4+ T-cell count, and the classic MRI findings of asymmetric pericortical lesions3 were most consistent with progressive multifocal leukoencephalopathy. Although AIDS-dementia complex also is seen in progressive HIV infection when CD4+ T-cell counts are lower than 200/μL, our patient's MRI findings were not consistent with AIDS-dementia complex. Cytomegalovirus encephalitis was considered unlikely in the setting of negative cytomegalovirus IgM antibody and PCR tests for the virus.
This case documents syncope as the presenting symptom of progressive multifocal leukoencephalopathy and appears to be unique in the medical literature. A search of the literature using the medical subject headings (MeSH) “Progressive Multifocal Leukoencephalopathy” and “syncope” reveals no other case reports or review articles citing syncope as a known presenting symptom in progressive multifocal leukoencephalopathy.
Management
Although no objective evidence of JC virus was found in our patient's cerebrospinal fluid, a working diagnosis of progressive multifocal leukoencephalopathy was made, and further attempts to confirm the diagnosis by tissue analysis were abandoned. The patient agreed to restart highly active antiretroviral therapy for treatment of AIDS. He was successfully treated for a community-acquired pneumonia with ceftriaxone and azithromycin and was discharged to home. However, he returned to the hospital 6 months later with worsened neurological function. He was referred to hospice, where he passed away shortly thereafter. At the family's request, no autopsy was performed.
Progressive multifocal leukoencephalopathy should be suspected in any patient who is immunocompromised and has new-onset neurological symptoms. The disease is rare in the era of antiretroviral therapy, but it continues to exhibit high morbidity and mortality. Early initiation of antiretroviral therapy is crucial once progressive multifocal leukoencephalopathy is suspected.
References
- . Syncope. N Engl J Med. 2000;343:1856–1861
- . Progressive multifocal leukoencephalopathy. Neurol Clin. 2008;26:833–854
- . Seizures and their outcome in progressive multifocal leukoencephalopathy. Neurology. 2006;66:262–264
- Prognostic significance of JC virus DNA levels in cerebrospinal fluid of patients with HIV-associated progressive multifocal leukoencephalopathy. Clin Infect Dis. 2005;40:738–744
Robert G. Stern, MD, Section Editor
Funding: None.
Conflict of Interest: None of the authors of this article have a conflict of interest to report.
Authorship: All the authors had access to the data and played a role in writing the manuscript.
PII: S0002-9343(10)00336-0
doi:10.1016/j.amjmed.2010.04.010
© 2010 Elsevier Inc. All rights reserved.
