Cerebral Abscess Associated With Odontogenic Bacteremias, Hypoxemia, and Iron Loading in Immunocompetent Patients With Right-to-Left Shunting Through Pulmonary Arteriovenous Malformations

Abstract

Background: Cerebral abscess is a recognized complication of pulmonary arteriovenous malformations (PAVMs) that allow systemic venous blood to bypass the pulmonary capillary bed through anatomic right-to-left shunts. Broader implications and mechanisms remain poorly explored.

Methods: Between June 2005 and December 2016, at a single institution, 445 consecutive adult patients with computed tomography-confirmed PAVMs (including 403 [90.5%] with hereditary hemorrhagic telangiectasia) were recruited to a prospective series. Multivariate logistic regression was performed and detailed periabscess histories were evaluated to identify potential associations with cerebral abscess. Rates were compared to an earlier nonoverlapping series.

Results: Thirty-seven of the 445 (8.3%) patients experienced a cerebral abscess at a median age of 50 years (range, 19-76 years). The rate adjusted for ascertainment bias was 27 of 435 (6.2%). Twenty-nine of 37 (78.4%) patients with abscess had no PAVM diagnosis prior to their abscess, a rate unchanged from earlier UK series. Twenty-one of 37 (56.7%) suffered residual neurological deficits (most commonly memory/cognition impairment), hemiparesis, and visual defects. Isolation of periodontal microbes, and precipitating dental and other interventional events, emphasized potential sources of endovascular inoculations. In multivariate logistic regression, cerebral abscess was associated with low oxygen saturation (indicating greater right-to-left shunting); higher transferrin iron saturation index; intravenous iron use for anemia (adjusted odds ratio, 5.4 [95% confidence interval, 1.4-21.1]); male sex; and venous thromboemboli. There were no relationships with anatomic attributes of PAVMs, or red cell indices often increased due to secondary polycythemia.

Conclusions: Greater appreciation of the risk of cerebral abscess in undiagnosed PAVMs is required. Lower oxygen saturation and intravenous iron may be modifiable risk factors.

Keywords: hereditary hemorrhagic telangiectasia; hypoxemia; intravenous iron; oxygen; transferrin saturation index.

Figure 1.

Persistent neurological deficits in the 37 cerebral abscess cases. Indirect neurological consequences (eg, postabscess strokes) are not included, but would increase the number of visual loss cases by 1. There were no fatalities in this group, but 3 patients with pulmonary arteriovenous malformation due to hereditary hemorrhagic telangiectasia had first-degree relatives who died as a direct result of a cerebral abscess. “?” represents cases where the final neurological outcome was not yet known.

Figure 2.

Comparison of the cerebral abscess risk receiver operating characteristic (ROC) model from oxygen saturation (SaO₂) alone (dotted line/open symbols) and final model with SaO₂, sex, transferrin saturation index, intravenous iron, and venous thromboembolus (solid black line/symbols). The 2 models provide areas under the curve of 0.63 and 0.73, respectively (P = .0012). Inclusion of feeding artery diameter marginally reduced the strength of the models, and the association was negative, implying that cerebral abscess were marginally more common for pulmonary arteriovenous malformations with smaller feeding artery diameters, once adjusted for other components of the model.

Figure 3.

Variation of parameters across the transferrin saturation index (TfSI) quartiles. A, TfSI (%), where the normal institutional range was 20%–40%. Note that because boundary values were allocated to a single quartile, the exact numbers across Q1–Q4 were 89, 103, 105, and 101, respectively. B, Percentage of patients with cerebral abscess. C, Oxygen saturation (SaO₂) where normal is ≥96%. D, Gender (% male). In all graphs, bars indicate mean and standard error of the mean. Across Q1–Q4, intravenous iron rates were 7.9%, 1.9%, 2.9%, and 5.0%, and venous thromboembolus rates were 3.4%, 7.8%, 5.7%, and 1.0%, respectively.