Rashi I. Mehta

Hydrophilic polymer emboli: an under-recognized iatrogenic cause of ischemia and infarct

With the increased use of percutaneous intravascular diagnostic and therapeutic devices, there is potential for embolization of materials introduced into the vasculature. We report nine cases of foreign body emboli in patients who underwent vascular procedures using hydrophilic-coated medical devices. The procedures performed included cardiac catheterization (four cases), diagnostic cerebral angiography (two cases), therapeutic cerebral angiography with coil embolization of intracerebral aneurysm (one case), lower extremity angiography (one case), and/or orthotopic cadaveric organ transplantation (three cases). Other procedures in these patients included hemodialysis and peripheral arterial or central venous catheterization. Clinical sequelae ranged from undetectable (no symptoms) to pulmonary infarction, stroke, ongoing gangrene, and/or death occurring within days to weeks of suspected embolization of foreign material. Microscopic findings in biopsy or autopsy tissue revealed aggregates of amorphous or lamellated, non-refractile, non-polarizable, predominantly basophilic foreign substances occluding intrapulmonary, intracerebral, or peripheral arteries. This is the largest series documenting embolization of polymer gel materials. Polymer gel is now widely used on several devices for interventional procedures worldwide, and we suspect that complications associated with iatrogenic embolization of this substance are under-recognized.

Intravascular polymer material after coil embolization of a giant cerebral aneurysm.

We report the case of an 87-year-old female who died after coil embolization of an intracerebral giant aneurysm. Guglielmi detachable (Boston Scientific Neurovascular, Fremont, CA) and Matrix2 coils (Boston Scientific Neurovascular, Fremont, CA) were used during the procedure to occlude the surgically untreatable left supraclinoid carotid artery aneurysm. Postprocedure imaging studies showed scattered areas of acute infarct involving multiple bilateral vascular territories. Autopsy confirmed widespread infarction due to embolized foreign material, morphologically consistent with hydrophilic polymer originating from the coated Matrix coil and Terumo glidewire (Terumo Medical, Somerset, NJ). Polymer gel is now widely used on several medical devices for interventional procedures worldwide, and we suspect that risks associated with iatrogenic embolization of this substance are underrecognized.

Polymer-induced central nervous system complications following vascular procedures: spectrum of iatrogenic injuries and review of outcomes

Polymer substances are commonly applied as surface coatings on endovascular catheters and vascular devices. Adverse effects related to their use have been reported, although the overall clinical significance and appropriate methods of detection of these complications have been unclear. In this analysis, we systematically reviewed clinical and diagnostic features in 32 patients (age, 36-87years; mean, 59years) in whom intracranial polymer reactions were documented following vascular interventions. Associated neuroradiologic and neuropathologic findings were variable and included cerebral vasculitis or vasculopathy (63%), abscess or granuloma formation (38%), ischemic infarcts (28%), parenchymal hematomas (28%), white matter change (25%), and/or chemical meningitis (22%). Location(s) of polymer reactions varied and included sites adjacent to and/or downstream from instrument insertion or implantation. Presenting clinical signs included focal neurologic deficits (41%), headache (22%), constitutional symptoms (19%), meningitis (16%), seizure and/or involuntary movements (9%), coma (6%), and syncope (3%). Adverse outcomes included stroke (31%), death (28%), delayed communicating hydrocephalus (9%), steroid dependency (9%), steroid complications (6%), and cerebral volume loss (3%). In some cases, these complications necessitated increased cost and length of medical care. In this review, we highlight the diverse features of polymer-induced reactions involving the central nervous system and summarize distinct diagnostic patterns that may enable earlier premortem detection of these lesions in the postprocedural clinical setting. Further work in this area is necessary to identify additional etiologic, preventative and therapeutic strategies. These data have potentially broad implications pertaining to the safety, efficacy, standards of use, storage, manufacturing, and regulation of new and emerging vascular devices and polymer nanotechnologies.

Associations between neurodevelopmental genes, neuroanatomy, and ultra high risk symptoms of psychosis in 22q11.2 deletion syndrome

22q11.2 deletion syndrome is a neurogenetic disorder resulting in the deletion of over 40 genes. Up to 40% of individuals with 22q11.2DS develop schizophrenia, though little is known about the underlying mechanisms. We hypothesized that allelic variation in functional polymorphisms in seven genes unique to the deleted region would affect lobar brain volumes, which would predict risk for psychosis in youth with 22q11.2DS. Participants included 56 individuals (30 males) with 22q11.2DS. Anatomic MR images were collected and processed using Freesurfer. Participants were genotyped for 10 SNPs in the COMT, DGCR8, GNB1L, PIK4CA, PRODH, RTN4R, and ZDHHC8 genes. All subjects were assessed for ultra high risk symptoms of psychosis. Allelic variation of the rs701428 SNP of RTN4R was significantly associated with volumetric differences in gray matter of the lingual gyrus and cuneus of the occipital lobe. Moreover, occipital gray matter volumes were robustly associated with ultra high risk symptoms of psychosis in the presence of the G allele of rs701428. Our results suggest that RTN4R, a relatively under‐studied gene at the 22q11 locus, constitutes a susceptibility gene for psychosis in individuals with this syndrome through its alteration of the architecture of the brain.

Polymer Coating Embolism: Cause of Cerebral Vasculopathy and Death following Congenital Heart Repair in Two Infants

To the Editor: We read with interest the article, “Embolic foreign material in the central nervous system of pediatric autopsy patients with instrumented heart disease (1).” In their analysis, Torre et al assessed the postmortem histologic frequency of foreign body emboli to the central nervous system (CNS) in pediatric patients who had undergone recent cardiac instrumentation for congenital heart disease. A detectable prevalence of 33% was identified at a single tertiary care center; foreign substances were attributed to catheter and interventional medical device components, including sheared fragments of surface polymer coats. Secondary inflammation was identified in all patients, with microand/or macroinfarcts additionally seen in 38%. This work adds to expanding medical literature which, over the past decade, provides evidence that hydrophobic and/or hydrophilic polymer (coating) emboli (HPE) are underdiagnosed complications in post-interventional clinical settings (2, 3). Findings are concordant with postmortem data from hospitalized adults that uncover HPE frequency of 13% (4), as well as prospective clinical evidence that document capture of coating emboli in 86% of adults undergoing mitral valve repair (5). In adults, these embolic complications have been shown to induce significant morbidity, with potential for chronic neurologic decline, cerebral volume loss, stroke, and occasionally death (3). Herein, we present two additional autopsy-proven cases of multifocal HPE in infants who were status-post repair for congenital heart disease. In these cases, iatrogenic HPE induced secondary vasculopathy that resulted in parenchymal hemorrhage and infarction, leading to infant demise. Patient 1 The decedent was a 9-month-old infant with history of tetralogy of Fallot, pulmonary atresia, and multiple aortopulmonary collaterals diagnosed at 3 months of age. He underwent unifocalization of his collaterals to a leftsided Blalock–Taussig shunt as well as balloon dilatation of a stenotic collateral at 8 months. One week later, the infant was admitted emergently with neurologic deficits and radiological evidence of massive intracranial hemorrhage (Fig. 1A). Emergent hemicraniectomy, decompression, and evacuation of left subdural and parenchymal hematomas were performed. Due to continued hemorrhage and worsening brain herniation, medical care was subsequently withdrawn. At autopsy, brain exam revealed a large left-sided hemispheric hematoma involving the subdural, subarachnoid, and intraparenchymal compartments. Vessels within zones of hemorrhage exhibited occlusive polymer emboli, with associated perivascular inflammation and fibrous response (Fig. 1B–E). No other vascular changes or embolic particles were identified in non-involved brain regions, although features of acute hypoxic-ischaemic encephalopathy were additionally found.