Medical treatment of polymeric cerebral granulomatous reactions following endovascular procedures.

BACKGROUND: Endovascular procedures are standard of care for an increasing range of cerebrovascular diseases. Many endovascular devices contain plastic and are coated with a hydrophilic polymer which has been rarely described to embolize, resulting in distal granulomatous inflammatory lesions within the vascular territory. METHODS: We reviewed three cases of cerebral granulomatous reactions that occurred after endovascular intervention for internal carotid aneurysms. The patient procedure details, presentation, relevant investigations, and treatment course are described. We also provide a literature review on endovascular granulomatous reactions. RESULTS: These three cases represent the largest biopsy proven series of cerebral granulomatosis following endovascular intervention. We highlight the variable clinical presentation, with two of the three cases having an unusually delayed onset of up to 4 years following the intervention. We show the characteristic histological findings of granulomatous lesions with foreign body material consistent with a type IV reaction, radiological abnormalities of enhancing lesions within the vascular territory of the intervention, and the requirement of prolonged immunosuppression for maintenance of clinical remission, with two of the three patients requiring a corticosteroid sparing agent. In comparison with the available literature, in addition to hydrophilic gel polymer, we discuss that plastic from the lining of the envoy catheter may be a source of embolic material. We also discuss the recommendations of the Food and Drug Administration and the implementation of novel biomaterials for the prevention of these reactions in the future. CONCLUSIONS: There is a need for increased awareness of this severe complication of cerebral endovascular procedures and further longitudinal studies of its prevalence, optimal management and preventative measures.

The Immune Dysregulation of Common Variable Immunodeficiency Disorders.

Common variable immunodeficiency (CVID) is established as a heterogeneous collection of disorders of immune dysregulation rather than an infectious complication of antibody deficiency. Approximately 70% of patients have one or more of the non-infectious complications of autoimmunity, enteropathy, polyclonal lymphocytic and malignancy. The CVID-disorders represent a particular challenge as they fall under an umbrella diagnosis governed currently by non-universal diagnostic criteria. The rubric of CVID is shrinking as next generation sequencing is progressively and rapidly identifying the genetic basis for many of its disorders. Although identification of monogenic cause of CVID allows for naming of separate or specific entities, it still provides valuable insight into the immune dysregulation of these disorders along with recognition of a polygenic basis of disease and cellular changes observed in innate and adaptive immune pathways. Cellular abnormalities in the T-cell (reduced regulatory T cells (Tregs) and increased T follicular helper cells), and B-cell compartments (reduced switched memory B-cells and increased peripheral CD21low cells) along with an increase in innate lymphoid cells type 3 promote a milieu for inflammation. Immune dysregulation also results from increased microbial translocation from impaired gastrointestinal barrier function in CVID-patients with loss of Tregs. An understanding of the manifestations and mechanisms of immune dysregulation allows for improved vigilance in screening for the diagnosis, monitoring for complications of disease and the continued development and introduction of targeted therapies for non-infectious phenotypes.

Resolution of aquaporin-4 antibodies in a woman with neuromyelitis optica treated with human autologous stem cell transplant.

We report a 47-year-old woman with highly active neuromyelitis optica (NMO) and persistent high titre anti-aquaporin-4 antibodies (anti-AQP-4) who was resistant to multiple immune therapies until she underwent autologous hematopoietic stem cell transplant (auto-HSCT). NMO is the only demyelinating disease with a clinically useful serum biomarker, aquaporin-4, a water channel protein expressed on astrocytes. Anti-AQP-4 antibodies correlate with NMO disease activity and animal models strongly suggest the antibody is pathogenic. Auto-HSCT was associated with clinical and radiological remission, improved disability and resolution of AQP-4 antibodies which are still undetectable 12 months later. The utility of auto-HSCT for refractory NMO warrants further investigation, particularly with regards to pre-conditioning regimens and the utility of AQP-4 antibodies as a biomarker for immunological and clinical remission.