Lumbar artificial disc replacement in Ehlers-Danlos syndrome: A case report and discussion of clinical management.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a heterogeneous collection of connective tissue disorders characterized by varying degrees of skin hyperextensibility, joint hypermobility, and tissue fragility. Surgical treatment of EDS patients is complicated by the extreme fragility of their vessels and tissues. The purpose of this case report is to present the management of an EDS patient with debilitating low-back pain. METHODS: A 52-year-old woman with a clinical diagnosis of EDS presented with degenerative disc disease at L4-5 that had not been alleviated by previous microdiscectomies. The clinical course, decision-making process, and treatment are discussed in this case report. RESULTS: The patient was referred for genetic evaluation, which classified her with type III EDS, or hypermobility type. We presented the patient with the risks and benefits of fusion versus artificial disc replacement (ADR), particularly with regard to her EDS diagnosis of the hypermobility subtype. Given the patient's lack of extreme spinal hypermobility on examination and the absence of clear contraindications regarding ADR in type III EDS, the decision was made to proceed with ADR. There were no surgical complications, and the patient's low-back pain and radicular symptoms resolved with no evidence of implant migration or hypermobility at 1 year postoperatively. CONCLUSIONS: In this case report, the referral to a geneticist and consultation with a vascular surgeon were integral steps in the decision to proceed with surgery. Although the clarified diagnosis of type III EDS did not eliminate the potential risk for vascular compromise during surgery, it placed the patient at lower risk than patients with other subtypes of EDS. Similarly, her lack of extreme hypermobility made us more comfortable with pursuing ADR. Although we emphasize extreme caution when considering surgical treatment, this case report suggests that some patients with less severe forms of EDS may be able to successfully undergo anterior spine surgery, including ADR.

Non-infectious aggregates of the prion protein react with several PrPSc-directed antibodies.

The key event in the pathogenesis of prion diseases is the conformational conversion of the normal prion protein (PrP) (PrP(C)) into an infectious, aggregated isoform (PrP(Sc)) that has a high content of beta-sheet. Historically, a great deal of effort has been devoted to developing antibodies that specifically recognize PrP(Sc) but not PrP(C), as such antibodies would have enormous diagnostic and experimental value. A mouse monoclonal IgM antibody (designated 15B3) and three PrP motif-grafted monoclonal antibodies (referred to as IgG 19-33, 89-112, and 136-158) have been previously reported to react specifically with infectious PrP(Sc) but not PrP(C). In this study, we extend the characterization of these four antibodies by testing their ability to immunoprecipitate and immunostain infectious and non-infectious aggregates of wild-type, mutant, and recombinant PrP. We find that 15B3 as well as the motif-grafted antibodies recognize multiple types of aggregated PrP, both infectious and non-infectious, including forms found in brain, in transfected cells, and induced in vitro from purified recombinant protein. These antibodies are exquisitely selective for aggregated PrP, and do not react with soluble PrP even when present in vast excess. Our results suggest that 15B3 and the motif-grafted antibodies recognize structural features common to both infectious and non-infectious aggregates of PrP. Our study extends the utility of these antibodies for diagnostic and experimental purposes, and it provides new insight into the structural changes that accompany PrP oligomerization and prion propagation.