A single-center study on 140 patients with cerebral cavernous malformations: 28 new pathogenic variants and functional characterization of a PDCD10 large deletion.

Cerebral cavernous malformation (CCM) is a capillary malformation arising in the central nervous system. CCM may occur sporadically or cluster in families with autosomal dominant transmission, incomplete penetrance, and variable expressivity. Three genes are associated with CCM KRIT1, CCM2, and PDCD10. This work is a retrospective single-center molecular study on samples from multiple Italian clinical providers. From a pool of 317 CCM index patients, we found germline variants in either of the three genes in 80 (25.2%) probands, for a total of 55 different variants. In available families, extended molecular analysis found segregation in 60 additional subjects, for a total of 140 mutated individuals. From the 55 variants, 39 occurred in KRIT1 (20 novel), 8 in CCM2 (4 novel), and 8 in PDCD10 (4 novel). Effects of the three novel KRIT1 missense variants were characterized in silico. We also investigated a novel PDCD10 deletion spanning exon 4-10, on patient's fibroblasts, which showed significant reduction of interactions between KRIT1 and CCM2 encoded proteins and impaired autophagy process. This is the largest study in Italian CCM patients and expands the known mutational spectrum of KRIT1, CCM2, and PDCD10. Our approach highlights the relevance of seeking supporting information to pathogenicity of new variants for the improvement of management of CCM.

Posterior Titanium Screw Fixation without Debridement of Infected Tissue for the Treatment of Thoracolumbar Spontaneous Pyogenic Spondylodiscitis.

STUDY DESIGN: Retrospective study. PURPOSE: The aim of our study was to analyze the safety and effectiveness of posterior pedicle screw fixation for treatment of pyogenic spondylodiscitis (PSD) without formal debridement of the infected tissue. OVERVIEW OF LITERATURE: Posterior titanium screw fixation without formal debridement of the infected tissue and anterior column reconstruction for the treatment of PSD is still controversial. METHODS: From March 2008 to June 2013, 18 patients with PSD underwent posterior titanium fixation with or without decompression, according to their neurological deficit. Postero-lateral fusion with allograft transplantation alone or bone graft with both the allogenic bone and the autologous bone was also performed. The outcome was assessed using the visual analogue scale (VAS) for pain and the Frankel grading system for neurological status. Normalization both of C-reactive protein (CRP) and erythrocyte sedimentation rate was adopted as criterion for discontinuation of antibiotic therapy and infection healing. Segmental instability and fusion were also analyzed. RESULTS: At the mean follow-up time of 30.16 months (range, 24-53 months), resolution of spinal infection was achieved in all patients. The mean CRP before surgery was 14.32±7.9 mg/dL, and at the final follow-up, the mean CRP decreased to 0.5±0.33 mg/dL (p <0.005). Follow-up computed tomography scan at 12 months after surgery revealed solid fusion in all patients. The VAS before surgery was 9.16±1.29 and at the final follow-up, it improved to 1.38±2.03, which was statistically significant (p <0.05). Eleven patients out of eighteen (61.11%) with initial neurological impairment had an average improvement of 1.27 grades at the final follow-up documented with the Frankel grading system. CONCLUSIONS: Posterior screw fixation with titanium instrumentation was safe and effective in terms of stability and restoration of neurological impairment. Fixation also rapidly reduced back pain.