Study Design Case report and review of the literature. Objective A retro-odontoid mass is a rare cause of cervical compression and myelopathy. The differential diagnosis includes the following: metastatic disease, primary tumor, collagen disorder, or inflammatory disease. Calcium pyrophosphate dihydrate (CPPD) deposition has been referred to as "crowned dens syndrome" when there are periodontoideal calcifications. There are only a few reported cases where CPPD presents as a cystic retro-odontoid mass in the atlanto-dens interval. In previous descriptions of surgical intervention, transoral resection of the mass is associated with significant morbidity and usually requires stabilization. The objective of this article is to report a case of an unusual presentation of CPPD disease of C1/C2, where we used a novel, minimally invasive surgical technique for decompression without fusion. Patients and Methods An 83-year-old female patient presented with progressive cervical myelopathy over a 3-month period. Computed tomography and magnetic resonance imaging demonstrated a cystic odontoid mass with a separate retro-odontoid compressive mass. A novel, minimally invasive transoral aspiration was performed. Histologic confirmation of CPPD was obtained. Results Postop imaging showed satisfactory decompression, which was maintained at the 6-month follow-up. This correlated with clinical improvement postop and 6-month follow-up. Conclusion CPPD in the atlanto-dens interval may present as a cystic retro-odontoideal mass and should be included in the differential. We used a transoral minimally invasive approach to aspirate the cyst. This novel technique avoided the need for a stabilization procedure or morbid transoral resection and provided excellent results immediately and at 6 months.

Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug discovery.