Opposed evolution of the osseous and soft parts of progestin-associated osteomeningioma after progestin intake discontinuation.

OBJECTIVE: Numerous studies have confirmed a strong association between progestins and meningiomas and the regression and/or stabilization of meningiomas after discontinuation of treatment. Osteomeningiomas represent a small subgroup of meningiomas that appear to be more common among progestin-related meningiomas. However, the specificity of the behavior of this subset of meningiomas after discontinuation of progestin has not yet been assessed. METHODS: Thirty-six patients (mean age 49.5 years) who presented with at least one progestin-related osteomeningioma (48 tumors total) were identified from a prospectively collected database of patients and had been referred to our department for meningioma and had documented use of cyproterone acetate, nomegestrol acetate, and/or chlormadinone acetate. Hormonal treatment was stopped at the time of diagnosis for all the patients, and the clinical and radiological evolution of this subgroup of tumors was evaluated. RESULTS: For half of the 36 patients, treatment was prescribed for signs of hyperandrogenism, such as hirsutism, alopecia, or acne. Most lesions were spheno-orbital (35.4%) or frontal (31.2%). Although the tissular part of the meningioma shrank in 77.1% of cases, the osseous part exhibited discordant behavior with 81.3% showing volume progression. The combination of estrogens, as well as the prolonged duration of progestin treatment, seems to increase the risk of progression of the osseous part after treatment discontinuation (p = 0.02 and p = 0.028, respectively). No patient required surgical treatment at diagnosis or during the study. CONCLUSIONS: These results show that while the soft intracranial part of progestin-related osteomeningioma tumor is the most likely to regress after treatment discontinuation, the bony part is more likely to increase in volume. These findings suggest the need for careful follow-up of these patients, especially those with tumors near the optical apparatus.

Non-Transgenic CRISPR-Mediated Knockout of Entire Ergot Alkaloid Gene Clusters in Slow-Growing Asexual Polyploid Fungi.

The Epichloë species of fungi include seed-borne symbionts (endophytes) of cool-season grasses that enhance plant fitness, although some also produce alkaloids that are toxic to livestock. Selected or mutated toxin-free endophytes can be introduced into forage cultivars for improved livestock performance. Long-read genome sequencing revealed clusters of ergot alkaloid biosynthesis (EAS) genes in Epichloë coenophiala strain e19 from tall fescue (Lolium arundinaceum) and Epichloë hybrida Lp1 from perennial ryegrass (Lolium perenne). The two homeologous clusters in E. coenophiala-a triploid hybrid species-were 196 kb (EAS1) and 75 kb (EAS2), and the E. hybrida EAS cluster was 83 kb. As a CRISPR-based approach to target these clusters, the fungi were transformed with ribonucleoprotein (RNP) complexes of modified Cas9 nuclease (Cas9-2NLS) and pairs of single guide RNAs (sgRNAs), plus a transiently selected plasmid. In E. coenophiala, the procedure generated deletions of EAS1 and EAS2 separately, as well as both clusters simultaneously. The technique also gave deletions of the EAS cluster in E. hybrida and of individual alkaloid biosynthesis genes (dmaW and lolC) that had previously proved difficult to delete in E. coenophiala. Thus, this facile CRISPR RNP approach readily generates non-transgenic endophytes without toxin genes for use in research and forage cultivar improvement.

Ophthalmoplegic complications in transsphenoidal pituitary surgery.

OBJECTIVE: Ophthalmoplegia is a rare complication of transsphenoidal surgery, only noted in a few studies. The purpose of this study was to analyze the complications of cranial nerve III, IV, or VI palsy after transsphenoidal surgery for pituitary adenoma and understand its physiopathology and outcome. METHODS: The authors retrospectively analyzed 24 cases of postoperative ophthalmoplegia selected from the 1694 patients operated via a transsphenoidal route in their department. RESULTS: Two patients were operated on via microscopy and 22 via endoscopy. Patients operated on endoscopically had a greater risk of presenting with an extraocular nerve deficit postoperatively (p = 0.0115). It was found that an extension into or an invasion of the cavernous sinus (Knosp grade 3 or 4 on MRI, 18/24 patients) was correlated with a higher risk of postoperative ophthalmoplegia (p < 0.0001). The deficit was apparent immediately after surgery in 2 patients. For these 2 patients, the mechanisms of ophthalmoplegia were compression or intraoperative nerve lesion. The other 22 patients became symptomatic in the 12-72 hours following the surgery. The mechanisms implied in these cases were intrasellar compressive hematoma (4/22 cases), intracavernous hemorrhagic suffusion, or incomplete resection of the intracavernous portion of the tumor. All patients who did not present with oculomotor palsy immediately after surgery completely recovered their deficits in the 3 months that followed, while the other 2 experienced permanent damage. CONCLUSIONS: Extraocular nerve dysfunction after transsphenoidal pituitary surgery is a rare complication that occurs more frequently in the case of the invasion or an important extension into the cavernous sinus. In this series, it also appears to be significantly more frequent in patients operated on via an endoscopic approach. Most patients have deficits that appear with a delay of 12-72 hours postoperatively and they are most likely to completely recover.

A case of junctional neural tube defect associated with a lipoma of the filum terminale: a new subtype of junctional neural tube defect?

The embryological development of the central nervous system takes place during the neurulation process, which includes primary and secondary neurulation. A new form of dysraphism, named junctional neural tube defect (JNTD), was recently reported, with only 4 cases described in the literature. The authors report a fifth case of JNTD. This 5-year-old boy, who had been operated on during his 1st month of life for a uretero-rectal fistula, was referred for evaluation of possible spinal dysraphism. He had urinary incontinence, clubfeet, and a history of delayed walking ability. MRI showed a spinal cord divided in two, with an upper segment ending at the T-11 level and a lower segment at the L5-S1 level, with a thickened filum terminale. The JNTDs represent a recently classified dysraphism caused by an error during junctional neurulation. The authors suggest that their patient should be included in this category as the fifth case reported in the literature and note that this would be the first reported case of JNTD in association with a lipomatous filum terminale.