PURPOSE: To evaluate the feasibility of a novel trajectory for C7 laminar screws and to compare it with an old trajectory.
OVERVIEW OF LITERATURE: The previously reported trajectory of C7 laminar screws has a horizontal direction without a fixed target point. Our new trajectory has a cephalad direction with a fixed target point.
METHODS: Computed tomographic scans of a total of 50 male and 50 female patients were utilized. The placement of C7 laminar screws was activated employing the new and old trajectories. The success rate, the causes of failure, and the maximum allowable length of each trajectory were compared.
RESULTS: Employing the new trajectory, the success rates of the unilaminar and bilaminar screws were 93% and 83%, respectively, which were significantly better than the old trajectory (80%, p<0.0001 and 70%, p=0.0003). The most prevalent cause of failure was laminar cortical breach followed by facet joint violation. The new trajectory also offered significantly longer maximum allowable screw length in unilaminar (32.5±4.3 mm vs. 26.5±2.6 mm, p<0.001), bilaminar cephalic (29.5±3.8 mm vs. 25.9±2.6 mm, p<0.0001) and bilaminar caudal (33.1±2.6 mm vs. 25.8±3.1 mm, p<0.001) screws than the old trajectory. With the new and old trajectories, 70% vs. 6% of unilaminar, 60% vs. 2% of bilaminar caudal, and 32% vs. 4% of bilaminar cephalic screws could be protracted perfectly into the corresponding lateral mass without any laminar cortical or facet joint violation (p<0.0001).
CONCLUSIONS: The novel trajectory possesses a substantially higher success rate, longer maximum allowable screw length, and higher chance to be extended into the lateral mass (a condition known as a lamino-lateral mass screw) than the old trajectory.
OBJECTIVE: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.
METHODS: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.
RESULTS: Prenatal features included hypokinesia or akinesia and growth restriction. Six pregnancies were terminated. Nine infants were born at or near term with severe-to-profound weakness and required resuscitation. Seven died following withdrawal of life support. Two surviving children require ongoing respiratory support. Most cohort members had at least 1 disease-causing variant predicted to result in some near-normal-length titin expression. The exceptions, from 2 unrelated families, had homozygous truncating variants predicted to induce complete nonsense mediated decay. However, subsequent analyses suggested that the causative variant in each family had an additional previously unrecognized impact on splicing likely to result in some near-normal-length titin expression. This impact was confirmed by minigene assay for 1 variant.
INTERPRETATION: This study confirms the clinical variability of congenital titinopathy. Severely affected individuals succumb prenatally/during infancy, whereas others survive into adulthood. It is likely that this variability is because of differences in the amount and/or length of expressed titin. If confirmed, analysis of titin expression could facilitate clinical prediction and increasing expression might be an effective treatment strategy. Our findings also further-support the hypothesis that some near-normal-length titin expression is essential to early prenatal survival. Sometimes expression of normal/near-normal-length titin is due to disease-causing variants having an additional impact on splicing. ANN NEUROL 2025;97:611-628.