Detection of somatic and germline pathogenic variants in adult cohort of drug-resistant focal epilepsies.

OBJECTIVE: This study investigates the prevalence of pathogenic variants in the mechanistic target of rapamycin (mTOR) pathway in surgical specimens of malformations of cortical development (MCDs) and cases with negative histology. The study also aims to evaluate the predictive value of genotype-histotype findings on the surgical outcome. METHODS: The study included patients with drug-resistant focal epilepsy who underwent epilepsy surgery. Cases were selected based on histopathological diagnosis, focusing on MCDs and negative findings. We included brain tissues both as formalin-fixed, paraffin-embedded (FFPE) or fresh frozen (FF) samples. Single-molecule molecular inversion probes (smMIPs) analysis was conducted, targeting the MTOR gene in FFPE samples and 10 genes within the mTOR pathway in FF samples. Correlations between genotype-histotype and surgical outcome were examined. RESULTS: We included 78 patients for whom we obtained 28 FFPE samples and 50 FF tissues. Seventeen pathogenic variants (22 %) were identified and validated, with 13 being somatic within the MTOR gene and 4 germlines (2 DEPDC5, 1 TSC1, 1 TSC2). Pathogenic variants in mTOR pathway genes were exclusively found in FCDII and TSC cases, with a significant association between FCD type IIb and MTOR genotype (P = 0.003). Patients carrying mutations had a slightly better surgical outcome than the overall cohort, however it results not significant. The FCDII diagnosed cases more frequently had normal neuropsychological test, a higher incidence of auras, fewer multiple seizure types, lower occurrence of seizures with awareness impairment, less ictal automatisms, fewer Stereo-EEG investigations, and a longer period long-life of seizure freedom before surgery. SIGNIFICANCE: This study confirms that somatic MTOR variants represent the primary genetic alteration detected in brain specimens from FCDII/TSC cases, while germline DEPDC5, TSC1/TSC2 variants are relatively rare. Systematic screening for these mutations in surgically treated patients' brain specimens can aid histopathological diagnoses and serve as a biomarker for positive surgical outcomes. Certain clinical features associated with pathogenic variants in mTOR pathway genes may suggest a genetic etiology in FCDII patients.

Comparative study of the incidence and severity of degenerative change in the transition zones after instrumented versus noninstrumented fusions of the lumbar spine.

The purpose of this study was to determine whether the addition of pedicle screws and rods to a fusion of two or more vertebrae of the lowest three motion segments of the lumbar spine increases the incidence or severity of transition zone change (TZC) above or below the fused area. A study group of 52 patients who had a fusion with fixation and a control group of 31 who had a nearly identical operation but without fixation were obtained. Radiographs and computed tomography scans of the area of study were taken preoperatively and were repeated approximately 7 years after the operation. Results showed that the addition of pedicle screw fixation does not increase the incidence or severity of TZC in the first 7 years after surgery.

Relationship of the dura, Hofmann's ligaments, Batson's plexus, and a fibrovascular membrane lying on the posterior surface of the vertebral bodies and attaching to the deep layer of the posterior longitudinal ligament. An anatomical, radiologic, and clinical study.

With the advent of computed tomography (CT) and magnetic resonance imaging (MRI), visualization of soft tissue structures in the spinal canal, which were previously undetectable, is possible. This study was undertaken to more accurately identify these soft tissue layers and to determine factors such as when is a disc contained and when is it not; in discography, when the disc leaks, into what layer is the contrast going; or when a nuclear fragment creeps upward or downward, just where is it. The works of Fick, Dommisse, Kikuchi, Schellinger, Hofmann, Batson, and Parke were studied. The professors of anatomy of four major medical schools were consulted along with several neuroradiologists and embryologists. Forty lumbar spines were dissected (20 fresh, 20 preserved). Magnetic resonance imaging scans were taken. Photographs and photomicrographs were made. A fibrous membrane, first mentioned by Fick, can be identified lying anterior to the posterior longitudinal ligament and attaching to the deep layer of the posterior longitudinal ligament. It has been given relatively little attention in the past. This membrane has about one fourth the toughness of the dura and is made up largely of fibrous tissue. The veins of Batson lie on its dorsal surface and pierce it to go ventral to this membrane and enter the vertebral body. Batson's plexus crosses the disc space. The peridural membrane extends from one side to the other, spanning the width of the vertebral body and encircling the bony canal around the outside of the dura. There is a potential space between it and the dura. It does not cross the disc space. A probe can easily be passed posterior or anterior to it, between it and the posterior longitudinal ligament or between it and the vertebral body. We also identified Hofmann's ligament anterior to the dura, attaching the dura to the posterior longitudinal ligament. Laterally, tiny attachments between this fibrovascular membrane and the circumneural sheaths of the spinal nerves can be observed as the nerves enter the foramina. The posterior longitudinal ligament (PLL) is very tough and strong and seldom ruptures. The annulus frequently ruptures. Fragments of nucleus pulposus can creep out at the vertebral rim and get under the PLL and the peridural membrane. Hematoma can form by the same route and have the exact appearance as a sequestrated disc. There is no periosteum inside the vertebral canal. With MRI, hematomas can be differentiated from an extruded fragment. They may cause symptoms similar to an extruded disc but will probably heal with time.(ABSTRACT TRUNCATED AT 400 WORDS)

Unilateral lumbar fusion.

Unilateral fusion of the lumbar spine is rarely necessary or indicated. However, in patients with a "far-out syndrome" requiring decompression or in cases where unilateral posterior element resection is necessary for any reason, it may be both necessary and indicated. This unilateral destabilization effectively removes one leg of the tripod, rendering that intervertebral joint potentially unstable. The charts and radiographs of 13 patients (seven men, six women) with an average age of 60 years (range, 25 to 76) who underwent unilateral fusion were retrospectively reviewed. Follow-up time ranged from 12 1/2 to 2 years with a median follow-up of 8 years. Eleven of the fusions were at one level, and two were at two levels. Seven patients had a far-out syndrome secondary to degenerative scoliosis; four were secondary to spondylolisthesis. Two patients had an osteoid osteoma involving a pedicle. A paraspinal approach was used in the majority of patients. Autologous bone graft was used in all patients. Unilateral pedicle screw fixation was used in the last patient in the series. The fusion rate was 85% (11/13). Three patients were smokers, two of whom developed pseudarthrosis. Disc space height did not appear to affect fusion rate. There was no progression of slip noted in any of the patients. One complication was noted in this group: a moderate postoperative infection, which cleared spontaneously.

The Wiltse pedicle screw fixation system. Early clinical results.

Ninety-nine patients were studied prospectively after spine fusion augmented with the Wiltse pedicle screw fixation system. Follow-up ranged from 12 to 34 months, averaging 20 months. There were 33 men and 66 women. Their ages ranged from 20 to 86, with the average age of 52. This was the first spine surgery in 23 patients. Seventy-six patients had had prior spine surgery. Spine fusion was attempted at one to four levels of the lumbosacral spine. Major perioperative complications were seen in seven patients (7%). Hardware failure was seen in seven cases (7%). Union was assessed by radiographs at 1 year or more after surgery in 82 patients (85%). In those 82 patients, union was seen in 56 (68%) and nonunion in 26 (32%). Change in lordosis was measured in 54 patients. The average change was a loss of 1.7 degrees lordosis per level fused. A questionnaire was answered by 79 patients (81%). Overall, 55 (70%) stated that they had some benefit from surgery, ten (13%) had no change, and 13 (17%) were worse.

Incidence of injuries in high school track and field athletes and its relation to performance ability.

Two hundred fifty-seven high school track athletes from 17 teams were observed prospectively for one complete season (77 days) to study the incidence and types of injuries and to establish the relationship among injuries, duration of training, and individual performance ability. One hundred seventy-four (68%) of the athletes were male and 83 (33%) were female. A total of 41 injuries was observed over this period of time. One injury occurred for every 5.8 males and every 7.5 females. On the average, an injury resulted in 8.1 days of missed practice, 8.7 days for males and 6.6 days for females. Sprinting events were responsible for 46% of all injuries. The majority (83%) of injuries involved the lower extremities. Management of these injuries varied greatly. A direct correlation was noted between performance level of the athlete and incidence of injuries. The average noninjured athlete ranked at the 57.4 percentile based on best seasonal performance while the average injured athlete ranked at the 75.4 percentile. This direct relationship was present for both sexes and within all events, although some variation was noted within these separate groups.