NF2-related schwannomatosis and other schwannomatosis: an updated genetic and epidemiological study.

OBJECTIVES: New diagnostic criteria for NF2-related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated in accordance with these, with an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted in genetic counselling). The distribution of variant types among de novo and familial NF2 cases was also assessed. METHODS: The UK National NF2 database identifies patients meeting updated NF2 criteria from a highly ascertained population cared for by England's specialised service. Diagnostic prevalence was assessed on 1 February 2023. Molecular analysis of blood and, where possible, tumour specimens for NF2, LZTR1 and SMARCB1 was performed. RESULTS: 1084 living NF2 patients were identified on prevalence day (equivalent to 1 in 61 332). The proportion with NF2 inherited from an affected parent was only 23% in England. If people without a confirmed molecular diagnosis or bilateral vestibular schwannoma are excluded, the frequency of de novo NF2 remains high (72%). Of the identified de novo cases, almost half were mosaic. The most common variant type was nonsense variants, accounting for 173/697 (24.8%) of people with an established variant, but only 18/235 (7.7%) with an inherited NF2 pathogenic variant (p<0.0001). Missense variants had the highest proportion of familial association (56%). The prevalence of LZTR1-related schwannomatosis and SMARCB1-related schwannomatosis was 1 in 527 000 and 1 in 1.1M, respectively, 8.4-18.4 times lower than NF2. CONCLUSIONS: This work confirms a much higher rate of de novo NF2 than previously reported and highlights the benefits of maintaining patient databases for accurate counselling.

Genome-wide association analysis identifies a susceptibility locus for sporadic vestibular schwannoma at 9p21.

Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2-related and LZTR1-related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants. To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 × 10-13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A/B, also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis.

A watch, wait, and rescan approach for incidental benign-appearing notochordal lesions of the skull base.

OBJECTIVE: The aim of this study was to describe the natural history of incidental benign-appearing notochordal lesions of the skull base with specific attention to features that can make differentiation from low-grade chordoma more difficult, namely contrast uptake and bone erosion. METHODS: In this retrospective case series, the authors describe the clinical outcomes of 58 patients with incidental benign-appearing notochordal lesions of the clivus, including those with minor radiological features of bone erosion or contrast uptake. RESULTS: All lesions remained stable during a median follow-up of almost 3 years. Thirty-seven (64%) patients underwent contrast-enhanced MRI; lesions in 14 (38%) of these patients exhibited minimal contrast enhancement. Twenty-seven (47%) patients underwent CT; lesions in 6 (22%) of these patients exhibited minimal bone erosion. CONCLUSIONS: These data make the case for monitoring selected cases of benign-appearing notochordal lesions of the clivus in the first instance even when there is minor contrast uptake or minimal bone erosion.

Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

Investigating the weekend effect in decompressive thoracolumbar hemilaminectomy for acute intervertebral disc extrusion: An observational cohort study of 460 cases (2018-2023).

OBJECTIVE: To investigate if weekend surgery is associated with poorer outcomes in dogs with acute thoracolumbar intervertebral disc extrusion (IVDE) undergoing decompressive thoracolumbar hemilaminectomy. STUDY DESIGN: Retrospective observational cohort study. SAMPLE POPULATION: A total of 460 consecutive cases were reviewed, with 401 dogs undergoing weekday surgery (Cohort WD), and 59 dogs undergoing weekend surgery (Cohort WE). METHODS: Medical records of a surgical referral center in the UK were reviewed. Preoperative patient demographic and clinical data, and postoperative outcome data were collected with a minimum 28-day follow-up period. Multivariable logistic regression analysis was used to model the odds of a negative outcome. RESULTS: Cohort WE had a higher preoperative proportion of nonambulatory dogs (p = .0115) but there were no significant differences between the nonambulatory (p = .3762) and deep-pain negative subgroups (p = .6199). Cohort WE had a higher risk of not recovering ambulation compared to Cohort WD [79.2% vs. 91.6% recovery; adjusted OR 3.010 (95% CI: 1.259-7.190); p = .0132] and had a higher risk of postoperative morbidity [32.2% vs. 17.2%; adjusted OR 2.015 (95% CI: 1.089-3.729); p = .0257]. There were no significant differences in other outcome measures between cohorts. CONCLUSION: Weekend surgery in canine decompressive thoracolumbar hemilaminectomy may be associated with poorer patient outcomes, specifically higher postoperative morbidity and a poorer rate of recovery of ambulation. CLINICAL SIGNIFICANCE: This study demonstrates a weekend effect in veterinary surgery, which may be important in surgical decision-making in acute thoracolumbar IVDE. Further scrutiny of the patient's journey through the veterinary healthcare system is warranted.

Sporadic vestibular schwannoma: a molecular testing summary.

OBJECTIVES: Cases of sporadic vestibular schwannoma (sVS) have a low rate of association with germline pathogenic variants. However, some individuals with sVS can represent undetected cases of neurofibromatosis type 2 (NF2) or schwannomatosis. Earlier identification of patients with these syndromes can facilitate more accurate familial risk prediction and prognosis. METHODS: Cases of sVS were ascertained from a local register at the Manchester Centre for Genomic Medicine. Genetic analysis was conducted in NF2 on blood samples for all patients, and tumour DNA samples when available. LZTR1 and SMARCB1 screening was also performed in patient subgroups. RESULTS: Age at genetic testing for vestibular schwannoma (VS) presentation was younger in comparison with previous literature, a bias resulting from updated genetic testing recommendations. Mosaic or constitutional germline NF2 variants were confirmed in 2% of patients. Pathogenic germline variants in LZTR1 were found in 3% of all tested patients, with a higher rate of 5% in patients <30 years. No pathogenic SMARCB1 variants were identified within the cohort. Considering all individuals who received tumour DNA analysis, 69% of patients were found to possess two somatic pathogenic NF2 variants, including those with germline LZTR1 pathogenic variants. CONCLUSIONS: Undiagnosed schwannoma predisposition may account for a significant minority of apparently sVS cases, especially at lower presentation ages. Loss of NF2 function is a common event in VS tumours and may represent a targetable common pathway in VS tumourigenesis. These data also support the multi-hit mechanism of LZTR1-associated VS tumourigenesis.

The importance of genetic counseling and screening for people with pathogenic SMARCE1 variants: A family study.

Clear cell meningioma (CCM) is a rare variant of meningioma. In recent years, an association between cranial and spinal CCMs and germline loss of function mutations in the SMARCE1 gene (SWI/SNF chromatin remodeling complex subunit gene) has been discovered. We report a family with an incidental large spinal clear cell meningioma in a young adult following reflex screening for a germline loss of function pathogenic variant (PV) in the SMARCE1 gene. The index patient's mother and maternal grandfather were both also tested positive presymptomatically for SMARCE1. His mother developed intracranial and spinal meningiomas and his maternal grandfather developed a spinal CCM 4 years following a clear spinal MRI scan which required surgical excision. In this report we particularly emphasize the importance of genetic counseling and screening in siblings, parents and offspring of patients who are diagnosed with intracranial or spinal CCM in the context of SMARCE1 PVs. We recommend brain and spine Imaging screening of asymptomatic SMARCE1 PV carriers at least every 3 years, even if the baseline scan did not show any tumors.

Incidence of mosaicism in 1055 de novo NF2 cases: much higher than previous estimates with high utility of next-generation sequencing.

PURPOSE: To evaluate the incidence of mosaicism in de novo neurofibromatosis 2 (NF2). METHODS: Patients fulfilling NF2 criteria, but with no known affected family member from a previous generation (n = 1055), were tested for NF2 variants in lymphocyte DNA and where available tumor DNA. The proportion of individuals with a proven or presumed mosaic NF2 variant was assessed and allele frequencies of identified variants evaluated using next-generation sequencing. RESULTS: The rate of proven/presumed mosaicism was 232/1055 (22.0%). However, nonmosaic heterozygous pathogenic variants were only identified in 387/1055 (36.7%). When variant detection rates in second generation nonmosaics were applied to de novo cases, we assessed the overall probable mosaicism rate to be 59.7%. This rate differed by age from 21.7% in those presenting with bilateral vestibular schwannoma <20 years to 80.7% in those aged ≥60 years. A mosaic variant was detected in all parents of affected children with a single-nucleotide pathogenic NF2 variant. CONCLUSION: This study has identified a very high probable mosaicism rate in de novo NF2, probably making NF2 the condition with the highest expressed rate of mosaicism in de novo dominant disease that is nonlethal in heterozygote form. Risks to offspring are small and probably correlate with variant allele frequency detected in blood.

Long-term outcomes after pantarsal arthrodesis with medial plate fixation without external coaptation in 30 dogs.

OBJECTIVE: To report long-term outcomes of dogs treated with pantarsal arthrodesis (PTA) with medial plate fixation without external coaptation. STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned dogs (n = 30). METHODS: Medical records of dogs that had undergone a PTA with a medially applied plate without adjunctive rigid external coaptation were reviewed. Data collected included signalment, complications, and assessment of function at last physical examination. Follow-up information was obtained by phone conversations with owners. Complications were classified as minor, major II, major I, and catastrophic. RESULTS: Thirty-six PTA were performed in 30 dogs. Recorded complications included eight (22.2%) minor complications, 11 (30.6%) major II complications and 11 (30.6%) major I complications. One (2.8%) dog required amputation because of catastrophic complication. Owners provided follow-up for 26 dogs at a median duration of 1215 days (range, 325-3495) after surgery. The outcome was reported as full function in 12 dogs and acceptable function in 14 dogs, with no owners reporting unacceptable function. The owner of the dog in which amputation was required was not contacted. Incorrect contact details prevented owner follow-up in the other three dogs, but all had acceptable function at last veterinary follow up. CONCLUSION: Dogs treated with PTA by medially applied plate had a high incidence of complications requiring surgical or medical management, although full or acceptable function was achieved in 29 of 30 dogs. CLINICAL SIGNIFICANCE: Pantarsal arthrodesis offers a predictably good medium to long-term outcome in spite of a high risk of complications.

Outcome following surgical stabilization of distal diaphyseal and supracondylar femoral fractures in dogs.

Signalment, clinical features, fixation techniques, complications, and outcome for dogs presenting with distal diaphyseal and supracondylar femoral fractures were retrospectively reviewed. A total of 45 dogs with unilateral femoral fractures were included. Supracondylar femoral plates were the most popular method of fixation. However, various fixation techniques resulted in favorable outcomes in most dogs with 19/45 cases achieving full function and 22/45 achieving acceptable function. Degree of fracture comminution did not appear to affect complication rate or be a surrogate for worse clinical outcome.

Résultats de stabilisation chirurgicale de fractures fémorales diaphysaires distales et supracondylaires chez le chien. Une étude rétrospective portant sur le signalement, la présentation clinique, les techniques de réduction de fracture, les complications et les résultats de chiens atteints de fractures fémorales supracondyliennes et diaphysaires distales a été réalisée. Quarante-cinq chiens présentant une fracture fémorale unilatérale ont été inclus au total. Les plaques fémorales supracondyliennes représentaient la méthode d'ostéosynthèse la plus courante. Diverses techniques de fixation ont abouti à des résultats favorables dans la majorité des cas, avec 19/45 cas récupérant une fonction complète et 22/45 une fonction considérée acceptable. Le degré de comminution de la fracture n'apparaissait pas comme étant un facteur de risque de complication ou étant associé à des résultats défavorables.(Traduit par Emilie Fauchon et Emilie Hanot).

Identifying the deficiencies of current diagnostic criteria for neurofibromatosis 2 using databases of 2777 individuals with molecular testing.

PURPOSE: We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2). METHODS: Two large databases of individuals fulfilling NF2 criteria (n = 1361) and those tested for NF2 variants with criteria short of diagnosis (n = 1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the positive predictive value (PPV) with regard to definite diagnosis. RESULTS: There was no evidence for usefulness of old criteria "glioma" or "neurofibroma." "Ependymoma" had 100% PPV and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced PPV (80%). Siblings as a first-degree relative, without an affected parent, had 0% PPV. All three individuals with unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with unilateral VS plus ≥2 nondermal schwannomas reduced PPV to 67%. CONCLUSIONS: The present study confirms important deficiencies in NF2 diagnostic criteria. The term "glioma" should be dropped and replaced by "ependymoma." Similarly "neurofibroma" should be removed. Dropping "sibling" from first-degree relatives should be considered and testing of LZTR1 should be recommended for unilateral VS.

Schwannomatosis: a genetic and epidemiological study.

OBJECTIVES: Schwannomatosis is a dominantly inherited condition predisposing to schwannomas of mainly spinal and peripheral nerves with some diagnostic overlap with neurofibromatosis-2 (NF2), but the underlying epidemiology is poorly understood. We present the birth incidence and prevalence allowing for overlap with NF2. METHODS: Schwannomatosis and NF2 cases were ascertained from the Manchester region of England (population=4.8 million) and from across the UK. Point prevalence and birth incidence were calculated from regional birth statistics. Genetic analysis was also performed on NF2, LZTR1 and SMARCB1 on blood and tumour DNA samples when available. RESULTS: Regional prevalence for schwannomatosis and NF2 were 1 in 126 315 and 50 500, respectively, with calculated birth incidences of 1 in 68 956 and 1 in 27 956. Mosaic NF2 causes a substantial overlap with schwannomatosis resulting in the misdiagnosis of at least 9% of schwannomatosis cases. LZTR1-associated schwannomatosis also causes a small number of cases that are misdiagnosed with NF2 (1%-2%), due to the occurrence of a unilateral vestibular schwannoma. Patients with schwannomatosis had lower numbers of non-vestibular cranial schwannomas, but more peripheral and spinal nerve schwannomas with pain as a predominant presenting symptom. Life expectancy was significantly better in schwannomatosis (mean age at death 76.9) compared with NF2 (mean age at death 66.2; p=0.004). CONCLUSIONS: Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2.

Ventral stabilization of thoracic kyphosis through bilateral intercostal thoracotomies using SOP (String of Pearls) plates contoured after a 3-dimensional print of the spine.

OBJECTIVE: To describe a novel vertebral body stabilization and report its outcome in dogs with thoracic kyphosis and secondary myelopathy. STUDY DESIGN: Case series. ANIMALS: Six pugs with thoracic kyphosis and secondary myelopathy. METHODS: Medical records (2012-2017) of dogs with chronic progressive pelvic limb ataxia and ambulatory proprioceptive paraparesis due to thoracic kyphosis were reviewed. Dogs were evaluated via MRI and computed tomography. A 3-dimensional print of the kyphotic vertebral segment was used to precontour the SOP (String of Pearls) plates. Bilateral double, dorsal intercostal thoracotomies were performed to place precontoured SOP on the vertebral bodies. Long-term (6-16 months) clinical outcome was determined on the basis of neurological scoring (NS) and owner questionnaire. RESULTS: The only intraoperative complication consisted of a lung laceration due to preexisting adhesions. Postoperative complications included seroma formation (n = 2) and incidental radiographic evidence of screw breakage (n = 2). NS at presentation ranged between 2 and 4 and improved to 1 at long-term follow-up in all dogs but 1 (NS = 2). All owners felt that their dog had excellent quality of life at follow-up. CONCLUSION: In spite of the challenging local anatomy, all dogs undergoing vertebral stabilization with SOP placement experienced a good clinical outcome. CLINICAL SIGNIFICANCE: Stabilization of vertebral bodies with precontoured SOP placed through bilateral thoracotomies may be considered as a treatment option for dogs with thoracic kyphosis and secondary myelopathy.

Entamoeba Clone-Recognition Experiments: Morphometrics, Aggregative Behavior, and Cell-Signaling Characterization.

Studies on clone- and kin-discrimination in protists have proliferated during the past decade. We report clone-recognition experiments in seven Entamoeba lineages (E. invadens IP-1, E. invadens VK-1:NS, E. terrapinae, E. moshkovskii Laredo, E. moshkovskii Snake, E. histolytica HM-1:IMSS and E. dispar). First, we characterized morphometrically each clone (length, width, and cell-surface area) and documented how they differed statistically from one another (as per single-variable or canonical-discriminant analyses). Second, we demonstrated that amebas themselves could discriminate self (clone) from different (themselves vs. other clones). In mix-cell-line cultures between closely-related (E. invadens IP-1 vs. E. invadens VK-1:NS) or distant-phylogenetic clones (E. terrapinae vs. E. moshkovskii Laredo), amebas consistently aggregated with same-clone members. Third, we identified six putative cell-signals secreted by the amebas (RasGap/Ankyrin, coronin-WD40, actin, protein kinases, heat shock 70, and ubiquitin) and which known functions in Entamoeba spp. included: cell proliferation, cell adhesion, cell movement, and stress-induced encystation. To our knowledge, this is the first multi-clone characterization of Entamoeba spp. morphometrics, aggregative behavior, and cell-signaling secretion in the context of clone-recognition. Protists allow us to study cell-cell recognition from ecological and evolutionary perspectives. Modern protistan lineages can be central to studies about the origins and evolution of multicellularity.

Multiple synchronous sites of origin of vestibular schwannomas in neurofibromatosis Type 2.

BACKGROUND: Neurofibromatosis Type 2 (NF2) is a dominantly inherited tumour syndrome with a phenotype which includes bilateral vestibular (eighth cranial nerve) schwannomas. Conventional thinking suggests that these tumours originate at a single point along the superior division of the eighth nerve. METHODS: High resolution MRI was performed in children genetically proven to have NF2. The superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) were visualised along their course with points of tumour origin calculated as a percentage relative to the length of the nerve. RESULTS: Out of 41 patients assessed, 7 patients had no identifiable eighth cranial nerve disease. In 16 patients there was complete filling of the internal auditory meatus by a tumour mass such that its specific neural origin could not be determined. In the remaining 18 cases, 86 discrete separate foci of tumour origin on the SVN or IVN could be identified including 23 tumours on the right SVN, 26 tumours on the right IVN, 18 tumours on the left SVN and 19 tumours on the left IVN. DISCUSSION: This study, examining the origins of vestibular schwannomas in NF2, refutes their origin as being from a single site on the transition zone of the superior division of the vestibular nerve. We hypothesise a relationship between the number of tumour foci, tumour biology and aggressiveness of disease. The development of targeted drug therapies in addition to bevacizumab are therefore essential to improve prognosis and quality of life in patients with NF2 given the shortcomings of surgery and radiation treatments when dealing with the multifocality of the disease.

Warming of the Antarctic ice-sheet surface since the 1957 International Geophysical Year.

Assessments of Antarctic temperature change have emphasized the contrast between strong warming of the Antarctic Peninsula and slight cooling of the Antarctic continental interior in recent decades. This pattern of temperature change has been attributed to the increased strength of the circumpolar westerlies, largely in response to changes in stratospheric ozone. This picture, however, is substantially incomplete owing to the sparseness and short duration of the observations. Here we show that significant warming extends well beyond the Antarctic Peninsula to cover most of West Antarctica, an area of warming much larger than previously reported. West Antarctic warming exceeds 0.1 degrees C per decade over the past 50 years, and is strongest in winter and spring. Although this is partly offset by autumn cooling in East Antarctica, the continent-wide average near-surface temperature trend is positive. Simulations using a general circulation model reproduce the essential features of the spatial pattern and the long-term trend, and we suggest that neither can be attributed directly to increases in the strength of the westerlies. Instead, regional changes in atmospheric circulation and associated changes in sea surface temperature and sea ice are required to explain the enhanced warming in West Antarctica.

Pediatric intracranial clear cell meningioma associated with a germline mutation of SMARCE1: a novel case.

PURPOSE: Intracranial clear cell meningioma (CCM) represents a rare and potentially more aggressive subgroup of meningioma that is observed more frequently in children and adolescents. Despite its characterization as a histological entity, there is little evidence identifying tumorigenic etiologies. Recently, a novel mutation in SMARCE1, encoding a subunit of the SWI/SNF chromatin remodeling complex, was identified in a cohort of spinal CCMs. To date, no intracranial CCM has been subjected to analysis. METHODS: We report the case of an isolated intracranial CCM in a 14-year-old girl. Gross total resection was achieved following a two-stage approach with no evidence of tumor recurrence 8 months following presentation. RESULTS: Exon sequencing identified a germline mutation in SMARCE1, which was also present in tumor DNA. Extensive literature review confirmed our study is the first to seek and report a genetic anomaly for childhood intracranial CCMs outside of the NF2 gene locus, and the first to make an association between a germline SMARCE1 mutation and childhood intracranial CCMs. CONCLUSIONS: Together with the previous description of SMARCE1 mutations in spinal CCMs, our report suggests that SMARCE1 aberrations may be implicated in establishing a clear cell histology irrespective of meningioma location. We would advocate that, where feasible, genetic sequencing is performed on future new cases of childhood neuraxial CCMs and includes interrogation of the SMARCE1 gene.

Progress of hearing loss in neurofibromatosis type 2: implications for future management.

The objective of this study was to describe changes in hearing over time in patients with neurofibromatosis type 2 (NF2) treated conservatively. A retrospective case review was conducted in a tertiary referral centre. Pure tone audiometry, speech discrimination scores, serviceable hearing (American Academy of Otolaryngology class A or B) and measurement of vestibular schwannoma (VS) size on magnetic resonance imaging were evaluated in 56 patients (89 ears) with NF2 with at least one conservatively managed VS. Over a mean follow-up period of 7 years (range 0.8-21 years) pure tone average thresholds increased gradually with a mean annual rate of 1.3 dB for the right ear (p = 0.0003) and 2 dB for the left ear (p = 0.0009). Speech discrimination scores dropped with an average annual rate of 1.3 and 0.34% in the right and left ear, respectively. Patients maintained serviceable hearing for an average of 7.6 years (range 2.7-19.3 years). The average annual VS growth was 0.4 mm without any correlation with hearing loss. There was a correlation between patients' age and pure tone threshold increase (p < 0.05 for both ears). In this selected population of patients with NF2, hearing threshold increases were very slow. In NF2 patients with indolently behaving tumours, serviceable hearing can be maintained for a significant length of time, making conservative management an attractive option.

Effect of screw type and distribution on the torsional stability of 3.5 mm string of pearls locking plate constructs.

OBJECTIVE: To evaluate the effects of screw type (mono- [M] versus bicortical [B]), number, and position on torsional stability of String of Pearls (SOP) locking plate constructs. STUDY DESIGN: In vitro mechanical study. METHODS: SOP plates (n = 32) were applied to bone models and divided into 8 groups named according to screw type (M or B) and position in each fragment relative to the fracture gap starting at the outermost plate hole. Positive and negative controls were MMM and BBB, respectively. Specimens were non-destructively tested in torsion. Compliance and angular deformation were statistically compared (P < .002). RESULTS: The MMM construct was most compliant (P < .001). Compliance decreased in groups with a single bicortical screw (P < .001). Compared to the MMM group, torsional compliance decreased in constructs where a single monocortical screw was replaced with a bicortical screw (P < .001). Compared with a centrally positioned bicortical screw, constructs with a bicortical screw in either outer- or innermost position were 15% and 23% less compliant, respectively (P < .001). Addition of a second bicortical screw/fragment further decreased compliance (P < .001). No significant difference was found between groups with 2 bicortical screws. The BBB construct was least compliant (P < .001). Group responses for angular deformation followed the same pattern of significance recorded for compliance. CONCLUSIONS: A minimum of 1 bicortical screw/fragment should be used to increase torsional stability of 3.5 mm SOP constructs. Positioning this screw at the inner- or outermost positions relative to the fracture is preferred, with the innermost position providing the greatest improvement in stability. Should further torsional stability be desired, increasing the number of bicortical screws is recommended. Clinically, these results may assist with preoperative planning of various fracture patterns.

Effect of Intramedullary Rod Diameter on a String of Pearls Plate-Rod Construct in Mediolateral Bending: An In Vitro Mechanical Study.

OBJECTIVE: To evaluate the effect of intramedullary rod (IMR) diameter on the mechanical behavior of string of pearls (SOP) plate-rod constructs. STUDY DESIGN: In vitro mechanical study. SAMPLE POPULATION: Synthetic bone models (n = 24). METHODS: Locking 3.5 mm SOP plates were fixed to a tibial bone model with a 50 mm fracture gap. Four experimental groups (n = 4) were tested: monocortical SOP construct alone and monocortical SOP constructs augmented with a 2.4, 3.2, or 4.0 mm IMR corresponding to 24, 32, or 40% filling of the medullary cavity diameter (SOP-24, SOP-32, SOP-40). Control groups (n = 4) were stabilized with either a bicortical SOP plate (SOP-B) or a 3.5 mm limited contact dynamic compression plate (LC-DCP) with a 4.0 mm IMR filling 40% of the medullary cavity diameter (LC-DCP-40). Specimens were tested in mediolateral bending. Construct compliance (CC) and angular deformation (AD) were compared between construct types (P < .05). RESULTS: CC and AD incrementally decreased with increasing IMR diameter (P < .001). There were no statistical differences between SOP-24 and SOP-B (P = .806) or between SOP-32 and LC-DCP-40 (P = .773), which was also the least compliant of all constructs (P < .001). AD followed an identical pattern of significance. CONCLUSIONS: Biological osteosynthesis often relies on more compliant bridging constructs to promote beneficial micromotion at the fracture. Our study suggests use of a smaller diameter IMR (SOP-32) is comparable to a conventional plate-rod construct (LC-DCP-40). Should greater compliance be desired, an even smaller diameter IMR (SOP-24) may prove beneficial while as stable as an accepted bicortical construct (SOP-B).