Collaborative approach to paediatric chronic non-bacterial osteomyelitis of the mandible: Great Ormond Street Hospital case series.

This paper outlines a 10-patient case series of chronic non-bacterial osteomyelitis (CNO) of the mandible at a tertiary paediatric hospital in the UK. Our findings highlight the homogeneous presenting signs and symptoms of an intermittently painful, swollen angle and ramus of the mandible. We present the typical laboratory investigative findings (normal inflammatory markers) and imaging appearances (sclerosis and periosteal oedema). Our paper outlines an investigation protocol, including recommendations for extraoral bone biopsies and systemic magnetic resonance imaging (MRI). We explain the importance of multidisciplinary care, with combined care by rheumatologists and infectious disease specialists. Finally we demonstrate the efficacy of our treatment algorithm for oral non-steroidal anti-inflammatory drugs (NSAIDs), and in those cases refractory to NSAIDS, intravenous pamidronate. This paper provides a useful addition to the literature by informing OMF surgeons of this rare condition and given the clinical equipoise in treatments, it can hopefully guide clinicians in an investigation pathway and management protocol.

Remodelling of mandibular condylar head after fixation of fractures with ultrasound activated resorbable pins: A retrospective case series.

The aim of this study was to assess whether the resorption of poly-lactic acid pins, used for condylar head fracture fixation, adversely affect remodelling of the condylar head. A retrospective review of patients was performed that underwent ORIF of CHF with ultrasound activated resorbable poly-lactic acid pins and had CT/CBCT scans of the condyle at least 18 months after surgery, at which point the fixation material was expected to be resorbed. We reviewed the size, shape and position of the condylar head and compared this to the normal side and compared this to the results of conservative management and ORIF with titanium screws in the literature. Most patients had condylar heads normally positioned and shaped, with minimal bone changes. The position of the condyle in the fossa, its shape and bone changes compare favourably with previous studies on CHF managed conservatively or with titanium screw fixation. There was no radiographic evidence of the pins after 18 months. In conclusion, ultrasound activated resorbable pins can provide suitable fixation for ORIF of condylar head fractures, avoiding the need for screw removal, and there was no evidence that the resorption process adversely affected the remodelling of the condylar head.

Predictive risk factors for persistent pain following total prosthetic temporomandibular joint replacement.

The aim of this study was to determine the rate of persistent pain following total TMJ replacement and to identify potential predictive risk factors. A retrospective review of case notes treated by a single surgeon in a tertiary unit was performed. For each patient a number of variables were recorded including visual analogue pain scores (0 to 10) and opioid usage pre surgery and at 12 months or last follow up beyond 12 months. Persistent pain scores of 5 to 7 were regarded as moderate and 8 to 10 as severe. The mean pain score at last follow-up was significantly lower than preoperatively (2.1 vs. 6.3, p < 0.001) with a mean follow-up time of 40.1 months (range 12-44). 16.4% of the patients reported moderate to severe pain and 13.7% were still on regular opioids at the last follow-up. Therefore 15 patients (20.5%) suffered from chronic postoperative pain after TMJ replacement surgery. Patients reporting severe preoperative pain scores (p = 0.04), regular opioid use (p = 0.001) or multiple previous open TMJ surgeries (p = 0.03) were more likely to suffer from chronic persistent pain and these should be regarded as predictive risk factors. The identification of these factors allows for better risk stratification of patients, informed consent and the agreement of expected outcomes. Patients with true articular disease and a single failed surgery should be considered for early total TMJ replacement to minimise multifactorial persistent pain.

Management of the secondary growth defect.

Temporomandibular reconstruction has clear aims including the restoration of mandibular form and function, to decrease patient disability and to prevent disease progression. In addition paediatric patients have growth and re-modelling considerations and the need to minimise any secondary growth defect. The involvement of a multidisciplinary team is deemed essential for both the child and parents. In some patients crisis intervention may be required and early reconstruction might be necessary dependant on the severity of impairment. The aetiology of end stage TMJ disease, unilateral/bilateral disease and the degree of patient compromise will guide timing and choice of treatment. Reducing repeated surgery and facilitating patient compliance may potentiate mandibular growth.

Autogenous Reconstruction of the Temporomandibular Joint.

Reconstruction of the temporomandibular joint can optimize many basic functions (airway obstruction, feeding, speech difficulties) and rectify facial deformity. In children, it can restore potential growth. Reconstruction in adults is now mainly performed with alloplastic techniques but autogenous vascularized grafts are often required in patients with large composite facial defects or postradiation treatment. In children, autogenous grafting remains the primary reconstructive choice despite a high further surgery rate and increasing interest in alloplastic techniques. The costochondral graft remains the most widely used technique due to the potential for growth restoration and low donor site morbidity.

The design of a randomized, placebo-controlled, dose-ranging trial to investigate the efficacy and safety of the ADAMTS-5 inhibitor S201086/GLPG1972 in knee osteoarthritis.

Objective: This study aims to assess the efficacy of the anticatabolic 'a disintegrin and metalloproteinase with thrombospondin motif-5' (ADAMTS-5) inhibitor, S201086/GLPG1972, in slowing cartilage loss in participants with knee osteoarthritis (OA). Design: ROCCELLA (NCT03595618) is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, phase 2 trial. We plan to enrol a total of 852 participants with knee OA across 12 countries. Participants will be randomized 1:1:1:1 to receive 75, 150 or 300 â€‹mg S201086/GLPG1972, or placebo orally, once daily for 52 weeks. Eligible participants will be aged 40-75 years and have predominantly medial knee OA with centrally read Kellgren-Lawrence grade 2 or 3, OARSI atlas medial femorotibial joint space narrowing grade 1 or 2, and consistent moderate to severe baseline pain. The primary endpoint will be the change from baseline to week 52 in magnetic resonance imaging-assessed central medial femorotibial compartment cartilage thickness. Secondary endpoints will include other structural outcomes, and patient-reported outcomes, as well as safety and pharmacokinetic assessments. Study sites will be assessed for eligibility based on factors including imaging quality, and images will be centrally read and quality checked. Conclusions: Using strict inclusion criteria and leading imaging techniques with stringent quality controls, the ROCCELLA trial will evaluate the efficacy of S201086/GLPG1972 in slowing cartilage loss in participants with knee OA. The selected eligibility criteria should enrich for participants with OA who experience sufficient cartilage loss to allow detection of a substantial treatment effect.

The ESTMJS (European Society of Temporomandibular Joint Surgeons) Consensus and Evidence-Based Recommendations on Management of Condylar Dislocation.

Although condylar dislocation is not uncommon, terminology, diagnostics, and treatment concepts vary considerably worldwide. This study aims to present a consensus recommendation based on systematically reviewed literature and approved by the European Society of TMJ Surgeons (ESTMJS). Based on the template of the evidence-based German guideline (register # 007-063) the ESTMJS members voted on 30 draft recommendations regarding terminology, diagnostics, and treatment initially via a blinded modified Delphi procedure. After unblinding, a discussion and voting followed, using a structured consensus process in 2019. An independent moderator documented and evaluated voting results and alterations from the original draft. Although the results of the preliminary voting were very heterogenous and differed significantly from the German S3 guideline (p < 0.0005), a strong consensus was achieved in the final voting on terminology, diagnostics, and treatment. In this voting, multiple alterations, including adding and discarding recommendations, led to 24 final recommendations on assessment and management of TMJ dislocation. To our knowledge, the ESTMJS condylar dislocation recommendations are the first both evidence and consensus-based international recommendations in the field of TMJ surgery. We recommend they form the basis for clinical practice guidelines for the management of dislocations of the mandibular condyle.

Treatment of calcium pyrophosphate deposition in the temporomandibular joint with resection and simultaneous reconstruction using a custom joint prosthesis.

PURPOSE: The authors present a rare case of calcium pyrophosphate deposition disease (CPPD) in the temporomandibular joint (TMJ), successfully treated with complete resection and immediate reconstruction using a custom-made prosthesis. This one-stage approach has prevented the patient from requiring two surgeries and has proven effective in the management of the condition. METHODS: Our patient, a 56-year-old male, presented with left TMJ pain and trismus. Investigations showed a destructive left TMJ mass, confirmed by biopsy to be tophaceous pseudogout. The treatment involved excising all the affected tissues followed by condylectomy, coronoidectomy, and a total TMJ replacement. The patient recovered well from surgery with good mouth opening. RESULTS: CPPD disease is a metabolic arthropathy of poorly understood aetiology. Management options vary from conservative non-surgical to surgical treatment depending on the severity. CONCLUSION: This case demonstrates the feasibility of a one-stage procedure with reconstruction using a custom-made prosthesis and virtual planning.

Combined internal and external Le Fort III distraction osteogenesis--the "elusive vector".

This article describes a modified surgical technique using both internal and external distractors for distraction osteogenesis at the Le Fort III level. This technique optimizes vector control, superior to single-device techniques, resulting in excellent control and, ultimately, a functional occlusion.

Regional grey matter volumetric changes in forensic schizophrenia patients: an MRI study comparing the brain structure of patients who have seriously and violently offended with that of patients who have not.

BACKGROUND: The aim was to carry out the first voxel-based morphometry study of grey matter changes in the whole brain in schizophrenia associated with a history of seriously and violently offending. METHODS: Structural cerebral magnetic resonance imaging scans of 26 patients with schizophrenia were analyzed using voxel-based morphometry: 13 of the patients had seriously and violently offended directly as a result of schizophrenia prior to admission, the offences consisting of homicide, attempted murder or wounding with intent to cause grievous bodily harm; the other 13 patients did not have a history of violence. There was no history of comorbid psychoactive substance misuse disorder in any of the patients. Voxelwise generalized linear modelling was applied to the processed magnetic resonance data using permutation-based non-parametric testing, forming clusters at t > 2.3 and testing clusters for significance at p < 0.05, corrected for multiple comparisons across space. RESULTS: The two groups of patients were matched with respect to age, gender and duration of illness, but the group with a history of serious violence was on average receiving a higher dose of antipsychotic medication than the group without a history of violence. There were local regions of reduced grey matter volume in the schizophrenia patient group with a history of serious and violent offending, compared with the schizophrenia patient group without such a history. Significant voxels (p < 0.05, corrected for multiple comparisons) were noted bilaterally in the cerebellum and in BA 39 and 40. CONCLUSION: These regions are important in verbal working memory. The cerebellum may integrate inputs from ventrolateral prefrontal cortex and parietal regions, providing a corrective signal that refines the process of rehearing the contents of the phonological store. A strong connection has been hypothesized between the supramarginal region corresponding to BA 39/40 and Broca's area, which may correspond largely to the arcuate fasciculus, with the connectional pattern of the language regions of this model fitting the network of parietotemporal-prefrontal connections that participate in working memory. Therefore our results point to the possibility of an abnormality in neural circuits involved in verbal working memory in this group of patients.

Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth.

BACKGROUND: We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment. METHODS AND FINDINGS: We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth. CONCLUSIONS: Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

Automatic quantification of changes in bone in serial MR images of joints.

Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions.

Treatment of fractures of the mandibular condylar head with ultrasound-activated resorbable pins: early clinical experience.

Controversy continues about the benefits and disadvantages of open reduction and internal fixation of fractures of the condylar head. Once a decision to treat surgically has been made, an appropriate method of fixation must be chosen. Standard titanium fixation has a number of complications, including the risk of protrusion of the screw beyond the condylar head and the possible need for removal later. Resorbable fixation is an alternative, and ultrasound-activated resorbable pins are a new innovation. We have treated a series of 15 patients with 17 fractures of the condylar head, in which the use of ultrasound-activated resorbable fixation has provided adequate strength and stability during early healing. Complications included technical difficulties in achieving complete anatomical reduction as a result of fragmentation of the condylar head, and three facial nerve palsies, two of which recovered within three months. No pins failed, and there was no sign of instability during healing.

MR imaging quantification of cerebellar growth following hypoxic-ischemic injury to the neonatal brain.

BACKGROUND AND PURPOSE: Cerebellar atrophy may occur as a result of a primary injury, such as infarction or hemorrhage. Impaired growth of a non-injured cerebellum may be seen as a secondary effect related to damage in other remote but connected areas of the brain, or so-called diaschisis. We sought to determine whether perinatal hypoxic-ischemic injury leads to poor cerebellar growth and whether such impairment occurs asymmetrically in infants with predominantly unilateral brain injury. METHODS: We used a computerized quantification program to measure cerebellar size by using serial MR images. Term-born infants presenting with encephalopathy and/or seizures presumed due to a hypoxic-ischemic insult within 48 hours of delivery were included if they had two or more volume acquisition images obtained at least 3 months apart but within the first 15 months of delivery. RESULTS: When data were grouped by MR appearances, significant differences in total cerebellum growth were seen between infants with focal infarction and those with basal ganglia and thalamic injury (P <.001). Unilateral forebrain lesions shown on MR imaging were not predictive of asymmetric cerebellar growth. CONCLUSION: Infants with focal infarction of the cerebral hemisphere had an apparently normal pattern of growth in both cerebellar hemispheres. However, in infants with severe basal ganglia and thalamic lesions, cerebellar growth was reduced, and the vermis showed little or no growth during the first year after birth.

Changes in brain size with treatment in patients with hyper- or hypothyroidism.

BACKGROUND AND PURPOSE: Although neuropsychological symptoms and signs are common in thyroid disease, their organic substrate is unknown. We performed brain MR imaging in patients with hyperthyroidism or hypothyroidism before and after treatment and correlated the results with hormonal markers. METHODS: Eight patients with hyperthyroid disease and three with hypothyroid disease underwent imaging within 1-2 days of a thyroid hormone testing. Images were registered, and brain and ventricular sizes were measured by using a semiautomated contour and thresholding technique. Changes in brain and ventricular volume were correlated with serum levels of total thyroxine (T(4)), unbound triiodothyronine (free T(3)), and thyroid-stimulating hormone (TSH) before and after treatment. RESULTS: With treatment, brain size decreased by 6,329-31,183 mm(3) in the hyperthyroid group and increased by 2,599-48,825 mm(3) in the hypothyroid group. Conversely, with treatment, ventricular size increased by 325-6,279 mm(3) in the hyperthyroid group and decreased by 760-2,376 mm(3) in the hypothyroid group. There was a highly significant correlation between reduction in brain size and reduction in T(4), as well as between the increase in ventricular size and reduction in T(4). There was a significant correlation between reduction in ventricular size and reduction in free T(3). There were highly significant correlations between reduced levels of TSH and increase in brain size, as well as between increased levels of TSH and increase in ventricular size. CONCLUSION: In thyroid disease, the size of the brain and ventricles significantly change after treatment, and these changes are correlated with T(4), free T(3), and TSH levels. The mechanism of these changes is uncertain, but it may involve osmolyte regulation, the sodium and water balance, and alterations in cerebral hemodynamics.

Change in brain size during and after pregnancy: study in healthy women and women with preeclampsia.

BACKGROUND AND PURPOSE: Qualitative decreases in maternal brain size have been observed late in pregnancy. The aim of this study was to quantitatively evaluate changes to the maternal brain during and after healthy pregnancy and to compare these changes with those observed in cases of preeclampsia. METHODS: Three-dimensional T1-weighted MR volume images were obtained in nine healthy participants before and after delivery. Additional images were obtained in some of these participants before pregnancy, during pregnancy, and within 52 weeks after delivery. Five women with preeclampsia were examined before delivery and 6 weeks after delivery. Three of these patients were examined within 52 weeks after delivery. Images were registered, and both brain and ventricular volumes were calculated by using a semiautomated computer program. RESULTS: Both the healthy and preeclamptic groups had a reduction in brain size during pregnancy that was maximal at term and that reversed by 6 months after delivery. The ventricular size showed a corresponding increase in size during pregnancy and a decrease in size after delivery. In the preeclamptic patients, brain size was significantly smaller (P =.05) than in healthy participants, both before and after delivery. CONCLUSION: The brain decreases in size during pregnancy and increases in size after delivery. The changes follow a consistent time course in each woman. The mechanism and physiologic importance of these findings are speculative at the present time.