Can Syndesmosis Screws Displace the Distal Fibula?

Background. There has been historical debate as to whether the distal tibiofibular syndesmosis can be overtightened during operative fixation. We used finite-element analysis to determine if overtightening of syndesmotic screws can cause widening of the lateral gutter clear space in the ankle joint. Methods. A 3D finite-element model was constructed and analyzed using geometries from a computed tomography scan of a cadaveric lower leg. Starting 2 cm from the plafond, screw fixation was simulated at 5-mm increments to a distance of 5 cm from the plafond. The fibula was compressed 2 mm toward the tibia at each interval, and the change in distance between the lateral talus and distal fibula was measured. Results. Medial deflection of the fibula resulted in widening of the lateral clear space, which was proportional to the amount of deflection. The effect increased as screws were placed closer to the plafond, with 1.5 mm of widening at 2 cm (0.76 mm/mm) versus 0.7 mm at 5 cm (0.34 mm/mm). Conclusion. Our finite-element model demonstrated that overtightening of the distal tibiofibular syndesmosis with medial fibular displacement can cause widening of the lateral clear space. Clinical relevance. The results suggest that screws placed farther from the plafond widen the lateral clear space to a lesser degree, which may be advantageous during surgical fixation to prevent clear space widening and increased tibiotalar contact forces.Levels of Evidence: Level I.

PatientsLikeMe and atopic dermatitis: characterizing the atopic dermatitis patient profile.

INTRODUCTION: Atopic Dermatitis (AD) is a common dermatologic disorder that affects 17.8 million individuals in the United States. Online medical communities have become increasingly popular over the last several years, providing an additional avenue of therapy for patients. PURPOSE: This retrospective analysis looks to characterize the AD patient profile to better assess features of the AD community and appraise PatientsLikeMe data with current AD literature. METHODS: PatientsLikeMe data recorded by April 2018 from persons who reported AD as their primary or secondary diagnosis were included in the analysis. RESULTS: The PatientsLikeMe database had 410 individuals reporting AD as of April 2018. Of these, 61.46% (252/410) report AD as their primary disease. Of those reporting, 180/199 (90.45%) were diagnosed by a medical professional whereas 19/199 (9.55%) were self-diagnosed. The number of persons recording predefined PatientsLikeMe symptoms are as follows: stress (20), fatigue (132), pain (126), anxious mood (118), and depressed mood (103). SIGNIFICANCE: Patient-oriented medical communities are a valuable resource for those affected by various conditions. Although clinical applications are still uncertain, this data allows practitioners access to profiles self-defined by online users.

Surgical debulking of pituitary adenomas improves responsiveness to octreotide lar in the treatment of acromegaly.

BACKGROUND: Studies comparing primary medical treatment of acromegaly with surgery are often non-randomized, and not stratified by illness severity. We prospectively compared primary medical therapy with pituitary surgery in patients with acromegaly. All patients had macroadenomas, at least one random human growth hormone (GH) level ≥12.5 ng/mL, elevated IGF-I levels and failure to suppress GH to <1 ng/mL during an oral glucose tolerance test (oGTT). METHODS: Forty-one patients from seven centers were randomized to primary treatment with octreotide LAR, 30 mg every 4 weeks × 3 months (ARM A, N = 15), or pituitary surgery (ARM B, N = 26) using a 1:2 randomization design. Patients cured by surgery (defined as nadir GH during oGTT <1 ng/mL and normal IGF-I) received no subsequent treatment. Those not cured surgically were then treated with octreotide LAR (SubArm B1) for 3 months. RESULTS: Only one of the 15 patients in ARM A (6.7%) had normalization of both GH and IGF-I. In contrast, 13/26 patients had normalization of both GH and IGF-I after surgery alone (50%). Of the remaining 13 patients who did not normalize with surgery alone, treatment with octreotide LAR resulted in a normal nadir GH and normal serum IGF-I in 7 (53.9%). In total, 20/26 in ARM B (76.9%) experienced normalization of defined biochemical acromegaly parameters. CONCLUSIONS: Pituitary surgery alone was more effective than primary medical treatment (p = 0.006), and the combination of surgery followed by medical therapy was even more effective (p < 0.0001). Subjects treated with medical therapy after surgical debulking had a significant improvement in response rate compared to matched subjects treated with primary medical therapy.

"Micromegaly": an update on the prevalence of acromegaly with apparently normal GH secretion in the modern era.

PURPOSE: Approximately 25 % of cases of clinically active acromegaly cases treated in our academic center between 1996 and 2000, were diagnosed in patients who had elevated plasma IGF-1 levels, but apparently "normal" 24-h mean plasma GH levels. The current study served to update the data for patients with acromegaly referred to our facility, after increasing awareness of this "normal" GH subpopulation throughout the medical community. METHODS: A retrospective chart review was conducted on 157 patients with acromegaly who underwent resection of a confirmed somatotroph pituitary adenoma at the University of Michigan Health System between the dates of 1 Jan 2001 to 23 Sept 2015. RESULTS: Overall prevalence of acromegalic patients with "normal" GH levels, defined as GH <4.7 ng/mL, was 31 %. Over time, the percentage of patients with "normal" GH at diagnosis did not decline: 26 % from 2001 to 2005, 19 % from 2006 to 2010, and 47 % from 2011 to 2015. Mean pituitary tumor size was 1.8 ± 0.1 cm for the group with elevated GH, and 1.2 ± 0.1 cm for the group with "normal" GH (p < 0.001). Percent microadenomas was higher in a group with "normal" GH as compared to those with elevated GH (48 vs. 12 %, p < 0.001), and tumors >2 cm in the maximal diameter were encountered more frequently in the group with elevated GH (43 vs. 14 %, p < 0.001). CONCLUSIONS: Our data show that a substantial percentage of patients with clinical acromegaly have "normal" GH, and therefore strengthens the growing body of evidence which supports the leading role of IGF-1 levels in diagnostic evaluation. At the present time, questions about the natural course of "micromegaly" and treatment benefits compared to the subpopulation with elevated GH levels remain unanswered, but research continues to build on our understanding of the heterogeneous population of individuals.

Outcome of Transsphenoidal Surgery for Cushing Disease: A Single-Center Experience Over 32 Years.

BACKGROUND: Transsphenoidal surgery is the standard approach for treating Cushing disease. Evidence is needed to document effectiveness. OBJECTIVE: To analyze results of transsphenoidal surgery in 276 consecutive patients, including 19 children. METHODS: Medical records were reviewed for patients treated initially with surgery for Cushing disease from 1980 to 2012. Radiographic features, pathology, remissions, recurrences, and complications were recorded. Patients were categorized for statistical analysis based on tumor size (microadenomas, macroadenomas, and negative imaging) and remission type (type 1 = morning cortisol ≤3 µg/dL; type 2 = morning cortisol normal). RESULTS: Females comprised 78% of patients and were older than men. Imaging showed 50% microadenomas, 13% macroadenomas, and 37% negative for tumor. Remission rates for microadenomas, macroadenomas, and negative imaging were 89%, 66%, and 71%, respectively. Patients with microadenomas were more likely to have type 1 remission. Pathology showed adrenocorticotropic hormone-secreting adenomas in 82% of microadenomas, in 100% of macroadenomas, and in 43% of negative imaging. The incidence of hyperplasia was 8%. The finding of hyperplasia or no tumor on pathology predicted treatment failure. The recurrence rate was 17%, with an average time to recurrence of 4.0 years. Patients with type 1 remission had a lower rate of recurrence (13% type 1 vs 50% type 2) and a longer time to recurrence. Children had similar imaging findings, remission rates, and pathology. There were no operative deaths. CONCLUSION: Transsphenoidal surgery provides a safe and effective treatment for Cushing disease. For both adults and children, the best outcomes occurred in patients with microadenomas and/or those with type 1 remission.

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease.

Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on the subcutaneous adipose tissue from patients with Cushing's disease (n=5) compared to patients with nonfunctioning pituitary adenomas (n=11). We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids.

Gene Expression Signature in Adipose Tissue of Acromegaly Patients.

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly.

Repeat endoscopic transsphenoidal surgery for acromegaly: remission and complications.

Reported biochemical remission rates following surgical intervention for acromegaly range from 38 to 83%. In patients not achieving surgical remission, few options remain, mostly limited to medical management and radiation therapy. There is debate over whether or not to offer reoperation to patients in whom surgical remission is not achieved with initial resection. Retrospective chart review was undertaken to determine all patients having acromegaly with persistently elevated GH and/or IGF-1 levels after initial pituitary adenoma resection, and who underwent reoperation using endoscopic endonasal approach at a single institution. Biochemical remission was defined as a postoperative GH level <1 ng/mL and a normal postoperative IGF-1 level in the absence of any medical therapy. In total, 14 patients underwent repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach. Of the 14 patients, 8 (57%) achieved biochemical remission following repeat surgical intervention. Lower preoperative GH levels were associated with greater chance of biochemical remission (P = 0.048). New endocrinopathies were seen in 2 patients (14%), and both were transient diabetes insipidus. Meningitis occurred in 2 patients (14%); both were aseptic meningitis with no sequelae. No mortality was encountered. Repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach appears safe and effective. With no mortality and minimal morbidity, repeat surgical intervention via endoscopic transsphenoidal approach appears a reasonable option for these hard-to-treat patients and should be considered for patients in whom surgical remission is not achieved with initial surgery.

Prevalence and natural history of pineal cysts in adults.

OBJECT: We reviewed our experience with pineal cysts to define the natural history and clinical relevance of this common intracranial finding. METHODS: The study population consisted of 48,417 consecutive patients who underwent brain MR imaging at a single institution over a 12-year interval and who were over 18 years of age at the time of imaging. Patient characteristics, including demographic data and other intracranial diagnoses, were collected from cases involving patients with a pineal cyst. We then identified all patients with pineal cysts who had been clinically evaluated at our institution and who had at least 6 months of clinical and imaging follow-up. All inclusion criteria for the natural history analysis were met in 151 patients. RESULTS: Pineal cysts measuring 5 mm or larger in greatest dimension were found in 478 patients (1.0%). Of these, 162 patients were male and 316 were female. On follow-up MR imaging of 151 patients with pineal cyst at a mean interval of 3.4 years from the initial study, 124 pineal cysts remained stable, 4 increased in size, and 23 decreased in size. Cysts that were larger at the time of initial diagnosis were more likely to decrease in size over the follow-up interval (p = 0.004). Patient sex, patient age at diagnosis, and the presence of septations within the cyst were not significantly associated with cyst change on follow-up. CONCLUSIONS: Follow-up imaging and neurosurgical evaluation are not mandatory for adults with asymptomatic pineal cysts.

Clinical problem solving: monster on the hook--case problems in neurosurgery.

BACKGROUND AND OBJECTIVE: Nonfunctioning and functioning pituitary tumors can present in numerous ways. They may be difficult to diagnose correctly and, even with proper treatment, may lead to complications. METHODS: We present the case of a patient who presented with a large, invasive sellar mass and underwent both medical and surgical treatment for this lesion. The patient's course did not progress as was expected from his initial workup. RESULTS: The patient's history, physical examination, laboratory values, pathologic specimens, and radiologic findings are discussed. His management before, during, and after medical therapy and surgery is reviewed by pituitary experts from 2 different institutions. Aspects of diagnosis and management of sellar lesions are presented and reviewed in the literature. CONCLUSION: Neurosurgeons frequently treat patients with sellar lesions and should remember that despite modern laboratory, pathologic, and radiologic techniques, the diagnosis and treatment of these lesions is not always clear.

Langerhans cell histiocytosis of the optic chiasm: case report.

BACKGROUND AND IMPORTANCE: Langerhans cell histiocytosis (LCH) is an uncommon disease, usually affecting the cranium and peripheral bones. We present a rare case of isolated optic chiasm involvement by LCH to highlight the importance of considering LCH in the differential diagnosis of optic chiasm lesions. CLINICAL PRESENTATION: A 71-year-old woman presented with a 6-week history of worsening peripheral vision, headaches, weakness, cold sensitivity, and fatigue. She was found to have dense bitemporal hemianopsia. Magnetic resonance imaging revealed a 2-cm lesion, contrast enhancing on T1 and bright on T2 signal, involving the optic chiasm but not the pituitary gland. Preoperative considerations included optic nerve glioma, choristoma of the stalk, sarcoid, hypothalamic glioma, and Langerhans cell histiocytosis. The patient underwent a right subfrontal craniotomy for biopsy of the lesion. The optic chiasm was grossly enlarged with no tissue external to the chiasm. A midline incision was made in the lamina terminalis, and multiple biopsies were taken of firm fibrous material. Histologically, the tumor was characteristic for LCH and included a mixture of histiocytes with features of Langerhans cells, eosinophils, small lymphocytes, macrophages, neutrophils, and plasma cells. CONCLUSION: LCH is a rare disease, generally affecting bone, skin, lymph nodes, and in more severe cases, visceral organs. LCH involving the optic pathways is a rare condition that should be included in the differential for adults with mass lesions involving the orbit, eye, optic nerve, or chiasm. Future clinical and basic science research is needed to better understand LCH, its molecular origin, and its growth pattern.

Dysphagia due to anterior cervical hyperosteophytosis.

BACKGROUND: Anterior cervical hyperosteophytosis describes the excessive formation of osteophytes along the ventral spine. Dysphagia due to ACH is considered an uncommon entity described mainly in case reports. Symptomatic ACH has been attributed to multiple etiologies including DISH, trauma, postlaminectomy syndromes, and cervical spondylosis. We report one of the largest series of patients with ACH-induced dysphagia requiring surgery. METHODS: After IRB approval, a retrospective chart review was completed. From 2001 to 2006, 9 patients presented with dysphagia due to ACH requiring surgical treatment. RESULTS: Eight patients were male, and the mean age was 65.1 years. Cervical spine x-rays and CT clearly demonstrated ACH in each case. Esophagram or a video fluoroscopic swallowing study was used to verify that dysphagia was caused by osteophytic overgrowth in all instances but one. In 2 patients, a focal osteophyte had formed adjacent to a previously fused segment. Of the remaining 7 patients, osteophytic formation was attributed to cervical spondylosis in 2 patients and DISH in 5 patients. All patients underwent osteophytectomy without spinal fusion. Average follow-up was 9.8 months. Although all 9 patients experienced resolution of dysphagia, improvement was delayed in 2 patients. CONCLUSIONS: Diffuse idiopathic skeletal hyperostosis and spondylosis are the most common etiologies accounting for ACH-induced dysphagia. Adjacent segment disease may also be a potential cause of symptomatic ACH and has not been previously reported. Regardless of etiology, surgical resection is highly successful if conservative measures fail.

Treatment of pituitary gigantism with the growth hormone receptor antagonist pegvisomant.

CONTEXT: Treatment of pituitary gigantism is complex and the results are usually unsatisfactory. OBJECTIVE: The objective of the study was to describe the results of therapy of three children with pituitary gigantism by a GH receptor antagonist, pegvisomant. DESIGN: This was a descriptive case series of up to 3.5 yr duration. SETTING: The study was conducted at a university hospital. PATIENTS: Patients included three children (one female, two males) with pituitary gigantism whose GH hypersecretion was incompletely controlled by surgery, somatostatin analog, and dopamine agonist. INTERVENTION: The intervention was administration of pegvisomant. MAIN OUTCOME MEASURES: Plasma IGF-I and growth velocity were measured. RESULTS: In all three children, pegvisomant rapidly decreased plasma IGF-I concentrations. Growth velocity declined to subnormal or normal values. Statural growth fell into lower growth percentiles and acromegalic features resolved. Pituitary tumor size did not change in two children but increased in one boy despite concomitant therapy with a somatostatin analog. CONCLUSIONS: Pegvisomant may be an effective modality for the therapy of pituitary gigantism in children. Titration of the dose is necessary for optimal efficacy, and regular surveillance of tumor size is mandatory.

Intraoperative acquisition of three-dimensional imaging for frameless stereotactic guidance during transsphenoidal pituitary surgery using the Arcadis Orbic System.

OBJECT: Intraoperative fluoroscopy has long been used for anatomical localization in transsphenoidal pituitary surgery. More recently, frameless stereotaxy has been used to supplement 2D sagittal radiographs with 3D multiplanar reconstructions. Use of Arcadis Orbic allows both conventional fluoroscopic views and multiplanar reconstructions to be acquired intraoperatively without need for preoperative planning studies. The authors report their initial experience using Arcadis Orbic during transsphenoidal pituitary surgery. METHODS: To test the system, the authors placed a dehydrated human skull in a radiolucent head holder, and obtained standard 2D fluoroscopic images of the skull base and sella turcica. Arcadis Orbic was then used with frameless stereotaxy to register 3D multiplanar reconstructed images of skull base anatomy. The authors then used Arcadis Orbic in 26 transsphenoidal pituitary tumor resections and compared image quality, accuracy, and ease-of-use to standard techniques. RESULTS: Arcadis Orbic 2D fluoroscopic images matched or exceeded the quality of images acquired by standard C-arm machines. Arcadis Orbic multiplanar reconstructions provided excellent images of the skull base when compared with preoperative Stealth computed tomography (CT) studies. Intraoperative frameless stereotactic navigation using Arcadis Orbic was highly accurate and more reliable than registering preoperative CT images. CONCLUSIONS: Arcadis Orbic provides excellent quality 2- and 3D images during transsphenoidal pituitary surgery, and intraoperative frameless navigation using these images is highly accurate. Arcadis Orbic is easy to use, even in patients with large body habitus, and image acquisition takes no longer than registration during a frameless stereotactic case. Based upon our preliminary experience, Arcadis Orbic precludes the need for preoperative CT studies in patients with pituitary lesions requiring frameless stereotactic navigation.

Treatment of pituitary tumors: a surgical perspective.

Surgical intervention is a necessary part of a multimodal approach to pituitary lesions. This article summarizes the surgical approach to different neoplastic processes affecting the sellar region.

Changes in the utilization of spinal fusion in the United States.

OBJECTIVE: Several reports suggest that spine surgery has experienced rapid growth in the past decade. Limited data exist, however, documenting the increase in spinal fusion. The objective of this work was to quantify and characterize the contemporary practice of spinal fusion in the United States. METHODS: Clinical data were obtained from the Nationwide Inpatient Sample for the years from 1993 to 2003. All patients with International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes indicating cervical fusion, thoracolumbar fusion, lumbar or unspecified fusion were identified (n = 471,990). Primary ICD-9-CM diagnosis codes were used to determine the rationale for surgical fusion. Population-based utilization rates overall and for each procedure were calculated from United States census data. Rank order of spinal fusion compared with other inpatient procedures from the Nationwide Inpatient Sample was reported for the years 1997 to 2003. RESULTS: Overall utilization increased during the time period for cervical, thoracolumbar, and lumbar fusions by 89, 31, and 134%, respectively. Patients aged 40 to 59 years experienced the rapid rise in utilization for cervical fusions (60-110 per 100,000) and lumbar fusions (35-84 per 100,000). For patients 60 years and older, utilization also increased for cervical (30-67 per 100,000), thoracolumbar (4-9 per 100,000), and lumbar (42-108 per 100,000). Spinal fusion rose from the 41st most common inpatient procedure in 1997 to the 19th in 2003. CONCLUSION: Cervical, thoracolumbar, and lumbar spinal fusion have experienced a rapid increase in utilization in isolation and compared with other surgical procedures in contemporary practice. These changes are most pronounced for patients over 40 years of age, and degenerative disc disease seems to account for much of this increase.