Mental health disorders in newly diagnosed non-functional pitutary adenoma under initial observation: an observational cohort study using the nationwide MarketScan database.

PURPOSE: Nonfunctioning pituitary adenomas account for 15-30% of pituitary tumors. Studies exploring the role of an intracranial tumor diagnosis, specifically nonfunctioning pituitary adenomas, on mental health disorders (MHDs) in patients have been limited. We characterize the incidence and factors affecting the development of MHDs in untreated pituitary adenomas. METHODS: Utilizing a large-scale private payor database, MarketScan, we performed a retrospective study of patients with an untreated pituitary adenomas and corresponding MHD. RESULTS: We found that in patients diagnosed with an untreated pituitary adenomas, approximately 15% were newly diagnosed with a MHD within 1 year of the pituitary adenoma diagnosis. Independent risk factors included female gender and substance abuse. Headaches, visual symptoms, and higher Charlson Co-morbidity indexes were also independently associated with a subsequent diagnosis of MHD. On multivariable analysis, patients in the pituitary tumor cohort were more likely to be diagnosed with a MHD than those in the matched cohort (aOR: 1.31, CI: 1.19-1.44). CONCLUSION: By identifying risk factors, advanced screening can focus on non-operative pituitary adenoma patients at high-risk for the development of MHD.

Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination.

Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing.

Telemedicine in a spine clinic setting: a large survey of patient preferences and experiences.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has greatly disturbed healthcare and the practice of neurosurgery. As healthcare systems evolve in the face of COVID-19, the use of telehealth platforms has expanded. We presented the results of a large survey of patient perspectives on the role of telehealth in the care of spine clinic patients. METHODS: All patients at the spine clinic of a large, tertiary, academic medical center were surveyed at their clinic visit from May 30, 2020-June 30, 2020. All responses were anonymous, and results were analyzed with standard statistical techniques. RESULTS: One hundred and seventy-six surveys were returned and 164 were entirely completed. 56.8% of patients were new while 24.4% were postoperative follow-up visits: 54.9% had lumbar symptoms. 85% had pain while more than half also reported weakness; 58% traveled greater than twenty-five miles for their appointment; 96% had transportation readily available. Of all respondents, only 15.3% preferred the appointment via video telehealth while 4% had no preference between in-person appointment or virtual visit. Preference for telehealth appointment was not associated with factors such as new or established in the practice, spinal region of symptoms, pain, weakness, comfort with technology, age, or duration of symptoms. There was a significant difference between how far the patient traveled for the clinic appointment and their preference for a telehealth appointment, with patients traveling further distances favoring telehealth (P=0.04). This effect remained significant when stratifying based on 25 miles (P=0.03) or 50 miles (P=0.03) but not when stratifying based on 100 miles (P=0.32). However, the sample size of patients traveling >100 miles was small, limiting any inference regarding that subgroup. Access to transportation was associated with preference for telehealth (88.89% vs. 97.18%, P=0.08) but did not reach statistical significance. CONCLUSIONS: Most spine patients prefer in-person clinic appointments to virtual appointments. These preferences should be considered when arranging patient encounters.

Rare septic arthritis of the wrist and carpus primary osteoarticular manifestation of Mycobacterium tuberculosis: A case report.

Mycobacterium tuberculosis is one of the oldest and most studied infections, yet it remains one of the most common causes of infection-related death worldwide. The majority concern pulmonary tuberculosis. Therefore, extrapulmonary cases are rare and are often neglected in the differential diagnosis, especially in chronic musculoskeletal complaints. Nevertheless, osteoarticular manifestation of tuberculosis can cause disabling destruction of bone, cartilage, and surrounding soft tissues which may be exacerbated by a delay in diagnosis. This case report documents a case of primary osteoarticular tuberculosis causing septic arthritis of the wrist and carpus. In our case, the patient had no pulmonary burden of tuberculosis, which further delayed diagnosis and lead to irreversible damage to the wrist as well as carpus. This case illustrates the need to consider this diagnosis in at risk populations in order to prevent a delay in diagnosis and treatment.

Major complications of dural venous sinus stenting for idiopathic intracranial hypertension: case series and management considerations.

BACKGROUND: Venous sinus stenting (VSS) is a safe, effective, and increasingly popular treatment option for selected patients with idiopathic intracranial hypertension (IIH). Serious complications associated with VSS are rarely reported. METHODS: Serious complications after VSS were identified retrospectively from multicenter databases. The cases are presented and management strategies are discussed. RESULTS: Six major acute and chronic complications after VSS were selected from a total of 811 VSS procedures and 1466 venograms for IIH. These included an acute subdural hematoma from venous extravasation, cases of both intraprocedural and delayed stent thrombosis, an ultimately fatal cerebellar hemorrhage resulting in acute obstructive hydrocephalus, venous microcatheter perforation during venography and manometry, and a patient who developed subarachnoid hemorrhage and subdural hematoma after cerebellar cortical vein perforation. The six cases are reviewed and learning points regarding complication avoidance and management are presented. CONCLUSION: We report on six rare, major complications after VSS for IIH. Familiarity with these potential complications and appropriate timely management may allow for good clinical outcomes.

Delayed Anterior Cervical Screw Migration Causing Swallowing Difficulty.

Cervical disc disease is a common pathology that may require surgical intervention. A common surgical intervention for cervical disc disease is anterior discectomy and fusion. A number of complications are associated with this technique, including hoarseness, dysphagia, pseudoarthrosis, adjacent segment disease, and hardware failure. Here, we present a case detailing a unique complication of delayed migration of an anterior cervical screw which resulted in swallowing difficulties. Subsequently, we discuss the related reports and highlight the literature on the topic. We conclude with a brief discussion on the principle of patient autonomy.

Dural venous sinus stenting for treatment of pediatric idiopathic intracranial hypertension.

BACKGROUND: Dural venous sinus stenting (VSS) is an effective treatment for idiopathic intracranial hypertension (IIH) in adult patients. There are no published series to date evaluating safety and efficacy of VSS in pediatric patients. OBJECTIVE: To report on procedural device selection and technique as well as safety and efficacy of VSS for pediatric patients with medically refractory IIH due to underlying venous sinus stenosis. METHODS: A multi-institutional retrospective case series identified patients with medically refractory IIH aged less than 18 years who underwent VSS. RESULTS: 14 patients were identified at four participating centers. Patient ages ranged from 10 to 17 years, and 10 patients (71.4%) were female. Mean body mass index was 25.7 kg/m2 (range 15.8-34.6 kg/m2). Stenting was performed under general endotracheal anesthesia in all except two patients. The average trans-stenotic gradient during diagnostic venography was 10.6 mm Hg. Patients had stents placed in the superior sagittal sinus, transverse sinus, sigmoid sinus, occipital sinus, and a combination. Average follow-up was 1.7 years after stenting. Six patients out of 10 (60%) had reduced medication dosing, 12 of 14 patients (85.7%) had improvements in headaches, two patients (100%) with pre-stent tinnitus had resolution of symptoms, and four (80%) of five patients with papilledema had improvement on follow-up ophthalmological examinations. Two patients (14.3%) developed postprocedural groin hematomas, one patient (7.1%) developed a groin pseudoaneurysm, and one patient (7.1%) had postprocedural groin bleeding. No other procedural complications occurred. Four patients (28.6%) required further surgical treatment (cerebrospinal shunting and/or stenting) after their first stenting procedure. CONCLUSIONS: This series suggests that VSS is feasible in a pediatric population with IIH and has a low complication rate and good clinical outcomes.

Non-Union After Multiple Lumbar Fusion Surgeries in a Patient With Facioscapulohumeral Muscular Dystrophy: A Case Report and Review of the Literature.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a rare condition affecting 1/20,000 persons and the third most common muscular dystrophy condition, with an autosomal dominant pattern of inheritance characterized by progressive muscular weakness primarily involving the face, shoulder girdle, and upper arm. The condition is associated with atrophic musculature of the trunk and core leading to difficulties with gait, posture, and function. FSHD leaves as many as 20% of patients wheelchair-bound and most commonly presents with low back, neck, and shoulder pain. CASE DESCRIPTION: We present the case of a patient with FSHD who underwent multiple spinal fusion surgeries without relief in her back pain. Imaging studies serve to highlight the extent of paraspinal muscle atrophy and provides the basis for a discussion on the preoperative factors that may predict patients most likely to benefit from surgery. We then provide a brief review of the literature on the role of paraspinal muscle atrophy in back pain. CONCLUSIONS: This case adds to our understanding of the surgical management of patients with FSHD and patients with atrophic core musculature as a whole.

Mental health disorders in patients with untreated meningiomas: an observational cohort study using the nationwide MarketScan database.

BACKGROUND: Meningiomas are the most common primary tumor of the CNS. Studies investigating the impact of a brain tumor diagnosis on mental health disorders (MHDs) in patients have been limited. The objective of this work is to characterize the incidence and factors affecting the presence of MHDs in untreated meningiomas. METHODS: Using a large-scale private payer database, MarketScan, we performed a retrospective study of patients with an untreated meningioma and corresponding MHD. RESULTS: We found that in patients diagnosed with an untreated meningioma, approximately 16% were diagnosed with an MHD within 1 year of the diagnosis of the meningioma. CONCLUSION: By identifying risk factors, appropriate screening can focus on patients at high-risk for the development of MHD.

External fixation of distal radius fractures: effect of distraction and duration.

PURPOSE: To assess the effects of the amount of distraction across the wrist and the duration of fixator placement on the clinical outcome of patients with distal radius fractures treated with external fixation. METHODS: A total of 42 patients with closed distal radius fractures were treated with a spanning external fixator plus supplementary percutaneous K-wires over a 6-year period. All fractures were extra-articular (A type) or simple intra-articular (C type). Twenty-four of these patients were evaluated retrospectively for clinical and radiographic outcomes at an average follow-up time of 22 months (range, 4-49 months). The amount of distraction attained by the fixator was determined by measuring the carpal height ratio on plain radiographs. Wrist and forearm range of motion were recorded, as well as grip and pinch strength. Standard radiographs were taken to evaluate healing and bony alignment. RESULTS: Using the Gartland Werley classification, there were 11 excellent, 10 good, and 3 fair results. Statistical analysis indicated that a higher carpal height ratio at the initial reduction positively correlated (p = .041) with an excellent outcome. Duration of external fixation did not have a significant impact on the final outcome within the parameters studied (p = .891). Average wrist range of motion at follow-up was as follows: flexion, 54.1 degrees (75% of the contralateral side); extension, 59.0 degrees (78%); radial deviation, 18.0 degrees (85%); ulnar deviation, 22 degrees (73%); pronation, 79.0 degrees (95%); and supination, 76.6 degrees (93%). None of the individual components of range of motion were negatively correlated with higher carpal height ratio at fixator application or duration of fixation, within the parameters studied. CONCLUSIONS: Moderately increased distraction of the carpus at the initial fracture reduction is correlated with improved clinical outcome and does not have an adverse affect on subsequent wrist range of motion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The Role of Anesthesia during Intra-Arterial Mechanical Thrombectomy for theTreatment of Acute Ischemic Stroke.

Background Type of sedation (conscious sedation (CS) or general anesthesia (GA)) during Intra-arterial mechanical thrombectomy (IAMT) for treatment of acute ischemic stroke may affect patient outcomes. Previous studies suggested that CS cohorts have a higher probability of good outcome than GA cohorts. However, CS cohorts had lower initial NIH stroke scores (NIHSS). This study offers an investigation into outcomes after IAMT based on sedation type. Methods Patients at our institution who underwent IAMT for treatment of acute ischemic stroke caused by anterior circulation occlusion between 2013-2015 were included in the study. Primary endpoint was functional outcome on the modified Rankin Scale (mRS) at 90 days post-IAMT. Secondary endpoints included NIHSS at 48 hours post-IAMT, time from CT scan to puncture and from puncture to initial recanalization, recanalization as defined by the Thrombolysis in Cerebral Ischemia (TICI) score, intensive care and hospital length of stay, and all-cause in-hospital mortality. Results Thirty nine patients were included in analysis; 17 received GA and 22 received CS. Cohorts were similar in baseline characteristics, including NIHSS. The 90-day mRS was not significantly different between cohorts, as was the case for most secondary endpoints. Successful recanalization was higher in both groups than previously reported and a significantly higher TICI 3 recanalization rate was achieved in the GA cohort. Conclusions We show that equal outcomes are possible with either CS or GA if initial NIHSS is comparable. It seems reasonable for neuro-interventionalists to continue practicing using their personal preference for sedation. However, prospective randomized trials are still needed.

Idiopathic Intracranial Hypertension Masking as Obstructive Hydrocephalus: A Case Report.

Idiopathic intracranial hypertension (IIH) is a poorly understood phenomenon and its presentation can both mimic and co-exist with other intra-cranial processes. Accurate diagnosis is imperative as ongoing advancements in treatment can yield dramatic positive results. Here we present the case of an individual with signs and symptoms of obstructive hydrocephalus who was ultimately found to have IIH secondary to venous sinus stenosis. After correction of the venous sinus stenosis, resolution in the patient's symptoms was noted. The case highlights some of the unique considerations in approaching patients with IIH and provides a framework for review of current literature related to IIH and venous sinus stenosis.

Heavily Calcified Esthesioneuroblastoma in a 72-year-old.

A 72-year-old female presented with the complaint of declining vision. Workup included magnetic resonance imaging (MRI) which revealed a large enhancing mass extending into the nasal cavity, nasopharynx, and anterior cranial fossa. Computed tomography (CT) imaging revealed extensive calcification. Subsequent endonasal biopsy revealed the tumor to be an unusually calcified esthesioneuroblastoma (ENB). The patient elected for palliative measures. The case provides a basis for a discussion on rare esthesioneuroblastomas and highlights the possibility of extensive calcification on such tumors.

Chromosomal translocations t(4;14), t(11;14) and proliferation rate stratify patients with mature plasma cell myelomas into groups with different survival probabilities: a molecular epidemiologic study on tissue microarrays.

Plasma cell myelomas (PMs) exhibit clinical and molecular heterogeneity. To date, morphology and immunohistochemistry on bone marrow trephines are of limited value to stratify patients into different prognostic categories. However, some chromosomal translocations are of prognostic and/or of predictive importance in PMs. In this study, the prognostic significance of morphology, CyclinD1 expression, proliferation index (Mib1) and presence of the translocations FGFR3/IgH [t(4;14)] and CCND1/IgH [t(11;14)] are compared in 119 patients with PM. Immunohistochemistry and fluorescence in situ hybridization analysis were carried out on a tissue microarray containing bone marrow trephines. Hundred and one PMs showed a mature morphology whereas 10 were immature. All but one PM carrying a translocation showed a mature morphology. Patients with a t(4;14) (12%) had a statistically significant shorter 1-year survival (P=0.004), whereas those with a t(11;14) (21%) had a trend towards a better clinical outcome. CyclinD1 protein expression was not significantly associated with survival. Besides the t(4;14), an immature morphology (P<0.001) and a proliferation index (Mib1) of more than 10% (P=0.002) were associated with a significantly worse outcome. A high occurrence of strong CyclinD1 protein expression in the tumor cells was predictive of either a t(11;14) or of a low level amplification of the CCND1 gene, suggesting that different molecular mechanisms may have lead to an over-expression of the CyclinD1 protein in PMs. These findings demonstrate that a high proliferation rate and translocations involving the IgH locus can stratify mature PMs into groups with distinct survival probabilities.

Prognostic value of cell cycle and apoptosis regulatory proteins in mismatch repair-proficient colorectal cancer: a tissue microarray-based approach.

Cell cycle and apoptosis regulatory proteins are markers of tumor progression in colorectal cancer. In a series of 1,274 mismatch repair-proficient colorectal cancers, immunohistochemical analysis of p21, p27, p53, and bcl-2 expression was performed using the tissue microarray technique. In univariate analysis, p21 expression was associated with tumor location and pN0; p27 expression with tumor location, lower tumor grade, early pT, and pN; p53 expression with tumor location; and bcl-2 with early pT and pN. Expression of p27 identified subgroups with worse prognosis in pT3 N0 and pT3 N+ patients. None of the 4 tumor markers were independent prognostic indicators of survival. The multimarker phenotypes p21/p27/p53 and p21/p27/bcl-2 were associated with survival. In mismatch repair-proficient colorectal cancer, p27 expression is associated with a better prognosis, and pT, pN, and vascular invasion are independent prognostic factors. In addition, multimarker phenotypes are useful to identify colorectal cancer subgroups with different prognoses.

Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning.

The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1-/- and the M1/M3-/- knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing.

EphB2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancers.

PURPOSE: To comprehensively evaluate ephrin receptor B2 (EphB2) expression in normal and neoplastic tissues. EphB2 is a tyrosine kinase recently implicated in the deregulation of cell-to-cell communication in many tumors. EXPERIMENTAL DESIGN: EphB2 protein expression was analyzed by immunohistochemistry on tissue microarrays that included 76 different normal tissues, >4,000 samples from 138 different cancer types, and 1,476 samples of colon cancer with clinical follow-up data. RESULTS: We found most prominent EphB2 expression in the intestinal epithelium (colonic crypts) with cancer of the colorectum displaying the highest EphB2 positivity of all tumors. Positivity was found in 100% of 118 colon adenomas but in 33.3% of 45 colon carcinomas. EphB2 expression was also observed in 75 tumor categories, including serous carcinoma of the endometrium (34.8%), adenocarcinoma of the esophagus (33.3%), intestinal adenocarcinoma of the stomach (30.2%), and adenocarcinoma of the small intestine (70%). The occasional finding of strong EphB2 positivity in tumors without EphB2 positivity in the corresponding normal cells [adenocarcinoma of the lung (4%) and pancreas (2.2%)] suggests that deregulation of EphB2 signaling may involve up-regulation of the protein expression. In colon carcinoma, loss of EphB2 expression was associated with advanced stage (P < 0.0001) and was an indicator of poor overall survival (P = 0.0098). CONCLUSIONS: Our results provide an overview on the EphB2 protein expression in normal and neoplastic tissues. Deregulated EphB2 expression may play a role in several cancer types with loss of EphB2 expression serving as an indicator of the possible pathogenetic role of EphB2 signaling in the maintenance of tissue architecture of colon epithelium.

Prognostic relevance of gene amplifications and coamplifications in breast cancer.

Multiple different oncogenes have been described previously to be amplified in breast cancer including HER2, EGFR, MYC, CCND1, and MDM2. Gene amplification results in oncogene overexpression but may also serve as an indicator of genomic instability. As such, presence of one or several gene amplifications may have prognostic significance. To assess the prognostic importance of amplifications and coamplifications of HER2, EGFR, MYC, CCND1, and MDM2 in breast cancer, we analyzed a breast cancer tissue microarray containing samples from 2197 cancers with follow-up information. Fluorescence in situ hybridizations revealed amplifications of CCND1 in 20.1%, HER2 in 17.3%, MDM2 in 5.7%, MYC in 5.3%, and EGFR in 0.8% of the tumors. All gene amplifications were significantly associated with high grade. HER2 (P < 0.001) and MYC amplification (P < 0.001) were also linked to shortened survival. In case of HER2, this was independent of grade, pT, and pN categories. MYC amplification was almost 3 times more frequent in medullary cancer (15.9%), than in the histologic subtype with the second highest frequency (ductal; 5.6%; P = 0.0046). HER2 and MYC amplification were associated with estrogen receptor/progesterone receptor negativity (P < 0.001) whereas CCND1 amplification was linked to estrogen receptor/progesterone receptor positivity (P < 0.001). Coamplifications were more prevalent than expected based on the individual frequencies. Coamplifications of one or several other oncogenes occurred in 29.6% of CCND1, 43% of HER2, 55.7% of MDM2, 65% of MYC, and 72.8% of EGFR-amplified cancers. HER2/MYC-coamplified cancers had a worse prognosis than tumors with only one of these amplifications. Furthermore, a gradual decrease of survival was observed with increasing number of amplifications. In conclusion, these data support a major prognostic impact of genomic instability as determined by a broad gene amplification survey in breast cancer.

High specificity of combined TRAP and DBA.44 expression for hairy cell leukemia.

Because of marrow fibrosis, bone marrow aspirations are often nonconclusive in patients with hairy cell leukemia (HCL). Therefore, histologic examination is important in HCL but often difficult in cases with low numbers of tumor cells. A combined immunohistochemical positivity for DBA.44 and tartrate-resistant phosphatase was previously found in 100% of HCL and suggested to be specific for this diagnosis. To further assess the diagnostic specificity and sensitivity of this immunohistochemical approach in a higher number of cases, we analyzed 56 HCLs and lymphoma tissue microarrays, including 840 cases of the most frequent non-Hodgkin lymphomas. All HCLs showed combined positivity for these two proteins (100% sensitivity). Both antibodies were often positive in other lymphoma types. DBA.44 reactivity was especially frequent in follicular lymphomas (46%), whereas tartrate-resistant acid phosphatase (TRAP) expression was often seen in mantle cell lymphomas (57%), primary mediastinal large B-cell lymphomas (54%), and chronic lymphocytic leukemia/small lymphocytic lymphoma (41%). A combined DBA.44/TRAP positivity was seen in only 3% of non-HCL non-Hodgkin lymphomas, including cases of diffuse large B-cell lymphomas, follicular lymphomas, chronic lymphatic leukemia/small lymphocytic leukemias, and mantle cell lymphomas. Overall, these data confirm the utility of combined immunohistochemical DBA.44/TRAP expression analysis in confirming the diagnosis of HCL. However, combined positivity for these markers is highly sensitive but not absolutely specific for HCL.