An analysis of suicidal and self-injurious behavior reports with antiseizure medications in the FDA adverse event database.

BACKGROUND: Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during clinical trials. We aimed to analyze twenty-five anti-seizure medications (ASMs) in FAERS to assess for increased reporting of suicidal and self-injurious behavior. METHODS: Twenty-five ASMs were analyzed: brivaracetam, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproate, vigabatrin, zonisamide. Reports of "suicidal and self-injurious behavior" were collected from January 1, 2004, to December 31, 2020, using OpenVigil 2.1 tool with indication as "Epilepsy". Relative reporting ratio, proportional reporting ratio, and reporting odds ratio were calculated utilizing all other drug reports for epilepsy patients as a control. RESULTS: Significant relative operating ratio, ROR (greater than 1, p<0.05) were observed for diazepam (2.909), pregabalin (2.739), brivaracetam (2.462), gabapentin (2.185), clonazepam (1.649), zonisamide (1.462), lacosamide (1.333), and levetiracetam (1.286). CONCLUSIONS: Of the 25 ASMs that were analyzed in this study, 4 (16%) were identified to have been linked with a likely true adverse event. These drugs included diazepam, brivaracetam, gabapenetin, and pregabalin. Although several limitations are present with the FAERS database, it is imperative to closely monitor patient comorbidities for increased risk of suicidality with the use of several ASMs.

A Novel Method for Angioscopic Imaging and Visualizing the Skull Base Using Complementary Metal Oxide Semiconductor Cameras.

BACKGROUND AND OBJECTIVES: Complementary metal oxide semiconductor (CMOS) electrode arrays are a novel technology for miniaturized endoscopes; however, its use for neurointervention is yet to be investigated. In this proof-of-concept study, we aimed to demonstrate the feasibility of CMOS endoscopes in a canine model by providing direct visualization of the endothelial surface, deploying stents and coils, and accessing the spinal subdural space and skull base. METHODS: Using 3 canine models, standard guide catheters were introduced into the internal carotid and vertebral arteries through the transfemoral route using fluoroscopy. A 1.2-mm CMOS camera was delivered through the guide catheter to inspect the endothelium. Next, the camera was introduced alongside standard neuroendovascular devices including coils and stents to provide direct visualization of their deployment within the endothelium during fluoroscopy. One canine was used for skull base and extravascular visualization. A lumbar laminectomy was performed, and the camera was navigated within the spinal subdural space until the posterior circulation intracranial vasculature was visualized. RESULTS: We successfully visualized the endothelial surface and performed several endovascular procedures such as deployment of coils and stents under direct endovascular, angioscopic vision. We also demonstrated a proof of concept for accessing the skull base and posterior cerebral vasculature using CMOS cameras through the spinal subdural space. CONCLUSION: This proof-of-concept study demonstrates the feasibility of CMOS camera technology to directly visualize endothelium, perform common neuroendovascular procedures, and access the base of the skull in a canine model.

Clival intraosseous myxoma treated with an endoscopic endonasal approach: illustrative case.

BACKGROUND: Solitary lesions of the clivus, especially nonchordomatous ones, are exceptionally rare pathologies representing only 0.1%-0.2% of intracranial tumors that may present diagnostic and therapeutic challenges. Intraosseous myxomas are benign tumors arising from mesenchymal cells with an unknown pathophysiology. OBSERVATIONS: In this article, a 15-year-old male with clival intraosseous myxoma who was treated via an endoscopic endonasal surgical approach is presented. The patient became symptomatic after a baseball struck his head, leading to throbbing headaches and visual difficulties for tracking objects. Examination noted diplopia, cranial nerve VI palsy, and ptosis. After imaging revealed a tumor extending to the left cavernous sinus with bulging of the dorsal clivus against the basilar artery/ventral pons, resection was performed. Postoperatively, the patient noted ocular motility and alignment improvement without further complications. LESSONS: Clival masses present with symptoms from compromised neurovascular structures including visual disturbances and trigeminal sensory deficits. Given the rarity of these entities, patients may postpone further treatment until workup; this patient was misdiagnosed for possible concussion until several weeks passed. A PubMed database review of cranial myxoma cases was conducted to identify solitary clival intraosseous myxoma cases. This case is one of the few in which this pathology was treated through an endoscopic endonasal operative approach without complications, demonstrating its safety and effectiveness.

Analysis of reported adverse events of pipeline stents for intracranial aneurysms using the FDA MAUDE database.

OBJECTIVE: Flow diverting stents (FDS) are a validated device in the treatment of intracranial aneurysms, allowing for minimally invasive intervention. However, after its approval for use in the United States in 2011, post-market surveillance of adverse events is limited. This study aims to address this critical knowledge gap by analyzing the FDA Manufacturer and User Facility Device Experience (MAUDE) database for patient and device related (PR and DR) reports of adverse events and malfunctions. METHODS: Using post-market surveillance data from the MAUDE database, PR and DR reports from January 2012-December 2021 were extracted, compiled, and analyzed with R-Studio version 2021.09.2. PR and DR reports with insufficient information were excluded. Raw information was organized, and further author generated classifications were created for both PR and DR reports. RESULTS: A total of 2203 PR and 4017 DR events were recorded. The most frequently reported PR adverse event categories were cerebrovascular (60%), death (11%), and neurological (8%). The most frequent PR adverse event reports were death (11%), thrombosis/thrombus (9%) cerebral infarction (8%), decreased therapeutic response (7%), stroke/cerebrovascular accident (6%), intracranial hemorrhage (5%), aneurysm (4%), occlusion (4%), headache (4%), neurological deficit/dysfunction (3%). The most frequent DR reports were activation/positioning/separation problems (52%), break (9%), device operates differently than expected (4%), difficult to open or close (4%), material deformation (3%), migration or expulsion of device (3%), detachment of device or device component (2%). CONCLUSIONS: Post-market surveillance is important to guide patient counselling and identify adverse events and device problems that were not identified in initial trials. We present frequent reports of several types of cerebrovascular and neurological adverse events as well as the most common device shortcomings that should be explored by manufacturers and future studies. Although inherent limitations to the MAUDE database are present, our results highlight important PR and DR complications that can help optimize patient counseling and device development.

Deep brain stimulation for refractory obsessive-compulsive disorder: A review and analysis of the FDA MAUDE database.

Background: Deep brain stimulation (DBS) is used as a treatment option for patients diagnosed with a form of obsessive-compulsive disorder (OCD) that is highly resistant to conventional treatment methods. In 2009, DBS was granted a humanitarian device exemption-approval by the Food and Drug Administration after promising preliminary data. Monitoring of long-term safety data through post market surveillance of adverse events has not yet been conducted for DBS in OCD patients. This study aims to address this critical knowledge gap. Methods: All patient- and device-related (PR; DR) reports from January 1, 2012, to December 31, 2021, were downloaded and compiled from the manufacturer and user facility device experience (MAUDE) database pertaining to DBS for OCD using the product class name "Deep Brain Stimulator For OCD." Data in this study were examined using descriptive statistics to evaluate for frequency of reporting. Results: The most frequently reported PR adverse event categories included psychiatric (40%), neurological (19%), other (14%), decreased therapeutic response (10%), and infections (10%). The most frequent DR reports were high impedance (14%), energy output problem (7%), battery problem (7%), malposition of device (7%), and improper/incorrect procedure or method (7%). Conclusion: The PR and DR adverse events in our study align with the previous findings of adverse events. They also further solidify that DBS for refractory OCD may be a viable option for the right patient population. However, further studies are essential given the limitations of the MAUDE database.

Second Case of Tumors Associated With Heterozygous NTHL1 Variant.

Homozygous mutations to NTHL1 are known to increase cancer risk, particularly in the colon and breast. NTHL1 tumor syndrome (NTS) is an autosomal recessive genetic condition. Little is known about the cancer risk in patients who have heterozygous NTHL1 mutations. We previously published a case of benign tumors associated with a heterozygous NTHL1 mutation. In this second case, we present a patient with a heterozygous NTHL1 mutation who developed a gastrointestinal stromal tumor, pilocytic astrocytoma, tall cell papillary thyroid cancer, invasive ductal papilloma, spinal nerve sheath tumors, and spinal hemangiomas. Here, we show that heterozygous NTHL1 mutations may increase cancer risk and may even manifest similarly to NTS.

Preoperative Thoracic Spine Magnetic Resonance Imaging for Spinal Cord Stimulation: Should Such a Recommendation Be an Absolute Requirement?

OBJECTIVE: Current published guidelines recommend advanced imaging, specifically, thoracic magnetic resonance imaging (MRI), prior to implantation of epidural paddle spinal cord stimulator (SCS) leads. Preoperative imaging may affect surgical approach to minimize risk of complications. We aimed to assess the impact of preoperative thoracic MRI on surgical planning in a large series of surgical paddle SCS lead placements in a real-world setting. MATERIALS AND METHODS: This is a retrospective study of a prospectively maintained data base of 160 patients treated by SCS with awake thoracic surgical paddle lead placement in a single academic functional neurosurgery center from 2013 to 2021. All patients had a thoracic MRI prior to implantation. Abnormal MRI findings were reviewed to determine their potential impact on the safety of surgical paddle lead placement. A minor impact was defined as anatomical areas to avoid with paddle lead placement. Major impacts included significant deviations from standard approach to electrode placement. RESULTS: None of the 160 patients had signs or symptoms referable to thoracic spine pathology prior to lead implant. Sixty-seven had abnormal thoracic MRI findings, and 36 had abnormal MRI findings that impacted surgical planning. Thirty-one patients had MRI findings with minor impact. Five patients (more than 3%) had findings with major impact. CONCLUSIONS: This is the largest case series assessing the impact of preoperative thoracic MRI on surgical planning for patients undergoing paddle SCS placement. Twenty-two percent of patients had MRI findings that impacted surgical planning with 3% requiring additional surgical decompression for safe paddle lead placement. Without advanced imaging to inform surgical planning, unnecessary risk may have been placed on these patients. Although such imaging has been recommended by consensus committees in published guidelines, our study is the first to present a large institutional experience of real-world data that demonstrates its importance.

MedCDI: A technology-based documentation and quality improvement initiative in neurosurgery.

Background: Clinical documentation of patient care alters coding accuracy of Medicare Severity Diagnosis-Related Groups (MS-DRGs), expected mortality, and expected length of stay (LOS) which impact quality metrics. We aimed to determine if neurosurgical quality metrics could be improved by facilitating accurate documentation and subsequently developed a mobile application and educational video to target areas of opportunity. Methods: Vizient software was used to analyze MS-DRGs and expected LOS for sample of patients requiring surgery for spinal pathology, brain tumors, and subarachnoid hemorrhage (SAH) between January 2019 and August 2021. Chart reviews were conducted to discover variables missed by documenting provider and/or coder. Results: Review of 114 spinal surgeries, 20 brain tumors, and 53 SAH patients revealed at least one additional variable impacting LOS in 43% of spine, 75% of brain tumor, and 92% of SAH patients, with an average of 1 (1.25), 2 (1.75), and 3 (2.89) new variables, respectively. Recalculated expected LOS increased by an average of 0.86 days for spine, 3.08 for brain tumor, and 6.46 for SAH cases. Conclusion: Efforts to accurately document patient care can improve quality metrics such as expected LOS, mortality, and cost estimates. We determined several missing variables which impact quality metrics, showing opportunity exists in neurosurgical documentation improvement. Subsequently, we developed an educational video and mobile-supported application to specifically target these variables. To the best of our knowledge, this represents the first initiative to utilize the proven powers of mobile phones in health care toward the novel application of specifically improving neurosurgical quality metrics.

Temporary standalone percutaneous fixation with pedicle screws for the treatment of subacute tuberculous osteomyelitis with kyphotic deformity in the lumbar spine.

Background: Tuberculous (TB) osteomyelitis is a rare, but challenging infection, that mandates antituberculosis antibiotics, and potentially surgical intervention. Per the Gulhane Askeri Tip Akademisi (GATA) classification system, corrective reconstruction is indicated in severe cases, where the kyphotic deformity is >20° (GATA Class III). Here, we describe a case of BCG vaccine-induced lumbar TB osteomyelitis at the L1-2 level in a patient presenting with mechanical pain and a focal, nonfixed kyphotic deformity of 36.1°. Surgery consisted of percutaneous fixation with pedicle screws without debridement, fusion arthrodesis, or anterior reconstruction. Case Description: A 77-year-old male presented with L1-2 TB osteomyelitis secondary to intravesical BCG application. A 36.1° focal nonfixed kyphotic deformity was evident on standing X-rays that reduced in the supine position. He underwent posterior percutaneous screw fixation with rods extending from the T12 to L3 levels, with resolution of his mechanical pain. Nine months later, the CT demonstrated reconstitution of the vertebral bodies (i.e., volume increase of 6.99 cm3 (21%) and 7.49 cm3 (27%) at L1 and L2, respectively). Standing X-rays after hardware removal demonstrated 32.7° of lumbar lordosis and a reduction of focal kyphosis to 12.9°. Conclusion: Here, we present an exceedingly rare case of BCG vaccine-induced L1-2 spinal tuberculosis with extensive vertebral body destruction and deformity. This was effectively treated with standalone temporary pedicle fixation instead of corpectomy and reconstruction.

Alopecia in Multiple Sclerosis Patients Treated with Disease Modifying Therapies.

BACKGROUND: There is currently limited literature addressing the reporting of alopecia in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs). Anecdotal reports of hair thinning from patients on various DMTs prompted further investigation of a large database. OBJECTIVE: To analyze total reports, source of reporting, age distribution, and sex distribution of alopecia associated with DMTs. METHODS: FDA Adverse Event Reporting System (FAERS) public dashboard and OpenFDA database were analyzed for alopecia reports between January 1, 2009, and June 30, 2020, attributed to usage in MS of FDA approved DMTs. The main outcomes included total reports for each drug, age, sex distribution, and reporting source. OpenFDA data was used for statistical analyses including reporting odds ratios (ROR) and information components. RESULTS: 8759 alopecia reports were identified among 44 114 adverse events in skin and subcutaneous tissue disorders (19.9%). 3701 (42.3%) with teriflunomide, 1675 (19.1%) with dimethyl fumarate, 985 (11.2%) with natalizumab, 926 (10.6%) with fingolimod, 659 (7.5%) with interferon beta-1a, 257 (2.9%) with glatiramer acetate, 243 (2.8%) with ocrelizumab, 124 (1.4%) with interferon beta-1b, 117 (1.3%) with alemtuzumab, 36 (.4%) with siponimod, 24 (.3%) with cladribine, and 12 (.1%) with rituximab. Reports were mostly made by patients (78.3%) and highest in fifth and sixth decades of life. OpenFDA analyses showed increased ROR (ROR 95% confidence interval) of alopecia in females with teriflunomide (18.00, 17.12-18.93), alemtuzumab (1.43, 1.16-1.76), dimethyl fumarate (1.26, 1.18-1.34), and ocrelizumab (1.28, 1.11-1.49). Increased ROR in males was associated with teriflunomide (24.65, 20.72-29.31). CONCLUSION: We identified many reports of alopecia for DMTs in addition to teriflunomide. Within the limitations of the database, increased RORs of alopecia were observed for females treated with alemtuzumab, dimethyl fumarate, and ocrelizumab. The source of reporting was largely driven by female patients. Possible alopecia, even if transient, should be considered during patient education when starting DMTs.

Atypical Presentation of Acute Mitral Regurgitation Secondary to Papillary Muscle Rupture.

Acute mitral regurgitation (MR) is a life-threatening condition presenting with severe decompensated heart failure due to sudden retrograde blood flow into the left atrium. The causes are broadly classified into ischemic and non-ischemic. Rapid and accurate diagnosis of acute MR and its potential causes is essential. This case uniquely highlights an atypical presentation of severe MR secondary to papillary muscle rupture without a known, identifiable cause. Therefore, suspicion of acute MR should be high if clinical symptoms are present, even without known risk factors, due to the high morbidity and mortality associated with delayed management.

Testosterone-Mediated Aggression in Angelman Syndrome Treated With Leuprolide and Orchiectomy.

Angelman syndrome (AS) is a rare genetic imprinting disorder characterized by a maternal microdeletion of the 15q11q13 locus. It is traditionally associated with intellectual disability, inappropriate laughing, and a happy demeanor. Here, we report a patient with AS who presented with aggression and hypersexuality and was successfully treated with leuprolide injections for nine years until a definitive orchiectomy was performed. To the best of our knowledge, this is the first report of castration as a treatment for refractory behavioral symptoms in a patient with AS.

Disproportional increase in psoriasis reports in association with B cell depleting therapies in patients with multiple sclerosis.

BACKGROUND: Some pathways involved in the pathogenesis of psoriasis share similarities with processes involved in multiple sclerosis (MS) pathogenesis. However, the association between MS and psoriasis is poorly understood. Since disease-modifying therapies for MS have various targets, it may be possible that the occurrence of psoriasis varies by drug. OBJECTIVE: To analyze the frequency of psoriasis reports in patients treated with various disease-modifying therapies for MS. METHODS: Data was collected using the FDA Adverse Event Reporting System (FAERS) and OpenFDA database between January 2009 and June 2020. The study analyzed total reports of psoriasis out of total reports in the "Skin and Subcutaneous Tissue Disorders" category for each drug and explored age, sex distribution, and report source. OpenFDA data was used to perform statistical analyses including reporting odds ratios (ROR) and information components. RESULTS: The study identified 517 psoriasis reports of 45,547 total skin and subcutaneous tissue disorders (1.13%) in FAERS. The highest proportions of reports in this study were associated with rituximab, ocrelizumab, and interferon beta 1a. The lowest proportion of reports were associated with glatiramer acetate, alemtuzumab, dimethyl fumarate and teriflunomide. Reports of other autoimmune skin disorders were minimal (29 vitiligo, 33 pemphigoid, and 7 pemphigus). Patients primarily drove reports for most DMTs versus healthcare providers. The proportion of reports from female patients were the highest for each DMT except alemtuzumab. OpenFDA query retrieved 302 total reports of psoriasis. Significantly increased reporting odds ratios (RORs, 95% confidence interval) of psoriasis were noted for rituximab (7.14, 3.92-13.00), ocrelizumab (3.79, 2.74-5.23), and fingolimod (1.33, 1.01-1.76). Significantly decreased RORs were noted for natalizumab (0.53, 0.36-0.80), glatiramer acetate (0.58, 0.35-0.96), and dimethyl fumarate (0.71, 0.53-0.94). CONCLUSION: There are frequent reports of psoriasis in MS patients treated with various DMTs. However, reports and RORs were disproportionally high in association with B cell depleting therapies. Further research is required to determine if certain DMTs may serve as better options for individuals affected by, or at high-risk for developing psoriasis.

Endovascular treatment of a sacral dural arteriovenous fistula.

Spinal dural arteriovenous fistula (SDAVF) is a rare pathological communication between arterial and venous vessels within the spinal dural sheath. Clinical presentation includes progressive spinal cord symptoms including gait difficulty, sensory disturbances, changes in bowel or bladder function, and sexual dysfunction. These fistulas are most often present in the thoracolumbar region. Diagnoses of SDVAFs are commonly missed, possibly due to the low index of suspicion, non-specific symptoms and challenging imaging. In this case report, we describe a rare presentation of a sacral SDAVF which was detected by collective efforts between endovascular neurosurgery and interventional radiology. We outline the diagnostic and imaging challenges we faced to discover the fistula. In particular, mechanical pump injection instead of hand injection during angiography was required to reveal the fistula. Following identification, the fistula was successfully treated endovascularly by using onyx (ethylene vinyl alcohol glue), a less invasive alternative to surgical intervention.