A Multicenter Allelic Analysis of Diffuse Idiopathic Skeletal Hyperostosis: Nature Versus Nurture?

BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is an incompletely defined disease process with no known unifying pathophysiological mechanism. OBJECTIVE: To our knowledge, no genetic studies have been performed in a North American population. To summarize genetic findings from previous studies and to comprehensively test for these associations in a novel and diverse, multi-institutional population. METHODS: Cross-sectional, single nucleotide polymorphism (SNP) analysis was performed in 55 of 121 enrolled patients with DISH. Baseline demographic data were available on 100 patients. Based on allele selection from previous studies and related disease conditions, sequencing was performed on COL11A2, COL6A6, fibroblast growth factor 2 gene, LEMD3, TGFB1, and TLR1 genes and compared with global haplotype rates. RESULTS: Consistent with previous studies, older age (mean 71 years), male sex predominance (80%), a high frequency of type 2 diabetes (54%), and renal disease (17%) were observed. Unique findings included high rates of tobacco use (11% currently smoking, 55% former smoker), a higher predominance of cervical DISH (70%) relative to other locations (30%), and an especially high rate of type 2 diabetes in patients with DISH and ossification of the posterior longitudinal ligament (100%) relative to DISH alone (100% vs 47%, P < .001). Compared with global allele rates, we found higher rates of SNPs in 5 of 9 tested genes ( P < .05). CONCLUSION: We identified 5 SNPs in patients with DISH that occurred more frequently than a global reference. We also identified novel environmental associations. We hypothesize that DISH represents a heterogeneous condition with both multiple genetic and environmental influences.

Hypertrophic olivary degeneration and palatal myoclonus from a Streptococcus intermedius infection of the brain: illustrative case.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare condition that can occur after disruption of the Guillain-Mollaret triangle. Clinically, HOD can present with palatal myoclonus with or without oculopalatal tremor, which sometimes results in symptomatic dysphagia and/or speech abnormalities. This condition is commonly associated with vascular lesions, with only three prior reported cases of HOD resulting from intracranial abscess. OBSERVATIONS: An otherwise healthy patient developed multiple intracranial abscesses. Biopsy showed gram-positive cocci; however, culture findings were negative. Polymerase chain reaction (PCR) identified Streptococcus intermedius. The patient demonstrated palatal myoclonus and vertical nystagmus, which resulted in persistent mild dysphagia and altered speech intonation. After appropriate antimicrobial therapy with resolution of the enhancing lesions, symptoms persisted. Follow-up imaging demonstrated progressive hypertrophy of the right olive with persistent disruption of the right-sided rubro-olivo fiber pathways. LESSONS: Although HOD classically occurs after vascular insult, it can also be seen as a postinfectious sequela. Despite eradication of the infection, palatal myoclonus and oculopalatal tremor may have a persistent impact on quality of life due to impaired speech and swallowing. This case emphasizes the utility of universal PCR in detecting fastidious organisms as well as diffusion tensor imaging for characterization of disrupted fiber pathways.

Techniques for management and avoidance of ventriculoatrial shunt disconnection: illustrative cases.

BACKGROUND: Ventriculoatrial (VA) shunt disconnection can result in distal catheter migration into the cardiopulmonary vasculature. There is little guidance in the current literature on how to prevent and manage this uncommon yet potentially serious complication. The authors reviewed the existing literature and described three instances of distal shunt migration VA shunts and offered insight on methods to mitigate such complications. OBSERVATIONS: Eighteen patients were identified with VA shunts. Of these patients, seven were identified as having a connector in the neck, three of which were associated with distal disconnection and migration. In all three cases, the distal catheter was retrieved via an endovascular approach in conjunction with transesophageal echocardiography to assess for retrieval feasibility. LESSONS: The authors recommended the avoidance of a straight connector when performing VA shunt placement. When distal catheter migration occurs, collaboration with interventional cardiology is advisable when possible.

Minimally Invasive Posterior Cervical Discectomy: 2-Dimensional Operative Video.

Minimally invasive posterior cervical microdiscectomy is an appropriate surgical approach for patients with foraminal stenosis from herniated disc with radicular symptoms that is not responsive to conservative management. While anterior cervical discectomy and fusion (ACDF) or arthroplasty is increasingly utilized to treat herniated disc, a posterior approach eliminates the risk of potential approach related injuries to the esophagus, carotid artery, or recurrent laryngeal nerve. Additional benefits of posterior decompression include avoidance of instrumentation, which represents an increased healthcare cost, as well as potential long-term risks of adjacent-level pathologies or device failures. A traditional open posterior cervical approach has the potential to cause significant postoperative pain due to dissection of the paraspinal musculature and the potential for disrupting the posterior tension band with inadvertent injury to the interspinous ligaments. Such disadvantages are reduced by utilizing the minimally invasive technique where a small tubular working channel is placed through a muscle splitting technique via a paramedian approach. This technique minimizes the need for muscle stripping, and thus decreases postoperative functional and structural disturbance. Discectomy in this case can also be safely performed with minimal retraction at the axilla of the nerve root. Additionally, this approach can be utilized in an ambulatory setting, which coupled with the lack of any additional instrumentation helps contribute to the overall healthcare cost savings of such a procedure. This video describes how the minimally invasive posterior cervical discectomy can be effectively and safely performed in this illustrative case. The patient consented to the procedure and publication.

Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study.

BACKGROUND: Despite the well-documented utility of responsive neurostimulation (RNS, NeuroPace) in adult epilepsy patients, literature on the use of RNS in children is limited. OBJECTIVE: To determine the real-world efficacy and safety of RNS in pediatric epilepsy patients. METHODS: Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers. Reduction of disabling seizures and complications were evaluated for children (<18 yr) and young adults (>18 yr) and compared with prior literature pertaining to adult patients. RESULTS: Of 35 patients identified, 17 were <18 yr at the time of RNS implantation, including a 3-yr-old patient. Four patients (11%) had concurrent resection. Three complications, requiring additional surgical interventions, were noted in young adults (2 infections [6%] and 1 lead fracture [3%]). No complications were noted in children. Among the 32 patients with continued therapy, 2 (6%) achieved seizure freedom, 4 (13%) achieved ≥90% seizure reduction, 13 (41%) had ≥50% reduction, 8 (25%) had <50% reduction, and 5 (16%) experienced no improvement. The average follow-up duration was 1.7 yr (median 1.8 yr, range 0.3-4.8 yr). There was no statistically significant difference for seizure reduction and complications between children and young adults in our cohort or between our cohort and the adult literature. CONCLUSION: These preliminary data suggest that RNS is well tolerated and an effective off-label surgical treatment of drug-resistant epilepsy in carefully selected pediatric patients as young as 3 yr of age. Data regarding long-term efficacy and safety in children will be critical to optimize patient selection.

Minimally Invasive Techniques for Iliac Bolt Placement: 2-Dimensional Operative Video.

As the popularity of minimally invasive surgery (MIS) continues to grow, novel techniques are needed to meet the demands of multisegment fixation for advanced spinal diseases. In one such example, iliac bolts are often required to anchor large fusion constructs, but MIS technical notes are missing from the literature. A 67-yr-old female presented with a symptomatic coronal deformity: preoperative pelvic incidence = 47°, pelvic tilt = 19°, and lumbar lordosis = 29°, sagittal vertical axis = +5.4 cm with 30° of scoliosis. The operative plan included T10-ilium fusion with transforaminal interbody grafts at L2-3, L3-4, L4-5, and L5-S1. The intraoperative video is of minimally invasive placement of iliac bolts using the O-Arm Surgical Imaging System (Medtronic®). The patient consented to the procedure. A mini-open exposure that remains above the fascial planes allows for multilevel instrumentation with appropriate decompression at the interbody segments. After the placement of the pedicle screws under image-guidance, the direction is turned to the minimally invasive iliac bolts. Following the trajectory described in the standard open approach,1 the posterior superior iliac spine (PSIS) is identified with the navigation probe, which will guide the Bovie cautery through the fascia. This opening assists in the trajectory of the navigated-awl tap toward the anterior superior iliac spine (ASIS). Next, 8.5 mm x 90 mm iliac screws were placed in the cannulated bone under navigation. After intraoperative image confirmation of screw placement, the contoured rods are threaded under the fascia. The setscrews lock the rod in position. MIS approaches obviate cross-linking the rods, rendering pelvic fixation more facile. This technique allows for minimal dissection of the posterior pelvic soft tissue while maintaining adequate fixation.

Acute thoracic disc heralded by change in spinal cord stimulation pattern: illustrative case.

BACKGROUND: Spinal cord stimulation (SCS) uses unique electric stimulation parameters to selectively treat specific regions of chronic or refractory back pain. Changing these parameters can lead to spreading paresthesia and/or pain beyond the desired region. OBSERVATIONS: A patient with a history of stable, successful SCS treatment presented with acute development of paresthesias that were relieved by reduction of stimulation parameters. The patient required paradoxically lower SCS settings for control of chronic back pain. This presentation prompted further investigation, which revealed a new disc protrusion and cord compression at the level of the paddle lead. LESSONS: In patients with SCS, a new onset of back pain accompanied by acute paresthesia that is reversible by reducing the SCS amplitude warrants investigation for new spine pathology.

Contemporary Analysis of Minimal Clinically Important Difference in the Neurosurgical Literature.

BACKGROUND: Minimal clinically important difference (MCID) is determined when a patient or physician defines the minimal change that outweighs the costs and untoward effects of a treatment. These measurements are "anchored" to validated quality-of-life instruments or physician-rated, disease-activity indices. To capture the subjective clinical experience in a measurable way, there is an increasing use of MCID. OBJECTIVE: To review the overall concept, method of calculation, strengths, and weaknesses of MCID and its application in the neurosurgical literature. METHODS: Recent articles were reviewed based on PubMed query. To illustrate the strengths and limitations of MCID, studies regarding the measurement of pain are emphasized and their impact on subsequent publications queried. RESULTS: MCID varies by population baseline characteristics and calculation method. In the context of pain, MCID varied based on the quality of pain, chronicity, and treatment options. CONCLUSION: MCID evaluates outcomes relative to whether they provide a meaningful change to patients, incorporating the risks and benefits of a treatment. Using MCID in the process of evaluating outcomes helps to avoid the error of interpreting a small but statistically significant outcome difference as being clinically important.

Risk Factors Associated with Symptomatic Deep Vein Thrombosis Following Elective Spine Surgery: A Case-Control Study.

BACKGROUND: Few studies provide insight into risk factors (RFs) associated with postoperative deep vein thrombosis (DVT) following elective spinal surgery. DVTs are detrimental in this population because of the risk of pulmonary embolization or surgical site hemorrhage with treatment. OBJECTIVE: Elective spine surgery patients have a low incidence of DVT, thus a case-control study was selected to investigate RFs associated with postoperative, symptomatic DVT. METHODS: Cases were matched to controls in a 1:2 ratio based on surgery type. Risk of having a prior DVT and choice of subcutaneous heparin dosing following surgery was analyzed in a multivariate regression model with other potentially confounding variables. RESULTS: A total of 195 patients were included in this study. Independent of patient age, history of DVT was associated with postoperative symptomatic DVT (odds ratio [OR], 4.09; 95% confidence interval [CI], 1.22-13.78). Two versus 3 times daily postoperative heparin dosing (OR, 1.56; 95% CI, 0.32-7.56), surgery length (OR, 1.32; 95% CI, 0.98-1.79), and patient age (OR, 1.04; 95% CI, 1.0-1.08) were not statistically significant, independent RFs. Older age and longer length of surgery trended toward association with DVT without reaching significance. Length of stay was increased from 3-5 days (P < 0.001) in DVT patients compared with controls. CONCLUSIONS: These results suggest that patients with a history of DVT undergoing elective spinal surgery are at higher risk of developing symptomatic DVT postoperatively resulting in significantly increased length of stay. Further studies on additional preoperative screening and medical optimization in elective spine surgery patients may help reduce the rate of symptomatic, postoperative DVT.

Surgical Treatment of Intracranial Anterior Ethmoidal Aneurysm: Case Report, Literature Review, and Surgical Video.

BACKGROUND: Anterior ethmoid aneurysms are rare with 5 cases of intracranial rupture and 3 cases of life-threatening epistaxis described in recent literature. We present a case of an intracranial ruptured anterior ethmoid aneurysm treated surgically with a favorable outcome. CASE DESCRIPTION: A 64-year-old male presenting with a headache was found to have a right frontal intracranial hemorrhage with an associated 1.5 cm length × 1.8 cm maximal width anterior ethmoidal artery aneurysm. No definitive etiology of the aneurysm was identified. The aneurysm was treated using a bifrontal craniotomy with interhemispheric microdissection, clip ligation, and resection of the aneurysm dome for pathologic analysis, which ruled out a mycotic etiology. He recovered uneventfully and returned to work with no identifiable neurologic deficit. CONCLUSIONS: Consistent with prior reports, an intracranial, anterior ethmoidal artery aneurysm can occur in isolation without an associated vascular malformation. On the basis of a literature review and this case, surgical ligation is considered effective and possibly superior over endovascular treatment due to the risk of injury to the orbital vascular supply with transarterial treatment.

Adapting to Space Limitations During Prone Real-Time Magnetic Resonance Imaging-Guided Stereotaxic Laser Ablation: Technical Pearls.

BACKGROUND: New techniques of intraoperative magnetic resonance imaging (MRI)-guided stereotaxy enable minimally invasive approaches to intracranial pathology. Laser interstitial thermal therapy (LITT), convection-enhanced drug delivery, and stereotactic biopsy can be performed with a real-time confirmation of location and the ability to adjust for intracranial shift during the procedure. However, these procedures are constrained by patient positioning and the need for trajectories that avoid collision between stereotactic elements and the small MRI bore. To our knowledge, this is the first report to outline the technical details of safe intraoperative MRI (iMRI)-guided stereotaxy, performed with prone positioning. OBJECTIVE: To present technical pearls to guide the safe conduction of iMRI-guided stereotaxy and LITT while in the prone position. METHODS: The details of the positioning and trajectories for a series of patients who underwent Clearpoint® (MRI Interventions Inc) frameless real-time MRI-guided stereotaxis using a posterior approach were reviewed. RESULTS: In this series, 5 patients underwent selective amygdalohippocampectomy, and 2 underwent tumor biopsy/ablation while in the prone position without any complications. CONCLUSION: Prone iMRI procedures can be performed safely even in a 60-cm MRI bore.

Diagnosis of Ventricular Shunt Infection in Children: A Systematic Review.

BACKGROUND: No widely accepted gold standard for diagnosis of shunt infection exists, with definitions variable among clinicians and publications. This article summarizes the utility of commonly used diagnostic tools and provides a comprehensive review of optimal measures for diagnosis. METHODS: A query of PubMed was performed extracting articles related to shunt infection in children. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, resulting in 1756 articles related to shunt infection, 49 of which ultimately met inclusion criteria. RESULTS: Of the 49 articles included in the analysis, 9 did not define infection, 9 used culture alone, 9 used cultures and/or symptomatology, and 4 used a combination of cultures, cerebral spinal fluid (CSF) pleocytosis and symptomatology. The remainder of the studies used definitions from the Centers for Disease Control and Prevention (n = 2) and the Hydrocephalus Clinical Research Network (n = 2) or borrowed elements from these definitions. Variation in definition stems from the lack of sensitivity and specificity of commonly used signs, symptoms, and tests. Shunt tap alone is considered half as sensitive as hardware culture. Fever upon presentation was present in 16% to 42% of cases. CSF pleocytosis combined with fever has a sensitivity of 82% and specificity of 99%. CSF eosinophilia, lactic acid, serum anti-Staphylococcus epidermidis titer, procalcitonin, and C-reactive protein are non-specific and their utility is not well established. CONCLUSIONS: The definition of shunt infection is variable across studies, with CSF culture and/or symptomatology being the most commonly utilized parameters.

Treatment of a Staphylococcus lugdunensis cervical epidural abscess.

First reported in 1988, Staphylococcus lugdunensis is a virulent coagulase-negative Staphylococcus species often associated with endocarditis. This is the first case report describing this infection in the cervical spine. A 58-year-old, left-handed Caucasian woman with no significant medical history presented with neck and left arm pain. Neurological examination revealed mild left deltoid 4/5 weakness and myelopathy. She was found to have an epidural cervical spinal cord mass that was causing severe cord compression and underwent partial anterior cervical decompression of the mass. On entering what was believed to be the mass, yellow-tinged fluid was encountered. An abscess was immediately suspected, so the dura was not entered. The specimen sent for culture was identified a day later as S. lugdunensis A two-dimensional echocardiogram was negative for vegetations. A peripherally inserted central catheter line was placed and the patient discharged on 6 weeks of physical therapy and 6-8 weeks of intravenous cefazolin.

Delirium and topographical disorientation associated with glioblastoma multiforme tumour progression into the isthmus of the cingulate gyrus.

Since there is no cure for glioblastoma multiforme (GBM), the goal of treatment becomes prolonging the survival through cytoreduction while minimising neurological deficits. In this case report, laser interstitial thermal therapy (LITT) was used once the tumour progressed into the isthmus of the cingulate gyrus. One year after temporal lobectomy, disorders of memory, emotion, personality and navigation, likely related to limbic system involvement along with hallucinations and fluctuating cognition occurred as the tumour progressed. After ablation of the posterior cingulum, worsening of topographical disorientation was observed.Per literature review, delirium has been noted in patients with strokes involving the right-sided temporo-parieto-occipital junction, and topographical disorientation has been associated with lesions of the right posterior cingulum. Alternative causes of these deficits were ruled out, leaving structural changes as the primary explanation. This is the first report of the neurological deficits associated with tumour progression and vasogenic oedema in this region.

Beta-2 transferrin is detectable for 14 days whether refrigerated or stored at room temperature.

BACKGROUND: The effect of time and temperature on beta-2 transferrin stability in cerebrospinal fluid (CSF) is not well established. After collecting nasal CSF for testing, beta-2 transferrin has been found to be stable and detectable for 1 week, whether being refrigerated or stored at room temperature. The purpose of this study was to determine if beta-2 transferrin remained detectable longer than 1 week and whether refrigeration improved its detectability. METHODS: In patients undergoing therapeutic CSF diversion, 2-mL CSF samples were collected from 18 patients. The samples were divided and stored either at room temperature, or at 4°C, and tested for beta-2 transferrin at 7 and 14 days. CSF was collected from external ventricular drains (EVDs) (n = 15), lumbar drains (n = 2), and subdural drains (n = 1). RESULTS: Of the 18 CSF samples originally testing positive for beta-2 transferrin, none turned negative at 7 or 14 days, in both the refrigerated and room temperature groups (95% confidence interval [CI], 0% to 18.5%). CONCLUSION: Beta-2 transferrin remained detectable for 14 days in all CSF samples, regardless of being stored at 4°C or room temperature.

Identification of miRNomes associated with adult neurogenesis after stroke using Argonaute 2-based RNA sequencing.

Neurogenesis is associated with functional recovery after stroke. However, the underlying molecular mechanisms have not been fully investigated. Using an Ago2-based RNA immunoprecipitation to immunoprecipated Ago2-RNA complexes followed by RNA sequencing (Ago2 RIP-seq) approach, we profiled the miRNomes in neural progenitor cells (NPCs) harvested from the subventricular zone (SVZ) of the lateral ventricles of young adult rats. We identified more than 7 and 15 million reads in normal and ischemic NPC libraries, respectively. We found that stroke substantially changed Ago2-associated miRNA profiles in NPCs compared to those in non-ischemic NPCs. We also discovered a new complex repertoire of isomiRs and multiple miRNA-miRNA* pairs and numerous novel miRNAs in the non-ischemic and ischemic NPCs. Among them, pc-3p-17172 significantly regulated NPC proliferation and neuronal differentiation. Collectively, the present study reveals profiles of Ago2-associated miRNomes in non-ischemic and ischemic NPCs, which provide a molecular basis to further investigate the role of miRNAs in mediating adult neurogenesis under physiological and ischemic conditions.

Quantification of Plasmodium falciparum malaria from complex infections in the Peruvian Amazon using quantitative PCR of the merozoite surface protein 1, block 2 (PfMSP1-B2): in vitro dynamics reveal density-dependent interactions.

The majority of Plasmodium falciparum field isolates are defined as complex infections because they contain multiple genetically distinct clones. Studying interactions between clones in complex infections in vivo and in vitro could elucidate important phenomena in malaria infection, transmission and treatment. Using quantitative PCR (qPCR) of the P. falciparum merozoite surface protein 1, block 2 (PfMSP1-B2), we provide a sensitive and efficient genotyping method. This is important for epidemiological studies because it makes it possible to study genotype-specific growth dynamics. We compared 3 PfMSP1-B2 genotyping methods by analysing 79 field isolates from the Peruvian Amazon. In vivo observations from other studies using these techniques led to the hypothesis that clones within complex infections interact. By co-culturing clones with different PfMSP1-B2 genotypes, and measuring parasitaemia using qPCR, we found that suppression of clonal expansion was a factor of the collective density of all clones present in a culture. PfMSP1-B2 qPCR enabled us to find in vitro evidence for parasite-parasite interactions and could facilitate future investigations of growth trends in naturally occurring complex infections.