Cytochemical Characterization of Cerebrospinal Fluid Macrophage Inclusions in Pediatric Patients Receiving Intrathecal Nusinersen (SPINRAZA®) for Spinal Muscular Atrophy.

INTRODUCTION: Spinal muscular atrophy (SMA) is a debilitating neuromuscular disorder caused by biallelic deletion of the SMN1 gene. Nusinersen, an antisense oligonucleotide delivered intrathecally, binds to the pre-mRNA of SMN1's pseudogene, SMN2, to prevent exon skipping and produce functional SMN protein to compensate for the deficiency caused by SMN1 deletion. CASE PRESENTATION: We reviewed 15 cerebrospinal fluid (CSF) cytology specimens from 8 patients receiving nusinersen for SMA. Macrophages with peculiar inclusions ("nusinophages") were seen in 8 specimens from 4 of the patients: 1 infant and 3 children with SMA type 1. This finding has only previously been reported in adults with SMA types 2 and 3 and in 2 infants with SMA type 1. DISCUSSION/CONCLUSION: Specimens containing nusinophages had a significantly higher proportion of macrophages and lower proportion of lymphocytes than those in which nusinophages were not detected. The macrophage inclusions do not represent iron or microorganisms and instead are composed, at least in part, of glycosaminoglycans. Because CSF is a common specimen type, cytotechnologists and cytopathologists need to be aware of these inclusions, so they do not interpret them erroneously as evidence of infection or hemorrhage, especially in light of the fact that oligonucleotide therapy has been approved for a variety of conditions and is currently under investigation for intrathecal delivery in several other neurodegenerative disorders.

A comprehensive institutional overview of intrathecal nusinersen injections for spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal-recessive neuromuscular disorder resulting in progressive muscle weakness. In December 2016, the U.S. Food and Drug Administration approved the first treatment for SMA, a drug named nusinersen (Spinraza) that is administered intrathecally. However many children with SMA have neuromuscular scoliosis or spinal instrumentation resulting in challenging intrathecal access. Therefore alternative routes must be considered in these complex patients. OBJECTIVE: To investigate routes of drug access, we reviewed our institutional experience of administering intrathecal nusinersen in all children with spinal muscular atrophy regardless of spinal anatomy or instrumentation. MATERIALS AND METHODS: We reviewed children with SMA who were referred for intrathecal nusinersen injections from March to December 2017 at our institution. In select children with spinal hardware, spinal imaging was requested to facilitate pre-procedure planning. Standard equipment for intrathecal injections was utilized. All children were followed up by their referring neurologist. RESULTS: A total of 104 intrathecal nusinersen injections were performed in 26 children with 100% technical success. Sixty procedures were performed without pre-procedural imaging and via standard interspinous technique. The remaining 44 procedures were performed in 11 complex (i.e. neuromuscular scoliosis or spinal instrumentation) patients requiring pre-procedural imaging for planning purposes. Nineteen of the 44 complex procedures were performed via standard interspinous technique from L2 to S1. Twenty-two of the 44 complex procedures were performed using a neural-foraminal approach from L3 to L5. Three of the 44 complex procedures were performed via cervical puncture technique. There were no immediate or long-term complications but there was one child with short-term complications of meningismus and back pain at the injection site. CONCLUSION: Although we achieved 100% technical success in intrathecal nusinersen administration, our practices evolved during the course of this study. As a result of our early experience we developed an algorithm to assist in promoting safe and effective nusinersen administration in children with spinal muscular atrophy regardless of SMA type, abnormal spinal anatomy and complex spinal instrumentation.

Safety and effectiveness of percutaneous cholecystostomy in critically ill children who are immune compromised.

BACKGROUND: Acalculous cholecystitis is known to develop in critically ill patients without cystic duct obstruction. In the past, treatment for acalculous cholecystitis has been cholecystectomy; however, many children who are critically ill are Percutaneous cholecystostomy is likely the procedure of choice in this subgroup of patients. OBJECTIVE: To assess the safety and effectiveness of percutaneous cholecystostomy in critically ill and immune-compromised children with acalculous cholecystitis. MATERIALS AND METHODS: Retrospective review of immune-compromised and critically ill children who underwent percutaneous cholecystostomy between 2006 and 2013. Diagnostic imaging performed included ultrasound, CT and hepatobiliary scintigraphy. Every percutaneous cholecystostomy was performed using imaging guidance. RESULTS: Ten critically ill and immune-compromised children with acalculous cholecystitis underwent percutaneous cholecystostomy. Seven boys and 3 girls, ranging in age from 10 months to 15 years 8 months, were treated. Six of the immune-compromised children had received a bone marrow transplant for leukemia (5 children) or severe combined immunodeficiency (SCID) (1 child), and ranged from 18 to 307 days post bone marrow transplant at the time of their percutaneous cholecystostomy. Of the remaining four immune-compromised children with acalculous cholecystitis who underwent percutaneous cholecystostomy, two had leukemia, one had SCID and lymphoma, and the fourth was undergoing treatment for undifferentiated germ cell tumor. The 10 percutaneous gallbladder drains were placed using a transhepatic approach, except one unintentional transperitoneal approach. There were no complications. Three gallbladder drains were removed in Interventional Radiology. Those three patients had a return to normal gallbladder function and didn't require cholecystectomy. Two drains were removed during cholecystectomy and another as an outpatient. Four patients died in the hospital due to multiorgan system failure, with indwelling gallbladder drains. CONCLUSION: Percutaneous cholecystostomy is a safe procedure in immune-compromised and critically ill children with acalculous cholecystitis. Percutaneous cholecystostomy may obviate the need for future cholecystectomy.

Benefit of fluoroscopically guided intraarticular, long-acting corticosteroid injection for subtalar arthritis in juvenile idiopathic arthritis.

BACKGROUND: Children with arthritis may endure a lifetime of disfigurement, dysfunction, and pain if acute inflammation progresses to chronic changes in the joint cartilage and underlying bone. Intraarticular steroids have become an integral component of treatment, but at times are difficult to deliver to joints, such as the subtalar joint, that have complex anatomies. OBJECTIVE: We describe our technique and outcomes using fluoroscopically guided intraarticular subtalar steroid injection in patients with active symptoms of juvenile idiopathic arthritis (JIA). MATERIALS AND METHODS: Fluoroscopically guided subtalar joint injections were performed in 38 children (mean age 6.7 years). Medical records were reviewed retrospectively and improvement was evaluated clinically by the degree of foot movement in eversion and inversion. RESULTS: Subtalar joint injection was technically successful in 100% of the JIA patients with improvement in physical symptoms in 34/38 (89%). Of the 38 children, 32 were followed up within 13 weeks of the initial injection and, therefore, satisfied the eligibility criteria for resolution of arthritis. Of these 32 children, 14 showed clinical resolution (44%). The mean duration of improvement was 1.2 +/- 0.9 years. Children with a longer interval (>1 year) from diagnosis to treatment had significantly less resolution (P = 0.04). Local subcutaneous atrophy or hypopigmentation were observed in 53% of the children after steroid injection (20/38). These minor complications were associated with a greater volume of steroid injected into the site per child (P = 0.02). CONCLUSION: Fluoroscopically guided subtalar joint injection is an effective treatment for subtalar arthropathy. Prompt referral for intraarticular steroid treatment in the acute phase improves response. Skin changes often occur at the injection site, and specific precautions should be employed to reduce this risk. Prospective study is indicated to determine the most effective treatment strategy to prevent long-term pain and disability.

CT-guided percutaneous steroid injection for management of inflammatory arthropathy of the temporomandibular joint in children.

OBJECTIVE: The purposes of this study were to retrospectively review an injection technique, to develop a grading system for evaluation of imaging findings, and to report preliminary outcome related to percutaneous CT-guided steroid injection into the temporomandibular joints of children with inflammatory arthropathy. CONCLUSION: CT-guided steroid injection into the temporomandibular joint of children with inflammatory arthropathy results in clinical and imaging improvement in a substantial proportion of children treated.

Benefit of intraarticular corticosteroid injection under fluoroscopic guidance for subtalar arthritis in juvenile idiopathic arthritis.

OBJECTIVE: To determine the demographics of subtalar arthritis, the response to intraarticular corticosteroid injection, and the injection complication rate in a clinic sample of children with juvenile idiopathic arthritis (JIA). METHODS: A chart review was performed of all patients at a tertiary medical center who underwent subtalar corticosteroid injection during the past 5 years. Injection of 1 ml of triamcinolone hexacetonide or acetonide into the midsubtalar joint was performed using a lateral oblique approach under fluoroscopic guidance. Improvement was defined by enhanced foot inversion and eversion at the following office visit. RESULTS: Thirty-eight patients underwent 55 subtalar injections during the study period. All 7 JIA subtypes were represented. Thirty-one patients (82%) had subtalar arthritis at time of JIA diagnosis and 32 (84%) had concomitant tibiotalar ankle arthritis. Improvement was observed following 34 (89%) of the initial 38 injections. The mean duration of improvement was 1.2 years (SD +/- 0.9). Twenty patients (53%) developed hypopigmentation or subcutaneous atrophy. This complication was associated with a higher volume of injected corticosteroid per patient weight (p = 0.02) and with less efficacious injections (p = 0.04). CONCLUSION: Subtalar arthritis in children with JIA is common. Similar to other joints, subtalar arthritis responds to corticosteroid injection in approximately 90% of cases and often remains improved for greater than one year. Hypopigmentation and subcutaneous atrophy are frequent complications and are likely related to the dose of injected corticosteroid and possibly the accuracy of needle placement.

Interventional radiology: a modular approach.

The authors offer a modular approach to the development of new procedures in the field of pediatric interventional radiology as a conceptual model and a springboard for further discussion.

Utility of corticosteroid injection for temporomandibular arthritis in children with juvenile idiopathic arthritis.

OBJECTIVE: To assess the effects of computed tomography (CT)-guided injection of corticosteroid into the temporomandibular joint (TMJ) in children with juvenile idiopathic arthritis (JIA) and clinical and magnetic resonance imaging (MRI) evidence of TMJ inflammation. METHODS: Twenty-three children ages 4-16 years with JIA and MRI evidence of TMJ inflammation received CT-guided TMJ injections of corticosteroid (triamcinolone acetonide [n = 16] or triamcinolone hexacetonide [n = 7]). Jaw pain or dysfunction and maximal incisal opening (MIO) distance were assessed before and after injection. Fourteen patients had followup MRI studies of the TMJ 6-12 months after injection. RESULTS: Of the 13 patients with symptoms of jaw pain prior to corticosteroid treatment, 10 (77%) had complete resolution of pain (P < 0.05). Prior to corticosteroid injection, MIO in all 23 patients was below age-matched normal values. After injection, the MIO was improved by at least 0.5 cm in 10 patients (43%) (P = 0.0017). Patients under 6 years of age at the time of injection showed the best response, with a postinjection MIO similar to that in age-matched controls (P = 0.2267). There was involvement of 23 TMJs in the 14 patients who had followup MRI studies; resolution of effusions was observed in 11 (48%) of the TMJs. Other than short-term facial swelling in 2 patients, there were no side effects. CONCLUSION: The majority of children with symptomatic TMJ arthritis improved after intraarticular corticosteroid injection. Approximately half the patients experienced significant improvement in MIO and TMJ effusion. These data suggest that corticosteroid injection may be a useful procedure for the prevention and treatment of morbidities associated with TMJ arthritis in JIA.

Transgluteal approach for draining pelvic fluid collections in pediatric patients.

PURPOSE: To evaluate a transgluteal approach for draining pelvic fluid collections in pediatric patients. MATERIALS AND METHODS: Institutional review board approval and informed consent for interventional procedures were obtained. From September 1995 to December 2002, 140 abdominopelvic fluid collections were drained at two institutions. Retrospective analysis of a prospectively gathered procedural database revealed that a transgluteal approach was used to drain 53 of these 140 collections (38%) in 51 patients (29 female, 22 male; mean age, 11.2 years; age range, 0.2-19 years). All patients received antibiotics before the procedure. A retrospective analysis was conducted of the patients' medical records and diagnostic imaging and interventional procedure findings, including the reason for referral; location, volume, and character of collections; method and equipment used for evacuation; duration of therapy; evidence of complications; results of microbiologic examination of specimens; and success rates. RESULTS: Transgluteal drainage was performed with computed tomographic (CT) guidance in 45 of the 53 collections (85%), with fluoroscopic guidance in three (6%), and with a combination of both modalities in five (9%). A drainage catheter was successfully placed in 49 collections; four small collections were aspirated without drain placement. Infected fluid was obtained from 41 collections, and serosanguineous fluid was obtained from 12 collections. The mean volume aspirated was 80 mL (2-600 mL). A positive culture was obtained at 28 of the 53 procedures. The mean duration of catheter placement was 4 days (range, 2-14 days). There were no major complications. CONCLUSION: The transgluteal approach to the drainage of abdominopelvic fluid collections with imaging guidance is safe and effective.

Inadvertent extra-epidural catheter placement in an infant.

We report the inadvertent passage of an epidural catheter threaded from the caudal space out of a lumbar intervertebral foramen and into the lower thoracic paravertebral space in an infant. We identified the errant catheter by radiography and removed it without sequelae.

Pseudoaneurysm in children: diagnosis and interventional management.

Pseudoaneurysms (PAn) are uncommon in adults and even less common in children. They are most often encountered after iatrogenic arterial injury. Presentation may be substantially delayed after the iatrogenic event, and diagnosis can be difficult, especially when the PAn occurs in an unexpected location. Treatment of PAn has evolved during the last two decades from a reliance on surgical resection to US-guided compression, coil embolization, covered stents, and stent-graft exclusion. More recently, direct percutaneous US-guided thrombin injection has been used in the treatment of PAn. We present three cases of successful PAn thrombosis by US-guided percutaneous thrombin injection in children, one of the epigastric artery and two of the femoral artery.

CT-guided percutaneous lung biopsy in children.

PURPOSE: To describe techniques and evaluate outcomes of computed tomography (CT)-guided percutaneous lung biopsy in children. MATERIALS AND METHODS: Between April 1992 and June 2003, 64 patients (32 male, 32 female) with a mean age of 10.8 years (0.6-20 years) were referred for 75 lung biopsies. Most biopsies were performed for suspected malignancy (n = 24; 32%) or to distinguish posttransplantation lymphoproliferative disorder from fungal infection in immunocompromised patients (n = 17; 23%). All children referred to the pediatric interventionalists in two children's hospitals for CT-guided biopsy of parenchymal or pleural-based lesions in the thorax were studied. Prospectively gathered procedural data were reviewed for medical history and indications for procedure, admission status, type of anesthesia, technical approach (core vs aspiration biopsy), procedural modifications, lesion size, number of passes required, and immediate complications. Medical records were retrospectively reviewed for diagnostic outcome, impact on patient management, and delayed complications. RESULTS: Procedures were performed under deep sedation whenever possible (n = 61; 81%) with use of a coaxial core biopsy technique (n = 56; 75%), a fine needle aspiration biopsy technique (n = 15; 20%), or both (n = 4; 5%). Mean lesion diameters were 2.5 cm (range, 1-10 cm) in the core biopsy group and 1.0 cm (range, 0.5-1.7 cm) in the aspiration biopsy group. Sixty-four biopsies (85%) were diagnostic. There was one major complication (1.3%), a tension pneumothorax treated with intraprocedural placement of a chest tube. CONCLUSION: Percutaneous CT-guided lung biopsy is a safe and accurate diagnostic procedure in children that obviates open surgical biopsy in most patients.

Closed reduction with CT-guided screw fixation for unstable sacroiliac joint fracture-dislocation.

BACKGROUND: Unstable posterior pelvic ring fractures and dislocations are uncommon but potentially life-threatening injuries in children. Early definitive management reduces risk of immediate complications as well as chronic pain and gait dysfunction. Conventional operative therapy carries substantial risk of extensive blood loss and iatrogenic neurological and vascular injury. Minimally invasive image-guided intervention may further reduce immediate risk and improve long-term outcome. OBJECTIVE: To describe CT-guided closed reduction and internal fixation (CRIF) and review outcomes of unstable fracture-dislocation of the sacroiliac (SI) joint in children. MATERIALS AND METHODS: Between 2000 and 2003, three children (two girls, one boy) age 8-14 years were referred to interventional radiology for treatment of unstable SI joint fracture-dislocation not adequately treated with anterior external fixation alone. RESULTS: The three affected SI joints (two left, one right) were treated in a combined approach by pediatric interventional radiologists and orthopedic surgeons, using a percutaneous approach under CT guidance. Over a threaded guiding pin, 7.3 mm cannulated screws were used to achieve stable reduction of the affected SI joints. One screw was removed after slight (2 mm) migration. No neurovascular or other complications occurred. All patients had satisfactory healing with near-anatomic reduction, although recovery of the youngest was delayed by associated spinal injury. CONCLUSIONS: Compared to open surgical alternatives, CRIF under CT guidance reduces operating time, decreases blood loss, and allows early definitive fixation and immediate non-weight-bearing mobilization with a low rate of complication for unstable posterior pelvic ring fractures. In addition, CT-guided placement of the guide pin may allow safer screw positioning and may minimize the total number of screws needed to achieve pelvic stability.

Oral and intravenous caffeine for treatment of children with post-sedation paradoxical hyperactivity.

BACKGROUND: Paradoxical hyperactivity (PH) is a known complication of sedation in children, especially with barbiturates such as pentobarbital. The accompanying inconsolable irritability and agitation, similar to behaviors reported in children with attention deficit hyperactivity disorder (ADHD), is uncomfortable for the child and anxiety-provoking for parents and health-care workers. Our objective was to describe our experience with oral (PO) and intravenous (IV) caffeine as a treatment for sedation-induced PH. MATERIALS AND METHODS: From January 2000 to April 2003, 19,894 children were sedated in our institution for radiology procedures. Of these, 360 children were diagnosed with PH. A total of 229 children exhibiting symptoms of PH after sedative administration were treated with PO caffeine ( n=88; 43 boys, 45 girls; mean age 4.5 years, mean weight 18.7 kg) or IV caffeine ( n=131; 73 boys, 58 girls; mean age 4.8 years, mean weight 20.1 kg) or both ( n=10; 8 boys, 2 girls; mean age 5.0 years, mean weight 19.9 kg). A positive effect was defined as a decrease in agitation, crying, or hyperactivity within 40 min of caffeine administration. A control group ( n=45) was obtained from those 141 children who experienced post-sedation PH but were not treated with caffeine, and matched for age and sex with samples of children treated with IV caffeine ( n=45) and PO caffeine ( n=45). RESULTS: Children treated intravenously received the equivalent of 20 mg/kg caffeine citrate (to a maximum of 200 mg). Of those treated with IV caffeine, 82/131 (63%) showed a positive effect, and returned to baseline behavioral status after an average of 33 min (SD=23 min). The untreated control group required a significantly longer time to recover ( P<0.01) than those treated with IV caffeine. Children treated orally received approximately 1.0-2.5 mg/kg caffeine in Mountain Dew (Pepsi-Cola Company), and 36/88 (41%) showed a positive effect and returned to baseline behavioral status after an average of 42 min (SD=27 min). Of the 10 children treated with both PO and IV caffeine, 6 showed a positive effect. There was no significant difference in recovery time between the untreated control group and either the matched orally treated group or the group treated with both IV and PO caffeine. No complications occurred after caffeine administration. CONCLUSION: IV caffeine appears to be an effective treatment for PH in children with sedation-induced PH. Further controlled prospective study is needed to determine the optimum dose and route of administration and to compare efficacy with other potential drug classes.

A multidisciplinary approach to the focal form of congenital hyperinsulinism leads to successful treatment by partial pancreatectomy.

BACKGROUND/PURPOSE: Congenital hyperinsulinism (HI) causes severe hypoglycemia in neonates and infants. Recessive mutations of the beta-cell K(ATP) channel genes cause diffuse HI, whereas loss of heterozygosity together with inheritance of a paternal mutation cause focal adenomatous HI. Although these 2 forms of HI are clinically identical, focal HI can be cured surgically. The authors reviewed their experience with partial pancreatectomy for focal HI. METHODS: From December 1998 to January 2003, 38 patients (ages 2 weeks to 14 months; median age, 10 weeks) were treated with partial pancreatectomy for focal HI. Before surgery, patients had localization studies using selective arterial calcium stimulation with venous sampling or transhepatic portal venous sampling. At operation, the focal lesion was found using the preoperative localization data and multiple pancreatic biopsies with frozen section analysis, followed by partial pancreatectomy. A complete response at follow-up was defined as no requirement for glycemic medications, no continuous tube feedings, and no diabetes mellitus. RESULTS: Nineteen pancreatic focal lesions were in the head; 15 were in the neck, body, or tail; and 4 had more extensive involvement. Lesions that required substantial resection of the pancreatic head underwent Roux-en-Y pancreaticojejunostomy to preserve the normal body and tail. Lesions of the body or tail were usually treated with partial distal pancreatectomy. Ninety-two percent (35 of 38) of patients had a complete response to surgery. Three patients have required glycemic medications. No patient is diabetic. Surgical complications included additional resection for residual disease (3), small bowel obstruction requiring laparotomy and enterolysis (2), and chylous ascites (3) that resolved with medical management. CONCLUSIONS: A multidisciplinary approach to patients with the focal form of congenital hyperinsulinism can distinguish focal from diffuse disease, localize focal lesions, and permit partial pancreatectomy with cure in most patients.

Transmural migration of gastrostomy tube retention discs.

BACKGROUND: Accidental dislodgment is one of the most frequent causes of avoidable cost and consternation related to gastrostomy tubes. The Sacks-Vine gastrostomy tube, inserted in an antegrade fashion by a percutaneous technique, is extremely stable due to the construction of its disc retention device. However, transmural migration of the retention disc is a known severe delayed complication associated with this tube. OBJECTIVE: To review the presentation, diagnosis, and treatment of transmural migration of gastrostomy retention discs, to propose a mechanism for the progressive development of this complication, and to recommend a method for preventing its occurrence. MATERIALS AND METHODS: From January 1991 to October 1999, pediatric interventional radiologists at two children's hospitals performed 300 antegrade gastrostomy and gastrojejunostomy primary insertion procedures. A "push-pull" variation of the antegrade approach used for 44 of these insertions is excluded from further analysis. Of the remaining 256 procedures, 5 boys and 3 girls with a mean age of 5.1 years (range 0.8-19 years) were identified from review of the prospectively gathered procedural database with significant complications related to the disc retention component of their gastrostomy tubes. A retrospective analysis was conducted of their medical records, diagnostic imaging, and interventional and surgical findings. RESULTS: Transmural migration was diagnosed on average 36 months after insertion (16-48 months). The diagnosis was made incidentally during endoscopy (n=1) or fluoroscopy (n=5) in six asymptomatic patients, and during barium enema to explore feculent vomiting and halitosis in two symptomatic patients. Migration of the retention disc fell along a continuum from intramural (n=4) to transmural and intracolonic (n=4), with gastric mucosal erosion, extensive granulation and inflammation in all eight patients. Although there was no evidence of free air in any patient, a gastrocolic fistula was demonstrated in four patients and a gastrocolocutaneous fistula in two of four patients with complete transmural migration. Surgical resection of the disc, gastrostomy, and fistula repair if needed was successfully performed in all patients. CONCLUSIONS: Gastrostomy tubes with an internal retention disc are at risk for progressive disc migration into and through the gastric wall, resulting in irretrievable fixation and potential fistula formation. This severe delayed complication results from prolonged traction on the retention disc. Transmural migration may be avoided through improved tube care education, daily disc mobilization, and earlier disc retrieval.

Imaging and intervention in the gastrointestinal tract in children.

Vascular and interventional techniques have become an integral component of modern pediatric healthcare. Minimally invasive procedures of the gastrointestinal tract now comprise a large part of any active pediatric interventional practice. Magnetic resonance cholangiopancreatography offers a reliable, non-invasive means to evaluate patients with possible pancreatic or biliary pathology. This article reviews treatment of esophageal strictures and placement of gastronomy and gastrojejunostomy tubes and discusses new developments. Placement of percutaneous cecostomy tubes is a relatively new procedure that creatively uses the techniques developed for placement of percutaneous gastronomy tubes. This procedure offers significant benefits and lasting positive lifestyle changes for patients suffering from fecal incontinence. Liver biopsy in high-risk patients can be performed safely using measures designed to significantly decrease the risk of post-biopsy hemorrhage, such as track embolization or the transjugular approach.