Diffusion tensor imaging in pediatric Chiari type I malformation.

AIM: Chiari type I malformation (C1M) may be symptomatic or asymptomatic as an incidental finding. In this retrospective study, we applied diffusion tensor imaging (DTI) to study the brainstem and cerebellar white matter tracts in C1M. METHOD: Diffusion tensor imaging (DTI) data were acquired on a 1.5T MR-scanner using balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements from regions of interest in each pontine corticospinal tract, medial leminscus, and middle cerebellar peduncle (MCP) and in the lower brainstem were obtained for fractional anisotropy and mean, axial, and radial diffusivity. Values in symptomatic and asymptomatic children, and children with and without hydromyelia were compared using analysis of variance. RESULTS: Fifteen children with C1M (10 males, five females; six symptomatic [four with hydromyelia] and nine asymptomatic) were included. Median age was 6 years 5 months (range 2y 10mo-15y 4mo). No significant differences in DTI scalars were found in the lower brainstem. In both MCPs, axial diffusivity values were lower in symptomatic than in asymptomatic children (p=0.049 and p=0.035 respectively) and higher in children with hydromyelia versus without hydromyelia (p=0.018 and p=0.006 respectively). In the left MCP, mean diffusivity values were lower in symptomatic than in asymptomatic children (p=0.047). INTERPRETATION: Our results show that microstructural tissue alterations may be present in C1M. Additionally, our study suggests a specific role for the MCPs in C1M. Further large-scale studies are warranted.

Computer-aided design and manufacturing in craniosynostosis surgery.

BACKGROUND: Considerable operative time is expended during the planning, shaping, and reconfiguring of the cranial vault in the pursuit of symmetry during open craniosynostosis surgery. Computer-aided design and manufacturing has recently been implemented in orthognathic surgery and complex craniomaxillofacial reconstruction as a means of optimizing operative accuracy and efficiency. In this report, we highlight our growing experience with this promising modality for the preoperative planning and intraoperative execution of cranial vault remodeling in patients with both simple and complex forms of craniosynostosis. METHODS: Computer-assisted surgical planning begins with acquisition of high-resolution computed tomography scans of the craniofacial skeleton. An Internet-based teleconference is then held between the craniofacial and biomedical engineering teams and provides a forum for virtual manipulation of the patient's preoperative three-dimensional computed tomography with real-time changes and feedback. Through virtual surgical planning, osteotomies are designed and calvarial bones reconfigured to achieve the desired cranial vault appearance. Cutting and positioning guides are manufactured to transform the virtual plan into a reality. RESULTS: From February to March 2012, 4 children (aged 9 months to 6 years) with craniosynostosis underwent computer-assisted simulation and surgery. Diagnoses included metopic, unicoronal (n = 2), and multisutural synostoses (sagittal and left unicoronal). Open craniofacial repairs were performed as virtually planned, including front o-orbital remodeling, fronto-orbital advancement, and anterior two-thirds calvarial remodeling, respectively. Cutting and final positioning guides demonstrated excellent fidelity and ease of use. CONCLUSIONS: Computer-aided design and manufacturing may offer a platform for optimizing operative efficiency, precision, and accuracy in craniosynostosis surgery, while accelerating the learning curve for future trainees.

Surgical treatment of pediatric trigeminal neuralgia: case series and review of the literature.

PURPOSE: Pediatric trigeminal neuralgia (TN) is a rare entity. The purpose of this study was to retrospectively analyze a small series of pediatric patients diagnosed with TN and surgically treated with microvascular decompression (MVD) at a single center. METHODS: Nine patients were identified who presented with TN symptoms that began before the age of 18. Four were excluded because of delayed surgical intervention or successful medical management. We retrospectively reviewed the charts of 5 patients with classical TN who underwent MVD at or before the age of 18. RESULTS: Patient ages ranged from 3 to 18 years (average, 11.7) at the time of procedure. All five patients were female. Four patients underwent a single procedure and one had bilateral MVDs. In all six cases, vascular compression of the trigeminal nerve was found during surgery. Compression was venous in three cases, arterial in two, and both in one. Pain relief was complete following the procedure in five of six cases. Pain relief was incomplete but substantial in one patient, allowing her to discontinue anticonvulsant medications. Follow-up duration ranges from 9.1 to 24.8 months with an average of 15.3 (± 6.1) and a median of 12.7 months follow-up. There were no complications such as CSF leak, infection, or cranial nerve deficits. CONCLUSIONS: Until now, there had been no reports on the effectiveness of MVD performed before the age of 18 to treat TN. These preliminary results suggest MVD may be performed with good pain relief and minimal side effects in the pediatric population.

Harvey Cushing's case series of trigeminal neuralgia at the Johns Hopkins Hospital: a surgeon's quest to advance the treatment of the 'suicide disease'.

BACKGROUND: A review of Dr. Harvey Cushing's surgical cases at the Johns Hopkins Hospital provided insight into his early work on trigeminal neuralgia (TN). There was perhaps no other affliction that captured his attention in the way that TN did, and he built a remarkable legacy of successful treatment. At the time, surgical interventions carried an operative mortality of 20%. METHODS: The Johns Hopkins Hospital surgical records from 1896-1912 were reviewed to contribute new cases to the 20 reports provided by Dr. Cushing in his early publications in 1900 and 1905. This review uncovered 123 TN cases, representing 168 interventions. RESULTS: At the start of his career, Cushing treated TN mainly through Gasserion ganglion extirpations and peripheral neurectomies; however, he nearly abandoned these methods in favor of sensory root avulsion after 1906 and did not perform alcohol injections until his later years at Hopkins. Overall, Cushing had a 0.6% mortality rate; additionally, 91% of patients were improved at the time of discharge. However, 26% of patients had a recurrence requiring further intervention by Cushing. CONCLUSION: Modern day interventions of TN are reflective of the legacy left to us by Harvey Cushing, a pioneering forefather in neurosurgery. He pioneered the infra-arterial approach to excision of the Gasserion ganglion in face of problematic bleeding and later the use of sensory root avulsion to spare motor function. Through the evolution of his legacy and the refinement of original approaches, the quest to advance the treatment of TN took him along the trigeminal nerve from the periphery into the brain.

Prognostic factors in pediatric high-grade astrocytoma: the importance of accurate pathologic diagnosis.

To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis should be suspected in patients who are long term survivors of a pediatric high grade astrocytoma.

Surgical decompression for lumbar stenosis in pediatric achondroplasia.

BACKGROUND: Spinal stenosis is a common complication of achondroplasia. To our knowledge, no study has evaluated a greater than 2-year outcome after surgical intervention for spinal stenosis in such children or compared decompression with and without instrumentation in relation to revision surgery. Our purpose was to assess the efficacy of lumbar decompression and instrumentation for symptomatic stenosis in children with achondroplasia. METHODS: We retrospectively reviewed our institution's database to identify children (< or =18 y old) with achondroplasia undergoing initial spinal decompression for lumbar stenosis from 1995 through 2003. We identified 18 such patients and reviewed their medical records for demographic data, presenting signs and symptoms, and treatment and outcome data. Mean follow-up was 72.0+/-27.6 months. We determined each patient's symptom score (SS) based on presence of leg weakness, numbness, or pain; abnormal reflexes; incontinence; and walking intolerance (unable to walk > or =5 blocks). Each finding was scored 1 point (6 points maximum). Nine patients requiring revision surgery were assigned a revision postoperative SS. All patients were contacted at the end of data collection and assigned a final follow-up SS. Baseline SS values were compared with postoperative, revision postoperative, and final follow-up scores using a paired t test (alpha=0.05). RESULTS: The mean preoperative and final SS values were significantly different: 4.0+/-0.9 (most common symptoms, leg weakness and incontinence) and 1.6+/-1.7 (most common symptom, leg weakness), respectively. Nine patients underwent decompression with instrumentation initially; 9 did not; 7 of the latter required instrumentation during revision; and 2 of the former also required revision. Those without initial instrumentation were 3.5 times more likely (odds ratio=12.3) to require revision. CONCLUSIONS: Surgical decompression with instrumentation significantly reduced the symptoms of lumbar stenosis and the likelihood of revision surgery in children with achondroplasia. LEVEL OF EVIDENCE: Level III therapeutic study.

Incidence of symptomatic retethering after surgical management of pediatric tethered cord syndrome with or without duraplasty.

BACKGROUND: Cord retethering and other postoperative complications can occur after the surgical untethering of a first-time symptomatic tethered cord. It is unclear if using duraplasty vs. primary dural closure in the initial operation is associated with decreased incidence of either immediate postoperative complications or subsequent symptomatic retethering. It is also unclear if different etiologies are associated with different outcomes after each method of closure. We reviewed our pediatric experience in first-time surgical untethering of symptomatic tethered cord syndrome (TCS) to identify the incidence of postoperative complications and symptomatic retethering after duraplasty vs. primary closure. MATERIALS AND METHODS: We retrospectively reviewed 110 consecutive pediatric (<18 years old) cases of first-time symptomatic spinal cord untethering at our institution over a 10-year period. Incidence of postoperative complications and symptomatic retethering were compared in cases with duraplasty vs. primary dural closure use. RESULTS: Mean age was 5.7 +/- 4.8 years old. "Complex" etiologies included lipomyelomeningocele or prior lipomyelomeningocele repair in 22 (20%) patients, prior myelomeningocele repair in 35 (32%), and concurrent lumbosacral lipoma in 18 (16%). "Noncomplex etiologies" included fatty filum in 26 (24%) and split cord malformation in five (4%). Seventy-five (68%) cases underwent primary dural closure vs. 35 (32%) with duraplasty. Twenty-nine (26%) patients experienced symptomatic retethering at a median [interquartile range (IQR)] of 30.5 [20.75-41.75] months postoperatively. There was no difference in incidence of postoperative cerebrospinal fluid leak, surgical site infection, or median [IQR] length of stay in patients receiving primary dural closure [4 (5%), 7 (9%), and 5 (4-6) days, respectively] vs. duraplasty [3 (9%), 3 (9%), and 6 [5-8] days, respectively], p > 0.05. Complex etiologies were more likely to retether than noncomplex etiologies after primary closure (33.6% vs. 6.6%, p = 0.05) but not after duraplasty (13.7% vs. 5.4%, p = 0.33). Duraplasty graft type (polytetrafluoroethylene vs. bovine pericardium) was not associated with pseudomeningocele or retethering. CONCLUSION: In our experience, the increased rate of symptomatic retethering observed with complex pediatric TCS (pTCS) etiologies after primary dural closures was not observed when duraplasty was instituted. Expansile duraplasty may be valuable specifically in the management of patient subgroups with complex pTCS etiologies.

Catheters for chronic administration of drugs into brain tissue.

Methods to infuse drugs into the parenchyma of the central nervous system (CNS) have been reported as inconsistent or unpredictable. The source of variability appears to be a compromised seal between the tissue and the outer surface of the cannula. Failure of the tissue to seal to the cannula creates a path of least resistance. Rather than penetrate the target area, the drug backflows along the path of the cannula. This artifact can be difficult to detect because drugs enter the systemic circulation and provide some fraction of the intended therapy. Decreasing the rate of the infusion can reduce backflow. However, this may not be an attractive option for certain therapeutic targets because decreased infusion rates decrease the volume of drug distribution in normal tissue. Cannula design plays a role. Rigid catheters that are fixed to the skull will oppose movements of the brain and break the seal between the catheter and the tissue during chronic infusions. Flexible infusion cannulas, which can be readily made by modifying commercially available brain infusion catheters with plastic tubing, appear to provide consistent infusion results because they can move with the brain and maintain their tissue seal.

Outcome analysis of childhood low-grade astrocytomas.

BACKGROUND: We aimed to determine the long-term natural history of low-grade astrocytomas (LGA) in children, with respect to pathology, and to evaluate influence of treatment on survival. PATIENTS AND METHODS: A consecutive cohort of patients < or =21 years with surgically confirmed LGA from 1965 to 1996 was assembled. All available pathology specimens were reviewed, masked to original diagnosis, patient data, and neuroimaging. RESULTS: Two hundred seventy-eight children (160 males; mean age 9.1 years; tumor location: 77 cerebrum, 62 cerebellum, 51 hypothalamic, 30 thalamus, 9 ventricle, 40 brainstem, and 9 spine) were assessed. Among 246 specimens reviewed, diagnoses were 135 pilocytic astrocytoma (PA), 27 diffuse astrocytoma (DA), 75 unclassifiable well-differentiated astrocytoma (NOS), and 9 subependymal giant cell astrocytoma. At 5 and 10 years from initial surgery, for all LGA overall survival (OS) was 87% and 83%, while progression-free survival (PFS) was 55% and 42%, respectively. Original pathology diagnoses did not predict PFS (P = 0.47), but reviewed diagnoses were significantly associated with PFS (P = 0.007). Reviewed diagnoses were highly associated with OS (P < 0.0001), with 5-year OS for PA 96%, DA 48%, and NOS 86%; these differences remained significant when stratified by location or extent of resection. Among patients with residual tumor after surgery, 5-year PFS was 48% with observation alone (n = 114), no different (P = 0.32) from that achieved with immediate irradiation (n = 86). CONCLUSION: LGA, particularly PA, have excellent long-term OS. While tumor location and resection extent affect outcome, pathologic diagnosis when carefully interpreted significantly influences long-term survival. Immediate postoperative irradiation does not confer an advantage in delaying first progression in children with residual PA.

Magnetic resonance imaging characteristics of pilomyxoid astrocytoma.

OBJECTIVE: Pilomyxoid astrocytoma (PMA) is a recently identified pediatric low-grade neoplasm that was previously classified as pilocytic astrocytoma (PA), yet demonstrates unique histological features and more aggressive behavior. These tumors have been shown to have significantly shorter progression-free and overall survival probability than classical low-grade astrocytomas, as well as a high rate of cerebrospinal fluid (CSF) dissemination. This paper describes the radiographic features of PMA. METHODS: Magnetic resonance imaging (MRI) was obtained for ten PMAs. Radiographic characteristics of the tumor were recorded in each case. All tissue samples were independently reviewed for confirmation of pathologic diagnosis. RESULTS: All tumors appeared well-circumscribed with no evidence of peritumoral edema or parenchymal infiltration on MRI. All tumors except one originated from the midline of the neuroaxis. Specifically, five tumors (50.0%) were located in the hypothalamic region, two (20.0%) were located in the spine, two (20.0%) were located in the dorsal brainstem and one was located in the right thalamus. Five tumors (50.0%) demonstrated solid composition, with the remaining five showing some cystic components. Mass effect, hydrocephalus and central necrosis were observed in 62.5, 50.0 and 0.0% of cases, respectively. Eight tumors (80%) were hyperintense on T1-weighted MRI. Seven tumors (77.8%) were hyperintense on T2-weighted MRI. All tumors were hyperintense on fluid attenuated inversion recovery (FLAIR) sequence and hypointense on diffusion weighted imaging (DWI). Upon contrast administration, six tumors (60.0%) enhanced heterogeneously and four tumors (40.0%) enhanced homogenously. CONCLUSION: Pilomyxoid astrocytoma is a well-circumscribed pediatric neoplasm that commonly originates from the midline of the neuroaxis and lacks peritumoral edema or central necrosis. It is critical to recognize the predominantly solid and well-circumscribed nature of the neoplasm to avoid confusion with an infiltrating astrocytoma.

Antibiotic-impregnated shunt catheters for the treatment of infantile hydrocephalus.

INTRODUCTION: Antibiotic-impregnated shunt (AIS) components decrease shunt infections by preventing bacterial colonization that occurs during implantation. Despite studies showing improved efficacy in preventing infection however, concern still exists regarding using AIS components in infants, especially premature ones. In this study, clinical outcomes were assessed in infants with hydrocephalus (<1 year) following AIS placement. METHODS: A prospective observational study was conducted involving pediatric patients <1 year of gestational age with hydrocephalus who underwent placement of AIS components (ventriculoperitoneal, ventriculoatrial, and cystoperitoneal) as initial treatments, shunt revision surgery, or following previous placement of a ventricular access device (VAD, Rickman reservoir). Measured outcomes included: infection, shunt revision surgery, and complications. RESULTS: Seventy-four infants underwent 108 AIS procedures, and all were followed for over 9 months. Twenty-seven patients (36.5%) possessed previous VADs. Average weight and gestational age at birth were 1,976 g (range: 560-3,500 g) and 32.8 weeks (range: 23-41 weeks), respectively. The average age at the time of surgery was 14.6 weeks (range: 1 day to 50 weeks). Five infections occurred in 5 patients (4.6% of procedures, 6.75% of patients), 60% of which were very premature (<32 weeks). Thirty-three patients (44.6%) required shunt revision surgery, 5 (15%) for infection and 28 (85%) for malfunction. Three cerebrospinal fluid leaks occurred perioperatively without significant sequelae, and no mortalities occurred from the procedures. CONCLUSION: AIS systems can safely be used to treat hydrocephalus in pediatric patients <1 year old, even for those with a history of prematurity. One possible therapeutic application for such premature patients may be the incorporation of antibiotic impregnation into VADs or ventriculosubgaleal components to treat infants with hydrocephalus prior to definitive CSF shunt placement.

PIK3CA gene mutations in pediatric and adult glioblastoma multiforme.

The phosphatidylinositol 3-kinases (PI3K) are a family of enzymes that relay important cellular growth control signals. Recently, a large-scale mutational analysis of eight PI3K and eight PI3K-like genes revealed somatic mutations in PIK3CA, which encodes the p110alpha catalytic subunit of class IA PI3K, in several types of cancer, including glioblastoma multiforme. In that report, 4 of 15 (27%) glioblastomas contained potentially oncogenic PIK3CA mutations. Subsequent studies, however, showed a significantly lower mutation rate ranging from 0% to 7%. Given this disparity and to address the relation of patient age to mutation frequency, we examined 10 exons of PIK3CA in 73 glioblastoma samples by PCR amplification followed by direct DNA sequencing. Overall, PIK3CA mutations were found in 11 (15%) samples, including several novel mutations. PIK3CA mutations were distributed in all sample types, with 18%, 9%, and 13% of primary tumors, xenografts, and cell lines containing mutations, respectively. Of the primary tumors, PIK3CA mutations were identified in 21% and 17% of pediatric and adult samples, respectively. No evidence of PIK3CA gene amplification was detected by quantitative real-time PCR in any of the samples. This study confirms that PIK3CA mutations occur in a significant number of human glioblastomas, further indicating that therapeutic targeting of this pathway in glioblastomas is of value. Moreover, this is the first study showing PIK3CA mutations in pediatric glioblastomas, thus providing a molecular target in this important pediatric malignancy.

Spinal stenosis surgery in pediatric patients with achondroplasia.

OBJECT: Achondroplasia is a hereditary form of dwarfism caused by a defect in endochondral bone formation, resulting in skeletal abnormalities including short stature, shortened limb bones, macrocephaly, and small vertebral bodies. In the pediatric population, symptomatic spinal stenosis occurs at all spinal levels due to the abnormally narrow bone canal. In this study, clinical outcomes were assessed in children with achondroplasia after spinal canal decompression. METHODS: A retrospective review was conducted involving pediatric patients with heterozygous achondroplasia and symptomatic stenosis after decompressive procedures at the authors' institution within a 9-year period. Measured outcomes included resolution of symptoms, need for repeated surgery, presence of fusion, development of deformity, and complications. Forty-four pediatric patients underwent a total of 60 decompressive procedures. The average patient age at surgery was 12.7 years (range 5-21 years). Forty-nine operations were performed for initial treatment of stenosis, and 11 were performed as revision surgeries on previously operated levels. A large proportion of patients (> 60%) required additional cervicomedullary decompressions, most often preceding the symptoms of spinal stenosis. Of the initial procedures, decompression locations included 32 thoracolumbar (65%), 10 lumbar (20%), four cervical (8%), two cervicothoracic (4%), and one thoracic (2%). Forty-three of the decompressive procedures (72%) included spinal fusion procedures. Of the 11 revisions, five were fusion procedures for progressive deformity at levels previously decompressed but not fused (all thoracolumbar), five were for decompressions of symptomatic junctional stenosis with extension of fusion, and one was for repeated decompression at the same level due to recurrence of symptomatic stenosis. CONCLUSIONS: Decompression of the spinal canal in pediatric patients with achondroplasia can be accomplished safely with significant clinical benefit. Patients with a history of cervicomedullary compression may be at an increased risk of developing symptomatic stenosis prior to adolescence. Fusion procedures are recommended in patients with a large decompression overlying a thoracolumbar kyphosis to avoid progressive postoperative deformity.

Cervicomedullary decompression for foramen magnum stenosis in achondroplasia.

OBJECT: Achondroplasia is the most common hereditary form of dwarfism, and is characterized by short stature, macrocephaly, and a myriad of skeletal abnormalities. In the pediatric population, stenosis and compression at the level of the cervicomedullary junction commonly occurs. The goal in this study was to assess the outcomes in children with achondroplasia who underwent cervicomedullary decompression. METHODS: Forty-three pediatric patients with heterozygous achondroplasia and foramen magnum stenosis underwent 45 cervicomedullary decompressions at the authors' institution over an 11-year period. After surgical decompression, complete resolution or partial improvement in the preoperative symptoms was observed in all patients. There were no deaths in the treated patients. The surgical morbidity rate was low and usually consisted of a cerebrospinal fluid (CSF) leak in patients in whom the dura mater had been opened (either intentionally or accidentally). This problem was successfully managed in all cases with local measures (wound oversewing) or CSF diversion. CONCLUSIONS: In this review the authors demonstrate that decompression of the cervicomedullary junction in the setting of achondroplasia may be accomplished safely with significant clinical benefit and minimal morbidity.

Local infusion therapy in the monkey brainstem: technical considerations.

This chapter assesses the safety of freehand placement of an infusion catheter (outer diameter, 0.3 mm) in brainstems of cynomolgus monkeys (Macaca fascicularis) for local infusion therapy. A posterior midline approach through the cerebellum and roof of the fourth ventricle was used to implant catheters into a pontine target area. Computer tomography (CT), magnetic resonance imaging (MRI), and histology were used to examine the position of the implants. The freehand placement of a catheter resulted in approximately 5-mm variations in anterior-posterior and dorsal-ventral locations of the targeted implantation site. No evidence of morbidity from the surgery, or from the infusion process was present. In conclusion, small-diameter catheters for chronic drug infusions can be implanted safely into the brainstem, an eloquent region that has been considered surgically inoperable. Infusion systems may offer a minimally invasive, generally applicable tool to provide chronic therapy for central nervous system (CNS) lesions.

Laser speckle imaging to improve clinical outcomes for patients with trigeminal neuralgia undergoing radiofrequency thermocoagulation.

OBJECTIVE: Percutaneous treatments for trigeminal neuralgia are safe, simple, and effective for achieving good pain control. Procedural risks could be minimized by using noninvasive imaging techniques to improve the placement of the radiofrequency thermocoagulation probe into the trigeminal ganglion. Positioning of a probe is crucial to maximize pain relief and to minimize unwanted side effects, such as denervation in unaffected areas. This investigation examined the use of laser speckle imaging during probe placement in an animal model. METHODS: This preclinical safety study used nonhuman primates, Macaca nemestrina (pigtail monkeys), to examine whether real-time imaging of blood flow in the face during the positioning of a coagulation probe could monitor the location and guide the positioning of the probe within the trigeminal ganglion. RESULTS: Data from 6 experiments in 3 pigtail monkeys support the hypothesis that laser imaging is safe and improves the accuracy of probe placement. CONCLUSIONS: Noninvasive laser speckle imaging can be performed safely in nonhuman primates. Because improved probe placement may reduce morbidity associated with percutaneous rhizotomies, efficacy trials of laser speckle imaging should be conducted in humans.

Flexible versus rigid catheters for chronic administration of exogenous agents into central nervous system tissues.

INTRODUCTION: Neuropharmacology studies depend on consistency in drug delivery. Drug infusions into central nervous system (CNS) tissues have been described as unreliable. Speculation has focused on infusion pumps as the source of variation. This report demonstrates that the catheter may be a source of variability. The inconsistency can be significantly reduced by a change in catheter design. METHODS: Normal and tumor cell-challenged (abnormal) brains of Fischer rats were infused with small and large molecular weight cytotoxic drugs via rigid and flexible catheters placed directly into the parenchyma. Coronal tissue sections rostral and caudal to the infusion point were analyzed for drug concentrations. Carboplatin, estimated through atomic absorption assays, and doxorubicin and transferrin-bound doxorubicin, measured by fluorescent spectroscopy, were mapped in serial sections at various distances from the infusion point. RESULTS: The expected drug distribution pattern approximates a bell-shaped curve with a maximum drug concentration near the infusion point and approximately equal, declining concentrations rostral and caudal to the infusion. This expected distribution was found in only 10 of the 17 normal brains and 15 of the 28 abnormal brains infused with a rigid catheter. In contrast, 10 of the 10 normal brains and 16 of the 16 abnormal rat brains infused with a flexible catheter had the expected distribution pattern. The distribution pattern was not associated with the molecular weight of the infused drug. CONCLUSION: Replacement of rigid infusion tubes with flexible tubing increases the reliability of local CNS drug infusions. Rigid catheters may allow backflow of the infused drug along the path of the catheters into the subdural space.

Infusion rates and drug distribution in brain tumor models in rats.

OBJECT: The aim of this study was to investigate the optimal delivery rates of chemotherapy for the treatment of central nervous system tumors and to determine whether local delivery can lower toxicity profiles and increase target concentrations of chemotherapy. METHODS: The authors used two brain tumor models in rats. Slow (1 microl/hour) and fast (10 microl/hour) pumps were used to deliver chemotherapy--carboplatin, doxorubicin, and a high-molecular-weight transferrin-doxorubicin conjugate to the brains of normal rats and rats previously injected with F98 or 9L rat brain tumor cells. Brains were cut in 1-mm sections rostral and caudal from the infusion point. Slices were analyzed for doxorubicin and platinum by fluorescence and atomic absorption, respectively. In the normal tissues, the volume of drug distribution is generally greater at the faster flow rate. In abnormal tissues, distribution is similar at slow and fast infusion rates for low-molecular-weight drugs and greater at slow rates for a high-molecular-weight targeted toxin. CONCLUSIONS: After local administration the distribution of chemotherapy appears to be significantly influenced by tumor metabolism. Additional studies are needed to determine the optimal delivery rates for the interaction of the drug with the targeted tumor.

Distal ventriculoperitoneal shunt failure caused by silicone allergy. Case report.

The placement of a ventriculoperitoneal (VP) shunt is the most common form of treatment for hydrocephalus. Although allergic reactions to the silicone in shunt hardware are very rare, the authors describe a case of silicone allergy causing multiple ventricular shunt revisions. A 24-year-old man, who had undergone multiple VP shunt revisions, presented with shunt malfunction caused by allergic reaction of the tissues surrounding the shunt tubing. The patient's existing silicone-based shunt was replaced with a new polyurethane system, including the proximal and distal catheters as well as the valve mechanism. Contrary to recommendations in previous studies of silicone shunt allergies, long-term immunosuppression was not initiated. The patient was followed up for more than 8 years without recurrence of an allergic reaction to the shunt. This outcome indicates that replacing the original silicone-based shunt system with a polyurethane-based system alone is sufficient in the treatment of a silicone shunt allergy.

A novel brainstem tumor model: guide screw technology with functional, radiological, and histopathological characterization.

OBJECT: Survival rates for high-grade brainstem tumors are approximately 10% and optimal therapy has yet to be determined. Development of a satisfactory brainstem tumor model is necessary for testing new therapeutic paradigms that may prolong survival. The authors report the technique, functional progression, radiological appearance, and histopathological features of a novel brainstem tumor model in rats. METHODS: Thirty female Fischer 344 rats were randomized (10 animals/group) to receive an injection of either 3 ml of 9L gliosarcoma cells (100,000 cells), 3 ml of F98 glioma cells (100,000 cells), or 3 ml of medium (Dulbecco modified Eagle medium) into the pontine tegmentum of the brainstem. Using a cannulated guide screw system implanted in the skull of the animal, rats in each group were injected at coordinates 1.4 mm to the right of the sagittal and 1 mm anterior to the lambdoid sutures, at a depth of 7 mm from the dura mater. The angle of the syringe during injection was anteflexed 5 degrees from the vertical. Postoperatively, the rats were evaluated for neurological deficits by using an automated rotarod test. High-resolution [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) fused with computerized tomography (CT) scans were acquired pre- and postoperatively through the onset of hemiparesis and correlated accordingly. Kaplan-Meier curves were generated for survival and disease progression, and brains were processed postmortem for histopathological investigation. The 9L and F98 tumor cells grew in 95% of the animals in which they were injected and resulted in a statistically significant mean onset of hemiparesis of 16.5 6 0.56 days (p = 0.001, log-rank test), compared with animals in the control group, which had no neurological deficits by Day 45. The FDG-PET studies coregistered with CT scans demonstrated space-occupying brainstem lesions, and this finding was confirmed by histological studies. Animals in the control group showed no functional, radiological, or pathological signs of tumor. CONCLUSIONS: Progression to hemiparesis was consistent in all tumor-injected animals, with predictable onset of symptoms occurring approximately 17 days postsurgery. The histopathological and radiological characteristics of the 9L and F98 brainstem tumors were comparable to those of aggressive primary human brainstem tumors. Establishment of this animal tumor model will facilitate the testing of new therapeutic paradigms for the treatment of these lesions.