Jonathan Pindrik

Local delivery of OncoGel delays paresis in rat metastatic spinal tumor model

OBJECT Spinal column metastatic disease clinically affects thousands of cancer patients every year. Local chemotherapy represents a new option in the treatment of metastatic disease of the spine. Despite the clinical impact of metastatic spine disease, the literature currently lacks an accurate animal model for the effective dosing of local chemotherapeutic agents within the vertebral column. METHODS Female Fischer 344 rats, weighing 150 to 200 g each, were used in this study. After induction of anesthesia, a transabdominal approach to the ventral vertebral body of L-6 was performed. A small hole was drilled and 5 microL of ReGel (blank polymer), OncoGel (paclitaxel and ReGel) 1.5%, OncoGel 3.0%, or OncoGel 6.0% were immediately injected to determine drug toxicity. Based on these results, efficacy studies were performed by intratumoral injection of 5 microL of ReGel, OncoGel 3.0%, and OncoGel 6.0% on Day 6 in a CRL- 1666 breast adenocarcinoma metastatic spine tumor model. Hind limb function was tested pre- and postoperatively using the Basso-Beattie-Bresnahan rating scale. Histological analysis of the spinal cord and vertebral column was performed when the animal died or was killed. RESULTS There were no signs of toxicity observed in association with any of the agents under study. No increased benefit was seen in the blank polymer group compared with the control group (tumor only). OncoGel 3.0% and OncoGel 6.0% were effective in delaying the onset of paralysis in the respective study groups. CONCLUSIONS These findings demonstrate the potential benefit of OncoGel in cases of subtotal resections of metastatic spinal column tumors. OncoGel 6.0% is the most efficacious drug concentration and offers the best therapeutic option in this experimental model. These results provide promise for the development of local chemotherapeutic means to treat spinal metastases.

Analysis of limited-sequence head computed tomography for children with shunted hydrocephalus: potential to reduce diagnostic radiation exposure

OBJECT Despite its diagnostic utility, head CT scanning imparts risks of radiation exposure. Children with shunt-treated hydrocephalus exhibit increased risks of radiation toxicity due to the higher vulnerability of developing, immature tissues and frequent scanning. Several methods have been used to achieve dose reduction, including modifications of CT scanner tube current and potential. This retrospective study explores the use of a newly defined limited sequence of axial head CT slices to evaluate children with shunted hydrocephalus and decrease radiation exposure from diagnostic CT scans. METHODS Consistent sequences of 7 axial slices were extracted from previously performed standard head CT scans in children with shunted hydrocephalus. Chronologically distinct limited sequences of each patient were blindly, retrospectively reviewed by 2 pediatric neuroradiologists and 1 pediatric neurosurgeon. Limited-sequence CT evaluation focused on the adequacy of portraying the ventricular system, changes in ventricular size, and visualization of the proximal catheter. Reviewers assessed all original full series head CT scans at least 4 months later for comparison. Adequacy and accuracy of the limited-sequence CT compared with the gold standard head CT was investigated using descriptive statistics. Effective dose (ED) estimates of the limited-sequence and standard head CT scans were compared using descriptive statistics and the Mann-Whitney test. RESULTS Two serial head CT scans from each of 50 patients (age range 0-17 years; mean age 5.5 years) were reviewed both in standard and limited-sequence forms. The limited-sequence CT adequately portrayed the ventricular system in all cases. The inaccuracy rate for assessing changes in ventricular size by majority assessment (2 of 3 reviewers evaluating inaccurately) was 3 (6%) of 50. In 1 case, the inaccurate assessment would not have altered clinical management, corresponding to a 2 (4%) of 50 clinically relevant inaccuracy rate. As compared with the gold standard complete head CT series, the limited-sequence CT exhibited high sensitivity (100%) and specificity (91%) for portraying changes in ventricular caliber. Additionally, the limited-sequence CT displayed the ventricular catheter in 91.7% of scans averaged across 3 observers. Among all scans reviewed, 97 pairs of standard head CT and complementary limited-sequence CT scans contained adequate dosing information to calculate the effective dose (ED). The ED50 of the limited-sequence CT (0.284 mSv) differed significantly from the ED50 of the standard head CT (4.27 mSv) (p < 0.0001). The limited-sequence CT reflected a median absolute reduction of 4.10 mSv and a mean percent reduction of 91.8% in ED compared with standard head CT. CONCLUSIONS Limited-sequence head CT scanning provided adequate and accurate diagnostic information in children with shunted hydrocephalus. Techniques including minimization of axial slice quantity and modification of CT scanner parameters can achieve significant dose reduction, maintaining a balance between diagnostic utility and patient safety.

Fractionated, single-port radiotherapy delays paresis in a metastatic spinal tumor model in rats

OBJECT Spinal column metastatic disease affects thousands of cancer patients every year. Radiation therapy frequently represents the primary treatment for this condition. Despite the enormous clinical impact of spinal column metastatic disease, the literature currently lacks an accurate animal model for testing the efficacy of irradiation on spinal column metastases. METHODS After anesthesia was induced, female Fischer 344 rats underwent a transabdominal approach to the ventral vertebral body (VB) of L-6. A 2- to 3-mm-diameter bur hole was drilled for the implantation of a section of CRL-1666 breast adenocarcinoma. After the animals had recovered from the surgery, they underwent fractionated, single-port radiotherapy beginning on postoperative Day 7. Each group of animals underwent five daily fractions of radiation treatment. Group I animals received a total dose of 10 Gy in 200-cGy daily fractions, Group II animals received a total dose of 20 Gy in 400-cGy daily fractions, and Group III animals received a total dose of 30 Gy in 600-cGy daily fractions. A control group of rats with implanted VB lesions did not receive radiation. To test the effects of radiation toxicity alone, additional rats without implanted tumors received radiation treatments in the same fractions as the rats with tumors. Hindlimb function in all rats was rated before and after radiation treatment using the Basso-Beattie-Bresnahan locomotor rating scale. Histological analysis of spinal cord and vertebral column sections was performed after each animals death. RESULTS Functional assessments demonstrated a statistically significant delay in the onset of paresis between the three treatment groups and the control group (tumor implanted but no radiotherapy). The rats in the three treatment groups, however, did not exhibit any significant differences related to hindlimb function. A dose-dependent relationship was found for the percentage of animals who had become paralyzed at the time of death, with all members of the control group and no members of the 30-Gy group exhibiting paralysis. The results of this study do not indicate any overall survival benefit for any level of radiation dose. CONCLUSIONS These findings demonstrate the efficacy of focal spinal irradiation in delaying the onset of paralysis in a rat metastatic spine tumor model, but without a clear survival benefit. Because of the dose-related toxicity observed in the rats treated with 30 Gy, this effect was most profound for the 20-Gy group. This finding parallels the observed clinical course of spinal column metastatic disease in humans and provides a basis for the future comparison of novel local and systemic treatments to augment the observed effects of focal irradiation.

Peripheral Nerve Surgery: Primer for the Imagers

Peripheral nerve surgery represents a broad field of pathologic conditions, medical specialties, and anatomic regions of the body. Anatomic understanding of hierarchical nerve structure and the peripheral nervous system aids diagnosis and management of nerve lesions. Many peripheral nerves coalesce into organized arrays, including the cervical, brachial, and lumbosacral plexuses, controlling motor and sensory functions of the trunk and extremities. Individual or groups of nerves may be affected by various pathologic conditions, including trauma, entrapment, tumor, or iatrogenic damage. Current research efforts focus on enhancing the peripheral nerve regenerative process by targeting Schwann cells, nerve growth factors, and nerve allografts.

Assuring optimal physiologic craniocervical alignment and avoidance of swallowing-related complications after occipitocervical fusion by preoperative halo vest placement

Study Design A retrospective review. Objective To assess the utility of preoperative halo immobilization in the avoidance of swallowing complications-associated occipitocervical fixation. Summary of Background Data The craniocervical region is commonly affected by a number of pathologic processes. Fixation of the upper cervical spine to the occiput provides an excellent means of treating these conditions. Occipitocervical fixation, however, is associated with a number of potential complications. One under-reported postoperative complication is the swallowing difficulty that some patients experience. Another is the overall patient dissatisfaction with postoperative head position. One means that the authors have used to avoid these complications is the use of preoperative halo vest fixation. Methods In this article, we report our experience with preoperative halo vest immobilization for occipitocervical fusion in 12 consecutive patients over a 5-month period and its effect on postoperative complications. We also report our experience with the index case of this series in which the patient required operative revision because of severe postoperative dysphagia and stridor after an occipitocervical fusion. Results All patients achieved satisfactory postoperative head position using the preoperative halo immobilization technique. One patient experienced transient dysphagia, which did not require intervention. No patients experienced any complications related to the placement of the halo vest itself. Conclusions Preoperative halo immobilization allows patients, who are going to have their head permanently fixed in a particular position, to determine if they are able to tolerate the new head position. This allows the surgeon to adjust the head position before permanently locking the patient in the position, if necessary. We, therefore, advocate the use of preoperative halo immobilization as a means of assuring physiologic craniocervical neutrality and the avoidance of the resultant complications.

Normative ranges of anthropometric cranial indices and metopic suture closure during infancy

OBJECTIVE Subjective evaluations typically guide craniosynostosis repair. This study provides normative values of anthropometric cranial indices that are clinically useful for the evaluation of multiple types of craniosynostosis and introduces 2 new indices that are useful in the evaluation and management of metopic and bicoronal synostosis. The authors hypothesize that normative values of the new indices as well as for established measures like the cephalic index can be drawn from the evaluation of CT scans of normal individuals. METHODS High-resolution 3D CT scans obtained in normal infants (age 0-24 months) were retrospectively reviewed. Calvarial measurements obtained from advanced imaging visualization software were used to compute cranial indices. Additionally, metopic sutures were evaluated for patency or closure. RESULTS A total of 312 participants were included in the study. Each monthly age group (total 24) included 12-18 patients, yielding 324 head CT scans studied. The mean cephalic index decreased from 0.85 at age 0-3 months to 0.81 at 19-24 months, the mean frontoparietal index decreased from 0.68 to 0.65, the metopic index from 0.59 to 0.55, and the towering index remained comparatively uniform at 0.64 and 0.65. Trends were statistically significant for all measured indices. There were no significant differences found in mean cranial indices between sexes in any age group. Metopic suture closure frequency for ages 3, 6, and 9 months were 38.5%, 69.2%, and 100.0%, respectively. CONCLUSIONS Radiographically acquired normative values for anthropometric cranial indices during infancy can be used as standards for guiding preoperative decision making, surgical correction, and postoperative helmeting in various forms of craniosynostosis. Metopic and towering indices represent new cranial indices that are potentially useful for the clinical evaluation of metopic and bicoronal synostoses, respectively. The present study additionally shows that metopic suture closure appears ubiquitous after 9 months of age.

Update on Peripheral Nerve Surgery

OBJECTIVE: Minimally invasive surgical techniques have been described for the treatment of spinal pathology. Tethered cord syndrome is an under-diagnosed condition of abnormally rigid fixation of the spinal cord that results in spinal cord tension leading to ischemia. It can be the cause of incontinence, scoliosis, and chronic back and leg pain. In situations of spinal cord tether owing to fatty filum or tight filum terminale, the symptoms can be relieved by sectioning of the filum. We present a novel, minimally invasive technique for surgical untethering of the spinal cord by filum sectioning. The pathophysiology of tethered spinal cord and the advantages of minimally invasive surgical management of this entity are discussed. METHODS: Three patients (ages 14, 35, and 46 yr) presented with long-standing leg and back pain and neuroradiological features of tethered cord syndrome and thickened, fatty filum terminale. Two patients presented with scoliosis and, upon further history, had subclinical incontinence; one of these patients had abnormal urodynamic studies. RESULTS: All three patients underwent a minimally invasive approach to the L4/L5 level using the X-tube (Medtronic, Inc., Memphis, TN). A laminotomy was performed and the dura exposed. The dura was then opened and intradural microdissection delivered the fatty filum into the durotomy. Electrical stimulation was performed while the lower extremities and the anal sphincter were monitored for electromyographic activity. After acquisition of positive controls, the filum was identified by the lack of sphincter and lower extremity electromyographic responses and was then cauterized and cut. Dura was repaired with the use of endoscopic instrumentation. All patients had significant improvement of their leg and back pain, and one patient had resolution of the abnormal urodynamics. CONCLUSION: Tethered spinal cords can be safely and effectively untethered using minimally invasive surgery. This technique provides the advantage of reduced soft tissue injury, less postoperative pain, minimal blood loss, a smaller incision, and a shorter hospitalization. The minimal amount of tissue injury generated by this technique may also provide the added advantage of reduced scar formation and risk of retethering.

Midline synovial and ganglion cysts causing neurogenic claudication

Typically situated posterolateral in the spinal canal, intraspinal facet cysts often cause radicular symptoms. Rarely, the midline location of these synovial or ganglion cysts may cause thecal sac compression leading to neurogenic claudication or cauda equina syndrome. This article summarizes the clinical presentation, radiographic appearance, and management of three intraspinal, midline facet cysts. Three patients with symptomatic midline intraspinal facet cysts were retrospectively reviewed. Documented clinical visits, operative notes, histopathology reports, and imaging findings were investigated for each patient. One patient presented with neurogenic claudication while two patients developed partial, subacute cauda equina syndrome. All 3 patients initially responded favorably to lumbar decompression and midline cyst resection; however, one patient required surgical stabilization 8 mo later. Following the three case presentations, we performed a thorough literature search in order to identify articles describing intraspinal cystic lesions in lateral or midline locations. Midline intraspinal facet cysts represent an uncommon cause of lumbar stenosis and thecal sac compression. Such entities should enter the differential diagnosis of midline posterior cystic lesions. Midline cysts causing thecal sac compression respond favorably to lumbar surgical decompression and cyst resection. Though laminectomy is a commonly performed operation, stabilization may be required in cases of spondylolisthesis or instability.

Thoracic osteomyelitis and epidural abscess formation due to cat scratch disease: case report.

Osteomyelitis of the spine with associated spinal epidural abscess represents an uncommon entity in the pediatric population, requiring prompt evaluation and diagnosis to prevent neurological compromise. Cat scratch disease, caused by the pathogen Bartonella henselae, encompasses a wide spectrum of clinical presentations; however, an association with osteomyelitis and epidural abscess has been reported in only 4 other instances in the literature. The authors report a rare case of multifocal thoracic osteomyelitis with an epidural abscess in a patient with a biopsy-proven pathogen of cat scratch disease. A 5-year-old girl, who initially presented with vague constitutional symptoms, was diagnosed with cat scratch disease following biopsy of an inguinal lymph node. Despite appropriate antibiotics, she presented several weeks later with recurrent symptoms and back pain. Magnetic resonance imaging revealed 2 foci of osteomyelitis at T-8 and T-11 with an associated anterior epidural abscess from T-9 to T-12. Percutaneous image-guided vertebral biopsy revealed B. henselae by polymerase chain reaction analysis, and she was treated conservatively with doxycycline and rifampin with favorable clinical outcome.

Severe brachial plexus palsy in women without shoulder dystocia.

To the Editor: Reviewing neonatal intensive care unit (NICU) records to identify cases of neonatal brachial plexus injury, Torki et al concluded “severe brachial plexus palsy occurs in women without shoulder dystocia.” Several concerns exist regarding this conclusion, including the authors’ definition of injury severity, reliance upon medical documentation, and limited follow-up duration. The severity of neonatal brachial plexus injury predicates upon factors unrelated to NICU admission, including the degree of structural damage and neurologic deficit. Higher neonatal brachial plexus injury severity corresponds to greater neuronal damage with functional impairment. Additionally, severe neonatal brachial plexus injuries exhibit lower propensity for spontaneous neural regeneration. While nearly two thirds of infants with mild neonatal brachial plexus injury exhibit functional recovery by 6 months of age, only 14% of those with substantial deficits recover function. Published reviews reflecting obstetric and surgical perspectives base neonatal brachial plexus injury severity on multiplicity of nerves involved, degree of functional impairment, and permanence of deficits. Focusing unilaterally on NICU admission and omitting descriptions of neurologic deficits, Torki et al provide a misleading and incomplete depiction of neonatal brachial plexus injury severity. Relying upon medical records and delivery summaries, Torki et al discounted the possibility of unrecognized or undocumented shoulder dystocia in their series of neonatal brachial plexus injury cases. However, the conclusion that an event did not occur based on absent documentation lacks scientific corroboration. Furthermore, the limited follow-up period raises questions regarding the accurate diagnosis of study participants. Experience in our specialty clinic reveals multiple cases in which the initial diagnosis of neonatal brachial plexus injury required modification based on further scrutiny.