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Jonathan Pindrik, George I. Jallo and Edward S. Ahn

This case series highlights multiple complications and subsequent removal of retained shunt hardware in pediatric patients after successful endoscopic third ventriculostomy (ETV). Removal or retention of existing shunt hardware following ETV represents an important dilemma. Prior studies have reported infections and organ perforation related to nonfunctioning shunts but none in the context of successful ETV. Data obtained in 3 children with hydrocephalus treated at the authors' institution were retrospectively reviewed after the patients experienced complications due to retained shunt hardware following ETV. Etiologies of hydrocephalus included tectal glioma and intraventricular hemorrhage. All 3 patients had a history of multiple shunt revisions and underwent urgent ETV in the setting of a shunt malfunction. In each case, the entire shunt system was left in situ, but it became the source of subsequent complications. Two of the 3 patients presented with the shunt infected by gram-negative bacilli 10 days and 4.5 months postoperatively, respectively. The remaining patient experienced wound dehiscence over the shunt valve 4.5 months after ETV. In all patients, the complications were managed successfully by removing the shunt hardware. None of the patients required repeat shunt insertion from the time of removal throughout the follow-up period (mean 24 months, range 9–36 months). During the study period, a total of 6 patients with indwelling shunt hardware underwent ETV with the expectation of being shunt independent. Among these 6 patients, 3 experienced no complications from the retained hardware whereas 3 patients (50%) ultimately experienced adverse consequences related to retained hardware. This case series illustrates complications involving retained shunt hardware after successful ETV. These examples support consideration of shunt removal at the time of ETV in the appropriate context.

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David Dornbos III, Jocelyn Morin, Joshua R. Watson and Jonathan Pindrik

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.

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Jonathan Pindrik, Joseph Molenda, Rafael Uribe-Cardenas, Amir H. Dorafshar and Edward S. Ahn

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.

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Jonathan Pindrik, Thierry A. G. M. Huisman, Mahadevappa Mahesh, Aylin Tekes and Edward S. Ahn

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.

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Carlos A. Bagley, Markus J. Bookland, Jonathan A. Pindrik, Tolga Ozmen, Ziya L. Gokaslan and Timothy F. Witham

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 μL 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 μL 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.

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Jonathan Pindrik, Brandon G. Rocque, Anastasia A. Arynchyna, James M. Johnston and Curtis J. Rozzelle

OBJECTIVE

Endoscopic third ventriculostomy (ETV) with choroid plexus (CP) cauterization (CPC) represents a viable treatment option for congenital hydrocephalus in infants younger than 2 years. Imaging studies complement clinical data in the evaluation of treatment success or failure. The objectives of this study were to investigate novel radiographic markers—cerebrospinal fluid (CSF) turbulence and CP visualization—and their ability to reflect or predict clinical outcomes following ETV/CPC.

METHODS

Hydrocephalic patients younger than 2 years who were initially treated by ETV/CPC at the senior authors' institution between March 2013 and February 2014 were retrospectively reviewed. Clinical data, as well as the visualization of CSF turbulence and CP on pre- and postoperative fast-sequence MRI, were recorded. Radiographic images were reviewed by a blinded observer based on specific criteria for the visualization of CSF turbulence and CP. Data were collected and analyzed using descriptive statistics, including Fisher's exact test for comparisons. The research team obtained appropriate institutional review board approval for this study, without the need for informed consent.

RESULTS

Among the 32 patients (53% male and 47% female) studied, 18 of 32 (56%) responded favorably to initial or repeat ETV/CPC, with 13 of 32 (41%) patients requiring 1 surgery. Of the 19 (59%) patients whose initial ETV/CPC failed, 8 of 19 (42%) patients underwent repeat ETV/CPC, with 5 of 8 (63%) patients responding favorably. Radiographic CSF turbulence appeared more frequently following ETV/CPC failure than after ETV/CPC success (55% vs 18%, respectively; p = 0.02). The sensitivity and specificity of CSF turbulence as a radiographic marker for ETV/CPC failure were 80% and 58%, respectively. The radiographic depiction of CP disappearance following ETV/CPC from pre- to postoperative imaging occurred in 20 of 30 patients (67%). Among the patients who responded unsuccessfully to ETV/CPC and ultimately required secondary shunt insertion, 71% (10 of 14 patients) demonstrated CP persistence on postoperative imaging. In contrast, 6% (1 of 18) of patients who were treated successfully by ETV/CPC demonstrated the presence of CP on follow-up imaging. This difference reached statistical significance (p = 0.0001). The visualization of CP persistence despite ETV/CPC reflected treatment failure with 91% sensitivity and 81% specificity. The sensitivity of either or both radiographic markers to suggest ETV/CPC failure was 77%, while their specificity (both markers absent, thereby indicating ETV/CPC success) was 81%.

CONCLUSIONS

Radiographic markers correlate with clinical outcomes following the treatment of infantile hydrocephalus with ETV/CPC. Specifically, CSF turbulence may indicate ongoing pathological CSF flow dynamics, while CP absence following ETV/CPC may predict shunt independence. Future studies that incorporate prospective review and formal intra- and interobserver reliability estimates may help corroborate the utility of these radiographic markers.

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Jonathan Pindrik, Nguyen Hoang, Luke Smith, Mark Halverson, Mary Wojnaroski, Kelly McNally, Satyanarayana Gedela and Adam P. Ostendorf

OBJECTIVE

Despite perioperative risks, epilepsy surgery represents a legitimate curative or palliative treatment approach for children with drug-resistant epilepsy (DRE). Several factors characterizing infants and toddlers with DRE create unique challenges regarding optimal evaluation and management. Epilepsy surgery within children < 3 years of age has received moderate attention in the literature, including mainly case series and retrospective studies. This article presents a systematic literature review and explores multidisciplinary considerations for the preoperative evaluation and surgical management of infants and toddlers with DRE.

METHODS

The study team conducted a systematic literature review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, targeting studies that investigated children < 3 years of age undergoing surgical treatment of DRE. Using the PubMed database, investigators selected peer-reviewed articles that reported seizure outcomes with or without developmental outcomes and/or perioperative complications. Studies were eliminated based on the following exclusion criteria: sample size < 5 patients; and inclusion of patients > 3 years of age, when demographic and outcomes data could not be separated from the cohort of patients < 3 years of age.

RESULTS

The study team identified 20 studies published between January 1990 and May 2017 that satisfied eligibility criteria. All selected studies represented retrospective reviews, observational studies, and uncontrolled case series. The compiled group of studies incorporated 465 patients who underwent resective or disconnective surgery (18 studies, 444 patients) or vagus nerve stimulator insertion (2 studies, 21 patients). Patient age at surgery ranged between 28 days and 36 months, with a mean of 16.8 months (1.4 years).

DISCUSSION

The study team provided a detailed summary of the literature review, focusing on the etiologies, preoperative evaluation, surgical treatments, seizure and developmental outcomes, and potential for functional recovery of infants and toddlers with DRE. Additionally, the authors discussed special considerations in this vulnerable age group from the perspective of multiple disciplines.

CONCLUSIONS

While presenting notable challenges, pediatric epilepsy surgery within infants and toddlers (children < 3 years of age) offers significant opportunities for improved seizure frequency, neuro-cognitive development, and quality of life. Successful evaluation and treatment of young children with DRE requires special consideration of multiple aspects related to neurological and physiological immaturity and surgical morbidity.

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Carlos A. Bagley, Jonathan A. Pindrik, Markus J. Bookland, Joaquin Q. Camara-Quintana and Benjamin S. Carson

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.

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Pablo F. Recinos, Jonathan A. Pindrik, Mazen I. Bedri, Edward S. Ahn, George I. Jallo and Violette Renard Recinos

Object

The aim of this study was to examine the feasibility and safety of ventriculoperitoneal (VP) shunt placement using a periumbilical approach for distal peritoneal access. By using this minimally invasive approach, the authors hypothesized that the cosmetic outcomes would be better than could be achieved by using a traditional minilaparotomy and that clinical results would be comparable.

Methods

A periumbilical approach was used for distal catheter insertion during a first-time VP shunt placement in 20 patients (8 males and 12 females). Median age at time of surgery was 3.0 months (range 7 days–11.9 years) and mean follow-up time was 17.8 months (range 1.2–28.0 months). The median weight of the patients was 3.99 kg (range 1.95–57.0 kg). A single incision was made along the natural crease inferior to the umbilicus. The linea alba was exposed and a 1-mm incision made while the patient was temporarily held in a Valsalva maneuver. A peritoneal trocar was then inserted through the fascial incision and the distal catheter was passed into the peritoneal space.

Results

The incision line in all patients healed well, did not require operative revision, and was described as minimally visible by the patients' families. Mean operative time was 35 minutes. Eight patients required revision surgery. One distal failure occurred when the distal shunt tubing retracted and became coiled in the neck; this was repaired by conversion to a minilaparotomy for distal replacement. There was 1 shunt infection (5%) requiring shunt removal and replacement. One patient had significant skin thinning around the valve and proximal catheter, which required replacement of the entire shunt system, and another patient underwent a conversion to a ventriculoatrial shunt due to poor peritoneal absorption. In the remaining 4 patients who required operative revision, the peritoneal portion of the shunt was not involved.

Conclusions

The periumbilical approach for peritoneal access during VP shunt placement is technically feasible, has low infection rates, and has cosmetically appealing results. It may be considered as an alternative option to standard VP shunt placement techniques.

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Carlos A. Bagley, Markus J. Bookland, Jonathan A. Pindrik, Tolga Ozmen, Ziya L. Gokaslan, Jean-Paul Wolinsky and Timothy F. Witham

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 animal's 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.