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John A. Boockvar, William Loudon, and Leslie N. Sutton

✓ The history of the treatment for hydrocephalus dates back to the Fertile Crescent thousands of years ago. Despite three millennia of management, significant advances in the surgical treatment of the disease have been infrequent. During the 1950s, a milestone occurred at the Children's Hospital of Philadelphia, with the successful development of the first working shunt valve for the treatment of hydrocephalus. In this historical vignette, based on recent interviews with John Holter, D.Sc. (Hon) and Eugene Spitz, M.D., and on a review of the available literature, the authors narrate the exciting story of the development of the Spitz-Holter valve, which took place in Philadelphia during the early 1950s.

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Cranial base reconstruction

Fredric B. Meyer

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Jennifer A. Moliterno, Lynn L. Mubita, Clark Huang, and John A. Boockvar

Endoscopic endonasal transsphenoidal surgery (ETSS) is an effective, minimally invasive approach for the resection of anterior skull base tumors. Cerebrospinal leakage is a common complication, and repair of the anterior skull base defect with alloplastic materials has been used to minimize the risk of postoperative CSF rhinorrhea and meningitis. Injectable cements, such as low-viscosity polymethylmethacrylate (PMMA), are useful for cranial base reconstruction because they are easy to shape to the contour of the defect. These low-viscosity materials, however, are more susceptible to leakage into the nasal cavity prohibiting their use and are prone to cracking upon hardening. Cement extravasation not only obstructs the operator's view during placement, but it is also associated with significant local and systemic complications. High-viscosity (HV) PMMA–based cement and its specialized delivery system have recently been shown to be safe and effective in human applications. Moreover, its constant high viscosity significantly reduces cement leakage and its associated complications. The authors hypothesized that this type of cement would therefore be ideal for ETSS to repair anterior skull base defects. The authors report their experience using HV-PMMA to reconstruct the anterior skull base in 12 patients following ETSS. The unique puttylike consistency of this material is easy to work, malleable, does not leak into the nasal cavity, does not aspirate into suction tubing, and hardens without cracks in less than 10 minutes. None of the 12 patients suffered postoperative CSF leaks or infections more than 8 months, on average, after surgery. Although not necessary in all cases of ETSS, the authors conclude that HV-PMMA, if needed, may be an excellent choice for reconstructing the anterior skull base after ETSS. Further studies are needed to better assess the long-term outcomes of HV-PMMA cement and its use in repairing skull base defects after extended ETSS.

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Malte Ottenhausen, Imithri Bodhinayake, Alexander I. Evins, Matei Banu, John A. Boockvar, and Antonio Bernardo

In this article the authors discuss the development of neurosurgical approaches and the advances in science and technology that influenced this development throughout history. They provide a broad overview of this interesting topic from the first attempts of trephination by ancient cultures to the work of the pioneers of neurosurgery and the introduction of microsurgery.

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John A. Boockvar, Matthew F. Philips, Albert E. Telfeian, Donald M. O'Rourke, and Paul J. Marcotte

Object. Stabilization of the cervicothoracic junction (CTJ) requires special attention to the operative approach and biomechanical requirements of the fixation construct. In this study the authors assess the morbidity associated with the anterior approach to the CTJ and define risks that may lead to construct failure after anterior CTJ surgery.

Methods. Data obtained for 14 patients (six men and eight women, mean age 50.1 years) who underwent surgical stabilization of the CTJ via an anterior cervical approach were retrospectively reviewed to assess the anterior approach—related morbidity and the risks of construct failure. The mean follow-up period was 21.1 months. Four patients (29%) had previously undergone CTJ surgery; in 11 patients (64%) more than one motion segment was involved (two levels, six patients; three levels, four patients; four levels, one patient); allograft was placed in three (21%) of 14 graft sites; and anterior plates were used for reconstruction augmentation in eight patients (57%). Postoperatively all patients improved, although four patients had residual deficits or pain. Graft/plate failure, requiring surgical revision and/or halo placement, occurred in five patients (36%). One patient experienced transient recurrent laryngeal nerve palsy. Postoperatively, the authors classified patients into one of two groups: those in whom surgery was successful (nine cases) and those in whom it had failed (five cases). Analysis of the characteristics of these two groups revealed that male sex (p < 0.0365), multiple levels of involvement (p < 0.0378), and the use of allograft as compared with autograft (p < 0.0088) were significant risk factors for construct failure. Prior CTJ surgery (p < 0.053) tended to be associated with graft failure.

Conclusions: Findings of this study, in the setting of these factors, indicate that anterior reconstruction alone may not meet the biomechanical needs of this spinal region and that supplementary fixation may be considered to augment stabilization for fusion success.

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Heather J. McCrea, Jana Ivanidze, Ashley O’Connor, Eliza H. Hersh, John A. Boockvar, Y. Pierre Gobin, Jared Knopman, and Jeffrey P. Greenfield


Delivery of drugs intraarterially to brain tumors has been demonstrated in adults. In this study, the authors initiated a phase I trial of superselective intraarterial cerebral infusion (SIACI) of bevacizumab and cetuximab in pediatric patients with refractory high-grade glioma (diffuse intrinsic pontine glioma [DIPG] and glioblastoma) to determine the safety and efficacy in this population.


SIACI was used to deliver mannitol (12.5 ml of 20% mannitol) to disrupt the blood-brain barrier (BBB), followed by bevacizumab (15 mg/kg) and cetuximab (200 mg/m2) to target VEGF and EGFR, respectively. Patients with brainstem tumors had a balloon inflated in the distal basilar artery during mannitol infusion.


Thirteen patients were treated (10 with DIPG and 3 with high-grade glioma). Toxicities included grade I epistaxis (2 patients) and grade I rash (2 patients). There were no dose-limiting toxicities. Of the 10 symptomatic patients, 6 exhibited subjective improvement; 92% showed decreased enhancement on day 1 posttreatment MRI. Of 10 patients who underwent MRI at 1 month, 5 had progressive disease and 5 had stable disease on FLAIR, whereas contrast-enhanced scans demonstrated progressive disease in 4 patients, stable disease in 2, partial response in 2, and complete response in 1. The mean overall survival for the 10 DIPG patients was 519 days (17.3 months), with a mean posttreatment survival of 214.8 days (7.2 months).


SIACI of bevacizumab and cetuximab was well tolerated in all 13 children. The authors’ results demonstrate safety of this method and warrant further study to determine efficacy. As molecular targets are clarified, novel means of bypassing the BBB, such as intraarterial therapy and convection-enhanced delivery, become more critical.

Clinical trial registration no.: NCT01884740 (

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Ranjodh Singh, William P. Cope, Zhiping Zhou, Michelle E. De Witt, John A. Boockvar, and Apostolos J. Tsiouris


Isolated cortical vein thrombosis (ICVT) accounts for less than 1% of all cerebral infarctions. ICVT may cause irreversible parenchymal damage, rendering early and accurate diagnosis critical. This case series and literature review presents the clinical and radiological findings in 7 patients with ICVT, and highlights risk factors and imaging modalities that may be most beneficial in rendering an accurate and timely diagnosis.


Patients with CT and MRI findings consistent with ICVT examined between January 2011 and June 2014 were included in this retrospective review.


Seven patients (5 females, 2 males), ranging in age from 11 months to 34 years, met the inclusion criteria. The most common clinical presentations were headaches (n = 4) and seizures (n = 3). The most common comorbidities noted in these patients were hypercoagulable states (n = 4) and intracranial hypotension (n = 3). Five patients had intraparenchymal involvement. CT suggested the correct diagnosis in 4 patients, and MRI confirmed the diagnosis in all 7 patients. All patients who received anticoagulation therapy (n = 5) experienced complete resolution of their symptoms.


The majority of these patients were adult females, consistent with published data. Seizures and headaches were the most common presenting symptoms. Hypercoagulable state and intracranial hypotension, both known risk factors for thrombosis, were the most commonly noted ICVT risk factors. Intraparenchymal involvement was prevalent in nearly all ICVT cases and presented as vasogenic edema, early intraparenchymal hemorrhage, or hemorrhagic venous infarction. Susceptibility-weighted imaging was the most sensitive imaging technique in diagnosing ICVT.

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Albert E. Telfeian, John A. Boockvar, Tanya Simuni, Jurg Jaggi, Brett Skolnick, and Gordon H. Baltuch

✓ Deep brain stimulation (DBS) of the ventralis intermedius nucleus (Vim) is a safe and effective treatment for essential tremor. Bipolar disorder and essential tremor had each been reported to occur in association with Klinefelter syndrome but the three diseases have been reported to occur together in only one patient. The genetic basis and natural history of these disorders are not completely understood and may be related rather than coincidental. The authors report on a 23-year-old man with Klinefelter syndrome (47,XXY) and bipolar disorder who was treated successfully with unilateral DBS of the thalamic Vim for essential tremor.

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Jennifer A. Moliterno, Jared Knopman, Karishma Parikh, Jessica N. Cohan, Q. Daisy Huang, Grant D. Aaker, Anastasia D. Grivoyannis, Ashwin R. Patel, Roger Härtl, and John A. Boockvar


The use of minimally invasive surgical techniques, including microscope-assisted tubular lumbar microdiscectomy (tLMD), has gained increasing popularity in treating lumbar disc herniations (LDHs). This particular procedure has been shown to be both cost-efficient and effective, resulting in outcomes comparable to those of open surgical procedures. Lumbar disc herniation recurrence necessitating reoperation, however, remains an issue following spinal surgery, with an overall reported incidence of approximately 3–13%. The authors' aim in the present study was to report their experience using tLMD for single-level LDH, hoping to provide further insight into the rate of surgical recurrence and to identify potential risk factors leading to this complication.


The authors retrospectively reviewed the cases of 217 patients who underwent tLMD for single-level LDH performed identically by 2 surgeons (J.B., R.H.) between 2004 and 2008. Evaluation for LDH recurrence included detailed medical chart review and telephone interview. Recurrent LDH was defined as the return of preoperative signs and symptoms after an interval of postoperative resolution, in conjunction with radiographic demonstration of ipsilateral disc herniation at the same level and pathological confirmation of disc material. A cohort of patients without recurrence was used for comparison to identify possible risk factors for recurrent LDH.


Of the 147 patients for whom the authors were able to definitively assess symptomatic recurrence status, 14 patients (9.5%) experienced LDH recurrence following single-level tLMD. The most common level involved was L5–S1 (42.9%) and the mean length of time to recurrence was 12 weeks (range 1.5–52 weeks). Sixty-four percent of the patients were male. In a comparison with patients without recurrence, the authors found that relatively lower body mass index was significantly associated with recurrence (p = 0.005), such that LDH in nonobese patients was more likely to recur.


Recurrence rates following tLMD for LDH compare favorably with those in patients who have undergone open discectomy, lending further support for its effectiveness in treating single-level LDH. Nonobese patients with a relatively lower body mass index, in particular, appear to be at greater risk for recurrence.

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Casey M. Chai, Matei A. Banu, William Cobb, Neel Mehta, Linda Heier, and John A. Boockvar

The authors report 2 cases of orthostatic headaches associated with spontaneous intracranial hypotension (SIH) secondary to CSF leaks that were successfully treated with an alternative dural repair technique in which a tubular retractor system and a hydrogel dural sealant were used. The 2 patients, a 63-year-old man and a 45-year-old woman, presented with orthostatic headache associated with SIH secondary to suspected lumbar and lower cervical CSF leaks, respectively, as indicated by bony defects or epidural fluid collection. Epidural blood patch repair failed in both cases, but both were successfully treated with the minimally invasive application of a hydrogel dural sealant as a novel adjunct to traditional dural repair techniques. Both patients tolerated the procedure well. Moreover, SIH symptoms and MRI signs were completely resolved at 1-month follow-up in both patients.

The minimally invasive dural repair procedure with hydrogel dural sealant described here offers a viable alternative in patients in whom epidural blood patches have failed, with obscure recalcitrant CSF leaks at the cervical as well as lumbar spinal level. The authors demonstrate that the adjuvant use of sealant is a safe and efficient repair method regardless of dural defect location.