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Vivek Sudhakar, Jerusha Naidoo, Lluis Samaranch, John R. Bringas, Russell R. Lonser, Massimo S. Fiandaca and Krystof S. Bankiewicz

OBJECTIVE

To develop and assess a convective delivery technique that enhances the effectiveness of drug delivery to nonspherical brain nuclei, the authors developed an occipital “infuse-as-you-go” approach to the putamen and compared it to the currently used transfrontal approach.

METHODS

Eleven nonhuman primates received a bilateral putamen injection of adeno-associated virus with 2 mM gadolinium-DTPA by real-time MR-guided convective perfusion via either a transfrontal (n = 5) or occipital infuse-as-you-go (n = 6) approach.

RESULTS

MRI provided contemporaneous assessment and monitoring of putaminal infusions for transfrontal (2 to 3 infusion deposits) and occipital infuse-as-you-go (stepwise infusions) putaminal approaches. The infuse-as-you-go technique was more efficient than the transfrontal approach (mean 35 ± 1.1 vs 88 ± 8.3 minutes [SEM; p < 0.001]). More effective perfusion of the postcommissural and total putamen was achieved with the infuse-as-you-go versus transfronatal approaches (100-µl infusion volumes; mean posterior commissural coverage 76.2% ± 5.0% vs 32.8% ± 2.9% [p < 0.001]; and mean total coverage 53.5% ± 3.0% vs 38.9% ± 2.3% [p < 0.01]).

CONCLUSIONS

The infuse-as-you-go approach, paralleling the longitudinal axis of the target structure, provides a more effective and efficient method for convective infusate coverage of elongated, irregularly shaped subcortical brain nuclei.

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Jawad M. Khalifeh, Christopher F. Dibble, Anna Van Voorhis, Michelle Doering, Martin I. Boyer, Mark A. Mahan, Thomas J. Wilson, Rajiv Midha, Lynda J. S. Yang and Wilson Z. Ray

OBJECTIVE

Patients with cervical spinal cord injury (SCI)/tetraplegia consistently rank restoring arm and hand function as their top functional priority to improve quality of life. Motor nerve transfers traditionally used to treat peripheral nerve injuries are increasingly being used to treat patients with cervical SCIs. In this study, the authors performed a systematic review summarizing the published literature on nerve transfers to restore upper-extremity function in tetraplegia.

METHODS

A systematic literature search was conducted using Ovid MEDLINE 1946–, Embase 1947–, Scopus 1960–, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and clinicaltrials.gov to identify relevant literature published through January 2019. The authors included studies that provided original patient-level data and extracted information on clinical characteristics, operative details, and strength outcomes after nerve transfer procedures. Critical review and synthesis of the articles were performed.

RESULTS

Twenty-two unique studies, reporting on 158 nerve transfers in 118 upper limbs of 92 patients (87 males, 94.6%) were included in the systematic review. The mean duration from SCI to nerve transfer surgery was 18.7 months (range 4 months–13 years) and mean postoperative follow-up duration was 19.5 months (range 1 month–4 years). The main goals of reinnervation were the restoration of thumb and finger flexion, elbow extension, and wrist and finger extension. Significant heterogeneity in transfer strategy and postoperative outcomes were noted among the reports. All but one case report demonstrated recovery of at least Medical Research Council grade 3/5 strength in recipient muscle groups; however, there was greater variation in the results of larger case series. The best, most consistent outcomes were demonstrated for restoration of wrist/finger extension and elbow extension.

CONCLUSIONS

Motor nerve transfers are a promising treatment option to restore upper-extremity function after SCI. Flexor reinnervation strategies show variable treatment effect sizes; however, extensor reinnervation may provide more consistent, meaningful recovery. Despite numerous published case reports describing good patient outcomes with nerve transfers, there remains a paucity in the literature regarding optimal timing and long-term clinical outcomes with these procedures.

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Jawad M. Khalifeh, Christopher F. Dibble, Anna Van Voorhis, Michelle Doering, Martin I. Boyer, Mark A. Mahan, Thomas J. Wilson, Rajiv Midha, Lynda J. S. Yang and Wilson Z. Ray

OBJECTIVE

Patients with cervical spinal cord injury (SCI)/tetraplegia consistently rank restoring arm and hand function as their top functional priority to improve quality of life. Motor nerve transfers traditionally used to treat peripheral nerve injuries are increasingly used to treat patients with cervical SCIs. In this article, the authors present early results of a prospective clinical trial using nerve transfers to restore upper-extremity function in tetraplegia.

METHODS

Participants with American Spinal Injury Association (ASIA) grade A–C cervical SCI/tetraplegia were prospectively enrolled at a single institution, and nerve transfer(s) was performed to improve upper-extremity function. Functional recovery and strength outcomes were independently assessed and prospectively tracked.

RESULTS

Seventeen participants (94.1% males) with a median age of 28.4 years (range 18.2–76.3 years) who underwent nerve transfers at a median of 18.2 months (range 5.2–130.8 months) after injury were included in the analysis. Preoperative SCI levels ranged from C2 to C7, most commonly at C4 (35.3%). The median postoperative follow-up duration was 24.9 months (range 12.0–29.1 months). Patients who underwent transfers to median nerve motor branches and completed 18- and 24-month follow-ups achieved finger flexion strength Medical Research Council (MRC) grade ≥ 3/5 in 4 of 15 (26.7%) and 3 of 12 (25.0%) treated upper limbs, respectively. Similarly, patients achieved MRC grade ≥ 3/5 wrist flexion strength in 5 of 15 (33.3%) and 3 of 12 (25.0%) upper limbs. Among patients who underwent transfers to the posterior interosseous nerve (PIN) for wrist/finger extension, MRC grade ≥ 3/5 strength was demonstrated in 5 of 9 (55.6%) and 4 of 7 (57.1%) upper limbs 18 and 24 months postoperatively, respectively. Similarly, grade ≥ 3/5 strength was demonstrated in 5 of 9 (55.6%) and 4 of 7 (57.1%) cases for thumb extension. No meaningful donor site deficits were observed. Patients reported significant postoperative improvements from baseline on upper-extremity–specific self-reported outcome measures.

CONCLUSIONS

Motor nerve transfers are a promising treatment option to restore upper-extremity function after SCI. In the authors’ experience, nerve transfers for the reinnervation of hand and finger flexors showed variable functional recovery; however, transfers for the reinnervation of arm, hand, and finger extensors showed a more consistent and meaningful return of strength and function.

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Daphne Li, Daniel M. Heiferman, Hasan R. Syed, João Gustavo Santos, Robin M. Bowman, Arthur J. DiPatri Jr., Tadanori Tomita, Nitin R. Wadhwani and Tord D. Alden

Atypical teratoid rhabdoid tumors (ATRTs) are rare malignant central nervous system tumors, commonly occurring before 3 years of age. Median overall survival (OS) of patients with these tumors is about 1 year, despite aggressive multimodal therapy. Pediatric primary spinal ATRTs are even more rare, with fewer than 50 cases reported. The authors present a series of four patients who were treated at Ann and Robert H. Lurie Children’s Hospital of Chicago in the period from 1996 to 2017.

These patients, with ages 2–11 years, presented with pain and a decline in motor functions. They were found to have lesions in the lumbar, thoracic, and/or cervical spine. One patient’s tumor was intramedullary with exophytic components, while another patient’s tumor had both intra- and extradural components. All patients underwent resection followed by chemotherapy (systemic and intrathecal). Two patients had fractionated radiation therapy and one had an autologous stem cell transplant. Three patients are known to be deceased (OS 8.5–45 months). The fourth patient was in remission 19 years after her initial diagnosis. To the authors’ knowledge, this is the largest series of pediatric primary spinal ATRTs documented at a single institution. These cases illustrate a variety of presentations of spinal ATRT and add to the body of literature on this aggressive pathology.

A systematic MEDLINE search was also conducted using the keywords “atypical teratoid rhabdoid tumor,” “pediatric spinal rhabdoid tumor,” and “malignant rhabdoid tumor spine.” Reports were included for patients younger than 21 years, without evidence of intracranial or systemic disease at the time of diagnosis. Clinical characteristics and outcomes of the four institutional cases were compared to those in the literature. This review yielded an additional 48 cases of primary pediatric spinal ATRTs reported in the English-language literature. Patients (ages 2 months to 19 years) presented with symptoms of pain, regression of motor function, and spinal cord compression. The majority of tumors were intradural (14 extramedullary, 8 intramedullary, 1 both). Eleven cases in the literature described tumors limited to extradural structures, while 10 tumors involved the intra- and extradural spine. Four reports did not specify tumor location. Although rare, spinal ATRT should be considered in the differential diagnosis of pediatric patients presenting with a new spinal mass.

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Natasha Ironside, Brandon Christophe, Samuel Bruce, Amanda M. Carpenter, Trae Robison, Nina Yoh, Serge Cremers, Donald Landry, Hans-Peter Frey, Ching-Jen Chen, Brian L. Hoh, Louis J. Kim, Jan Claassen and Edward Sander Connolly Jr.

OBJECTIVE

Delayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH.

METHODS

In this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH.

RESULTS

Of the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm.

CONCLUSIONS

The power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.

Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov)

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Ki Young Lee, Jung-Hee Lee, Kyung-Chung Kang, Won-Ju Shin, Sang Kyu Im and Seong Jin Cho

OBJECTIVE

The incidence of proximal junctional kyphosis (PJK) after long-segment fixation in patients with adult spinal deformity (ASD) has been reported to range from 17% to 61.7%. Recent studies have reported using “hybrid” techniques in which semirigid fixation is introduced between the fused and flexible segments at the proximal level to allow a more gradual transition. The authors used these hybrid techniques in a clinical setting and analyzed PJK to evaluate the usefulness of the flexible rod (FR) technique.

METHODS

The authors retrospectively selected 77 patients with lumbar degenerative kyphosis (LDK) who underwent sagittal correction and long-segment fixation and had follow-up for > 1 year. An FR was used in 30 of the 77 patients. PJK development and spinal sagittal changes were analyzed in the FR and non-FR groups, and the predictive factors of PJK between a PJK group and a non-PJK group were compared.

RESULTS

The patient population comprised 77 patients (75 females and 2 males) with a mean (± SD) follow-up of 32.0 ± 12.7 months (36.7 ± 9.8 months in the non-FR group and 16.8 ± 4.7 months in the FR group) and mean (± SD) age of 71.7 ± 5.1 years. Sagittal balance was well maintained at final follow-up (10.5 and 1.5 mm) in the non-FR and FR groups, respectively. Thoracic kyphosis (TK) and lumbar lordosis (LL) were improved in both groups, without significant differences between the two (p > 0.05). PJK occurred in 28 cases (36.4%) in total, 3 (10%) in the FR and 25 (53.2%) in the non-FR group (p < 0.001). Postoperatively, PJK was observed at an average of 8.9 months in the non-FR group and 1 month in the FR group. No significant differences in the incidence of PJK regarding patient factors or radiological parameters were found between the PJK group and non-PJK group (p > 0.05). However, FR (vs non-FR) and interbody fusion except L5–S1 using oblique lumbar interbody fusion (vs non–oblique lumbar interbody fusion), demonstrated a significantly lower PJK prevalence (p < 0.001 and p = 0.044) among the surgical factors.

CONCLUSIONS

PJK was reduced after surgical treatment with the FR in the patients with LDK. Solid long-segment fixation and the use of the FR may become another surgical option for spine surgeons who plan and make decisions regarding spine reconstruction surgery for patients with ASD.

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Ali Tayebi Meybodi, Michael T. Lawton, Leandro Borba Moreira, Xiaochun Zhao, Michael J. Lang, Peter Nakaji and Mark C. Preul

OBJECTIVE

Harvesting the occipital artery (OA) is challenging. The subcutaneous OA is usually found near the superior nuchal line and followed proximally, requiring a large incision and risking damage to the superficially located OA. The authors assessed the anatomical feasibility and safety of exposing the OA through a retromastoid-transmuscular approach.

METHODS

Using 10 cadaveric heads, 20 OAs were harvested though a 5-cm retroauricular incision placed 5 cm posterior to the external auditory meatus. The underlying muscle layers were sequentially cut and recorded before exposing the OA. Changes in the orientation of muscle fibers were used as a roadmap to expose the OA without damaging it.

RESULTS

The suboccipital segment of the OA was exposed without damage after incising two consecutive layers of muscles and their investing fasciae. These muscles displayed different fiber directions: the superficially located sternocleidomastoid muscle with vertically oriented fibers, and the underlying splenius capitis with anteroposteriorly (and mediolaterally) oriented fibers. The OA could be harvested along the entire length of the skin incision in all specimens. If needed, the incision can be extended proximally and/or distally to follow the OA and harvest greater lengths.

CONCLUSIONS

This transmuscular technique for identification of the OA is a reliable method and may facilitate exposure and protection of the OA during a retrosigmoid approach. This technique may obviate the need for larger incisions when planning a bypass to nearby arteries in the posterior circulation via a retrosigmoid craniotomy. Additionally, the small skin incision can be enlarged when a different craniotomy and/or bypass is planned or when a greater length of the OA is needed to be harvested.

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Peter Shih-Ping Hung, Sarasa Tohyama, Jia Y. Zhang and Mojgan Hodaie

OBJECTIVE

Gamma Knife radiosurgery (GKRS) is a noninvasive surgical treatment option for patients with medically refractive classic trigeminal neuralgia (TN). The long-term microstructural consequences of radiosurgery and their association with pain relief remain unclear. To better understand this topic, the authors used diffusion tensor imaging (DTI) to characterize the effects of GKRS on trigeminal nerve microstructure over multiple posttreatment time points.

METHODS

Ninety-two sets of 3-T anatomical and diffusion-weighted MR images from 55 patients with TN treated by GKRS were divided within 6-, 12-, and 24-month posttreatment time points into responder and nonresponder subgroups (≥ 75% and < 75% reduction in posttreatment pain intensity, respectively). Within each subgroup, posttreatment pain intensity was then assessed against pretreatment levels and followed by DTI metric analyses, contrasting treated and contralateral control nerves to identify specific biomarkers of successful pain relief.

RESULTS

GKRS resulted in successful pain relief that was accompanied by asynchronous reductions in fractional anisotropy (FA), which maximized 24 months after treatment. While GKRS responders demonstrated significantly reduced FA within the radiosurgery target 12 and 24 months posttreatment (p < 0.05 and p < 0.01, respectively), nonresponders had statistically indistinguishable DTI metrics between nerve types at each time point.

CONCLUSIONS

Ultimately, this study serves as the first step toward an improved understanding of the long-term microstructural effect of radiosurgery on TN. Given that FA reductions remained specific to responders and were absent in nonresponders up to 24 months posttreatment, FA changes have the potential of serving as temporally consistent biomarkers of optimal pain relief following radiosurgical treatment for classic TN.