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M. Benjamin Larkin, John P. McGinnis, Rita I. Snyder, Eric A. Storch, Wayne K. Goodman, Ashwin Viswanathan and Sameer A. Sheth

Posttraumatic stress disorder (PTSD) is a widespread and often devastating psychiatric condition. Core symptoms include intrusive and distressing thoughts, heightened reactivity, mood changes, cognitive impairments, and consequent avoidance of trauma-related stimuli. Symptoms of PTSD are often refractory to standard treatments, and neuromodulatory techniques have therefore drawn significant interest among the most treatment-resistant patients. Transcranial magnetic stimulation has demonstrated minimal efficacy, and deep brain stimulation trials are currently ongoing. PTSD is a disorder of neural circuitry; the current understanding includes involvement of the amygdala (basolateral and central nuclei), the prefrontal cortex (ventral medial and dorsolateral regions), and the hippocampus. Neuroimaging and optogenetic studies have improved the understanding of large-scale neural networks and the effects of microcircuitry manipulation, respectively. This review discusses the current PTSD literature and ongoing neurostimulation trials, and it highlights the current understanding of neuronal circuit dysfunction in PTSD. The authors emphasize the anatomical correlations of PTSD’s hallmark symptoms, offer another potential deep brain stimulation target for PTSD, and note the need for continued research to identify useful biomarkers for the development of closed-loop therapies. Although there is hope that neuromodulation will become a viable treatment modality for PTSD, this concept remains theoretical, and further research should involve institutional review board–approved controlled prospective clinical studies.

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John K. Houten, Joshua R. Buksbaum and Michael J. Collins

OBJECTIVE

Paresis of the C5 nerve is a well-recognized complication of cervical spine surgery. Numerous studies have investigated its incidence and possible causes, but the specific pattern and character of neurological deficits, time course, and relationship to preoperative cord signal changes remain incompletely understood.

METHODS

Records of patients undergoing cervical decompressive surgery for spondylosis, disc herniation, or ossification of the longitudinal ligament, including the C4–5 level, were reviewed from a 15-year period, identifying C5 palsy cases. Data collected included age, sex, diabetes and smoking statuses, body mass index, surgical levels, approach, presence of increased cord signal intensity, and modified Japanese Orthopaedic Association (mJOA) scores. Narrative descriptions of the patterns and findings on neurological examination were reviewed, and complications were noted. The minimum follow-up requirement for the study was 12 months.

RESULTS

Of 642 patients who underwent cervical decompressive surgery, 18 developed C5 palsy (2.8%). The incidence was significantly lower following anterior surgery (6 of 441 [1.4%]) compared with that following cervical laminectomy and fusion (12 of 201 [6.0%]) (p < 0.001). There were 10 men and 8 women whose mean age was 66.7 years (range 54–76 years). The mean preoperative mJOA score of 11.4 improved to 15.6 at the latest follow-up examination. There were no differences between those with and without C5 palsy with regard to sex, age, number of levels treated, or pre- or postoperative mJOA score. Fifteen patients with palsy (83%) had signal changes/myelomalacia on preoperative T2-weighted imaging, compared with 436 of 624 (70%) patients without palsy; however, looking specifically at the C4–5 level, signal change/myelomalacia was present in 12 of 18 (67%) patients with C5 palsy, significantly higher than in the 149 of 624 (24%) patients without palsy (p < 0.00003). Paresis was unilateral in 16 (89%) and bilateral in 2 (11%) patients. All had deltoid weakness, but 15 (83%) exhibited new biceps weakness, 8 (44%) had triceps weakness, and 2 (11%) had hand intrinsic muscle weakness. The mean time until onset of palsy was 4.6 days (range 2–14 days). Two patients (11%) complained of shoulder pain preceding weakness; 3 patients (17%) had sensory loss. Recovery to grade 4/5 deltoid strength occurred in 89% of the patients. No patient had intraoperative loss of somatosensory or motor evoked potentials or abnormal intraoperative C5 electromyography activity.

CONCLUSIONS

Postoperative C5 nerve root dysfunction appears in a delayed fashion, is predominantly a motor deficit, and weakness is frequently appreciated in the biceps and triceps muscles in addition to the deltoid muscle. Preoperative cord signal change/myelomalacia at C4–5 was a significant risk factor. No patient had a detectable deficit in the immediate postoperative period or changes in intraoperative neuromonitoring status. Neurological recovery to at least that of grade 4/5 occurred in nearly 90% of the patients.

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Eduardo A. Iunes, Enrico A. Barletta, Telmo A. B. Belsuzarri, Franz J. Onishi, André Y. Aihara, Sergio Cavalheiro and Andrei F. Joaquim

OBJECTIVE

The goal of this study was to evaluate the incidence of pseudarthrosis after the treatment of cervical degenerative disc disease (CDDD) with anterior cervical discectomy and fusion (ACDF) in which self-locking, stand-alone intervertebral cages filled with hydroxyapatite were used.

METHODS

The authors performed a retrospective cohort study of 49 patients who underwent 1- to 3-level ACDF with self-locking, stand-alone intervertebral cages without plates, with a minimum 2 years of follow-up. The following data were extracted from radiological and clinical charts: age, sex, time and type of pre- and postoperative signs and symptoms, pain status (visual analog scale [VAS]), functional status (Neck Disability Index [NDI]), history of smoking, bone quality (bone densitometry), and complications. Pseudarthrosis was diagnosed by a blinded neuroradiologist using CT scans. Clinical improvement was assessed using pre- and postoperative comparison of VAS and NDI scores. The Wilcoxon test for paired tests was used to evaluate statistical significance using a p value of < 0.05.

RESULTS

Three patients (6%) developed symptomatic pseudarthrosis requiring reoperation, with only 1 patient showing clinical worsening due to pseudarthrosis, while the other 2 with pseudarthrosis had associated disc disease at an adjacent level. The rate of symptomatic pseudarthrosis according to the number of operated levels was 0% for 1 level, 8.7% (2/23 patients) for 2 levels, and 7.7% (1/13 patients) for 3 levels. The total pseudarthrosis rate (including both symptomatic and asymptomatic patients) was 16.4%. Considering the clinical outcomes, there was a significant improvement of 75.6% in neck pain and 95.7% in arm pain, as well as a 64.9% improvement in NDI scores. Complications were observed in 18.4% of patients, with adjacent-level degenerative disease being the most prevalent at 14.3%.

CONCLUSIONS

ACDF with self-locking, stand-alone cages filled with a hydroxyapatite graft can be used for the surgical treatment of 1- to 3-level CDDD with clinical and radiological outcomes significantly improved after a minimum 2-year follow-up period. Comparative studies are necessary.

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Masayoshi Iwamae, Akinobu Suzuki, Koji Tamai, Hidetomi Terai, Masatoshi Hoshino, Hiromitsu Toyoda, Shinji Takahashi, Shoichiro Ohyama, Yusuke Hori, Akito Yabu and Hiroaki Nakamura

OBJECTIVE

Although numbness is one of the chief complaints of patients with cervical spondylotic myelopathy (CSM), preoperative factors relating to residual numbness of the upper extremity (UE) and impact of the outcomes on cervical surgery are not well established. The authors hypothesized that severe preoperative UE numbness could be a risk factor for residual UE numbness after surgery and that the residual UE numbness could have a negative impact on postoperative outcomes. Therefore, this study aimed to identify the preoperative factors that are predictive of residual UE numbness after cervical surgery and demonstrate the effects of residual UE numbness on clinical scores and radiographic parameters.

METHODS

The study design was a retrospective cohort study. The authors analyzed data of 103 patients who underwent cervical laminoplasty from January 2012 to December 2014 and were followed up for more than 2 years postoperatively. The patients were divided into two groups: the severe residual-numbness group (postoperative visual analog scale [VAS] score for UE numbness > 40 mm) and the no/mild residual-numbness group (VAS score ≤ 40 mm). The outcome measures were VAS score, Japanese Orthopaedic Association scores for cervical myelopathy, physical and mental component summaries of the 36-Item Short-Form Health Survey (SF-36), radiographic film parameters (C2–7 sagittal vertical axis, range of motion, C2–7 lordotic angle, and C7 slope), and MRI findings (severity of cervical canal stenosis, snake-eye appearance, severity of foraminal stenosis). Following univariate analysis, which compared the preoperative factors between groups, the variables with p values < 0.1 were included in the multivariate linear regression analysis. Additionally, the changes in clinical scores and radiographic parameters after 2 years of surgery were compared using a mixed-effects model.

RESULTS

Among 103 patients, 42 (40.8%) had residual UE numbness. In the multivariate analysis, sex and preoperative UE pain were found to be independent variables correlating with residual UE numbness (p = 0.017 and 0.046, respectively). The severity of preoperative UE numbness did not relate to the residual UE numbness (p = 0.153). The improvement in neck pain VAS score and physical component summary of the SF-36 was significantly low in the severe residual-numbness group (p < 0.001 and 0.040, respectively).

CONCLUSIONS

Forty-one percent of the CSM patients experienced residual UE numbness for at least 2 years after cervical posterior decompression surgery. Female sex and preoperative severe UE pain were the predictive factors for residual UE numbness. The patients with residual UE numbness showed less improvement of neck pain and lower physical status compared to the patients without numbness.

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David S. Hersh, Rahul Kumar, Kenneth A. Moore, Luke G. F. Smith, Christopher L. Tinkle, Jason Chiang, Zoltan Patay, Amar Gajjar, Asim F. Choudhri, Jorge A. Lee-Diaz, Brandy Vaughn and Paul Klimo Jr.

OBJECTIVE

Biopsies of brainstem lesions are performed to establish a diagnosis in the setting of an atypical clinical or radiological presentation, or to facilitate molecular studies. A better understanding of the safety and diagnostic yield of brainstem biopsies would help guide appropriate patient selection.

METHODS

All patients who underwent biopsy of a brainstem lesion during the period from January 2011 to June 2019 were reviewed. Demographic, radiological, surgical, and outcome data were collected.

RESULTS

A total of 58 patients underwent 65 brainstem biopsies during the study period. Overall, the median age was 7.6 years (IQR 3.9–14.2 years). Twenty-two of the 65 biopsies (34%) were open, 42 (65%) were stereotactic, and 1 was endoscopic. In 3 cases (5%), a ventriculoperitoneal shunt was placed, and in 9 cases (14%), a posterior fossa decompression was performed during the same operative session as the biopsy. An intraoperative MRI (iMRI) was performed in 28 cases (43%). In 3 of these cases (11%), the biopsy was off target and additional samples were obtained during the same procedure. New neurological deficits were noted in 5 cases (8%), including sensory deficits, ophthalmoparesis/nystagmus, facial weakness, and hearing loss; these deficits persisted in 2 cases and were transient in 3 cases. A pseudomeningocele occurred in 1 patient; no patients developed a CSF leak or infection. In 8 cases (13%) an additional procedure was needed to obtain a diagnosis.

CONCLUSIONS

Brainstem biopsies are safe and effective. Target selection and approach should be a collaborative effort. iMRI can be used to assess biopsy accuracy in real time, thereby allowing any adjustment if necessary.

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Fedor Panov, Sara Ganaha, Jennifer Haskell, Madeline Fields, Maite La Vega-Talbott, Steven Wolf, Patricia McGoldrick, Lara Marcuse and Saadi Ghatan

OBJECTIVE

Approximately 75% of pediatric patients who suffer from epilepsy are successfully treated with antiepileptic drugs, while the disease is drug resistant in the remaining patients, who continue to have seizures. Patients with drug-resistant epilepsy (DRE) may have options to undergo invasive treatment such as resection, laser ablation of the epileptogenic focus, or vagus nerve stimulation. To date, treatment with responsive neurostimulation (RNS) has not been sufficiently studied in the pediatric population because the FDA has not approved the RNS device for patients younger than 18 years of age. Here, the authors sought to investigate the safety of RNS in pediatric patients.

METHODS

The authors performed a retrospective single-center study of consecutive patients with DRE who had undergone RNS system implantation from September 2015 to December 2019. Patients were followed up postoperatively to evaluate seizure freedom and complications.

RESULTS

Of the 27 patients studied, 3 developed infections and were treated with antibiotics. Of these 3 patients, one required partial removal and salvaging of a functioning system, and one required complete removal of the RNS device. No other complications, such as intracranial hemorrhage, stroke, or device malfunction, were seen. The average follow-up period was 22 months. All patients showed improvement in seizure frequency.

CONCLUSIONS

The authors demonstrated the safety and efficacy of RNS in pediatric patients, with infections being the main complication.

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Kathrin Zimmerman, Bobby May, Katherine Barnes, Anastasia Arynchyna, Elizabeth N. Alford, Caroline Arata Wessinger, Laura Dreer, Inmaculada Aban, James M. Johnston, Curtis J. Rozzelle, Jeffrey P. Blount and Brandon G. Rocque

OBJECTIVE

Childhood hydrocephalus is a common chronic medical condition. However, little is known about the burden of headache and psychological comorbidities in children living with hydrocephalus. The purpose of this study was to determine the prevalence and severity of these conditions among the pediatric hydrocephalus population.

METHODS

During routine neurosurgery clinic visits from July 2017 to February 2018, the authors administered four surveys to children ages 7 years and older: Pediatric Migraine Disability Assessment (PedMIDAS), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, PROMIS Depression, and PROMIS Fatigue. The PedMIDAS is an assessment of headache disability in pediatric and adolescent patients. The PROMIS measures are pediatric self-reported instruments to assess social and emotional health. PROMIS measures utilize T-scores (mean 50, SD 10) to compare anxiety, depression, and fatigue in specific populations to those in the US general population. Clinical and demographic data were collected from the medical record (hydrocephalus etiology, shunt infection, race, etc.) and tested for associations with survey measure scores.

RESULTS

Forty children completed the PedMIDAS. Ten percent of them were in the severe headache range, 5% were in the moderate range, and 5% were in the mild range. There was a statistically significant association between undergoing a cluster of shunt operations and headache burden (p = 0.003).

Forty children completed all three PROMIS measures. The mean anxiety score was 45.8 (SD 11.7), and 2.5% of children scored in the severe anxiety range, 17.5% in the moderate range, and 20% in the mild range. The mean depression score was 42.7 (SD 10.0), with 2.5% of children scoring in the severe depression range, 5% in the moderate range, and 12.5% in the mild range. The mean fatigue score was 45.1 (SD 16.4), with 15% percent of children scoring in the severe fatigue range, 10% in the moderate range, and 7.5% in the mild range. There were no statistically significant associations between child anxiety, depression, or fatigue and clinical or demographic variables.

CONCLUSIONS

Children with hydrocephalus have an average burden of headache, anxiety, depression, and fatigue as compared to the general population overall. Having a cluster of shunt operations correlates with a higher headache burden, but no clinical or demographic variable is associated with anxiety, depression, or fatigue.

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Constantin Tuleasca, Iulia Peciu-Florianu, Henri-Arthur Leroy, Maximilien Vermandel, Mohamed Faouzi and Nicolas Reyns

OBJECTIVE

Arteriovenous malformations (AVMs) present no pathologic tissue, and radiation dose is confined in a clear targeted volume. The authors retrospectively evaluated the role of the biologically effective dose (BED) after Gamma Knife radiosurgery (GKRS) for brain AVMs.

METHODS

A total of 149 consecutive cases of unruptured AVMs treated by upfront GKRS in Lille University Hospital, France, were included. The mean length of follow-up was 52.9 months (median 48, range 12–154 months). The primary outcome was obliteration, and the secondary outcome was complication appearance. The marginal dose was 24 Gy in a vast majority of cases (n = 115, 77.2%; range 18–25 Gy). The mean BED was 220.1 Gy2.47 (median 229.9, range 106.7–246.8 Gy2.47). The mean beam-on time was 32.3 minutes (median 30.8, range 9–138.7 minutes). In the present series, the mean radiation dose rate was 2.259 Gy/min (median 2.176, range 1.313–3.665 Gy/min). The Virginia score was 0 in 29 (19.5%), 1 in 61 (40.9%), 2 in 41 (27.5%), 3 in 18 (12.1%), and 4 in 0 (0%) patients, respectively. The mean Pollock-Flickinger score was 1.11 (median 1.52, range 0.4–2.9). Univariate (for obliteration and complication appearance) and multivariate (for obliteration only) analyses were performed.

RESULTS

A total of 104 AVMs (69.8%) were obliterated at the last follow-up. The strongest predictor for obliteration was BED (p = 0.03). A radiosurgical obliteration score is proposed, derived from a fitted multivariable model: (0.018 × BED) + (1.58 × V12) + (−0.013689 × beam-on time) + (0.021 × age) − 4.38. The area under the receiver operating characteristic curve was 0.7438; after internal validation using bootstrap methods, it was 0.7088. No statistically significant relationship between radiation dose rate and obliteration was found (p = 0.29). Twenty-eight (18.8%) patients developed complications after GKRS; 20 (13.4%) of these patients had transient adverse radiological effects (perilesional edema developed). Predictors for complication appearance were higher prescription isodose volume (p = 0.005) and 12-Gy isodose line volume (V12; p = 0.001), higher Pollock-Flickinger (p = 0.02) and Virginia scores (p = 0.003), and lower beam-on time (p = 0.03).

CONCLUSIONS

The BED was the strongest predictor of obliteration of unruptured AVMs after upfront GKRS. A radiosurgical score comprising the BED is proposed. The V12 appears as a predictor for both efficacy and toxicity. Beam-on time was illustrated as statistically significant for both obliteration and complication appearance. The radiation dose rate did not influence obliteration in the current analysis. The exact BED threshold remains to be established by further studies.

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Dag Ferner Netteland, Magnus Mejlænder-Evjensvold, Nils O. Skaga, Else Charlotte Sandset, Mads Aarhus and Eirik Helseth

OBJECTIVE

Cerebral venous thrombosis (CVT) is increasingly recognized in traumatic brain injury (TBI), but its complications and effect on outcome remain undetermined. In this study, the authors characterize the complications and outcome effect of CVT in TBI patients.

METHODS

In a retrospective, case-control study of patients included in the Oslo University Hospital trauma registry and radiology registry from 2008 to 2014, the authors identified TBI patients with CVT (cases) and without CVT (controls). The groups were matched regarding Abbreviated Injury Scale 1990, update 1998 (AIS’98) head region severity score 3–6. Cases were identified by AIS’98 or ICD-10 code for CVT and CT or MR venography findings confirmed to be positive for CVT, whereas controls had no AIS’98 or ICD-10 code for CVT and CT venography or MR venography findings confirmed to be negative for CVT. All images were reviewed by a neuroradiologist. Rates of complications due to CVT were recorded, and mortality was assessed both unadjusted and in a multivariable logistic regression analysis adjusting for initial Glasgow Coma Scale score, Rotterdam CT score, and Injury Severity Score. Complications and mortality were also assessed in prespecified subgroup analysis according to CVT location and degree of occlusion from CVT. Lastly, mortality was assessed in an exploratory subgroup analysis according to the presence of complications from CVT.

RESULTS

The CVT group (73 patients) and control group (120 patients) were well matched regarding baseline characteristics. In the CVT group, 18% developed venous infarction, 11% developed intracerebral hemorrhage, and 19% developed edema, all representing complications secondary to CVT. Unadjusted 30-day mortality was 16% in the CVT group and 4% in the no-CVT group (p = 0.004); however, the difference was no longer significant in the adjusted analysis (OR 2.24, 95% CI 0.63–8.03; p = 0.215). Subgroup analysis by CVT location showed an association between CVT location and rate of complications and an unadjusted 30-day mortality of 50% for midline or bilateral CVT and 8% for unilateral CVT compared with 4% for no CVT (p < 0.001). The adjusted analysis showed a significantly higher mortality in the midline/bilateral CVT group than in the no-CVT group (OR 8.41, 95% CI 1.56–45.25; p = 0.032).

CONCLUSIONS

There is a significant rate of complications from CVT in TBI patients, leading to secondary brain insults. The rate of complications is dependent on the anatomical location of the CVT, and midline and bilateral CVT is associated with an increased 30-day mortality in TBI patients.

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Neil S. Patel, Matthew L. Carlson, Michael J. Link, Brian A. Neff, Jamie J. Van Gompel and Colin L. W. Driscoll

OBJECTIVE

The object of this study was to ascertain outcomes of cochlear implantation (CI) following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS).

METHODS

The authors conducted a retrospective chart review of adult patients with VS treated with SRS who underwent CI between 1990 and 2019 at a single tertiary care referral center. Patient demographics, tumor features, treatment parameters, and pre- and postimplantation audiometric and clinical outcomes are presented.

RESULTS

Seventeen patients (18 ears) underwent SRS and ipsilateral CI during the study period. Thirteen patients (76%) had neurofibromatosis type 2 (NF2). Median age at SRS and CI were 44 and 48 years, respectively. Median time from SRS to CI was 60 days, but notably, 4 patients underwent SRS and CI within 1 day and 5 patients underwent CI more than 7 years after SRS. Median marginal dose was 13 Gy. Median treatment volume at the time of SRS was 1400 mm3 (range 84–6080 mm3, n = 15 patients). Median post-CI PTA was 28 dB HL, improved from 101 dB HL preoperatively (p < 0.001). Overall, 11 patients (12 ears) exhibited open-set speech understanding. Sentence testing was performed at a median of 10 months (range 1–143 months) post-CI. The median AzBio sentence score for patients with open-set speech understanding was 76% (range 19%–95%, n = 10 ears). Two ears exhibited Hearing in Noise Test (HINT) sentence scores of 49% and 95%, respectively. Four patients achieved environmental sound awareness without open-set speech recognition. Two had no detectable auditory percepts.

CONCLUSIONS

Most patients who underwent CI following SRS for VS enjoyed access to sound at near-normal levels, with the majority achieving good open-set speech understanding. Implantation can be performed immediately following SRS or in a delayed fashion, depending on hearing status as well as other factors. This strategy may be applied to cases of sporadic or NF2-associated VS.