Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Translaminar Full Endoscopic Technique with Tom Shidi Needles for Highly- and Dorsally-Migrated Lumbar Disc Herniations.

BACKGROUND: Thirty years have passed since Kambin's first clinical series of lumbar disc herniations (LDH) treated by arthroscopic microdiscectomy. Despite several advances in this interim, sequestrated LDHs over the dorsal aspect of the dura, and high-grade up- or downward disc migration have been a relative limitation of the transforaminal endoscopic technique. The interlaminar window was the next step to deal with such highly migrated LDHs. Favorable outcomes were obtained in 70-90% of the patients in the long-term, but recurrence rates remained high (approximately 12%), and the approach could be limited by the size of the interlaminar window. Few relevant studies have addressed the role of translaminar full endoscopic technique for migrated LDHs. To describe an innovative modification of the translaminar full endoscopic approach with Tom Shidi needles. METHODS: This technical modification is presented in a detailed fashion for treating these challenging LDHs and illustrated through a clinical case. RESULTS: The patient underwent successful translaminar full endoscopic technique with complete pain resolution postoperatively. The postprocedural course was uneventful. A follow-up imaging showed no evidence of residual LDHs fragments. CONCLUSIONS: Translaminar full endoscopic technique with Tom Shidi needles is a promising modification of the previously presented interlaminar and translaminar endoscopic routes in the treatment of migrated LDHs to fasten surgical procedures and increase the safety of spinal canal manipulation.

Surgical treatment of an all-spine epidural empyema.

Spinal epidural empyema (SEE) is a severe infectious disease of the spine which may cause significant morbidity and mortality. Surgical drainage of the empyema is a key feature. However, approach-related morbidity may be significant in very extensive collections. We present the case of a 55-year-old female with an empyema due to methicillin-susceptible Staphylococcus aureus spawning from C2 to S1. She underwent drainage of the pus through skip-level laminectomies and catheter epidural saline irrigation. The technique described was both safe and effective at treating the SEE, and the patient returned to normal life.

A survey on the early management of spinal trauma in low and middle-income countries: From the scene of injury to the diagnostic phase (part II).

•Most spinal trauma worldwide occurs in low-and middle-income countries (LMICs). Several factors may limit the applicability of current guidelines as regards the early management of spinal injury.•The pre-hospital management per se of spinal trauma in LMICs is subject to partial adherence to recommendations, with possible impact on patient outcomes.•The use of clinical (eg ASIA) and morphological (eg SLIC, TLICS, AO Spine) grading scales is not homogeneous.•The availability and cost of diagnostic equipment, and the timing of emergency imaging can vary significantly from one region to another, probably affecting the timely management of spinal injury patients.•The introduction of resource-targeted guidelines for spinal trauma may be a valuable option to overcome the limitations of real-life application of current guidelines.

Exploring perspectives and adherence to guidelines for adult spinal trauma in low and middle-income healthcare economies: A survey on barriers and possible solutions (part I).

•Most spinal trauma occurs in low- and middle-income countries (LMICs), but some elements may limit the application of current guidelines.•In LMICs, a respectable proportion of physicians treating spinal trauma is not aware of any guidelines on this topic.•Most physicians managing spinal trauma in LMICs believe that following the guidelines may positively affect patient outcomes.•Most believed they have the capability to apply, the guidelines, but variation according to income and geographical region exists.•The perceived limitations and their relevance to guideline adherence vary across different income and geographic areas worldwide.•Resource-targeted guidelines for spinal trauma are considered a valuable option to overcome the limitations of real-life application of the current guidelines.

Secondary damage management of acute traumatic spinal cord injury in low and middle-income countries: A survey on a global scale (Part III).

•In LMICs, several factor may affect the applicability of guidelines for secondary damage control of spinal cord injury.•In LMICs, the use of steroids for spinal cord injury is heterogeneous and admissions to an intensive care units are limited.•The delays for surgical decompression of spinal cord injury can be significan and vary across income and geographic region.•Transfer times seem to be the most common reason for surgical delay in all income and geographic regions.•Costs for surgery for spinal trauma may be a significant barrier to guideline adherence, especially in low-resource settings.

Outcome of Anterior and Posterior Endoscopic Procedures for Cervical Radiculopathy Due to Degenerative Disk Disease: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: Cervical spine endoscopic discectomy and decompression have gained popularity in the last decade. This review aimed to shed light on the current outcomes of cervical spine endoscopic procedures for degenerative disc disease (DDD) and to calculate a pooled estimate of various outcome measures. METHODS: We retrieved articles published in English related to endoscopic cervical spine procedures from 3 central databases from inception until September 2020. A subgroup analysis based on the anterior versus the posterior approach was performed. RESULTS: Thirty-one articles fulfilled the eligibility criteria and included 1,410 patients. A successful outcome was observed in 91.3% (88.6-93.4%, P = 0.000). This percentage was lower for the anterior approach (89.6% [85.8-92.5%], P = 0.000) than for the posterior approach (94.2% [90.4-96.5%], P = 0.000). A higher percentage of poor outcomes was reported for the anterior approach (5.7% [3.2-10.1%], P = 0.000 vs. 2.3% [1-5.5%], P = 0.000 for the posterior approach). The overall complication rate was 7.2% (5.2-9.8%, P = 0.000). There was a slightly higher complication rate for the anterior approach (7.9% [4.5-13.3%], P = 0.000) than for the posterior approach (6.7% [4.4-10%], P = 0.000). The revision rate was 4.2% (2.6-6.8%, P = 0.000); and 4.2% (1.8-9.7%, P = 0.000) for the anterior approach and 4.00% (2.2-7.4%, P = 0.000) for the posterior approach. CONCLUSIONS: There is a higher success rate and lower complication rate with the posterior approach than with the anterior approach. However, high-quality randomized controlled trials are vital to evaluate the efficacy of these procedures.

Cervical Total Disc Replacement: Expanded Indications.

Cervical total disc replacement (cTDR) is now a firm alternative to anterior cervical discectomy and fusion (ACDF) for degenerative disc disease (DDD). Robust level 1 data from Federal Drug Administration-approved clinical trials demonstrated that cTDR is in any case equally safe and effective compared with ACDF for 1- or 2-level DDD. Furthermore, from early postoperative to long-term follow-up of 10 to 15 years, cTDR rates superiorly in many primary clinical outcomes. According to the published literature, at least nine different cTDR devices share this consistent pattern. On the other hand, the surgical treatment of more than 2-level disc disease is haunted by an elusive paradox. It is easily understandable that 3- and 4-level ACDF, with the well-known associated limitations, is not the superlative intervention for a spine segment anatomically designed to provide motion, as cervical spine is. Furthermore, multilevel ACDF exacerbates many of the clinical and biomechanical complications related with single-level fusion. However, as cTDR is not immaculate of constraints and failures, its clinical safety and efficacy and cost-effectiveness in multilevel anterior compressive pathology need to be established. This article analyses the current available evidence supporting the expanded indication of cTDR to 3- and 4-level disc disease, either stand-alone or adjacent to fusion, from a less stringent European perspective.

Minimally invasive surgery for spinal fractures due to multiple myeloma.

BACKGROUND: Multiple myeloma (MM) presents with spinal lesions in 60% of cases. The combination of osteolytic lesions with multifactorial osteopenia raises specific surgical treatment challenges. Minimally invasive spine surgery (MISS) could be a potential option for MM spinal lesions treatment. OBJECTIVE: The objective of this study is to evaluate MISS techniques to treat patients presenting with spine fractures due to MM. METHODS: Retrospective analysis of consecutive patients with histology-proven pathological fractures caused by MM treated with MISS between 2009 and 2018. We collected the data from the clinical records on epidemiology, topography of spine lesions, surgical techniques, blood loss, operation time, complications, mean in-hospital time, and clinical evolution. RESULTS: Twenty-one patients were studied - 13 males and 8 females, with a mean age of 64 years (range 43-83). Mean preoperative spinal instability neoplastic score was 9.8 ± 6 (range 5-16). All cases had a thoracolumbar location - 15 patients underwent kyphoplasty (KP) or vertebroplasty (VP) and 6 were treated with other more complex procedures. All patients had a reduction of pain and/or analgesic load. Vertebral body height increased by a mean of 2.9 mm after VP/KP. Mean hospital stay was 1.3 days for KP/VP and 5.0 days for other MISS procedures. Three patients had complications. CONCLUSIONS: The heterogeneity of techniques used reflected the variety of spine involvement by MM. KP and VP led to shorter hospital stays and less complications, being adequate for lesions without major instability. More complex MISS techniques offer an effective treatment with short delay for starting MM adjuvant treatment.

New methodology to assess in-vivo quality of motion in cervical spine.

BACKGROUND: Understanding the kinematics of the spine in the interaction with an implanted device is of utmost importance from a clinical point of view. The characterization of the biomechanical movement of the spine occurring at each functional unit is a difficult task as it involves the measurement of complex patterns of motion while identifying more delicate abnormalities that could result in longer-term disease complications. Center of rotation is a biomechanical parameter that represents the ratio between rotation and translation. It has been recognized as a valid and reliable parameter to identify any delicate abnormal movement of the spine as opposed to the range of motion. However, center of rotation is still not widely used in clinical practice. METHODS: In this study, an algorithm intended to easily identify an imbalanced spine through the center of rotation calculation and a new parameter called distance to the ellipse is presented. In this new approach the distance to the ellipse is a key parameter which represents the distance of the center of rotation lying outside the ellipse that represents the asymptomatic group, from the ellipse itself. FINDINGS: The presented algorithm allows the comparison of pre-op and post-op outcomes, and the rapid identification of cases needing more attention. INTERPRETATION: When a comprehensive analysis is required, a dashboard is provided with detailed information for each functional spine unit at each follow-up appointment. It is found that the new approach has the potential to become a new methodology in clinical practice. LEVEL OF EVIDENCE: Biomechanical Study.

Posterior fossa metastasis of lung carcinoid tumor: case report.

Carcinoid tumors are generally indolent neoplasms. Brain metastases are rare and when present, yield a poor prognosis. We present the case of a 76-year old female surgically treated for an atypical bronchial carcinoid, staged as T2aN0M0G2. Without further adjuvant treatment she remained stable for four years, when she presented with headaches and gait imbalance. Brain MRI revealed a midline, intra-axial infratentorial lesion that was completely removal, of which histolology confirmed a carcinoid metastasis. At 14 months of follow-up, the patient showed no signs of systemic disease or brain recurrence, and thus no adjuvant radiotherapy was prescribed.

Decompressive Surgery for Lumbar Spinal Stenosis: WFNS Spine Committee Recommendations.

OBJECTIVE: Lumbar spine stenosis is a common disease with a prevalence progressively increasing due to the aging of the population. Despite many papers having been published over the last decades, there still remain many doubts regarding its natural history and appropriate treatment. To overcome these problems and reach some globally accepted recommendations, the World Federation of Neurosurgical Society Spine Committee organized a consensus conference on this topic. This paper describes recommendations about the efficacy of surgical decompression, the difference between surgical techniques, and complications of surgery. METHODS: World Federation of Neurosurgical Society Spine Committee aimed to standardize clinical practice worldwide as much as possible and held a 2-round consensus conference on lumbar spinal stenosis. A team of expert spine surgeons reviewed literature regarding surgical treatment from over the last 10 years, and then drafted and voted on some statements based on the presented literature. RESULTS: Ten statements were voted. The committee agreed on the effectiveness of surgical decompression in patients with moderate-to-severe symptoms or with neurologic deficits. There was no consensus on the best surgical technique and, in particular, about the equivalence of microscopic techniques and an open approach. Regarding complications, we agreed that the most frequent complications are incidental durotomy and general complications in the elderly. CONCLUSIONS: Surgical decompression represents the treatment of choice for symptomatic lumbar spinal stenosis with a low complication rate. However, which surgical technique is the best is still under debate. Further studies with standardized outcome measures are needed to understand the real complication rate and frequency of different unwanted events.

Multilevel cervical arthroplasty-clinical and radiological outcomes.

BACKGROUND: Cervical disc arthroplasty (CDA) is a valid option for single-level cervical disc disease (CDD) as an alternative to fusion. However, the use in 3- and 4-level disc disease is under scrutiny with scarce data published so far. Our aim was to study clinical and radiological outcomes of arthroplasty in patients with multilevel CDD. METHODS: Retrospective analysis of clinical records, pre- and post-operative neutral/dynamic X-rays of patients who underwent CDA in multilevel CDD (2-4 levels). We evaluated sagittal balance parameters (C2-7 and index angle, SVA), global and segmental range of motion (ROM)), neck and arm VAS, Odom's criteria, re-operation rate, adjacent segment disease (ASD), willingness to undertake the same procedure again. Rate of heterotopic ossification (HO) was studied for follow-up >2 years. A subgroup analysis was performed regarding 2-level versus 3- or 4-level arthroplasty. RESULTS: Thirty-two patients were included, 6 males and 26 females, mean age of 46 years (range, 30-63). Seventy-seven cervical disc levels were treated with the same artificial disc. Twenty-one patients were operated on 2 levels, nine in 3 levels, and 2 patients in 4 levels. Post-operatively, there was a decrease in SVA (-2.2±8.36 mm, P=0.098) and an increase in global (3.7±9.6º, P=0.042) and index (1.3±6.1º, P=0.071) ROM. Mean nVAS and aVAS decreased (7.5±1.1 to 2.5±1.5; 6.3±1.9 to 2.2±1.7, P<0.05). Two-level versus 3-4 level patient subgroups showed a lower SVA (-1.3±8.1 mm P=0.47; -3.4±6.3 mm P=0.107), a slight increase in global (1.6±9.4º P=0.44; 7.2±11.7º P=0.07) and index (1.1±4.7º P=0.12; 1.3±8.1º P=0.35) ROM. HO was present in 9.9% (7/71) of disc levels operated, none of them with grade 3 or 4. CONCLUSIONS: Multilevel CDA provides good clinical and radiological outcomes, preserving global and segmental cervical mobility, while having a beneficial effect on sagittal balance. These results hold for 2 to 4 levels, making this technique a valuable option in selected patients with cervical multilevel CDD.

Subaxial Cervical Spine Injuries: WFNS Spine Committee Recommendations.

To formulate specific guidelines for the recommendation of subaxial cervical spine injuries concerning classification, management, posttraumatic locked facets and vertebral artery injury. Computerized literature was searched on PubMed and google scholar database from 2009 to 2020. For classification, keywords "Sub Axial Cervical Spine Classification," resulting in 22 articles related to subaxial cervical spine injury classification system (SLICS) system and 11 articles related to AO (Arbeitsgemeinschaft für Osteosynthesefragen, German for "Association for the Study of Internal Fixation") Spine system. The literature search yielded 210 and 78 articles on "management of subaxial cervical spine injuries" and the role of "SLICS" and "AO Spine" respectively. Keywords "management of traumatic facet locks" were searched and closed reduction, traction, approaches and techniques were studied. "Vertebral artery injury and cervical fracture" exhibited 2,328 references from the last 15 years. The objective was to identify the appropriate diagnostic tests and optimal treatment. Up-to-date information was reviewed, and statements were produced to reach a consensus in 2 separate consensus meetings of World Federation of Neurosurgical Societies (WFNS) Spine Committee. The statements were voted and reached a positive or negative consensus using Delphi method. Based on the most relevant literature, panelists in Moscow consensus meeting conducted in May 2019 drafted the statements, and after a preliminary voting session, the consensus was identified on various statements. Another meeting was conducted at Peshawar in November 2019, where in addition to previous statements, few other statements were discussed and voted. Specific recommendations were then formulated guiding classification, management, locked facets and vertebral artery injuries. This review summarizes the WFNS Spine Committee recommendations on subaxial cervical spine injuries.

Upper Cervical Spine Trauma: WFNS Spine Committee Recommendations.

Craniovertebral junction (CVJ) trauma is a challenging clinical condition. Being a highly mobile functional unit at the junction of the skull and the vertebral column, traumatic events in this area may produce devastating neurological complications and death. Additionally, many of the CVJ traumatic injuries can be left undiagnosed or even raise difficult treatment dilemmas. We present a literature review in the format of recommendations on the diagnosis and management of different scenarios for upper cervical trauma and produce recommendations, which can be applicable to various areas of the globe.

Value of Surgery and Nonsurgical Approaches for Cervical Spondylotic Myelopathy: WFNS Spine Committee Recommendations.

Cervical spondylotic myelopathy (CSM) is a common cause of adult spinal cord dysfunction. Although the therapeutic options for moderate to severe CSM patients have been established well, the existing guidelines for therapeutic decisions in mild cases of CSM are unclear. We present a review of literature on conservative treatment and surgery for CSM and suggest general recommendations applicable in various clinical presentations and in different geographic locations across the globe, with due considerations to available resources and locally prevalent practices.

Cervical Spondylotic Myelopathy: Natural Course and the Value of Diagnostic Techniques -WFNS Spine Committee Recommendations.

OBJECTIVE: This study presents the results of a systematic literature review conducted to determine most up-to-date information on the natural outcome of cervical spondylotic myelopathy (CSM) and the most reliable diagnostic techniques. METHODS: A literature search was performed for articles published during the last 10 years. RESULTS: The natural course of patients with cervical stenosis and signs of myelopathy is quite variable. In patients with no symptoms, but significant stenosis, the risk of developing myelopathy with cervical stenosis is approximately 3% per year. Myelopathic signs are useful for the clinical diagnosis of CSM. However, they are not highly sensitive and may be absent in approximately one-fifth of patients with myelopathy. The electrophysiological tests to be used in CSM patients are motor evoked potential (MEP), spinal cord evoked potential, somatosensory evoked potential, and electromyography (EMG). The differential diagnosis of CSM from other neurological conditions can be accomplished by those tests. MEP and EMG monitoring are useful to reduce C5 root palsy during CSM surgery. Notable spinal cord T2 hyperintensity on cervical magnetic resonance imaging (MRI) is correlated with a worse outcome, whereas lighter signal changes may predict better outcomes. T1 hypointensity should be considered a sign of more advanced disease. CONCLUSION: The natural course of CSM is quite variable. Signal changes on MRI and some electrophysiological tests are valuable adjuncts to diagnosis.

Cerebral Metastasis as First Systemic Event in a Patient with Prostate Adenocarcinoma

Prostate adenocarcinoma (PAC) is the second most common malignant tumor in men, and it is usually diagnosed because of its symptoms and/or because of an increase in the value of the prostate-specific antigen (PSA) in asymptomatic patients. The lymph nodes and the bones are the most common sites in which metastases occur, while the brain is a rare site, with metastases occurring in < 2% of the cases, and usually only after the aforementioned sites have been affected. Considering the brain as the only site where a metastasis can occur, the incidence is of 0.15%. We present the case of a 63-year-old male diagnosed with PAC, with a Gleason score of 7 (3þ4), who underwent radiotherapy and anti-hormonal therapy in 2012. After biochemical recurrence early in 2015 (PSA: 8 ng/mL), he was re-staged, and the bone and node metastases were excluded. The patient then resumed the hormone therapy with bicalutamide. He was admitted in August 2015 to the emergency department of our institution with headache and behavioral changes. The imaging study revealed a single right temporo-parieto-occipital lesion, which was then resected. The histological analysis confirmed it to be a PAC brain metastasis. The patient went through a cycle of brain radiotherapy, and evolved favorably after one year of follow-up.

O adenocarcinoma da próstata (ACP) é a segunda neoplasia maligna mais comum em homens, sendo habitualmente diagnosticada por meio de seus sintomas e/ou pelo aumento do valor do antígeno prostático específico (APE) em doentes assintomáticos. As metastizações óssea e ganglionar são as mais frequentes, sendo o cérebro um local raro de disseminação desta neoplasia, ocorrendo em menos de 2% dos casos, e geralmente surgindo apenas após a disseminação nos locais previamente descritos. Considerando o cérebro como único local de metastização, a incidência é de 0,15%. Os autores apresentam o caso de um homem de 63 anos com diagnóstico de ACP, com pontuação 7 (3 þ 4) na escala de Gleason, submetido a radioterapia e bloqueio hormonal em 2012. Por recidiva bioquímica (APE de 8 ng/mL) no início de 2015, o paciente foi re-estadiado, tendo-se excluído as metastizações óssea e ganglionar. Ele reiniciou a hormonoterapia com bicalutamida. Em agosto de 2015, foi admitido no serviço de urgência de nossa instituição com um quadro de cefaleias associadas a alterações no comportamento. O estudo imagiológico revelou uma lesão cerebral temporo-parieto-occipital direita única, e o paciente foi submetido a uma craniotomia com remoção completa; o diagnóstico histológico revelou tratar-se de metástase de ACP. O paciente foi posteriormente submetido a radioterapia cerebral, apresentando uma evolução favorável após um ano de acompanhamento.

Concurrent monitoring of cerebral electrophysiology and metabolism after traumatic brain injury: an experimental and clinical study.

Multiparameter cerebral monitoring has been widely applied in traumatic brain injury to study posttraumatic pathophysiology and to manage head-injured patients (e.g., combining O(2) and pH sensors with cerebral microdialysis). Because a comprehensive approach towards understanding injury processes will also require functional measures, we have added electrophysiology to these monitoring modalities by attaching a recording electrode to the microdialysis probe. These dual-function (microdialysis/electrophysiology) probes were placed in rats following experimental fluid percussion brain injuries, and in a series of severely head-injured human patients. Electrical activity (cell firing, EEG) was monitored concurrently with microdialysis sampling of extracellular glutamate, glucose and lactate. Electrophysiological parameters (firing rate, serial correlation, field potential occurrences) were analyzed offline and compared to dialysate concentrations. In rats, these probes demonstrated an injury-induced suppression of neuronal firing (from a control level of 2.87 to 0.41 spikes/sec postinjury), which was associated with increases in extracellular glutamate and lactate, and decreases in glucose levels. When placed in human patients, the probes detected sparse and slowly firing cells (mean = 0.21 spike/sec), with most units (70%) exhibiting a lack of serial correlation in the spike train. In some patients, spontaneous field potentials were observed, suggesting synchronously firing neuronal populations. In both the experimental and clinical application, the addition of the recording electrode did not appreciably affect the performance of the microdialysis probe. The results suggest that this technique provides a functional monitoring capability which cannot be obtained when electrophysiology is measured with surface or epidural EEG alone.

Cytotoxic edema is independent of NMDA ion channel activation following middle cerebral artery occlusion (MCAO). An in vivo autoradiographic and MRI study.

Massive glutamate release is an important factor leading to ionic imbalance after occlusive stroke, which in turn contributes to cytotoxic edema formation. Currently, measurements of cytotoxic edema using 'diffusion weighted' MRI, is being used in human stroke studies, as a 'surrogate' end point for neuroprotective drug trials, including studies with glutamate antagonists. However, it is not fully understood to what extent glutamate-mediated N-methyl-D-aspartate (NMDA) receptor activation is related to 'cytotoxic' edema formation, and thus, to what degree apparent diffusion coefficient (ADC) changes, assessed by magnetic resonance imaging with 'ACD mapping', represent NMDA receptor activation. To study this relationship, four cats underwent permanent middle cerebral artery occlusion (MCAO). Edema formation was investigated using MRI with 'ACD mapping', while NMDA receptor activation was simultaneously detected in the same animals, using radio labeled 125IodoMK-801, which binds only in activated and open NMDA channels. At 5 h post-occlusion, a large area of edema could be found with significantly lower ADC values in the core and penumbral area of the ischemic lesion when compared to contralateral values. On corresponding sections of the feline brains, increased 125I-MK-801 binding was found in the infarct penumbra. However, there was no significant topographical correlation between ADC values and measured radioactivity. The results indicate that there is not a significant linkage between NMDA receptor activation and 'cytotoxic' edema following permanent MCAO. The detection of a large area of NMDA channel activation within regions of low ADC does however indicate an area of 'penumbral' ischemia susceptible to treatment with NMDA channel blockers.