Repeat single-session stereotactic radiosurgery for arteriovenous malformation: a systematic review and meta-analysis.

BACKGROUND: Stereotactic radiosurgery is the preferred option for treating brain arteriovenous malformation (AVM) when the risks associated with surgery outweigh the potential benefits. However, some patients require repeat radiosurgery due to residual AVM after the first procedure. This systematic review and meta-analysis aimed to investigate the safety and efficacy of repeated procedure of radiosurgery for AVM. METHOD: A systematic review was conducted according to the PRISMA guideline. The search was conducted on PubMed, Scopus, Embase, and Web of Science, using a pre-designed search string. Studies investigating the efficacy of repeat radiosurgery for residual AVM following initial single session radiosurgery were included. The risk of bias was assessed using the JBI tool. Meta-analysis and met-regression were performed to pool and inspect data. RESULTS: Our meta-analysis, with a mean follow-up of 45.57 months, reveals repeat radiosurgery as a viable option for arteriovenous malformations (AVMs), achieving a 60.82% obliteration rate with a mean time to obliteration of 33.18 months. Meta-regression identifies AVM volume and Spetzler-Martin (SM) grade as factors influencing obliteration, with smaller volume and lower SM grades associated with higher rates. Complications include 10.33% radiation-induced changes, 5.26% post-radiosurgery hemorrhage, 2.56% neurologic deficits, and 0.67% cyst formation. Heterogeneity in complications is primarily attributed to male proportion and SM grade, while factors influencing post-radiosurgery hemorrhage remain unclear. The type of radiosurgery, whether Gamma Knife Radiosurgery (GKRS) or LINAC, does not significantly impact outcomes. CONCLUSION: Repeat radiosurgery is a feasible, effective, and safe treatment for AVMs following failure of initial radiosurgery. When utilized in appropriate patient subgroups, it provides an acceptable risk-to-benefit profile. Feature studies are required to clarify its clear indications.

A rare presentation of Rosai-Dorfman disease as a single dural-based lumbar intradural lesion: A case report.

Central nervous system Rosai Dorfman disease (RDD) is a rare condition and it is just reported in 5% of 600 registered RDD cases. In previously reported patients, the intradural extramedullary spinal lesion is extremely rare. In this article, we aim to report a case of intradural extramedullary Rosai-Dorfman lesion of the lumbar spine which was managed with gross total resection. Lumbar meningioma was the pre-operative diagnosis for this patient, the final correct diagnosis of Rosai-Dorfman disease was made after histological examination. RDD should be considered in the differential diagnosis of single intradural extramedullary lesions of the lumbar spine.

Unexpected positive culture (UPC) in adults revision spine surgery: a systematic review and meta-analysis of incidence, risk factors, and management.

BACKGROUND: Without clear signs of infection, spinal implant failure is attributed to mechanical overloads and aseptic loosening. However, how low-grade infections contribute to seemingly aseptic implant failure is unclear. PURPOSE: The systematic review examined unexpected positive cultures (UPCs) in revision spine surgery regarding prevalence, isolated pathogens, risk factors, and strategies to reduce infection among asymptomatic patients undergoing revision spine surgery. METHODS: We followed the PRISMA guidelines and searched four main databases (PubMed, EMBASE, SCOPUS, Web of Science) comprehensively until January 2023 for articles reporting UPC after presumed aseptic adult revision spine surgery. The UPC rates were pooled, and risk factors were compared with the culture-negative control group and represented as odds ratio (OR) or mean difference (MD). RESULTS: Fifteen studies of 1057 individuals were included in two groups: culture-positive or UPCs (n = 317) and culture-negative or control (n = 740). The overall UPC prevalence was 33.2% (317/1057, range: 0 to 53%, 95% CI = 30.2%-36.4%), and Cutibacterium acnes (43.0%, 95% CI = 37.4%-48.8%), Coagulase-negative Staphylococci (CoNS), (39.5%, 95% CI = 33.2%-46.2%), and Staphylococcus species in general (49.5%, 95%CI = 43.7%-55.4%) were reported the most common isolated microbes. 16.1% of the UPCs were polymicrobial. Risk factors associated with UPC rates were female sex (OR = 2.62, 95%CI = 1.76-3.90, P < 0.001), screw loosening (OR = 4.43, 95%CI = 1.31-15.02, P = 0.02), number of operated levels (MD = 0.77, 95%CI = 0.33-1.22, P = 0.0007), and shorter time since index surgery (MD = - 8.57 months, 95%CI = - 14.76, -2.39, P = 0.02). CONCLUSIONS: One-third of patients undergoing spine revision surgery revealed UPC in this study. Each UPC pathogen interpretation and antibiotic use decision should be interpreted case by case. LEVEL OF EVIDENCE: IV.

Efficacy and Challenges: Minimally Invasive Procedures for Trigeminal Neuralgia Treatment in Multiple Sclerosis - A Systematic Review and Meta-Analysis.

INTRODUCTION: Trigeminal neuralgia (TGN) poses a therapeutic challenge, particularly within the context of multiple sclerosis (MS). This study aimed to conduct a comprehensive meta-analysis and systematic review of four less-invasive treatment modalities for TGN in MS patients, namely, gamma knife radiosurgery (GKRS), glycerol rhizotomy (GR), balloon compression (BC), and radiofrequency ablation (RFA). METHODS: Single-armed meta-analyses were employed to assess the overall efficacy of each treatment, while double-armed analyses compared the efficacy between different treatment options in double-armed studies. Outcome evaluations included acute pain relief (within 1 month post-procedure), recurrence rates throughout 18 months of follow-up, and reported complication rates. RESULTS: The meta-analysis revealed diverse outcomes for each intervention. GKRS demonstrated favorable outcomes, achieving a 77% success rate in alleviating pain among a pooled cohort of 863 patients, reinforcing its status as a viable therapeutic option. Additionally, GR, BC, and RFA exhibited efficacy, with success rates of 77%, 71%, and 80%, respectively, based on outcomes observed in 611, 385, and 203 patients. Double-armed analyses highlighted distinctions between the treatments, providing nuanced insights for clinical decision-making. CONCLUSION: This meta-analysis provides a comprehensive overview of less-invasive treatments for TGN in MS patients. GKRS emerges as a leading option with comparable efficacy and fewer complications. However, the study underscores the nuanced efficacy and considerations associated with GR, BC, and RFA. The findings offer valuable insights for clinicians navigating treatment choices in this challenging patient population, considering acute pain relief, recurrence rates, and complication profiles.

Surgical management of idiopathic acute cervical kyphosis; A case-based review of an extremely rare entity.

INTRODUCTION AND IMPORTANCE: Acute idiopathic cervical kyphosis (AICK) represents a rare entity, and its management remains controversial. Preoperative surgical planning and individual decision-making seem necessary. To date, there is a lack of sufficient evidence and clear guidelines. CASE PRESENTATION: A 21-year-old male was referred with a progressive cervical deformity detected 3 months earlier. The patient suffered from severe progressive myelopathy and represented neither neck trauma nor a familial history of similar expected conditions. His cervical imaging revealed 95 degrees of cervical kyphosis. After 3 separate surgical sessions for 360-degree fixation, the cervical kyphosis was reduced by 90 degrees. No facet dislocation was observed, and laminectomy was unnecessary. Post-operative neurological examination detected significant improvement. Six months and 2-year follow-ups were favorable. To the authors' knowledge, the current case had the most extensive degree of cervical kyphosis reported in the literature. CLINICAL DISCUSSION: Multistage correction of AICK would result in a favorable outcome and reduce the risk of complications. Particular attention should be paid to the wide inter-spinous spaces in high grades of kyphosis during sub-periosteal dissection to prevent iatrogenic spinal cord injuries. CONCLUSION: The present work may provide the first report on the role of cervical postural habits in patients with opiate substance abuse disorder, which could have triggered cervical kyphosis in this particular patient. Multistage correction of AICK would result in a favorable outcome and reduce the risk of complications.

Mini-Review: Role of Drugs Affecting Renin-Angiotensin System (RAS) in Traumatic Brain Injury (TBI): What We Know and What We Should Know.

Traumatic brain injuries (TBIs) are among the most important clinical and research areas in neurosurgery, owing to their devastating effects and high prevalence. Over the last few decades, there has been increasing research on the complex pathophysiology of TBI and secondary injuries following TBI. A growing body of evidence has shown that the renin-angiotensin system (RAS), a well-known cardiovascular regulatory pathway, plays a role in TBI pathophysiology. Acknowledging these complex and poorly understood pathways and their role in TBI could help design new clinical trials involving drugs that alter the RAS network, most notably angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. This study aimed to briefly review the molecular, animal, and human studies on these drugs in TBI and provide a clear vision for researchers to fill knowledge gaps in the future.

Incidentally diagnosed multiple intradural extramedullary spinal hydatidosis in a young adult: A case report and review of the literature.

Key Clinical Message: Although quite rare, vertebral hydatidosis should always be considered as a differential diagnosis for spinal presentations, particularly in endemic areas for echinococcosis. Abstract: In this paper, we report a rare case of asymptomatic multiple intradural, extramedullary spinal hydatidosis, incidentally diagnosed in a patient with signs and symptoms of a true protruded disc. Although quite rare, vertebral hydatidosis should always be considered as a differential diagnosis for spinal presentations, particularly in endemic areas for echinococcosis.

Psychological and Psychiatric Aspects of Brain and Spinal Cord Tumors.

Central nervous system (CNS) tumors are mainly diagnosed by physical symptoms such as paralysis, visual field defect, seizure, and loss of consciousness. The psychological and psychiatric background of CNS tumors, whether in preoperative or postoperative period, has long been a neglected topic; however, lately, many authors and researchers have paid more attention to these manifestations. Neurocognition is a subset of parameters, including attention, memory, mood, emotions, language production, personality, executive function, problem-solving, calculation, and spatial cognition, making up the patient's cognitive performance. Also, it is worthy to say that neurocognition is considered a parameter of quality of life (QoL). Currently, we know that neurocognitive disorders are a group of symptoms presenting by the patients. These symptoms may be the first picture of CNS lesions, which result in incorrect treatment, a higher financial burden on the patient and health system, and finally, poorer QoL and performance scale if they are not diagnosed early. Psychological and psychiatric problems such as depression, anxiety, and phobia following the CNS tumors have two aspects. These may present before any treatment resulting from the tumoral mass effect, peritumoral edema, or cerebral tissue disruption due to the space-occupying lesion. On the other hand, we can see these features after a kind of therapy such as surgery, medical therapy, or adjuvant therapy. Sometimes, the CNS tumors lead to psychosocial complications postoperatively. Indeed, considering tumor surgery complications, some patients may find various degrees of deficits that make the patient isolated either socially or professionally. Obviously, the improvement rate and outcome of this specific situation depend on the mechanism of occurrence and its causes. For instance, postoperative symptom relief would be expected when the symptoms are related to the tumoral mass effect. Getting familiar with this constellation of the symptoms, realizing them, and then localizing them to the correct area of the CNS are very crucial. Accordingly, because of their importance in QoL, their influence on patient's survival even more than the extent of resection of the tumor, and somehow their ignorance, we will discuss different neurocognitive manifestations related to CNS tumors in this chapter.

Indirect Spinal Canal Decompression Using Ligamentotaxis Compared With Direct Posterior Canal Decompression in Thoracolumbar Burst Fractures: A Prospective Randomized Study.

Background: There is still no standard of care to manage thoracolumbar burst fractures. With all the recent advances, posterior approaches are still one of the mainstays of treatment. On the other hand, while spinal canal decompression in neurological impaired patients is an important goal of treatment, its technique remains controversial.This study compared the effects of direct laminectomy decompression against ligamentotaxis/indirect canal decompression on neurological and radiographic improvements. Methods: A prospective double-blind randomized clinical trial was conducted on 60 thoracolumbar burst-fracture patients meeting our inclusion and exclusion criteria. They were randomized into 2 treatment arms: (1) direct decompression using laminectomy and (2) indirect decompression using ligamentotaxis/distraction. Each patient was observed for 6 months, and their neurological and radiographical data were collected prospectively. Statistical analysis was done by the Student t test, Friedman test, Mann Whitney-U test, Wilcoxon ranked test, and 1-way analysis of variance. Results: Among 60 patients enrolled in our study, each treatment arm had an improvement in Frankel scores but there was no difference between the groups at any given time. After 6 months of surgery, local sagittal kyphosis improved in both groups (from 32.2 to 7.43 and 29.93 to 8.77 for the indirect and direct groups, respectively), as well as anterior vertebral height ratio (from 57.73 to 70.7 and 62.17 to 66.27 for the indirect and direct group, respectively) and posterior vertebral height ratio (from 61.17 to 74.87 and 64 to 67.5 for the indirect and direct group, respectively). For between-group comparisons after 6 months, there was a significant difference only for posterior vertebral height ratio (P = 0.040). Conclusion: Posterior approaches with ligamentotaxis have shown to be safe and may present the same outcome as direct decompression techniques using wide laminectomy.

Stereotactic radiosurgery outcome for deep-seated cerebral arteriovenous malformations in the brainstem and thalamus/basal ganglia: systematic review and meta-analysis.

Deep-seated unruptured AVMs located in the thalamus, basal ganglia, or brainstem have a higher risk of hemorrhage compared to superficial AVMs and surgical resection is more challenging. Our systematic review and meta-analysis provide a comprehensive summary of the stereotactic radiosurgery (SRS) outcomes for deep-seated AVMs. This study follows the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We conducted a systematic search in December 2022 for all reports of deep-seated arteriovenous malformations treated with SRS. Thirty-four studies (2508 patients) were included. The mean obliteration rate in brainstem AVM was 67% (95% CI: 0.60-0.73), with significant inter-study heterogeneity (tau2 = 0.0113, I2 = 67%, chi2 = 55.33, df = 16, p-value < 0.01). The mean obliteration rate in basal ganglia/thalamus AVM was 65% (95% CI: 0.58-0.72) with significant inter-study heterogeneity (tau2 = 0.0150, I2 = 78%, chi2 = 81.79, df = 15, p-value < 0.01). The presence of deep draining veins (p-value: 0.02) and marginal radiation dose (p-value: 0.04) were positively correlated with obliteration rate in brainstem AVMs. The mean incidence of hemorrhage after treatment was 7% for the brainstem and 9% for basal ganglia/thalamus AVMs (95% CI: 0.05-0.09 and 95% CI: 0.05-0.12, respectively). The meta-regression analysis demonstrated a significant positive correlation (p-value < 0.001) between post-operative hemorrhagic events and several factors, including ruptured lesion, previous surgery, and Ponce C classification in basal ganglia/thalamus AVMs. The present study found that radiosurgery appears to be a safe and effective modality in treating brainstem, thalamus, and basal ganglia AVMs, as evidenced by satisfactory rates of lesion obliteration and post-surgical hemorrhage.

Complications in Endoscopic Endonasal Pituitary Adenoma Surgery: An Institution Experience in 310 Patients.

Objective Endoscopic endonasal approaches (EEAs) have shown excellent results for majority of hypophyseal tumors. The aim of this study was to evaluate and report the complications of EEA in patients with pituitary adenoma (PA) who underwent surgery between 2013 and 2018. Methods We performed a retrospective review of 310 consecutive patients/325 procedures with PA treated with an EEA from May 2013 to January 2018. Minor complications including transient diabetes insipidus (DI) or new anterior pituitary hormone insufficiency in one axis and major complications including CSF leakage, hematoma needing reoperation, vascular damage, brain infection, new pan-hypopituitarism permanent DI, new visual impairment, neurological deficits, and mortality were recorded. Results We encountered 58 complications in 310 patients (18.7%) and 325 procedures (17.7%). Minor complications were 43 (13.9 and 13.2%) in 310 patients and in 325 procedures, respectively; whereas, major complications were 28 (9 and 8.6%, respectively). Total complications were associated with diameter group 2 (>30 mm), diaphragm sella violation, suprasellar extension, parasellar involvement, nonfunctional secretory type, and intraoperative arachnoid tearing. Conclusion EEA can be considered as a safe surgical treatment which has acceptable complications in the management of PAs.

The efficacy of intrathecal methyl-prednisolone for acute spinal cord injury: A pilot study.

Study design: Randomized clinical trial. Objectives: To evaluate the safety and effectiveness of intrathecal methyl-prednisolone compared to intravenous methyl-prednisolone in acute spinal cord injuries. Setting: Imam Reza Hospital, Tabriz University of Medical Sciences. Methods: Patients meeting our inclusion and exclusion criteria were enrolled in the study and divided randomly into two treatment arms: intrathecal and intravenous. Standard spinal cord injury care (including surgery) was given to each patient based on our institutional policy. Patients were then assessed for neurological status (based on ASIA scores, Frankel scores) and complications for six months and compared to baseline status after injury. To better understand the biological bases of methyl-prednisolone on spinal cord injuries, we measured two biomarkers for oxidative stress (serum malondialdehyde and total antioxidant capacity) in these patients at arrival and day three after injury. Results: The present study showed no significant difference between the treatment arms in neurological status (sensory scores or motor scores) or complications. However, the within-group analysis showed improvement in neurological status in each treatment arm within six months. Serum malondialdehyde and total antioxidant capacity were analyzed, and no significant difference between the groups was seen. Conclusion: This is the first known clinical trial investigating the effect of intrathecal MP in acute SCI patients. Our finding did not show any significant differences in complication rates and neurological outcomes between the two study arms. Further studies should be conducted to define the positive and negative effects of this somehow novel technique in different populations as well.

Internal carotid artery injury during endoscopic endonasal surgery for skull base pathologies: an institutional incidence, management, and outcome.

BACKGROUND: Endoscopic endonasal surgery (EES) has become a popular approach to deal with skull base pathologies. The most catastrophic intra-operative complication of EES is internal carotid artery (ICA) injury. We aim to discuss and introduce our institutional experience with ICA injury during EES. METHODS: A retrospective review of patients who underwent EES from 2013 to 2022 was performed to determine the incidence and outcomes of intraoperative ICA injuries. RESULTS: There were six patients (0.56%) with intraoperative ICA injury in our institution during the last 10 years. Fortunately, there was no morbidity or mortality in our patients with intraoperative ICA injuries. The sites of injury were equally in paraclival, cavernous sinus, and preclinoidal segments of ICA. CONCLUSION: Primary prevention is the best solution for this condition. Regarding our institutional experience, the best option for primary management just after an injury is packing the surgical site. In cases where packing is not enough for temporary control of bleeding, common carotid artery occlusion should be considered. We have presented our experience and reviewed previous studies regarding different treatments and suggested our intra and post-operative management algorithm.

Transverse sinus obstruction caused by extradural supra-infratentorial hydatid cyst: A case report and literature review.

Approximately 1-3% of cases of hydatid disease involve the central nervous system (CNS). This study aims to report an extremely rare case of supra-infratentorially located epidural hydatid cyst with transverse venous sinus obstruction which presented with chronic cerebral vein thrombosis (CVT) signs and symptoms.

A case of chronic ossified hematoma presented as a skull lesion: A literature review on two rare conditions, cephalhematoma, and intradiploic hematoma.

Cephalhematoma is a frequent condition in newborn infants due to birth-related trauma, but ossified cephalhematoma (OCH) is a rare condition, especially when it presents as a skull lesion in the older pediatric population. Chronic intradiploic hematoma (CIH) is another rare condition caused by an organized hematoma between the inner and outer tables of the skull. Differentiating CIH from OCH could be difficult for young neurosurgeons. We present an 18-month-old girl with an OCH presented as a skull lesion, which was managed with craniectomy and en-bloc excision of the organized hematoma. This manuscript discusses the differences between OCH and CIH in diagnosis and management.

Brain and Spinal Cord Tumors Among the Life-Threatening Health Problems: An Introduction.

As one of the global concerns, cancers, including brain and spinal cord tumors, are responsible for mortalities and irreversible morbidities in the affected patients. Although advancements in molecular pathology and imaging of tumors may have influenced the incidence rate due to higher diagnosis in early stages, exposure to environmental risk factors could be another explanation for increased incidence of these tumors over the past decades. Similar to many other tumors, the CNS tumors begin in cellular dimension with activation of different molecular pathways. Several genetic, epigenetic, and immunologic pathways and processes are already discovered to play roles in pathophysiology of these tumors, which mostly will eventually become symptomatic. Each of these tumors may exhibit imaging characteristics, making it possible to list a series of differential diagnosis before histopathologic examination. Advances in molecular pathology have resulted in better understanding and categorization of CNS tumors, leading to better decision-making on the most appropriate therapeutic approach for each category, as well as proposing new therapeutic modalities to treat these tumors. As an introduction to the 2-volume book, this chapter addressed different types of human brain and spinal cord tumors based on the fifth version of WHO classification of CNS tumors.

VEGF gene polymorphisms in Iranian patients with intracranial glioblastoma.

BACKGROUND: Glioblastoma is one of the most common malignant brain tumors in adults with poor prognosis. Neovascularization is one of the characteristics of these tumors, which is associated with overexpression of vascular endothelial growth factor (VEGF). Accordingly, single nucleotide polymorphisms of this gene could play an important role in structural and functional alterations leading to overexpression of this gene in GBM. METHODS: A total number of 49 patients with GBM and 50 healthy controls were included in the current study. The Genomic DNA was extracted from brain tumor/tissue samples, and after purification assessment, the alleles, and genotypes of rs3025039 and rs2010963 polymorphisms of the VEGF gene were investigated using T-ARMS-PCR. RESULTS: The "T" allele of rs3025039 was 2.79 times more frequent in GBM patients compared to controls (P=0.01). Moreover, the "CT" genotype was 2.83 times more common among patients (P=0.015), while the "CC" was more frequent in controls (P=0.009). The mean overall survival was significantly different between three genotypes of rs3025039, with the longest survival time in "CT" genotype (15.10±5.21, P=0.041). Besides, rs2010963, was significantly associated with GBM occurrence, with the "G" allele being 1.96 times more frequent in patients (P=0.01), as well as the "GG" genotype, which was 7.87 times more common in patients (P<0.001). CONCLUSIONS: Polymorphisms of VEGF could potentially play a role in pathogenesis of GBM, as the allele and genotype distributions of rs3025039 and rs2010963 SNPs were significantly associated with GBM occurrence.

Traumatic acute convexity interdural hematoma: a case report and literature review.

INTRODUCTION: Interdural hematoma (IDH) is an extremely rare hemorrhage between the outer periosteal dura mater and the inner meningeal dura mater. There are 8 cases of convexity IDH reported previously but none of them were acute post traumatic one. We report the case of a patient with an initial diagnosis of acute epidural hematoma (EDH) that was eventually revealed to be an acute convexity IDH. CASE REPORT: A 57-year-old man presented to the emergency department with a complaint of falling from 2 meters. Imaging findings revealed an expanding intracranial hematoma with a linear skull fracture extending to sagittal suture, which was mistaken as an EDH. Emergent surgical evacuation was performed; the hematoma was lodged between two dural layers. DISCUSSION: This is the first case of acute convexity IDH following trauma that has been reported. In chronic and sub-acute hematomas MRI scans could be very useful, but in acute cases under emergent circumstances, CT scan cannot make a proper differentiation between an EDH and IDH. IDH should be considered during craniotomy when extradural findings do not explain the CT scan findings. This case showed a linear skull fracture expanding to the sagittal suture, and this can be a possible explanation for IDH formation. Surgical evacuation of the hematoma without inner nor outer layer resection and leaving the outer layer open, to connect the interdural space to epidural space was first described in this report.

A placebo-controlled randomized clinical trial of amantadine hydrochloride for evaluating the functional improvement of patients following severe acute traumatic brain injury.

BACKGROUND: Considering the known derangements in the dopaminergic neurotransmitter systems following traumatic brain injury (TBI), dopamine agonists are used as a pharmacologic option. In this study, we evaluate the effects of amantadine hydrochloride on the functional improvement of severe TBI patients. METHODS: Within a triple-blinded (patients, intervention administrators, and outcome assessors) placebo-controlled randomized clinical trial, we evaluated the effects of amantadine (100 mg BD (twice a day) for 14 days, then 150 mg BD for another 7 days, and 200 mg BD for another 21 days) on outcome measurements of weekly mean Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS), through six weeks of trial for 57 patients (29 amantadine, 28 placeboes) with severe TBI admitted in our hospital. RESULTS: Although both groups had improvement in their DRS, the change from baseline was significantly better in the amantadine group (10.88±5.24 for amantadine vs. 8.04±4.07 for placebo, P=0.015). No significant difference was observed between groups for GOS (1.04±0.55 for amantadine vs. 1.12±1.05 for placebo, P=0.966). CONCLUSIONS: Based on our findings, amantadine hydrochloride might improve the speed of functional ability improvement in severe TBI patients, evaluated by DRS, and is also well tolerated by patients. Although, there were some limitations in this study, including small sample size, short time interval, not providing a wash-off period and invalidity of GOS for measuring recovery rates in short-term periods.

Comparing Therapeutic versus Prophylactic Enoxaparin Therapy in Severe COVID-19 Patients: A Randomized Clinical Trial.

Background: Coronavirus disease 2019 (COVID-19) has been associated with a hypercoagulopathy state; however, the efficacy of different anticoagulant regimens in preventing thrombotic events is not clear. We aimed to compare therapeutic versus prophylactic enoxaparin therapy in severe COVID-19 patients. Methods: In this single-center, open-label, randomized controlled trial, adult patients with severe COVID-19 presentations and an increased D-dimer level of more than 4 times the normal upper limit were randomly assigned to receive either prophylactic or therapeutic dose of enoxaparin. All patients were observed for at least 4 months regarding the overall survival as the primary outcome. Hospitalization duration, the need for intensive care unit (ICU) admission, the need for mechanical ventilation, and major adverse events (MAEs) were also analyzed as the secondary outcomes. Survival analysis was done via Kaplan-Meier curves and the Log-rank test. Cox regression was used, adjusting for baseline variables. Results: Overall, 237 patients (152 men and 85 women) were randomized to either arm (121 to prophylactic and 116 to therapeutic groups). The mortality rate was 27 (22.3%) and 52 (44.8%) in prophylactic and therapeutic arms, respectively. Prophylactic enoxaparin was associated with better survival in the log-rank test (P < 0.001; HR, 0.42). Additionally, a significantly lower rate of ICU admission, a lower rate of MAEs, and shorter hospitalization were observed in the prophylactic arm (P < 0.001, P = 0.009, and P = 0.028, respectively). Conclusion: The results of the current study were in favor of anticoagulant treatment with prophylactic doses of enoxaparin. Still, due to the limitations of this paper, we suggest that these findings be treated cautiously.