Traumatic brain injury and stem cell treatments: A review of recent 10 years clinical trials.

Traumatic brain injury (TBI) is damage to the brain by an external physical force. It may result in cognitive and physical dysfunction. It is one of the main causes of disability and death all around the world. In 2016, the worldwide incidence of acute TBI was nearly 27 million cases. Therapeutic interventions currently in use provide poor outcomes. So recent research has focused on stem cells as a potential treatment. The major objective of this study was to conduct a systematic review of the recent clinical trials in the field of stem cell transplantation for patients with TBI. The Cochrane Library, Web of Science, SCOPUS, PubMed and also Google Scholar were searched for relevant terms such as "traumatic brain injury", " brain trauma", "brain injury", "head injury", "TBI", "stem cell", and "cell transplantation" and for publications from January 2013 to June 2023. Clinical trials and case series which utilized stem cells for TBI treatment were included. The data about case selection and sample size, mechanism of injury, time between primary injury and cell transplantation, type of stem cells transplanted, route of stem cell administration, number of cells transplanted, episodes of transplantation, follow-up time, outcome measures and results, and adverse events were extracted. Finally, 11 studies met the defined criteria and were included in the review. The total sample size of all studies was 402, consisting of 249 cases of stem cell transplantation and 153 control subjects. The most commonly used cells were BMMNCs, the preferred route of transplantation was intrathecal transplantation, and all studies reported improvement in clinical, radiologic, or biochemical markers after transplantation. No serious adverse events were reported. Stem cell therapy is safe and logistically feasible and leads to neurological improvement in patients with traumatic brain injury. However, further controlled, randomized, multicenter studies with large sample sizes are needed to determine the optimal cell and dose, timing of transplantation in acute or chronic phases of TBI, and the optimal route and number of transplants.

Glioma segmentation with DWI weighted images, conventional anatomical images, and post-contrast enhancement magnetic resonance imaging images by U-Net.

Glioma segmentation is believed to be one of the most important stages of treatment management. Recent developments in magnetic resonance imaging (MRI) protocols have led to a renewed interest in using automatic glioma segmentation with different MRI image weights. U-Net is a major area of interest within the field of automatic glioma segmentation. This paper examines the impact of different input MRI image-weight on the U-Net output performance for glioma segmentation. One hundred forty-nine glioma patients were scanned with a 1.5T MRI scanner. The main MRI image-weights acquired are diffusion-weighted imaging (DWI) weighted images (b50, b500, b1000, Apparent diffusion coefficient (ADC) map, Exponential apparent diffusion coefficient (eADC) map), anatomical image-weights (T2, T1, T2-FLAIR), and post enhancement image-weights (T1Gd). The U-Net and data augmentation are used to segment the glioma tumors. Having the Dice coefficient and accuracy enabled us to compare our results with the previous study. The first set of analyses examined the impact of epoch number on the accuracy of U-Net, and n_epoch = 20 was selected for U-Net training. The mean Dice coefficient for b50, b500, b1000, ADC map, eADC map, T2, T1, T2-FLAIR, and T1Gd image weights for glioma segmentation with U-Net were calculated 0.892, 0.872, 0.752, 0.931, 0.944, 0.762, 0.721, 0.896, 0.694 respectively. This study has found that, DWI image-weights have a higher diagnostic value for glioma segmentation with U-Net in comparison with anatomical image-weights and post enhancement image-weights. The results of this investigation show that ADC and eADC maps have higher performance for glioma segmentation with U-Net.

Safety of Intraparenchymal Injection of Allogenic Placenta Mesenchymal Stem Cells Derived Exosome in Patients Undergoing Decompressive Craniectomy Following Malignant Middle Cerebral Artery Infarct, A Pilot Randomized Clinical Trial.

Background: Malignant middle cerebral artery infarct (mMCAI) largely contributes to high mortality and physical disability among adults. Surviving individuals may not have proper outcomes and suffer from severe lasting disabilities. Utilization of stem cells and paracrine factor for regenerative purposes is considered as a potential strategy for patients with neurological deficits. While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) reduce post-treatment neurological deficits and prevent disability and also promote recovery, few randomized clinical trials (RCT) have assessed exosome therapy in humans. Methods: In this RCT, we assessed the safety of intraparenchymal injection placenta MSC-derived Exosome in mMCAI patients with average age of 62 years between January, 2019, till September, 2020. The study was done in a single-center as an open-label RCT, with a 3-months follow-up. Primary outcomes assessed the safety and also disability indexes were followed. Results: Five mMCAI patients were included with mean NIHSS: 17.6 ± 5.02. The mean MRS was 3.25 ± 0.95 in three patients. No serious adverse events were observed. Hematoma or local reaction as excessive edema were not seen at the site of injection. Conclusions: Intraparenchymal implantation of MSC-EXO showed no post-interventional adverse effects in five ischemic stroke patients. It is proposed Local injection Exosome treatment following mMCAI can be safe and in future, it would be applied as a supportive, restorative and preventive treatment in patients who suffer from acute ischemic stroke and post ischemic disability.

Preliminary study of multiple b-value diffusion-weighted images and T1 post enhancement magnetic resonance imaging images fusion with Laplacian Re-decomposition (LRD) medical fusion algorithm for glioma grading.

BACKGROUND: Grade of brain tumor is thought to be the most significant and crucial component in treatment management. Recent development in medical imaging techniques have led to the introduce non-invasive methods for brain tumor grading such as different magnetic resonance imaging (MRI) protocols. Combination of different MRI protocols with fusion algorithms for tumor grading is used to increase diagnostic improvement. This paper investigated the efficiency of the Laplacian Re-decomposition (LRD) fusion algorithms for glioma grading. PROCEDURES: In this study, 69 patients were examined with MRI. The T1 post enhancement (T1Gd) and diffusion-weighted images (DWI) were obtained. To evaluated LRD performance for glioma grading, we compared the parameters of the receiver operating characteristic (ROC) curves. FINDINGS: We found that the average Relative Signal Contrast (RSC) for high-grade gliomas is greater than RSCs for low-grade gliomas in T1Gd images and all fused images. No significant difference in RSCs of DWI images was observed between low-grade and high-grade gliomas. However, a significant RSCs difference was detected between grade III and IV in the T1Gd, b50, and all fussed images. CONCLUSIONS: This research suggests that T1Gd images are an appropriate imaging protocol for separating low-grade and high-grade gliomas. According to the findings of this study, we may use the LRD fusion algorithm to increase the diagnostic value of T1Gd and DWI picture for grades III and IV glioma distinction. In conclusion, this article has emphasized the significance of the LRD fusion algorithm as a tool for differentiating grade III and IV gliomas.

Comparison of subcutaneous pocket with cryopreservation method for storing autologous bone flaps in developing surgical wound infection after Cranioplasty: A randomized clinical trial.

BACKGROUND: Following a decompressive craniectomy (DC), the harvested bone flap is stored for future cranioplasty. There are two different methods proposed for bone banking, namely subcutaneous pocketing (SP) in the abdominal wall and cryopreservation (CP) in a refrigerator. This study was designed to evaluate the risk of developing infection in each study group. METHODS: In this randomized clinical trial design, a total of 143 patients underwent a primary decompressive craniectomy. Thereafter, they were randomly allocated into two groups, as SP and CP, and they were then scheduled for a future cranioplasty. Next, 108 patients underwent cranioplasty using an autologous bone flap and then followed-up for 18 months. Some variables, including demographic data, indications for primary DC, rate of post-operative clinical infection, bacterial culture results, the interval between craniectomy and cranioplasty, post-operative hospitalization duration, new morbidities, mortality rate, bone flap resorption rate, and several possible associated risk factors, were also recorded. The obtained data were analyzed by an expert bio-statistician using proper bio-statistical methods. A P value < 0.05 was considered as statistically significant. RESULTS: Four patients in the cryopreservation group (n = 50) indicated post-operative bone flap infection (8%), which was statistically significant (P = 0.041). Accordingly, all of them were resulted as positive for Methicillin-Resistant-Staphylococcus aureus (MRSA). Using the subcutaneous pocket method, no post-operative infection was observed after cranioplasty. The overall postoperative infection rate was estimated as 4%. The mean of age in the post-operative infection group's participants was 50.25 years old, and in the non-infected, it was 34.93 years old, which was also significant (P = 0.048). Bone flap resorption (BFR) rate was found to be higher by the use of CP method in comparison to SP technique (p = 0.0001). Of note, no other risk factor was found attributable to a higher BFR rate (p-values > 0.05). CONCLUSIONS: Older age and cryopreservation method at higher storage temperature (-18C˚) may be associated with infection's development after performing cranioplasty. BFR is more prevalent in the use of CP method rather than SP preservation technique.

The effect of fampridine on the risk of seizure in patients with multiple sclerosis.

BACKGROUND: Fampridine was first approved by the US Food and Drug Administration (FDA) to improve walking in multiple sclerosis (MS) patients, which was demonstrated by an increase in their walking speed. Nevertheless, the medication has been reported to possess an epileptogenic effect since it blocks the voltage-gated potassium channels in neural fibers. Several studies have indicated that the risk of seizure among fampridine consumers is not substantially higher than that in the general MS population, however. The objective of this study is to describe 97 MS patients for whom fampridine was prescribed and to assess the incidence of post-medication seizures. METHODS: This cohort study included 97 MS patients with gait problems who referred to the Isfahan Clinic of MS from August 2017 to September 2019. The exclusion criteria were a previous or family history of seizure or a history of renal impairment. Fampridine was prescribed for all the patients at a dose of 10 mg twice daily (12 hours apart). RESULTS: three patients (with an approximate incidence rate of 0.015 per 100 patient-years) presented with generalized tonic-clonic seizures, 7, 9, and 14 months after initiating fampridine consumption. The radiological findings revealed significant cortical and subcortical lesions in the three patients. Further, two of them consumed baclofen or fingolimod simultaneously with fampridine. CONCLUSION: The reported incidence rate is relatively higher than that in the general MS population. The extensive (sub) cortical lesions and the concomitant medications probably have an important role in the epileptogenesis, regardless of fampridine. However, the potential pro-convulsant properties of fampridine should not be overlooked.

Association Study between Functional Polymorphisms of MMP9 Gene Promoter and Multiple Sclerosis Susceptibility in an Iranian Population.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) polymorphisms, C-1562 T and -90 (CA) n repeats, which influence transcriptional activity of this gene, are proposed to play a role in MS susceptibility and its development. In the present study, the possible association of MMP-9 polymorphisms in Iranian MS patients is studied. METHODS: Association of MMP-9 mentioned gene polymorphisms with MS susceptibility was evaluated in unrelated Iranian subjects referred to Al-Zahra Hospital, Isfahan, Iran during 2014 to 2017. RESULTS: -1562 T allele of MMP-9 was associated with increased MS risk. However, we found no overall significant effect of -90 (CA)n repeat on MS susceptibility. CONCLUSION: For as much as MMP-9 molecule is a potential target for MS therapy, to determine whether any of MMP-9 polymorphisms influence MS susceptibility in Iranian MS patients or not, concerning the significant influence of T allele on MS susceptibility and the non-significant association regarding CA repeats, further research is needed before proposing any definite conclusion.

Effects of progesterone and vitamin D on outcome of patients with acute traumatic spinal cord injury; a randomized, double-blind, placebo controlled study.

BACKGROUND: Steroid hormones offer promising therapeutic perspectives during the acute phase of spinal cord injury (SCI) while the role of progesterone and vitamin D remain controversial. The aim of the current study was to investigate the effects of progesterone and vitamin D on functional outcome of patients with acute traumatic SCI. METHODS: This was a randomized clinical trial including 64 adult patients with acute traumatic SCI admitted within 8 hours of injury. All the patients received methylprednisolone on admission according to standard protocol (30 mg/kg as bolus dose and 15 mg/kg each 3 hours up to 24 hours). Patients were randomly assigned to receive intramuscular injection of 0.5 mg/kg progesterone twice daily and 5µg/kg oral vitamin D3 twice daily up to 5 days (n = 32) or placebo (n = 32). Patients were visited 6 days, 3 and 6 months after injury and motor and sensory function was assessed according to American Spinal Injury Association (ASIA) score. RESULTS: There was no significant difference between two study groups regarding age (P = 0.341), sex (P = 0.802) and therapy lag (P = 0.609). The motor powers and sensory function increased significantly after 6 months in both study groups. Those who received progesterone and vitamin D had significantly higher motor powers and sensory function after 6 months of therapy. Those who received the therapy within 4 hours of injury, had significantly higher motor powers and sensory function 6 months after treatment in progesterone and vitamin D group. Therapy lag was negatively associated with 6-month motor powers and sensory function in progesterone and vitamin D group. CONCLUSIONS: Administration of progesterone and vitamin D in acute phase of traumatic SCI is associated with better functional recovery and outcome.

A case report of cemento-ossifying fibroma presenting as a mass of the ethmoid sinus.

Cemento-ossifying fibroma is a lesion containing both fibrous and osseous components. Such lesions include fibrous dysplasia, ossifying fibroma, cemento-ossifying fibroma and cementifying fibroma. Periodontal membrane is the origin of fibro-osseous lesions other than fibrous dysplasia.Here a clinical case of a young woman referred for evaluation of a mass in the right side of face between eye and nose is presented. The first time she noticed the mass was 2 years ago and was growing larger inwards. She was treated with surgical resection.In this case of a cemento-ossifying fibroma, histological interpretation was critical, and was the basis of correct treatment.

The comparative study on diagnostic validity of cerebral aneurysm by computed tomography angiography versus digital subtraction angiography after subarachnoid hemorrhage.

BACKGROUND: In order to declare the preoperative diagnostic value of brain aneurysms, two radiological modalities, computed tomographic angiography and digital subtraction angiography were compared. METHODS: In this descriptive analytic study, diagnostic value of computed tomographic angiography (CTA) was compared with digital subtraction angiography (DSA). Sensitivity, specificity, positive and negative predictive values were calculated and compared between the two modalities. All data were analyzed with SPSS software, version 16. RESULTS: Mean age of patients was 49.5 ± 9.13 years. 57.9 % of subjects were female. CTA showed 89% sensitivity and 100% specificity whereas DSA demonstrated 74% sensitivity and 100% specificity. Positive predictive value of both methods was 100%, but negative predictive value of CTA and DSA was 85% and 69%, respectively. CONCLUSIONS: Based on our data, CTA is a valuable diagnostic modality for detection of brain aneurysm and subarachnoid hemorrhage.

Central nervous system aspergillosis in an immunocompetent patient.

A 12-year-old girl was admitted to the Emergency Department with seizures and headache for 2 months. A CT scan and MRI showed a mass in the right frontal lobe with obvious mass effect. Surgery was carried out, and the resultant pathology was found to be aspergillosis. This study reports aspergillosis in an immunocompetent host following recurrent fungal otitis media. Although this condition is rare, it should be considered in patients with a history of fungal infections.

Indications for brain CT scan in patients with minor head injury.

OBJECTIVES: Minor head injury is the most common type of head injury. Despite of high incidence and numerous studies performed, there is much controversy about correct evaluation of these patients. The aim of this study was to find clinical signs and symptoms which help to predict the indications for brain CT scan following minor head injury. METHODS: A series of 682 consecutive patients who had been attended at two university hospitals (Alzahra and Kashani) with minor head injury (GCS=15) were prospectively enrolled in this cohort study. In all cases clinical signs and symptoms were collected and a cranial computerized tomography (CT) scan was obtained. The relationship between the occurrence of clinical findings and appearance of intracranial posttraumatic lesions on cranial CT was analyzed by chi-square tests and statistic logistic regression methods, with 95% confidence intervals. RESULTS: Of 682 patients, 46 (6.7%) presented brain injuries on CT scan. All patients with abnormal CT scans had at least one of the following factors (risk factors): posttraumatic amnesia, loss of consciousness, posttraumatic seizure, headache, vomiting, focal neurological deficit, skull fracture, coagulopathy or antecedent of treatment with anticoagulants and patient age older than 60 years. No abnormal CT scans were found among patients without any of those risk factors on admission. Vomiting, skull fracture and age greater than 60 years were risk factors significantly correlated to an abnormal cranial CT after head injury. The presence of several risk factors in a patient increased the probability of posttraumatic lesion on CT scan. CONCLUSION: Some clinical risk factors can be used as a guide to predict the probability of abnormal CT following minor head injury.