关键词： nose-to-brain delivery   neurological diseases   drug delivery systems   in situ-based gels   brain tumor   Alzheimer's disease  

摘要： In situ-based gel drug delivery systems that can bypass the blood-brain barrier, deliver the therapeutics to the desired site, reduce peripheral toxicity and control drug release kinetics have been developed. Some of the therapeutics used to treat neurological diseases suffer from poor bioavailability. Preclinical reports from several researchers have proven that the delivery of drugs to the brain via the nose-to-brain route using in situ gels holds great promise. However, safety issues on the toxicity of the nasal mucosa, transportation of the drugs to specific brain regions and determination of the required dose are factors that must be considered when designing these gels. This review will be focused on in situ-based gels that are used for the delivery of therapeutics via the nose-to-brain route, preclinical reports and challenges.

关键词： Kallikrein-Kinin system   Bradykinin   Kinin   Brain injury   Neurological disorders   Biomarkers  

摘要： Neurological disorders represent major health concerns in terms of comorbidity and mortality worldwide. Despite a tremendous increase in our understanding of the pathophysiological processes involved in disease progression and prevention, the accumulated knowledge so far resulted in relatively moderate translational benefits in terms of therapeutic interventions and enhanced clinical outcomes. Aiming at specific neural molecular pathways, different strategies have been geared to target the development and progression of such disorders. The kallikrein-kinin system (KKS) is among the most delineated candidate systems due to its ubiquitous roles mediating several of the pathophysiological features of these neurological disorders as well as being implicated in regulating various brain functions. Several experimental KKS models revealed that the inhibition or stimulation of the two receptors of the KKS system (B112 and B2R) can exhibit neuroprotective and/or adverse pathological outcomes. This updated review provides background details of the KKS components and their functions in different neurological disorders including temporal lobe epilepsy, traumatic brain injury, stroke, spinal cord injury, Alzheimer's disease, multiple sclerosis and glioma. Finally, this work will highlight the putative roles of the KKS components as potential neurotherapeutic targets and provide future perspectives on the possibility of translating these findings into potential clinical biomarkers in neurological disease.

摘要： In the original publication of the article, the corrections for the typographical errors in the equations for variance that affects the footpath (V) and the total variance (V) should be as following.

关键词： Kiimmell's disease   Percutaneous vertebroplasty (PVP)   Percutaneouslcyphoplasty (PKP)   Hyperextensionposition   Cement leakages  

摘要： Purpose The purpose of this study was to compare and evaluate the safety and efficacy of percutaneous vertebroplasty at a hyperextension position (PVPHP) and percutaneous kyphoplasty at a hyperextension position (PKPHP) for the treatment of osteoporotic Kilmmell's disease. Methods This study was a retrospective, single-centre study. There were 35 patients with osteoporotic Kilmmell's disease who were analyzed. Twenty-two of them underwent PVPHP and the other 13 patients underwent PKPHP from January 2013 to January 2015. The volume of bone cement injection and operation costs were compared. We compared the visual analogue score (VAS) and vertebral Cobb's angle at pre-operation, the second day after operation, and the final follow-up. We compared the Oswestry disability index (ODI) score at the pre-operation and the final follow-up. Results There were no significant differences in gender, age, course of disease, bone mineral density (BMD), and mean follow-up time between the two groups (P > 0.05). Regarding the costs of the operation, the PKPHP group was significantly higher than the PVPHP group (P < 0.05). Compared with the pre-operation (P < 0.05), the post-operative ODI score, VAS, and Cobb's angle of the two groups were improved significantly. Even though the correction of Cobb's angle in the PKPHP group was slightly better than the PVPHP position group, there were no significant differences between two groups (P > 0.05). At the final follow-up, the Cobb's angle was increased in both groups, but there was no significant difference (P > 0.05). There was no significant difference in the bone cement leakage rate between the two groups (P > 0.05). Conclusion For the treatment of Kiimmell's disease, PVPHP and PKPHP are both safe and effective, but PVPHP is more economical and can be considered a preferred method of treatment.

关键词： Congenital CMV   MRI   Epilepsy   Sensorineural hearing loss   Developmental delay  

摘要： Background: The aim of this study is to predict the neurological outcomes of patients with congenital cytomegalovirus infection by analysis of magnetic resonance images of the brain. Methods: From June 2007 to June 2016, 31 patients were diagnosed with symptomatic congenital cytomegalovirus infection at Asan Medical Center. The medical records and magnetic resonance imaging (MRI) findings of these patients were reviewed, and the relationships between MRI findings and neurological outcomes were analyzed. Results: Of the 31 patients, 17 were male and 12 were born prematurely (gestation age less than 37 weeks). Twenty-one patients presented with delayed development, 11 with microcephaly, and 10 with sensorineural hearing loss. Eleven patients developed epilepsy. The most common abnormal findings on brain MRI were ventriculomegaly (N = 21, 67.7%) and polymicrogyria (N = 14, 45.2%). Delayed development significantly correlated with the presence of polymicrogyria (P = 0.001). Epilepsy was significantly associated with polymicrogyria (P= 0.012), ventriculomegaly (P= 0.045), calcification (P= 0.006), and white matter abnormalities (P= 0.018). Sensorineural hearing loss was not associated with any abnormal findings on brain MRI. Based on these data, a new brain magnetic resonance cytomegalovirus scoring scale was built and this scoring scale can predict the development of epilepsy with odds ratio 3.62 (confidence interval 1.52 to 8.67, P = 0.004). Conclusions: In patients with congenital cytomegalovirus infections, brain MRI abnormalities could predict poor developmental outcomes and epilepsy, but not sensorineural hearing loss. Stratified magnetic resonance findings can be suggested as the predictors of neurological outcomes in individuals with congenital cytomegalovirus infections. (C) 2018 Elsevier Inc. All rights reserved.

关键词： Amygdalohippocampectomy   Complication rate   Epilepsy surgery   Modification   Temporal lobe epilepsy  

摘要： BACKGROUND: Temporal lobe resection (TIM) including amygdalohippocampectomy (AHE) is the most frequent performed procedure in epilepsy surgery. Owing to the close anatomic relationship of the mesial temporal structures and the midbrain and choroidal fissure, the incidence of severe complications, such as postoperative stroke, is as high as 2.5%. METHODS: We developed a modification of the classical technique for AHE that involves entering the choroidal fissure early via the anterior part of the frontomesial temporal horn cleft to identify the crux cerebri, posterior cerebri artery, and oculomotor nerve. In a second step, after visualization of the cleavage plane between the midbrain and middle cerebral artery, the uncus and amygdala are removed. RESULTS: A total of 01 patients (47 females and 34 males;mean age at surgery, 40 years) underwent TLR including AHE with our surgical modification to treat heterogeneous pathologies. The cohort included 45 patients with hippocampal sclerosis, 11 with ganglioglioma, 2 with dysembryoplastic neuroepithelioma, 2 with diffuse glioma, and 21 with other pathologies, including cavernoma, scar tissue, and mild cortical dysplasia, among others. In all patients, anterior temporal resection was performed via AHE using our modified technique. Seizure outcome was favorable after a mean follow-up of 27 months (range, 3 56 months);64% of the patients were completely seizure-free (Engel class 1A), and 75% had an Engel class 1 outcome. There was no mortality or permanent severe neurologic complications, and the rate of surgical complications was 3.7%. CONCLUSIONS: Our modified AHE technique is associated with a low rate of complications in TLR for medically refractory temporal lobe epilepsy, and helps avoid permanent severe neurologic complications.

关键词： NEUROLOGICAL disorders   MENTAL illness   GENOME editing   NEUROGENETICS   BIOLOGICAL research  

摘要： Although mice have been the most frequently used experimental animals in many research fields due to well established gene manipulation techniques, recent evidence has revealed that rodent models do not always recapitulate pathophysiology of human neurological and psychiatric diseases due to the differences between humans and rodents. The recent developments in gene manipulation of non-human primate have been attracting much attention in the biomedical research field, because non-human primates have more applicable brain structure and function than rodents. In this review, we summarize recent progress on genetically-modified non-human primates including transgenic and knockout animals using genome editing technology.

关键词： chronic hyperglycaemia   diabetes mellitus   hydration therapy   ischaemic stroke   neurological deterioration   NIHSS score  

摘要： Objectives: To determine whether chronic hyperglycaemia predisposes patients to dehydration, which may promote neurological deterioration, and to investigate whether dehydration control improves functional outcome. Patients and Methods: This study included 355 patients hospitalized with acute ischaemic stroke and diabetes mellitus who fulfilled the glycaemic gap <= 0. We used the following cut-offs: (i) no chronic hyperglycaemia (glycated haemoglobin A1c [HbA1c] < 7%) and (ii) chronic hyperglycaemia (HbA1c >= 7%). The chronic hyperglycaemic patients were randomly divided into the control group and the hydration group. Hydration therapy was only initiated in the hydration group. The blood urea nitrogen (BUN)/creatinine (Cr) ratio was used as an indicator of dehydration. Stroke severity on admission and discharge was assessed by means of National Institutes of Health Stroke Scale (NIHSS). Results: The mean baseline BUN/Cr ratios were higher in the control group and hydration group than in the no chronic hyperglycaemia group. The mean BUN/Cr ratio decreased from 91.22 +/- 29.95 on the first day to 77.03 +/- 18.23 on the third day (P <. 001) in the hydration group. On the third day after admission, there was no significant difference in the BUN/Cr ratio between the hydration group and the no chronic hyperglycaemia group (P = .831). Moreover, neurological deterioration was highest in the control group (33.6%, 36/107), followed by the hydration group (10.5%, 11/105) and the no chronic hyperglycaemia group (5.6%, 8/143). Conclusions: Chronic hyperglycaemia was associated with the admission NIHSS score and neurological deterioration after excluding the effect of stress hyperglycaemia. Furthermore, hydration therapy may help prevent neurological deterioration.

关键词： Intraoperative neurophysiologic monitoring   Transcranial electrical motor evoked potentials   Spine surgery   Induction rate   Facilitation   Motor function score  

摘要： This study sought to evaluate the facilitation effect of repetitive multi-train transcranial electrical stimulation (mt-TES) at 2 repetition rates on transcranial electrical motor evoked potential (Tc-MEP) monitoring during spinal surgery, and to assess the induction rate in patients with impaired motor function from a compromised spinal cord or spinal nerve. We studied 32 consecutive patients with impaired motor function undergoing cervical or thoracic spinal surgery (470 muscles). A series of 10 TESs with 5 pulse trains were preoperatively delivered at 2 repetition rates (1 and 5 Hz). All peak-topeak amplitudes of the MEPs of the upper and lower extremity muscles elicited by the 10 TESs were measured. The induction rates of the lower extremity muscles were also assessed with muscle and preoperative lower extremity motor function scores. In each of the muscles, MEP amplitudes were augmented by about 2-3 times at 1 Hz and 5-6 times at 5 Hz. Under the 5-Hz condition, all limb muscles showed significant amplification. Also, in all preoperative motor function score groups, the amplitudes and induction rates of the lower extremity muscles were significantly increased. Moreover, the facilitation effects tended to peak in the last half of the series of 10 TESs. In all score groups of patients with preoperative neurological deficits, repetitive mt-TES delivered at a frequency of 5 Hz markedly facilitated the MEPs of all limb muscles and increased the induction rate. We recommend this method to improve the reliability of intraoperative monitoring during spinal surgery.

关键词： Craniocervical junction   Palsy   Predictive factors   Franckel score   Neurological recovery   Surgery  

摘要： Background Neurologic manifestations of craniovertebral junction (CVJ) disease may generate dramatic brainstem damage, which could evolve to paralysis. In most cases, patients are referred with advanced neurological symptoms such as tetraplegia/paresis. The aim of this study was to identify predictive factors of favorable neurological evolution after non-traumatic brainstem compression. Methods A prospective study evaluated 143 consecutive patients who had undergone CVJ anterior brainstem decompression. The mean age was 45.1 +/- 19.1 years. The study analyzed clinical, surgical, and imagery characters to determine predictive factors of neurological improvement. Results The mean follow-up of our series was 10.2 years (range 0.5-23.9). Seventy-one (49.6%) presented initial tetrapalsies resulting from spinal cord compression. Multivariable analysis revealed that Frankel score [odds ratio (OR) 5.7, CI 95% 1.01-31.8;p < 0.04] and preoperative symptoms < 6 months [OR 0.33, CI 95% 0.125-0.9;p < 0.025] were independently associated with partial neurological improvement, while the only independent factor associated with total neurologic recovery was the preoperative symptom evolution < 6 months [odd ratio (OR) 4.3, CI 95% 1.6-11.4;p < 0.003]. None of the following were identified as predictive factors: demographic characteristics, medical history, the etiology of compression, or initial spinal cord MRI. Conclusion The earlier the decompression is performed, the better the neurological improvement. Whatever the initial Frankel score, if neurological palsy or disorders evolved for less than 6 months, complete recovery is possible.