Common Central Nervous System Complication Research Articles

Microbiota-gut-brain axis in perioperative neurocognitive and depressive disorders: Pathogenesis to treatment

An increasing number of people undergo anesthesia and surgery. Perioperative neurocognitive and depressive disorders are common central nervous system complications with similar pathogeneses. These conditions pose a deleterious threat to human health and a significant societal burden. In recent years, numerous studies have focused on the role of the gut microbiota and its metabolites in the central nervous system via the gut-brain axis. Its involvement in perioperative neurocognitive and depressive disorders has attracted considerable attention. This review aimed to elucidate the role of the gut microbiota and its metabolites in the pathogenesis of perioperative neurocognitive and depressive disorders, as well as the value of targeted interventions and treatments.

The neuroprotective effect of near infrared light therapy in aged mice with postoperative neurocognitive disorder by upregulating IRF7

BackgroundPostoperative neurocognitive disorder (PND) is a common central nervous system complication after undergoing surgery and anesthesia especially in elderly patients, while the therapeutic options are very limited. This study was carried out to investigate the beneficial effects of transcranial near infrared light (NIRL) which was employed to the treatment of PND and propose the involved mechanisms. MethodsThe PND mice were established through left carotid artery exposure under isoflurane anesthesia and received transcranial NIRL treatment. Behavioral testing was performed to evaluate the cognitive function of PND mice after transcranial NIRL therapy. Changes in the transcriptomic profiles of prefrontal cortex (PFC) and hippocampus (HP) were identified by next generation sequencing (NGS), and the molecular mechanisms involved were examined by both in vivo mouse model and in vitro cell culture studies. ResultsWe found that transcranial NIRL therapy effectively ameliorated learning and memory deficit induced by anesthesia and surgery in aged mice. Specifically, we identified down-regulation of interferon regulatory factor 7 (IRF7) in the brains of PND mice that was mechanistically associated with increased pro-inflammatory M1 phenotype of microglia and elevated neuroinflammatory. NIRL treatment produced protective effects through the upregulation of IRF7 expression and reversing microglial phenotypes from pro-inflammatory to neuroprotective, resulting in reduced brain damage and improved cognitive function in PND mice. ConclusionOur results indicate that transcranial NIRL is an effective and safe therapy for PND via alleviating neuroinflammation, and IRF7 plays a key transcription factor in regulating the M1-to-M2 switch of microglia.

Phosphatidate phosphatase Lipin1 involves in diabetic encephalopathy pathogenesis via regulating synaptic mitochondrial dynamics

Diabetic encephalopathy (DE) is a common central nervous system complication of diabetes mellitus without effective therapy currently. Recent studies have highlighted synaptic mitochondrial damages as a possible pathological basis for DE, but the underlying mechanisms remain unclear. Our previous work has revealed that phosphatidate phosphatase Lipin1, a critical enzyme involved with phospholipid synthesis, is closely related to the pathogenesis of DE. Here, we demonstrate that Lipin1 is significantly down-regulated in rat hippocampus of DE. Knock-down of Lipin1 within hippocampus of normal rats induces dysregulation of homeostasis in synaptic mitochondrial dynamics with an increase of mitochondrial fission and a decrease of fusion, then causes synaptic mitochondrial dysfunction, synaptic plasticity deficits as well as cognitive impairments, similar to that observed in response to chronic hyperglycemia exposure. In contrast, an up-regulation of Lipin1 within hippocampus in the DE model ameliorates this cascade of dysfunction. We also find that the effect of Lipin1 that regulating mitochondrial dynamics results from maintaining appropriate phospholipid components in the mitochondrial membrane. In conclusion, alterations in hippocampal Lipin1 contribute to hippocampal synaptic mitochondrial dysfunction and cognitive deficits observed in DE. Targeting Lipin1 might be a potential therapeutic strategy for the clinical treatment of DE.

Perioperative neurocognitive disorder changes in elderly diabetes patients within 30days after surgery: a retrospective cohort study.

Perioperative neurocognitive disorders (PND) are a common central nervous system complication that predominantly affects the elderly. PND after surgery includes postoperative delirium (POD), delayed neurocognitive recovery up to 30days (DNR), and postoperative neurocognitive disorder up to 12months. Diabetes is an important independent risk factor for PND. Over the years, few studies have assessed the incidence of PND and the difference in serum biomarkers between diabetic and non-diabetic patients. We sought to examine the difference in the incidence of PND between elderly diabetic and non-diabetic patients in China and identify the risk factors of PND in elderly diabetics. We conducted a secondary and exploratory data analysis from our prior studies, including patients aged 65years or older who underwent non-cardiac elective surgery with general anesthesia. We used the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Montreal Cognitive Assessment (MoCA) to assess patient cognition. A total of 236 patients were analyzed; the incidence of PND was significantly higher in diabetic than in non-diabetic patients within 30days (59.2% vs. 36.8%) (P = 0.022). Multivariate logistic regression analysis showed that the preoperative MoCA was an independent risk factor for PND (odds ratio, 0.88 [0.8 to 0.97]; P = 0.014), and Hosmer-Lemeshow tests showed that it could predict PND in diabetic patients (P = 0.360). According to the maximum Youden index, the optimal cutoff for preoperative MoCA was 21.5 points, yielding a specificity and sensitivity of 88.0% and 55.2% for PND. The levels of glial fibrillary acidic protein (GFAP) and Tau in diabetic patients before and after surgery were significantly higher than in non-diabetic patients among cases of PND (P = 0.002 and 0.011, respectively). The incidence of PND is higher in diabetic than in non-diabetic patients in China, and preoperative MoCA is an independent risk factor for PND in diabetics. Meanwhile, the changes in GFAP and p-Tau in diabetic patients who experienced PND were significantly higher than in non-diabetic ones.

Research progress of postoperative cognitive dysfunction in cardiac surgery under cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is often used in cardiothoracic surgery because its nonphysiological state causes pathophysiological changes in the body, causing multiorgan and multitissue damage to varying degrees. Postoperative cognitive dysfunction (POCD) is a common central nervous system complication after cardiac surgery. The etiology and mechanism of POCD are not clear. Neuroinflammation, brain mitochondrial dysfunction, cerebral embolism, ischemia, hypoxia, and other factors are related to the pathogenesis of POCD. There is a close relationship between CPB and POCD, as CPB can cause inflammation, hypoxia and reperfusion injury, and microemboli formation, all of which can trigger POCD. POCD increases medical costs, seriously affects patients' quality of life, and increases mortality. Currently, there is a lack of effective treatment methods for POCD. Commonly used methods include preoperative health management, reducing inflammation response during surgery, preventing microemboli formation, and implementing individualized rehabilitation programs after surgery. Strengthening preventive measures can minimize the occurrence of POCD and its adverse effects.

Dexmedetomidine Ameliorated Cognitive Dysfunction Induced by Intestinal Ischemia Reperfusion in Mice with Possible Relation to the Anti-inflammatory Effect Through the Locus Coeruleus Norepinephrine System

Cognitive impairment is a common central nervous system complication that occurs following surgery or organs damage outside the nervous system. Neuroinflammation plays a key role in the molecular mechanisms of cognitive impairment. Dexmedetomidine alleviates neuroinflammation and reduces cognitive dysfunction incidence; however, the mechanism by which dexmedetomidine alleviates cognitive dysfunction remains unclear. This study evaluated the effect of dexmedetomidine on attenuation of early cognitive impairment induced by intestinal ischemia–reperfusion in mice and examined whether the locus coeruleus norepinephrine (LCNE) system participates in the anti-inflammatory effect of dexmedetomidine. The superior mesenteric artery was clamped for 45 min to induce intestinal ischemia reperfusion injury. Dexmedetomidine alone or combined with DSP-4, a selective locus coeruleus noradrenergic neurotoxin, was used for pretreatment. Postoperative cognition was assessed using the Morris water maze. Serum and hippocampal levels of IL-1β, TNF-α, norepinephrine (NE), and malondialdehyde (MDA) were assessed by enzyme-linked immunosorbent assay. Immunofluorescence, immunohistochemistry, and hematoxylin and eosin staining were used to evaluate the expression of tyrosine hydroxylase (TH) in the locus coeruleus, hippocampal microglia, and intestinal injury. Pretreatment with dexmedetomidine alleviated intestinal injury and decreased the serum and hippocampal levels of NE, IL-1β, TNF-α, and MDA at 24 h after intestinal ischemia reperfusion, decreased TH-positive neurons in the locus coeruleus, and ameliorated cognitive impairment. Similarly, DSP-4 pre-treatment alleviated neuroinflammation and improved cognitive function. Furthermore, α2-adrenergic receptor antagonist atipamezole or yohimbine administration diminished the neuroprotective effects and improved cognitive function with dexmedetomidine. Therefore, dexmedetomidine attenuated early cognitive dysfunction induced by intestinal ischemia–reperfusion injury in mice, which may be related to its anti-inflammatory effects through the LCNE system.

Cerebral infarction after cardiac surgery.

Cerebral infarction, a common central nervous system complication after adult cardiac surgery, is one of the main factors leading to the poor prognosis of cardiac surgery patients besides cardiac insufficiency. However, there is currently no effective treatment for cerebral infarction. Therefore, early prevention and diagnosis of postoperative cerebral infarction are particularly important. There are many factors and mechanisms during and after cardiac surgery that play an important role in the occurrence of postoperative cerebral infarction, such as intraoperative embolism, systemic inflammatory response syndrome, atrial fibrillation, temperature regulation, blood pressure control, use of postoperative blood products, and so forth. The mechanism by which most risk factors act on the human body, leading to postoperative cerebral infarction, is not well understood, and further research is needed. Therefore, this paper aims to summarize and explain the relevant risk factors, mechanisms, clinical signs, imaging characteristics, and early diagnosis methods of cerebral infarction complications after cardiac surgery, and provides useful data for the establishment of related diagnosis and treatment standards.

Elevated neuron-specific enolase level is associated with postoperative delirium and detection of phosphorylated neurofilament heavy subunit: A prospective observational study

Delirium is the most common central nervous system complication after surgery. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage within the central cervous system and is associated with the severity of postoperative delirium. Neuron-specific enolase and S100 calcium-binding protein β have been identified as possible serum biomarkers of postoperative delirium. This study examined the association of the levels of these markers with incidence of postoperative delirium and detection of phosphorylated neurofilament heavy subunit. This study represents a post hoc analysis of 117 patients who participated in a prospective observational study of postoperative delirium in patients undergoing cancer surgery. Patients were clinically assessed for development of postoperative delirium within the first five days of surgery. Serum levels of phosphorylated neurofilament heavy subunit, neuron-specific enolase, and S100 calcium-binding protein β levels were measured on postoperative day 3. Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Neuron-specific enolase level (P < 0.0001) and the proportion of patients positive for phosphorylated neurofilament heavy subunit (P < 0.0001) were significantly higher in the group of patients with postoperative delirium. Neuron-specific enolase level discriminated between patients with and without clinically diagnosed postoperative delirium with significantly high accuracy (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.79-0.95; P < 0.0001). Neuron-specific enolase level was associated with incidence of postoperative delirium independently of age (adjusted odds ratio, 8.291; 95% Cl, 3.506-33.286; P < 0.0001). The AUC for the serum neuron-specific enolase level in detecting phosphorylated neurofilament heavy subunit was significant (AUC, 0.78; 95% CI, 0.66-0.90; P < 0.0001). Elevated serum neuron-specific enolase was associated with postoperative delirium independent of age as well as detection of phosphorylated neurofilament heavy subunit in serum. Serum neuron-specific enolase and phosphorylated neurofilament heavy subunit might be useful as biomarkers of postoperative delirium. University Medical Information Network (UMIN) trial ID: UMIN000010329; https://clinicaltrials.gov/.

Neuroimaging findings of posterior reversible encephalopathy syndrome (PRES) following haematopoietic stem cell transplantation in paediatric recipients

BackgroundHaematopoietic stem cell transplantation (HSCT) is used worldwide in various malignant and nonmalignant childhood diseases, including haematologic, genetic, autoimmune and metabolic disorders, and is the only curative treatment for many of these illnesses. The survival rates of many childhood diseases have been increased due to HSCT treatment. However, associated complications are still important for management. Central nervous system (CNS) complications in paediatric HSCT recipients can be associated with high morbidity and significantly contribute to mortality. Posterior reversible encephalopathy syndrome (PRES) is one of the most common CNS complications in patients with neurological symptoms following HSCT. Magnetic resonance imaging (MRI) is the modality of choice and shows typical bilateral vasogenic oedema at the posterior parts of the cerebral hemispheres; however, various atypical imaging manifestations can also occur. In this study, we retrospectively examined CNS complications in our paediatric HSCT recipients with a focus on the typical and atypical neuroimaging manifestations of PRES following HSCT.MethodsWe retrospectively reviewed the medical records of 300 consecutive paediatric HSCT recipients from January 2014 to November 2018. A total of 130 paediatric HSCT recipients who experienced neurological signs and symptoms and were evaluated with neuroimaging studies following HSCT were enrolled in the study. The timing of CNS complications was defined according to immune status, including the pre-engraftment period (< 30 days after HSCT), the early postengraftment period (30–100 days after HSCT), and the late postengraftment period (> 100 days after HSCT), which were defined as phases 1, 2 and 3, respectively.ResultsOverall, 130 paediatric HSCT recipients experienced neurological signs and symptoms and therefore underwent neuroimaging examinations. Among these 130 patients, CNS complications were present in 23 patients (17.6%, 23/130), including 13 (56.5%) females and 10 (43.5%) males with a median age of 8.0 years (range, 8 months to 18.0 years). Among these 23 patients, 14 cases of PRES (60.9%), 5 (21.7%) cases of leukoencephalopathy, 3 cases of acute subdural haemorrhage (ASDH) (13%) and 1 (4.3%) case of fungal CNS infection were identified by neuroimaging. On MRI, typical parietooccipital vasogenic oedema was present in 78.5% of the PRES cases (11/14). The following atypical neuroimaging manifestations were observed: isolated involvement of the bilateral frontal lobes in 1 case, isolated cerebellar vermis involvement in 1 case, and isolated basal ganglia involvement in 1 case. Restricted diffusion associated with cytotoxic damage was demonstrated in 2 of 14 cases, one of which also showed subacute cytotoxic injury with ADC pseudonormalization.ConclusionPaediatric HSCT recipients presenting with CNS signs and symptoms should be evaluated by neuroimaging studies for timely diagnosis and early management. PRES is the most common CNS complication and may present with atypical MRI manifestations, which should not dissuade a PRES diagnosis in appropriate clinical settings.

CT-285: Patterns of Central Nervous System Complications Post-Hematopoietic Stem Cell Transplant in Pediatric Oncology Patients: A Single-Institute Experience

Context Hematopoietic stem cell transplantation (HSCT) became an integral component of the treatment of various pediatric malignancies. Post-transplant central nervous system complications (CNSC) are major contributors to morbidities in transplanted patients. Objective To describe the patterns of CNSC after HSCT in pediatric oncology patients using brain imaging. Design This retrospective study included pediatric patients transplanted between 2011 and 2019. Setting Cases were treated at the Children’s Cancer Hospital Egypt (CCHE-57357), which is a specialized center for pediatric oncology. Patients or Other Participants The study included pediatric cases who had undergone allogeneic- or autologous-HSCT. Interventions Computed tomography (CT) and/or magnetic resonance imaging (MRI) studies were evaluated for the detection and characterization of CNSC. Imaging was done following any neurological symptoms post-transplant. Brain structural abnormalities were classified as cerebrovascular complications (intra-parenchymal hemorrhage and venous thrombosis), infection, disease recurrence, atrophy, and treatment-related toxicities (posterior reversible encephalopathy syndrome [PRES] and leukoencephalopathy). Main Outcome Measures To describe the pattern of CNSC post-HSCT in pediatric oncology patients using CT and/or MRI. Results A total of 525 cases were included, of whom 311 and 214 had undergone autologous-HSCT and allogeneic-HSCT, respectively. Median follow-up for survivors was 48 months (range: 6–109 months). Hematological malignancies constituted 58% of cases. The median age was 6.5 years (range: 0.9–25 years). Sixty-eight cases (13%) presented cumulatively with 77 clinical episodes of neurological complications. The cumulative frequency of CNSC at 100 days was 5.3%. A higher incidence was observed in allogeneic-HSCT (15.9 %) compared to autologous-HSCT (11%). The most common CNSC was disease recurrence in 28/77 (36.4%), with 89% occurrence after autologous-HSCT, followed by PRES in 17/77 (22%) episodes. Females were 4.2 times as susceptible to developing PRES as males (p Conclusion The frequency of post-transplant CNSC is higher in allogeneic-HSCT compared to autologous-HSCT. The pattern of CNSC differs according to the time interval post-HSCT. Expert imaging interpretation is needed for early detection and proper management of CNSC post-HSCT.

ApoE transiently regulates hippocampus amyloid-beta deposition to stable learning and memory ability in adult rats exposed in sevoflurane.

Post-operative cognitive dysfunction (POCD) is a common central nervous system complication after surgery. Inhaled anesthetic sevoflurane is thought to have harmful effects on the developing and aged nerves, but its effects on adults' nervous system are less studied and the mechanism is not clear. Male adult rats were divided into control group and sevoflurane group. Rats from sevoflurane group were received 3.2% sevoflurane + carrier gas (1L/min O2+1L/min air) for 2h, while control group received carrier gas for 2h. Each group was subsequently divided into 3 subgroups according to the Day 1, Day 3, Day 7 after sevoflurane anesthesia. Morris Water Maze, amyloid-beita (Abeta) and apolipoprotein E (ApoE) mRNA in hippocampus were analyzed. Then, adult ApoE-/- rats were also divided into control group and sevoflurane group. Each group was divided into 3 subgroups according to Day 1, Day 3 and Day 7. Abeta mRNA and protein expression in hippocampus were analyzed. Compared with the control group, hippocampal Abeta mRNA and protein expression in rats from sevoflurane group significantly increased in hippocampus on Day 7, while ApoE mRNA and protein expression increased on Day 1 and Day 3. There was no difference in times of crossing platforms, time during platform, times across platform quadrant and time percent during platform quadrant between each group. Compared with the control group, hippocampal Abeta and ApoE-/- rats in sevoflurane group did not change. ApoE modulates hippocampal Abeta deposition and stabilizes learning and memory ability in adult rats after sevoflurane exposure, but this effect is not constant.

Clinical Interventions for HIV-Associated Neurocognitive Disorder (HAND): A Systematic Review

Despite the widespread use of antiretroviral therapy, HIV-associated neurocognitive disorder (HAND) continues to be one of the most common central nervous system complications of human immunodeficiency virus type 1 (HIV-1). The severity and prevalence of HAND underscores the need for safe, effective therapies to mitigate or eliminate the impacts of the disorder to improve the quality of life of individuals living with HAND. The current study conducted a systematic review of the literature regarding experimental studies of clinical therapeutic interventions for HAND. An electronic search of four databases (PsycINFO, SCOPUS, Ovid MEDLINE, and CINAHL) initially returned 4,280 articles, 31 of which met the inclusion criteria for this study. Articles were selected for inclusion based on several criteria, including the use of a clinical experimental study design and measurement of neuropsychological performance. A large number of studies were excluded due to utilizing observational or cross-sectional designs, relevance, or for otherwise not meeting inclusion criteria. The results of this review revealed 31 articles that investigated both pharmaceutical and cognitive therapies for HAND. Pharmaceutical interventions range from common antiretroviral therapies to novel drug classes with various mechanisms of action. Importantly, this review revealed a number of limitations present in the greater body of HAND research including inconsistencies among methods of diagnosis of HAND and study design, which ultimately make comparisons across studies difficult. This review presents the current evidence that exists regarding therapies for HAND and broadly discusses trends, limitations, and gaps in the literature.

Central Nervous System Complications in COVID-19 Patients; a Systematic Review and Meta-Analysis based on Current Evidence.

Several studies have confirmed neurological involvements, such as acute cerebrovascular disease and impaired consciousness in COVID-19. In the present study, our aim is to investigate the current evidence regarding central nervous system (CNS) complications in patients with confirmed COVID-19. An extensive search was conducted in electronic databases including Medline (using PubMed), Embase, Scopus, and Web of Science, in addition to the manual search in Google and Google scholar search engines, for articles published from 2019 until April 21st, 2020. Inclusion criteria was articles that were reviewed and reported the incidence of neurological outcomes in patients with confirmed COVID-19 disease. The initial search yielded 638 records, from which 7 articles were included. Overall, the incidence of CNS complications was calculated to be 6.27% (95% CI: 3.32 to 9.98). The incidence of the most common CNS complications, encephalopathy and acute cerebrovascular disease, were 9.14% (95%CI: 2.20 to 19.81) and 2.59% (95% CI: 1.31 to 4.25), respectively. CNS complications do exist in COVID-19 patients, encephalopathy being the most concerning one. The heterogeneity in the existing literature causes an uncertainty in reporting the definite prevalence rate for each complication. Thus, further studies are needed for scientists to reach a more accurate estimate of the prevalence of these complications in COVID-19 patients. However, healthcare providers should consider the possibility of CNS involvements in patients with SARS-CoV-2 infection.

A Novel Mutation in Neurofibromatosis Type 1 with Optic Glioma

Neurofibromatosis type 1 is an autosomal dominant disorder which is characterized by multiple café-au-lait spots in the body, intertriginous freckles, Lisch nodules, neurofibroma, optic glioma and bone dysplasia. One of the clinical characteristics of Neurofibromatosis type 1 is the risk of benign and malignant tumor development. Optic gliomas, a type of astrocytoma, are the most common central nervous system complication in children with Neurofibromatosis type 1 and are seen in 10–15% of cases. In this case report, a patient with an optic glioma and a mutation that was not previously identified in the NF1 gene is presented in the light of the literature. Identification of new mutations that cause Neurofibromatosis type 1 disease and reporting of clinical findings caused by the mutations will allow a large proportion of genotypephenotype correlation. Early diagnosis has a great importance in terms of followup of patients for malignancies that may develop in the future.

Graphene oxide improves postoperative cognitive dysfunction by maximally alleviating amyloid beta burden in mice.

Rationale: Graphene oxide (GO) based nanomaterials have shown potential for the diagnosis and treatment of amyloid-β (Aβ)-related diseases, mainly on Alzheimer's disease (AD). However, these nanomaterials have limitations. How GO is beneficial to eliminate Aβ burden, and its physiological function in Aβ-related diseases, still needs to be investigated. Moreover, postoperative cognitive dysfunction (POCD) is an Aβ-related common central nervous system complication, however, nanomedicine treatment is lacking.Methods: To evaluate the effects of GO on Aβ levels, HEK293T-APP-GFP and SHSY5Y-APP-GFP cells are established. Intramedullary fixation surgery for tibial fractures under inhalation anesthesia is used to induce dysfunction of fear memory in mice. The fear memory of mice is assessed by fear conditioning test.Results: GO treatment maximally alleviated Aβ levels by simultaneously reducing Aβ generation and enhancing its degradation through inhibiting β-cleavage of amyloid precursor protein (APP) and improving endosomal Aβ delivery to lysosomes, respectively. In postoperative mice, the hippocampal Aβ levels were significantly increased and hippocampal-dependent fear memory was impaired. However, GO administration significantly reduced hippocampal Aβ levels and improved the cognitive function of the postoperative mice.Conclusion: GO improves fear memory of postoperative mice by maximally alleviating Aβ accumulation, providing new evidence for the application of GO-based nanomedicines in Aβ-related diseases.

Central Nervous System Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children

Central nervous system complications (CNSCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are common and may be a significant source of morbidity and mortality. We performed a retrospective study of 153 pediatric patients who underwent allo-HSCT to determine CNSC type, incidence, and impact on survival. A total of 34 patients (22.2%) developed CNSCs. The cumulative incidence of CNSCs at 100 days and 3 years was 18.30 and 22.73%, respectively. The most common CNSC was calcineurin inhibitor (CNI)-associated neurotoxicity (50.0%). Risk factors for CNSCs were the time from diagnosis to HSCT ≥4.8 months (p = 0.032) and the development of acute graft-versus-host disease (aGVHD) grade III–IV (p = 0.002). CNSCs after allo-HSCT negatively impacted overall survival (hazard ratio [HR] 1.97, p = 0.043) and nonrelapse mortality (HR 4.84, p < 0.001). In conclusion, CNSCs after allo-HSCT are associated with poor outcomes; patients with severe aGVHD and/or late transplantation should be given more attention.

Type 2 Diabetes Leads to Axon Initial Segment Shortening in db/db Mice.

Cognitive and mood impairments are common central nervous system complications of type 2 diabetes, although the neuronal mechanism(s) remains elusive. Previous studies focused mainly on neuronal inputs such as altered synaptic plasticity. Axon initial segment (AIS) is a specialized functional domain within neurons that regulates neuronal outputs. Structural changes of AIS have been implicated as a key pathophysiological event in various psychiatric and neurological disorders. Here we evaluated the structural integrity of the AIS in brains of db/db mice, an established animal model of type 2 diabetes associated with cognitive and mood impairments. We assessed the AIS before (5 weeks of age) and after (10 weeks) the development of type 2 diabetes, and after daily exercise treatment of diabetic condition. We found that the development of type 2 diabetes is associated with significant AIS shortening in both medial prefrontal cortex and hippocampus, as evident by immunostaining of the AIS structural protein βIV spectrin. AIS shortening occurs in the absence of altered neuronal and AIS protein levels. We found no change in nodes of Ranvier, another neuronal functional domain sharing a molecular organization similar to the AIS. This is the first study to identify AIS alteration in type 2 diabetes condition. Since AIS shortening is known to lower neuronal excitability, our results may provide a new avenue for understanding and treating cognitive and mood impairments in type 2 diabetes.

Neurological presentations of intravascular lymphoma (IVL): meta-analysis of 654 patients.

BackgroundPatients with intravascular lymphoma (IVL) frequently have neurological signs and symptoms. Prompt diagnosis and treatment is therefore crucial for their survival. However, the spectrum of neurological presentations and their respective frequencies have not been adequately characterized. Our aim is to document the spectrum of clinical symptoms and their respective frequencies and to create a clinical framework for the prompt diagnosis of IVL.MethodsA comprehensive meta-analysis of 654 cases of IVL published between 1957 and 2012 was performed to provide better insight into the neurological presentations of this disease. Neurologic complications were mainly divided into central nervous system (CNS) and peripheral nervous system (PNS) presentations.ResultsThere were no differences in occurrences of CNS IVL based on gender or geographic locations (Asian Vs non-Asian). However, most patients with CNS IVL were younger than 70 years of age (p < 0.05). Our limited data do not support the treatment efficacy of methotrexate.CNS symptoms were seen in 42 % of all cases. The most common CNS complications identified were cognitive impairment/dementia (60.9 %), paralysis (22.2 %), and seizures (13.4 %). PNS complications were seen in 9.5 % of cases. Out of these, muscle weakness (59.7 %), neurogenic bladder (37.1 %), and paresthesia (16.1 %) were the most common presentations.ConclusionsCNS complications are more common among IVL patients. Out of these, dementia and seizures outnumber stroke-like presentations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0509-8) contains supplementary material, which is available to authorized users.

Neurological Complications after Renal Transplantation: A Retrospective Clinical Study.

The aim of this study was to evaluate the incidence and types of neurological complications (NCs) and associated factors in renal transplantation (RT) patients. Three hundred and forty-four patients who had RT performed at our institution between January 2005 and July 2014 were retrospectively evaluated. File records of the patients revealed 19 who experienced a total of 22 episodes of NCs, of whom three had more than one episode. The mean age of 19 patients included in the study, of whom eight were female, was 37.52±13.08 (range, 18-65) years. NCs were classified into central or peripheral depending on the location of involvement of the central nervous system (CNS). CNS involvement was found in 16 (84.2%) of the 19 patients. Tremor (36.8%) was the most common CNS complication in these patients. Encephalopathy, generalized tonic-clonic seizures, and status epilepticus were observed in two patients (10.5%). Delirium and dementia were observed in one patient (5.2%). Headache was experienced by one patient, and agitated depression was observed in one patient. Six patients (26.3%) had the peripheral nervous system involvement. One patient had the numbness of hands with normal electromyography findings, and four patients had polyneuropathy. In one patient, lumbar plexopathy was observed. Seventeen of the 22 NCs were considered to be caused by immunosuppressive agents. Each incidence of amyloidosis, infection, septic emboli, and hypoglycemia caused a neurological episode. The etiology of one episode was unknown. Different neurological disorders can be seen after RT, and most of them are caused by immunosuppressive drugs. NCs seen after RT can be treated by decreasing the dose or changing the immunosuppressive drug.

Use of corticosteroids in Mycoplasma pneumoniae encephalitis: A case report and review of literature

Encephalitis is the most common central nervous system (CNS) complication of Mycoplasma pneumoniae infection. CNS involvement represents the second most common organ system involved other than respiratory system by M. pneumoniae. We report a case of 11-year old male child, who was referred to us with recurrent episodes of status epilepticus and worsening level of consciousness. M. pneumoniae encephalitis was diagnosed on the basis of positive serology and exclusion of other causes. High dose corticosteroid therapy was given, which resulted in rapid improvement in the patient's neurological condition and full recovery without any neurological sequel. This case emphasizes the importance of CNS complications of M. pneumoniae and shows that corticosteroid therapy has a place for treatment of mycoplasma encephalitis. The available literature regarding this subject is also presented.