关键词： autopsy   Computed Tomography (CT)   Magnetic Resonance Imaging (MRI)   neuroimaging   post mortem   radiology  

摘要： Aims Methods To develop an expert consensus statement regarding appropriate clinical and forensic post mortem neurological imaging. An expert panel of clinicians were recruited from registered members of the British Neuropathological Society (BNS) and the International Society of Forensic Radiology and Imaging (ISFRI) with post mortem expertise. Following a focus group meeting, 16 core statements were incorporated into an online modified Delphi survey and each panellist was asked to score their level of agreement. Following the first iteration, two statements that failed to reach consensus were modified and re-rated. Consensus was predefined as 75% agreement across responders. Results Conclusion Seventeen experts joined the panel and 12 (70.6%) attended the focus group meeting;14 (82%) completed both iterations of the survey. Consensus was reached for need of adequate clinical history, multidisciplinary discussion, establishment of special interest groups to discuss cases, gathering further evidence to inform imaging choices, establishment of methods for quality assessment in reporting standards and adequate funding for imaging services. The panel agreed that pathologists should be responsible for neuroimaging referrals, collating results of ancillary tests, and producing the final post mortem report. Areas requiring further discussion include the impact of double reporting, indications for neuroimaging and utilities of three-dimensional printing. The BNS/ISFRI statement represents current views of an expert panel of health professionals engaged in post-mortem neuroimaging. We hope this provides a working guideline for less experienced operators, stimulates discussion and highlights the most pressing clinical and research questions.

关键词： Gait disorders   Neuroimaging   Neurological conditions   Methods   Review   Dementia   Parkinson's disease   Stroke   Multiple Sclerosis  

摘要： Impaired locomotion is a frequent and major source of disability in patients with neurological conditions. Different neuroimaging methods have been used to understand the brain substrates of locomotion in various neurological diseases (mainly in Parkinson's disease) during actual walking, and while resting (using mental imagery of gait, or brain-behavior correlation analyses). These studies, using structural (i.e., MRI) or functional (i.e., functional MRI or functional near infra-red spectroscopy) brain imaging, electrophysiology (i.e., EEG), non-invasive brain stimulation (i.e., transcranial magnetic stimulation, or transcranial direct current stimulation) or molecular imaging methods (i.e., PET, or SPECT) reveal extended brain networks involving both grey and white matters in key cortical (i.e., prefrontal cortex) and subcortical (basal ganglia and cerebellum) regions associated with locomotion. However, the specific roles of the various pathophysiological mechanisms encountered in each neurological condition on the phenotype of gait disorders still remains unclear. After reviewing the results of individual brain imaging techniques across the common neurological conditions, such as Parkinson's disease, dementia, stroke, or multiple sclerosis, we will discuss how the development of new imaging techniques and computational analyses that integrate multivariate correlations in "large enough datasets" might help to understand how individual pathophysiological mechanisms express clinically as an abnormal gait. Finally, we will explore how these new analytic methods could drive our rehabilitative strategies. (C) 2018 Elsevier Masson SAS. All rights reserved.

摘要： TTS has not only been reported in association with epilepsy, subarachnoid bleeding, ischemic, stroke, intracerebral bleeding, migraine, Guillain–Barre syndrome, and traumatic brain injury as mentioned in the article by Morris et al., but also in association with amyotrophic lateral sclerosis, mitochondrial disorder, thrombolysis of ischemic stroke, non-convulsive status epilepticus, zoster virus encephalitis, HLTV1-associated myelopathy, myasthenia gravis, Miller–Fisher syndrome, posterior reversible encephalopathy syndrome, syndrome of inadequate ADH secretion, transient global amnesia, multiple sclerosis, baclofen withdrawal, post-anoxic encephalopathy, Alzheimer’s disease, myotonic dystrophy type 1, acute disseminated encephalomyelitis, eclampsia, delirium, panhypopituitarism, and botulism. A further shortcoming of the study is that only diagnoses at dismissal from the hospital were considered. In summary, this interesting study could be more meaningful if additional neurological disorders would have been considered as triggers of TTS, if the ICD10 codes for TTS would have been additionally used, and if the time relation between the neurological event and TTS would have been clarified.

摘要： INTRODUCTION: The incidence of extramedullary hematopoiesis (EH) in patients with thalassemia intermedia (TI) may reach up to 20%, because they are not transfused regularly, in contrast to poly-transfused β-thalassemia patients, where the incidence is significantly lower and varies from 1-5%. Transfusion independence in TI increases the incidence of EH, because the body attempts to compensate for ineffective erythropoiesis, insufficient bone marrow function and inadequate red cell replacement, leading to unsuccessful expansion of the hematopoietic tissue, outside of the bone marrow medulla in the form of masses. However, the rare possibility of localization of these masses in anatomic areas of the body, causing nerve compression and neurological manifestations of various degrees, from mild or moderate symptoms to severe paraplegia, fecal and urinary incontinence has not been studied thoroughly. MATERIALS AND METHODS: 7 patients, all male, diagnosed with TI were evaluated. All these patients presented with neurological manifestations due to EH at a median young age of 32 years (range 18 - 40). RESULTS: In the majority of the patients, the masses of EH were located in the thoracic and/or lumbar part of the spinal cord. In 4 of them, magnetic resonance imaging (MRI) showed additional expansion of these masses inside the vertebral and sacral canal, causing severe nerve compression, leading to paraparesis, paraplegia and hypoesthesia of the corresponding neurotomes. 2 patients presented with bowel and urinary incontinence. An impressive deterioration of the ability to walk to complete paraplegia within a week was observed in 3 cases. Milder manifestations, such as difficulty in ladder climbing, various sensory derangements, and numbness in the cauda were also described. 6 of them received radiotherapy (dose range 500-2000 cGy) at the affected areas and resolution of the masses, along with massive improvement in the clinical setting was observed. The administration of hyd

摘要： Introduction: Despite high prevalence of Sickle Cell Anemia (SCA) in sub-Saharan Africa, systematic evaluation of structural and functional impact of pediatric sickle cerebrovasculopathy has been limited. In a cross-sectional study of children with HbSS, ages 1-12 years, receiving care at the Mulago Hospital SCD clinic in Kampala, we hypothesized there would be high prevalence of multi-modal brain injury and stroke risk, as defined by 4 different adverse outcomes. Here we present our completed study results. Methods: Patients were randomly selected from the electronic clinic roster. None was taking hydroxyurea. Exclusion criteria: acute illness, Hb <6.0gm/dl, transfusion within the prior 3 months or participation in an unrelated clinical study. Adverse outcome was defined as abnormalities in ≥1 of 4 modalities examined. Stroke examination: were performed by pediatric NIH Stroke Scale (NIHSS). Psychometric testing: Age-appropriate Mullen Scales of Early Learning or Kaufman Assessment Battery, 2nd edition for Children-II, for ages 1-4 or 5-12, respectively, performed by skilled testers using validated versions in English or a predominant local language. Abnormal results defined as >2 Z scores below age-specific established community norms. Transcranial doppler ultrasounds (TCDs): Non-imaging TCDs (SonaraTek) were performed by two study trained staff (excellent inter-operator reliability >0.85); read by a U.S.-certified co-investigator. Brain magnetic resonance imaging (MRI), including arterial imaging (MRA): Subset of 81 (30.1%) of subjects (n=81), enriched for 1 or more testing abnormality, underwent non-contrast MRI/MRA imaging by a single 1.5T scanner. Two radiologists performed clinical reads. Statistical methods: ANOVA, multivariate, chi square, logistic regression. Results: Of 287 patients screened, all 265 eligible subjects were enrolled. Mean age was 5.5 SD 2.9 years, 52.3% male (Table 1). Mean Hb was 7.3 SD1.0 gm/dl. Each outcome was normally ***

摘要： Introduction: Children and adolescents with sickle cell anemia (SCA) without history of neurological manifestations remain at risk of stroke and require cost effective screening as evidence-based stroke prevention interventions are developed. Although there are data on the prevalence of Transcranial Doppler (TCD) abnormality, there are relatively few studies on the prevalence of silent cerebral infarction (SCI) on magnetic resonance imaging (MRI) and vasculopathy on MR angiography (MRA), paricularly in Africa, where the burden of disease is greatest. In this study in Africa, we determined the prevalence of SCI on MRI and cerebral vasculopathy on MRA, and explored associations with age, sex, internal carotid/middle cerebral artery (ICA/MCA) and basilar cerebral blood flow velocities (CBFV) on TCD, and hematological variables. Patients and methods: We prospectively studied children with homozygous SCA (HbSS) without prior clinically overt stroke or TIA or seizures. Clinical information and blood for full blood count was collected for all patients. All were offered TCD using non-imaging equipment (Compumedics) and MRI and MRA of intracranial arteries on a Philips 1.5 Tesla scanner. MRA was graded as 1 Turbulence, 2 Stenosis, 3 Occlusion, 4 Occlusion with collaterals (moyamoya). Imaging was reviewed by 2 neuroradiologists (MJ and DS) and consensus was reached. Results: Within a period of 12 months, 395 children with SCA were recruited. Mean age was 12.7+/-4 (range 5-19 years); 199 (50.4%) were male. Mean hemoglobin was 7.6±1.1 (range 4.1-13.5) g/dl. 381 had TCD, of whom 227 (57%) have had brain MRI and MRA so far. Only 14/395 (3.5%) of patients had abnormal CBFV, 8 (2%) with maximum CBFV <50 cm/sec, 3 with CBFV 150-169 cm/sec, 1 with conditional (170-199 cm/sec) and 2 (0.5%) with abnormal CBFV (>200cm/sec). Prevalence of silent cerebral infarction was 29% (65/227) and was similar in males (30%; 34/114) and females (28%; 31/110) but was lower in children aged <9 years (2

摘要： Introduction: Despite advances in the field, diagnosis and management of the wide spectrum of neurological events as sequelae of allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated the incidence, diagnosis, management and long-term prognosis of neurological complications in alloHCT recipients. Methods: We enrolled consecutive allogeneic HCT recipients transplanted in our center (7/1990-9/2017). We performed a retrospective review of data in our prospectively acquired database. Results: Among 758 alloHCT recipients, 127 (16.8%) patients presented with neurological complications. Interestingly, neurological complications were more common in unrelated or alternative donors (p<0.001), ALL diagnosis (p<0.001) reduced intensity or toxicity regimens (p=0.037). In the multivariate model, these variables remained independent predictors of neurological complications. Neurological adverse events presented late post-transplant (median +140day, interquartile range/IR 232). Timing of neurological complications was associated only with acute and chronic graft-versus-host-disease/GVHD (p=0.001 and p<0.001, respectively). The majority of patients developed central nervous system/CNS complications (89.7%). 11 patients (8.7%) presented with >1 episodes (median 10.4 months, IR 25.1). Based on symptoms, timing and additional testing, neurological complications were classified into: CNS relapse (24), thrombotic microangiopathy (12), CNS hemorrhage (7), posterior reversible encephalopathy (6), drug-associated polyneuropathy (7) and seizure (6), other leukoencephalopathy (8), thromboembolic events (5), neuralgia (4), myopathy (3), sinusoidal obstruction syndrome (1), Guillain-Barre syndrome (1), Wernicke encephalopathy (1), myelitis (1) and multiple sclerosis (1). Opportunistic CNS infections were attributed to aspergillosis (12), mucormycosis (3), Cytomegalovirus (9), Epstein-Barr encephalitis (3) or lymphoproliferative disease (4), Human

关键词： Cytomegalovirus   White matter abnormality   Sensorineural hearing loss   Ganciclovir   Neurodevelopment  

摘要： BackgroundCongenital cytomegalovirus (cCMV) infection leads to sensorineural hearing loss (SNHL) and neurodevelopmental delays. However, the long-term outcomes of cCMV infection with severe neurological manifestations in infancy remain *** presentationThe patient was a one-month-old girl visited owing to abnormalities in neonatal hearing screening. Central nervous system involvement including intracranial calcification and extensive white matter abnormalities was identified. Right SNHL (50dB) was detected by auditory brain response (ABR) testing. The cause of her hearing loss was determined to be cCMV infection by polymerase chain reaction (PCR) using a dried blood spot. At 1.5months of age, the patient was treated with intravenous ganciclovir (GCV) for 5weeks followed by oral valganciclovir (VGCV) for an additional 6weeks. Cytomegalovirus (CMV) loads in her urine continued to be detected until she was 10years old. Fortunately, during this time, her right hearing loss did not deteriorate, and her left hearing remained normal. Furthermore, the extensive abnormal areas of white matter observed at 1month of age mostly disappeared by the time the patient was 9years old. Her neurodevelopmental score was normal, and motor milestones were not delayed as of 10years of ***, we report the 10-year follow-up of a patient with cCMV who showed normal neurodevelopment, no progression of hearing loss, and ameliorating magnetic resonance imaging (MRI) findings, despite having various complications and severe neurological findings during infancy.

关键词： Cerebrum   cancer cell culture   FKBP12 Rapamycin Complex Associated Protein 1   Central Nervous System Diseases   Neurologic Disorders   tumor growth   Cancer Cell Growth   Protein Kinases  

摘要： Mechanistic target of rapamycin (mTOR) promotes cell proliferation, growth, and survival and is overactivated in many tumors and central nervous system disorders. PQR620 (3) is a novel, potent, selective, and brain penetrable inhibitor of mTORC1/2 kinase. PQR620 (3) showed excellent selectivity for mTOR over PI3K and protein kinases and efficiently prevented cancer cell growth in a 66 cancer cell line panel. In C57BL/6J and Sprague-Dawley mice, maximum concentration (C-max) in plasma and brain was reached after 30 min, with a half-life (t(1/2)) > 5 h. In an ovarian carcinoma mouse xenograft model (OVCAR-3), daily dosing of PQR620 (3) inhibited tumor growth significantly. Moreover, PQR620 (3) attenuated epileptic seizures in a tuberous sclerosis complex (TSC) mouse model. In conclusion, PQR620 (3) inhibits mTOR kinase potently and selectively, shows antitumor effects in vitro and in vivo, and promises advantages in CNS indications due to its brain/plasma distribution ratio.

摘要： Manganese superoxide dismutase (MnSOD) lysine acetylation is a critical post-translational modification that regulates its detoxification activity to direct cellular ROS levels and metabolic balance. In this regard, our lab has shown the change in structural configuration and gain of peroxidase function upon MnSOD-K68 acetylation. As such, this study aims to investigate the role of MnSOD-K68 acetylation (K68-Ac) status, as well as its potential biological significance both in vitro and in vivo. To experimentally evaluate the effects of MnSOD acetylation, recombinant mutants were constructed where lysine was substituted with glutamine (Q) or arginine (R), an acetylation or deacetylation mimic, respectively. The results showed that enforced expression of MnSOD^K68Q disrupts mitochondrial metabolism and ultrastructure, and functions as an in vitro oncogene. To examine the physiological significance of MnSOD acetylation, a genetically engineered whole-body MnSOD^K68Q knock-in mouse has been constructed. Biallelic knock-in (MnSOD^K68Q/K68Q) mice around 3 weeks of age display a significant phenotype that includes (1) small size, (2) lean body mass, (3) significant weight loss, and (4) a fatal neurological disorder involving loss of lower extremity movement, tremors, and dyskinesia. Daily injection of GC4419, a Mn-based chemical drug that replaces MnSOD activity by removing superoxide, extended the lifespan (from 25 days to 45 days), partially rescued motor coordination loss (as tested by rotarod) and delayed the onset of the profound neurological symptoms. In addition, electron microscopy identified disrupted mitochondrial structure in multiple tissues including liver, skeletal muscles, and the substantia nigra. Lastly, whole-body monoallelic female mice (MnSOD^WT/K68Q) of six months also display mammary tissue with smaller, disorganized fat cells, characteristics of ductal hyperplasia, and areas of cells consistent with ductal carc