Signs Of Brain Damage Research Articles

Portable Six-Channel Laser Speckle System for Simultaneous Cerebral Blood Flow and Volume Measurement with Potential Application for Characterization of Brain Injury.

In regional cerebrovascular monitoring, cerebral blood flow (CBF) and cerebral blood volume (CBV) are key metrics. Simultaneous, non-invasive measurement of CBF and CBV at different brain locations would advance cerebrovascular monitoring and pave the way for brain injury detection, as current brain injury diagnostic methods are often constrained by high costs, limited sensitivity, and reliance on subjective symptom reporting. This study's aim is to develop a multi-channel non-invasive optical system for measuring CBF and CBV at different regions of the brain simultaneously with a cost-effective, reliable, and scalable system capable of detecting potential differences in CBF and CBV across different regions of the brain. The system is based on speckle contrast optical spectroscopy (SCOS) and consists of laser diodes and board cameras which have been both tested and investigated for safe use on the human head. Results on a cohort of five healthy subjects indicated that the dynamics of both CBF and CBV were synchronized and exhibited similar cardiac period waveforms across all six channels. As a preliminary investigation, we also explored the potential use of our six-channel system for detecting the physiological sequela of brain injury, involving a subject with significant structural brain damage compared to another with lesser structural brain damage. The six-point CBF and CBV measurements were compared to MRI scans, revealing that regions with altered blood dynamics closely correlated with the injury sites identified by MRI.

Addressing the oversight medical cases in low-middle-income countries: poor mention of shaken baby syndrome in Nigeria; reasons, challenges, and recommendations.

Shaken baby syndrome (SBS) is a severe form of child abuse that results in a triad of clinical findings: subdural hematoma, retinal hemorrhages, and encephalopathy. These injuries can lead to significant brain damage, developmental delays, disabilities, or even death. In addition to these, other indicative signs include bruises, vomiting, full fontanelles, sleepiness, seizures, and fractures. This paper reviews the existing literature on SBS in Nigeria, identifies the challenges contributing to its underrecognition, and provides evidence-based recommendations for improving diagnosis, management, and prevention strategies in the region. Despite the profound impact of SBS, its recognition and management are inadequate, particularly in low- and middle-income countries (LMICs) like Nigeria, due to limited diagnostic capabilities and documentation. Addressing these gaps is crucial for safeguarding the well-being of infants and young children in Nigeria.

2,3-Diphosphoglyceric Acid Alleviating Hypoxic-Ischemic Brain Damage through p38 MAPK Modulation.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a critical condition characterized by significant brain damage due to insufficient blood flow and oxygen delivery at birth, leading to high rates of neonatal mortality and long-term neurological deficits worldwide. 2,3-Diphosphoglyceric acid (2,3-DPG), a small molecule metabolite prevalent in erythrocytes, plays an important role in regulating oxygen delivery, but its potential neuroprotective role in hypoxic-ischemic brain damage (HIBD) has yet to be fully elucidated. Our research reveals that the administration of 2,3-DPG effectively reduces neuron damage caused by hypoxia-ischemia (HI) both in vitro and in vivo. We observed a notable decrease in HI-induced neuronal cell apoptosis, attributed to the downregulation of Bax and cleaved-caspase 3, alongside an upregulation of Bcl-2 expression. Furthermore, 2,3-DPG significantly alleviates oxidative stress and mitochondrial damage induced by oxygen-glucose deprivation/reperfusion (OGD/R). The administration of 2,3-DPG in rats subjected to HIBD resulted in a marked reduction in brain edema and infarct volume, achieved through the suppression of neuronal apoptosis and neuroinflammation. Using RNA-seq analysis, we validated that 2,3-DPG offers protection against neuronal apoptosis under HI conditions by modulating the p38 MAPK pathway. These insights indicated that 2,3-DPG might act as a promising novel therapeutic candidate for HIE.

Neurotoxicity of Combined Exposure to the Heavy Metals (Pb and As) in Zebrafish (Danio rerio).

Lead (Pb) and arsenic (As) are commonly occurring heavy metals in the environment and produce detrimental impacts on the central nervous system. Although they have both been indicated to exhibit neurotoxic properties, it is not known if they have joint effects, and their mechanisms of action are likewise unknown. In this study, zebrafish were exposed to different concentrations of Pb (40 μg/L, 4 mg/L), As (32 μg/L, 3.2 mg/L) and their combinations (40 μg/L + 32 μg/L, 4 mg/L + 3.2 mg/L) for 30 days. The histopathological analyses showed significant brain damage characterized by glial scar formation and ventricular enlargement in all exposed groups. In addition, either Pb or As staining inhibited the swimming speed of zebrafish, which was enhanced by their high concentrations in a mixture. To elucidate the underlying mechanisms, we examined changes in acetylcholinesterase (AChE) activity, neurotransmitter (dopamine, 5-hydroxytryptamine) levels, HPI axis-related hormone (cortisol and epinephrine) contents and neurodevelopment-related gene expression in zebrafish brain. The observations suggest that combined exposure to Pb and As can cause abnormalities in swimming behavior and ultimately exacerbate neurotoxicity in zebrafish by interfering with the cholinergic system, dopamine and 5-hydroxytryptamine signaling, HPI axis function as well as neuronal development. This study provides an important theoretical basis for the mixed exposure of heavy metals and their toxicity to aquatic organisms.

The emerging role of α7nAChRs/caspase-3/Nrf-2 signaling pathway in citicoline improved autistic behavior induced by thimerosal in mice

AimsAutism spectrum disorder (ASD) is a global concern,affecting around 75 million individuals.Various factors contribute to ASD,including mercury-containing preservatives like thimerosal (Thim) found in some vaccines.This study explored whether citicoline could be a therapeutic option for Thim-induced neuronal damage in a mouse model of ASD.Additionally,the study investigated the effects of citicoline on the α7nAChRs/Akt/Nrf2/caspase-3 pathway,which may be involved in the development of ASD. Materials and methodsThe study separated newborn mice into four groups.The control group received saline injections,while the Thim group received intramuscular injections of 3000 μg Hg/kg Thim on days 7,9,11,and 15 after birth.The two citicoline groups were administered Thim followed by intraperitoneal injections of 250 mg/kg or 500 mg/kg citicoline for three weeks.Afterward,various parameters were assessed, including growth,behavior,brain histopathology,oxidative stress,apoptotic,and inflammatory markers. Key findingsUntreated Thim-exposed mice exhibited significant brain damage,which was substantially alleviated by citicoline treatment.This beneficial effect was associated with increased expressions and concentrations of brain α7nAChRs and Akt, increased brain content of Nrf2, and the hippocampus contents of acetylcholine. Citicoline treatment decreased the brain levels of oxidative stress markers (MDA and NO),the apoptotic marker caspase-3,and pro-inflammatory markers (NF-κB,TNF-α,and IL-1β). The drug also increased the brain GPx activity. SignificanceBased on the results of this study,the α7nAChRs pathway appears to be essential for the therapeutic effectiveness of citicoline in treating Thim-induced ASD in mice.

Clinical and Electrophysiological Evaluation of Neonatal Seizures

Neonatal seizures are the most prevalent and distinctive sign of neurologic dysfunction in early-life. In spite the recent advances in medical care and technology in newborn intensive care units (NICU), it remains an important clinical issue of diagnosis, treatment, and prognosis. This was a retrospective, observational cohort study of neonates with seizures treated in the Ondokuz Mayıs University Faculty of Medicine NICU. Demographics of the babies, risk factors and etiology of seizure, type of clinical seizure, electroencephalographic and radiological findings, and anti-seizure treatments were recorded. The incidence of neonatal seizures was 4.5% in NICU admissions. Seventy-two babies with seizures included, 69,4% were diagnosed with electroclinical seizures. The most common seizure types were clonic (35.8%) and motor automatisms (32.8%). Perinatal asphyxia/hypoxic ischemic encephalopathy (HIE) (29.2%) was the most common etiological factor, whereas hypoglycemia was the most common metabolic problem (15.3%). Eighty-one percent of seizures due to HIE were observed in the first 48 h. Hyperbilirubinemia (kern icterus), hypocalcemia, and idiopathic neonatal convulsions were observed after the first 48 h. Abnormal findings were detected in 76.4% of electroencephalographies obtained during the neonatal period. Phenobarbital was the first-line therapy in 98.6% of babies, and 83.3% of the infants were seizure-free with phenobarbital. Seizures are common in the neonatal period and may be associated with significant brain damage. Seizures appear as an important symptom of the underlying pathology and not as a disease.

Evaluation of the relationship between serum BDNF concentration and indicators of oxidative stress and inflammation in COVID-19 patients with neurological disorders - a pilot study

ABSTRACTIntroductionThe aim of this study was to determine the effect of serum level of brain-derived neurotrophic factor (BDNF) on the development of neurological disorders in COVID-19 patients and the probable role of oxidative stress and inflammation in this phenomenon.MethodsThe present case-control study included 42 COVID-19 patients referring to Golestan and Sina hospitals of Ahvaz, Iran, for treatment. Patients with (n = 18) and without (n = 24) neurological disorders were allocated into test and control groups, respectively. Following blood sampling, serum isolation was done, and the serum was stored at −80°C until biochemical assessment for measuring BDNF, oxidative stress indices, and inflammatory factors.ResultsAlthough no significant brain damage was observed in the COVID-19 patients with neurological disorders, the results showed that the serum level of BDNF in the test group increased compared to that in the control group, and this increment was accompanied with increased Tumor Necrosis Factor-alpha (TNF-α) and decreased Interferon gamma (IFN-γ) levels in the serum. Moreover, compared to the control group, patients in the test group had a decreased level of Thiol and an increased level of Malondialdehyde (MDA) in the serum. Furthermore, there was a significant positive correlation between the serum concentration of BDNF and nitric oxide (NO) in the test group.ConclusionUsing over-the-counter (OTC) medicines which include thiol-group-related agents or any other antioxidants can alleviate oxidative stress and the associated increased inflammation in COVID-19 patients with neurological symptoms.

Neuroprotective Effects of Piceatannol on Olfactory Bulb Injury after Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) accounts for 5% of all stroke cases and is responsible for significant permanent brain and neurological damage within the first few days. Loss of smell is one of those neurological disorders following olfactory bulb injury after SAH. Olfaction plays a critical role in several aspects of life. The primary underlying mechanism of olfactory bulb (OB) injury and loss of smell after SAH remains unknown. Piceatannol (PIC), a natural stilbene, possesses anti-inflammatory and anti-apoptotic effects against various diseases. In this study, we aimed to investigate the potential therapeutic effects of PIC on OB injury following SAH at molecular mechanism based on SIRT1, inflammatory (TNF-α, IL1-β, NF-κB, IL-6, TLR4), and apoptosis (p53, Bax, Bcl-2, caspase-3)-related gene expression markers and histopathology level; 27 male Wistar Albino rats were used in a pre-chiasmatic subarachnoid hemorrhage model. Animals were divided into groups (n = 9): SHAM, SAH, and PIC. Garcia's neurological examination, brain water content, RT-PCR, histopathology, and TUNEL analyses were performed in all experimental groups with OB samples. Our results indicated that PIC administration significantly suppressed inflammatory molecules (TNF-α, IL-6, IL1-β, TLR4, NF-κB, SIRT1) and apoptotic molecules (caspase-3, p53, Bax). We also evaluated edema levels and cell damage in OB injury after SAH. Ameliorative effects of PIC are also observed at the histopathology level. Garcia's neurological score test performed a neurological assessment. This study is the first to demonstrate the neuroprotective effects of PIC on OB injury after SAH. It suggests that PIC would be a potential therapeutic agent for alleviating OB injury after SAH.

Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring.

X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder caused by variants in the ABCD1 gene. The main phenotypes observed in men with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral ALD (cALD). Cerebral ALD consists of a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical decline and is fatal if left untreated. Hematopoietic stem cell transplantation is the standard treatment for cALD as it stabilizes WM degeneration when performed early in the disease. For this reason, early diagnosis is crucial, and several countries have already implemented their newborn screening programs (NBS) with the assessment of C26:0-lysophosphatidylcholine (C26:0-LPC) values as screening for X-ALD. In June 2021, an Italian group in Lombardy launched a pilot study for the implementation of X-ALD in the Italian NBS program. A three-tiered approach was adopted, and it involved quantifying the values of C26:0-LPC and other metabolites in dried blood spots with FIA-MS/MS first, followed by the more specific ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique and, finally, the genetic confirmation via focused NGS. Genetically confirmed patients are set to undergo a follow-up protocol and are periodically evaluated to promptly start a specific treatment if and when the first signs of brain damage appear, as suggested by international guidelines. A specific disease monitoring protocol has been created based on literature data and personal direct experience. The primary aim of this study was to develop a model able to improve the early diagnosis and subsequent follow-up and timely treatment of X-ALD. The study was approved by the local ethics committee. The research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Knockdown of interleukin-6 plays a neuroprotective role against hypoxia-ischemia in neonatal rats via inhibition of caspase 3 and Bcl-2-associated X protein signaling pathway.

This study aimed to investigate the role of interleukin-6 (IL-6) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (NHIE). Sprague-Dawley (SD) rats were used for the establishment of hypoxic-ischemic (HI) model. The Zea-Longa scoring was used to evaluate the extent of the neurological deficits. Triphenyl tetrazolium chloride (TTC) staining was used to measure the volume of infarction in the brain following HI protocol. The expression of IL-6 in the cortex and/or hippocampus at multiple time points after HI was examined by immunohistochemistry, western blotting and immunofluorescence. Moreover, small interfering RNAs (siRNA) were used to inhibit the expression of IL-6 in-vitro and in-vivo, and the concomitant expression of the Bcl-2 associated X protein (BAX) and caspase 3 was also measured. HI induced a significant brain damage, and these pathological changes were accompanied by IL-6 upregulation which was found localized in cortical neurons. The inhibition of IL-6 expression fostered neuronal and axonal growth, and a reduction in cellular apoptosis in cortical neuronal cultures, and cortex and hippocampus of neonatal rats. The expression of apoptotic markers such as BAX and caspase 3 was closely associated with IL-6. Downregulation of IL-6 could ameliorate HI-induced deficiencies by mediating the expression of caspase 3 and BAX.

MRI study of cerebroprotective effects of renal denervation in patients with resistant hypertension and type 2 diabetes mellitus

Objective. To assess the changes in subclinical MRI signs of brain damage in relationship with the changes in blood pressure, proinflammatory cytokines, and endothelial function one year after renal denervation (RDN) in patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM).Material and Methods. The prospective interventional study (ClinicalTrials.gov identifiers NCT02667912 and NCT01499810) analyzed qualitative brain MRI imaging data from 39 patients with RHTN and T2DM. All patients underwent 24-h ambulatory blood pressure monitoring (ABPM), brain MRI scan (1.5 T), blood tests for high-sensitivity C-reactive protein (hsCRP), and brachial artery flow-mediated dilation (FMD) measurements by high-resolution ultrasound. Patients were taking an average of 4.5 (3–6) antihypertensive drugs and were instructed not to change the therapy regimen throughout the study. A total of 29 patients completed the one-year follow-up.Results. A significant decrease in average daily systolic/diastolic blood pressure by 12 [95% CI 4.1; 19.8]/5.9 [95% CI 0.4; 11.3] mmHg (p = 0.004/0.038) according to 24-h ABPM, increase in FMD (p = 0.008), and a decrease in hsCRP level (p = 0.04) were observed one year after RHTN. Over half of patients (57%) had a decrease in 24-h systolic blood pressure by ≥ 10 mm Hg; target level of blood pressure was achieved in 38% patients. No changes in the MRI signs of brain damage (linear dimensions of liquor systems, white matter lesions [WMLs], brain damage MRI score, and intensity of MRI signal from the basal nuclei and WMLs) were observed except for a decrease in the severity of liquorodynamic disturbances. Reduction or stabilization of WML degree was observed in 24 patients (86%). No relationships were found between the dynamics of WMLs and the changes in blood pressure, FMD, and hsCRP.Conclusion. Administration of RDN to patients with RHTN and T2DM allowed to limit the WMLs in most cases and reduce the severity of liquorodynamic disorders during one-year of follow up.

Application of Space Technologies Aimed at Proprioceptive Correction in Terrestrial Medicine in Russia.

Space technologies greatly contributed not only to space medicine but also to terrestrial medicine, which actively involves these technologies in everyday practice. Based on the existing countermeasures, and due to similarities of sensorimotor alterations provoked by the weightlessness with various neurological disorders, a lot of work has been dedicated to adaptation and introduction of these countermeasures for rehabilitation of patients. Axial loading suit and mechanical stimulation of the soles’ support zones are used in mitigation of stroke and traumatic brain injury consequences. They are also applied for rehabilitation of children with cerebral palsy. Complex application of these proprioceptive correction methods in neurorehabilitation programs makes it possible to effectively treat neurological patients with severe motor disturbances and significant brain damage.

Dynamics and diagnosis of severe pneumocephalus of unknown etiology in dog

Modern veterinary medicine and its subdivision – veterinary neurology, are constantly evolving. New diagnostic methods are emerging every day, and the list of new, previously unexplored animal diseases is expanding. Much information about the pathogenesis and etiology of diseases is borrowed from human medicine, which is a big problem, because human physiology is different from animals and, as a consequence, the dynamics of the disease are also different. That is why the continuous improvement of veterinary therapy and diagnosis of diseases is relevant and necessary. One of the rare and severe pathologies is pneumocephalus. It is reported that this is a condition in which there is a gradual accumulation of air in the cranial cavity or ventricles of the brain, creating a life-threatening condition. It is considered that pneumocephalus can occur spontaneously but, in most cases, is diagnosed after trauma or surgery with impaired integrity of the skull bones and meninges. This article describes a case of pneumocephalus of unknown etiology in a young dog who suffered a head injury while playing with the owner. During the neurological examination of the animal conducted immediately after the incident was diagnosed with severe central nervous system lesions (sopor, opisthotonus, tetraparesis); magnetic resonance imaging revealed significant brain damage with pronounced ventricular dilatation and the formation of a cavity filled with air. Re-diagnosis after 14 days showed progression of pneumocephalus with gas accumulation in the brain cavities. The contents of the ventricles have a division into liquid (cerebrospinal fluid), and air, progressive inflammatory processes in the brain's parenchyma were not observed; a fistula or canal connecting the cranial cavity and the external environment was not detected. Symptomatic and supportive therapy, carried out during the entire period of the dog's stay in the veterinary clinic, did not have positive results. The animal was euthanized according to medical indications and the owner's wishes.

Clinical and morphological features of SARS-COV-2 associated acute hemorrhagic necrotizing encephalopathy: case report

BackgroundThe current case report presents acute hemorrhagic necrotizing encephalopathy (AHNE) as an example of a fatal complication, the etiology of which could be coronavirus disease 2019 (COVID-19) with multiple organ damage along with the existing respiratory tuberculosis.Case presentationA male in his 20s had severe symptoms of central nervous system lesion, which developed against the background of COVID-19 and respiratory tuberculosis, for which he was treated in the intensive care unit. Autopsy confirmed that he died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated AHNE in adults with severe fatal endothelial dysfunction and respiratory tuberculosis. The main morphological signs of brain damage were desquamative endotheliitis, thrombosis, parenchymal hemorrhagic necrosis, encephalitis, severe necrobiotic neuronal damage.ConclusionThe defeat of endothelial cells with the development of generalized endotheliitis in COVID-19, especially in conjunction with comorbid pathology, in particular tuberculosis, can lead to a fatal complication that affects the nervous system—AHNE. Therefore, it is worth paying close attention to the appearance of neurological symptoms in patients with a similar combination of diseases.

Persephin as a diagnostic marker of acute brain injury in critically ill newborns: a clinical trial

Aim. To study the correlation of serum persephin with clinical, instrumental and biochemical indicators of brain damage and with an adverse outcome in critically ill newborns.Materials and Methods. The study included 44 critically ill newborns. Blood samples were collected on the 1stand 7thday of life. Brain injury was assessed by recording Apgar score, depression of consciousness and brainstem reflexes in unsedated patients over 7 days of life, convulsions, neurosonographic signs of cerebral edema, serum protein S100B on the 1stand 7thday of life, and using indicators of adverse neurological outcome. The correlation of serum persephin on the 1stand 7thday of life with signs of brain damage was evaluated using the Spearman's rank correlation coefficient and Mann-Whitney U-test.Results. No statistically significant correlation was found between the concentrations of serum persephin on the 1stand 7thday of life and Apgar score (p = 0.721 and 0.222, respectively), depression of consciousness and stem reflexes (p < 0.05), convulsions (p = 0.673 and 0.432, respectively), cerebral edema (p = 0.737 and 0.558, respectively), and serum protein S100B both on the 1stday (p = 0.095 and 0.475, respectively) and 7thday of life (p = 0.988 and p = 0.775, respectively). Further, there was no statistically significant association of the serum persephin on the 1stday of line with an unfavorable outcome (p = 0.294). Yet, we revealed an association of serum persephin on the 7thday of life with an unfavorable outcome (p = 0.013), with a cut-off point of 828 ng/mL, a sensitivity of 39%, and a specificity of 100%.Conclusion. Persephin has poor diagnostic and prognostic significance for assessing the severity of brain damage in critically ill newborns. The obtained data on the correlation of the concentration of persephin for 7 days with an unfavorable outcome are doubtful due to the lack of data on its correlation with signs of severe brain damage.

SGK1.1 limits brain damage after status epilepticus through M current-dependent and independent mechanisms

Epilepsy is a neurological condition associated to significant brain damage produced by status epilepticus (SE) including neurodegeneration, gliosis and ectopic neurogenesis. Reduction of these processes constitutes a useful strategy to improve recovery and ameliorate negative outcomes after an initial insult. SGK1.1, the neuronal isoform of the serum and glucocorticoids-regulated kinase 1 (SGK1), has been shown to increase M-current density in neurons, leading to reduced excitability and protection against seizures. For this study, we used 4–5 months old male transgenic C57BL/6 J and FVB/NJ mice expressing near physiological levels of a constitutively active form of the kinase controlled by its endogenous promoter. Here we show that SGK1.1 activation potently reduces levels of neuronal death (assessed using Fluoro-Jade C staining) and reactive glial activation (reported by GFAP and Iba-1 markers) in limbic regions and cortex, 72 h after SE induced by kainate, even in the context of high seizure activity. This neuroprotective effect is not exclusively through M-current activation but is also directly linked to decreased apoptosis levels assessed by TUNEL assays and quantification of Bim and Bcl-xL by western blot of hippocampal protein extracts. Our results demonstrate that this newly described antiapoptotic role of SGK1.1 activation acts synergistically with the regulation of cellular excitability, resulting in a significant reduction of SE-induced brain damage in areas relevant to epileptogenesis.

How much oxygen for the injured brain - can invasive parenchymal catheters help?

Each year in the United States there are over 2.5 million visits to emergency departments for traumatic brain injury (TBI), 300,000 hospitalizations, and 50,000 deaths. TBI initiates a complex cascade of events which can lead to significant secondary brain damage. Great interest exists in directly measuring cerebral oxygen delivery and demand after TBI to prevent this secondary injury. Several invasive, catheter-based devices are now available which directly monitor the partial pressure of oxygen in brain tissue (PbtO2), yet significant equipoise exists regarding their clinical use in severe TBI. There are currently three ongoing multicenter randomized controlled trials studying the use of PbtO2 monitoring in severe TBI: BOOST-3, OXY-TC, and BONANZA. All three have similar inclusion/exclusion criteria, treatment protocols, and outcome measures. Despite mixed existing evidence, use of PbtO2 is already making its way into new TBI guidelines such as the recent Seattle International Brain Injury Consensus Conference. Analysis of high-fidelity data from multimodal monitoring, however, suggests that PbtO2 may only be one piece of the puzzle in severe TBI. While current evidence regarding the use of PbtO2 remains mixed, three ongoing clinical trials are expected to definitively answer the question of what role PbtO2 monitoring plays in severe TBI.

'My Bewildering Brain Toils in Vain': Traumatic Brain Injury, the Criminal Trial Process, and the Case of Lisa Montgomery

Individuals with traumatic brain injuries (TBI) have a greater risk of becoming justice-involved due to the role that many TBIs play in impulse control and judgment. Attorneys assigned to represent this cohort may not have encountered individuals with TBI before, and may not be familiar with behavioral manifestations that could be relevant as a defense or as mitigation in individual cases. In this regard, TBI is grossly misunderstood. A grave example of this point, and a foundation for this article, is the case of Lisa Montgomery, who despite evidence of serious mental illness and significant brain damage, was convicted, sentenced to death, and ultimately executed for the murder of a pregnant woman and the kidnapping of the woman’s unborn child. Her case reflects all that is wrong with the way we treat criminal defendants with traumatic brain injuries. In this paper, we discuss common ways that individuals with traumatic brain injuries become involved in the criminal justice system, and how attorneys can better prepare an effective defense or mitigation. We consider, in some depth, several of the substantive areas of criminal law and procedure in which an understanding of TBI is especially significant (including, but not limited to, competency status, the insanity defense and the death penalty), and assess the quality of counsel –and experts -- in such cases, again, in some instances, using the Montgomery case as a prism. We believe that one (at least partial) remedy for the current situation is a turn to therapeutic jurisprudence (TJ) The TJ doctrine emphasizes giving an individual client dignity, voice, validation and voluntariness of action and decision. This is particularly important for an individual with TBI, who will likely have the capacity to make the majority of decisions about his case, but who may still need behavioral treatment or interventions for symptoms of the TBI. We will discuss the ways that TJ plays into these issues, and how TJ must be the grounding of any representation of this population. We conclude with some modest suggestions as to how we can begin to make needed changes in the criminal justice system to take all of these issues into account.

Overview of dominantly inherited AD and top‐line DIAN‐TU results of solanezumab and gantenerumab

AbstractBackgroundAlzheimer’s disease (AD) prevention trials aim to intervene prior to significant neuronal loss, brain damage, and symptom onset to delay or slow cognitive decline. In dominantly inherited AD (DIAD), mutation carriers develop symptomatic AD at predictable ages with near 100% penetrance. In 2012, the Dominantly Inherited Alzheimer Network Trials Unit Adaptive Prevention Trial (DIAN‐TU APT) platform launched a double‐blind, randomized, placebo‐controlled, parallel group trial of two anti‐amyloid‐beta monoclonal antibodies with two different antigenic targets, gantenerumab and solanezumab (NCT01760005). The DIAN‐TU scientific development, implementation of the first AD prevention trial, trial challenges and opportunities, including dose escalation, and top‐line results will be presented.MethodDIAN was established in 2008 in response to a call from the National Institute of Aging to establish a network to study DIAD and enable future clinical trials. Successive breakthroughs in understanding disease processes enabled the launch of the DIAN‐TU adaptive prevention trial, a global adaptive platform trial supporting testing multiple drugs in parallel. The DIAN‐TU partners include patients and families at risk for DIAD, global academic researchers, the NIH, Alzheimer’s Association, philanthropic supporters, the DIAN‐TU Pharma Consortium, and pharmaceutical companies with drugs being tested. Important milestones include developing a platform to enable a comprehensive efficient treatment trial for this rare population, adding tau PET as part of AMP AD, adapting dosing mid‐trial and extending the original biomarker trial to continue randomized dosing to test a cognitive endpoint until the last patient reaches 4 years, developing a disease progression statistical model and inclusion of DIAN observational data to increase the power to determine drug effects.ResultThe primary and key secondary outcomes of the DIAN‐TU trial will be presented for each therapy in the context of targeting amyloid‐beta at pre‐clinical and clinically symptomatic stages of disease.ConclusionThese results inform about AD hypotheses, timing of treatment and the prospect of slowing, or preventing AD in DIAD and sporadic AD.

Особливості патогенезу бойового психічного розладу. Огляд літератури

SummaryBased on the study of literature data, an analysis of the pathogenesis of combatmental disorder (CMD) in combatants was carried out. The introduction of the clinicaldefinition «Complex post-traumatic stress disorder (PTSD)» into ICD – 11 allowsdoctors to provide more accurate diagnosis and treatment of CMD, considering themultiple links in the pathogenesis of this group of pathological conditions in veterans.This determines the need for an in-depth study of the multifactorial nature (complexity)of pathogenesis. On the one hand, considering the equal influence, together with thetraditional for ICD-10 «mental» – «behavioral» (pathocharacterological) component.On the other hand, this is associated with the determination of the influence ofpathogenetic factors of organic and somatogenic origin with signs of brain damage. Thearticle substantiates an in-depth look at the problem of CMD / PTSD as a result of theaction of social, psychogenic, physiogenic, endogenous and somatogenic etiopathogenetic factors and their combinations, determines the polyetiology of CMD and thepolymorphism of their symptoms.The practical necessity and situational feasibility of revising and supplementing theexisting concept of the pathogenesis of CMD/ PTSD within the framework of thenosologies defined in ICD-10 common in practice and the relevance of the trend ofpolyfactoriality (and the corresponding components) of etiopathogenesis within theextended positioning of the nosology «complex PTSD» (ICD-11). The severity of mentaldisorders in combatants is determined by the comorbidity of mental pathology caused bya combination of factors: premorbid personality traits, pathological soil and the natureof the mental trauma received by a combatant with an organic radical. The growth ofexogenous organic pathology during combat stress requires a different conceptualassessment, justifies the introduction of the concept of «CMD», which are progressive innature and are not limited to signs of PTSD.The necessity of an integrated and interdisciplinary approach to further research ofthe problem of CMD and PTSD has been substantiated. There is a problem of«moralization» of combat trauma, which takes it beyond the framework of both thephysiological response of the body to mental stress and individual-personal reactions,and is, among other things, a consequence of the combatant’s moral and ethicalformations, which in turn are associated with social trends and cultural-anthropologicalbasis