Persistent Brain Damage Research Articles

Severe course of whooping cough in a month-old child

Acute respiratory diseases are more and more being registered among the population. According to Rospotrebnadzor, the incidence of acute respiratory infections in the Russian Federation in 2023 amounted to 15911.94 per 100.000 of population. Whooping cough plays a special role in the structure of acute respiratory infections. The largest increase is noted in the last months of 2023. In total, 20.497 cases of whooping cough were registered in the Russian Federation for 9 months of 2023. Whooping cough is an acute anthroponotic infection caused by whooping cough bacteria (Bordetella pertussis), accompanied by catarrhal phenomena in the upper respiratory tract and paroxysmal spasmodic cough. In young children, severe forms of whooping cough are still the most common, leading to a fatal outcome. One of the severe complications in children of the first years of life is encephalopathy, with persistent organic brain damage. In adolescents and adults, whooping cough often occurs in atypical forms and is manifested by a prolonged cough, for which they receive, as a rule, ineffective therapy from a pediatrician, therapist, allergist and otorhinolaryngologist. Whooping cough refers to diseases controlled by specific prevention. However, for children of an earlier age, infection from older children in the family or from adults is typical. This article presents a clinical observation of a severe course of whooping cough in a child aged 1 month, the disease proceeded with a paroxysmal cough, mainly nocturnal, with long reprises and redness of the face, ending with apnea of varying severity and duration. Determination of the severity of the course of pertussis infection is based on a complex of clinical and laboratory data. An early and effective method of etiological verification of whooping cough in children of the first year of life is PCR (polymerase chain reaction) of nasal/oropharyngeal smears.

Persistent brain damage in reversible cerebral vasoconstriction syndrome on 99mTc-ethyl cysteinate dimer single-photon emission computed tomography: A long-term observational study

BackgroundBlood-brain barrier (BBB) breakdown is considered a key step in the pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS); however, its temporal course remains unclear. Based on the characteristics and dynamics of 99mTc-ethyl cysteinate dimer (99mTc-ECD) as a tracer, 99mTc-ECD single-photon emission computed tomography (SPECT) can detect not only hypoperfusion but also BBB breakdown and/or brain tissue damage. Therefore, this study aimed to investigate this course using 99mTc-ECD SPECT. MethodsBetween 2011 and 2019, we enrolled seven patients (one male and six female patients) with RCVS without ischemic or hemorrhagic stroke or posterior reversible encephalopathy syndrome. 99mTc-ECD SPECT was performed repeatedly in each patient. SPECT data were statistically analyzed using an easy Z-score imaging system. ResultsThunderclap headache was the initial symptom in all the patients and was most commonly triggered by bathing (three patients). All the patients exhibited vasoconstriction and reduced cerebral uptake of 99mTc-ECD during the acute stage. Follow-up assessment from 3 to 16 months showed that reduced cerebral uptake persisted in all the patients, even after the vasoconstriction had resolved. ConclusionReduced cerebral uptake of 99mTc-ECD persisted in the late stage of RCVS, even after vasoconstriction and headache subsided. BBB breakdown and/or brain tissue damage may underlie this phenomenon. 99mTc-ECD SPECT is an effective neuroimaging method to detect brain functional abnormalities, reflecting BBB breakdown or tissue damages, throughout the treatment course of RCVS.

Transcellular blood-brain barrier disruption in malaria-induced reversible brain edema.

Brain swelling occurs in cerebral malaria (CM) and may either reverse or result in fatal outcome. It is currently unknown how brain swelling in CM reverses, as brain swelling at the acute stage is difficult to study in humans and animal models with reliable induction of reversible edema are not known. In this study, we show that reversible brain swelling in experimental murine CM can be induced reliably after single vaccination with radiation-attenuated sporozoites as proven by in vivo high-field magnetic resonance imaging. Our results provide evidence that brain swelling results from transcellular blood-brain barrier disruption (BBBD), as revealed by electron microscopy. This mechanism enables reversal of brain swelling but does not prevent persistent focal brain damage, evidenced by microhemorrhages, in areas of most severe BBBD. In adult CM patients magnetic resonance imaging demonstrate microhemorrhages in more than one third of patients with reversible edema, emphasizing similarities of the experimental model and human disease. Our data suggest that targeting transcellular BBBD may represent a promising adjunct therapeutic approach to reduce edema and may improve neurological outcome.

Successful Therapy of a Patient with Prospected Autoimmune Encephalitis and Negative Laboratory Results-Confirmation of Diagnosis by Immunocytochemistry

Autoimmune encephalitis (AIE) presents with a broad spectrum of neurological and psychiatric symptoms and can cause persistent brain damage. However, the absence of pathognomonic findings in CT and MRI screening, and the fact that relevant antigens for laboratory detection of autoantibodies mostly are unknown, makes its diagnosis still a challenging task. In the present report the latter problem is overcome by the immunocytochemical detection of autoantibodies using brain sections, which in fact present nearly all neuronal antigens. Furthermore, we used a highly optimized immunoperoxidase technique, which allowed morphological high-resolution analyses of the immunoproducts. The 82-old female patient presented with unsteady gait pattern, ataxia, myoclonus, apraxia, as well as an unclear language. She suffered from panic attacks, cognitive and mnestic deterioration as well as delusions. She was alert but disoriented. Despite of normal MRI and EEG results and normal CSF laboratory data we prospectively diagnosed autoimmune encephalitis. After five days high dose corticosteroid therapy all symptoms disappeared completely. The autoimmune pathogenesis subsequently was verified unequivocally, when the patient´s CSF strongly stained neuronal and glial cell bodies in brain sections. This report should be taken as proof of principle that immunocytochemistry with CSFs of neurological patients provides the possibility to recognize a considerable number morphological details at high resolution. This will provide the possibility to form groups of patients showing similar distributions of immunoreactivities. Such groups may represent distinct nosological entities and finally may allow for elaborating selective treatments for patients with distinct types of autoimmune inflammation of the CNS.

Adolescent Binge-Type Ethanol Exposure in Rats Mirrors Age-Related Cognitive Decline by Suppressing Cholinergic Tone and Hippocampal Neurogenesis.

Heavy alcohol consumption followed by periods of abstinence (i.e., binge drinking) during adolescence is a concern for both acute and chronic health issues. Persistent brain damage after adolescent intermittent ethanol exposure in rodents, a model of binge drinking, includes reduced hippocampal neurogenesis and a loss of neurons in the basal forebrain that express the cholinergic phenotype. The circuit formed between those regions, the septohippocampal pathway, is critical for learning and memory. Furthermore, this circuit is also altered during the aging process. Thus, we examined whether pathology in septohippocampal circuit and impairments in spatial behaviors are amplified during aging following adolescent intermittent ethanol exposure. Female and male rats were exposed to intermittent intragastric gavage of water (control) or 20% ethanol (dose of 5 g/kg) for a 2 days on/off cycle from postnatal days 25–55. Either 2 (young adult) or 12–14 (middle-age) months post exposure, rats were tested on two spatial tasks: spontaneous alternation and novel object in place. Acetylcholine efflux was assessed in the hippocampus during both tasks. There was no adolescent ethanol-induced deficit on spontaneous alternation, but middle-aged male rats displayed lower alternation rates. Male rats exposed to ethanol during adolescence had blunted behavioral evoked acetylcholine during spontaneous alternation testing. All ethanol-exposed rats displayed suppression of the cholinergic neuronal phenotype. On the novel object in place task, regardless of sex, ethanol-exposed rats performed significantly worse than control-treated rats, and middle aged-rats, regardless of sex or ethanol exposure, were significantly impaired relative to young adult rats. These results indicate that male rats display earlier age-related cognitive impairment on a working memory task. Furthermore, male rats exposed to ethanol during adolescence have blunted behavior-evoked hippocampal acetylcholine efflux. In addition, middle-aged and ethanol-exposed rats, regardless of sex, are impaired at determining discrete spatial relationship between objects. This type of pattern separation impairment was associated with a loss of neurogenesis. Thus, binge-type adolescent ethanol exposure does affect the septohippocampal circuit, and can accelerate age-related cognitive impairment on select spatial tasks.

ALL-113: Pattern, Risk Factors, and Outcome Predictors of Posterior Reversible Encephalopathy Syndrome in Pediatric Cancer Patients

Context: Although PRES is considered to have a benign clinical course, some studies have reported associated mortality of 5–19% and severe functional impairments in 44% of patients. Objective: To describe the risk factors and clinical and radiological patterns of PRES and to assess different predictors related to its outcome in pediatric cancer patients. Design/Setting: A retrospective study included pediatric cancer patients who developed PRES during their treatment at the Children’s Cancer Hospital Egypt (CCHE-57357) from January 2013 to June 2017. Patients or Other Participants: This study included 50 patients (32 hematologic malignancies, 13 solid tumors, and 5 post-BMT. ALL was the most common diagnosis encountered in 19 patients (38%), followed by lymphoma in 8 patients (16%) and AML in 5 (10%). Main Outcomes Measures: Clinical outcome of PRES was assessed using the Modified Rankin scale (mRS) after 2 weeks and 3 months from the episode. Patients were classified either good outcome; those who had complete recovery from all PRES symptoms without or with mild neurological deficit (mRS 0–2), or bad outcome for those who had significant neurological deficit (mRS 3–5), and those who died due to PRES (mRS 6). Results: Convulsions were the most common presenting clinical finding (found in 45 patients), and initial motor affection was encountered in 6 patients. Hypertension was reported in 86% at the time of onset. Regarding the MRI findings, occipital affection was the most common (92%), followed by frontal and temporal lobe involvement in 32% and 22%, respectively, and advanced PRES was described in 8 patients. Among all patients, 80% had complete clinical resolution, and 60% showed complete radiological resolution at 2 weeks’ evaluation, and 2 patients died out of PRES. An unfavorable outcome was associated with those who had motor dysfunction (p=0.0001) and status epilepticus (p=0.004) at presentation. Moreover, frontal lobe and thalamic affection and atypical PRES were also associated with poor outcome. Conclusions: Most children with cancer who develop PRES have favorable clinical and radiologic outcomes, but exceptionally persistent brain damage and even death may occur. Unfavorable outcome is associated with many factors, including motor dysfunction, status epilepticus, frontal lobe or thalamic affection, and atypical PRES. Although PRES is considered to have a benign clinical course, some studies have reported associated mortality of 5–19% and severe functional impairments in 44% of patients. To describe the risk factors and clinical and radiological patterns of PRES and to assess different predictors related to its outcome in pediatric cancer patients. A retrospective study included pediatric cancer patients who developed PRES during their treatment at the Children’s Cancer Hospital Egypt (CCHE-57357) from January 2013 to June 2017. This study included 50 patients (32 hematologic malignancies, 13 solid tumors, and 5 post-BMT. ALL was the most common diagnosis encountered in 19 patients (38%), followed by lymphoma in 8 patients (16%) and AML in 5 (10%). Clinical outcome of PRES was assessed using the Modified Rankin scale (mRS) after 2 weeks and 3 months from the episode. Patients were classified either good outcome; those who had complete recovery from all PRES symptoms without or with mild neurological deficit (mRS 0–2), or bad outcome for those who had significant neurological deficit (mRS 3–5), and those who died due to PRES (mRS 6). Convulsions were the most common presenting clinical finding (found in 45 patients), and initial motor affection was encountered in 6 patients. Hypertension was reported in 86% at the time of onset. Regarding the MRI findings, occipital affection was the most common (92%), followed by frontal and temporal lobe involvement in 32% and 22%, respectively, and advanced PRES was described in 8 patients. Among all patients, 80% had complete clinical resolution, and 60% showed complete radiological resolution at 2 weeks’ evaluation, and 2 patients died out of PRES. An unfavorable outcome was associated with those who had motor dysfunction (p=0.0001) and status epilepticus (p=0.004) at presentation. Moreover, frontal lobe and thalamic affection and atypical PRES were also associated with poor outcome. Most children with cancer who develop PRES have favorable clinical and radiologic outcomes, but exceptionally persistent brain damage and even death may occur. Unfavorable outcome is associated with many factors, including motor dysfunction, status epilepticus, frontal lobe or thalamic affection, and atypical PRES.

The predictive value of 'red flags' as milestones of psychomotor development of premature babies - preliminary study.

Premature babies are a special group at risk of persistent brain damage caused by diseases, the most serious of which are cerebral palsy(CP), autism spectrum disorders (ASD) and mental retardation, among others. These conditions may occur concurrently, but appear more often as separate disease syndromes in the same group of at-risk children. Long-term observation of psychomotor development by an interdisciplinary medical team closely cooperating with parents is necessary. It is important to detect the risk of developing these diseases as soon as possible in all development spheres. The research was conducted to demonstrate the prognostic value of 'red flags' of developmental milestones and the ability to detect early signs of risk of developing CP and ASD in extremely premature babies. In this preliminary study, 42 preterm babies, born after less than 32 weeks pregnancy participated. The occurrence of 'red flags'in the spheres: gross motor, fine motor and cognitive at 9 months was strongly associated with their presence at 24 months. The sensitivity and specificity were: gross motor - 0.91 (95% CI: 0.59, 1.00) and 0.94 (95% CI: 0.79, 0.99); fine motor - 0.83 (95% CI 0.36-1.00) and 1.00 (95% CI: 0.90-1.00); cognitive - 1.00 (0.40, 1.00) and 0.97 (0.86, 1.00). Other spheres had lower sensitivity but high specificity. The conclusion is that the 'red flags'at the 9 months milestones already predict the normal or developmental delay of premature babies, and predict the risk of CP and ASD. Due to the availability and lack of the need for specialized and costly training, it is worth considering their use in everyday life medical practice.

Evaluation of Anti-inflammatory Nutraceuticals in LPS-induced Mouse Neuroinflammation Model: An Update.

It is known that peripheral infections, accompanied by inflammation, represent significant risk factors for the development of neurological disorders by modifying brain development or affecting normal brain aging. The acute effects of systemic inflammation on progressive and persistent brain damage and cognitive impairment are well documented. Anti-inflammatory therapies may have beneficial effects on the brain, and the protective properties of a wide range of synthetic and natural compounds have been extensively explored in recent years. In our previous review, we provided an extensive analysis of one of the most important and widely-used animal models of peripherally induced neuroinflammation and neurodegeneration - lipopolysaccharide (LPS)-treated mice. We addressed the data reproducibility in published research and summarized basic features and data on the therapeutic potential of various natural products, nutraceuticals, with known anti-inflammatory effects, for reducing neuroinflammation in this model. Here, recent data on the suitability of the LPS-induced murine neuroinflammation model for preclinical assessment of a large number of nutraceuticals belonging to different groups of natural products such as flavonoids, terpenes, non-flavonoid polyphenols, glycosides, heterocyclic compounds, organic acids, organosulfur compounds and xanthophylls, are summarized. Also, the proposed mechanisms of action of these molecules are discussed.

SOP: antibody-associated autoimmune encephalitis

BackgroundAntibody-mediated and paraneoplastic autoimmune encephalitides (AE) present with a broad spectrum of clinical symptoms. They often lead to progressing inflammatory changes of the central nervous system with subacute onset and can cause persistent brain damage. Thus, to promptly start the appropriate and AE-specific therapy, recognition of symptoms, initiation of relevant antibody diagnostics and confirmation of the clinical diagnosis are crucial, in particular as the diseases are relatively rare.AimThis standard operating procedure (SOP) should draw attention to the clinical presentation of AE, support the diagnostic approach to patients with suspected AE and guide through the necessary steps including therapeutic decisions, tumour screening and exclusion of differential diagnoses.MethodBased on existing diagnostic algorithms, treatment recommendations and personal experiences, this SOP gives an overview of clinical presentation, diagnostic procedures and therapy in AE. Additional information is provided within an accompanying text and a table describing the most important autoantibodies and their characteristics.ResultsThe initial steps of the AE flow chart are based on clinical symptoms and the patient’s history. Assignment to paraneoplastic or antibody-mediated AE is sometimes clinically possible. Diagnostics should include MRI, EEG and CSF analysis with antibody panel diagnostic. Definite AE can be diagnosed if the underlying antibody is compatible with the clinical presentation. Classification of probable AE may be possible even with negative anti-neuronal autoantibodies if the clinical presentation and laboratory abnormalities are highly suggestive of AE. The confirmed AE diagnosis requires immediate initiation of immunotherapy.ConclusionThe SOP facilitates the recognition of patients with AE and presents the necessary diagnostic and therapeutic steps.

The activation of group II metabotropic glutamate receptors protects neonatal rat brains from oxidative stress injury after hypoxia-ischemia.

Birth asphyxia resulting in brain hypoxia-ischemia (H-I) can cause neonatal death or lead to persistent brain damage. Recent investigations have shown that group II metabotropic glutamate receptor (mGluR2/3) activation can provide neuroprotection against H-I but the mechanism of this effect is not clear. The aim of this study was to investigate whether mGluR2/3 agonists applied a short time after H-I reduce brain damage in an experimental model of birth asphyxia, and whether a decrease in oxidative stress plays a role in neuroprotection. Neonatal H-I in 7-day-old rats was used as an experimental model of birth asphyxia. Rats were injected intra peritoneally with mGluR2 (LY 379268) or mGluR3 (NAAG) agonists 1 h or 6 h after H-I (5 mg/kg). The weight deficit of the ischemic brain hemisphere, radical oxygen species (ROS) content levels, antioxidant enzymes activity and the concentrations of reduced glutathione (GSH) were measured. Both agonists reduced weight loss in the ischemic hemisphere and mitigated neuronal degeneration in the CA1 hippocampal region and cerebral cortex. Both agonists reduced the elevated levels of ROS in the ipsilateral hemisphere observed after H-I and prevented an increase in antioxidant enzymes activity in the injured hemisphere restoring them to control levels. A decrease in GSH level was also restored after agonists application. The results show that the activation of mGluR2 and mGluR3 a short time after H-I triggers neuroprotective mechanisms that act through the inhibition of oxidative stress and ROS production. The prevention of ROS production by the inhibition of glutamate release and decrease in its extracellular concentration is likely the main mechanism involved in the observed neuroprotection.

The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study

To quantify clinical and structural white matter tract changes over six months, in patients with mild traumatic brain injury (mTBI) following early structured cognitive therapy. This was a non-randomized quasi-experimental study design. All patients with mTBI received written information and education on symptom(s) management before being assigned to structured cognitive therapy or conventional cognitive therapy at two weeks post injury. Structured therapy was one hour per week session by using computer-based and metacognitive training for the first three months followed by one hour per month session for the remaining three months. Conventional therapy was patient focused symptom(s) management and coping strategies. Neuropsychological assessment and Diffusion Tensor Imaging (DTI) were performed at baseline and six months post injury. Each group consisted of four male participants ( n = 8). Mean cognitive therapy duration was 7 hours (SD ± 1.8). There was no demographic, Glasgow Coma Scale, Post Traumatic Amnesia and loss of consciousness duration statistical difference between groups. Although all cognitive domains tested were not statistically significant, the scores for Attention, Memory, Language, and Executive Function domains were higher than conventional group at six months. We analysed nine white matter tracts. Almost all Fractional Anisotropy mean values were lower (Corpus Callosum genu: P = 0.03; splenium: P = 0.05) whereas Mean Diffusivity and Radial Diffusivity mean values were higher at six months. We quantified deficits in various cognitive domains as early as two weeks following mTBI, with higher normal scores in the structured therapy group as compared to conventional group at six months. Abnormal values of DTI parameters may suggest chronic axonal damage of various white matter locations and bundles. We did not yield statistical significance in our analysis due to small sample size caused by high drop-out rate. However, we concluded that early structured cognitive therapy may improve cognitive deficits beyond spontaneous recovery, despite persistent microstructural brain damage.

Pretreatment with Group II Metabotropic Glutamate Receptor Agonist LY379268 Protects Neonatal Rat Brains from Oxidative Stress in an Experimental Model of Birth Asphyxia.

Hypoxia-ischemia (H-I) at the time of birth may cause neonatal death or lead to persistent brain damage. The search for an effective treatment of asphyxiated infants has not resulted in an effective therapy, and hypothermia remains the only available therapeutic strategy. Among possible experimental therapies, the induction of ischemic tolerance is promising. Recent investigations have shown that activation of group II metabotropic glutamate receptors (mGluR2/3) can provide neuroprotection against H-I, but the mechanism of this effect is not clear. The aim of this study was to investigate whether an mGluR2/3 agonist applied before H-I reduces brain damage in an experimental model of birth asphyxia and whether a decrease in oxidative stress plays a role in neuroprotection. Neonatal H-I on seven-day-old rats was used as an experimental model of birth asphyxia. Rats were injected intraperitoneally with the mGluR2/3 agonist LY379268 24 or 1 h before H-I (5 mg/kg). LY379268 reduced the infarct area in the ischemic hemisphere. Application of the agonist at both times also reduced the elevated levels of reactive oxygen species (ROS) in the ipsilateral hemisphere observed after H-I and prevented the increase in antioxidant enzyme activity in the injured hemisphere. The decrease in glutathione (GSH) level was also restored after agonist application. The results suggest that the neuroprotective mechanisms triggered by the activation of mGluR2/3 before H-I act through the decrease of glutamate release and its extracellular concentration resulting in the inhibition of ROS production and reduction of oxidative stress. This, rather than induction of ischemic tolerance, is probably the main mechanism involved in the observed neuroprotection.

Sirolimus in the treatment of three infants with diffuse congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia and brain damage. Therapeutic strategies to avoid near total pancreatectomy in patients who are unresponsive to maximum doses of diazoxide and octreotide remain to be identified, although sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used successfully to treat diffuse type CHI. We used sirolimus to treat three infants with diffuse CHI. Diagnosis was confirmed clinically, biochemically and by genetic testing. Homozygous mutations in KCNJ11, ABCC8 and KCNJ11 were identified in infants 1, 2 and 3, respectively. Each infant had received the therapy for at least 2 months with close monitoring of glycemic response, serum insulin and C-peptide. None of the infants responded to the therapy. We conclude that sirolimus is less effective in the treatment of diffuse CHI in patients with severe mutations in the homozygous state compared with those with the mutations in the heterozygous.

Chapter 41 - Posttraumatic functional movement disorders

Traumatic injury to the nervous system may account for a range of neurologic symptoms. Trauma location and severity are important determinants of the resulting symptoms. In severe head injury with structural brain abnormalities, the occurrence of trauma-induced movement disorders, most commonly hyperkinesias such as tremor and dystonia, is well recognized and its diagnosis straightforward. However, the association of minor traumatic events, which do not lead to significant persistent structural brain damage, with the onset of movement disorders is more contentious. The lack of clear clinical-neuroanatomic (or symptom lesion) correlations in these cases, the variable timing between traumatic event and symptom onset, but also the presence of unusual clinical features in a number of such patients, which overlap with signs encountered in patients with functional neurologic disorders, contribute to this controversy. The purpose of this chapter is to provide an overview of the movement disorders, most notably dystonia, that have been associated with peripheral trauma and focus on their unusual characteristics, as well as their overlap with functional neurologic disorders. We will then provide details on pathophysiologic views that relate minor peripheral injuries to the development of movement disorders and compare them to knowledge from primary organic and functional movement disorders. Finally, we will comment on the appropriate management of these disorders.

Effect of Phenobarbital on Bcl-2 and Bax expressions in brain tissue of young rats

Objective To study the effect of Phenobarbital (PB) on experimental rats, observe the histological changes of immature brain and the expressions of apoptosis-related proteins Bcl-2 and Bax in neurons detected by immunohistochemistry, and to explore the influence and mechanism of PB on brain damage at therapeutic levels to immature brain maturation of rat in order to provide the theoretical and experimental base for clinic. Methods A total of 40 healthy 18-day-old Sprague-Dawley(SD) rats(male or female) were randomly assigned into 2 groups: normal saline(NS) treated as control group(20 cases), PB group(20 cases). Each group was further randomly divided into long-term(4 weeks) treated group and short-term(2 weeks) treated group(10 rats in each group). The rats in PB group received intragastricadministration with PB (30 mg/kg). The rats in control group were handled by injection of NS into stomach and abdomen according to 4 mL/kg.All performances were undertaken for twice every day.At the end of the therapeutic period, body and brain weight were measured when the rats were sacrificed.Histological studies on the tissues of frontal lobes and hippocampus were performed by Hematoxylin-Eosin(HE) staining and Nissl staining.Expressions of apoptosis-related proteins Bcl-2 and Bax in neurons were detected by immunohistochemistry. Results There were no significant differences in body and brain weights or histological studies index among control group as well as PB group before and after treatment for short term(P>0.05). Remarkable reduction of brain weight was only observed in immature rats exposed to PB compared to control group for long period, and significant neurodegeneration, neuronal necrosis were observed in immature rats exposed to PB compared to control group(all P<0.01). The expression of Bax protein in the frontal lobe increased significantly in immature rats receiving PB for long period comparing with control(P<0.01). In contrast, expression of Bcl-2 protein did not change at therapeutic level.The ratio of Bax/Bcl-2 was obviously increased. Conclusions Chronic treatment with PB will result in significant neuronal apoptosis and necrosis and persistent cognitive impairment and brain damage to immature rates.Brain damage of PB at therapeutic level to immature brain may be irreversible.The significant expression of Bax protein in the frontal lobe and the high rate of Bax/Bcl-2 are probably the main reasons which cause brain weight decreasing and brain damage by PB in immature brain tissue. Key words: Rat; Antiepileptic drug; Brain tissue

Severe hyperphosphatemia after administration of sodium-phosphate containing laxatives in children: case series and systematic review of literature

Sodium phosphate-containing laxatives are commonly used as first-line treatment option for constipation in children and adolescents. Hyperphosphatemia is an infrequent, but potentially life-threatening complication of laxative application. We report a case series of three children exhibiting severe hyperphosphatemia and hypocalcemia after utilization of sodium phosphate-containing laxatives, necessitating intensive care services in two of three cases. Additionally, we reviewed 32 case reports of similar occurrences. We identified 28 publications on the subject dating from 1968 to 2010. Mean age of all children in reports was 2.83 years; sex was approximately equally distributed. While 18 patients suffered from either pre-existing gastrointestinal comorbidity or other major systemic disease, no or only unrelated, minor conditions were present in ten children. One-third of patients received laxatives repeatedly before the incident. Findings associated with hyperphosphatemia include lethargy, dizziness, stiffness, tachypnea, tachycardia and severe dehydration in almost all cases, and tetany, carpopedal spasm, and prolonged QT interval in a subset. While about 80% of children recovered without residual findings, three deceased and one incurred persistent hypoxic brain damage. Physicians should be alerted to the possibility of phosphate toxicity in children and adolescents treated with laxatives.

Étiologies des perforations de la cloison nasale observées dans un service de médecine interne

The purpose of this study was to describe and evaluate neuroimaging findings of patients with neurosyphilis.The neuroimaging studies of 14 patients with documented neurosyphilis were reviewed. Diagnosis was established in 14 patients with cerebrospinal fluid for a Treponema Pallidum Particle Agglutination (TPPA) test. All patients had reactive TPPA and Unheated Serum Regain test (USR) in their sera. Imaging studies included plain, contrast-enhanced CT of the brain, plain and gadolinium-enhanced MR, and MR angiography.In the 14 HIV-negative patients with neurosyphilis, CT and MR showed the presence of cerebral infarction in six cases, arteritis in four cases, nonspecific white matter lesion in three cases, acute syphilitic meningitis in one case and normal neuroimaging finding in one case. In addition, 4 in 14 patients had general paresis, and MRI showed high signal intensity on T2 -weighted images involving frontotemporal lobes, hippocampus and periventricular area. Treatment with penicillin significantly diminished the size of these high signal intensity on T2-weighted images with general paresis.These results suggest that MR and CT images have some characteristic manifestations in patients of neurosyphilis. Because early diagnosis and treatment of neurosyphilis are crucial to avoid persistent brain damage, the neuroimaging findings are valuable adjunct to clinical diagnosis and to provide useful information to follow-up after therapy.

Major complications of airway management in the UK: results of the Fourth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 1: Anaesthesia

This project was devised to estimate the incidence of major complications of airway management during anaesthesia in the UK and to study these events. Reports of major airway management complications during anaesthesia (death, brain damage, emergency surgical airway, unanticipated intensive care unit admission) were collected from all National Health Service hospitals for 1 yr. An expert panel assessed inclusion criteria, outcome, and airway management. A matched concurrent census estimated a denominator of 2.9 million general anaesthetics annually. Of 184 reports meeting inclusion criteria, 133 related to general anaesthesia: 46 events per million general anaesthetics [95% confidence interval (CI) 38-54] or one per 22,000 (95% CI 1 per 26-18,000). Anaesthesia events led to 16 deaths and three episodes of persistent brain damage: a mortality rate of 5.6 per million general anaesthetics (95% CI 2.8-8.3): one per 180,000 (95% CI 1 per 352-120,000). These estimates assume that all such cases were captured. Rates of death and brain damage for different airway devices (facemask, supraglottic airway, tracheal tube) varied little. Airway management was considered good in 19% of assessable anaesthesia cases. Elements of care were judged poor in three-quarters: in only three deaths was airway management considered exclusively good. Although these data suggest the incidence of death and brain damage from airway management during general anaesthesia is low, statistical analysis of the distribution of reports suggests as few as 25% of relevant incidents may have been reported. It therefore provides an indication of the lower limit for incidence of such complications. The review of airway management indicates that in a majority of cases, there is 'room for improvement'.

A rude awakening after our fourth ‘NAP’: lessons for airway management

A rude awakening after our fourth ‘NAP’: lessons for airway management

Interleukin-1β-induced brain injury and neurobehavioral dysfunctions in juvenile rats can be attenuated by α-phenyl-n-tert-butyl-nitrone

Our previous study showed that perinatal exposure to interleukin-1β (IL-1β), an inflammatory cytokine, induces acute injury to developing white matter in the neonatal rat brain, and α-phenyl-n-tert-butyl-nitrone (PBN), a free radical scavenger and antioxidant, protects against IL-1β-induced acute brain injury. The objective of the present study was to further examine whether perinatal exposure to IL-1β resulted in persistent brain damage and neurological disabilities, and whether PBN offers lasting protection. Intracerebral injection of IL-1β (1 μg/kg) was performed in postnatal day 5 (P5) Sprague-Dawley rat pups and PBN (100 mg/kg) or saline was administered intraperitoneally 5 min after IL-1β injection. Perinatal IL-1β exposure significantly affected neurobehavioral functions in juvenile rats. Although some neurobehavioral deficits such as performance in negative geotaxis, cliff avoidance, beam walking, and locomotion were spontaneously reversible, sustained deficits such as poor performance in the vibrissa-elicited forelimb-placing test, the pole test, the passive avoidance task, and the elevated plus-maze task were still observable at P21. Perinatal IL-1β exposure resulted in persistent brain damage including enlargement of ventricles, loss of mature oligodendrocytes, impaired myelination as indicated by the decrease in myelin basic protein immunostaining, axonal and dendritic injury, and loss of hippocampal CA1 neurons and tyrosine hydroxylase positive neurons in the substantia nigra and ventral tegmental areas of the rat brain. Treatments with PBN provided lasting protection against the IL-1β-induced brain injury and improved the associated neurological dysfunctions in juvenile rats, suggesting that prompt treatments for brain injury induced by perinatal infection/inflammation might have important long-term consequences.