Permanent Central Nervous System Research Articles

Brief isoflurane administration as an adjunct treatment to control organophosphate-induced convulsions and neuropathology.

Organophosphate-based chemical agents (OP), including nerve agents and certain pesticides such as paraoxon, are potent acetylcholinesterase inhibitors that cause severe convulsions and seizures, leading to permanent central nervous system (CNS) damage if not treated promptly. The current treatment regimen for OP poisoning is intramuscular injection of atropine sulfate with an oxime such as pralidoxime (2-PAM) to mitigate cholinergic over-activation of the somatic musculature and autonomic nervous system. This treatment does not provide protection against CNS cholinergic overactivation and therefore convulsions require additional medication. Benzodiazepines are the currently accepted treatment for OP-induced convulsions, but the convulsions become refractory to these GABAA agonists and repeated dosing has diminishing effectiveness. As such, adjunct anticonvulsant treatments are needed to provide improved protection against recurrent and prolonged convulsions and the associated excitotoxic CNS damage that results from them. Previously we have shown that brief, 4-min administration of 3%-5% isoflurane in 100% oxygen has profound anticonvulsant and CNS protective effects when administered 30min after a lethal dose of paraoxon. In this report we provide an extended time course of the effectiveness of 5% isoflurane delivered for 5min, ranging from 60 to 180min after a lethal dose of paraoxon in rats. We observed substantial effectiveness in preventing neuronal loss as shown by Fluoro-Jade B staining when isoflurane was administered 1h after paraoxon, with diminishing effectiveness at 90, 120 and 180min. In vivo magnetic resonance imaging (MRI) derived T2 and mean diffusivity (MD) values showed that 5-min isoflurane administration at a concentration of 5% prevents brain edema and tissue damage when administered 1h after a lethal dose of paraoxon. We also observed reduced astrogliosis as shown by GFAP immunohistochemistry. Studies with continuous EEG monitoring are ongoing to demonstrate effectiveness in animal models of soman poisoning.

Biomarkers of Neurological Injury for Emerging Viral Threats and Post Viral Disease

Abstract Neurotropic viral infection and the ensuant immune response are a significant cause of morbidity and mortality worldwide, which can range in severity from mild to permanent central nervous system (CNS) damage and death. Encephalitic alphaviruses include Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV; Alphavirus; Togaviridae). Injury to the CNS is an important determinant of poor outcome and tools to predict this outcome are lacking. Neurons are the primary target cells of encephalitic alphaviruses where cytopathology plays a major role in CNS dysfunction. Proteins are released following cell death, such as ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are neuromarkers of CNS tissue injury which could serve as biomarkers to assess injury severity, monitor disease progression, direct treatment, and as reliable endpoints to help develop novel medical countermeasures. Recent advances in the use of blood-based biomarkers for diagnosis of traumatic brain injury (TBI) which have FDA approved assays have provided a scientific foundation for expanding the biomarker technology to brain damage caused by other CNS pathologies like viral encephalitis. Here we evaluated the ability to detect these biomarkers for encephalitic alphaviruses, encephalitis of unknown origin, and hospitalized patients with severe coronavirus disease (COVID-19). Higher levels of specific biomarkers were detected in patients diagnosed with alphavirus or unknown encephalitis which may be useful in prognosis and treatment guidance of post viral disease. Collectively, our results suggest that these blood-based biomarkers may be a good indicator for brain injury resulting from viral infection.

Continuous Glucose Monitoring in Enterally Fed Children with Severe Central Nervous System Impairment.

This prospective, observational study included nineteen patients (median (25-75 pc) age: 12.75 (6.17-15.55) years) with permanent CNS damage (Gross Motor Function Classification System V) receiving long-term tube enteral feeding, recruited from two paediatric university nutritional treatment centres. Patients with acute conditions and diagnosed diabetes were excluded. The nutritional status and nutritional support were analysed in all the inpatients in accordance with a uniform protocol. Using the CGM system (Medtronic iPro2), glycaemic curves were analysed, and in addition, HbA1C levels were determined in fourteen patients. CGM results were analysed using GlyCulator2.0. Statistical analysis was performed using the Statistica version 11 software (StatSoft Inc. Tulsa, OK, USA). More than half (11/19; 58%) of the patients were undernourished (BMI < 3 pc for age and gender), with the stature age being significantly lower than calendar age (5 (4.5-9) vs. 12.75 (6.17-15.55) years; p = 0.0010). The actual caloric intake was 50 (37.7-68.8) kcal/kg (median; 25-75 pc). In patients fed using the bolus method, the number of calories consumed per day was statistically significantly higher than in children subjected to a continuous feeding supply (56.00 (41.00-75.00) vs. 33.40 (26.70-50.00) kcal/kg BW (body weight; p = 0.0159). Decreases in blood glucose levels below the alarm level (<70 mg/dL) were recorded in fifteen patients (78.9%), including two patients with episodes of clinically significant hypoglycaemia (<54 mg/dL). The minimum and maximum glycaemic values recorded in any individual CGM records were 67 mg/dL (median) (minimum: 41 mg/dL; maximum: 77 mg/dL) and 146 (minimum: 114 mg/dL; maximum: 180 g/dL), respectively, for the entire recording. The maximum percentage of glycaemic concentrations > 140 mg/dL (TAR 140) recorded overnight in children with BMI ≥ 3 amounted to 1.6% vs. 0% in undernourished patients (TAR 140: 0.0 (0.00-1.6%) vs. 0% (0.00-0.0%; p = 0.0375); the percentage of glycaemic concentrations <70 mg/dL in the entire recording was comparable (0.77% (0.13-2.2%) vs. 1.8% (0.5-14.4%) vs. p = 0.2629). There was a positive correlation between the mean daily glucose recorded using the CGM method and patients' BMI z-scores (R = 0.48, p = 0.0397). No statistically significant relationship was demonstrated between the occurrence of alarm hypoglycaemia events in the CGM records and undernutrition expressed by BMI z-scores (OR = 1.50 (95%CI: 0.16-13.75), the type of diet (for commercially manufactured OR = 0.36 (95%CI: 0.04-3.52), and the modality of diet delivery (for bolus feeding OR = 2.75 (95%CI: 0.28-26.61). In children with chronic OU damage, enteral feeding is associated with a risk of hypoglycaemia, but further studies involving a larger number of patients are needed, and CGM might be a useful tool to estimate the metabolic adequacy of enteral nutritional support in terms of glucose control.

Bone marrow mesenchymal stem cells improve cognitive impairments induced by methamphetamine in rats and reduce relapse.

Introduction: Chronic exposure to methamphetamine (Meth) results in permanent central nervous system damage and learning and memory dysfunction. This study aimed at investigating the therapeutic effects of bone marrow mesenchymal stem cells (BMMSCs) on cognitive impairments in Meth addicted rats and comparing intravenous (IV) delivery with intranasal (IN) delivery of BMMSCs. Methods: Adult Wistar rats were randomly divided into 6 groups; Control; Meth-addicted; IV-BMMSC (Meth administered and received IV BMMSCs); IN-BMMSC (Meth administered and received IN BMMSCs); IV-PBS (Meth administered and received IV Phosphate-buffered saline (PBS); IN-PBS (Meth administered and received IN PBS). BMMSCs were isolated, expanded in vitro, immunophenotyped, labeled, and administered to BMMSCs-treated groups (2 × 106 cells). The therapeutic effect of BMMSCs was measured using Morris water maze and Shuttle Box. Moreover, relapse-reduction was evaluated by conditioning place preference after 2 weeks following BMMSCs administration. The expression of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) in rat hippocampus was assessed using immunohistochemistry method. Results: Administration of BMMSCs caused a significant improvement in the learning and memory functions of Meth-addicted rats and reduced the relapse (P<0.01). In behavioral tests, comparison of IV and IN BMMSC-treated groups did not show any significant difference. Administration of BMMSCs improved the protein level of BDNF and GDNF in the hippocampus, as well as causing behavioral improvement (P<0.001). Conclusion: BMMSC administration might be a helpful and feasible method to treat Meth-induced brain injuries in rats and to reduce relapse. BMMSCs were significantly higher in IV-treated group compared to the IN route. Moreover, the expression of BDNF and GDNF was higher in IN-treated rats compared with IV treated group.

Focal Seizures and Posterior Reversible Encephalopathy Syndrome as Presenting Signs of IgA Vasculitis/Henoch-Schoenlein Purpura-An Educative Case and Systematic Review of the Literature.

Background: IgA vasculitis/Henoch-Schoenlein purpura (IgAV/HSP) is a systemic small vessel vasculitis of unknown pathogenesis predominantly affecting children. While skin, GI tract, joints, and kidneys are frequently affected and considered, central nervous system (CNS) involvement of this disease is underestimated.Methods: We provide a case report and systematically review the literature on IgAV, collecting data on the spectrum of neurological manifestations.Results: We report on a 7-year-old girl with IgAV who presented with diplopia and afebrile focal seizures, which preceded the onset of purpura. Cranial magnetic resonance imaging was consistent with posterior reversible encephalopathy syndrome (PRES), showing typical focal bilateral parietal swelling and cortical and subcortical high signal intensities on T2-fluid attenuated inversion recovery (FLAIR) images predominantly without diffusion restriction. Cerebrospinal fluid analysis and blood tests excluded systemic inflammation or vasculitis. Interestingly, hypertension was not a hallmark of the developing disease in the initial phase of PRES manifestation. Renal disease and other secondary causes for PRES were also excluded. Supportive- and steroid treatment resulted in restitution ad integrum. Reviewing the literature, we identified 28 other cases of IgAV with CNS involvement. Severe CNS involvement includes seizures, cerebral edema, or hemorrhage, as well as PRES. Thirteen patients fulfilled all diagnostic criteria of PRES. The mean age was 11.2 years (median 8.0, range 5-42 years), with no reported bias toward gender or ethnic background. Treatment regimens varied from watchful waiting to oral and intravenously steroids up to plasmapheresis. Three cases showed permanent CNS impairment.Conclusion: Collectively, our data demonstrate that (I) severe CNS involvement such as PRES is an underappreciated feature of IgAV, (II) CNS symptoms may precede other features of IgAV, (III) PRES can occur in IgAV, and differentiation from CNS vasculitis is challenging, (IV) pathogenesis of PRES in the context of IgAV remains elusive, which hampers treatment decisions. We, therefore, conclude that clinical awareness and the collection of structured data are necessary to elucidate the pathophysiological connection of IgAV and PRES.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, a mimicker of malignancy: a case report and review of the literature

BackgroundChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a clinically and radiographically distinct inflammatory syndrome affecting multiple structures of the brain, including the cerebellum, brainstem, and spinal cord. The clinical presentation can be variable, including ataxia, nystagmus, dysarthria, dysphagia, and other subacute brainstem, cranial nerve, or cerebellar symptoms. These symptoms can be subacute to chronic, episodic, and progressive, making the diagnosis challenging. The hallmark radiographic magnetic resonance imaging findings are gadolinium-enhancing punctate lesions predominantly “peppering” the pons in a perivascular pattern.Case presentationHere, we describe a case and literature review of a 74-year-old Caucasian male who presented with subacute symptoms of ataxia, diplopia, and generalized fatigue. Physical examination was notable for horizontal nystagmus and wide-based gait. Magnetic resonance imaging revealed angiocentric enhancement predominantly in the brainstem and cerebellum, with involvement of the basal ganglia, thalami, and supratentorial white matter. Meanwhile, a screening computed tomography scan demonstrated a right upper lobe mass with biopsy proving primary lung cancer. Biopsy of one of the brain lesions showed perivascular infiltrate primarily composed of CD3+ T cells, scattered CD20+ B cells, and no signs of malignancy. The patient was started on high-dose glucocorticoids followed by a maintenance regimen with rapid improvement clinically and radiographically. Given extensive work-up was negative, these clinical and radiographic findings were consistent with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.ConclusionsThis case illustrates the difficulty of diagnosing chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, given its variable presentation, lack of specific laboratory findings, and poorly understood pathogenesis. We demonstrate a case that responded well to oral corticosteroid burst followed by a taper to the lowest corticosteroid dose clinically possible. Failure to recognize this syndrome could result in permanent central nervous system morbidity. Therefore, earlier recognition is crucial for this treatable condition.

Multiple Sclerosis and Serotonin: Potential Therapeutic Applications.

Multiple sclerosis (MS) is a neurodegenerative disease with a complex autoimmune component, and it has a high prevalence among middle-aged females. The manifestations of the disease range from episodic somatosensory dysfunction to progressive and permanent central nervous system (CNS) damage. Due to a high prevalence of psychiatric comorbidities and proven abnormalities in serotonin (5-HT) levels among MS patients, they are usually on drugs that modify the serotonergic system. Through a comprehensive literature review of studies published in the last 10 years related to 5-HT in MS and its therapeutic applications, we aimed to elucidate the mechanism behind the neurotransmitter (NT) levels’ abnormalities. Most importantly, we endeavored to gather the most up-to-date information about the full therapeutic potential of agents acting on this system. We discovered that multiple processes cause low levels of 5-HT in MS patients. The varying levels of the availability of the 5-HT transporter (SERT) in the CNS decreasing overall tryptophan (TRP) levels, and diversion of the amino acid away from its synthetic pathway constitute some of those. Studies in animals have shown that 5-HT levels’ elevations could cause immune-modulating effects and could probably slow down the disease progression rate. Human studies have shown a more diverse and complex response. Promising results have been obtained in the last 10 years regarding 5-HT’s immune-modulatory role in MS patients and its therapeutic applications. Human studies with a larger population and feasible designs are still needed to fully ascertain the effects of serotonin on the immune system and disease progression in patients with MS.

The role of surgery in primary central nervous system lymphomas.

Background Primary central nervous system lymphomas (PCNSL) are infrequent. The traditional treatment of choice is chemotherapy. Complete resections have generally not been recommended, because of the risk of permanent central nervous system deficits with no proven improvement in survival. The aim of the current study was to compare survival among patients with PCNSL who underwent biopsy versus surgical resection. Methods A retrospective study was conducted on 50 patients with a confirmed diagnosis of PCNSL treated at our center from January 1994 to July 2015. Results Patients in the resection group exhibited significantly longer median survival time, relative to the biopsy group, surviving a median 31 months versus 14.5 months; p = 0.016. Conclusions In our series, patients who had surgical resection of their tumor survived a median 16.5 months longer than patients who underwent biopsy alone.

Neuroangiostrongyliasis: The "Subarachnoid Phase" and Its Implications for Anthelminthic Therapy.

Infection with the Rat Lungworm Angiostrongylus cantonensis is the leading cause of human eosinophilic meningoencephalitis worldwide. From its origins in southeastern Asia, the parasite was spread extensively throughout the twentieth century and is now established in many of the world's warmer regions. Its clinical effects range from mild and transient symptoms, usually headache with peripheral nerve dysfunction, to severe and permanent central nervous system (CNS) damage, occasionally fatal. The severity and prognosis of disease are determined by the larval dose, acquired by ingesting infected intermediate hosts (slugs and snails) or, less often, paratenic hosts, such as crabs, shrimps, frogs, and monitor lizards. Early diagnosis is critical for treatment and depends on clinical suspicion, for laboratory confirmation from blood and cerebrospinal fluid can be delayed and unreliable. Treatment is fraught with difficulty, compounded by conflicting published results. Corticosteroids play a useful role in suppressing early CNS inflammation, but their duration for maintenance becomes problematic in severe infections. Because most of the pathogenesis results from host immuno-inflammatory responses to migrating and dead larvae in the CNS, anthelminthic therapy remains controversial: if effective, it kills viable larvae, arresting them in the CNS and so exacerbating the pathology. In human infections, it is now clear that many larvae do leave the CNS and reach the pulmonary arteries, sometimes with clinical consequences. Pioneering life-cycle studies in rats demonstrated a "subarachnoid phase" in larval development and migration; recent autopsy findings, outlined here, show it also occurs in humans and has some bearing on treatment. One new and four previously reported cases of human infection are analyzed here, with findings indicating that anthelminthic treatment is effective only when given early and should not be commenced beyond 3 weeks after exposure to infection. In endemic areas, treatment should start as soon as this infection is suspected, even without a clear history of exposure, given the unacceptable risks of waiting for diagnostic laboratory confirmation.

Combined in utero hypoxia-ischemia and lipopolysaccharide administration in rats induces chorioamnionitis and a fetal inflammatory response syndrome

IntroductionPreterm birth is a major cause of infant morbidity and long-term disability, and is associated with numerous central nervous system (CNS) deficits. Infants exposed to intrauterine inflammation, specifically chorioamnionitis, are at risk for very early preterm birth and neurological complications including cerebral palsy, epilepsy, and behavioral and cognitive deficits. However, placenta-brain axis abnormalities and their relationship to subsequent permanent CNS injury remain poorly defined. MethodsIntrauterine injury was induced in rats on embryonic day 18 (E18) by transient systemic hypoxia-ischemia (TSHI) and intra-amniotic lipopolysaccharide (LPS) injection. Placenta, brain and serum were collected from E19 to postnatal day 0 (P0). Histology, TUNEL staining, western blot and multiplex immunoassays were used to quantify placental and brain abnormalities, and fetal serum cytokine levels. ResultsPrenatal TSHI + LPS caused acute and subacute placental injury hallmarked by inflammatory infiltrate, edema, hemorrhage and cell death along with placental increases in IL-1β and TNFα. TSHI + LPS increased a diverse array of circulating inflammatory proteins including IL-1β, TNFα, IL-6, IL-10, IL-4, IFNγ and CXCL1, both immediately after TSHI + LPS and in live born pups. CNS inflammation was characterized by increased CXCL1. DiscussionPrenatal TSHI + LPS in rats induces placental injury and inflammation histologically consistent with chorioamnionitis, concomitant with elevated serum and CNS pro-inflammatory cytokines. This model accurately recapitulates key pathophysiological processes observed in extremely preterm infants including placental, fetal, and CNS inflammation. Further investigation into the mechanism of CNS injury following chorioamnionitis and the placental-brain axis will guide the use of future interventions.

Deletion of IL-4Rα in the BALB/c mouse is associated with altered lesion topography and susceptibility to experimental autoimmune encephalomyelitis

The regulation of cytokine expression by immune deviation from a pro-inflammatory to anti-inflammatory or “regulatory” milieu is crucial to the prevention of permanent central nervous system (CNS) damage in neuroinflammation. Earlier studies in the murine experimental autoimmune encephalomyelitis (EAE) model pointed to an anti-inflammatory role for the Th2 cytokine, IL-4, which was not confirmed in IL-4Rα-deficient mice (IL-4Rα−/−). To examine the pathological consequences of loss of responsiveness to Th2 cytokines, we compared lesion evolution in IL-4Rα−/− and wild type (WT) BALB/c mice immunized with PLP180–199 and investigated how altering the magnitude of the antigen-specific autoimmune response in this model affected the pathology. We found that while changing the magnitude of the peripheral antigen-specific response differentially affected the incidence of clinical disease in WT BALB/c relative to IL-4Rα−/− mice, the differences in incidence did not correlate to differences in pro-inflammatory cytokine production. Additionally, although only approximately 75% of WT mice developed clinical disease, lesions were observed in 100% of the mice, principally in the cerebellum, mid-brain and cerebral hemispheres, and lesion load increased with increasing pro-inflammatory cytokine production. Despite being resistant to disease induction with increasing pro-inflammatory cytokine production, lesion incidence in IL-4Rα-deficient animals was equal to their WT counterparts. However, lesion severity in IL-4Rα-deficient animals was preferentially reduced in the mid-brain and cerebral hemispheres. From these studies, we conclude that signaling through IL-4Rα has little effect on regulating the peripheral pro-inflammatory cytokine profile in this EAE variant but has distinct effects on the determination of lesion topography.

Analysis of seizure risk factors after allogeneic hematopoietic stem cell transplantation: A 8 case report and literature review

The clinical characteristics of patients with seizures after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were analyzed. A total of 8 cases of seizures after allo-HSCT were investigated. Clinical data of these cases were studied retrospectively. Of 159 cases subjected to allo-HSCT, seizure occurred in 8 cases during 29-760 days after transplantation, median survival time was 46 days, and there were 6 cases of tonic-clonic seizure. The incidence of seizure after matched unrelated HSCT was higher than that after related HSCT (P=0.017). Of 7 cases treated with cyclosporine A (CsA), 4 cases obtained high blood levels of CsA. In addition, hyponatremia was diagnosed in 5 cases. Abnormal electroencephalogram and brain MRI findings were found in some cases. During 20 days after seizure, 2 cases died due to infection and graft-versus-host disease (GVHD), respectively. It was suggested that multiple factors are associated with seizures after allo-HSCT. Rapid identification and correction of the causative factors are very important to prevent permanent central nervous system damage and reduce the mortality.

Emerging methods for evaluating the effectiveness of intramuscular interferon beta-1a for relapsing-remitting multiple sclerosis.

Newer outcome-based assessment methods have been developed that complement and improve upon the ability of historical clinical and magnetic resonance imaging (MRI) outcome measures to measure multiple sclerosis (MS) disease activity, patient functionality, treatment efficacy, and the risk of MS disease progression. These newer MS outcome assessments include instruments to evaluate cognitive function and patient quality of life; enhanced measures of disability, such as the Multiple Sclerosis Functional Composite instrument; and newer MRI measures of MS disease activity and neuronal changes, such as permanent T₁ hypointensities and central nervous system atrophy. When utilized in conjunction with standard MS outcome measures, these newer MS outcomes provide a more comprehensive picture of disease status and course and hold promise as tools for use in the development and testing of future MS therapies. The well-established first-line MS therapy intramuscular interferon beta-1a, which has been evaluated using a broad range of assessment methods, was used as a reference MS disease-modifying therapy to provide specific examples of studies utilizing newer evaluation methods. Utilization of evolving disease and assessment measures for patients with MS should improve MS patient diagnosis, treatment decisions, and monitoring of therapy.

Gemcitabine-induced posterior reversible encephalopathy syndrome: A case report

Gemcitabine is a commonly used chemotherapeutic agent for a variety of tumors. Although this nucleoside analog antineoplastic agent is similar in structure to cytarabine, central nervous system toxicities have rarely been attributed to gemcitabine. The posterior reversible encephalopathy syndrome (PRES) is a condition characterized by reversible neurological and radiological findings that has been associated with use of chemotherapeutic and more recently novel targeted therapies. We describe one case of a 41-year-old woman with PRES under treatment for leiomyosarcoma because of the probable association with gemcitabine. Our case, to our knowledge, represents the seventh published report of this particular toxicity. Naranjo algorithm, efficacious method for assessing the causality of adverse drug reactions (ADRs) from a case report, suggests a direct casual relationship. PRES is probably a rare complication of gemcitabine, but the oncologist should take it into careful consideration, because PRES is reversible with treatment of current hypertension or removal of the causative agent. However, failure to quickly recognize the syndrome and discontinue the offending agent may result in profound and permanent central nervous system dysfunction or death.

Neuropathology of vaccination in infants and children

Documentation of clinical-pathological features of 37 infants/children whose parents alleged a relationship between vaccination and death or permanent central nervous system (CNS) damage, and sought compensation through the National Vaccine Injury Compensation Program. Of the 5545 claims filed during the 10-year period (1990-1999), CNS tissue was available for evaluation by a pediatric neuropathologist in 37; 33 died and 4 had a biopsy or lobectomy. Most commonly implicated vaccines were DTP/DTaP, followed by MMR and IPV/OPV, but almost all of the vaccines currently given to infants/children were alleged to be responsible for the illness/death. No lesions were found in 5 of 37 (13.5%). The most frequent abnormality consisted of acute anoxic encephalopathy (14 of 37 - 37.8%), consequent to several different causes, such as positional asphyxia, cardio-respiratory arrest during status epilepticus, etc. The remaining children manifested other lesions, including inflammation (5 of 37 - 13.5%), vascular and developmental anomalies (4 each of 37 or 10.6%), cerebral edema and system degeneration (2 each of 37 or 5.4%), and one case of heavy metal exposure in a child living near an abandoned mine (2.2%). There was no obvious relationship between type of vaccine (or vaccines simultaneously administered) to time of onset of symptoms, nature of symptoms or the lesions found.

A Case of Posterior Reversible Encephalopathy Syndrome Following Hypopharyngeal Cancer Surgery

Posterior reversible encephalopathy syndrome (PRES) features headache, seizures, abnormal mental state, altered visual perception, and hypertension. While rare, it has become increasingly identifiable with clinicoradiological processes in cancer associated with cytotoxic and immunosuppressive agents. Such processes include vasogenic edema mainly involving the white matter of the parietooccipital lobes. PRES is reversible when adequately managed. Failure to quickly recognize it may, however, result in profound, permanent central nervous system dysfunction or death. We reported a 48-year-old woman with advanced hypopharyngeal cancer who developed PRES after total pharyngolaryngoesophagectomy. Her condition gradually improved and she recovered completely without neurological deficit 46 days after PRES onset.

Outcomes of central nervous system cryptococcosis vary with host immune function: Results from a multi-center, prospective study

Central nervous system (CNS) cryptococcosis is most commonly encountered among HIV-infected and other immunosuppressed hosts but is less well-characterized among non-immunosuppressed patients. We conducted a three year, prospective, observational study to compare the clinical manifestations and outcome of CNS cryptococcosis in three patient populations: HIV-infected patients (n=54), HIV-negative immunosuppressed patients (n=21), and non-immunosuppressed patients (n=11). Time from initial symptoms to presentation did not differ between the groups. HIV-infected patients were significantly more likely to present with fevers (p<0.0001), but were less likely to have abnormal mental status, CNS mass lesions and pulmonary involvement (p=0.001, 0.01 and 0.03, respectively). The clinical manifestations among HIV-negative immunosuppressed patients were generally intermediate to the other groups. Overall, acuity of illness was worse among non-immunosuppressed patients, as measured by APACHE II scores (p=0.02). Intracranial pressure was higher in HIV-infected and non-immunosuppressed patients than immunosuppressed patients (p=0.008 and 0.01, respectively). Repeated lumbar punctures were more common among HIV-infected patients (p=0.01). There was a trend toward more frequent placement of permanent CNS shunts among non-HIV patients (p=0.05). The mortality rate was greatest for non-immunosuppressed patients (p=0.04). CNS cryptococcosis in non-immunosuppressed patients was associated with poorer prognosis. Our findings suggest that host immune responses may contribute to pathogenesis of CNS cryptococcosis, with more intact immune function associated with increased CNS-related morbidity and overall mortality.

Is the Intra-Aortic Balloon Pump a Method of Brain Protection During Cardiogenic Shock After Drug Intoxication?

Cardiovascular medications are ubiquitous and are frequently implicated in accidental or intentional overdose. It is common that combined use of these drugs may lead to hypotension and even shock, followed by metabolic derangements. We report a case in which an intra-aortic balloon pump (IABP) was used in the management of self-poisoning with verapamil, amlodipine, metoprolol, and ibuprofen. In presenting this case of combined massive drug ingestion, we outline early strategy in the Emergency Department and some alternative treatment options. Beyond pharmacological and conservative procedures, we implemented an invasive approach that included temporary pacing, mechanical ventilation, and intra-aortic balloon counterpulsation (IABP). Such intense treatment was necessary due to the critical state of the patient. In our opinion, the use of the IABP contributed to the final recovery of our adolescent patient. Combined mechanical and pharmacological treatment may protect from multi-organ insufficiency, including permanent central nervous system injury. It is hoped that reporting our experience will raise awareness of alternative treatment options for ingestions of cardiovascular medications.

Tickborne encephalitis in an area of high endemicity in lithuania: disease severity and long-term prognosis.

Of 250 consecutively admitted patients with central nervous system (CNS) infections who were treated during a 1-year period, all 133 patients with tickborne encephalitis (TBE) were included in a prospective follow-up study. TBE presented as mild (meningeal) in 43.6% of patients and as moderate or severe (encephalitic) in 43.6% and 12.8% of patients, respectively. Paralytic disease was observed in 3.8% of the subjects, and cranial nerve injury was observed in 5.3%. One patient died of TBE. Permanent CNS dysfunction after 1 year was found in 30.8% of patients; in 8.5% of all TBE cases, severe disabilities required adjustment of daily activities. Corticosteroid treatment did not seem to improve outcome. A progressive course of TBE was noted in 2 patients. The risk of incomplete recovery was significantly higher among patients with the encephalitic form of TBE (odds ratio, 4.066; 95% confidence interval, 1.848-8.947). In conclusion, TBE is an important pathogen in CNS infection in the Kaunas region of Lithuania, and it causes long-lasting morbidity in one-third of cases.

Emergency anaesthesia for the compromised fetus

Emergency anaesthesia for the compromised fetus encompasses anaesthesia for both acute fetal distress and the chronically hypoxic fetus. Fetal distress, a poorly defined term, is still used by clinicians today. Parer and Livingston defined fetal distress as “progressive fetal asphyxia, that if not corrected or circumvented, will result in decompensation of the physiologic responses (primarily redistribution of blood flow to preserve oxygenation of vital organs) and cause permanent central nervous system and other organ damage or death.” More recently the term “non-reassuring fetal status” has been adopted as a better descriptor than fetal distress.