Toxic Encephalopathy Research Articles

Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma with Renal Impairment

Aim. To study the efficacy and adverse event spectrum of high-dose chemotherapy with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with acute renal impairment, including hemodialysis (HD) dependence. Materials & Methods. The retrospective single-center study enrolled 64 MM patients (30 men and 34 women) with renal impairment, aged 19-65 years (median 54 years), who received auto-HSCT in the period from 2013 to 2019. Newly diagnosed patients had a median creatinine of 462 nmol/L and a median glomerular filtration rate of 10 ml/min/1,73 m<sup>2</sup> (CKD-EPI). HD dependence was reported in 23 (36 %) patients on diagnosis date. As a result of the induction therapy, in 13 (57 %) out of 23 patients HD could be discontinued. Prior to auto-HSCT, overall antitumor response was 91 % (complete remission was 45 %), overall renal response was 80 % (complete renal response was 28 %). In the course of auto-HSCT 10 patients remained HD dependent. Two groups were analyzed: “HD-” (program HD-independent patients during auto-HSCT, n = 54) and “HD+” (program HD-dependent recipients of auto-HSCT, n = 10). Results. Herpes virus infection reactivation and reversible toxic encephalopathy were observed significantly more often in “HD+” than in “HD-” group (30 % vs. 6 %, p = 0.04 and 20 % vs. 0 %, p = 0.02, respectively). HD-dependent patients required red blood cell transfusion significantly more often than HD-independent patients (100 % vs. 35 % of cases; p = 0.0001). In 100 days after auto-HSCT, overall antitumor response increased from 91 % to 96 %, the rate of complete remission increased from 45 % to 64 %. After auto-HSCT the rate of complete renal response increased from 28 % to 34 %, however, overall renal response remained within the range of 80 %. After auto-HSCT, in a single case HD was discontinued. As a result of the treatment, 14 (61 %) patients became HD-independent. Transplantation-associated mortality was not reported. During median follow-up of 48 months, 5-year overall survival was 70 % and 5-year disease-free survival was 42 %. Conclusion. Auto-HSCT is a feasible, safe, and effective treatment of MM patients with acute renal impairment. Induction therapy with subsequent auto-HSCT resulted in less need for HD which was 36 % at MM onset and 14 % on completing the treatment.

Long COVID Syndrome Presenting as Hyperferritenemia Associated Toxic Encephalopathy in a Deferoxamine Compliant Patient of Beta Thalassemia

Ferritin overload is a frequent problem encountered in patients with beta thalassemia amounting to various complications. One of rare but important complication of ferritin overload is ferritin overload induced toxic encephalopathy. Serum ferritin has been recognised as a important marker of inflammation and cytokine storm in COVID19.We present a case of Long COVID syndrome presenting as toxic encephalopathy in a case of beta thalassemia in spite of the patient being compliant to desferroxamine therapy.This report highlights the synergistic effect of Severe Acute Respiratory Syndrome Coronavirus. 2(SARS CoV 2) mediated neuroinflammation through direct viral invasion and the release of inflammatory cytokines including ferritin resulting in toxic encephalopathy in a beta thalassemia major patient who was already prone to develop hyperferritenemia.Ferritin functions as a pro-inflammatory cytokine and it’s level increases in both thalassemia and COVID-19 and the index case presented here had both the conditions predisoposing him to develop toxic encephalopathy even after being compliant to deferoxamine therapy. It is important to recognise and treat this condition in order to prevent mortality and morbidity in patients of beta thalassemia who contract COVID19.

Acute liver failure caused by Amanita verna: a case series and review of the literature

BackgroundAmanita verna is one of the most harmful wild fungi in China. Amanita verna poisoning occurs every year, and the mortality is as high as 50%. However, its clinical manifestations are complex and diverse.Case presentationIn March 2019, three patients took a large amount of Amanita, and one of them received liver transplantation in Zhongshan hospital, Sun Yat-sen University. All patients had vomiting and diarrhea 8–12 h after eating wild mushrooms (Amanita). The patients were initially diagnosed with Amanita poisoning. One case (case 3) was complicated and diagnosed as mushroom poisoning (fatal Amanita), toxic hepatitis, acute liver failure, toxic encephalopathy, hemorrhagic colitis, toxic myocarditis, disseminated intravascular coagulation (DIC) and pregnancy. The general clinical data of all patients were recorded, who received early treatment such as hemodialysis, artificial liver plasma exchange, hormone shock and anti-infection. One case (case 1) recovered smoothly after liver transplantation, and the indexes of liver, kidney, coagulation function and infection were improved. The other two cases died of intracerebral hemorrhage.ConclusionLiver transplantation is an effective method for the treatment of acute liver failure caused by mushroom poisoning and can improve the survival rate of patients with toxic liver failure.

Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL): One-Year Follow-up of ZUMA-1 Cohort 6 (C6)

Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL): One-Year Follow-up of ZUMA-1 Cohort 6 (C6)

A Case Report on Korean Medical Treatment for a Patient with Quadriplegia and Impaired Cognition as Neurological Sequelae after Ingestion of Herbicides

This study is a case report of Korean medicine treatment for a patient with quadriplegia and impaired cognition as neurological sequelae after ingestion of herbicides. A 59-year-old man with toxic encephalopathy and hypoxic encephalopathy after the ingestion of herbicides was treated with acupuncture, <i>Hyulbuchuko-tang</i> mixed with <i>Ondam-tang-gami</i> (血府逐瘀湯合溫膽湯加味), cupping, moxibustion, and rehabilitation. Clinical symptoms were measured with the Manual Muscle Test (MMT), Korean Mini Mental Status Exam (K-MMSE), Functional Independence Measure (FIM), and Modified Barthel Index (MBI). After three months of treatment, clinical symptoms improved. The motor function improved (MMT on both sides, Gr. 3+F/4G →Gr. 4-G~4G/4+G), cognition improved (K-MMSE, 13→21), and ADL (Activities of Daily Living) scores also improved (FIM 41→74; MBI 20→63). Korean medical treatment could effectively treat neurological sequelae after ingestion of herbicides in this case.

Carbon monoxide: modern concepts to the treatment of acute poisonings (literature review)

Introduction. Carbon monoxide (CO) is one of the most common causes of chemical injuries and the main toxic factor in the people death in fires. The mechanism of the toxic effect of CO, associated with the formation of carboxyhemoglobin and the development of hypoxia, determines the rapid development of the clinical picture of acute intoxication and the need for emergency first aid and medical care to the poisoned. Material and methods. Literature sources, summarized in the bibliographic databases eLIBRARY.RU, PubMed and Scopus, were the material for analysis. Results. First aid is based on quickly removing the victim from the fire zone or other area with a high concentration of CO and providing him with oxygen as soon as possible. During medical evacuation, it is necessary to carry out continuous inhalation of 80-100% oxygen, to ensure rest and warmth of the victim. In the emergency department of the hospital, oxygen inhalation and maintenance therapy should be continued, clinical and laboratory diagnostic measures aimed at assessing the severity of intoxication, identifying complications and concomitant pathology should be performed. In the case of severe CO poisoning, medical care continues to be provided to the victims in the intensive care unit or in the oxygen-barotherapy unit. The main antidote for CO poisoning is oxygen, which can be used in two versions - normobaric or hyperbaric oxygenation. As a pharmacological antidote to CO, zinc bisvinylimidazole diacetate (acizol) which can accelerate the breakdown of carboxyhemoglobin, improve the oxygen-binding and gas-transport properties of blood, as well as the dissociation of oxyhemoglobin in tissues is used. Along with antidotes, an important role in the treatment of CO poisoning is played by pathogenetic and symptomatic therapy aimed at the prevention and treatment of toxic encephalopathy, brain edema, cognitive dysfunction, toxic myocardiodystrophy and arrhythmia, prevention of pneumonia, correction of the acid-base state, compensation of the energy needs of the body, etc. Conclusion. Further improvement of existing means and methods for the treatment of intoxication, the development and introduction of new antidots into medical practice will increase the effectiveness of therapeutic measures, reduce the number of deaths and disabilities after acute poisoning with carbon monoxide.

Autoimmune Encephalitis After SARS-CoV-2 Infection: Case Frequency, Findings, and Outcomes.

Background and ObjectivesAutoimmune encephalitis (AE) cases after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, but the frequency is unknown. We aimed to determine the frequency and diagnostic features of coronavirus disease 2019 (COVID-19)–related AE.MethodsResidual sera from 556 consecutive Mayo Clinic Rochester patients (laboratory cohort) who underwent autoimmune encephalopathy neural immunoglobulin G (IgG) evaluation were tested for total antibodies against the SARS-CoV-2 spike glycoprotein using a Food and Drug Administration–authorized chemiluminescence assay (October 2019–December 2020). Clinical records from patients with a positive SARS-CoV-2 antibody result and available research consent were reviewed. This laboratory cohort was cross-referenced with the Department of Neurology's COVID-19–related consultative experience (encephalopathy cohort, n = 31).ResultsEighteen of the laboratory cohort (3%) were SARS-CoV-2 antibody positive (April–December 2020). Diagnoses were as follows: AE, 2; postacute sequelae of SARS CoV-2 infection (PASC), 3; toxic-metabolic encephalopathy during COVID-19 pneumonia, 2; diverse non–COVID-19 relatable neurologic diagnoses, 9; unavailable, 2. Five of the encephalopathy cohort had AE (16%, including the 2 laboratory cohort cases that overlapped), representing 0.05% of 10,384 patients diagnosed and cared for with any COVID-19 illness at Mayo Clinic Rochester in 2020. The 5 patients met definite (n = 1), probable (n = 1), or possible (n = 3) AE diagnostic criteria; median symptom onset age was 61 years (range, 46–63); 3 were women. All 5 were neural IgG negative and 4 tested were SARS-CoV-2 PCR/IgG index negative in CSF. Phenotypes (and accompanying MRI and EEG findings) were diverse (delirium [n = 5], seizures [n = 2], rhombencephalitis [n = 1], aphasia [n = 1], and ataxia [n = 1]). No acute disseminated encephalomyelitis cases were encountered. The 3 patients with possible AE had spontaneously resolving syndromes. One with definite limbic encephalitis was immune therapy responsive but had residual mood and memory problems. One patient with probable autoimmune rhombencephalitis died despite immune therapy. The remaining 26 encephalopathy cohort patients had toxic-metabolic diagnoses.DiscussionWe encountered occasional cases of AE in our 2020 COVID-19 experience. Consistent with sporadic reports and small case series during the COVID-19 pandemic, and prior experience of postinfectious AE, our cases had diverse clinical presentations and were neural IgG and CSF viral particle negative. Application of diagnostic criteria assists in differentiation of AE from toxic-metabolic causes arising in the setting of systemic infection.

A RARE CAUSE OF PARAPLEGIA: DISTRIBUTIVE SHOCK CAUSING BORDER ZONE STROKES

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Simultaneous bilateral cerebrovascular infarction is relatively uncommon and is an entity seen rarely in watershed cerebral infarctions which occur at the border between cerebral vascular territories in the setting of severe hypotension. CASE PRESENTATION: 84-year-old male with history of CAD, cerebellar stroke, peripheral arterial disease was admitted to the ICU with distributive shock and intubated for toxic metabolic encephalopathy. Initial CT head on admission was unremarkable. On day 2 of hospitalization his neuro assessment was notable for bilateral lower extremity paresis with preservation of sensation, proprioception and temperature but had sluggish reflexes and loss of motor strength. Repeat CT head did not show a bleed and subsequently, MRI brain with MRA head and neck revealed bilateral acute anterior cerebral artery strokes. Given the location and duration of symptoms he was not a TPA candidate and was treated with medical management with aspirin and statin. Echocardiogram and carotid ultrasounds were done that were unremarkable for embolic cause of stroke. DISCUSSION: The anterior cerebral artery is a major vessel supplying blood to the interhemispheric region. ACA territory infarction accounts for only 0.3% to 4.4% of cerebral infarctions. Bilateral ACA infarction is even rarer. Twenty-seven cases of ACA territory infarction were reported among 1490 cases of cerebral infarction in the Lausanne Stroke Registry; among them, only two cases had bilateral ACA territory infarction. Bilateral ACA infarction can occur due to vasospasm in the setting of subarachnoid hemorrhage caused by a rupture of aneurysms of the anterior communicating arteries or distal ACAs, thrombosis or embolism in case of anomaly of circle of Willis or bilateral anaplastic ACAs. In our patient the area of infarction was in a watershed zone bilaterally, unfortunately affected by hypotension which is rare in the absence of any of the above-mentioned anomalies as predisposing factors. The true incidence of bilateral ACA infarction is unknown, with few cases reported in the literature. CONCLUSIONS: This case report highlights the possibility of developing simultaneous bilateral cerebral infarctions in the setting of profound systemic hypotension and shock, especially if the patient has baseline chronic small vessel changes. REFERENCE #1: Orlandi G, Moretti P, Fioretti C, Puglioli M, Collavoli P, Murri L. Bilateral medial frontal infarction in a case of azygous anterior cerebral artery stenosis. Ital J Neurol Sci. 1998;19:106–108. doi: 10.1007/BF02427567. [PubMed] [CrossRef] [Google Scholar] REFERENCE #2: Gacs G, Fox AF, Barnett HJ, Vinuela F. Occurrence and mechanisms of occlusion of the anterior cerebral artery. Stroke. 1983;14:952–959. [PubMed] [Google Scholar] REFERENCE #3: Bogousslavsky J, Regli F. Anterior cerebral artery territory infarction in the Lausanne Stroke Registry. Clinical and etiologic patterns. Arch Neurol. 1990;47:144–150. [PubMed] [Google Scholar] DISCLOSURES: No relevant relationships by Imama Ahmad, source=Web Response No relevant relationships by Christine Blaski, source=Web Response No relevant relationships by Sneha Lakshman, source=Web Response

Toxic Metabolic Encephalopathy presenting as Bilateral Symmetrical Basal Ganglia Lesion.

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The application of narrative therapy in convalescent patients with occupational acute chemical toxic encephalopathy

Objective: To explore the effects of narrative therapy on cognition, emotion and treatment satisfaction of convalescent patients with occupational acute chemical toxic encephalopathy. Methods: From June to July 2019, 60 convalescent patients with occupational chemical poisoning encephalopathy were randomly divided into narrative group and control group, with 30 cases in each group. The control group received routine clinical treatment. On the basis of receiving the original clinical treatment, patients in the narrative group added narrative treatment once a week to explain discomfort in specific life situations through conversation from the perspective of disease and psychology. 30 min each time for 6 weeks. The patients were investigated with Montreal Cognitive Assessment Scale (MoCA scale) every 2 weeks to evaluate the degree of cognitive impairment. The changes of depression, anxiety and treatment satisfaction were investigated before and after intervention. Results: There was no significant difference in MoCA scores between the two groups before intervention (P>0.05) . After 6 weeks of treatment, MoCA scores of narrative group and control group gradually increased with the extension of treatment time, and the increase degree of MoCA score of narrative group was greater than that of control group (P<0.01) . Before intervention, there was no significant difference in depression, anxiety score, prevalence and satisfaction index between narrative group and control group (P>0.05) . After the intervention, the scores and prevalence of depression and anxiety in the narrative group were significantly lower than those in the control group, and the scores of feeling in the process of seeing a doctor and how to obtain their own disease information were significantly higher than those in the control group (P<0.05) . Conclusion: Narrative therapy can improve the cognitive function and emotion of patients with occupational chemical poisoning, and improve the treatment satisfaction of patients.

The Effect of Data Length on the Assessment of Dynamic Cerebral Autoregulation with Transfer Function Analysis in Neurological ICU Patients.

BackgroundCerebral autoregulation plays an important role in safeguarding adequate cerebral perfusion and reducing the risk of secondary brain injury, which is highly important for patients in the neurological intensive care unit (neuro-ICU). Although the consensus white paper suggests that a minimum of 5 min of data are needed for assessing dynamic cerebral autoregulation with transfer function analysis (TFA), it remains unknown if the length of these data is valid for patients in the neuro-ICU, of whom are notably different than the general populations. We aimed to investigate the effect of data length using transcranial Doppler ultrasound combined with invasive blood pressure measurement for the assessment of dynamic cerebral autoregulation in patients in the neuro-ICU.MethodsTwenty patients with various clinical conditions (severe acute encephalitis, ischemic stroke, subarachnoid hemorrhage, brain injury, cerebrovascular intervention operation, cerebral hemorrhage, intracranial space-occupying lesion, and toxic encephalopathy) were recruited for this study. Continuous invasive blood pressure, with a pressure catheter placed at the radial artery, and bilateral continuous cerebral blood flow velocity with transcranial Doppler ultrasound were simultaneously recorded for a length of 10 min for each patient. TFA was applied to derive phase shift, gain, and coherence function at all frequency bands from the first 2, 3, 4, 5, 6, 7, 8, 9, and 10 min of the 10-min recordings in each patient on both hemispheres. The variability in the autoregulatory parameters in each hemisphere was investigated by repeated measures analysis of variance.ResultsForty-one recordings (82 hemispheres) were included in the study. According to the critical values of coherence provided by the Cerebral Autoregulation Research Network white paper, acceptable rates for the data were 100% with a length ≥ 7 min. The final analysis included 68 hemispheres. The effects of data length on trends in phase shift in the very low frequency (VLF) band (F1.801,120.669 = 6.321, P = 0.003), in the LF band (F1.274,85.343 = 4.290, P = 0.032), and in the HF band (F1.391,93.189 = 3.868, P = 0.039) were significant for 3–7 min, for 4–7 min, and for 5–8 min, respectively. Effects were also significant on the gain in the VLF band (F1.927,129.134 = 3.215, P = 0.045) for 2–8 min and on the coherence function in all frequency bands (VLF F2.846,190.671 = 90.247, P < 0.001, LF F2.515,168.492 = 55.770, P < 0.001, HF F2.411, 161.542 = 33.833, P < 0.001) for 2–10 min.ConclusionsConsidering the acceptable rates for the data and the variation in the TFA variables (phase shift and gain), we recommend recording data for a minimum length of 7 min for TFA in patients in the neuro-ICU.

Glial decline and loss of homeostatic support rather than inflammation defines cognitive aging.

Glial decline and loss of homeostatic support rather than inflammation defines cognitive aging.

Recommendations from the EXTRIP workgroup on extracorporeal treatment for baclofen poisoning

Baclofen toxicity results from intentional self-poisoning (acute baclofen poisoning) oraccumulation of therapeutic dose in the setting of impaired kidney function. Standard care includes baclofen discontinuation, respiratory support and seizure treatment. Useof extracorporeal treatments (ECTRs) is controversial. To clarify this, a comprehensive review of the literature on the effect of ECTRs in baclofen toxicity was performed and recommendations following EXTRIP methods were formulated based on 43 studies (1 comparative cohort, 1 aggregate results cohort, 1 pharmacokinetic modeling, and 40 patient reports or series). Toxicokinetic data were available for 20 patients. Baclofen's dialyzability is limited by a high endogenous clearance and a short half-life in patients with normal kidney function. The workgroup assessed baclofen as "Moderately dialyzable" by intermittent hemodialysis for patients with normal kidney function (quality of evidence C) and "Dialyzable" for patients with impaired kidney function (quality of evidence C). Clinical data were available for 25 patients with acute baclofen poisoning and 46 patients with toxicity from therapeutic baclofen in kidney impairment. No deaths or sequelae were reported. Mortality in historical controls was rare. No benefit of ECTR was identified in patients with acute baclofen poisoning. Indirect evidence suggests a benefit of ECTR in reducing the duration of toxic encephalopathy from therapeutic baclofen in kidney impairment. These potential benefits were balanced against added costs and harms related to the insertion of a catheter, the procedure itself, and the potential of baclofen withdrawal. Thus, the EXTRIP workgroup suggests against performing ECTR in addition to standard care for acute baclofen poisoning and suggests performing ECTR in toxicity from therapeutic baclofen in kidney impairment, especially in the presence of coma requiring mechanical ventilation.

Optimal Targets of the First 24-h Partial Pressure of Carbon Dioxide in Patients with Cerebral Injury: Data from the MIMIC-III and IV Database.

It is generally believed that hypercapnia and hypocapnia will cause secondary injury to patients with craniocerebral diseases, but a small number of studies have shown that they may have potential benefits. We assessed the impact of partial pressure of arterial carbon dioxide (PaCO2) on in-hospital mortality of patients with craniocerebral diseases. The hypothesis of this research was that there is a nonlinear correlation between PaCO2 and in-hospital mortality in patients with craniocerebral diseases and that mortality rate is the lowest when PaCO2 is in a normal range. We identified patients with craniocerebral diseases from Medical Information Mart for Intensive Care third and fourth edition databases. Cox regression analysis and restricted cubic splines were used to examine the association between PaCO2 and in-hospital mortality. Nine thousand six hundred and sixty patients were identified. A U-shaped association was found between the first 24-h PaCO2 and in-hospital mortality in all participants. The nadir for in-hospital mortality risk was estimated to be at 39.5mm Hg (p for nonlinearity < 0.001). In the subsequent subgroup analysis, similar results were found in patients with traumatic brain injury, metabolic or toxic encephalopathy, subarachnoid hemorrhage, cerebral infarction, and other encephalopathies. Besides, the mortality risk reached a nadir at PaCO2 in the range of 35-45mm Hg. The restricted cubic splines showed a U-shaped association between the first 24-h PaCO2 and in-hospital mortality in patients with other intracerebral hemorrhage and cerebral tumor. Nonetheless, nonlinearity tests were not statistically significant. In addition, Cox regression analysis showed that PaCO2 ranging 35-45mm Hg had the lowest death risk in most patients. For patients with hypoxic-ischemic encephalopathy and intracranial infections, the first 24-h PaCO2 and in-hospital mortality did not seem to be correlated. Both hypercapnia and hypocapnia are harmful to most patients with craniocerebral diseases. Keeping the first 24-h PaCO2 in the normal range (35-45mm Hg) is associated with lower death risk.

WS1.11. EEG in the ICU: Status Epilepticus and the Ictal-Interictal Continuum

Epileptic seizures and nonconvulsive status (NCSE) are common in the critically ill, but non- epileptic movements and posturing are even more common. EEG can provide clarification when seizures are suspected. Different EEG patterns form a continuum of non-seizure to seizure activity, and over- interpretation of these patterns may lead to inappropriate advice and treatment. Recurrent seizures are easiest to recognise, with rhythmic discharges having spatiotemporal evolution in frequency (>4Hz), morphology and distribution. Periodic patterns are the most difficult. Generalised periodic discharges (GPDs) may or may not be ictal, and the specific EEG findings combined with the clinical context determines the approach. Severe myoclonic encephalopathy may occur after cardiac arrest, and the EEG may show burst suppression, unreactive GPDs separated by isoelectric intervals, ± electrographic seizures. The prognosis is extremely poor irrespective of treatment. Lateralised periodic discharges (i.e. PLEDs) may be an interictal finding in epilepsy and after any acute cerebral insult such as stroke or herpes encephalitis, and usually indicates a predisposition to seizures rather than ongoing seizure activity. Generalised triphasic waves are mainly seen with metabolic and toxic encephalopathies and are usually not an ictal finding. Whilst they can be sharply contoured, they are recognised by their other characteristics including morphology, state-dependent reactivity, and lag in phase and/or morphology changes from front to back. Triphasic waves (and almost all periodic patterns) are suppressed by benzodiazepines, along with consciousness and respiration. Such EEG suppression, in the absence of clinical improvement, does not diagnose NCSE. Ambiguous patterns can also be seen, with stimulus-induced rhythmic, periodic or evolving discharges. Whilst non-convulsive seizures and NCSE may be detected in comatose patients, prognosis is largely determined by the underlying aetiology and its complications. Unresolved questions include what particular EEG patterns should consistently prompt aggressive treatment. It is not always possible to be certain that an EEG pattern is ictal or non- ictal, and in the correct clinical context (especially patients presenting with seizures or with a history of epilepsy) a treatment trial may be indicated to see if temporally associated clinical improvement occurs. EEG interpretation needs to be made within the clinical context by an expert reporter.

Do Triphasic Waves and Nonconvulsive Status Epilepticus Arise From Similar Mechanisms? A Computational Model.

Triphasic waves arising in patients with toxic metabolic encephalopathy (TME) are often considered different from generalized periodic discharges (GPDs) in patients with generalized nonconvulsive status epilepticus (GNCSE). The primary objective of this study was to investigate whether a common mechanism can explain key aspects of both triphasic waves in TME and GPDs in GNCSE. A neural mass model was used for the simulation of EEG patterns in patients with acute hepatic encephalopathy, a common etiology of TME. Increased neuronal excitability and impaired synaptic transmission because of elevated ammonia levels in acute hepatic encephalopathy patients were used to explain how triphasic waves and GNCSE arise. The effect of gamma-aminobutyric acid-ergic drugs on epileptiform activity, simulated with a prolonged duration of the inhibitory postsynaptic potential, was also studied. The simulations show that a model that includes increased neuronal excitability and impaired synaptic transmission can account for both the emergence of GPDs and GNCSE and their suppression by gamma-aminobutyric acid-ergic drugs. The results of this study add to evidence from other studies calling into question the dichotomy between triphasic waves in TME and GPDs in GNCSE and support the hypothesis that all GPDs, including those arising in TME patients, occur via a common mechanism.

Atypical or Typical Triphasic Waves-Is There a Difference? A Review.

The entity of triphasic waves (TWs) and TW encephalopathy has derived from the subjective art of EEG interpretation. Indeed, there are few if any guidelines regarding many different aspects of TWs. The authors seek to shed light on the nature and the diagnostic characteristics of various types of TWs, differentiating "typical" from "atypical" forms. The authors conclude that morphologies in the form of bursts of well-formed, smoothly contoured, negative-positive-negative, bilateral, symmetrical and synchronous, regular, reactive, periodic or rhythmic, 1.5 to 2.0 Hz, fronto-central, triphasic complexes with fronto-occipital lag meet the criteria for typical TWs and are highly suggestive of toxic-metabolic encephalopathies. These are most frequently hepatic, uremic, or sepsis-associated encephalopathies with multi-organ failure. In such cases, atypical TWs (frontopolar or parieto-occipital maximum, negative-positive or negative-positive-negative, asymmetric and asynchronous, unreactive, irregular, multifocal, continuous with spatiotemporal evolution, sharper and without fronto-occipital/occipito-frontal lag, or triphasic delta waves) are rarely seen. Atypical TWs are encountered in Angelman syndrome, toxic encephalopathies, hyperthyroidism/hypothyroidism, Hashimoto encephalopathy, nonconvulsive status epilepticus, dementia, sepsis-associated encephalopathy, cerebrovascular disorders, and certain boundary syndromes. Investigations describing TWs with uncommon etiologies revealed few with typical TWs, suggesting that the term "TWs" has been overused in the past. Triphasic waves arise from the interaction of multiple factors including toxic, metabolic, infectious, and structural disorders that affect circuits between thalamus and cortex. The patient's metabolic status, presence of potentially neurotoxic drugs, cerebral atrophy, white matter disease, dementia, or seizures help differentiate typical from typical TWs. Future studies will determine whether this dichotomy is heuristically and clinically helpful.

Pharmacogenetics of the Central Nervous System-Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia.

Simple SummaryDespite recent improvements in cure rates, pediatric acute lymphoblastic leukemia (ALL) patients remain at risk to develop relapse disease or suffer from therapy-associated side effects. Over 5% of adverse events appear in the central nervous system (CNS) and can impact survival or quality of life of the patients. Inherited genetic variations are possible predictive factors for these adverse events. This retrospective study aimed to investigate if inherited genetic variations in genes encoding drug-metabolizing enzymes and drug transporters localized in the blood-brain barrier are predictive for CNS events. Our results suggest that certain ABCB1, ABCG2 and GSTP1 gene polymorphisms influence CNS toxicity and CNS relapse. A more effective drug-clearance could lead to less toxicity but contribute to a higher chance of relapse and vice versa. Genetic variants in ABCB1, ABCG2 or GSTP1 genes are promising candidates for personalized medicine.Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations’ matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.

English

In this case report we discuss a patient with neurological manifestations thought to be a case of hepatic encephalopathy. With no improvement in symptoms despite treatment, it created a diagnostic dilemma. Eventually, toxicological investigations were done which revealed that heavy metal poisoning could be the possible culprit. Encephalopathy is characterised by impaired mental state as a result of a diffuse brain dysfunction or other psychiatric condition that induces unconsciousness, typically followed by diffuse electroencephalogram (EEG) anomalies. Both primary neurological and systemic disorders are root causes of encephalopathy. Encephalopathy results from several causes such as liver failure or liver cancer, metabolic abnormalities, anoxic encephalopathy, infections, exposure to harmful compounds such as lithium paint, synthetic contaminants (toxins), inflammations (systemic lupus erythematous, sarcoidosis), drug induced, demyelination (e.g., multiple sclerosis), degenerative process like Alzheimer disease, Parkinson disease and hereditary encephalopathies such as leukodystrophy of the white matter. 1 Humans have used heavy metals since many years. While many harmful health effects of heavy metals have long been established, exposure to heavy metals continues to rise in some parts of the world, especially in underdeveloped countries. Emissions have decreased over the past 100 years in most developed countries. Heavy metals are prevalent and remain in the ecosystem, in general causing bio amplification. Living systems frequently associate with heavy metals in different proportions in the habitat. Heavy metal exposure induces lipid peroxidation, Deoxyribonucleic Acid (DNA) damage and protein modification by generation of oxygen free radicals. Exposure to these metals occurs in occupational areas by equipment, air, food and drinking water. Prolonged exposure to heavy metals may lead to neurotoxicity and brain damage. When symptoms of toxic encephalopathy emerge immediately following single acute exposure to high levels of toxic chemicals it is termed as acute toxic encephalopathy. Other than that if symptoms emerge insidiously over time in association with repeated or chronic exposure to low levels of neurotoxins it is called as chronic toxic encephalopathy. 2 In some cases, diagnosis of toxic encephalopathy is complicated by the fact that toxic chemicals can also damage liver and kidneys. In these cases hepatic dysfunction must be successfully treated before diagnosis of toxic encephalopathy can be considered. It is a diagnosis of exclusion, so a full work up for other possible aetiologies such as hepatic, uremic and infectious should be done. In this case report we have discussed heavy metal encephalopathy masquerading as hepatic dysfunction.

Neurologic aspects of coronavirus disease of 2019 infection.

Central and peripheral nervous system manifestations of coronavirus disease 2019 (COVID-19) have been frequently reported and may cause significant morbidity and mortality. This review details the latest evidence on the neuropathogenesis and neurologic complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported neurologic complications include toxic-metabolic encephalopathy, acute cerebrovascular disorders, seizures, and anoxic-brain injury. These complications represent secondary injury due to COVID-19 related hypoxia, sepsis, hypercoagulability, or hyperinflammation. Postinfectious complications, such as encephalitis, postinfectious demyelination, and Guillain-Barré syndrome have been reported, but are rare. Recent reports of persistent neurocognitive symptoms highlight the possibility of lasting impairment. Although some neurologic complications should be treated with standard practices, further investigations are still needed to determine the optimal treatment of COVID-related neurologic complications, such as ischemic stroke. Entering into the next phase of the pandemic, investigations into the long-term neurologic and cognitive impacts of SARS-CoV-2 infection will be needed. Clinicians must have a high clinical suspicion for both acute and chronic neurologic complications among COVID-19 patients.