Cytotoxic Lesions Research Articles

Silent Devastation: Acute Marchiafava-Bignami Disease Unmasked by Chronic Alcoholism in a 24-Year-Old Male: A Case Report

Marchiafava-Bignami disease (MBD) is an uncommon condition that is mainly linked to prolonged alcoholism and nutritional deficits. It is characterised by necrosis and demyelination of the corpus callosum. Due to its rarity and vague clinical signs, this disorder can frequently be misdiagnosed. It manifests as a range of neurological symptoms, from altered awareness to motor impairments. We present a 24-year-old man in this case report who has a history of intravenous drug use, chronic alcohol intake, and recent binge drinking.He presented with a 10-day history of constipation, vomiting, and a high-grade continuous fever. Over two days, the patient’s condition deteriorated into a drowsy state with abdominal pain.On examination, the patient was drowsy but arousable, with stable vital signs except for hypertension. Neurological findings indicated reduced deep tendon reflexes, hypotonia, and neck stiffness. A systemic workup revealed normal brain CT findings, however, diffusion limitation was seen in the corpus callosum's splenium on MRI, along with mild oedema and T2/FLAIR hyperintensity. The lumbar puncture showed lymphocytic predominance, low CSF glucose, and elevated protein levels suggestive of a possible CNS infection. The differential diagnosis included Marchiafava-Bignami disease (MBD) and cytotoxic lesions of the corpus callosum (CLOCCs).The patient was managed with intravenous steroids, empirical antitubercular therapy (ATT), broad-spectrum antibiotics, and supportive care, including airway protection via intubation. Despite the late diagnosis, the clinical history of chronic alcoholism, recent binge, and imaging findings confirmed MBD. Early recognition and treatment of this disorder can improve neurological outcomes. The present study emphasises how crucial it is to take MBD into account when making a differential diagnosis for alcohol-related encephalopathies, especially in individuals who have neurological decline and prolonged alcohol consumption.

Transient HR enhancement by RAD51-stimulatory compound confers protection on intestinal rather than hematopoietic tissue against irradiation in mice

DNA double-strand breaks (DSBs) are cytotoxic lesions that compromise genomic integrity and trigger cell death. Homologous recombination (HR) is a major pathway for repairing DSBs in cycling cells. However, it remains unclear whether transient modulation of HR could confer protection to adult stem cells against lethal irradiation exposure. In this study, we investigated the radio-protective effect of the RAD51-stimulatory compound RS-1 on adult stem cells and progenitor cells with varying cycling rates in intestinal and hematopoietic tissues. Treatment with RS-1 even at high doses did not induce noticeable cell death or proliferation of intestinal crypt cells in vivo. Pretreatment with RS-1 before irradiation significantly decreased mitotic death, promoted DNA repair and enhanced the survival of intestinal stem cells and progenitor cells and increased the number of regenerative crypt colonies thereby mitigating IR-induced gastrointestinal syndrome. Moreover, RS1 pretreatment could increase the survival and regeneration of irradiated intestinal organoid in vitro, which can be rescued by RAD51 inhibitor. However, pretreatment with RS-1 in vivo did not elevate nucleated cell count or HSPCs in bone marrow after 6Gy irradiation. Additionally, there was no impact on mouse survival due to drug treatment observed. Thus, our data suggest that targeting HR as a strategy to prevent tissue damage from acute irradiation exposure may depend on cell cycling rates and intrinsic DNA repair mechanisms.

Alterations in the mechanical properties of single dsDNA molecules, bare or cell-encapsulated, upon exposure to UVA-only radiation and sunlight

Exposure to ultraviolet radiation, which leads to the formation of mutagenic and cytotoxic DNA lesions such as cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts (6–4 PPs), can be potentially fatal. The way UVA forms DNA lesions and alters DNA topology and mechanics is still unclear, unlike the cases of UVC and UVB. Herein, Atomic Force Microscopy (AFM) and AFM-based Force Spectroscopy (AFS) have been employed to investigate the topological and mechanical properties of single DNA molecules, bare or E. coli cell-encapsulated, with or without UVA (solar or from UV lamp) treatment. It is observed that both the dsDNA transitions, i.e., ‘B' to stretched ‘S' conformation and melting transition, are lost in UVA dose-dependent manner. Presumably, this is due to formation of the CPDs and 6–4 lesions that form inter-strand cross-links, causing dsDNA strand separation difficult. Gradual reduction in DNA extension length upon prolonged treatment with UVA-only radiation or sunlight (where, 95 % of solar UV is UVA) also indicates formation of the inter-strand cross-links, since such cross-links can reduce DNA flexibility and increase DNA stiffness. Although these observations are common for both bare and cell-encapsulated DNA, the UV dose at which the distinctive reversible BS and melting transition faded away varied widely from 240 kJ/m2 (bare DNA) to 900 kJ/m2 (cellular DNA). The UV-induced DNA damage was also evident in observation of increased number of open circular and linearized topologies, as formed due to single-strand and double-strand breaks, respectively, at damage sites, upon combined action of the apurinic/apyrimidinic site-specific endonucleases IV and V. The extent of DNA damage was further quantified by enzyme-linked immunosorbent assay, which is found to be correlated to the single molecule information.

Cytotoxic Lesions of the Corpus Callosum Associated with Influenza B and Levosulpiride-Induced Dystonia

Cytotoxic Lesions of the Corpus Callosum Associated with Influenza B and Levosulpiride-Induced Dystonia

Cytotoxic Lesion of the Corpus Callosum Caused by Dengue Virus Infection

ABSTRACT Dengue virus infection can cause a wide spectrum of clinical manifestations, ranging from mild fever to lethal dengue shock syndrome. Neurological manifestations include encephalitis, acute disseminated encephalomyelitis, Transverse myelitis, Guillain-Barre syndrome, and neuro-ophthalmic complications. We report a case of a 44-year-old male who was admitted to our hospital with high-grade fever, myalgia, retro-orbital pain, visual disturbances, and drowsiness. Hematological and serological parameters confirmed the diagnosis of dengue fever. Brain imaging demonstrated altered signal intensity in the splenium of the corpus callosum and eventually a diagnosis of a cytotoxic lesion of the corpus callosum (CLOCC) was made. The patient was managed conservatively and discharged 7 days after admission and imaging findings were resolved completely 3 weeks later.

Cytotoxic lesions of the corpus callosum due to FOLFIRINOX chemotherapy

Cytotoxic lesions of the corpus callosum (CLOCCs) have gained attention due to their various clinical presentations and potential neurotoxic etiologies. The splenium connects visual areas across cerebral hemispheres and plays a vital role in processing visual cues. Previously, these reversible lesions were associated with mild encephalitis or encephalopathy, but in fact, they belong to a broader spectrum encompassing various syndromes. Often triggered by cytokinopathy, CLOCCs are usually hyperintense on T2/FLAIR, non-enhancing and show diffusion restriction.A 47-year-old woman with pancreatic ductal adenocarcinoma undergoing FOLFIRINOX chemotherapy (folinic acid, fluorouracil, irinotecan and oxaliplatin) developed strabismus and dizziness two days post-chemo. Neurological examination identified an incomplete wall-eyed bilateral internuclear ophthalmoplegia – a rare finding. Neuroimaging revealed restricted diffusion involving the splenium of the corpus callosum, discreetly hyperintense on T2/FLAIR, non-enhancing and without significant associated mass effect. Neurotoxicity and encephalopathy related to 5-FU were considered, leading to hospitalization. Ammonia levels and liver function were normal. Following discontinuation of the drug, the patient had a fast full clinical recovery and a follow-up MRI confirmed total resolution of splenium lesions. Posteriorly, she completed six cycles of Gemcitabine, uneventfully.This case highlights the spectrum of CLOCCs and the potential neurotoxicity of chemotherapy agents, specifically 5-FU. The patient's unique presentation of bilateral internuclear ophthalmoplegia, enriches the understanding of its manifestations. This case emphasizes the need to consider toxic etiologies alongside conventional triggers. Further research into the neurological effects of chemotherapeutic agents, especially 5-FU, on the corpus callosum is crucial.

Magnetic resonance imaging (MRI) and computed tomography angiography (CTA) assisted diagnosis of cytotoxic lesions of the corpus callosum (CLOCC) mimicking Splenial Infarction: A case report

Magnetic resonance imaging (MRI) and computed tomography angiography (CTA) assisted diagnosis of cytotoxic lesions of the corpus callosum (CLOCC) mimicking Splenial Infarction: A case report

Deciphering seizure semiology in corpus callosum injuries: A comprehensive systematic review with machine learning insights

IntroductionSeizure disorders have often been found to be associated with corpus callosum injuries, but in most cases, they remain undiagnosed. Understanding the clinical, electrographic, and neuroradiological alternations can be crucial in delineating this entity. ObjectiveThis systematic review aims to analyze the effects of corpus callosum injuries on seizure semiology, providing insights into the neuroscientific and clinical implications of such injuries. MethodsAdhering to the PRISMA guidelines, a comprehensive search across multiple databases, including PubMed/Medline, NIH, Embase, Cochrane Library, and Cross-ref, was conducted until September 25, 2023. Studies on seizures associated with corpus callosum injuries, excluding other cortical or sub-cortical involvements, were included. Machine learning (Random Forest) and deep learning (1D-CNN) algorithms were employed for data classification. ResultsInitially, 1250 articles were identified from the mentioned databases, and additional 350 were found through other relevant sources. Out of all these articles, 41 studies met the inclusion criteria, collectively encompassing 56 patients The most frequent clinical manifestations included generalized tonic-clonic seizures, complex partial seizures, and focal seizures. The most common callosal injuries were related to reversible splenial lesion syndrome and cytotoxic lesions. Machine learning and deep learning analyses revealed significant correlations between seizure types, semiological parameters, and callosal injury locations. Complete recovery was reported in the majority of patients post-treatment. ConclusionCorpus callosum injuries have diverse impacts on seizure semiology. This review highlights the importance of understanding the role of the corpus callosum in seizure propagation and manifestation. The findings emphasize the need for targeted diagnostic and therapeutic strategies in managing seizures associated with callosal injuries. Future research should focus on expanding the data pool and exploring the underlying mechanisms in greater detail.

Cytotoxic Lesion of Corpus Callosum after COVID-19 Vaccination: Case Report

Purpose: Cytotoxic lesions of corpus callosum (CLOCCs) are associated with many disease entities. Serious neurological complications after coronavirus disease 2019 (COVID-19) vaccination are rare. Case report: A 20-year-old man presented with severe headache for 2 days. He had received the first dose of ChAdOx1nCoV-19 COVID-19 vaccine 5 days ago. Persistent dull headache occurred on the third day after vaccination and intensified gradually to awaken him from sleep at night. No neck stiffness was observed. Brain magnetic resonance angiography (MRA) 9 days after vaccination revealed an oval-shaped diffusion-weighted restriction lesion at the splenium of corpus callosum with a mildly high signal intensity on T2-weighted images (T2WI) and low signal intensity on apparent diffusion coefficient (ADC) imaging but without enhancement after contrast injection. A COVID-19 polymerase chain reaction test was negative. A blood test revealed slight leukocytopenia, thrombocytopenia, and hyponatremia. Further autoimmune and hematological studies were normal. A cerebrospinal fluid study revealed normal intracranial pressure. The patient’s headache improved gradually. Follow-up brain MRA 5 weeks after vaccination revealed complete disappearance of the diffusion-weighted restriction lesion of the splenium. Conclusion: CLOCCs are rare transient adverse effect of COVID-19 vaccination possibly related to a cytokine storm. The splenic lesion might disappear spontaneously with a good prognosis.

Cytotoxic Lesions of the Corpus Callosum Associated with Aneurysmal Subarachnoid Hemorrhage May Influence Shunt-Dependent Chronic Hydrocephalus

BackgroundCytotoxic lesions of the corpus callosum (CLOCCs) are occasionally associated with aneurysmal subarachnoid hemorrhage (aSAH). The effects of aSAH on clinical outcomes in such cases are unclear. The present study aimed to investigate the frequency and characteristics of CLOCCs associated with aSAH to ascertain the predictors of shunt-dependent chronic hydrocephalus (SDCH) after aSAH. MethodsWe retrospectively investigated cases of aSAH treated by coil embolization. Patients were divided into those with and without CLOCCs. Between-group differences were evaluated, including clinical outcomes and the characteristics of both the patients and the aneurysms. Patients were divided into those with and without SDCH to identify predictive factors of SDCH after aSAH focusing on CLOCCs. ResultsThis single-center study included 196 patients with aSAH. All patients received coil embolization between April 2013 and March 2020. CLOCCs were detected in 38 (19.4%) patients. In the group with CLOCCs, male sex, poor severity grade at onset, acute hydrocephalus, SDCH (all P < 0.01), and Fisher group 3 or 4 (P = 0.04) were significantly more common than in the group without CLOCCs. Diabetes and CLOCCs were significant predictors of SDCH after aSAH in multivariate analysis (diabetes: P < 0.01, odds ratio [OR]: 6.73, 95% confidence interval [CI]: 1.61–28.09; CLOCCs: P < 0.01, OR: 6.86, 95% CI: 2.87–16.38). ConclusionsCLOCCs and SDCH were common in patients with poor-grade aSAH, and CLOCCs were independent predictors of SDCH after aSAH. Meticulous follow-up is necessary to detect SDCH after aSAH, especially in patients with poor-grade aSAH and CLOCCs.

Cytotoxic lesion of corpus callosum secondary to phenytoin toxicity.

Cytotoxic lesion of corpus callosum secondary to phenytoin toxicity.

Etiologic factors and imaging features of cytotoxic lesions of the corps callosum (Cloccs): A series of 5 patients

Cytotoxic Lesions of the Corpus Callosum (CLOCCS) are secondary lesions associated with various etiologies, including trauma, infection, and metabolic disorders. Recognizing these lesions is crucial as they can mimic primary callosal lesions such as ischemia. This retrospective study presents a series of five patients with CLOCCS, evaluating their clinical and radiological characteristics over a one-year period. Imaging, particularly MRI, plays a pivotal role in diagnosis, with diffusion-weighted sequences revealing characteristic features of cytotoxic edema. Clinical context, additional imaging findings, and patient history aid in distinguishing CLOCCS from other pathologies. The study highlights diverse etiologies contributing to CLOCCS, including trauma, infection (e.g., Malaria, COVID-19), and metabolic disorders. Treatment strategies depend on addressing the underlying cause. Understanding the spectrum of etiologies and imaging features of CLOCCS is vital for accurate diagnosis and appropriate management.

Diagnosis of Transient Brain Lesion in the Corpus Callosum Splenium in Emergency Service and Elucidation of Accompanying Conditions

Corpus Callosum Cytotoxic Lesion (CLOCCs) once rarely seen in the literature has been more often diagnosed in emergency services nowadays with widespread use of cranial magnetic resonance imaging (MRI). CLOCCs is defined as a clinical and radiological spectrum disorder. Patient’s neurological symptoms usually improve completely within 1 month after the onset of the disease without any sequel. This is generally associated with cytotoxic edema of the splenium corpus callosum. It is important investigate the primary causes that lead to this condition and start the appropriate treatment according to the real diagnosis. We present a case diagnosed as CLOCCs secondary to pneumonia upon admission to our emergency service.

Cytotoxic Lesion of the Corpus Callosum: A Case of Metabolic Disease in a New Mother

Cytotoxic lesions of the corpus callosum (CLOCCs) represent an array of different conditions involving the corpus callosum. CLOCCs do not demonstrate definite signs or symptoms of hemispheric disconnection, such as alien hand syndrome, pseudo-neglect, apraxia of the left hand, agraphia, alexia, and visual apraxia. In fact, symptoms are generally related to the primary cause of the cytotoxic lesion, such as pharmaceutical agents, malignancies, infections, metabolic disorders, trauma, and others.

Posterior Reversible Leukoencephalopathy With Hemorrhagic Features: A Case Series.

Introduction Posterior reversible leukoencephalopathy syndrome (PRES) is a clinical-radiological condition characterized by reversible subcortical vasogenic cerebral edema of acute or subacute onset in circumstances that disrupt capillary permeability, unfrequently accompanied by cytotoxic and/or hemorrhagic lesions. We describe a case series of PRES with hemorrhagic features. Subjects and methods Electronic medical records of hospitalized patients diagnosed with PRES from January 2009 to December 2021 were collected. Demographic data, medical history, clinical presentation, and outcome were recorded. Variables were compared between patients with and without hemorrhagic features using the Wilcoxon-Mann-Whitney test with a statistical significance level of p<0.05. Results Over a 12-year period, 33 patients were diagnosed with PRES, of whom 10 had hemorrhagic features: seven cortical microbleeds, two intraparenchymal hematomas, and one subarachnoid hemorrhage. Half of the patients were women, with a median age of 45.8 years (interquartile range (IQR) 21.8), and were admitted for non-neurological reasons. The sample included nine transplant recipients (six solid organa, three bone marrowa), with four patients in the immediate post-transplant period. PRES occurred in the context of infections and blood pressure fluctuations under cytotoxic drugs, such as immunosuppressants. Seventy percent showed improvement/resolution on neuroimaging at a median of 70 days (IQR 62.9). The three major hemorrhages occurred in the context of thrombocytopenia. The recorded in-hospital mortality was 10%. When compared to PRES without hemorrhagic features, patients with hemorrhagic features had a lower use of corticosteroids (50% vs. 78.8%; p=0.02) and a higher presence of restrictive lesions on neuroimaging (60% vs. 17%; p=0.04), with no differences in the other analyzed variables. Conclusion Patients with PRES and hemorrhagic features had a lower use of corticosteroids and a higher presence of restrictive lesions on neuroimaging. Further studies are needed to better understand the clinical implications and management of PRES with hemorrhagic manifestations.

Diffusion Restriction in the Splenium: A Comparative Study of Cytotoxic Lesions of the Corpus Callosum (CLOCCs) versus Lesions of Vascular Etiology.

Cytotoxic lesions of the corpus callosum (CLOCCs) have broad differential diagnoses. Differentiating these lesions from lesions of vascular etiology is of high clinical significance. We compared the clinical and radiological characteristics and outcomes between vascular splenial lesions and CLOCCs in a retrospective cohort study. We examined the clinical and radiologic characteristics and outcomes in 155 patients with diffusion restriction in the splenium of the corpus callosum. Patients with lesions attributed to a vascular etiology (N = 124) were older (64.1 vs. 34.6 years old, p < 0.001) and had >1 vascular risk factor (91.1% vs. 45.2%, p < 0.001), higher LDL and A1c levels, and echocardiographic abnormalities (all p ≤ 0.05). CLOCCs (N = 31) more commonly had midline splenial involvement (p < 0.001) with only splenial diffusion restriction (p < 0.001), whereas vascular etiology lesions were more likely to have multifocal areas of diffusion restriction (p = 0.002). The rate of in-hospital mortality was significantly higher in patients with vascular etiology lesions (p = 0.04). Across vascular etiology lesions, cardio-embolism was the most frequent stroke mechanism (29.8%). Our study shows that corpus callosum diffusion restricted lesions of vascular etiology and CLOCCs are associated with different baseline, clinical, and radiological characteristics and outcomes. Accurately differentiating these lesions is important for appropriate treatment and secondary prevention.

Ubiquitin signaling and the proteasome drive human DNA-protein crosslink repair.

DNA-protein crosslinks (DPCs) are large cytotoxic DNA lesions that form following exposure to chemotherapeutic drugs and environmental chemicals. Nucleotide excision repair (NER) and homologous recombination (HR) promote survival following exposure to DPC-inducing agents. However, it is not known how cells recognize DPC lesions, or what mechanisms selectively target DPC lesions to these respective repair pathways. To address these questions, we examined DPC recognition and repair by transfecting a synthetic DPC lesion comprised of the human oxoguanine glycosylase (OGG1) protein crosslinked to double-stranded M13MP18 into human cells. In wild-type cells, this lesion is efficiently repaired, whereas cells deficient in NER can only repair this lesion if an un-damaged homologous donor is co-transfected. Transfected DPC is subject to rapid K63 polyubiquitination. In NER proficient cells, the DPC is subject to K48 polyubiquitination, and is removed via a proteasome-dependent mechanism. In NER-deficient cells, the DNA-conjugated protein is not subject to K48 polyubiquitination. Instead, the K63 tag remains attached, and is only lost when a homologous donor molecule is present. Taken together, these results support a model in which selective addition of polyubiquitin chains to DNA-crosslinked protein leads to selective recruitment of the proteasome and the cellular NER and recombinational DNA repair machinery.

Role of the rostral dorsomedial column of the periaqueductal gray during social defeat in rats.

Previous studies showed that the dorsal premammillary nucleus of the hypothalamus (PMD) is involved in social passive defensive behaviors likely to be meditated by descending projections to the periaqueductal gray (PAG). We focused on the rostral dorsomedial PAG (rPAGdm) to reveal its putative neural mechanisms involved in mediating social defensive responses. By combining retrograde tracing and FOS expression analysis, we showed that in addition to the PMD, the rPAGdm is influenced by several brain sites active during social defeat. Next, we found that cytotoxic lesions of the rPAGdm drastically reduced passive defense and did not affect active defensive responses. We then examined the rPAGdm's projection pattern and found that the PAGdm projections are mostly restricted to midbrain sites, including the precommissural nucleus, different columns of the PAG, and the cuneiform nucleus (CUN). Also, we found decreased FOS expression in the caudal PAGdm, CUN, and PMD after the rPAGdm was lesioned. The results support that the rPAGdm mediates passive social defensive responses through ascending paths to prosencephalic circuits likely mediated by the CUN. This study provides further support for the role of the PAG in the modulation of behavioral responses by working as a unique hub for influencing prosencephalic sites during the mediation of aversive responses.

A case of reversible cytotoxic lesion of corpus callosum (CLOCCs) secondary to septic encephalopathy caused by suspected enteric fever

Abstract not available Bangladesh Crit Care J September 2023; 11 (2): 140-141

Diffusion-Restricted Lesions of the Splenium: Clinical Presentation, Radiographic Patterns, and Patient Outcomes.

Diffusion-restricted (DR) lesions of the splenium are encountered in a wide variety of pathologies, and their significance is often unclear. We sought to report the spectrum of clinical presentations, neuroimaging patterns, and the predictors of radiographic and clinical outcomes from DR splenial lesions. This was a single-center, retrospective cohort study from January 1, 2009, to August 1, 2020. A consecutive sample of 3,490 individuals who underwent brain MRI with reported corpus callosum lesions during the study period were evaluated for DR lesions in the corpus callosum. DR lesions were defined as increased signal intensity on diffusion-weighted imaging sequences with decreased signal intensity on apparent diffusion coefficient. Patients with prior neurosurgical procedures, hemorrhage-associated DR, anoxic brain injury, and chronic or previously known or characterized disease processes in the corpus callosum were excluded. Clinical and radiologic outcomes were ascertained, including readmissions within 1 year, in-hospital mortality rates, and resolution of DR at first follow-up imaging. Outcomes were defined a priori. Two hundred patients met criteria for inclusion. The average age was 57 years (standard deviation 19 years). Near half of the patients were women (47%). Encephalopathy (55%), focal weakness (46.5%), and cortical signs (44%) were the most common presenting clinical features. Thirty-five cases (17.5%) had features consistent with cytotoxic lesions of the corpus callosum (CLOCCs). Vascular causes were most frequent (61%), followed by malignancy-related (15%) and trauma (8%). In-hospital mortality occurred in 8.5% of cases, 46.5% were readmitted to the hospital within 1 year, and 49.1% of patients had resolution of the splenial DR at the next scan. Backward stepwise regression models showed that mass effect was negatively associated with splenial DR resolution (odds ratio [OR]: 0.12, confidence interval [CI] 0.03-0.46, p = 0.002). Encephalopathy was significantly associated with in-hospital mortality (OR: 4.50, CI 1.48-17.95, p = 0.007). Patients with a CLOCC had less frequent readmissions at 1-year compared with patients without a CLOCC, p = 0.015. Vascular DR lesions of the splenium were more common than CLOCCs and other etiologies in this cohort. While splenial DR lesions can present a clinical challenge, their associated clinical and radiographic characteristics may predict outcome and guide prognosis.