Laminar Necrosis Research Articles

Paracetamol overdose associated with cortical blindness-complicated acute leukoencephalopathy: a case report

BackgroundParacetamol is one of the most used antipyretics and analgesics among pediatrics, and its overdose is highly encountered among pediatrics especially in the pre-school age. While it is well-known that paracetamol overdose may lead to toxicities including severe hepatic toxicity, some recent reports have highlighted its “in situ” toxicity on brain tissue at high doses, even in the absence of hepatotoxicity. This can result in acute leukoencephalopathy (AL), coma, or even death. This report describes a case of a child who developed cortical blindness-complicated AL, following a paracetamol overdose.Case presentationAn 18-month-old previously healthy girl accidentally ingested 300 mg/kg of paracetamol suspension. After ingestion, the child was in an initial bad condition that has gradually improved. Several days after ingestion, the patient lost her vision, and she remained blind since then despite a newer appreciation to light. The initial brain magnetic resonance imaging (MRI) suggested AL demonstrated as a faint high T2/fluid-attenuated inversion recovery (FLAIR) signal intensity in the cortical and subcortical regions of both parieto-occipital lobes with sulcal effacement and restricted diffusion. After around 3 months, the subsequent brain MRI showed involutional changes that were manifested as a brain volume loss in the same areas with evidence of gyri-form laminar necrosis in both parieto-occipital regions without restricted diffusion. Other brain MRI findings include right cerebral convexity hyperacute subdural hematoma with prominent subarachnoid spaces.ConclusionsThe child developed cortical blindness-complicated AL following a paracetamol overdose. It is well- known that AL may result from several toxins by their direct and/or indirect effect on the cerebral white matter. However, there is still no enough data in the literature clearly explaining the relation of paracetamol overdose to AL. The generally proposed effect of paracetamol on the brain is mainly justified by the excessive oxidative stress. Further studies at the cellular and genetic levels are still needed to investigate the exact association between paracetamol overdose and AL, as well as the underlying mechanisms involved.

Vascular variant of Eagle syndrome: a review.

Eagle syndrome is defined as an elongated styloid process (ESP) that compresses nearby vasculo-nervous structures. The vascular variant of Eagle syndrome can lead to neurological symptoms including syncope, transient ischemic attack, or stroke; however, it has also been associated with other atypical presentations, making its diagnosis challenging. This review aimed to depict the characteristics of patients with the symptomatic vascular variant of Eagle syndrome. The literature search identified 56 reported cases of vascular variants of Eagle syndrome, with a mean age at onset of 51 years (range: 15-85 years), and the male-to-female ratio was 2:4. The ESP was bilateral in 63% of the cases, and the mean length was 48 mm (range: 31-77 mm). Vascular complications were mostly represented by internal jugular vein (IVJ) stenosis (n = 28), followed by internal carotid artery (ICA) dissection (n = 15). Additionally, eight cases of ICA thrombosis and two cases of severe chronic stenosis of the ICA > 90% were reported. Vascular complications may lead to cerebral ischemia due to either a thromboembolic mechanism or, less frequently, reduced blood flow. Laminar cortical necrosis, as a cerebral complication of ICA compression, was exceptionally described in one case, and such an atypical clinical presentation may be regarded as a diagnostic pitfall.

Simultaneous combined keyhole mini-transcranial approach and endoscopic transsphenoidal approach to remove multi-lobulated pituitary neuroendocrine tumor with suprasellar extension

BackgroundTranssphenoidal surgery (TSS) is the main method to remove pituitary neuroendocrine tumor (PitNET), but large or multi-lobulated one is still challenging. ObjectiveThe less invasive simultaneous combined keyhole mini-transcranial approach and standard transsphenoidal approach was used to remove multi-lobulated or hourglass-shaped non-functioning PitNET to avoid the specific complications related to extended TSS. MethodsTwenty-one patients of large multi-lobulated or hourglass-shaped PitNET (6 patients were recurrent cases after TSS or transcranial approach) were treated by this simultaneous combined approach. The supraorbital or midline keyhole approach was performed under the operating microscope so that the fine arteries feeding optic apparatus were dissected from the tumor capsule safely and securely and the suprasellar part of the tumor was removed in the extra-capsular fashion in combination with transsphenoidal approach. ResultsVisual function improved after the surgery in 14 (74 %) of 19 patients with preoperative disturbance of the visual fields. Four patients (19 %) developed postoperative deterioration of pituitary endocrine functions requiring permanent hormonal replacement. One patient (4.2 %) suffered cortical laminar necrosis without permanent disorders and another patient (4.2 %) suffered cerebrospinal fluid rhinorrhea but neither was permanent. Postoperative computed tomography detected no subarachnoid hemorrhage in any patient. Gross total removal was achieved in 15 patients (71 %). Five patients (24 %) with subtotal removal and one patient (4.2 %) with partial removal had lateral tumor extension with Knosp classification 3 or 4. ConclusionThe combined method is an effective treatment option to remove complex PitNET safely and securely with dissecting fine arteries on the tumor capsule.

THE OUTCOME OF COGNITIVE THERAPY IN PATIENTS WITH FIRST-EVER STROKE AND RECURRENT STROKE

Background: Vascular dementia (VaD) is the second most prevalent type of dementia that impacts elderly adults, succeeding Alzheimer's disease. In contrast to Alzheimer's disease, Vascular Dementia (VaD) presents a wide range of cognitive changes, which are greatly influenced by the specific neural regions that are impacted by vascular pathology. The incidence of dementia in adults with a prior history of stroke is 30%, demonstrating a frequency that is 3-5 times more than those without any discernible stroke-related impairments. In addition, the intensity or frequency of strokes may contribute to a decrease in cognitive reserve in persons with vascular dementia. Case Report: We presented two cases of VaD. The first case was a 62-year-old man with a history of ischemic stroke without sequelae a year before the complaints of frequent forgetfulness and cognitive impairment. Neuropsychological examination showed neurocognitive disturbances in orientation, attention, memory, and visuospatial domain with impaired daily activities function. The MRI result showed senile brain atrophy with chronic infarction on the right temporoparietooccipital lobe, left side mesencephalon, right side pons accompanied by cortical laminar necrosis on the right frontal lobe and left temporoparietal lobe. The second case was a 79-year-old man with history of recurrent ischemic stroke (three times since 2021-2022) with sequelae of left hemiparesis and complaints of frequent forgetfulness and cognitive impairment in the last 1 year. Neuropsychological examination showed neurocognitive disturbances in orientation, attention, and visuospatial domain with impaired daily activities function. The MRI result showed subacute multiple lacunar infarctions in right insular cortex, right frontotemporal lobe cortex, right corona radiata, with multiple chronic infarcts on the right frontotemporoparietal lobe, right corona radiata, right internal genu capsule, right lateral periventricular anterior horn, pons, right left cerebellum, also senile brain atrophy. Both patients were diagnosed as VaD and given donepezil 1x10mg and memantine 1x5mg to treat the cognitive impairment. Both cases showed improvements after 6 months of therapy with MMSE from 17 to 28, MoCA-INA from 12 to 22 and MMSE from 19 to 23, MoCA-INA from 14 to 21 respectively. Discussion: The probability of acquiring vascular dementia (VaD) was strongly associated with the incidence and frequency of strokes. The prevalence of newly developed dementia after the initial stroke is approximately 10%, which increases to 30% with recurrent strokes. The likelihood of experiencing cognitive impairment and dementia after a stroke is primarily determined by the specific attributes of the stroke. While pharmacological therapy largely focuses on cognitive impairment, other factors, such as the stroke's characteristics, might contribute to neuronal and molecular abnormalities that result in cognitive loss. Two instances were shown, both demonstrating enhancements, with the initial instance, involving primary strokes, exhibiting a superior outcome compared to the subsequent instance with recurring strokes. A more profound or recurring stroke has the potential to reduce cognitive reserve, hence potentially heightening vulnerability to neurodegenerative disorders, either directly or by means of modifications in social contacts or lifestyle, which can subsequently affect cognitive performance. Conclusion: Recurrent stroke plays a role in reducing cognitive reserve and increasing the risk of dementia. Patients with VaD have shorter life expectancy, thus the severity of VaD is best managed by providing optimum acute stroke care and recurrent stroke prevention.

A Cautionary Note on Pembrolizumab use in Patients with Ascending Aortic Aneurysms.

We describe a case of a patient treated with pembrolizumab (an immune checkpoint inhibitor) for metastatic scalp melanoma. He had a previous history of colorectal cancer, prostatic cancer and chronic polymyalgia rheumatica. The patient was known to have a stable ascending aortic aneurysm of 4.5 cm. However, he developed a rapid expansion of the ascending aortic aneurysm with the size crossing the threshold for surgery. The patient was referred to the cardiothoracic surgery service for intervention and he subsequently underwent surgery. The patient was electively admitted one week later for resection of aortic aneurysm, aortoplasty and external graft fixation. Pathologically, gross evidence of dissection was not identified; however, the histological analysis of the media showed laminar medial necrosis, multifocal in nature, with occasional clusters of histiocytic cells appreciated at their edge reminiscent of that seen in an inflammatory aortitis (granulomatous/giant cell type). Immune checkpoint inhibitor-induced aortitis is becoming increasingly evident, and its presentation can vary. It has been discovered incidentally on surveillance imaging with the use of nivolumab. In other cases, patients have been symptomatic to severely symptomatic. Atezolizumab with carboplatin and etoposide has been reported to cause abdominal aortitis which was responsive to corticosteroids and subsequent discontinuation of atezolizumab. Pembrolizumab has been linked to a case of transverse aortic arch aortitis. In our case, the inflammatory aortitis due to pembrolizumab was the cause of the rapid expansion of the ascending aortic aneurysm. Patients with known aortic aneurysms should undergo careful surveillance when commencing immune-checkpoint inhibitor therapy. Immune checkpoint inhibitors are being increasingly used in the treatment of metastatic malignancy. However, they are a relatively new group of medications, and the side effect profile of each is yet to be fully recognised. Aortitis has occurred with several different immune checkpoint inhibitors.Patients with known aortic aneurysms should undergo careful surveillance when commencing immune checkpoint inhibitors.All interventional therapeutic options should be considered early in these patients on the development of aneurysmal expansion.

Rogue AI: Cautionary Cases in Neuroradiology and What We Can Learn From Them.

Introduction In recent years, artificial intelligence (AI) in medical imaging has undergone unprecedented innovation and advancement, sparking a revolutionary transformation in healthcare. The field of radiology is particularly implicated, as clinical radiologists are expected to interpret an ever-increasing number of complex cases in record time. Machine learning software purchased by our institution is expected to help our radiologists come to a more prompt diagnosis by delivering point-of-care quantitative analysis of suspicious findings and streamlining clinical workflow. This paper explores AI's impact on neuroradiology, an area accounting for a substantial portion of recent radiology studies. We present a case series evaluating an AI software's performance in detecting neurovascular findings, highlighting five cases where AI interpretations differed from radiologists' assessments. Our study underscores common pitfalls of AI in the context of CT head angiograms, aiming to guide future AI algorithms. Methods We conducted a retrospective case series study at Stony Brook University Hospital, a large medical center in Stony Brook, New York, spanning from October 1, 2021 to December 31, 2021, analyzing 140 randomly sampled CT angiograms using AI software. This software assessed various neurovascular parameters, and AI findings were compared with neuroradiologists' interpretations. Five cases with divergent interpretations were selected for detailed analysis. Results Five representative cases in which AI findings were discordant with radiologists' interpretations are presented with diagnoses including diffuse anoxic ischemic injury, cortical laminar necrosis, colloid cyst, right superficial temporal artery-to-middle cerebral artery(STA-MCA) bypass, and subacute bilateral subdural hematomas. Discussion The errors identified in our case series expose AI's limitations in radiology. Our case series reveals that AI's incorrect interpretations can stem from complexities in pathology, challenges in distinguishing densities, inability to identify artifacts, identifying post-surgical changes in normal anatomy, sensitivity limitations, and insufficient pattern recognition. AI's potential for improvement lies in refining its algorithms to effectively recognize and differentiate pathologies. Incorporating more diverse training datasets, multimodal data, deep-reinforcement learning, clinical context, and real-time learning capabilities are some ways to improve AI's performance in the field of radiology. Conclusion Overall, it is apparent that AI applications in radiology have much room for improvement before becoming more widely integrated into clinical workflows. While AI demonstrates remarkable potential to aid in diagnosis and streamline workflows, our case series highlights common pitfalls that underscore the need for continuous improvement. By refining algorithms, incorporating diverse datasets, embracing multimodal information, and leveraging innovative machine learning strategies, AI's diagnostic accuracy can be significantly improved.

Abstract WP129: Half of Acute Cortical Lesions in Minor Acute Ischemic Stroke Patients Persist on Flair at 30-day

Introduction: Ischemic lesions seen on acute DWI often result in chronic infarction on FLAIR. However, in minor stroke a proportion of cortical lesions seem to disappear. The objective of this study was to characterize the persistence rate of acute cortical lesions on FLAIR and associated imaging markers on 3DT1 at 30-day. Methods: Consented minor stroke patients (NIHSS<6) presented acutely (<24 hrs) received MRI at baseline, 5-day, and 30-day. One qualifying cortical lesion per patient was evaluated on baseline DWI for volume, white matter involvement, and on follow-up FLAIR for signal intensity ratio (SIR): comparison of lesion vs contralateral homologous tissue. Three independent raters blinded to hemisphere and exact location of the DWI lesion evaluated 3DT1 and FLAIR on follow-up (Figure). Results: Of 159 consented patients, 30 met criteria, and lesions of 28 patients (18%) evolved as hyperintense on FLAIR at 5-day. The 28 patients had a median age of 70 years, 54% female, median admit NIHSS of 2, and 32% were treated with IV alteplase. Of the 28 lesions, 17 (61%) had white matter involvement at baseline, and 14 (50%) were not evident on FLAIR at 30-day. Comparing those hyperintense vs not evident on FLAIR, raters identified 79% vs 21% (p<0.003) cavitation in white matter, 36% vs 0% (p<0.01) cavitation in gray matter, 57% vs 0% (p<0.001) laminar necrosis, and 100% vs 14% (p<0.001) cortical thinning on 3DT1. Lesions that persisted on FLAIR vs lesions not evident at 30-day had larger baseline DWI lesion volume: 2.2mL vs 0.3mL (p=0.024), and differences in SIR: 1.63 vs 1.3 (p=0.009) at 5-day, and 1.56 vs 1.1 (p=0.003) at 30-day. Conclusions: Half of the acute cortical lesions persisted on FLAIR at 30-day. Imaging markers on 3DT1 were more frequently associated with FLAIR evident lesions, but in ~1/3 of lesions not hyperintense, readers identified 3DT1 changes. Quantitative analysis is underway to confirm this observation.

Microbleeds within Mitochondrial Stroke-Like Lesion Rather Result from Their Vulnerability Than from Microangiopathy

MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episode) is one of the most common syndromic mitochondrial disorders (MID) and is due to the variant m.3243A>G in MT-TL1 in approximately 80% of cases. MELAS is a multisystem disorder with stroke-like episodes (SLEs) as a pathognomonic feature. The morphological correlate of SLEs in cerebral imaging are stroke-like lesions (SLLs). SLLs present on cerebral MRI with a T2, FLAIR, DWI, and PWI-hyperintense and OEF-hypointense lesion that is not confined to a vascular territory and extends to a nadir before disappearing or terminating as a structural lesion. Occasionally, these features are accompanied by microbleeds within the SLL, usually along the cortex. These microbleeds are thought to result from laminar cortical necrosis, and end-stage of a SLL or seizures, a common manifestation of SLEs.

Characterizing Cerebrovascular Pathologies in Brain Donors Exposed to Repetitive Head Impacts

AbstractBackgroundRepetitive head impacts (RHI) from American style football (ASF) and other contact sports are a known risk factor for the neurodegenerative disease chronic traumatic encephalopathy (CTE). RHI can also lead to mixed neuropathologies that uniquely contribute to clinical symptoms. Here, we compared various types of vascular and white matter pathologies between brain donors with and without exposure to RHI from different types of contact and collision sports (CCS).MethodsThe sample included 79 deceased male ASF players (RHI‐ASF) and 49 deceased male non‐ASF CCS athletes (RHI‐CCS) from the UNITE brain bank. Each RHI group had a comparison group that included similar aged (+/‐ 5 years) male brain donors without RHI from the Boston University Alzheimer’s Disease Research Center and Framingham Heart Study brain banks. The modified Ischemic Injury Scale (mIIS) served as a global indicator of vascular and white matter pathologies and is a sum of hippocampal sclerosis, infarct/lacune, microinfarct, microbleeds, laminar necrosis, arteriolosclerosis, atherosclerosis of Circle of Willis, cerebral amyloid angiopathy, and white matter rarefaction. Dementia diagnoses were made during consensus conferences. Linear or logistic regression compared the RHI vs non‐RHI groups on the mIIS and its subcomponents. Logistic regression models examined the association between mIIS and dementia. Models were adjusted for age.Results Table 1 shows sample characteristics. The RHI‐CCS group was comprised of boxers, amateur wrestlers, and ice hockey, soccer, rugby, and lacrosse players. 94 decedents had CTE, all of whom were in an RHI exposed group. Of the mIIS components, arteriolosclerosis was the most common across all groups. White matter rarefaction was also the most frequent mIIS component for both RHI groups, but not for non‐RHI groups. Compared to their respective controls, RHI‐ASF and RHI‐CCS were associated with higher mIIS scores (Table 2). Higher mIIS scores corresponded to increased odds for having dementia in both the RHI‐ASF and RHI‐CCS groups (Table 2). White matter rarefaction best discriminated both RHI groups from non‐RHI; atherosclerosis also discriminated RHI‐CCS group (Table 3).ConclusionThese results support vascular and white matter pathologies, specifically white matter rarefaction, as prominent and clinically relevant sequelae of RHI from CCS.

Posterior Reversible Encephalopathy Syndrome in a Hospitalized Pregnant Woman with SARS-CoV-2 Infection: A Case Report

: During pregnancy, SARS-CoV-2 infection (COVID-19) can be complicated, and the mother and neonate's prognosis is not fully documented. We are presenting the case of a 33-week pregnant patient with confirmed COVID-19 who developed encephalopathy. During the disease and hospitalization in a critical care setting, an emergency C-section was performed with general anesthesia in the ICU due to acidosis and maternal-fetal instability. The baby boy was delivered with an APGAR score of 8, showing no obvious anomalies, and was subsequently intubated. Eight days later, brain imaging revealed posterior reversible encephalopathy syndrome. The mother received treatment and was discharged without further complications. At the final follow-up six months after discharge, the patient's MRI showed laminar necrosis in the two occipitoparietal cortex areas. However, she remained symptom-free and did not report any complications. We also discussed the possible reasons for these findings and their relationship to the infection.

Abstract 117: Digitally Subtracted Angiogram & Biopsy Negative Recurrent Spontaneous Bilateral Anterior Cerebral Artery Territory Intracranial Hemorrhage

Introduction Up to 18% of spontaneous intracerebral hemorrhages are cryptogenic despite a thorough workup, usually noted in a lobar location. Although undetected on DSA, a significant proportion of these represent ruptured micro‐AVM/AVF or cavernous malformations that ultimately are amenable to surgical resection if detected on biopsy. However, occult cerebral amyloid angiopathy can also present similarly, and their management is markedly different. Methods We present a case of recurrent bilateral medial frontal hemorrhage in a patient without known cerebrovascular disease that evaded diagnosis despite hematologic evaluation, MRI, CTA, two DSAs, three clot evacuations with pathology, and brain biopsy. Results The patient is a 60‐year‐old previously healthy woman who presented with sudden onset right hemiparesis and speech arrest. CT revealed a left parasagittal hemorrhage. She was brought to the OR for clot evacuation. Pathology from the clot revealed blood vessels of multiple sizes consistent with meningeal vessels or underlying AVM/AVF. A 6‐vessel cerebral angiogram as unremarkable. The patient’s inpatient course was complicated by new onset Afib with RVR and asymptomatic DVT with PE, however no etiology of coagulopathy was detected. MRI brain showed no evidence of cerebral microbleed or other underlying pathology, noting only DWI + FLAIR hyperintensity in the left ACA territory. The patient was diagnosed with ACA territory stroke complicated by PH2‐type hemorrhagic conversion. She was initially placed on IV Heparin, before transition to apixaban uneventfully. She continued to recover in the hospital and was eventually discharged to rehab. She re‐presented 1 month later with worsening behavioral arrest and right hemiparesis. CT head revealed recurrence of left parasagittal ICH. She underwent clot evacuation in the OR again and repeat pathology was unrevealing. A repeat MRI showed only the evident bleed and a subtle hyperintensity in the right occipital cortex suspicious for an interval subacute occipital lobe stroke with laminar necrosis, ostensibly from Afib. She improved clinically and was discharged to rehab with a diagnosis of recurrent hemorrhage attributed to anticoagulant use and recent stroke. She was discharged this time on no anticoagulant or antiplatelets. She re‐presented 1 month later with sudden onset speech arrest, but now with left hemiparesis. CT revealed a right parasagittal hemorrhage. She was brought to the OR for emergent clot evacuation and parenchymal biopsy – which was initially normal. A repeat 6‐vessel DSA was again unremarkable as was repeat brain MRI. The patient’s parenchymal biopsy was sent for specific congo‐red and immunohistochemistry for beta‐amyloid. IHC revealed beta‐amyloid plaques in the parenchyma and vessel walls, confirming a diagnosis of CAA. Conclusion Apparently cryptogenic lobar hemorrhage may be caused by both occult micro‐AVM/fistula and CAA. As in this case, when a patient experiences recurrent DSA negative lobar hemorrhages, biopsy should be pursued. This case was particularly challenging given the anatomical plausibility of parasagittal AVM/fistula given its midline location and venous drainage, considering the patient’s evident predisposition to systemic venous thrombosis hemorrhagic venous infarction mimicking lobar ICH is also possible. We present this case to raise awareness of the potential need for early biopsy, especially in patients who may also require anticoagulation or antiplatelet medications.

Polioencephalomalacia in Buffaloes in the Amazon Biome.

The epidemiological and clinical pathological aspects of polioencephalomalacia (PEM) in five buffaloes in the Amazon biome are described. Epidemiological data were obtained during the clinical visit in which buffalos were submitted to an examination of the nervous system. The diagnosis of PEM was based on epidemiological, clinical-pathological, and histopathological findings, similar to findings in other ruminants. In the clinical examination, all buffaloes had a body score between 2.5 and 3 (scale from 1 to 5), with decreased alertness, postural changes, marked hypermetria when stimulated to move, total or partial blindness demonstrated by colliding with the corral structures, head pressing and circumduction of the hindquarters when supported on the thoracic limbs, opisthotonos, muscle tremors, convulsions, paddling movements, sialorrhea, decrease in palpebral and pupillary reflexes, and eyeball rotation placing the pupillary slit in a vertical position. At necropsy, mild lesions characterized by edema and flattening of the cerebral convolutions were observed. A histopathological examination showed laminar necrosis of the cerebral cortex. The cause of PEM in the studied buffaloes was not established, which indicates the need for further studies to elucidate this disease in the species, particularly in the Amazon region.

Delayed Death Due to Methanol Poisoning: An Autopsy Case Report

Methanol is a non-drinking type of alcohol used for industrial and automotive purposes. Methanol itself is not dangerous, but its harmful metabolites may cause the accumulation of acid in the blood, leading to metabolic acidosis, permanent blindness, and death. In this case report study, the case was a 28-year-old Nepalese man who was admitted in a semi-unconscious state to the emergency department. A working diagnosis of methanol poisoning was made. After more than two weeks, he succumbed to death due to a worsening cerebral infarction. At autopsy, extensive hemorrhagic infarction was observed, involving bilateral cerebral hemispheres. Well-defined subcortical hemorrhages leading to laminar necrosis were seen at the frontoparietal lobes. Cystic or lacunar necrosis was present at the basal ganglia. The brainstem showed the presence of duret hemorrhage. The man died approximately three weeks after the methanol ingestion. This case highlights the important pathological changes and accumulating effects of methanol in the brain.

Histological Alterations in Placentas of Pregnant Women with SARS-CoV-2 Infection: A Single-Center Case Series.

This study aimed to investigate the histopathological changes associated with SARS-CoV-2 infection in placentas. A case series of anatomopathological analysis was conducted on the placentas of pregnant women with SARS-CoV-2 who delivered between March and December 2020 at Santo Amaro Hospital (HSA) in Salvador, Brazil. Out of the 29 placentas examined, the median weight was 423.0 (IQR: 385.0-521.0) g. Among them, 58.3% (n = 14) had inadequate weight relative to the newborn's weight. The histopathological findings revealed that 86.2% (n = 25) of the placentas had poorly defined lobes, and the fetal and maternal surface color was normal in 89.7% (n = 26) and 93.1% (n = 27), respectively. Additionally, 51.7% (n = 15) of the umbilical cords displayed hypercoiling. The most frequent microscopic finding was infarction, present in 35.3% (n = 6) of the cases, followed by 11.8% (n = 2) for each of chorioamnionitis, chronic villitis, focal perivillositis, and laminar necrosis. Analysis of the umbilical cords identified 23.5% (n = 4) cases of intervillous thrombosis, while amnion analysis showed 13.8% (n = 4) cases of squamous metaplasia. Extraplacental membrane examination revealed fibrin deposition in 93.1% (n = 27) of the cases, necrosis in 62.0% (n = 18), calcifications in 51.7% (n = 15), cysts in 37.9% (n = 11), neutrophilic exudate in 17.2% (n = 5), thrombosis in 13.7% (n = 4), and delayed placental maturation in 6.9% (n = 2). All analyzed placentas exhibited histopathological changes, primarily vascular and inflammatory, which indicate SARS-CoV-2 infection in term pregnancies. These alterations could be associated with impaired placental function, fetal growth restriction, preeclampsia, and prematurity. However, further prospective studies are required to validate the type, prevalence, and prognosis of each of these changes.

Hearing Impairment and Neuroimaging Results in Mitochondrial Diseases.

Mitochondrial diseases (MDs) are heterogeneous genetic disorders characterized by mitochondrial DNA (mtDNA) defects, involving tissues highly dependent on oxidative metabolism: the inner ear, brain, eye, skeletal muscle, and heart. We describe adult patients with genetically defined MDs, characterizing hearing function and neuroimaging results. We enrolled 34 patients (mean age: 50.02 ± 15 years, range: 18-75 years; 20 females and 14 males) classified in four groups: MELAS, MIDD, PEO, and Encephalopathy/Polyneuropathy. Audiological evaluations included psychoacoustical tests (pure-tone and speech audiometry), electrophysiological tests (Auditory Brainstem Responses, ABRs), and Impedenzometry. Neuroimaging evaluations considered global MRI abnormalities or structural brain changes. In total, 19/34 patients carried the m.3243A > G mutation (6 affected by MELAS, 12 affected by MIDD, and 1 affected by PEO); 11 had an mtDNA deletion (all affected by PEO); 3 had nuclear genes associated with MDs (POLG1 and OPA1); and 1 patient had an mtDNA deletion without an identified nuclear gene defect (affected by PEO). Sensory neural, bilateral, and symmetrical hearing loss was present in 25 patients (73.5%) to different degrees: 9 mild, 9 moderate, 5 severe, and 2 profound. The severe/profound and mild hearing losses were associated with pantonal and high-frequency audiograms, respectively. Instead, moderate hearing losses were associated with both high-frequency (five cases) and pantonal (five cases) audiogram shapes. In addition, 21/25 patients showed a cochlear site of lesion (84%), and 4/25 (16%) showed a retrocochlear site. We found global MRI abnormalities or structural brain changes in 26/30 subjects (86.6%): 21 had white matter abnormalities, 15 had cortical atrophy, 10 had subcortical atrophy, 8 had basal nuclei involvement or cerebellar atrophy, 4 had stroke-like lesions or laminar necrosis, and 1 had cysts or vacuolated lesions. We concluded that genetic alterations are associated with different clinical presentations for both auditory function and neuroradiological findings. There is no fixed relationship between genotype and phenotype for the clinical conditions analyzed.

Neuropathological hallmarks in autopsied cases with mitochondrial diseases caused by the mitochondrial 3243A>G mutation.

The mitochondrial (m.) 3243A>G mutation is known to be associated with various mitochondrial diseases including mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Their clinical symptoms have been estimated to occur with an increased mitochondrial DNA (mtDNA) heteroplasmy and reduced activity of oxidative phosphorylation (OXPHOS) complexes, but their trends in the central nervous system remain unknown. Six autopsied mutant cases and three disease control cases without the mutation were enrolled in this study. The mutant cases had a disease duration of 1-27 years. Five of six mutant cases were compatible with MELAS. In the mutant cases, cortical lesions including a laminar necrosis were frequently observed in the parietal, lateral temporal, and occipital lobes; less frequently in the frontal lobe including precentral gyrus; and not at all in the medial temporal lobe. The mtDNA heteroplasmy in brain tissue samples of the mutant cases was strikingly high, ranging from 53.8% to 85.2%. The medial temporal lobe was preserved despite an inhospitable environment having high levels of mtDNA heteroplasmy and lactic acid. OXPHOS complex I was widely decreased in the mutant cases. The swelling of smooth muscle cells in the vessels on the leptomeninges, with immunoreactivity (IR) against mitochondria antibody, and a decreased nuclear/cytoplasmic ratio of choroidal epithelial cells were observed in all mutant cases but in none without the mutation. Common neuropathological findings such as cortical laminar necrosis and basal ganglia calcification were not always observed in the mutant cases. A high level of mtDNA heteroplasmy was observed throughout the brain in spite of heterogeneous cortical lesions. A lack of medial temporal lesion, mitochondrial vasculopathy in vessels on the leptomeninges, and an increased cytoplasmic size of epithelial cells in the choroid plexus could be neuropathological hallmarks helpful in the diagnosis of mitochondrial diseases.

Cortical Laminar Necrosis: Imaging Features and Etiological Oorientation

Cortical laminar necrosis corresponds to neuronal ischemic remodeling with gliosis and accumulation of lipid-rich macrophages secondary to various etiologies: hypoxia, prolonged arterial hypotension, hypoglycemia, status epilepticus or arrest. Diffusion and T2 (FLAIR) show cortical and basal ganglia hypersignal from the first 24 hours. T1 shows cerebral edema during the first two weeks and a characteristic spontaneous cortical and basal ganglia hypersignal delayed and transient (3rd week). On T2*, the cortical lesions do not show any asignal, which makes it possible to differentiate them from a hemorrhagic transformation. Cortical contrast can be observed from the first weeks and for several months (up to 9 months in case of focal ischemia) and translates a rupture of the blood-brain barrier. In CT, hypodense and hyperdense gyriform density abnormalities are seen depending on the time.

Investigation of CD56, ADAM17 and FGF21 Expressions in the Placentas of Preeclampsia Cases.

Objective: In the present study, we investigated the expression of CD56, ADAM17 and FGF21 antibodies (Ab), which we think have an effect on the pathophysiology of preeclampsia (PE), in pregnant patients with healthy placentas and placentas with PE. The expression of these antibodies has been investigated in a limited amount of former research, but their role in PE has not yet been clarified. With this study, we aimed to contribute to the elucidation of the pathophysiology of PE and the detection of new target molecules for treatment. Materials and Methods: Parturients with singleton pregnancy at 32 weeks or above without any maternal or fetal pathology who were admitted to the Department of Obstetrics and Gynecology, Zonguldak Bülent Ecevit University Practice and Research Hospital between 11 January 2020 and 7 January 2022 were included in the present study. Pregnant women with coexisting disease or a pathology related to the placenta (ablation placenta, vasa previa, hemangioma, etc.) were excluded. CD56, ADAM17 and FGF21 antibodies were histopathologically and immunohistochemically detected in 60 placentas with PE (study group) and 43 healthy placentas (control group). Results: CD56, ADAM17 and FGF21 proteins were all more intensely expressed in preeclamptic placentas and a statistically significant difference was found between the two groups for all three antibodies (p < 0.001). Deciduitis, perivillous fibrin deposition, intervillous fibrin, intervillous hemorrhage, infarct, calcification, laminar necrosis and syncytial node were found to be significantly more common in the study group (p < 0.001). Conclusions: We observed that CD56, ADAM17 and FGF21 expressions increased in preeclamptic placentas. These Ab may be responsible for the pathogenesis of PE, which can be illuminated with further studies.

Placental lesions attributed to shallow implantation, excess extravillous trophoblast and decidual hypoxia: Correlation with maternal vascular malperfusion and related obstetric conditions

IntroductionMaternal vascular malperfusion (MVM) is one of four main patterns of placental injury defined by the Amsterdam consensus statement and is associated with adverse fetal and maternal outcomes. Laminar decidual necrosis (DLN), extravillous trophoblast islands (ETIs), placental septa (PS), and basal plate multinucleate implantation-type trophoblasts (MNTs) are lesions attributed to decidual hypoxia, excess trophoblast, and shallow implantation, but are not included in the current MVM diagnostic criteria. We aimed to investigate the relationship between these lesions and MVM. MethodsA case-control model was used to evaluate for DLN, ETIs, PS, and MNTs. Placentas with MVM on pathologic examination (defined as ≥2 related lesions) constituted the case group, and maternal age- and GPA-status-matched placentas with less than 2 lesions constituted the control group. MVM-related obstetric morbidities were recorded, including hypertension, preeclampsia, and diabetes. These were correlated with the lesions of interest. Results200 placentas were reviewed: 100 MVM cases and 100 controls. MNTs and PS showed significant enrichment in the MVM group (p < .05). Furthermore, larger foci of MNTs (>2 mm linear extent) were significantly associated with chronic or gestational hypertension (OR = 4.10; p < .05) and preeclampsia (OR = 8.14; p < .05). DLN extent correlated with placental infarction, but DLN and ETIs (including size and number) lacked association with MVM-related clinical conditions. DiscussionAs a marker of abnormally shallow placentation and related maternal morbidities, MNT merits inclusion within the MVM pathologic spectrum. Consistent reporting of MNTs >2 mm in size is recommended, as these lesions correlate with other MVM lesions and MVM-predisposing morbidities. Other lesions, particularly DLN and ETI, lacked such association questioning their diagnostic utility.

Calcifications in Cerebral Infarcts: Report of Two Cases

Calcification in cerebral infarcts has been reported as an uncommon finding. CT hyperdensity in an infarct can also be due to hemorrhagic transformation and in MRI can be mimicked by cortical laminar necrosis seen as gyriform T1 hyper and T2 hypointensities. Susceptibility-weighted imaging (SWI) with phase image has been reported to differentiate calcification and hemorrhage. We report 2 cases of cerebral infarcts with a review of the literature. The first patient showed early gyriform calcification 10 days after the onset and showed partial resolution of the calcification on follow-up. The second patient showed plaque-like calcification within perisylvian infarct that was confirmed by SWI phase imaging.