Clinical Presentation Features Research Articles

Evaluating the Clinical Characteristics and Ophthalmic Manifestations in Children and Adolescents with Acquired Demyelinating Disorders in China

Aims/Background Pediatric acquired demyelinating disorders (ADS) include various monophasic and recurrent inflammatory conditions of the central nervous system (CNS). Optic neuritis (ON) is a demyelinating disease primarily affecting the optic nerve axons due to autoimmune inflammation. To investigate the clinical characteristics, ophthalmic manifestations, laboratory test results, and prognostic indicators of Chinese children and adolescents with ADS. Methods The clinical data of 57 patients with ADS treated in the Beijing Children’s Hospital from March 2021 to December 2023, were retrospectively collected and analyzed. The primary outcomes include best-corrected visual acuity (BCVA) at onset, peripapillary retinal nerve fiber layers (RNFL) thickness, serum myelin oligodendrocyte glycoprotein (MOG) antibody level, aquaporin-4 (AQP4) antibody level, and final BCVA after hormone therapy. Results The analyses included 57 children and adolescents in the study, including 38 optic neuritis (ON), 12 neuromyelitis optica spectrum disorder (NMOSD), 5 acute disseminated encephalomyelitis (ADEM), and 2 multiple sclerosis (MS) patients. The median age of patients facing the initial attack of ON was 9 years (3–15 years), with 23 children and adolescents (40.4%) aged eight years or younger, and 37 patients (64.9%) were bilaterally affected. Half of the children and adolescents (15/30) were MOG-Ab seropositive, and 19.4% (6/31) were AQP4-Ab seropositive. Children and adolescents with NMOSD were more likely to have severe visual impairment at acute onset (p < 0.05), with 84.2% of them having low vision acuity (BCVA worse than 0.1), as compared with 64.9% in the ON group. The RNFL thickness of affected eye was thinner than unaffected eyes (median 72.0 μm vs. median 102.0 μm, p < 0.05). Patients with NMOSD exhibited lower RNFL thickness across all measured sectors compared to those with ON. Significant differences were noted in the average RNFL and in each specific region of the retina, including the temporal RNFL, nasal RNFL, nasal superior RNFL, nasal inferior RNFL, temporal superior RNFL, and temporal inferior RNFL (all p < 0.05). After the treatment with intravenous methylprednisolone, both patients with ON (52 eyes; 86.7%) or NMOSD (20 eyes; 90.9%) group had functional visual recovery (BCVA better or equal 0.4). Conclusion This study shows that Chinese children and adolescents with ADS present distinctive clinical features, including earlier onset and more bilateral involvement. Furthermore, NMOSD patients experience more severe visual acuity impairment and thinner peripapillary RNFL. All children and adolescents of ON or NMOSD respond well to methylprednisolone treatment.

Radiological and clinical prognosis of posterior lumbar intervertebral body cage versus posterior transpedicular screw fixation in patient with isthmic spondylolisthesis

Background and objectives: Isthmic type of Spondylolisthesis, resulting from the failure of the anterior column, requires fixation by a transpedicular screw posteriorly. The research aimed to distinguish discrepancies in clinical presentation, functional outcomes, and mechanical characteristics by evaluating clinical, radiographic, activity, and pain information. Methods: A Prospective study was conducted from January 2016 until March 2020, at Erbil Teaching and Paky Hospital, Pedicle screw fixation was performed on 70 consecutive patients diagnosed with isthmic spondylolisthesis. Posterior transpedicular screw fixation was performed in 36 persons, while posterior lumbar intervertebral body fusion was performed in 34 persons. The assessments of the activity and pain statuses were performed prior to and post the surgical procedure. Results: There was no statistically significant divergence of the modifications. The statistical analysis conducted within the groups has demonstrated that the surgery had a significant impact on the subluxation percentage, angle of slippage, and foraminal area. Nevertheless, it had no impact on the sacral inclination or the segmental lordosis. The 3-year follow-up examination did not demonstrate any statistical intergroup differences regarding improvement neurologically (p=1.01), Activity outcome (p=0.52), Pain outcome (p=0.87), fusion rate (p=0.47). Nonetheless, the group that underwent PLIF procedure showed maintained subluxation correction, disc height, and foraminal area which was not observed in the fusion by only posterolateral approach group (p_0.07). Conclusion: The interbody fusion procedure provides enhanced mechanical strength to the spinal structure in instances of Isthmic spondylolisthesis. It is anticipated that the degree of correction attained will slowly decrease when posterior transpedicular fixation clinically.

Predictors of visual outcome in optic neuropathy of sarcoidosis.

Predictors of visual outcome in optic neuropathy of sarcoidosis.

CDK1 inhibitor RO-3306 enhances BTKi potency in diffuse large B-cell lymphoma by suppressing JAK2/STAT3 signaling.

CDK1 inhibitor RO-3306 enhances BTKi potency in diffuse large B-cell lymphoma by suppressing JAK2/STAT3 signaling.

Hypophophatasia: the importance of knowing in advance.

Hypophosphatasia (HPP) is a rare and highly variable genetic disorder of metabolism characterized by markedly reduced serum alkaline phosphatase (ALP) activity as a result of defective production of tissue-non-specific alkaline phosphatase (TNSALP). HPP is known to affect fetuses in utero and also neonates, children, and adults. Severity ranges significantly, from lethal to mild and clinical presentations include rickets or osteomalacia, osteoporosis, respiratory failure and seizures. Odontohypophosphatasia has only dental manifestations. Low total ALP in serum is the hallmark of HPP, whereas elevated serum concentrations of pyridoxal-5-phosphate and phosphoethanolamine levels represent sensitive and specific biomarkers for HPP. Several pathognomonic radiographic changes are suggestive of HPP. Recently, asfotase alfa, a bone targeted recombinant TNSALP has been used to treat HPP with significant success, highlighting the importance of early diagnosis and intervention. This review describes our current knowledge of HPP, reporting on the epidemiology, classification, clinical presentation and main diagnostic features of the disease, as well as more recent therapeutic approaches.

Prediction of Pulmonary Hypertension in Patients with Diffuse Parenchymal Lung Disease using Forced Vital Capacity/ Diffusion Capacity of Lung using Carbon Monoxide Ratio: A Cross-sectional Study

Introduction: Diffuse Parenchymal Lung Disease (DPLD) comprise a heterogeneous group of diseases that occur when an abnormal healing response is induced by injury to the lungs. The diagnosis of DPLD is based on clinical presentation and radiological features. The initial diagnostic work-up includes Pulmonary Function Tests (PFT), such as spirometry and diffusion tests. Aim: To evaluate the accuracy of the Forced Vital Capacity/ Diffusion Capacity of Lung for Carbon Monoxide (FVC/DLCO) ratio in predicting the presence of pulmonary hypertension in patients with DPLD. Materials and Methods: A cross-sectional study was conducted from January 2023 to March 2024 in the Inpatient Department (IPD) and Outpatient Department (OPD) of Nilratan Sircar (NRS) Medical College and Hospital, Kolkata, West Bengal, India. A total of 50 patients underwent High-Resolution Computed Tomography (HRCT) thorax and spirometry with DLCO, along with some other ancillary investigations. The parameters evaluated primarily include a descriptive account of the spirometry values, which were Forced Expiratory Volume in 1 second (FEV1), FVC and DLCO, as well as the 6-Minute Walk Distance (6MWD) for physiological assessment and ECHO 2D for the evaluation of pulmonary hypertension. Simple logistic regression was performed between the FVC/DLCO ratio and the presence or absence of pulmonary hypertension based on ECHO 2D with Doppler as the binary outcome. The Receiver Operating Characteristic (ROC) curve was obtained and the FVC/DLCO cut-off ratio was adjusted to achieve the highest sensitivity for predicting pulmonary hypertension based on this dataset. Results: Out of 50 patients (30 females and 20 males), the most common HRCT thorax pattern was Usual Interstitial Pneumonia (UIP), observed in 19 patients (38%), followed by Non Specific Interstitial Pneumonia (NSIP) in 11 patients (22%). The single most common DPLD was Idiopathic Pulmonary Fibrosis (IPF), with 11 patients (22%), while the most common group was Connective Tissue Disease-related DPLD (CTD-DPLD), comprising 22 patients (44%). An FVC/DLCO ratio of 0.97 was found to have a sensitivity of 81%, specificity of 77%, a Positive Predictive Value (PPV) of 86%, a Negative Predictive Value (NPV) of 70% and a diagnostic accuracy of 80% in predicting pulmonary hypertension. Conclusion: The FVC/DLCO ratio of 0.97 represents a modality that could aid in the diagnosis of pulmonary hypertension.

Cerebral Amyloid Angiopathy: Clinical Presentation, Sequelae and Neuroimaging Features—An Update

The prevalence of cerebral amyloid angiopathy (CAA) has been shown to increase with age, with rates reported to be around 50–60% in individuals over 80 years old who have cognitive impairment. The disease often presents as spontaneous lobar intracerebral hemorrhage (ICH), which carries a high risk of recurrence, along with transient focal neurologic episodes (TFNE) and progressive cognitive decline, potentially leading to Alzheimer’s disease (AD). In addition to ICH, neuroradiologic findings of CAA include cortical and subcortical microbleeds (MB), cortical subarachnoid hemorrhage (cSAH) and cortical superficial siderosis (cSS). Non-hemorrhagic pathologies include dilated perivascular spaces in the centrum semiovale and multiple hyperintense lesions on T2-weighted magnetic resonance imaging (MRI). A definitive diagnosis of CAA still requires histological confirmation. The Boston criteria allow for the diagnosis of a probable or possible CAA by considering specific neurological and MRI findings. The recent version, 2.0, which includes additional non-hemorrhagic MRI findings, increases sensitivity while maintaining the same specificity. The characteristic MRI findings of autoantibody-related CAA-related inflammation (CAA-ri) are similar to the so-called “amyloid related imaging abnormalities” (ARIA) observed with amyloid antibody therapies, presenting in two variants: (a) vasogenic edema and leptomeningeal effusions (ARIA-E) and (b) hemorrhagic lesions (ARIA-H). Clinical and MRI findings enable the diagnosis of a probable or possible CAA-ri, with biopsy remaining the gold standard for confirmation. In contrast to spontaneous CAA-ri, only about 20% of patients treated with monoclonal antibodies who show proven ARIA on MRI also experience clinical symptoms, including headache, confusion, other psychopathological abnormalities, visual disturbances, nausea and vomiting. Recent findings indicate that treatment should be continued in cases of mild ARIA, with ongoing MRI and clinical monitoring. This review offers a concise update on CAA and its associated consequences.

Clinical Presentation and Histopathological Characteristics of Sporotrichosis.

Sporotrichosis is the most prevalent deep mycosis worldwide. The differential diagnosis of its clinical symptoms and histopathological features presents considerable complexity. A thorough understanding of the clinical manifestations and pathological characteristics of sporotrichosis is crucial for its accurate clinical diagnosis. This study involved a retrospective analysis of cases diagnosed with sporotrichosis at our hospital between April 2017 and April 2019, summarizing their clinical and histopathological characteristics. Among the 323 patients included in this study, a higher prevalence was observed in females. The disease predominantly affected middle-aged and elderly patients, aged between 41 and 67 years, with a higher incidence noted in winter and spring. Among the 323 patients, 170 patients (52.7%) presented with the fixed pattern, 128 (40%) with the lymphatic type, 24 (7%) with the special type, and one patient with the cutaneous-disseminated type. There were no cases of the systemic type. Histopathological findings included diffuse infectious granulomas and inflammatory infiltration, primarily characterized by diffuse and non-specific mixed inflammatory cell infiltration (without granulomas). The granulomas were primarily tuberculoid and purulent, with a lesser occurrence of granulomas exhibiting a three-zone structure, which is typically uncommon. An increase in lymphocytes, plasmacytes, and neutrophils was noted as one of the pathological features of the disease. In this region, sporotrichosis was more prevalent among female patients compared to male patients, with the fixed pattern being more common than the lymphatic type. Histopathological manifestations included diffuse infectious granulomas, with inflammatory infiltration primarily characterized by diffuse infiltration and non-specific mixed inflammatory cell infiltration (without granulomas).

Groove Pancreatitis in Focus: Tumor-Mimicking Phenotype, Diagnosis, and Management Insights.

Background/Objectives: Groove pancreatitis (GP) is an uncommon pancreatic condition implying a challenging differential diagnosis. This study aims to comprehensively evaluate the main risk factors, clinical presentation, imaging and endoscopic characteristics of patients with GP, providing insights into an effective diagnostic approach and therapeutic strategies. Methods: A retrospective analysis was conducted on patients diagnosed with GP, with demographic and clinical data collected. The diagnostic route was followed by an upper endoscopy and was finally confirmed by cross-sectional imaging. In patients with high malignancy suspicion or with an uncertain diagnosis, a pancreatic endoscopic ultrasound (EUS) was further performed. According to imaging features, we divided patients into two categories: with and without tumor-like appearance. Results: Altogether, 23 patients were included, 11 in the tumor-like category, and 12 in the non-tumor-like group; 95.6% were men, 78.2% alcohol consumers, and 73.9% smokers. In both groups, the main symptom was abdominal pain, followed by nausea and vomiting. The most frequent finding at upper endoscopy was edematous duodenal mucosa (16 patients, 80%), followed by mucosal hyperemia (8 patients, 40%). The main finding at cross-sectional imaging was duodenal wall thickening (14 patients, 60.9%), followed by pancreatic head enlargement and duodenal wall cysts (both seen in 12 patients, 52.2%). The EUS predominantly showed duodenal wall thickening (13 patients, 68.4%), and intramural and paraduodenal cysts (10 patients, 52.6%). Conclusions: GP predominantly affects men with a history of chronic alcohol and tobacco use. Its primary diagnostic challenge lies in distinguishing it from pancreatic carcinoma, with an accurate diagnostic workup being crucial in clinical practice.

The use of fine needle aspiration and frozen section in parotid tumors: a review

Introduction: Parotid gland tumors, although uncommon, present clinical and radiological features that don’t demonstrate their aggressiveness and behavior. Objective: In this study, we aimed to deepen the applicability of Fine Needle Aspiration and Frozen Sections as diagnostic methods. Materials and Methods: A search was conducted in the PubMed, Web of Science, Embase, and Scopus databases using the combination (Frozen Sections) AND (parotid gland) AND ((Surgical Procedures, Operative) OR (Elective Surgical Procedures)). A total of 170 articles were obtained, which underwent a selection based on title and abstract, resulting in 46 articles. From these articles, a second selection was made through complete reading, resulting in 24 articles. Results: 70.83% of the articles reported that Fine Needle Aspiration can provide reliable diagnoses. According to 54.17%, surgical planning can be obtained through Fine Needle Aspiration. No article addressed the chance of recurrences with the use of Fine Needle Aspiration. Frozen Sections can modify surgical planning, as reported in 91.67%. The use of Frozen Sections to modify neck dissection was indicated in 50%. In 8.33%, it was highlighted that Frozen Sections reduce the chance of recurrences. Among the articles that clearly expressed their ideas, 7 out of 11 advocated for the application of Frozen Sections with reservations, while 4 out of 11 supported their routine use. Conclusion: Fine Needle Aspiration is a widely used method for initial evaluations but has limitations in terms of accurate diagnosis and individualized treatment. Frozen Sections are a method that can assist the surgeon in intraoperative decision-making.

Sex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic study

BackgroundThis study investigated sex differences in the associations between Alzheimer’s disease (AD) biomarkers, cognitive performance, and decline in memory clinic settings.Methods249 participants (females/males:123/126), who underwent tau-PET, amyloid-PET, structural MRI, and plasma glial fibrillary acidic protein (GFAP) measurement were included from Geneva and Lausanne Memory Clinics. Mann-Whitney U tests investigated sex differences in clinical and biomarker data. Linear regression models estimated the moderating effect of sex on the relationship between biomarkers and cognitive performance and decline. Sex differences in cognitive decline were further evaluated using longitudinal linear mixed-effect models with three-way interaction effects.ResultsWomen and men present similar clinical features, amyloid, and neurodegeneration. Women had higher tau load and plasma levels of GFAP than men (p < 0.05). Tau associations with amyloid (standardized β = 0.54,p < 0.001), neurodegeneration (standardized β=-0.44,p < 0.001), and cognition (standardized β=-0.48,p < 0.001) were moderated by a significant interaction with sex. Specifically, the association between amyloid and tau was stronger among women than men (standardized β=-0.19,p = 0.047), whereas the associations between tau and cognition and between tau and neurodegeneration were stronger among men than in women (standardized β=-0.76,p = 0.001 and standardized β=-0.56,p = 0.044). Women exhibited faster cognitive decline than men in the presence of severe cortical thinning (p < 0.001).ConclusionWomen showed higher tau load and stronger association between amyloid and tau than men. In individuals with high tau burden, men exhibited greater neurodegeneration and cognitive impairment than women. These findings support that sex differences may impact tau deposition through an upstream interplay with amyloid, leading to downstream effects on neurodegeneration and cognitive outcomes.

Clinical presentation and demographic characteristics of polypoid melanoma on the back: A case study

Polypoid melanoma (PM) is a variant of nodular melanoma characterized by exophytic growth, an irregular surface, and a cauliflower-like appearance. Its reported incidence varies widely, ranging from 2% to 43%, and it is associated with a poor prognosis. This study presents a case of this rare melanoma subtype, along with its demographic characteristics, as reported in the international literature. PM is recognized as an independent risk factor in the evolving landscape of melanoma and requires tailored management strategies. Dermatologists and surgical oncologists should maintain a high level of suspicion to improve patient outcomes.

Incidence and Clinicopathological Correlation of Periapical Granulomas Associated with Extracted Teeth in Jeddah, Saudi Arabia

Objectives: study the incidence and clinicopathological correlation, focusing on the histologic diagnosis of periapical granulomas associated with extracted teeth. Methods: Over the course of one year, a prospective study was conducted involving the routine biopsy of retrievable periapical tissues from patients undergoing tooth extraction. Additionally, routine histopathologic examinations were performed on recoverable Periapical tissues from the extracted teeth. The study involved the participation of 120 patients, of whom 52 (43.33%) were diagnosed with histopathological peri-radicular lesions. Findings: The male-to-female incidence ratio was 2:1, and most of the patients with lesions identified by histopathology were in their first, second, or third decades of life, comprising 41 (34%) cases. Among the 52 (43.33%) cases with histopathologically diagnosed periradicular lesions, the most common types were periapical abscess 8 (15.38%) and inflammatory (periapical) granuloma 27 (92%). Remarkably, clinically confirmed acute apical periodontitis was shown to be associated with periapical granuloma, which is primarily characterized by foamy cells and macrophages. Several clinical and radiologic features exhibited significant associations with the histopathologic diagnosis of specific periradicular lesions (P&lt;0.05). Furthermore, a significant correlation was observed between clinical diagnosis and histopathologic diagnosis, specifically for inflammatory (periapical) granuloma and periapical abscess. Novelty: The study strengthens the link between clinical presentation and histopathological characteristics of periapical granulomas. The study uncovers several clinical signs that could help predict the histopathological diagnosis of periapical granulomas. This is an important finding, as it could improve the accuracy of diagnosis and help dental professionals identify these lesions earlier, which may lead to more effective and timely interventions. Keywords: Periapical lesion, Extracted tooth, Periapical granuloma, Histopathology, Clinical diagnosis, Biopsy

Mesenteric inflammatory myofibroblastic tumor (IMT), a rare neoplasm in a pediatric patient: imaging findings and literature review.

Inflammatory myofibroblastic tumors (IMTs) are rare neoplasms commonly classified as having "intermediate malignancy" due to their unique clinical, pathological, and molecular features. These tumors can exhibit aggressive biological behavior, including local invasion, recurrence, and, on rare occasions, distant metastasis. IMTs may arise in various anatomical locations, with the lung, mesentery, and omentum being the most frequent sites. Although IMTs can occur at any age, they are more commonly diagnosed in children and young adults. Their clinical manifestations and imaging findings are often nonspecific and may resemble malignant pathology, making diagnosis challenging. Moreover, the histopathological characteristics of IMTs can overlap with those of other conditions. In this report, we present a case of multicentric abdominal IMT in a pediatric patient and review the imaging features of abdominal IMTs in children, as documented in the limited number of available cases. Accurate differential diagnosis requires a comprehensive understanding of both the clinical presentation and radiographic features of these tumors. Radiologists should be familiar with the distinctive imaging characteristics of IMTs to ensure that this rare pathology is considered in the differential diagnosis of any abdominal mass in pediatric patients.

Incidence, sociodemographic and presenting clinical features of childhood non-infectious uveitis: findings from the UK national inception cohort study

BackgroundWe aimed to provide, through the Uveitis in Childhood National Cohort Study, population-based evidence on incidence, distribution and disease characteristics for childhood onset non-infectious uveitis.MethodsEligible children and young people (<18...

Leiomyosarcomas of the inferior vena cava: diagnostic features on contrast-enhanced CT, ultrasonography and MRI.

To evaluate clinical presentation and imaging characteristics of leiomyosarcomas of the inferior vena cava (IVC LMS) using contrast-enhanced CT (CECT), ultrasonography (US), magnetic resonance imaging (MRI), and to identify features that facilitate early and accurate pre-operative diagnosis. Our study enrolled 21 patients with pathologically confirmed IVC LMS from October 2015 to June 2022. All participants underwent CECT, and additionally, 12 participants had US examinations and 3 had MRI. Images were independently reviewed by two experienced radiologists. The clinical presentations and diagnostic characteristics were recorded. The study involved 16 female and 5 male patients, with an average age of 55 ± 11 years (ranging from 34 to 80 years). Common clinical symptoms included abdominal pain, back pain, leg discomfort, abdominal distension, jaundice, and the presence of an abdominal mass. On CT scans, a large, lobulated, heterogeneous mass with progressive enhancement was typically seen in 13 of the 21 patients (61.9%). Ultrasonography revealed that IVC LMS typically presented as a lobulated, heterogeneous, hypoechoic mass. Color Doppler imaging evaluated lumen obstruction in 8 of the 12 patients (66.7%), and high velocity flow signals were detected by Pulsed wave Doppler in 4 of the 12 patients (33.3%). On MRI, IVC LMS presented as a heterogeneous mass that exhibited intermediate intensity on T1-weighted images, slightly high intensity on T2-weighted images and high intensity on diffusion-weighted images. Several diagnostic characteristics on CECT, US and MRI could aid in the diagnosis of IVC LMS. The detection of a heterogeneous mass with progressive enhancement along the inferior vena cava on CECT was strongly indicative of IVC LMS. Both CT and US are effective in accurately indicating the location of the tumor within the IVC.

Severity, complications and outcome of meconium aspiration syndrome in neonates.

Objective: To determine the severity, complications, and outcomes of meconium aspiration syndrome (MAS) in neonates. Study Design: Cross-sectional study. Setting: Neonatal Intensive Care Unit (NICU) of the National Institute of Child Health, Karachi, Pakistan. Period: January 2024 to June 2024. Methods: Neonates aged 1-28 days of either gender, and having MAS were analyzed. Vital signs were noted and necessary laboratory investigations were done. Presenting clinical features and associated complications of MAS were noted. Outcome was noted in the form of discharged, admitted to pediatric unit, or mortality. Results: In a total of 92 neonates, 66 (71.7%) were male. The mean age was 12.47±6.55 days. Evaluation of MAS severity revealed mild, moderate, and severe cases among 2 (2.2%), 16 (17.4%), and 74 (80.4%) neonates, respectively. The most frequently noted complications were sepsis 65 (70.7%), hyperinflated lungs 55 (59.8%), respiratory distress 34 (37.0%), and pulmonary hypertension 31 (33.7%), were the most commonly associated complications of MAS. Two neonates left against medical advice so those were excluded from the final outcome analysis. In the remaining 90 neonates, mortality was reported in 6 (6.7%). Mortality had significant association with bluish skin at presentation (p=0.044), severe MAS (p=0.001), and pulmonary hypertension (p=0.001). Conclusion: Vast majority of the neonates (80.4%) presented with severe MAS which should raise alarm about the time identification of these high risk neonates. The most frequently noted MAS associated complications were sepsis, hyperinflated lungs, respiratory distress, and pulmonary hypertension. At presentation, bluish skin, pulmonary hypertension, and severe MAS were significantly associated with mortality.

Sociodemographic Characteristics, Dementia, and Familiar Risk in Patients With Paraphrenia: A Danish Register-Based Cohort Study.

Sociodemographic Characteristics, Dementia, and Familiar Risk in Patients With Paraphrenia: A Danish Register-Based Cohort Study.

Isolation of a novel human prion strain from a PRNP codon 129 heterozygous vCJD patient.

The epizootic prion disease of cattle, bovine spongiform encephalopathy (BSE), caused variant Creutzfeldt-Jakob disease (vCJD) in humans following dietary exposure. Codon 129 polymorphism of the human prion protein gene (PRNP), encoding either methionine (M) or valine (V), dictates the propagation of distinct human prion strains and up to now all but one neuropathologically confirmed vCJD patients have had a 129MM genotype. Concordant with this genetic association, transgenic modelling has established that human PrP 129V is incompatible with the vCJD prion strain and that depending on codon 129 genotype, primary human infection with BSE prions may, in addition to vCJD, result in sporadic CJD-like or novel phenotypes. In 2016 we saw the first neuropathologically confirmed case of vCJD in a patient with a codon 129MV genotype. This patient's neuropathology and molecular strain type were pathognomonic of vCJD but their clinical presentation and neuroradiological features were more typical of sporadic CJD, suggestive of possible co-propagation of another prion strain. Here we report the transmission properties of prions from the brain and lymphoreticular tissues of the 129MV vCJD patient. Primary transmissions into transgenic mice expressing human PrP with different codon 129 genotypes mainly produced neuropathological and molecular phenotypes congruent to those observed in the same lines of mice challenged with prions from 129MM vCJD patient brain, indicative that the vCJD prion strain was the dominant propagating prion strain in the patient's brain. Remarkably however, some transgenic mice challenged with 129MV vCJD patient brain propagated a novel prion strain type which at secondary passage was uniformly lethal in mice of all three PRNP codon 129 genotypes after similar short mean incubation periods. These findings establish that cattle BSE prions can trigger the co-propagation of distinct prion strains in humans.

Treatment-resistant inflammatory demyelinating pseudotumor with Marburg-like features: A narrative review-based treatment approach

Inflammatory demyelinating pseudotumor (IDP) mimics intracranial neoplasms in terms of both clinical presentation and imaging features. IDP with Marburg-like features represents a severe form of inflammatory demyelinating encephalomyelitis, marked by a dramatic onset, aggressive course, absence of remission, and the presence of tumor-like central nervous system demyelinating lesions. Key features of IDP in brain magnetic resonance imaging include open or incomplete ring enhancement, low T2 rim, peripheral diffusion restriction, absent or mild mass effect, and perilesional edema. In brain magnetic resonance spectroscopy (MRS), elevated glutamate, choline, and lactate peaks are observed; however, brain MRS findings can be nonspecific and nondifferentiating. Pathologic findings show prominent perivascular lymphoid infiltrates consisting predominantly of leukocyte common antigen (LCA)+ and PAX5+ B lymphocytes in immunohistochemistry staining, parenchymal and perivascular macrophages (CD68+), some with visible myelin globules on Luxol Fast Blue staining, preferential loss of myelin with relative axonal preservation and the formation of axonal spheroids (swellings), reactive astrocytosis (GFAP+ and ATRX−), and remyelination with thinner myelin sheaths than background axons at the periphery of the plaque. A review of previous case reports revealed that prompt aggressive immunosuppression therapy in the IDP with Marburg-like features may lead to a favorable response. Initiating treatment with a cycle of high-dose corticosteroids followed by rescue immunosuppressive therapy using cyclophosphamide, mitoxantrone, rituximab, or alemtuzumab demonstrated positive outcomes. In addition, maintenance immunosuppressive therapy with B-cell-depleting agents, such as rituximab and ocrelizumab, showed potential for controlling disease activity and improving long-term prognosis.