Polymicrobial brain abscesses: A complex condition with diagnostic and therapeutic challenges.

Brain abscesses (BA) are focal parenchymal infections that remain life-threatening conditions. Polymicrobial BAs (PBAs) are complex coinfections of bacteria or bacterial and nonbacterial pathogens such as fungi or parasites, with diagnostic and therapeutic challenges. In this article, we comprehensively review the prevalence, pathogenesis, clinical manifestations, and microbiological, histopathological, and radiological features of PBAs, as well as treatment and prognosis. While PBAs and monomicrobial BAs have some similarities such as nonspecific clinical presentations, PBAs are more complex in their pathogenesis, pathological, and imaging presentations. The diagnostic challenges of PBAs include nonspecific imaging features at early stages and difficulties in identification of some pathogens by routine techniques without the use of molecular analysis. Imaging of late-stage PBAs demonstrates increased heterogeneity within lesions, which corresponds to variable histopathological features depending on the dominant pathogen-induced changes in different areas. This heterogeneity is particularly marked in cases of coinfections with nonbacterial pathogens such as Toxoplasma gondii. Therapeutic challenges in the management of PBAs include initial medical therapy for possibly underrecognized coinfections prior to identification of multiple pathogens and subsequent broad-spectrum antimicrobial therapy to eradicate identified pathogens. PBAs deserve more awareness to facilitate prompt and appropriate treatment.

Spinal calcifying pseudoneoplasm of the neuraxis (CAPNON) associated with facet joint pathologies: CAPNON diagnostic and pathogenic insights.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like fibro-osseous lesion that can develop anywhere in the neuraxis. Approximately a half of reported CAPNONs developed in the spinal region, mostly close to the facet joint (FJ). The diagnosis of spinal CAPNONs is challenging given the existence of mimics and associated pathologies including calcific degeneration of the FJ ligaments (DFJL) and synovial cysts (SCs). The pathogenesis of CAPNON remains elusive, although there have been a few hypotheses including degenerative, reactive, proliferative and immune-mediated processes. Our present study examined clinical, radiological and pathological features of 12 spinal CAPNONs in comparison to 9 DFJL foci, and diagnostic and pathogenic relationship between CAPNONs and FJ pathologies. On imaging, CAPNONs were all tumor-like and typically bigger than DFJL foci. All CAPNONs showed pathologically diagnostic features including characteristic cores, consistently identifiable core-surrounding/peripheral palisading of macrophages and other cells including multinucleated giant cells, variable infiltration of CD8+ T-cells, and multifocal immunopositivity of neurofilament light chain (NF-L). These features were absent or limited in the DFJL foci with statistically significant differences from CAPNONs, except calcifications. Spinal CAPNONs co-existed with DFJL foci in all cases; some had transitional foci with overlapping focal CAPNON and DFJL-like features. These findings, along with our previously reported relationship between CAPNONs and SCs, suggest that spinal CAPNONs may occur in association with or in transition from calcifying/calcified degenerative lesions of FJ ligaments and/or SCs when a reactive proliferative process is complemented by other pathogenic changes such as immune-mediated pathology and NF-L deposition/expression.

Clinicopathologic characteristics of Nocardia brain abscesses: Necrotic and non-necrotic foci of various stages.

Nocardia brain abscesses are rare bacterial infections associated with a high mortality rate, and their preoperative diagnosis can be difficult for various reasons including a nonspecific clinical presentation. While late-stage nocardial brain abscesses may be radiologically characteristic, early-stage lesions are nonspecific and indistinguishable from another inflammatory/infectious process and other mimics. Despite the paucity of previous histopathological descriptions, histopathological examination is critical for the identification of the pathogen, lesion stage(s), and possible coexisting pathology. In this study, we examined the clinical, radiological and histopathological features of 10 patients with brain nocardiosis. Microscopic findings were analysed in correlation with clinical and radiological features in 9 patients, which revealed that brain nocardiosis was characterized by numerous necrotic and non-necrotic foci of various stages (I-IV) along with Nocardia identification, as well as the leptomeningeal involvement in most cases, and co-infection of brain nocardiosis with toxoplasmosis in 2 patients. The imaging features were characteristic with a multilobulated/bilobed ring-enhancing appearance in 8 patients including 2 patients with multiple lobulated and non-lobulated lesions and 1 patient showing the progression from a non-lobulated to lobulated lesion. These findings suggest that nocardial brain abscesses particularly at late-stages share common characteristics. Nevertheless, given the complex pathologic features, including possible co-infection by other pathogens, nocardial brain abscesses remain a therapeutic challenge.

Spinal calcifying pseudoneoplasm of the neuraxis (CAPNON) and CAPNON-like lesions: CAPNON overlapping with calcified synovial cysts.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumour-like fibro-osseous lesion in the neuraxis including the spine. It is diagnosed by the presence of the following histological features: granular amorphous to chondromyxoid fibrillary cores with calcification/ossification, peripheral palisading of spindle to epithelioid cells, variable fibrous stroma, and foreign body reaction with multinucleated giant cells, as well as positive NF-L immunostaining. Spinal CAPNON is sometimes named as tumoural calcinosis that is tumour-like dystrophic calcification usually in the periarticular tissue and also described in calcified synovial cyst (CSC). We examined clinical, radiological and pathological features of five spinal CAPNONs and 21 spinal CSCs including three recurrent lesions. The results demonstrated some radiological and pathological overlaps between these two entities, as well as distinct features of each entity to be diagnosed. All CAPNONs showed the diagnostic histological features with NF-L positivity mainly in lesion cores and variable CD8+ T-cells. In contrast, CSCs exhibited the synovial lining and variable degenerative/reactive changes with some CAPNON-like features, but mostly no to occasionally limited NF-L positivity and less CD8+ T-cells with statistically significant differences between groups of CAPNONs and CSCs. Four CSCs contained CAPNON-like foci with the CAPNON diagnostic features including prominent NF-L positivity, and some transitional features from CSC to CAPNON. As the pathogenesis of CAPNON is likely reactive/degenerative in association with an inflammatory/immunological process involving NF-L protein deposition, our findings suggest the link between spinal CAPNON and CSC, with possible transition from CSC to CAPNON or CAPNON developing in reaction to CSC.

Radiographic horizontal gaze deviation in the setting of acute PICA territory ischemia: A potential mimic of large vessel occlusion.

PURPOSE: Horizontal gaze deviation (HGD) is a predictor of acute large vessel occlusion (LVO) and helps to expedite the triage of patients to CTA and endovascular-capable sites. Patients with acute cerebellar ischemia, particularly involving the PICA territory, can also exhibit HGD. MATERIALS AND METHODS: We reviewed 2260 CTA stroke assessment cases between January 2016 and May 2020. Forty-six patients with CTA-proven acute PICA occlusions were identified and compared with 114 patients with acute LVO (ICA, M1, and M1/2). Both clinical and radiographic HGD were examined. The degree of radiographic HGD was measured for each patient. Site of ischemia was confirmed on subsequent MRI. RESULTS: Of the 46 patients with acute PICA occlusions, 20 (43.5%) patients had radiographic (+) HGD with either ipsilateral or contralateral gaze deviation, 6 of whom (13.0%) displayed clinical HGD. Of the 114 patients with LVO (control group), 72 (63.2%) patients had radiographic (+) HGD, all ipsilateral, 49 of whom (68.0%) displayed clinical HGD. The mean degree of HGD between PICA and LVO were 30.0° vs. 22.9°, respectively, p < 0.001; AUC = 0.68. CONCLUSION: Patients with acute PICA occlusion can exhibit either ipsilateral or contralateral HGD and a higher degree of HGD than LVO occlusion on NECT. In hyperacute stroke, the presence of radiographic HGD > 30° in the absence of ischemic changes in the MCA territory should prompt clinicians to closely evaluate for features of early ischemic changes in the cerebellar hemispheres that suggest acute PICA occlusion.

Toxoplasmosis of the central nervous system: Manifestations vary with immune responses.

Toxoplasmosis is an opportunistic infection caused by Toxoplasma gondii (TG), which affects one third of the global human population and commonly involves the central nervous system (CNS)/brain despite the so-called CNS immune privilege. Symptomatic clinical disease of TG infection is much more commonly associated with immunodeficiency; clinicopathological manifestations of CNS toxoplasmosis are linked to individual immune responses including the CNS infiltration of T-cells that are thought to prevent the disease. In patients with autoimmune diseases, immune status is complicated mainly byimmunosuppressant and/or immunomodulatory treatment but typically accompanied by infiltration of T-cells that supposedly fight against toxoplasmosis. In this article, we review characteristics of CNS toxoplasmosis comparatively in immunocompromised patients, immunocompetent patients, and patients with coexisting autoimmune diseases, as well as CNS immune responses to toxoplasmosis with a representative case to demonstrate brain lesions at different stages. In addition to general understanding of CNS toxoplasmosis, our review reveals that clinical manifestations of CNS toxoplasmosis are commonly nonspecific, and incidental pathological findings of TG infection are relatively common in immunocompetent patients and patients with autoimmune diseases (compared to immunocompromised patients); CNS immune responses such as T-cell infiltrates vary in acute and chronic lesions of brain toxoplasmosis.

Artery of Percheron infarction with persistent amnesia: a case report of bilateral paramedian thalamic syndrome.

BACKGROUND: The artery of Percheron is an uncommon anatomic variant which supplies the bilateral paramedian thalami and rostral midbrain. While infarction of its vascular territory can result in a wide range of symptoms, paramedian thalamic syndrome is classically described as a triad of symptoms including vertical gaze disturbances, fluctuating level of consciousness, and amnesia. There is minimal evidence to date to characterize the long-term cognitive consequences of infarction of the artery of Percheron utilizing neuropsychological assessment. CASE PRESENTATION: We describe a 40-year-old female patient initially presenting with dizziness, confusion and falls with unremarkable head CT scans. Subsequent MRI, more than 24 h after symptom onset, identified evidence of bilateral thalamic and rostral midbrain infarction. Neuropsychological testing was administered at 4 months post-stroke, with follow up testing at 1 year. The patient was found to have profound anterograde and retrograde amnesia, which did not change significantly over the first year of rehabilitation, and which was not easily identifiable in everyday encounters due to her relatively intact working memory and social skills. CONCLUSIONS: As early diagnosis of infarction of the artery of Percheron is challenging, patients have frequently missed the time window for acute management of ischemic stroke. Moreover, this case study highlights the need for further research in deciphering the role of the paramedian thalamus in memory and cognition, as well as the importance of standardized neuropsychological testing for the artery of Percheron stroke patients to identify safety and rehabilitation concerns that may be overlooked.

Levodopa-responsive parkinsonism in a patient with corticobasal degeneration and bilateral choroid plexus xanthogranulomas.

Corticobasal degeneration (CBD) has substantial overlap of clinical features with other neurodegenerative diseases including Parkinson's disease (PD). Its clinical diagnostic accuracy is the lowest among the common neurodegenerative diseases, and its antemortem diagnosis is more challenging when CBD is comorbid with another brain disease. We report an elderly male patient with multiple medical conditions and a family history of essential tremor. He presented with progressive tremor that was initially thought to be essential tremor and later diagnosed as PD despite head computerized tomography showing bilateral intraventricular masses and other minor changes. The clinical diagnosis of PD was supported by his responsiveness to low-dose levodopa. However, postmortem neuropathological examination revealed CBD and bilateral choroid plexus xanthogranulomas with mild ventricular enlargement and multifocal ependymal lining injury presumably due to mild hydrocephalus. CBD is typically levodopa-unresponsive, but hydrocephalus-associated parkinsonism is commonly levodopa-responsive. We raise awareness of the present comorbidity and atypical parkinsonism due to the choroid plexus xanthogranuloma-induced hydrocephalus for the clinical diagnosis and management of parkinsonism.

Hemorrhagic giant cerebral capillary telangiectasia resulting in death: Case report and literature review.

We report a rare case of death caused by hemorrhage of a giant cerebral central nervous system capillary telangiectasia (CCT). A 49-year-old female presented comatose after suffering a traumatic head injury due to an unwitnessed fall. Computed tomography of the head revealed an acute 8.1 × 5.2 cm right intraparenchymal hematoma. Postmortem pathology found thin-walled dilated capillaries consistent with a giant cerebral CCT. The radiological complexity and rarity of giant CCTs result in these malformations often going undiagnosed. We review other cases of giant intracranial CCTs reported in the English literature and confirm that this is the first case of a hemorrhagic giant cerebral CCT causing death. This report emphasizes the existence and complications of giant CCTs and stresses the importance of their investigation to ensure patients receive optimal treatment and follow-up.

Using Magnetic Resonance Perfusion to Stratify Overall Survival in Treated High-Grade Gliomas.

BACKGROUND: MR perfusion imaging is a relatively new technique that may aid in identifying recurrent tumor (RT) in those with radically treated high-grade gliomas (HGG). We aim to assess the relationship between dynamic susceptibility contrast-enhanced MR perfusion (DSC-MRP) and overall survival to establish a baseline for future research and to determine the utility of DSC-MRP as a clinical decision-making and prognostic tool. METHODS: We conducted a retrospective cohort study. Adults with pathologically confirmed HGG at the Juravinski Cancer Centre, Ontario between January 2011 and April 2014 with at least one post-treatment DSC-MRP were included. DSC-MRP was interpreted as positive or negative for tumor recurrence by experienced radiologists. The primary outcome was overall survival. RESULTS: Sixty-one patients were enrolled. Median survival for patients with a positive DSC-MRP scan was 4.5 months compared with 10.2 months for those with a negative DSC-MRP scan (hazard ratio [unadjusted] = 2.51; 95% confidence interval = 1.10-5.67; p-value = 0.03). Multivariable modeling (adjusted) that included all pre-selected variables showed similar results. CONCLUSION: Survival time in patients with HGG is generally low, and almost all patients will demonstrate RT. Our data suggest a positive DSC-MRP correlates with lower overall survival and may signify the presence of highly active RT. These results generate a hypothesis that there may be a prognostic role for the use of serial DSC-MRP for tumor surveillance. More importantly, this biomarker may aid in decision making for treatment plans and palliation.

Utiliser l'IRM de perfusion pour déterminer la survie globale de patients traités pour des gliomes de haut grade. Contexte: L'IRM de perfusion est une technique relativement nouvelle qui pourrait aider à identifier la récurrence tumorale dans le cas de gliomes de haut grade. Notre objectif est d'évaluer l'association pouvant exister entre les IRM de perfusion dynamique de contraste de susceptibilité (dynamic susceptibility contrast-enhanced MR perfusion) et la survie globale des patients afin d'établir des lignes directrices pour la recherche à venir et de déterminer l'utilité diagnostique de cette technique d'imagerie en ce qui concerne la prise de décisions cliniques. Méthodes: Nous avons ainsi effectué une étude de cohorte rétrospective incluant des patients adultes atteints de gliomes de haut grade. Ces patients du Juravinski Cancer Centre (Ontario) ont vu leur maladie être confirmée entre janvier 2011 et avril 2014. À la suite d'un traitement dans cet établissement, ils ont aussi bénéficié d'au moins une IRM de perfusion dynamique de contraste de susceptibilité. Un tel examen médical a été jugé positif ou non par des médecins radiologues expérimentés en tenant compte de la réapparition de tumeurs. Enfin, le principal indicateur évalué a été la survie globale des patients. Résultats: Soixante et un patients ont fait partie de cette étude. La survie globale médiane des patients dont l'IRM de perfusion dynamique de contraste de susceptibilité était positive était de 4,5 mois comparativement à 10,2 mois pour ceux dont la même IRM était négative (rapport de risque [sans ajustement] = 2,51 ; IC 95 % = 1,10 à 5, 67 ; p = 0,03). Une approche de modélisation multi-variable (avec ajustement) ayant inclus toutes nos variables présélectionnées a produit des résultats semblables. Conclusion: La survie globale des patients atteints de gliomes de haut grade est généralement faible ; de plus, presque tous les patients vont finir par donner à voir une récurrence tumorale. Nos données suggèrent donc que les patients dont l'IRM de perfusion dynamique de contraste de susceptibilité était positive peuvent être associés à une survie globale plus faible, ce qui pourrait signifier la présence d'une tumeur récurrente fortement active. Ces résultats laissent à penser que l'IRM de perfusion dynamique de contraste de susceptibilité pourrait jouer un rôle diagnostique dans le suivi des tumeurs. Plus important encore, il est possible que ce biomarqueur soit utile dans le processus décisionnel qui concerne les plans de traitement et les soins palliatifs.

Degree of Conjugate Gaze Deviation on CT Predicts Proximal Vessel Occlusion and May Expedite Endovascular Therapy.

PURPOSE: Recent trials have demonstrated superior outcomes with combination IV-tPA and endovascular therapy (EVT) within 6 hours of symptom onset in patients with proximal vessel occlusion (ICA, M1, or proximal M1/M2) compared to IV-tPA alone. The current standard of diagnosis for consideration of EVT is CT angiogram (CTA). Unfortunately, not all hospitals are equipped with CTA, and the decision to transfer to tertiary centers is often based on nonenhanced CT. Ipsilateral conjugate gaze deviation (CGD) is associated with worse outcomes and larger infarcts in acute ischemic stroke. We predicted that the more proximal the occlusion, the higher the degree of CGD. MATERIALS AND METHODS: Over a period of 12 months, 182 consecutive patients with acute ischemic stroke treated at our institution were prospectively analyzed. Stroke locations were categorized based on CTA. Average degree of CGD was measured. Patient demographics, ASPECTS, collateral score, National Institutes of Health Stroke Scale, modified Rankin Scale, TICI score, length-of-stay, and mortality were collected. The median follow-up was 30 days. RESULTS: Out of ninety one of 182 patients with (+) CGD, 82 (90%) patients had ICA or middle cerebral artery (MCA) territory infarcts. The median was 25.0° in those with proximal occlusion and 13.7° in those with distal MCA occlusion (P < .001). A higher degree of CGD is positively correlated with proximity of vessel occlusion (correlation coefficient 0.2; P < .05). A cut-off greater than 20.25° (area under the curve = .76) showed a sensitivity of 64.0% and specificity 84.2%. CONCLUSIONS: Measuring degree of CGD may help in early identification of proximal vessel occlusions and expedite transfer for clot retrieval.

Unusual features of ependymoma in a patient with Parkinson's disease.

The diagnosis and management of ependymoma may be challenging when there is a comorbidity of ependymoma and Parkinson's disease (PD). We report the first case to demonstrate unusual clinical and pathological features of an ependymoma associated with PD. A 77-year-old male with a history of PD had brain magnetic resonance imaging (MRI) that showed signal abnormalities in the right temporal lobe, most consistent with a low-grade glioma. He underwent an imaging-guided resection of that lesion, which pathological examination revealed mild hypercellularity with gliosis but no neoplasm, as well as Lewy bodies (LBs) and α-synucleinopathy in the temporal cortex compatible with advanced PD. Follow-up MRI exhibited tumor-like progression of signal abnormalities in that brain region. Twenty-nine months after the first resection, a head computerized tomography scan disclosed an obvious mass centered in the right temporal lobe. A second resection was performed for the mass, which pathological examination revealed an ependymoma with focal anaplasia and additional unusual features including an infiltrative growth pattern and intermixed α-synuclein positivity with electron microscopy finding of LB-like inclusions. Our observation suggests that an ependymoma in the patient with PD may present with unusual features possibly due to altered tumorigenesis and disease progression associated with α-synucleinopathy.

Tumor-to-Lesion Metastasis: Case Report of Carcinoma Metastasis to Multiple Sclerosis Lesion.

BACKGROUND: The term "tumor-to-lesion metastasis" is an extension of "tumor-to-tumor metastasis," which is a rare but well-documented phenomenon. Tumor metastasis to the meninges and/or central nervous system (CNS) is rare in patents with multiple sclerosis (MS), although MS lesions bear many similarities to the primary tumor microenvironment and metastatic niche. We present the first case of malignant tumor metastasis to MS lesions with immunophenotyping of inflammatory cells in the metastatic foci. CASE DESCRIPTION: A 45-year-old male patient with a 6-year history of MS and newly diagnosed lung carcinoma developed carcinoma metastases in the meninges and CNS, as well as into mixed active/inactive MS lesions. The carcinoma-hosting MS lesions exhibited abundant macrophages/microglia with ongoing demyelination but rare T cells. In comparison, a 46-year-old female patient with a 21-month history of MS and newly diagnosed gastric carcinoma was found to have leptomeningeal carcinomatosis and separate active MS lesions containing not only frequent macrophages/microglia but also T cells. CONCLUSIONS: The carcinoma-hosting MS lesions are unlike typical active lesions but recapitulate the CNS metastatic niche. Our observations suggest that metastasis-hosting MS lesions might require a distinct immune microenvironment to be permissive to the seeding and growth of metastatic tumors.