Diffusion basis spectrum imaging and diffusion tensor imaging predict persistent black hole formation in multiple sclerosis.

BACKGROUND AND OBJECTIVES: Diffusion basis spectrum imaging (DBSI) extracts multiple anisotropic and isotropic diffusion tensors, providing greater histopathologic specificity than diffusion tensor imaging (DTI). Persistent black holes (PBH) represent areas of severe tissue damage in multiple sclerosis (MS), and a high PBH burden is associated with worse MS disability. This study evaluated the ability of DBSI and DTI to predict which acute contrast-enhancing lesions (CELs) would persist as T1 hypointensities (i.e. PBHs) 12 months later. We expected that a higher radial diffusivity (RD), representing demyelination, and higher DBSI-derived isotropic non-restricted fraction, representing edema and increased extracellular space, of the acute CEL would increase the likelihood of future PBH development. METHODS: In this prospective cohort study, relapsing MS patients with ≥1 CEL(s) underwent monthly MRI scans for 4 to 6 months until gadolinium resolution. DBSI and DTI metrics were quantified when the CEL was most conspicuous during the monthly scans. To determine whether the CEL became a PBH, a follow-up MRI was performed at least 12 months after the final monthly scan. RESULTS: The cohort included 20 MS participants (median age 33 years; 13 women) with 164 CELs. Of these, 59 (36 %) CELs evolved into PBHs. At Gd-max, DTI RD and AD of all CELs increased, and both metrics were significantly elevated for CELs which became PBHs, as compared to non-black holes (NBHs). DTI RD above 0.74 conferred an odds ratio (OR) of 7.76 (CI 3.77-15.98) for a CEL becoming a PBH (AUC 0.80, CI 0.73-0.87); DTI axial diffusivity (AD) above 1.22 conferred an OR of 7.32 (CI 3.38-15.86) for becoming a PBH (AUC 0.75, CI 0.66-0.83). DBSI RD and AD did not predict PBH development in a multivariable model. At Gd-max, DBSI restricted fraction decreased and DBSI non-restricted fraction increased in all CELs, and both metrics were significantly different for CELs which became PBHs, as compared to NBHs. A CEL with a DBSI non-restricted fraction above 0.45 had an OR of 4.77 (CI 2.35-9.66) for becoming a PBH (AUC 0.74, CI 0.66-0.81); a CEL with a DBSI restricted fraction below 0.07 had an OR of 9.58 (CI 4.59-20.02) for becoming a PBH (AUC 0.80, 0.72-0.87). CONCLUSION: Our findings suggest that greater degree of edema/extracellular space in a CEL is a predictor of tissue destruction, as evidenced by PBH evolution.

Ring-Enhancing Progressive Multifocal Leukoencephalopathy Mimicking Glioma in a Presumed Immunocompetent Patient With a History of Multiple Sclerosis: A Case Report and Review of the Literature.

The differential diagnoses of ring-enhancing lesions of the brain parenchyma is broad, but complete ring-enhancing lesions often indicate a neoplastic or infectious process. We present a case of a 70-year-old female with a history of multiple sclerosis (MS) who was not on current disease-modifying therapy (DMT) and was found to have a ring-enhancing lesion that mimicked a high-grade glioma. The patient underwent gross total resection, and histopathologic and molecular analysis revealed a diagnosis of progressive multifocal leukoencephalopathy (PML). A subsequent medical workup on the patient was unrevealing aside from mild lymphopenia. This is a unique case that highlights both an unusual clinical presentation and radiographic appearance of PML. There is a known associated increased risk of PML with the use of some DMTs for MS. However, this case raises the question of the possibility of developing PML years after interferon beta-1a therapy in a patient without overt immunosuppression.

AI-based detection of contrast-enhancing MRI lesions in patients with multiple sclerosis.

BACKGROUND: Contrast-enhancing (CE) lesions are an important finding on brain magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) but can be missed easily. Automated solutions for reliable CE lesion detection are emerging; however, independent validation of artificial intelligence (AI) tools in the clinical routine is still rare. METHODS: A three-dimensional convolutional neural network for CE lesion segmentation was trained externally on 1488 datasets of 934 MS patients from 81 scanners using concatenated information from FLAIR and T1-weighted post-contrast imaging. This externally trained model was tested on an independent dataset comprising 504 T1-weighted post-contrast and FLAIR image datasets of MS patients from clinical routine. Two neuroradiologists (R1, R2) labeled CE lesions for gold standard definition in the clinical test dataset. The algorithmic output was evaluated on both patient- and lesion-level. RESULTS: On a patient-level, recall, specificity, precision, and accuracy of the AI tool to predict patients with CE lesions were 0.75, 0.99, 0.91, and 0.96. The agreement between the AI tool and both readers was within the range of inter-rater agreement (Cohen's kappa; AI vs. R1: 0.69; AI vs. R2: 0.76; R1 vs. R2: 0.76). On a lesion-level, false negative lesions were predominately found in infratentorial location, significantly smaller, and at lower contrast than true positive lesions (p < 0.05). CONCLUSIONS: AI-based identification of CE lesions on brain MRI is feasible, approaching human reader performance in independent clinical data and might be of help as a second reader in the neuroradiological assessment of active inflammation in MS patients. CRITICAL RELEVANCE STATEMENT: Al-based detection of contrast-enhancing multiple sclerosis lesions approaches human reader performance, but careful visual inspection is still needed, especially for infratentorial, small and low-contrast lesions.

Streptococcus constellatus Brain Abscess in a Middle-Aged Man With an Undiagnosed Patent Foramen Ovale.

Brain abscess is a rare diagnosis. Common sources of infection include direct spread from otic sources, sinuses, or oral cavities, and hematogenous spread from distant sources, including the heart and lungs. Brain abscess with cultures growing oral flora species, in rare cases, may develop from bacteria in the oral cavity entering the bloodstream and then traveling to the brain via a patent foramen ovale. This report highlights a case of brain abscess caused by Streptococcus constellatus in a middle-aged man with an undiagnosed patent foramen ovale.

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case-control study.

Background: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity. Methods: In a case-control study, we recruited patients with relapsing-remitting multiple sclerosis (RRMS). Patients were divided into two groups based on positive COVID-19 PCR at the end of the enrollment phase. Each patient was prospectively followed for 12 months. Demographical, clinical, and past medical history were collected during routine clinical practice. Assessments were performed every six months; MRI was performed at enrollment and 12 months later. Results: Three hundred and sixty-two patients participated in this study. MS patients with COVID-19 infection had significantly higher increases in the number of MRI lesions (p: 0.019, OR(CI): 6.37(1.54-26.34)) and EDSS scores (p: 0.017), but no difference was found in total annual relapses or relapse rates. COVID-19 infections were positively correlated with EDSS progression (p: 0.02) and the number of new MRI lesions (p: 0.004) and predicted the likelihood of the number of new MRI lesions by an odds of 5.92 (p: 0.018). Conclusion: COVID-19 may lead to higher disability scores in the RRMS population and is associated with developing new Gd-enhancing lesions in MRI imaging. However, no difference was observed between the groups regarding the number of relapses during follow-up.

Antecedentes: La esclerosis múltiple (EM) es una enfermedad inmunomediada que se ha relacionado con varios factores de riesgo, como diversas infecciones virales. Realizamos este estudio para establecer una relación entre la infección por COVID-19 y la gravedad de la EM. Métodos: En un estudio de casos y controles, reclutamos pacientes con esclerosis múltiple remitente-recurrente (EMRR). Los pacientes se dividieron en dos grupos según la PCR positiva para COVID-19 al final de la fase de inscripción. Cada paciente fue seguido prospectivamente durante 12 meses. Los antecedentes demográficos, clínicos y médicos anteriores se recogieron durante la práctica clínica habitual. Las evaluaciones se realizaron cada 6 meses. La resonancia magnética se realizó en el momento de la inscripción y 12 meses después. Resultados: Trescientos sesenta y dos pacientes participaron en este estudio. Los pacientes con EM con infección por COVID-19 tuvieron aumentos significativamente más altos en el número de lesiones de resonancia magnética (p = 0,019; OR = 6,37 [IC 95%: 1,54-26,34]) y puntajes EDSS (p = 0,017), pero no se encontraron diferencias en el total de recaídas anuales o en las tasas de recaída. Las infecciones por COVID-19 se correlacionaron positivamente con la progresión de EDSS (p = 0,02) y la cantidad de nuevas lesiones en la resonancia magnética (p = 0,004) y predijeron la probabilidad de la cantidad de nuevas lesiones en la resonancia magnética con una probabilidad de 5,92 (p = 0,018). Conclusión: COVID-19 puede conducir a puntajes de discapacidad más altos en la población de EMRR y está asociado con el desarrollo de nuevas lesiones realzadas con Gd en imágenes de resonancia magnética. Sin embargo, no se observó diferencia entre los grupos en cuanto al número de recaídas durante el seguimiento.

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case–control study / COVID-19 y sus implicaciones en el curso clínico-radiológico de la esclerosis múltiple: un estudio de casos y controles

Background: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity.MethodsIn a case–control study, we recruited patients with relapsing–remitting multiple sclerosis (RRMS). Patients were divided into two groups based on positive COVID-19 PCR at the end of the enrollment phase. Each patient was prospectively followed for 12 months. Demographical, clinical, and past medical history were collected during routine clinical practice. Assessments were performed every six months; MRI was performed at enrollment and 12 months later.ResultsThree hundred and sixty-two patients participated in this study. MS patients with COVID-19 infection had significantly higher increases in the number of MRI lesions (p: 0.019, OR(CI): 6.37(1.54–26.34)) and EDSS scores (p: 0.017), but no difference was found in total annual relapses or relapse rates. COVID-19 infections were positively correlated with EDSS progression (p: 0.02) and the number of new MRI lesions (p: 0.004) and predicted the likelihood of the number of new MRI lesions by an odds of 5.92 (p: 0.018).ConclusionCOVID-19 may lead to higher disability scores in the RRMS population and is associated with developing new Gd-enhancing lesions in MRI imaging. However, no difference was observed between the groups regarding the number of relapses during follow-up. (AU)

Antecedentes: La esclerosis múltiple (EM) es una enfermedad inmunomediada que se ha relacionado con varios factores de riesgo, como diversas infecciones virales. Realizamos este estudio para establecer una relación entre la infección por COVID-19 y la gravedad de la EM.MétodosEn un estudio de casos y controles, reclutamos pacientes con esclerosis múltiple remitente-recurrente (EMRR). Los pacientes se dividieron en dos grupos según la PCR positiva para COVID-19 al final de la fase de inscripción. Cada paciente fue seguido prospectivamente durante 12 meses. Los antecedentes demográficos, clínicos y médicos anteriores se recogieron durante la práctica clínica habitual. Las evaluaciones se realizaron cada 6 meses. La resonancia magnética se realizó en el momento de la inscripción y 12 meses después.ResultadosTrescientos sesenta y dos pacientes participaron en este estudio. Los pacientes con EM con infección por COVID-19 tuvieron aumentos significativamente más altos en el número de lesiones de resonancia magnética (p=0,019; OR=6,37 [IC 95%: 1,54-26,34]) y puntajes EDSS (p=0,017), pero no se encontraron diferencias en el total de recaídas anuales o en las tasas de recaída. Las infecciones por COVID-19 se correlacionaron positivamente con la progresión de EDSS (p=0,02) y la cantidad de nuevas lesiones en la resonancia magnética (p=0,004) y predijeron la probabilidad de la cantidad de nuevas lesiones en la resonancia magnética con una probabilidad de 5,92 (p=0,018).ConclusiónCOVID-19 puede conducir a puntajes de discapacidad más altos en la población de EMRR y está asociado con el desarrollo de nuevas lesiones realzadas con Gd en imágenes de resonancia magnética. Sin embargo, no se observó diferencia entre los grupos en cuanto al número de recaídas durante el seguimiento. (AU)

To intervene or not to intervene: A case of symptomatic neurocysticercosis complicated by ventriculitis.

Although well described in the current literature, Neurocysticercosis [NCC] remains an enigma when confronted by practitioners. This is in part due to the haphazard nature of the parasitic infection on the central nervous system [CNS]. These include single or multiple anatomic sites of infection, stage of parasitosis, and the resultant inflammatory response. As a result, NCC can present with a complex constellation of symptomatic presentations, making therapeutic regiments highly individualized. Despite intervention, other impediments may arise post-therapy due to the nature of the infection. We present a case of rapidly progressive symptomatic NCC that initially was successfully treated, however would eventually succumb to complications of ventriculitis.

Two for the Price of One: A Case of Methicillin-Resistant Staphylococcus aureus (MRSA) Brain Abscess With Atypical Lymphoplasmacytic Infiltrate With Underlying Clonal Lymphoproliferative Process in a Patient Infected With HIV.

Multiple etiologies can coexist and trigger CNS symptoms in individuals infected with HIV. This article reviews a case of a cerebellar mass in an HIV patient who, on biopsy, grew methicillin-resistant Staphylococcus aureus (MRSA) and by pathology, showed an atypical lymphoplasmacytic infiltrate concerning a clonal lymphoproliferative process, which may be a precursor of CNS lymphoma. The patient, a 36-year-old male with multiple comorbidities including HIV Infection, presented to the hospital for evaluation of a one-week course of headache and photophobia. Remarkable physical examination findings included dilated pupils and anisocoria. Initial CT brain imaging revealed vasogenic edema seen throughout the left cerebellar hemisphere provoking mass effect on the fourth ventricle and pontocerebellar cistern resulting in mild hydrocephalus, new findings compared to prior. MRI brain displayed a T1 isointense, T2 hypointense ring-enhancing lesion in the left cerebellar hemisphere, with restricted diffusion, and surrounding vasogenic edema resulting in mass effect over the fourth ventricle, left cerebellar peduncle, and pontocerebellar cistern causing mild hydrocephalus. The patient underwent left suboccipital craniotomy with evacuation of the cerebellar lesion by neurosurgery. Tissue cultures grew MRSA. Pathology was sent to New York-Presbyterian Columbia University Irving Medical Center due to the presence of atypical lymphoplasmacytic infiltrates. The final diagnosis was polyclonal B-cell population in the sample; however, prominent peaks were also seen above the polyclonal background, possibly representing a clonal proliferation. Therefore, the lymphoplasmacytic infiltrates remained atypical and the possibility of the underlying clonal lymphoproliferative process could not be entirely ruled out.

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case-control study.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity. METHODS: In a case-control study, we recruited patients with relapsing-remitting multiple sclerosis (RRMS). Patients were divided into two groups based on positive COVID-19 PCR at the end of the enrollment phase. Each patient was prospectively followed for 12 months. Demographical, clinical, and past medical history were collected during routine clinical practice. Assessments were performed every six months; MRI was performed at enrollment and 12 months later. RESULTS: Three hundred and sixty-two patients participated in this study. MS patients with COVID-19 infection had significantly higher increases in the number of MRI lesions (p: 0.019, OR(CI): 6.37(1.54-26.34)) and EDSS scores (p: 0.017), but no difference was found in total annual relapses or relapse rates. COVID-19 infections were positively correlated with EDSS progression (p: 0.02) and the number of new MRI lesions (p: 0.004) and predicted the likelihood of the number of new MRI lesions by an odds of 5.92 (p: 0.018). CONCLUSION: COVID-19 may lead to higher disability scores in the RRMS population and is associated with developing new Gd-enhancing lesions in MRI imaging. However, no difference was observed between the groups regarding the number of relapses during follow-up.

Atypical clinical and radiologic findings in a patient with brain metastatic lesions.

We report the case of a 47-year-old man who was admitted to our clinic with an intractable headache, nausea, and sporadic vomiting, as well as speech difficulties and a 'floating' sensation. This man had no prior medical history. MRI of the brain showed evidence of over 20 supra- and infratentorial capsulated ring-enhancing lesions. All other paraclinical investigations done in our clinic were unremarkable and we excluded our first assumption of neurocysticercosis, as well as other parasitic infections. The patient was then referred to the Oral and Maxillofacial Surgery Clinic for an excisional biopsy of a submandibular formation, which was later verified to represent a lymph node metastasis from a poorly differentiated adenocarcinoma. A chest X-ray failed to demonstrate any significant pathology and the immunohistochemical constellation of the lymph node metastasis excluded the possibility of the primary tumor originating in the lung or the prostate. Due to the unresolved diagnostic query, a whole-body PET/CT was performed demonstrating a formation with malignant characteristics in the basal segment of the left lung, reaching the pleura and the left hilum, as well as solitary enlarged mesenteric and mediastinal lymph nodes. Following clinical consultations, it was determined that the patient was inoperable and chemotherapy and palliative CNS irradiation were recommended.

Role of MRSI Major Metabolite Ratios in Differentiating Between Intracerebral Ring-Enhancing Neoplastic and Non-Neoplastic Lesions, High-Grade Gliomas and Metastases, and High-Grade and Low-Grade Gliomas.

Introduction The purpose of this study was to determine whether multi-voxel magnetic resonance spectroscopic imaging (MRSI) can differentiate between intracranial neoplastic and non-neoplastic and between neoplastic ring-enhancing lesions (RELs) based on differences in major metabolite ratios in their enhancing and peri-enhancing regions. Methods In a prospective observational study involving patients with an intracerebral RELs, MRSI using the two-dimensional multi-voxel point-resolved spectroscopy (PRESS) chemical-shift imaging (CSI) sequence at an echo time (TE) of 135 milliseconds (ms) was performed on a total of 38 patients. Of 38 lesions, 23 (60.5%) were neoplastic and 15 (39.5%) were non-neoplastic. Of the 23 neoplastic lesions, 12 were high-grade gliomas (HGGs), seven were metastases, and four were low-grade gliomas (LGGs). Major metabolite ratios, i.e., choline-to-N-acetylaspartate (Cho/NAA), choline-to-creatine (Cho/Cr), and N-acetylaspartate-to-creatine (NAA/Cr), were calculated in the enhancing and peri-enhancing regions of the RELs. A Mann-Whitney U test was run to determine differences in metabolite ratios at different voxel locations between neoplastic versus non-neoplastic lesions, HGGs versus metastatic lesions, and HGGs versus LGGs. A receiver operating characteristic (ROC) curve analysis was performed to derive cut-off values for Cho/NAA and NAA/Cr ratios in the enhancing and peri-enhancing portions of the lesions. Results The sensitivity, specificity, positive predictive value, and negative predictive value for categorizing an REL in either neoplastic or non-neoplastic lesions using MRSI with magnetic resonance imaging (MRI) were 91.3%, 73.3%, 84%, and 84.6%, respectively. There was a statistically significant difference between Cho/NAA (p = 0.006) and NAA/Cr (p = 0.021) ratios in the enhancing region of 23 neoplastic and 15 non-neoplastic lesions. In the voxel placed in the peri-enhancing portions, the differences between Cho/Cr ratios were just significant (p = 0.047). A cut-off score of Cho/NAA >1.67 in the enhancing regions gave a sensitivity of 82.6% and specificity of 60%. The cut-off score for NAA/Cr of <0.80 in the enhancing regions showed a sensitivity and specificity of 60.9% and 86.7%, respectively. Of the 23 neoplastic lesions, 12 HGGs and seven metastases were differentiated using the Cho/NAA ratio in the peri-enhancing region with a cut-off value of 1.21, sensitivity of 100%, and specificity of 85%. A cut-off value of Cho/Cr ≥1.45 in the peri-enhancing regions showed a sensitivity of 83% and a specificity of 71.4%. For discriminating between 12 HGGs and four LGGs both from the 23 neoplastic REL group, using the cut-off score for Cho/NAA in the enhancing portions ≥4.16 showed a sensitivity of 0.75 and specificity of 100%. In the peri-enhancing regions, a cut-off score of ≥2.07 provided a sensitivity and specificity of 83% and 100%, respectively. Conclusion Conventional MRI sometimes poses a diagnostic challenge in distinguishing between neoplastic and non-neoplastic lesions and other neoplastic RELs. Interpreting MRSI findings by comparing the major metabolite ratios in the enhancing and peri-enhancing regions of these lesions may enable distinction between the two.

Primary angiitis of the central nervous system as a mimic of multiple sclerosis: A case report.

BACKGROUND: Primary angiitis of the central nervous system is a rare inflammatory vasculopathy and it is a difficult diagnosis to make because of its kaleidoscopic presentation and its multiple mimics, including multiple sclerosis. CASE PRESENTATION: A 21-year-old men presented a four-year history of progressive gait deterioration. Magnetic resonance imaging of the brain and spine showed hyperintense round-shaped lesions on T2 images, many with contrast enhancement, in supra/infratentorial and spinal segments. He received treatment for multiple sclerosis but presented clinical worsening, and follow-up neuroimaging showed persistent contrast enhancement lesions and a cerebellar hematoma. Brain biopsy was performed and demonstrated inflammatory infiltrations in blood vessels. The patient received 6 monthly schedules of 5 g methylprednisolone and 1 g cyclophosphamide with clinical stabilization. DISCUSSION: Our patient presented a primary angiitis central nervous system according to the Birnbaum and Hellmann proposed criteria. This case reinforces the importance of advancing the differential diagnosis of patients that present red flags in brain neuroimaging. CONCLUSION: The presence of the micro/macrobleeds and persistent contrast enhancing lesions should raise the suspicion of vasculitis in the differential diagnosis of multiple sclerosis.

Safety and efficacy of tyrosine kinase inhibitors for the treatment of multiple sclerosis: A systematic review and meta-analysis from randomized controlled trials.

Background: Multiple sclerosis (MS), an autoimmune disease, is characterized by inflammatory demyelinating lesions in the white matter of the central nervous system. Drugs targeting tyrosine kinase, a critical component of immune cell receptor signaling, have been developed to treat MS. However, the exact efficacy and safety of tyrosine kinase inhibitors (TKIs) are still controversial, and comprehensive analysis with a high level of evidence is needed. Methods: Medline, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials (RCTs) evaluating TKIs versus placebo for MS were searched up to April 1st, 2022. The risk ratio (RR) and mean difference (MD) or standard mean difference (SMD) were analyzed using dichotomous outcomes and continuous outcomes, respectively, with a random effect model. Results: A total of 1,043 patients derived from four clinical trials were included to investigate the efficacy and safety of TKI therapy for MS. According to our analysis, TKIs decreased the cumulative number of gadolinium-enhancing lesions on T1-weighted MRI with the application of high dose (SMD = -0.61, 95% CI: -0.93 to -0.30, P = 0.0001). Meanwhile, TKIs prevented the expanded disability status scale (EDSS) from rising (MD = -0.10, 95% CI: -0.19 to -0.00, P = 0.046). In terms of MS relapse, TKIs have not revealed an obvious statistical difference compared with placebo (RR = 0.96, 95% CI: 0.55-1.65, P = 0.8755). However, more adverse events seem to occur in the TKIs group, both for adverse events (RR = 1.12, 95% CI: 1.05-1.19, P = 0.0009) and serious adverse events (RR = 1.91, 95% CI: 1.30-2.81, P = 0.001). Conclusion: Tyrosine kinase inhibitors have shown promise in treating MS. Generally, TKIs that attain the effective dose demonstrate definite efficacy and have tolerable side effects. More clinical trials and validation are needed, and we anticipate that TKIs will be a viable alternative for MS patients.

Spontaneous Escherichia coli Meningitis and Brain Abscess in an Immunocompetent Adult.

Escherichia coli is widely known to be a common cause of gram-negative bacterial meningitis in neonates and infants but is a rare cause of central nervous system infection in adults. Risk factors for E. coli meningitis (e.g., penetrating head trauma or neurosurgery) have been broadly discussed in the literature. Here, we describe a case of spontaneous E. coli meningitis with multiple enhancing brain lesions and liver abscess in an immunocompetent adult that presented as generalized weakness.

Reactivation of Disseminated Histoplasmosis With Central Nervous System Involvement Following a Primary Gastrointestinal Histoplasmosis Infection: A Case Report.

A 78-year-old white male with chronic pancytopenia presented with acute transient aphasia and dysarthria. He had a National Institutes of Health Stroke Scale (NIHSS) of zero. Physical examination revealed slight aphasia with mild dysarthria. Brain magnetic resonance imaging (MRI) revealed nine ring-enhancing lesions in the left precentral gyrus with significant vasogenic edema. Lung computed tomography (CT) showed no evidence of pulmonary nodules. The serology of blood and urine for infectious organisms was negative. Four weeks later, the patient was re-admitted with worsening dysarthria and right upper extremity weakness. Repeat head MRI showed a slight increase in the size of the multiple supratentorial ring-enhancing lesions. The magnetic resonance spectroscopy (MRS) findings of the evaluated lesion suggested a fungal etiology. Empiric amphotericin B treatment was initiated, which mitigated central nervous system (CNS) ring-enhancing lesions and resolved the patient's neurological deficits. Early empiric medical treatment of CNS histoplasmosis should be considered in the setting of multiple CNS ring-enhancing lesions and a positive history of histoplasmosis infection, despite negative serological studies.

Multiple rim-enhancing brain lesions and pulmonary cavitary nodules as the presentation of Nocardia cyriacigeorgica in a patient with non-small cell lung cancer.

Nocardiosis is caused by various strains of the genus Nocardia, a gram-positive, acid-fast bacillus found in organic matter. Disseminated nocardiosis with central nervous system involvement is a rare infection that is most commonly seen in immunocompromised patients. We present a case of a 67-year-old veteran with stage IV adenocarcinoma of the lung undergoing chemotherapy who presented with new cavitary pulmonary lesions. Three weeks into his hospitalization, a sputum culture with acid-fast staining returned positive for Nocardia cyriacigeorgica. A subsequent computed tomography scan of the head demonstrated numerous rim-enhancing lesions presumed to be due to disseminated nocardiosis with central nervous system involvement. Disseminated nocardiosis has a high mortality rate, making prompt detection and treatment paramount for these patients. Our case highlights the importance of considering central nervous system involvement in the evaluation of a patient with nocardiosis.

Malignant Acute Disseminated Encephalomyelitis (ADEM) Presenting as a Stroke Alert: A Case Report.

Acute disseminated encephalomyelitis (ADEM) is a rare illness. Generally characterized by encephalopathy and non-specific, heterogeneous neurological deficits depending on the location of the demyelinated lesions, ADEM is considered a clinical diagnosis with radiological findings that may or may not have supportive features based on the temporal relationship of an inciting factor and symptom onset. Even rarer, hyperacute or malignant ADEM can be defined by rapid symptom onset followed by catastrophic brain edema and its sequelae. We present a case of a patient who presented with an acute stroke with activation of a rapid sequence care pathway (stroke alert protocol) to mobilize resources that could expedite his care to determine eligibility for thrombolysis. ADEM was the definitive diagnosis with a subsequent rapid and treatment-refractory decline.

The timed 25-foot walk is a more sensitive outcome measure than the EDSS for PPMS trials: an analysis of the PROMISE clinical trial dataset.

BACKGROUND: Clinical trials in primary progressive MS (PPMS) generally use the Expanded Disability Status Scale (EDSS) as their primary outcome measure, although different clinical outcomes may be more useful. Disability worsening in PPMS trials may be influenced by baseline factors, such as age, sex, and contrast-enhancing lesions. METHODS: We used the dataset of PROMISE, a large randomized controlled trial of glatiramer acetate (GA) versus placebo, to compare the clinical outcomes EDSS, timed 25-foot walk (T25FW), and nine-hole peg test (NHPT). We used Cox regression analyses to investigate the association of the baseline factors age, sex, treatment arm, contrast-enhancing lesions (CELs), and EDSS on the time to 3-month confirmed disability worsening (3MCDW) on the EDSS and the T25FW. RESULTS: PROMISE included 943 participants. Worsening on the T25FW or EDSS or occurred much more frequently than on the NHPT. Having CELs at baseline was associated with a shorter time to 3MCDW on both the EDSS and T25FW. An additional resampling experiment using the PROMISE dataset showed that increasing representation of participants with CELs at baseline increases the likelihood of having a positive trial result in favor of GA treatment. CONCLUSION: Our investigation suggests that the T25FW may be a more useful primary outcome measure than the EDSS in PPMS trials, and that its use may shorten clinical trials. Our findings on the impact of CELs at baseline on disability outcomes inform the critical appraisal of clinical trials in PPMS.

Impact of disease-modifying therapies on MRI outcomes in patients with relapsing -remitting multiple sclerosis: A systematic review and network meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system. The clinical presentation supported by characteristic findings on MRI forms the backbone of the current diagnostic criteria. This study was aimed to investigate the efficacy based on MRI outcomes of FDA approved disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) of DMTs. The outcome measures were the mean number of T2 [new/enlarging lesions], new T1 [gadolinium-enhancing (Gd+) T1 and hypointense T1] lesions in brain MRI performed at 12 months or 24 months. We performed a network meta-analysis using the frequentist approach in STATA version 16.0. RESULTS: We identified 26 RCTs for final analysis. Interferon ß-1a and placebo were the most common comparison treatment. Ocrelizumab was more effective in reducing the number of Gd+T1 lesions. Dimethyl fumarate 480 mg was relatively better in reducing the number of new T2 lesions. The treatment ranking showed that ocrelizumab and dimethyl fumarate 480 mg were more efficacious (1 and 0.9 in SUCRA, respectively) for reducing the number of new Gd+T1/hypointense lesions; dimethyl fumarate 480 mg/720 mg and natalizumab were more efficacious (1.0, 0.9 and 0.8 in SUCRA, respectively) to reduce the number of new T2 lesions. CONCLUSION: Ocrelizumab, dimethyl fumarate 480/720 mg and natalizumab demonstrated favourable MRI outcomes in patients with the RRMS.

Non-enhancing intraventricular tumours in adults.

Intraventricular tumours are relatively uncommon among all brain tumours, and non-enhancing lesions, mostly subependymoma, are even less frequently reported. Select cases of subependymoma can show variable contrast enhancement as well. Gross total surgical resection is recommended for treating these lesions, with no significant role of adjuvant chemotherapy or radiotherapy.