Immunologic analysis of CSF in patients with de novo diagnosed RRMS. The role of chemokines in the early phase of the disease.

OBJECTIVES: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by demyelination and neurodegeneration. Chemokines regulate leukocyte migration and inflammation in MS. In the present study, we evaluated selected chemokine levels in the cerebrospinal fluid of patients with multiple sclerosis diagnosed de novo compared to healthy controls. METHODS: We measured EOTAXIN, IP-10, MCP-1, MIP-1a, MIP-1b and RANTES in the cerebrospinal fluid of 118 patients with de novo RRMS and 112 controls, analyzing correlations with time from symptom onset to diagnosis and changes in MRI. RESULTS: Higher levels of EOTAXIN, IP-10, MIP-1B and RANTES, and lower MCP-1 were observed in MS patients compared to controls. MIP-1A did not show statistical significance. EOTAXIN and IP-10 concentrations increased with time. RANTES concentration correlated positively with T2 changes in MRI of the cervical spine, and EOTAXIN concentration correlated negatively with gadolinium (Gd+) changes in the cervical spine. There was no correlation with changes in the thoracic spine or brain. CONCLUSIONS: Chemokines play a significant role in the early phase of MS by influencing inflammatory activity. They may represent potential therapeutic targets for the treatment of this disease.

A Case Series of Scrub Meningoencephalitis from a Tertiary Care Center in North India.

Scrub typhus infection is reemerging leading cause of acute febrile illnesses in post-rainy or monsoon season in Southeast Asia. It is caused by Orientia tsutsugamushi and spread by the bite of chiggers, larval forms of trombiculid mites. The clinical picture can range from simple acute febrile illness to multiorgan dysfunction. Neurological manifestations also vary from aseptic meningitis, meningoencephalitis, cerebral infarction, acute disseminated encephalomyelitis, transverse myelitis, and psychiatric manifestations. Here, we present a case series of eight cases of scrub meningoencephalitis diagnosed based on clinical, laboratory, and radiological criteria.

Healthcare-Associated Ventriculitis in Children during COVID-19 Pandemic: Clinical Characteristics and Outcome of a First Infection.

During the COVID-19 pandemic, patients in need of neurosurgical care suffered. Elective procedures were postponed, and emergency care visits decreased. Healthcare-associated ventriculitis (HAV) is a serious problem in children, with poor outcomes and frequent relapses. Our objective was to describe the clinical characteristics and the factors associated with a first HAV in children during two years of the pandemic. A retrospective cross-sectional study was performed from January 2021 to December 2022. The inclusion criteria were patients who developed a first HAV after a primary cerebrospinal fluid diversion procedure. The controls included patients without a first infection. Intraoperative and clinical data were extracted from medical records. A total of 199 CSF diversion surgeries were registered. A first infection occurred in 17 patients (8.5%), including 10 with external ventricular drain (EVD) and 6 with ventricular shunts. Gram-positive cocci were identified in 70.6%. Six patients recovered uneventfully, eight had relapse or superinfections, and three eventually died. Twenty patients were included as controls. Factors associated with a first infection were a younger age (median 9 vs. 102 months, p < 0.01), malnutrition (23.5% vs. 0%, p = 0.03), and an EVD placement (58.8% vs. 10%, p = 0.03). None of the intraoperative factors showed statistically significant differences. The rate of HAV was high. Most cases presented in children <1 year and with an EVD.

Salivary levels of disease-related biomarkers in the early stages of Parkinson's and Alzheimer's disease: A cross-sectional study.

Introduction: Finding a non-invasive and repeatable tool has been recommended to make an accurate diagnosis of Alzheimer's disease (AD) and Parkinson's disease (PD). Methods: 70 volunteers participated in three groups: 24 with mild dementia of AD, 24 in the first and second stages of PD, and 22 healthy controls. After valuing the scores of cognitive tests, the salivary levels of phosphorylated tau (p-tau), total alpha-synuclein (α-syn), and beta-amyloid 1-42 (Aß) proteins have been evaluated. Finally, the cutoff points, receiver operating characteristic (ROC), sensitivity, and specificity have been calculated to find accurate and detectable biomarkers. Results: Findings showed that the salivary level of Aß was higher in both PD (p < 0.01) and AD (p < 0.001) patients than in controls. Moreover, the level of α-syn in both PD and AD patients was similarly lower than in controls (p < 0.05). However, the level of p-tau was only higher in the AD group than in the control (p < 0.01). Salivary Aß 1-42 level at a 60.3 pg/ml cutoff point revealed an excellent performance for diagnosing AD (AUC: 0.81). Conclusion: Evaluation of p-tau, α-syn, and Aß 1-42 levels in the saliva of AD and PD patients could help the early diagnosis. The p-tau level might be valuable for differentiation between AD and PD. Therefore, these hopeful investigations could be done to reduce the usage of invasive diagnostic methods, which alone is a success in alleviating the suffering of AD and PD patients. Moreover, introducing accurate salivary biomarkers according to the pathophysiology of AD and PD should be encouraged.

HTLV-1-associated demyelinating neuropathy: A case report and review of the literature.

A 78-year-old man developed paresthesias in the extremities. He was referred to our hospital because of positive anti-human T-cell leukemia virus type 1 (HTLV-1) antibodies in the serum and the presence of abnormal lymphocytes. He was diagnosed as chronic-type adult T-cell leukemia/lymphoma. Neurological examination revealed sensory impairment in the distal parts of the extremities with loss of deep tendon reflexes. Nerve conduction study showed motor and sensory demyelinating polyneuropathy, indicating a diagnosis of HTLV-1-associated demyelinating neuropathy. Corticosteroid therapy followed by intravenous immunoglobulin therapy improved his symptoms. Since demyelinating neuropathy associated with HTLV-1 infection is not well recognized, we here report its characteristics and clinical course through our case report and literature review.

Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys.

Mucopolysaccharidosis Type IIIB (MPS IIIB) is an ultrarare, fatal pediatric disease with no approved therapy. It is caused by mutations in the gene encoding for lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). Tralesinidase alfa (TA) is a fusion protein comprised of recombinant NAGLU and a modified human insulin-like growth factor 2 that is being developed as an enzyme replacement therapy for MPS IIIB. Since MPS IIIB is a pediatric disease the safety/toxicity, pharmacokinetics and biodistribution of TA were evaluated in juvenile non-human primates that were administered up to 5 weekly intracerebroventricular (ICV) or single intravenous (IV) infusions of TA. TA administered by ICV slow-, ICV isovolumetric bolus- or IV-infusion was well-tolerated, and no effects were observed on clinical observations, electrocardiographic or ophthalmologic parameters, or respiratory rates. The drug-related changes observed were limited to increased cell infiltrates in the CSF and along the ICV catheter track after ICV administration. These findings were not associated with functional changes and are associated with the use of ICV catheters. The CSF PK profiles were consistent across all conditions tested and TA distributed widely in the CNS after ICV administration. Anti-drug antibodies were observed but did not appear to significantly affect the exposure to TA. Correlations between TA concentrations in plasma and brain regions in direct contact with the cisterna magna suggest glymphatic drainage may be responsible for clearance of TA from the CNS. The data support the administration of TA by isovolumetric bolus ICV infusion to pediatric patients with MPS IIIB.

Predictive model for preoperative risk calculation of cerebrospinal fluid leak after resection of midline craniofacial mass lesions.

Background: Complex anterior skull base defects produced by resection of mass lesions vary in size and configuration and may be extensive. We analyzed the largest single-center series of midline craniofacial lesions extending intra- and extracranially. The study aims at the development of a predictive model for preoperative measurement of the risk of the postoperative cerebrospinal fluid (CSF) leak based on patients' characteristics and surgical plans. Methods: 166 male and 149 female patients with mean age 40,5 years (1 year and - 81 years) operated for benign and tumor-like midline craniofacial mass lesions were retrospectively analyzed using logistic regression method (Ridge regression algorithm was selected). The overall CSF leak rate was 9.6%. The ROSE algorithm and 'glmnet' software suite in R were used to overcome the cohort's disbalance and avoid overtraining the model. Results: The most influential modifiable negative predictor of the postoperative CSF leak was the use of extracranial and combined approaches. Use of transbasal approaches, gross total resection, utilization of one or two vascularized flaps for skull base reconstruction were the foremost modifiable predictors of a good outcome. Criterium of elevated risk was established at 50% with a specificity of the model as high as 0.83. Conclusions: The performed study has allowed for identifying the most significant predictors of postoperative CSF leak and developing an effective formula to estimate the risk of this complication using data known for each patient. We believe that the suggested web-based online calculator can be helpful for decision making support in off-pattern clinical situations.

Metal artifact reduction by virtual monoenergetic reconstructions from spectral brain CT.

Purpose: Conventional computed tomography (CT) images are severely affected by metal artifacts in patients with intracranial coils. Monoenergetic images have been suggested to reduce metal artifacts.The aim of this study was to assess metal artifacts in virtual monoenergetic images (VMIs) reconstructed from spectral brain CT. Methods: Thirty-two consecutive patients with intracranial coils examined by spectral non contrast brain CT (NCCT) at our center between November 2017 and April 2019 were included. Attenuation and standard deviations were measured in regions of interest (ROIs) at predefined areas in artifact-free and artifact-affected areas. Measurements were performed in conventional polyenergetic images (CIs) and the corresponding data for VMIs were retrieved through spectral diagrams for the each ROI. Subjective analysis was performed by visual grading of CIs and specific VMIs by two neuroradiologists, independently. Results: In artefact-affected image areas distal from the metal objects, the attenuation values decreased with higher energy level VMIs. The same effect was not seen for artefact-affected image areas close to the metal.Subjective rating of the artefact severity was significantly better in VMIs at 50 keV for one of the two reviewers compared to the CIs. Overall image quality and tissue differentiation scores were significantly higher for both reviewers in VMIs at 60 and 70 keV compared to CIs. Conclusion: Our quantitative and qualitative image analysis shown that there is a small significant reduction of intracranial coils artifacts severity by all monoenergetic reconstructions from 50 to 200 keV with preserved or increased overall subjective image quality compared to conventional images.

Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions.

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation of the angiotensin system. ARNi therapy is very effective in reducing the risks of death and hospitalization for HF in patients with HF and New York Heart Association functional class II to III symptoms, but studies failed to show any benefits with ARNi when compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker in patients with advanced HF with reduced ejection fraction or in patients following myocardial infarction with left ventricular dysfunction but without HF. These raise the questions about whether the enzymatic breakdown of natriuretic peptides may not be a very effective solution in advanced HF patients when there is downstream blunting of the response to natriuretic peptides or among post-myocardial infarction patients in the absence of HF when there may not be a need for increased natriuretic peptide availability. Furthermore, there is a need for additional studies to determine the long-term effects of ARNi on albuminuria, obesity, glycemic control and lipid profile, blood pressure, and cognitive function in patients with HF.

A case report: Ruptured aneurysm with a wide neck treated by flow diverter stent and coil embolization.

Diagnosis and endovascular treatment for ruptured wide neck aneurysms are challenges in clinics, particularly in developing countries. In the present study, we described a clinical case with a ruptured wide neck aneurysm in Vietnam treated by flow diverter stent and coil embolization. A 77-year-old- female patient had a right droopy eyelid for 2 months. The patient was admitted to hospital on the second day after being presented with a sudden-severe headache. Cerebral computed tomography (CT) and magnetic resonance imaging (MRI) were taken on the second day and fifth day after the onset of the headache. The results showed an aneurysm in the right internal carotid artery but no potential subarachnoid hemorrhage (SAH) was displayed. An uncoagulated blood was found in cerebrospinal fluid indicated by a lumbar puncture test. Digital subtraction angiography provided images with one wide-neck right internal carotid aneurysm. The patient was treated by flow diverter stent and coil embolization and the dual antiplatelet therapy with ticagrelor and aspirin at home. After 45 days, the patient did not face with any complication, no neurological symptoms, and the aneurysm was partially thrombosed indicated by MRI images. These results suggested that a lumbar puncture should be analyzed on the patient with brain aneurysm appeared a sudden severe headache and even no potential SAH on brain MRI or CT was found. The combination of flow diverter stent and coil embolization to treat cases with ruptured wide necked aneurysms should be considered in the future.

Invasive Nocardiosis Versus Colonization at a Tertiary Care Center: Clinical and Radiological Characteristics.

Objective: To describe the clinical and radiographic findings in a large cohort of patients with positive cultures for Nocardia emphasizing the differences between invasive disease and colonization. Patients and Methods: We conducted a single-center, retrospective cohort study of 133 patients with a positive Nocardia isolate between August 1, 1998, and November 30, 2018, and a computed tomography (CT) of the chest within 30 days before or after the bacteria isolation date. Results: Patients with colonization were older (71 vs 65 years; P=.004), frequently with chronic obstructive pulmonary disease (56.8% vs 16.9%; P<.001) and coronary artery disease (47.7% vs 27%, P=.021), and had Nocardia isolated exclusively from lung specimens (100% vs 83.1%; P=.003). On CT of the chest, they had frequent airway disease (84.1% vs 51.7%; P<.001). Patients with invasive nocardiosis had significantly (P<.05) more diabetes, chronic kidney disease, solid organ transplant, use of corticosteroids, antirejection drugs, and prophylactic sulfa. They had more fever (25.8% vs 2.3%; P<.001), cutaneous lesions (14.6% vs 0%; P=.005), fatigue (18% vs 0%; P=.001), pulmonary nodules (52.8% vs 27.3%; P=.006), and free-flowing pleural fluid (63.6% vs 29.4%; P=.024). The patterns of nodule distribution were different-diffuse for invasive nocardiosis and peribronchiolar for Nocardia colonization. Conclusion: The isolation of Nocardia in sputum from a patient with respiratory symptoms does not equal active infection. Only by combining clinical and chest CT findings, one could better differentiate between invasive nocardiosis and Nocardia colonization.

CLIPPERS: Multiparametric and quantitative MRI features.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare chronic central-nervous-system inflammatory disorder that became known only recently, and the pathogenesis of CLIPPERS remains poorly understood. This report presents clinical and radiological features of a rare case: a young female patient who rapidly died of suspected CLIPPERS. Helpful multiparametric MRI diagnostic criteria are proposed that can help discriminate CLIPPERS from non-CLIPPERS pathologies. We reviewed clinical history, symptoms, quantitative data from brain multiparametric MRI before and after treatment, and histopathological data. Perfusion-weighted imaging revealed a decrease in regional cerebral blood flow by 31% and in cerebral blood volume by 64%, with a moderate increase in transit time and in time to peak by up to 23% in affected pontine and cerebral white matter. As estimated by diffusion tensor imaging, there was elevated density of tracts (n/mm2) and a decrease of fraction anisotropy (×10-3 mm/s2) in the patient's pons as compared to a healthy control: density of tracts = 13.5 vs 12.4 and fraction anisotropy = 0.32 vs 0.45, respectively. Macromolecular proton fraction values proved to be reduced (15.8% and 14.5% in the control, respectively) in the patient's cerebral peduncles by 3% and in the pons by 4.1% and in a periventricular white matter lesion by 6.4% (11.3% in the normal-looking contralateral hemisphere). Based on our findings, we argue that quantitative MRI techniques may be a valuable source of biomarkers and reliable diagnostic criteria and can shed light on the pathogenesis and exact nosological position of this disorder.

Decompressive Craniectomy and Shunt-Amenable Post-Traumatic Hydrocephalus: A Single-Center Experience.

Background: Prior studies have shown that decompressive craniectomy may be an independent risk factor for the development of post-traumatic hydrocephalus (PTH). It is upon this background that we chose to conduct our single-center retrospective study to establish the possibility of an association between decompressive craniectomy and PTH. Methods: A retrospective review involving a database of all patients with traumatic brain injury was undertaken. All referrals and admissions with traumatic brain injury, as defined by the Mayo Classification, from January 2012 to May 2022, were included in the subsequent analysis. Statistical analysis was carried out using IBM SPSS version 28.0.1. Results: The mean age of the cohort was 44.91 ± 19.16 with more males (82.3%) than females (17.7%). Vehicle incident/collision was the most common cause of traumatic brain injury. 84% of the cohort was alive at 30 days, 4% were noted to have an intracranial infection, and 3% underwent shunt insertion procedures, while 14% received decompressive craniotomies as part of their clinical management. There was a statistically significant association between undergoing decompressive craniectomy, and the development of PTH (odds ratio, 4.759 [95% confidence interval, 1.290-17.559]; P = 0.019). The presence of intracranial infection and insertion of an external ventricular drain insertion were also independent predictors of developing PTH. Conclusions: This study adds to the growing body of work regarding the immediate and long-term effects of the procedure. Although life-saving, PTH, needing shunt insertion, is one of the possible complications that surgeons and patients should be aware of.

Conserved YKL-40 changes in mice and humans after postoperative delirium.

Delirium is a common postoperative neurologic complication among older adults. Despite its prevalence (14%-50%) and likely association with inflammation, the exact mechanisms that underpin postoperative delirium are unclear. This project aimed to characterize systemic and central nervous system (CNS) inflammatory changes following surgery in mice and humans. Matched plasma and cerebrospinal fluid (CSF) samples from the "Investigating Neuroinflammation Underlying Postoperative Brain Connectivity Changes, Postoperative Cognitive Dysfunction, Delirium in Older Adults" (INTUIT; NCT03273335) study were compared to murine endpoints. Delirium-like behavior was evaluated in aged mice using the 5-Choice Serial Reaction Time Test (5-CSRTT). Using a well established orthopedic surgical model in the FosTRAP reporter mouse we detected neuronal changes in the prefrontal cortex, an area implicated in attention, but notably not in the hippocampus. In aged mice, plasma interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40), and neurofilament light chain (NfL) levels increased after orthopedic surgery, but hippocampal YKL-40 expression was decreased. Given the growing evidence for a YKL-40 role in delirium and other neurodegenerative conditions, we assayed human plasma and CSF samples. Plasma YKL-40 levels were similarly increased after surgery, with a trend toward a greater postoperative plasma YKL-40 increase in patients with delirium. However, YKL-40 levels in CSF decreased following surgery, which paralleled the findings in the mouse brain. Finally, we confirmed changes in the blood-brain barrier (BBB) as early as 9 h after surgery in mice, which warrants more detailed and acute evaluations of BBB integrity following surgery in humans. Together, these results provide a nuanced understanding of neuroimmune interactions underlying postoperative delirium in mice and humans, and highlight translational biomarkers to test potential cellular targets and mechanisms.

Cerebral syphilitic gumma mimicking a brain tumor that enlarged temporarily after commencing antibiotic treatment.

In this case report, we describe a 60-year-old man who presented with headaches for 1 year and mild confusion for 3 weeks and was initially diagnosed as having a cerebral tumor on the basis of finding a round lesion in the right lenticular nucleus with ring enhancement on gadolinium-enhanced T1-weighted brain magnetic resonance imaging. However, the discovery of positive serology for Treponema pallidum infection on routine tests on admission prompted analysis of cerebrospinal fluid, which was also positive on Treponema pallidum hemagglutination (TPHA), rapid plasma reagin (RPR), and treponemal antibody absorption (FTA-ABS) tests. Thus, he was diagnosed as having an intracranial syphilitic gumma. After commencing treatment with penicillin G, the lesion temporarily increased in size, but subsequently resolved completely with continuing antibiotic treatment. In the present era of increasing prevalence of syphilitic infection and because they are eminently treatable, syphilitic gummas should be included in the differential diagnosis of apparent brain tumors. Additionally, temporary enlargement of a probable gumma after instituting antibiotic treatment should not prompt cessation or change of the antibiotics.

Vascular intracranial malformations and dementia: An under-estimated cause and clinical correlation. Clinical note.

Cerebrovascular malformations (CVMs) such as arteriovenous malformations (AVMs) or dural arteriovenous fistulas (DAVFs) represent a possible source of intracranial hemorrhage, but these malformations can also manifest with neurologic disorders secondary to ischemic penumbra from vascular steal. In the latter case, the clinical manifestations are less obvious and characteristic, and may include a varied clinical spectrum ranging from focal deficits to generalized malfunction of the brain parenchyma resulting in dementia. Dementias secondary to CVMs constitute a probably underestimated subpopulation of patients of great interest because they present with devastating but potentially reversible cognitive impairment. We examined the pertinent literature regarding the clinical manifestations of CVMs characterized by cognitive impairment and describe the distinctive clinical features. Our results confirm that cognitive impairment is one of the clinical manifestations of CVMs and is a frequently misrecognized and often late-diagnosed cause of reversible dementia.

MOG antibody associated disease (MOGAD) presenting with extensive brain stem encephalitis: A case report.

Background: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a relatively new entity of demyelinating diseases, clinically presenting with optic neuritis, transverse myelitis, or encephalic symptoms. Typical radiological features include demyelinating cerebral and spinal lesions, cortical involvement, leptomeningeal enhancement, or tumefactive lesions. Here we present a rare case of a young patient with extensive brain stem lesion on the MRI while exhibiting nystagmus, singultus and somnolence. Case presentation: A 30-year-old male patient presented initially with fever and impaired consciousness, but furthermore developed nystagmus, singultus and tetraparesis during the following week. Repeated MRI examinations revealed extensive brain stem edema with notable bilateral affection of the cerebellar peduncles and the pons. Antiviral and antibiotic treatment was changed to intravenous corticosteroids and immunoglobulins as soon as the diagnosis of MOGAD was established by testing serum and cerebrospinal fluid positive for MOG specific antibodies. MRI alterations vanished completely over time with a delayed, nearly complete clinical recovery of our patient. Conclusion: Brain stem affection in MOGAD is rare. However, in patients presenting with an unclear brain stem encephalitis the possibility of MOGAD should be considered and tested using MOG antibodies. In case of a positive testing treatment with steroids and immunoglobulins seems recommendable.