Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis

OBJECTIVES: Most patients with anti-NMDA receptor (NMDAR) encephalitis have intrathecal synthesis of antibodies, which cause a decrease of cell surface and synaptic NMDAR. Antibodies are immunoglobulin G (IgG)1 and IgG3 subtypes and can potentially activate complement. We examined whether complement immunoreactivity and antibody-secreting cells (plasma cells/plasmablasts) are present in the brain of these patients. METHODS: Cultured rat hippocampal neurons were used in an immunocytochemical assay to test whether patients' antibodies can fix complement. Using the same reagents (antibodies to C9neo, C(5b-9), C3), complement immunoreactivity was determined in the brain of 5 patients, the teratoma of 21 patients, and appropriate control tissues. A set of markers for B (CD20), T (CD3, CD4, CD8) and antibody-secreting cells (plasma cells/plasmablasts, CD138) were used to examine the brain inflammatory infiltrates. RESULTS: Patients' antibodies were able to bind complement in vitro, but deposits of complement were not detected in patients' brain. Parallel experiments with teratomas showed that in contrast to the brain, the neural tissue of the tumors contained complement. Analysis of the inflammatory infiltrates in brain samples from autopsy or biopsy performed 3-4 weeks after symptom presentation demonstrated numerous antibody-secreting cells (CD138+) in perivascular, interstitial, and Virchow-Robin spaces, and B and T cells predominantly located in perivascular regions. CONCLUSIONS: Complement-mediated mechanisms do not appear to play a substantial pathogenic role in anti-NMDAR encephalitis. In contrast, there are copious infiltrates of antibody-secreting cells (plasma cells/plasmablasts) in the CNS of these patients. The demonstration of these cells provides an explanation for the intrathecal synthesis of antibodies and has implications for treatment

Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction

Nimodipine is a 1,4-dihydropyridine derivative that shows a preferential cerebrovascular activity in experimental animals. Clinical data suggest that nimodipine has a beneficial effect on the neurologic outcome of patients suffering an acute ischemic stroke. Our double-blind placebo-controlled multicenter trial was designed to assess the effects of oral nimodipine on the mortality rate and neurologic outcome of patients with an acute ischemic stroke. One hundred sixty-four patients were randomly allocated to receive either nimodipine tablets (30 mg q.i.d.) or identical placebo tablets for 28 days. Treatment was always started less than or equal to 48 hours after the acute event. The Mathew Scale, slightly modified by Gelmers et al, was used for neurologic assessment. Mortality rate and neurologic outcome after 28 days were used as evaluation criteria. We considered 123 patients to be valid for the analysis of efficacy. Mortality rates did not differ significantly between groups. Neurologic outcome after 28 days of therapy did not differ between groups. However, when only those patients most likely to benefit from any intervention (Mathew Scale sum score of less than or equal to 65 at baseline) were analyzed separately in post hoc-defined subgroups, the nimodipine-treated subgroups showed a significantly better neurologic outcome. This result suggests that some patients with acute ischemic stroke will benefit from treatment with nimodipine tablets

Afasias infantiles congénitas y adquiridas

El amplio capítulo de las "disfasias o afasias del desarrollo" y el síndrome de "afasia infantil adquirida y persistente con comicialidad", son ocasión de estudio de modelos clínicos neuro-lingüísticos en los cuales se alteran y recuperan las funciones de decoficiación y codificación verbal en el cerebro en desarrollo . Dos pacientes ejemplifican cada una de las situaciones cita- das

Tomografía de emisión de fotones cerebral. Valor del índice corticocerebeloso y patrones gammagráficos en la enfermedad de Alzheimer y otras afecciones

Brain single photon emission computed tomography (SPECT) with 99mTc-HMPAO is a diagnostic tool for evaluating regional cerebral blood flow. Recently, the diagnostic possibilities of the method are being investigated in some neurologic disorders, such as cerebrovascular accidents, seizures and dementia. This work has been carried out with 54 subjects, 9 healthy volunteers and 45 patients (31 dementia and 14 epileptics), in order to evaluate gammagraphic patterns and the utility of cortico/cerebellar activity indexes. An interesting diagnostic finding is a significant decrease (p less than 0.001) in perfusion of temporoparietal regions in the patients with Alzheimer's disease in relation with the healthy volunteers' group. We have not found significant changes in perfusion in the group of epileptic patients during the interictal phase. We conclude emphasizing the interest of the SPECT in the differential diagnosis of dementia

Defining Treatment‐Related Adverse Effects in Patients with Glioma: Distinctive Features of Pseudoprogression and Treatment‐Induced Necrosis

Background: Pseudoprogression (PP) and treatment‐induced brain tissue necrosis (TN) are challenging cancer treatment–related effects. Both phenomena remain insufficiently defined; differentiation from recurrent disease frequently necessitates tissue biopsy. We here characterize distinctive features of PP and TN to facilitate noninvasive diagnosis and clinical management. Materials and Methods: Patients with glioma and confirmed PP (defined as appearance 5 months after RT) were retrospectively compared using clinical, radiographic, and histopathological data. Each imaging event/lesion (region of interest [ROI]) diagnosed as PP or TN was longitudinally evaluated by serial imaging. Results: We identified 64 cases of mostly (80%) biopsy‐confirmed PP (n = 27) and TN (n = 37), comprising 137 ROIs in total. Median time of onset for PP and TN was 1 and 11 months after RT, respectively. Clinically, PP occurred more frequently during active antineoplastic treatment, necessitated more steroid‐based interventions, and was associated with glioblastoma (81 vs. 40%), fewer IDH1 mutations, and shorter median overall survival. Radiographically, TN lesions often initially manifested periventricularly (n = 22/37; 60%), were more numerous (median, 2 vs. 1 ROIs), and contained fewer malignant elements upon biopsy. By contrast, PP predominantly developed around the tumor resection cavity as a non‐nodular, ring‐like enhancing structure. Both PP and TN lesions almost exclusively developed in the main prior radiation field. Presence of either condition appeared to be associated with above‐average overall survival. Conclusion: PP and TN occur in clinically distinct patient populations and exhibit differences in spatial radiographic pattern. Increased familiarity with both conditions and their unique features will improve patient management and may avoid unnecessary surgical procedures. Implications for Practice: Pseudoprogression (PP) and treatment‐induced brain tissue necrosis (TN) are challenging treatment‐related effects mimicking tumor progression in patients with brain cancer. Affected patients frequently require surgery to guide management. PP and TN remain arbitrarily defined and insufficiently characterized. Lack of clear diagnostic criteria compromises treatment and may adversely affect outcome interpretation in clinical trials. The present findings in a cohort of patients with glioma with PP/TN suggest that both phenomena exhibit unique clinical and imaging characteristics, manifest in different patient populations, and should be classified as distinct clinical conditions. Increased familiarity with PP and TN key features may guide clinicians toward timely noninvasive diagnosis, circumvent potentially unnecessary surgical procedures, and improve response assessment in neuro‐oncology

The impact of silent vascular brain burden in cognitive impairment in Parkinson's disease

White matter hyperintensities (WMHs) detected by magnetic resonance imaging (MRI) of the brain are associated with dementia and cognitive impairment in the general population and in Alzheimer's disease. Their effect in cognitive decline and dementia associated with Parkinson's disease (PD) is still unclear. METHODS: We studied the relationship between WMHs and cognitive state in 111 patients with PD classified as cognitively normal (n = 39), with a mild cognitive impairment (MCI) (n = 46) or dementia (n = 26), in a cross-sectional and follow-up study. Cognitive state was evaluated with a comprehensive neuropsychological battery, and WMHs were identified in FLAIR and T2-weighted MRI. The burden of WMHs was rated using the Scheltens scale. RESULTS: No differences in WMHs were found between the three groups in the cross-sectional study. A negative correlation was observed between semantic fluency and the subscore for WMHs in the frontal lobe. Of the 36 non-demented patients re-evaluated after a mean follow-up of 30 months, three patients converted into MCI and 5 into dementia. Progression of periventricular WMHs was associated with an increased conversion to dementia. A marginal association between the increase in total WMHs burden and worsening in the Mini Mental State Examination was encountered. CONCLUSIONS: White matter hyperintensities do not influence the cognitive status of patients with PD. Frontal WMHs have a negative impact on semantic fluency. Brain vascular burden may have an effect on cognitive impairment in patients with PD as WMHs increase overtime might increase the risk of conversion to dementia. This finding needs further confirmation in larger prospective studies

The DNDN, πΣc\pi \Sigma_c interaction in finite volume and the Λc(2595)\Lambda_c(2595) resonance

In this work the interaction of the coupled channels $DN$ and $\pi \Sigma_c$ in an SU(4) extrapolation of the chiral unitary theory, where the $\Lambda_c(2595)$ resonance appears as dynamically generated from that interaction, is extended to produce results in finite volume. Energy levels in the finite box are evaluated and, assuming that they would correspond to lattice results, the inverse problem of determining the phase shifts in the infinite volume from the lattice results is solved. We observe that it is possible to obtain accurate $\pi \Sigma_c$ phase shifts and the position of the $\Lambda_c(2595)$ resonance, but it requires the explicit consideration of the two coupled channels. We also observe that some of the energy levels in the box are attached to the closed $DN$ channel, such that their use to induce the $\pi \Sigma_c$ phase shifts via L\"uscher's formula leads to incorrect results.Comment: 10 pages, 13 figures, accepted for publication in Eur. Phys. J.

Correlaciones entre la SPECT cerebral y la evaluación neuropsicológica en los estadios leve y moderado de la enfermedad de Alzheimer

Se evaluaron 34 pacientes con enfermedad de Alzheimer (EA) probable (EA leve = 16; EA moderada = 18) y 12 controles mediante un estudio semicuantitativo de SPECT con 99mTc-HMPAO y la batería de tests neuropsicológicos CERAD. Resultados: La hipoperfusión temporal (p < 0,01) y los tests de memoria (p < 0,001) permitieron diferenciar los controles de los pacientes con EA leve. En estos pacientes se observaron también correlaciones significativas (p < 0,05) entre: test de recuerdo diferido-hipoperfusión temporal, test de aprendizaje-hipoperfusión temporoparietal y frontal y praxis visuoconstructiva-hipoperfusión temporal posterior. Los pacientes con EA moderada mostraron, respecto a la EA leve, una mayor hipoperfusión temporal (p < 0,01), parietal y frontal (p < 0,05), junto a un empeoramiento de la praxis (p < 0,001) y los test de memoria (p < 0,05). Conclusiones: La SPECT y la evaluación neuropsicológica permiten distinguir entre controles y pacientes con estadios leve y moderado de la EA, existiendo una estrecha correlación entre ambos métodos desde las etapas iniciales de la enfermedad