Encephalic hemodynamic phases in subarachnoid hemorrhage: how to improve the protective effect in patient prognoses

Subarachnoid hemorrhage is frequently associated with poor prognoses. Three different hemodynamic phases were identified during subarachnoid hemorrhage: oligemia, hyperemia, and vasospasm. Each phase is associated with brain metabolic changes. In this review, we correlated the hemodynamic phases with brain metabolism and potential treatment options in the hopes of improving patient prognoses.     

Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

     

Degenerative parkinsonism in patients with psychogenic parkinsonism: A dopamine transporter imaging study

Objectives

To evaluate patients with “clinically established” psychogenic parkinsonism (PsyP) using single-photon emission computer tomography (SPECT) with the technetium-99m labeled tracer TRODAT-1, a dopamine transporter (DAT) ligand, and investigate whether these patients have an underlying degenerative parkinsonism.

Patients and methods

Five patients with PsyP were assessed using demographic data, standard clinical scales for Parkinson's Disease (PD), and a neuropsychiatric interview. DAT imaging using SPECT with TRODAT-1 was performed, and values for caudate/putamen DAT binding potentials (BP) registered. Patients with PsyP were matched with PD (n = 5) and healthy control subjects (n = 5).

Results

The mean age (years-old) at first evaluation in the PsyP group was 37.4 ± 3.7, and the mean disease duration (years) was 3.9 ± 1.2. DAT BPs (means ± standard deviations) on right/left caudate were, respectively, 0.69 ± 0.18 and 0.70 ± 0.18 in the PD group versus 1.17 ± 0.06 and 1.12 ± 0.10 in the control group. DAT BPs on right/left putamen were, respectively, 0.48 ± 0.10 and 0.45 ± 0.06 in the PD group versus 1.10 ± 0.10 and 1.21 ± 0.43 in the control group. Two out of five patients from the PsyP group had values for DAT BP in the putamen under the cut-off (≤0.70) for controls, implying pre-synaptic dopaminergic deficit.

Conclusions

Our data in this small group of patients suggest that DAT imaging is a tool that may help in the identification of underlying degenerative parkinsonism in PsyP.     

Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine

Background  Resistance to drug is a major cause of treatment failure in pediatric brain cancer. The multidrug resistance (MDR) phenotype can be mediated by the superfamily of adenosine triphosphate-binding cassette (ABC) transporters. The dynamics of expression of the MDR genes after exposure to chemotherapy, especially the comparison between pediatric brain tumors of different histology, is poorly described. Objective  To compare the expression profiles of the multidrug resistance genes ABCB1, ABCC1, and ABCG2 in different neuroepithelial pediatric brain tumor cell lines prior and following short-term culture with vinblastine. Methods  Immortalized lineages from pilocytic astrocytoma (R286), anaplasic astrocytoma (UW467), glioblastoma (SF188), and medulloblastoma (UW3) were exposed to vinblastine sulphate at different schedules (10 and 60 nM for 24 and 72 h). Relative amounts of mRNA expression were analyzed by real-time quantitative polymerase chain reaction. Protein expression was assessed by immunohistochemistry for ABCB1, ABCC1, and ABCG2. Results  mRNA expression of ABCB1 increased together with augmenting concentration and time of exposure to vinblastine for R286, UW467, and UW3 cell lines. Interestingly, ABCB1 levels of expression diminished in SF188. Following chemotherapy, mRNA expression of ABCC1 decreased in all cell lines other than glioblastoma. ABCG2 expression was influenced by vinblastine only for UW3. The mRNA levels showed consistent association to protein expression in the selected sets of cell lines analyzed. Conclusions  The pediatric glioblastoma cell line SF188 shows different pattern of expression of multidrug resistance genes when exposed to vinblastine. These preliminary findings may be useful in determining novel strategies of treatment for neuroepithelial pediatric brain tumors. Financial support: FAPESP (grant 2007/04065-9).     

GABA inactivation of area V4 changes receptive-field properties of V2 neurons in Cebus monkeys

To investigate the contribution of feedback circuits from area V4 to the receptive-field properties of V2 neurons, we used tungsten microelectrodes to record extracellular single units in these visual areas, before and after pressure injections of a solution of 0.25 mol/L of GABA in two anesthetized and paralyzed Cebus apella monkeys. The visual stimulus consisted of a single bar moving in one of eight directions. Using a device made of four stainless steel pipettes and one central tungsten electrode, we inactivated, with different amounts of GABA, topographically corresponding areas of V4, while studying V2 neurons. We studied a total of 36 V2 neurons during six sessions of GABA injections into area V4. GABA inactivation of visual area V4 produced a general decrease in the excitability of the neurons, which included a decrease in spontaneous and driven activities, followed by changes in direction selectivity. The changes in selectivity were toward an increase in directional selectivity and decrease in orientation selectivity. Thus, feedback connections arising from V4, an area of the ventral steams of visual information processing, are capable of not only modulating the spontaneous and driven activity of V2 neurons, but also of modifying V2 receptive field properties, such as its direction and/or orientation selectivity.     

Long-term follow-up of the ketogenic diet for refractory epilepsy: Multicenter Argentinean experience in 216 pediatric patients

Purpose

In this Argentinean retrospective, collaborative, multicenter study, we examine the efficacy and tolerability of the ketogenic diet (KD) for different epilepsy syndromes.

Materials and methods

we evaluated the clinical records of 216 patients started on the KD between March 1, 1990 and December 31, 2010.

Results

One hundred forty of the initial patients (65%) remained on the diet at the end of the study period. Twenty-nine patients (20.5%) became seizure free and 50 children (36%) had a 75–99% decrease in seizures. Thus, 56.5% of the patients had a seizure control of more than 75%. The best results were found in patients with epilepsy with myoclonic-astatic seizures, Lennox–Gastaut syndrome, and West syndrome. Good results were also found in patients with Dravet syndrome, in those with symptomatic focal epilepsy secondary to malformations of cortical development, and in patients with tuberous sclerosis. Seizures were significantly reduced in four patients with fever-induced refractory epileptic encephalopathy in school-age children and in two patients with epileptic encephalopathy with continuous spikes and waves during slow sleep. The median period of follow-up after discontinuation of the diet was 6 years. Twenty patients who had become seizure free discontinued the diet, but seizures recurred in five (25%). Of 40 patients with a seizure reduction of more than 50% who discontinued the diet, 10 presented with recurrent seizures.

Conclusion

The ketogenic diet is a good option in the treatment of refractory epilepsy. After discontinuing the diet, seizures recurrence occurred in few patients.     

Machado-Joseph disease in Brazil: from the first descriptions to the emergence as the most common spinocerebellar ataxia

Machado-Joseph disease is an autosomal dominant inherited disorder of Azorean ancestry firstly described in 1972. Since then, several Brazilian researchers have studied clinical and genetic issues related to the disease. Nowadays, Machado-Joseph disease is considered the most common spinocerebellar ataxia worldwide. Machado-Joseph disease still has no specific therapy to arrest progression, but the unclear pathophysiological mechanism, features related to genetic characteristics, phenotype variability, apparently global involvement of the nervous system in the disease and the therapeutic challenges continue to attract investigators in the field of spinocerebellar ataxias. Brazilian researchers have distinguished themselves in the ongoing investigation seeking new knowledge about Machado-Joseph disease.     

MK-801 alters Na+, K+-ATPase activity and oxidative status in zebrafish brain: reversal by antipsychotic drugs

Schizophrenia is a debilitating mental disorder with a global prevalence of 1% and its etiology remains poorly understood. In the current study we investigated the influence of antipsychotic drugs on the effects of MK-801 administration, which is a drug that mimics biochemical changes observed in schizophrenia, on Na(+), K(+)-ATPase activity and some parameters of oxidative stress in zebrafish brain. Our results showed that MK-801 treatment significantly decreased Na(+), K(+)-ATPase activity, and all antipsychotics tested prevented such effects. Acute MK-801 treatment did not alter reactive oxygen/nitrogen species by 2'7'-dichlorofluorscein (H2DCF) oxidation assay, but increased the levels of thiobarbituric acid reactive substances (TBARS), when compared with controls. Some antipsychotics such as sulpiride, olanzapine, and haloperidol prevented the increase of TBARS caused by MK-801. These findings indicate oxidative damage might be a mechanism involved in the decrease of Na(+), K(+)-ATPase activity induced by MK-801. The parameters evaluated in this study had not yet been tested in this animal model using the MK-801, suggesting that zebrafish is an animal model that can contribute for providing information on potential treatments and disease characteristics.     

Diagnostic criteria for depression in Parkinson's disease: A study of symptom patterns using latent class analysis

Although major depression is one of the most frequent psychiatric disorders among patients with Parkinson's disease, diagnostic criteria have yet to be validated. The main aim of our study was to validate depressive symptoms using latent class analysis for use as diagnostic criteria for major depression in Parkinson's disease. We examined a consecutive series of 259 patients with Parkinson's disease admitted to 2 movement disorders clinics for regular follow‐ups. All patients were assessed with a comprehensive psychiatric interview that included structured assessments for depression, anxiety, and apathy. The main finding was that all 9 Diagnostic and Statistical Manual (4th edition) diagnostic criteria for major depression (ie, depressed mood, diminished interest or pleasure, weight or appetite changes, sleep changes, psychomotor changes, loss of energy, feelings of worthlessness or inappropriate guilt, poor concentration, and suicidal ideation) identified a patient class (severe depression group) with high statistical significance. Latent class analysis also demonstrated a patient class with minimal depressive symptoms (no‐depression group), and a third patient class with intermediate depressive symptoms (moderate depression). Anxiety and apathy were both significant comorbid conditions of moderate and severe depression. Taken together, our findings support the use of the full Diagnostic and Statistical Manual (4th edition) criteria for major depression for use in clinical practice and research in Parkinson's disease and suggest that anxiety may be included as an additional diagnostic criterion. © 2011 Movement Disorder Society     

Increased dopamine transporter density in Parkinson's disease patients with Social Anxiety Disorder

Social Anxiety Disorder (SAD) is more common among PD patients than in the general population. This association may be explained by psychosocial mechanisms but it is also possible that neurobiological mechanism underlying PD can predispose to SAD. The aim of this study was to investigate a possible dopaminergic mechanism involved in PD patients with SAD, by correlating striatal dopamine transporter binding potential (DAT-BP) with intensity of social anxiety symptoms in PD patients using SPECT with TRODAT-1 as the radiopharmaceutical. Eleven PD patients with generalized SAD and 21 PD patients without SAD were included in this study; groups were matched for age, gender, disease duration and disease severity. SAD diagnosis was determined according to DSM IV criteria assessed with SCID-I and social anxiety symptom severity with the Brief Social Phobia Scale (BSPS). Demographic and clinical data were also collected. DAT-BP was significantly correlated to scores on BSPS for right putamen (r=0.37, p=0.04), left putamen (r=0.43, p=0.02) and left caudate (r=0.39, p=0.03). No significant correlation was found for the right caudate (r=0.23, p=0.21). This finding may reinforce the hypothesis that dopaminergic dysfunction might be implicated in the pathogenesis of social anxiety in PD.