Extracellular glutamate and GABA transients at the transition from interictal spiking to seizures.

Focal epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood. We used fluorescent glutamate and GABA sensors in an awake rodent model of neocortical seizures to resolve the spatiotemporal evolution of both neurotransmitters in the extracellular space. Interictal spikes were accompanied by brief glutamate transients which were maximal at the initiation site and rapidly propagated centrifugally. GABA transients lasted longer than glutamate transients and were maximal ∼1.5 mm from the focus where they propagated centripetally. Prior to seizure initiation GABA transients were attenuated, whilst glutamate transients increased, consistent with a progressive failure of local inhibitory restraint. As seizures increased in frequency, there was a gradual increase in the spatial extent of spike-associated glutamate transients associated with interictal spikes. Neurotransmitter imaging thus reveals a progressive collapse of an annulus of feed-forward GABA release, allowing seizures to escape from local inhibitory restraint.

Anti-seizure gene therapy for focal cortical dysplasia.

Focal cortical dysplasias are a common subtype of malformation of cortical development, which frequently presents with a spectrum of cognitive and behavioural abnormalities as well as pharmacoresistant epilepsy. Focal cortical dysplasia type II is typically caused by somatic mutations resulting in mammalian target of rapamycin (mTOR) hyperactivity, and is the commonest pathology found in children undergoing epilepsy surgery. However, surgical resection does not always result in seizure freedom, and is often precluded by proximity to eloquent brain regions. Gene therapy is a promising potential alternative treatment and may be appropriate in cases that represent an unacceptable surgical risk. Here, we evaluated a gene therapy based on overexpression of the Kv1.1 potassium channel in a mouse model of frontal lobe focal cortical dysplasia. An engineered potassium channel (EKC) transgene was placed under control of a human promoter that biases expression towards principal neurons (CAMK2A) and packaged in an adeno-associated viral vector (AAV9). We used an established focal cortical dysplasia model generated by in utero electroporation of frontal lobe neural progenitors with a constitutively active human Ras homolog enriched in brain (RHEB) plasmid, an activator of mTOR complex 1. We characterized the model by quantifying electrocorticographic and behavioural abnormalities, both in mice developing spontaneous generalized seizures and in mice only exhibiting interictal discharges. Injection of AAV9-CAMK2A-EKC in the dysplastic region resulted in a robust decrease (∼64%) in the frequency of seizures. Despite the robust anti-epileptic effect of the treatment, there was neither an improvement nor a worsening of performance in behavioural tests sensitive to frontal lobe function. AAV9-CAMK2A-EKC had no effect on interictal discharges or behaviour in mice without generalized seizures. AAV9-CAMK2A-EKC gene therapy is a promising therapy with translational potential to treat the epileptic phenotype of mTOR-related malformations of cortical development. Cognitive and behavioural co-morbidities may, however, resist an intervention aimed at reducing circuit excitability.

Heated environment increases blood pressure drop and postural sway during initial orthostasis in healthy subjects.

PURPOSE: We tested the hypothesis that heat stress influences the closed-loop cardio-postural control by an increased blood pressure (BP) drop and postural sway. METHODS: Fourteen healthy individuals (eight women) performed two orthostatic tests under thermal reference (TC; ~ 24 ºC) and HOT (~ 38 ºC) conditions. The center-of-pressure (COP) displacements and the electromyography (EMG) activity of the calf muscles (medial gastrocnemius and tibialis anterior) were recorded during the initial orthostasis (ORT onset) after the supine-to-stand challenge. At the same period, BP (beat-to-beat) was continuously monitored, and supine-to-stand variations (∆%) were calculated. Sublingual temperature (Tsl) was measured as a surrogate of internal temperature. RESULTS: Tsl increased in HOT compared to TC (TC 36.5 ± 0.3 vs. HOT 36.7 ± 0.3 ºC; p < 0.01). COP distance was greater in HOT compared to TC condition (TC 596.6 ± 242.4 vs. HOT 680.2 ± 249.1 mm; p < 0.01). EMG activity of the gastrocnemius decreased in HOT compared to TC condition (TC 95.5 ± 19.8 vs. HOT 78.4 ± 22.8%mV; p = 0.02). EMG of tibialis did not change between TC and HOT (TC 83.5 ± 42.9 vs. HOT 66.1 ± 31.9% mV; p = 0.29). BP showed a greater fall in HOT compared to TC condition (∆%TC - 24.5 ± 13.2 vs. ∆%HOT - 33.2 ± 20.2%; p = 0.01). CONCLUSION: Heat stress causes a greater fall in blood pressure and a reduction in musculoskeletal pump activity during orthostatic onset. These effects could be potential mechanisms that underlie augmented postural instability under a heated environment.

Sexual Dysfunction in Parkinson's Disease: A Systematic Review of the Arizona Sexual Experience Scale Sexual Dysfunction in Parkinson Disease: A Systematic Review of the Arizona Sexual Experience Scale.

OBJECTIVE: Parkinson's disease (PD) affects older individuals and can cause sexual dysfunction (SD). SD is a determinant of general well-being; but is infrequently assessed in professionally. The Arizona Sexual Experience Scale (ASEX) measures SD; unlike other scales, it is minimally invasive and requires little time to complete. This review aimed to assess the prevalence of SD in patients with PD using ASEX. METHODS: Were searched the keywords, "sexual dysfunction," "Parkinson's disease" and "ASEX" in 9 databases. RESULTS: The prevalence of SD ranged from 65%-90%. SD was associated with older age at disease onset, higher Unified Parkinson Disease Rating Scale scores, age and depression (p ranged from .001 to <.05). The most observed SD was erectile dysfunction in men. CONCLUSION: SD is common among patients with PD. ASEX, although not specific to PD, is an easy and quickly applied tool that can help evaluate SD and guide treatments in PD.

A genetically encoded fluorescent sensor for in vivo imaging of GABA.

Current techniques for monitoring GABA (γ-aminobutyric acid), the primary inhibitory neurotransmitter in vertebrates, cannot follow transients in intact neural circuits. To develop a GABA sensor, we applied the design principles used to create the fluorescent glutamate receptor iGluSnFR. We used a protein derived from a previously unsequenced Pseudomonas fluorescens strain and performed structure-guided mutagenesis and library screening to obtain intensity-based GABA sensing fluorescence reporter (iGABASnFR) variants. iGABASnFR is genetically encoded, detects GABA release evoked by electric stimulation of afferent fibers in acute brain slices and produces readily detectable fluorescence increases in vivo in mice and zebrafish. We applied iGABASnFR to track mitochondrial GABA content and its modulation by an anticonvulsant, swimming-evoked, GABA-mediated transmission in zebrafish cerebellum, GABA release events during interictal spikes and seizures in awake mice, and found that GABA-mediated tone decreases during isoflurane anesthesia.

LGI1 downregulation increases neuronal circuit excitability.

OBJECTIVE: Leucine-rich glioma-inactivated 1 (LGI1) is a secreted transsynaptic protein that interacts presynaptically with Kv1.1 potassium channels and a disintegrin and metalloprotease (ADAM) protein 23, and postsynaptically influences α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors through a direct link with the ADAM22 cell adhesion protein. Haploinsufficiency of LGI1 or autoantibodies directed against LGI1 are associated with human epilepsy, generating the hypothesis that a subacute reduction of LGI1 is sufficient to increase network excitability. METHODS: We tested this hypothesis in ex vivo hippocampal slices and in neuronal cultures, by subacutely reducing LGI1 expression with shRNA. RESULTS: Injection of shRNA-LGI1 in the hippocampus increased dentate granule cell excitability and low-frequency facilitation of mossy fibers to CA3 pyramidal cell neurotransmission. Application of the Kv1 family blocker, α-dendrotoxin, occluded this effect, implicating the involvement of Kv1.1. This subacute reduction of LGI1 was also sufficient to increase neuronal network activity in neuronal primary culture. SIGNIFICANCE: These results indicate that a subacute reduction in LGI1 potentiates neuronal excitability and short-term synaptic plasticity, and increases neuronal network excitability, opening new avenues for the treatment of limbic encephalitis and temporal lobe epilepsies.

Activity Clamp Provides Insights into Paradoxical Effects of the Anti-Seizure Drug Carbamazepine.

A major challenge in experimental epilepsy research is to reconcile the effects of anti-epileptic drugs (AEDs) on individual neurons with their network-level actions. Highlighting this difficulty, it is unclear why carbamazepine (CBZ), a frontline AED with a known molecular mechanism, has been reported to increase epileptiform activity in several clinical and experimental studies. We confirmed in an in vitro mouse model (in both sexes) that the frequency of interictal bursts increased after CBZ perfusion. To address the underlying mechanisms, we developed a method, activity clamp, to distinguish the response of individual neurons from network-level actions of CBZ. We first recorded barrages of synaptic conductances from neurons during epileptiform activity and then replayed them in pharmacologically isolated neurons under control conditions and in the presence of CBZ. CBZ consistently decreased the reliability of the second action potential in each burst of activity. Conventional current-clamp recordings using excitatory ramp or square-step current injections failed to reveal this effect. Network modeling showed that a CBZ-induced decrease of neuron recruitment during epileptic bursts can lead to an increase in burst frequency at the network level by reducing the refractoriness of excitatory transmission. By combining activity clamp with computer simulations, the present study provides a potential explanation for the paradoxical effects of CBZ on epileptiform activity.SIGNIFICANCE STATEMENT The effects of anti-epileptic drugs on individual neurons are difficult to separate from their network-level actions. Although carbamazepine (CBZ) has a known anti-epileptic mechanism, paradoxically, it has also been reported to increase epileptiform activity in clinical and experimental studies. To investigate this paradox during realistic neuronal epileptiform activity, we developed a method, activity clamp, to distinguish the effects of CBZ on individual neurons from network-level actions. We demonstrate that CBZ consistently decreases the reliability of the second action potential in each burst of epileptiform activity. Network modeling shows that this effect on individual neuronal responses could explain the paradoxical effect of CBZ at the network level.

Low Sensitivity of the Mini-Mental State Examination for Cognitive Assessment of Brazilian Patients With Parkinson Disease.

INTRODUCTION: Recent publications have highlighted the low sensitivity of the Mini-Mental State Examination (MMSE) for the cognitive assessment of patients with Parkinson disease (PD). The Montreal Cognitive Assessment (MoCA), otherwise, has shown greater sensitivity when compared to the MMSE. Based on this, we have searched for the cognitive impairment measurable by the MoCA and the functional performance on activities of daily living in a sample of Brazilian patients with PD and normal MMSE. We hypothesized that the low sensitivity of the MMSE, already shown by other authors, could be replicated in a low-income country. OBJECTIVE: To describe the performance on the MoCA and the dependence on third parties for activities of daily living in a sample of Brazilian patients with PD and normal MMSE. METHODS: We evaluated 43 volunteers with PD and normal MMSE considering the Brazilian cutoffs. Cognitive performance was assessed through the MoCA and functional performance through a modified version of the Disability Assessment for Dementia Scale. RESULTS: Despite normal score on the MMSE, considering the Brazilian cutoffs, 62.7% of the volunteers performed below the literature cutoff for the MoCA (26 points). Furthermore, 30.2% had dependence on third party for activities of daily living. By using a strict cutoff for the MMSE (26 points), 56.7% performed below the MoCA cutoff and 24.3% had dependence for activities of daily living. CONCLUSIONS: Our findings confirm the limitations of the MMSE for the cognitive screening of patients with PD in a low-income country.

Ballistocardiogram artifact correction taking into account physiological signal preservation in simultaneous EEG-fMRI.

The ballistocardiogram (BCG) artifact is currently one of the most challenging in the EEG acquired concurrently with fMRI, with correction invariably yielding residual artifacts and/or deterioration of the physiological signals of interest. In this paper, we propose a family of methods whereby the EEG is decomposed using Independent Component Analysis (ICA) and a novel approach for the selection of BCG-related independent components (ICs) is used (PROJection onto Independent Components, PROJIC). Three ICA-based strategies for BCG artifact correction are then explored: 1) BCG-related ICs are removed from the back-reconstruction of the EEG (PROJIC); and 2-3) BCG-related ICs are corrected for the artifact occurrences using an Optimal Basis Set (OBS) or Average Artifact Subtraction (AAS) framework, before back-projecting all ICs onto EEG space (PROJIC-OBS and PROJIC-AAS, respectively). A novel evaluation pipeline is also proposed to assess the methods performance, which takes into account not only artifact but also physiological signal removal, allowing for a flexible weighting of the importance given to physiological signal preservation. This evaluation is used for the group-level parameter optimization of each algorithm on simultaneous EEG-fMRI data acquired using two different setups at 3T and 7T. Comparison with state-of-the-art BCG correction methods showed that PROJIC-OBS and PROJIC-AAS outperformed the others when priority was given to artifact removal or physiological signal preservation, respectively, while both PROJIC-AAS and AAS were in general the best choices for intermediate trade-offs. The impact of the BCG correction on the quality of event-related potentials (ERPs) of interest was assessed in terms of the relative reduction of the standard error (SE) across trials: 26/66%, 32/62% and 18/61% were achieved by, respectively, PROJIC, PROJIC-OBS and PROJIC-AAS, for data collected at 3T/7T. Although more significant improvements were achieved at 7T, the results were qualitatively comparable for both setups, which indicate the wide applicability of the proposed methodologies and recommendations.

Tracking slow modulations in synaptic gain using dynamic causal modelling: validation in epilepsy.

In this work we propose a proof of principle that dynamic causal modelling can identify plausible mechanisms at the synaptic level underlying brain state changes over a timescale of seconds. As a benchmark example for validation we used intracranial electroencephalographic signals in a human subject. These data were used to infer the (effective connectivity) architecture of synaptic connections among neural populations assumed to generate seizure activity. Dynamic causal modelling allowed us to quantify empirical changes in spectral activity in terms of a trajectory in parameter space - identifying key synaptic parameters or connections that cause observed signals. Using recordings from three seizures in one patient, we considered a network of two sources (within and just outside the putative ictal zone). Bayesian model selection was used to identify the intrinsic (within-source) and extrinsic (between-source) connectivity. Having established the underlying architecture, we were able to track the evolution of key connectivity parameters (e.g., inhibitory connections to superficial pyramidal cells) and test specific hypotheses about the synaptic mechanisms involved in ictogenesis. Our key finding was that intrinsic synaptic changes were sufficient to explain seizure onset, where these changes showed dissociable time courses over several seconds. Crucially, these changes spoke to an increase in the sensitivity of principal cells to intrinsic inhibitory afferents and a transient loss of excitatory-inhibitory balance.

Electrophysiological correlates of the BOLD signal for EEG-informed fMRI.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG-fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level-dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological-haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG-fMRI mapping), or exploring a range of EEG-derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG-fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG-fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations.

Peer review of the pesticide risk assessment of the active substance metconazole.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Belgium, and co-rapporteur Member State, the United Kingdom, for the pesticide active substance are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of metconazole as a fungicide on cereals and oilseed rape and as a plant growth regulator on oilseed rape. The reliable end points appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Parkinson's Disease Medication Adherence Scale: Conceptualization, Scale Development, and Clinimetric Testing Plan.

Background: Medication adherence is a crucial component in the management of patients with chronic diseases needing a long-term pharmacotherapy. Parkinson's disease (PD) is a chronic, degenerative disease with complex drug treatment that poses challenging barriers to patient adherence. The adoption of best practices of scale development can contribute to generate solid concepts and, in the long run, a more stable knowledge base on the underlying constructs of medication adherence in PD measured by the items of the first scale to be created for this purpose. Purpose: To present the development process and clinimetric testing plan of the Parkinson's Disease Medication Adherence Scale (PD-MAS). Method: We adopted a hybrid approach plan based on the United States Food and Drug Administration and Benson and Clark Guide that will create a patient-reported outcome instrument. We presented an overview of consecutive and interrelated steps, containing a concise description of each one. International research centers from Brazil and United States were initially involved in the planning and implementation of the methodological steps of this study. Results: We developed a four-phase multimethod approach for the conceptualization and the clinimetric testing plan of the PD-MAS. First, we describe the development process of the conceptual framework of the PD-MAS underpinning the scale construct; second, we formalized the development process of the first version of the PD-MAS from the generation of item pools to the content validation and pre-testing; third, we established the steps for the first pilot testing and revision; fourth, we describe the steps plan for the first pilot testing and revision, to finally describe its clinimetric testing plan and validation. Conclusion: The overview presentation of the development phases and the clinimetric testing plan of the PD-MAS demonstrate the feasibility of creating an instrument to measure the multidimensional and multifactorial components of the medication adherence process in people with PD.

On-demand cell-autonomous gene therapy for brain circuit disorders.

Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity. Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and "healthy" surrounding or intermingled neurons. We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy. We used an immediate early gene promoter to drive the expression of Kv1.1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity. Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors. Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders.

Effects of cold water immersion on the recovery of physical performance and muscle damage following a one-off soccer match.

The aim of this study was to assess the effects of a single session of cold or thermoneutral water immersion after a one-off match on muscular dysfunction and damage in soccer players. Twenty-male soccer players completed one match and were randomly divided into cryotherapy (10 min cold water immersion, 10°C, n = 10) and thermoneutral (10 min thermoneutral water immersion, 35°C, n = 10) groups. Muscle damage (creatine kinase, myoglobin), inflammation (C-reactive protein), neuromuscular function (jump and sprint abilities and maximal isometric quadriceps strength), and delayed-onset muscle soreness were evaluated before, within 30 min of the end, and 24 and 48 h after the match. After the match, the players in both groups showed increased plasma creatine kinase activity (30 min, 24 h, 48 h), myoglobin (30 min) and C-reactive protein (30 min, 24 h) concentrations. Peak jump ability and maximal strength were decreased and delayed-onset muscle soreness increased in both groups. However, differential alterations were observed between thermoneutral water and cold water immersion groups in creatine kinase (30 min, 24 h, 48 h), myoglobin (30 min), C-reactive protein (30 min, 24 h, 48 h), quadriceps strength (24 h), and quadriceps (24 h), calf (24 h) and adductor (30 min) delayed-onset muscle soreness. The results suggest that cold water immersion immediately after a one-off soccer match reduces muscle damage and discomfort, possibly contributing to a faster recovery of neuromuscular function.

Exercise training and detraining effects on body composition, muscle strength and lipid, inflammatory and oxidative markers in breast cancer survivors under tamoxifen treatment.

AIMS: The present study aimed to verify the effects of resistance training (RT) and successive detraining on body composition, muscle strength and lipid profile as primary outcome, and the oxidative stress and inflammatory markers as second outcome of postmenopausal Breast Cancer (BC) survivors undergoing tamoxifen (TA). MAIN METHODS: Fourteen postmenopausal BC survivors underwent 12 weeks of resistance exercise training and subsequently 12 weeks of detraining. Anthropometric parameters, lipid profile, muscle strength, inflammatory cytokines and the oxidative stress markers, were assessed before, after the training period and after detraining period. KEY FINDINGS: One-way ANOVA showed that fat mass decrease (39.4 ± 6.9 to 37.7 ± 6.8%) and free-fat mass increase (39.3 ± 4.9 to 40.3 ± 5.6%) after RT. Muscle strength increased in response to training but decreased after the detraining period. Triglycerides (156 ± 45 to 123 ± 43 mg/dL) and total cholesterol (202 ± 13 to 186 ± 16 mg/dL) decreased after the RT and HDL-cholesterol (47 ± 9 to 56 ± 9 mg/dL) increased after RT and remained higher (53 ± 10 mg/dL) than after detraining. IL-6 increases (24.65 ± 10.85 to 41.42 ± 22.88 pg/mL) and IL-17 (2.42 ± 0.32 to 1.69 ± 0.19 pg/mL), TBARS (1.91 ± 0.19 to 1.03 ± 0.1 µmol/L), SOD (24.65 ± 10.85 to 41.42 ± 22.88 U/gHb) and Catalase activity (445.9 ± 113.0 to 345.8 ± 81.7 k/gHb·s) reduced after RT and remained lower after detraining. SIGNIFICANCE: Resistance exercise training improves health markers of BC survivors undergoing TA and detraining are not sufficient to reverse the positive effects in oxidative stress markers.

Study of the effects of kinesthetic motor imagery in patients with heart failure.

OBJECTIVE: The aim was to investigate the acute effect of kinesthetic motor imagery of the 2-minute walk test on hemodynamic and cardiopulmonary variables in patients with heart failure. METHODS: Twenty participants were recruited for the analysis of these variables before and after the execution and imagination of the 2-minute walk test, with the number of laps executed and imagined being recorded. RESULTS: The main results observed showed that (1) there was no difference in the number of laps executed and imagined (p=0.41), indicating that the participants actually imagined the test and (2) the motor imagery of the 2-minute walk test immediately increased (p<0.001) the heart and respiratory rates. CONCLUSION: The motor imagery seems to have acute effects on the cardiopulmonary anticipatory responses of a patient with heart failure.

Application of physical exercise therapies in breast cancer survivors and their effects on the inflammatory profile: A narrative review.

BACKGROUND: One of the adverse effects of cancer treatments is the exacerbation of inflammation, which generates numerous limitations and contributes to the development of several comorbidities and the recurrence of cancer itself. Physical exercise (PE) has been proposed as an efficient complementary strategy to combat the inflammatory effects of oncological treatments and to prevent the development of comorbidities, but its adequate application in breast cancer survivors (BCS) requires the establishment of consensuses and practical recommendations. OBJECTIVE: This study aimed to review the randomized controlled trials that evaluated the influence of PE in the inflammatory profile of BCS. METHODS: The search for articles published between 1999 and 2020 was done in PsycINFO, PubMed, Cochrane, Science Direct, and Scopus databases. RESULTS: Current knowledge reveals the effectiveness of PE in the functional independence and health of BCS. Evidence of the capacity of PE to improve the inflammatory profile and the immune response in BCS has also been described. However, the heterogeneity of the studies regarding structural training variables, types of exercise, stages of intervention, and severity of the disease, still do not allow the establishment of precise guidelines for the prescription and progression of exercise to improve the inflammatory process in BCS. DISCUSSION: . This review suggests a possible strategy to be used in the assessment, training prescription, and rehabilitation of BCS, to support the development of new studies and the work of exercise professionals in the prescription and application of physical training to improve health and inflammatory status in BCS.

Measuring Medication Adherence in Parkinson's Disease: A Systematic Review of Contributing Components in Rating Scales.

BACKGROUND: Poor medication adherence in chronic illnesses such as Parkinson's disease (PD) is a significant but potentially addressable issue if core components are systematically measured. OBJECTIVE: To assess whether rating scales used in PD adequately cover essential components of medication adherence. METHODS: We accessed 5 databases targeting articles published before October 2019 and using rating scales to measure medication adherence in PD. The ABC Taxonomy from the European Ascertaining Barriers to Compliance Consortium and World Health Organization recommendations were used as the evaluation standard of 5 essential adherence dimensions (patient-based, health system-based, social-based, therapy-based, and health condition-based), 3 phases (initiation, implementation, and discontinuation), and 2 factors (intentional and nonintentional). RESULTS: We screened 192 and selected 16 studies, collectively using 5 medication adherence rating scales. No scale covered all essential components of medication adherence (dimensions, phases, factors). The Morisky Medication Adherence Scales were the most frequently used (11 studies), but they measure only 2 dimensions and phases. The Stendal Adherence to Medication Score (used in 1 study) measured all phases but only 2 dimensions, and the Brief Medication Questionnaire (used in 3 studies) measured 3 dimensions and 2 phases. Distinctions between intentional and nonintentional factors were not completely considered in any scale. CONCLUSIONS: Although multiple studies target medication adherence in PD, the used scales did not measure all recommended components, highlighting the need to develop a sensitive, specific, and comprehensive tool for measuring medication adherence among patients with PD.

The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT): one-year follow-up of a single case.

In this article, we report the case history of a 44-year-old female patient with bipolar disorder who developed the so-called Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT). A detailed description of our patient's neurologic status is provided at baseline (i.e. during lithium intoxication) and after one year of follow-up, confirming the persistency of cerebellar signs and symptoms. Although rare, our report - which shows a severe and disabling form of SILENT - underscores the need to perform a strict control of the putative risk factors argued to be associated with the development of this syndrome. In our case, the presence of fever and the administration of multiple doses of antipsychotics may have contributed to the poor outcome exhibited by the patient.