Neurosonological Findings Related to Non-Motor Features of Parkinson's Disease: A Systematic Review.

Non-motor symptoms (NMS) in Parkinson's disease (PD), including neuropsychiatric or dysautonomic complaints, fatigue, or pain, are frequent and have a high impact on the patient's quality of life. They are often poorly recognized and inadequately treated. In the recent years, the growing awareness of NMS has favored the development of techniques that complement the clinician's diagnosis. This review provides an overview of the most important ultrasonographic findings related to the presence of various NMS. Literature research was conducted in PubMed, Scopus, and Web of Science from inception until January 2021, retrieving 23 prospective observational studies evaluating transcranial and cervical ultrasound in depression, dementia, dysautonomic symptoms, psychosis, and restless leg syndrome. Overall, the eligible articles showed good or fair quality according to the QUADAS-2 assessment. Brainstem raphe hypoechogenicity was related to the presence of depression in PD and also in depressed patients without PD, as well as to overactive bladder. Substantia nigra hyperechogenicity was frequent in patients with visual hallucinations, and larger intracranial ventricles correlated with dementia. Evaluation of the vagus nerve showed contradictory findings. The results of this systematic review demonstrated that transcranial ultrasound can be a useful complementary tool in the evaluation of NMS in PD.

Effectiveness and safety of PCSK9 inhibitors in real-world clinical practice. An observational multicentre study. The IRIS-PCSK9I study.

Background and aims: The benefits of the PCSK9 inhibitors, alirocumab and evolocumab, in lowering LDL-cholesterol and preventing major adverse cardiac events (MACE) have been demonstrated in pivotal clinical trials. However, few studies of routine clinical practice have been conducted to analyse and compare the efficacy and safety of the two drugs. Methods: Retrospective observational study of patients treated with a PCSK9 inhibitor in five hospitals in Andalusia (southern Spain). Baseline demographic and clinical data, LDL-cholesterol levels and the occurrence of MACEs during the follow-up period were recorded. Results: A total of 141 patients were included in the study: 90 were treated with alirocumab and 51 with evolocumab. The patients' mean age (IQR) was 58 (11) years and 58 (41%) were women. The most frequent concomitant medications were statins, 94 (66.7%), followed by antiplatelet therapy (66%) and ezetimibe (65.2%). The median (IQR) follow-up period was 18 (18) months, with 18 (24) for alirocumab and 11 (18) for evolocumab. At the six-month follow-up visit, LDL-cholesterol values had decreased to pre-treatment levels and remained significantly decreased (p < 0.05) over time, for both drugs, and a greater reduction was achieved in patients with established cardiovascular disease and concomitant treatment with statins. With respect to adverse effects, there were nine MACEs (6.4%), of which seven were with alirocumab (7.8%) and two with evolocumab (3.9%) (p NS). Other adverse effects (9.2%) included local erythema (3.5%), muscle cramps (2.1%), respiratory symptoms (2.1%) and asthaenia (1.4%). Conclusions: The efficacy and safety of alirocumab and evolocumab in routine clinical practice are consistent with the findings of the pivotal clinical trials.

Eslicarbazepine acetate and carotid intima-media thickness in epileptic patients.

OBJECTIVE: Evaluate if eslicarbazepine acetate (ESL) in combination with other non-inducer antiepileptic drugs (AEDs) in the treatment of epilepsy may represent a positive impact in the cardiovascular risk profile. METHODS: multicentre, retrospective, observational, non-interventional, real-life study comparing patients treated with cytochrome P450 (CYP) inducer vs. ESL plus non-inducer AEDs. Primary endpoint: Carotid intima-media thickness (CIMT) measured following the Manheim Consensus criteria. RESULTS: Patients included: 163. The main demographic, clinical and vascular risk parameters were comparable between the two groups except for duration of the disease, prevalence of dyslipidemia and use of lipid-lowering drugs (significantly higher in the inducers group) and number of previous antiepileptic drugs (significantly higher in the non-inducers group). Bivariate analysis of the main endpoint showed almost significant differences (p=0.05) in CIMT measures favourable to non-inducers (average 0.617mm+SD=0.148) vs. inducers (average 0.663mm+SD=0.147). Other variables reaching statistical significance were: age >50 years (p<0.001), high blood pressure (p<0.01) and dyslipidemia (p<0.05). A multivariate analysis including these variables and biochemical vascular risk factors showed a predictor model including two variables: inducers group (p=0.031; Coefficient ß=0.234) and age >50 years (p=0.001; Coefficient ß=0.387). Regarding gender, the mean CIMT in males was significantly higher in the inducers (0.693mm; SD=0.139) than in the non- inducers groups (0.628mm; SD=0.151; p<0.05). In females the differences were not significant. SIGNIFICANCE: The use of CYP inducer AEDs is associated with a significant increase in CIMT as compared with ESL and other non-inducer AEDs. The study shows a decrease in the vascular risk measured by ultrasound criteria in male patients treated with ESL compared with patients treated with inducer AEDs.

[Eslicarbazepine acetate in clinical practice. Efficacy and safety results]. / Acetato de eslicarbazepina en la practica clinica. Resultados de eficacia y seguridad.

INTRODUCTION. Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) licensed in Spain in February 2011 as an adjunctive therapy in adults with partial seizures with or without secondary generalization. Clinical trials with ESL have demonstrated acceptable efficacy and safety. AIM. To evaluate the results of ESL in our epilepsy unit during its first year of clinical experience with this AED. PATIENTS AND METHODS. We included all patients who started treatment with ESL at our epilepsy unit from March 2011 to May 2012. We collected the following variables: gender, aetiology of epilepsy, epileptogenic area, reason for switch to ESL, clinical response after initiation of ESL, adverse effects of ESL, refractoriness criteria and treatment discontinuation. A bivariate factor-to-factor correlation study was carried out to establish associations between the independent variables and the clinical response. RESULTS. We recruited 105 patients (51.4% male). 20,7% of patients remained seizure-free and 58.4% showed > 50% improvement after introduction of ESL. At 6 months, 18.1% had experienced some type of side effect, with cognitive disorders being the most common, and 11.5% had discontinued treatment. Combination with lacosamide proved to be significantly less effective in the control of seizures. Combination of ESL with the rest of sodium channel inhibitors was similar in efficacy to others combinations. CONCLUSIONS. ESL is a well-tolerated and effective AED when is used as adjunctive treatment with most of other AED in clinical practice.

Characteristics of temporal lobe epilepsy with no ictal impairment of consciousness.

INTRODUCTION: The predominant manifestations of temporal lobe epilepsy (TLE) are partial seizures with impairment of consciousness (type I.B of ILAE classification), although consciousness impairment is not necessary in all seizures of patients with TLE. Nevertheless, there have been very few reports of TLE patients with exclusive seizures with no impairment of consciousness (i.e. isolated auras). The objective of this study was to determine any differential characteristics of this subgroup of TLE patients. MATERIAL AND METHODS: Retrospective case-control study in 163 consecutive TLE patients from our hospital database. The patients were divided between those with and without ictal impairment of consciousness, based on directed semi-structured questionnaire to the patient and relatives and on video-EEG records. Ten independent variables (8 clinical and 2 paraclinical) were compared between the groups. RESULTS: 14 patients (8.5%) formed the "TLE without ictal impairment of consciousness" group. This group was less refractory to medical treatment [Odds Ratio: 0.14 (0.03-0.64); p<0.01] and had frequent ictal motor behaviour [Odds ratio: 5.33 (1.65-17.14); p=0.008] and less frequent presence of automatisms [p<0.001]. Non-significant tendencies were observed for a higher frequency of lesional substrate and fewer generalization episodes. DISCUSSION: TLE without ictal impairment of consciousness appears to be more frequent than previously thought. This subgroup of TLE patients shows differential characteristics that may possibly result from a differential propagation of the original epileptic activity towards frontal areas rather than towards neocortical and diencephalic structures, which may be related to the more frequent presence of structural lesions.

Predictive model for refractoriness in temporal lobe epilepsy based on clinical and diagnostic test data.

INTRODUCTION: Temporal Lobe Epilepsy (TLE) is frequently resistant to drug treatment, but a high percentage of these patients can be free of seizures after epilepsy surgery. Delay in the surgical decision has been related to quality of life impairment, social and work limitations, and increased mortality risk. A predictive model for refractoriness based on clinical and diagnostic factors may allow its earlier detection and a shorter delay before surgery. MATERIAL AND METHODS: A case-control study was conducted in TLE patients over 16 years old. The dependent variable was resistance to medical treatment according to ILAE 2010 criteria. Independent variables were clinical, semiological, therapeutic, neurophysiological, radiological, and neuropsychological variables. A multivariate study was conducted to identify the variables associated with refractoriness, calculating the positive and negative predictive values and positive likelihood ratios of these variables individually and in combination. These data were used to construct a refractoriness predictive model. RESULTS: ILAE refractoriness criteria were met by 83 patients (50.9%). In the multivariate analysis, refractoriness was significantly associated with one semiological variable, one neuroradiological variable, one neurophysiological variable, and two therapeutic variables but not with neuropsychological test outcomes. These significant variables were used to construct a predictive model. CONCLUSION: Assessment of semiological, neurophysiological, and neuroradiological data can serve to stratify the risk of refractory epilepsy in TLE patients.