Exome sequencing is a useful diagnostic tool for complicated forms of hereditary spastic paraplegia.

Hereditary spastic paraplegias constitute a heterogeneous group of neurodegenerative diseases encompassing pure and complicated forms, for which at least 52 loci and 31 causative genes have been identified. Although mutations in the SPAST gene explain approximately 40% of the pure autosomal dominant forms, molecular diagnosis can be challenging for the sporadic and recessive forms, which are often complicated and clinically overlap with a broad number of movement disorders. The validity of exome sequencing as a routine diagnostic approach in the movement disorder clinic needs to be assessed. The main goal of this study was to explore the usefulness of an exome analysis for the diagnosis of a complicated form of spastic paraplegia. Whole-exome sequencing was performed in two Spanish siblings with a neurodegenerative syndrome including upper and lower motor neuron, ocular and cerebellar signs. Exome sequencing revealed that both patients carry a novel homozygous nonsense mutation in exon 15 of the SPG11 gene (c.2678G>A; p.W893X), which was not found in 584 Spanish control chromosomes. After many years of follow-up and multiple time-consuming genetic testing, we were able to diagnose these patients by making use of whole-exome sequencing, showing that this is a cost-efficient diagnostic tool for the movement disorder specialist.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice.

BACKGROUND AND PURPOSE: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. METHODS: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. RESULTS: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2-4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. CONCLUSIONS: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies.

BACKGROUND: Herpetic (HE) and autoimmune (AE) encephalitis share clinical and radiological features. We compared both types of encephalitis with the aim of making a differential clinical-radiological pattern. MATERIALS AND METHODS: All cases with a clinical diagnosis of encephalitis who attended our hospital between 1999 and 2012 were reviewed. We selected those cases with positive polymerase chain reaction for herpes simplex virus 1 (HSV-1) in the cerebrospinal fluid (CSF), and those with antineuronal antibodies or paraneoplastic etiology. We compared epidemiological, clinical, CSF, electroencephalographic and radiological findings. RESULTS: Twelve patients with positive polymerase chain reaction for HSV-1, and 10 patients with antineuronal antibody or paraneoplastic etiology were found. The only features found exclusively in one group were the presence of psychiatric symptoms and tumors in AE. Acute onset of symptoms, fever and aphasia were more frequent in HE, which showed higher level of proteins and erythrocyte count in CSF. Neuroimaging was abnormal in all cases of HE, but only in 60% of AE. Insular and diffuse temporal lobe involvement and absence of basal ganglia involvement were more frequent in HE, and mesial temporal involvement in AE. The highest diagnostic values for differentiating HE from AE were the association of acute onset of symptoms and fever (sensitivity 0.92, specificity 1), and the absence of basal ganglia involvement (sensitivity 0.82, specificity 1). CONCLUSIONS: There are few differences between HE and AE. Psychiatric symptoms and association with tumors were unique for AE. Acute onset with fever and absence of basal ganglia involvement in magnetic resonance imaging support a diagnosis of HE.

[Severe aortic stenosis in a critical condition]. / Estenosis aórtica grave en situación crítica.

There is little information about patients with severe aortic stenosis (SAS) who require admission to acute care units. We studied 27 patients with SAS admitted in a tertiary hospital coronary care unit. The most frequent reasons for admission were severe heart failure (42%), acute coronary syndrome (39%) and cardiac arrest (8%). At a mean follow-up of 6.5 months, 11 patients died. Cumulative survival was 74±8%, 70±9%, and 62±10% at 7, 30 and 60 days, respectively. Out of the 27 patients, 13 (48%) underwent surgical intervention, these patients having lower Euroscore (13±11 vs. 34±18%, p=0.002) and higher survival (92±7% at 7, 30 and 60 days vs. 50±13%, 40±14% and 30±14%; p=0.002). Thus, patients with SAS who require hospitalization in the intensive care units constitute a very high risk population, with very high mortality, especially during the first week after admission and in patients who have not undergone surgery.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice.

BACKGROUND AND PURPOSE: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. METHODS: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. RESULTS: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2-4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. CONCLUSIONS: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

COVID-19 in Parkinson's disease: what holds the key?

INTRODUCTION: Parkinson's disease (PD) is more frequent in the elderly and increases the risk of respiratory infections. Previous data on PD and SARS-CoV-2 are scarce, suggesting a poor prognosis in advanced disease and second-line therapies. METHODS: A retrospective case-control study comparing patients with PD and COVID-19 and patients with PD without COVID-19 was conducted during the pandemic period in Spain (March 1st-July 31st 2020) in a tertiary university hospital. RESULTS: Thirty-nine (COVID-19 +) and 172 (COVID-19-) PD patients were included. Fifty-nine percent were males in both groups, with similar age (75.9 ± 9.0 COVID-19 + , 73.9 ± 10.0 COVID-19-), disease duration (8.9 ± 6.2 COVID-19 + , 8.5 ± 5.6 COVID-19-) and PD treatments. COVID-19 was mild in 10 (26%), required admission in 21 (54%) and caused death in 8 (21%) patients. Dementia was the only comorbidity more frequent in COVID-19 + patients (36% vs. 14%, p = 0.0013). However, in a multivariate analysis, institutionalization was the only variable associated with COVID-19 + (OR 17.0, 95% CI 5.0-60.0, p < 0.001). When considering severe COVID-19 (admission or death) vs. mild or absent COVID-19, institutionalization, neoplasm, dementia and a lower frequency of dopamine agonists were associated with severe COVID-19. In multivariate analysis, only institutionalization [OR 5.17, 95% CI 1.57-17, p = 0.004] and neoplasm [OR 8.0, 95%CI 1.27-49.8, p = 0.027] remained significantly associated. CONCLUSION: In our experience, institutionalization and oncologic comorbidity, rather than PD-related variables, increased the risk of developing COVID-19, and impacted on its severity. These findings suggest that epidemiologic factors and frailty are key factors for COVID-19 morbidity/mortality in PD. Appropriate preventive strategies should be implemented in institutionalized patients to prevent infection and improve prognosis.

Use of e-mail for Parkinson's disease consultations: Are answers just a clic away? / El correo electrónico en la consulta de Parkinson: ¿soluciones a un clic?

INTRODUCTION: The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs). METHODS: We retrospectively reviewed all consecutive emails sent and received over a period of 4 months, one year after implementation of the e-mail inquiry system. All patients received the during consultations, and PCPs, during scheduled informative meetings. We recorded and later analysed the profile of the questioner, patients' demographic and clinical data, number of queries, reason for consultation, and actions taken. RESULTS: From 1 January 2015 to 30 April 2015, the service received 137 emails from 63 patients (43% male, mean age 71±10.5) diagnosed with Parkinson's disease (76%), atypical parkinsonism (10%), and others (14%); 116 responses were sent. Twenty (32%) emails were written by patients, 38 (60%) by their caregivers, and 5 (8%) by their PCPs. The reasons for consultation were clinical in 50 cases (80%): 16 (32%) described clinical deterioration, 14 (28%) onset of new symptoms, and 20 (40%) side effects or concerns about medications. In 13 cases (20%), the query was bureaucratic: 11 were related to appointments (85%) and 2 were requests for clinical reports (15%). In response, new appointments were scheduled in 9 cases (14%), while the rest of the questions were answered by email. Patients were satisfied overall and the additional care burden on specialists was not excessive. CONCLUSIONS: Implementing an e-mail-based consultation system is feasible in MD units. It facilitates both communication between neurologists and patients and continued care in the primary care setting.

Influence of collateral circulation on in-hospital death from anterior acute myocardial infarction.

OBJECTIVES: Our purpose was to study whether the in-hospital prognosis of anterior acute myocardial infarction (AMI) is influenced by preexistent collateral circulation to the infarct-related artery. BACKGROUND: Collateral circulation exerts beneficial influences on the clinical course after AMI, but demonstration of improved survival is lacking. METHODS: We studied 238 consecutive patients with anterior AMI treated by primary angioplasty within the first 6 h of the onset of symptoms. Fifty-eight patients with basal Thrombolysis in Myocardial Infarction (TIMI) flow >1 in the infarct-related artery or with inadequate documentation of collateral circulation were excluded. Collateral channels to the infarct-related artery before angioplasty were angiographically assessed, establishing two groups: 115 patients (64%) without collateral vessels (group A) and 65 patients (36%) with collateral vessels (group B). RESULTS: There were no differences in baseline characteristics between groups A and B, except for the greater prevalence of previous angina in group B (15% vs. 34%, p = 0.003). During the hospital stay, 26 patients (23%) in group A and 5 (8%) in group B died (p = 0.01). Cardiogenic shock accounted for 74% of deaths. Cardiogenic shock developed in 30 patients (26%) in group A and in 4 (6%) in group B (p = 0.001). The absence of collateral circulation appeared to be an independent predictor of in-hospital death (odds ratio 3.4, 95% confidence interval 1.2 to 9.6, p = 0.02) and cardiogenic shock (odds ratio 5.6, 95% confidence interval 1.9 to 17, p = 0.002). CONCLUSIONS: Preexistent collateral circulation decreases in-hospital death from anterior AMI by reducing the incidence of cardiogenic shock.

Primary angioplasty versus systemic thrombolysis in anterior myocardial infarction.

OBJECTIVES: This study compares the efficacy of primary angioplasty and systemic thrombolysis with t-PA in reducing the in-hospital mortality of patients with anterior AMI. BACKGROUND: Controversy still exists about the relative benefit of primary angioplasty over thrombolysis as treatment for AMI. METHODS: Two-hundred and twenty patients with anterior AMI were randomly assigned in our institution to primary angioplasty (109 patients) or systemic thrombolysis with accelerated t-PA (111 patients) within the first five hours from the onset of symptoms. RESULTS: Baseline characteristics were similar in both groups. Primary angioplasty was independently associated with a lower in-hospital mortality (2.8% vs. 10.8%, p = 0.02, adjusted odds ratio 0.23, 95% confidence interval 0.06 to 0.85). During hospitalization, patients treated by angioplasty had a lower frequency of postinfarction angina or positive stress test (11.9% vs. 25.2%, p = 0.01) and less frequently underwent percutaneous or surgical revascularization after the initial treatment (22.0% vs. 47.7%, p < 0.001) than did patients treated by t-PA. At six month follow-up, patients treated by angioplasty had a lower cumulative rate of death (4.6% vs. 11.7%, p = 0.05) and revascularization (31.2% vs. 55.9%, p < 0.001) than those treated by t-PA. CONCLUSIONS: In centers with an experienced and readily available interventional team, primary angioplasty is superior to t-PA for the treatment of anterior AMI.

Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status.

BACKGROUND: Early prognosis in comatose survivors after cardiac arrest due to ventricular fibrillation (VF) is unreliable, especially in patients undergoing mild hypothermia. We aimed at developing a reliable risk-score to enable early prediction of cerebral performance and survival. METHODS: Sixty-one out of 239 consecutive patients undergoing mild hypothermia after cardiac arrest, with eventual return of spontaneous circulation (ROSC), and comatose status on admission fulfilled the inclusion criteria. Background clinical variables, VF time and frequency domain fundamental variables were considered. The primary and secondary outcomes were a favorable neurological performance (FNP) during hospitalization and survival to hospital discharge, respectively. The predictive model was developed in a retrospective cohort (n = 32; September 2006-September 2011, 48.5 ± 10.5 months of follow-up) and further validated in a prospective cohort (n = 29; October 2011-July 2013, 5 ± 1.8 months of follow-up). RESULTS: FNP was present in 16 (50.0%) and 21 patients (72.4%) in the retrospective and prospective cohorts, respectively. Seventeen (53.1%) and 21 patients (72.4%), respectively, survived to hospital discharge. Both outcomes were significantly associated (p < 0.001). Retrospective multivariate analysis provided a prediction model (sensitivity = 0.94, specificity = 1) that included spectral dominant frequency, derived power density and peak ratios between high and low frequency bands, and the number of shocks delivered before ROSC. Validation on the prospective cohort showed sensitivity = 0.88 and specificity = 0.91. A model-derived risk-score properly predicted 93% of FNP. Testing the model on follow-up showed a c-statistic ≥ 0.89. CONCLUSIONS: A spectral analysis-based model reliably correlates time-dependent VF spectral changes with acute cerebral injury in comatose survivors undergoing mild hypothermia after cardiac arrest.

The impact of different echocardiographic diagnostic criteria on the prevalence of left ventricular hypertrophy in essential hypertension: the VITAE study. Ventriculo Izquierdo Tension Arterial España.

BACKGROUND: The prevalence of echocardiographic left ventricular hypertrophy in essential hypertension ranges from 12 to 96% depending on the threshold values used to define it, and on the selection bias. OBJECTIVE: To estimate the prevalence of echocardiographic left ventricular hypertrophy by different criteria in essential hypertensives seen in primary care centres. METHODS: Cross-sectional study in a population-based sample of 946 essential hypertensives randomly selected in 39 primary care centres across Spain. Echocardiographic studies were performed in reference hospitals by trained observers (concordance Cohen kappa index > 0.7) and analysed by a single observer. RESULTS: Prevalence of left ventricular hypertrophy ranged from 59.2% [95% confidence interval (CI) 56.1 -62.3] by Framingham criteria to 72.7% (95% CI 69.9-75.6) using the criteria of De Simone et al. (J Am Coll Cardiol 1995; 25: 1056-1062). Prevalence was higher in males by the Cornell-Penn criteria, but higher in females when using Framingham or De Simone et al. criteria. Eccentric hypertrophy was more frequent (51.3-54.1%) independently of the criteria used, particularly when adjusting wall-thickness-ratio for age (56.2-58.9%). Concentric remodelling was present in 6.5-11.4% and only 20.8-29.7% of patients had no evidence of left ventricular structural alterations. Factors independently associated with left ventricular hypertrophy in the logistic regression analysis were age, gender, systolic blood pressure, pulse pressure and body mass index. CONCLUSION: Prevalence of echo left ventricular structural alterations among essential hypertensives seen in primary care centres in Spain ranged from 70.3 to 79.2% depending on the threshold values used. Left ventricular hypertrophy ranged from 59.2 to 72.7% and age-adjusted concentric remodelling ranged from 6.5 to 11.4% depending on the criteria used. Only one-quarter of hypertensive patients were free from morphological alterations.

Prognosis of medically stabilized unstable angina pectoris with a negative exercise test.

Three hundred twenty seven patients with medically stabilized unstable angina and a negative exercise test were followed-up during a mean of 39 months. Male gender, diabetes mellitus, and previous myocardial infarction, but not exercise parameters, were predictors of death or acute myocardial infarction.

Frequency of left ventricular free-wall rupture in patients with acute myocardial infarction treated with primary angioplasty.

A total of 590 patients with myocardial infarction treated with primary angioplasty were studied, to assess the incidence and related factors of free-wall rupture in patients with acute myocardial infarction when treated with primary angioplasty. The incidence of free-wall rupture was 2.2% (13 patients); this incidence was higher in patients >65 years old, women, nonsmokers, as well as in those with anterior location and an initial TIMI grade 0 flow, but it was similar in patients with a successful or unsuccessful angiographic result.

Efficacy of invasive strategy for the management of acute myocardial infarction complicated by cardiogenic shock.

This retrospective study evaluates the influence of an invasive strategy of urgent coronary revascularization on the in-hospital mortality of patients with acute myocardial infarction (AMI) complicated early by cardiogenic shock. Among 1,981 patients with AMI admitted to our institution from 1994 to 1997, 162 patients (8.2%) developed cardiogenic shock unrelated to mechanical complications. The strategy of management was considered invasive if an urgent coronary angiography was indicated within 24 hours of symptom onset. Every other strategy was considered conservative. Fifty-seven patients who developed the shock late or after a revascularization procedure, or who died on admission, were excluded. The strategy was invasive in 73 patients (70%). Five of them died before angiography could be performed and 65 underwent angioplasty (success rate 72%). By univariate analysis the invasive strategy was associated with a lower mortality than conservative strategy (71% vs 91%, p = 0.03), but this association disappeared after adjustment for baseline characteristics. Older age, nonsmoking, and previous ischemic heart disease were independent predictors of mortality. In conclusion, we have failed to demonstrate that a strategy of urgent coronary revascularization within 24 hours of symptom onset for patients with AMI complicated by cardiogenic shock is independently associated with a lower in-hospital mortality. This strategy was limited by the high mortality within 1 hour of admission in patients with cardiogenic shock, the modest success rate of angioplasty in this setting, and the powerful influence of some adverse baseline characteristics on prognosis.

Determinants of a positive exercise test in patients admitted with acute non-infarct chest pain.

BACKGROUND AND OBJECTIVES: Some patients with suspected unstable angina show ischemia at the exercise treadmill test despite having been medically stabilized. The objective of this study was to determine clinical characteristics predicting a positive exercise treadmill test in patients with suspected unstable angina after medical stabilization. METHODS: In 885 hospitalized patients with medically stabilized unstable angina, the relationship between the result of the pre-discharge exercise treadmill test and clinical characteristics was studied. RESULTS: Mean age was 62+/-9 years and 668 (75%) were male. Exercise test was positive (chest pain and/or ST depression > or =1 mm) in 288 patients (33%). Univariate analysis showed the following associated with ischemia at the exercise test: male gender (56% vs. 20%, P<0.001 ), diabetes mellitus (41% vs. 31%, P=0.009), previous unstable angina (41% vs. 24%, P=0.001), previous stable angina (44% vs. 30%, P<0.001), previous coronary artery bypass grafting (43% vs. 31%, P=0.043), peripheral artery disease (45% vs. 31%) and progressive angina (55% vs. 31%, P<0.001). Multivariate analysis showed the following as independent predictors of ischemia: male gender (OR=2.25), diabetes (OR=4.12), previous unstable angina (OR=3.89), previous stable angina (OR=3.74) and progressive angina (OR=4.05). CONCLUSIONS: In patients with suspected unstable angina, after medical stabilization: (1) the exercise treadmill test is positive in one-third of cases; (2) male gender, diabetes, previous angina (unstable and stable) and progressive angina are independent predictors of ischemia.

Early coronary angioplasty for acute myocardial infarction: predictors of poor outcome in a non-selected population.

AIMS: The objective of this study was to report the experience in the treatment of acute myocardial infarction (AMI) with early coronary angioplasty (PTCA) in a single European center during one decade, attempting to identify the characteristics associated with a poor prognosis in these patients. METHODS AND RESULTS: Eight hundred patients with AMI were treated with PTCA < 12 hours after symptom onset. Mean age was 64 +/- 13 years, 12% were in cardiogenic shock, AMI location was anterior in 61% and PTCA was performed after failed thrombolysis in 5%. Coronary stents and abciximab were used in 51% and 10%, respectively. An angiographic successful result was obtained in 93%, and final TIMI flow grade 3 was achieved in 83%. The overall in-hospital mortality rate was 12.5% (2.7%, 16.1%, 25.7% and 63.8% in patients in Killip class I, II, III and IV, respectively). Over the years, an improvement in the angiographic results and a reduction in the rates of reinfarction and target vessel revascularization were observed. The independent predictors of death were age > 70 years, absence of hyper-cholesterolemia, anterior location, cardiogenic shock, multi-vessel disease and unsuccessful PTCA. The leading causes of mortality were cardiogenic shock (63%) and ventricular free wall rupture (14%). The rates of non-fatal reinfarction, documented reocclusion and in-hospital repeated revascularization were 2%, 3% and 4%, respectively. CONCLUSION: In most cases, PTCA performed in a non-selected patient population with AMI results in angiographic success. Mortality especially occurs in patients who are in cardiogenic shock at the beginning of the procedure. We have observed an improvement in the results throughout the course of the decade.

[Comparison of clinical efficacy of thrombolytic drugs in patients with acute myocardial infarction]. / Comparación de la eficacia clínica de los fármacos trombolíticos en pacientes con infarto agudo de miocardio.

Thrombolytic therapy has prove to be effective to recanalize the occluded coronary artery in patients with acute myocardial infarction, reducing infarct size, preserving ventricular function and improving short and long term survival. In a number of studies the relative efficacy of the available thrombolytic agents has been studied an are discussed in this revision of the comparative, randomized trials. Some differences have been found in the relative efficacy of streptokinase, APSAC, urokinase and tPA to recanalized the occluded infarct related coronary artery. Reocclusion is probably highest with tPA and lowest with urokinase or the combination of urokinase and tPA. No differences were found in the reduction of infarct size and improving of left ventricular function. The mortality rate of patients treated with streptokinase, APSAC or tPA was found to be similar in two multicentric studies: GISSI-2 and ISIS-3. Major complications related with the use of thrombolytics include systemic or cerebral haemorrhage, allergic reactions, hypotension and probably heart rupture. Systemic and cerebral hemorrhages are more frequently associated with the use of tPA and APSAC than with streptokinase. Allergic reactions are more frequent after administration of streptokinase and APSAC than after tPA or urokinase and the same occurs with hypotension requiring treatment. The analysis of the available data from the comparative studies do not offer enough clinical evidence to consider any of the thrombolytic agents as the drug of choice in most patients with acute myocardial infarction.