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Most patients with Parkinson's disease experience motor fluctuations or 'off' periods, which impact on their daily activities, increase their disability and diminish their quality of life. They suffer from these fluctuations despite multiple adjustments to the schedules, doses and intake of medication. In this context, on-demand or rescue treatments are necessary to attempt to improve 'off' periods, with drugs that have the pharmacokinetic advantage of a much faster onset of action because their routes of administration are not oral. There are currently three on-demand therapies for the treatment of fluctuations: subcutaneous apomorphine, inhaled levodopa and sublingual apomorphine. Of the three alternatives, subcutaneous apomorphine generally has the fastest onset of action, sublingual apomorphine provides the longest clinical effect, and inhaled levodopa has the most favourable side effect profile. Each of these drugs has its own characteristics: the time before onset of action, the duration of action and different side effect profiles. The choice for each patient will depend on their individual needs and circumstances. To mark the first year of the introduction of inhaled levodopa, we review these therapies, focusing on the experience with this new dosage form of levodopa.

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., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Functional neurological disorders (FND) are a frequent reason for visits in neurology. However, specific training on these disorders during undergraduate and residency training is limited. This study assesses the knowledge, attitude and exposure of medical students to FNDs before completing their medical degree., Patients and Methods: We conducted a 15-item survey to explore understanding, exposure and attitudes towards FNDs among sixth-year medical students at four Spanish universities., Results: A total of 118 students (mean age 23.6 ± 1.2 years; 71.2% female) returned the survey. Of these, 88 (74.6%) were aware of the concept of FNDs and 78 (66.1%) had studied them in psychiatry classes. The term 'psychosomatic' was chosen by 54.1% of the students as the most appropriate term to refer to these disorders, and 111 (94.1%) believed that a history of sexual or physical abuse was common among FND patients. Fifty-seven students (48.3%) assumed that the diagnosis of FND was mostly a clinical diagnosis of exclusion and 63 (53.4%) indicated that it is managed only by psychiatry. One hundred and one students (85.6%) considered that adequate training on FNDs is an important aspect of their medical training., Conclusions: Medical students are aware of the existence of FNDs, but their preferred terminology, as well as the perceived aetiological factors, reflect that the historical view of these disorders is still deeply rooted. Medical students feel that they should receive adequate education on FNDs from specialists in neurology and psychiatry as part of their training.

Competing Interests: Competing interests: None declared.

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., (Copyright © 2021 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

The role of immunosuppression among coronavirus disease 2019 (COVID-19) patients has not been elucidated and management may be challenging. This observational study included confirmed COVID-19 patients. The primary endpoint was the development of moderate-severe acute respiratory distress syndrome (ARDS). Time to moderate-severe ARDS, the need for mechanical or noninvasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints. Of 138 patients included, 27 (19.6%) were immunosuppressed (IS) and 95 (68.8%) were male, with a median (IQR) age of 68 (54-78) years. A significantly lower proportion of IS patients (25.9%) compared to non-IS patients (52.3%) developed moderate-severe ARDS, in both unadjusted (0.32; 95% CI, 0.13-0.83; p = .017) and adjusted (aOR, 0.25; 95% CI, 0.08-0.80; p = .019) analyses. After stratifying by pathologies, only IS patients with autoimmune diseases remained significant (aOR 0.25; 95% CI, 0.07-0.98; p = .046). Nonsignificant trends toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected among IS. In our cohort of COVID-19 patients, nonsevere immunosuppression was associated with a lower risk of moderate-severe ARDS, especially among AD. This suggests a potential protective effect from a hypothesized hyper-inflammatory response., (© 2020 Wiley Periodicals LLC.)

Introduction: An increased incidence of stroke in HIV-infected patients has already been reported, suggesting that HIV infection may be a cerebrovascular risk factor. The objective of this study was to assess temporal trends in the proportion of HIV infection among patients with stroke in Spain., Methods: Data were obtained from the minimum basic dataset (MBDS) of all patients hospitalized in Spain between 1997 and 2012 with a primary or secondary diagnosis of stroke. The annual proportion of HIV infection and time trends (stratifying by type of stroke and HIV stage) were calculated, and predictors of HIV infection and the social and economic impact of HIV-infected (HIV+) and non-infected (HIV-) patients were analyzed., Results: Of 857,371 patients hospitalized with an incident stroke, 2134 (0.25%) had HIV infection. A 2.5% year-on-year increase (OR 1.025, 95% CI 1.015-1.036, p<0.0001) of the proportion of HIV-infected patients was observed due to an increase in the asymptomatic stage of the infection (per year OR 1.077, 95% CI 1.057-1.097, p<0.0001), as the proportion of patients with AIDS remained stable. Factors independently associated with HIV infection and stroke were active smoking, stimulating drugs and hepatitis C virus (HCV) infection. A higher mortality rate, longer hospital stay and a higher cost per hospitalized patient was observed among HIV+ patients., Conclusions: From 1997 to 2012, there was an increase in the proportion of HIV infection among patients hospitalized with stroke irrespective of the classical vascular risk factors, reinforcing the role of HIV infection as a cerebrovascular risk factor., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

KCNJ10 encodes the inward-rectifying potassium channel (Kir4.1) that is expressed in the brain, inner ear, and kidney. Loss-of-function mutations in KCNJ10 gene cause a complex syndrome consisting of epilepsy, ataxia, intellectual disability, sensorineural deafness, and tubulopathy (EAST/SeSAME syndrome). Patients with EAST/SeSAME syndrome display renal salt wasting and electrolyte imbalance that resemble the clinical features of impaired distal tubular salt transport in Gitelman's syndrome. A key distinguishing feature between these two conditions is the additional neurological (extrarenal) manifestations found in EAST/SeSAME syndrome. Recent reports have further expanded the clinical and mutational spectrum of KCNJ10-related disorders including non-syndromic early-onset cerebellar ataxia. Here, we describe a kindred of three affected siblings with early-onset ataxia, deafness, and progressive spasticity without other prominent clinical features. By using targeted next-generation sequencing, we have identified two novel missense variants, c.488G>A (p.G163D) and c.512G>A (p.R171Q), in the KCNJ10 gene that, in compound heterozygosis, cause this distinctive EAST/SeSAME phenotype in our family. Electrophysiological characterization of these two variants confirmed their pathogenicity. When expressed in CHO cells, the R171Q mutation resulted in 50% reduction of currents compared to wild-type KCNJ10 and G163D showed a complete loss of function. Co-expression of G163D and R171Q had a more pronounced effect on currents and membrane potential than R171Q alone but less severe than single expression of G163D. Moreover, the effect of the mutations seemed less pronounced in the presence of Kir5.1 (encoded by KCNJ16), with whom the renal Kir4.1 channels form heteromers. This partial functional rescue by co-expression with Kir5.1 might explain the lack of renal symptoms in the patients. This report illustrates that a spectrum of disorders with distinct clinical symptoms may result from mutations in different parts of KCNJ10, a gene initially associated only with the EAST/SeSAME syndrome.

Introduction: Substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is frequent in Parkinson's disease (PD), while lenticular nucleus hyperechogenicity (LN+) and 3rd ventricle enlargement (3V+) are typical of Atypical Parkinsonisms (AP). However, there are no studies assessing the diagnostic yield of all TCS biomarkers in the three AP (progressive supranuclear palsy, PSP, multiple system atrophy, MSA, corticobasal degeneration, CBD). Previous references lack homogeneous criteria and data are incomprehensive., Methods: Analysis of TCS performed in routine clinical practice in AP and PD patients from two tertiary hospitals. Expert recommendations were strictly followed. Previous literature was critically analysed., Results: 155 AP (98 PSP, 40 MSA, 14 CBD), 254 PD, 145 control subjects were included. We confirmed good sensitivity for SN+ in PD (80%), but specificity was lower than reported (61%). LN+ and 3V + had moderate sensitivity for AP and PSP diagnosis respectively (65%, 63%), but specificity was higher than reported (87%, 91%). We confirmed high specificity and positive predictive value of the combination SN/LN (98%, 93% AP; 83%, 86% PD). The combinations of two or three echofeatures, previously unreported, showed high specificity but lower sensitivity (SN/3V: 75% sensitivity, 87% specificity PD; 42% sensitivity, 98% specificity PSP) (SN + LN+: 79% sensitivity, 86% specificity CBD) (SN/3V/LN: 67% sensitivity, 89% specificity PD; 29% sensitivity, 99% specificity PSP; 41% sensitivity, 95% specificity MSA; 57% sensitivity 91% specificity CBD)., Conclusions: We present a large comprehensive study of TCS, confirming its usefulness and certain limitations in AP diagnosis. Adherence to consensus criteria is critical to implement TCS for clinical and research purposes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Purpose: There are no recommendations regarding how to treat cardioembolic recurrent strokes when patients are well anticoagulated. We evaluated the safety and efficacy of combining oral anticoagulation (OAC) with percutaneous left atrial appendage closure (LAAC) in patients with well-anticoagulated atrial fibrillation (AF) with recurrent strokes., Methods: In an explorative, prospective, observational study, LAAC was performed in patients with AF with at least two ischaemic strokes in the previous year, despite good anticoagulation using the Amplatzer Cardiac Plug (St Jude Medical, St Paul, MN, USA) or Amulet Abbot device (Abbot Vascular, Santa Clara, CA, USA). We recorded age, type of AF, CHA 2 DS 2 -VASC and HAS-BLED scores, types of OAC and risk factors. After closure, treatment with aspirin (100 mg/day) was continued for 3 months in combination with indefinite OAC. Clinical status, recurrent embolisms and bleeding complications were recorded during follow-up., Results: A total of 19 patients were included (mean age, 72.1 ± 9.6 years; mean CHA 2 DS 2 -VASC score, 5.3 ± 1.48; mean number of previous strokes, 2.78 ± 1.15). Thirteen had spontaneous echocardiographic contrast and all had dilatation of the left atrium. Eighteen patients had a multilobulated left atrial appendage, 17 with 'chicken-wing' morphology and one patient had a left atrial appendage thrombus. There were no complications during the procedure. Only one patient had a transient ischaemic attack and no major bleeding occurred during a mean follow-up of 17.4 ± 11.5 months., Conclusion: Combination therapy with indefinite OAC plus LAAC in patients with AF with recurrent strokes despite good anticoagulation should be considered in order to prevent a new stroke., (© 2018 EAN.)

Objectives: To analyse the incidence, risk factors, aetiology, treatment and clinical evolution of young patients with stroke., Patients and Methods: Retrospective registry of patients aged 55 years or younger hospitalised in a stroke unit during 2014. We recorded the incidence rate for all strokes and analysed demographic data, risk factors, degree of stress, stroke type and aetiology, reperfusion treatments and clinical evolution., Results: The study included 110 patients, the majority of whom were men (60.9%, 1.6:1 ratio). The incidence rate was 13.3% (110 of 830 strokes). Most of the patients had cardiovascular risk factors. Smoking was the most common risk factor (56.4%), followed by arterial hypertension (50%), dyslipidaemia (42.7%), obesity (33%), diabetes (18.2%) and emboligenic heart disease (12.7%). Some 64.3% of the heart disease cases and 51.1% of the dyslipidaemia cases were discovered during hospitalisation. Some 57.2% of the patients experienced psychosocial stress in the stage prior to the stroke. Some 83.6% of the stroke cases were ischaemic, 12.7% were haemorrhagic and 3.6% were venous sinus thrombosis. Of the ischaemic stroke cases, 30.4% were cryptogenic, 23.9% were lacunar, 16.3% were from uncommon causes, 15.2% were atherothrombotic and 14.1% were cardioembolic. Some 78.6% of the cerebral haemorrhage cases were hypertensive. Some 23.3% of the ischaemic stroke cases underwent reperfusion treatments in the acute phase, achieving levels of functional independence at 3 months of 62.5%., Conclusions: The majority of stroke events in patients 55 years of age or younger appear to be related to a high prevalence of classical cardiovascular risk factors and possibly to psychosocial stress., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Background: HHV7 reactivation has been occasionally reported as a cause of encephalitis or myelitis in transplant recipients, but to our knowledge it has never been associated with neurological disease in HIV-infected patients. We report a case of acute myelitis in an HIV-infected patient, with sustained HHV-7 DNA amplification in cerebrospinal fluid (CSF) and a favourable response to foscarnet., Case Report: A 40 year-old man with HIV infection was admitted with asymmetric hypoesthesia in legs and paraparesis. He was receiving treatment with efavirenz, emtricitabine and tenofovir, his CD4 count was 580/mm3 and HIV viral load was undetectable. Magnetic resonance imaging showed a focal central hyperintensity on T2 and STIR sequences, on the torathic spinal cord, with slight enhancement after intravenous gadolinium. All microbiological studies were negative except for HHV-7 DNA amplification in CSF. With a diagnosis of idiopathic transverse myelitis, treatment with high-dose intravenous methylprednisolone was initiated. However, paraparesis continued worsening, and a second CSF obtained 12 days after the first one resulted again in HHV-7 amplification., Results: The patient was treated with a 2 week course of foscarnet, and a rapid neurological improvement was noted. After treatment, PCR for HHV-7 in CSF was negative. Neurological exam was normal one month after treatment initiation., Conclusion: HHV-7 reactivation may cause neurological disease in patients with HIV infection. Foscarnet is an effective treatment in HHV-7 associated myelitis., (Copyright © 2016 Elsevier B.V. All rights reserved.)