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Objective: Patients with essential tremor (ET) may experience cognitive-affective impairment. Deep brain stimulation (DBS) of different targets, such as the ventral intermediate nucleus (VIM) of the thalamus or the posterior subthalamic area (PSA), has been shown to be beneficial for refractory ET. However, there is little evidence regarding the possible neuropsychological effects of PSA-DBS on patients with ET, and there are few studies comparing it with VIM-DBS in this population.In this study, we aim to present the evaluation protocol and neuropsychological battery as used in an ongoing trial of DBS for ET comparing the already mentioned targets., Methods: As part of a randomized, double-blind, crossover clinical trial comparing the effectiveness and safety of PSA-DBS vs. VIM-DBS, 11 patients with refractory ET will undergo a multi-domain neuropsychological battery assessment. This will include a pre-/post-implantation assessment (3 months after the stimulation of each target and 6 months after an open stage of DBS on the most optimal target)., Conclusion: Evidence on the neuropsychological effects of DBS in patients with refractory ET is very scarce, particularly in lesser-explored targets such as PSA. This study could contribute significantly in this field, particularly on pre-procedure safety analysis for tailored patient/technique selection, and to complete the safety analysis of the procedure. Moreover, if proven useful, this proposed neuropsychological assessment protocol could be extensible to other surgical therapies for ET., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Triguero-Cueva, Marín-Romero, Madrid-Navarro, Pérez-Navarro, Iáñez-Velasco, Mínguez-Castellanos, Katati and Escamilla-Sevilla.)

Introduction: Acute ischemic stroke therapy has improved in recent decades, decreasing the rates of disability and death among stroke patients. Unfortunately, all health care systems have geographical disparities in infrastructure for stroke patients. A centralized telestroke network might be a low-cost strategy to reduce differences in terms of geographical barriers, equitable access, and quality monitoring across different hospitals., Aims: We aimed to quantify changes in stroke patients' geographic access to specialized evaluation by neurologists and to intravenous acute stroke reperfusion treatments following the rapid implementation of a centralized telestroke network in the large region of Andalusia (8.5 million inhabitants)., Methods: We conducted an observational study using spatial and analytical methods to examine how a centralized telestroke network influences the quality and accessibility of stroke care for a large region., Results: In the pre-implementation period, 5,005,477 (59.72% of the Andalusian population) had access to specialized stroke care in less than 30 min. After the 5-month process of implementing the telestroke network, 7,832,988 (93.5%) inhabitants had an access time of less than 30 min, bridging the gap in acute stroke care in rural hospitals., Conclusions: A centralized telestroke network may be an efficient tool to reduce the differences in stroke care access and quality monitoring across different hospitals, especially in large regions with low population density., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases., (© 2022. The Author(s).)

Objective: We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature., Methods: A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed., Results: Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively., Conclusions: There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype., (© 2020 European Academy of Neurology.)

Introduction: Ischaemic stroke has been reported in patients with COVID-19, particularly in more severe cases. However, it is unclear to what extent this is linked to systemic inflammation and hypercoagulability secondary to the infection., Methods: We describe the cases of 4 patients with ischaemic stroke and COVID-19 who were attended at our hospital. Patients are classified according to the likelihood of a causal relationship between the hypercoagulable state and ischaemic stroke. We also conducted a review of studies addressing the possible mechanisms involved in the aetiopathogenesis of ischaemic stroke in these patients., Results: The association between COVID-19 and stroke was probably causal in 2 patients, who presented cortical infarcts and had no relevant arterial or cardioembolic disease, but did show signs of hypercoagulability and systemic inflammation in laboratory analyses. The other 2 patients were of advanced age and presented cardioembolic ischaemic stroke; the association in these patients was probably incidental., Conclusions: Systemic inflammation and the potential direct action of the virus may cause endothelial dysfunction, resulting in a hypercoagulable state that could be considered a potential cause of ischaemic stroke. However, stroke involves multiple pathophysiological mechanisms; studies with larger samples are therefore needed to confirm our hypothesis. The management protocol for patients with stroke and COVID-19 should include a complete aetiological study, with the appropriate safety precautions always being observed., (Copyright © 2020 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Deep brain stimulation (DBS) is used to treat movement disorders, severe psychiatric disorders, and neuropathic pain, among other diseases. Advanced neuroimaging techniques allow direct or indirect localization of the target site, which is verified in many centers by the intraoperative recording of unitary neuronal activity. Intraoperative image acquisition technology (e.g., O-Arm) is increasingly used for accurate electrode positioning throughout the surgery. The aim of our study is to analyze the initial experience of our team in the utilization of O-Arm for planning DBS and monitoring its precision and accuracy throughout the procedure. The study included 13 patients with movement disorders. All underwent DBS with the intraoperative O-arm image acquisition system (iCT) and Medtronic StealthStation S7 cranial planning system, placing a total of 25 electrodes. For each patient, we calculated the difference between real and theoretic x, y, z coordinates, using the paired Student's t test to evaluate absolute and directional differences and the one-sample Student's t test to analyze differences in Euclidean distances. No statistically significant differences were found in absolute, directional, or Euclidean distances between intended and actual x, y, and z coordinates, based on iCT scan. Our experience confirms that utilization of the O-Arm system in DBS provides accurate and precise verification of electrode placements throughout the procedure. Recent studies found no significant differences between iCT and postoperative MRI, the current gold standard. Further prospective studies are warranted to test the elimination of postoperative MRI when this system is used.

Background: The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases., Objectives: To perform the largest PD genome-wide association study restricted to a single country., Methods: We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses., Results: We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls., Conclusions: Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Objectives: To analyse the association between aminosalicylate-treated inflammatory bowel disease (IBD) and Parkinson's disease (PD) at population level., Design: Cross-sectional study., Setting: The study was performed based on electronic drug prescription and dispensation records of the Andalusian Public Health System., Participants: All individuals aged ≥50 years with at least one drug dispensation during December 2014 were identified from the records., Primary and Secondary Outcome Measures: Groups were formed: 'possible PD' group, including all who received an anti-Parkinson agent; 'possible IBD' group, those treated with mesalazine and/or derivatives (5-aminosalicylic acid (5-ASA)); and 'possible PD and IBD', including those receiving both anti-Parkinson agent and 5-ASA. Prevalence of possible PD was determined among those with possible IBD and among those without this condition. The age-adjusted and sex-adjusted OR was calculated., Results: We recorded 2 020 868 individuals (68±11 years, 56% female), 19 966 were included in possible PD group (75±9 years, 53% female) and 7485 in possible IBD group (64±10 years, 47% female); only 56 were included in both groups (76±8 years, 32% female). The prevalence of possible PD was 0.7% among those with possible IBD and 1% among those without this condition (adjusted OR=0.94; 95% CI 0.72 to 1.23; p=0.657). OR was 0.28 in individuals aged ≤65 years (95% CI 0.10 to 0.74; p=0.01) and 1.17 in older individuals (95% CI 0.89 to 1.54; p=0.257)., Conclusions: Within the limitations of this study, the results suggest a protective role for IBD and/or 5-ASA against PD development, especially among under 65-year olds. Further studies are warranted to explore this association given its scientific and therapeutic implications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Parkinson's disease (PD) is associated with several non-motor symptoms that may precede the diagnosis and constitute a major source of frailty in this population. The digital era in health care has open up new prospects to move forward from the qualitative and subjective scoring for PD with the use of new wearable biosensors that enable frequent quantitative, reliable, repeatable, and multidimensional measurements to be made with minimal discomfort and inconvenience for patients. A cross-sectional study was conducted to test a wrist-worn device combined with machine-learning processing to detect circadian rhythms of sleep, motor, and autonomic disruption, which can be suitable for the objective and non-invasive evaluation of PD patients. Wrist skin temperature, motor acceleration, time in movement, hand position, light exposure, and sleep rhythms were continuously measured in 12 PD patients and 12 age-matched healthy controls for seven consecutive days using an ambulatory circadian monitoring device (ACM). Our study demonstrates that a multichannel ACM device collects reliable and complementary information from motor (acceleration and time in movement) and common non-motor (sleep and skin temperature rhythms) features frequently disrupted in PD. Acceleration during the daytime (as indicative of motor impairment), time in movement during sleep (representative of fragmented sleep) and their ratio (A/T) are the best indexes to objectively characterize the most common symptoms of PD, allowing for a reliable and easy scoring method to evaluate patients. Chronodisruption score, measured by the integrative algorithm known as the circadian function index is directly linked to a low A/T score. Our work attempts to implement innovative technologies based on wearable, multisensor, objective, and easy-to-use devices, to quantify PD circadian rhythms in huge populations over extended periods of time, while controlling at the same time exposure to exogenous circadian synchronizers.

Vanishing white matter disease (VWM) was described by Van der Knaap in 1996. This association with premature ovarian failure is known as ovarioleukodystrophy. This is a rare entity caused by a mutation in one of the subunits of eukaryotic initiation factor 2B (EIF2B). The onset in adulthood or late in adolescence is very infrequent. A 41-years-old woman and her 37-years-old sister developed epilepsy in association with premature ovarian failure at the age of 13 and 18 respectively. The oldest-one started 17 years later progressive subcortical cognitive decline with predominant behavioural disorders and a progressive spastic paraparesis in association with symmetric cystic changes in the with matter of both hemispheres. In both patients we found the c.1117C>T (p.Arg373Cys) mutation in homozygosis in the EIF2B4 gen., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Stroke is a very common cause of death, especially in southern Spain. The present study analyses in-hospital mortality associated with stroke in an Andalusian tertiary care hospital., Methods: We gathered the files of all patients who had died at Hospital Universitario Virgen de las Nieves in Granada in 2013 and whose death certificates indicated stroke as the cause of death. We also gathered stroke patients discharge data and compared them to that of patients with acute coronary syndrome (ACS)., Results: A total of 825 patients had a diagnosis of stroke (96 deaths, 11.6%); of these, 562 had ischaemic stroke (44 deaths, 7.8%) and 263 haemorrhagic stroke (52 deaths, 19.7%). Patients with haemorrhagic stroke therefore showed greater mortality rate (OR=2.9). Patients in this group died after a shorter time in hospital (median, 4 vs 7 days; mean, 6 days). However, patients with ischaemic stroke were older and presented with more comorbidities. On the other hand, 617 patients had a diagnosis of ACS (36 deaths, 5.8%). The mortality odds ratio (MOR) was 2.1 (stroke/SCA). Around 23% of the patients who died from stroke were taking anticoagulants. 60% of the deceased patients with ischaemic stroke and 20% of those with haemorrhagic stroke had atrial fibrillation (AF); 35% of the patients with ischaemic stroke and AF were taking anticoagulants., Conclusions: Stroke is associated with higher admission and in-hospital mortality rates than SCA. Likewise, patients with haemorrhagic stroke showed higher mortality rates than those with ischaemic stroke. Patients with fatal stroke usually had a history of long-term treatment with anticoagulants; 2 thirds of the patients with fatal ischaemic stroke and atrial fibrillation were not receiving anticoagulants. According to our results, optimising prevention in patients with AF may have a positive impact on stroke-related in-hospital mortality., (Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Advanced Parkinson's disease (APD) is characterized by increased functional disability, caused by motor complications, the presence of axial symptoms, and emergent disease- and drug-related non-motor symptoms. One of the advanced therapies available is intrajejunal infusion of levodopa/carbidopa intestinal gel (LCIG); however, patient selection for this treatment is sometimes difficult, particularly because of overlapping indications with other alternatives. In recent years, strong evidence has supported the use of LCIG in treating motor fluctuations associated with APD, and several clinical studies provide emerging evidence for additional benefits of LCIG treatment in certain patients. This article provides an overview of the published literature on the benefits, limitations, and drawbacks of LCIG in relation to PD symptoms, the psychosocial impact of the disease, and the quality of life of patients, with the aim of determining candidates for whom treatment with LCIG would be beneficial. According to current evidence, patients with APD (defined as inability to achieve optimal control of the disease with conventional oral treatment), a relatively well-preserved cognitive-behavioral status, and good family/caregiver would count as suitable candidates for LCIG treatment. Contraindications in the opinion of the authors are severe dementia and active psychosis.

There are a number of clinical questions for which there are no easy answers, even for well-trained doctors. The diagnostic tool commonly used to assess cognitive impairment in neurodegenerative diseases is based on established clinical criteria. However, the differential diagnosis between disorders can be difficult, especially in early phases or atypical variants. This takes on particular importance when it is still possible to use an appropriate treatment. To solve this problem, physicians need to have access to an arsenal of diagnostic tests, such as neurofunctional imaging, that allow higher specificity in clinical assessment. However, the reliability of diagnostic tests may vary from one to the next, so the diagnostic validity of a given investigation must be estimated by comparing the results obtained from "true" criteria to the "gold standard" or reference test. While pathological analysis is considered to be the gold standard in a wide spectrum of diseases, it cannot be applied to neurological processes. Other approaches could provide solutions, including clinical patient follow-up, creation of a data bank or use of computer-aided diagnostic algorithms. In this article, we discuss the development of different methodological procedures related to analysis of diagnostic validity and present an example from our own experience based on the use of I-123-ioflupane-SPECT in the study of patients with movement disorders. The aim of this chapter is to approach the problem of diagnosis from the point of view of the clinician, taking into account specific aspects of neurodegenerative disease.

Background: An autonomic denervation and abnormal vasomotor reflex in the skin have been described in Parkinson's disease (PD) and might be evaluable using thermography with cold stress test., Methods: A cross-sectional pilot study was undertaken in 35 adults: 15 patients with PD and abnormal [(123)I]-metaiodobenzylguanidine cardiac scintigraphy and 20 healthy controls. Baseline thermography of both hands was obtained before immersing one in cold water (3 ± 1 °C) for 2 min. Continuous thermography was performed in: non-immersed hand (right or with lesser motor involvement) during immersion of the contralateral hand and for 6 min afterward; and contralateral immersed hand for 6 min post-immersion. The region of interest was the dorsal skin of the third finger, distal phalanx., Results: PD patients showed a lower mean baseline hand temperature (p = 0.037) and greater thermal difference between dorsum of wrist and third finger (p = 0.036) and between hands (p = 0.0001) versus controls, regardless of the motor laterality. Both tests evidenced an adequate capacity to differentiate between groups: in the non-immersed hand, the PD patients did not show the normal cooling pattern or final thermal overshoot observed in controls (F = 5.29; p = 0.001), and there was an AUC of 0.897 (95%CI 0.796-0.998) for this cooling; in the immersed hand, thermal recovery at 6 min post-immersion was lesser in patients (29 ± 17% vs. 55 ± 28%, p = 0.002), with an AUC of 0.810 (95%CI 0.662-0.958)., Conclusions: PD patients reveal abnormal skin thermal responses in thermography with cold stress test, suggesting cutaneous autonomic dysfunction. This simple technique may be useful to evaluate autonomic dysfunction in PD., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: A recent genome-wide association study (GWAS) has identified a putative association, not statistically confirmed, of cervical dystonia within several regions in a British population. Hence, the authors proposed dysfunction of the ion channel NALCN (for sodium leak channel, nonselective) as a plausible cause of cervical dystonia. The objective of our study was to investigate the association of five single nucleotide polymorphisms (SNPs) previously reported with high signals as putative genetic risk factors for cervical dystonia in a British GWAS, including two located in the NALCN gene region., Methods: We performed a case-control association study in a Spanish population. The SNPs selected for genotyping were two SNPS in the NALCN gene (rs61973742 and rs1338041), one SNP in the OR4X2 gene (rs67863238), one SNP in the COL4A1 region (rs619152), and one intergenic SNP (rs1249277). Genomic DNA was collected from 252 patients with cervical dystonia, with a mean age of 55.3 ± 14.1 years (mean age at onset, 43.5 ± 15.7 years), and 342 unrelated control subjects with a mean age of 56.3 ± 14.3 years. Genotyping of SNPs was performed using TaqMan assays and SimpleProbe assays., Results: The SNP rs619152 had to be excluded because of assay failure. No significant differences were found in allele distribution between cases and controls for all analyzed SNPs. Therefore, we found no association with cervical dystonia for the analyzed SNPs in our Spanish population., Conclusions: We did not find any evidence supporting the association of NALCN with cervical dystonia, indicating that this gene is not implicated in the pathogenesis of this disorder in our cervical dystonia population., (© 2014 International Parkinson and Movement Disorder Society.)

Background: A polymorphism in brain-derived neurotrophic factor (BDNF) (Val66Met) has been reported as a risk factor in primary dystonia. However, overall the results have been inconclusive. Our aim was to clarify the association of Val66Met with primary dystonia, and with the most prevalent clinical subtypes, cervical dystonia and blepharospasm., Methods: We conducted a Spanish multicenter case-control study (including 680 primary dystonia patients and 788 healthy controls) and performed a meta-analysis integrating our study and six previously published studies (including a total of 1,936 primary dystonia patients and 2,519 healthy controls)., Results: We found no allelic or genotypic association with primary dystonia, cervical dystonia, or blepharospasm risks, for the allele A (Met) from a BDNF Val66Met polymorphism in our case-control study. This was confirmed by results from our meta-analysis in white and mixed ethnic populations in any genetic model., Conclusion: We did not find any evidence supporting the association of the BDNF Val66Met polymorphism with primary dystonia., (© 2014 International Parkinson and Movement Disorder Society.)

Hemiparkinsonism secondary to a vascular mesencephalic lesion is infrequent; these patients offer an exceptional opportunity to study neuropsychological alterations attributable to unilateral dopaminergic denervation, shedding light on the pathophysiology of cognitive disorders in early-stage idiopathic Parkinson's disease (PD). From the investigation of our case, we conclude that destruction of the right nigrostriatal pathway is accompanied by deficits in executive functioning and verbal/visual memory similar to those observed in many patients with early-stage idiopathic PD. The more complex neuropsychological dysfunction developed by other PD patients must therefore be related to the additional involvement of other brain structures.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor function in selected patients with Parkinson's disease (PD) but can be associated with variable changes in cognitive functions., Methods: We studied 21 patients selected for STN-DBS and compared 6-month clinical and neuropsychological outcomes between those who underwent surgery (n = 9) and those who voluntarily refused it (n = 12)., Results: Motor and quality of life outcomes were markedly superior in the STN-DBS group versus controls. A wide neuropsychological battery was administered, and the whole sample showed a statistically significant worsening in phonemic verbal fluency, time to perform the Trail Making Test part B, Digit Symbol score of WAIS-III and color-naming score of the Stroop Test. In comparison to controls, a trend to a slightly worse deterioration in phonemic verbal fluency was observed in the STN-DBS patients and was significantly correlated with reductions in the L-dopa-equivalent daily dose (r = 0.850, p = 0.007)., Conclusion: Our study confirms the safety of STN-DBS from a cognitive standpoint; a reduction in verbal fluency at 6 months after surgery can also be related to PD progression and medication reduction., (Copyright © 2012 S. Karger AG, Basel.)

OBJECTIVES - Determine whether bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson's disease (PD) is associated with an increase in neuropeptide Y (NPY) and/or resistance to inhibition by leptin in relation to post-surgery weight gain. MATERIALS AND METHODS - This prospective study included 20 patients who underwent bilateral STN-DBS and 17 who refused surgery. Data were obtained at baseline, 3 and 6 months on neurological and nutritional status, including determination of body mass index (BMI) and serum NPY and leptin levels. RESULTS -  NPY and leptin levels changed over time, with a distinct pattern. The BMI increase at 6 months was greater in the surgical group (5.5 ± 6.3% vs 0.5 ± 3.5%; P = 0.035). Medical group exhibited a reduction in leptin level (-2.0 ± 4.3 ng/ml) and a consequent increase in NPY level (72.4 ± 58.7 pmol/ml). However, STN-DBS patients showed an increase in leptin (3.1 ± 5.0 ng/ml; P = 0.001 vs medical group) and also in NPY (12.1 ± 53.6 pmol/ml; P = 0.022 vs medical group) levels, which suggests resistance to inhibition by leptin. Rise in NPY level correlated with higher stimulation voltages. CONCLUSIONS -  Bilateral STN-DBS causes disruption of the melanocortin system, probably related to diffusion of the electric current to the hypothalamus. This mechanism may in part explain the weight gain of patients with PD after surgery., (© 2011 John Wiley & Sons A/S.)

Determining the eligibility of patients with Parkinson's disease (PD) for deep brain stimulation (DBS) can be challenging for general (non-specialised) neurologists. We evaluated the use of an online screening tool (Stimulus) that aims to support appropriate referral to a specialised centre for the further evaluation of DBS. Implementation of the tool took place via an ongoing European multicentre educational programme, currently completed in 15 DBS centres with 208 referring neurologists. Use of the tool in daily practice was monitored via an online data capture programme. Selection decisions of patients referred with the assistance of the Stimulus tool were compared to those of patients outside the screening programme. Three years after the start of the programme, 3,128 patient profiles had been entered. The intention for referral was made for 802 patients and referral intentions were largely in accordance with the tool recommendations. Follow-up at 6 months showed that actual referral took place in only 28%, predominantly due to patients' reluctance to undergo brain surgery. In patients screened with the tool and referred to a DBS centre, the acceptance rate was 77%, significantly higher than that of the unscreened population (48%). The tool showed a sensitivity of 99% and a specificity of 12% with a positive and negative predictive value of 79 and 75%, respectively. The Stimulus tool is useful in assisting general neurologists to identify appropriate candidates for DBS consideration. The principal reason for not referring potentially eligible patients is their reluctance to undergo brain surgery.

The field of movement disorders largely covers subacute or chronic diseases that are usually treated in outpatient clinics. However, the much less frequent acute disorders require urgent recognition and treatment. The present article reviews the entities that frequently require neurointensive management and whose development can prove "calamitous". These include neuroleptic malignant syndrome and related conditions, status dystonicus, and hemiballism., (Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

Background: Dystonia is a complex clinical syndrome originated by a wide range of aetiologies. The diagnosis of dystonia is made after the evaluation of aetiological, phenomenological and genetic factors. Medications, except in patients with dopa-responsive dystonia, are of limited efficacy. Botulinum toxin injections are not applicable to patients with generalised dystonia, since many muscular groups contribute to disability. Clinical studies in children and adults with primary generalised dystonia (PGD) have reported beneficial effects of bilateral GPi deep brain stimulation (DBS) in both motor symptoms and disability produced by dystonia as well as a favourable impact of DBS in the health-related quality of life (HRQoL). Some clinical aspects of GPi stimulation in primary dystonia still remain controversial such as the influence of disease duration or age at onset in determining the postoperative clinical outcome., Results: The authors report the results of a multicentric study designed to assess the tolerability and clinical effects of bilateral pallidal DBS on motor impairment, functional disability, quality of life, pain and mood in patients with medically refractory primary generalised or segmental dystonia.

Introduction: Lewy body disorders such as Parkinson's disease (PD) and Lewy body dementia (LBD) are associated with cardiac sympathetic denervation, which can be visualized on 123I-MIBG scintigraphy. Our objectives were to study the diagnostic value of this technique in Lewy body disorders and its relationship with PD clinical variables., Patients and Methods: We studied 90 patients: 51 with PD, 19 with LBD, 9 with multiple system atrophy (MSA) and 11 controls. Scintigraphy images were qualitatively evaluated and early and delayed heart-to-mediastinum ratios (HMR) were calculated. The main confounding factors (ischemic heart disease, diabetes, hypertension and drugs) were controlled by multivariate linear regression analysis. We investigated correlations between scintigraphy variables and PD variables., Results: The delayed HMR, which showed better discriminative ability was 2.03 +/- 0.32 in controls, 1.37 +/- 0.30 in PD (p<0.001 vs controls), 1.47+/-0.45 in LBD (p=0.001 vs controls) and 1.69+/-0.28 in MSA (p=0.02 vs controls; p=0.004 vs PD). This ratio was influenced by PD/LBD diagnosis (beta= -0.638; p<0.001) and to a lesser degree, by ischemic heart disease (beta= -0.244; p=0.028). Optimal cut-off value between PD/LBD and controls was 1.71 (83% sensitivity and 82% specificity). Within the PD group, those with a family history of PD/LB showed higher delayed HMR values (1.65+/-0.34 vs 1.30+/-0.24 without history; p<0.001) and proportion with normal scintigraphy (56% vs 5%; p=0.001)., Conclusions: Cardiac 123I-MIBG scintigraphy is useful in the diagnosis of Lewy body disorders, although its value in PD is conditioned by having a family history of PD.

Background: Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD)., Objective: We conducted a phase I-II clinical study to assess the feasibility, long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD., Methods: Thirteen patients with advanced PD underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed before surgery and up to 1-3 years after surgery according to CAPIT (Core Assessment Programme for Intracerebral Transplantation) and CAPSIT-PD (Core Assessment Programme for Surgical Interventional Therapies in Parkinson's Disease) protocols. The primary outcome measure was the change in video blinded Unified Parkinson's Disease Rating Scale III score in the off-medication state. Seven patients had 18F-dopa positron emission tomography scans before and 1 year after transplantation., Results: Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analysed patients, which was maximal at 6-12 months after transplantation (5-74%). Overall, mean improvement at 6 months was 23%. In the long term (3 years), 3 of 6 patients still maintained improvement (15-48%). None of the patients developed off-period dyskinesias. The main predictive factors for motor improvement were the histological integrity of the CB and a milder disease severity. We observed a non-significant 5% increase in mean putaminal 18F-dopa uptake but there was an inverse relationship between clinical amelioration and annual decline in putaminal 18F-dopa uptake (r = -0.829; p = 0.042)., Conclusions: CB autotransplantation may induce clinical effects in patients with advanced PD which seem partly related to the biological properties of the implanted glomus cells.

Objective: To review, from a mainly clinical standpoint, the different strategies applied to regenerate or restore the nigrostriatal dopaminergic system in Parkinson's disease (PD). A previous first part focused on the results of adrenal medulla and human fetal mesencephalic transplants, and this second part addresses transplants of other cell types, administration of trophic factors, and gene therapy., Development: As an alternative to human fetal mesencephalic neurons, other donor cells types (porcine mesencephalic neurons, retinal pigment epithelial cells) with similar 'dopaminergic' action mechanism have been tried, although with heterogeneous results. Transplantation of carotid body cell aggregates may be a promising therapy because of its neurotrophic action mechanism. The perspectives of cell therapies based on genetically modified cells and precursor cells of different origin are also reviewed. Among other neuroregenerative approaches, the clinical outcomes of direct administration of neurotrophic factors and the perspectives for in vivo gene therapy are also addressed., Conclusions: The objective of neuroregenerative therapy for PD should include trophic restoration of damaged neuronal systems, since improvement in striatal dopaminergic function is not sufficient. After the recent failure of the direct (intraventricular or intraputaminal) administration of glial cell line-derived neurotrophic factor (GDNF), attention of researchers has focused on indirect methods, including transplantation of GDNF-producing cells (carotid body cell aggregates or different genetically modified cells), and in vivo gene therapy.

Objective: To review, from a mainly clinical standpoint, the different strategies applied to regenerate or restore the nigrostriatal dopaminergic system in Parkinson's disease. This first part focuses on the results of adrenal medulla and human fetal mesencephalic transplants, and a second part will address transplants of other cell types, administration of trophic factors, and gene therapy., Development: Adrenal medulla transplants were abandoned because of their inconsistent results and high morbidity. Although fetal mesencephalic transplantation can produce long-term restoration of striatal dopamine deficiency, this neurochemical effect is clinically inadequate in presence of progressive neuronal loss. Other strategies with similar 'dopaminergic' action mechanism are not a therapeutic option in this setting., Conclusions: The objective of neuroregenerative therapy for Parkinson's disease should include trophic restoration of damaged neuronal systems, since improvement in striatal dopaminergic function is not sufficient. After the recent failure of the direct (intraventricular or intraputaminal) administration of glial cell line-derived neurotrophic factor (GDNF), attention of researchers has focused on indirect methods, including transplantation of GDNF-producing cells (carotid body cell aggregates or different genetically modified cells, including stem cells), and in vivo gene therapy.

Introduction: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) have demonstrated efficacy in advanced Parkinson's disease (PD). We aimed to assess the clinical utility of these procedures in terms of the quality of life, and to determine the pre and postsurgical characteristics related to the outcome., Method: A prospective study was conducted on a cohort of 20 patients with advanced PD who underwent bilateral DBS: 14 in STN and 6 in GPi. They were assessed according to the CAPSIT-PD protocol before and after surgery, with a mean follow-up of 9 and 11 months, respectively. The main outcome variables were change in the UPDRS III score in off efficacy and the PDQ-39 quality of life questionnaire score (clinical utility)., Results: The STN group improved their UPDRS III in off by a mean of 35% (p = 0.001) and their PDQ-39 by 21% (p = 0.026). The GPi group improved their UPDRS III in off by 21% (p = 0.028) and their PDQ-39 by 37% (p = 0.116). The presurgical levodopa-equivalent dose was a positive predictor of the efficacy and clinical utility of STN DBS and a negative predictor of the efficacy of GPi DBS. In both groups, the clinical utility was determined by improvement in functional disability in off scales., Conclusions: Bilateral DBS demonstrated middle-term efficacy and clinical utility in the treatment of advanced PD. The presurgical levodopa-equivalent dose was a predictor of the efficacy and clinical utility of DBS.

Objective: In this study, we assessed the feasibility of autotransplantation of carotid body (CB) cell aggregates into the striatum for the treatment of patients with Parkinson's disease (PD)., Methods: Six patients with advanced PD underwent bilateral autotransplantation of CB cell aggregates into the striatum. They were evaluated clinically preoperatively and for 18 months after surgery according to the recommendations of the Core Assessment Program for Intracerebral Transplantation., Results: No major complications or adverse events resulted from the cell implantation or surgical procedures. During the course of the study, there was no significant aggravation of dyskinesia or decline in cognitive function in any of the patients. Five of the six patients who underwent transplantation manifested a measurable degree of clinical improvement evidenced by standardized clinical rating scales for PD. A decrease in the blinded Unified Parkinson's Disease Rating Scale Part III in the "off" state, the main measure of transplant efficacy in our study, was found to be maximal (between 26 and 74%) at 6 months after surgery. At 1 year, clear reductions in the blinded Unified Parkinson's Disease Rating Scale Part III were maintained in three patients (24, 38, and 52%, respectively). Modest improvement was seen in two patients (13 and 17%), and the sole patient who showed no improvement had the most fibrosis in the CB. The age of the patient and the state of the CB tissue were adversely correlated with clinical improvement after CB autotransplantation., Conclusion: This pilot study indicates that CB autograft transplantation is a relatively simple, safe, and viable therapeutical approach for the treatment of patients with advanced PD. More studies are needed to optimize the procedure and to assess its general applicability for the treatment of patients with PD.

We present a 24-year-old man with idiopathic segmental cervical and truncal dystonia of juvenile onset. His condition improved after unilateral stimulation of the internal globus pallidus ipsilateral to the contracting sternocleidomastoid muscle., (Copyright 2002 Movement Disorder Society)

At the present time corpus callosotomy is a valuable option in the management of some patients with drug-resistant epilepsy who are not candidates for resective procedures. The records of six patients who underwent callosotomy at 'Hospital Virgen de las Nieves' (Granada, Spain) in the past four years were retrospectively analyzed. The patients all had intractable primary or secondarily generalized seizures, were severely handicapped by its frequency and nature (especially with drop attacks and multiple injuries) and were not suitable for other surgical procedure. The results of surgery (five anterior callosotomies and one subtotal section) are described after an average follow-up period of 2.5 years. Overall, four patients achieved significant improvement (at least 50% reduction in seizure frequency, severity, or both, affecting quality of life), with a marked reduction (> 75%) in two of them. There was no clinical deterioration, significant surgical complication nor relevant additional long-term neuro-psychological deficit in any case. Previous studies have been reviewed mainly to find those prognostic factors associated with a better seizure outcome or with the occurrence of complications. The best results are obtained in those patients with drop attacks (including atonic seizures) as the most frequent and disabling seizure type. According to the type of epilepsy, patients with localization-related epilepsy (especially when symptomatic of a focal brain damage) and those with the Lennox-Gastaut syndrome are the most likely to benefit from the procedure. It is suggested that, in the first place, a two-thirds anterior callosotomy should be performed particularly with atonic seizure are the most frequent seizure type. We may proceed with completion of callosal division as a second stage in those patients in whom a significant improvement has not been observed. In severely retarded patients with multiple seizure types, one-stage complete section may be performed. The procedure is relatively safe, with a low incidence of morbidity and clinically significant long-term neuro-psychological deficits. Further larger clinical studies are necessary to elucidate many aspects which are still unresolved. More uniformity would be desirable in the evaluation of patients, surgical technique, follow-up and presentation of results.

Most cases of temporal arteritis are of the giant cell variety, with cases involving other histologic patterns occurring rarely. There are only 4 descriptions in the literature of non giant cell temporal arteritis as a manifestation of Churg-Strauss syndrome. We report the case of a 74-year-old man with a history of bronchial asthma who presented with systemic symptoms and right temporal cephalea with diplopia, diffuse muscle pain and transient skin lesions on the extremities. The right temporal artery was enlarged and painful but pulsatile. Tests showed a high erythrocyte sedimentation rate and leukocytosis with relative and absolute eosinophilia. Biopsy of the temporal artery revealed polymorphic inflammatory infiltration throughout the vas, with numerous eosinophils and non giant cells, confirming a diagnosis of Churg-Strauss syndrome with extension to the temporal artery. Temporal arteritis should be considered a syndrome with variable substrate pathology; the possibility that it is a rare manifestation of systemic necrotizing vasculitis should not be ruled out.

An acute attack of cephalea and third nerve palsy with pupillary involvement may be caused by a variety of entities, but aneurysm of the posterior communicating artery must certainly be ruled out. We describe a 22 year old patient in whom this clinical profile was an unusual first sign of multiple sclerosis.

We report a patient with monophasic inflammatory demyelinizing disease whose initial symptoms and imaging studies led to the undertaking of a cerebral biopsy for suspicion of an expansive process. The evolution of the both the CT and MR imaging studies with contrast and overall the surprising size of the lesions in MR when the patient was clinically asymptomatic support the hypothesis of residual dysfunction in the hemato-encephalic barrier as a cause of the persistence of MR images. This explanation appears more acceptable than its attribution to a gliosis secondary to previous inflammation.