Miquel Aguilar

Hospital Universitari Mutua de Terrassa, Terrassa, Catalonia, Spain

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Publications (26)68.66 Total impact

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    ABSTRACT: Substantia nigra hyperechogenicity (SN+) has been proposed as a risk marker of Parkinson's disease (PD). Asymptomatic LRRK2 mutation carriers (aLRRK2+), at high risk for developing PD, provide an opportunity for the study of preclinical biomarkers. To assess SN echogenicity and other echographic features in LRRK2 G2019S carriers and their clinical and imaging correlates. Transcranial sonography was performed in 26 LRRK2 G2019S PD patients, 50 first-degree relatives, 31 idiopathic PD (IPD) patients and 26 controls. SN echogenicity and other echographic features were assessed in all study subjects. Dopamine transporter imaging (DAT-SPECT) was performed in 29 first-degree relatives. 75% of the LRRK2-PD and 87.5% of the IPD showed SN+ (p = 0.087). aLRRK2+ had a higher frequency of SN+ than non carriers (58.3% vs. 25%, p = 0.039) and controls (58.3% vs. 12.5%; p = 0.002) and had a larger area of SN echogenicity than non carriers (p = 0.030) and controls (p < 0.001). The width of the third ventricle was significantly lower in LRRK2-PD than in IPD (1.9 mm [1.38; 2.75] vs. 3.0 mm [2.3; 5.3]; p = 0.003). Four out of 5 (80%) of the aLRRK2+ with an abnormal DAT-SPECT and four of the 5 (80%) of those with REM sleep behaviour disorder (RBD) had SN+. SN+ is very frequent in LRRK2-PD and aLRRK2+. Most aLRRK2 with possible surrogate markers of PD such as abnormal DAT-SPECT or RBD, also had SN+, which supports that this echofeature might be a marker of PD in these asymptomatic population. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 08/2015; 10.1016/j.parkreldis.2015.08.007. DOI:10.1016/j.parkreldis.2015.08.007 · 4.13 Impact Factor
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    ABSTRACT: Nonmotor symptoms (NMS) in Parkinson's disease (PD) can precede onset of motor symptoms. Relationship between premotor symptoms onset and motor features is limited. Our aim is to describe the presence and perceived onset of NMS in PD as well as their possible association with motor phenotype. Presence and onset of NMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls from 11 Spanish and Austrian centers. Seventeen of thirty-one NMS were more common in patients than controls (P < 0.05). They were usually mild and frequently reported to occur at different time-spans before motor symptoms. Anhedonia, apathy, memory complaints, and inattention occurred more frequently during the 2-year premotor period. Those reported more frequently in the 2- to 10-year premotor period were smell loss, mood disturbances, taste loss, excessive sweating, fatigue, and pain. Constipation, dream-enacting behavior, excessive daytime sleepiness, and postprandial fullness were frequently perceived more than 10 years before motor symptoms. No correlation between NMS burden and motor severity, age, or gender was observed. NMS associated in four clusters: rapid eye movement sleep behavior disorder symptoms-constipation, cognition-related, mood-related, and sensory clusters. No cluster was associated with a specific motor phenotype or severity. NMS are common in early unmedicated PD and frequently reported to occur in the premotor period. They are generally mild, but a patient subgroup showed high NMS burden mainly resulting from cognition-related symptoms. Certain NMS when present at the time of assessment or in the premotor stage, either alone or in combination, allowed discriminating PD from controls. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 11/2014; 30(2). DOI:10.1002/mds.26077 · 5.68 Impact Factor
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    ABSTRACT: Background: Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined. Objective: To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients. Methods: The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated. Results: University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5 +/- 6.8 vs 18.4 +/- 6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9 +/- 4.7 vs 19.4 +/- 6.8; p < 0.01). The frequency of sleep and neuropsychiatric disturbances and of dysautonomic symptoms in LRRK2-G2019S-PD was not significantly different from that in IPD. Hyposmia, depression, constipation and excessive daytime sleepiness, were reported to occur before the onset of classical motor symptoms in more than 40% of LRRK2-PD patients in whom these symptoms were present at the time of examination. Conclusion: Neuropsychiatric, dysautonomic and sleep disturbances occur as frequently in patients with LRRK2-G2019S-PD as in IPD but smell loss was less frequent in LRRK2-PD. Like in IPD, disturbances such as hyposmia, depression, constipation and excessive daytime sleepiness may antedate the onset of classical motor symptoms in LRRK2-G2019S-PD.
    PLoS ONE 10/2014; 9(10):e108982. DOI:10.1371/journal.pone.0108982 · 3.23 Impact Factor
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    ABSTRACT: Mutations in the leucine-rich repeat kinase 2 (LRRK2) and α-synuclein (SNCA) genes are known genetic causes of Parkinson's disease (PD). Recently, a genetic variant in SNCA has been associated with a lower age at onset in idiopathic PD (IPD). We genotyped the SNCA polymorphism rs356219 in 84 LRRK2-associated PD patients carrying the G2019S mutation. We found that a SNCA genetic variant is associated with an earlier age at onset in LRRK2-associated PD. Our results support the notion that SNCA variants can modify the pathogenic effect of LRRK2 mutations as described previously for IPD.
    Journal of Molecular Neuroscience 06/2012; 48(1):245-7. DOI:10.1007/s12031-012-9820-7 · 2.76 Impact Factor
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    ABSTRACT: The H1 MAPT haplotype in the 17q21 chromosomal region has been associated with several neurodegenerative diseases. Some reports have suggested that there is an association between genetic variants within the H1 haplotype with Parkinson's disease (PD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Here we report a genetic association study using seven SNPs located along the 17q21 region, in PD patients and controls. In addition, we compared these results with a dataset of previously published PSP/CBD patients from the same population. Our results show that the H1-rs242557(G) allele sub-haplotype is increased in PD (p=0.005), while the H1-rs242557(A) allele sub-haplotype is increased in PSP/CBD (p=0.0002), comparing to controls. The rs242557 polymorphism could act modulating the phenotypic expressivity of the H1 risk on these parkinsonisms. The location of this polymorphism in the 5' regulatory region of MAPT gene suggests the presence of a functional mechanism involved in the variation of MAPT expression levels.
    Neurobiology of aging 10/2009; 32(3):547.e11-6. DOI:10.1016/j.neurobiolaging.2009.09.011 · 4.85 Impact Factor
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    ABSTRACT: The Rey–Osterrieth complex figure (ROCF) and the free and cued selective reminding test (FCSRT) are frequently used in clinical practice. The ROCF assesses visual perception, constructional praxis, and visuospatial memory, and the FCSRT assesses verbal learning and memory. As part of the Spanish Normative Studies (NEURONORMA), we provide age- and education-adjusted norms for the ROCF (copy and memory) and for the FCSRT. The sample consists of 332 and 340 participants, respectively, who are cognitively normal, community dwelling, and ranging in age from 50 to 94 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. Although age and education affected the score of the ROCF and FCSRT, sex was found to be unrelated in this normal sample. The normative data presented here were obtained from the same study sample as all other NEURONORMA norms and the same statistical procedures were applied. These co-normed data will allow clinicians to compare scores from one test with all the tests included in the project.
    Archives of Clinical Neuropsychology 09/2009; 24(4):371-93. DOI:10.1093/arclin/acp041 · 1.92 Impact Factor
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    ABSTRACT: This study forms part of the Spanish Multicenter Normative Studies (NEURONORMA project). Normative data for people aged over 49 years are presented for selected tasks of the visual object and space perception battery (VOSP) and for the judgment of line orientation (JLO) test. Age-adjusted norms were derived from a sample of 341 participants who are cognitively normal and community-dwelling. Age- and education-adjusted norms are also provided. Years of education were modeled on age-scaled scores to derive regression equations that were applied for further demographic adjustments. The normative information provided here should prove useful for characterizing and interpreting individual test performances as well as comparing the scores from these tests with any other test using NEURONORMA norms.
    Archives of Clinical Neuropsychology 09/2009; 24(4):355-70. DOI:10.1093/arclin/acp040 · 1.92 Impact Factor
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    ABSTRACT: As part of the Spanish Multicenter Normative Studies (NEURONORMA project), we provide age- and education-adjusted norms for the Boston naming test and Token test. The sample consists of 340 and 348 participants, respectively, who are cognitively normal, community-dwelling, and ranging in age from 50 to 94 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. Age and education affected the score of the both tests, but sex was found to be unrelated to naming and verbal comprehension efficiency. Our norms should provide clinically useful data for evaluating elderly Spaniards. The normative data presented here were obtained from the same study sample as all the other NEURONORMA norms and the same statistical procedures for data analyses were applied. These co-normed data allow clinicians to compare scores from one test with all tests.
    Archives of Clinical Neuropsychology 09/2009; 24(4):343-54. DOI:10.1093/arclin/acp039 · 1.92 Impact Factor
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    ABSTRACT: As part of the Spanish Multicenter Normative Studies (NEURONORMA project), we provide age- and education-adjusted norms for the following instruments: verbal span (digits), visuospatial span (Corsi's test), letter-number sequencing (WAIS-III), trail making test, and symbol digit modalities test. The sample consists of 354 participants who are cognitively normal, community-dwelling, and age ranging from 50 to 90 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. The current norms should provide clinically useful data for evaluating elderly Spanish people. These data may be of considerable use for comparisons with other normative studies. Limitations of these normative data are mainly related to the techniques of recruitment and stratification employed.
    Archives of Clinical Neuropsychology 09/2009; 24(4):321-41. DOI:10.1093/arclin/acp038 · 1.92 Impact Factor
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    ABSTRACT: As part of the NEURONORMA project, we provide age- and education-adjusted norms for the Stroop color-word interference test (SCWT)-Golden version and the Tower of London-Drexel University version (TOL(DX)). The sample consists of 344 and 347 participants, respectively, who are cognitively normal, community dwelling, and ranging in age from 50 to 90 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. Demographic variables, age, and education significantly affect scores of the SWCT and TOL(DX), sex, however, was found to be unrelated to performance in this sample. The normative data presented here were obtained from the same study sample as all the other NEURONORMA tests. In addition, the same statistical procedures for data analyses were applied. These co-normed data allow clinicians to compare scores from one test with all tests.
    Archives of Clinical Neuropsychology 09/2009; 24(4):413-29. DOI:10.1093/arclin/acp043 · 1.92 Impact Factor
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    ABSTRACT: Lexical fluency tests are frequently used in clinical practice to assess language and executive function. As part of the Spanish multicenter normative studies (NEURONORMA project), we provide age- and education-adjusted norms for three semantic fluency tasks (animals, fruit and vegetables, and kitchen tools), three formal lexical tasks (words beginning with P, M, and R), and three excluded letter fluency tasks (excluded A, E, and S). The sample consists of 346 participants who are cognitively normal, community dwelling, and ranging in age from 50 to 94 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. The current norms should provide clinically useful data for evaluating elderly Spanish people. These data may also be of considerable use for comparisons with other international normative studies. Finally, these norms should help improve the interpretation of verbal fluency tasks and allow for greater diagnostic accuracy.
    Archives of Clinical Neuropsychology 09/2009; 24(4):395-411. DOI:10.1093/arclin/acp042 · 1.92 Impact Factor
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    ABSTRACT: This paper describes the methods and sample characteristics of a series of Spanish normative studies (The NEURONORMA project). The primary objective of our research was to collect normative and psychometric information on a sample of people aged over 49 years. The normative information was based on a series of selected, but commonly used, neuropsychological tests covering attention, language, visuo-perceptual abilities, constructional tasks, memory, and executive functions. A sample of 356 community dwelling individuals was studied. Demographics, socio-cultural, and medical data were collected. Cognitive normality was validated via informants and a cognitive screening test. Norms were calculated for midpoint age groups. Effects of age, education, and sex were determined. The use of these norms should improve neuropsychological diagnostic accuracy in older Spanish subjects. These data may also be of considerable use for comparisons with other normative studies. Limitations of these normative data are also commented on.
    Archives of Clinical Neuropsychology 07/2009; 24(4):307-19. DOI:10.1093/arclin/acp027 · 1.92 Impact Factor
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    ABSTRACT: Currently used antiparkinsonian drugs neither stop nor slow-down the progressive nature of the disease. The final phase of PD is characterized by the presence of symptoms and signs resistant to dopaminergic agents, such as depression, dementia, freezing and falls. Therefore, it is urgent to develop therapies able to positively modify this outcome. Despite neuroprotection is a research priority in PD, no effective strategies have been found so far. A key informants study was conducted. A group of experts in PD fulfilled a questionnaire of 10 questions to explore the most important topics related to neuroprotection. Afterwards a consensus about the current situation of neuroprotection in PD was established and future directions of development were suggested. Most of the answers emphasized the need of new concepts, the limitations of animal models and the difficulties in the difficulties in demonstrating a neuroprotective effects in humans owing to a lack of biomarkers. Some of the experts believe that we are already exerting a disease modifying effect. The concept of neuroprotection should be widened. Animal models should be improved. A reliable biomarker to start neuroprotective therapies long before the appearance of motor symptoms and to evaluate the neuroprotective effect of any therapy should be urgently developed.
    Neurologia (Barcelona, Spain) 04/2009; 24(2):113-24. · 1.35 Impact Factor
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    ABSTRACT: INTRODUCTION: Currently used antiparkinsonian drugs neither stop nor slow-down the progressive nature of the disease. The final phase of PD is characterized by the presence of symptoms and signs resistant to dopaminergic agents, such as depression, dementia, freezing and falls. Therefore, it is urgent to develop therapies able to positively modify this outcome. Despite neuroprotection is a research priority in PD, no effective strategies have been found so far. METHOD: A key informants study was conducted. A group of experts in PD fulfilled a questionnaire of 10 questions to explore the most important topics related to neuroprotection. Afterwards a consensus about the current situation of neuroprotection in PD was established and future directions of development were suggested. RESULTS: Most of the answers emphasized the need of new concepts, the limitations of animal models and the difficulties in the difficulties in demonstrating a neuroprotective effects in humans owing to a lack of biomarkers. Some of the experts believe that we are already exerting a disease modifying effect. CONCLUSIONS: The concept of neuroprotection should be widened. Animal models should be improved. A reliable biomarker to start neuroprotective therapies long before the appearance of motor symptoms and to evaluate the neuroprotective effect of any therapy should be urgently developed.
    Neurologia 03/2009; 24(2):113-24. · 1.35 Impact Factor
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    ABSTRACT: Alzheimer disease is the most common form of dementia in Western countries and the leading cause of disability in the over-65 population. Apolipoprotein E (APOE) is a multifunctional protein implied in lipid metabolism and neurobiology. Polymorphisms of the APOE gene have been associated with a variety of medical disorders, from arteriosclerosis to AD. A high frequency of the APOE epsilon4 allele has been found in patients with AD and they seem to have a higher risk of developing the disease. Various authors have suggested a possible relationship between the efficacy of cholinesterase inhibitors and the presence of the APOE epsilon4 allele. The purpose of the present study was to compare prospectively the efficacy of rivastigmine in patients with mild to moderately severe AD presenting different polymorphisms of the APOE gene on chromosome 19 and to determine if there was a difference in the response to rivastigmine treatment in AD patients with the APOE epsilon4 allele (heterozygous or homozygous) versus patients who had other forms of APOE, such as epsilon2 and epsilon3. This was an open-label, nonrandomized, multicenter study in patients over 50 years of age diagnosed with mild to moderately severe AD. The results of the analysis of this study indicate that the presence of at least one APOE epsilon4 allele does not determine a difference in the response to treatment with rivastigmine. The data indicate that knowledge of the patient's genotype is not necessary for treatment with rivastigmine. It would be interesting in the future to analyze the interaction between these 2 factors using other available anticholinesterase drugs.
    Alzheimer Disease and Associated Disorders 09/2006; 20(4):248-54. DOI:10.1097/01.wad.0000213880.93665.c7 · 2.69 Impact Factor
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    ABSTRACT: The 8993 T>G mutation in mitochondrial DNA has been associated with variable syndromes of differing severity ranging from maternally inherited Leigh's syndrome (MILS) to neuropathy, ataxia, retinitis pigmentosa (NARP), depending on the mutation loads in affected patients. We report a kindred with several members in the same generation suffering NARP or Leigh's syndrome due to a 8993 T>G mutation. Post-mortem studies of the brain in one affected member clinically presenting with a neurological disorder intermediate between adult Leigh's syndrome and NARP showed symmetrical lesions of the basal ganglia and brainstem closely resembling those usually described in typical Leigh's syndrome. Analysis of mtDNA in different tissues showed a high proportion of mutant genome in brainstem, cerebral cortex, putamen, cerebellum and thalamus. These observations illustrate the continuum of clinical and neuropathological manifestations associated with the 8993 T>G mutation of the mtDNA.
    Acta Neuropathologica 07/2006; 111(6):610-6. DOI:10.1007/s00401-006-0040-5 · 10.76 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) is frequently associated with freezing of gait. Patients with advanced PD learn to use tricks to relieve freezing of gait. Recently one of our patients informed us that he could overcome freezing of gait by crawling. Since crawling is a sort of quadruped gait that humans develop transiently, we wondered whether quadruped gait is preserved in PD. We recruited 16 patients with PD who had frequent and disabling freezing of gait. Under experimental conditions, after 12 hours without medication, seven patients developed biped freezing of gait. Of these seven patients, only two patients (the patients with the most severe freezing) also developed quadruped freezing of gait. This experiment suggests that bipedal gait is affected early in PD, while quadruped gait is preserved until late in this disease.
    Neurologia (Barcelona, Spain) 04/2004; 19(2):77-9. · 1.35 Impact Factor
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    A Rojo · M Aguilar · M T Garolera · E Cubo · I Navas · S Quintana
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    ABSTRACT: Depression has been shown to be more common in Parkinson's disease (PD) than in other chronic and disabling disorders. Neurochemical and functional disturbances are important etiopathogenic factors. The prevalence and clinical features associated with depression in PD remain controversial. The purpose of this study is to estimate the prevalence of depressive symptoms in our patients, as related to other clinical data, and to assess clinical outcomes of these symptoms. A series of PD patients were evaluated over a 9-year period, using the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr stage (HY), Schwab and England Scale (SE), Mini-Mental State Examination (MMSE), and Yesavage Geriatric Depression Scale (GDS). Presence of depressive symptoms was considered if GDS score was higher than 10: mild-moderate (MD) for GDS scores between 11 and 20 and moderate-severe (SD) for GDS scores greater than 20. Three hundred and fifty-three patients were included in this study and additional follow up information was obtained for 184 patients. MD and SD were found in 40.2 and 16.7% of PD patients, respectively. Female gender, high HY, high UPDRS total and subtotal, and low MMSE and SE scores were significantly associated with depressive symptoms. According to changes in GDS score, 34% of patients remained stable, 35% showed an improvement, and 30.9% worsened in the follow up study. Gender, age, age of onset, HY, UPDRS, and PD duration are not related to depression outcome.
    Parkinsonism & Related Disorders 11/2003; 10(1):23-8. DOI:10.1016/S1353-8020(03)00067-1 · 4.13 Impact Factor
  • E Cubo · A Rojo · S Ramos · S Quintana · M Gonzalez · K Kompoliti · M Aguilar
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    ABSTRACT: To define the factors correlated with quality of life (QoL) in patients with idiopathic Parkinson's disease (PD). PD has a substantial impact on QoL. Although several clinical factors have been associated with QoL in PD, the influence of patient's education still remains controversial. A consecutive series of patients with PD were examined using the unified Parkinson's Disease Rating Scale (UPDRS part I, II, III), Schwab and England (SE), and Hoehn and Yahr stage (H&Y). QoL was rated with the PDQ-39, cognition with the Mini-Mental State examination (MMSE), and the presence of depressive symptoms with the geriatric depression scale (GDS). Patient's characteristics, estimated cumulative levodopa dose (CLD), UPDRS, H&Y, MMSE and GDS were correlated with the PDQ-39 using univariate and multiple regression analysis. A total of one hundred 58 patients (68 men, 90 women) with a mean age of 65.6 +/- 9.3 years, PD duration of 8.1 +/- 10.6 years, and education of 6.6 +/- 3.9 years were included. The mean PDQ-39 was 48.8 +/- 27.8, mean MMSE was 25.7 +/- 4, and mean GDS was 11.7 +/- 6.8. Using stepwise multiple regression analysis, the most important predictive factors were depression, UPDRS part I, UPDRS part II, and educational background, which accounted for a 61% of the variability of the PDQ-39 scores. In our PD sample, educational, behavioural, and psychological factors influenced life satisfaction more than physical ones.
    European Journal of Neurology 12/2002; 9(6):589-93. DOI:10.1046/j.1468-1331.2002.00484.x · 3.85 Impact Factor
  • I Bonaventura · E Muñoz · M Aguilar · J Tarroch
    Neurologia (Barcelona, Spain) 12/1998; 13(9):436. · 1.35 Impact Factor

Publication Stats

385 Citations
68.66 Total Impact Points

Institutions

  • 1993–2014
    • Hospital Universitari Mutua de Terrassa
      Terrassa, Catalonia, Spain
  • 2004
    • Fundación Jiménez Díaz
      • Servicio de Neurología
      Madrid, Madrid, Spain