COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation.

BACKGROUND AND PURPOSE: In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). METHODS: This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. RESULTS: In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 ± 8.9 years old, 60.3% males), 273 caregivers (58.5 ± 11.9 years old, 31.8% males) and 207 controls (61 ± 8.3 years old, 49.5% males). The mean disease duration was 5.5 ± 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 ± 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). CONCLUSIONS: Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.

Myoclonic epilepsy in Down syndrome and Alzheimer disease. / Epilepsia mioclónica en el síndrome de Down y en la enfermedad de Alzheimer.

INTRODUCTION: Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges. METHOD: We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. RESULTS: In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. CONCLUSIONS: The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment.

Influence of manipulative skills on quality of life and activities of daily living in multiple sclerosis. / Influencia de la capacidad manipulativa en la calidad de vida y actividades de la vida diaria en la esclerosis múltiple.

INTRODUCTION: More than 50% of patients diagnosed with multiple sclerosis report problems with manipulative function and impairments in their daily lives due to this disorder. Therefore, the aim of the present study is to determine how pinch strength, prey strength and manipulative dexterity affect the quality of life and personal autonomy of people diagnosed with multiple sclerosis and to study whether there is a difference in these aspects between different types of multiple sclerosis. SUBJECTS AND METHODS: There was a total sample of 126 participants, of which 57 were controls and 69 cases. All of them were assessed with a Multiple Sclerosis Quality of Life-54 test, Nine-Hole Peg Test and Barthel Index. RESULTS: People with multiple sclerosis have worse pinch strength, prey strenght, manipulative dexterity, performance in basic activities of daily living and quality of life (p < 0.001). Prey strength is a conditioning factor for performance and quality of life in people with multiple sclerosis. As for the type of multiple sclerosis, relapsing-remitting multiple sclerosis presented better values (p < 0.001). CONCLUSIONS: The findings of this study point to the fact that patients diagnosed with multiple sclerosis have a decrease in prey strength, pinch strength, manipulative dexterity, quality of life and autonomy in activities of daily living compared to the healthy population.

TITLE: Influencia de la capacidad manipulativa en la calidad de vida y actividades de la vida diaria en la esclerosis múltiple.Introducción. Más de un 50% de los pacientes diagnosticados con esclerosis múltiple (EM) comunican problemas con la función manipulativa e impedimentos en su vida diaria a causa de esta alteración. Por ello, el objetivo del presente estudio es determinar la afectación que la fuerza de pinza, la fuerza de presa y la destreza manipulativa ejercen sobre la calidad de vida y la autonomía personal de las personas diagnosticadas de EM, y estudiar si existe diferencia de estos aspectos entre los distintos tipos de esta enfermedad. Sujetos y métodos. Se contó con una muestra total de 126 participantes, de los cuales 57 fueron controles, y 69, casos. A todos ellos se les evaluó con el Multiple Sclerosis Quality of Life-54, el Nine-Hole Peg Test, la dinamometría de pinza y de presa para la medición de la fuerza, y el índice de Barthel para la evaluación de las actividades básicas de la vida diaria. Resultados. Las personas con EM presentaron peores fuerza de pinza, fuerza de presa, destreza manipulativa, desempeño en actividades básicas de la vida diaria y calidad de vida (p < 0,001). La fuerza de presa es un factor condicionante en el desempeño de actividades básicas y calidad de vida en personas con EM. En cuanto al tipo de EM, el tipo remitente-recurrente presentó mejores valores (p < 0,001). Conclusiones. Los hallazgos de este estudio apuntan a que los pacientes diagnosticados con EM presentan una disminución en la fuerza de pinza, la fuerza de presa, la destreza manipulativa, la calidad de vida y la autonomía en las actividades de la vida diaria en comparación con la población sana.

A variant in GRN of Spanish origin presenting with heterogeneous phenotypes.

INTRODUCTION: The variant c.1414-1G>T in the GRN gene has previously been reported as probably pathogenic in subjects of Hispanic origin in the American continent. METHODS: We report 5 families of Spanish origin carrying this variant, including the clinical, neuroimaging, and laboratory findings. RESULTS: Phenotypes were strikingly different, including cases presenting with behavioral variant frontotemporal dementia, semantic variant primary progressive aphasia, rapidly progressive motor neuron disease (pathologically documented), and tremor-dominant parkinsonism. Retinal degeneration has been found in homozygous carriers only. Ex vivo splicing assays confirmed that the mutation c.1414-1G>T affects the splicing of the exon, causing a loss of 20 amino acids in exon 11. CONCLUSIONS: We conclude that variant c.1414-1G>T of the GRN gene is pathogenic, can lead to a variety of clinical presentations and to gene dosage effect, and probably has a Spanish founder effect.

[Description of a novel test for the early detection of Alzheimer's disease]. / Descripción de un nuevo test para la detección precoz de la enfermedad de Alzheimer.

INTRODUCTION: Diagnosing Alzheimer's disease (AD) as soon as possible is critical to achieve an effective treatment of patients. AIM: To make up a test capable of differentiating those patients suffering from the early stages of AD compared to healthy people or patients with mild cognitive impairment (MCI). SUBJECTS AND METHODS: A test with 10 memory and language tasks was applied to 85 people: 34 in the early stage of probable AD, 26 with MCI, and 25 healthy people. The groups did not differ with regard to age, sex or studies. RESULTS: The analysis of variance showed significative differences between groups in all tasks as well as in the global score. Sensibility and specificity were calculated to MCI and AD. CONCLUSIONS: We designed a new test to detect AD patients on an early stage that is quick and easy to apply. The preliminary scale results in controls, MCI and early AD are shown.

[Clinical epidemiological study of vascular epilepsy]. / Estudio clínico epidemiológico de la epilepsia vascular.

INTRODUCTION: Little research has been conducted on vascular epilepsy (VE) in our environment, although some authors claim it accounts for 45% of all symptomatic epilepsies in persons over 60 year of age. PATIENTS AND METHODS: We obtained a cross-sectional sample of the hospital admissions that took place in our health area between 1999 and 2005 using the diagnosis-related group coding system with numbers 14 (specific cerebrovascular disorders, except transient ischemic attacks and intracerebral haemorrhages) and 810 (intracerebral haemorrhages), and crossing them with an admission diagnosis of epileptic seizures or symptomatic status epilepticus. We recruited 101 patients who had been diagnosed with VE (taking into account only those who had seizures two weeks after the acute event). This represented 9.14% of all new cases of epilepsy over that period of time. RESULTS: After rejecting patients who had had their stroke before 1999 and those for whom no accurate record of the event was available, we obtained an incidence of VE in ischaemic strokes of 6.5%, with a figure of 11.6% for haematomas. Status epilepticus was reported in 27.7% of cases. Early status epilepticus was associated with a mortality rate of 77.7%. CONCLUSIONS: Although the incidence of VE is higher than in other series that have appeared in the literature, our sample is too small to be able to extract data concerning demographic characteristics. Nevertheless, its prevalence makes it an important health issue that increases the rate at which resources are used and adds further insecurity in the case of individuals who already suffer some degree of disability.

[Wallenberg's syndrome secondary to dissection of the vertebral artery caused by chiropractic manipulation]. / Sindrome de Wallemberg secundario a disección de la arteria vertebral por manipulación quiropráctica.

INTRODUCTION: Chiropractic manipulations of the cervical region are techniques that are used more and more frequently to treat a number of osteomuscular pathologies, but can give rise to important complications, such as the dissection of the cervical arteries. Dissection of the vertebral artery generally presents as alternating syndromes, of which Wallenberg s syndrome, either complete or incomplete, is the most frequent. In this paper we review the literature published to date on the pathogenesis, risk factors, clinical features, chronopathology, diagnosis, treatment and prognosis of this complication. CASE REPORT: We describe the case of a young patient who suffered from incomplete Wallenberg s syndrome a few hours after a single session of cervical chiropractic manipulation, and we also show the resonance images that were used to support the diagnosis. CONCLUSIONS: The appearance of a pain in the neck and neurological symptoms in a patient who has undergone chiropractic manipulation in the last few hours or days must lead us to consider a possible dissection of the cervical arteries. Dissection of the vertebral artery usually gives rise to alternating syndromes, the most frequent of which is lateral bulbomedullary infarction or Wallenberg s syndrome due to proximal occlusion of the posteroinferior cerebellar artery. Magnetic resonance angiography of the supra aortic trunks and cranial magnetic resonance scanning are valid techniques for demonstrating the dissection of the artery and the associated ischemic lesion.

[The chronopathology of prion encephalopathies]. / Cronopatología de las encefalopatías priónicas.

INTRODUCTION: Prion encephalopathies are a group of diseases with a hereditary or acquired origin which, after a long asymptomatic period, give rise to rapidly progressing neurological disorders. This progression can only be explained by an exponential growth of the pathogenic protein load, which allows to keep the load in low levels for many years and then to grow swiftly in a few months. DEVELOPMENT: Bearing in mind the knowledge currently available about the pathogenesis of prion diseases and patients' clinical progression, it becomes possible to distinguish several different periods of progression, the length of which can be estimated for each disease by reviewing the series of cases published to date. In general, the infectious prion diseases have a shorter period of latency than the hereditary ones and those caused by insertion of genetic material are associated to shorter latencies and to longer periods of illness than those caused by sporadic mutations. CONCLUSIONS: The rate of growth of the prion load depends essentially on how fast the pathogenic prion protein replicates; nevertheless, this growth is also modulated by other factors, many of which are polymorphisms in certain positions on the gene coding for prion protein or in other genes.

APP processing and the APP-KPI domain involvement in the amyloid cascade.

Alternative APP mRNA splicing can generate isoforms of APP containing a Kunitz protease inhibitor (KPI) domain. KPI is one of the main serine protease inhibitors. Protein and mRNA KPI(+)APP levels are elevated in Alzheimer's disease (AD) brain and are associated with increased amyloid beta deposition. In the last years increasing evidence on multiple points in the amyloid cascade where KPI(+)APP is involved has been accumulated, admitting an outstanding position in the pathogenesis of AD to the KPI domain. This review focuses on the APP processing, the molecular activity of KPI and its physiological and pathological roles and the KPI involvement in the amyloid cascade through the nerve growth factor, the lipoprotein receptor-related protein, the tumor necrosis factor-alpha converting enzyme and the Notch1 protein.

[Memory loss: a reason for consultation]. / Pérdida de memoria como motivo de consulta.

INTRODUCTION: Memory loss is an increasingly frequent reason for consultation in neurology. The aim of this work is to know the current frequency as well as the characteristics and disorders of the patients who come for this reason. METHODS: We studied 200 patients who came to general neurology consultation due to loss of memory. RESULTS: 18.47% of the patients who came for the first time to a general neurology consultation did so due to memory loss, this being subjective loss of memory (SLM) in 39% of the cases and referred loss of memory (RLM) in 61% of the cases. The diagnostic groups to which the patients belonged are, in diminishing order, the following: degenerative primary dementia type Alzheimer's disease, mild cognitive impairment, mixed dementia, pure vascular dementia, depressive pseudodementia, attributable to drugs, secondary to systemic disease, non-Alzheimer's type disease primary degenerative dementia, structural reasons, transitory global amnesia and epilepsy. No disease was found in 13% of them, and the generally came due to SLM. CONCLUSIONS: Frequency of memory loss as a reason for consultation continues to growing. Patients studied due to memory loss, in whom no disease is found, are generally those having SLM. In spite of this, SLM is a good predictor of cognitive deterioration. It is important to systematically study of every patient and consults for loss of memory and to investigate the possible use of drugs or toxics that could alter the memory.