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Objectives: To compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain., Methods: A retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients' clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation., Results: Significant differences were observed between CAs for several baseline variables: duration of disease progression prior to CIILC onset, off time (34.9-59.7%) and on time (2.6-48.0%; with or without disabling dyskinesia), Hoehn and Yahr score during on time, Unified Parkinson's Disease Rating Scale-III score during both on and off time, presence of≥ 4 motor symptoms, and CIILC dose. Significant differences were observed during follow-up (> 24 months in 9 of the 11 CAs studied) for the percentage of off time and on time without disabling dyskinesia, adverse events frequency, and Clinical Global Impression scores. The rate of CIILC discontinuation was between 20-40% in 9 CAs (78 and 80% in remaining 2 CAs)., Conclusions: This study reveals a marked variability between CAs in terms of patient selection and CIILC safety and effectiveness. These results may have been influenced by patients' baseline characteristics, the availability of multidisciplinary teams, and clinical experience., (Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

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.

Levodopa remains the mainstay treatment for Parkinson's disease (PD). Chronic treatment is associated with motor complications (MC) that marred the clinical benefit of levodopa. These problems and experimental data in cell cultures indicating a neurotoxic effect of levodopa have led to the idea of delaying the introduction of levodopa treatment for as long as possible. We here review recent data regarding the mechanism of action of levodopa and its application in clinical practice on the light of the marketing of the combination levodopa-carbidopa- entacapone. Accumulated evidence indicates that MC are mainly the consequence of disease severity governing the degree of dopaminergic depletion and the "pulsatile" dopaminergic stimulation provided by levodopa short plasma half-life. There is no in vivo or clinical evidence of a relevant neurotoxic effect of levodopa. In fact, the recent ELLDOPA study may suggest a neuroprotective effect. Entacapone reduces homocysteine plasma levels which could provide a mechanism to reduce cell death in PD. Currently, the combination levodopa-carbidopa-entacapone is particularly indicated for the treatment of "wearing off" fluctuations. Experimental evidence suggests that early treatment with levodopa-carbidopa-entacapone may substantially ameliorate the incidence of MC. Such a clinical study in "de novo" patients is underway. At present, the combination levodopa-carbidopa-entacapone is indicated when levodopa is judged necessary.

A case of gliomatosis cerebri which clinically presented with a syndrome of intracranial hypertension (ICH), involvement of bilateral sixth cranial nerves, and oppressive holocranial headache of one week of evolution. Cranial MR and CT were performed demonstrating diffuse hypodense cortical-subcortical lesions on tomography and in T1 sequences and hyperdense lesions in T2 sequences with irregular contrast enhancement. Intracranial pressure was measured by ventricular catheter with the appearance of high, maintained pressure waves (Lundberg A waves). Ventricular LCR study and cerebral angiography did not provide additional data. Meningeal and cerebral biopsies showed infiltration by pleomorphous glioma leading to the diagnosis of gliomatosis cerebri. The patient was treated with steroids, hyperosmolar agents, external LCR derivation and tumoral radiotherapy. Nonetheless, the patient dies at six months of initiation of the symptoms. Gliomatosis cerebri should be taken into account in the differential diagnosis of clinical pictures presenting with ICH.

Background: Controlled-release levodopa-carbidopa (CRLC) improves some aspects of Parkinson's disease (PD) in patients previously treated with standard levodopa formulations (SL). However, little is known about the effect of this strategy on the health-related quality of life (QoL)., Objective: To assess the QoL and clinical changes due to the conversion of treatment from SL to CRLC in patients with mild to moderate PD., Patients and Methods: Through the Nottingham Health Profile (NHP), QoL was measured in 276 non-selected PD patients included in a multicenter, open study. Guidelines for switching to CRLC and optimization of treatment were given. Assessment of patients was carried out by means of the Hoehn & Yahr, UPDRS, and Schwab & England scales, and questionnaires for dyskinesias and sleep. Examination of the NHP-Spanish Version-scaling properties by fitting data to the Rasch model, disclosed that 3 NHP scales (Emotional reactions, Pain, and Physical mobility) and the NHP distress index (NHPD) were suitable for efficacy analysis., Results: Comparison of scores at baseline and at the end of the study showed significant improvement (paired Student t-test, p < 0.0001) in all these four scales associated with the change to CRLC. Responsiveness to change of the NHP was high. In the present study, changes in QoL were not contingent to baseline factors such as age, gender, stage of disease or ADL capabilities., Conclusion: Conversion to CRLC significantly improves the QoL of patients with mild to moderate PD.

Pramipexol is a novel nonergot dopamine agonist which has high selectivity for intereacting with dopamine D2 receptors (especially with D3 receptor subtype). It has been effective in early Parkinson's disease as monotherapy and as adjunctive therapy with L-dopa in advanced stages of the disease. Clinical improvement can be observed after 3 or 4 weeks of treatment. The adverse events profile of pramipexol is similar, in general, to that of other dopamine receptor agonists, although it can be foreseen that pramipexol should not induce side effects related to the ergot chemical structure such as eritromelalgia, distal vasospasm, retroperitoneal fibrosis or pleural effusions. Nevertheless, the potential advantages of this promising dopamine agonist should be tested in well-designed prospective comparative studies with other available ergot and nonergot dopamine agonists.

A case that combines cerebral eyelid ptosis and blepharospasm secondary to cerebral hemisphere infarction is shown. EMG recording from the facial and eyelid muscles revealed lack of the levator palpebrae superioris, orbicularis oculi and corrugator muscles activity. Any voluntary opening attempt lead to a simultaneous contraction of the three muscles. Blink reflex responses were normal although showed facilitation features on the right side and mild inhibition characteristics from the left side. Median nerve SEP revealed a loss of precentral components (P22-N30) as well as a delay and amplitude decrease of N20. Transcranial magnetic stimulation disclosed a complete lesion of corticospinal pathway for right upper limb. In this case, a right hemisphere lesion caused an unusual eyelid motor abnormality: cerebral eyelid ptosis and blepharospasm induced by the voluntary eyelid opening.

We studied the histories of 173 patients with Parkinson's disease (1985-1987) chronically treated with levodopa + dopa decarboxylase inhibitor. Ninety four patients had daily motor fluctuations and 79 showed stable motor response. The most significant differences between fluctuating and stable patients were given by age at disease onset and duration of levodopa therapy. Patient with disease onset before 60 had a greater risk (p less than 0.001) of developing fluctuations. Delaying the initiation of levodopa treatment was not associated with a smaller incidence of fluctuations.

The response to different therapeutic methods was evaluated in a series of 264 patients with blepharospasm. The most effective drug therapy were anticholinergic agents, which resulted in the initial improvement of symptoms in 20% of treated patients. There was improvement in isolated cases treated with levodopa, dopaminergic agonists, neuroleptics, benzodiazepines and tricyclic antidepressants. Bilateral avulsion of the facial nerve was carried out in 29 patients; 27 of these (93%) improved. Spasms relapsed in 22 cases, after a mean period of 12 months. Myectomy of the orbicular muscle was performed in 8 patients. In only 2 cases some improvement was obtained. One hundred and fifty-one patients were treated with infiltrations of botulinum toxin A in the orbicular muscle. 78% of cases improved. The mean duration of the benefit of each injection was 9.2 weeks. The most common secondary effects were local (ptosis, diplopia) and transient.