[Multiple mononeuropathy associated to treatment with pravastatin]. / Mononeuropatía múltiple asociada a tratamiento con pravastatina.

INTRODUCTION: The first reports of neuropathy due to treatment with statins appeared in 1994, although it is an infrequent complication. It usually consists of an axonal polyneuropathy, which is predominantly sensory, distal and symmetric, and may be subacute or chronic. We present here the second case reported in the literature of multiple mononeuropathy associated to the use of statins. CASE REPORT: A 51-year-old female patient who, after beginning therapy with pravastatin, presented with progressive, asymmetrically distributed, distal paresthesias in the limbs and an unstable gait. An electromyographic study was compatible with multiple mononeuritis. Results of complementary tests that were carried out to preclude other causes of multiple mononeuropathy were normal. The patient's condition improved on withdrawing treatment with the drug and it became worse again when therapy was restarted. When pravastatin therapy was stopped for good, the patient's condition progressively improved until she was practically free of symptoms. CONCLUSIONS: The relationship between treatment with statins and the appearance of polyneuropathy has been proved in different epidemiological case-control studies. It does not only appear as the classical distal symmetrical polyneuropathy, but has also been reported as taking on atypical clinical forms including a few cases, like ours, of multiple mononeuropathy. The risk of developing this complication is low and is offset by the cardiovascular benefits offered by statins, although it may become more common in the future due to the increasing rate of use of these agents. It is important to bear this cause of neuropathy in mind, given the fact that it is potentially reversible.

[Differences between Spanish ischemic stroke patients and those from Central and Northern Europe. A case-control study]. / Diferencias entre pacientes con ictus isquémico españoles frente a centro y nordeuropeos: un estudio de casos y controles.

INTRODUCTION: Studies conducted in the American population have revealed the existence of differences in cerebral vascular pathologies and in the prevalence of vascular risk factors between races. The few studies carried out in Hispanic populations have found a higher prevalence of diabetes mellitus, as well as a lower frequency of cardioembolic strokes and extracranial carotid atheromatosis, in comparison with whites of Anglo-Saxon extraction. PATIENTS AND METHODS: We performed a case-control study in which one case was paired with two controls, according to age and sex. The cases were people from Central and Northern Europe and the controls were Spaniards. All of them had been admitted to hospital because of ischemic stroke or TIA. We compared the frequency of conventional risk factors (RF), the subtype of ischemic stroke and the results from carotid duplex scans. The odds ratio and confidence intervals (CI) at 95% were calculated for paired data. RESULTS: Arterial hypertension (AHT) was less frequent in the cases, with an OR of 0.45 (CI 0.24-0.83). No statistically significant differences were found in the prevalence of diabetes, hypercholesterolemia, heart disease and atrial fibrillation. Fast recovery stroke and TIA were observed more frequently in the cases than in the controls (OR: 3.73; CI: 1.72-8.07), which we interpreted as being due to a bias in admissions. Carotid duplex scanning revealed stenosis > 70% in 21.9% of the cases and in 13% of the controls. CONCLUSIONS: This study did not reveal any differences between Spaniards and Northern Europeans in conventional RF, except for a higher prevalence of AHT in Spaniards. Severe carotid pathology seems to be less frequent in Spaniards. Future research should take into account other RFs (such as cholesterol subfractions, homocysteine, etc.), which are possibly race-linked and may account for the differences described.

[Prevalence of neurosonographic disturbances in chronic instability]. / Prevalencia de alteraciones neurosonológicas en la inestabilidad crónica.

INTRODUCTION: Dizziness is a common symptom at the outpatient clinic of family doctors. Its origin is usually multifactorial and its outcome is often benign. However, exists a tendency to relate the dizziness with a cerebrovascular disturbance. AIM. To determine if there are cerebrovascular disorders in patients with chronic dizziness using a non invasive technique. PATIENTS AND METHODS: A prospective study was conducted. It included 404 patients without limit of age. The patients were evaluated in a Neurology Outpatient Clinic, to select those patients with chronic instability. A neurosonographic exam was performed to all those selected patients. This exam included colour duplex of the cervical arteries and transcranial Doppler. RESULTS: Up to 54 % of the patients who were included in the study had a normal carotid study. For the rest of the patients, the thickness intima-media was the most prevalent finding. At the vertebrobasilar system the study of the vertebral arteries was completely normal in 81.7% followed by the presence of microangiopathy in 12.1%. The basilar system was also normal in a high figure (78%) followed by the microangiopathy (17.1%). CONCLUSIONS: The vascular disturbances in the vertebrobasilar system are an exceptional finding in patients with chronic instability.

Alkylating nucleosides. 4. Synthesis and cytostatic activity of chloro- and iodomethylpyrazole nucleosides.

The synthesis and cytostatic activity of several chloromethyl- and iodomethylpyrazole nucleosides are described. Glycosylation of ethyl 3(5)-(chloromethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(chloromethyl)pyrazole-5(3)-carboxamide (4) with poly(O-acetylated) sugars via an acid-catalyzed fusion method gave the corresponding 3-(chloromethyl)-5-carboxylate and 3-(chloromethyl)-5-carboxamide substituted nucleosides 7 and 9, respectively. From the reaction of 4 with tetra-O-acetyl-beta-D-ribofuranose, the 5-(chloromethyl)-3-carboxamide-substituted derivative 11 was also obtained. Reaction of 7, 9, and 11 with sodium iodide in acetone provided the related iodomethylpyrazole nucleosides 8, 10, and 12. In general, chloromethyl-substituted nucleotides showed moderate activities against HeLa cells, while all the corresponding iodomethyl derivatives exhibited high activities. Some of these latter compounds increased the life span of mice bearing ECA tumor.

[Ambulatory neurological care in the Marina Baixa area, Alicante]. / Asistencia neurológica ambulatoria en el área de la Marina Baixa, Alicante.

INTRODUCTION: The demand for neurological care depends on the type of population to be attended, among other variables. The Marina Baixa area, which includes towns such as Altea and Benidorm, has its own peculiar characteristics due to its being one of the places that is often chosen by pensioners from northern and central Spain and Europe to set up residence. AIM: The aim of this study was to determine the characteristics of the ambulatory neurological care in our health area. PATIENTS AND METHODS: Data on 1,000 patients attended in the Neurological Clinic at the Specialty Centre in Benidorm (age, sex, reason for visit, tests requested and destination on discharge) were recorded prospectively and consecutively. RESULTS: The mean age was 58.04 years (range 14-94) and 56.4% were females. 25% of the patients attended were over 75 years old. The main reasons for visiting were headache (28.2%) and cognitive impairment (21%). 26.5% were first-time visits, with a mean age of 55.02 years, which is significantly lower than that of the review patients (59.12 years; p = 0.003). 15.6% of the patients were discharged from hospital. A prolonged follow-up was foreseen for over 50% of them. The demand for care in 2003 was 27.5 per 1,000 inhabitants/year in the population above the age of 14 years. CONCLUSIONS: The higher the mean age of the population is, the greater the prevalence of neurodegenerative diseases will become and the more demand there will be for ambulatory care. Resources must be adjusted to this new situation and there is also a need to adopt the most suitable model of health care for chronic neurological patients.

[Carcinomatosis of the choroid plexus: clinical case and necropsy findings]. / Carcinomatosis de plexos coroideos: caso clínco y hallazgos necrópsicos.

INTRODUCTION: Carcinomas of the choroid plexus are a rare malignant variety of papillary tumours which originate in the choroid plexus. Their occurrence in adults has been questioned because of the difficulty in differentiating them from the metastases of adenocarcinomas. CLINICAL CASE AND CONCLUSIONS: We present the case of a 57 year old man with a rapidly progressive illness characterized by disorientation, behaviour changes and amnesia, progressive deterioration of the level of consciousness until he was in deep coma and died (all within one month). There was no clinical evidence of the presence of a primary extra-cranial tumour. On magnetic resonance there was obliteration of the ventricular system with a protein material and thickening and increased marking of the ependyma walls, compatible with ventriculitis. Necropsy, limited to the skull, showed the presence of a malignant infiltrating tumour with papillary morphology, which affected the choroid plexuses of the whole ventricular system, infiltrated the adjacent nervous tissue and extended to the leptomeninges. These findings suggest a differential diagnosis between carcinoma of the choroid plexus and metastatic meningeal carcinoma.

[Atherosclerosis and brain circulation]. / Aterosclerosis y circulación cerebral.

INTRODUCTION: Atherosclerosis affects the vascular system in a diffuse way and its is clearly implicated in some of the most prevalent diseases in western countries such as cerebrovascular and cardiovascular diseases. Knowing more about the underlying pathogenic mechanisms may contribute to a better understanding of this entities and the development of therapies for both its treatment and prevention. DEVELOPMENT: We review herein the concepts included in the term atherosclerosis, the growth of the atheromatous plaque and its complications and the cellular mechanisms which intervene in its development. We analyze how it influences brain hemodynamics and its implication in cerebrovascular ischemic disease paying attention to the dissimilarities with other vascular territories and the clinical syndromes which derive from its development on different vascular structures. CONCLUSIONS: Under the concept of ischemic cerebrovascular disease we can find a group of heterogeneous clinical syndromes, usually associated to different etiopathogenic mechanisms: cardioembolic, atherothrombotic or hemodynamic. Although their risk factors may be common, these processes are clearly different form each other. Therefore including ischemic brain infarctions all together without attending to their etiology may produce important methodological biases when interpreting the results in clinical trials or other studies, and may also be a suitable explanation for differences between authors.

[Neurological clinical findings as the initial manifestation of a peripheral lymphoma]. / Clínica neurológica como primera manifestación de un linfoma periférico.

INTRODUCTION: Lymphomas of the central nervous system include primary and secondary lymphomas of Hodgkin and non-Hodgkin types. For a long time central nervous system involvement during the course of systemic non-Hodgkin lymphoma has been considered unusual, to occur late on in the disease process and usually to be located in the meninges. CLINICAL CASE: We describe the case of a 27 year old man initially diagnosed as having a primary cerebral lymphoma after having had repeated convulsive crises. Two months later he was found to have a retroperitoneal mass. On anatomopathological study of the mass, a peripheral T lymphoma was confirmed. CONCLUSIONS: Dissemination of systemic lymphomas to the central nervous system is usually seen in persons with advanced systemic disease. It is atypical to find a peripheral T lymphoma with initial clinical findings that were neurological, and even less frequent that these neurological findings were due to an intraparenchymatous lesion. In this article we describe a patient with these characteristics, and conclude that it is necessary to study patients with a diagnosis of primary cerebral lymphoma very fully to establish where the primary focus is.

[Evaluation of hemodynamic parameters by transcranial Doppler in patients with leukoaraiosis]. / Estudio de los parámetros hemodinámicos en pacientes con leucoaraiosis mediante Doppler transcraneal.

INTRODUCTION: Leukoaraiosis is commonly found in neuroimaging in ancient people. The pathogenic theory that most suitably explains its origin is the vascular one, mainly linked to cerebral hemodynamic abnormalities. The techniques most frequently used in cerebral hemodynamic evaluation (PET and SPECT) are expensive and not widespread. Transcranial Doppler instead is cheaper and much more widespread. OBJECTIVE: Our aim has been to show whether transcranial Doppler is a useful tool for cerebral hemodynamic evaluation in leukoaraiosis. PATIENTS AND METHODS: We have prospectively included 116 patients aged 60-90 who came to the Neurology department with unspecific complaints such as dizziness or mild headache. Patients with recent history of stroke or moderate to severe cognitive impairment were excluded. RESULTS: Mean age was 74.4 +/- 6.3 years old. The prevalence of leukoaraiosis was 68.7%. Leukoaraiosis was significantly correlated with older age, lacunar infarctions, past history of stroke, cognitive impairment and to lower systolic and diastolic velocities in middle cerebral artery (MCA) and higher pulsatility index. Multivariate analysis only retained the lower diastolic velocity in MCA in the model. CONCLUSIONS: Transcranial Doppler can detect hemodynamic abnormalities in patients with leukoaraiosis and is therefore a very useful technique for the evaluation of this entity.

[The relation between carotid ultrasound changes and seropositivity to Chlamydia pneumoniae in patients with acute stroke]. / Relación entre alteraciones ultrasonográficas carotídeas y seropositividad frente a Chlamydia pneumoniae en pacientes con ictus agudo.

INTRODUCTION: Several infectious agents have been found to be involved in atherogenesis over the past decade. Chlamydia pneumoniae is one of the commonest associated agents. In this study we have analysed the possible relationship between a high level of antibodies to Chlamydia, and the presence of carotid ultrasound changes in patients who have had strokes. PATIENTS AND METHODS: We studied 230 patients admitted consecutively to the Stroke Unit in our hospital, with the diagnosis of stroke. All the patients in the group had carotid duplex ultrasound studies to assess the degree of stenosis. All these patients also had serological studies using micro-immunofluorescence to detect antibodies to Chlamydia pneumoniae. RESULTS: Only 35 patients were found to have positive Chlamydia pneumoniae serology. The degree of atheromatosis was similar in the patients with high levels of IgG for Chlamydia pneumoniae and in those with normal serology. There was no statistically significant relation between the degree of stenosis and being seropositive for Chlamydiae. CONCLUSIONS: Our findings suggest that in an unselected population of stroke patients there is no relations between carotid atheromatosis and positive serology findings to Chlamydia pneumoniae. If there is any relationship between Chlamydia pneumoniae and carotid atheromatosis, serology does not seem to be a technique which is suitable for its assessment.

[Descriptive epidemiology of the vascular risk factors in Bañeres. Study group 'Bañeres Project']. / Epidemiología descriptiva de los factores de riesgo vascular en Bañeres. Grupo de Estudio 'Proyecto Bañeres'.

INTRODUCTION: Epidemiological studies of the risk factors of cerebrovascular disease are of great interest, particularly the identification of factors which may be modified. Previous studies carried out in the Alcoi region of Alicante province, showed a high prevalence of cerebrovascular disease. The town of Bañeres was therefore chosen for confirmation of this data and identification of the frequency of vascular risk factors. OBJECTIVE: To compare the group of patients with cerebrovascular disease with the remainder of the population interviewed. PATIENTS AND METHODS: In a door-to-door study in Bañeres 1,832 people were interviewed as part of the Bañeres Project. The population aged over 45 years was interviewed and filled in a questionnaire for diagnosis of transient ischemic accidents. RESULTS: Arterial hypertension: estimated prevalence 500/1,000 inhabitants, relative risk 3.24; diabetes mellitus: estimated prevalence 195/1,000, relative risk 2.18; coronary artery disease: estimated prevalence 58/1,000, relative risk 1.88; peptic ulcer: estimated prevalence 75/1,000, relative risk 1.23; smoking: estimated prevalence 110/1,000, relative risk 0.46; complete arrhythmia: prevalence 73/1,000, relative risk 5.23. Family histories of cerebrovascular accident, arterial hypertension, diabetes and coronary artery disease were not significant. CONCLUSIONS: Arterial hypertension, diabetes mellitus and arrhythmia were significantly more prevalent amongst patients with vascular disease in our setting. We found no association with the other risk factors analyzed.

[Sporadic familial meningiomas]. / Meningiomas familiares esporádicos.

INTRODUCTION: Meningiomas are primary tumours of the central nervous system. Usually they are sporadic. The occurrence in more than one member of a family is unusual. Up till now this coincidence had been related with type 2 neurofibromatosis. In this paper we comment on two siblings who did not fulfil neurofibromatosis diagnostic criteria as an example of sporadic familial meningiomas. CLINICAL CASES: Two siblings (a 79 years old female and a 77 years old male) were diagnosed of a meningioma in an interval of two years, with surprising clinical and neuroimaging similarities. In sporadic meningiomas, abnormalities in the long arm of chromosome 22 have been found. Type 2 neurofibromatosis causative gene has also been found in this chromosome. Meningiomas are quite often found in this entity, and therefore, this gene was implicated as a main factor in the genesis of an important number of meningiomas. However, several studies have not found an association between these tumours and the locus for neurofibromatosis, leading to think that there may be other genes that may influence on meningiomas development.

[Neurosonological studies in patients over 80 years old]. / Estudio neuroecográfico en mayores de 80 años.

INTRODUCTION: The link between cardiovascular risk factors and carotid atheromatosis has been shown to be more important in middle aged subjects than in the elderly. AIMS: Our aim was to study the frequency of carotid and intracranial atheromatosis in a population over the age of 80 and to compare the presence of neurosonological anomalies depending on whether the patients have suffered a stroke or not. We also wished to compare the findings according to the sex of the patient. PATIENTS AND METHODS: Patients over the age of 80 were studied at our Neurosonology laboratory using carotid and transcranial Doppler ultrasonography. The patients were analysed according to whether they had suffered an ischemic stroke or not. With regard to the carotid, a distinction was made between normal, non-significant atheromatosis and significant atheromatosis (stenosis > 50%). Intracranially, both the middle cerebral artery (normal, stenosis, microangiopathy and post-stenosis) and the basilar artery (normal, stenosis, microangiopathy and hyperdynamics) were studied. RESULTS: We recorded data concerning 832 patients: 342 males (44.1%), mean age 83.63 +/- 3.25 years, and 527 (63.3%) with stroke. The carotid study was pathological, with a higher frequency in stroke patients (32.1% compared with 41.9%; p = 0.002). The presence of atheromatosis was significantly linked to a higher risk of suffering a stroke and more intensely to its being more severe. Carotid studies were pathological with a higher frequency among males (28.7% compared with 40%; p < 0.001). No significant differences were found intracranially in any of the parameters analysed. CONCLUSIONS: There is a high frequency of carotid atheromatosis in patients over 80 years of age. Regardless of the age, carotid atheromatosis appears even more frequently in patients who have suffered a stroke and in males, and is significantly associated to the risk of suffering a stroke. Intracranially, no differences were found.

[The phenomenon of immigration within the European Community and its impact on neurological care in the Marina Baixa area, Alicante]. / El fenómeno de la inmigración en la Europa comunitaria y su impacto en la asistencia neurológica en el área de la Marina Baixa, Alicante.

INTRODUCTION: Immigration is shaping a new model of society, with new needs and demands, whose characteristics must guide health-care policies. AIM. To determine the repercussions of the phenomenon of immigration on the extra-hospital neurological care carried out in Department 16 of the Agencia Valenciana de Salud (Valencian Health Service) and how language problems affect visits. PATIENTS AND METHODS: We conducted a prospective study during 26 consecutive outpatient visits in the first three months of 2006. RESULTS: Of all the patients who were attended, 9.5% were foreigners. Of these, 77.7% came from EU countries. And of those from outside the Community, 13% were from Latin American countries, 5% came from European countries that do not belong to the EU and 5% were from Africa. Mean ages were 61.5 years for the EU group and 42.6 years for the other nationalities. The main reasons for visiting were headache and cognitive impairment. The poorer the quality of communication was, the longer the visit lasted. CONCLUSIONS: The high prevalence of immigrants from the EU, mostly elderly persons and with chronic neurological pathologies, together with the ageing of the autochthonous population, have led to a progressive growth in the demand for health care in our area. The language barrier makes clinical practice more complicated and results in an increase in the time needed for each patient. These facts must be taken into account when planning both the health care resources in our area and visiting times per patient.

[Synthesis, cytostatic activity and mechanism of action of N-glycosylhalomethylazoles. A new class of alkylating agents]. / Sintesis, actividad citostática y mecanismo de acción de N-glicosil-halometil-azoles. Un nuevo tipo de agentes alquilantes.

A model to produce a new type of alkylating agents having anti-cancer activity is described. They consist of a halomethyl-azol group of the benzyl type as alkylating center, and a sugar moiety as a carrier fragment. Alkylating nucleosides were produced as halomethyl-pyrazole, -imidazole, 1.2.3-triazole, and 1.2.4-triazole derivatives following the model, and tested upon Ehrlich ascites cancer and P-388 lymphocytic leukemia.