The natural history of Parkinson's disease in the province of Segovia: mortality in a longitudinal study (20-year follow-up).

OBJECTIVE: We determined mortality rates and predictors of survival in 273 patients with Parkinson's disease based on a 20-year follow-up longitudinal study. MATERIAL AND METHODS: We examined 273 patients with Parkinson's disease during a 20-year follow-up, recruited between 1978 and 1998. All patients were regularly followed at the Department of Neurology until December 31, 1998, or death. RESULTS: By then, 69 patients had died, crude mortality was rate 4.43, and standardized mortality ratio for the total patient group was 1.39 (95% CI, 1.10-1.50). As Parkinson's disease is a chronic progressive disorder in adult life, disease-related mortality would be expected to increase in later stages after 15 or 20 years. Mean age at death in our cohort was 78.27 (95% CI, 76.90-79.20). Median time of death was 11 years (95% CI, 9.50-12.49). Independent predictors of mortality during the follow-up were age at onset (hazard ratio, 1.05; 95% CI, 1.01-1.09; P = 0.01), clinical form - akinesia and rigidity (hazard ratio, 2.20; 95% CI, 1.06-4.88; P = 0.03) - and treatment with dopaminergic agonist (hazard ratio, 0.49; 95% CI, 0.23-1.03; P = 0.06). Cardiovascular disease was the most frequent cause of death in 42%. CONCLUSIONS: This study suggests a link between mortality with age of onset and treatment without dopamine agonists as initial treatment. So, there is an association between decreased mortality and tremor as initial clinical forms at onset.

[Clinico-epidemiological study of neurolisteriosis in the province of Segovia]. / Estudio clinicoepidemiológico de la neurolisteriosis en la provincia de Segovia.

INTRODUCTION: Listeria monocytogenes is a microorganism with marked tropism towards the central nervous system. One of the commonest forms of presentation is as a meningeal infection. The objective of this study is to describe the epidemiological, clinical and laboratory characteristics and therapeutic implications. PATIENTS AND METHODS: We made a retrospective analysis of four patients, admitted to hospital with the diagnosis of meningeal infection and positive culture for L. monocytogenes in the cerebrospinal fluid (CSF), who were admitted to our centre between 1 January 1996 and 31 December 2000. The overall rate of meningitis due to L. monocytogenes in the province of Segovia is similar to that reported from the USA and Europe (six cases per million inhabitants per year). All the patients were male, aged between 19 and 79 years. The commonest form of presentation was a meningeal syndrome. Analysis of the CSF showed pleocytosis with high protein and low glucose levels. Gram staining was negative in all cases. Initial empirical treatment proved to be correct in two of the four patients. The only predisposing factors observed were alcoholism and diabetes mellitus. All four cases recovered. CONCLUSION: We emphasize the difficulty in diagnosing meningitis due to L. monocytogenes, since the presenting symptoms are relatively non specific, CSF analysis gives variable results and Gram staining is of little use. Clinical suspicion is important so that specific antibiotic treatment may be given to improve the prognosis.

Estudio clinicoepidemiológico de la neurolisteriosis en la provincia de Segovia / Clinico-epidemiological study of neurolisteriosis in the province of Segovia

Introducción. Listeria monocytogenes es un microorganismo con especial tropismo por el sistema nervioso central. Una de sus manifestaciones clínicas más frecuentes es la infección meníngea. El objetivo de este estudio es describir las características epidemiológicas, clínicas, analíticas e implicaciones terapéuticas. Pacientes y métodos. Análisis retrospectivo de cuatro pacientes ingresados con el diagnóstico de infección meníngea con positividad en el cultivo de líquido cefalorraquídeo (LCR) para L. monocytogenes, atendidos en nuestro centro entre el 1 de enero de 1996 y el 31 de diciembre de 2000. Resultados. La tasa global de meningitis por L. monocytogenes en la provincia de Segovia es similar a la publicada en EE.UU. y Europa (seis casos por millón de habitantes/año). Todos los pacientes eran varones, con edades comprendidas entre 19 y 79 años. La forma de presentación más frecuente fue un síndrome meníngeo. El análisis del LCR mostró pleocitosis, hiperproteinorraquia e hipoglucorraquia. La tinción de Gram fue negativa en todos los casos. El tratamiento empírico inicial fue correcto en dos de los cuatro pacientes. El alcoholismo y la diabetes mellitus fueron los únicos factores predisponentes encontrados. La evolución fue favorable en los cuatro casos. Conclusiones. Queremos resaltar la dificultad del diagnóstico de meningitis por L. monocytogenes, probablemente sobre la base de la baja especificidad de los síntomas de presentación, la variabilidad de los resultados del análisis del LCR y el bajo rendimiento de la tinción de Gram. La importancia de la sospecha clínica radica en la necesidad de instaurar un tratamiento antibiótico específico para mejorar su pronóstico (AU)

Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family.

The clinical presentation and evolution, neuropathological findings, and genotyping of three members of a Spanish family affected with fatal familial insomnia are reported. The mother and two of her offspring developed a rapidly evolving disease with insomnia and behavioural disorders as the initial symptoms and died between 5 and 10 months after the onset of the illness. Frontal brain biopsy in the mother disclosed only non-significant spongiosis, and full neuropathological examination of her offspring showed thalamic and olivary degeneration with isolated focal cortical spongiosis. Genetic examination could only be performed in the contemporary patients and both harboured the prion protein (PrP) 178Asn mutation and homozygous 129 Met/Met genotype.

[Side effects of antithrombotic treatment in the secondary prevention of cerebrovascular disease]. / Efectos secundarios del tratamiento antitrombótico en la prevención secundaria de la enfermedad cerebrovascular.

OBJECTIVE: To determine the incidence of adverse effects of antithrombotic drugs (platelet anti-aggregants and anticoagulants) in patients with transient ischemic attacks (TIA) and mild ischemic strokes (IL). PATIENTS AND METHODS: Clinical follow-up data on the patients with TIA and IL included in a community-based observational study undertaken in the province of Segovia. Adverse effects which led to suspension of treatment or were a potential danger for the patient's life were recorded. RESULTS: The groups studied included 235 patients and the average initial age was 70.8 years. The average follow-up time was 3.6 years. The treatment initially given included: aspirin (75.7%), ticlopidine (12.8%) and acenocumarol (9.4%). Adverse effects led to suspension of treatment in 6% (5% with aspirin and acenocumarol, 17% with ticlopidine). The adverse effects of ticlopidine were mild and patients did not need admission to hospital (cutaneous exanthema, diarrhoea and reversible leucopenia). Aspirin was associated with digestive tract bleeding (2.8%) and cerebral hemorrhage (1.7%) which required hospital admission in most cases. One patient treated with acenocumarol presented with a retroperitoneal hematoma. CONCLUSIONS: In general antithrombotic drugs are well-tolerated by patients with TIA and LI. Hemorrhagic complications, particularly of the digestive tract, associated with aspirin limit tolerance to it.

Etiopathogenesis of transient ischemic attacks and minor ischemic strokes: a community-based study in Segovia, Spain.

BACKGROUND AND PURPOSE: We sought to analyze the etiology and underlying vascular risk factors of transient ischemic attacks (TIAs) and minor ischemic strokes (MISs). METHODS: We prospectively studied the vascular risk factors and etiologic categories in 235 patients with TIAs and MISs from a community-based register in a rural area of Spain. Five etiologic categories were considered: (1) cardioembolism, (2) large-artery atherosclerosis, (3) small-artery disease, (4) other etiologies, and (5) undetermined etiology. Systematic investigations included neuroimaging (CT/MRI) and vascular studies (duplex scan/MR angiography and angiography in selected cases). RESULTS: The two most frequent etiologic categories were small-artery disease (31%) and cardioembolism (26%). Large-artery atherosclerosis was detected in 11% of the patients. Significant carotid stenosis (> or =50%) was present in 13% of patients with carotid territory events. No cause could be found or it was uncertain in almost one third of the patients. The distribution of etiologic categories was similar in TIAs and MISs. The most prevalent vascular risk factors were as follows: arterial hypertension (50%), smoking (26%), atrial fibrillation (20%), hypercholesterolemia (17%), diabetes (15%), ischemic heart disease (12%), and peripheral vascular disease (3%). Carotid bruits were detected in 3% of the patients. CONCLUSIONS: An etiologic classification of TIAs and MISs is feasible. The two most frequent pathogenetic mechanisms in our study were small-artery disease and cardioembolism. The prevalence of large-artery atherosclerosis was low.

Combined effect of HLA-DRB1*1501 and interleukin-1 receptor antagonist gene allele 2 in susceptibility to relapsing/remitting multiple sclerosis.

Susceptibility to multiple sclerosis (MS) is associated with HLA-DRB1*1501. Many reports have suggested associations with other loci but these results remain unconfirmed. We studied the IL-1 receptor antagonist (IL-1ra) gene polymorphism and the HLA-DR and DQ allele frequencies by DNA-based methods in both the primary chronic progressive form (PP MS) and the relapsing/remitting form (R/R MS). The frequency of DRB1*1501 and IL-1ra allele 2 were significantly higher in R/R MS. Association was more marked in the female sex and in patients with benign forms of R/R MS. On the other hand DR4 subtypes carrying a Val at position 86 in the DR beta chain were increased in PP MS. The present study indicates that MS is genetically heterogeneous and shows a combined effect of HLA-DR and IL-1ra genes in susceptibility to the R/R form of the disease.

Postural myoclonus induced by phenytoin.

Involuntary movements are an infrequent complication of treatment with phenytoin and include tremor, asterixis, myoclonus, parkinsonism, and dyskinesias. The mechanism by which phenytoin exerts its actions is unclear. Phenytoin has been observed to exert variable effects on dopamine metabolites and also may induce changes in serotonergic activity. In this report, we discuss the available experimental evidence concerning the possible mechanisms of involuntary movements induced by phenytoin. We describe a case of postural myoclonus during treatment with phenytoin.

Headache of recent onset in adults: a prospective population-based study.

One hundred consecutive adult patients with headache of recent onset were prospectively studied. Every patient was examined by craneal CT scan. Their mean age was 46 years (range 17-82). Neurological examination was normal in 80 patients. Organic headache represented 39% of the entire group, and 26% of them had a normal neurological examination. The yield of CT scan in patients with headaches and a normal neurological examination was 22.5% (95% IC: 14%-33%); of which we encountered the following pathologies: intracranial tumors (13), hydrocephalus (2), arachnoid cyst (1), toxoplasmic abscess (1) and parenchymal hemorrhage (1). The clinical characteristics of the headache on their own was insufficient to rule out the possibility of an intracranial tumor. Neuroimaging studies should be performed in all adult patients with non-vascular headache of recent onset, and previously headache-free individuals.

Incidence of transient ischemic attacks and minor ischemic strokes in Segovia, Spain.

BACKGROUND AND PURPOSE: The aim of this study was to determine the incidence of transient ischemic attacks (TIAs) and minor ischemic strokes (MISs) in Segovia, Spain. METHODS: A 2-year prospective community-based register of TIAs and MISs established in Segovia from February 16, 1992, to February 15, 1994. Every patient underwent underwent a complete clinical evaluation and cranial CT scan. Sex- and age-specific incidence rates with 95% confidence intervals (CIs) were calculated for all ages. RESULTS: The total series included 235 patients; 103 suffered TIAs and 132 suffered MISs. Mean age was 70.8 years (range, 29 to 96 years); 92 were women and 143 were men. The crude annual incidence was 0.80/1000 (95% CI, 0.70 to 0.90): 0.35/1000 (95% CI, 0.28 to 0.42) for TIAs and 0.45/1000 (95% CI, 0.37 to 0.53) for MISs. The incidence of TIAs and MISs increased with age. Approximately 78 of TIAs and MISs were in the carotid distribution, 19% were vertebrobasilar, and 3% were considered of uncertain vascular distribution. Cranial CT scan was performed in all patients. CT showed cerebral infarcts in 30.1% (31/103; 95% CI, 21% to 39%) of TIAs and 70% (92/132; 95% CI, 62% to 78%) of MISs (P<.00001). CONCLUSIONS: Our study is the first community-based register that provides sex-and age-specific rates for MISs and in which a CT scan was obtained in all patients. The incidence of TIAs in Segovia is comparable to that in other previous similar studies.