Dipyridamole plus aspirin versus aspirin alone in secondary prevention after TIA or stroke: a meta-analysis by risk.

OBJECTIVES: To study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient ischaemic attack (TIA) or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D. DATA SOURCES: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (n = 2,739); trials without data on the comparison of A+D versus ASA were excluded. REVIEW METHODS: A meta-analysis was performed using Cox regression, including several subgroup analyses and following baseline risk stratification. RESULTS: A total of 7612 patients (five trials) were included in the analyses, 3800 allocated to A+D and 3812 to ASA alone. The trial-adjusted hazard ratio (HR) for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval (CI) 0.72 to 0.92). HRs did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischaemic heart disease, aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke; HR 0.78 (95% CI 0.68 to 0.90). CONCLUSION: The combination of aspirin and dipyridamole is more effective than aspirin alone in patients with TIA or ischaemic stroke of presumed arterial origin in the secondary prevention of stroke and other vascular events. This superiority was found in all subgroups and was independent of baseline risk.

Measurement of plasma levels of clomipramine in the treatment of chronic pain.

The analgesic effect of clomipramine and the possible relationships between the antalgic action and the plasma levels of this tricyclic drug have been studied in 30 patients with chronic pain induced by nervous lesions determining a deafferentation. Twenty of 30 patients treated with clomipramine reported a significant improvement (up to 50%) observed as soon as the 4th day, with few side effects. The pharmacokinetic analysis shows the existence (r = 0.358; p less than 0.001) of a relationship between analgesia and plasma levels of clomipramine for each individual patient. This study also indicates a "therapeutic window" of plasma levels between 20 and 85 ng/ml. These results permit discussion of measurement of plasma levels of clomipramine in the treatment of chronic pain.

[Value of the study of latent atrial vulnerability in unexplained ischemic cerebrovascular accident of young subjects]. / Intérêt de l'étude de la vulnérabilité auriculaire latente dans l'accident vasculaire cérébral ischémique inexpliqué du sujet jeune.

This study searched for abnormalities of the atrial electrophysiological substrate in young subjects with unexplained ischaemic cerebrovascular accidents. Thirty-seven patients (18 to 45 years) underwent programmed atrial stimulation at 2 sites in the right atrium after an unexplained ischaemic cerebrovascular accident. Seventeen of them underwent repeat study at 6 months. The following parameters were analysed: indices of atrioventricular conduction and sinus node automaticity; indices related to atrial hyperexcitability: effective refractory period; adaptation of the refractory periods to heart rate, intraatrial conduction and the index of latent vulnerability; the inducibility test by the extrastimulus technique. The following results were obtained: 54% of patients had an inducible atrial arrhythmia; the effective refractory periods and index of latent vulnerability were lower (204 +/- 21 ms and 2.25 +/- 0.7) in the inducible patients than in the non-inducible patients (232 +/- 28 ms and 3.4 +/- 1.1) (p < 0.001 and p < 0.002 respectively); 76% of patients had latent atrial vulnerability indicating and underlying arrhythmogenic substrate; this substrate was still present 6 months later in 80% of these cases; in patients with an abnormality of the interatrial septum, there was an abnormality of the electrophysiological investigation in 85% of cases compared with 65% in those with normal transoesophageal echocardiography. These results confirm the presence of an arrhythmogenic substrate similar to that of patients with paroxysmal atrial fibrillation in over two thirds of cases. Programmed atrial stimulation is a reproducible technique. The relationship between latent atrial vulnerability and abnormalities of the interatrial septum requires confirmation in a series with a larger numbers of patients.

[Is there any desensitization of presynaptic alpha 2-adrenergic receptors in hypertension? Experimental and clinical studies]. / Existe-t-il une désensibilisation des récepteurs alpha 2-adrénergiques présynaptiques dans l'hypertension artérielle? Etudes expérimentales et cliniques.

Several authors have discussed an alteration of adrenergic receptivity in arterial hypertension. De Champlain (Hypertension 1990; 8: S77-S85) suggested that postsynaptic alpha 1-adrenergic functions became dominant while beta-adrenergic functions are attenuated in arterial hypertension. However, the status of presynaptic alpha 2-adrenoceptors remains unknown. The present study investigates presynaptic alpha 2-adrenoceptors in hypertension through the measurement of plasma levels of noradrenaline after administration of yohimbine, an alpha 2-adrenoceptor antagonist, in essential hypertension. Yohimbine (0.2 mg/kg per os) induced a 73% increase of plasma levels of noradrenaline in hypertensive patients (n = 12) and a 178% one in normotensive subjects (n = 6, p < 0.05). A similar significant difference was found in experimental neurogenic hypertension observed in awake dogs 3 weeks after sinoaortic denervation: the increase in plasma concentrations of noradrenaline after yohimbine (0.5 mg/kg i.v.) was +279% in hypertensive versus +642% in normotensive dogs (p < 0.05). The results show that the magnitude of the yohimbine-induced sympathetic activation is lower in hypertensives than in normotensives. They suggest the existence of a presynaptic alpha 2-adrenoceptor desensitization in arterial hypertension. The abnormality of this presynaptic inhibitory mechanism can increase the sympathetic tone and help to develop and maintain arterial hypertension.

[Bromocriptine as the 1st treatment of Parkinson's disease. Long term results]. / La bromocriptine comme premier traitement de la maladie de Parkinson. Résultats à long terme.

Bromocriptine (mean dose: 48 mg daily) was studied during 38 months (mean value) in 20 patients with Parkinson's disease who had never received levodopa treatment. Eight of these 20 patients were treated during a period up to 4 years. Fourteen patients had an "excellent" or "good" improvement with a significant decrease of extrapyramidal symptoms. The side effects were those seen with levodopa but they did not lead to stop the treatment. The most important finding was the lack of long term side effects similar to those usually seen under levodopa treatment: in this group, dyskinesia, oscillations in performance (and specially "on-off" effect) were not noted. A tendency for deterioration of therapeutic efficiency was observed in 2 (or 3) cases. Bromocriptine could be an useful antiparkinsonian drug for previously untreated patients. The pharmacological (importance of the post-synaptic action of bromocriptine) and therapeutic (indications of bromocriptine versus levodopa) implications are discussed.

[Risk of recurrent stroke in adults aged under 45 years following a first ischemic stroke: a five-year study of 95 patients]. / Risque de récidive d'infarctus cérébral chez des adultes jeunes âgés de moins de 45 ans ayant présenté un premier infarctus cérébral. Etude à 5 ans d'une population de 95 patients.

Few data are available concerning the risk of recurrence of cerebral ischemic infarction in young adults (less than 45-years-old) after a first episode of ischemic stroke. From 1992 to 1996, 95 patients less than 45 years old were enrolled in a prospective study in order to define the etiology of their ischemic infarction with systematic and exhaustive explorations. They were recalled five years later (mean follow-up of 67,07 +/- 25,6 months) to determine the risk of stroke recurrence, the rate of cardiac and vascular events and the mortality. At 5 years, 4 patients had a recurrence of ischemic stroke (4.7 p. cent). Seven patients had a coronary event (4 myocardial infarction and 4 angina). Eleven patients died (6 during the acute period). No recurrence of stroke was noticed in patients with stroke of undetermined cause or with minor cardiopathy (abnormalities of the atrial septum). The risk of recurrence of ischemic stroke in young adults appears to be very low.

[Role of the thalamus in subcortical aphasias]. / Le rôle du thalamus dans les aphasies sous-corticales.

27 cases of patients who presented language disorders of aphasic nature consecutive to a strictly subcortical lesion of vascular origin are reported. From a topographic point of view, the population is divided into 3 groups: thalamic lesions (15 cases), striatal lesions (9 cases), isolated lesions of the white matter (3 cases). The results of the neurolinguistic analysis of the aphasia show a great symptomatological variety. Nevertheless, in spite of this apparent diversity, certain semiologic elements appear to be common to all of the observed linguistic profiles, no matter where the lesion is: hypophonia, non fluent speech, verbal paraphasias, normal repetition, comprehension generally good. A discussion is proposed as to the specific part which certain structures, notably the thalamus, might play in the origin of these various disturbances.

[Ischemic cerebrovascular complications in Rendu-Osler disease: a case]. / Accidents vasculaires cérébraux ischémiques dans le cadre de la maladie de Rendu-Osler: 1 cas.

Rendu-Osler disease is a familial disorder transmitted as an autosomal dominant trait of high penetrance. It is characterized by telengiectasias of the skin, mucous membranes and viscera, associated with recurrent bleedings. Neurological complications (brain abcesses and hemorrhagic manifestations) occur in 10% of the patients. Neurological symptoms are often associated with arteriovenous fistula of the lung (50%). Ischaemic strokes occuring in such patients with an hemorrhagic disease while unfrequent, have been described. The pathophysiology of stroke in that case remains unclear. Polycythemia causing hyperviscosity, air embolism following hemoptysis, paradoxical embolism through right-to-left shunt have been proposed. We report a new case of ischaemic strokes occuring in a caucasian forty-year-old woman, with Rendu-Osler disease (familial history, epistaxis, telengiectasias) and with an arteriovenous malformation of the right lung. She presented two strokes and one transient ischaemic attack. Her pulmonary malformation was occluded by embolization. The role of arteriovenous malformation in the pathophysiology of strokes is discussed.

[Mechanisms of motor recovery after cerebrovascular accident]. / Mécanismes de la récupération motirce après accident vasculaire cérébral.

Recovery from motor deficit after a stroke remains a puzzling scientific question as well as public health problem. The natural history of deficits after stroke is given to us through published series of patients and we know from them that neurological deficits, spontaneously but most of the time partially, recover. Neuroimaging modern techniques (PET scan, fMRI, evoked potentials) allowed us to identify the main aspects of the post-stroke intracerebral reorganisation. Reorganisation of basal cerebral metabolism, changes in the somatotopia of primary motor cortex, recruitment of remote cortices, participation of associative cortices are clearly part of the rearrangement processes. It is likely that such mechanisms represent the basis of clinical recovery of our patients. However, despite those important advances, very few is known about the effect of treatments on the recovery phenomenon. Some lines of evidence appear now to give rationale to rehabilitation procedures and to drugs suspected to improve clinical recovery.

[Analysis of the cerebrospinal fluid by isoelectrofocusing on agarose in multiple sclerosis]. / Analyse du LCR par isoélectrofocalisation en agarose dans la sclérose en plaques.

Intrathecal synthesis of immunoglobulins can be proved by means of two methods: quantitatively by immunoglobulins titration in CSF, the results expressed with several ratios; qualitatively by demonstration of oligoclonal distribution of gammaglobulins. IEF is the most sensitive of the qualitative methods. From a technical point of view Agarose Isoelectrofocusing seems to be a better method than polyacrylamide isoelectrofocusing and permits, when the interpretation is difficult, immunofixation into the gel. The authors report the results of a comparative study between the evaluation of the IgG Index and agarose isoelectrofocusing of 281 CSF divided into 113 CSF from patients with Multiple Sclerosis (MS) and 168 CSF from patients with other neurological diseases (OND). Sensitivity of IEF was higher than IgG index to prove intrathecal IgG synthesis: in the group of patients with MS, 91 p. 100 of CSF were abnormal instead of 72 p. 100 of IgG Index. In the group of patients with OND, abnormalities in IEF were low (5 p. 100) but the number of inflammatory diseases was poor. These results were similar with the findings of many authors using the same methods. In our opinion, IEF is the best technique which a specialized laboratory can use in routine to prove an immunoglobulin intrathecal synthesis.

[Subcortical aphasia. Neruolinguistic and x-ray computed tomography studies of 25 cases]. / Aphasies sous-corticales. Etude neurolinguistique avec scanner X de 25 cas.

Twenty five cases of subcortical aphasia of vascular origin (15 haemorrhagic, 10 ischaemic), have been studied in detail by means of neurolinguistic and brain-scanning approaches. The neurolinguistic investigation allowed three groups to be distinguished. Group 1 comprised 4 cases of dysarthria. Group 2 was made up of 9 classical syndromes of aphasia: 2 global aphasias, 3 Broca's aphasias, 3 cases of Wernicke's aphasia and 1 case of conduction aphasia. Group 3 consisted in 12 unusual aphasic syndromes, i.e. 2 mixed aphasias and 10 cases which did not correspond with any traditional semiological description and are spoken of as "dissident" (or anomalous) cases. The CT scan results revealed a wide range of focal lesions for the same clinical syndrome; the 10 "dissident" cases were, in particular, associated with a large variety of lesions. After a discussion of the anatomical limits of the subcortical lesions, 2 points emerge: 1) in the current state of technological experience no anatomo-clinical correlation can be drawn as regards language-deficiencies of subcortical origin. 2) in almost half the cases a "unique" syndrome of aphasia has been observed and described, which at first might suggest the diagnosis of a subcortical lesion.

[Transverse myelitis caused by Mycoplasma pneumoniae infection]. / Myélite transverse induite par une infection à Mycoplasma pneumoniae.

A twenty-six year old man was admitted for febrile atypical pneumoniae. Few hours later, he presented an acute flaccid paraplegia with dorsal pain. Cerebrospinal fluid analysis showed a high leukocyte count with raised protein level. Neuroradiological examinations (myelography and MRI) were normal. Seric immunological disorders were reported. High complement-fixing antibody titers to Mycoplasma pneumoniae were found in the serum and in the CSF. The patient was treated with antibiotic and corticosteroids. He improved dramatically within one month. Neurological complications of Mycoplasma pneumoniae infections have been described (meningoencephalitis, meningitidis, polyradiculoneuropathies, cerebellar ataxia, cranial nerve palsies). Nineteen cases of transverse myelitis induced by Mycoplasma pneumoniae have been previously reported. Pathophysiological mechanisms of nervous system complications induced by Mycoplasma pneumoniae were discussed. Vascular mechanisms, direct invasion by the pathogen, toxic, immunological causes were examined.