Previous infection and the risk of ischaemic stroke in Italy: the IN2 study.

BACKGROUND AND PURPOSE: There is an increasing interest in new risk factors for ischaemic stroke. Acute and chronic infections could contribute to different aetiological mechanisms of atherosclerosis that lead to cerebrovascular disease. The aim of this study was to investigate the hypothesis that previous infections and Chlamydia pneumoniae in particular increase the risk of ischaemic stroke in the population. METHODS: This was a prospective case-control study involving 11 Italian stroke units. Controls were age- and sex-matched with cases, represented by patients admitted to hospital for acute ischaemic stroke. For each participant classical vascular risk factors and previous inflammatory and infectious events up to 1 month before were registered. Blood samples were collected to analyse inflammatory markers and titres of antibodies against C. pneumoniae. RESULTS: A total of 1002 participants were included (mean age 69 years) with 749 ischaemic stroke patients. Infections occurred within 1 month previously in 12% of the entire sample with a higher prevalence in the case group (14.4% vs. 3.9%). At multivariate analysis of the seropositivity of IgA antibodies against C. pneumoniae increased the risk of stroke significantly (relative risk 2.121; 95% confidence interval 1.255-3.584) and an early previous infection (up to 7 days before the event) contributed to a rise in probability of acute cerebral ischaemia (relative risk 3.692; 95% confidence interval 1.134-6.875). CONCLUSIONS: Early previous infections and persistent chronic infection of C. pneumoniae could contribute to increase the risk of ischaemic stroke significantly, in the elderly especially.

Moderate alcohol use and health: a consensus document.

AIMS: The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. DATA SYNTHESIS: In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. CONCLUSIONS: The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered.

Safe implementation of thrombolysis in stroke-monitoring study in Italy.

BACKGROUND AND PURPOSE: The safe implementation of thrombolysis in stroke-monitoring (SITS-MOST) study was an unique opportunity to test in Italy, where only few centres were expert in thrombolytic treatment before, safety and efficacy of i.v. alteplase within 3 h of ischaemic stroke outside the setting of clinical trials. METHODS: In Italy to participate in the study the clinical centres had to possess organizational and structural characteristics certified by Regional Health Authorities. RESULTS: Seventy-one centres were activated, 56 (79%) treated patients of which 41 (73%) had never used thrombolysis before the study. Globally, 586 patients were included. Baseline median National Institute of Health Stroke Scale of Italian patients was 13 vs. 12 in other European centres (P = 0.0001). Symptomatic intracerebral haemorrhage as per the NINDS/Cochrane definition, mortality and independence (modified Rankin Scale 0-2) rates at 3 months occurred respectively in 6.7% (95% CI: 4.8-9.1), 11.7% (9.2-14.6) and 51.6% (47.4-55.7) of Italian patients compared with 7.3% (6.7-8.0) (P = 0.56), 11.2% (10.4-12.1) (P = 0.75) and 55.1% (53.8-56.4) (P = 0.09) in the European patients and in 8.6% (40/65; 6.3-11.6), 17.3% (14.1-21.1) and 50.1% (44.5-54.7) of the patients treated in the pooled randomized controlled trials. CONCLUSIONS: The SITS-MOST study showed that in Italy i.v. alteplase is safe and effective in routine clinical use also in non-expert centres.

With time on our side? Task-dependent compensatory processes in graceful aging.

Graceful aging has been associated with frontal hyperactivations in working- and episodic long-term memory tasks, a compensatory process, according to some, that allows the best normal elders to perform these tasks at a juvenile level, in spite of natural cortical impoverishment. In this study, 24 young and 24 healthy elderly participants were compared. Graceful aging was explored by investigating domains where most healthy elders perform like youngers (e.g. lexical-semantic knowledge) and tasks that are typically more challenging, like episodic long-term recognition memory tasks. With voxel-based morphometry, we also studied to what extent changes of fMRI activation were consistent with the pattern of brain atrophy. We found that hyperactivations and hypoactivations of the elders were not restricted to the frontal lobes, rather they presented with task-dependent patterns. Only hypoactivations and normal levels of activation systematically overlapped with regional atrophy. We conclude that compensatory processes associated with graceful aging may not necessarily be a sign of early saturation of executive resources, if this was to be represented by a systematic frontal hyperactivation, but rather they may represent the ability of recruiting new cognitive strategies. We discuss two possible approaches to further test this hypothesis.

Air pollution positively correlates with daily stroke admission and in hospital mortality: a study in the urban area of Como, Italy.

Some current evidences suggest that stroke incidence and mortality may be higher in elevated air pollution areas. Our study examined the hypothesis of a correlation between air pollution level and ischemic stroke admission and in Hospital mortality in an urban population. Data on a total of 759 stroke admissions and 180 deaths have been obtained over a 4-year period (2000-2003). Five air ambient particles have been studied. A general additive model estimating Poisson distribution has been used, adding meteorological variables as covariates. NO(2) and PM(10) were significantly associated with admission and mortality (P value < 0.05) and with estimated RR of 1.039 (95% CI 1.066-1.013) and 1.078 (95% CI 1.104-1.052) for hospital admission at 2- and 4-day lags, respectively. In conclusion, this study suggests an association between short-term outdoor air pollution exposure and ischemic stroke admission and mortality.

Intravenous immunoglobulin is effective in patients with diabetes and with chronic inflammatory demyelinating polyneuropathy: long term follow-up.

BACKGROUND AND AIMS: Chronic inflammatory demyelinating polyneuropathy (CIDP) seems to be more common in patients with diabetes than in the general population. The long term outcome of these patients after receiving intravenous immunoglobulin is unclear and the precise optimal regimen needed has yet to be ascertained. Moreover, the influence of chronic hyperglycaemia on this neuropathy is not clear. METHODS: This prospective follow-up study included all consecutive patients with diabetes with a CIDP referred to our department during the 18 months of the study. RESULTS: 198 consecutive patients were referred to our neuromuscular unit and exhaustively screened. 16 patients with diabetes (8%) had a demyelinating polyneuropathy fulfilling the most restrictive diagnostic criteria for CIDP. They were treated with at least one course of intravenous immunoglobulin and, if responders, retreated in case of relapse. All patients were followed for at least 40 months. Patients with diabetes with CIDP significantly improved after immunotherapy and during follow-up. The Neuropathy Impairment Score changed from 38 at presentation to 16 at the end of the follow-up. Eight patients developed distal sensory disturbances during follow-up and four of these patients complained of distal paresthesias but no neuropathic pain. Sensory disturbances were detected after 30 months (mean time) from baseline. CONCLUSION: CIDP is not an unusual neuropathy in patients with diabetes. Our study underlines the importance of extensively investigating patients with diabetes with polyneuropathy to identify those with a treatment responsive demyelinating polyneuropathy.

Anatomy of the episodic buffer: a voxel-based morphometry study in patients with dementia.

In 2000 Baddeley proposed the existence of a new component of working memory, the episodic buffer, which should contribute to the on-line maintenance of integrated memory traces. The author assumed that this component should be critical for immediate recall of a short story that exceeds the capacity of the phonological store. Accordingly, patients with Alzheimer's dementia (AD) should suffer of a deficit of the episodic buffer when immediate recall of a short story is impossible. On the other hand, the episodic buffer should be somewhat preserved in such patients when some IR can occur (Baddeley and Wilson, 2002). We adopted this logic for a voxel-based morphometry study. We compared the distribution of grey-matter density of two such groups of AD patients with and of a group of age-matched controls. We found that both AD groups had a significant atrophy of the left mid-hippocampus; on the other hand, the anterior part of the hippocampus was significantly more atrophic in patients who were also impaired on the immediate prose recall task. Six out of ten patients with no immediate recall were spared at "central executive" tasks. Taken together our findings suggest that the left anterior hippocampus contributes to the episodic buffer of the revised working memory model. We also suggest that the episodic buffer is somewhat independent from the central executive component of working memory.

Temozolomide and thalidomide in the treatment of glioblastoma multiforme.

OBJECTIVE: The aim of this study was to assess efficacy and toxicity of temozolomide given alone or in combination with thalidomide, an anti-angiogenetic drug, in patients with newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS: 46 patients with histologically proven GBM were eligible for inclusion. Twenty-three patients (15 males and 8 females) received temozolomide on a conventional schedule; 23 patients (12 males and 11 females) received temozolomide on the same schedule and thalidomide was dose-adjusted in each individual patient based on their tolerance. RESULTS: The median survival time was 12 months for temozolomide and 13 months for temozolomide + thalidomide. CONCLUSION: The administration of temozolomide in association with thalidomide after radiotherapy (RT) does not offer an advantage over temozolomide alone in adults with newly diagnosed GBM. The two therapeutic strategies produce similar results for survival, but the latter regimen shows a moderate increase in toxicity.

Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headaches.

BACKGROUND: Headache is a common medical problem. In view of recent discoveries about the role of serotonin in pain mechanisms, selective serotonin re-uptake inhibitors (SSRIs) have been evaluated for the prevention of migraine and tension-type headaches (TTH). OBJECTIVES: To evaluate the efficacy and tolerability of SSRIs for preventing migraine and TTH. SEARCH STRATEGY: We searched MEDLINE (1966-2004), EMBASE (1994-2003), the Cochrane Central Register of Controlled Trials (Issue 4, 2003), and reference lists of retrieved articles. Headache Quarterly was hand searched from 1990 to 2003. SELECTION CRITERIA: We included randomised controlled trials comparing SSRIs with any type of control intervention in patients of either sex, over 18 years of age, with migraine or TTH. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data (headache frequency, index, severity, and duration; use of symptomatic/analgesic medication; days off work; quality of life; mood improvement; cost-effectiveness; and adverse events) and assessed the methodological quality of trials. MAIN RESULTS: Thirteen studies utilizing five SSRIs met the inclusion criteria (636 participants). Most of the included studies had methodological and/or reporting shortcomings; follow up rarely extended beyond 3 months. After 2 months SSRIs did not significantly lower headache index scores in patients with migraine when compared to placebo (SMD -0.14; 95% CI -0.57 to 0.30). Patients with chronic TTH treated with an SSRI had a significantly higher analgesic intake of 5 more doses per month when compared to patients treated with a tricyclic antidepressant (WMD 4.98; 95% CI 1.12 to 8.84). Tricyclics also significantly reduced headache duration by 1.26 hours per day (WMD 1.26; 95% CI 0.06 to 2.45) and marginally reduced headache indexes (SMD 0.42; 95% CI 0.00 to 0.85) when compared to SSRIs in patients with chronic TTH. When the data on adverse events were considered without regard to headache diagnostic subgroups, there were no significant differences between SSRIs and placebo for withdrawals due to adverse events (Peto OR 1.02; 95% CI 0.31 to 3.34). For minor adverse events, SSRIs were generally more tolerable than tricyclics (OR 0.34; 95% CI 0.13 to 0.92). However, there were no differences in the number of patients withdrawing due to any reason in the SSRI and tricyclic groups (OR 1.01; 95% CI 0.56 to 1.80). AUTHORS' CONCLUSIONS: Over 2 months of treatment, SSRIs are no more efficacious than placebo in patients with migraine. In patients with chronic TTH, SSRIs are less efficacious than tricyclic antidepressants. In comparison with SSRIs, the burden of adverse events in patients receiving tricyclics was greater. These results are based on short-term trials and may not generalise to longer-term treatment.

Hemianesthesia, sensory neglect, and defective access to conscious experience.

We report a patient with an ischemic stroke in the vascular territory of the right middle cerebral artery who had left spatial neglect and left hemianesthesia. The patient showed a dissociation between defective verbal reporting of somatosensory stimuli delivered to the left hand and physiologic evidence from an autonomic index. This indicates that there was processing of undetected stimuli without the patient's awareness, and suggests that the hemianesthesia was due, at least in part, to somesthetic hemi-inattention.

Left hemisphere contribution to motor programming of aphasic speech: a reaction time experiment in aphasic patients.

Simple reaction time to lateralized visual dot stimuli was studied in 10 fluent and 10 nonfluent right-handed chronic aphasics with left hemisphere lesions. As well as the standard simple reaction time condition, the patients were given a concomitant verbal task, requiring overt articulation while reacting to the visual stimuli. Compared with the control condition, in both aphasic groups the verbal task produced an overall lengthening of latencies, with a significant slowing down of responses to the stimuli located in the right visual half-field. According to these results the verbal concurrent activity appears to involve the left hemisphere as in normal subjects, suggesting that the undamaged regions of the left hemisphere have a role to play in the motor programming of aphasic speech. As a collateral finding, the difference between latencies to stimuli ipsilateral and contralateral to the responding hand--a measure of interhemispheric transmission time--is greatly increased in patients with motor deficits. This is consistent with the view that, in simple visuo-motor reaction time, interhemispheric transfer takes place between anterior regions of the brain.

Selective visual interference with right hemisphere performance in verbal recall. A divided field study.

Three experiments were performed in normal subjects to find out whether interhemispheric functional asymmetries in oral recall of meaningless trigrams of consonants, laterally presented through a tachistoscope, were affected by the subsequent presentation and the immediate recall of visual (verbal and geometrical) vs auditory information. It was shown that the visual presentation of after-target information brought about a right hemisphere disadvantage, which did not occur when the additional information was presented auditorily. The results are consistent with the view that, as to visually presented letters, the right hemisphere processing systems run along a physical code.

Remission of hemineglect and anosognosia during vestibular stimulation.

The effects of vestibular stimulation on extrapersonal and personal neglect and on awareness of disease were investigated in four patients with severe neglect and anosognosia. Neglect phenomena improved in all patients, while an effect on anosognosia was found in two cases. These preliminary findings indicate a possible role of vestibular stimulation on hemispheric activation.

Topographic disorientation--a case report.

Topographical disorientation can be dissociated in two levels, agnosic and amnesic. A case of topographical disorientation due to a glioma of the splenium of corpus callosum illustrates the dissociation between the topographical memory impairment and the normal performances on the perceptual topographic tests.

Dissociation between normal hemispheres in delayed recognition of verbal and spatial cues of the same visual pattern.

Is each hemisphere capable of disentangling a specific kind of information from a complex 3-target set of stimuli in an expectancy-free delayed recognition experiment on normals? A tachistoscopical study set out to answer this question. It provided evidence for a double dissociation between the hemisphere of input of complex stimuli (comprising both spatial and verbal information) and the kind of information to be retrieved.

Bilateral perisylvian softenings: bilateral anterior opercular syndrome (Foix-Chavany-Marie syndrome).

Five cases of facio-pharyngo-glosso-masticatory diplegia with automatic voluntary dissociation, i.e., bilateral anterior opercular syndrome (Foix-Chavany-Marie syndrome), are described together with the morphological correlations in four. The localizing value of the syndrome and of CT scanning are stressed.

Neurological complications of liver transplantation.

We examined 199 consecutive patients who underwent 220 liver transplantations, to define the type, frequency and aetiology of posttransplant neurological complications and their prognostic value. We found neurological complications in 63 patients (32%), mostly involving the central nervous system. The most frequent complications were mental status changes ranging from delirium to coma and seizures. The aetiology was multifactorial, cyclosporin A neurotoxicity being the main cause. Patients with neurological complications had a higher mortality rate than those without. In our series, neurological complications represented a major medical problem with increased morbidity and mortality.

Brain-stem haematoma with complete recovery.

A case of CT-diagnosed brain-stem haematoma associated with signs of dorsal medullary involvement is reported. The patient recovered completely within 1 month.

The hemispheric side of neocortical damage does not affect memory for unidimensional position. An experiment wih Posner and Konick's test.

The role of neocortical areas in visuo-spatial memory was investigated by testing unilateral hemisphere-damaged patients for their ability to reproduce the position of a dot on a horizontal line after a delay. One hundred and eleven patients, divided into 4 groups on the basis of the side of damage and of the presence or absence of visual field defects, and 56 controls were tested. There were 2 sets of experimental conditions: (i) a free delay condition of 0, 20 or 180 sec., and (ii) a 20 sec. delay condition filled with 2 kinds of interpolated perceptual activity. Forgetting was significantly affected by presence of hemisphere damage, but not by the side and the intrahemispheric locus of lesion. It was concluded that the memory ability involved by this task is not related to the functioning of a specific cortical area.

Hemispheric lateralization of the decisional stage in choice reaction times to visual unstructured stimuli.

Simple manual RTs to lateral visual stimuli were found to be faster in uncrossed than in crossed anatomical conditions. Neither hand nor hemifield effects were found. By contrast significant asymmetries were found in Choice RTs involving both hemispheres, even in uncrossed condition. The field effect was marked when the responding hand was the right but insignificant when the responding hand was the left. The data seem consistent with a model which assumes the location of the decisional structures in the left hemisphere.