Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study.

BACKGROUND: Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES: To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS: In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS: Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P < 0.001] and were more frequently hospitalized in intensive care medicine [ICU; 11 (21%) vs. 5 (5%); P = 0.004]. In multivariate analysis, factors associated with thrombolysis-related AE were female sex [odds ratio (OR), 3.04; 95% confident interval (CI), 1.32-7.01; P = 0.009] and treatment with angiotensin-converting enzyme inhibitors [(OR), 6.08; 95% (CI), 2.17-17.07; P < 0.001]. CONCLUSIONS: This case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykinin AE associated with thrombolysis for ischemic stroke.

Transcranial direct current stimulation of the affected hemisphere does not accelerate recovery of acute stroke patients.

BACKGROUND AND PURPOSE: Transcranial direct current stimulation (TDCS) is a potential tool to improve motor deficits in chronic stroke patients. Safety and efficacy of this procedure in acute stroke patients have not yet been addressed. METHODS: We performed in our stroke unit a single-centre randomized, double-blind, sham-controlled study to investigate safety and efficacy of anodal TDCS of the affected hemisphere in acute stroke patients. The second day from stroke onset, 50 acute stroke patients received either five-daily sessions of anodal (n=25) at 2mA for 20min or sham TDCS (n=25) to the ipsilesional primary motor cortex (M1). Motor deficit was assessed by the short form of the Fugl-Meyer motor scale (FM) and overall neurological deficit by the National Institute of Health Stroke Scale (NIHSS) at onset, at 5days after stroke and after 3months. RESULTS: No side effects were detected during either TDCS or sham. In both groups, there was a significant improvement in NIHSS and FM scores, which did not significantly differ when comparing TDCS and sham. CONCLUSIONS: Five-daily sessions of anodal TDCS to the ipsilesional M1 appear to be safe in acute stroke patients but do not improve clinical outcome.

Acute stroke with hyperdense middle cerebral artery sign benefits from IV rtPA.

OBJECTIVES: The current management of acute ischemic stroke is intravenous (IV) recombinant tissue plasminogen activator (rtPA). The presence of a hyperdense middle cerebral artery sign (HMCAS) on pre-treatment head computed tomogram (CT) is considered a poor prognostic sign. We compared the clinical outcome in IV rtPA-treated patients with and without a HMCAS. DESIGN: Retrospective analysis of prospectively collected cases treated with IV rtPA within three hours. Inclusion criteria were the presence of: i) an anterior circulation stroke; ii) a pre-treatment CT available; iii) a pre-treatment National Institutes of Health (NIH) stroke scale (NIHSS) score; and iv) a modified Rankin Score (mRS) at three months. RESULTS: One hundred and thirty patients were eligible for the analysis, 64 (49%) had a HMCAS. The HMCAS group had a trend toward a higher mean (+/-SD) pre-treatment NIHSS score compared to the non-HMCAS group (13.9+/-6 vs. 12.2+/-6; p=0.12). Accordingly, there were more patients with severe strokes (NIHSS>10) in the HMCAS group compared to the non-HMCAS one (48/64=75% vs. 35/66=53%; p=0.009). The mean (+/-SD) NIHSS score 24 hours after treatment was 10.6 (+/-8) in the HMCAS group and 8.3 (+/-7) in the non-HMCAS group (p=0.08). In a multiple logistic regression analysis, the only independent predictor of poor outcome (mRS 3-6) was pre-treatment NIHSS score (p<0.001). CONCLUSION: Patients with a HMCAS receiving IV rtPA did not fare worse at three months despite a greater proportion of patients with more severe strokes. Based on the current knowledge, IV rtPA remains a good treatment for patients with a HMCAS within three hours of symptom onset.

Diazepam effects on the cerebral responses to tonic pain: a SPET study.

RATIONALE: Pain is a complex phenomenon with a strong affective-emotional component in addition to a sensory-discriminative one. This causes the activation of multiple brain areas, which process different aspects of pain simultaneously. OBJECTIVES: We investigated the effects of diazepam (DZ) on a well-known pattern of brain regions activated by cold, tonic pain stimuli. METHODS: Quantitative cerebral blood flow (CBF) was assessed by single photon emission tomography (SPET) and the Xe-133 inhalatory method, at rest and during tonic pain activation in eight normal, right-handed, male volunteers. The cold pressor test (CPT) was performed by immersion of the left hand in cold water twice, first during CPT alone, and again 30 min after intravenous administration of diazepam (CPT+DZ). RESULTS: During CPT we observed a significant CBF increase in the right thalamus, primary sensory-motor cortex (S1/M1), frontal and temporal regions, and in the left temporal region and anterior cingulate cortex (ACC). During CPT+DZ, the average CBF was significantly lower than during the CPT state (-11%, P<0.05). After normalisation, during CPT+DZ we again observed a significant CBF increase in the right thalamus, S1/M1 and frontal regions, and in the left ACC, though not in the temporal regions. DZ administration first causes a global reduction in CBF, then modifies the pattern of brain activation. CONCLUSIONS: During CPT, activation of the temporal regions has been interpreted as part of the affective-emotional component of pain response. DZ seems to affect the "pain-related" pattern of activation by abolishing the CBF increase in the temporal regions, without, however, modifying the pain perception or determining a sedating effect.

Joint effect of stroke and APOE 4 on dementia risk: the Canadian Study of Health and Aging.

BACKGROUND: Although stroke and APOE 4 are independent risk factors for dementia, their combined effect remains uncertain. We assessed their joint effect on dementia risk. METHODS: Subjects participated in Phases 1 and 2 of the Canadian Study of Health and Aging (CSHA). Dementia was diagnosed by consensus, and stroke was diagnosed by history or clinical examination. Analyses were first conducted among clinical participants only, and then rerun with the screening sample included as well. RESULTS: Analyses included 949 participants from CSHA-1 and 1,413 from CSHA-2. During a median 4.6-year follow-up, 740 were included in the CSHA-1 to -2 incidence study. Among clinical participants, the highest prevalence (40.6% for CSHA-1 and 57.6% for CSHA-2) and incidence (8.4 per 100 person-years) of dementia occurred in elderly having both stroke and APOE 4; the lowest prevalence (19.8% for CSHA-1 and 23.3% for CSHA-2) and incidence (4.3 per 100 person-years) were among persons having neither. These findings held true when the screening sample was included. The adjusted hazard ratios of incident dementia, relative to elderly with neither stroke nor APOE 4, were 1.33 (95% CI 0.73 to 2.43) for stroke alone, 2.06 (95% CI 1.42 to 2.99) for APOE 4 alone, and 2.57 (95% CI 1.11 to 5.94) for both. No interaction on additive or multiplicative scales was suggested. CONCLUSIONS: The joint presence of stroke and APOE 4 was associated with a greater risk of dementia compared with absence of these two factors. The effect of stroke on dementia does not seem to be modified by APOE 4.

Monthly brain magnetic resonance imaging scans in patients with clinically isolated syndrome.

We investigated if monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) can assist the clinician in anticipating the diagnosis of multiple sclerosis (MS) in the very first few months following a clinically isolated syndrome (CIS). A consecutive series of CIS patients with > or = 3 T2-weighted (T2W) hyperintense brain MRI lesions suggestive of MS were followed up for the first six consecutive months after enrollment with monthly triple-dose Gd-enhanced brain MRI scan. MRI conversion to MS was defined by the presence of either > or = 1 new Gd-enhancing lesion or > or = 1 new T2W lesions in the subsequent MRI scan. Sixty patients were included. Of them, 30 (50%) had at least one Gd-enhancing lesion on the baseline MRI scan. After three months, MRI conversion to MS was observed in 80% and 62% of patients based on the appearance of > or = 1 new T2 lesion and > or = 1 new Gd-enhancing lesions, respectively. The presence of > or = 1 new T2W lesion was observed in 90% and 82% of patients who had, at baseline, a Gd-positive MRI scan and dissemination in space based on the new McDonald's criteria, respectively The rate of MRI conversion remained almost stable in the last two MRI scans. Our study suggests that the majority of CIS patients with an abnormal baseline scan showed an MRI conversion to MS after three months. The model of six months as the optimal interval for repeating MRI exam is not supported by the present data.

Anticipation of onset age in hereditary essential tremor.

The genetic anticipation phenomenon has been described in several neurological disorders, often associated with unstable trinucleotide repeats in the affected genes. The occurrence of this phenomenon in hereditary essential tremor is still debated. We describe a family in which three male members with essential tremor showed a progressive anticipation in onset age and an increased severity of clinical symptomatology.

Usefulness of primitive reflexes in demented and non-demented cerebrovascular patients in daily clinical practice.

The aim of this study was to investigate the usefulness of primitive reflexes (PRs) as additional alert signs in a routine clinical setting of cognitive decline in an elderly population of chronic ischemic cerebrovascular patients. We considered the occurrence of grasp, palmomental, glabellar and snout reflexes in 75 demented (VaD) and 75 non-demented (VaND) patients, and in 75 healthy elderly controls. We never elicited more than two PRs in controls. The occurrence of three or four PRs provided the strongest correlation with dementia (p < 0.0001), with 93% specificity irrespective of low sensitivity. In conclusion, the occurrence of more than two PRs might serve as an additional warning sign of possible mild cognitive impairment in chronic ischemic cerebrovascular patients.

Aminergic tone correlates of migraine and tension-type headache: a study using the tridimensional personality questionnaire.

BACKGROUND: Aminergic neurotransmitter activity has been studied in many neuropsychiatric diseases by means of a self-administered questionnaire proposed by Cloninger. Given that central aminergic modulation plays a major role in the pathophysiology of primary headaches, we investigated the personality dimensions related to aminergic neurotransmitter activity in patients with migraine and tension-type headache. METHODS: From a consecutive series of 230 patients, we selected those presenting with migraine and tension-type headache according to the International Headache Society criteria. All patients were assessed by means of the Cloninger 100-item self-report Tridimensional Personality Questionnaire and a depression scale. The four dimensions of personality are novelty seeking (dopaminergic), harm avoidance (serotonergic), reward dependence (noradrenergic), and persistence (glutaminergic). RESULTS: One hundred twenty-one patients presenting with migraine and 42 with tension-type headache were recruited. The results indicate significantly higher harm avoidance scores (P<.001) in both patients with migraine and those with tension-type headache than in controls. Furthermore, patients with migraine had a significantly low score in the novelty seeking dimension (P<.001). When we compared only the two groups of patients with headache, we found that the persistence dimension alone was significantly higher in patients with migraine than in those with tension-type headache (P<.05). No differences were observed either in the overall scores of the other personality dimensions or in the depression scale scores. CONCLUSIONS: The Tridimensional Personality Questionnaire results support a role of the serotonergic system in both migraine and tension-type headache pathophysiology. A dysfunction of dopaminergic and glutaminergic tone seems to be a specific feature of migraine.

Longitudinal evaluation of depression and anxiety in patients with clinically isolated syndrome at high risk of developing early multiple sclerosis.

We investigated the relationship between emotional changes, brain lesion burden and development of multiple sclerosis (MS). Thirty-seven consecutive patients with clinically isolated syndrome (CIS) were prospectively assessed with the Expanded Disability Status Scale (EDSS), the 21-item Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI) and gadolinium enhanced (Gd+) MRI scans. BDI and STAI were also administered to 36 age-matched controls. Conversion to MS was defined as the occurrence of a clinical relapse. CIS patients were more likely to endorse symptoms of anxiety and depression than controls. Baseline scores for depression and anxiety did not correlate with the total lesion load (i.e., volume of Gd+, T2 and T1 lesions) and the number of Gd+ lesions during the first six months of follow-up. A positive correlation was found between severity of depressive scores and the lesion load in the right temporal region (P = 0.005). After 33+/-6 months of the study entry, patients who had a clinical relapse were more frequently depressed (P = 0.001) than those relapse free. Emotional disturbances are frequently observed in CIS patients and show a tendency towards a normalization in relapse-free patients. The increased rate of depressive symptoms observed in patients who developed MS seems to result from a combination of psychological and organic features. The lesion load in the right temporal region is confirmed as a key area for developing depressive symptoms, even in the early phase of the disease.

Vascular dementia: a cognitive SPET-CBF activation study.

OBJECTIVE: We investigated the pattern of regional cerebral blood flow (rCBF) responses to a cognitive task in vascular patients with and without dementia. METHOD: We studied 8 controls and 18 vascular patients by quantitative rCBF assessed by (133)Xe inhalation method and SPET, both at rest and during a cognitive figure recognition task. Eight were mildly demented and 10 were nondemented vascular patients. According to their task performance, 12 patients were classified as 'good performers' (GPs) and 6 patients as 'poor performers' (PPs). RESULTS: Vascular patients activated a larger number of brain areas than controls. No differences were observed between controls, nondemented and mildly demented patients in the pattern of rCBF activation. GPs presented a lower mean percentage of rCBF increase than either controls or PPs. GPs had lower values than PPs in the left temporal, parietal and occipital regions and in the right posterior cingulate and occipital regions. CONCLUSIONS: These data suggest that vascular patients may functionally compensate for vascular damage by activating more brain areas than controls do and, consequently, by increasing the rate of regional activation.

Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis.

OBJECTIVES: The present study was planned to investigate the relationship between the plasma lipid profile and disease activity in patients with a first clinical episode suggestive of multiple sclerosis (MS). MATERIAL AND METHODS: Eighteen consecutive out-patients underwent a monthly brain magnetic resonance imaging (MRI), blood sample and neurological assessment over 6 months. Blood samples were used to evaluate total cholesterol and triglyceride levels as well as their lipoprotein fractions. Plasma total apolipoprotein E concentration was also determined. RESULTS: We found a significant correlation between the mean number of enhancing lesions and the mean plasma level of both total and low density lipoprotein cholesterol. The total plasma cholesterol level increased on average by 4.4 mg/dl for each enhancing lesion. CONCLUSION: Our preliminary data suggest a potential role of plasma cholesterol level as a biological marker of disease activity after a first demyelinating event. Further studies need, however, to be designed to determine whether the plasma cholesterol level is of practical use in monitoring the disease course.

Carotid endarterectomy and gliofibrillar S100b protein release.

Increased levels of the gliofibrillar S100b protein can be detected during carotid endarterectomy (CEA). Whether the S100b protein increase is marker of brain ischemic sufferance and predictor of cognitive decline is controversial. Twenty-eight patients underwent clinical assessment and cranial computed tomography (CT) 24-48 hours before and 3 months after CEA. S100b serum levels were evaluated before surgery, at cross-clamping, 10 minutes later, at declamping, and 24-48 hours and 10-12 weeks after CEA. Increased S100b levels were detected in 11 patients (39%); eight (73%) of these patients had symptomatic carotid artery disease. Increased S100b level correlated with history of TIA or stroke ( p=0.005), low mini-mental state examination score ( p=0.02), and ischemic infarctions at preoperative CT ( p=0.03). Slight and transient increased S100b levels were detected in 39% of patients during CEA. The protein levels increased despite the absence of clinical events during surgery. Our findings suggest a failure of compensatory hemodynamic or metabolic mechanisms in peri-ischemic tissue, whose longterm effects on cognition remain to be investigated.