Giovanni Orlandi

Silent Cerebral Ischemia Detected With Diffusion-Weighted Imaging in Patients Treated With Protected and Unprotected Carotid Artery Stenting

Background and Purpose— Percutaneous transluminal angioplasty with stent (CAS) is an alternative method to endarterectomy in the revascularization of carotid artery stenosis. Protected CAS is currently used to prevent distal embolization. Diffusion-weighted MRI (DWI) is the most sensitive tool to evaluate silent cerebral ischemia. The purpose of this research was to assess the incidence of cerebral embolic lesions during CAS and to evaluate whether cerebral protection devices can reduce the number of silent cerebral ischemia with respect to unprotected CAS. Methods— Fifty-two patients with high-grade internal stenosis underwent CAS; 30 patients (group a) were treated with a cerebral protection device, and 22 (group b) were treated without it. All of the patients were evaluated preoperatively and postoperatively with fluid-attenuated inversion recovery and DWI sequences to depict the number of new embolic silent cerebral lesions. Results— Embolic silent cerebral lesions occurred in 30% of CAS. Cerebral protection devices reduce the number of new lesions significantly reducing the consistent lesions ipsilateral to the treated vessel. Inconsistent lesions do not differ in both groups of patients. Clinical, radiological, and procedural variables do not correlate with the appearance of new cerebral lesions. Conclusions— Embolic cerebral lesions detected with DWI are more frequent with unprotected CAS, although they are present also with the use of cerebral protection devices. Probably a part of silent cerebral lesions arise from the procedural maneuver in the aortic arch.

Transient autonomic nervous system dysfunction during hyperacute stroke

Forty‐four patients suffering a stroke for the first time were examined within 10 h of the onset of symptoms; the tests performed on their admission to hospital, and thereafter on the third and seventh day, were 24‐h Holter EKG with spectral analysis of heart rate variability, evaluation of arterial blood pressure and the levels of catecholamine in the blood and 24‐h urine. The dynamic EKG on admission revealed that 31 (70.5%) out of the 44 patients already had arrhythmia. These alterations were observed in 9 (75%) out of 12 haemorrhagic patients with a significant (P<0.05) prevalence compared to 22 (68.8%) of the 32 ischaemic ones. Arrhythmia showed up in 16 (76.2%) out of 21 cases with right hemisphere lesions and in 12 (63.2%) out of 19 cases of left hemisphere lesions; this difference was also significant (P<0.05). Arrhythmia was still present in 19 (43.2%) patients after 3 days and only in 2 (6.5%) patients after 7 days. The spectral analysis parameters on admission and after 3 days were significantly (P<0.05) modified in patients with stroke plus arrhythmia, compared to patients with stroke alone and to control subjects, whereas no further differences were observed on the seventh day. Moreover, the percentage of patients with arterial hypertension and high levels of catecholamine greatly decreased from the third day onwards. A transient autonomic nervous system imbalance with prevalent sympathetic activity may justify this cardiovascular impairment during the hyperacute phase of stroke.

Intravenous thrombolysis with rt-PA in acute ischemic stroke patients aged older than 80 years in Italy.

Background: Intravenous (i.v.) thrombolysis with rt-PA within 3 h from symptom onset is the only approved treatment of pharmacological revascularization in acute ischemic stroke. However, little information exists on its use in elderly patients, in particular those aged >80 years, who at present are excluded from treatment. Methods: In a multicenter Italian study on i.v. thrombolysis, patients aged >80 years (n = 41) were compared with those aged ≤80 years (n = 207) regarding the percentage of symptomatic (nonfatal and fatal) intracerebral hemorrhage (SICH), favorable 3-month functional outcome (modified Rankin Scale score 0–2) and poor outcome (death or dependence, i.e. modified Rankin Scale score 3–5). Results: The percentage of SICH (nonfatal and fatal) was comparable between older (2.4%, 2.4%) and younger (2.4%, 2.4%) patient groups (p = 1.0). At 3 months, favorable outcome occurred in 44% and dependence in 22% of the older, and respectively in 58.5 and in 30.9% of the younger patients (p = 0.897). Patients aged >80 years had a higher mortality (34.1%) as compared to those aged ≤80 years (10.6%) (p < 0.001). Baseline National Institute of Health Stroke Scale score was the only statistically significant predictor of both mortality (OR = 1.26; 95% CI = 1.07–1.50) and poor outcome (OR = 1.39; 95% CI = 1.14–1.68) in the >80-year-old group. Conclusions: Acute ischemic stroke patients aged >80 years treated with i.v. rt-PA have a higher mortality than younger patients, but there are no differences for SICH nor for favorable outcome. Our data suggest that thrombolytic therapy should not be a priori denied for appropriately selected >80-year-old patients but randomized controlled clinical trials are necessary before definite recommendations can be given.

Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study

Background and Purpose— The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods— ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0–2) or unfavorable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Results— Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03–3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36–3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87–58.71; P=0.068) in the cases than in the controls. Conclusions— In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

Changes in pattern electroretinograms to equiluminant red-green and blue-yellow gratings in patients with early Parkinson's disease

Summary In Parkinson’s disease (PD), the luminance pattern electroretinogram (PERG) is reported to be abnormal, indicating dysfunction of retinal ganglion cells (RGCs). To determine the vulnerability of different subpopulations of RGCs in PD patients, the authors recorded the PERG to stimuli of chromatic (red-green [R-G] and blue-yellow [B-Y]) and achromatic (yellow-black [Y-Bk]) contrast, known to emphasize the contribution of parvocellular, koniocellular, and magnocellular RGCs, respectively. Subjects were early PD patients (n = 12; mean age, 60.1 ± 8.3 years; range, 46 to 74 years) not undergoing treatment with levodopa and age-sex-matched controls (n = 12). Pattern electroretinograms were recorded monocularly in response to equiluminant R-G, B-Y, and Y-Bk horizontal gratings of 0.3 c/deg and 90% contrast, reversed at 1Hz, and presented at a viewing distance of 24 cm (59.2 × 59 degree field). In PD patients, the PERG amplitude was significantly reduced (by 40 to 50% on average) for both chromatic and luminance stimuli. Pattern electroretinogram latency was significantly delayed (by about 15 ms) for B-Y stimuli only. Data indicate that, in addition to achromatic PERGs, chromatic PERGs are altered in PD before levodopa therapy. Overall, chromatic PERGs to B-Y equiluminant stimuli exhibited the largest changes. Data are consistent with previous findings in PD, showing that visual evoked potentials (VEP) to B-Y chromatic stimuli are more delayed than VEPs to R-G and achromatic stimuli. The results suggest that the koniocellular subpopulation of RGCs may be particularly vulnerable in early stages of Parkinson’s disease.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Effect of Anticoagulation and Its Timing: The RAF Study

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Silent Cerebral Microembolism in Asymptomatic and Symptomatic Carotid Artery Stenoses of Low and High Degree

124 carotid arteries of 62 patients with unilateral or bilateral carotid stenosis proven by selective angiography were investigated by transcranial Doppler to detect high-intensity transient signals (HITS) in the middle cerebral arteries (MCAs). HITS identified as embolic signals were detected in 29 of 124 (23.3%) MCAs and in all cases were asymptomatic. HITS were more common in the MCAs on the same side as high-degree (> 70%) carotid stenoses (24 of 57 = 42.2%) compared with low-degree (< 70%) carotid stenoses (5 of 28 = 17.9%, p < 0.05). No HITS were detected in the MCAs on the same side as normal (24) and occluded (15) carotid arteries. About the clinical features related to the stenoses, HITS were detected with a nonsignificant prevalence in the MCAs on the same side as symptomatic stenoses (16 of 43 = 37.2%) compared with asymptomatic stenoses (13 of 42 = 30.9%) and a relationship between HITS number and time elapsed from symptoms was observed. All symptomatic carotid stenoses > 70% (33) underwent endarterectomy and none of them showed HITS after surgical treatment. These results encourage the feasibility of prognostic studies to evaluate the clinical significance of embolic signals and suggest that silent microembolism could be helpful in selecting a high-risk group of asymptomatic or < 70% carotid stenoses for endarterectomy.

MMP9 Variation After Thrombolysis Is Associated With Hemorrhagic Transformation of Lesion and Death

Background and Purpose— Experimentally, matrix metalloproteinases (MMPs) play a detrimental role related to hemorrhagic transformation and severity of an ischemic brain lesion. Tissue-type plasminogen activator (tPA) enhances such effects. This study aimed to expand clinical evidence in this connection. Methods— We measured MMPs 1, 2, 3, 7, 8, 9, and tissue inhibitors of metalloproteinases 1, 2, 4 circulating level in blood taken before and 24 hours after tPA from 327 patients (mean age, 68.9±12.1 years; median National Institutes of Health Stroke Scale, 11) with acute ischemic stroke. Delta median values ([24 hours post tPA–pre tPA]/pre tPA) of each MMP or tissue inhibitors of metalloproteinase were analyzed across subgroups of patients undergoing symptomatic intracerebral hemorrhage, 3-month death, or 3-month modified Rankin Scale score 3 to 6. Results— Adjusting for major clinical determinants, only matrix metalloproteinase-9 variation proved independently associated with death (odds ratio [95% confidence interval], 1.58 [1.11–2.26]; P=0.045) or symptomatic intracerebral hemorrhage (odds ratio [95% confidence interval], 1.40 [1.02–1.92]; P=0.049). Both matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 changes were correlated with baseline, 24 hours, and 7 days National Institutes of Health Stroke Scale (Spearman P from <0.001 to 0.040). Conclusions— Our clinical evidence corroborates the detrimental role of matrix metalloproteinase-9 during ischemic stroke treated with thrombolysis, and prompts clinical trials testing agents antagonizing its effects.

The THRombolysis and STatins (THRaST) study

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. Results: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26–2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11–1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18–2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19–0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28–0.82; p = 0.007). Conclusion: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.

Vertebral and carotid artery dissection following chiropractic cervical manipulation

Abstract A 50-year-old woman presented a sudden left occipital headache and a posterior circulation stroke after cervical manipulation for neck pain. Magnetic resonance imaging documented a left intracranial vertebral artery occlusive dissection associated with an ipsilateral internal carotid artery dissection with vessel stenosis in its prepetrous tract. This is the first reported case showing an associate vertebral and carotid artery dissection following cervical manipulation. Carotid dissection was asymptomatic and, therefore, its incidence may be underestimated. We emphasize that cervical manipulation should be performed only in patients without predisposing factors for artery dissection and after an appropriate diagnosis of neck pain.