Manuel Cappellari

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.

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.

Variable presentations of TTR-related familial amyloid polyneuropathy in seventeen patients

Autosomal‐dominant transthyretin (TTR)‐related amyloidosis usually manifests in the second to fourth decade with a length‐dependent axonal neuropathy with prominent involvement of the small fibers and multi‐organ systemic failure. We retrospectively analyzed seventeen probands, including thirteen apparently isolated cases, carrying eight mutations of TTR gene (age of onset = 60.4 ± 13.5 years). Thirteen patients were initially un/misdiagnosed; interval from onset to definite diagnosis was 3.3 ± 2.3 years. Inaugural syndromes were a length‐dependent motor‐sensory neuropathy in seven cases, a sensory neuropathy in four, an isolated carpal tunnel syndrome in three, a pure dysautonomia in two, and a painful neuropathy in one. Atypical presentations included demyelinating nerve conduction changes with increased cerebrospinal fluid proteins resembling chronic inflammatory demyelinating polyradiculoneuropathy and a predominantly motor involvement resembling a motor neuron disorder. Misleading findings also included amyloid‐negative abdominal fat aspirate/biopsy, biclonal gammopathy, and hepatitis C virus (HCV) seropositivity. Sural nerve biopsy detected amyloid deposits in thirteen of fifteen patients, including one case with a previous negative biopsy. TTR‐immunohistochemistry was necessary to complete the diagnosis of primary amyloidosis light chain in a patient with biclonal gammopathy. A recurrent p.Phe64Leu mutation manifested in the seventh decade with painful motor‐sensory polyneuropathy, dysautonomia, bulbar palsies, and fasciculations. TTR should be tested in a wide clinical spectrum of cryptogenetic, progressive, and motor‐sensory neuropathies even manifesting with a very late onset.

Does statin in the acute phase of ischemic stroke improve outcome after intravenous thrombolysis? A retrospective study

BACKGROUND In recent years, the medical literature has shown that statin treatment before and in the acute phase of ischemic stroke has a positive impact on outcome. The possible effect of statins during the acute phase has never been assessed in thrombolysed patients, and the few studies investigating a possible association between prior statin use and outcome after thrombolysis have reported controversial results. The aim of the present study was to assess whether statin treatment started in the acute phase of stroke (within 24h) or before stroke and continued during the acute phase may influence short- and long-term outcome in patients receiving intravenous (IV) thrombolysis. METHODS We conducted a retrospective analysis of 250 patients treated with IV thrombolysis. Outcome measures were 3-month good functional outcome (modified Rankin Scale ≤ 2); neurological improvement (reduction ≥ 4 points on the National Institutes of Health Stroke Scale [NIHSS]) between 24 and 72 h; and symptomatic intracerebral hemorrhage (brain hematoma associated with NIHSS deterioration ≥ 4 points) within 72 h. RESULTS Multivariate analysis showed that statin treatment started in the acute phase of stroke was associated with both good functional outcome (OR: 6.18; 95% CI: 1.43-26.62; P=0.015) and neurological improvement (OR: 9.47; 95% CI: 1.98-45.37; P=0.005), whereas statin treatment started before stroke and continued in the acute phase was associated with symptomatic intracerebral hemorrhage (OR: 6.65; 95% CI: 1.58-29.12; P=0.010). CONCLUSIONS Our data suggest that statin treatment started within 24h after IV thrombolysis, but not statin treatment started before stroke and continued in the acute phase, may improve short- and long-term outcome.

Intravenous thrombolysis for acute ischemic stroke associated to extracranial internal carotid artery occlusion: the ICARO-2 study.

Background and Purposes: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. Methods: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke – International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3–6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. Results: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0–1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9–11.1) and mortality or disability (OR 5.0; 95% CI 2.9–8.7) at 90 days. Conclusions: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome.

Ataxia in posterior circulation stroke: Clinical-MRI correlations.

OBJECTIVE Ataxia is characterized clinically by four signs (gait and limb ataxia, dysarthria and nystagmus). Although ataxia has been described in posterior circulation (PC) stroke series, there are no prospective studies that have investigated a possible differential role of the cerebellum or its input/outputs in causing ataxia. METHODS Ataxia was semi-quantified according to the International Cooperative Ataxia Rating Scale (ICARS) in 92 consecutive patients with acute PC stroke. Four topographical patterns based on magnetic resonance imaging (MRI) findings were identified: picaCH pattern (posterior inferior cerebellar artery infarct); scaCH pattern (superior cerebellar artery infarct); CH/CP pattern (infarct involving both the cerebellum and the brainstem cerebellar pathways); and CP pattern (infarct involving the brainstem cerebellar pathways). RESULTS Gait ataxia was present in 95.7%, limb ataxia in 76.1%, dysarthria in 56.5% and nystagmus in 65.2% of patients. Gait ataxia frequency did not differ between the patterns, but was significantly more severe in the CH/CP pattern than in either picaCH (P=0.0059) or CP (P=0.0065) pattern. Limb ataxia was significantly less frequent (P<0.001) and less severe (P<0.001) in picaCH pattern than other patterns. Dysarthria was less frequent in picaCH pattern than in other patterns (P=0.018) and less severe than in scaCH (P=0.0043) or CP (P=0.0047) pattern. No differences in nystagmus frequency or severity were observed across all four patterns. CONCLUSION In PC stroke gait ataxia was almost always present, regardless of the lesion site. Limb ataxia and dysarthria were less frequent in the picaCH pattern, whereas nystagmus, when present, did not differ among the topographical patterns.

Intravenous thrombolysis for stroke in patients taking non-VKA oral anticoagulants: an update

Intravenous thrombolysis for stroke in patients taking non-VKA oral anticoagulants: an update -

Repeated intravenous thrombolysis after recurrent stroke. A case series and review of the literature.

BACKGROUND The likelihood of severe disability and death increases with each recurrent stroke. Repeated intravenous (IV) thrombolysis remains one of the therapeutic options when secondary prevention fails; however, its effects after recurrent stroke are largely unknown. The aim of the present review was to assess the risks and benefits of IV re-thrombolysis after recurrent stroke as compared with IV thrombolysis after index stroke. METHODS We identified 8 patients who repeated IV thrombolysis after recurrent stroke from among the 615 consecutive stroke patients who received IV thrombolysis at our Stroke Unit and 22 cases of IV re-thrombolysed patients extracted for the literature review of case reports and case series. RESULTS After excluding the 6 patients treated with endovascular procedures, we included in the analyses 21 patients for which we had data on pre-stroke functional status and baseline neurological severity for each stroke event and post-treatment functional status for each IV thrombolysis. We compared second (n=21) and third (n=3) IV thrombolytic treatments with first IV thrombolytic treatments (n=21). Also, we compared IV thrombolytic re-treatments ≤3 months from previous IV thrombolysis (n=10) with those >3 months (n=14). No significant differences in the rate of intracranial hemorrhage with neurological deterioration, mortality and restitution of the pre-existing functional status were observed in the comparative analyses. CONCLUSIONS IV re-thrombolysis may be safe and effective when recurrent stroke occurs after a period of complete neurologic regression lasting at least 24h or minor disability (mRS score ≤2) lasting at least 3 months since the previous stroke.

Blue rubber bleb nevus syndrome with late onset of central nervous system symptomatic involvement

Blue rubber bleb nevus syndrome is a rare vascular disorder characterized by cavernous angiomas of skin and other organs including the gastrointestinal tract. The central nervous system involvement is seldom reported, and neurological symptoms at onset in adulthood are extremely rare. Here, we describe a case of 82-year-old patient presenting multiple skin haemangiomas for some years, who was admitted for a brain hemorrhage. The MRI demonstrated the presence of multiple cavernous angiomas within the cerebral tissue.

Intravenous thrombolysis on early recurrent cardioembolic stroke: “Dr. Jekyll” or “Mr. Hyde”?

Early recurrent cardioembolic stroke on the previously unaffected side has very rarely been reported during or after intravenous recombinant tissue plasminogen activator for acute ischemic stroke. For these cases, thrombolysis guidelines lack any clear recommendation. We report two cases of thrombolysed stroke patients, with paroxysmal atrial fibrillation but normal sinus rhythm on admission, who respectively developed recurrent ischemic stroke within few hours after complete improvement and during intravenous recombinant tissue plasminogen activator infusion. Intravenous thrombolysis was successfully repeated after echocardiographic evidence of left appendage thrombus in the first case and discontinued before complete administration in the second.