Simona Fanucchi

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.

Prevalence of stroke and transient ischaemic attack in the elderly population of an Italian rural community

Objectives: To evaluate the prevalence of stroke and transient ischaemic attack in the elderly population, including the oldest residents, of a rural Italian community. Methods: A door-to-door survey was performed between April and October 2001 in 2390 subjects aged 65 years and over. A symptom questionnaire validated by medical records and neurological examination was employed. Results: Complete information was available for 2260 subjects. The overall prevalence of stroke was 8.2% in males and 5.1% in females. In the very elderly, this increased to 10.7% in males and 10% in females and decreased only in males aged 90 years or over. The overall prevalence of transient ischaemic attack was 7% in males and 4.9% in females. This, too, increased with age, reaching 10.2% in males and 7.4% in females and decreased only in subjects of both sexes aged 85 years or over. Conclusions: An actual estimate of the high prevalence of cerebrovascular disease in the elderly population, even in very old subjects, was thus achieved. Appropriate health care services consequently need to be planned.

The extent of right-to-left shunt fails to correlate with severity of clinical picture in migraine with aura

Several investigations have documented an increased incidence of right-to-left shunt (RLS) in migraine with aura (MA) and have emphasised its role in the physiopathology of aura; so far, however, no data are available concerning a possible correlation between the extent of the RLS and the clinical picture of MA patients. To investigate the possible relationship between the extent of the RLS, revealed by the number of microbubbles (MB) detected during transcranial Doppler with IV injection of ultrasound contrast (TCDc), and the clinical characteristics of MA (age at first onset of migraine, mean annual frequency of attacks and mean duration of the aura phase), 30 consecutive patients with typical aura and migraine headache positive on TCDc evaluation for RLS were enrolled. Permanent RLS was found in 12 patients and latent RLS was found in 18 patients; of these, 6 had a high-grade RLS, 5 medium-grade RLS and 7 low-grade RLS. No correlation has been documented between the number of MBs and the clinical parameters of both patients with latent shunts and those with permanent ones, nor between the clinical parameters of the two groups of patients. These data show that RLS does not seem to affect the clinical manifestation of MA and that the extent of RLS fails to correlate with the severity of the clinical picture of the disorder.

Can microembolic signals identify unstable plaques affecting symptomatology in carotid stenosis

To the Editor: We read with interest the article by Liapis et al1 on factors affecting symptomatology in carotid stenosis and agree that factors other than the degree of stenosis are important in determining increased risk of neurological events. Authors observed that ultrasonically echolucent plaques show a trend toward higher frequency of neurological events likely due to an increased lipid content, rendering them more vulnerable to rupture. Nevertheless, ultrasonographic evaluation of plaque morphology may fail to identify unstable plaques showing embolic activity likely due to inflammatory factors2 able to determine from time to time fluctuations of the risk of neurological events. Previous small studies have suggested that asymptomatic microembolic signals (MES) detected by transcranial Doppler (TCD) in middle cerebral arteries may predict symptoms occurrence,3,4⇓ and a large multicenter study was planned to determine whether MES are an independent predictor of neurological events in patients with asymptomatic ≥70% carotid stenosis.5 We evaluated 21 patients (13 males and 8 females, mean age 75.2 years, range 62 to 84 years) with asymptomatic ≥70% carotid stenosis documented by selective angiography according to NASCET criteria. Echocardiography was performed to exclude cardioembolic sources, and antiplatelet treatment (acetylsalicylic acid 100 mg daily in 15 cases and ticlopidine 500 mg daily in …

Stroke Symptoms and the Decision to Call for an Ambulance: Turn on People’s Minds!

To the Editor: We read with great interest the article by Mosley et al1 on factors related to calling an ambulance for stroke patients. The authors reported that “stroke” was referred as the problem (unprompted) by ≈50% of callers, whereas fewer than half of the calls were made within 1 hour from symptom onset. We agree with the authors on the necessity of interventions to more strongly link stroke recognition to immediate action to increase the number of stroke patients …

dissection and atherosclerosis of carotid arteries in the young: role of the apolipoprotein E polymorphism

Twenty‐seven young (<50 years old) patients with spontaneous carotid artery dissection in 11 cases and carotid atherosclerosis in 16 cases were evaluated to determine the apolipoprotein E polymorphism. At the DNA analysis the ɛ3/ɛ3 genotype was observed in all patients with dissection, in 13 of 16 (81.2%) patients with atherosclerosis and in 27 of 30 (90%) controls. Three of 16 (18.8%) patients with atherosclerosis and 3 of 30 (10%) controls presented with the ɛ4/ɛ3 genotype, and this difference was not statistically significant. Moreover, observation of the ɛ4/ɛ3 genotype was not significantly higher in patients with atherosclerosis compared with those with dissection. No homozygote ɛ4/ɛ4, ɛ2/ɛ2 or heterozygote ɛ2 genotype was observed. No correlation was found between the presence of the ɛ4/ɛ3 genotype and vascular risk factors. Therefore, the ɛ4 allele seems to be involved in carotid premature atherosclerosis development whereas it may appear to be protective for artery dissection occurrence. A larger sample size is needed to support this suggestion.

Thrombolysis for Acute Stroke: What about the Actual Impact on Patients Older Than 80 Years?

abled at discharge (median mRS at discharge 3.9, range 3–5 vs. median mRS at admission 2.4, range 2–3). Both hospital stay length [4] and disability rate [5] could probably have been reduced by thrombolysis. In our analysis, 2 patients aged 80 with ischemic stroke were admitted within 3 h of symptom onset and were excluded from thrombolysis because of severe stroke. Treatment of 80-year-old patients – according to Zeevi’s age dichotomization data [1] – would have further increased the number of elderly patients who could have benefited from treatment. Based on our data, we estimate that about one third of patients aged 1 80 years with ischemic stroke arriving at hospital within 3 h of stroke onset could be treated, that is 7/62 (11.3%) of elderly stroke patients. This percentage could be higher if we consider that late admission to a hospital providing thrombolysis represents the most relevant modifiable barrier to delivering treatment, involving up to 84% of stroke patients [6, 7] . Our data confirm that rtPA treatment should also be implemented in carefully selected elderly patients. We read with great interest the study by Zeevi et al. [1] evaluating acute stroke management in the elderly. The authors found that early treatment with rtPA in patients 1 80 years appears to be both safe and efficacious. The issue of thrombolysis in the elderly has previously been addressed by other groups and is summarized in a recent review [2] , which concluded that, in spite of a poorer outcome compared to younger patients, there is a spectrum of benefit from thrombolysis in this group. Even if the results of a specific trial are not available at the moment, these data support the hypothesis that older age stroke patients should not be excluded from thrombolysis because of age alone [3] . Thus, the elderly could benefit from thrombolysis, but what would its actual impact in clinical practice be? To elucidate this issue, we retrospectively reviewed data from patients admitted to our hospital for acute stroke in 2005. Twohundred and fifty-eight patients [median age 71 years, range 19– 97, 62/258 (24.0%) at age 1 80 years] were admitted, but only 102/258 (39.5%) arrived within 3 h of stroke onset and, in 72/102 (70.6%), cranial computed tomography showed no hemorrhage or neoplasm. Fifty-one of 72 (70.8%) patients were aged ̂ 80 and 12/51 (23.5%) had undergone thrombolysis, with no subsequent symptomatic intracranial hemorrhage. Twenty-one of 72 (29.2%) were 1 80 years old (median age 84 years, range 81–90) and none of them was treated according to the SITS-MOST selection criteria, which prevent thrombolysis in the elderly. However, only 7/21 (33.3%) presented no other defined exclusion criteria [minor neurological deficit or symptoms rapidly improving before start of infusion in 2/21 (9.5%); severe stroke in 7/21 (33.3%); prior stroke within the previous 3 months in 2/21 (9.5%); major surgery in the previous 3 months in 1/21 (4.8%); oral anticoagulant treatment with INR 1 1.7 in 1/21 (4.8%); arrival at the limit of the 3-hour time window in 1/21 (4.8%)]. These patients (median age 85.6 years, range 82–90; median NIHSS at admission 15.7, range 8–24) had a median hospital stay of 22.7 days (range 12–35) and were all disPublished online: November 27, 2007

Contents Vol. 24, 2007

483 Third International Stroke Summit Wuhan, China, November 1–3, 2007 Chairpersons: Liu, X. (Nanjing); Kaste, M. (Helsinki); Zhang, S.; Zhang, J. (Wuhan); Chopp, M. (Detroit, Mich.); Li, C.; Chen, G. (Wuhan); Xu, G. (Nanjing) (available online only)

Stroke in the young as the clinical onset of non‐Hodgkin's lymphoma with paraneoplastic endocarditis

Stroke in the young is rather unusual, because <5% of strokes occur in subjects under 45 years of age, with a global incidence of 10 of 100000 people (Marini and Carolei, 2003) and it presents an undetermined aetiology in 23.5% of cases (Lee et al., 2002). Non-bacterial thrombotic endocarditis (NTE) is a rare cause of cardioembolic stroke (Di Tullio and Homma, 2002) because of complex pathological processes involving platelets and fibrin leading to blunt fibrin-platelet thrombus on cardiac valves in the absence of microorganisms . The valvular lesions of NTE usually affect the mitral and aortic valves (Biller et al. 1982; Lopez et al., 1987) and can complicate any type of cancer except brain tumour leading to a risk of cerebral embolism. The highest incidence has been reported with lymphoma, carcinoma of the gastrointestinal tract and carcinoma of the lung, as documented both in autopsic (Ondrias et al., 1985; Reisner et al., 1992) and in echocardiographic findings (Edoute et al., 1997). In autopsies of the general population the prevalence of NTE ranges from 0.3 to 9.3% (Chino et al., 1975), whereas the post-mortem prevalence among cancer patients has been reported to be up to 1.3% (Ondrias et al., 1985). Nevertheless, ante-mortem diagnosis of NTE is rare (Edoute et al., 1997). We report the case of a young man suffering from cardioembolic stroke as the clinical onset of nonHodgkin’s lymphoma with paraneoplastic endocarditis. A 47-year-old White male, a smoker and without other vascular risk factors, arrived in hospital 6 days after sudden impairment of the vision in his left side. The neurological examination showed left homonymous hemianopsia and no other deficit. A cranial computed tomography (CT) scan documented a hypodense area in the right occipital-mesial cortical-subcortical region indicating an ischaemic lesion. Both duplex-scanner of the cervical arteries and transcranial Doppler showed no stenosis, whereas transcranial Doppler microembolic signals were detected in the posterior cerebral arteries. Transthoracic echocardiography demonstrated a mild aortic valvular regurgitation and the transesophageal approach revealed an aortic valvular vegetation (4 · 7 mm) indicating endocarditis (Fig. 1). Laboratory blood tests including rheumatological (ACA, FANHEP 2, AMA, ASMA, ANTI-ENA, ACLA) and coagulative tests (AT-III, C-Protein, S-Protein, APC resistance and V Factor) were normal. Repeated cultures of blood yielded no growth of microorganisms. A cranial magnetic resonance imaging performed a few days afterwards confirmed a right occipital-mesial cortical-subcortical ischaemic lesion with a slightly haemorrhagic transformation. Chest X-rays documented a right paramediastinal lesion diagnosed as non-Hodgkin’s lymphoma through CT scan and biopsy. The patient was treated first with oral anticoagulants and then with acetylsalicylic acid 100 mg daily because of the high risk of bleeding due to the progression of the neoplastic disease. A clinical systemic impairment with persistence of the left hemianopsia and the echocardiographic valvular vegetation was observed after 6 months of follow-up. This case stresses the need to investigate for a neoplastic disease in young patients with stroke because cerebral infarction can be the first manifestation of a potentially curable cancer. In fact, in this case the non-Hodgkin’s lymphoma was asymptomatic and it was diagnosed only during the aetiopathogenetic study of the stroke. Approximately 15% of patients with cancer have cerebrovascular disease and the care and prognosis of these patients differ from those in patients with stroke but without neoplastic disease (Arboix et al., 2001). Both valvular deformation and a hypercoagulable state have been involved in the genesis of this paraneoplastic endocarditis. On this matter, Chatuverdi et al. (1994) reported that hypercoagulopathy caused the stroke in 10 of 33 patients with cancer. In particular, acquired Protein C and Protein S deficiencies may be associated with a variety of diseases including malignancies (Coull et al., 1998). The negativity of coagulative markers such as Protein C and Protein S deficiencies increases the unusual presentation of this case. Therefore, especially when stroke in the young results to be because of an undetermined cause, a systematic cancer search program is recommended because a neoplastic disease may be underestimated in these cases.