Alvaro Andreoli

Subarachnoid hemorrhage: frequency and severity of cardiac arrhythmias. A survey of 70 cases studied in the acute phase.

The frequency and severity of cardiac arrhythmias were studied in 70 patients with spontaneous subarachnoid hemorrhage investigated prospectively with 24-hour Holter monitoring. Patients were less than 70 years old and without clinical and/or ECG signs of previous heart disease; Holter monitoring was initiated within 48 hours of subarachnoid hemorrhage. Arrhythmias were detected in 64 of the 70 patients (91%). Twenty-nine of the 70 patients (41%) showed serious cardiac arrhythmias; malignant ventricular arrhythmias, i.e., torsade de pointe and ventricular flutter or fibrillation, occurred in 3 cases. Serious ventricular arrhythmias were associated with QTc prolongation and hypokalemia. No correlation was found between the frequency and severity of cardiac arrhythmias and the neurologic condition, the site and extent of intracranial blood on computed tomography scan, or the location of ruptured malformation. The extremely high incidence of cardiac arrhythmias, sometimes serious, in the acute period after subarachnoid hemorrhage and the absence of clinical and radiologic predictors make systematic continuous ECG monitoring compulsory to improve the overall results of subarachnoid hemorrhage, irrespective of early or delayed surgical treatment.

Holter detection of cardiac arrhythmias in intracranial subarachnoid hemorrhage

To determine the frequency and severity of cardiac arrhythmias in intracranial subarachnoid hemorrhage, 120 nonselected patients were prospectively studied by 24-hour Holter monitoring. Arrhythmias were found in 96 of 107 patients (90%) with adequate Holter recording: ventricular premature complexes in 49, nonsustained ventricular tachycardia in 5, supraventricular premature complexes in 29, paroxysmal supraventricular tachycardia or atrial fibrillation in 9, sinoatrial block and arrest in 29, second-degree atrioventricular block in 1, atrioventricular dissociation in 4 and idioventricular rhythm in 2. Life-threatening ventricular arrhythmias (torsades de pointes-type ventricular tachycardia) occurred in 4 patients, degenerating into either ventricular flutter or fibrillation in 2. ST-segment changes suggestive of acute transitory myocardial ischemia were found in 8 patients (1.5 mm or more of ST depression in 7 patients and 1.5 mm or more of ST elevation in 1 patient). The frequency and severity of arrhythmias were significantly higher in patients studied within 48 hours of subarachnoid hemorrhage; serious ventricular arrhythmias were associated with QTc prolongation more than 550 ms and with hypokalemia less than 3.5 mEq/liter. No correlation was found between age, clinical condition, site and extent of subarachnoid hemorrhage and either the occurrence or severity of arrhythmias. The results of our study indicate an extremely high incidence of arrhythmias, sometimes serious, in subarachnoid hemorrhage, especially in the first 48 hours after hemorrhage. Continuous electrocardiographic monitoring is therefore mandatory.

Cerebral ischemia and asymptomatic coronary artery disease: a prospective study of 83 patients.

A prospective cardiologic evaluation was performed in 83 consecutive patients with transient cerebral ischemia or mild stroke and without symptoms or electrocardiographic signs of ischemic heart disease. Patients were studied with an electrocardiographic exercise test; a positive test was followed by exercise Thallium-201 myocardial scintigraphy. Results were compared to those obtained in a group of 83 age and sex-matched healthy subjects submitted to the same study protocol. Asymptomatic coronary artery disease was detected in 28% of cerebrovascular patients with adequate electrocardiographic exercise test. A scintigraphic perfusion defect of variable extension was found in 19 of them. In the control group the electrocardiographic exercise test was positive in only 6% (p less than 0.01). Our results support the concept that: asymptomatic ischemic heart disease is often associated with cerebrovascular disease; therefore cerebral ischemic attacks may be a marker of coronary artery disease, an active investigation of the heart should be considered in cerebrovascular patients in order to plan optimal, comprehensive management.

O6-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications

O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age > or = 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval > or = 3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.

Preoperative noninvasive coronary risk stratification in candidates for carotid endarterectomy.

Patients with symptomatic carotid stenosis who are candidates for carotid endarterectomy are at high short- and long-term risk of coronary events. To stratify patients at different risk of coronary events we investigated the usefulness of a noninvasive preoperative cardiological workup. Methods We studied 172 consecutive patients admitted to the Neurosurgical Department for symptomatic high-grade (70% to 99%) carotid stenosis (age, 42 to 74 years; mean, 57.8 years). Patients without history of coronary artery disease (CAD) and able to exercise were submitted to exercise electrocardiographic testing (EET) and, if abnormal, to exercise thallium myocardial imaging (TMI). Patients were classified into four groups: group 1, patients without CAD: no history of CAD, normal EET, or normal TMI in the presence of indeterminant EET (n=93, 54%); group 2, patients with silent CAD: no history of CAD and concordant abnormal EET and TMI (n=28, 16%); group 3, patients unable to exercise: no history of CAD and inability to perform adequate EET because of previous stroke or claudication (n=29, 17%); and group 4, patients with known CAD: history of angina or myocardial infarction (MI) (n=22; 13%). Results The four groups were comparable in regard to age, sex, and computed tomographic scan of the brain. The prevalence of stroke was higher in patients unable to exercise; hypercholesterolemia was more frequent in patients with known CAD. During the perioperative period (≤30 days after carotid endarterectomy), coronary events occurred in 3 patients (2%): fatal MI in 2 patients in group 4 and 1 patient in group 3. One hundred percent of patients were followed up for 6.2 years. Coronary events occurred in 23 of the 168 patients discharged from the hospital (13.7%); these were fatal in 11 (6.5%): 3 patients of group 1 (3%; sudden death in 2, fatal MI in 1), 8 patients of group 2 (29%; fatal MI in 5, unstable angina in 3), 8 patients of group 3 (28%; fatal MI in 4, nonfatal MI in 4), and 4 patients of group 4 (18%; fatal MI in 2, sudden death in 1, unstable angina in 1). Kaplan-Meier estimated curves of survival free from fatal and nonfatal coronary events were 97%, 51%, 49%, and 59%, respectively (P<.001, group 1 versus groups 2 and 3; P<.01, group 1 versus group 4). Conclusions Among patients undergoing carotid endarterectomy, coronary events occurred twice as often as cerebral recurrences. A preoperative noninvasive cardiac investigation, including EET, can adequately identify groups of patients with diverse short- and long-term prognoses. In addition to patients with known CAD, those with silent CAD or who are unable to exercise represent, without the need of further investigation, groups at high risk of coronary events in long-term follow-up.

Late seizures in patients with internal carotid and middle cerebral artery occlusive disease following ischaemic events.

The occurrence of post-infarction epilepsy was investigated in 68 patients with angiographically proven internal carotid artery occlusion and in 56 patients with middle cerebral artery occlusion. Epileptic seizures occurred during follow-up in 9% of the carotid artery group and in 21.4% of the middle cerebral artery group. The different incidence of seizures in the two groups was statistically significant. The physiopathological mechanism of the late post-infarction epilepsy is discussed.

Ischemic stroke in young adults: the relevance of migrainous infarction

Sixty-one consecutive patients, £40 years old, were hospitalized for cerebral infarction between 1977 and 1985. Evaluation included computed tomographic brain scan, arteriography, echocardiography, and blood tests. A probable migrainous infarction was diagnosed in six patients (10%) (all women with a history of migraine) who survived the initial stroke and were followed-up for an average of four years. In five patients the stroke occurred during a common migraine attack and in one patient during a classic migraine attack. The site of infarction was invariably the occipital lobe. During the follow-up, no subject had a further stroke. All six women had a permanent hemianopic deficit.

Etiopathogenesis and prognosis of cerebral ischemia in young adults.

ABSTRACT Etiology and long‐term prognosis were prospectively investigated in 155 consecutive patients (96 men and 59 women), aged 16 to 45 years, referred to our Neurosurgical Unit with cerebral transient ischemic attacks or infarction during the period 1978‐1988. All patients underwent neurological and medical‐cardiological evaluation, cerebral computerized tomography scanning, electrocardiogram, and laboratory tests. Two‐dimensional echocardiography was performed in 123 cases (79%), cerebral angiography in 147 (95%). Atherosclerosis was the leading etiology occurring in 48 patients (31%). A cardioemboiic disorder was considered the probable cause of ischemia in 8 cases (5.1%). Further possible etiologies were contraceptive pill assumption (5.8% of the total, but 15.3% within the female group), spontaneous arterial dissection (4.5%), migraine (4%), puerperium (2.6%), cervical trauma (2.6%), and other, more uncommon conditions. Despite extensive evaluation, the cause of cerebral ischemia remained unknown in 40% of cases. All patients received antiplatelet medication and 16 underwent surgery. The long‐term outcome at a mean follow‐up of 5.8 years was favorable: 91% of subjects resumed their work on a full or part‐time basis.

Torsade de pointes and ventricular flutter-fibrillation following spontaneous cerebral subarachnoid hemorrhage

Five cases (3.8%) in a series of 132 patients with spontaneous subarachnoid hemorrhage, studied by 24-hour Holter monitoring, presented with ventricular tachycardia of torsade de pointes variety. In all cases, the arrhythmias were observed within 24 hours after the bleeding. The QTc interval was prolonged more than 0.55 sec, and hypokalemia of less than 3.5 mEq/liter was present in all patients. The clinical status was not significant. Torsade de pointes occurred in comatose patients (3 cases) as well as in alert patients (2 cases). The arrhythmia was reversed by therapy in 3 patients, one of whom survived while 2 died due to cerebral damage. Our observations confirm the presence of life-threatening ventricular arrhythmias in the acute phase of subarachnoid hemorrhage. Continuous electrocardiographic monitoring is therefore advisable in view of its potential role in alerting to the need for treatment.

Cardioembolic stroke from atrial septal aneurysm.

Atrial septal aneurysm is an uncommon occult cardiac source of cerebral embolism. It is usually asymptomatic, and clinical cardiologic examination and electrocardiography fail to reveal its presence. We report a case of a 34-year-old woman with sudden right hemiplegia and aphasia from occlusion of the left carotid siphon in whom an atrial septal aneurysm was detected by two-dimensional echocardiography. The absence of atherosclerotic risk factors and vascular lesions proximal to the carotid occlusion strengthened a causal relation between atrial septal aneurysm and cerebral infarction. Consequently, two-dimensional echocardiography may be advisable in every patient with unexplained ischemic stroke to detect possible occult embolic cardiac abnormalities.