Plasma homocysteine and severe white matter disease.

The objective of this study was to assess if high total plasma homocysteine (tHcy) levels are a risk factor for severe leukoaraiosis (LA). This case-control study was done in a primary care neurology ward and included 178 consecutive patients. Patients with severe LA at CT scan were compared with patients without any LA regarding age, cerebrovascular risk factors, tHcy, vitamin B12, folate, creatinine levels and dementia. Multivariate logistic regression was used to find variables independently associated with severe LA. Age (odds ratio [OR], 1.10 per year; p<0.0001), tHcy (OR, 1.07/micromol/l increase; p=0.045) and hypertension (OR, 2.97; p=0.007) were significantly associated with severe LA. Total homocysteine levels are associated with severe LA independently of other risk factors for cerebrovascular disease. This may suggest that decreasing tHcy may help preserve the integrity of the brain white matter.

Spontaneous dissection of carotid and coronary arteries.

The authors report a case of spontaneous dissection of both carotid arteries, followed by spontaneous dissection of the left anterior descending coronary artery after a few days. No major abnormalities of collagen production were found. This case may be underlain by a dysplasia of common precursors of the carotid and coronary walls.

Large demyelinating brain lesion mimicking a herniating tumor.

We describe the case of a large brain lesion whose computed tomography appearance and clinical evolution mimicked a herniating tumor. The patient progressed to coma within 6 days of hospitalization despite high-dose steroid treatment. Emergency excision of the lesion was carried out. Histological analysis showed massive demyelination, axon preservation and no tumor cells. No lesion recurrence was seen during a 55-month follow-up. Recognition of such lesions through magnetic resonance imaging or spectroscopy may spare unnecessary surgery or biopsy. However, our case shows that such lesions may still require resection in the face of a rapid clinical progression and poor response to medical treatment.

Experience with a questionnaire administered by emergency medical service for pre-hospital identification of patients with acute stroke.

We prospectively verified whether an ad-hoc questionnaire administered by phone supports pre-hospital suspicion of stroke in order to reduce the time before care is given. From June 1996 to May 1997, physicians of the Emergency Medical Service in the area of Bergamo, Italy asked all people calling for a patient with symptoms and signs suggesting a cerebral vascular injury to immediately answer some questions on common symptoms and signs of stroke. The medical records of the patients hospitalized at Ospedali Riuniti of Bergamo were reviewed at the end of the study by a single neurologist, skilled in stroke management and blinded to the questionnaires. Sensitivity and specificity, in addition to positive and negative predictive values, of single questions versus final diagnosis were assessed. Logistic regression analysis was also performed to identify those questions useful to suspect strokes. We collected 143 valid questionnaires, related to 63 men and 80 women, aged 34-99 years (mean, 71.8 years). The question concerning headache had the lowest sensitivity and specificity, respectively 57.1% and 36.5%, and the question concerning leg palsy had the highest sensitivity and specificity, respectively 82.0% and 52.4%. Multivariate analysis identified questions on facial and leg palsy as independent predictors of a final diagnosis of stroke. A few questions on motor deficits proposed by emergency medical service operators may be useful in the pre-hospital identification of stroke patients. Concordance of any questions versus final diagnosis of stroke was, however, far to be satisfying. Thus, our experience supports the need for an educational program to improve the efficiency of a pre-hospital diagnosis of stroke.

Doppler microembolic signals predict ischemic recurrences in symptomatic carotid stenosis.

OBJECTIVE: To assess if Doppler microembolic signals (MES) associated with > or = 60% symptomatic extracranial carotid stenosis may predict ischemic recurrences before endarterectomy or angioplasty. METHODS: All patients with > or = 60% carotid stenosis with symptoms in the preceding 2 months were prospectively considered. MES were identified using current criteria. All patients were followed-up until endarterectomy or angioplasty. RESULTS: We studied 50 patients, at a median of 7 days from their last symptom. Twenty patients showed MES (40.0%); median embolus rate was 4/h. During a median follow-up of 19 days 7 patients had recurrences (transient monocular blindness = 2; TIAs=4; stroke=1); 6 of them had shown MES. The association between recurrences and MES was significant (P=0.012). CONCLUSIONS: MES may identify patients with symptomatic carotid stenosis who are likely to suffer an ischemic recurrence before endarterectomy. This information may affect medical treatment and referral to the vascular surgeon.

Recurrence after first cerebral infarction in young adults.

OBJECTIVE: We have investigated recurrence of stroke in a consecutive series of young adults, aged 16 to 45 years, after a first cerebral infarction. METHODS: From January 1, 1988 to December 31, 1996 we submitted those patients to a diagnostic protocol including angiographic, cardiological, and haematological investigations. The patients were followed at 6 month intervals up to December 31, 1998. RESULTS: We have evaluated and followed-up 135 patients, 71 men and 64 women, who were 3.99% of all the admitted stroke patients. At 12 months after stroke, 83 patients had returned to work, 40 patients were mildly to moderately handicapped, 4 were using a wheel-chair, and 8 had died. Follow-up was 26 to 123 months (mean 68.8). Recurrence of stroke, always of ischaemic nature, was seen in 15 patients (11.1%), 3 to 76 months after the first stroke (mean 27.4), for an annual incidence of 2.26%. Recurrence was significantly associated with Partial Anterior Circulation Syndrome and Haematological subtype of first stroke (respectively, P = 0.0209 and P = 0.0135, chi2 test), but not with age (< or = or > 35 years) or risk factors. Repetition of stroke was never fatal, but it caused heavy disability in 13 patients, 8 of whom had completely or nearly completely recovered after the first event. CONCLUSIONS: Our data suggest that recurrence of stroke is a major clinical problem also for the patients aged less than 45 years and that it might be more frequent with specific clinical syndromes and etiologic subtypes of first stroke.

Carotid stents are not a source of microemboli late after deployment.

OBJECTIVES: To evaluate the presence of microembolic signals (MES) in the middle cerebral artery distal to a stented carotid artery late after stent deployment. MES may be a signal of thrombus formation at the stent level. PATIENTS AND METHODS: Two patient groups were studied with transcranial Doppler at different intervals after deployment of Palmaz stents or Wallstents for stenosis of the internal or common carotid artery. Group 1: from 6 to 12 months after stent deployment; Group 2: > 12 months after stenting. RESULTS: One out of 19 patients in Group 1 showed MES (5.0%); however, this patient also had two mechanical heart valves. None out of 17 patients in Group 2 had MES. CONCLUSIONS: Carotid stents seem to have a very low emboligenic potential after the early post-deployment period. This is a reassuring message for present and future patients harboring such stents.

Length of hospitalization of patients with transient ischemic attacks.

OBJECTIVE: To investigate factors that influence length of stay (LOS) in patients hospitalized for transient ischemic attacks (TIAs). This may help to reduce unnecessary days of hospitalization. DESIGN: Retrospective study. SETTING: A large, non-academic general hospital. PATIENTS: All patients hospitalized for TIAs during the years 1996-1998 were retrospectively studied. We analyzed the relationship between demographic, clinical and management features and LOS. RESULTS: We studied 157 patients. Median LOS was 8 days (range, 1 to 21 days). Statistical analysis showed that female sex, being hospitalized in 1996, hospitalization from Wednesday through Saturday, and second-level cardiological, neuroradiological and miscellaneous investigations significantly increased LOS. CONCLUSIONS: The LOS of patients with TIAs may be reduced through measures that accelerate the diagnostic work-up and by scheduling the admission to the first days of the week, when this is possibile.

An analysis of the costs of ischemic stroke in an Italian stroke unit.

OBJECTIVE: To determine the direct costs of hospital care of acute ischemic stroke in a large Italian hospital, and to identify the main components of such costs. BACKGROUND: Cost containment in stroke care requires an up-to-date assessment of expenditures in the different areas of stroke management. However, costs may vary among countries because of different health system organizations. METHODS: All patients with ischemic stroke admitted during 1996 were considered. Total cost was the sum of a daily component, reflecting personnel wages and general care, and an ancillary component, reflecting mostly investigations and treatments. The real costs were used, not fixed charges. RESULTS: We included 245 patients, with a mean length of stay (LOS) of 13.1+/-7.0 days, and an in-hospital case fatality rate of 8.2%. The mean total cost per patient was 5,087,000+/-2,536,000 Italian Lira (LIT; $3,289+/-$1,640), with a mean cost per day of 388,000 LIT ($251). Approximately 80% of total costs were due to the daily component and 20% to the ancillary component. A multiple linear regression model of length of stay, which determines the daily cost, showed that the Rankin score at entry, the clinical syndrome type, and the destination at discharge independently contributed to LOS. A second linear regression model showed that younger age and longer LOS significantly increased ancillary costs. CONCLUSIONS: The containment of hospital costs of ischemic stroke may be achieved mostly through measures that reduce LOS, such as effective treatments and a quicker deployment.

Malignancy and sensory neuropathy of unexplained cause: a prospective study of 51 patients.

OBJECTIVE: To investigate the frequency of cancer developing in patients with peripheral sensory neuropathy of unexplained cause. DESIGN: Prospective study. SETTING: A neurologic unit in a general hospital. METHODS: Following the diagnosis of neuropathy, we searched for occult malignancy. This search was repeated together with neurologic evaluations every 6 months thereafter. Patient recruitment began January 1, 1988, and ended December 31, 1995. The end point of the study was December 31, 1996. RESULTS: In the study period, we observed 363 patients with peripheral sensory neuropathy. Of these, 53 patients without any identified cause of neuropathy were invited to participate in the study. Of the 53, 2 patients refused. Thus, we examined and followed up 51 patients, 42 men and 9 women, with a mean age of 64.5 years (range, 19-80 years). The range between the onset of neurologic symptoms and the diagnosis of neuropathy was 2 to 72 months (mean, 13.9 months). The follow-up period ranged from 14 to 94 months (mean, 51.4 months). In 18 patients (35.3%) (16 men and 2 women) whose mean age at diagnosis of neuropathy was 66.5 years. malignant growths were found 3 to 72 months (mean, 27.4 months) after the onset of the neuropathy. The cancer was in the liver in 4 patients (all had a primary hepatoma), the bladder in 3, the lymph nodes in 3 (all with non-Hodgkin lymphoma), the prostate gland in 2, the lungs in 2 (small cell lung cancer in both), the breast in 1, the pancreas in 1, the sublingual gland in 1, and the bone in 1 (a metastatic sarcoma). CONCLUSIONS: More than one third of the patients with peripheral sensory neuropathy of unexplained cause developed cancer without any predominating type of malignancy.

Early transoesophageal echocardiography in cryptogenic and lacunar stroke and transient ischaemic attack.

OBJECTIVES: To test the hypothesis that transoesophageal echocardiography (TOE) carried out within three days of a first stroke or transient ischaemic attack of cryptogenic or lacunar type may disclose more thrombi or spontaneous echo contrast (SEC) than previously reported. This finding may help early treatment decisions. METHODS: Patients aged between 40 and 80 years, admitted for transient ischaemic attack or ischaemic stroke during a 40 month period, were prospectively considered. TOE was carried out within 72 hours of symptom onset with a 5 MHz biplanar transducer. Subjects with recurring events, very severe strokes, large artery obstructions, or obvious cardiac sources of embolism were excluded. RESULTS: Sixty five patients were studied, 43 with a cryptogenic stroke or transient ischaemic attack (66.2%), and 22 with a lacunar stroke (33.8%). The mean (SD) interval between symptom onset and TOE was 43.4 (17.2) hours for cryptogenic, and 48.5 (19.5) hours for lacunar patients. Atrial thrombi were found in one patient with a cryptogenic stroke (2.32% of cryptogenic events; 95% confidence interval 0.06-12.29), whereas SEC was found in five patients (7.7% overall), two with a lacunar and three with a cryptogenic stroke. CONCLUSIONS: An early TOE does not seem to increase substantially the detection of atrial thrombi or SEC in patients with a first stroke or transient ischaemic attack of cryptogenic or lacunar nature. Therefore, this examination can be carried out when the patients' conditions are stable, and without overloading the cardiovascular laboratory daily schedule.

Cerebral venous thrombosis in young adults. Experience in a stroke unit, 1988-1994.

We report a series of nine patients younger than 45 years with angiographically-documented cerebral venous thrombosis, consecutively referred to our Stroke Unit from 1988 to 1994. Two of them were men and seven were women. Eight patients initially complained of headache, often associated with other symptoms of increased intracranial pressure. Seven patients had focal motor deficits and four suffered from epileptic seizures. None of the patients died. Only one patient remained severely disabled, whereas the others recovered self-sufficiency within two months. The use of oral contraceptives was closely associated with the occurrence of venous thrombosis in the women. Cerebral venous thrombosis is to be kept in mind in the differential diagnosis of stroke in the young.

Dementia after first stroke.

BACKGROUND AND PURPOSE: Cognitive deficits may significantly worsen the quality of life after stroke. Our aim was to determine the frequency of dementia in a consecutive series of previously nondemented patients between the ages of 40 and 79 years at 3 months after a first ischemic stroke. METHODS: All patients admitted to our department during an 18-month period who met the above criteria were visited and tested and underwent a CT scan 3 months after their stroke. Dementia was diagnosed according to criteria of the National Institute of Neurological Disorders and Stroke and AIREN, but cases with aphasia were not excluded. RESULTS: Of 304 patients admitted for stroke, 146 were eligible for study. Eleven refused to participate, 25 were dead at 3 months, and 110 were tested. Fifteen patients were demented (13.6%; 95% confidence interval [CI], 7.8% to 21.5%), and six had severe isolated aphasia, neglect, or memory deficit (5.4%). Excluding patients with aphasia, 5.0% of cases showed dementia (95% CI, 1.6% to 11.3%). The frequency of dementia was 24.6% (95% CI, 14.5% to 37.3%), considering only patients with supratentorial lesions and with residual deficits of elementary functions (paresis, sensory deficits) at the time of examination. Demented patients had significantly more diabetes (P<.029), atrial fibrillation (P=.032), aphasia at entry (P<.001), large middle cerebral artery infarctions (P=.001), and a more severe neurological deficit at entry (P=.003) and at 3 months (P=.001). At CT scan, demented patients had a larger mean volume of the recent lesion (P<.001) and more lesions in the frontal lobe (P=.041). An exploratory multivariate analysis selected age between 60 and 69 years (odds ratio [OR], 45.8; 95% CI, 2.9 to 726.0), diabetes (OR 59.4; 95% CI, 4.3 to 821.0), aphasia (OR, 14.8; 95% CI, 2.0 to 111.0), a large middle cerebral artery infarction (OR, 30.0; 95% CI, 2.7 to 334.0), and lesions of the frontal lobe (OR, 9.8; 95% CI, 1.3 to 72.8) as significant independent correlates of poststroke dementia. CONCLUSIONS: Dementia is relatively frequent after a clinical first stroke in persons younger than 80 years, and aphasia is very often associated with poststroke dementia. If aphasic patients are not considered, it may be necessary to screen a very large number of subjects to collect an adequate sample of demented cases.

Prognostic use of ultrasonography in acute non-hemorrhagic carotid stroke.

In order to evaluate whether the results of ultrasound examination may be associated with 30-day outcome, 76 consecutive patients (43 men and 33 women; mean age 68.1 +/- 8.9 years) underwent duplex scanning of the carotid bifurcations and transcranial doppler investigation of the basal skull arteries within the first few hours of the onset of an acute carotid stroke. Forty-three patients (56.6%) had appropriate arterial occlusion at ultrasounds examination. On day 30, 22 patients (28.9%) were self-sufficient, 41 (53.9%) were disabled and 13 (17.1%) were dead. The chi-squared test showed that the ultrasound results were significantly related to 30-day outcome (p = .0003). After logistic regression analysis, the ultrasound results remained independent predictors of 30-days outcome (p = .0129), together with neurological impairment 24 hours after stroke onset and lesion size at control computed tomography. Our study suggests that the results of ultrasound examination may be useful in the management of acute carotid stroke as an early indicator of patients with a worse prognosis.

Intra-arterial thrombolysis in acute ischaemic stroke: experience with a superselective catheter embedded in the clot.

OBJECTIVES: To report experience of intra-arterial thrombolysis for acute stroke, performed with a microcatheter navigated into the intracranial circulation to impale the clot. METHODS: Patients were selected on the following criteria: (1) clinical examination suggesting a large vessel occlusion in stroke patients between 18 and 75 years; (2) no radiographic signs of large actual ischaemia on CT at admission; (3) angiographically documented occlusion of the middle cerebral artery (MCA) stem or of the basilar artery (BA), without occlusion of the ipsilateral extracranial internal carotid artery or of both the vertebral arteries; (4) end of the entire procedure within six hours of stroke. 12 patients with acute stroke were recruited, eight of whom had occlusion of the MCA stem and four of the BA. Urokinase was used as the thrombolytic agent. RESULTS: Complete recanalisation in six MCA stem and in two BA occurred, and partial recanalisation in two MCA stem and one BA. There was no recanalisation in one BA. A clinically silent haemorrhage occurred in two patients, and a parenchymal haematoma in one patient, all in MCA occlusions. At four months five patients achieved self sufficiency (four with MCA and one with BA occlusion). Six patients were dependent (three totally), and one died. CONCLUSIONS: The strict criteria of eligibility allowing the enrollment of very few patients and the procedure itself, requiring particular neuroradiological expertise, make this procedure not routine. Nevertheless, the approach can be considered a possible option for patients with acute ischaemic stroke.

Anticardiolipin antibodies in acute non-hemorrhagic stroke seen within six hours after onset.

INTRODUCTION: We have undertaken a prospective study to measure anticardiolipin antibodies of IgG isotype within the first few hours of an acute non-hemorrhagic stroke. MATERIAL AND METHODS: We have collected blood samples at entry from one hundred patients (53 men and 47 women), mean age 67.4 years, referred within 6 h of a first-ever non-hemorrhagic stroke, and from an equal number of age- and gender-matched control patients. RESULTS: IgG anticardiolipin antibodies were > or = 10 GPL in 26 patients and in 5 controls (p < 0.0001, X2 test). After logistic regression analysis, increase of IgG anticardiolipin antibodies remained independently associated with stroke (p = 0.0034), together with hypertension (p = 0.0009) and atrial fibrillation (p = 0.0238). CONCLUSION: Our data suggest that the occurrence of elevation of IgG anticardiolipin antibodies in stroke patients should antedate stroke onset and might be a risk factor per se.

Comparative study of terfenadine and cetirizine in hay fever: assessment of efficacy and central nervous system effects.

A daily dose of either terfenadine 120 mg or cetirizine 10 mg was compared in two parallel groups of patients suffering from hay fever. According to a double-blind, double-dummy, randomized design, 28 patients were treated with one of the two drugs once daily in the morning for 2 weeks during the 1990 grass pollen season. The severity of nasal congestion, rhinorrhea, sneezing, nasopharyngeal itching and itchy, watery, red eyes was evaluated by the investigator after a 1-week run-in period and at the end of the treatment. The patients made a daily record of the severity of symptoms on a diary card. In addition, drug-related central nervous system (CNS) effects were assessed at baseline and at the end of the treatment by neuropsychological tests aimed at investigating selective and sustained attention, visuomotor abilities and anxiety, and by quantitative, bit-mapped EEG. Both terfenadine and cetirizine produced a significant improvement in symptoms at endpoint without any significant difference between the two drugs. Drowsiness was referred by one patient in each treatment group. No significant impairment of psychomotor performance occurred with either drug. Quantitative EEG showed a significant power increase in the relative (%) delta band in both groups of treated patients. Although the difference was not statistically significant, a tendency towards greater involvement of the CNS was observed with the use of cetirizine. In conclusion, the results of this study confirm that terfenadine and cetirizine are equally effective in the management of hay fever. Some differentiated untoward EEG changes were also observed in relation to the drugs used, without any variation in neuropsychological performance.

Essential thrombocytemia and ischemic stroke: report of six cases.

Essential thrombocytemia (ET) is a clonal myeloproliferative disorder of unknown cause, characterized by an increased number of apparently normal platelets. It has been related to a large number of mild ischemic complications, but rarely to acute stroke associated with documented large vessel thrombosis. We report the cases of 6 patients with acute ischemic stroke associated with ET (4 men and 2 women; mean age 61.7: range 49-78 years). The diagnosis of ET followed the onset of the stroke. The number of platelets was never greatly increased at the time of the stroke, and two patients presented no major risk factors for stroke. The involvement of the posterior circulation was observed in three patients, that of the anterior circulation in two patient and that of the border territory in one. The obstruction of large intracranial or extracranial vessels was detected in all of the patients, and all of them were treated with antiplatelet agents (aspirin or ticlopidine). The outcome was good in 3 patients, fair in one and bad in two. We retain that ET might be a cause of acute ischemic stroke as a result of large vessel obstruction.

Brain involvement in myotonic dystrophy: MRI features and their relationship to clinical and cognitive conditions.

A prospective, case-control study was carried out on 25 patients with myotonic dystrophy (MyD) and 25 healthy subjects using brain magnetic resonance imaging (MRI). The frequency and severity of white matter hyperintense lesions (WMHL) and brain atrophy in MyD patients were compared with their clinical features and cognitive impairment using an extensive neuropsychological battery. Eighty-four per cent of MyD patients showed WMHL, compared with 16% of controls (p < 0.0001). These lesions involved all cerebral lobes, without hemispheric prevalence. Twenty-eight per cent of MyD patients also showed particular WMHL at their temporal poles. Myotonic patients had significantly more cortical atrophy than controls. No relationship between atrophy and WMHL was found on the MRI scans. The extent of brain abnormalities (WMHL or atrophy) was not correlated to age, disease duration, physical disability or severity of neuropsychological impairment. Central nervous system abnormalities revealed by MRI appear to be an almost constant feature of MyD, but they are not found to be related to clinical or cognitive parameters. Their nature is still unclear: some of them, located at the temporal poles, seem to be characteristic of the disease, while others small, diffuse WMHLs, similar to the age related alterations revealed by MRI occurring during young and adult age in MyD patients.

Immediate anticoagulation with heparin for first-ever ischemic stroke in the carotid artery territories observed within 5 hours of onset.

OBJECTIVE: To evaluate the safety and possible efficacy of heparin sodium anticoagulation within 5 hours of the onset of first-ever nonlacunar ischemic strokes in the internal carotid artery territories. DESIGN: Pilot study, prospective and open. SETTING: Inpatient stroke unit. PATIENTS: Of 360 stroke patients observed during 13 months, 45 (12.5%) were included in the study. INTERVENTIONS: Heparin sodium was administered intravenously, starting with a bolus of 10,000 U, followed by continuous infusion over 4 days at a rate adjusted to maintain an activated partial thromboplastin time ratio between 2 and 2.5. The mean interval from stroke to treatment was 197 minutes. RESULTS: Two patients had cerebral hemorrhage, one of which was fatal. None had extracranial major bleeding, while six had minor bleeding. The conditions of 23 patients improved, 16 patients were stable, and six patients worsened by day 1, while 29 patients improved, eight patients were stable, and eight patients worsened by day 7. Six patients died by the first month and five more by the sixth month. Twenty-one patients were self-sufficient, both at 1 and 6 months. Hemorrhagic complications were unrelated to any investigated factor. Multivariate analysis indicated that short-term outcome was predicted only by infarct size (P < .0001) and long-term outcome by infarct size (P = .002) and large vessel status (P = .0235). CONCLUSIONS: Our study suggests that immediate heparin treatment for ischemic carotid stroke is feasible and generally safe and that patients whose conditions improve are those with smaller infarct size and no evidence of large vessel obstruction.