Antti Muuronen

Outcome of 314 patients with transient ischemic attacks.

Between 1967 and 1976, 314 patients with transient ischemic attack (TIA) were evaluated and treated. Follow-up has been from 2.8 to 13.2 years (mean 7.8). As of 1979, 55 of the patients had succumbed to cardiovascular disease (28), cerebrovascular disease (9), malignancy (10), and other causes (8). During the follow-up period, 15 patients suffered brain infarction (4.8% under the risk) while 40 had myocardial infarction (12.7%) under the risk). Brain infarction occurred as often in patients with carotid TIA as in those with vertebral-basilar TIA, and was more common in patients under anticoagulation therapy than in those without it (p less than 0.05). Arterial hypertension, heart disease, peripheral arterial disease and diabetes did not increase the risk of brain infarction, but all (except diabetes) increased the risk of myocardial infarction. Combination of TIA with arterial hypertension, heat disease, or peripheral arterial disease increased the mortality (p less than 0.001). A life table analysis of surviving 1, 5, and 10 years gave probabilities of 99 and 100%, 89 and 91%, and 60 and 75% for males and females respectively. In the case of normotensive and hypertensive patients, a life table analysis of chances of surviving 1, 5, and 10 years gave probabilities of 100 and 95%. 94 and 80%, and 76 and 49% in both groups respectively. The result clearly emphasize treating of arterial hypertension, and demonstrate that TIA is not only a warning sign of impending stroke but also that of myocardial infarction.

Visual and spectral EEG analysis in the evaluation of the outcome in patients with ischemic brain infarction

Serial EEGs were recorded in 15 patients with acute cerebral infarctions in order to study clinical and prognostic correlations. The EEG was recorded within 48 h from the first symptoms and thereafter weekly for 4 weeks. The EEGs were analyzed both visually and with a computerized spectral analysis. Eight of the patients recovered fully and seven had permanent neurological deficits. On admission, 87% of the patients had an abnormal EEG by visual analysis. The spectral parameters correlated well with visual findings, especially the delta and alpha bands. The spectral analysis was superior to visual in predicting the correct laterality of the lesion. It showed the correct side of the lesion in 87%, while the visual did it in only 54% of the cases. The first EEG records reliably predicted the outcome of the patients. The degree of background abnormality was most important in visual EEG analysis. In spectral analysis, parameters from single derivations were superior to the average of all derivations. A high proportion of delta or low proportion of alpha power were reliable indicators of poor outcome.

Mortality from ischaemic heart disease among patients using anticonvulsive drugs: a case-control study.

Patients who use phenytoin and some other anticonvulsive drugs have been shown to have raised concentrations of plasma high density lipoprotein. As this lipoprotein is known to be inversely associated with the incidence of ischaemic heart disease the causes of death of all patients with epilepsy known to be taking anticonvulsive drugs who died during 1978-80 were studied. Of 1399 deaths of anticonvulsant users, 258 (18.4%) were caused by ischaemic heart disease. This was significantly less (p less than 0.001) than the 382 deaths from ischaemic heart disease (27.3%) observed among paired controls matched for sex, age, and date of death. The total cardiovascular mortality was also lower among patients with epilepsy than among controls (p less than 0.02) despite there being more deaths due to cerebrovascular disease among patients. The difference in mortality from ischaemic heart disease was significant for both sexes and was not accounted for by excess deaths due to any other single cause. Users of phenytoin, carbamazepine, and barbiturates (alone or in combination) showed 29% less mortality due to ischaemic heart disease than respective controls (p less than 0.001).

Encephalopathy and neuropathy in end-stage liver disease before and after liver transplantation

The nervous system involvement of 8 patients with end-stage liver disease was evaluated by means of clinical neurological, neuropsychological, neurophysiological and neuroradiological investigation before and 6-12 months after a successful liver transplantation. Preoperatively, all subjects (7 women, 1 man; mean age 40 years, range 30-54 years) exhibited decreased muscle strength and 2 patients manifested clinical signs of polyneuropathy. In neuropsychological tests, slight visuoconstructive apraxia, and disturbances of verbal memory and cognitive function were observed. Magnetic resonance imaging (MRI) revealed cerebral lesions in two patients. After transplantation, muscle strength reverted to normal in all patients, polyneuropathy improved and in all but 2 patients recovery of neuropsychological functioning was observed. Clinical signs of encephalopathy had disappeared. All patients were emotionally better adjusted after transplantation. Four subjects showed new, albeit mild changes in neurophysiological and neuropsychological tests postoperatively. We conclude that the majority of neurological impairment disappeared after liver transplantation. We want to stress that evaluation of neurological sequelae of liver transplantation needs to be based on assessments both before and after liver transplantation.

The clinical versus radiological diagnosis of alcoholic cerebellar degeneration

We report the clinical characteristics of 65 patients with alcoholic cerebellar degeneration as verified by computerized tomography of the brain. Thirty-two patients (49%) had clear clinical signs of the disease such as broad-based staggering gait, impaired heel-to-toe walking, terminal oscillations in heel-knee test and slow (3/s) leg tremor. These signs were virtually absent in 33 patients (51%) who, nevertheless, had radiological signs of cerebellar degeneration. Traumatic brain injuries were more frequent in those patients who had both clinical and radiological signs of alcoholic cerebellar degeneration. Furthermore, this group showed longer periods of heavy drinking, more severe cerebral atrophy and more profound neuropsychological impairment than a control group of 92 alcoholics with neither clinical nor radiological signs of cerebellar disease. We conclude that careful clinical neurological examination is needed to diagnose alcoholic cerebellar degeneration which is apparently a more common disease than first realized. Subclinical cases can be diagnosed with the help of computerized tomography of the brain.

Effects of ethanol on platelet function.

To obtain evidence for an ethanol mediated disruption of hemostasis we compared the effects of acute and chronic ethanol ingestion on platelet reactivity. Since ADP may be important for hemostasis in vivo it was used to induce platelet aggregation in platelet-rich plasma. Thromboxane B2 (TXB2) formed during the aggregation was measured by radioimmunoassay. Ethanol (1.5 g/kg) given to 8 healthy non-alcoholic male volunteers increased platelet reactivity to ADP and the associated TXB2 formation rose from 289 +/- 60 (mean +/- SE) to 984 +/- 263 fmol/10(7) platelets (p less than 0.025). The effects lasted for as long as ethanol was present in blood. In 13 non-cirrhotic male alcoholics the withdrawal of ethanol caused a 4-fold increase in TXB2 formation within one week but the basal levels before ethanol withdrawal were the same as in controls. These findings are discussed in relation to the higher risk of brain infarction seen in alcoholics and even associated with binge drinking. Further studies are needed to establish the effects of ethanol on prostacyclin formation.

Administration of Nonionic Iodinated Contrast Medium Does Not Influence the Outcome of Patients with Ischemic Brain Infarction

Some reports indicate that exposure to iodinated contrast medium (CM) could worsen the outcome of patients with brain infarction. In this prospective study, we compared the outcome of 77 patients receiving and 128 not receiving nonionic iodinated CM. Stroke severity was assessed by the Scandinavian Prognostic Stroke Score, and outcome by the Rankin Scale. All radiological studies using intravenous or intra-arterial CM were registered. Two nonionic iodinated CM (iopamidol and iohexol) were used. Exposure to CM did not influence case fatality, ability to live at home, ability to walk, disability and stroke severity. Initial stroke severity and arterial hypertension were independent determinants of poor neurological recovery or death. Large infarct, age, male gender, and baseline stroke severity were independent determinants of major disability or death. CM enhancement on CT did not show any harmful effect on stroke severity or outcome. As a conclusion, intravascular administration of nonionic iodinated CM did not influence stroke severity or outcome of our patients.

Increase of low serum concentrations of high-density lipoprotein (HDL) cholesterol in TIA-patients treated with phenytoin.

Serum high density lipoprotein (HDL) cholesterol and other lipoproteins were measured in 27 TIA-patients with a mean age of 49 +/− 10 years before and during phenytoin therapy. The pretreatment concentrations of HDL-cholesterol (mmol/l, mean +/− SD) were lower (p less than 0.001) in male (1.03 +/− 0.25) and in female patients (1.15 +/− 0.44) than in healthy male (1.28 +/− 0.34) and female controls (1.52 +/− 0.31) respectively. After one months phenytoin therapy HDL cholesterol concentrations reached normal levels (men 1.33 +/− 0.38, women 1.61 +/− 0.27) and after 9 months of therapy even surpassed them (men 1.47 +/− 0.27, p less than 0.05; women 1.91 +/− 0.33, p less than 0.01). Percent increase of HDL cholesterol after 9 months of therapy was 42 +/− 25 in men and 68 +/− 46 in women. There was a positive correlation (r = 0.43, p less than 0.05) between serum phenytoin level and increase of HDL cholesterol. HDL/LDL cholesterol ratio increased (p less than 0.01) also during 9 months of therapy (men from 0.26 +/− 0.05 to 0.36 +/− 0.10, women from 0.26 +/− 0.07 to 0.43 +/− 0.13) and showed a positive correlation (r = 0.91, p less than 0.001) with increase of serum HDL cholesterol. The HDL cholesterol levels achieved have been maintained with a mean serum phenytoin level of 5.6 +/− 3.6 mg/l. Phenytoin induced increase in serum HDL levels should not yet be equated with protection against atherosclerosis.

Effects of exercise and ethanol ingestion on platelet thromboxane release in healthy men

We studied the effects of repeated bicycle exercises and ethanol ingestion (1.5 g/kg) on platelet aggregation and thromboxane (TxB2) release in 10 healthy male volunteers. After a bicycle exercise performed in the morning, the adenosine diphosphate (ADP)-induced platelet aggregation and the aggregation-associated thromboxane release were found to be decreased in fasting men. In contrast, after ingestion of fruit juice and a second exercise at noon, platelet aggregation and thromboxane release were increased. These latter changes were negligible when ethanol was ingested together with fruit juice. A third exercise, performed in the evening, again caused a decrease in the aggregation and associated thromboxane release during the control session, but provoked an increase during the ethanol session. Exercise increased the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha. Changes in the plasma arachidonic acid (AA) concentration probably influenced the platelet thromboxane release. The results suggest that both physical exercise and ingestion of ethanol in fruit juice influence the ADP-stimulated platelet thromboxane release.

Increased Visceral Adipose Tissue as a Potential Risk Factor in Patients with Embolic Stroke of Undetermined Source (ESUS)

Purpose The etiology of an ischemic stroke remains undetermined in 20–35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke. Methods Altogether 58 patients (mean age 57.7±10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered. Results Mean VAT area was significantly higher in stroke patients (205±103 cm2 for men and 168±99 cm2 for women) compared to all reference populations (P<0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors. Conclusion Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients.