Health outcomes and costs of ischemic stroke patients in Finland.

OBJECTIVES: Stroke case fatality is decreasing over time. Less, however, is known about patients' health-related quality of life (HRQoL), quality-adjusted life years (QALYs), and costs. We studied all these with two data sets collected in Finland 10 years apart. METHODS: A total of 468 and 355 first-ever ischemic stroke patients were followed up 1 year in two studies (Study 1 in 1989-1991 and Study 2 in 2001-2003). Case fatality, HRQoL measured by the 15D, QALYs, costs, and first-year cost/QALY were compared. Regression analysis was used to examine the effects of various factors on QALYs. RESULTS: In the later study, the case fatality rates were lower and the mean 15D scores higher. During the follow-up year, patients experienced on average 0.519 (95% CI 0.453-0.555) and 0.646 (95% CI 0.613-0.680) QALYs in Study 1 and Study 2, respectively (P < 0.001). Age, modified Rankin Scale before stroke onset, acute phase Scandinavian Stroke Scale, and the study group explained the variance of QALYs. The first-year mean total costs were 10 626 € and 14 603 € and the mean cost/QALY 20 474 € and 22 605 € in Study 1 and Study 2, respectively. The incremental cost-effectiveness ratio of Study 2 compared with Study 1 was 31 315 € without and 60 684 € with patient characteristics standardization. CONCLUSIONS: Stroke patients' improved outcome is clear, but it remains uncertain to what extent it is attributable to the development of care. More research is needed to study the cost-effectiveness of stroke care.

The functional status and perceived quality of life in long-term survivors of out-of-hospital cardiac arrest.

BACKGROUND: Limited data exist on how long-term survivors after pre-hospital cardiac arrest lead their lives. This study assessed functional status and perceived quality of life in patients surviving for 15 years after successful resuscitation from witnessed out-of-hospital cardiac arrest as a result of ventricular fibrillation. METHODS: A 15-year follow-up study of 59 1-year survivors after successful pre-hospital resuscitation who were thoroughly evaluated at 3 and 12 months after out-of-hospital cardiac arrest. Eleven patients were still alive 15 years later. Ten of them were reached and underwent a comprehensive neuropsychological and neurological examination. Cognitive performance was evaluated and compared with individual results 15 years earlier and with an age-matched control group. The cause and time of death of the non-survivors were established. RESULTS: All 10 evaluated long-term survivors lived at home and were independent in their activities of daily living. Their mean age was 72 years. In nine patients there was no change in the present neurological status compared with the status at 1 year after resuscitation, and in one patient it had improved. Five patients were cognitively intact. In four patients mild cognitive problems had emerged or slightly progressed. All but one were satisfied with their perceived quality of life. By the time of examination, the mean survival time for the 1-year survivors was 7 years, and the mean age at the time of death was 70 years. CONCLUSION: Once good outcome after cardiac arrest is achieved, it can be maintained for more than 10 years.

Subtle cognitive deficits after cerebellar infarcts.

The role of the cerebellum in cognitive functions has been under debate. We investigated the neuropsychological functioning of patients with cerebellar lesions (infarcts) and evaluated the significance of laterality in cognitive symptoms. Twenty-six patients with exclusive cerebellar lesions as verified by clinical and neuroradiological findings underwent a neuropsychological assessment at the acute stage and at 3 months. Their performance was compared with 14 controls, also assessed twice. The focus was on four domains: visuospatial/motor functions, episodic memory, working memory and attentional shifting/execution. Both groups improved over time. Statistical differences emerged in tests in the visuomotor domain as well as in the episodic and working memory domains. Patients with left cerebellar lesion were slow in a visuospatial task, whereas those with right cerebellar lesions had verbal memory difficulty compared with controls. By 3 months, 77% of the patients had returned to work, and only one had cognitive impairment and did not return to work. Our results indicate that cerebellar infarcts may result in subtle cognitive changes perhaps primarily related to working memory deficit. The symptoms may be mediated by the contralateral cortical hemisphere, left cerebellar infarcts producing mild right hemispheral dysfunction and right cerebellar infarct producing mild left hemispheral dysfunction.

Comparison of 30 and the 100% inspired oxygen concentrations during early post-resuscitation period: a randomised controlled pilot study.

OBJECTIVES: High oxygen concentration in blood may be harmful in the reperfusion phase after cardiopulmonary resuscitation. We compared the effect of 30 and 100% inspired oxygen concentrations on blood oxygenation and the level of serum markers (NSE, S-100) of neuronal injury during the early post-resuscitation period in humans. METHODS: Patients resuscitated from witnessed out-of-hospital ventricular fibrillation were randomised after the return of spontaneous circulation (ROSC) to be ventilated either with 30% (group A) or 100% (group B) oxygen for 60 min. Main outcome measures were NSE and S-100 levels at 24 and 48 h after ROSC, the adequacy of oxygenation at 10 and 60 min after ROSC and, in group A, the need to raise FiO(2) to avoid hypoxaemia. Blood oxygen saturation <95% was the threshold for this intervention. RESULTS: Thirty-two patients were randomised and 28 (14 in group A and 14 in group B) remained eligible for the final analysis. The mean PaO(2) at 10 min was 21.1 kPa in group A and 49.7 kPa in group B. The corresponding values at 60 min were 14.6 and 46.5 kPa. PaO(2) values did not fall to the hypoxaemic level in group A. In another group FiO(2) had to be raised in five cases (36%) but in two cases it was returned to 0.30 rapidly. The mean NSE at 24 and 48 h was 10.9 and 14.2 microg/l in group A and 13.0 and 18.6 microg/l in group B (ns). S-100 at corresponding time points was 0.21 and 0.23 microg/l in group A and 0.73 and 0.49 microg/l in group B (ns). In the subgroup not treated with therapeutic hypothermia in hospital NSE at 24h was higher in group B (mean 7.6 versus 13.5 microg/l, p=0.0487). CONCLUSIONS: Most patients had acceptable arterial oxygenation when ventilated with 30% oxygen during the immediate post-resuscitation period. There was no indication that 30% oxygen with SpO(2) monitoring and oxygen backup to avoid SpO(2)<95% did worse that the group receiving 100% oxygen. The use of 100% oxygen was associated with increased level of NSE at 24h in patients not treated with therapeutic hypothermia. The clinical significance of this finding is unknown and an outcome-powered study is feasible.

Therapeutic hypothermia after prolonged cardiac arrest due to non-coronary causes.

Mild resuscitative hypothermia has been shown to improve neurological outcome after cardiac arrest presenting with ventricular fibrillation (VF) due to cardiac causes. We describe the experience of inducing mild hypothermia in three patients with non-cardiac causes of arrest and long delays before a return of spontaneous circulation (ROSC). In one patient, extreme metabolic acidosis due to inadvertent oesophageal intubation complicated therapy, and the role of point-of-care diagnostics in the prehospital setting is briefly discussed. All patients survived to discharge from hospital, and neuropsychological examinations revealed good recovery. It is concluded that mild resuscitative hypothermia may be beneficial also in patients with obvious non-coronary causes for cardiac arrest.

Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis.

OBJECTIVE: To evaluate with electromyography the incidence and the time of appearance of neuromuscular abnormality in patients with systemic inflammatory response syndrome (SIRS) and/or sepsis. DESIGN: Follow-up study. SETTING: Intensive care unit of Helsinki University Hospital, Finland. PATIENTS: Nine mechanically ventilated patients with SIRS and/or sepsis. INTERVENTIONS: Electromyography and conduction velocity measurements on the 2nd-5th day after admission to the intensive care unit. MEASUREMENTS AND RESULTS: In all nine patients electromyography revealed signs of neuromuscular abnormality. The means of compound muscle action potential amplitudes of the median and ulnar nerves were decreased. Fibrillation was observed in four patients out of nine. CONCLUSION: Because neuromuscular abnormalities seem to develop earlier than previously reported, electroneuromyography should be used more frequently as a diagnostic test.

The future of stroke treatment.

The concept of the therapeutic window of opportunity in ischemic neuronal injury and understanding the necessity of well organized stroke services revolutionized the management of acute ischemic stroke during the last years of the second millennium. Thrombolysis with IV rt-PA within 3 hours from the onset of symptoms is an established therapy for selected patients. The challenge of stroke therapy at the outset of this millennium is how to translate basic pathophysiologic evidence of ischemic neuronal injury into novel neuroprotective therapies either independently or combined with thrombolysis. Great hopes are placed in identification of pivotal molecular events in ischemic brain tissue and design of effective pharmacological interventions to target them. Aggressive, invasive procedures are also being developed and therapies such as intra-arterial clot lysis, hemicraniectomy and mild hypothermia may improve the bleakest outcomes associated with the most severe forms of ischemic stroke, but their role must be rigorously evaluated. There is, however, no need to wait for future breakthroughs. The existing evidence strongly implies that good care of patients with stroke starts with organization of the entire stroke chain; from the prehospital scene, through the emergency room, to the stroke unit. Without structured stroke services no pharmacological or intervening therapy is likely to improve the outcome of the patient with a stroke.

Specific changes in somatosensory evoked magnetic fields during recovery from sensorimotor stroke.

We studied recovery-induced changes in the responsiveness of the primary somatosensory cortex in stroke patients with sensory and/or motor symptoms. Somatosensory evoked magnetic fields, in response to median nerve stimulation, were recorded in 14 patients with their first symptomatic unilateral stroke 1 to 15 days from the first symptoms and again 2 to 3 months later. Neuronal activity at the contralateral primary somatosensory cortex was modeled with equivalent current dipoles at the peak latencies of the first two cortical deflections at about 20 msec (N1m) and at 28 to 91 msec (P1m). Twenty-three age-matched healthy volunteers, 9 of whom were tested also in serial recordings, served as control subjects. At follow-up, 6 patients showed a significant increase of P1m amplitude, whereas N1m increased only in 1. Clinical improvement of two-point discrimination ability, but not of other basic somatosensory skills, was significantly correlated with the increase of P1m. We conclude that the recovery of discriminative touch after stroke is paralleled by the growth of the P1m somatosensory evoked magnetic field deflection, and we propose that this may reflect re-establishment of lateral inhibitory functions at the primary somatosensory cortex.

Somatosensory evoked magnetic fields from the primary somatosensory cortex (SI) in acute stroke.

We recorded somatosensory evoked magnetic fields (SEFs) to median nerve stimulation from 15 patients in the acute stage (1-15 days from the onset of the symptoms) of their first-ever unilateral stroke involving sensorimotor cortical and/or subcortical structures in the territory of the middle cerebral artery (MCA). Neuronal activity corresponding to the peaks of the N20m, P35m and P60m SEF deflections from the contralateral primary somatosensory cortex (SI) was modelled with equivalent current dipoles (ECDs), the locations and strengths of which were compared with those of an age-matched normal population. Four patients with pure motor stroke had symmetric SEFs. In one of the 4 patients with pure sensory stroke, and in 5 of the 7 patients with sensorimotor paresis, the SEFs were markedly attenuated or missing. All except one patient with abnormal SEFs had deficient two-point discrimination ability; especially the attenuation of N20m was more clearly correlated with two-point discrimination than with joint-position or vibration senses. Of the different SEF deflections, P35m and P60m were slightly more sensitive indicators of abnormality than N20m, the former being affected in two patients with symmetric N20m. Three patients with pure sensory stroke and lesions in the opercular cortex had normal SEFs from SI. We conclude that the SEF deflections N20m, P35m and P60m from SI are related to cutaneous sensation, in particular discriminative to touch. The results also demonstrate that basic somatosensory perception can be affected by lesions in the opercular cortex in patients with functionally intact SI.

Somatosensory evoked magnetic fields to median nerve stimulation: interhemispheric differences in a normal population.

The objective of the present study was to evaluate the normal interhemispheric variability of the locations and activation strengths of the somatosensory cortices. Somatosensory evoked magnetic fields (SEFs) were recorded with a 122-channel magnetometer in 23 healthy subjects (mean age 57 years) to stimulation of left and right median nerves. Equivalent current dipole (ECD) strengths and locations were determined for the main SEF deflections at the contralateral primary sensorimotor (SMI) and secondary somatosensory (SIIc) cortices. In a Cartesian co-ordinate system, defined by the preauricular points and the nasion, the SMI sources were slightly but significantly more laterally and anteriorly located in the right than in the left hemisphere. No systematic co-ordinate asymmetries were found for the SIIc sources. In individual subjects, the interhemispheric differences in the ECD co-ordinates averaged less than 6 mm at both SMI and SIIc. The group means of the source strengths did not differ between the hemispheres, but individual differences were on average 20% for the SMI and 65% for the SIIc sources. We conclude that at the individual level, the median nerve SEFs from SMI can be used to detect abnormally large interhemispheric asymmetries of source locations in the centimetre scale.

Cerebral resuscitation from cardiac arrest: treatment potentials.

In 1961, in Pittsburgh, PA, "cerebral" was added to the cardiopulmonary resuscitation system (CPR --> CPCR). Cerebral recovery is dependent on arrest and cardiopulmonary resuscitation times, and numerous factors related to basic, advanced, and prolonged life support. Postischemic-anoxic encephalopathy (the cerebral postresuscitation disease or syndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of special, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based on mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limit for neurologic recovery after 5 mins of arrest must be extended to achieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinically relevant cardiac arrest-intensive care outcome models in large animals. These studies are expensive, but essential, because positive treatment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clinical trials of CPCR are limited in their ability to statistically document the effectiveness of treatments found to be beneficial in controlled outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusion overcomes multifocal no-reflow and improves outcome. Physical combination treatments, such as mild resuscitative (early postarrest) hypothermia (34 degrees C) plus cerebral blood flow promotion (e.g., with hypertension, hemodilution, and normocapnia), each having multiple beneficial effects, achieved complete functional and near-complete histologic recovery of the dog brain after 11 mins of normothermic, ventricular fibrillation cardiac arrest. Calcium entry blockers appear promising as a treatment for postischemic-anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have failed to improve neurologic outcome. Assembling and evaluating combination treatments in further animal studies and determining clinical feasibility inside and outside hospitals are challenges for the near future. Treatments without permanent beneficial effects may at least extend the therapeutic window. All of these investigations will require coordinated efforts by multiple research groups, pursuing systematic, multilevel research--from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about optimizing extracerebral life support for cerebral outcome.

Propofol in prehospital treatment of convulsive status epilepticus.

We studied the safety and efficacy of intravenous propofol in the out-of-hospital treatment of convulsive status epilepticus (SE) in 8 patients (age 29-70 years), 4 of them with posttraumatic epilepsy. Four patients had no history of seizures. Convulsions ceased promptly after patients received a bolus of 100-200 mg propofol administered before hospital admission by staff of a mobile intensive care unit (ICU). The median duration of coma was 3 h 15 min (range 2-41 h), and the median duration of hospital treatment was 3 1/2 days (range 12 h to 23 days). Only 1 patient was admitted to the hospital's ICU. No adverse effects was observed except for a transient decrease in systolic blood pressure (SBP). Propofol may be a useful drug for the prehospital treatment of recurrent seizures not responding to intravenous diazepam (DZP).