6. Jahrestagung der Zerebrovaskulären Arbeitsgruppe der Schweiz 6^e Réunion du Groupe suisse de travail pour les maladies cérébrovasculaires

Post-stroke hypersomnia

C. Bassetti

Zürich

Hypersomnia, defined as excessive sleepiness or sleep-like behaviour, can reflect insufficient arousal (de-arousal) following disruption of the ascending reticular activating formation, increased production of sleep, or both. The frequency and clinical characteristics of post-stroke hypersomnia are poorly known.

In a series of 100 consecutive patients with acute ischaemic stroke the presence of early poststroke hypersomnia was assessed within the first week after stroke onset by means of a standard questionnaire (n = 100), automatic CPAP-device, and 1-week actigraphy (n = 20).

Early post-stroke hypersomnia was present in 22% of patients and was observed in patients with different stroke topographies. Compared to patients without hypersomnia (noH), patients with hypersomnia (H) had a higher NIH-stroke scale (p >0.0001), as well as a lower Barthel-Index (p = 0.0049) and a higher Rankin-score (p = 0.0011) at hospital discharge. The actigraphic sleep-wake ratio was also significantly different between noH and H (0.5 vs 1.3 p = 0.001). Conversely, the apnoea-hypopnoea index, as well as the pre-stroke Epworth sleepiness score and estimated sleep duration/24 hours were similar in noH and H.

Early post-stroke hypersomnia is frequent, can be documented by actigraphy, and correlates with a worse short-term stroke outcome.

Infarct volume on diffusion-weighted MR imaging does not correlate with functional outcome in infratentorial infarcts

St. Engelter^a, St. Wetzel^b, E. Radü^b, M. Rausch^b,A. J. Steck^a, Ph. Lyrer^a

Neurological Clinic and Stroke Unit^a and Department of Radiology^b, University Hospital Basel

Objective: For supratentorial strokes, lesion volume on early diffusion-weighted MR imaging (DWI) correlates well with functional outcome. As yet, it is unclear, whether such a prognostic impact exists also for infratentorial infarcts. We therefore studied whether lesion volume on DWI correlates with stroke severity and functional outcome after 3 months in patients with acute ischaemic infratentorial stroke.

Design: Prospective cohort study.

Study population: 22 consecutive patients (mean age 61 ± 11 years) with acute infratentorial strokes and DWI within 17.9 ± 12.1 hours after stroke onset.

Methods: Lesion volume on DWI was compared to initial NIH Stroke Scale score (NIHSSS) as well as to the rate of community discharge and functional outcome assessed with modified Rankin score (mRS) and Barthel-index (BI) after 3 months. Outcome was dichotomised, with recovery defined as mRS 0.1 and BI ≥95.

Results: Lesion volume ranged from 0.0 to 35.22 cm³ (mean ± SD: 7.39 ± 10.42 cm³) and NIHSSS ranged from 1 to 22 points (mean ± SD: 6.5 ± 5.3). However, DWI lesion volume and initial NIHSSS showed no correlation (r = 0.17, p = 0.46). After 3 months, 54.5% (12/22) according to mRS and 63.6% (14/22) of the patients according to BI had recovered. However, neither mRS nor BI showed any significant correlation to the initial lesion volume on DWI (p = 0.08 [mRS]; p = 0.3 [BI]). 73% (16/22) of the patients lived at home 3 months after stroke onset, whereas 23% (5/22) had ongoing in-hospital rehabilitation and 4% (1/22) had died. However, DWI lesion volume did not differ significantly between patients discharged home within 3 months versus those who did not.

Conclusion: For infratentorial infarcts lesion volume on early DWI was neither correlated with initial stroke severity nor with clinical outcome parameters after 3 months.

Wärmeaustauschkatheter: eine neue Methode für die Einleitung und Aufrechterhaltung einer kontrollierten Hypothermie

S. Gasser, H. G. Imhof, Y. Yonekawa, E. Keller

Neurochirurgische Klinik,Universitätsspital Zürich

Hintergrund: Rasches Kühlverfahren, Konstanz der Temperatur während der Behandlung mit kontrollierter Hypothermie und eine gute Kontrolle bei der Wiedererwärmung sind wichtige Faktoren für eine optimale Hypothermiebehandlung.

Ziel: Evaluation im klinischen Gebrauch von neuen Wärmeaustauschkathetern.

Patienten und Methoden: 20 Patienten mit schwerer Subarachnoidalblutung (Hunt & Hess 4–5) wurden wegen nicht beherrschbarem Anstieg des intrakraniellen Druckes hypotherm behandelt. Stündlich registrierten wir die Körperkerntemperaturen (KKT), insgesamt 1544 Werte. Foley-Temperaturkatheter (Genauigkeit ± 0,1 °C) wurden benutzt, um die KKT in der Blase zu messen (Mon-a-therm, Mallinckrodt, Hazelwood, MO, USA). Bei allen Patienten wurde versucht die Ziel-KKT von 33 bis 34 °C so rasch wie möglich zu erreichen. Bei den ersten 10 Patienten (Gruppe 1) wurde die Hypothermie mittels Kühlmatten (Bair HuggerTM, Augustine Medical, Saint Prarie, MN, USA and Blanketrol, CSZ, Cincinnatti, OH, USA) erreicht und aufrechterhalten. Die nächsten 10 Patienten (Gruppe 2) kühlten wir mittels eines 8,5-French Wärmeaustauschkatheters (Cool Line Catheter), welcher in eine zentrale Vene (V. femoralis oder V. subclavia) mittels Seldinger-Technik eingelegt und an das Coolgard-System (Alsius Corporation, Irvine, CA, USA) angeschlossen wurde. Die Kühlflüssigkeit (sterile 0,9prozentige Natriumchloridlösung) zirkuliert lediglich im Kühlkatheter in einem geschlossenen Ballonsystem und hat keinen Kontakt zum Blut der Patienten. Die Zeit bis zum Erreichen der Ziel-KKT und das Abweichen von dieser Ziel-KKT während der Hypothermiebehandlung wurden in beiden Gruppen erfasst und miteinander verglichen.

Resultate: Es kam zu keinen spezifischen, katheterassoziierten Komplikationen. Die Zeit bis zum Erreichen der Ziel-KKT in der Gruppe 2 war signifikant kürzer als in der Gruppe 1 (197 ± 108 min vs. 375 ± 219 min; p = 0,028). In der Gruppe 1 waren signifikant mehr Werte ausserhalb der Ziel-KKT von 33 bis 34 °C als in der Gruppe 2 (133 von 792 Werten; 16,79% vs. 28 von 752 Werten; 3,72%; p <0,0001).

Schlussfolgerung: Die neue Kühlmethode mittels Wärmeaustauschkatheter scheint sicher und geeignet zu sein, um eine rasche Kühlung zu erreichen und danach sehr stabile Ziel-KKT zu gewährleisten.

Langzeit-Hypothermie nach Subarachnoidalblutung (SAB): Resultiert eine Hypothermiedauer von mehr als 72 Stunden in einer erhöhten intensivmedizinischen Mortalität?

S. Gasser, A. Terzic, Y. Yonekawa, E. Keller

Neurochirurgische Klinik,Universitätsspital Zürich

Ziel: Evaluation der Mortalitätsrate und Infektionsrate bei Patienten, die länger als 72 Stunden einer Hypothermiebehandlung unterzogen wurden.

Patienten und Methoden: Zwischen 1999 und 2001 wurden 19 Patienten mit schwerer Subarachnoidalblutung (SAB) Hunt & Hess Grad 4–5 und Anstiegen des intrakraniellen Drucks (ICP) nach frühem Aneurysma-Clipping einer Therapie mit Hypothermie und Barbituratkoma unterzogen. Hypothermiebehandlung (Zielkörperkerntemperatur 33–34 °C) und Barbituratkoma (Pentothal 10 mg/kg KG Aufsättigungsdosis, Erhaltungsdosis nach Burst-Suppression-Muster im kontinuierlichen EEG) wurden aufrechterhalten, bis über 24 Stunden keine ICP-Anstiege >15 mm Hg mehr auftraten. Als Pneumonie wurde ein CRP-Anstieg mit Infiltrat im Thorax-Röntgen und positiver Bakteriologie im Trachealsekret bezeichnet. Bei einer Sepsis lagen CRP-Anstieg, Zeichen des Multiorganversagens und positiver Keimnachweis auf Kathetern und/oder Blutkulturen vor. Die Patienten wurden retrospektiv auf Hospitalisationsmortalität, Infektionen und Outcome nach drei Monaten untersucht.

Resultate: 10 Patienten wurden länger als 72 Stunden mit Hypothermie/Barbituratkoma behandelt. Davon verstarb ein Patient (10%) an Pneumonie, ARDS und Sepsis im Multiorganversagen. 9 Patienten wurden weniger lang als 72 Stunden hypotherm behandelt. Davon verstarben 2 Patienten (22%), einer im kardiogenen Schock und einer an ARDS, Sepsis und Multiorganversagen. Die durchschnittliche Hypothermiedauer aller Patienten betrug 88,05 ± 64,21 Stunden, die kürzeste 8 und die längste 286 Stunden. Bei den länger als 72 Stunden hypotherm behandelten Patienten war die durchschnittliche Hypothermiedauer 129,3 ± 61,95 Stunden. Bei allen 19 Patienten (100%) traten im Krankheitsverlauf Zeichen einer manifesten Infektion auf. Bei 15 Patienten (78,9%) als Pneumonie, bei 2 Patienten (10,5%) als Sepsis, bei einem Patienten (5,3%) als Wundinfekt und bei einem Patienten mit mykotischem Aneurysma (5,3%) als Endokarditis. In der Gruppe der Patienten, die länger als 72 Stunden hypotherm behandelt wurden, fanden sich nach drei Monaten folgende Glasgow-Outcome Score (GOS): GOS 5 oder 4 bei fünf Patienten (50%), GOS 3 oder 2 bei drei Patienten (30%) und GOS 2 oder 1 bei zwei Patienten (20%). In der Gruppe der Patienten, die weniger lang als 72 Stunden hypotherm behandelt wurden, fanden sich nach drei Monaten folgende GOS: GOS 5 oder 4 bei vier Patienten (44,4%), GOS 3 oder 2 bei zwei Patienten (22,2%) und GOS 2 oder 1 bei drei Patienten (33,3%).

Schlussfolgerung: Bei Patienten mit schwerer SAB kann bei selektiver Indikation und bei aufwendiger und qualitativ hochstehender intensivmedizinischer Versorgung eine Langzeithypothermiebehandlung länger als 72 Stunden sinnvoll sein. Die Langzeithypothermie, kombiniert mit Barbituratkoma ist bei Patienten mit schwerer SAB nicht mit einer massiv erhöhten Mortalitätsrate vergesellschaftet. In der vorliegenden Untersuchung kam es bei allen Patienten zu Infektionen, v.a. Pneumonien, die jedoch in der Regel durch resistenzgerechte Antibiose, Volumensubstitution und Katecholamin-Therapie beherrscht werden konnten und nicht zum Abbruch der Hypothermie führten.

Hemicraniectomy and moderate hypothermia in severe ischaemic stroke

D. Georgiadis, S. Schwarz, A. Aschoff, S. Schwab

Department of Neurology, University of Heidelberg, Heidelberg (D)

Objective: We compared the clinical course of 36 consecutive patients with severe acute ischaemic stroke (>2/3 of the middle cerebral artery territory), treated with hemicraniectomy (CE, n = 17) or moderate hypothermia (MH, n = 19), in terms of intracranial pressure control (ICP), mortality and specific treatment parameters.

Methods: Over a period of 18 months, patients with a severe ischaemic stroke were treated with CE, when the non-dominant hemisphere and MH, when the dominant hemisphere was affected. MH (33 ° Celsius) was induced using either cold blankets and fans (n = 11) or endovascular cooling (n = 8). Intracranial pressure (ICP) was monitored invasively in all cases.

Results: Age, sex, CCT findings, level of consciousness and time to treatment were similar between the two groups; significant differences were noted in NIHSS (20 [18–22] and 17 [16–18], MH and CE, respectively), but were not present when NIHSS was corrected for aphasia (17 [15–19] and 17 [16–18], MH and CE, respectively). Mortality was 12% for CE and 47% for MH, respectively, whereby one patient treated with MH died on treatment complications (sepsis) and 3 on ICP crises which occurred during rewarming. Duration of mechanical ventilation and of NICU stay did not significantly differ, but duration of catecholamine application and maximal catecholamine dosage were significantly higher in the MH group.

Conclusions: MH and CE are able to reduce mortality in patients with severe ischaemic stroke. Our results suggest that CE results in a lower mortality and lower complication rates, as compared to MH. Both treatment modalities are associated with intensive medical treatment, and a prolonged stay in NICU.

Recombinant tissue-plasminogen activator (rt-PA)-induced fibrinolysis after focal ischaemia in mice: implications for clinical stroke therapy

D. M. Hermann, C. Bassetti

Neurologische Klinik und Poliklinik, Universitätsspital Zürich

Background and aim: Fibrinolysis using recombinant tissue-plasminogen activator (rt-PA; actilyse) is currently the only effective stroke treatment available in humans. At present, however, only a small percentage of patients benefits from this type of therapy, since the efficacy of rt-PA lysis has only been documented for a narrow time window (3 h after onset of symptoms). This may be explained by the fact that delayed secondary mechanisms of injury are activated after a stroke, once the duration of ischaemia exceeds a critical threshold. On the other hand, it has been suggested that toxic side effects might limit the clinical use of rt-PA. Unfortunately, the biological effects of rt-PA cannot be assessed systematically enough in human stroke patients to elucidate such possible side actions. For this reason, it became necessary to study the effects of rt-PA in a more detailed way in rodents.

Methods: Adult male C57BL/6j mice were submitted to reversible episodes of focal brain ischaemia by interruption of blood flow in the middle cerebral artery (MCA) using thread occlusion and cerebral thromboembolism models. At defined time points before, during and after ischaemia, rt-PA was administered at various doses (0.2–10 mg/kg b.w.). During the experiments, cerebral blood flow was assessed by laser Doppler flowmetry as well as quantitative cerebral blood flow (CBF) autoradiography using 14C-iodoantipyrine. Brain injury was assessed histochemically 24 hours after ischaemia.

Results and conclusions: Our results show that rt-PA treatment reduces infarct size after cerebral thromboembolism in mice. This effect obviously may be attributed to an improvement of brain perfusion due to clot lysis, which could be demonstrated by laser Doppler flowmetry. On the other hand, our data also demonstrate that rt-PA increases brain injury in non-embolic ischaemia, i.e. reversible thread occlusion. This increase in infarct size may most likely be attributed to a secondary hypoperfusion, which was demonstrated in the ischaemic tissue 11⁄2–2 hours after the onset of reperfusion. Our observations point towards the notion that accompanying therapeutic strategies should be developed for rt-PA lysis, which prevent the secondary perfusion deficits and interrupt the evolution of delayed tissue injury. As we have already been able to show, both the post-ischaemic hypoperfusion and the increase in brain damage after rt-PA treatment may be prevented by additional administration of heparin (200 IU/kg b.w.). Besides, systemically applicable therapeutics have become available in the animal laboratory (i.e. fusion proteins of membrane-permeable peptides with anti-apoptotic proteins; e.g. TAT-Bcl-X_L), which, as could be demonstrated, reduce brain injury in experimental stroke and might also be used in humans some day. Concerted efforts of experimental and clinical research will be required in the future for the development of a promising stroke therapy.

Neurointensivmedizinische Therapie von Patienten mit schweren intrazerebralen Blutungen nach endovaskulärer Therapie arteriovenöser Missbildungen

E. Keller, Y. Yonekawa, H. G. Imhof, M. Tanaka, A. Valavanis

Zürich

Zielsetzung: Evaluation der Bedeutung der notfallmässigen neurochirurgischen und intensivmedizinischen Therapie von Patienten mit schweren intrazerebralen Blutungen nach endovaskulärer Therapie arteriovenöser Missbildungen (AVMs).

Methodik: Die Krankengeschichten von 18 Patienten mit schweren intrazerebralen Blutungen nach AVM-Embolisa-tion zwischen 1986 und 2001 wurden retrospektiv analysiert. Während dieser 15 Jahre änderte sich das Therapieregimen: Vor 1993 wurden Patienten mit schweren intrazerebralen Blutungen nicht operiert und verstarben. Nach 1994 wurden alle Patienten notfallmässig operiert. Im Mai 1998 wurde ein standardisiertes neurointensivmedizinisches Therapieprotokoll eingeführt, und alle Patienten wurden möglichst schnell nach Auftreten von Symptomen einer intrazerebralen Blutung operiert. Die postoperative Intensivbehandlung wurde standardisiert.

Resultate: Während dieser 15 Jahre traten bei 605 Patienten mit 1066 endovaskulären Interventionen 24 peri- oder postinterventionelle Blutungen auf. Davon lagen bei 18 Patienten schwere intrazerebrale Blutungen vor (2,97% der Patienten; 1,69% der Interventionen). Alle Patienten waren neurologisch schwer kompromittiert (mittlere Glasgow Coma Scale 4,2), 8 Patienten hatten uni- oder bilaterale Pupillenstörungen. Während der Zeitspanne von 1989 bis April 1998 verstarben 4 von 13 Patienten (31%), ein Patient überlebte in einem vegetativen Zustandsbild (7,5%) und 8 Patienten überlebten mit einem guten Outcome (61,5%). Zwischen 1998 und 2001 überlebten alle 5 Patienten mit gutem Outcome. Das Zeitintervall zwischen Symptombeginn der intrazerebralen Blutung bis zur notfallmässigen Hämatomevakuation war zwischen 1989 und 1998 129 min und zwischen 1998 und 2001 24 min.

Schlussfolgerungen: Eine standardisierte Neurointensivmedizinische Therapie mit notfallmässiger kardiopulmonaler Stabilisierung und minimaler neuroradiologischer Diagnostik vor der möglichst frühzeitigen Hämatomevakuation verbessert das Outcome von Patienten mit schweren intrazerebralen Blutungen nach AVM-Embolisation. Ein kurzes Zeitintervall zwischen Symptombeginn der intrazerebralen Blutung bis zur chirurgischen Hämatomevakuation scheint der entscheidende Faktor für ein gutes Outcome zu sein.

Die Differenzierung zwischen arteriosklerotischen und thromboembolischen Stenosen oder Verschlüssen intrakranieller Gefässe mit der transkraniellen Duplexsonographie

C. Kremer, D. Benninger, M. Arnold, R. W. Baumgartner

Zürich, Bern

Eine Differenzierung zwischen thromboembolischen und arteriosklerotischen Obstruktionen intrakranieller Arterien gelingt mit der transkraniellen Duplexsonographie in der Akutphase nicht.

Im Rahmen von engmaschigen Follow-up-Untersuchungen besteht über eine Bestimmung der Latenzzeit bis zur Rekanalisation die Möglichkeit Rückschlüsse auf die Ätiologie des intrakraniellen Verschlusses oder der Stenose zu ziehen.

Hierzu wurden 105 Patienten mit spontanen Dissektionen der A. carotis interna (ICA) erhoben, die von 1992 bis 1999 behandelt wurden, 31 boten Stenosen oder Verschlüsse intrakranieller Gefässe. Bei allen Patienten wurden wiederholte extrakranielle und transkranielle duplexsonographische Untersuchungen bis zur Rekanalisation durchgeführt. Parallel wurden von 1997 bis 1999 die Daten von Patienten mit erstem Schlaganfall und extrakranieller arteriosklerotischer Makroangiopathie erhoben, darunter 21 mit zusätzlichen intrakraniellen Obstruktionen. Es fanden mindestens dreimonatliche Follow-up-Untersuchungen statt.

Bei 60% dieser Patienten kam es innerhalb 58 Tagen zu einer Rekanalisation, eine Persistenz der Obstruktion über 58 Tage machte eine zusätzliche intrakranielle Makroangiopathie wahrscheinlich. Bei 95% der Patienten mit Dissektionen und intrakraniellen Obstruktionen kam es innerhalb 83 Tagen zur Rekanalisation, bei 5% dieser Patienten ist eine zusätzliche arteriosklerotische Genese der intrakraniellen Obstruktion bei Nachweis nach 83 Tagen möglich, eine thromboembolische Genese bei 95% wahrscheinlich.

Cerebral venous thrombosis and D-dimer

P. Lalive, R. Sztajzel

Clinique de Neurologie, Hôpital Cantonal Universitaire de Genève

Clinical expression of cerebral venous thrombosis varies widely and its diagnosis may be very difficult. Since appropriate treatment influences prognosis, early recognition of this condition is extremely important. Head CT scan may be normal in up to 20% of the cases and MRI, the gold standard for accurate diagnosis, is not available at any time. We therefore wondered whether the D-dimer blood test could be helpful in the diagnostic approach in the emergency room. We collected prospectively 30 patients coming in emergency room for headaches suggesting CVT. All of them were tested for blood D-dimer (Elisa test) in the emergency room. 6 of the 30 patients tested had CVT confirmed either by Head MRI or CT scan and 24 of the 30 patients had another diagnosis. 5 of the 6 patients with CVT + had D-dimer positive (>500 Fg/L). 22 of 24 patients without CVT had negative D-dimer values (<500 Fg/L). These preliminary results suggest that testing D-dimer could be very helpful in the diagnostic approach of CVT in the emergency room.

Embolic stroke types of MRI stroke patterns according to different aetiologies

Ph. Lyrer, D. Gisler, St. Wetzel, St. Engelter, E.-W. Radü

Neurological Clinic and Stroke Unit Neuroradiology, Department of Radiology, University Hospital Basel

Objective: The appearance of stroke patterns according to arteriogenic or cardioembolism is controversial. There is an overlap in clinical presentation as well as in radiological pattern for patients with embolic disease due to high-grade carotid stenosis or to cardioembolism. The aim of this study was to identify magnetic resonance imaging (MRI) stroke patterns for patients with definite carotideal stroke in comparison to cardioembolism.

Methods: From 1994 to 1998 109 stroke patients with cardioembolism as the only possible aetiology were identified. From these, 78 patients (72%) were investigated with MRI of the brain. Out of 67 patients with high-grade carotid disease 41 (61%) were investigated by MRI. The number and the size of lesion was determined on T₂-weighted images. The clinical stroke syndrome was assessed according to the OCSP classification.

Results: The radiological analysis showed that patients with cardioembolism had significantly more large territory infarcts than those with carotid stenosis (58.5 vs 25.4%, p = 0.0001). Deep basal ganglia infarctions were also significantly more frequent (26.8 vs 4.5%, p = 0.001). There was no difference in the individual number of infarcts counted for each patient. Clinically, total anterior circulation syndromes were significantly more frequent in the cardioembolism group (17.1 vs 4.5%, p = 0.028).

Conclusion: Cardioembolism caused larger infarcts than carotid stenosis measured by T₂-weighted MRI pattern. Correspondingly, total anterior circulation syndromes were more frequent in these patients.

TCD: Is a reduced flow velocity in the MCA inducing chronic ischaemia of the watershed region?

K. Minkner, R. Sztajzel, D. A. Rüfenacht

Geneva

Purpose: To investigate whether there is interest in measuring middle cerebral artery flow velocity by TCD to assess the risk for producing lesions that are compatible with chronic ischaemia in the anterior watershed area of the brain such as visualised on MRI.

Materials and methods: Retrospective evaluation of imaging and flow data was performed for a group of 30 patients presenting with stenosis of the cervical carotic artery. All underwent MRI, ultrasound of the cervical arteries as well as TCD. Velocities of the MCA were measured on both sides.

MRI was used to evaluate signs of low flow chronic ischaemia in the white matter of the watershed areas of each hemisphere. For this, lesions with hyperintense signal on FLAIR or T₂-weighted sequences were considered. Lesions located closer than within 5 mm distance from the ventricular surface or in cortical grey matter were not considered to be due to low flow.

Flow speed of MCA in the TCD was correlated for each hemisphere with the presence of the hyperintensities in MRI of presumed low flow chronic ischaemia.

Results: The mean flow speed in the MCA of hemispheres with chronic ischaemic lesions was 48 cm/s. The mean flow speed in the MCA of hemispheres without chronic ischaemic lesions on MRI was 57 cm/s.

Conclusions: Reduction of flow velocity in the MCA was seen in presence of chronic ischaemic lesions in the anterior watershed areas. Low flow as detected on TCD may be an indicator of chronic brain ischaemia.

Intra-arterial thrombolysis in 24 consecutive patients with internal carotid arteryT-occlusion

K. Nedeltchev^a, M. Arnold^a, H. Mattle^a, Th. Loher^a, F. Stepper^a, G. Schroth^b, M. Sturzenegger^a, L. Remonda^b

Departments of Neurology^a and Neuroradiology^b, University of Berne

Background and purpose: To determine safety, efficacy and predictors of favourable outcome in acute stroke due to internal carotid T-occlusion.

Methods: We analysed 24 consecutive patients with T-occlusions of the internal carotid artery treated by local intraarterial thrombolysis using urokinase.

Results: The median baseline National Institutes of Health Stroke Scale (NIHSS) was 19. The average time from symptom onset to treatment was 267 minutes. 5 patients (21%) had a favourable outcome (mRS ≤2) and 12 patients (50%) a bad outcome (mRS 3 or 4) after 3 months. 7 patients (29%) died. One (4%) symptomatic cerebral haemorrhage occurred. Partial recanalisation (TIMI 2) was achieved in 17 patients (71%). Complete recanalisation could never be achieved. Sufficient collaterals as seen on initial angiography were the only predictor of favourable outcome (p = 0.003).

Conclusions: Acute stroke due to carotid T-occlusion remains a condition with a generally poor prognosis especially in patients with insufficient leptomeningeal collaterals even when early intraarterial thrombolysis can be performed. Further research is needed to decide whether more aggressive therapeutic approaches can improve recanalisation rates and clinical outcome in these selected patients.

Increased ventilatory oxygen improves braintissue oxygenation in patients with severe head injury

M. Reinert, A. Barth, R. Guzman, H. U. Rothen, J. Takala, R. W. Seiler

Departments of Neurosurgery and Intensive Care Medicine, Inselspital, University of Berne

Ischaemia is considered as the end-stage mechanism of neuronal damage in different acute brain injuries. Early intervention in the intensive care unit are needed to prevent deleterious secondary ischaemia and neuronal cell death. In traumatic brain injury (TBI), the acute disturbance of ionic homeostasis is followed by an early increase in the metabolic load. Consequently, intracerebral oxygen and glucose utilisation are increased in the hours to days following severe head injury. On the other side, brain-tissue oxygen (ptiO₂) has been shown to be decreased when cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) are reduced. Thus, an amelioration of ptiO₂ may be crucial to prevent ischaemic episodes further aggravating the secondary insults. In this prospective study, we tried to improve oxygen delivery to the brain by increasing ventilatory oxygen (FiO₂) early in the posttraumatic period. We monitored the effects of increased FiO₂ upon ptiO₂, glucose, and lactate. The influence of CPP and end tidal CO₂ (EtCO₂) upon ptiO₂ was also studied during the full observation period.

20 patients with severe TBI (Glasgow Coma Score = 8) were included in the study. A 6-hour 100% oxygen challenge (FiO₂ = 1.0) was induced as soon as the patient was stabilised in the intensive care unit. Thereafter, FiO₂ was progressively reduced to usual standard levels around 0.4. Intracranial pressure (ICP), ptiO₂, and microdialysate of glucose and lactate were measured using a multiple lumen probe inserted into the frontal brain parenchym. The vital parameters EtCO₂, arterial blood O₂, and CPP were continuously recorded on the multimodal monitor (Licox MMM).

During the 6-hour oxygen challenge, significant increases of ptiO₂ of up to 50% were observed in comparison with baseline values (p <0.001) in 19/20 patients. This increase in ptiO₂ was positively correlated with increased FiO₂ (p <0.01) and arterial blood O₂ (p <0.0001). Microdialysate lactate values were significantly lower at times of increased ptiO₂ (p <0.01). CPP was positively correlated (p <0.01) with ptiO₂ and showed a peak increase in ptiO₂ around a CPP value of 78 mm Hg. The correlation of EtCO₂ with ptiO₂ demonstrated a positive peak around 37 mm Hg for EtCO₂.

These results demonstrate that cerebral brain tissue oxygen and cerebral metabolism can be influenced by changes in FiO₂ and that higher arterial oxygen tensions contribute to improve oxygen availability to the injured brain. They also confirm that CPP values around 80 mm Hg and EtCO₂ values around 35 mm Hg optimise ptiO₂. We suggest that this intervention may prevent secondary ischaemia after acute brain injury.

Onkotische Aneurysmata: Therapie und Verlauf anhand von 2 Kasuistiken

A. Schiller^a, G. Schwegler^a, A. Mironov^b, H. Hungerbühler^a

Neurologische Klinik^a und Neuroradiologie^b, Kantonsspital Aarau

Einleitung: Zerebrale onkotische Aneurysmen stellen eine Seltenheit dar. Sie sind, analog den mykotischen im Rahmen von streuenden Bakterien oder Pilzen, Folge von Endothelinfiltrationen durch Tumorzellen. Die am häufigsten vorkommenden Tumoren sind das Chorionkarzinom und das Herzmyxom. Wir stellen 2 Patientinnen vor.

Kasuistiken: Die erste Patientin war, nach 2 kurz hintereinander aufgetretenen okzipitalen Blutungen, blind. Angiographisch stellten sich 2 Aneurysmata spuria dar. Weitere Abklärungen führten zur Diagnose eines metastasierenden Chorionkarzinoms (ohne fassbare Hirnmetastasen im MRI). Durch raschen Therapiebeginn mit Hirnbestrahlung und Chemotherapie wurden weitere Blutungen verhindert.

Die zweite Patientin mit einem Schlaganfall durch Embolien eines rezidivierenden Herzmyxoms (Swiss-Syndrom/Carney-Komplex) zeigte angiographisch multiple Aneurysmata, welche am ehesten ebenfalls tumorbedingt sind. Wahrscheinlich durch eine thromboembolisch bedingte Komplikation eines grösseren Aneurysmas erlitt sie später einen weiteren Hirninfarkt.

Diskussion: Eine onkotische Genese von Aneurysmata sollte bei unklaren Hirnblutungen in die Differentialdiagnose miteinbezogen werden. Eine rasche Diagnose kann insbesondere beim Chorionkarzinom lebensrettend sein. Andererseits ist bei gewissen bereits diagnostizierten Tumoren, insbesondere bei Herzmyxomen, an das Vorhandensein von Aneurysmata zu denken, welche sekundäre Komplikationen (Blutungen,Thrombo-embolien) verursachen und eventuell therapeutisch angegangen werden können.

Pitfalls in the management of stroke emergencies

M. Siccoli, C. Bassetti

Zurich

Stroke is increasingly recognised as a medical emergency in part because of the proven efficacy of such treatments as thrombolysis and stroke unit.

Four patients’ histories will illustrate some diagnostic pitfalls in the management of stroke emergencies:

• headache and vomiting in a 21-year-old patient with known migraine,
• Todd’s palsy in a 42-year-old man,
• headache, fever, pleocytosis and left temporal lobe lesion in a 30-year-old man,
• acute hand palsy in a 30-year-old woman.

Our cases emphasise the importance of the presence of a skilled clinician trained in neurology in the triage of neurological emergencies including stroke.

Efficacité clinique des injections de toxine botulique chez l’hémiplégique vasculaire: discordance entre la mesure objective de la spasticité et celle de la force

P. Vuadens^a, A. D. Pandyan^b, F. M. J. van Wijck^b, S. Stark^c, G. R. Johnson^b, M. P. Barnes^c

^a 

Clinique romande de réadaptation, Sion

^b 

Centre for Rehabilitation and Engineering Studies, Newcastle upon Tyne (GB)

^c 

Regional Neurorehabiliation Centre, Hunters Moor Hospital, Newcastle upon Tyne (GB)

Introduction: L’effet paralysant de la toxine botulique est de plus en plus utilisé dans le traitement de la spasticité focale. Pour juger de l’effet de cette substance, la plupart des études ont mesuré la sévérité de la spasticité avec des échelles qui ne sont pas validées.

Objectifs: Quantifier les modifications de la spasticité, de la force et des fonctions motrices du membre supérieur après un traitement de toxine botulique chez l’hémiplégique vasculaire.

Méthodes: Etude pilote de 14 patients hémiplégiques à la suite d’un AVC avec une spasticité du membre supérieur. Les muscles injectés sont le biceps (dose moyenne 70 U), le long supinateur (dose moyenne 56,5 U), les fléchisseurs des doigts (dose moyenne 83,3 U). Les mesures furent prises avant et un mois après les injections de toxine botulique. Les échelles de mesure furent l’échelle d’Ashworth modifiée (MAS), l’activité EMG du biceps et triceps, la force isométrique des fléchisseurs et extenseurs du coude, la force de préhension et le score de l’Action Research Arm Test. Les tests non paramétriques furent utilisés pour l’étude statistique.

Résultats: Un mois après les injections, on note une réduction significative de l’activité EMG des fléchisseurs du bras (p <0,05) durant les mouvements passifs. Cette réduction n’est pas associée à une diminution du score de spasticité (MAS). La force des fléchisseurs augmente chez 6/14 patients, et même si cela n’était pas significatif, une diminution de l’activité EMG moyenne était notée dans les fléchisseurs (p = 0,084). La force des extenseurs du bras augmente chez 10/14 sujets, cependant cela n’est pas significatif. La force de préhension augmente chez 9/14 patients de façon non significative. La fonction du bras s’améliore chez 6/14 patients (score d’ARAT: p <0,05). Tous les sujets avaient un certain degré de contractures.

Discussion: Ces résultats démontrent que la toxine botulique diminue l’activité musculaire de façon appropriée mais la MAS n’est pas capable de mesurer cette modification. L’amélioration des fonctions motrices et de la force est contraire à ce qui était attendu. Ces améliorations pourraient être attribuées à l’amélioration du contrôle moteur associé à une diminution des degrés de liberté à la jonction neuromusculaire due à la paralysie induite par la toxine et à la plasticité neuronale.

Microembolic signals and carotid plaque morphology: a study of 43 patients with moderate or high-grade stenosis

I. Mayor^a, E. Vassileva^b, C. Fossati^a, P. H. Lalive^a, R. Sztajzel^a

^a 

Department of Neurology, Neurosonology Unit, University Hospital Geneva

^b 

Department of Neurology, Medical University Hospital Sofia (BG)

Objective: Microembolic signals (MES) detected by transcranial Doppler have been reported in symptomatic and asymptomatic patients presenting increasing degrees of carotid artery stenosis. Several studies, moreover, have demonstrated that MES may be a marker of increased risk of stroke.A few observations have further considered a possible relationship between MES and carotid plaque morphology, describing mainly an association with ulcerated carotid lesions. Echolucent plaques, on the other hand, have also been associated with an increased risk of stroke and therefore we sought to determine whether particular carotid plaque features assessed by ultrasound are more likely to produce MES.

Patients and methods: We have reviewed 43 patients with moderate or high-grade carotid stenosis established by ultrasound. A total of 53 carotid stenoses were screened, with degrees varying from 30 to 99%. Plaque appearance was classified according to 5 subtypes considering different ultrasonic plaque features. Transcranial monitoring of the right and left middle cerebral arteries was performed on each patient during 30 minutes.

Results: MES were more frequently found in patients with anechogenic/hypoechogenic plaques compared to isoechogenic/hyperechogenic lesions (p = 0.05). Compared to MES patients, those with MES presented also more frequently an irregular surface of the plaque; however, the difference between these two groups was not significant.

Conclusion: Patients with MES presented more frequently echolucent plaques. Since MES may be a marker of increased risk of stroke and/or stroke recurrence, the clinical significance of this particular association should be further investigated.

Influence of the type and rate of subarachnoid fluid infusion on lethal neurogenic pulmonary oedema in rats

B. Walder^a, M.-A. Bründler^b, M. Tötsch^b, N. Elia^c, D. R. Morel^c

^a 

Division of Surgical Intensive Care,

^b 

Division of Clinical Pathology,

^c 

Division d’Investigations Anesthésiologiques, University Hospitals Geneva

Introduction: In patients with sudden death from spontaneous subarachnoid haemorrhage (SAH), over 90% present an acute pulmonary oedema, but the underlying pathogenesis of this complication is poorly understood. In addition, the specific role of the extravasated blood products and the associated elevation in intracranial pressure (ICP) leading to the systemic and pulmonary effects during SAH are not well established. We tested a new model of acute and severe SAH of rats.

Methods: We compared fresh whole autologous blood (n = 20) with 5% albumin (n = 19) injected at two different rates (35 sec vs 24 min) into the cisterna magna of anaesthetised, mechanically ventilated rats. Cerebral and systemic haemodynamics and the associated pulmonary function were evaluated.

Results: The type of fluid injected had no influence on survival or haemodynamic and respiratory parameters. Rapid infusion of either blood or albumin (n = 14) produced an acute and transient rise in ICP (>35 mm Hg) associated with sustained systemic hypertension and increased cerebral perfusion pressure. Slow infusion (n = 23) produced a more progressive increase in ICP to similar levels without systemic hypertension or increased perfusion pressure in survivors. 64% of animals (rapid infusion) and 48% (slow infusion) survived the challenge and presented no pulmonary alterations. In contrast, non-surviving rats presented a reduced lung compliance and gas exchange, an increased alveolar-arterial protein concentration ratio (0.36 ± 0.02 vs 0.17 ± 0.03 in survivors; p <0.0001) and lung weight (5.8 ± 0.2 g vs 2.0 ± 0.1 g; p <0.0001), demonstrating a fulminant increased permeability pulmonary oedema leading to death within one hour.

Conclusions: Compared to surviving rats, nonsurvivors presented similar levels of ICP, but a more pronounced systemic vascular response during slow fluid infusion. Our results indicate that, rather than the degree of ICP or the type of fluid administered, an excessive host’s response to a similar intra-cisternal fluid challenge is a determinant factor in the development of neurogenic pulmonary oedema that is characterised by an acutely increased capillary permeability to proteins.

Haemostatic risk factors in adults with cryptogenic stroke and patent foramen ovale

R. Bühler^a, H. P. Mattle^a, W. A. Wuillemin^b, L. Alberio^c, B. Lämmle^c, F. Demarmels-Biasiutti^c

^a 

Department of Neurology, Inselspital, University of Berne

^b 

Division of Haematology, Department of Internal Medicine, Kantonsspital, Lucerne

^c 

Central Haematology Laboratory, Inselspital, University of Berne

Objective: The aim of the present study was to investigate whether adults with cryptogenic cerebrovascular infarction and patent foramen ovale (PFO) show a higher prevalence of haemostatic risk factors of venous thromboembolism than stroke patients without PFO.

Patients and methods: Between 1988 and 07/2000 a total number of 355 patients referred to our departments with a history of cerebrovascular infarction (CVI) were investigated for putative haematological and coagulation disorders. Diagnosis of stroke was defined by a focal neurological deficit on clinical assessment and confirmed by corresponding findings on either computerised tomography or magnetic resonance imaging. All patients underwent routine examinations for known causes of stroke. Based on these findings patients were classified into groups according to the TOAST classification. Diagnosis of PFO was made by transthoracic and mostly transoesophageal echocardiography. The analysis of haematological and coagulation parameters was done according to standardised methods.

Results: After exclusion of patients with defined aetiology of stroke 227 non-anticoagulated adults (129 male [m], 98 female [f], median age 40.5 years [y], range 16–71 y) having survived ischaemic stroke for at least 2 months were investigated in our study. In 47 patients a PFO could be demonstrated. 1/47 patient of the group with stroke and PFO as well as 13/180 stroke patients without PFO (p = 0.098) had a history of additional venous thromboembolism. 6/180 of the patients without PFO had suffered further arterial events in other localisations (p = 0.205). The prevalence of deficiency of protein C, protein S, antithrombin and of the resistance to activated protein C (APC resistance) did not differ between these two groups. Also the clotting activities of factors (F) II (FII:C), FV (FV:C), FVII (FVII:C), FX (FX:C) as well as plasma levels of fibrinogen were equal in both groups and the differences in prevalence of antiphospholipid antibodies did not reach statistical significance either.

Conclusions: In the 47 patients with ischaemic stroke and patent foramen ovale thrombophilias being accepted as risk factors for venous thromboembolism were as frequent as in the 180 stroke patients without PFO. Thus, further studies are needed to elucidate this unsolved question.