A consecutive and prospective stroke database covers the state of Baden-Wuerttemberg with 10.8 million inhabitants in Germany.

BACKGROUND: In 1998 Baden-Wuerttemberg (BW), a federal state in southwest Germany with 10.8 million inhabitants, implemented a structured medical concept for the treatment of acute stroke. METHODS: Since 2004 participation in the BW stroke database is mandatory for all hospitals in BW involved in acute stroke care. The stroke database includes all inpatients ≥18 years of age who have suffered an ischemic or hemorrhagic stroke within 7 days before hospitalization. This article presents methodological aspects and first results of the BW stroke database in the time period from 2007 to 2011. RESULTS: Annual inclusion numbers increased continuously (29,422 vs. 35,724, p < 0.001). Median age of stroke onset was stable over time. The proportion of stroke patients ≥80 years increased from 36.9 to 38.8% (p < 0.001). Rates of patients treated in neurology departments rose from 50.7 to 60.9% (p < 0.001) and numbers of patients treated in stroke units rose from 59.1 to 68.4% (p < 0.001). Admission via emergency medical systems increased from 42.8 to 49.7% (p < 0.001) and arrival within 3 h increased from 29.8 to 34.4% (p < 0.001). CONCLUSION: We present results from a large, prospective and consecutive stroke patient database. This first analysis demonstrates a continuous increase of absolute and relative numbers of stroke patients who arrive within 3 h after onset, are hospitalized in neurology departments and treated in stroke units, and are aged ≥80 years.

Spermidine: A predictor for neurological outcome and infarct size in focal cerebral ischemia?

BACKGROUND AND PURPOSE: Polyamines are mainly restricted to the intracellular space. During focal cerebral ischemia, polyamines are released from the intracellular compartment. Experimental studies have implicated a marked elevation in brain tissue and blood. The aim of our study was to investigate whether the elevation of polyamines in the blood of patients with focal cerebral ischemia correlates with the clinical outcome and the infarct volume. METHODS: Polyamines were measured in 16 patients with focal cerebral ischemia and in 8 healthy control subjects. Blood samples for polyamine measurement were taken at admission and at fixed time points for the next 28 days. Polyamines were analyzed in red blood cells by a high-pressure liquid chromatography system. Clinical findings were recorded with the NIH Stroke Scale score. Volume of infarction was analyzed from cranial CT at admission and on days 4 to 6 after ischemia. RESULTS: A significant increase of the spermidine level in the peripheral blood could be observed in all patients with focal cerebral ischemia as compared with control subjects (P:<0.01), starting with the admission. Spermidine values correlated positively with the clinical outcome at several time points in the first 48 hours (r=0.90 to 0.40; P:<0.01) and with the infarct volume in cranial CT on days 4 to 6 (r=0.91; P:<0.01). CONCLUSIONS: As hypothesized from experimental data, polyamine levels in blood increase in patients after focal cerebral ischemia. The results indicate that the peripheral spermidine level is closely associated with the clinical outcome as well as with the infarction volume. Therefore, polyamines may be used as a novel predictor for the prognosis of patients with focal cerebral ischemia.

Flow pattern and structural changes at carotid bifurcation in hypertensive cynomolgus monkeys.

Blood flow pattern and morphological changes within the extracranial carotid system were studied in M. fascicularis before, immediately after, and at various intervals (4 hours, 4 days, 10 days, and 4 weeks) after the introduction of systemic hypertension by surgical coarctation of the thoracic aorta. Intra-arterial hemodynamics were assessed by means of both continuous-wave Doppler signal spectrum analysis and multigate pulsed-wave Doppler flow velocity profile processing. Diminished peak frequencies throughout the carotid system and enlargement of the lumen diameter in the common carotid artery and the carotid bulb were major findings and were suspected to be due to cerebral autoregulation at high levels of intracranial vascular resistance. In the internal carotid artery of pure muscular type, the lumen diameter was diminished so the carotid bulb became an area of structural and hemodynamic transition. As a consequence, flow irregularities already observed in this region before surgery considerably increased during hypertension. In addition, endothelial disarray and leucocytic adherence and activation were associated with these hemodynamic alterations within the carotid bulb. Their mutual role in early atherogenesis is discussed.

Cerebral blood flow velocity alterations during obstructive sleep apnea syndrome.

We recorded cerebral blood flow velocity (CBFV) for the assessment of CO2-regulated alterations during apnea by means of transcranial Doppler ultrasound in a patient with obstructive sleep apnea syndrome. CBFV increased up to doubled peak flow values during obstructive apneic phases. The results provide evidence for a normal CO2 regulation of CBFV leading to periodic vascular stress during the night.

Arterial gas embolism after decompression: correlation with right-to-left shunting.

Paradoxical gas embolism is a possible cause of neurologic sequelae after decompression in divers. The authors detected arterial bubbles after decompression from chamber dives in two of six divers using transcranial Doppler sonography (TCD). Arterial bubbles correlated with the size of right-to-left shunting as diagnosed by contrast TCD. The pathway of spontaneous paradoxical embolism was tracked for the first time, supporting the concept of paradoxical gas embolism as a cause of early neurologic sequelae after decompression in at-risk divers.

Assessment of gait in subcortical vascular encephalopathy by computerized analysis: a cross-sectional and longitudinal study.

In subcortical vascular encephalopathy (SVE) gait disturbance is a common and early clinical sign which might be used to monitor disease progression. In the absence of reliable scales and with regard to the equivocal results of highly complex gait imaging devices we assessed the natural course of SVE in a prospective study, using a new straight forward technique to quantify and compare sequential gait studies. We report the results of 300 computerized gait analyses in 119 patients with SVE and 63 age-matched controls. Thirty-nine SVE patients were re-evaluated to monitor the natural course of the disease and to study the correlation of gait disturbances with MRI changes and neuropsychological findings. The system consists of a set of shoes containing 16 load sensors and a measuring-unit reading each sensor at 20-ms intervals. By off-line analysis we graded each recording on a Gait Disorder Score (GDS) with six variables indicating gait steadiness: step frequency, length of gait lines (which represent the movement of the centre of gravity during heel to toe movement), length of single support lines, variability of single and of double support lines, and double support time. In cross-sectional analysis, patients with SVE showed cadence (steps/min) to be reduced at 87.3 +/- 19.5 (96.4 +/- 7.8 in controls, P < 0.05). Length of gait lines was significantly less: 0.70 +/- 0.13 vs. 0.80 +/- 0.05 in controls, with length of single support gait lines reduced at 0.42 +/- 0.14 in SVE (0.58 +/- 0.06 in controls, P < 0.05). Variability of both single support lines (5.69 +/- 1.90%; 4.24 +/- 1.07% in controls, P < 0.05) and double support lines was elevated (3.59 +/- 1.62% vs. 2.54 +/- 0.59%), while duration of double support phases was increased (0.19 +/- 0.10 s vs. 0.13 +/- 0.02 s in controls, P < 0.05). The progressive character of the disease was demonstrated by increasing GDS values in 39 SVE patients with a frontal gait disorder who were re-investigated after a mean interval of 26 months (5.4 +/- 4.5 vs. 8.4 +/- 5.5, P < 0.05). This study shows the value of a new and practicable gait analysis system for the evaluation of gait disorders and it quantifies the deterioration of gait in SVE patients.

Cerebrovascular involvement in the acute phase of bacterial meningitis.

Cerebral ischaemia is a common complication of bacterial meningitis. Although cerebrovascular involvement in the acute phase of inflammation may be particularly important for the still unacceptably high morbidity and mortality, only, a few studies have investigated cerebrovascular changes in bacterial meningitis. We prospectively investigated changes of intracranial cerebral blood flow velocities (CBFV) in 22 patients (12 men, 10 women, mean age 48 years, 19 years, SD) with bacterial meningitis, by means of transcranial Doppler sonography (TCD). According to previously published criteria the degree of arterial narrowing was assessed and related to the patients' outcome. Elevated CBFVs in the middle cerebral artery were documented in 18/22 patients with markedly increased systolic peak velocities (CBFV of > 210 cm/s) in 7 patients. Serial examinations performed in 11 patients showed elevated CBFV as early as day 1, reaching peak CBFV between day 3 and day 6 after onset of symptoms in most cases. Furthermore, cerebrovascular involvement was also documented by disturbances of physiological slow spontaneous oscillations of blood flow velocities in 5/10 patients examined with TCD. Low Glasgow Coma Scales (< 7) on admission (29% vs 0%), focal cerebral ischaemic deficits (29% vs 7%) and, seizures (43% vs 7%) were more frequent in patients with CBFV of > 210 cm/s. Finally, a poor clinical outcome was significantly related to severe vascular involvement (P < 0.05). In conclusion, cerebrovascular complications are frequently found in patients with bacterial meningitis. TCD is an easily applicable technique for revealing vascular changes non-invasively, even in severely ill patients. Since our data suggest an unfavourable course of the disease in association with increased CBFV in intracranial arteries, probably indicating vasospasm, TCD could potentially be used to identify high-risk patients who could benefit from adjuvant therapeutic interventions.

Assessment of local sympathetic function in patients with erectile dysfunction.

Fifty men with erectile dysfunction (ED) were urologically investigated for autonomic deficit by evaluation of the sympathetic skin response at the penis. They were additionally subjected to thorough urological, vascular, psychiatric and neurological examinations, and well-established neurophysiological tests of the somatosensory, sympathetic, and parasympathetic function. Patients with clinical evidence of neurological deficit showed abnormal results (68%) in at least one test of the autonomic nervous system. The sympathetic skin response at the penis was absent in 11 cases (37%) with clinical evidence of neuronal aetiology of the erectile dysfunction and was normal in all cases with positive evidence of a psychiatric origin of erectile dysfunction and no clinical indication of a neuronal deficit. Moreover, the sympathetic skin response at the penis was abnormal in three cases with normal results in the other neurophysiological tests. The results emphasize that the local sympathetic skin response at the penis is a useful extension of autonomic testing in ED patients since this method tests local sympathetic pathways and is sometimes the only evidence for autonomic deficit. From a clinical viewpoint, the sympathetic skin response at the penis is a very simple and time-saving neurophysiological method suitable for clinical routine and also for the investigation of outpatients.

Efficacy of sonothrombolysis in a rat model of embolic ischemic stroke.

The key goal in the treatment of acute ischemic stroke is fast vessel recanalization. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is efficient in humans but mean time for recanalization is within hours. Ultrasound bio-effects has been shown to facilitate rt-PA mediated thrombolysis in peripheral arteries. We used an embolic stroke model in the rat. In all rats we induced an ischemic stroke by a selective occlusion of the middle cerebral artery with whole blood clots. From an entire collective of 54 rats 47 completed the protocol (n = 7 died early). Four different groups (no treatment n = 6; full dose rt-PA treatment only [10 mg/kg per body weight] n = 14, half dose rt-PA treatment plus ultrasound n = 10, and full dose rt-PA treatment plus ultrasound n = 17) were investigated. We found a significant reduction of absolute as well as relative infarct volume in the full dose rt-PA plus ultrasound group (81+/-72 mm(3); P< 0.05) in comparison to untreated rats (253+/-159 mm(3); P < 0.05) as well as in comparison to rats treated with full dose rt-PA only (167+/-91 mm(3); P < 0.05). There were five intracranial bleedings giving a bleeding rate of 9.3%. In summary: ultrasound treatment in addition to rt-PA is more effective than single rt-PA treatment in reducing infarct volume and safe with regard to bleeding.

Failure to identify cerebral infarct mechanisms from topography of vascular territory lesions.

PURPOSE: Our purpose was to determine whether topographic patterns of ischemic damage seen on brain imaging studies are useful for evaluating different mechanisms of infarction and for distinguishing embolic from hemodynamic disorders. METHODS: Early CT scans were reviewed to identify brain infarctions in the middle cerebral artery territory in 800 patients with either significant obstructive lesions of the internal carotid artery (70% stenosis, n = 17; occlusion, n = 85) or nonvalvular atrial fibrillation (n = 186) as the only identified source of stroke. Ninety-nine CT studies were considered suitable for entry into the final analysis. The scans were digitized and superimposed on postmortem brain sections by matching algorithms to display the variability of the cerebrovascular territories. RESULTS: Cortical borderzone-type infarctions were rare and evenly distributed among patients with cardiac sources of embolism (3.2%) and severe carotid obstructions (3.6%). In contrast, subcortical borderzone infarcts occurred significantly more often in patients with carotid obstructive disease (36% versus 16%). However, on computerized segmentation analysis, the topography of infarction was the same in both groups. CONCLUSION: The current concept that stroke mechanisms can be inferred from interpretation of stroke patterns on brain scans is heavily confounded by the variability in intracranial arterial territory distributions. Since individual arterial territories cannot be identified in vivo, interpretation of stroke topography is invalidated. In particular, the cortical wedge-type of borderzone infarction, said to result from hemodynamic compromise in low-flow perfusion territories, is an ambiguous observation and may be seen in patients with cerebral embolism and hemodynamic compromise due to severe carotid disease.

Vasoneuronal coupling in migraineurs after subcutaneous sumatriptan: a TCD study.

According to the trigeminovascular model of pain in migraine, sterile neurogenic inflammation of dural vessels stimulates nociceptive fibres of the trigeminal nerve. Sumatriptan, a 5-HT1 receptor agonist, blocks this reaction and mediates vasoconstriction of meningeal arteries. However, it is uncertain, whether sumatriptan also has a vasoconstrictive effect on cerebral arteries, which may influence vasoneuronal coupling and induce secondary cerebral blood flow changes. We studied changes of cerebral blood flow velocity (CBFV) and the pulsatility index (PI) in the posterior cerebral artery (PCA) after stimulus activation before, 10 min and 30 min after subcutaneous application of 6 mg sumatriptan, in order to assess potential vasoactive effects on cerebral circulation. CBFV was recorded from both PCAs simultaneously in 27 migraineurs (twenty women, seven men, mean age 29 years), and arterial blood pressure (BP), heart rate (HR) and respiration rate (RR) were monitored. Although the mean diastolic blood pressure rose significantly from 75 mm Hg to 81 mm Hg (P<0.05) and systolic blood pressure and respiration rates remained constant, average CBFV values remained constant. Similarly, the relative increase of CBFV by visual stimulation, which is clearly higher compared to controls in other studies (55.0% before, 52.6% after 10 min, and 52.4% after 30 min), and absolute mean values for CBFV and PI did not change after visual stimulation. These results provide evidence against the hypothesis that sumatriptan produces vasoconstriction in the intracranial human arterial circulation as a potential risk of cerebral ischemia.

Orthostatic changes of cerebral blood flow velocity in patients with autonomic dysfunction.

Simultaneous registrations of intracranial blood flow velocity parameters achieved by transcranial Doppler sonography and basic cardiovascular parameters were carried out during orthostatic changes in normal controls, diabetic patients and patients with pandysautonomia. Normal subjects had a rapid increase in heart rate at a constant blood pressure and a slight decrease in cerebral blood flow velocities associated with a mild increase of the pulsatility index (PI) after being tilted from a horizontal to a vertical position. Diabetics showed a fixed heart rate reflecting the disturbed autonomic innervation but only minor changes of cerebral blood flow velocity, which is similar to normal cerebrovascular autonomic regulation. Patients with pandysautonomia had a fixed heart rate associated with a decrease of systemic blood pressure but a failure of compensatory cerebral autoregulation to maintain normal flow velocity values after standing up. The results suggest that in diabetics cerebrovascular autonomic regulation is intact in contrast to cardiac autonomic function, while in patients with pandysautonomia both functions are disturbed. Criteria for the interpretation of autonomic regulatory mechanisms involved in cerebrovascular flow measurements are discussed.

Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease.

The release of the proinflammatory cytokines IL-1 beta, IL-6, TNF-alpha and soluble TNF-receptors p55 and p75 in peripheral blood was serially determined in 19 patients with acute cerebral ischemia. Only patients admitted within 4 h following onset of symptoms were studied. In contrast to serum levels of IL-1 beta, TNF-alpha and TNF-receptors, which did not exhibit a significant response, IL-6 showed a significant increase of serum levels already within the first hours following onset of disease and reached a plateau at 10 h until day 3 and returned to baseline by day 7. The increase of levels of this cytokine was significantly (P < 0.05) correlated with increasing volumes of brain lesion and was also significantly (P < 0.005) associated with poor functional and neurological outcome. The increase of levels of IL-6 despite a considerable dilution in peripheral blood shown in this preliminary study suggests an early inflammatory response in ischemic brain lesion.

Leakage of brain-originated proteins in peripheral blood: temporal profile and diagnostic value in early ischemic stroke.

The clinical value of determination of CNS-specific proteins in peripheral blood at the acute phase of ischemic stroke is unclear. S-100 protein and neurone specific enolase were serially quantified in peripheral blood at the acute and subacute phase of ischemic stroke (hours 4, 8, 10, 24 and 72 after onset of symptoms). Whereas S-100 protein was detected in none of the matched control subjects. this protein was observed in 17/24 of the stroke patients. Patients with detectable S-100 protein had significantly larger infarctions. Cortical infarctions had already significantly increased S-100 concentrations at days 1 and 3 compared to subcortical or brainstem infarctions. Patients with volumes of brain lesion of >5 ccm exhibited significantly increased serum levels of S-100 at hours 10, 24 and 72 compared to those with lesion volumes of <5 ccm. At hours 10, 24 and 72, concentrations of S-100 correlated with scores of neurological outcome. Although kinetics of release of neurone specific enolase showed a similar pattern of release in blood, no significant association to outcome or extent of brain damage was observed. These results suggest that S-100 protein and not NSE may represent a useful serum marker of brain damage in acute stroke.

Factors influencing acute blood pressure values in stroke subtypes.

The aim of this prospective observational study was to determine the association of acute blood pressure values with independent factors (demographic, clinical characteristics, early complications) in stroke subgroups of different aetiology. We evaluated data of 346 first-ever acute (<24 h) stroke patients treated in our stroke unit. Casual and 24-h blood pressure (BP) values were measured. Stroke risk factors and stroke severity on admission were documented. Strokes were divided into subgroups of different aetiopathogenic mechanism. Patients were imaged with CT-scan on admission and 5 days later to determine the presence of brain oedema and haemorrhagic transformation. The relationship of different factors to 24-h BP values (24-h BP) was evaluated separately in each stroke subgroup. In large artery atherosclerotic stroke (n=59), history of hypertension and stroke severity correlated with higher 24-h BP respectively. In cardioembolic stroke (n=87), history of hypertension, stroke severity, haemorrhagic transformation and brain oedema were associated with higher 24-h BP, while heart failure with lower 24-h BP. History of hypertension and coronary artery disease was related to higher and lower 24-h BP, respectively, in lacunar stroke (n=75). In patients with infarct of undetermined (n=57) cause 24-h BP were mainly influenced by stroke severity and history of hypertension. An independent association between higher 24-h BP and history of hypertension and cerebral oedema was documented in intracerebral haemorrhage (n=68). In conclusion, different factors influence acute BP values in stroke subtypes of different aetiology. If the clinical significance of these observations is verified, a differentiated approach in acute BP management based on stroke aetiology may be considered.

Modification of low-frequency spontaneous oscillations in blood flow velocity in large- and small-artery disease.

During a 30-minute period, the blood flow velocity of both middle cerebral arteries (MCAs) was measured bilaterally in 27 patients with obstructive carotid disease (n = 18, large-artery disease) or subcortical vascular encephalopathy (n = 9, small-artery disease) and in control subjects of similar age and sex distribution (n = 14). To identify low-frequency spontaneous oscillations (LFSOs), MCA envelope curves were Fourier transformed with filter application to select low-frequency spectra (0.01-0.05, 0.05-0.15, 0.15-0.50 Hz). To measure the extent of LFSO amplitudes, a coefficient of variation (CoV) was calculated. In addition, a coefficient of correlation (CoC) was calculated to assess LFSO bilateral synchronicity. Normal ranges for CoV (mean = 5.38 +/- 1.82%) and CoC (mean = 0.91 +/- 0.06) were established in control subjects. In patients with large-artery disease, a significant CoV reduction was observed ipsilateral to the carotid lesion (CoV mean = 3.91 +/- 1.10%; p < 0.05, Wilcoxon's test) with a contralateral compensatory increase (CoV mean = 5.68 +/- 1.79%). In addition, a significant desynchronization of LFSOs was found in patients with large-artery disease (CoC = 0.39 +/- 0.35, p < 0.05). This was less obvious in patients with small-artery disease, who demonstrated a marked bilateral reduction of LFSO activity (CoV mean = 3.60 +/- 0.71%, p < 0.05) and CoC values.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-frequency, low-intensity ultrasound accelerates thrombolysis through the skull.

Systemic thrombolysis of acute ischemic stroke with recombinant tissue plasminogen activator (rt-PA) has been established recently. Whereas the delay to and the rate of vessel recanalization are unknown, they are likely slower and smaller than for local application of rt-PA. This may contribute to the small benefits of recovery reported and stimulate further investigations to improve clot lysis. Pilot studies indicate that continuous-wave low-frequency ultrasound (US) can accelerate rt-PA-mediated recanalization of peripheral thrombotic vessel occlusion. For the hypothesized therapeutical purpose in stroke treatment, we measured the attenuation of ultrasound through the skull at different frequencies and intensities (33.3 and 71.4 kHz; 0.5 and 3.4 W/cm2), and investigated thrombolysis in vitro (n = 125 clots). Attenuation was lowest by transtemporal insonation of 33.3 kHz, 0.1 dB (0.9). Thrombolysis (artificial fibrin-rich clots) was significantly increased after 1 h (p < 0.025) and after 3 h (p < 0.01) for US treatment in combination with rt-PA vs. rt-PA alone. Results suggest that US increases rt-PA-mediated thrombolysis through the skull and may improve benefits of thrombolytic stroke treatment in vivo.

Comparison of transcranial Doppler flow velocity and cerebral blood flow during focal ischemia in rabbits.

The predictive value of transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) measurements for cerebral blood flow (CBF) calculations in humans is still controversial, and experimental correlative studies are lacking. The aim of the present study was to validate TCD signals of CBFV during focal cerebral ischemia. Therefore, CBFV determined in the middle cerebral artery (MCA) was compared with values of CBF obtained from autoradiograms of ischemic brain areas. To determine CBFV, a transcranial Doppler ultrasound probe (TCD) adapted to small sample volumes was used in 9 rabbits. CBF was quantified after a final infusion of [14C]-iodoantipyrine in the same animals. For focal cerebral ischemia induction, two threads were flushed upward simultaneously into the internal carotid artery, resulting in a flow reduction in the ipsilateral MCA. After thread occlusion, mean systolic CBFV in the MCA decreased from 49 +/- 9 cm/s to 22 +/- 3 cm/s. CBF in the caudate nucleus was reduced (19 +/- 8 mL/100 g/min) compared to the contralateral nonischemic side (52 +/- 18 mL/100 g/min). The decrease in hemispheric CBF correlated well with the decrease in both mean systolic (r = 0.97) and diastolic (r = 0.94) CBFV in the MCA (p < 0.01). The decrease in CBFV determined by transcranial Doppler ultrasound in the MCA appears to reflect the reduction in CBF in the affected brain hemisphere and can be used as a quantitative in vivo parameter for tissue perfusion.

Acceleration of thrombolysis with ultrasound through the cranium in a flow model.

Thrombolysis is an efficient therapy for hyperacute stroke within a limited time window. Neurological outcome depends on the recanalization time of the occluded vessel. Nonthermal effects of low-frequency ultrasound (US) accelerate enzymatic fibrinolysis in vitro. We examined the effects of transcranially applied US on recombinant tissue plasminogen activator (rt-PA)-mediated thrombolysis in a flow model in vitro. Pure fibrin clots were placed in a continuous-pressure flow model and treated with rt-PA during 1-MHz US exposure (0.5 W/cm(2); spatial peak, temporal peak intensity). Transcranial and direct US application in combination with rt-PA significantly (p<0.001) shortened recanalization time, increased perfusion flow and reperfusion rate in comparison with rt-PA-mediated thrombolysis alone. Recanalization rate within 30 min was 90-100% in the US-exposed clots vs. 30% in the clots treated only with rt-PA. Our results suggest that transcranial application of 1-MHz US may accelerate reperfusion and recanalization rate of occluded intracerebral vessels by enhancing rt-PA-mediated thrombolysis. Shortening of recanalization time could contribute to optimizing effects of acute thrombolytic stroke therapy.

Transcranial ultrasound-improved thrombolysis: diagnostic vs. therapeutic ultrasound.

Success of stroke treatment with rt-PA depends on rapid vessel recanalization. Enzymatic thrombolysis may be enhanced by additional transcranial application of ultrasound (US). We investigated this novel technique using a 185-kHz probe and compared it to standard diagnostic US. In vitro studies were performed in a continuous pressure tubing system. Clots were placed in a postmortem skull and treated with rt-PA together with or without transtemporal 185-kHz US insonation (2W/cm(2)) and in comparison to 1-MHz diagnostic US (0.5 W/cm(2)). Recanalization time was significantly (p < 0.01) shorter in the 185-kHz (14.1 min) and 1-MHz (17.1 min) US rt-PA treatment group compared to rt-PA treatment alone (29.3 min.). Flow rate was significantly higher (p < 0.025) and increased faster in the combined treatment group with rt-PA + 185-kHz US compared to rt-PA + 1-MHz US. We investigated the blood-brain barrier in rats after 90-min exposure time of the brain with 185-kHz US, but no damage was observed. Results suggest efficacy and safety of the 185-kHz transducer, which is superior to diagnostic US. Such a novel US probe may be able to optimize thrombolytic stroke treatment.