[Neurosyphilis: important differential diagnosis of herpes simplex encephalitis]. / Neurosyphilis: Wichtige Differenzialdiagnose einer Herpesenzephalitis.

Diagnosis of herpes simplex encephalitis in the acute stage is based on clinical symptoms (nonspecific prodromi, neuropsychological deficits, epileptic seizures) in combination with typical CSF abnormalities (lymphomonozytic pleocytosis) and MR imaging abnormalities assumed to be typical for herpes simplex encephalitis (increased fluid-attenuated inversion recovery and T2 hyperintensities in the mesiotemporal lobe region). Definite diagnosis of herpes simplex encephalitis is based on positive polymerase chain reaction in the CSF, usually available some days after hospital admission. Suspected herpes simplex encephalitis requires immediate treatment with acyclovir. Bacterial encephalitis caused by spirochetes may present with similar features but requires different treatment. This should therefore be considered in the differential diagnosis of herpes simplex encephalitis. We report a young patient with neurosyphilis whose correct diagnosis could be made only several days after beginning specific treatment.

[Long term follow-up after intracranial vertebro-basilar artery stenting]. / Langzeitergebnisse nach Behandlung intrakranieller vertebrobasilärer Stenosen mit Stents.

PURPOSE: Recurrent ischemic symptoms attributable to intracranial high-grade vertebrobasilar artery stenoses are associated with a high risk of ischemic stroke, particularly if these occur in spite of aggressive medical treatment. Long term efficacy data for endovascular stent angioplasty of symptomatic intracranial stenoses are lacking. The purpose of this prospective study is to determine the rates of deaths, of ischemic events and of restenosis during long-term follow-up. MATERIALS AND METHODS: Between June 2001 and February 2004 twelve patients (11 male, 1 female; median 63 yrs; range, 46 - 75 yrs) with recurrent ischemic symptoms attributed to > or = 70 % intracranial vertebro-basilar artery stenoses, who had failed aggressive medical treatment, were included. Median follow-up was 24 months (range: 6 to 36 months). Intracranial stenoses were measured using 3D rotation angiography data sets and treated with balloon expandable stents. All patients were scheduled for follow-up including clinical (Barthel Index) and transcranial Doppler examinations and intraarterial angiography at 6 months after intervention. Clinical outcome was defined as the rate of stroke in any vascular territory or death during follow-up. Vascular outcome was determined by the rate of in-stent restenosis 50 % on follow-up as examined by intraarterial angiography at 6 months or by transcranial color-coded duplex sonography. RESULTS: Stent placement was technically successful in all patients. No patient had further cerebral ischemic symptoms; two patients died (1 myocardial infarct, 1 sudden death) during follow-up of median 24 months. The degree of stenoses was reduced from median 81 % (range 69 - 94 %) to 19 % (range 10 - 36 %) immediately after stent placement and to 32 % (range 22 - 48 %) after 6 months. No restenosis > or = 50 % occurred during follow-up. CONCLUSION: Based on this limited series, we believe that in patients, with recurrent symptoms despite aggressive medical treatment, endovascular stent placement in intracranial high-grade vertebrobasilar artery stenoses can be an effective and safe treatment option.

Fibrous cap thickness and smooth muscle cell apoptosis in high-grade carotid artery stenosis.

OBJECTIVE: There is growing evidence that, in high-grade internal carotid artery (ICA) stenosis, continuous fibrous cap thinning is not mandatory for plaque rupture and symptom development. The possibility that smooth muscle cell (SMC) apoptosis is involved in loss of fibrous cap volume has only been examined in a limited number of patients with high grade carotid artery stenosis. METHODS: Endarterectomy specimens from n = 38 consecutive patients undergoing surgery for high-grade ICA stenosis (> or = 70%) were transversely sectioned at 2 mm intervals. Plaque instability was defined clinically, by a history of recent ischemic symptoms (< 60 days before surgery; n = 19) attributable to the stenosis, or histopathologically by the presence of plaque rupture (n = 14). Detailed morphometric analyses of the fibrous cap was based on routine stains; for DNA in situ end labeling the TUNEL technique was used. SMCs were identified by immunostaining for SMC actin. RESULTS: We found no significant difference between symptomatic/asymptomatic or ruptured/unruptured plaque with respect to various morphometric measures of the fibrous cap (i.e. mean area, number of plaque sections with fibrous cap, necrotic core-to-lumen distance at its thinnest or thickest part). The mean (+/- SD) apoptotic SMCs per thousand within the fibrous cap was significantly higher in symptomatic vs. asymptomatic (64.53 +/- 77.3 vs. 6.71 +/- 11.9; P<0.001) but not in ruptured plaques (43.3 +/- 64.4 vs. 30.1 +/- 60.9; P=0.117). CONCLUSIONS: These data suggest that continuous thinning of the fibrous cap is not an essential prerequisite for plaque rupture in ICA stenosis. Symptomatic, but not ruptured plaque, were associated with the highest number of apoptotic SMC. Thus, it seems unlikely that SMC apoptosis promotes plaque rupture by fibrous cap thinning.

S100B as a surrogate marker for successful clot lysis in hyperacute middle cerebral artery occlusion.

OBJECTIVES: The astroglial protein S100B is a marker of cerebral tissue damage. This study investigated whether the serum kinetic of S100B may serve as a surrogate marker of successful clot lysis and early recanalisation (<6 hours) in hyperacute proximal middle cerebral artery (MCA/M1) occlusion. METHODS: The authors prospectively included 23 patients (mean (SD) age, 70.2 (11.0) years) presenting with MCA/M1 occlusion on magnetic resonance angiography (n=18), intra-arterial angiography (IA; n=2), or transcranial Doppler sonography (TCD; n=3) within five hours after symptom onset. Rates of recanalisation and their point of time were determined using TCD or IA. Individual S100B values were determined at hospital admission, every eight hours within the first three days, and at 12 hour intervals from day 4 to day 6. Additionally, the S100B area under the curve (AUC) and the S100B peak value were obtained. RESULTS: Early recanalisation (<6 hours after symptom onset, n=7) was associated with a significantly lower mean S100B AUC compared with no recanalisation (22.2 (40.1) versus 406.8 (284.4) micro g/l per hour; p<0.001). Using receiver operating calculations, a single S100B value obtained 48-96 hours after stroke onset of less than 0.4 micro g/l (cut off point) provided a 86% sensitivity and 100% specificity for sufficient MCA/M1 clot lysis <6 hours. The overall accuracy for a single S100B value obtained in the 48-96 hours time window was as high as for the AUC (95.7%). CONCLUSION: A single S100B value <0.4 micro g/l obtained 48-96 hours after stroke onset indicates successful clot lysis <6 hours in MCA/M1 occlusion with a high degree of accuracy. Thus, determination of a single S100B value may serve as a surrogate marker of early and sufficient MCA/M1 recanalisation in large scale thrombolytic studies.

Expression of tissue factor in high-grade carotid artery stenosis: association with plaque destabilization.

BACKGROUND AND PURPOSE: The procoagulant protein tissue factor (TF) has been implicated in thromboembolic complications associated with advanced atherosclerosis. In this study, we investigated whether TF expression in high-grade stenoses of the internal carotid artery (ICA) is associated with clinical features of plaque destabilization and addressed the relationship between TF expression and plaque inflammation. METHODS: In 36 consecutive patients undergoing surgery for high-grade ICA stenosis, clinical evidence of plaque instability was provided by the recent occurrence of ischemic symptoms attributable to the stenosis and the detection of cerebral microembolism by means of transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. Endarterectomy specimens were stained immunocytochemically for TF expression as well as macrophage (CD68) and T cell (CD3) infiltration. RESULTS: Morphologically, TF immunoreactivity was codistributed with plaque inflammation and predominantly localized to CD68+ macrophages. Accordingly, statistical analysis revealed a significant association of TF expression with plaque infiltration by macrophages (P<0.0001) and T cells (P=0.013). Plaques extensively stained for TF (median of TF+ total section area >40% in semiquantitative assessment) were more frequent in symptomatic (12/27) than in asymptomatic patients (1/9). Conversely, plaques exhibiting little TF expression (median of TF+ section area <20%) were more frequent in asymptomatic (3/9) than in symptomatic (1/27) patients (P=0.016). Likewise, we found a highly significant association of TF expression with the occurrence of cerebral microembolism (P=0.008). CONCLUSIONS: Induction of TF at sites of plaque inflammation may play an important role in the destabilization of high-grade ICA stenosis.

Cysteine-specific radioiodination of proteins with fluorescein maleimide.

A protocol is described for coupling of carrier-free iodine to protein sulfhydryl groups via fluorescein maleimide. 125I is first coupled to fluorescein maleimide in the presence of chloramine T. Iodination is stopped with sodium thiosulfate, and the iodine-substituted fluorescein maleimide is reacted with free cysteines of the protein. Excess label is then removed by gel-permeation chromatography. The procedure avoids exposition of the protein to oxidative conditions and does not require purification of the labeled carrier reagent. Suitability of the method for a given protein can be evaluated spectrophotometrically without employing radioactivity. It can be applied under denaturing conditions and may be particularly useful with mutant proteins carrying engineered single cysteine residues at sites that are not functionally critical.