Operative management of carotid artery in-stent restenosis: first experiences and duplex follow-up.

OBJECTIVES: Carotid Artery Stenting (CAS) may be comparable to Carotid Endarterectomy (CEA) as a durable and effective procedure in stroke prevention. Concern remains about the incidence of restenosis after stenting and its management. We evaluated the surgical management of restenosis after CAS. DESIGN: prospective study. METHODS: between December 1997 and April 2001, 217 CAS procedures were performed in 217 patients (155 men and 62 women; age 70 years +/- 8.2). After a mean of 8 months post-stenting four patients (two symptomatic, two asymptomatic with contralateral occlusion) with severe haemodynamic in-stent restenosis (90-99%) had surgical reintervention. RESULTS: standard CEA with removal of the stent was performed in all four patients. No major complications occurred. Intima hyperplasia showed to be the predominant mechanism leading to in-stent restenosis. All four surgically treated patients remained asymptomatic and without recurrent restenosis over a mean follow-up time of 13 months (range 3-20 months). CONCLUSION: the optimal treatment of in-stent restenosis has yet to be defined, but standard CEA with removement of the stent appears to be feasible.

Restenosis after carotid angioplasty and stenting: a follow-up study with duplex ultrasonography.

OBJECTIVES: To prospectively document the incidence, location, risk factors for and clinical consequences of restenosis after carotid artery angioplasty and stenting (CAS). METHODS: Serial duplex and neurological examinations were performed in 217 patients one day (n = 216), 3 (n = 189), 12 (n = 129) and 24 (n = 48) months, after CAS. The relationship between patient, lesion and procedure variables and restenosis was determined at 12 months. RESULTS: The prevalence of restenosis > or = 50% was 14, 16, 18, and 21%, respectively, and was only significantly related with loss of proximal stent apposition (odds ratio 3.4, 95% confidence interval: 1.0-11.7, p < 0.05). Four restenoses were symptomatic. CONCLUSIONS: Restenosis after CAS is common, unpredictable but infrequently symptomatic.

CO(2) fixation by Rubisco: computational dissection of the key steps of carboxylation, hydration, and C-C bond cleavage.

Despite intensive experimental and computational studies, some important features of the mechanism of the photosynthetic CO(2)-fixing enzyme, Rubisco, are still not understood. To complement our previous investigation of the first catalytic step, the enolization of D-ribulose-1,5-bisphosphate (King et al., Biochemistry 1998, 44, 15414-15422), we present the first complete computational dissection of subsequent steps of the carboxylation reaction that includes the roles of the central magnesium ion and modeled residues of the active site. We investigated carboxylation, hydration, and C-C bond cleavage using the density functional method and the B3LYP/6-31G(d) level to perform geometry optimizations. The energies were determined by B3LYP/6-311+G(2d,p) single-point calculations. We modeled a fragment of the active site and substrate, taking into account experimental findings that the residues coordinated to the Mg ion, especially the carbamylated Lys-201, play critical roles in this reaction sequence. The carbamate appears to act as a general base, not only for enolization but also for hydration of the beta ketoacid formed by addition of CO(2) and, as well, cleavage of the C2-C3 bond of the hydrate. We show that CO(2) is added directly, without assistance of a Michaelis complex, and that hydration of the resultant beta ketoacid occurs in a separate subsequent step with a discrete transition state. We suggest that two conformations of the hydrate (gem-diol), with different metal coordination, are possible. The step with the highest activation energy during the carboxylation cycle is the C-C bond cleavage. Depending on the conformations of the gem-diol, different pathways are possible for this step. In either case, special arrangements of the metal coordination result in bond breaking occurring at remarkably low activation energies (between 28 and 37 kcal mol(-1)) which might be reduced further in the enzyme environment.

[An infant with pain and meningeal irritation due to Guillain-Barré syndrome]. / Een zuigeling met pijn en meningeale prikkeling door het syndroom van Guillain-Barré.

In a five-month-old girl, who for a week had cried and displayed a relapse in the motor development, generalised hypotonia and meningism were found. Eventually, the results of the cerebrospinal fluid analysis and electromyography indicated Guillain-Barré syndrome. She was treated with immunoglobulins and made a quick recovery. Guillain-Barré syndrome is an acute or subacute inflammatory demyelinating polyradiculoneuropathy that can occur at any age. In children, the classic symptoms such as a flaccid paralysis and areflexia are not always predominant. Instead, pain is often the most prominent symptom, along with meningism. These symptoms are often insufficiently recognised in practice and as a result of this, delays in the diagnosis of this potentially life-threatening disease often occur.

Stroke from carotid endarterectomy: when and how to reduce perioperative stroke rate?

OBJECTIVES: To analyse four years of CEA with respect to the underlying mechanisms of perioperative stroke and the role of intraoperative monitoring in the prevention of stroke. PATIENTS AND METHODS: From January 1996 through December 1999, 599 CEAs were performed in 404 men and 195 women (mean age: 65 years, range: 39-88). All operations were performed under general anaesthesia using computerised electroencephalography (EEG) and transcranial Doppler (TCD). Any new or any extension of an existing focal cerebral deficit, as well as stroke-related death were registered. Perioperative strokes were classified by time of onset (intraoperative or postoperative), outcome (minor or major stroke), and side (ipsilateral or contralateral). Stroke aetiology was assessed intraoperatively by means of EEG, TCD, completion arteriography or immediate re-exploration, and postoperatively by duplex sonography, computerised tomography (CT) or magnetic resonance imaging (MRI) of the head. RESULTS: Perioperative stroke or death occurred in 20 (3.3%) patients. In four operations stroke was apparent immediately after surgery. Mechanisms of these strokes were ipsilateral carotid artery occlusion (1) and embolisation (3). In 16 patients stroke developed after a symptom-free interval (2-72 h, mean 18 h) due to occlusion of the internal carotid artery on the side of surgery (9). Other mechanisms were: contralateral occlusion of the internal carotid artery (1), postoperative hyperperfusion syndrome (1), intracerebral haemorrhage (1), and contralateral ischaemia due to prolonged clamping (1). In three procedures the cause was unknown. CONCLUSIONS: In our experience most strokes from CEA developed after a symptom-free interval and mainly due to thromboembolism of the operated artery. We suggest the introduction of additional TCD monitoring during the immediate postoperative phase.

Bleeding risk of cerebrovascular malformations in hereditary hemorrhagic telangiectasia.

OBJECT: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominant vascular dysplasia with a high prevalence of cerebrovascular malformations (CVMs), mostly manifested as arteriovenous malformations (AVMs). The natural history and bleeding risk of these CVMs is unknown. The authors investigated the risk of bleeding in conjunction with clinical and radiological features in patients with HHT and proven CVMs. METHODS: Intravenous digital subtraction (DS) angiography was used to screen 196 patients with HHT for the presence of CVMs. Patients with abnormal results on DS angiography were asked to undergo a conventional cerebral angiographic study. All patients with a proven CVM were assessed by a neurologist. The bleeding risk was retrospectively and prospectively calculated for patients with AVMs only, as well as for the whole cohort of patients with CVMs. Twenty-four patients (12.2%; 16 female and eight male), aged 14 to 66 years (mean 35.4 years) with one or more CVMs were identified. Fifteen patients (62.5%) had a CVM and a pulmonary AVM. Eleven patients (45.8%) exhibited no neurological signs of their CVM; six (25%) had headache or migraine; four (16.7%) had seizures; and three (12.5%) had an intracranial hemorrhage. Twenty-two patients had at least one AVM (with a total of 28 AVMs), whereas two patients only had telangiectases. Twenty-seven AVMs were small (96%), 36% were located in eloquent areas of the brain, and 82% had superficial venous drainage. One third of the patients had multiple CVMs. The bleeding risk for patients with at least one AVM ranged from 0.41 to 0.72% per year, and for the whole cohort the range was 0.38 to 0.69% per year. Calculation of the bleeding risk as determined by lesion-years ranged from 0.36 to 0.56% per year for patients with AVMs and from 0.27 to 0.46% per year for all patients with CVMs. CONCLUSIONS: Patients with HHT have a high risk of harboring a CVM, especially in the presence of a pulmonary AVM. These CVMs are mostly low-grade AVMs (Spetzler-Martin Grade I or II), are frequently multiple, and have a lower risk of bleeding than that associated with sporadic AVMs. Female patients are more often affected than male patients. The inherent low sensitivity of DS angiography screening for CVMs may yield false negative results.

Temporary occlusion of middle cerebral artery by macroembolism in carotid surgery.

Two patients are presented who during carotid endarterectomy (CEA) temporarily showed an obstruction of the middle cerebral artery (MCA) mainstem by a macroembolus resulting in cerebral ischaemia. Both cases are unusual examples of CEA and selected from a cohort of more than 1,500 operations. During surgery with general anaesthesia, brain function was monitored with computerized electroencephalography (EEG) and transcranial Doppler (TCD) ultrasonography. The simultaneous use of EEG and TCD monitoring allowed us to witness the development of intraoperative cerebral ischaemia and to relate these events to a temporary occlusion of the MCA mainstem by a macroembolus. This is the first life report that describes obstruction of a cerebral artery by arterial embolism resulting in cerebral ischaemia.

Bilateral sequential facial palsy during chickenpox.

UNLABELLED: Facial palsy is a rare neurological complication of chickenpox. A 5-year-old girl exhibited a right facial palsy followed by the appearance of the characteristic chicken pox exanthem. Subsequently she suffered a left facial palsy. In this patient both pathophysiological mechanisms responsible and their relation to the phase of infection are illustrated. CONCLUSION: Facial palsy as a complication of chickenpox can result from pre-eruptive haematogenous or neurogenous spread of varicella-zoster virus.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease): new insights in pathogenesis, complications, and treatment.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a hereditary disorder leading to easily bleeding telangiectases on skin and mucosal surfaces, and it is associated with the presence of arteriovenous malformations (AVMs) in multiple organ systems. These AVMs may cause serious complications when they are located in the lungs, liver, or brain. The prevalence of AVMs in patients with HHT might be higher than previously estimated. Nowadays, treatment is often possible. In some families, mutations have been shown in the gene encoding for a transforming growth factor receptor, endoglin. Genetic heterogeneity has been demonstrated, suggesting involvement of other transforming growth factor receptors. This might explain the variable clinical expression of the disease. In view of the high prevalence of pulmonary and cerebral AVMs, all patients with HHT should be screened for their presence, and relatives of patients with HHT should be investigated for presence of the disease.

The significance of microemboli detection by means of transcranial Doppler ultrasonography monitoring in carotid endarterectomy.

PURPOSE: Carotid endarterectomy (CEA) performed with continuous transcranial Doppler monitoring provides a unique opportunity to determine the number of cerebral microemboli and to relate their occurrence to the surgical technique. The purpose of this study was to assess in CEA the impact of cerebral microembolism on clinical outcome and brain architecture. We also evaluated the influence of the audible transcranial Doppler signal on the surgeon and his or her technique. METHODS: In a prospective series of 301 patients, CEA was monitored with electroencephalography and transcranial Doppler ultrasonography of the ipsilateral middle cerebral artery. Preoperative and intraoperative risk factors were entered in a logistic regression analysis program to assess their correlation with cerebral outcome. To evaluate the impact of cerebral microembolism on brain architecture, we compared preoperative and postoperative computed tomography scans or magnetic resonance images of the brain in two subgroups of 58 and 40 patients, respectively. RESULTS: Seven (2.3%) patients had intraoperative transient ischemic symptoms, three (1%) had intraoperative strokes, 1 (0.3%) had transient ischemic symptoms after operation, and 10 (3.3%) had postoperative strokes. Four (1.3%) patients died. Microemboli (> 10) noticed during dissection were related to both intraoperative (p < 0.002) and postoperative (p < 0.02) cerebral complications. Microemboli that occurred during shunting were also related to intraoperative complications (p < 0.007). Microembolism never resulted in new morphologic changes on postoperative computed tomography scans. On the contrary, the phenomenon of more than 10 microemboli during dissection was significantly (p < 0.005) related to new hyperintense lesions on postoperative T2-weighted magnetic resonance images. CONCLUSIONS: During CEA the presence of microembolism (> 10 microemboli) during dissection shows a statistically significant relationship with perioperative cerebral complications and with new ischemic lesions on magnetic resonance images of the brain. Moreover, microembolism during shunting is also related to intraoperative complications. Surgeons can be guided by the audio Doppler and emboli signals by changing their technique. This change may result in a decrease of microembolism and consequently in a decline of the intraoperative stroke rate.

Detection of cerebral microemboli by means of transcranial Doppler monitoring before and after carotid endarterectomy.

BACKGROUND AND PURPOSE: The main purpose of carotid endarterectomy (CEA) for neurologically symptomatic high-grade extracranial carotid artery stenosis is to remove the suspected source of cerebral microemboli. Transcranial Doppler (TCD) ultrasonography has the potential for detecting solid microemboli in the basal cerebral arteries. Therefore, TCD monitoring provides the opportunity to assess the rate of microemboli to the brain in patients with symptomatic high-grade carotid artery stenosis and to verify whether these phenomena have ceased after CEA. METHODS: TCD monitoring was performed in 41 patients to detect high-intensity transient signals indicating microemboli in the middle cerebral artery before and after CEA. In the event that, within 1 week after CEA, TCD monitoring revealed ongoing cerebral microemboli on the side of surgery, the examination was repeated 3 months later. RESULTS: High-intensity transient signals were detected preoperatively on the side of the affected carotid artery in 22 patients (54%; mean, 10.2 per hour; range, 1 to 88). Linear regression analysis demonstrated a trend toward an inverse relationship between the number of high-intensity transient signals per hour and the time interval since the last episode of neurological symptoms (P < .1). CEA resulted in a significant reduction in the number of high-intensity transient signals per hour 7 days after surgery (mean, 6.0 versus 0.4 per hour; median, 0 versus 0; n = 37; P < .005) and 3 months later (mean, 6.3 versus 0 per hour; median, 1.3 versus 0; n = 41; P < .0001). CONCLUSIONS: Clearly, TCD monitoring can be helpful in assessing the effect of CEA in removing the suspected source of cerebral microemboli. Ongoing microemboli to the brain should prompt reassessment of the operated carotid artery or a search for other potential sources of cerebral embolism. Carotid artery plaques seem to produce cerebral microemboli for a limited period, which implies that the prophylactic effect of CEA might decrease if the operation is delayed.

Combined carotid and coronary revascularization.

A series of 295 patients with combined extracranial and coronary revascularization procedures is analyzed. Operations were combined in patients with symptomatic or severe carotid lesions. Hospital mortality was 3.5%; hospital morbidity was mainly neurological with 5% reversible neurological deficits or strokes. The independent risk factors for hospital mortality and morbidity as well as for long-term survival and morbidity were statistically analyzed. The 10-year survival was 47% and predominantly determined by the cardiac 10-year survival (61%).

Kinetic analysis of second order reactions using UV-VIS spectroscopy.

A new method was recently developed for the spectroscopic kinetic analysis of reactions with two linearly independent concentration variables. Firstly, the results of this theory applied to experimental data are represented. For this investigation, reactions of the mechanism type A + Bk (1)--> C + D and A + E uc-->|k(2)|F + G were chosen since both reaction steps can be studied separately. The evaluation of the reaction system consisting of both reaction steps gives satisfactory results when the methods of "formal integration" and "singular value decomposition" (SVD) are used. Absorption coefficients of absorbing species are not needed for the evaluation. Only time dependent spectroscopic measuring values and initial concentrations are used in the presented practical example.