[The second (main) phase of an open, randomised, multicentre study to investigate the effectiveness of an INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2): protocol and baseline characteristics of patients included in France]. / La seconde phase d'une étude randomisée, multicentrique évaluant en ouvert l'effet de la réduction intensive de la pression artérielle dans l'hémorragie cérébrale (INTERACT2) : protocole et caractéristiques des patients inclus en France.

RATIONALE AND AIM: The INTERACT pilot study demonstrated the feasibility of the protocol, safety of early intensive blood pressure (BP) lowering, and effects on hematoma expansion within 6hours of onset of intracerebral hemorrhage (ICH). This article describes the design of the second, main phase, INTERACT2. INTERACT2 aims to compare the effects of a management strategy of early intensive BP lowering with a more conservative guideline-based BP management policy in patients with acute ICH. This article also compares the baseline characteristics of the patients included in France with the baseline characteristics of the patients included in the pilot study INTERACT1. DESIGN OF THE STUDY: INTERACT2 is an international, prospective, multicentre, open, assessor-blinded outcome (PROBE), randomised, controlled trial. Patients with a systolic BP greater than 150mmHg are centrally randomised to either to an intensive BP lowering treatment (Systolic BP≤140mmHg within 1hour) or to a conservative treatment strategy (target systolic BP of 180mmHg). A projected 2800 subjects are to be enrolled from approximately 140 centres worldwide to provide 90% power (α 0.05) to detect a beneficial effect of early treatment on the primary outcome. STUDY OUTCOMES: The primary outcome is the combined endpoint of death and dependency according to the modified Rankin Scale (mRS) at 90 days. The key secondary outcome is the primary endpoint in those patients treated within 4hours of ICH. Other predefined secondary outcomes are the separate components of the primary endpoint, grades of physical function on the mRS, health-related quality of life on the EuroQoL, recurrent stroke and other vascular events, days of hospitalisation, requirement for permanent residential care, and unexpected serious adverse events. The study is registered under NCT00716079, ISRCTN73916115, and ACTRN12608000362392. POPULATION: As of early July, 152 patients have been included in France. When compared with the patients randomised in the INTERACT1 pilot study, these patients are older, less likely to have had a previous ICH, more often on antiplatelet or warfarin therapy, have a lower diastolic BP, arere more severe clinically (higher NIHSS) and experience their first ICH.

Successful Reperfusion is Associated with Favorable Functional Outcome despite Vessel Perforation during Thrombectomy: A Case Series and Systematic Review.

BACKGROUND: Arterial perforation is a potentially serious complication during endovascular thrombectomy. PURPOSE: Our aim was to describe interventional approaches after arterial perforation during endovascular thrombectomy and to determine whether reperfusion remains associated with favorable outcome despite this complication. DATA SOURCES: Data from consecutive patients with acute stroke undergoing endovascular thrombectomy were retrospectively collected between 2015 to 2020 from a single-center cohort, and a systematic review was performed using PubMed, EMBASE, and Ovid MEDLINE up to June 2020. STUDY SELECTION: Articles reporting functional outcome after arterial perforation during endovascular thrombectomy were selected. DATA ANALYSIS: Functional outcomes of patients achieving successful reperfusion (TICI 2b/3) were compared with outcomes of those with unsuccessful reperfusion in our single-center cohort. We then summarized the literature review to describe interventional approaches and outcomes after arterial perforation during endovascular thrombectomy. DATA SYNTHESIS: In our single-center cohort, 1419 patients underwent endovascular thrombectomy, among whom 32 (2.3%) had vessel perforation and were included in the analysis. The most common hemostatic strategy was watchful waiting (71% of cases). Patients with successful reperfusion had a higher proportion of favorable 90-day mRS scores (60% versus 12.5%; P = .006) and a lower mortality rate (13.3% versus 56.3%, P = .01) than patients without successful reperfusion. Thirteen articles were included in the systematic review. Successful reperfusion also appeared to be associated with better outcomes. LIMITATIONS: Given the low number of published reports, we performed only a descriptive analysis. CONCLUSIONS: Arterial perforation during endovascular thrombectomy is rare but is associated with high mortality rates and poor outcome. However, successful reperfusion remains correlated with favorable outcome in these patients.

Tandem Carotid Lesions in Acute Ischemic Stroke: Mechanisms, Therapeutic Challenges, and Future Directions.

Approximately 15% of patients undergoing endovascular thrombectomy for anterior circulation acute ischemic stroke have a tandem lesion, defined as a severe stenosis or occlusion of the cervical internal carotid artery ipsilateral to its intracranial occlusion. Patients with tandem lesions have worse outcomes than patients with isolated intracranial occlusions, but the optimal management of their carotid lesions during endovascular thrombectomy remains controversial. The main options commonly used in current practice include acute stent placement in the carotid lesion versus thrombectomy alone without definitive revascularization of the carotid artery. While treatment decisions for these patients are often complex and strategies vary according to clinical, anatomic, and technical considerations, only results from randomized trials comparing these approaches are likely to strengthen current recommendations and optimize patient care.

Exophthalmos following mechanical thrombectomy for anterior circulation stroke: A retrospective study and review of literature.

BACKGROUND: Anecdotal cases of exophthalmos after acute mechanical thrombectomy have been described. We sought to estimate the incidence in a large cohort of patients with acute anterior circulation stroke treated with mechanical thrombectomy. Secondarily, we aimed to evaluate the underlying mechanism and to differentiate it on imaging from other pathology with similar clinical orbital features. METHODS: Between November 2016 and November 2018, we performed a retrospective single-center study of 250 patients who underwent anterior circulation mechanical thrombectomy. Development of exophthalmos was independently evaluated by two readers on preprocedure and 24-h postprocedure non-contrast cerebral CT. RESULTS: In the mechanical thrombectomy cohort, six individuals (2.4%) developed interval ipsilateral exophthalmos at 24 h. Of these, at least two patients developed clinical symptoms. There was almost perfect agreement between assessments of the two readers (Cohen's kappa = 0.907 (95% confidence interval: 0.726, 1.000)). In two patients, there was delayed ophthalmic artery filling on digital subtraction angiography. None of the patients had features of a direct carotid-cavernous fistula. CONCLUSIONS: Exophthalmos is not uncommon after mechanical thrombectomy (2.4%). The underlying mechanism is difficult to confirm, but it is most likely due to orbital ischemia from hypoperfusion or distal emboli.

Vascular risk factors and morphometric data in cervical artery dissection: a case-control study.

BACKGROUND: Limited knowledge exists on vascular risk factors, body height and weight in patients with spontaneous cervical artery dissection (sCAD). PATIENTS AND METHODS: In this case-control study, major vascular risk factors, body weight, body height and body mass index (BMI) of 239 patients obtained from a prospective hospital-based sCAD registry were compared with 516 age- and sex-matched healthy controls undergoing systematic health examinations in the Clinical and Preventive Investigations Center, Paris. Gender-specific analyses were performed. RESULTS: The mean body height was higher in sCAD patients than in controls (171.3 cm (SD 8.6) vs 167.7 cm (8.9); p<0.0001) and sCAD patients had a significantly lower mean body weight (67.5 (12.2) kg vs 69.3 (14.6) kg; p<0.001) and mean BMI (22.9 (3.3) kg/m2 vs 24.5 (4.2) kg/m2; p<0.0001) than controls. The overall frequency of hypertension, diabetes, current smoking, past smoking and hypercholesterolaemia did not differ significantly between sCAD patients and controls. The mean total plasma cholesterol level was identical in both groups (5.5 mmol/l, SD 1.1). Gender specific subgroup analyses showed similar results for men and women. CONCLUSION: Patients with sCAD had a higher body height and a lower body weight and BMI than controls, while major vascular risk factors were similar in sCAD patients and controls.

Triple and quadruple spontaneous cervical artery dissection: presenting characteristics and long-term outcome.

BACKGROUND: Spontaneous cervicocephalic artery dissection (sCAD) of more than two cervical arteries is rare. PATIENTS AND METHODS: Vascular and potential sCAD risk factors, triggering events, clinical and neuroimaging findings, and outcome of patients with multiple sCAD were studied. Patients were drawn from prospective hospital-based sCAD registries. RESULTS: Of 740 consecutive patients with sCAD, 11 (1.5%) had three, and one had four (0.1%) sCAD. Eight of these 12 patients were women. One patient had additional dissections of the celiac trunk and hepatic artery. Vascular risk factors included hypertension (n = 1), hypercholesterolaemia (n = 6), current smoking (n = 5) and migraine (n = 6). No patient had a family history of sCAD, fibromuscular dysplasia (FMD) or connective tissue disease. SCAD was preceded by a minor trauma in five and infection in four patients. Clinical manifestations included ischaemic stroke (n = 8), transient ischaemic attack (n = 3), headache (n = 9), neck pain (n = 4), Horner syndrome (n = 5), pulsatile tinnitus (n = 2) and dysgeusia (n = 1). Brain MRI revealed ischaemic infarcts that affected one vessel territory in seven and two territories in two patients. The 3-month outcome was favourable (modified Rankin scale score 0-1) in 10 patients (83%). No new recurrent stroke or sCAD occurred during a mean follow-up of 50 (SD 29) months. CONCLUSION: Multiple sCAD occurred preferentially in women and caused clinical symptoms and signs mainly in one vascular territory. In none of the patients was FMD or any other underlying arteriopathy apparent. The majority of multiple sCAD was preceded by a minor trauma or infection. Clinical outcome was favourable in most patients, and long-term prognosis benign. The data suggest that transient vasculopathy may be a major mechanism for multiple sCAD.

[Unruptured brain arteriovenous malformations]. / Malformations artérioveineuses cérébrales non rompues.

Cerebral arteriovenous malformations (AVMs) often become symptomatic in young adults with a variety of neurological symptoms such as epileptic seizures, recurrent headaches, progressive neurological deficits or sudden intracranial hemorrhage. However, recent epidemiological data suggest a large number of AVMs are found without signs of hemorrhage and a relatively low rupture risk of less than 1% per year. Continuous technical progress has led to several specific treatment options for brain AVMs including endovascular embolization, microneurosurgery, and stereotactic radiotherapy, either alone or in any combination. Depending on AVM topography and vascular anatomy, interventional treatment strategies have shown successful occlusion rates ranging between 50 and 100% and a relatively low average procedural morbidity of 10% overall. For unruptured brain AVMs, however, the clinical benefit of invasive treatment remains as yet to be determined. To address this issue, A randomized trial of unruptured brain AVMs (ARUBA) is currently underway evaluating long-term outcome of best possible standard interventional therapy as compared to the natural history risk in a prospective multidisciplinary international study (www.arubastudy.org).

Diagnosis and treatment of dural carotid-cavernous fistulas: a consecutive series of 27 patients.

OBJECTIVES: To report clinical characteristics, angiographical findings and results of endovascular treatment of patients presenting with dural carotid-cavernous fistulas (DCCFs). METHOD: Retrospective analysis of 27 consecutive patients with DCCF referred to a specialised interventional neuroradiology department. RESULTS: Orbital and neuro-ophthalmological symptoms were the most common clinical presentation at diagnosis (n = 25). The venous drainage of the fistula involved the ipsilateral superior ophthalmic vein in 24 patients, the contralateral cavernous sinus in 6 and a leptomeningeal vein in 5 patients. Thrombosis of at least one petrosal sinus was found in 23 patients. 7 patients did not receive endovascular treatment: 3 had spontaneous DCCF obliteration, and 4 had only minor clinical symptoms and no leptomeningeal venous drainage on an angiogram. 20 patients received endovascular treatment via either a transvenous (n = 16) or a transarterial approach (n = 4). Complete occlusion of the fistula was obtained in 14 of 16 (87%) patients treated by the transvenous approach and in 1 of 4 (25%) patients treated by the transarterial approach. 16 patients had early clinical improvement after endovascular treatment. One patient had a cerebral haemorrhage after transvenous embolisation of a DCCF with leptomeningeal drainage. On follow-up, all patients treated by the transarterial route remained symptomatic, whereas 10 of 14 (71%) patients cured by the transvenous route were asymptomatic. CONCLUSIONS: Transvenous embolisation is a safe and efficient endovascular approach to treat patients with DCCF. However, this technique requires a long learning curve.

Pain as the only symptom of cervical artery dissection.

BACKGROUND: Headache or neck pain is a frequent symptom of spontaneous cervical artery dissection (sCAD). PATIENTS AND METHODS: Patients were drawn from an ongoing hospital-based registry of consecutive cases diagnosed with sCAD. Only patients with isolated pain were included in this series. Pain topography, dynamics, severity and quality, imaging findings and outcome were analysed. RESULTS: 20 of 245 (8%) patients with sCAD presented with pain as the only symptom (mean (SD) age 39 (8) years; 14 (70%) women). Of them, 12 had vertebral artery dissection, 3 had internal carotid dissection and 5 had multiple dissections. The median delay from symptom onset to diagnosis was 7 days (range 4 h to 29 days). 6 patients presented with headache, 2 with neck pain and 12 with both. Onset of headache was progressive in 6, acute in 8 and thunderclap-type in 4 patients; neck pain was progressive in 7 and acute in 7. Headache was throbbing in 13 and constrictive in 5 patients; neck pain was throbbing in 4 and constrictive in 10. Pain was unilateral in 11 and bilateral in 9. Pain was different from earlier episodes in all but one case. All patients were pain free at 3 months. CONCLUSION: Pain may be the only symptom in sCAD, even when multiple arteries are dissected. Pain topography, dynamics, quality and intensity were heterogeneous. Data from this study lend support to recommendations favouring imaging studies of the cervical arteries in patients with new-onset unexplained headache or neck pain.

[The neurology of cerebral arteriovenous malformations]. / Neurologie des malformations artérioveineuses cérébrales.

INTRODUCTION: Brain arteriovenous malformations (AVMs) constitute a neurovascular disorder that comes to clinical attention mainly in young adults in their mid thirties. Associated symptoms often require neurological treatment for symptomatic seizures (focal or generalized), headaches (episodic or chronic), progressive neurological deficits, or spontaneous AVM rupture leading to intracerebral, intraventricular, and/or subarachnoid hemorrhage. STATE OF ART: Little data exist in the medical literature regarding the natural history risk of the disease and no controlled studies are available on the risk of invasive AVM treatment (endovascular, neurosurgery, radiotherapy). PERSPECTIVES: This review focuses on all aspects of neurological brain AVM management and discusses possible predictors of the natural history risk as well as the benefit and risk of invasive treatment. CONCLUSIONS: AVM patient management is ideally based on a trans-disciplinary approach via a neurovascular team of neurologists, neuroradiologists, neurosurgeons, and radiotherapists. A newly diagnosed AVM does not necessarily represent an a priori indication for interventional treatment. The decision in favor or against therapy mainly depends on clinical criteria (ruptured versus unruptured AVM, neurological exam, patient age and co-morbidity, etc.) and the angioarchitecture of the malformation. The ARUBA study is going to be the first randomized clinical trial comparing the risk of invasive treatment versus non-invasive management.

Peripheral hemodialysis shunt with intracranial venous congestion.

BACKGROUND: Intracranial venous congestion is often caused by local venous thrombosis or brain arteriovenous fistulas. Hemodialysis shunts are known to cause venous enlargement in the arm or chest but have not been related to intracranial vascular pathology. Case Description- A 59-year-old woman who presented with increasing headache, gait instability, and memory loss was a renal transplant recipient who still carried a left upper arm shunt. Cranial CT scan showed enlarged veins in the posterior fossa with incipient hydrocephalus. Extracranial duplex sonography revealed reversed flow in the left internal jugular vein, which normalized on cuff inflation around the shunt-carrying arm. The reversed flow, intracranial venous congestion, and neurological status improved after surgical shunt ligation. CONCLUSIONS: To our knowledge, this is the first case description of an intracranial venous outflow obstruction caused by a peripheral arteriovenous shunt.

Determinants of neurological outcome after surgery for brain arteriovenous malformation.

BACKGROUND AND PURPOSE: We sought to define determinants of neurological deficit after surgery for brain arteriovenous malformation (AVM). METHODS: One hundred twenty-four prospective patients (48% women, mean age 33 years) underwent microsurgical brain AVM resection. Patients were examined by 3 study neurologists immediately before surgery, postoperatively in-hospital, by in-person long-term follow-up, and with a structured telephone follow-up. They were classified according to the 5-point Spetzler-Martin grading system, with its 3 elements: size, venous drainage pattern, and location. The functional neurological status was classified with the modified Rankin scale. Multivariate logistic regression models were applied to test the effect of patient age, gender, and the 3 Spetzler-Martin elements on early and long-term postoperative neurological complications. RESULTS: Twelve patients (10%) were classified as Spetzler-Martin grade 1; 36 (29%) as grade 2; 47 (38%) as grade 3; 26 (21%) as grade 4; and 3 (2%) as grade 5. Postoperatively, in-hospital, 51 patients (41%) showed new neurological deficits (15% disabling [ie, Rankin scale score >2] and 26% nondisabling [ie, Rankin 1 or 2]). At long-term follow-up (mean follow-up time 12 months), 47 patients (38%) revealed surgery-related neurological deficits (6% disabling; 32% nondisabling). The rate of neurological complications increased by Spetzler-Martin grade. Female gender, AVM size, and deep venous drainage were significantly associated with neurological deficits at in-hospital and long-term evaluation. For patient age and AVM location, no significant association was found. CONCLUSIONS: The findings suggest that female gender, AVM size, and AVM drainage into the deep venous system may be determinants of neurological deficit after microsurgical AVM resection.

Incident hemorrhage risk of brain arteriovenous malformations located in the arterial borderzones.

BACKGROUND AND PURPOSE: We sought to assess the relative risk of hemorrhagic presentation of brain arteriovenous malformations (AVMs) located in the arterial borderzone territories. METHODS: The 464 consecutive, prospectively enrolled patients from the New York AVM Databank were analyzed. AVM borderzone location was coded positive when the malformation was supplied by branches of at least 2 of the major circle of Willis arteries (anterior, middle, and/or posterior cerebral arteries). AVMs fed by branches of only 1 major pial or any other single artery served as a comparison group. Clinical presentation (diagnostic event) was categorized as (1) intracranial hemorrhage, proven by brain imaging, or (2) seizure, focal neurological deficit, headache, or other event with no signs of AVM hemorrhage on brain imaging. RESULTS: In 48% (n=222) of the patients, AVMs were located in the arterial borderzone territories; in 52% (n=242) a non-borderzone location was found. Hemorrhage was the presenting symptom in 44% (n=205); 28% (n=132) presented with seizures, 11% (n=52) with headaches, 7% (n=34) with a neurological deficit, and 9% (n=41) with other or no AVM-related symptoms. The frequency of incident AVM hemorrhage was significantly lower in borderzone AVMs (27%, n=61) than in non-borderzone malformations (60%, n=144; P:<0.001). This difference remained significant in a multivariate model controlling for age, sex, AVM size, deep venous drainage, and presence of aneurysms (odds ratio, 0.4; 95% CI, 0.25 to 0.66). CONCLUSIONS: Our findings suggest that borderzone location is an independent determinant for a lower risk of AVM hemorrhage at initial presentation.

Risk of endovascular treatment of brain arteriovenous malformations.

BACKGROUND AND PURPOSE: Independently assessed data on frequency, severity, and determinants of neurological deficits after endovascular treatment of brain arteriovenous malformations (AVMs) are scarce. METHODS: From the prospective Columbia AVM Study Project, 233 consecutive patients with brain AVM receiving > or =1 endovascular treatments were analyzed. Neurological impairment was assessed by a neurologist using the Rankin Scale before and after completed endovascular therapy. Multivariate logistic regression models were used to identify demographic, clinical, and morphological predictors of treatment-related neurological deficits. The analysis included the components used in the Spetzler-Martin risk score for AVM surgery (AVM size, venous drainage pattern, and eloquence of AVM location). RESULTS: The 233 patients were treated with 545 endovascular procedures. Mean follow-up time was 9.6 months (SD, 18.1 months). Two hundred patients (86%) experienced no change in neurological status after treatment, and 33 patients (14%) showed treatment-related neurological deficits. Of the latter, 5 (2%) had persistent disabling deficits (Rankin score >2), and 2 (1%) died. Increasing patient age [odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01 to 1.08], number of embolizations (OR, 1.41; 95% CI, 1.16 to 1.70), and absence of a pretreatment neurological deficit (OR, 4.55; 95% CI, 1.03 to 20.0) were associated with new neurological deficits. None of the morphological AVM characteristics tested predicted treatment complications. CONCLUSIONS: From independent neurological assessment and prospective data collection, our findings suggest a low rate of disabling treatment complications in this center for endovascular brain AVM treatment. Risk predictors for endovascular treatment differ from those for AVM surgery.

Association of infratentorial brain arteriovenous malformations with hemorrhage at initial presentation.

BACKGROUND AND PURPOSE: The goal of this study was to analyze the association of hemorrhagic presentation with infratentorial brain arteriovenous malformations (AVMs). METHODS: The 623 consecutive, prospectively enrolled patients from the Columbia AVM Databank were analyzed in a cross-sectional study. Clinical presentation (diagnostic event) was categorized as intracranial hemorrhage or nonhemorrhagic presentation. From brain imaging and cerebral angiography, AVM location was classified as either infratentorial or supratentorial. Univariate and multivariate statistical models were applied to test the effect of age, sex, AVM size and location, venous drainage pattern, and associated (ie, feeding artery or intranidal) arterial aneurysms on the likelihood of hemorrhage at initial AVM presentation. RESULTS: Of the 623 patients, 72 (12%) had an infratentorial and 551 (88%) had a supratentorial AVM. Intracranial hemorrhage was the presenting symptom in 283 patients (45%), and infratentorial AVM location was significantly more frequent (18%) among patients who bled initially (6%; odds ratio [OR], 3.60; 95% confidence interval [CI], 2.09 to 6.20). This difference remained significant (OR, 1.99; 95% CI, 1.07 to 3.69) in the multivariate logistic regression model controlling for age, sex, AVM size, deep venous drainage, and associated arterial aneurysms. In the same model, the effect of other established determinants for AVM hemorrhage--ie, AVM size (in 1-mm increments; OR, 0.95; 95% CI, 0.94 to 0.96), deep venous drainage (OR, 3.09; 95% CI, 1.87 to 5.12), and associated aneurysms (OR, 2.78; 95% CI, 1.76 to 4.40)--remained significant. CONCLUSIONS: Our findings suggest that infratentorial AVM location is independently associated with hemorrhagic AVM presentation.

Dysplastic vessels after surgery for brain arteriovenous malformations.

BACKGROUND AND PURPOSE: The cause and clinical significance of residual dysplastic vessels after surgery for brain arteriovenous malformations (AVM) are unclear. We studied predictors and frequency of residual dysplastic vessels on cerebral angiography after AVM surgery. METHODS: The 240 prospectively enrolled surgical patients from the New York AVM Databank underwent 269 AVM-related surgical procedures. Reported postoperative brain angiographic findings were classified post hoc as showing (1) persistent dysplastic vessels, (2) a residual AVM, (3) focal hyperemia in the surgical bed, (4) other changes, or (5) a normal angiogram. Univariate and multivariate models were applied to test for an association between residual dysplastic vessels and patient age, sex, preoperative AVM size, anatomic AVM location, number of embolization procedures before surgery, and the time interval between AVM surgery and the postoperative angiogram. RESULTS: Of the 224 documented postoperative angiograms, 78 (35%) showed dysplastic vessels, 24 (11%) had evidence for a residual AVM, 16 (7%) showed focal hyperemia, 6 (2%) revealed other findings, and 100 (45%) were normal. The number of cases showing angiographic evidence for dysplastic vessels was significantly associated with increasing size of the AVM (in millimeter increments; P=0.0001); the mean diameter of AVMs in patients showing dysplastic vessels after surgery was significantly larger (41 mm, SD +/-14) than in those without residual dysplastic vessels (27 mm, SD +/-13; P<0.001). Symptomatic postoperative intracerebral hemorrhage occurred in 4 patients (1%), in 2 of whom dysplastic vessels were seen on the postoperative angiogram. CONCLUSIONS: The findings suggest that persistent dysplastic vessels may be found in approximately one third of angiograms after AVM surgery. Preoperative AVM size was found to be an independent predictor for the occurrence of dysplastic vessels on the postoperative angiogram.

The New York Islands AVM Study: design, study progress, and initial results.

BACKGROUND AND PURPOSE: Prospective population-based data on the incidence of brain arteriovenous malformation (AVM) hemorrhage are scarce. We studied lifetime detection rates of brain AVM and incident AVM hemorrhage in a defined population. METHODS: The New York islands (ie, Manhattan Island, Staten Island, and Long Island) comprise a 9,429,541 population according to the 2000 census. Since March 15, 2000, all major New York islands hospitals have prospectively reported data on consecutive patients living in the study area with a diagnosis of brain AVM and whether the patient had suffered AVM hemorrhage. Patients living outside the ZIP code-defined study area were excluded from the study population. RESULTS: As of June 14, 2002, 284 prospective AVM patients (mean+/-SD age, 35+/-18 years; 49% women) were encountered during 21,216,467 person-years of observation, leading to an average annual AVM detection rate of 1.34 per 100,000 person-years (95% CI, 1.18 to 1.49). The incidence of first-ever AVM hemorrhage (n=108; mean age, 31+/-19 years; 45% women) was 0.51 per 100,000 person-years (95% CI, 0.41 to 0.61). The estimated prevalence of AVM hemorrhage among detected cases (n=144; mean age, 33+/-19 years; 50% women) was 0.68 per 100,000 (95% CI, 0.57 to 0.79). CONCLUSIONS: Our prospective data, spanning 27 months, suggest stable rates for AVM detection and incident AVM hemorrhage. Approximately half of AVM patients may suffer intracranial hemorrhage.

Effect of age on clinical and morphological characteristics in patients with brain arteriovenous malformation.

BACKGROUND AND PURPOSE: The goal of this work was to determine the effect of age at initial presentation on clinical and morphological characteristics in patients with brain arteriovenous malformation (AVM). METHODS: The 542 consecutive patients from the prospective Columbia AVM database (mean+/-SD age, 34+/-15 years) were analyzed. Univariate statistical models were used to test the effect of age at initial presentation on clinical (AVM hemorrhage, seizures, headaches, neurological deficit, other/asymptomatic) and morphological (AVM size, venous drainage pattern, AVM brain location, concurrent arterial aneurysms) characteristics. RESULTS: Hemorrhage was the presenting symptom in 46% (n=247); 29% (n=155) presented with seizures, 13% (n=71) with headaches, 7% (n=36) with a neurological deficit, and 6% (n=33) without AVM-related symptoms. Increasing age correlated positively with intracranial hemorrhage (P=0.001), focal neurological deficits (P=0.007), infratentorial AVMs (P<0.001), and concurrent arterial aneurysms (P<0.001); an inverse correlation was found with seizures (P<0.001), AVM size (P=0.001), and lobar (P<0.001), deep (P=0.008), and borderzone (P=0.014) location. No age differences were found for sex, headache, asymptomatic presentation, and venous drainage pattern. CONCLUSIONS: Our data suggest a significant interaction of patient age and clinical and morphological AVM features and argue against uniform AVM characteristics across different age classes at initial presentation. In particular, AVM patients diagnosed at a higher age show a higher fraction of AVM hemorrhage and are more likely to harbor additional risk factors such as concurrent arterial aneurysms and small AVM diameter. Longitudinal population-based AVM data are necessary to confirm these findings.

Unraveling the neuron jungle: the 1879-1886 publications by Wilhelm His on the embryological development of the human brain.

The neuron doctrine, one of the central paradigms of the neurological sciences, states that neurons are individual units. Wilhelm His helped to lay the scientific foundation for the neuron doctrine. This Swiss researcher's experimental approach, which was based on the examination of embryological material, is of particular interest because few investigators at that time were using it. Only selected excerpts from His' seminal 1886 work have been translated into English. Therefore, details regarding his experimental materials and primary observations are unavailable to the American reader. Our objective was to translate additional sections of the seminal 1886 publication and, when relevant, portions of previously untranslated works dating back to 1879 and 1883 so that we could better understand this embryologist's experimental materials, his primary observations, and the basis for his conclusions. By 1886, His had compiled a collection of 12 human embryos of various measured lengths and estimated gestational ages ranging from 2.15 mm to 24 mm, and 2 weeks to 8.5 weeks. He had studied the embryological development of nerve fibers in successively older specimens. For example, he contrasted the young embryo N, whose "nerves. stop only halfway and the distal part [of the extremity] is completely nerve-free," with the older embryo Zw, in which the nerves had already reached "the root of the fingers but none [were] in the territory of the end phalanges." In the 1870s and 1880s, using a discrete collection of 12 human embryos of consecutively older ages, His observed the development of nerve fibers and, from this pattern of growth, eventually suggested that nerve cells were individual units and that the transmission of impulses was possible without direct continuity between neurons. Although this age-based embryological approach seems relatively straightforward by today's standards, few other researchers were using it at the time.

Co-existence of NADPH-diaphorase, fibroblast growth factor-2 and fibroblast growth factor receptor in spinal autonomic system suggests target-specific actions.

In the rat spinal cord, we found substantial co-existence of fibroblast growth factor-2, fibroblast growth factor receptor (type-1 or flg) immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity (a histochemical marker for neuronal nitric oxide synthase) in preganglionic autonomic cell groups of intermediate layers VI, VII and X. Anti-fibroblast growth factor-2 and anti-nitric oxide synthase binding sites were confined to the cytoplasm of reactive neurons as judged by immunogold electron microscopy. Within the major autonomic nucleus, i.e. intermediolateral column, three different populations were identified: (i) fibroblast growth factor and fibroblast growth factor receptor, (ii) fibroblast growth factor/NADPH-diaphorase and (iii) NADPH-diaphorase-only stained cell groups. Sympathoadrenal neurons were prelabelled with fluorescent tracer Fast Blue and co-stained for fibroblast growth factor-like protein and NADPH-diaphorase, suggesting heterologous diversification of neuronal phenotypes and functional organization in the spinal autonomic system. Our findings suggest intriguing roles for nitric oxide and fibroblast growth factor-2 cytokine in the preganglionic sympathetic spinal cord system: The "short-term" diffusible messenger nitric oxide may act as "tonic" and/or "phasic" signal within rostrocaudally oriented function-specific preganglionic units necessary for integrated target control. The "long-term" messenger fibroblast growth factor-2 may be involved in, for example, cytokine-dependent regulation of neuronal NADPH-diaphorase/nitric oxide synthase. Furthermore, co-existence of NADPH-diaphorase, fibroblast growth factor-2 and receptor in sympathoadrenal neurons suggest mutual target-specific regulatory functions, e.g. hormone release and blood perfusion or maintenance of phenotype and plasticity responsiveness of adrenal medullary tissue.