Alexander V. Khaw

Predictors of hemorrhage in patients with untreated brain arteriovenous malformation

Background: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear. Methods: The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up. Results: The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors. Conclusions: Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.

Clinical Outcome After First and Recurrent Hemorrhage in Patients With Untreated Brain Arteriovenous Malformation

Background and Purpose— The morbidity from spontaneous hemorrhage of untreated brain arteriovenous malformations (AVM) is not well described. Methods— The 241 consecutive AVM patients (mean age 37±16 years, 52% women) from the prospective Columbia AVM Databank initially presenting with hemorrhage were evaluated using the Rankin Scale (RS) and the National Institute of Health Stroke Scale (NIHSS). From the 241 AVM patients, 29 (12%) had subsequent intracranial hemorrhage during follow-up. For further comparisons, 84 non-AVM patients with intracerebral hemorrhage from the Northern Manhattan Study (NOMAS) served as a control group. Results— In 241 AVM patients presenting with hemorrhage the median RS was 2 and the median NIHSS was 1 (49% RS 0 to 1, 61% NIHSS <2). The median time between hemorrhage and clinical evaluation was 11 days (mean 219 days). Recurrent AVM hemorrhage during follow-up resulted in no significant increase in morbidity (median RS 2, P=0.004; median NIHSS 3, P=0.322; time between hemorrhage and study evaluation: median 55 days, mean 657 days). Among AVM-hemorrhage subtypes, parenchymatous AVM hemorrhage was associated with higher stroke morbidity (odds ratio, 2.9; 95% CI, 1.5 to 5.8 for NIHSS ≥2) than nonparenchymatous hemorrhages. Parenchymatous AVM hemorrhage had a significantly better outcome (median NIHSS 1) than non-AVM related hemorrhage (median NIHSS 12; P<0.0001). Conclusions— Hemorrhage, either at initial presentation or during follow-up of untreated AVM patients appears to carry a lower morbidity than intracranial hemorrhage from other causes. These findings support a careful weighing of risks from interventional treatment and natural history.

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.

Clinicoradiologic subtypes of Marchiafava-Bignami disease

Abstract.The clinical diagnosis of Marchiafava-Bignami disease (MBD) has considerably changed during recent decades with brain MRI providing the opportunity of a reliable in-vivo diagnosis. However, semiologic and neuroimaging characteristics of the currently known spectrum of MBD have not been investigated systematically, and knowledge of clinicoradiologic associations is sketchy. We report an illustrative case with limited callosal involvement on MRI and a favorable outcome and have reviewed literature on clinical and radiologic features in 50 cases of MBD diagnosed in vivo since 1985. Our reviewed data suggest the differentiation of two clinicoradiologic subtypes: Type A is characterized by major impairment of consciousness, T2-hyperintense swelling of the entire corpus callosum on early MRI and poor outcome. Type B shows at most slight impairment of consciousness, partial callosal lesions on MRI and a favorable outcome. Differentiation of these clinicoradiologic subtypes may help resolve inconsistencies of the established clinical classification resulting from new insights into the clinical course and prognosis of MBD by structural neuroimaging.

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.

Determinants of Staged Endovascular and Surgical Treatment Outcome of Brain Arteriovenous Malformations

Background and Purpose— Therapy of brain arteriovenous malformations (AVMs) often requires the combination of different treatment modalities. Independently assessed data on neurologic outcome after multidisciplinary AVM therapy are scarce. Methods— The 119 consecutive patients (49% women, mean age 34±13 years) with brain AVMs receiving endovascular embolization followed by surgical treatment were analyzed. Neurologic impairment was assessed prospectively by a neurologist using the modified Rankin Scale (mRS) before, during, and after completed AVM therapy. The association of demographic, clinical, and morphologic characteristics with new treatment-related neurologic deficits was calculated. Results— The 119 patients were treated with 240 superselective embolizations (median, 2; range, 1 to 8) using n-butyl cyanoacrylate. Mean follow-up time after surgery was 9.6±13.2 months. On the Spetzler-Martin scale, 8% of the AVMs were grade 1, 27% grade 2, 40% grade 3, 22% grade 4, and 3% grade 5. Disabling treatment-related complications (mRS≥3) occurred in 5% (95% confidence interval [CI], 1% to 9%) of the patients. Nondisabling new deficits were observed in another 42% (95% CI, 33% to 51%). No patient died. Nonhemorrhagic AVM presentation (odds ratio [OR], 5.00; 95% CI, 1.75 to 14.29), deep venous drainage (OR, 3.09; 95% CI, 1.43 to 6.64), AVM location in an eloquent brain region (OR, 2.42; 95% CI, 1.10 to 5.33), and large AVM size (OR, 1.05; 95% CI, 1.01 to 1.09) were independently associated with new treatment-related deficits. Conclusions— Our results suggest an increased treatment risk for patients with previously unbled AVMs from combined endovascular and surgical AVM therapy. Additional risk factors for treatment-related neurologic deficits may be large AVM size, deep venous drainage, and AVM location in eloquent brain regions.

Marchiafava–Bignami disease: Diffusion-weighted MRI in corpus callosum and cortical lesions

The clinical diagnosis of Marchiafava–Bignami disease (MBD) can be difficult. Acute demyelination of the corpus callosum is characteristic of the disease. The authors report the use of MR diffusion-weighted imaging (DWI) in six cases of acute MBD. They show that apparent diffusion coefficient restriction of the corpus callosum and cortical lesions were associated with a higher mortality rate and more severe cognitive sequelae.

Time-Dependent Computed Tomographic Perfusion Thresholds for Patients With Acute Ischemic Stroke

Background and Purpose— Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. Methods— Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion–weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. Tmax, cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver–operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. Results— One hundred and thirty-two patients were included. Tmax thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min−1·100 g−1 were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and Tmax (P<0.001; r=−0.68 and −0.60 for gray and white matter, respectively) parameters. Conclusions— Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion.

Endovaskuläre Therapie des akut ischämischen Schlaganfalls unter Analgosedierung im Vergleich zur Intubationsnarkose – Durchführbarkeit, periprozedurale Sicherheit, klinisches und radiologisches Outcome

PURPOSE Vessel recanalization is an important predictor of clinical outcome in the treatment of acute ischemic stroke. Endovascular therapies are used with increasing frequency. There is no general agreement on the policy of anesthesia during endovascular therapy, ranging from general anesthesia (GA) to local anesthesia at the puncture site with conscious sedation (CS) as needed. The aim of the study was to evaluate the safety and feasibility and radiological and clinical outcome of endovascular stroke therapy under CS. MATERIALS AND METHODS We retrospectively included all patients with acute ischemic stroke who were treated with endovascular therapy over a five-year period. Data was evaluated with respect to type of sedation, conversion from CS to GA, recanalization rate, infarct volume and peri- and post-procedural complications. RESULTS There was a technical failure in 7 patients. Of the remaining 124 patients (mean age 68.8 ± 14.6 years), 65 were female (52 %). The site of occlusion was located in the anterior circulation in 94 patients (76 %) and in the posterior circulation in 30 cases (24 %). 105 patients (85 %) were treated under CS and 16 cases (13 %) primarily under GA. In 3 cases (2 %) peri-procedural conversion to GA was necessary. Primary intra-arterial thrombolysis, mechanical recanalization only, and combination therapy were performed in 60 (48 %), 27 (22 %) and 37 (30 %) patients, respectively. There were no significant differences for recanalization rate and complications between GA and CS. The mean procedure time was significantly shorter in patients treated under CS (p < 0.01). CONCLUSION Endovascular stroke therapy with CS is feasible, can be performed safely and is faster than with GA.

Long-term health-related quality of life after decompressive hemicraniectomy in stroke patients with life-threatening space-occupying brain edema

BACKGROUND Although randomized clinical trials have reported significant improvement in mortality and functional outcome as measured with modified Rankin Scale (mRS) or Barthel index (BI) in stroke patients with space-occupying anterior circulation infarctions treated with hemicraniectomy, many clinicians are still concerned about the long-term health-related quality of life (HRQoL). AIM Assessment of HRQoL after hemicraniectomy to holistically reevaluate clinical outcome. METHODS Eleven patients (6 men, 5 women; mean age 48 (SD 5.8) years) were examined at 9-51 months after hemicraniectomy. Test batteries comprised NIH stroke scale, BI, mRS, neuropsychological tests (Visual Object and Space Perception Battery and clock test), and HRQoL-scales (Short Form 36 Health Survey (SF-36), Nottingham Health Profile (NHP), Questions on Life Satisfaction, Hospital Anxiety and Depression Scale and EQ-5D). RESULTS Median values for NIHSS, BI and mRS were 11.5, 55 and 3.5. In HRQoL-scales, subscales related to physical mobility and functioning were consistently severely impaired, while subscales related to psychological well-being were impaired to a lesser extent. Mean scores for physical functioning and physical role were 10.5 and 12.5 in the SF-36, and 61.3 and 43.3 for physical mobility and energy in the NHP; emotional role and mental health scored 63.3 and 66.4 (SF-36), scores for emotional reaction and social isolation were 18.9 and 16.0 (NHP), respectively. CONCLUSION Although, physical components of HRQoL are highly impaired, these stroke patients achieved a satisfying level of psychological well-being which was endorsed by a nearly unanimous retrospective appraisal of life-saving hemicraniectomy.